HK1153112B - Self-expanding devices and methods therefor - Google Patents

Description

Self-expanding device and method therefor

RELATED APPLICATIONS

Priority of this application is claimed in U.S. provisional application No.61/014,653 filed on 18.12.2007 and U.S. provisional application No.61/058,803 filed on 4.6.2008, both of which are incorporated herein by reference in their entirety.

Technical Field

The present invention relates generally to delivery devices for delivering one or more implants to or near a sinus. At least a portion of the implants may be self-expanding (self-flaring), and at least a portion of the implants may be biodegradable and configured for drug delivery. Methods of using the delivery device are also described herein.

Background

Self-expanding devices may be used to hold, open, or enlarge a body structure, such as a vein, artery, ureter, urethra, hollow body organ, nasal passage, sinus cavity, and the like. Even though these devices may provide various advantages, it is desirable to have additional self-expanding devices. In particular, it would be desirable to have a self-expanding device that can provide advantageous physical and/or functional characteristics. In addition, it is desirable to have delivery devices for delivering self-expanding devices and other implants.

Disclosure of Invention

Self-expanding devices and methods of using and making them are described herein. The device may be used at various locations within the body for a variety of different purposes. In some variations, the device has a first compressed configuration enabling low profile delivery by the delivery device and a second expanded configuration for apposition against tissue, and comprises a single continuous filament or at least two non-intersecting filaments. In other variations, the device comprises two or more intersecting, joined, or contacting (e.g., in an overlapping, twisted, intertwined, or joined manner) filaments. At least a portion of these devices typically comprise a polymer, such as a biodegradable polymer. In the case of biodegradable polymers, the device (or a portion thereof) is typically capable of biodegrading over a predetermined period of time. The polymer may be any suitable or useful polymer and the device may comprise or include any additional suitable material. In some variations, for example, the device comprises at least one wire, at least one flexible section, and the like.

In some variations, the device is adapted to deliver a drug. In these variations, the polymer or at least a portion of the device may be coated or impregnated with a drug, at least partially coated with a drug eluting layer, or include one or more drug reservoirs. The drug may be configured to be released from the drug-eluting layer or drug reservoir over a period of time (e.g., from about 5 days to about 120 days, or even longer). Any suitable drug or formulation may be used, and in some variations more than one drug or formulation may be used. For example, multiple drugs may be configured to be released from a single drug eluting layer, or multiple drug eluting layers may be configured to release multiple drugs. The drug or formulation may be an anti-inflammatory agent, an anti-allergen agent, an anticholinergic agent, an antihistamine agent, an anti-infective agent, an antiplatelet agent, an anticoagulant (antithrombotic agent), an anti-scarring agent, an antiproliferative agent, a chemotherapeutic agent, an antineoplastic agent, a healing promoter, a decongestant, a vitamin, a high permeability agent, an immunomodulator, an immunosuppressant, or combinations and mixtures thereof. In some variations, the drug is an anti-inflammatory drug, such as mometasone furoate. The drug eluting layer may be discontinuous/intermittent and may include a release rate modifier. In some variations, the release rate modifier is a polyethylene glycol, such as PEG 6000.

Some of the devices described herein are sized and configured for implantation within one or more sinus cavities or sinus regions, such as an ethmoid sinus cavity, a maxillary sinus cavity, a frontal sinus cavity, a sphenoid sinus cavity, a osteomeatal complex, a nasal passage, or combinations thereof. However, as mentioned above, the device may be used in any hollow body organ (throat, bile duct, organ or passage of the excretory system, etc.) or cavity or even the vascular system.

In some variations, a self-expanding device is described having a first compressed configuration enabling low profile delivery through a delivery device and a second expanded configuration for apposition against tissue, wherein at least a portion of the device comprises a biodegradable material and the device is formed into a shape having a series (series) of peaks and valleys. In other variations, the device is formed in a shape having at least two series of peaks and/or valleys. In some variations, the shape of the device includes a diamond shape (diamond shape), an arrowhead shape, or a rectangular pattern/configuration. Some variations further include an engagement portion.

At least one of the peaks and valleys may have a loop at an end thereof. The loop may or may not be coated or impregnated with a drug or polymer for delivery of a drug therefrom. When a loop is used, it may be configured to achieve an even distribution of bending stresses (e.g., stresses exerted on the device when it is placed in its first configuration and loaded into a delivery device). The loop may include or define an eyelet for passage of a suture therethrough, such that the device collapses from its second configuration to its first configuration, for example, when the suture is pulled. The angle defined by the top of the loop may be any suitable angle, for example, the angle may be about 30 ° to about 150 ° when the device is in its expanded configuration. In some variations, the angle is about 75 °.

In some variations, a portion of the device or a portion of the polymer is at least partially coated with a drug or a drug-eluting layer. The polymer and drug-eluting layers may include PLG having different molar ratios of lactide to glycolide. As with the device described immediately above, any suitable drug or formulation may be delivered and the selection of such a drug or formulation is largely determined based on the intended use of the device. Further, as described above, the plurality of drugs may be configured to be released from the one or more drug eluting layers over a plurality of time periods. In variations where multiple drugs are released, each drug may or may not be released at the same time as the other drugs. In some variations, the device can be used to treat inflammation, and the drug eluting layer includes an anti-inflammatory agent.

In other variations, the device is described herein as having a first compressed configuration enabling low profile delivery through the delivery device and a second expanded configuration for apposition against the tissue wall, wherein the device has a geometry that facilitates its conforming (conformation) against the irregular tissue wall. In these variations, the device defines a lumen (having any suitable cross-sectional geometry) in its expanded configuration that is sized to facilitate the passage of one or more fluids (e.g., mucus or other discharge, water, saline or other irrigation fluid, etc.) therethrough.

In other variations, the device is described herein as having both unexpanded and expanded configurations, and wherein the device comprises at least two component parts, or a single continuous wire wound upon itself. The component parts may be discrete wires, discrete devices, combinations thereof, and the like. In some of these variations, the at least two components are formed in a shape having a series of peaks and valleys. The components may or may not be joined together, and in variations where they are joined together, they may be joined using welding (e.g., heat welding, ultrasonic welding, tack welding, rivet welding, etc.), adhesives (cements, adhesive polymers, etc.), polymers (e.g., low melting temperature polymers, etc.), sutures, clamps, clips, other mechanical fasteners, chemical bonds, or some combination thereof. They may also be connected by interwoven portions of the component parts. In some variations, the at least two component parts comprise at least two discrete expandable devices, and as such, for example, the entire device may be modular.

In other variations, a self-expanding biodegradable device is described having a size and configuration suitable for implantation in one or more sinus regions or sinus cavities or their ostia, wherein the device comprises one or more polymer filaments and has a shape approximating a repeating diamond-shaped pattern. The diamond pattern is generally defined by a series of repeating peaks and valleys. In some of these variations, the device may comprise at least two component parts (device or wire, etc.). In some variations, the biodegradable device comprises poly (lactic-co-glycolic acid). As with the devices described above, these modified devices may include joints formed in any suitable manner and having any suitable configuration.

Methods of treating one or more sinus cavities or one or more locations from which sinus cavities have been removed are also described herein. Generally, these methods include advancing a device adjacent to a sinus cavity and delivering at least a portion of the device into the sinus cavity. The devices are typically biodegradable. In some variations, the device comprises a polymer at least partially coated with a drug or drug-eluting layer and is formed in a shape having a series of peaks and valleys. The device can be advanced in a compressed configuration to the vicinity of the sinus cavity and then delivered or configured in any suitable manner to allow at least partial expansion within the sinus cavity. The device is typically constricted before it is advanced to enable low profile delivery, and the ratio of the device before and after constriction may be in the range of about 1: 1.1 to 1: 20 (i.e. for 1: 1.1 the diameter of the device before constriction is 1.1 times the diameter of the device after constriction). The apparatus used in these methods may be any of those described above, or other similar such apparatus having any of the characteristics described above. In variations where the device defines a lumen in its expanded configuration, the method may further comprise irrigating one or more sinus cavities.

Methods of making self-expanding devices are also described. In general, the method comprises: extruding a polymer filament, wherein the polymer filament comprises PLG having a mole percent of glycolide from about 70% to about 100% or a mole percent of lactide from about 70% to about 100%; coating the polymer filaments with a drug-eluting layer; and shaping the device. The device is typically capable of collapsing by at least 10% from the expanded configuration to the delivery configuration. The method may further comprise collapsing the device, or any additional suitable step.

Transfer devices and methods of using them are also described herein. The delivery device may deliver any suitable device or implant, including the self-expanding devices described herein. In some variations, the delivery device includes a handle and a cannula. In some variations, the cannula may have one or more curved sections. Each curved section may have any suitable angle. In some variations, the angle may be between about 10 ° and about 120 °. In other variations, the angle may be between about 50 ° and about 120 °. In other variations, the angle may be between 10 ° and about 110 °. In some variations, the cannula may be steerable. In addition, the cannula may have any suitable number of lumens (e.g., 1, 2, 3,4, or 5 or more lumens).

Additionally, in some variations, the cannula includes a cannula end having one or more markings. The indicia may or may not assist in direct visualization of the cannula tip and may or may not assist in indirect visualization of the cannula tip. Further, the cannula tip may have any suitable configuration of elements. In some variations, the cannula tip may include a groove and a branch (prong). In some of these variations, the branches may point inward. In some of these variations, the branch may be approximated as a point. In other variations, the sleeve end may comprise a plate extension, an expandable funnel-shaped end, a bulbous end, a slotted tube, a wedge-shaped end, a formable or deformable end, combinations thereof, and the like.

In some variations, the delivery device may include one or more casings. In some variations, the shell is disposed around an exterior of the cannula. In other variations, the housing is disposed inside the sleeve. In some variations, the shell is releasably connected to the cannula. The shell may or may not be configured to release one or more drugs. Further, in some variations, the delivery device may include one or more dilators or other implants disposed about the exterior of the cannula.

Further, in some variations, the delivery devices described herein may include a deployment mechanism for deploying one or more implants from the cannula. In some variations, the deployment mechanism comprises a plunger. In some of these variations, the plunger may include one or more operators (runners). In other variations, the deployment mechanism may include one or more stops.

Further, the handle may have any suitable configuration of elements. In some variations, the handle may include a plunger or trigger that may be connected to the deployment mechanism. In other variations, a plunger or trigger may be coupled to the cannula. In some variations, the handle may be adjustable. In some of these variations, the handle includes one or more adjustable rings. In other variations, the handle includes a plunger or trigger having an adjustable length.

In addition, methods of delivering one or more implants using the delivery devices described herein are also described herein. In some variations, the method comprises: contracting the self-expanding device from an expanded configuration to a compressed configuration, wherein the self-expanding device comprises at least two polymer filaments and has a shape approximating a repeating diamond-shaped pattern defined by a series of repeating peaks and valleys; loading the device in its compressed configuration into a delivery device comprising a cannula, wherein the cannula comprises one or more curved sections; advancing the cannula into the sinus cavity or ostium; and deploying the self-expanding device into the sinus cavity or ostium such that the self-expanding device expands to its expanded configuration. The transfer device may have any feature or combination of features described above.

In some variations, the method comprises piercing one or more tissues using a delivery device. In some of these variations, the one or more tissues are pierced using a slotted sheath. In other variations, the method includes viewing the delivery device. In some of these variations, the delivery device is viewed directly. In other of these variations, the delivery device is viewed indirectly (e.g., by fluoroscopy or ultrasound). In other variations, the method comprises irrigating or spraying the sinus cavity or ostium. In other variations, the method comprises dilating one or more tissues.

Further, the self-expanding device may be released from the delivery device in any suitable manner. In some variations, the self-expanding device may be released from the device by advancing a pusher through the cannula. In other variations, the self-expanding device may be delivered by withdrawing the sleeve relative to the stopper or shell. In other variations, the self-expanding device may be released by rotating the sleeve relative to the stopper or shell.

Drawings

FIG. 1A is an exemplary illustration of one variation of the devices described herein shown in an expanded configuration. FIG. 1B is a side view of the device of FIG. 1A shown in its compressed delivery configuration.

Fig. 2A-2E illustrate various loop configurations that may be used with the devices described herein.

Fig. 3A is a side view of an exemplary filament that may be used with the devices and methods described herein. Fig. 3B is a cross-sectional view of the filament of fig. 3A.

Fig. 4A and 4B illustrate one variation of how the devices described herein may be compressed using sutures made of other suitable materials that are passed through loop eyelets or other openings of the devices.

Fig. 4C shows how the device is loaded into the transfer device.

Fig. 5A and 5B provide examples of various delivery devices that may be used with the devices and methods described herein. Fig. 5C highlights various dimensions associated with the delivery device described herein.

Fig. 6 is a diagrammatic view of the anatomy of a sinus after typical sinus surgery.

Figures 7A-7C illustrate an exemplary method of delivering a device to an ethmoid sinus cavity.

Fig. 8A-8C illustrate an exemplary method of delivering a device to a maxillary sinus cavity.

Fig. 9A-9C illustrate an exemplary method of delivering a device to the vasculature.

Figures 10A-10C illustrate an exemplary method of delivering a device to bypass urine from an obstruction.

FIG. 11 is a flow chart summarizing how one variation of the devices described herein can be made.

Figure 12 provides the drug release profiles for three different devices.

Figure 13 shows in vivo release rate data for three exemplary devices described herein.

Fig. 14 shows the cumulative release of mometasone furoate from two different exemplary devices described herein.

Fig. 15-16 are exemplary illustrations of suitable variations of the devices described herein shown in their expanded configurations.

Fig. 17A is a perspective view of a suitable device wherein the pattern of the device approximates a repeating diamond-shaped pattern. Fig. 17B and 17C show side views of other variations of suitable devices having a similar pattern to that of fig. 17A.

Figure 18 shows a side view of a variant of a suitable device having a shape approximating an overlapping crown.

Fig. 19 is a side view of a suitable device wherein the device is in a pattern approximating a repeating arrowhead pattern.

Fig. 20 is an exemplary illustration of a suitable device variation shown in its expanded configuration.

21A-21C illustrate exemplary illustrations of variations of the apparatus including a slotted tube. Fig. 21A and 21C are side views of these variations in their unexpanded configuration. Fig. 21B and 21D are side views of these variations in their expanded configurations.

Fig. 22A-22M illustrate various joint configurations that may be used with the devices described herein.

Fig. 23A and 23B show exemplary illustrations of steerable cannulas that can be used with the delivery devices described herein.

FIGS. 24A-24Q illustrate various cannula tips that may be used with the delivery devices described herein.

Fig. 25A-25G illustrate various exemplary illustrations of a multi-lumen cannula.

Fig. 26A and 26B are side and cross-sectional views, respectively, of the distal end of a variation of a delivery device including a pusher, a cannula, and a sheath.

Fig. 27-28B illustrate an exemplary variation of a delivery device including a pusher.

Fig. 29A and 29B illustrate a variation of a delivery device that includes a stopper.

FIG. 30A is a perspective view of a variation of a delivery device including a stopper and a cannula. FIGS. 30B and 30C are side views of the stopper and cannula, respectively. Fig. 30D-30F illustrate one manner of manipulating the transfer device shown in fig. 30A.

Fig. 31A-32B provide examples of the distal ends of various delivery devices described herein.

Fig. 33 shows an example of a transfer device as described herein.

FIG. 34A is a cross-sectional side view of a handle for the delivery device described herein. Fig. 34B-34D are examples of adjustable handles suitable for use with the delivery devices described herein.

Figures 35A and 35B show side views of another variant of a suitable device having a shape approximating that of the superposed crowns.

Detailed Description

Described herein are self-expanding devices for use within hollow body organs, sinus cavities, vasculature, and the like. Methods for treating various conditions or diseases and methods for making the devices are also described. The device may be used in any area of the body that can benefit from the support or function provided by the device. In some variations, the device is used in one or more sinus cavities (before or after functional endoscopic sinus surgery). In other variations, the devices are used in the vasculature to help improve vessel patency or to provide support or functional benefits (e.g., in plaque or potential plaque formation areas, etc.). In other variations, the device may be used in the bladder, ureter, urethra, and the like. Further, a delivery device and a method of using the delivery device are also described herein. The delivery device may be used to deliver one or more of the self-expanding devices described herein, or may be used to deliver one or more different implants.

I. Device for measuring the position of a moving object

Self-expanding device

In general, the devices described herein are self-expanding devices having a first, compressed configuration and a second, expanded configuration. The devices may or may not be configured to conform or bear against one or more tissue surfaces in their expanded configuration, and in some cases such compliance may be enhanced by devices having geometries or configurations capable of conforming to irregular tissue surfaces or irregular body cavities. Indeed, the device may have any suitable configuration. In some variations, the device comprises a single continuous wire or at least two non-intersecting wires. Non-intersecting generally means that the filaments do not cross over each other in a typical weave pattern. In other variations, the device comprises two or more discrete elements, which may be wires or discrete devices, and which may or may not be joined or intersecting. The device may be made of any suitable material and may or may not be configured for drug delivery. Typically, at least a portion of the device comprises a biodegradable polymer, and the device is configured to degrade over a predetermined period of time. This is not to say that the device is not removable when necessary, in some configurations the device is configured to be easily retrieved and/or removed.

Referring now in particular to the drawings, fig. 1A and 1B show a variation of the device (100) in its expanded and compressed configurations, respectively. In this variation, the device comprises a single continuous wire and is formed in a shape having a series of peaks (102) and valleys (104). Although a large number of peaks and valleys are shown in fig. 1A and 1B, it should be understood that the device may include any number of peaks or valleys. Further, it should also be understood that while the exemplary device shown in FIGS. 1A and 1B has peaks and valleys, the device need not have any peaks or valleys. As such, the devices described herein may have from zero to many peaks and valleys.

In the variation shown in fig. 1A and 1B, the device also has a series of loops (106) formed at the ends of the peaks and valleys. It will be appreciated that the device need not have such a loop, but in some cases it may be desirable to have such a loop. Any number of loops may be formed on the device, and as described in more detail below, the loops may have any suitable configuration. The loop may be formed on the ends of all of the peaks and valleys, or on the ends of some of the peaks and valleys, or not on the ends of any of the peaks and valleys. Similarly, the loops may be formed on all or some of the peaks but not on any of the valleys, or on all or some of the valleys but not on any of the peaks, etc.

In certain cases, a loop may be desirable as it helps to achieve an even distribution of bending stresses applied when the device is collapsed to its compressed configuration. The ability of the loop to distribute stress also contributes to the ability of the device to self-expand upon deployment by reducing plastic deformation of the device. As described in more detail below, the one or more loops may also serve as a location for drug delivery. In these variations, the ring may be coated or impregnated with a drug, or coated or impregnated with a polymer for delivery of a drug therefrom. The loop may also be used to manufacture the device, for example, as an aid for positioning and manipulating the device, as described below.

