HK1189841B - Preservative-free follicle stimulating hormone solution delivery device - Google Patents

Abstract

A one-time use device to deliver preservative-free follicle stimulating hormone (FSH) solution is disclosed. The device includes a needle covered by a sliding needle shield, which covers the needle in all modes of the device. The device can be placed into a ready-to-use position in four or fewer user steps. The device has a knob for setting a desired dose of FSH. The knob includes longitudinally spaced elements respectively corresponding to the lock position and the seven or fewer discrete dosing positions. The device locks after one use and cannot be reused thereafter.

Description

Preservative-free follicle stimulating hormone solution delivery device

This international application claims priority to U.S. provisional application No. 61/361,319, filed on 7/2/2010, which is incorporated herein by reference in its entirety.

Background

The present invention relates to devices for delivering a follicle stimulating hormone solution, and more particularly to a single-use and variable-dose self-injection device for self-injection of a preservative-free formulation of a follicle stimulating hormone solution.

Follicle stimulating hormone solution (FSH) is used to treat infertility in women by stimulating the development and maturation of one or more follicles (and eggs contained within the follicles). FSH treatment is used when a woman desires conception and has an ovary capable of producing follicles but at physiological levels insufficient for the follicles to mature so that the ovulation required for the desired conception occurs. For assisted fertility techniques (including in vitro fertilization), FSH treatment is also used to stimulate the development of multiple follicles and ova to achieve the desired conception. Follicle stimulating hormone can also treat male infertility by increasing sperm production.

Self-administered treatment of FSH has existed for over a decade. Two well-known approved FSH formulations are EMD Serono, incAnd Merck&Of Co.IncBoth products were approved by the U.S. Food and Drug Administration (FDA) in 1997 and required reconstitution with a diluent prior to injection for lyophilized (or powder) formulations. A typical FSH treatment regimen requires injections once or twice daily for several days. For most patients, it is simply impractical to administer FSH once a day or twice a day. Accordingly, the manufacturing industry has provided pen-type injection devices using liquid FSH formulations, which were approved in 2004 (Gonal-f)Pen sum and follistatFollistim for useA cartridge) that is typically adapted from an insulin injection device for self-administration of a dose of FSH by a patient. However, these devices include several drawbacks that increase the complexity of self-administration of FSH and the possibility of needle-leak or injection anxiety, dosage errors, or lack of compliance.

These pens are difficult to use for the average person. Each of the prior devices requires several steps which, if not performed correctly and in the correct order, may lead to incorrect administration of FSH. The following includes examples of the user steps required for two pen injection devices provided by industry leaders of FSH self-administration therapy.

At present, Gonal-f occupies about 53% of the market share (Europe, North America and Japan), and(also referred to as outside the United states as) Occupying about 47%. The manufacturers of the pens corresponding to these products compete directly with each other, but none has improved the above-mentioned complex steps that exist with these devices. The complexity of self-administered needles has been identified in published articles as a challenge in FSH treatment. Although when it comes toPre-sold pens may offer less complexity than simple needles, syringes and vials, but they still do not fully address the needs of the patient population. One of these pens was a modified pen, originally intended for insulin injection. Therefore, the dose markings on the pen are not clearly related to the dose required for FSH injection and must therefore be interpreted. The dose increments available are quite small and are independent of the usual FSH dose. For example, FollistimThere are 54 dose settings available. This is because the pen is actually a modified insulin pen in which each dose increment corresponds to 1 International Unit (IU) of insulin. Thus, only a very small dose setting (about 10%) of the available doses is utilized. This only increases the likelihood of user confusion and dosage errors.

Current FSH pens are designed as multi-use pens. One commercially available pen is equipped with a specified amount of protein (in IU) which is usually more than the amount required for a single administration. Another commercially available pen needs to be assembled with a multiple use cartridge containing usually more amounts of protein IU than required for a single administration. The advantage of a multi-use pen is that the patient can use the same pen for multiple administrations and subsequent injections with the same pen can reduce part of the complex steps involved. However, one pen or cartridge is not sufficient to complete one treatment cycle, which requires the patient to use at least 2-3 pens or cartridges, and as many as 14 pens or cartridges to complete their treatment cycle. The total number of pens or cartridges used before treatment is unpredictable because the daily dose and the total number of days to complete the course of treatment vary depending on the clinical response of the patient. This often results in waste of residual drug in one or more pens or cartridges or the need to administer 2 separate injections to administer a dose. Thus, the patient must comply with the administration protocol surrounding the available amount of FSH solution for the pen or cartridge prescribed by the patient. The patient must also be responsible for calculating the difference between the total dose contained in the pen or cartridge minus the last dose delivered from the pen or cartridge and the current dose to ensure that the pen or cartridge currently used by the patient has sufficient FSH solution to provide the required dose. For chronic diseases, such as diabetes, this approach may be appropriate because patients have months to years of skill in properly selecting dosages and using pens. However, the current options are too complex for a treatment cycle of 9-14 days to treat infertility in healthy women attempting to conceive.

The complexity of use is not the only problem that has long been unsolved by manufacturers. In general, the use of needles can cause a mental condition known as needle fainting or injection anxiety. Looking at and manipulating the needle alone can cause many patients to experience symptoms of anxiety, or an enhanced physiological response that can lead to nausea, dizziness, and fainting and may cause an enhanced pain response. Furthermore, the need for the patient to manually push down the plunger rod of these pen syringes is an alert to the patient that he/she is injecting himself/herself with medication, which adds to potential anxiety. Some patients do not seek treatment simply due to fear or anxiety of needles and injections. Other patients require their partner to administer the injection. Thus, needle-fainting and injection anxiety can lead to general anxiety and fear, resulting in excessive stress, needle stick accidents, lack of compliance, dizziness or fainting, and the pursuit of treatment.

Furthermore, many pens or cartridges utilize FSH preparations that are intended to be preserved for multiple use. This requires formulations containing preservatives such as benzyl alcohol or m-cresol. However, such side effects may be the pain sensation caused by the injection of preservatives into the patient. This is often described as a scorching sensation, as opposed to pain resulting from a needle stick alone. In addition, benzyl alcohol is associated with significant side effects, such as neonatal jaundice and death.

There is clearly a long felt need to solve the above-mentioned problems that have not been solved by industry leaders. The problems indicated above are not merely separate and independent, but are interwoven, complex and intertwined. The complexity of use is obviously caused by the handling of reusable pens requiring a new needle for each use or the combined handling of reusable FSH cartridges and reusable pens. In addition, needle-sickness or injection anxiety is caused by the need to directly manipulate and fixate the needle of the reusable pen and the need to manually push down the piston rod. However, existing pens do not address the problem of needle fainting because these pens require repeated use and therefore require the attachment and manipulation of a new needle for each use. The prior art pens also fail to address the painful scorching caused by the preservative in the FSH solution, which requires the use of FSH cartridges for multiple treatments. Thus, preservatives must be used in liquid formulations to minimize or prevent bacterial overgrowth of residual liquid in the pen or cartridge.

While all of the above issues raise safety concerns and may reduce the efficacy of FSH treatment, they are also considered as independent solutions in their own right, which further complicates the identification of the problem. The use of a preservative in the FSH solution is considered to be beneficial in one aspect, since the pen or cartridge can be used multiple times. Furthermore, pens are currently provided that are compatible with syringes and cartridges for other medical conditions (e.g., insulin cartridges for diabetes), which reduces costs. Thus, one problem reinforces or leads to another problem, but is valuable in addressing some aspects of the individual problems. Some of these problems are considered to reduce costs, but when safety issues arise, the harm to the patient and the general society that bear these costs is also enhanced.

Therefore, identification of problematic issues of FSH self-administration is complicated in that all currently practiced solutions are considered solutions to their own other problems. Therefore, the industry tends to adhere to these solutions. It would be beneficial to have a device that could address these problems without detracting from the advantages of the prior art pens. Embodiments of the present invention address these matters, and others.

