HK1114001A - An ultrasonically detectable intrauterine system and a method for enhancing ultrasound detection - Google Patents

Description

Ultrasonically detectable intrauterine systems and methods of enhancing ultrasonic detection

Technical Field

The present invention relates to ultrasonically detectable intrauterine systems (intrauterine systems) and methods of enhancing the ultrasonic detection of these systems.

Background

Intrauterine systems, commonly referred to as IUS's, have long been known and they are constructed in various shapes and sizes from various materials. IUS' S are usually composed of a plastic frame having the shape of the letter T or 7, but the shapes of the letters S and ω are also feasible. IUS's containing drugs may be used to administer these drugs locally to the uterus at a controlled release rate over a long period of time. It has been found that well-approved medicated IUS's in contraception and hormonal therapy can be divided into copper and hormonal devices. In copper IUDs (intrauterine devices), a copper wire or silver-cored copper wire is wound around a vertical rod of a frame, while in hormone IUS an elastomeric capsule containing the hormone is placed on the vertical rod. The capsule may be coated with an elastomeric or polymeric film that controls the release of the drug from the elastomer-hormone capsule. Monofilament withdrawal strings for withdrawing the IUS after the use period are tied to the loops at the ends of the vertical rods.

Adverse complications associated with the use of IUS's are infection, bleeding, uterine perforation, cervical laceration, septic abortion, ectopic pregnancy, and IUS expulsion. Expulsion is undesirable because the IUS is no longer able to provide contraception. The most common side effect of copper IUD's is perhaps abnormal bleeding, manifested in the form of menorrhagia, metrorrhagia, or both. The hormone IUS's that can be used for the treatment of menorrhagia in fact did not find this side effect. The differences between the size and/or shape of the uterine cavity and the IUS and the imprecise (non-fundal) placement of the system upon insertion are both associated with increased uterine bleeding caused by the IUS.

In addition to optimizing the design and composition, it is important to place the IUS in the correct position. For many complications, the physician must be able to detect the location and placement of the IUS in order to diagnose the problem, and prevent further complications.

Currently, there are several techniques for determining the presence and location of IUS's in the uterus. One technique involves the use of X-rays. However, the use of X-rays in the area of the uterus and ovaries should be avoided whenever possible. Another detection technique involves the use of acoustic waves. The physician will also often examine a marker rope attached to the IUS to detect the presence and location of the IUS and remove the system at the end of the use period. Another technique is to operate the uterus under fluoroscopy. In some cases, a second IUS is inserted into the uterus to serve as an intrauterine marker to detect the relative placement of a missing IUS.

Ultrasound imaging is widely used in medical applications to non-invasively observe structures within the human body. In addition to imaging physiological structures and tissues, ultrasound imaging is also used to image medical instruments inserted into the tissues or passageways of a patient.

By adjusting the position of the IUS and the position of the uterus, the uterus is visible to ultrasound. In adjusting the relative position of the uterus and the IUS, a health care examiner can determine whether the IUS is properly placed in the uterus. The medical personnel will be able to determine whether the IUS has punctured (perforate) the uterus or cervix. If the IUS partially or completely pierces the uterus or cervix, the physician is able to better plan the appropriate strategy for removal of the IUS by knowing the location of the IUS.

In a typical imaging system, a transducer (transducer) is used to direct a short burst of ultrasound energy into the body of a patient. The returned reflected ultrasound energy or echo is received by the same transducer and converted into an electrical signal. The signal representing the reflected energy is processed and formatted into a video image of the target area. This technique is particularly useful for medical imaging applications because diagnostic ultrasound procedures are safe, patient acceptance is high, and it is less expensive than other digital imaging techniques. Moreover, instruments are widely available and generate images in real time.

Most medical devices have acoustic impedances similar to the tissue into which the device is inserted. Thus, the visibility of the instrument is poor and accurate placement becomes extremely difficult, even when not impossible. Another problem affecting the visibility of the instrument is the scattering angle. For example, a stainless steel needle has a significantly different acoustic impedance than tissue and is highly visible under ultrasound imaging when the needle is in the plane of the ultrasound beam. If the needle is moved to some other angle off-axis, the ultrasound beam is scattered in a direction different from the transducer, so that the needle becomes less visible or even invisible under ultrasound imaging.