In some variations, the loop includes or defines an eyelet through which a suture is passed. As described in detail below, sutures may be used, for example, to help collapse the device to its compressed configuration when drawn. In other variations, a suture (whether threaded through an eyelet or otherwise connected to the device) may be used to retrieve the device temporarily (e.g., in the event of an initial misplacement) or permanently (e.g., in the event that the device is not fully degraded or in the event that the device requires early withdrawal, e.g., in the event of an infection, complication, etc.). The angle (a) defined by the top of the collar may be any suitable angle. For example, the angle may be between about 10 ° and 170 °, between about 10 ° and 150 °, between about 10 ° and 130 °, between about 10 ° and 110 °, between about 10 ° and 90 °, between about 10 ° and 70 °, between about 10 ° and 30 °, between about 30 ° and 170 °, between about 30 ° and 150 °, between about 30 ° and 130 °, between about 30 ° and 110 °, between about 30 ° and 90 °, between about 30 ° and 70 °, between about 30 ° and 50 °, between about 50 ° and 170 °, between about 50 ° and 150 °, between about 50 ° and 130 °, between about 50 ° and 110 °, between about 50 ° and 90 °, between about 50 ° and 70 °, between about 60 ° and 120 °, between about 60 ° and 90 °, between about 70 ° and 170 °, between about 70 ° and 150 ° and 110 °, between about 50 ° and 90 °, between about 50 ° and 70 °, between about 60 ° and 120 °, between about 60 ° and 90 °, between about 70 ° and 170 °, between about 70 ° and 110 ° between about 70 °, between about 70 ° and 90 °, between about 90 ° and 170 °, between about 90 ° and 150 °, between about 90 ° and 130 °, between about 90 ° and 110 °, between about 110 ° and 170 °, between about 110 ° and 150 °, between about 110 ° and 130 °, between about 130 ° and 170 °, between about 130 ° and 150 °, between about 150 ° and 170 °, and so forth. In some variations, the angle is about 75 °. It should be noted that the angle (a) defined by the loop tops may be reduced to a smaller angle than those listed above when the device is collapsed into a self-expanding device or placed in a portion of the anatomy. Indeed, the angle (a) may be reduced to any suitable angle. For example, the angle may be reduced to an angle between about 0 ° and 30 °, between about 0 ° and 25 °, between about 0 ° and 20 °, between about 0 ° and 15 °, between about 0 ° and 10 °, between about 0 ° and 5 °, between about 5 ° and 15 °, between about 5 ° and 10 °, between about 1 ° and 5 °, between about 2 ° and 4 °, and the like.

The devices described herein are generally capable of self-expansion when configured. The rate of expansion may depend on a number of environmental factors such as temperature, pH, etc., as well as the specific physical characteristics of the device itself such as the materials used and the configuration of the device. In this way, the device can be designed to expand at a particular rate under certain conditions. In some variations, the device may still be self-expanding, but may also be assisted in its deployment by an inflatable balloon, an expansion device, or a heated element. In some variations, a sphere or other structure is pulled through the inner diameter of the device to assist in expansion of the device. In other variations, the device may be deformed into its expanded configuration.

Returning to fig. 1A and 1B, the device (100) has an expanded diameter (D) shown in fig. 1A and a compressed diameter (D) shown in fig. 1B. The ratio of expanded diameter (D) to compressed diameter (D), or D: D, may represent how effectively the device can be compressed. The ratio may be any suitable ratio. For example, the ratio can be from about 2: 1 to about 20: 1, from about 2: 1 to about 15: 1, from about 2: 1 to about 12: 1, from about 2: 1 to about 8: 1, from about 2: 1 to about 5: 1, from about 5: 1 to about 20: 1, from about 5: 1 to about 15: 1, from about 5: 1 to about 12: 1, from about 5: 1 to about 8: 1, from about 8: 1 to about 20: 1, from about 8: 1 to about 15: 1, from about 8: 1 to about 12: 1, from about 12: 1 to about 20: 1, from about 12: 1 to about 15: 1, from about 15: 1 to about 20: 1, about 10: 1, and the like. The actual values of the expanded and compressed diameters typically depend on the target location of the configuration so that proper tissue apposition can be achieved. In general, however, the compressed configuration has a diameter suitable for low profile delivery using a delivery device. For example, the diameter (d) of the device in the compressed configuration may be from about 0.05mm to about 5.5mm, from about 0.05mm to about 3mm, from about 0.05mm to about 1mm, from about 1mm to about 5.5mm, from about 1mm to about 3mm, from about 3mm to about 5.5mm, and the like. In some variations, the diameter (d) of the device in its compressed configuration is about 4.5 mm. It should also be understood that while the device may provide support for a given area, the device need only make physical contact with a portion of that area, for example, about 5% of that area.

It should be understood that although shown in fig. 1A and 1B as having a generally crown shape, the device may take any shape that enables an expanded configuration for apposition against tissue and a compressed configuration for low profile delivery. For example, the device may have a generally bi-coronal shape, may have a generally smooth undulating shape, may have a generally helical shape, and the like.

Fig. 15 shows a variant of a suitable device (1500) in its expanded configuration. This variation may have particular utility where it is desired to provide different amounts of support to different areas of the surrounding tissue. In this variation, the device comprises a single continuous filament formed into a shape having a series of valleys (1502), a series of lower peaks (1504), and a series of higher peaks (1506) that combine to form a device having a generally varying crown shape. Although a number of higher peaks, lower peaks and valleys are shown in fig. 15, the device may include any number of peaks or valleys. When the device (1500) is in its expanded configuration, each higher peak (1506) will have a higher peak height (H) relative to a valley (1502), while each lower peak (1504) will have a lower peak height (H) relative to a valley (1502). The higher (H) and lower (H) peak heights may be any suitable values, and these values may be selected or determined based on the desired manner in which the device will be used.

While the peaks of the device (1500) shown in fig. 15 alternate between higher peaks (1506) and lower peaks (1504), they may be in any suitable arrangement or pattern. In some variations, the arrangement may, but need not, employ a repeating pattern. Furthermore, in some variations, the number of higher peaks (1506) may be equal to the number of lower peaks (1504). Of course, in other variations, the number of higher peaks (1506) is not equal to the number of lower peaks (1504). Indeed, all but one of the peaks may be higher peaks (1506), all but one of the peaks may be lower peaks (1504), or the peaks may include some mix of higher (1506) and lower (1504) peaks. Further, the device (1500) may have a series of loops (1508) formed at the ends of the higher peaks, lower peaks, and valleys, but this is not required. The loops described briefly above and in more detail below may be formed on all or some of the higher peaks or not on any of the higher peaks, or on all or some of the lower peaks or not on any of the lower peaks, or on all or some of the valleys or not on any of the valleys, or some combination of these.

Although shown in fig. 15 as having two different series of peaks (upper (1506) and lower (1504)), the device (1500) may alternatively have three or more different series of peaks. Each series of peaks can have any number of peaks of that type, and each series of peaks can have any height relative to a valley. Further, the peaks of each series may have any suitable arrangement or pattern as described above.

Fig. 16 shows another variant of a suitable device (1600) in its expanded configuration. In this variation, the device (1600) comprises a single continuous wire and is formed in a shape having a series of higher valleys (1602), lower valleys (1604), higher peaks (1606) and lower peaks (1608). As with all of the devices described above and throughout, the modified device may have any number of peaks or valleys, and the peaks (higher or lower) may have any suitable height relative to the valleys (higher or lower). The peaks and valleys may have any arrangement or pattern as described above with respect to the example of fig. 15. For example, in the variation shown in fig. 16, higher peaks (1606) alternate with lower peaks (1608), and higher valleys (1602) alternate with lower valleys (1604), to form a device having a generally quasi-crown shape. Further, the device (1600) may have a series of loops (1610) formed at the ends of higher peaks, lower peaks, higher valleys, lower valleys, or some combination thereof. Of course, the device may not necessarily have any loops. Further, it should be understood that the loops (described throughout) may be formed on all or some of the higher peaks or not on any of the higher peaks, or on all or some of the lower peaks or not on any of the lower peaks, or on all or some of the lower valleys or not on any of the lower valleys, or on all or some of the higher valleys or not on any of the higher valleys, or some combination thereof.

The type of device selected (i.e., length, geometry, number of loops, etc.) may be selected based on the particular application of the device. In some cases, it may be desirable to select a device that has a longer length than the above-described devices, but has sufficient radial strength to overcome the forces applied to it during use. Fig. 17A shows a variation of the device (1700) having a longer length than the device described above, shown here in its expanded configuration. In this variation, the device includes one or more wires and is formed in a shape having a series of peaks (1702), valleys (1704), and junctions (1706). Although a plurality of peaks, valleys, and junctions are shown in fig. 17A, the device (1700) may include any suitable number of each of these elements. Further, while in the exemplary device shown in fig. 17A the joints (1706) are located between peaks (1702) and valleys (1704) to form a generally diamond-shaped pattern, it should be appreciated that the device may take on any pattern. Indeed, in some variations, the device may take a substantially kite-shaped pattern, and so on.

In addition, the device (1700) may have a series of loops (1708) on peaks, valleys, junctions, or some combination thereof. It should be noted that the device may not necessarily have such a loop, but in some cases the loop may be required throughout. Further, any number of loops may be formed on the device, and each loop may have any suitable configuration as described below. For example, the loops may be formed on all or some of the peaks, valleys, joins, or none of the peaks, valleys, joins, or a combination thereof.

The overall structure of the device shown in fig. 17A can be implemented in any of a number of different ways. In some variations (not shown), the discrete filaments are bonded together to form a generally diamond shape. In other variations, as shown in fig. 17B, the structure of device (1710) may be achieved by placing an upper crown device (1712), such as the exemplary device shown in fig. 1A, over a lower crown device (1714). In this way, a modular or composite device is formed. Of course, the device may include any number of modular or discrete units to form a device having any suitable length or geometry.

In these variations, each upper (1712) and lower (1714) crown arrangement has a series of peaks (1716) and valleys (1718). In this way, the crests of the crest forming devices (1710) of the upper crown (1712) and the troughs of the lower crown (1714) form the troughs of the crest forming devices (1710). The valleys of the upper crown (1712) engage the peaks of the lower crown (1714) to form joints (1720). In some variations, upper crown portion (1712) and lower crown portion (1714) may have different axial lengths, and thus may have different radial strengths. Although modular or composite devices are described with respect to this variation, it will of course be appreciated that these types of devices may also be formed from a single continuous wire.

In other variations, as shown in fig. 17C, the device (1722) may be formed by placing a first crown device (1724), such as the exemplary device shown in fig. 1A, in a phase offset position relative to a second crown device (1726). Both the first (1724) and second (1726) crown means have a series of peaks (1728) and valleys (1730) that make up the peaks and valleys of the means (1722). Furthermore, a joint (1732) is formed by the crossing of the filaments of the two crown-shaped devices. The device (1722) may be formed from a single continuous filament, or may be formed from a combination of two separate devices. Of course, when the devices are modular in nature, each individual device may be formed from a single continuous wire or more than one wire.

While the crown devices shown in FIG. 17C are arranged such that the peaks of one crown device are above the valleys of another crown device, the crown devices may have any relative positioning. Depending on the relative rotation (or phase offset) between first crown device (1724) and second crown device (1726), devices (1724) may not have the general configuration generally shown in fig. 17A-17C, but rather may be in the form of a rectangle or other shape (not shown). If the phase shift between the two devices is of sufficient magnitude, the devices (1800) are formed such that the peaks (1806) of the first and second crown devices (1802, 1804) are disposed substantially in alignment, as shown in fig. 18. In this variation, the valleys (1808) of the first and second crown devices (1802, 1804) are also substantially aligned. While the junction (1810) may be disposed substantially equidistant between peaks and valleys of the first crown device (1802) as shown in fig. 18, the first crown device (1802) and the second crown device (1804) may be axially offset relative to one another. For example, in some variations (not shown), the first and second crown devices are axially positioned such that the peaks of the respective crown devices engage to form the junction. In other variations, the valleys of each crown may join to form a joint.

Fig. 35A and 35B illustrate another modular variation of device (3500) comprising first crown device (3502) and second crown device (3504). Fig. 35B shows first crown device (3502) and second crown device (3504) separated, while fig. 35A shows first crown device (3502) and second crown device (3504) connected at junction (3506) to form device (3500). As shown in fig. 35B, a joint (3506) may be formed by connecting the filaments (3508) of the respective crown-shaped devices such that the filaments (3508) do not overlap. The joints (3506) can be formed in any suitable manner (e.g., adhesive, welding, mechanical fastening). When device (3500) is retracted, filament (3508) in junction (3506) can be rotated in the same direction without being rotated in a different direction, which in turn helps prevent separation of filament (3508). This in turn may increase the overall strength of the device (3500). However, it should be noted that each engagement portion of device (3500) may be any suitable engagement portion as described in more detail below.

In other variations, as shown in fig. 19, the device (1900) includes first (1902), second (1904), and third (1906) crown devices, each having a series of peaks (1907) and valleys (1908). The device (1900) may be made from a single continuous filament, or may be made from individual crown devices in a composite fashion (e.g., where each crown device is made from a separate continuous filament). In some variations, the first (1902) and second (1904) crown devices are positioned such that the peaks of the respective devices engage to form a higher junction (1910). In some of these variations, the first (1902) and third (1906) crown devices are axially positioned such that the valleys of each device engage to form a lower junction (1912). In these variations, the overall structure of the device (1900) forms a generally repeating arrowhead-shaped pattern. It will be appreciated that the overall configuration of these devices may be altered by phase shifting one or more of the crown devices relative to the overall device, by axially shifting one or more of the crown devices relative to the overall device, by a combination of the foregoing, or the like.

Fig. 20 shows a further variant of the device (2000) in its expanded configuration. First (2002) and second (2004) quasi-crown devices are shown, such as the device shown in fig. 16. In these variations, the first (2002) and second (2004) quasi-crown devices have higher (2006) and lower (2008) peaks, higher (2010) and lower (2012) valleys, and joints (2014). In some variations, one of the quasi-crown devices may be phase offset relative to the other, axially offset relative to the other, a combination thereof, or the like. In other variations (not shown), one or more of the quasi-crown devices may be replaced by one or more deformable crown devices. In other variations, one or more of the quasi-crown devices may be replaced by a crown device as described above. Further, some variations may include more than two devices that are quasi-crowns, deformed crowns, some combinations thereof, and the like.

The entire device (2000) may be made from one continuous filament, or may be modular or composite in nature. The device may additionally include a series of loops (2016), but is not required. These loops may take any suitable configuration as described below. The loops may be formed on all or some of the peaks, valleys and joins, or none of the peaks, valleys and joins, or some combination of these. The engagement portion may have any suitable configuration as described below.

When loops are used in the devices described herein, they can have any suitable configuration. Figures 2A-2E provide various examples of suitable loop configurations for any of the devices. Fig. 2A shows a variation of the collar (200) including a drug reservoir (202). In this variation, the device wire (204) has crimped more than about 360 °, but less than about 720 ° to form a complete loop. Fig. 2B shows a variation of loop (206) in which device wire (208) has crimped less than about 360 °. Fig. 2C shows a variation of loop (210) in which device wire (212) has been crimped more than 720 ° to form two loops. Fig. 2D shows loop (214) with device wire (216) crimped in several complete turns to form a spring-like configuration. Fig. 2E shows loops (218) in which the device wire (220) has been rotated less than 360 ° in one direction to form a first loop and then rotated about 360 ° in the opposite direction to form a second loop, whereby the two loops approximate the shape of the numeral 8. Of course, these are just a few of the many available loop configurations.

Although only the drug reservoir (202) is shown in fig. 2A, the drug reservoir or drug delivery site may be used in conjunction with any loop configuration when drug delivery is desired. As noted above, some or all of the loops of the device may contain drug reservoirs or drug delivery sites, or none of the loops of the device may contain drug reservoirs or drug delivery sites. Furthermore, the drug reservoir may be included on or in any part of the device. In some variations, the drug reservoir is in the form of a polymeric coating and is similar to the polymeric drug eluting layer described throughout. In other variations, the drug reservoir (202) may be in the form of droplets or beads of drug-filled material disposed within, on, or around the outer region of the collar. Where the device comprises a wire having perforations such as slots, holes or channels, a drug reservoir may also (or alternatively) be contained therein. When more than one drug reservoir is used, the drugs delivered therefrom may be the same or different. Similarly, the drug released from the drug reservoir may be the same or different from the drug released from other portions of the device. The drug reservoir may release the drug at the same rate as the rest of the device, or at a different rate.

Although some splices include one or more loops as described below, it should be noted that a substantial difference between these splices and loops is that the splice occurs at the intersection or intersection of two or more wires or wire segments. When the joints are used in the devices described herein, they can have any suitable configuration. The configuration of a given junction may be the same or different from other junctions in the same device. Fig. 22A-22M provide examples of suitable joint configurations. Fig. 22A shows a variation of the junction (2200) comprising two straight wires (2202) and a suture tie (2204). While fig. 22A shows inclusion of suture tie (2204), the joint (2200) may not necessarily include it. Indeed, in some junctions, the two wires are not tied, joined, or connected in any way. In other variations, one or more elastic bands, washers, gaskets, clamps, sutures, clips, other mechanical fasteners, or combinations thereof may be used to join the two filaments. In other variations, the two filaments may be bonded using welding (e.g., heat welding, ultrasonic welding, tack welding, rivet welding, etc.), may be bonded using an adhesive, bonding agent, or low melt temperature polymer, etc. In variations where a polymer is used, the polymer may be biodegradable. Further, the polymer may be configured to release one or more drugs over a period of time. In other variations, as shown in fig. 22B, the joint (2206) includes a bolt or other biocompatible (and in some variations biodegradable) cylinder (2210) that passes through a hole or channel (not shown) formed in the wire (2208). In this way, bolt (2210) may facilitate rotation between wires (2208) but not allow lateral movement therebetween. Although fig. 22B is shown with bolts (2210), the joints (2206) may include any suitable rod, screw, pin, peg, or cylinder (in most cases made of biocompatible and biodegradable materials). It will also be appreciated that any suitable combination of the methods and structures described above for bonding or adhering two or more filaments may be used in these junctions.

Fig. 22C shows another variation of joint (2212) in which wire (2214) is bent around each other. The wire (2214) may additionally be joined using any combination of the methods and structures described above. Although fig. 22C shows bending at an angle of about 90 °, wire (2214) can be bent at any suitable angle. In other variations, as shown in fig. 22D, the joint (2216) may be formed by wrapping the wire (2218) around each other to form a generally helical structure. These modified spirals can include any number of turns or loops. In addition, while the wound wires (2218) are configured vertically, they may alternatively be configured horizontally, as shown in fig. 22E, or at an angle (not shown).

In some variations, one or more of the filaments form loops at the junctions. In these variations, the loop may have any of the configurations described above. In variations where more than one filament forms a loop, the loops may have the same or different configurations. Fig. 22F shows a variation of a splice (2220) comprising a wire (2222) and a loop (2224). In this variant, one wire is passed straight through the loop formed by the other wire. In other variations, such as the splice (2226) shown in fig. 22G, the wire (2228) passes through the loop (2230) at an angle or in a curved manner. These splices may be formed by winding a first wire around a second wire or by passing the first wire through a preformed loop.

In other variations, the joint comprises at least two loops formed by at least two filaments. Fig. 22H shows one such variation of a joint (2232), including a filament (2234), a loop (2236), and a suture tie (2238). In the example shown in fig. 22H, two loops (2236) are tied to each other using a suture tie (2238). However, it should be recognized that any combination of the above structures or methods may be used to join the loops. Further, in some variations, one loop has a particular orientation relative to another loop. For example, fig. 22I and 22J show a side view and a front view, respectively, of one variation of the joint (2242). There are shown the rings (2240) engaged with the barbell-shaped structure (2244) such that the ring holes (not shown) are aligned. The barbell-shaped structures (2244) generally allow the rings (2240) to rotate relative to each other, but cannot move laterally relative to each other. In some variations (not shown), the barbell-shaped structure has a channel through which a drug reservoir may be placed or through which a suture may be passed. While shown in fig. 22I and 22J as having a barbell-shaped structure (2244), any suitable structure may be used. For example, threads may be formed through a hole defined by the collar.

Fig. 22K shows another variation of a joint (2246) comprising a wire (2248) and a loop (2250). For each loop, the wire forming that loop is wound through an aperture (2252) defined by the other loop. In some variations, this allows for relative rotation between the collars. The joint (2246) may be formed by winding one wire around a preformed loop or by simultaneously winding two wires. It should also be appreciated that any of the methods or structures described above may be used to further bind or join the loops.