Summary of The Invention

One embodiment of the present invention provides a single-use, automatic injection device for self-delivery of a follicle stimulating hormone solution. The apparatus includes an elongated main housing having a distal portion and a proximal portion disposed along a longitudinal axis. The elongate rotary member is connected to the proximal portion of the main housing and is rotatable relative to the main housing about a longitudinal axis. A knob extends from a proximal portion of the housing and is rotatable relative to the main housing between a locked position and seven or fewer independent dose positions for setting a variable dose delivery of Follicle Stimulating Hormone (FSH) solution. The knob has longitudinally spaced elements corresponding to a locking position and seven or fewer independent dose positions, respectively. The piston rod is rotatably engaged with a portion of the rotational member and longitudinally spring biased. The piston rod is rotationally locked to the knob in a locked position on the member corresponding to the locked position. The piston rod is movable in increments along the longitudinal axis between an element corresponding to the locking position and one of seven or fewer individual dose positions. A permanently encased needle assembly has a permanently attached needle. The needle has an inner end and a working end. The cartridge holder is connected near the needle assembly. The cartridge holder contains an elongate cartridge containing a FSH solution. The FSH solution is sterile and preservative free, allowing only a single use of the device. The cartridge is permanently enclosed in a cartridge holder and has a pierceable membrane or disc (referred to in ISO11608-3: 2000) adjacent the inner end of the needle and a movable piston distal to and adjacent the piston rod. When the knob is in the locked position, the cartridge is not fluidly connected to the inner end of the needle. The needle shield is slidable relative to the main housing along a longitudinal axis between a covering position distal to the working end of the needle and an injection position proximal to the working end of the needle. The needle shield is spring biased to normally be in the covering position and is opaque so as to substantially prevent a user from viewing the working end of the needle in the covering position. The needle shield has a cam or follower which is rotatably and longitudinally connected with a further cam or follower of the rotor during the compression stroke of the needle shield from the covering position to the injection position. A removable cap is located distal to the needle shield tip to cover the working end of the needle contained within the needle assembly. The needle assembly or cartridge may be moved along the longitudinal axis to a ready position by engagement with the cap or piston rod respectively, with the inner end of the needle piercing the membrane and being in fluid connection with the cartridge, thereby preparing the needle for the FSH solution. During the compression stroke, the needle shield is moved to the injection position and the rotational member is rotated, thereby rotatably engaging the piston rod and causing the piston rod to move to one of seven or fewer individual dose positions and compressing the movable piston to automatically inject or deliver a corresponding individual dose of FSH solution from the working end of the needle. The device-specific user steps required to place the unpackaged device from the locked state into a ready-to-use state are four steps or less.

In one aspect of the device, the knob is rotatable relative to the main housing between a locked position and a ready position.

In another aspect of the device, the knob includes longitudinally spaced priming elements corresponding to the priming position, the priming elements being located between the locking position and seven or fewer individual dose positions.

In another aspect of the device, rotating the knob to or past the priming position rotates the piston rod from the locked position and incrementally moves the piston rod along the longitudinal axis between the element corresponding to the locked position and the priming element.

In another aspect of the device, the piston rod is moved incrementally along the longitudinal axis, thereby moving the cartridge into the needle assembly and causing the membrane to be pierced by the inner end of the needle and priming the needle with the FSH solution.

In another aspect of the device, the user steps required to place the unpackaged device from the locked state into a ready-to-use state consist of: priming the needle with the FSH solution by rotating the knob from the locked position through the ready position to one of seven or fewer individual dose positions, and removing the needle cap.

In another aspect of the device, moving the main housing distally relative to the needle shield held against the relatively fixed tissue results in a compression stroke and auto-injection of the FSH solution.

In another aspect of the device, the turn piece knob is marked with visible independent positions indicating seven or fewer independent dose positions.

In another aspect of the device, the ready position is not marked on the knob.

In another aspect of the device, the needle assembly includes a hub connected to the needle, the hub being in threaded engagement with the cartridge holder member of the needle assembly.

In another aspect of the device, a removable cap is rotatably engaged with the cartridge holder member, rotation of the removable cap enabling disengagement of the removable cap from the device and also enabling proximal movement of the hub relative to the cartridge holder member and thus causing the membrane to be pierced by the inner end of the needle, priming the needle with the FSH solution.

In another aspect of the device, the user steps required to place the unpackaged device from the locked state into a ready-to-use state consist of: priming the needle with the FSH solution by removing the needle cap, and rotating the knob from the locked position to one of seven or fewer individual dose positions.

In another aspect of the device, the needle shield comprises a locking element that is capable of locking the rotational member or the main housing during a decompression stroke of the needle shield from the injection position to the recovery position to recover the working end of the needle, and the needle shield is not movable relative to the main housing after moving to the recovery position.

In another aspect of the device, the piston rod contacts one of the elements of seven or fewer individual dose positions with sufficient force to cause the user to hear a click sound

In another aspect of the device, the cartridge has a volume of 1.5 ml.

In another aspect of the device, the piston rod is configured to deliver a maximum dose of FSH solution within five seconds after the needle shield is placed in the injection position.

In another aspect of the device, the FSH solution is free of preservatives such as benzyl alcohol or m-cresol.

In another aspect of the device, the needle shield completely obstructs the view of the working end of the needle to the user during the entire injection from when the needle shield is in the covering position to before and after the occurrence of the compression stroke, with the distal end of the needle shield abutting against the tissue of the user.

These and other embodiments of the present invention are described in more detail below, which provide exemplary implementations of various embodiments and aspects disclosed herein.

Brief description of the drawings

Fig. 1A is a perspective view of a FSH delivery device according to an embodiment of the present invention.

FIG. 1B shows an exploded view of the device of FIG. 1A.

Fig. 2A is a perspective view of the tubular housing of the device of fig. 1A.

Fig. 2B is a perspective view of a piston rod assembly of the device of fig. 1A.

Fig. 2C is a perspective view of a rotating member of the device of fig. 1A.

Fig. 2D and 2E are perspective views of the actuator of the device of fig. 1A.

Fig. 2F is a perspective detail view of the medicament container holder of the device of fig. 1A.

Fig. 2G is a perspective detail view of the device of fig. 1A in a locked state.

Fig. 3A and 3B are side and cross-sectional views, respectively, of a dose knob assembly of the device of fig. 1A.

Fig. 4A and 4B are exploded and distal perspective views of the cap/priming assembly of the device of fig. 1A.

Fig. 5 is a cross-sectional view of the cap/priming assembly of fig. 4A.

Fig. 6A-6C are cross-sectional side views of the cap/priming assembly of fig. 4A at various stages of operation.

Fig. 7A and 7B are perspective views of the dose knob of fig. 3A in locked and unlocked states, respectively.

Fig. 8A-8C illustrate the drug delivery device in perspective views in different modes of operation.

Fig. 9A shows a side view and a cross-sectional view of a FSH delivery device according to an embodiment of the present invention.

Fig. 9B and 9C are perspective views of a dose setting assembly for use with the device of fig. 1A and 9A.

Fig. 10A and 10B are different side views of a tubular FSH delivery device according to an embodiment of the present invention.

Fig. 10C is a side view of the FSH delivery device of fig. 10A in an operational mode.

Fig. 10D and 10E are distal and proximal end views, respectively, of the FSH delivery device of fig. 10A.

Fig. 10F is a perspective view of the FSH delivery device of fig. 10A in an operational mode.

Fig. 11A and 11B are different side views of a rectangular FSH delivery device according to an embodiment of the present invention.

Fig. 11C is a side view of the FSH delivery device of fig. 11A in an operational mode.

Fig. 11D and 11E are distal and proximal end views, respectively, of the FSH delivery device of fig. 11A.

Fig. 11F is a perspective view of the FSH delivery device of fig. 11A in an operational mode.