Both of the above problems are addressed by attempting to increase the scattering power of the instrument so that the instrument becomes visible even when not completely in the plane of the ultrasound beam. Various methods are also used to enhance ultrasound imaging by modifying the reflective surface characteristics of these instruments. Many ultrasound contrast agents are known, including non-agglomerated particles of uniform porous size. Contrast agents can enhance the visibility of the target tissue into which they are injected, but they cannot enhance the ultrasound visibility of insertable medical devices.

U.S. patent No.5,201,314 describes a medical device that is insertable into a tissue or a channel and imageable with an acoustic imaging device. The instrument includes an elongate insertable element having an interface with a shape that is sensitive to an acoustic beam used to generate the image. The elongated member includes a substance, such as a spherical or other geometric shaped particle having a predetermined profile for establishing the interface. The contoured substance is contained within the material of the elongated member or alternatively or additionally attached to or embedded in the outer surface of the member material. In one embodiment, the interfacial layer may include a high density metal such as titanium, tungsten, barium, bismuth, platinum, silver, gold, or palladium.

U.S. Pat. No.6,306,125 relates to a system for delivering an implant to tissue to be treated. To enhance the visibility of the implant to the imaging system, an echogenic contrast agent may be added to the implant. Alternatively the implant may comprise an element, molecule, compound or composition having an atomic weight sufficient to render the implant radiopaque. Particularly preferred radiopaque materials are, for example, barium, gold, platinum, tantalum, bismuth and iodine. The radiopaque agent may be added to the implant in several ways. Biocompatible non-immunogenic metals such as gold and platinum can be added as very fine dispersions with particle sizes less than a few microns. Other heavy atoms may be added in the form of inorganic salts, such as barium sulfate.

Several attempts have been made to enhance the echogenicity of medical devices by modifying the surface of the device. U.S. Pat. No.4,869,259 relates to enhancing the echogenicity of needles by particle blasting with 50 micron particles to produce a uniformly roughened surface. U.S. Pat. No.4,977,897 relates to machining a sound hole in the needle to match the incident beam wavelength, which improves sonogram visibility. U.S. Pat. No.5,289,831 relates to the modification of catheters and other devices by the addition of glass spheres or high density metal particles or partial spherical indentations in the range of 0.5-100 microns. U.S. patent No.5,327,891 relates to the use of microbubble-containing media contained in a vane (vane) and/or track (track) to enhance catheter echogenicity. U.S. patent No.5,759,154 is directed to the use of masking techniques to create depressions on the surface around the instrument that comprise alternating rows of squares and diamonds.

In our studies, the known internal modifications of IUS's (mixing with hollow glass microspheres, slotting, inserting a metal core in the body of the intrauterine system) do not lead to the expected effect, i.e. they do not sufficiently improve the visibility of IUS in ultrasound detection. Referring to fig. 1, there is shown the difference between a metal core T-shaped body (fig. 1A, left side) and a surface modified T-shaped body (fig. 1B). Any material between the probe and the ultrasound enhancing material partially or completely attenuates (fade out) the brightness echogenicity of the ultrasound visibility enhancer. However, suitable means for improving the visibility of IUS's have been found by modifying the surface of the IUS with an inert metal. Although metals are known to generally improve echogenicity in ultrasound detection, metals are used in prior art methods either because of their contraceptive effect or to enhance detection using X-rays. The present invention is directed to a device that improves ultrasound detection and makes certain parts of the T-shaped body of the product more visible than others, i.e. the location and position of the IUS in the uterus can be quickly studied under the direction of the same clinician.

Disclosure of Invention

The present invention thus provides an improved ultrasonically detectable intrauterine system (IUS) for insertion into the uterine cavity for a longer period of time. The IUS of the invention comprises at least one image enhancing means for ultrasound imaging of the system. The device is selected from:

a) an inert metal coating on at least a portion of the body of the intrauterine system;

b) at least one inert metal clip, pin, ring and/or sleeve fixedly positioned on the body of the intrauterine system; and

c) a metal loop anchored to the vertical arm of the body of the intrauterine system instead of a normal loop (loop).