In other variations, such as the one shown in fig. 22L, the joint (2254) includes an outer ring (2256) that wraps around the outside of the inner ring (2258). The apertures defined by the two rings may be concentric. In some of these variations, the drug reservoir may be placed in the hole defined by the inner loop (2258), or the suture may be passed through the hole. In some of these variations, the inner ring loop (2258) is rotatable relative to the outer ring loop (2256). Fig. 22M also shows another variation of the interface (2260), including a helically wound collar (2262). The aperture (2264) defined by the helically wound loop (2262) may hold one or more drug reservoirs therein, or may have a suture threaded therethrough. It should also be appreciated that the modified joint may be further combined using any combination of the above structures and methods. Of course, the variations described herein are but a few of the many joint configurations that can be used with the devices described herein.

In various variations of the devices described herein, the device may be formed from one or more individual filaments, but need not be formed in this manner. For example, fig. 21A and 21B illustrate variations of a suitable device (2100) in its unexpanded and expanded configurations, respectively. In this variation, the apparatus (2100) includes a slotted tube (2102). The tube may, in turn, include a series of alternating grooves (2104) and strips (2106). Although a plurality of grooves (2104) and bars (2106) are shown in fig. 21A and 21B, any suitable number of grooves and bars may be included. When the device (2100) is in its unexpanded configuration, the strip (2106) is substantially in-line with the tube (2102). When the device (2100) is in its expanded configuration, the strips (2106) may bend, or deform away from the body of the tube (2102). This expansion reduces the length of the tube (2102) while increasing the radius of a portion of the tube (2102). While fig. 21A and 21B are shown with an alternating set of grooves (2104) and strips (2106), the device can have any number of sets of grooves and strips. For example, as shown in fig. 21C and 21D in their unexpanded and expanded configurations, respectively, the device (2108) has two alternating sets of slots (2110) and strips (2112) located within the tube (2114). While shown in fig. 21A-21D as being generally rectangular in shape, the slots and tubes may have any suitable shape or configuration. Of course, the strip (2112) itself may be made of one or more wires as described herein.

Fig. 3A and 3B provide exemplary illustrations of suitable wires for any of the devices described herein. Fig. 3A shows a side view of the wire and fig. 3B shows a cross-sectional view of the wire of fig. 3A. In these figures, the filament (302) and drug-eluting layer (304) are shown. The filaments (302) may be made of any suitable biocompatible material. Typically, the filament (302) comprises a biodegradable polymer that is capable of degrading within a predetermined time. The polymer may be semi-crystalline, crystalline or amorphous in nature. Suitable polymers for use in the device are described in detail below.

While shown as being completely solid in fig. 3A and 3B, the filaments (302) may also include features (e.g., one or more porous beads, etc.) that promote the flow of myxoid or other bodily fluids around them. The filaments (302) may also include features that increase the surface area available for deposition of the drug-eluting layer (304). In some variations, the wire (302) may be formed as a perforated structure, including holes, slots, channels, and the like. It should be understood that while the filaments shown in fig. 3A and 3B include a drug-eluting layer (304), the devices described herein need not have such a layer. It should also be understood that while the drug-eluting layer (304) is shown as being substantially continuous in nature, this is not required. Indeed, the layer may be discontinuous, covering only a portion or selected portions of the polymer filaments. Similarly, although the wire is shown in fig. 3A as having a generally cylindrical cross-section, the cross-section may be any suitable geometric shape. Additionally, while the drug-eluting layer (304) is shown as having a greater thickness than the wire (302) it surrounds, it should be understood that the respective thicknesses of these components may be selected based on the end use of the device. These figures are exemplary only, and any number of additional configurations may be used as desired.

Although shown in fig. 3B as comprising a polymer (306) containing drug particles (308), the drug-eluting layer (304) may be made of any suitable biocompatible material capable of releasing a drug over a period of time, and may be constructed in any suitable manner. The drug delivery time may be varied as desired, and the drug-eluting layer (304) may be correspondingly configured to release the drug over a predetermined period of time. In some variations, the time period is configured to be as long as required to biodegrade the filament (302). In other variations, the time period may be on the order of hours, days, weeks, or months. The time of drug delivery can be determined taking into account the use of the device. For example, when the device is used to treat one or more sinus conditions, the period of time can be between about 1 day and about 10 days, between about 1 day and about 8 days, between about 1 day and about 5 days, between about 1 day and about 3 days, between about 5 days and about 120 days, between about 5 days and about 90 days, between about 5 days and about 60 days, between about 5 days and about 45 days, between about 5 days and about 20 days, between about 20 days and about 90 days, between about 20 days and about 60 days, between about 20 days and about 45 days, between about 45 days and about 90 days, between about 45 days and about 60 days, or about 30 days. In some variations, the drug delivery rate may not be constant over the period of time, as described below.

As noted above, the drug-eluting layer may (although need not) include a polymer. In some variations, the drug eluting includes a biodegradable polymer, such as poly (DL-lactide-co-glycolide) (i.e., PLG), polylactide, polyglycolide, trimethylated chitosan (trymethyllatedchitosan), or any of the biodegradable polymers described below. In variations where PLG is used, any suitable molar ratio of lactide to glycolide may be used. For example, the mole percent of lactide or the mole percent of glycolide can be any suitable amount, e.g., between about 0% and about 100%, between about 30% and about 100%, between about 50% and about 100%, between about 70% and about 100%, between about 0% and about 70%, between about 30% and about 70%, between about 50% and about 70%, between about 0% and about 50%, between about 30% and about 50%, between about 0% and about 50%, etc. In some variations, the molar ratio of lactide to glycolide is about 70: 30.

In a similar manner, the filament (302) may comprise a polymer, such as a biodegradable polymer, such as PLG, polylactide, polyglycolide, or any of the biodegradable polymers described below. In variations where PLG is used, any suitable molar ratio of lactide to glycolide may be used. For example, the mole percent of lactide or the mole percent of glycolide is between about 70% and 100%. In some variations, the molar ratio of lactide to glycolide is about 10: 90. In other variations, the filaments do not include a polymer, but are still capable of degrading over a period of time. For example, the silk can include poly-tyrosine carbonate, tepalflex, hyaluronic acid, collagen, mixtures thereof, and the like.

The wire may additionally comprise one or more metallic regions. This may be desirable, for example, to help control the rate of degradation of the device, to provide radiopacity to the device, to increase the mechanical integrity of the device, and the like. In some variations, the metal region may comprise a bar having a cylindrical or substantially cylindrical cross-section. Alternatively, the strips may have a square, rectangular, oval or other cross-sectional shape. In other variations, the metallic region may include metallic particles mixed with a portion of the wire material. The metal region is capable of degrading upon exposure to bodily fluids and may be surrounded by any suitable polymer or other material. The metal region may also have one or more pores configured to include drug particles. Examples of suitable metallic materials include, but are not limited to, zinc, magnesium, and iron.

In variations that include a metallic region, the device wire may be configured to degrade more slowly than the metallic region upon exposure to bodily fluids. In some of these variations, the wire may be configured to retard, inhibit, or prevent degradation of the metal region in a manner that allows the metal region to provide additional mechanical support to the device wire over a selected period of time. This may be achieved by a wire that shields the metal area from bodily fluids for a selected period of time. The metallic region may begin to degrade when the wire material is only partially degraded or may begin to degrade when the wire material is fully degraded. In some variations, the metallic region may be configured to completely or nearly completely degrade before the wire material completely degrades. In other variations, the wire material may be configured to completely or nearly completely degrade before the metallic region completely degrades.

The device may also include one or more flexible segments. The flexible section may optionally be arranged to inhibit or prevent the device from cracking when subjected to applied stresses in use. For example, in device variations having loops, the flexible section may be disposed within or adjacent to the loops. This may be helpful because the stresses applied during use, such as shrinkage, transfer, deployment, etc., may cause deformation or strain in structural elements of the device, and may be greater in elements configured to bend (e.g., loops). In some variations, the flexible section includes a region having a cavity formed in the device, including but not limited to a loop. Such cavities may be formed by laser cutting and may or may not be filled with a polymer or polymer-solvent mixture.

In use, the flexible segments may have any suitable cross-sectional shape, including but not limited to rectangular, circular, and oval. In some variations, the cross-section of the flexible section is variable over the thickness of the device. For example, the width of the flexible section along the length of the loop may be proportional to the magnitude of the strain along the loop when the device is stressed. In these variations, the flexible section may be widest at or near the center of the curvature of the loop and decrease in either direction along the length of the loop. Any number of flexible segments may be used, and in some variations, a single loop may have two or more flexible segments. Multiple cavities may be used to reduce strain in high strain regions without degrading the structural integrity of the device.

In device variations where the filaments comprise one or more polymers, the device further comprises one or more plasticizers. Plasticizers, for example, can be used to increase the total strain that can be borne by the device wire before it fails (e.g., when the device no longer remains properly open and, if desired, no longer properly expands the passageway or cavity, or when the device ruptures and/or breaks in a high strain region). The rupture may be caused by shrinkage of the device prior to delivery or by configuration of the device, and the plasticizer helps prevent the formation of such ruptures. The plasticizer may leach out of the device after it is deployed at the target location, potentially contributing to the rigidity and potentially mechanical integrity of the device. Leaching of the plasticizer can be timed. For example, it may be timed to leach out as stress is placed on the device, potentially increasing mechanical integrity when it is needed most.

It should be understood that the terms "plasticizer" and "plasticizer" are used interchangeably throughout. Plasticizers can include any agent or combination of agents that can be added to alter the mechanical properties of the polymeric component or the product formed from the polymeric component. In some variations, the plasticizer may be combined with an aqueous or lipid-containing solvent at a temperature from about room temperature to about body temperature to form a liquid or semi-solid. In other variations, the plasticizer may be dissolved in a limited amount of water and leached from the polymeric material. In other variations, the plasticizer may be dissolved in the body fluid.

Without being bound by any theory or mechanism of action, it is believed that the plasticizer helps to reduce crystallinity, lower glass transition temperature (Tg), or weaken intermolecular forces between polymers, thereby forming or enhancing component flow between polymers. Mechanical properties that may be altered include, but are not limited to, Young's modulus, tensile strength, impact strength, tear strength, and strain to failure. Plasticizers can be monomeric, polymeric, copolymeric, or combinations thereof, and can be added to the polymer composition with or without covalent bonds.

Examples of classes of plasticizers include, but are not limited to, low molecular weight polymers, e.g., monoblock polymers, multiblock polymers, and copolymers; oligomers, such as lactic acid oligomers, including, but not limited to, ethyl-terminated lactic acid oligomers; dimers of cyclic lactic acid and glycolic acid; an organic small molecule; hydrogen bond-forming organic compounds with and without hydroxyl groups; polyols, such as low molecular weight polyols having aliphatic hydroxyl groups; saturated alkanols, such as butanol, pentanol and hexanol; sugar alcohols and anhydrides of sugar alcohols; polyethers such as polyalkylene glycols; esters, such as citrate, phthalate, sebacate and adipate; a polyester; an aliphatic acid; saturated and unsaturated fatty acids; a fatty alcohol; cholesterol; a steroid; phospholipids, such as lecithin; proteins, such as animal proteins and plant proteins; oils, such as vegetable oils and animal oils; a silicone resin; acetylated monoglycerides; a diglyceride; a triglyceride; an amide; an acetamide; a sulfoxide; a sulfone; a pyrrolidone; an oxyacid (oxa acid); diglycolic acid; and any analogs, derivatives, copolymers, and combinations thereof.

In some variations, plasticizers include, but are not limited to, polyols such as caprolactone diol, caprolactone triol, sorbitol, erythritol, epoxypropanol, mannitol, sorbitol, sucrose, and trimethylolpropane. In other variations, plasticizers include, but are not limited to, glycols, such as ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, propylene glycol, butylene glycol, 1, 2-butylene glycol, 2, 3-butylene glycol, phenylethanediol, pentamethylene glycol, hexamethylene glycol; glycol ethers such as monopropylene glycol monoisopropyl ether, propylene glycol monoethyl ether, ethylene glycol monoethyl ether, and diethylene glycol monoethyl ether; and any analogs, derivatives, copolymers, and combinations thereof.

In other variations, plasticizers include, but are not limited to, esters, for example, glycol esters, such as diethylene glycol dibenzoate, dipropylene glycol dibenzoate, triethylene glycol decanoate-caprylate; stearic acid, such as glycerol monostearate; a citric acid ester; an organic acid ester; an aromatic carboxylic acid ester; an aliphatic dicarboxylic acid ester; fatty acid esters such as stearic acid, oleic acid, myristic acid, palmitic acid, and sebacic acid esters; triacetin; poly (esters) such as phthalate polyesters, adipate polyesters, glutarate polyesters, phthalates such as dialkyl phthalates, dimethyl phthalate, diethyl phthalate, isopropyl phthalate, dibutyl phthalate, dihexyl phthalate, dioctyl phthalate, diisononyl phthalate, and diisodecyl phthalate; sebacates, such as alkyl sebacates, dimethyl sebacate, dibutyl sebacate; hydroxy-esters such as lactate, alkyl lactate, ethyl lactate, butyl lactate, allyl glycolate, ethyl glycolate, and glycerol monostearate; citrates, such as alkyl acetyl citrate, triethyl acetyl citrate, tributyl acetyl citrate, trihexyl acetyl citrate, alkyl citrates, triethyl citrate, and tributyl citrate; castor oil esters, such as methyl ricinoleate; aromatic carboxylic acid esters such as trimellitic acid ester, benzoic acid ester, and terephthalic acid ester; aliphatic dicarboxylic acid esters such as dialkyl adipate, alkyl allyl ether diester adipate, dibutoxyethoxyethyl adipate, diisobutyl adipate, sebacate, azelate, citrate and tartrate; and fatty acid esters, such as glycerol mono-, di-or triacetate and sodium diethyl sulfosuccinate; and any analogs, derivatives, copolymers, and combinations thereof.

In other variations, plasticizers include, but are not limited to, ethers and polyethers, such as polyalkylene glycols, e.g., polyethylene glycol (PEG), polypropylene glycol, and polyethylene-propylene glycol; PEG derivatives, such as methoxypolyethylene glycol (mPEG); and ester-ethers such as diethylene glycol dibenzoate, dipropylene glycol dibenzoate, and triethylene glycol decanoate-octanoate; and any analogs, derivatives, copolymers, and combinations thereof.

In other variations, plasticizers include, but are not limited to, amides such as oleamide, erucamide, and palmitamide; alkyl acetamides such as dimethylacetamide; sulfoxides, such as dimethyl sulfoxide; pyrrolidones, such as n-methylpyrrolidone; sulfones, such as sulfolane; acids, such as oxo monoacids, oxo diacids, such as 3, 6, 9-trioxaundecanedioic acid, polyoxaandioic acid (polyoxa diacide), acetylated ethyl citrate, acetylated butyl citrate, acetylated capryl citrate, and diglycolic acids, such as dimethylolpropionic acid; and any analogs, derivatives, copolymers, and combinations thereof.

In other variations, plasticizers include, but are not limited to, vegetable oils, including, but not limited to, epoxidized soybean oil; linseed oil; castor oil; coconut oil; grading coconut oil; an epoxidized resinate; and fatty acid esters such as stearic acid, oleic acid, myristic acid, palmitic acid, and sebacic acid esters; essential oils, including, but not limited to, angelica oil, anise oil, arnica oil, lime oil (aurantii aetheroleum), valerian oil, perilla oil, bergamot oil, peppermint oil, bucco aetheroleum oil, camphor, cardamom oil, cinnamon oil, golden larch oil, chrysanthemum oil, Japanese datura oil (cinaeaetetheroleum), citronella oil, lemon oil, mandarin oil, costus oil, turmeric oil, echinacea oil (caralina oil), elemi oil, tarragon oil, eucalyptus oil, fennel oil, pine leaf oil, pine oil, cotton oil, gelcap oil, wintergreen oil (gaultheria aetheroleum), geranium oil, guaiaca oil, asarum oil, orris oil, hypericum oil, calamus oil, chamomile oil, fir oil, garlic oil, coriander oil, bay oil, myrtle oil, lemon oil, peppermint oil, lemon oil, olive oil, thyme oil, olive oil, peppermint oil, thyme oil, peppermint oil, lemon oil, peppermint oil, olive oil, peppermint oil, lemon oil, olive oil, peppermint oil, lemon oil, peppermint, Menthol, yarrow oil, peppermint oil, salvia oil, garden sorrel oil, spikenard oil, clove oil, neroli oil, melaleuca oil, frankincense oil, pedunculate mango oil, ledebouriella oil (opoprax oil), orange oil, oregano oil, orthosiphon oil, patchouli oil, parsley oil, orange leaf oil, peppermint oil, chrysanthemum oil, rosewood oil, rose oil, rosemary oil, ruta oil, juniper oil, saffron oil, saxifraga oil, sandalwood oil, sassafras oil, celery oil, mustard oil, thyme oil (serphylli aetheroleum), neem oil, fir leaf oil, tea tree oil, turpentine oil, thyme oil, juniper oil, indanthrene oil, hyssop oil, cedar oil, cinnamon oil, and cypress oil; and other oils, such as fish oil; and any analogs, derivatives, copolymers, and combinations thereof.

It will be appreciated that in some variations, one skilled in the art may select one or more particular plasticizers to exclude any one or any combination of the above plasticizers. In some variations, the plasticizer may include a water-soluble component. In other variations, the plasticizer may be modified to be water soluble. In some variations, the plasticizer may include a fat-soluble component. In other variations, the plasticizer may be modified to be fat soluble. Any functional group may be added to modify the properties of the plasticizer in a solvent, such as a body fluid present in the body. Any other suitable functional group may also be used.

In some variations, the device comprises one or more movable members, or one or more locking or interlocking members. For example, an interlock may be required to help minimize inadvertent collapse of the device from its expanded configuration back to its compressed configuration or to its partially expanded configuration with less use in use. Any number of locking or interlocking members may be used. For example, the device may be made entirely of interlocking elements, and these interlocking elements may be made of a single unitary material. The interlocking members may be made to operate in any suitable manner. In some variations, the interlocking pieces slide and lock into place, such as those described in U.S. patent nos.6,033,436, 6,224,626 and 6,951,053, the disclosures of these features being incorporated herein by reference in their entirety.

In variations where the device has a crown shape, a quasi-crown shape, a diamond shape, or any other shape described above, the locking or interlocking members may be provided at locations between the peaks and valleys (although they may indeed be provided at any suitable location or locations along the device). These pieces may be formed during the device manufacturing process, or may be subsequently mounted to the device (e.g., when the device is in its compressed configuration). When the device expands, the locking element engages, thereby preventing inadvertent, undesirable, or premature collapse of the device.

Exemplary polymers

As noted above, one or more components of the device may be made of a biodegradable polymer. The rate of biodegradation of the component parts of the device can be affected by a number of factors, including but not limited to the type of material from which it is formed, the shape and configuration of the device. In addition, changing the cross-sectional area or cross-sectional shape of the polymer filament can affect the degradation time. For example, a hollow filament may have a different degradation time than a solid filament of comparable size. As a result, the choice of material and geometry for the polymer filaments may vary depending on the location and therapeutic needs.