Detailed Description

Embodiments of the present invention address the deficiencies of the prior art by providing an easy to use self-injection device for which the number of device-specific user steps required to place an unpackaged FSH solution delivery device from a locked state (unpackaged state) into a ready-to-use state is four steps or less, or in some embodiments, consists of only two or three steps. Furthermore, the total number of steps required to fully use the device is only nine steps, including discarding. Exemplary steps are as follows:

this list of user steps indicates that the device disclosed herein is far less complex to use than the prior art pens described above. The device solves the problem of convenience of use caused by prior art pens due to the relatively low complexity of use of the device. Here, the device can be used in nine easily followed steps, which is in contrast to the approximately 30 steps required for prior art pens.

Further, after unpacking of the device, it can be set to a ready-to-use state in four or fewer steps, or in some embodiments, in only two steps. It should be understood that these steps involve mechanical input by the user to a setting member (e.g., knob) on the device and/or user removal of a component (e.g., tip cover) to change the device from a safe, unusable setting (e.g., non-movable, locked, and unprepared) to a ready-to-use setting (e.g., movable, unlocked, and ready). In contrast to prior art pens, it is most obvious that there is no need to manipulate or even look at the needle to load the cartridge, and no need to manually push the piston rod, as these steps are all removed from the delivery device disclosed herein.

The device disclosed herein is a single use FSH delivery device which provides a preservative-free FSH solution formulation and thus prevents any potential side effects of the preservative. Preservatives added to available FSH preparations are not part of the active pharmaceutical ingredient and are added to the preparation to minimize bacterial growth and enable the product to be sold as a multiple use device. However, benzyl alcohol and m-cresol are both associated with injection pain. Also, more dangerous side effects such as kernal jaundice and neonatal death are reported for benzyl alcohol. The field of infertility also contemplates that FSH preparations used in the device have a preservative, as devices used only for FSH are multiple use devices. Thus, such a single-use device with a preservative-free formulation is outside the normal model established by the industry, as the FSH solution is sterile before use, whereas the device is unusable after a single use.

During use of the device, there is no need for the user to manipulate or directly look at the needle that injects the FSH solution. Before use, the opaque needle shield completely obstructs the view of the needle when viewed from the side of the device, and during use, when the shield is moved into the main housing of the device, the needle is moved into the skin for injection. From the outside, all that can be seen is the cylinder that is pressed against the user. This arrangement can prevent or significantly reduce the occurrence of needle fainting by preventing the user from viewing the needle, and also prevents the public from viewing the needle. This arrangement requires the use of pre-assembled and single-use devices, since no patient manipulation and fixation of the needle is necessary to achieve this feature. Furthermore, this goes beyond the normal mode established by the industry, which calls for reusable devices, which necessarily accompany needle manipulation.

During use of the device, the patient is not required to manually push the piston rod to self-inject the drug. The "auto-injection" part of the device causes the FSH solution to be automatically injected into the skin of the patient when the patient presses the device far enough against the skin to activate the "auto-injection" part. This feature helps prevent or reduce injection anxiety because the patient does not have to worry about they not injecting the entire drug because they do not push the piston rod downward enough. This feature can also help remove the feeling of direct injection due to the user's continued physical input to the device and injection of FSH solution (which can increase anxiety) by removing the user's control over the injection rate of delivery.

Typically, self-injection by non-medical personnel (e.g., a treatment recipient user of the device) also results in a relatively long injection procedure, as untrained individuals are likely to spend time ensuring that the injection is properly completed, however, to the extent that it is often of excessive concern and unnecessary. Together, the patient may be more concerned about the injection, which may cause more discomfort or anxiety to the patient. With this device, the needle is not visible and the user is primarily concerned only with compressing the spring-loaded telescopic tube against his skin, with the injection taking place from the secondary mechanical drive initiated by the compression movement. The rate of injection is determined by the mechanical release or transfer of stored energy (such as the release of a spring) rather than by the continuous input to the syringe by the user. Therefore, in many cases, the sensation of direct injection of FSH solution can be alleviated.

The preservative-free FSH solution is provided in a 1.5ml cartridge that is specifically used with the device, and the cartridge is permanently enclosed within the device, which reduces the number of assembly steps required for the patient. The device also becomes permanently locked after one use, thereby preventing any intention to reuse the preservative-free FSH solution.

The device may be adapted for use with different maximum drug delivery rates representing the most commonly used initial dose of FSH based on extensive review of medical records in the united states and europe. Settings on each device of up to 6 less than the maximum dose are also selected to approximately align with the dose that the physician would use when reducing from the initial higher dose. The intended use of the device is that the patient will use only one device per injection and in most cases will inject the full dose of FSH solution present in the device (i.e. the maximum setting).

Typically, up to 6 settings less than the maximum dose (i.e., an available dose below the maximum setting) are included on the device so that when the patient's physician chooses to reduce the dose, the patient can use the available and held devices at the same time (e.g., on the same day). Thus, the adjustability of the device eliminates the need to purchase a new device as the prescription changes. At a later time, a relatively lower maximum dose of the device (i.e., lower than the initial dose of the intended treatment regimen) may be used, enabling the patient to use a reduced dose of the device. For example, the user may have a device with a maximum available dose of 225IU FSH solution, and the user's physician can change the dose prescription to 150IU FSH solution. Thus, the user may set the device to reduce the delivered dose and achieve a simultaneous dose change. The next day, the user may obtain a device with a maximum available dose of 150IU FSH solution.

The use of different maximum doses of the device provides the patient with the advantage that at lower doses the medicament is less costly and less likely to waste unused medicament. It will be appreciated that the cost of FSH solutions currently accounts for almost 100% of the consumer/retail cost of all available FSH delivery devices. The application of a variable maximum dose allows the device to require only 7 or fewer dose settings, in contrast to the many dose settings required by prior art pens. These dosage options simplify dose setting and facilitate ease of use, as the user in almost all cases only needs to set the device to the maximum dose setting.

The user sets the dose of the device by turning an adjustable knob having seven or fewer positions, corresponding to seven or fewer doses respectively. The dose is a usual dose of FSH, preset with a designated simple marker (e.g., 1, 2, 3, 4, 5, 6, etc.) without requiring interpretation, correlation or calculation by the user. There are no useless dose levels present since the device is intended for FSH delivery only, as may be present with prior art pens modified from the non-FSH industry. This greatly reduces user confusion by simplifying the complexity of setting dose levels. Thus, the user need only simply set the dial and use the device.

As indicated above, the user does not yet have to insert a new FSH cartridge to use the device. By using a custom made preservative-free FSH cartridge of 1.5ml size, the device is not limited to the usual "off-the-shelf" volume of a preservative-containing FSH formulation. The customized device may be adapted for the most commonly prescribed dosage for treating infertility. This ultimately reduces user steps by avoiding the need to reload the device and can thus provide an easy to follow dosage regimen as the device can be simply set up, used and discarded. These advantages are demonstrated by the preservative-free FSH solution contained within the permanently encased cartridge (which prevents reuse of the device).

Combining all these features allows the device to have higher efficacy than prior art pens and results in a more successful FSH treatment. The single use device is in contrast to industry standard reusable pens that reuse the device and cartridge. However, the inability to anticipate the total dose required for a given treatment cycle and the lesser available doses of the existing pens and cartridges makes it almost impossible to avoid wasting medication, which increases the cost of the treatment because unused medication cannot be returned to the pharmacy. The present invention reduces costs as a whole by improving use efficiency, reducing dosage errors and minimizing drug waste.

Accordingly, embodiments of the present invention fully solve the problems with the prior art by providing a relatively easy to use device with fewer required steps. It should be understood that FSH in the following disclosure is intended to refer to sterile and preservative-free FSH solutions. A preservative-free FSH solution is a solution that, if not under sterile conditions, will support the growth of microorganisms sufficient to render the pharmaceutical product dangerous for human use. The preservative-free solution is free of pharmaceutically acceptable antimicrobial agents suitable for injection into humans, such as benzyl alcohol or m-cresol. Preservative-free FSH solutions fail the standard antimicrobial efficacy Test of the pharmaceutical industry (antimicrobial efficacy Test), also known as the Preservative Challenge Method described in the united states pharmacopeia <51>, which demonstrates the antimicrobial efficacy of Preservative systems. Acceptable criteria for antimicrobial efficacy are described in detail in USP <51>, but in general, formulations without antimicrobial preservatives fail the test, and in particular, fail to exhibit an exponential decrease in bacterial count from the initial level of 1 to 3, or an increase in yeast and mold counts within one to two weeks.