The invention also relates to a method of improving the visualization of an intrauterine system in the uterine cavity in an ultrasound examination. The method comprises the following steps: the body of the IUS is provided with at least one inert metal clip, pin, ring and/or sleeve, an inert metal coating is applied to at least a portion of the body of the IUS, or a metal loop is anchored to an upright arm (arm) of the body of the IUS.

The improved visibility of the IUS in ultrasound examinations has the advantage of allowing the health care professional to more easily detect the positioning of the device, thereby facilitating the detection of problems with the placement of the device and problems with the device itself.

Another advantage of this feature is that the location of the IUS can be determined without physical intrusion into the body area into which the device is inserted. Vaginal or abdominal ultrasound is today a routine outpatient procedure, which almost completely replaces the use of X-ray examination in the detection of IUS's in determining the correct positioning of the device. The ability to detect an IUS with ultrasound examination is crucial in various clinical situations, such as bleeding problems, pain, suspicious expulsion (i.e. displacement of the IUS), or other possible adverse effects during use of the IUS. The correct position is determined by ultrasound examination by measuring the distance between the upper end of the vertical rod of the system and the outer surface of the fundus of the uterus. When the uterus is not distinguishable in an X-ray examination, the use of ultrasound enables a more accurate determination of the correct position of the IUS than in an X-ray examination, for example in case of partial expulsion of the device. Furthermore, the use of X-rays should be strictly avoided in the general user population of IUS's, i.e. women of reproductive age, to minimize exposure of the reproductive organs to X-rays. In particular, the ovaries are very sensitive to the potentially mutagenic effects of X-rays, without ultrasound examination carrying any such inherent risks. In summary, the present invention enables the use of safer and more reliable detection techniques.

Drawings

Fig. 1.a) the metal core T-shaped body is on the left and the reference IUS is on the right. B) Surface modified T-shaped body (with metal). The surface modification significantly enhances the echogenicity of the T-shaped body. Views were obtained in an extracorporeal medium with a convex probe.

2-dimensional views are typically used in medical sectors (medical sectors). Thus only the horizontal arm (lateral view) or the vertical arm (sagittal view) can be seen at a time with the convex probe (fig. 2A). The vertical arm is also sometimes visible through the vaginal probe (fig. 2B).

Fig. 2.a) transverse view of a T-shaped body in water with a male probe. The schematic model shows which part of the T-shaped body is visible in the picture. B) A view of the T-shaped body from the bottom of the T-shaped body in water with the vaginal probe (the vertical arm is also visible).

Fig. 3 shows a comparative sagittal view of the vertical arm of a conventional hormone IUS (on the left) and a hormone IUS with a metal (Au) coated T-shaped body (on the right). The convex probe is in the potato starch thickener. Hormone capsules, especially IUS, are known to reduce the echogenicity of the material underneath them. The Au coating improved echogenicity of the T-shaped body and the T-shaped body was seen as a bright image inside the hormone capsule.

Fig. 4 is a comparative sagittal view of the vertical arms of the T-shaped body (a) with metal (Ag) rings in the upper and lower portions of the rod and the conventional T-shaped body (B). The metal ring is seen as a bright echo behind the vertical arm. The convex probe is in the potato starch thickener.

FIG. 5 optimal position of the echo enhancer: in order to locate the distance of the IUS from the fundus, the echogenicity of position a or position a-B is of utmost importance. The echogenicity of the positions C-D is important in order to correctly delineate the position of the horizontal arm in the uterus.

Fig. 6. hormonal contraceptive with Au coated T-shaped body.

Figure 7.a) no Ag rings embedded at the upper and lower ends of the vertical arm of the hormonal IUS. B) Double loops are embedded in the upper and lower ends of the vertical arms of the hormone IUS.

FIG. 8 shows the results obtained in MIRENABehind the horizontal arm. Note the triple shading from the thickest part of the horizontal arm. MIRENAIs an intrauterine system (IUS) for the release of levonorgestrel, consisting of a hormone elastomer capsule mounted on a T-shaped body and coated with an opaque tube, said capsule regulating the release of levonorgestrel。

Figure 9 comparison of glass microsphere modified 7-frame and standard T-frame obtained from vaginal probe in potato starch thickener. The entire horizontal arm of the 7-shaped frame is visible, while the T-shaped frame is only visible with the three thickest parts and their acoustic shadows.