Examples of biodegradable polymers suitable for use in the methods and devices described herein include, but are not limited to, alginates, celluloses and esters, dextrans, elastin, fibrin, hyaluronic acid, polyacetals, polyarylates (derived from L-tyrosine, or free acids), poly (alpha-hydroxy esters), poly (beta-hydroxy esters), polyamides, poly (amino acids), polyalkanoates, polyalkylene alkylates, polyalkylene oxalates, polyalkylene succinates, polyanhydrides, polyanhydride esters, polyaspartamides, polybutylene diglycolate, poly (caprolactone)/poly (ethylene glycol) copolymers, poly (carbonates), L-tyrosine-derived polycarbonates, polycyanoacrylates, polydihydropyrans, polydioxanones, polyamides, and the like, Poly (p-dioxanone), poly (e-caprolactone-dimethyltrimethylene carbonate), poly (ester amide), polyester, aliphatic polyester, poly (ether ester), polyethylene glycol-polypropylene glycol copolymer, polyglutamic acid, polyglycolide-polyethylene glycol copolymer, poly (glycolide-trimethylene carbonate), polyhydroxyalkanoate, polyhydroxybutyrate, hydroxybutyrate-valerate copolymer, poly (iminocarbonate), polyacetal, polylactic acid, lactic acid-glycolic acid copolymer, poly (lactic acid-glycolic acid)/polyethylene glycol copolymer, polylactide, poly (lactide-caprolactone), poly (DL-lactide-co-glycolide), poly (lactide-glycolide)/polyethylene glycol copolymer, poly (lactide-co-glycolide), poly (epsilon-caprolactone) -dimethyltrimethylene carbonate, poly (epsilon-caprolactone), poly (epsilon-caprolactone), poly (glycolide-co-trimethylene carbonate), poly (, Polylactide/polyethylene glycol copolymers, polylactide/polyglycolide copolymers, polyorthoesters (polyorthoesters), polyoxyethylene/polyoxypropylene copolymers, polypeptides, polyphosphazenes, polyphosphates, polyphosphoester urethanes, propylene fumarate-ethylene glycol copolymers, polytrimethylene carbonate, polytyrosine carbonate, polyurethanes, PorLastin or silk elastin polymers, spider silk, tepaflex, terpolymers (copolymers of glycolide, lactide, or dimethyltrimethylene carbonate), and combinations, mixtures, or copolymers thereof.

Drug delivery

When the device is configured for drug delivery, the amount of drug released from the device will depend on the desired dose. Each drug should be released at a rate that provides a healthy, safe and effective dose to the patient, and should be administered at a dose that is also healthy, safe and effective. In some variations, for example when the device is used to treat one or more sinus conditions, the device may be configured to deliver mometasone furoate at a daily dose of about 500 μ g or less per day. In other variations, the device is configured to deliver mometasone furoate in the following daily doses: about 200 μ g, between about 5 μ g and about 100 μ g, between about 5 μ g and about 60 μ g, between about 5 μ g and about 40 μ g, between about 5 μ g and about 20 μ g, between about 5 μ g and about 10 μ g, between about 10 μ g and about 100 μ g, between about 10 μ g and about 60 μ g, between about 10 μ g and about 40 μ g, between about 10 μ g and about 20 μ g, between about 20 μ g and about 100 μ g, between about 20 μ g and about 60 μ g, between about 20 μ g and about 40 μ g, between about 40 μ g and about 100 μ g, between about 40 μ g and about 60 μ g, between about 60 μ g and about 100 μ g, and so forth.

The drug can be released from the device at a constant rate, but this is not essential. Indeed, the device may be configured with any suitable release rate profile. In some variations, the daily amount of drug release may decrease over time. For example, the device may release an amount of drug (e.g., between about 40 μ g and about 60 μ g) for a first period of time (e.g., one week), and then may release a second amount of drug (e.g., between about 20 μ g and about 40 μ g) for a second period of time. Similarly, the drug delivery amount may be changed any number of times over a period of time. In addition, multiple drug-eluting layers may be used, and each layer may be configured to have a different and specific release profile. Of course, it should be understood that each layer may include, contain, or be configured to release one or more than one drug or agent therefrom. When multiple layers are used, each layer may include or contain or be configured to release the same or different drugs or agents therefrom. Similarly, filaments comprising drug particles may be used to provide a different release profile than a drug eluting layer. Further, as described below, the drug reservoir may be used to achieve a varying release profile.

In other variations, the device may include one or more barrier layers. These layers may or may not release the one or more drugs and may delay the release of the one or more drugs from the one or more drug release layers. The barrier layer may or may not be a bulk eroding polymer, or may not be a surface eroding polymer. In some variations, the barrier layer may prevent passage of the drug therethrough. In these variations, the barrier layer may provide time for no drug to be released from at least a portion of the drug-releasing layer. Once the barrier layer has sufficiently degraded or otherwise eroded, the drug may continue to be released. In other variations, the barrier layer may allow an amount of drug to pass therethrough. In some of these variations, the amount of drug passing through the barrier layer may be less than the amount of drug that would be released from the drug release layer in the absence of the barrier layer. The barrier layer may thereby provide a period of time during which a lesser amount of drug is released from at least a portion of the drug-releasing layer. Once the barrier layer has sufficiently degraded or otherwise eroded, the amount of drug released from the device may increase.

These variations and combinations thereof may allow the device to provide a variable drug release profile, or provide an initial or delayed mutation, in addition to the device's base release profile. Furthermore, these variations may allow the device to provide different drug release profiles separated in time. For example, the device may include two drug-releasing layers separated by a barrier layer. The outer drug-releasing layer may release an initial amount of drug over an initial period of time and may follow any suitable drug release profile. The barrier layer may then degrade or erode over a specified period of time during which some or none of the drug is released from the second drug-releasing layer. Once such degradation has occurred, the second drug-releasing layer may release a second amount of drug over a second period of time, and such release may also follow any suitable drug release profile. As described above, each drug-releasing layer may release any suitable amount of any suitable drug over any suitable length of time.

In addition, one or more release rate modifiers may also be used. The release rate modifier may be any suitable biocompatible material for modifying the rate of release of the drug from the device. In some variations, the release rate modifier may comprise a hydrophilic agent. In some variations, the release rate modifier is a polyethylene glycol, for example, a polyethylene glycol having the following molecular weight: between about 3000 and about 13000, between about 3000 and about 11000, between about 3000 and about 9000, between about 3000 and about 7000, between about 3000 and about 5000, between about 5000 and about 13000, between about 5000 and about 11000, between about 5000 and about 9000, between about 5000 and about 7000, between about 7000 and about 13000, between about 7000 and about 11000, between about 7000 and about 9000, between about 9000 and about 13000, between about 9000 and about 11000, between about 11000 and about 13000, etc. In some variations, the release rate modifier is polyethylene glycol having a molecular weight of about 6000.

In some variations, the device may be configured to deliver multiple drugs, which may or may not be encapsulated (in, for example, a small reservoir or other material). In some variations, multiple types of drug particles are contained in a single drug-eluting layer. In other variations, the drug-eluting layer is discontinuous, with different segments containing different drugs. In these variations, different sections may have different compositions and thus may also provide different release rates. In other variations, multiple drug-eluting layers may be used, wherein each layer contains a different drug or combination of drugs. As described above, the drug reservoirs may also hold different drugs therein, or may collectively release a drug different from the drug released from the drug eluting layer. In other variations, the silk may release a different drug or combination of drugs than the drug released by the drug eluting layer. Any combination of these variations may also be used to achieve a desired drug delivery profile.

Exemplary formulations

The device may comprise any suitable drug or formulation, and the formulation selected is largely determined by the intended use of the device. It should be understood that the terms "formulation" and "drug" are used interchangeably herein. The device may include, for example, a diagnostic agent, or may include a therapeutic agent. Diagnostic agents can be used, for example, to diagnose the presence, nature, and/or extent of a disease or medical condition in a subject. Thus, for example, the diagnostic agent can be any agent suitable for use in conjunction with a method for imaging an internal region of a patient and/or diagnosing the presence or absence of a disease in a patient.

Diagnostic agents include, for example, contrast agents used in conjunction with ultrasound imaging, Magnetic Resonance Imaging (MRI), Nuclear Magnetic Resonance (NMR), Computed Tomography (CT), Electron Spin Resonance (ESR), nuclear medicine imaging, optical imaging, elastography, fluorescence imaging, Positron Emission Tomography (PET), Radio Frequency (RF), and microwave laser. Diagnostic agents may also include any other agent useful to facilitate diagnosis of a disease or other condition in a patient, whether or not imaging methods are employed.

Examples of specific diagnostic agents include radiopaque materials, such as iodine or iodine derivatives, such as iohexol (iohexal) and iopamidol. Other diagnostic agents such as radioisotopes can be detected by tracing the radioactive radiation. Examples of agents detectable by MRI are typically paramagnetic agents, including but not limited to gadolinium chelates. Examples of agents detectable by ultrasound include, but are not limited to perflexane. Examples of fluorescers include, but are not limited to, indocyanine green. Examples of formulations used in diagnostic PET include, but are not limited to, fluorodeoxyglucose, sodium fluoride, methionine, choline, deoxyglucose, butanol, raclopride, spiperone, bromospiperone, carfentanil, and flumazenil.

The device may also include any suitable therapeutic agent. Suitable classes of therapeutic agents include, for example, anti-inflammatory agents, anti-allergens (anti-allergens), anticholinergics, antihistamines, anti-infective agents, antiplatelet agents, anticoagulants, antitachycating agents, antiproliferative agents, chemotherapeutic agents, antineoplastic agents, decongestants, healing promoters and vitamins (e.g., retinoic acid, vitamin A, depaxa panthenol, vitamin B, and derivatives thereof), hyperosmotic agents, immunomodulators, immunosuppressants, and combinations and mixtures thereof.

Anti-infective agents typically include antibacterial, antifungal, antiparasitic, antiviral and disinfectant agents. Anti-inflammatory agents generally include steroidal and non-steroidal anti-inflammatory agents.

Examples of anti-allergic agents suitable for use in the methods and devices include, but are not limited to, pemirolast potassium (ALAMAST)Santen, Inc.), and any prodrugs, metabolites, analogs, homologs, derivatives, salts, and combinations thereof. Examples of antiproliferative agents include, but are not limited to, actinomycin D, actinomycin IV, actinomycin I₁Actinomycin X₁Actinomycin C₁And dactinomycin (COSMEGEN)Merck &Co., Inc.). Examples of antiplatelet agents, anticoagulant agents, antifibrotic agents, and anticoagulant agents include, but are not limited to, heparin sodium, low molecular weight heparin, heparinoids, hirudin, argatroban, forskolin (forskolin), vapreotide, prostacyclin and prostacyclin analogs, dextran, D-phenylalanine-proline-arginine-chloromethyl ketone hydrochloride (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antagonist antibodies, recombinant hirudin, and thrombin inhibitors (ANGIOMAX @)Biogen, Inc.), and any prodrugs, metabolites, analogs, homologs, derivatives, salts, and combinations thereof. Examples of healing promoters include, but are not limited to, sirolimus, everolimus, temsirolimus, and vitamin a.

Examples of cytostatins or antiproliferative agents that may be suitable for use in the methods and devices include, but are not limited to, angiostatin, angiotensin converting enzyme inhibitors, such as Captopril (CAPOTEN)And CAPOZIDEBristol-Myers Squibb Co.), cilazapril or lisinopril (PRINITIIL)And PRIZIDEMerck &Co, Inc.); calcium channel blockers, such as nifedipine; colchicine; fibroblast Growth Factor (FGF) antagonists, fish oil (omega 3-fatty acids); a histamine antagonist; lovastatin (MEVACOR)Merck &Co, Inc.); monoclonal antibodies, including but not limited to antibodies specific for the Platelet Derived Growth Factor (PDGF) receptor; nitroprusside; a phosphodiesterase inhibitor; a prostaglandin inhibitor; suramin; a serotonin blocking agent; a steroid; thiol protease inhibitors; PDGF antagonists including, but not limited to, triazolopyrimidines; and nitric oxide, and any prodrugs, metabolites, analogs, homologs, derivatives, salts, and combinations thereof.

Examples of antimicrobial agents that may be suitable for use in the methods and devices include, but are not limited to, aminoglycosides, amidoalcohols, ansamycins, β -lactams such as penicillins, lincosamides, macrolides, nitrofurans, quinolones, sulfonamides, sulfones, tetracyclines, vancomycin, and any derivatives or combinations thereof. Examples of penicillins that may be suitable for use in the method and apparatus include, but are not limited to, amoxicillin, ampicillin, apacillin, aspoxicillin, doxicillin, azlocillin, bacampicillin, benzylpenicillic acid, benzylpenicillin sodium, carbenicillin, cairinin, cloxacillin, ciclacillin, dicloxacillin, epicillin, fenbecillin, flucloxacillin, natacillin, lenampicillin, maytansillin, methicillin sodium, mezlocillin sodium, oxacillin, pencillin, penethacillin G, benzathine G, benzetheine G, penicillin G calcium, hydrabamycin G, penicillin G potassium, procaine penicillin G, penicillin N, penicillin O, penicillin V, benzathine V, Rapamycin V, penicillin, potassium phenacillin, piperacillin, pivampicillin, propicillin, quinacilin, sulbenicillin, sultamicillin, phthalacillin, temocillin and ticarcillin.

Examples of antifungal agents suitable for use in the methods and devices include, but are not limited to, allylamines, imidazoles, polyenes, thiocarbamates, triazoles, and any derivatives thereof. Antiparasitic agents that may be used include, but are not limited to, atovaquone, clindamycin, dapsone, diiodoquinoline, metronidazole, pentamidine, primary amine quinolines, pyrimethamine, sulfadiazine, trimethoprim/sulfamethoxazole, trimetrexate, and combinations thereof.

Examples of antiviral agents suitable for use in the methods and devices include, but are not limited to, acyclovir, famciclovir, valacyclovir, edexuridine, ganciclovir, foscarnet, cidofovir (vistide), vitrasert, fomivirsen, HPMPA (9- (3-hydroxy-2-phosphonomethoxypropyl) adenine), PMEA (9- (2-phosphonomethoxyethyl) adenine), HPMPG (9- (3-hydroxy-2- (phosphonomethoxypropyl) guanine), PMEG (9- [2- (phosphonomethoxy) ethyl ] guanine), HPMPC (1- (2-phosphonomethoxy-3-hydroxypropyl) -cytosine), ribavirin, EICAR (5-ethynyl-1-beta-D-ribofuranosyl imidazole-4-carboxamide), Pyrazolofuranidin (3- [ beta-D-ribofuranosyl ] -4-hydroxypyrazole-5-carboxamide), 3-deazaguanine, GR-92938X (1-beta-D-ribofuranosyl pyrazole-3, 4-dicarboxamide), LY253963(1, 3, 4-thiadiazol-2-yl-cyanamide), RD3-0028(1, 4-dihydro-2, 3-benzodithiol), CL387626(4, 4' -bis [4, 6-D ] [ 3-aminophenyl-N- -, N-bis (2-carbamoylethyl) -sulfonimide ] -1, 3, 5-triazine-2-amino-biphenyl- -2- -, 2' -disulfonic acid disodium salt), BABIM (bis [ 5-amidino-2-benzimidazolyl-1 ] -methane), NIH351, and combinations thereof.

Examples of suitable disinfectants for use in the methods and devices include, but are not limited to, ethanol, chlorhexidine, iodine, triclosan, hexachlorophene, and silver-based agents, such as silver chloride, silver oxide, and silver nanoparticles.

Anti-inflammatory agents may include steroidal and non-steroidal anti-inflammatory agents. Examples of suitable steroidal anti-inflammatory agents include, but are not limited to, 21-acetoxypregnenolone, alclometasone, aleurone, amcinonide, beclomethasone, betamethasone, budesonide, prednisolone, clobetasol, clobetasone, clocortolone, prednolone, corticosterone, cortisone, codevazole, deflazacort, desonide, desoximetasone, dexamethasone, diflorasone, diflucortolone, difluprednate, glycyrrhetinic acid, fluzacort, fluocinolone acetonide, flumethasone, flunisolide, fluocinonide, fluocortebutate, fluocortolone, fluoromethalone, flupredlone acetate, fluprednidene, flupredlone, fluticasone propionate, fomocortat, halcinonide, halobetasol propionate, halopredone acetate, hydrocortisone, lotione, Methylprednisolone, medrysone, methylprednisolone, mometasone furoate, paramethasone, prednisolone, 25-diethylamino acetominoprednisolone, prednisolone sodium phosphate, prednisone, prednisolone valerate, prednisolone, rimexolone, tixolone, triamcinolone acetonide, triamcinolone hexacetonide, any of their derivatives, and combinations thereof.

Examples of suitable non-steroidal anti-inflammatory agents include, but are not limited to COX inhibitors. These COX inhibitors may include COX-1 or COX non-specific inhibitors, such as salicylic acid derivatives, acetylsalicylic acid, sodium salicylate, choline magnesium trisalicylate, salsalate, diflunisal, sulfasalazine, and olsalazine; para-aminophenol derivatives, such as acetaminophen; indole and indene acetic acids such as indomethacin and sulindac; heteroaryl acetic acids such as tolmetin, diclofenac, and ketorolac; arylpropionic acids such as ibuprofen, naproxen, flurbiprofen, ketoprofen, fenoprofen and oxaprozin; anthranilic acids (fenamates), such as mefenamic acid and meloxicam; enolic acids, such as oxicams (piroxicam, meloxicam), and alkanones, such as nabumetone. COX inhibitors may also include selective COX-2 inhibitors, for example, diaryl substituted furanones, such as rofecoxib; diaryl substituted pyrazoles, such as celecoxib; indoleacetic acids, such as etodolac, and sulfonamides, such as nimesulide).

Examples of chemotherapeutic/antineoplastic agents that may be used in the devices described herein include, but are not limited to, anticancer agents (e.g., cancer chemotherapeutic agents, biological response modifiers, vascularization inhibitors, hormone receptor blockers, cryotherapy agents, or other agents that destroy or inhibit neoplasia or tumorigenesis), such as alkylating agents, or other agents that kill cancer cells directly by attacking their DNA (e.g., cyclophosphamide, ifosfamide), nitrosoureas, or other agents that kill cancer cells by inhibiting changes required for cellular DNA repair (e.g., momustine (BCNU) and lomustine (CCNU)), antimetabolites, or other agents that prevent cancer cell growth by interfering with specific cellular functions (usually DNA synthesis) (e.g., 6-mercaptopurine and 5-fluorouracil (5FU), antitumor antibiotics, and other compounds that act by binding or intercalating DNA and preventing RNA synthesis (e.g., doxorubicin, daunorubicin, epirubicin, idarubicin, mitomycin-C, and bleomycin), plant (vinca) alkaloids and other antineoplastic agents derived from plants (e.g., vincristine and vinblastine), steroid hormones, hormone inhibitors, hormone receptor antagonists, and other agents that affect growth of hormone sensitive cancers (e.g., tamoxifen, herceptin, aromatase inhibitors such as aminoglutethimide and fulvestrant, triazole inhibitors such as letrozole and anastrozole, steroid inhibitors such as exemestane), anti-angiogenic proteins, small molecules, gene therapy and/or other agents that inhibit angiogenesis or vascularization of tumors (e.g., meth-1, meth-2, thalidomide), bevacizumab (avastin), squalamine, endostatin, angiostatin, Angiozyme, Angiozyme, AE-941 (neovastat), CC-5013(Revimid), medi-522(Vitaxin), 2-methoxyestradiol (2ME2, Panzem), Carboxyamidotriazole (CAI), capptatin A4 prodrug (CA4P), SU6668, SU11248, BMS-275291, COL-3, EMD 121974, IMC-IC11, IM862, TNP-470, celecoxib (Celebrex), rofecoxib (Vioxx), alpha-interferon, interleukin-12 (IL-12), or any of the compounds described in Vol.289 of Science, pp.1197-1201 (17.8.2000) (expressly incorporated herein by reference), bioresponse modulators (e.g., interferons, calmette-Guerin (PGSF), GCS 2 antagonists, interleukin 2 (BCG SF), receptor stimulating antibodies such as Herceptin, asparaginase, busulfan, carboplatin, cisplatin, carmustine, chlorambucil, cytarabine, dacarbazine, etoposide, flecapazine, fluorouracil, gemcitabine, hydroxyurea, ifosfamide, irinotecan, lomustine, melphalan, mercaptopurine, methotrexate, thioguanine, thiotepa, raltitrexed, topotecan, troxsuprine, vinblastine, vincristine, mitoxantrone, oxaliplatin, procarbazine, grisein, taxol or paclitaxel, taxotere, azathioprine, docetaxel, analogs/homologues, derivatives of these compounds and combinations thereof.