FSH is commercially available. The typical concentration delivered by the injection pen is 600 to 833IU per ml of solution. The available doses for one commercial product are 300IU, 450IU and 900 IU. The available doses for another commercial product are 150IU, 300IU, 600IU and 900 IU. The usual dose per injection is 75IU to 225IU for one of the female infertility indications and 150 to 450IU for the other, with some doses being within or between the above ranges for each indication. Thus, the available dose settings for any one commercial product are not tailored for effective use in infertility treatment.

The device generally comprises a tubular main housing that is elongated along a longitudinal axis. The main housing is the portion of the patient that is grasped during use of the device. A tubular needle shield extends from the distal end of the main housing. The needle shield retracts into the main housing and is spring-loaded to assume a covered state extending over the needle. In some embodiments, the needle shield is locked in the extended state until the dose knob is turned to select a dose, at which point the needle is primed and the needle shield is unlocked. A removable cap is located at the distal end of the needle shield. Once the cap is removed and the needle shield is unlocked by selecting a dose, the needle shield can be retracted into the main housing by a compression stroke, thereby assuming an injection condition allowing the needle to penetrate the skin. The needle shield is opaque and substantially obstructs a user's view of the needle in the covered state and the injection state during use. Once the compression stroke is completed and the device and needle are withdrawn from the skin, the needle shield assumes an extended state and locks in place so that the device and disposable cartridge cannot be reused. This also prevents accidental needle stick events because the used needle is again covered by the needle shield. The main housing and the needle shield together present an elongated tube. A removable cap is located at the distal end of the needle shield.

A knob extends from the proximal end of the main housing. The knob may be rotated from an initial locked position to a number of separate dose settings of sterile and preservative-free FSH solution, typically seven or less. The knob is visually marked with a rotational indicator relative to the main housing for seven or fewer doses and, in some embodiments, ready/unlocked positions. An elongated inner portion of the knob extends into the main housing and is locked with the needle shield in the locked position. Rotating the knob from the locked position unlocks the needle shield. The inner portion of the knob is also connected to the rotor and the piston rod. The inner portion includes longitudinally spaced elements corresponding to a plurality of dose settings. The element interfaces with the piston rod and limits the maximum proximal to distal movement of the piston rod.

The rotatable member is an elongated tube that is rotatable within the main housing. The rotational member is rotatably and linearly engaged with the needle shield by a cam or follower arrangement. The rotor is also rotatably engaged with the piston rod. The rotational member can be rotated by a cam or follower arrangement and linear movement of the needle shield. This in turn causes the piston rod to rotate during the compression stroke of the needle shield.

The piston rod is located within the main housing and is slidable along the longitudinal axis. The piston rod includes corresponding elements that interface with longitudinally spaced elements of the interior portion of the knob. The piston rod is movable in incremental distal movement corresponding to one of the dose positions, and in some embodiments, movable to a ready position corresponding between a locked position and the dose position.

The needle assembly is permanently encased within the distal region of the main housing. The needle assembly includes a permanently attached needle having an interior end and a working end. The user cannot remove or replace the needle assembly and needle without destroying the device. The working end extends beyond the distal end of the main housing and is configured to penetrate tissue and deliver an FSH solution. The working end of the needle is typically enclosed by a needle shield. When the needle shield is in a proximal-most position relative to the main housing, i.e. in case of a compression stroke, the working end of the needle will extend beyond the needle shield. The needle shield is not transparent, thereby obstructing the user from viewing the needle in the covered position.

The cartridge assembly is disposed proximal to the needle assembly. The cartridge assembly permanently encloses a cartridge containing a sterile and preservative-free FSH solution. Since the solution is preservative-free, it can only be used safely once and cannot be stored for re-use. After injection with the device, the needle shield assumes an extended position and is locked in place so that the device and the single use cartridge cannot be used again. The inner end of the needle is adjacent to the distal pierceable membrane of the cartridge. The inner end of the needle is not in fluid connection with the cartridge in the initially locked position of the needle shield. A movable piston is located at the proximal end of the cartridge and is arranged to be connected to and moved by the piston rod. In some embodiments, the cartridge is slidably disposed within the cartridge assembly.

The piston rod is initially locked in a proximal-most position by interfacing with the locking element of the knob. In this position, the compressed piston rod spring maintains tension on the piston rod, which when released, results in distal actuation of the piston rod. The piston rod can be disengaged from the locking element by rotation, either by the needle shield through the rotation member or by the knob.

For the latter embodiment, i.e. the piston rod can be disengaged by the knob, rotating the knob to the unlocked position or directly to the dose position causes the piston rod to disengage from the locking element and to be moved incrementally in the distal direction by the piston rod spring, stopping at the priming element of the knob. This action prepares the needle by moving the piston rod distally to move the cartridge into the needle assembly. Thus, the membrane is pushed in and pierced by the inner end of the needle, thereby bringing the needle into fluid connection with the FSH solution. The piston rod also incrementally pushes the movable seal distally a distance only long enough to prime the needle and empty it of any air therein. For ease of use, the knob need not be marked with a ready position, as ready can be made by rotating the knob directly to one of seven or fewer individual dose positions, which removes another required step for the user.

With the former embodiment, i.e. the piston rod is disengaged by the needle shield, the needle assembly may be actuated by the cap, and when the cap is unscrewed from the needle shield, the needle assembly is rotated and moved proximally by the thread arrangement. This movement causes the inner end of the needle to be driven towards and pierce the cartridge membrane and thus prime the needle as described above. For this embodiment, movement of the knob does not prime the needle, but only sets the maximum stroke of the piston rod, i.e. the required dose.

During use, the user rotates the knob to the unlocked/ready position or directly to the desired dose to set the maximum travel distance of the piston rod and thus limit the deliverable dose of FSH solution. The user also removes the cap. Through these steps, the device is in a ready-to-use state. The needle can be prepared by the embodiments indicated above. In both embodiments, the device can be placed in a ready-to-use state in four or fewer user steps.

The user may then place the distal end of the needle shield against the tissue. The main housing is then driven in a distal direction, toward the relatively stationary needle shield and tissue, during the compression stroke. This places the needle shield in a proximal-most position relative to the main housing. The working end of the needle penetrates the tissue at this location. The needle is not visible because the distal end of the opaque needle shield always remains against the tissue. When the needle shield is at or near its proximal-most position, the needle shield rotates the rotational member, which correspondingly rotates the plunger rod and releases the plunger rod from the locking element of the knob. The piston rod is then released and driven distally by the piston rod spring until the piston rod stops at one of seven or fewer elements of the knob corresponding to each dosage level. The FSH solution is then automatically delivered to the tissue in a short period of time (typically less than five seconds). In some embodiments, a click may be heard when the piston rod is released, which signals the start of the injection. In some embodiments, the user may hear a second audible click when the piston rod is in contact with one of the seven or fewer elements of the knob, which may provide an audible indication that the FSH solution has been completely infused into the tissue.

After the FSH solution is administered, the user pulls the device out of the tissue, which causes the main housing to move in a proximal direction via the spring bias during the decompression stroke. The needle shield blocks the view of the needle during the decompression stroke until the needle shield is fully extended. When fully extended, the shield can interface with the rotor, the main housing, or a portion of the rotor, permanently re-locking the shield in place in the covering position. Thus, the disposable device cannot be reused after the decompression stroke.