Fig. 10. positioning the spherical end of the Au coated T-shaped body by the sponge-water system (marked by arrows).

Figure 11 comparison of brightness for Ag rings on vertical arm (lateral view, vaginal probe). A) An embedded single ring, B) a benchmark (acyclic), C) an embedded double ring.

Figure 12. T-shaped body design with embedded metal ring positioned at the end of the vertical arm.

Figure 13 is a schematic illustration of a different loop design and T-shaped body design for the metal clip at the end of the vertical arm.

Detailed Description

The ultrasound visibility or echogenicity of an intrauterine device depends on the density difference of adjacent materials, the difference in the propagation speed of sound in adjacent materials, the surface roughness, and the echogenicity of the surrounding material. The ultrasound visibility of different material modifications of IUS's can be estimated by assessing the echogenicity of the material from the calculated reflected energy.

Sound propagates through a material under the influence of acoustic pressure. The overpressure causes a wave to propagate through the solid, since molecules or atoms are elastically bound to each other. Acoustic impedance Z (10)⁵g/cm²s) determining the acoustic transmission and reflection at the boundary of adjacent materials:

Z＝ρ·V

where ρ ═ density (g/cm)³) And v ═ propagation velocity (mm/. mu.s).

The reflected energy R may be from the acoustic impedance (Z) of the adjacent material₁And Z₂) Calculating:

for transmitted acoustic energy: t is 1-R. Using these formulas, the ultrasound visibility of different modifications of the IUS can be estimated. The higher the reflected energy, the better the echogenicity of the material.

In table 1, the reflected and transmitted energies of various material combinations are compared.

TABLE 1 comparison of different material combinations

Material 1-Material 2 reflects Acoustic energy, R transmits Acoustic energy, T

Human tissue-copper 0.8600.140

Human tissue-MED 4735 tubing 0.0320.996

Human tissue-PDMS 373 TW tubing 0.0200.980

Human tissue-PE-LD 0.0040.997

Human tissue-glass (soda lime) 0.6250.375

(PDMS ═ polydimethylsiloxane)

(PE-LED ═ low density polyethylene)

It can be seen from table 1 that the copper wires and glass of copper IUDs reflect most of the acoustic energy back, thus providing good echogenicity and a bright picture. Common host raw materials for elastomers and IUS (PE-LD and 20-24% BaSO)₄) Is less echogenic. Most of the acoustic energy is transmitted through the material.

The intrauterine system of the invention comprises at least one image enhancing means for improving the ultrasound imaging of the system. The device is selected from:

a) an inert metal coating on at least a portion of the body of the intrauterine system;

b) at least one inert metal clip, pin, ring and/or sleeve fixedly positioned on the body of the intrauterine system; and

c) an inert metal loop that replaces the normal loop anchored to the vertical arm of the body of the intrauterine system.

The metal is advantageously selected such that the reflected energy at the boundary of adjacent materials is as high as possible. Preferably the metal is selected from inert metals such as silver, gold, titanium, tungsten, barium, bismuth, platinum, palladium. Preferred metals are silver, gold, titanium and platinum, which are known to be compatible with the human body (i.e., physically inert). However, copper may also be used.

In a preferred embodiment of the invention, a metal coating or a metal clip, pin, ring or sleeve is located at the end of the vertical arm(s) of the IUS having the shape of the letter T or 7. This enables the physician to reliably measure the distance of the IUS from the fundus. It is also possible to wrap a "loop" around the end of the vertical arm of the IUS, or to secure a metal ring, pin or sleeve to the base of the loop. In a further preferred embodiment, the metal coating or metal clip, pin, ring or sleeve is only located at the "upper" end of the vertical arm of the IUS.

It is sometimes important to locate the position of the horizontal arm of the T-shaped body. This can be achieved by coating the entire T-shaped body with metal or also by bonding a metal clip, ring or sleeve to the end of the horizontal arm(s) (before the spherical end) (fig. 5).

Typically the thickness of the metal coating may vary between about 0.1nm and about 500nm, preferably between about 1nm and about 50 nm. However, thicker coatings of about 0.1mm are also possible.