Decongestants that may be used in the devices and methods described herein include, but are not limited to, epinephrine, pseudoephedrine, oxymetazoline, phenylephrine, tetrahydrozoline, and xylometazoline. Mucolytics that may be used in the devices and methods described herein include, but are not limited to, acetylcysteine, alpha-deoxyribonuclease, and guaifenesin. Antihistamines such as azelastine, diphenhydramine, and loratadine can also be used in the methods and devices described herein.

Suitable high permeability agents that may be used in the devices described herein include, but are not limited to, furosemide, sodium chloride gel, and other saline preparations that absorb water from tissue or matter that directly or indirectly alter mucosal osmolality.

Other bioactive agents that may be used in the present invention include, but are not limited to, free radical scavengers; a nitric oxide donor; rapamycin; methyl rapamycin; everolimus; tacrolimus; 40-O- (3-hydroxy) propyl-rapamycin; 40-O- [2- (2-hydroxy) ethoxy ] ethyl-rapamycin; tetrazoles comprising rapamycin analogs, such as those described in U.S. Pat. No.6,329,386; estradiol; clobetasol; idoxifene; tazarotene; an alpha-interferon; host cells, including but not limited to prokaryotes and eukaryotes, such as epithelial cells and genetically engineered epithelial cells; dexamethasone; and any prodrugs, metabolites, analogs, homologs, derivatives, salts and combinations thereof.

Examples of free radical scavengers include, but are not limited to, 2 ', 6, 6' -tetramethyl-1-piperidinyloxy, free radical (TEMPO); 4-amino-2, 2 ', 6, 6' -tetramethyl-1-piperidinyloxy, radical (4-amino-TEMPO); 4-hydroxy-2, 2 ', 6, 6' -tetramethyl-piperidin-1-oxyl (TEMPOL), 2 ', 3,4, 5, 5' -hexamethyl-3-imidazolinium-1-yloxy, methyl sulfate; 16-oxyl-stearic acid; superoxide dismutase mimics (SODm) and any analogs, homologs, derivatives, salts and combinations thereof. Nitric oxide donors include, but are not limited to, S-nitrosothiols, nitrites, N-oxo-N-nitrosamines, substrates of nitric oxide synthase, diazenium dialates such as spermine diazenium dialate, and any analogs, homologs, derivatives, salts, and combinations thereof.

Conveying device

Also described herein are delivery devices that can be used to deliver one or more of the self-expanding devices described above. While generally described herein as being used to deliver the self-expanding devices described above, it is important to recognize that the delivery device may be used to deliver any suitable implant. Indeed, the delivery device may be used to deliver one or more self-expanding devices, non-expanding devices, expandable devices, shape-changing devices, combinations thereof, and the like. The delivered implant can have any suitable size, shape, and configuration, and in some cases can be modified depending on the anatomy (which can be any suitable portion of the anatomy) to which the implant is to be delivered. For example, in some variations the delivery device may deliver one or more implants to one or more sinuses. In other variations, the delivery device may be used to deliver one or more devices to other portions of the anatomy, such as the eustachian tube, urethra, or tonsil.

The delivery device typically includes a cannula defining a lumen, hole or other opening for retaining the implant therein. When the delivery device is used to deliver a self-expanding device, the delivery device may be configured to receive the self-expanding device in a compressed configuration or an unexpanded configuration. The delivery device may be operated with a single hand and may be ergonomically designed to assist the operator in delivering and configuring the device. In some variations, endoscopic guidance or other forms of visualization means, such as ultrasound or fluoroscopy, may be used to assist in the delivery. The delivery device may be configured for a single use (e.g., terminally sterilized with electron beam radiation) or may be configured for multiple uses (e.g., capable of being sterilized multiple times). In some variations, one or more components of the delivery device may be configured for a single use, while one or more components may be configured for multiple uses.

Figure 5A shows a variation of a suitable conveyor. As shown therein, the delivery device (500) includes a cannula (502) defining an inner lumen (not shown) in which one or more implants may be received. Also shown is an advancer (504) coupled to the plunger (508) and slidably disposed in the handle body (510). Although the arrangement shown here is in the form of a push rod mechanism, any suitable actuation mechanism may be used, as will be described in more detail below. In the variation shown in fig. 5A, the pusher (504) is slidable within the lumen of the cannula (502) such that as the plunger (508) is moved distally relative to the handle body (510), the pusher (504) is advanced distally and can push the implant out of the distal end of the cannula.

In the variation shown in fig. 5A, the proximal end of the cannula (502) is connected to the handle body (510). In some variations, the connection may be reversible or releasable such that the sleeve (502) may be disengaged from the handle body (510). The handle body (510) may facilitate one-handed use and provide an intuitive and ergonomic user interface. For example, the handle body (510) shown in fig. 5A is designed so that the operator holds it in a "pen-grip" manner while actuating the plunger (508) to deliver the implant as described above. Fig. 5B shows another variation of a delivery device (512) having similarly configured elements, but designed to be held in a "syringe-like" manner. Shown are a cannula (514), a handle body (516) including a gripping portion (518), and a plunger (520) coupled to a pusher (522). In these variations, an operator may grasp grip portion (518) with one or more fingers and may apply pressure (e.g., with a human thumb) to plunger (520) to advance pusher (522).

Sleeve pipe

Although shown in fig. 5A and 5B as having a single curve at its distal end, the cannula can be shaped in any manner and can have any number of shaped curves. In some variations, the cannula may be preformed. In other variations, the shape of the cannula may be set or changed during delivery. In variations that include one or more shaping curves, the shaping curves can have any suitable dimensions. Indeed, fig. 5C shows a curved cannula (526), with some relevant dimensions that may be associated with the shaping curve being noted. Shown is a cannula (526) having a curve (528) with a radius of curvature (R), an angle (θ), and a curve height (H). These dimensions may have any suitable value or range depending on the intended use of the device and the size of the intended implant.

For example, the curve 528 may have any suitable angle θ when delivering the implant to the frontal or maxillary sinuses. Suitable angles (θ) include, but are not limited to, about 50 °, about 60 °, about 70 °, about 80 °, about 90 °, about 100 °, about 110 °, and about 120 °. In some variations, the angle (θ) may be between about 50 ° and about 120 °, between about 60 ° and about 120 °, between about 70 ° and about 120 °, between about 80 ° and 120 °, between about 90 ° and about 120 °, between about 100 ° and about 120 °, between about 110 ° and about 120 °, between about 50 ° and about 110 °, between about 60 ° and about 110 °, between about 70 ° and about 110 °, between about 80 ° and about 110 °, between about 90 ° and about 110 °, between about 100 ° and about 110 °, between about 50 ° and about 100 °, between about 60 ° and about 100 °, between about 70 ° and about 100 °, between about 80 ° and about 100 °, between about 90 ° and about 100 °, between about 50 ° and about 90 °, between about 60 ° and about 90 °, between about 70 ° and about 90 °, between about 80 ° and about 90 °, between about 50 ° and about 80 °, between about 60 ° and about 80 °, between about 70 ° and about 80 °, between about 50 ° and about 70 °, or between about 60 ° and about 70 °. Further, suitable radii of curvature (R) for delivery to the frontal sinus include, but are not limited to, about 6mm, about 7mm, about 8mm, about 9mm, about 10mm, about 11mm, and about 12 mm. In some variations, the radius of curvature (R) may be between about 6mm and about 12mm, between about 7mm and about 12mm, between about 8mm and about 12mm, between about 9mm and about 12mm, between about 10mm and 12mm, between about 11mm and about 12mm, between about 6mm and about 11mm, between about 7mm and about 11mm, between about 8mm and about 11mm, between about 9mm and about 11mm, between about 10mm and 11mm, between about 6mm and about 10mm, between about 7mm and about 10mm, between about 8mm and about 10mm, between about 9mm and about 10mm, between about 6mm and about 9mm, between about 7mm and about 9mm, between about 8mm and about 9mm, between about 6mm and about 8mm, between about 7mm and about 8mm, or between about 6mm and about 7 mm. Suitable heights (H) for delivery to the frontal or maxillary sinuses include, but are not limited to, about 23mm, about 25mm, about 28mm, and about 30 mm. Additionally, in some variations the height (H) may be between about 23mm and about 30mm, between about 25mm and about 30mm, between about 28mm and about 30mm, between about 23mm and about 28mm, between about 25mm and about 28mm, or between about 23mm and about 25 mm.

Similarly, suitable angles (θ) include, but are not limited to, about 10 °, about 20 °, about 30 °, about 40 °, about 50 °, about 60 °, about 70 °, about 80 °, about 90 °, about 100 °, and about 110 ° when delivering an implant to the ethmoid sinus. In some variations, the angle (θ) may be between about 10 ° and about 110 °, between about 30 ° and about 110 °, between about 50 ° and about 110 °, between about 70 ° and about 110 °, between about 90 ° and about 110 °, between about 10 ° and about 90 °, between about 30 ° and about 90 °, between about 50 ° and about 90 °, between about 70 ° and about 90 °, between about 10 ° and about 70 °, between about 30 ° and about 70 °, between about 50 ° and about 70 °, between about 10 ° and about 50 °, between about 30 ° and about 50 °, or between about 10 ° and about 30 °. Examples of suitable radii of curvature (R) for delivery to the ethmoid sinus include, but are not limited to, about 17mm, about 19mm, about 21mm, about 23mm, about 25mm, and about 27 mm. In some variations, the radius of curvature (R) may be between about 17mm and about 27mm, between about 19mm and about 27mm, between about 21mm and about 27mm, between about 23mm and about 27mm, between about 25mm and about 27mm, between about 17mm and about 25mm, between about 19mm and about 25mm, between about 21mm and about 25mm, between about 23mm and about 25mm, between about 17mm and about 23mm, between about 19mm and about 23mm, between about 21mm and about 23mm, between about 17mm and about 21mm, between about 19mm and about 21mm, or between about 17mm and about 19 mm. Suitable heights (H) for delivery to the frontal or maxillary sinuses include, but are not limited to, about 23mm, about 25mm, about 28mm, and about 30 mm. Further, in some variations, the height (H) may be between about 23mm and about 30mm, between about 25mm and about 30mm, between about 28mm and about 30mm, between about 23mm and about 28mm, between about 25mm and about 28mm, or between about 23mm and about 25 mm.

Additionally, the cannula may define an inner diameter capable of receiving any number of sized implants. The inner diameter of the cannula may or may not be constant along the length of the cannula. Indeed, in some variations, the inner diameter of the cannula may vary over the entire length of the cannula, or the cannula may be made of a material that is stretchable or deformable while retaining the implant therein. In some of these variations, the inner diameter of the cannula may be substantially smaller than the one or more implants to be delivered, but may nonetheless be extendable to accommodate the one or more implants. By allowing the cannula to have a smaller profile while still maintaining the same size implant, the operator is given additional space in the body where other devices, such as an endoscope, may be positioned.

Examples of suitable cannula inner diameters include, but are not limited to, about 0.05mm, about 1mm, about 2mm, about 3mm, about 4mm, about 5mm, about 6mm, or greater than about 7 mm. In some variations, the inner diameter may be between about 0.05mm and about 6mm, between about 1mm and about 6mm, between about 2mm and about 6mm, between about 3mm and about 6mm, between about 4mm and about 6mm, between about 5mm and about 6mm, between about 0.05mm and about 5mm, between about 1mm and about 5mm, between about 2mm and about 5mm, between about 3mm and about 5mm, between about 4mm and about 5mm, between about 0.05mm and about 4mm, between about 1mm and about 4mm, between about 2mm and about 4mm, between about 3mm and about 4mm, between about 0.05mm and about 3mm, between about 1mm and about 3mm, between about 2mm and about 3mm, between about 0.05mm and about 2mm, between about 1mm and about 2mm, or between about 0.05mm and about 1 mm.

As noted above, in some variations, the shape of the cannula may be set and changed during operation of the device. Indeed, while one or more portions of the cannula may be pre-shaped, one or more portions of the cannula may be flexible, bendable, or non-shaped. In some of these variations, one or more inserts may be provided in the cannula to impart any flexible portion with a set shape. These inserts may be of any size, shape or configuration. In some variations, the insert may be a rigid tube. In other variations, the insert may be a rigid wire. These variations may be particularly useful where the cannula has two or more lumens, as will be described in more detail below.

In other variations, the cannula may be steerable or have one or more features that may lock a flexible cannula other than this into a set shape. The cannula may or may not be configured for remote or automated operation, and may or may not have one or more articulated or articulatable sections. Fig. 23A and 23B show a variant of the steerable and lockable transfer device (2300). A flexible sleeve (2302), a backbone (2304) and left (2306) and right (2308) control wires for controlling the sleeve (2302) are shown. Backbone (2304) may be configured to freely bend between a straight configuration shown in fig. 23A, a left curved configuration shown in fig. 23B, and a right curved configuration (not shown). This free motion may be limited by applying tension on one or both of the left (2306) and right (2308) control wires. More specifically, if equal tension is applied on both the left (2306) and right (2308) control wires, sleeve (2302) may remain in the straight configuration shown in fig. 23A. If more tension is applied to the left control line (2306), the sleeve (2302) may bend to the left. Conversely, if the tension applied on the right control line (2308) is greater, the sleeve (2302) may bend to the right. Depending on the amount of tension applied to the left (2306) and right (2308) control wires, the sleeve (2302) may be maintained in a particular configuration regardless of the applied force. In some variations, the delivery device is configured such that the device naturally places the left (2306) and right (2308) control wires under a predetermined amount of tension, and the user can temporarily release the tension to allow the sleeve (2302) to become flexible. It is important to note that while the transfer device (2300) is shown in fig. 23A and 23B as having two control wires and a sleeve (2302) that is capable of bending in two directions, the transfer device (2300) can have any number of control wires and the sleeve (2302) can bend in any corresponding number of directions. Indeed, the sleeve (2300) may have one, two, three or four or more control wires and may have a backbone (2304) that enables the sleeve (2302) to bend in one, two, three or four or more directions.

The sleeve may be made of any suitable or desirable material. Examples of suitable casing materials include, but are not limited to, polyvinyl chloride, pebaxPolyethylene, silicone rubber, polyurethane and any analogs, homologs, derivatives, copolymers and mixtures thereof. In some variations, the sleeve may comprise one or more metals or metal alloys, such as, but not limited to, magnesium, nickel-cobalt alloys, nickel-titanium alloys, copper-aluminum-nickel alloys, copper-zinc-aluminum-nickel alloys, combinations thereof, and the like. The cannula may be made of one material, or may be made of a mixture or combination of different materials. In some variations, one portion of the sleeve may be made of one or more materials, while another portion of the sleeve may be made of a different material or combination of materials. In other variations, one or more portions of the sleeve may be braided to increase the strength or rigidity of the sleeve. Further, the sleeve may or may not be made of a translucent or transparent material. The transparent or translucent material may allow an operator to directly view the positioning of the implant when it is received within the cannula.

The distal end or tip of the cannula may have any suitable size or configuration. For example, the cannula tip may or may not have the same diameter as the rest of the cannula. Similarly, the cannula tip may or may not be made of the same material as the rest of the cannula. In some variations, the cannula tip is made of a soft, atraumatic material to minimize damage during delivery and deployment. Additionally, the shape of the cannula or cannula tip can help minimize damage during delivery and deployment. For example, the edges of the cannula tip may be rounded or chamfered to further minimize tissue damage. In some of these variations, the sleeve end may be deformable. In these variations, the operator may deform the cannula tip before or after one or more implants have been disposed within the cannula. For example, an operator may use one or more tools to compress a cannula tip having a circular cross-sectional shape, which may deform the tip to have an elliptical cross-sectional shape. This may allow the tip to more easily pass through the adjoining tissue. In addition, the tip may be deformed again when one or more implants are expelled from the cannula.

In some variations, the cannula tip may include one or more features or components that facilitate advancement of the delivery device or delivery/deployment of one or more implants. Fig. 24A-24Q show different variations of suitable cannula tips. It is important to note that the end features or components described herein may or may not be integral with the cannula end. Indeed, any of the cannula tips described herein may be formed separately from the delivery device and subsequently attached to the delivery device. These attachable tips may be configured to attach to standard cylindrical cannula tips as shown in fig. 5A and 5B, or may be configured to attach to either cannula tip as described below. Attachable tips may provide great leeway for a user in selecting a cannula tip suitable for a given situation without having to replace the entire cannula or delivery device. These attachable ends can be attached in any suitable manner, including but not limited to press fitting, welding (e.g., heat welding, ultrasonic welding, tack welding, rivet welding, etc.), chemical bonding, mechanical attachment (sutures, clips, or other mechanical fasteners), or attachment with adhesives (cements, adhesive polymers, etc.) or other materials (sugars, low melting temperature polymers, etc.), or some combination thereof. The attachable tip may or may not be permanently attached to the cannula. Indeed, in some variations, the attachable tip can be releasably attached to the sleeve. When releasable, the attachable end may be releasable in vivo, or may be releasable in vitro. When released in vivo, the attachable tip may or may not be biodegradable and may or may not be removed by suction or other suitable means. Furthermore, the attachable tip may have additional functions in the body, such as drug delivery, expansion, or use as a marker.

In some variations, the cannula tip may include one or more markings that may facilitate cannula visualization. Fig. 24A shows such a variation of a cannula end (2400) with markings (2402). In some variations, the marker (2402) may be configured to assist in direct visualization of the cannula. Indeed, when the cannula is substantially transparent, the indicia may be opaque or otherwise opaque, which in turn may enable an operator to identify and distinguish the cannula tip from the cannula body. Similarly, the indicia may be a different color than the sleeve body, or may reflect a different amount of light than the sleeve body. The marker (2402) may or may not be a radiographic or ultrasound marker, and may or may not assist in viewing the cannula indirectly by methods such as ultrasound or fluoroscopy. In other variations, the marker (2402) is configured to emit one or more signals detectable by one or more visualization devices. The cannula end (2400) can also have any number or combination of the above-described markings.

Fig. 24B and 24C show another variation of a sleeve tip (2404) including an expandable funnel-shaped tip (2406). The funnel-shaped end (2406) may or may not collapse into the low profile configuration shown in fig. 24B. The funnel-shaped tip (2406) may be held in a low profile configuration by a sheath or other constraining device (not shown) and may assist the operator in positioning the sleeve tip (2404) relative to an opening, such as a sinus ostium, when expanded. Once the cannula end (2404) has passed through the opening, the shell or restraining device can be removed and the funnel-shaped end (2406) can expand to the expanded configuration shown in fig. 24C. The funnel-shaped tip (2406) may or may not self-expand to its expanded configuration, and may or may not be configured to expand in response to one or more stimulus factors. Further, although shown as a frustoconical shape in fig. 24C, the funnel-shaped tip may have any cross-sectional profile. Once the funnel-shaped tip (2406) is expanded, the sleeve may be withdrawn proximally relative to the opening. The increased diameter of the funnel-shaped tip (2406) may impede its passage through the opening, which may provide tactile feedback to the user of the positioning of the cannula tip relative to the opening. Once the one or more implants have been delivered, the funnel-shaped tip (2406) may or may not be withdrawn into the restraining device to restore its low profile configuration.

The funnel-shaped tip (2406) may also assist in the controlled delivery of one or more self-expanding devices. For example, the funnel-shaped tip (2406) may be used to help ensure that the implant is positioned adjacent to the tissue wall. Once expanded, the funnel-shaped tip (2406) may be placed against the tissue wall, and the self-expanding device may be advanced into the funnel-shaped tip (2406), where the self-expanding device may be at least partially expanded. The funnel-shaped tip (2406) can then be withdrawn away from the tissue wall to leave the implant in place.