Exemplary configurations of FSH delivery devices

Fig. 1A is a perspective view of an intact FSH delivery device 100 according to an embodiment of the present invention, and also illustrates a simplified and exploded perspective view of the FSH injection device 100. An initial, unactuated state of the pre-assembled FSH injection device 100 is shown in fig. 1A, the FSH injection device 100 having an outer cap 410 mounted thereon. The device 100 comprises a tubular housing 110, an intermediate longitudinal member 119 (see fig. 1B) and a distal annular contact member 121, the tubular housing 110 having a distal end 111 and an opposite proximal end 112, a needle shield 120 being slidably and coaxially arranged within the tubular housing 110. A first spring 117 (see fig. 1B) is arranged at the distal end of the needle shield 120 between the annular ridge 202 (see fig. 2A) of the tubular housing 110 and the annular ridge 235 (see fig. 2B) of the intermediate longitudinal member 119 for moving the needle shield in the distal direction.

The FSH delivery device 100 comprises a FSH cartridge holder 150 coaxially arranged within the needle shield 120 and fixedly connected to the tubular housing 110 by means of a radially extending portion 234 (see fig. 2F), which radially extending portion 234 protrudes through a corresponding opening 113 (see fig. 1A) in the tubular housing 110. The FSH cartridge 130 is arranged within a FSH cartridge holder 150 (see fig. 1B). The FSH cartridge comprises movable/slidable stoppers 131, 132 (see fig. 1A). The FSH cartridge 130 comprises a membrane 133, which membrane 133 is pierceable by a needle. The dimensions of the FSH cartridge 130 are set according to the specifications in ISO11608-3:2000 for a 1.5ml type a cartridge.

Referring to fig. 1B, a rotor 118 is shown, the rotor 118 having a groove, contour or follower on its inner surface and an external protrusion on its outer surface. A piston rod 116 and a second spring 115 are arranged within the piston rod and the piston rod support member 114. A knob 160 is provided at the proximal end of the tubular housing 110 for activating the FSH delivery device 100, i.e. for unlocking and dose setting the FSH delivery device. Knob 160 may be rotatable about a longitudinal axis extending from the proximal end to the distal end of FSH delivery device 100. The knob 160 includes seven or fewer incremental positions for setting seven or fewer FSH delivery doses, respectively. The knob 160 includes indicia that visually clearly indicate these doses. The turn piece 118 is rotatably disposed between the cartridge holder 150 and the knob 160. The FSH delivery device 100 further includes a distally located needle assembly 140 (see fig. 1A).

Fig. 2A shows a perspective detail view of tubular housing 110, tubular housing 110 having a corresponding opening 113 for receiving a radial extension 234 (see fig. 2F), radial extension 234 being used for fixedly connecting FSH cartridge holder 150 to tubular housing 110. Fig. 2A also shows a second opening 201, the second opening 201 enabling the user to view the cartridge and FSH solution, thereby ensuring that glass breakage does not occur and that a clear, particle-free solution is available for safe injection. The tubular housing 110 has an annular rib 202 for supporting the first spring 117 in a pre-tensioned state between the tubular housing 110 and the intermediate longitudinal member 119 (see fig. 1B).

Fig. 2B shows the piston rod support member 114, the second spring 115 and the piston rod 116 assembled and in an untensioned state. The outer radial surface of the piston rod 116 includes a protrusion 235, the protrusion 235 being adapted to cooperate with an internal ridge 236 (see fig. 3B) of the knob 160 to maintain the piston rod 116 in a pre-tensioned, non-activated state.

Fig. 2C shows a perspective detail view of the rotary member 118. The rotor 118 has at least one groove 210, 211, 212 on its outer surface arranged such that a radially inwardly extending protrusion 222 (see fig. 2E) of the intermediate longitudinal member 119 is adapted to be guided within the at least one groove, contour or follower 210, 211, 212, such that the rotor 118 is caused to rotate when the intermediate longitudinal member 119 is axially displaced due to axial displacement of the interconnected needle shields 120. A resilient tongue 213 is provided on the turn piece 118 and is connected in an alternating manner to the intermediate longitudinal member 119 and thus to the needle shield 120. The resilient tongue 213 is arranged to lock the second protrusion, e.g. the radially inwardly extending protrusion 222 of the intermediate longitudinal member 119, when the needle shield 120 has been fully extended in the distal direction.

Fig. 2C also shows a radially inwardly extending protrusion 216 on the inner surface of the rotational member 118, the protrusion 216 being configured to lock against a radially outwardly extending resilient protrusion 203 on the proximal end of the piston rod 116 (see fig. 2B) when the piston rod 116 passes inside the rotational member 118 (i.e., when the piston rod 116 is moved in a distal direction). Fig. 2C also shows the inner ribs and grooves 215 of the rotary member 118 in a cross-sectional perspective view.

A protrusion 235 (see fig. 2B) of the piston rod 116 is releasably connected to a groove 215 (see fig. 2C) of the turning member 118 for keeping the piston rod 116 (see fig. 2B) and the second spring 115 in a pre-tensioned state, such that when the needle shield 120 is pressed towards the delivery site, the turning member 118 is turned, whereby said protrusion 235 is released from the groove 215 of the turning member 118 and the piston rod is driven distally by the force of the second spring 115, such that the piston rod 116 exerts a pressure on the slidable piston 131, thereby expelling FSH through the needle assembly 140.

A variable dose tubular member (not shown) is fixedly connected to the knob 160 and is rotatably arranged relative to the rotational member 118. The variable dose tubular member comprises seven or less longitudinally spaced elements shaped as a stepped pimple. The piston rod 116 includes a mating protrusion on its outer surface for abutting against the at least one rib. When the knob 160 is further manually operated to select a preset dose, the variable dose tubular member is also rotated such that the distance between the protrusion 235 (see fig. 2B) of the piston rod 116 and the stepped ledge on the inner surface of the variable dose member determines the size of the dose to be delivered. When the needle shield 120 is pressed towards the delivery site, the rotational member 118 is rotated such that the mating protrusion of the piston rod 116 is released from the groove 215 (see fig. 2C) of the rotational member 118 and the piston rod 116 is driven distally by the force of the second spring 115 (see fig. 2B) such that the piston rod 116 exerts a pressure on the slidable pistons 131, 132 causing the set dose of FSH to be expelled through the needle assembly 140 until the protrusion 235 of the piston rod 116 abuts the stepped ledge on the inner surface of the variable dose member. Other exemplary dose setting mechanisms that may be used with the present invention are described in U.S. patent No. 7,597,685, which is incorporated herein in its entirety for all purposes.

Fig. 2D illustrates the needle shield 120 in a perspective view. The needle shield 120 comprises a recess or opening 224, the recess or opening 224 being arranged to receive a corresponding protrusion 223 of the intermediate longitudinal member 119 for fixedly connecting the intermediate longitudinal member 119 to the needle shield 120. The needle shield 120 further comprises an annular contact member 121, the annular contact member 121 being arranged for pressing against the skin of the patient.

Fig. 2E is a perspective view of the intermediate longitudinal member 119. The intermediate longitudinal member 119 comprises a protrusion 221 adapted to cooperate with a protrusion 301 (see fig. 3A) of the knob 160 for keeping the piston rod 116 and the first spring 117 in a pre-tensioned state. The projections 221 are located on the proximal annular wall of the intermediate longitudinal member 119, while the corresponding projections 301 are radially inwardly extending projections.

Fig. 2F is a perspective detail view of FSH cartridge holder 150 showing opening 233. There may be a corresponding opening 233 (not shown) on the other side of the FSH cartridge holder 150. FSH cartridge holder 150 further comprises a radially extending portion 234 for fixedly connecting FSH cartridge holder 150 to tubular housing 110 through a corresponding opening 113 (see fig. 2A). The FSH cartridge holder 150 has an opening 233, the opening 233 being for mating with a corresponding part of a needle assembly (see fig. 4A) and the FSH cartridge holder 150, and the FSH cartridge holder 150 further has a predetermined profile 231, 232 for being fixed in a corresponding profile of the intermediate longitudinal member 119.

Fig. 2G shows the first spring 117 in a perspective view, the first spring 117 being reciprocally connected in a pre-tensioned state to the annular protrusion 202 of the tubular housing 110 and to the corresponding protrusion 225 of the intermediate longitudinal member 119.