The metal clip, pin, ring or sleeve may not be embedded or at least partially embedded in the body of the IUS. Partial embedding of the rings smoothes the surface of the IUS compared to non-embedded counterparts, while also not compromising visibility. In case a ring is used, it is advantageous to use a double ring to enhance echogenicity. In the case of a clip or sleeve, the wider the clip or sleeve, the better the visibility. The width of the metal clip, pin, ring or sleeve may vary, for example, from 0.2 mm to a few mm, preferably about 1mm, or about 0.5mm in the case of double rings. Other embodiments are to secure a metal pin of appropriate size by a loop so that the end of the pin larger than the diameter of the loop is visible.

The intrauterine system of the invention may also have locking means, typically at least two locking parts, between which the drug containing capsule is mounted. The locking portion holds the capsule in the correct position during insertion, use and removal of the IUS. The locking portion may have a different shape, for example a truncated cone shape. They may be made of a polymeric material, which may be the same or different from the material of the body, but other materials may also be used, for example an inert metal in this case to improve the visibility of the IUS in ultrasound examinations.

The intrauterine system of the invention is designed for a longer period of insertion into the uterine cavity. However, long-term insertion can vary greatly, e.g., from weeks to years, with maximum IUS service life typically being as high as five years.

The invention also relates to a method of improving the visualization of an intrauterine system in a uterine cavity in an ultrasound examination, said method comprising at least one of the following steps:

-applying an inert metal coating onto at least a part of the body of the IUS, or

-providing the body of the IUS with at least one inert metal clip, pin, ring and/or sleeve, or

-anchoring the metal loop to the vertical arm of the body of the IUS;

the IUS is inserted into the uterine cavity and the position of the IUS within the uterine cavity is examined in an ultrasound examination at the appropriate moment.

Experiment of

In vitro experimental conditions:

the PE container is filled with water, a corn starch thickener or a potato starch thickener

Place the test specimen in the sponge and immerse the system in water

The device comprises the following steps:

sonosite 180PLUS with a convex probe (2-4MHz) and a vaginal (4-7) probe or

Aloka SSD900 with a male (3.5MHz) and vaginal (7.5MHz) probe

Modifications studied:

group 1: hollow glass microspheres are added to the raw material of the frame (body). Echogenicity is improved due to the high density and air trapped inside.

Group 2: hollow glass microspheres are added to the hormone releasing core.

Group 3: the entire T-shaped body was coated with Au using a Jeol Fine Coat ion sputtering JFC-1100 apparatus (1kV voltage and 1mA current for 20 minutes). The thickness of the Au layer obtained was several nanometers. See fig. 6.

Group 4: a ring or double ring of 0.5mm thick silver wire is positioned adjacent the end of the vertical arm of the T-shaped body. Both embedded and non-embedded fixtures were examined with the currently available T-shaped framework. The rough embedding is performed by manually scribing a groove having a depth of about 0.25 mm. See fig. 7.

Other in vitro conditions:

potato starch thickeners and corn starch thickeners perform similarly in sonography.

Scattering and attenuation of sound waves and the inevitable presence of air in the sponge system is so high that only NOVAT is present380 (vertical arm) are positioned. (NOVAT)Is a T-shaped plastic frame with copper wire or silver-cored copper wire around the vertical arms of the T. )

Water was found to be inferior as an in vitro medium to other media, since the echogenicity of the investigated sample in water was too good. No echogenic differences were detected between samples. The sound waves easily propagate through the water without forming disturbing echoes. Acoustic shadows, a typical phenomenon of IUD's and IUS's, are difficult to detect in water because water is seen to be black in an acoustic image. (MIRENA in Potato starch thickeners is presented in FIG. 8Examples of acoustic shadowing. )

Comparison of different modifications:

glass microspheres in a T-shaped frame slightly improve echogenicity. Referring to fig. 9, glass microsphere modified 7-frames are compared to standard T-frames in a corn starch thickener.

The Au coating improves the echogenicity of the T-shaped body. The T-shaped body was seen as a bright image under the hormone releasing capsule. See fig. 3. Even in sponge systems that find an extracorporeal medium to be very challenging, the spherical end is located. See fig. 10.

0.5mm thick Ag wires placed at the upper and lower ends of the vertical arm enhance echogenicity. See fig. 4. The metal rings were seen as bright white spots and their positioning was easy during the study. Partial embedding of the ring in any projection does not compromise visibility compared to an uninserted counterpart. However, it is clear that bicyclic rings work better than monocyclic rings. The acoustic image from the dual ring is larger and brighter. Referring to the comparative fig. 11, rings, double rings and no rings are examined in the best projection.