Additionally, in some variations, the sleeve tip may have one or more tabs. Fig. 24D shows a variation of such a sleeve tip (2408), including an olive tip (2410). The olive-shaped tip (2410) may aid in the expansion of the passage opening and may temporarily or permanently displace one or more obstructions, such as nasal polyps. Furthermore, due to its rounded nature, the olive-shaped tip (2410) may reduce the risk of tissue damage that may persist in dilatation or metastasis. Additionally, depending on the size of the olive-shaped end (2410), the olive-shaped end (2410) may have a sealing function when engaged with the opening. This may allow the user to introduce fluid through the cannula without passing the fluid through the opening, which may be particularly useful in situations where it is desirable to flush or fill the sinus with a liquid or gas without allowing the liquid or gas to exit the sinus cavity through the ostium.

Although shown as olive-shaped in fig. 24D, the sleeve tip (2408) may have tabs of any suitable element shape, size, or configuration, which may be disposed anywhere along the length of the sleeve tip (2408). Indeed, the protrusion may be wedge-shaped, frustoconical, elliptical, or three-dimensional having any regular or irregular geometric shape. In some of these variations, the tab may provide one or more additional functions. For example, fig. 24E shows a sleeve end (2412) including a wedge-shaped protrusion (2414). In addition to the potential dilating, distracting, or sealing functions described above, the wedge-shaped tip may also provide a structure that allows the attachable tip to be removed from the cannula. The wedge shaped protrusion (2414) may pass through an opening (not shown) that may be temporarily expanded during the process. If the widest diameter of the wedge (2414) is wider than the diameter of the opening, the opening may block the sleeve end (2412) from returning through the opening. Assuming the wedge (2414) is part of the attachable tip, the obstruction may provide a force sufficient to loosen the attachable tip from the sleeve.

Fig. 24F and 24G show front and side views, respectively, of another variation of a cannula end (2416) with a plate extension (2418). The plate extension (2418) may be substantially flat, or may have one or more bends. In general, the plate extension (2418) provides a thin cross-sectional portion that can allow the cannula tip (2416) to be manipulated between adjacent tissues. Because the plate extension (2418) is thinner along one plane than the body (2420) of the cannula tip (2416), as shown in fig. 24G, the plate extension (2418) is better able to wedge between two contacting tissues (not shown). Once the plate extension (2418) has been placed within two tissues, the cannula end (2416) may or may not be rotated to separate the two tissues. In some variations, the plate extension (2418) engages the body (2420) with an increased thickness or with a bend.

Additionally, the plate extension (2418) may be used for directional delivery of one or more implants. For example, the plate extension (2418) may limit the direction of expansion of the self-expanding device relative to the cannula end (2416) when the self-expanding device is expelled from the aperture (2422) of the cannula end (2416). For example, if the cannula end (2416) is positioned as shown in fig. 24G, the self-expanding device may expand to the left upon expulsion from aperture (2422). The directional expansion may allow a user to control the placement and expansion of the self-expanding element. For example, a user may position the cannula end (2416) and plate extension (2418) adjacent to a tissue wall (not shown). As the self-expanding device is expelled from aperture (2422), its expansion may be limited on one side by the tissue wall and on the other side by plate extension (2418). The user can then move the cannula end (2416) away from the tissue wall to allow continued expansion of the self-expanding device.

Other cannula ends may include one or more slots or struts. Indeed, fig. 24H and 24I show a variation of cannula end (2424) including slots (2426) and struts (2428). Cannula end (2424) may include any suitable number of slots (2426) and struts (2428) (e.g., one, two, three, four, five, six, seven, eight, or nine or more), although typically the number of slots (2426) and struts (2428) is the same. Additionally, each slot (2426) and strut (2428) can have any suitable size, shape, and configuration, and each slot (2426) and strut (2428) may or may not have the same size, shape, or configuration. Indeed, slot (2426) and strut (2428) may be rectangular, triangular, curved, sinusoidal, or may have one or more shapes that are geometrically irregular. It is important to note, however, that the size and shape of each slot (2426) is determined by the shape and relative positioning of the branches (2428) on either side thereof. Further, although shown in fig. 24H and 24I as being oriented parallel to the longitudinal axis of the cannula, slots (2426) and struts (2428) may be angled relative to the longitudinal axis of the cannula.

Additionally, a cannula end (2424) including a slot (2426) and a prong (2428) may assist in the delivery of one or more implants. In some cases, the implant (2430) can include one or more tabs (2432) that can protrude through one or more slots (2426) when the implant (2430) is received in the cannula, as shown in fig. 24I. When the delivery device is proximally withdrawn, one or more tabs (2432) may engage surrounding tissue. As the delivery device continues to be withdrawn, the implant (2430) may be held in place by the engagement and may be pulled out of the cannula. Additionally, the tab (2432) can be configured to help minimize injury to tissue caused by the tab (2432) as the delivery device is advanced through the body. For example, the tab (2432) may be angled away from the distal end of the cannula, or may have one-way flexibility that allows the tab (2432) to press against the body of the cannula.

The branches may or may not be substantially rigid, and may or may not be able to bend, or deform in response to one or more forces or stimuli. In variations where the struts are capable of bending, buckling, or deforming in response to a force or stimulus, the struts may assist in the controlled release of the self-expanding device. Depending on the size, shape, and configuration of the self-expanding device, in some cases, the self-expanding device may have a tendency to "pop" out of the end of the cannula, and the movable struts can prevent this "pop" by allowing controlled expansion. Fig. 24J shows such a variation of the cannula end (2434) including the slot (2436) and the strut (2438), where the strut (2438) curves away from the cannula end (2434). In the variation shown in fig. 24J, the struts (2438) may be substantially rigid, but capable of bending away from the cannula end (2434) at the connection point (2440). In other variations, one or more of the braces (2438) may or may not be made of fabric, such as felt, or other materials that are easily deformable.

In some cases, the expansion force provided by the self-expanding element may be sufficient to bend, or deform the branch. In these variations, the device can be released from the cannula in any suitable manner. In some variations, the self-expanding device may be held within a branch, which in turn may be held by a housing or holder. Once the shell or retainer is withdrawn relative to the branch, the branch may bend, or deform in response to expansion of the self-expanding device. In other variations, the self-expanding device may be advanced from the body of the cannula into the tip to bend, kink or deform the struts.

In other variations, the branch may be configured to naturally bend, or deform away from the cannula tip. These variations are particularly useful where it is desired to position the cannula tip relative to an opening, such as a sinus ostium. In these variations, the branch may be held in an unexpanded configuration by a shell or retainer, and the cannula tip may be advanced through an opening. Once through the opening, the shell or retainer may be withdrawn to release the struts and thereby allow them to naturally bend, buckle or deform away from the cannula end. The released branch may impede withdrawal through the opening and, as such, may provide tactile feedback to the user indicating to the user that the cannula tip is contacting the opening.

In some variations where the cannula tip includes slots and struts, the slots may be directed inward toward the center of the cannula tip. Fig. 24K shows such a variation of the sleeve end (2442) which includes a slot (2444) and inwardly directed branches (2448). The inwardly directed struts (2448) are particularly useful in passing through narrow spaces or separating adjacent tissue due to the reduced cross-sectional profile of the cannula tip (2442) due to this configuration. Additionally, the cannula tip (2442) can be configured to move the inwardly directed struts (2448) to allow delivery of one or more implants from the end of the cannula tip (2442). In some cases, simply advancing one or more implants through the cannula end (2442) may provide sufficient force to separate the struts. In other variations, the struts (2448) may be configured to bend or bend away from their low profile configuration when the cannula tip (2442) is subjected to one or more stimulus factors. In other variations, a balloon or other expandable element (not shown) disposed within the cannula tip (2442) may be expanded to separate the struts (2448). The balloon or other expandable member may or may not define a lumen or aperture for passage of one or more implants. In addition, as described above, when the branches (2448) are separated, they can help position the cannula tip (2442) relative to an opening.

The inwardly directed branches may also be configured to pierce one or more tissues, such as the bleb. Fig. 24L shows a suitable variation of a cannula end (2450) with a strut (2452) and a slot (2454). As shown in fig. 24L, the struts (2452) can be shaped to approach a tip when pointing inward toward the center of the cannula tip (2450). The tip may or may not be sufficiently sharp to allow the cannula tip (2450) to pierce tissue. Additionally, in some cases, it is desirable for any tissue perforation to be substantially circular and free of tissue fragments. Thus, it is desirable that the cannula end (2450) not have any clearance from the slots (2454). Thus, as shown in fig. 24L, the strut (2452) can be configured to substantially eliminate the slot (2454) when the strut (2452) is directed inward. Although shown as approaching a point in fig. 24L, the struts (2452) may be combined to approximate any suitable shape that can cut or pierce tissue. In some variations, the branches (2452) may approximate a shape that serves as a blade.

Additionally, the cannula tip (2450) can include one or more materials that can form a coating on and/or within the cannula tip (2450). The coating can serve multiple functions. In some cases, the coating may cover any gaps formed between the struts (2452). In other cases, the coating may reinforce the struts (2452) so that they can withstand greater forces exerted thereon. In some variations, the coating may be dissolved or weakened upon contact with one or more liquids or gases. Indeed, once the cannula tip (2450) has completed its piercing function, the coating may dissolve or weaken, which may allow the struts (2452) to separate and allow one or more implants to be deployed through the cannula tip (2450). Examples of suitable coating materials include, but are not limited to, polyethylene glycol, one or more sugars, chitosan, polycaprolactone, and the like.

In other variations, the sleeve end may include one or more slotted tubes. Fig. 24M and 24N show a variation of a cannula tip (2455) comprising a slotted tube (2456) with slots (2458) and buttresses (2460). Typically, the first end of the slotted tube (2456) may be fixed relative to the cannula tip (2455) while the second end may be movable relative to the first end. When the second end is moved relative to the first end, as shown in fig. 24N, one or more struts (2460) may bend, buckle, or deform away from the cannula tip (2455). In some cases, such expansion of the slotted tube (2456) can temporarily or permanently dilate one or more tissues or openings. In other cases, as described above, an expanded slotted tube (2456) can be used to position the cannula tip (2455) relative to an opening.

The shape of the expanded slotted tube (2456) can depend on the size, shape, and orientation of the slots (2458) and the struts (2460), as well as the manner in which the first end of the slotted tube (2456) moves relative to the second end. As such, the slot (2458) and the branches (2460) can have any suitable size, shape, or orientation. Additionally, while the first and second ends of the slotted tube (2456) may be moved toward or away from each other, they may alternatively be rotated to expand the slotted tube (2456). Indeed, fig. 24P and 24Q show one such variation of a sleeve tip (2462) comprising a slotted tube (2464) having angled slots (2466) and buttresses (2468). In this variation, as shown in fig. 24Q, rotation of the first end of the slotted tube (2464) relative to the second end thereof causes the angled braces (2468) to expand away from the slotted tube (2464).

Although generally described above as having one cannula defining only one lumen or aperture, the delivery devices described herein may include any number of cannulas and each cannula may include any number of lumens or other apertures. Indeed, in some variations, the delivery devices described herein comprise two or more cannulae. These sleeves may or may not be connected to each other. In addition, the different cannulas may or may not be the same size, may or may not be made of the same material, and may or may not have the same number of lumens or other holes. Any number of cannulae may be steerable, and each cannula may or may not be independently steerable. Furthermore, different sleeves may be used for the same function, or may be used for different functions. For example, each cannula may be used to deliver one or more implants, carry a punch or other tissue piercing device, carry a viewing device or light source, deliver one or more drugs, liquids, gases, or combinations thereof, provide suction, carry one or more of the above-described steering or shaping elements, carry a dilator or other tissue expansion device, carry a guide wire, carry a tissue biopsy device or tissue ablation material, carry one or more devices for laterally deflecting the middle turbinate, or combinations thereof.

Where a single cannula has more than one lumen or aperture, the lumens may be of any size, shape or configuration. Indeed, FIGS. 25A-25G illustrate a number of variations of suitable multilumen cannulae. In some variations, one or more lumens may be provided in one or more additional lumens. For example, fig. 25A shows the distal end of one variation of a cannula (2500) comprising a first lumen (2502) disposed in a second lumen (2504). Although both the first lumen (2502) and the second lumen (2504) are shown as circular in fig. 25A, the respective lumens may have any suitable shape, size, or configuration. Additionally, although shown in fig. 25A as being concentrically disposed within second lumen (2504), first lumen (2502) may have any suitable position relative to second lumen (2504).

In other variations, one or more walls may divide the lumen into two or more discrete lumens. Fig. 25B-25G show several variations of a cannula divided into multiple lumens. Fig. 25B and 25C show two additional variations where the cannula (2506) is divided into two lumens (2508). Similarly, fig. 25D-25F show three variations of the cannula (2510) being divided into three lumens (2512), and fig. 24G shows a variation of the cannula (2514) having been divided into four lumens (2516). The respective lumens may or may not be the same size and may or may not be the same shape. Additionally, as described above, each lumen may serve one or more functions. It is important to note that the variations of the cannulae shown herein are merely exemplary variations, and that any suitable number of lumens having any suitable configuration and size may be used without departing from the intended scope of these devices.

The delivery devices described herein may have one or more additional features that may assist in the operation of the delivery device. For example, one or more sleeves of the delivery device may be configured to release one or more drugs, or may include one or more coatings configured to release one or more drugs. Any suitable drug or combination of drugs described herein may be used. In some cases, one or more drugs with anesthetic or numbing effects may be particularly useful in minimizing any pain or discomfort associated with device delivery. In other instances, one or more antibiotics, antibacterial agents, antifungal agents, antiviral agents, disinfectants, or combinations thereof may or may not be used to prevent infection associated with device delivery. In other variations, the delivery device may include one or more drugs that may help maintain homeostasis.

In some variations, the delivery device may include one or more dilators attached to or otherwise engaged with the cannula. For example, in some variations, a balloon or other expandable element may be disposed along at least a portion of the outer surface of the cannula. Typically, at least a portion of the balloon or expandable element is expandable away from the cannula to permanently or temporarily dislodge one or more tissues adjacent the cannula. The dilator may or may not surround the cannula and may or may not expand to move tissue in multiple directions. Additionally, the dilator may be detached from the cannula. This may be particularly useful when it is desired to keep a particular access open during a surgical procedure. For example, in some cases, the middle turbinates in the sinus anatomy may be pressed against the nasal sidewall. In order to deliver the device into the ethmoid sinus, it is useful to remove the middle turbinate from the nasal sidewall. Thus, once the cannula has passed between the middle turbinate and the nasal sidewall, the dilator may be expanded to move the middle turbinate further away from the nasal sidewall. Once expanded, the dilator may be detached from the cannula. The dilator may maintain a passageway between the middle turbinate and the nasal sidewall, thereby allowing the operator to remove and reinsert the delivery device from the nasal passageway without having to move the middle turbinate each time. The dilator may or may not be configured to degrade in vivo, and may or may not be removed after delivery of the one or more implants.

Similarly, the delivery device may include one or more implants positionable along or otherwise engageable with the outer surface of the cannula. In some cases, the implant may be an expandable device. In some of these variations, the implant may be a self-expanding device, such as described above. In other of these variations, the implant may expand due to external forces exerted on the implant. In addition, the implant can be disposed along or coupled to the cannula in any suitable manner. In some variations, a shell or retainer may hold the implant in place against the cannula. In other variations, one or more coatings may hold the implant in place. In variations where the implant is an inflatable balloon, the implant can be releasably attached to the balloon. Generally, the implant can be released from the cannula to provide support to one or more tissues. In some variations, the implant may temporarily or permanently expand one or more tissues, as described above. The implants may or may not be biodegradable, may or may not be configured to deliver one or more drugs, and may or may not be removed from the body after delivery of the one or more implants.

Additionally, any of the delivery devices described herein may include one or more casings connected or otherwise engaged with one or more cannulas. These casings may be made of any suitable material or combination of materials and may or may not include any of the sleeve ends or features described above. For example, the sleeve may include a funnel-shaped end, an olive-shaped end, a wedge-shaped end, a slotted end, a paddle-shaped end, a slotted tube, one or more markers, one or more dilators, one or more stents, or a combination thereof. The one or more casings may be connected or joined with the one or more sleeves in any suitable manner. For example, in some variations, one or more casings may be disposed along the outer surface of the cannula. In other variations, the shell may be disposed inside the lumen of one or more cannulae.

Fig. 26A and 26B show side and cross-sectional side views, respectively, of the distal end of a variation of a delivery device (2600) comprising a cannula (2602), a housing (2604), and a pusher (2606), and receiving an implant (2608) therein. As shown in fig. 26, the housing (2604) is configured with prongs forming tissue piercing tips, as described above. Indeed, the cannula (2602) may be advanced through a portion of the anatomy to the delivery position, and the housing (2604) may be passed through tissue as desired as the delivery device (2600) is advanced. Once the cannula (2602) is in the delivery position, the sheath (2604) may be proximally withdrawn relative to the cannula (2602) and the prongs may be opened to allow the implant (2608) to pass through the distal end of the sheath (2604). The opening of the prong may or may not result from engagement between the shell (2604) and the pusher (2606). It should be noted that although jacket (2604) is shown between cannula (2602) and pusher (2606) in fig. 26, jacket (2604) may alternatively be disposed around the outside of cannula (2602).

In some variations, the delivery device may be configured to release the sheath. In some of these variations, the shell may be released in vivo. In some cases, the shell may be configured to be retained in one or more portions of the body. For example, in variations where the shell includes a slotted tip, the struts of the slotted tip may expand in vivo. Once expanded, the branch may resist movement through an opening (e.g., sinus ostium) and the shell may remain substantially in place. The shell may or may not be configured to degrade and may or may not be configured to release the one or more drugs. Further, in some cases, the shell may serve as a conduit for the passage of one or more liquids or gases into the body.

Propeller

In variations of the delivery device described herein that include a pusher, such as the variations shown in fig. 5A and 5B, the pusher can have any suitable size, shape, and configuration. In addition, the transfer device may include any number of pushers. Each cannula or cannula lumen may include one or more pushers slidably disposed therein. In addition, each impeller may or may not include one or more lumens therethrough, and may or may not allow the passage of liquids or gases therethrough. Fig. 27 shows a variation of pusher (2700) comprising body (2702) and head (2704) and disposed within cannula (2706). Generally, the pusher (2700) can be advanced relative to the cannula (2706) and the head (2704) can engage the one or more implants (2708) to push the one or more implants (2708) out of the distal end of the cannula (2706). The body (2702) and the head (2704) may or may not be made of the same material, and may or may not have the same width. In some cases, it is desirable to maintain a particular ratio between the diameter of the cannula (c) and the diameter of the pusher (p). For example, the ratio of the diameter of the cannula to the diameter of the impeller, or c: p, may be about 10: 1, about 9: 1, about 8: 1, about 7: 1, about 6: 1, about 5: 1, about 4: 1, about 3: 1, about 2: 1, and the like. Indeed, the specific ratios may allow the delivery device to have a substantially rigid pusher body (2702) and a curved cannula (2706) without the pusher body (2702) substantially affecting the shape of the cannula (2706).

In some variations, the pusher may include one or more features that can assist in loading one or more implants into the cannula. Fig. 28A and 28B show a modification of such a pusher (2800) including a body (2802) and a head (2804), the head (2804) including an operating bar (runner) (2806). Generally, the head (2804) and handle bar (2806) may fit within the sleeve (2808), as shown in fig. 28A. As pusher (2800) advances and operating bar (2806) exits cannula (2808), operating bar (2806) may or may not bend, bend or rotate away from each other, as shown in fig. 28B. To assist in loading the implant into the cannula (2808), the pusher (2800) may be first advanced such that the handle bar (2806) is out of the cannula (2808), the implant may be positioned in the aperture defined by the handle bar (2806), and the pusher (2800) may be withdrawn into the cannula (2808). As the manipulator strips are pulled back into the sleeves (2808), the sleeves (2808) may return the manipulator strips (2806) to their original position, and thus may grasp or grip the implant. As pusher (2800) continues to be withdrawn proximally, handle bar (2806) may pull the implant into the interior of cannula (2808).