Fig. 3A shows a side view of the knob 160. The knob 160 has resilient tongues 302 for connecting the knob 160 to corresponding grooves in the distal end of the tubular housing 110. The knob 160 further comprises a protrusion 301 for interactively connecting the knob 160 to a corresponding protrusion 221 of the intermediate longitudinal member 119 (see fig. 2E).

Fig. 3B is a cross-sectional perspective view of the knob 160 showing the groove as a rib 236, the rib 236 being configured to mate with a corresponding protrusion 235 (see fig. 2B) of the piston rod 116 to maintain the piston rod 116 assembly in a pre-tensioned state.

Exemplary self-contained needle assemblies

Fig. 4A shows a perspective view of the needle assembly 140. The retention member 430 is fixedly connected to the FSH cartridge holder 150. The hub 421 holds a needle having a working end 424 and an inner end 425. The hub includes threads 423, the threads 423 adapted to interactively connect to corresponding threads 431 of the retention member 430. The inner cap 416 (see fig. 4B) is interactively connected to the hub 421 and the retention member 430. The outer cap 410 is arranged coaxially with the inner cap 416, wherein said outer cap 410 is rotatable relative to said inner cap 416 when the piston rod 116 and the first spring 117 are in a pre-tensioned state. The cap interlock member 413 is axially slidable, but rotationally locked to the inner cap 416, and is disposed against the annular contact member 121 (see fig. 1A). Cap interlock member 413 is also arranged to interact with outer cap 410 when actuator piston rod 116 and first spring 117 are released from their pre-tensioned state.

The hub 421 also includes a radial recess 422 at the distal end of the hub 421. The radial recesses 422 are interactively connected to corresponding radially inward extensions 415 of the inner cap 416 (see fig. 4B). The hub 421 is coaxially movable within the retention member 430. When the hub 421 is moved in a proximal direction, the inner end 425 will pierce the membrane 133 (see fig. 1A). Cap interlock member 413 is a middle annular member having tabs adapted to engage corresponding annular tabs 417 on the inner sleeve of outer cap 410 to enable rotation of outer cap 410.

Fig. 4B is a perspective view of outer cap 410 viewed from the proximal end of outer cap 410. The outer cap 410 comprises one or more radially outwardly extending torsion members 411 on its outer surface, the torsion members 411 being provided for enabling a user to conveniently and easily grip the outer cap 410 when closing the outer cap 410. Alternatively, a smaller inward recess may be provided in outer cap 410 to facilitate gripping or to provide an increased cross-sectional diameter for the portion of outer cap 410 disposed distally of needle shield 120 when cap 410 is attached to FSH delivery device 100. Also visible in fig. 4B is an inner cap 416 having internal threads 414, the internal threads 414 being interactively connected to corresponding internal threads 432 of the retention member 430 (see fig. 4A). Internal threads 414 are provided on the inner surface of the outer sleeve of the cylindrical inner cap 416. It should be noted, however, that the threads 414, 432 between the inside of the inner cap 416 and the outer surface of the retention member 430 and the threads 423, 431 between the hub 421 and the inner surface of the retention member 431 have different helical directions.

Subsequently, when the user starts to turn the outer cap 410, with the outer cap 410 engaged with the inner cap by the cap interlock means, the hub 421 is screwed into the retention means 430 so that the inner end 425 of the injection needle pierces the membrane 133 of the FSH cartridge 130 and, due to the different screwing directions, the inner cap 416 is unscrewed and the outer and inner caps can be removed. The hub 421 may apply sufficient force to the FSH cartridge 130 to prime the needle with the FSH solution during removal of the cap. Preferably, the pitch of the threads is selected so that the hub 421 moves longitudinally primarily in the proximal direction, but with a small angle of rotation, so as to prevent the needle's inner end 425 from turning into or "digging into" the membrane 133 as much as possible. Also, preferably, the pitch of the threads between the outer cap 410 and the retention member 430 is selected such that the user need only rotate the outer cap 410 about one-half turn to operate, so as to avoid the need to change grip positions in order to complete the operation.

Further illustrated in fig. 4B is cap interlock member 413 for locking outer cap 410 with inner cap 416. When the cap interlock member 413 is in its unlocked position, the outer cap 410 may be rotated relative to the inner cap, i.e., it is not possible to remove the outer cap 410. Thus, when the cap interlock member 413 is in its unlocked position, the FSH delivery device 100 cannot be used. When the knob 160 is turned, the protrusion 221 on the outer annular wall of the middle longitudinal member 192 is released from the mating protrusion 301 of the knob 160 (see fig. 7A and 7B) and the needle shield 120 is forced to move in a distal direction by the force exerted by the first spring 117, so that the annular contact member 121 in contact with the cap interlock member 413 pushes the cap interlock member 413 distally, so that the outer cap is locked with the inner cap, which is the locked position of the cap interlock member 413 (see fig. 6A to 6C). The device 100 can also utilize a needle preparation mechanism as shown in International publication WO/2009/150078A1, which is incorporated by reference herein in its entirety for all purposes.

Exemplary operating modes:

preparation by removal of the cap:

fig. 5 is a cross-sectional perspective view of the delivery assembly showing the retention member 430 fixedly connected to the FSH cartridge holder 150, the outer cap 410, the inner cap 416 and the hub 421.

Fig. 6A illustrates a cross-sectional side view of the outer cap 410 and retention member 430 assembly in an initial mode, wherein the cap interlock member 413 is in an unlocked position.

Fig. 6B shows the same cross-sectional side view of the outer cap 410 and retention member 430 assembly, wherein the cap interlock member 413 is pushed axially in the proximal direction by the needle shield 120 to the locked position.

Fig. 6C again illustrates the same cross-sectional side view of the outer cap 410 and retention member 430 assembly in a ready mode, wherein the cap interlock member 413 is still in the locked position and the outer cap 410 is removed, causing the hub 421 to move axially in a proximal direction, pushing the needle distal end 425 to pierce the membrane 133 of the FSH cartridge 130 and ready the needle.

Unlocking the needle shield:

fig. 7A is a perspective view of the knob 160 in an initial non-activated state, the knob 160 being interactively connected to the intermediate longitudinal member 119. In the initial state, the protrusion of the intermediate longitudinal member 119 engages with the corresponding protrusion of the knob 160.

Fig. 7B is a perspective view of the knob 160 in a second activated state, the knob 160 being interactively connected to the intermediate longitudinal member 119. The knob 160 has been rotated to unlock the device. The knob 160 may include visual indicia and/or indentations that indicate to the user that the device has been unlocked. The unlocking means may also occur by rotating the knob 160, which knob 160 may be rotated directly to the dose setting described herein. In the unlocked state, the protrusion of the intermediate longitudinal member 119 is released from its engagement with the protrusion of the knob 160 and, thus, allows the needle shield 120 to move in the proximal direction when a force is applied to the housing 110. The current devices are readily available.

Using a device:

fig. 8A-8C illustrate the FSH delivery device 100 in perspective view, with the inner end 425 of the needle (see also fig. 4A) having pierced the membrane 133 (fig. 1A) in the activated state of the FSH delivery device 100 (as shown in fig. 8A), with the FSH delivery device 100 in a ready-to-use state; fig. 8B illustrates the actual injection state, showing the needle distal end 424 ready for expelling the FSH solution; finally fig. 8C shows the locked state of the FSH delivery device 100, i.e. the injection has been completed.

When the FSH delivery device 100 is ready for use and the user is about to inject, he/she presses the distal end (i.e., the annular contact member 121) against the tissue (i.e., the skin) of the user, resulting in a compression stroke of the device. Housing 110 is then moved in a distal direction relative to needle shield 120, which is relatively stationary against the tissue, and needle proximal end 425 penetrates the skin. The injection is performed when the needle shield 120 is about to reach a proximal most position with respect to the tubular housing 110, i.e. the start of the injection state is achieved when the needle shield 120 passes a predetermined injection position close to its proximal most position. The device 100 may emit a first "click" sound caused by the interaction between the rotary member 118 and the piston rod 116 indicating that the injection state has begun. The device 100 may emit a second audible click, caused by the interaction of the piston rod 116 with the dose stop/setting member, indicating to the user that the injection is complete. The injection period may take less than five seconds to complete.