The claims (modification according to treaty clause 19)

1. An ultrasonically detectable intrauterine system (IUS) for chronic insertion into the uterine cavity comprising at least one image enhancing device for improving the ultrasound imaging of the system, wherein the device is selected from the group consisting of:

a) at least one inert metal clip, pin, ring and/or sleeve fixedly positioned on and at least partially embedded in the body of the intrauterine system; and

b) a metal loop or a loop with a metal coating, which replaces the ordinary loop anchored to the vertical arm of the body of the intrauterine system.

2. An intra-uterine system according to claim 1, wherein a metal clip, pin, ring or sleeve is located at the end of a vertical arm or at the end of one or more vertical and horizontal arms of the IUS.

3. An intra-uterine system according to claim 1, wherein the metal clip, ring or sleeve is positioned at the bottom of the loop.

4. An intrauterine system according to any of the preceding claims, wherein the inert metal is selected from silver, gold, titanium, tungsten, barium, bismuth, platinum and palladium.

5. An intra-uterine system according to any of the preceding claims, having at least two locking means to keep the medicated capsule in the correct position during insertion, use and removal of the IUS.

6. A method of improving visualization of the intrauterine system (IUS) within the uterine cavity in an ultrasound examination, comprising at least one of the following steps:

-applying an inert metal coating onto at least a portion of the body of the IUS;

-providing the body of the IUS with at least one inert metal clip, pin, ring and/or sleeve; and

-anchoring the metal loop to the vertical arm of the body of the IUS;

the IUS is then inserted into the uterine cavity and the position of the IUS within the uterine cavity is examined in an ultrasound examination at the appropriate moment.

7. The method of claim 6, wherein the metal clip, pin, ring or sleeve is at least partially embedded in the body of the IUS.

8. The method of claim 6, wherein the inert metal is selected from the group consisting of silver, gold, titanium, tungsten, barium, bismuth, platinum and palladium.

Claims (9)

1. An ultrasonically detectable intrauterine system (IUS) for chronic insertion into the uterine cavity comprising at least one image enhancing device for improving the ultrasound imaging of the system, wherein the device is selected from the group consisting of:

a) an inert metal coating on at least a portion of the body of the intrauterine system;

b) at least one inert metal clip, pin, ring and/or sleeve fixedly positioned onto the body of the intrauterine system; and

c) a metal loop that replaces the normal loop anchored to the vertical arm of the body of the intrauterine system.

2. An intra-uterine system according to claim 1, wherein a metal coating or a metal clip, pin, ring or sleeve is located at the end of the vertical arm or at the end of one or more of the vertical and horizontal arms of the IUS.

3. An intra-uterine system according to claim 1, wherein the loop at the end of the vertical arm of the IUS has a metal coating, or a metal clip, ring or sleeve is positioned at the bottom of the loop.

4. An intra-uterine system according to claim 1, wherein the metal clip, pin, ring or sleeve is at least partially embedded in the body of the IUS.

5. An intrauterine system according to any of the preceding claims, wherein the inert metal is selected from silver, gold, titanium, tungsten, barium, bismuth, platinum and palladium.

6. An intra-uterine system according to any of the preceding claims, having at least two locking means to keep the medicated capsule in the correct position during insertion, use and removal of the IUS.

7.A method of improving visualization of the intrauterine system (IUS) within the uterine cavity in an ultrasound examination, comprising at least one of the following steps:

-applying an inert metal coating onto at least a portion of the body of the IUS;

-providing the body of the IUS with at least one inert metal clip, pin, ring and/or sleeve; and

-anchoring the metal loop to the vertical arm of the body of the IUS;

the IUS is then inserted into the uterine cavity and the position of the IUS within the uterine cavity is examined in an ultrasound examination at the appropriate moment.

8. The method of claim 7, wherein the metal clip, pin, ring or sleeve is at least partially embedded in the body of the IUS.

9. The method of claim 7, wherein the inert metal is selected from the group consisting of silver, gold, titanium, tungsten, barium, bismuth, platinum and palladium.