Although described above as including a pusher, the transfer device described herein need not necessarily have a pusher. Indeed, any suitable actuation mechanism may be used. For example, the delivery may be actuated by introducing one or more gases or liquids (e.g., compressed air, inert gas, water, saline, etc.) into the cannula. In other variations, a stopper may be used to help release one or more implants. Fig. 29A and 29B show a variation of a transfer device (2900) that includes a stopper (2902). Shown in fig. 29A is a stopper (2902) comprising a retention section (2904) and a head (2906) and disposed within a cannula (2908). Typically, one or more implants (not shown) are received within cannula (2908) in retention section (2904) or stopper (2902), and head (2906) prevents the one or more implants from prematurely releasing from cannula (2908). Indeed, to release the one or more implants, cannula (2908) may be withdrawn relative to stopper (2902), or stopper (2902) may be advanced relative to cannula (2908) to expose retaining section (2904) and the one or more implants, as shown in fig. 29B.

While shown in fig. 29A and 29B as having a narrower diameter than the remainder of the stopper (2902), the retention section (2904) may have any suitable size, shape, or configuration. Indeed, in some variations, the retention section (2904) may include one or more channels at least partially through the stopper (2902). Additionally, one or more implants may or may not be releasably connected to the stopper (2902).

In general, delivery devices that include a stopper may provide greater latitude to the user in controlling the placement of one or more implants. Indeed, in variations where the implant is pushed out of the distal end of the device, it is difficult to ensure proper placement relative to one or more structures. In variations with a stopper, the distal end of the delivery device may be disposed proximate to one or more tissue structures. The retaining structure may be exposed to release the one or more implants by withdrawing the cannula relative to the stopper. This may be used to allow a user to position the implant adjacent to one or more tissue structures.

Fig. 30A-30F illustrate another variation of a delivery device (3000) that includes a stop (3002). Fig. 30A shows a perspective view of the transfer device (3000). Also shown is a stopper (3002) including a retention portion (3004) and a limiting element (3006), and a cannula (3008) including a cannula opening (3010). Fig. 30B shows a side view of the stopper (3002), and fig. 30C shows a side view of the sleeve (3008). Generally, the stopper (3002) is configured to receive one or more implants in the retention portion (3004), the retention portion (3004) defining a stopper opening (3012) and through which the one or more implants may be released. Additionally, a restraining element (3006) may or may not be slidably disposed within the stopper (3002), and may or may not releasably connect one or more implants to the stopper (3002). For example, in variations where the delivery device (3000) is used to deliver an implant defining a lumen or aperture, the restraining element (3006) may pass through the lumen or aperture, thereby preventing the implant from becoming detached from the delivery device (3002). It is important to note that while shown in fig. 30A-30F as having a limiting element (3006), the stop (3002) need not be.

In practice, one or more implants may be placed in the holding portion (3004) and the stopper (3002) may be disposed in the cannula (3008). The stop (3002) may or may not be configured to rotate within the sleeve (3008). In variations where the stop (3002) is rotatable within the cannula (3008), rotation of the stop (3002) or cannula (3008) may be used to release one or more implants. When the stop (3002) is disposed in the cannula (3008), the delivery device may have an open configuration and a closed configuration depending on whether the (3010) and stop (3012) openings of the cannula are aligned. When the openings are misaligned, the delivery device (3000) is "closed" as the stopper opening (3012) is covered by the body of the sleeve (3008), as shown in the top view of fig. 30D. To open the device, the user may rotate the sleeve (3008) or stopper (3002) to align the openings. In this position, one or more implants may be released from the delivery device (3000) through the opening.

However, in the variant comprising a restraining element (3006), the release of one or more implants requires an additional step. Assuming that the restraining element (3006) has been configured to releasably attach the implant to the delivery device (3000), the restraining element (3006) needs to be withdrawn before the implant can be released, as shown in the top view of fig. 30F. The restraining element (3006) may provide additional control to the user in properly positioning the self-expanding device (not shown), such as those described above. When a delivery device (3000) holding the self-expanding device is rotated from a closed configuration to an open configuration, the self-expanding device may tend to expand through the opening (3010) of the cannula, but still be at least partially connected to the delivery device (3000) by the restraining element (3006). If not, the self-expanding device may be completely released from the device, thereby making it difficult to reposition the self-expanding device once it has been expanded. Instead, the connection may allow the user to reposition the expanded self-expanding device as desired. Once the self-expanding device has been properly positioned, the user may retract the restraining element (3006) to release the self-expanding device.

Although shown in fig. 30C as having cannula opening (3010), cannula (3008) need not be. Indeed, in some variations, the same effect may be achieved by retracting the cannula (3008) relative to the stopper (3002) or by advancing the stopper (3002) relative to the cannula (3008). In these variations, the delivery device (3000) may release one or more implants as the cannula (3008) is withdrawn or the stopper (3002) is advanced to expose the stopper opening (3012). As described above, the restraining element (3006) may limit or control the release of the one or more implants.

Fig. 31A-31C illustrate cross-sections of other exemplary configurations of the distal end of the delivery device. Fig. 31A provides a cross-sectional view of one variation of the distal end of a suitable delivery device (3120). Shown in this variation are a cannula (3122), a guide wire or guide element (3124), and an expandable balloon (3126). In this variation, the device (3128) is disposed about the expandable balloon (3126) in its compressed configuration. Once the delivery device has been advanced to the desired target location, the sleeve (3122) may be withdrawn proximally, or the guide wire (3124) may be advanced distally to expose the balloon (3126) and device (3128) to the target tissue. The balloon can then be expanded to help the device better place adjacent the target tissue. In some variations, the balloon may be heated to assist in expansion or deformation of the device. Once the device (3128) has been deployed, the expandable balloon (3126) may be deflated and the delivery device (3120) may be withdrawn, leaving the expanded device (3128) at the target location.

Of course, while shown in fig. 31A as an expandable balloon (3126), it should be understood that any expandable structure may be used. The expandable structure may be made of any suitable material, such as latex, polyamide, nylon, polyethylene, low density polyethylene, DuralynDuramaxpebaxPolyurethanes, and any analogs, homologs, derivatives, salts, copolymers, and mixtures thereof.

Fig. 31B shows another variation of the distal end of the delivery device (3130). This variation is similar to the variation described immediately above with reference to fig. 31A, except that no air bag is used. Shown in this variation is a cannula (3132), a guide wire or guide element (3134), and a device (3136) disposed about the guide wire (3134). In use, once the delivery device is advanced to or near the target location, the cannula (3132) may be withdrawn proximally, or the guide wire (3134) may be advanced distally to place the device (3136) at the desired location. The guide wire (3134) may then be withdrawn, leaving the device (3136) to self-expand.

Fig. 31C shows yet another variation of the distal end of the delivery device (3140). In this variation, the delivery device (3140) includes a guide wire (3142) having a distal tip (3144) about which the device (3146) is disposed. The device (3146) is releasably attached to a suture (3148) or other such material, with the ends of the suture extending through a suture housing (3150). In this variation, the delivery device (3140) may be advanced to the target location and the suture (3148) may be proximally withdrawn through the suture housing (3150), thereby releasing the device (3146) and allowing it to self-expand. It will be appreciated that the variations described above are but a few of the many possible variations that are suitable for the delivery device described herein.

Fig. 32A and 32B illustrate another variation of delivery device (3200) comprising cannula (3202) having cannula opening (3204) and jacket (3206) comprising jacket opening (3208). Although shown in fig. 32A as being disposed on casing (3202), jacket (3206) may also be disposed in casing (3202) and may be configured with any feature or combination of features described above in any manner. Sleeve (3202) and jacket (3206) may or may not be able to rotate relative to one or the other, or may not be able to slide relative to one another. The delivery device (3200) may have an open configuration and a closed configuration. In the closed configuration, sleeve opening (3204) is covered by a portion of jacket (3206), and jacket opening (3208) is blocked by a portion of jacket (3202), as shown in the side view in fig. 32A. To release one or more implants from delivery device (3200), sleeve (3202) and jacket (3206) may be moved by a rotational or sliding actuation such that at least a portion of sleeve opening (3204) and jacket opening (3208) overlap, as shown in the side view in fig. 32B. When the cannula opening (3204) and the housing opening (3208) overlap, the device can exit the delivery device (3200) through the openings.

Handle (CN)

The handle of the delivery device may have any suitable size or configuration of elements and may include any suitable means of actuating the device. Indeed, each handle may have any suitable number of buttons, knobs, triggers, cranks, levers, or other actuation elements for actuating one or more of the above-described features of the delivery device. Each actuating element may control one or more features of the device, or may control multiple features simultaneously. For example, in variations where the device comprises two control wires for manipulating the casing, each control wire may be controlled by a separate actuating element, or both may be controlled by the same actuating element. For example, the handle may include a knob that affects the amount of tension placed on each control wire. The tension may increase on a first line and decrease on a second line when the knob is rotated in one direction and vice versa when the knob is rotated in the other direction.

In variations where the handle includes a pusher or stopper as described above, the handle may be configured to actuate the pusher or stopper in any suitable manner. In some variations, the handle may be configured to advance the pusher or stopper relative to the cannula. For example, in the variation shown in FIG. 5B above, the handle body (516) is coupled to the cannula (514) and the plunger (520) is coupled to the pusher (522). Thus, when the plunger (520) is pushed relative to the handle body (516), the pusher (522) advances relative to the cannula (514). In other variations, the handle may be configured to retract the cannula relative to the pusher or stopper. Fig. 33 shows a variation of the delivery device (3300) including a handle (3302), stopper (3304), and cannula (3306). As shown in fig. 33, the handle (3304) includes a grip (3308) and a trigger (3310) connected to the body (3312). In this variation, the sleeve (3306) may be permanently or releasably connected to the body (3312) and the stopper (3304) may be connected with the handle (3308). To release the implant from the delivery device (3300), the operator may grip the handle (3308) and pull the trigger (3310) proximally relative to the handle (3308). As the trigger (3310) moves proximally, the sleeve (3306) moves proximally, thereby withdrawing the sleeve (3306) relative to the stopper (3304).

In variations that include a pusher or stopper, the handle may be adjusted to control the amount of movement of the pusher, stopper or cannula when the trigger is actuated. FIG. 34A shows a cross-sectional view of one variation of the handle (3400), while FIGS. 34B-34D show a suitable variation of the adjustable handle. Fig. 34A shows a handle (3400) comprising a handle body (3402), a spring (3404), a pusher (3406), a plunger (3408), and a connector (3410). Typically, the handle body (3402) houses a spring (3404) and a connector (3410) such that the spring (3404) biases the connector (3410) away from the proximal end of the handle body (3402). Additionally, a connector (3410) may connect the plunger (3408) with the propeller (3406). To actuate the device, a user may depress the plunger (3408), advance the pusher (3406), and compress the spring (3404). When the plunger (3408) is no longer depressed, the spring (3404) may press against the connector (3410) to return the handle to its pre-actuated configuration.

Fig. 34B shows a variation of the handle (3412) including an adjustable ring (3414). The remaining elements of the handle (3412) are the same as shown in fig. 34B and are labeled the same. An adjustable ring (3414) is releasably connected to a portion of the plunger (3408) and limits the amount the plunger (3408) is depressed. This is particularly useful when different lengths of cannula are used for the same handle (3412). For each cannula, the operator can adjust the adjustable ring (3414) to provide the proper range of motion for the plunger (3408) and the pusher (3406).

Fig. 34C and 34D illustrate a variation of the adjustable handle in which one or more elements may have threads. Fig. 34C shows a variation of the delivery device (3416) in which the trigger (3408) has threads (3418) that correspond to the tracks (3420) in the hollow portion (3422) of the connector (3410). To adjust the length of the trigger (3408) and thus the amount by which the trigger (3408) may be depressed, the trigger (3408) may be rotated to screw a portion of the trigger (3408) into the hollow portion (3422) of the connector (3410). Similarly, fig. 34D shows a variation of the delivery device (3424) in which the pusher (3406) includes threads (3426) that can be threaded into tracks (3428) within the hollow portion (3430) of the connector (3410). This can adjust the relative length of the propeller (3406).

Methods of use

The self-expanding devices and delivery devices described herein may be used at various locations within the body for a number of different purposes. For example, self-expanding devices may help provide support to or expand tissue, or may be used to treat various conditions or diseases. The self-expanding device may indeed be used in any area of the body which may benefit from the structural and functional features of the self-expanding device.

For example, the device may be delivered to one or more tonsils, sinus cavities, arteries, veins, one or more openings or cavities, such as the middle ear or tympanic cavity, hollow body organs, such as the ureter, fallopian tube, bile duct; lung organs such as trachea, bronchi and bronchioles; and gastrointestinal organs such as the esophagus, stomach, intestine, and colon, among others. For sinuses, the device may be used before or after surgery. In some variations, the devices described herein are used in the sinus cavities of pediatric patients. This is particularly advantageous for pediatric patients compared to traditional treatment options, as the use of the device and method may reduce the risk of a patient not fitting well.

The devices may also be used to treat and/or ameliorate one or more symptoms of various diseases, including, but not limited to, urinary incontinence, atherosclerosis, benign prostatic hypertrophy, recoil damage following percutaneous transluminal angioplasty and in dissection, long-term occlusion, anastomotic hyperplasia in vein grafts and artificial blood vessel grafts, vulnerable plaques, aneurysms in the aorta and aorta, arteriovenous fistulas and traumatic leaks, malignant stenosis of the gastrointestinal tract, acute ileus in colorectal cancer, biliary occlusion of the hepatobiliary tract or other liver cancers, benign tracheal compression and malignant tracheobronchial obstruction, one or more diseases or conditions of the sinuses, and the like.

The device can be transported and configured in a suitable manner. In some variations, the device is configured in an open surgical manner. In other variations, the device is configured in a less invasive manner (e.g., laparoscopically, endoscopically, or intravascularly using a catheter). Where the devices are delivered in a generally minimally invasive manner, the devices are delivered in their compressed configuration. The device may be pre-installed in the transfer device, but this is not essential. For example, where the device has only a limited ability to expand sufficiently after it has been held in its compressed state for an extended period of time (i.e., the device may relax over time, resulting in a loss of shape memory, for example), it may be more desirable to collapse and load the device into a delivery device shortly before delivery and deployment. The device may be retracted directly into the transfer device.

While other methods of collapsing the devices described herein will be discussed in detail below with specific reference to manufacturing methods, fig. 4A-4C illustrate one possible method by which the device (400) may be reduced to its compressed configuration using sutures (402), fibers, or other similar materials, and then placed in the lumen (404) of a delivery device (406). In variations of the device (400) having multiple loops (408), the suture (402) may pass through all or some of the loops, and may pass through the loops one or more times, when the device (400) is in its expanded configuration. Once the suture (402) has passed through the desired number of loops, the ends of the suture (402) may be pulled to reduce the device (400) to its compressed configuration, as shown in fig. 4B. In some variations, the ends of the suture (402) are pulled in the same direction, while in other variations they are pulled in opposite directions. In other variations, the ends of the suture may be pulled at different angles. As shown in fig. 4C, the suture (402) may then be removed and discarded, and the compressed device (400) may be loaded into the lumen (404) of the delivery device (406) via the distal (or proximal, as the case may be) end of the delivery device. The suture may be removed before or after the device is loaded into the lumen, and in the event that retrieval or withdrawal of the device is desired, the suture (402) may also remain threaded through the loop (408), as described above.

Other methods may also be used to reduce the device (400) to its compressed configuration. For example, the device may be manually compressed using a person's fingers, or may be placed in a cartridge-type device that reduces its diameter. The device can even be manufactured in its compressed configuration and then expanded or deformed into its expanded configuration manually or thermally.

In another method, the device may be placed on a tapered mandrel and slid down the mandrel, thereby reducing the diameter of the device. An outer jacket or funnel may be provided on the tapered mandrel to control the outer diameter of the device. The end of the tapered mandrel may then be placed in the transfer device and the outer jacket/funnel removed, thereby leaving the device in its compressed configuration within the transfer device.

In yet another method, the device may be disposed in an opening of a funnel. Filaments attached to the device can be withdrawn through the funnel, pulling the device and contracting it as its diameter decreases. Similarly, a bladder may be positioned within the funnel, expanded at least partially, and pulled through the funnel to collapse the device. Such a balloon may provide uniform deflation due to friction between the device and the balloon.

In other approaches, a roll retractor is used to reduce the device to its compressed configuration. In these methods, the device is first slid loosely onto a balloon portion of a guide wire. The assembly is placed between the plates of a rolling retractor. By means of an automated rolling shrinker, the plates are brought together and exert a certain amount of force. The plate is moved back and forth a set distance in a direction perpendicular to the guide wire. Under this motion the wire is guided to roll back and forth and the diameter of the device is reduced. The process can be broken down into more than one step, each with its own force level, travel distance, and cycle number.

Still other methods utilize a sliding wedge or iris retractor to reduce the device to its reduced configuration. In a sliding wedge or iris retractor, adjacent pie-shaped sections move inward and twist, much like blades in a camera iris. The retractor can be designed to have two different types of end points. It can stop at a final diameter or it can exert a fixed force and allow the final diameter to float. The sliding wedge retractor provides an approximately cylindrical inner surface to the device even as it retracts. This means that the shrinkage load is distributed over the entire outer surface of the device. In addition, the Self-expanding device may be contracted using any of the Methods or Devices described in U.S. provisional application No.61/085,795, entitled "Methods and Devices for crimming Self-expanding Devices," which is incorporated herein by reference in its entirety.

Any of the delivery devices described above may be used to deploy the self-expanding devices described herein, as well as any other suitable implant. Typically, the distal end of the delivery device is introduced into the body. In some variations, the distal end of the delivery device may be introduced into a natural opening in the body, such as the ear canal or nostril. In other variations, the distal end of the delivery device may be introduced into an artificially created opening in the body. In some of these variations, the artificially created opening may be preformed using one or more tools separate from the delivery device. In variations where the delivery device has a cannula or sheath configured to pierce tissue or otherwise carry one or more tissue piercing devices, the delivery device may be used to form the opening.

Once the delivery device has obtained access to the body, at least a portion of the delivery device (which may be part of one or more cannulae) may be advanced to the target location. In some variations, this advancement is under direct view. This direct visualization may be accomplished by a device external to the delivery device, such as an endoscope, or may be accomplished by one or more visualization devices disposed within one or more lumens of the cannula or one or more visualization devices connected to the delivery device. In other variations, the advancement is performed under indirect visualization, such as fluoroscopy or ultrasound.

During advancement, it may be desirable to provide an anesthetic or other anesthetic drug to help minimize the pain associated with the procedure. In some variations, the delivery device may spray or jet one or more liquids or gases including one or more drugs. In other variations, a portion of the delivery device, such as the cannula, may release one or more drugs, or may include a coating that releases one or more drugs.

In addition, during advancement of the delivery device, it may be desirable to temporarily or permanently transfer one or more tissues. In some variations, one or more sleeves or shells of the delivery device may include a tip as described above that may be used to displace one or more tissues. In addition, one or more dilators or additional implants may be used to temporarily or permanently dilate one or more tissues and may be used to maintain an open passageway between a body opening and a target site. In other variations, one or more dilators separate from the delivery device may be used to temporarily or permanently dilate or otherwise displace one or more tissues. The one or more dilators may transfer tissue prior to advancement of the delivery device, or may transfer tissue while the delivery device is advanced. Further, the one or more dilators may or may not sequentially dilate the tissue (e.g., by introducing dilator(s) of increasing size, or sequentially increasing the size of the dilators).

Once the delivery device has reached the target location, the end of the cannula or sheath may be positioned relative to one or more tissues or tissue openings. Once the tip is properly positioned, the delivery device may release or otherwise expel one or more self-expanding devices or other implants. In some variations, the released device may be repositioned as desired.