It will be appreciated that the needle shield 120 is opaque so that the needle is not visible before, during and after the compression stroke of the device used to inject the FSH solution into the patient. Thus, by preventing the user from seeing the needle before and after the compression stroke, and thus during the state of final locking and non-use of the device before and after the decompression stroke, motion sickness can be alleviated.

The penetration and injection conditions are shown in fig. 8A-8C. Upon completion of the injection, the user removes FSH delivery device 100 from the skin, thereby effecting a decompression stroke of needle shield 120 (see fig. 8C). During the decompression stroke, the force exerted by the first spring 117 moves the housing 110 proximally relative to the needle shield 120 and eventually reaches its final position, i.e., the locked state. In the locked state, the needle shield 120 is again in the most distal position shown in fig. 8C. In this state, the needle shield 120 fully protects the working end 424 of the needle, and the needle shield 120 is also locked in this position, thereby inadvertently exposing the working end 424. Therefore, to activate the FSH delivery device 100, the user has to press the annular contact member 121 against the skin, thereby releasing the piston rod 116 in the distal direction with respect to the tubular housing 110 by the force of the second spring 115. Thus, the piston rod 116 pushes the movable pistons 131, 132 to also move in a distal direction relative to the tubular housing 110, resulting in the FSH solution being expelled from the needle.

Exemplary variable dose setting and preparation mechanisms:

figures 9A to 9C show a dose setting member according to one embodiment of the present invention. This component can be used with syringes providing different doses of FSH solution.

As shown in fig. 9B, the intermediate longitudinal member 119 is disposed between the dose set knob 160 and the rotational member 126. The intermediate longitudinal member 119 is rotationally locked to the dose setting knob 160 by outwardly extending, oppositely arranged pawls 903 (see fig. 9C), between which pawls 903 there are corresponding inwardly extending pawls on the dose setting knob 160. A set of oppositely arranged outwardly extending knobs 906 on the intermediate longitudinal member 119 abut a first series of longitudinal spacing elements, which may be ridges 904 arranged on the inner surface of the dose setting knob 160, holding the piston rod support member 114 in the initial position.

Rotating the knob 160 to the ready position or directly to the desired dose position causes the knob 906 to slide down the rib 904. In some embodiments, no ready position is marked on the knob, and rotating the knob 906 directly to the desired set position will cause the knob 906 to slide down the rib 904. The force of the second spring 115 pushes the piston rod support member 114 forward to the incremental ready position, expelling any air present in the cartridge 130.

In this embodiment, the cartridge is slidable relative to a stationary needle assembly 910, as shown in fig. 9A. In this embodiment, the device also includes a distally located needle cap (not shown) that can be removed prior to use, but which does not rotationally engage the needle assembly for priming purposes. Thus, the piston rod is arranged to move the cartridge 130 into the needle assembly 910 to first pierce the membrane 133 during preparation. The piston rod continues to push the movable pistons 131, 132, preparing the cartridge 130. The movement stops when a second set of knobs (not shown) of the piston rod supporting member 114 abuts a second set of ribs provided on the inner surface of the rotational member 126.

In this state, the dose setting knob may be rotated to set a dose. For this purpose, the inner surface of the tubular member 902 is provided with a second series of longitudinally spaced elements at a distance from the proximal end of the syringe, namely ribs 908 (see fig. 9B), forming a set of gradually descending ribs, each corresponding to a certain dose to be delivered by limiting the maximum stroke of the piston rod support member 114. Typically, seven or fewer pimples are provided for seven or fewer separate doses of FSH solution. Incremental rotation of the knob is indicated by suitable markings or indicia to indicate to the user what dose is set. As shown in fig. 9A, the distance X corresponds to the length of travel of the piston during injection and thus corresponds to the dose delivered.

In this state, the device is ready for injection. When the device is pressed against the injection site and penetrates the skin, the guiding knob of the intermediate longitudinal member 119 rotates the rotating member 126 as described above, and the outwardly extending knob 906 of the piston slides down the second set of ribs 149. This causes the piston rod 116 to move forward and effect injection until the outwardly extending knob 906 abuts one of the progressively descending ribs 908 provided for a dose. The outwardly extending knob 906 can impact one of the descending ribs with sufficient force to cause the user to hear a "click" indicating that the desired dose has been delivered. Furthermore, the maximum possible dose may be delivered in five seconds or less (i.e. within five seconds after the needle shield is in the injection position).

When the injection is complete, the user removes the device and after the needle shield 120 decompression stroke, the needle shield 120 will lock permanently and thus render it unusable. Other exemplary dose setting mechanisms that may be used with the present invention are described in U.S. patent No. 7,597,685.

Exemplary FSH delivery device

Fig. 10A-10F show various views of an FSH delivery device 1000 designed according to an embodiment of the present invention. The FSH delivery device 1000 operates and is constructed in accordance with the various embodiments disclosed herein, and thus includes various portions of the interior (such as the elongate rotational member, the piston rod, the needle assembly, the cartridge holder, and the FSH cartridge), which have been fully described above in connection with all embodiments of the FSH delivery device 100.

The FSH delivery device 1000 includes a tubular housing 1010. The tubular housing 1010 comprises a window 1012 to allow inspection of the FSH cartridge inside the tubular housing 1010. The tubular housing 1010 is functionally connected to a dose knob 1015, and the dose knob 1015 can be rotated from a locked position to a desired dose position, as shown in fig. 10F.

A removable needle cap 1020 is removably connected with the tubular housing 1010. Removal of the needle cap 1020 by rotation causes an internal needle assembly (not shown) to prime the FSH cartridge and extend the needle shield 1025. In an alternative embodiment, the priming process is triggered by the dose knob 1015 and removal of the cap 1020 causes the needle shield to extend. Such preparation mechanisms are described in detail above.

In use, a user rotates the dose knob 1015 to a specified dose by rotating the dose knob 1015 from the locked position shown in fig. 10A to a desired dose aligned with the indicators on the knob 1015. The user also removes the needle cap 1020 to extend the needle guard 1025 and cover the fixed needle so that the user does not see the needle and does not accidentally touch the needle before or after setting the dose.

The user then applies the distal-most edge of the needle shroud 1025 to a portion of the user's (or another person's) skin and pushes the tubular housing 1010 against the skin. This action partially retracts the needle shroud 1025 into the tubular housing 1010 so that the distal most edge of the needle shroud 1025 is proximal to the tip of the fixed needle. The fixed needle thus penetrates the skin and delivers the FSH solution by the internal action of the plunger rod on the FSH cartridge, as already described herein.

In this step, the user holds the tubular housing 1010 in place against the skin for a while (e.g., five seconds) to fully deliver the selected dose. The user can also confirm that the FSH solution is being delivered or has been delivered by observing the consumption of the FSH solution through window 1012. Removal of FSH delivery device 1000 from a skin portion causes needle shield 1025 to simultaneously extend and recapture the secured needle, thereby keeping the secured needle from view by the user. In some embodiments, the needle guard 1025 will lock in the extended position and thus be rendered immobile, preventing reuse. Thus, a given FSH dose can be delivered in four or fewer steps using FSH delivery device 1000.

Fig. 11A-11F show a FSH delivery device 1100 designed according to an embodiment of the present invention. The FSH delivery device 1100 operates and is constructed in accordance with the various embodiments disclosed herein, and thus includes various portions of the interior (such as the elongate rotational member, the piston rod, the needle assembly, the cartridge holder, and the FSH cartridge), which have been fully described above in connection with all embodiments of the FSH delivery device 100.

FSH delivery device 1100 includes a rectangular housing 1110. The rectangular housing 1110 is functionally equivalent to the tubular housing 1010 described above. The rectangular housing 1110 includes a window 1112 to allow inspection of the FSH cartridge within the tubular housing 1110. The rectangular housing 1110 is also functionally connected to a dose knob 1115, which dose knob 1115 can be rotated from a locked position (shown in fig. 10A) to a desired dose position (shown in fig. 11C and 11F). The knob 1115 is functionally connected with the inner dose drum 1117, and the inner dose drum 1117 rotates together with the knob 1115 to indicate the different doses that may be delivered by the FSH delivery device 1100.

A removable needle cap 1120 is removably connected with the rectangular housing 1110. Removal of the needle cap 1120 by rotation causes an internal needle assembly (not shown) to prime the FSH cartridge and extend the needle shield 1125. In an alternative embodiment, the priming process is triggered by the dose knob 1115, and removal of the cap 1120 causes the needle shield 1125 to extend. Such preparation mechanisms are described in detail above.

In use, a user rotates the dose knob 1115 to a given dose by rotating the dose knob 1115 from the locked position shown in fig. 11A until the desired dose marked on the inner dose drum 1117 is visible through the rectangular housing 1110 (as shown in fig. 11C and 11F). The user also removes the needle cap 1120 to extend the needle shield 1125 and shield the fixed needle so that the user does not see the needle and accidentally touch the needle before or after setting the dose.

The user then applies the distal-most edge of the needle shield 1125 to a portion of the user's (or another person's) skin and pushes the rectangular housing 1110 toward the skin. This action partially retracts the needle shroud 1025 into the rectangular housing 1110 so that the distal most edge of the needle shroud 1125 is located proximal to the tip of the secured needle. The fixed needle thus penetrates the skin and delivers the FSH solution by the internal action of the plunger rod on the FSH cartridge, as already described herein.

In this step, the user holds the rectangular housing 1100 in place against the skin for a while (e.g., five seconds) to fully deliver the selected dose. The user can also confirm that the FSH solution is being delivered or has been delivered by observing the consumption of the FSH solution through window 1112. Removal of the FSH delivery device 1100 from the skin segment causes the needle shield 1025 to simultaneously extend and recapture the fixed needle, thereby keeping the fixed needle from view by the user. In some embodiments, the needle shield 1125 will lock in the extended position and thus be rendered immobile, thereby preventing reuse. Thus, a given FSH dose can be delivered in four or fewer steps using FSH delivery device 1100.

The above description is illustrative and not restrictive. Many variations of the invention will become apparent to those skilled in the art upon reading the present disclosure. The scope of the invention should, therefore, be determined not with reference to the above description, but instead should be determined with reference to the pending claims along with their full scope or equivalents.

Claims (19)

1. A single-use device for self-delivery of a follicle stimulating hormone solution, the device comprising:

an elongate main housing having a distal portion and a proximal portion disposed along a longitudinal axis;

an elongate rotatable member coupled to a proximal portion of the main housing and rotatable relative to the main housing about the longitudinal axis;

a knob extending from a proximal portion of the housing and rotatable relative to the main housing between a locked position and seven or fewer independent dose positions for setting variable dose delivery of a follicle stimulating hormone solution, the knob having longitudinally spaced elements corresponding to the locked position and seven or fewer independent dose positions, respectively;

a piston rod rotatably engaged with a portion of the rotational member and biased by the longitudinal spring, the piston rod being rotatably locked to the knob in a locked position on the element corresponding to the locked position, the piston rod being incrementally movable along the longitudinal axis between the element corresponding to the locked position and one of the seven or fewer individual dose positions;

a permanently encased needle assembly having a permanently attached needle having an inner end and a working end;

a cartridge holder connected proximally to the needle assembly, the cartridge holder holding an elongate cartridge containing a follicle stimulating hormone solution, the follicle stimulating hormone solution being sterile and preservative-free allowing only single use of the device, the cartridge being permanently encased in a cartridge retaining member and having a pierceable membrane adjacent the inner end of the needle and a movable plunger adjacent the plunger rod, the cartridge being not in fluid connection with the inner end of the needle when the knob is in the locked position;

a needle shield movable relative to said main housing along a longitudinal axis between a covering position distal to the working end of the needle and an injection position proximal to the working end of the needle, said needle shield being spring biased to normally be placed in the covering position and being opaque so as to substantially obstruct a user's view of the working end of the needle in the covering position, said needle shield having a cam or follower that rotationally and longitudinally interfaces with another cam or follower of said rotational member during a compression stroke of said needle shield from the covering position to the injection position; and

a removable cap configured to cover the working end of the needle,

wherein the needle assembly or cartridge is movable along a longitudinal axis to a ready position by engagement with the cap or piston rod, respectively, causing the inner end of the needle to pierce the membrane and come into fluid connection with the cartridge, thereby priming the needle with follicle stimulating hormone solution,

wherein during a compression stroke the needle shield moves to an injection position and rotates the rotational member to rotatably engage the piston rod and move the piston rod to one of seven or fewer individual dose positions and compresses the movable piston to deliver a corresponding individual dose of follicle stimulating hormone solution from the working end of the needle.

2. The device of claim 1, wherein the knob is rotatable relative to the main housing between a locked position and a ready position.

3. The device of claim 2, wherein the knob includes longitudinally spaced priming elements corresponding to priming positions, the priming elements being located between the locked position and seven or fewer individual dose positions.

4. The device of claim 3, wherein rotation of the knob to or past the ready position rotates the piston rod from the locked position and incrementally moves the piston rod along the longitudinal axis between an element corresponding to the locked position and the ready element.

5. The device of claim 4, wherein the piston rod is incrementally moved along the longitudinal axis to move the cartridge into the needle assembly and cause the membrane to be pierced by the inner end of the needle and prime the needle with the follicle stimulating hormone solution.

6. The device of claim 5, wherein the user steps required to place the unpackaged device from the locked state into a ready-to-use state consist of:

priming the needle with a follicle stimulating hormone solution by rotating the knob from a locked position, through a priming position, to one of seven or fewer independent dosage positions; and

the needle cap is removed.

7. The device of claim 6, wherein moving the main housing distally relative to the needle shield against the relatively fixed tissue results in a compression stroke.

8. The device of claim 6, wherein the rotation member knob is marked with visible independent positions indicating seven or fewer independent dose positions.

9. The device of claim 8, wherein the ready position is not marked on the knob.

10. The device of claim 1, wherein the needle assembly includes a hub connected to a needle, the hub being threadably engaged with a retaining member of the needle assembly.

11. The device of claim 10, wherein the removable cap is rotatably engaged with the retention member, and wherein rotating the removable cap disengages the removable cap from the device and also moves the hub in a proximal direction relative to the retention member and thereby causes the membrane to be pierced by the inner end of the needle, leaving the needle ready for the follicle stimulating hormone solution.

12. The device of claim 11, wherein the user steps required to place the unpackaged device from the locked state into a ready-to-use state consist of:

preparing the needle with the follicle stimulating hormone solution by removing the needle cap; and

rotating the knob from the locked position to one of seven or fewer independent dose positions.

13. The device of claim 12, wherein moving the main housing distally relative to the needle shield against the relatively fixed tissue results in a compression stroke.

14. The device of claim 1, wherein the needle shield comprises a locking element that can lock the rotational member or the main housing during a decompression stroke of the needle shield from the injection position to the recovery position for recovering the working end of the needle, and wherein the needle shield is immovable relative to the main housing after being moved to the recovery position.

15. The device of claim 1, wherein the piston rod can contact one of the elements of seven or fewer individual dose positions with sufficient force to cause a click sound to be heard by the user.

16. The device of claim 1, wherein the cartridge has a volume of 1.5 ml.

17. A device as in claim 16, wherein the piston rod is configured to deliver a maximum dose of follicle stimulating hormone solution within five seconds after the needle shield is in the injection position.

18. The device of claim 1, wherein the follicle stimulating hormone solution is free of benzyl alcohol or m-cresol.

19. The device of claim 1, wherein the needle shield in the covering position completely obstructs view of the working end of the needle to the user when the distal end of the needle shield is against the tissue of the user before and after the compression stroke occurs.