In some variations, the device is sized and shaped to be delivered within one or more sinus cavities, or at one or more locations where a sinus cavity has been removed. Any of the devices and methods described herein may also be used to treat one or more sites of the osteomeatal complex, as described in U.S. patent application No.11/775,157 filed on 9.7.2007, which is incorporated herein by reference in its entirety. Fig. 6 shows a diagrammatic view of the anatomy of a sinus after typical sinus surgery. Shown are the maxillary sinus (600) with a surgically enlarged maxillary sinus opening (602), the surgically enlarged ethmoid sinus (604), and the nasal cavity (606). It should be understood that although the methods described below refer to devices delivered and deployed to one or more sinus cavities after a typical sinus surgery, any of the devices described herein may be delivered to one or more sinus cavities prior to a typical sinus surgery.

Deployment of one or more of the devices described herein into one or more sinus cavities can help maintain patency of the sinus cavity, help prevent blockage caused by adhesions between healing or inflamed mucosal surfaces, and help deliver an effective topical dose of the drug. When placed in the ethmoid sinus after sinus surgery, the device can help prevent lateral deviation of the middle turbinate, which could otherwise lead to the formation of adhesions that occlude the sinus opening. In addition, the devices described herein may facilitate a natural healing process when configured to deliver one or more drugs to one or more sinus cavities following sinus surgery. In addition, when using a device (e.g., the device shown in fig. 1A) defining a lumen (having any suitable cross-sectional geometry) in its expanded configuration, the device may provide additional advantages in providing better access to the surgical site for post-operative cleaning and subsequent treatment. That is, in contrast to conventional tamponade materials, devices defining a lumen may facilitate more natural clearance of mucus and sinus discharge, and facilitate easier irrigation and removal of other debris.

Fig. 7A-7C illustrate a method of delivering a device (704) to an ethmoid sinus (700) using a delivery device (702). Referring now to fig. 7A, the delivery device (702) is first advanced (e.g., under endoscopic guidance) through the nasal cavity (706) and into the ethmoid sinus (700). Once the delivery device (702) reaches the desired location in the ethmoid sinus (700), as shown in fig. 7B, the device (704) may be configured. Once the device (704) is fully deployed (i.e., it changes to its expanded configuration), the delivery device (702) may be removed from the body as shown in fig. 7C. While a delivery cannula or other introducer device having a push rod (not shown) is shown in FIGS. 7A-7C, the delivery device (702) may be any device suitable for deploying the device (704) as described above.

Fig. 8A-8C illustrate a method of delivering a device (804) to a maxillary sinus (800) using a delivery device (802). Referring now to fig. 8A, the delivery device (802) is first advanced (e.g., under endoscopic guidance) through the nasal cavity (806) and into the maxillary sinus (800). Once the delivery device (802) reaches the desired location in the maxillary sinus (800), the device (804) may be configured as shown in fig. 8B. Once the device (804) is fully deployed (i.e., it changes to its expanded configuration), the delivery device (802) may be removed from the body as shown in fig. 8C. While a delivery cannula or other introducer device having a push rod (not shown) is shown in fig. 8A-8C, the delivery device (802) may be any device suitable for deploying the device (804) as described above.

As described above, the device may be repositioned during or after delivery, if desired. Similarly, the device may be removed (by sutures or other such material, by grasping the device in jaws or the like, or by suction or aspiration, or the like).

Although shown in fig. 7A-7C and 8A-8C as delivering to the ethmoid sinus and maxillary sinus, respectively, it should be clear that the device may be delivered to any sinus cavity. For example, the device may be delivered to the frontal or sphenoid sinuses. Similarly, the device may be delivered to the mouth of the nasal passage or any sinus cavity. The device may be disposed at any location and may or may not be configured to deliver a drug.

Fig. 9A-9C illustrate a method of delivering a device (904) into one or more vessels in the vasculature. As shown in fig. 9A, the delivery device (900) is first introduced into the body (e.g., via the femoral or carotid arteries, or via any other suitable known access), and then advanced through the vasculature to the target location. In the variation shown in fig. 9A, the delivery device includes an expandable balloon (902) having a device (904) disposed thereon. Of course, the transfer device need not be so configured, and any suitable transfer device may be used.

Once the delivery device (900) has been advanced and positioned at the desired location, the cannula may be withdrawn proximally or the balloon (902) advanced distally to expose the device (904) to the target location, as shown in fig. 9B. The balloon is then expandable and the device (904) is deployed. Once fully expanded, the transfer device (900) may be removed as shown in fig. 9C. The device may be placed in a vein or artery at the site of plaque formation (e.g., vulnerable plaque formation) or potential plaque formation. Further, the device may have a configuration that is particularly desirable or suitable for use with bifurcated vessel segments.

The devices described herein may have particular application in treating thin-capped fibrous atheromatous plaque (TCFA) or other types of plaque, relative to use within the vasculature. TCFA is a type of plaque that, if ruptured, can cause rapid lumen occlusion and heart attack. Such plaques have multiple structural features that make them more difficult to treat than stable lesions. By providing a device capable of releasing tissue adhesion-promoting molecules to TCFA, the cap of TFCA can be stabilized and enhanced, which in turn allows TCFA to be treated like a stable lesion. Since TFCA is prone to cap rupture, the device may be made of a material that opens or can open in a slow, controlled manner. Furthermore, in some variations, it is desirable to release one or more healing-promoting drugs to the TCFA.

Fig. 10A-10C illustrate a method of bypassing an obstruction (1000) of a ureter (1002) with a device described herein. As shown in fig. 10A, the delivery device (1004) is advanced to a position between the wall of the ureter (1002) and the obstruction (1000). Once the transfer device (1004) is positioned at the desired location, as shown in fig. 10B, the device (1006) may be configured. When deployed, the device (1006) forms a channel in the ureter (1002) through which urine can pass, thereby bypassing the obstruction (1000), as shown in fig. 10C. The delivery device (1004) may then be withdrawn.

The devices described herein may also be used to treat urinary incontinence. For example, the device may be placed in the bladder and/or urethra to prevent the urinary channel from being blocked by a growing prostate or other condition. Drugs that may be used to treat urinary incontinence include, but are not limited to, alpha-blockers, imipramine, spasmolytics, and 5-alpha reductase inhibitors.

Production method

The devices described herein can be made in any suitable way. Generally, the method includes producing a polymer filament and forming the filament into the device. The method can optionally include coating the polymeric filaments with a drug eluting layer, applying a drug reservoir to the filaments, and the like. Other steps may include heat setting and quenching the device, packaging the device, and sterilizing the device. The steps may be performed in any suitable order, and various steps or combinations of steps may be removed or replaced with other steps as desired or appropriate.

The polymer filaments can be produced by any suitable method. Methods of producing polymer filaments include, but are not limited to, extrusion, wet spinning, dry spinning, gel spinning, laser cutting, and injection molding. In methods using injection molding, injection molding can be used to produce fully molded devices. Where an extrusion molding process is used, a suitable polymer may be extruded using melt phase processing to form a polymer of a particular diameter. In these processes, the polymer will reach a temperature above the melting temperature of the polymer. Here, the molten polymer is pushed or pulled through a die to form a filament. The filaments can also be drawn further to smaller diameters to orient the polymer molecules. The draw ratio may be any suitable ratio, for example 6.

When a drug-eluting layer or reservoir is desired, a coating formulation (which may form the layer or reservoir) may be prepared. The coating formulation may be formed by mixing a combination of a degradable polymer, a release rate modifier and a pharmaceutical ingredient. The coating formulation may be configured to have a particular viscosity depending on what process is used to coat the filaments. Since the drug delivery profile may depend in part on viscosity, the coating formulation may have a viscosity suitable for both coating and drug delivery.

Once the filaments have been formed and the coating formulation prepared, the filaments may be coated with the coating formulation to form a drug-eluting layer. In some variations, the filaments are first plasma cleaned to improve adhesion of the coating formulation to the filaments. The coating process may be any suitable process including, but not limited to, spraying, sprinkling, spraying, dipping, brushing, pouring, dripping, spin coating, roll coating, meniscus coating, powder coating, and ink jet processes. In some variations, the filaments are formed into their final configuration prior to coating. In these variations, a coating fixture may be used to hold the device during coating. In some of these variations, the coating fixture may hold the formed wire with its tip to facilitate spray or dip coating without depositing the coating formulation on the coating fixture. In variations of the device that include a collar, the collar may be used to secure the device to a coating fixture.

In some variations, a spray process is employed in which the spray follows or tracks the pattern of the device. In these variations, the device is rotated and moved back and forth under the spray head to track the device's pattern. Tracking the design of the device in this manner can achieve delivery efficiencies as high as 20%, with a typical efficiency for a device applicator being about 5%. In these variations, the device loop may be used to provide proper orientation of the device when it is placed on the coating fixture. Further, in these variations, the coating fixture may include a spring that provides an axial force, thereby allowing the device to retain its shape.

For devices containing multiple drug-eluting layers, multiple coating processes may be employed to form the different layers. In one variation of the multiple coating process, the device wire may be passed through a coating bath or micropump that deposits a first coating on the device wire, and then passed through a heating or ultraviolet element to harden the layer. The device wire may then be passed through other deposition and hardening elements to form additional layers.

The device wire can then be manipulated into a device configuration in any suitable manner. In some variations, a shaped fixture is used to determine the final shape of the device. In these variations, a constant tension may be applied to the device wire as it is wound around the forming fixture into its final configuration. This allows control of the percent strain of the device wire. In addition, loops can be formed on the device by winding the device wire around posts strategically placed on the forming fixture. In other variations, the forming fixture is flat and the device must be finally manipulated into its final configuration.

Once the device wire is on the forming fixture or otherwise placed in its final configuration, the ends of the wire may be joined to form a continuous wire loop. In some variations, the bonding is achieved by a biodegradable polymer glue in a suitable solvent, and the polymer glue may be the same polymer as the coating polymer. In the variant comprising polymer filaments, the solvent for the polymer glue is generally a non-solvent for the polymer filaments. In other variations, the joining may be achieved by heat welding, laser welding, ultrasonic welding, or RF welding the ends of the device wires.

Once the device has been formed, it can be heat set. The device is typically heat set under tension and any suitable heating parameter may be used, for example heating at 120 ℃ for 10 minutes. In a variant employing polymer filaments, the device may be heated at a temperature between the glass transition temperature of the polymer filaments and their melting temperature. Once the device has been heated, it can be quenched. Any suitable quenching parameter may be used, for example cooling at-20 ℃ for 10 minutes. In variations employing polymer filaments, the device may be quenched at a temperature below the glass transition temperature of the polymer filaments.

Once the device has been formed, heated and quenched, a drug reservoir may be added or filled with a drug. The device may be weighed multiple times during the process to determine the amount of drug added. Once the device has been manufactured, it can be inspected, packaged and sterilized by any suitable process. In some methods, the device may be packaged with a support to support and maintain the device configuration during sterilization and/or transportation. Similarly, sutures or filamentary material may be used to prevent the device from changing shape during these steps. Sterilization may employ any suitable process including, but not limited to, gamma sterilization and electron beam sterilization.

Fig. 11 provides a flow chart of one method of manufacturing the devices described herein according to the above-described technique. However, the device may be formed by a variety of alternative methods. In some variations, the device may be cut from a film (e.g., a rolled cylinder). Alternatively, the device may be cut from a film and then rolled into a cylinder. In other methods, the device may be formed by joining smaller, non-intersecting filament segments together. In these variations, the wire segments may be joined using any of the joining methods described above.

In other variations, the device may be formed by pressing, injection molding, or foam molding. In compression molding, a solid polymeric material is added to a mold and then pressurized and heated until the polymeric material conforms to the mold. The solid form may require additional processing to obtain the desired form of the final product. In injection molding, a solid polymeric material is added to a heated barrel, softened, and pressed under pressure into a mold to form a solid form. The solid form may require additional processing to obtain the desired form of the final product. In foam molding, a solid polymeric material is expanded and molded into a desired morphology using a blowing agent, and the volume of the solid polymeric material is expandable from about 2 to about 50 times its initial volume. The polymeric material may be pre-expanded with steam and air and then shaped in a mold with additional steam; or mixed with a gas to form a polymer/gas mixture that is forced into a mold at a lower pressure. The solid form may require additional processing to obtain the desired form of the final product.

IV. examples

Device preparation

Poly (L-lactide-co-glycolide) polymer filaments having a lactide to glycolide ratio of about 10: 90 were prepared by extrusion of the polymer using melt phase processing. The filaments were then drawn at a draw ratio of about 6 to give a diameter of about 0.36 mm. The resulting filaments had a tensile strength of about 580MPa, a young's modulus of about 7400MPa, and a strain failure between 50% and 60%. These values can be determined using the Instron tensile test at room temperature with a strain rate of 25 mm/min.

The crown device described above and shown in fig. 1A and 1B was formed using a polymer filament and coated with a drug eluting layer. The device is also capable of reduction from an expanded configuration diameter of about 5cm to a reduced profile diameter of about 4.5 mm. The expanded device can provide a range of up to about 23.5cm²The area of (a). The device may then be sterilized using an electron beam sterilization dose of 28 ± 10% KGy. The sterilized apparatus had an intrinsic viscosity of about 1.0dL/g in HFIP at 25 ℃ as determined by a model 75Cannon-Ubbelohde viscometer.

Mechanical Strength test

The mechanical strength of a variant of the device described here was tested as a function of time. A number of the above-described crown devices are fabricated from poly (L-lactide-co-glycolide) device filaments having a ratio of lactide to glycolide of about 10: 90. The drug eluting coating was formed with polyethylene glycol having a molecular weight of about 6000, mometasone furoate, acetone, and poly (DL-lactide-co-glycolide) having a ratio of lactide to glycolide of about 70: 30. The devices were packaged in pouches made of Foil/PE plies and sterilised using electron beam at a total dose of 28kGy ± 10%. The devices were removed from their packaging and stored with Sepragel (Genzyme Biosurgery, Cambridge, MA) and Meropack (medtronic, inc., Jacksonville, FL) in 50mmol phosphate buffered saline at pH values in the range of 7.4 ± 0.2 at about 37 ℃ (to mimic body temperature).

The three crown devices were subjected to compressive strength testing and creep resistance testing was performed on all three devices. The tests were performed at the initial time point, at 3 days, 5 days, 7 days, 11 days and 14 days. For the compression test, five new device samples were used at each time point, totaling 30 device samples. For creep resistance testing, each sample of each device was tested at each time point and multiple samples of each device were tested (5 samples for both the crown and the Meropack devices and 4 samples for the sephagel device).

In the compressive strength test, the force required to compress each sample by 25% of the original nominal diameter of about 50mm is measured. To collect these measurements, each sample was held between two plates that were initially separated by about 50 mm. The plates were then moved together at a rate of 5mm/min and the force required to bring the plates to a final separation of about 37.5mm was recorded. The device is considered to have passed the compressive strength test if the strength of the device at 7 days is at least 25% of its initial value.

In the creep resistance test, samples of various devices were placed in models of the ethmoid sinus after Functional Endoscopic Sinus Surgery (FESS), each with a free floating middle turbinate represented by a free floating clear acrylic plate. The dimensions of the model (about 30mm long, about 14mm high, about 15mm deep) are based on the average dimensions of the ethmoid sinus after FESS surgery, as described in clinical anatomy of the Head of Lang j: such as those provided in neurocium, orbit, cryptobiological regions (Springer, New York 1981). The samples were positioned such that they prevented the acrylic plate from contacting the substrate of the mold. At each time period, the distance between the bottom of the model and the acrylic plate was measured for each sample to evaluate the ability of the implant to support the free-floating middle turbinate. The device is considered to pass the creep resistance test if the panel height at 7 days is at least 50% of the initial height (i.e., about 7 mm).

Table 1 shows the compressive strength of the device samples at each test point. Specifically, table 1 shows the average radial strength of the sample test groups at each time period, the standard deviation of these strengths, and the number of cracks that occurred on that day. At 7 days, the devices retained 47.7% of their initial strength, and thus all devices passed the test. At 14 days, four of the five device samples had ruptured, and thus the standard deviation could not be calculated for this test group.

TABLE 1

Table 2 shows the creep resistance values of the respective samples. More specifically, table 2 shows the average plate height and the corresponding standard deviation for each set of devices at each time period. At 14 days, the devices still provided a separation distance of about 14mm between the free floating plate and the model substrate, and thus all devices passed the creep resistance test. The Sepragel device did not achieve separation at 3 days. The Meropack devices provided their maximum separation distance, on average 8.58mm at 3 days, but at 14 days these separation distances were reduced to an average of 1.28 mm.

TABLE 2

Drug delivery

The crown-shaped device described above is made from poly (L-lactide-co-glycolide) filaments having a ratio of lactide to glycolide of about 10: 90. The drug eluting coating is formed to contain mometasone furoate, acetone, and poly (DL-lactide-co-glycolide) having a ratio of lactide to glycolide of about 70: 30. One coating had no PEG, one coating had 5% by weight of PEG 6000, and the other had 20% by weight of PEG 6000. Figure 12 shows how the release of the formulation is varied with the addition of a release rate modifier, in this case polyethylene glycol.

The in vivo release of mometasone furoate was studied using a rabbit model. The crown device as described above was made with poly (L-lactide-co-glycolide) filaments having a ratio of lactide to glycolide of about 10: 90. The drug eluting coating is formed to contain mometasone furoate, acetone, and poly (DL-lactide-co-glycolide) having a ratio of lactide to glycolide of about 50: 50. One coating had no PEG and the second coating contained 20% by weight of PEG 6000. The crown device was implanted into the maxillary sinus of a rabbit. The devices were then explanted at different time points. For each time point, the amount of mometasone furoate remaining on the device was measured using a High Performance Liquid Chromatography (HPLC) based assay analysis. The release rate of mometasone furoate is then calculated based on the amount left on the device. Fig. 13 shows the in vivo release data and shows how the release rate profile can be adjusted by changing the coating formulation.

Accelerated HPLC release rate assay analysis was used to study the in vitro release of mometasone furoate. The crown device as described above was made with poly (L-lactide-co-glycolide) filaments having a ratio of lactide to glycolide of about 10: 90. The drug eluting coating is formed to contain mometasone furoate, acetone, and poly (DL-lactide-co-glycolide) having a ratio of lactide to glycolide of about 50: 50. One coating had no PEG and the second had 20% by weight of PEG 6000. Fig. 14 shows the cumulative release of mometasone furoate for two formulations.

Claims (11)

1. A self-expanding device having a first compressed configuration enabling low profile delivery through a delivery device and a second expanded configuration for apposition against a tissue wall,

the self-expanding device comprises at least one polymeric filament formed into a shape having a plurality of peaks and valleys, wherein the shape approximates a repeating diamond-shaped pattern, wherein at least one of the peaks or valleys comprises a loop formed at an end thereof, the loop being formed by winding the at least one polymeric filament, and wherein the self-expanding device is configured to be biodegradable.

2. The self-expanding device according to claim 1, wherein said loop comprises a complete loop, said at least one polymer filament being crimped over 360 ° and less than 720 °.

3. The self-expanding device according to claim 2, wherein each loop comprises an eyelet.

4. The self-expanding device according to claim 1, wherein said at least one polymer filament is at least partially coated with at least one drug eluting layer.

5. The self-expanding device according to claim 4, wherein said drug eluting layer is configured to release an anti-inflammatory agent.

6. The self-expanding device according to claim 1, wherein said shape is formed from a single polymer filament.

7. The self-expanding device according to claim 1, wherein said shape is formed from two discrete polymeric filaments, and wherein each of said two discrete polymeric filaments is formed into a crown shape comprising a plurality of peaks and valleys, and wherein said two discrete polymeric filaments intersect to form a plurality of junctions.

8. The self-expanding device according to claim 7, wherein said two discrete polymeric filaments are bonded together at said plurality of junctions.

9. The self-expanding device according to claim 1, further comprising a plasticizer.

10. The self-expanding device according to claim 1, wherein the device is used in a sinus cavity.

11. The self-expanding device according to claim 1, wherein said shape is formed by winding said at least one polymer filament.