WO2010112095A1

WO2010112095A1 - Improvement to intrauterine copper contraceptive devices

Info

Publication number: WO2010112095A1
Application number: PCT/EP2009/067709
Authority: WO
Inventors: Dirk Wildemeersch
Original assignee: BIO MATERIAL SYSTEMS NV/SA
Current assignee: BIO MATERIAL SYSTEMS NV/SA
Priority date: 2009-04-03
Filing date: 2009-12-21
Publication date: 2010-10-07
Anticipated expiration: 2011-10-03

Abstract

The invention relates to an intrauterine contraceptive device (IUD) comprising a plurality of hollow, metabolically active element (2), open at both ends and arranged longitudinally onto a thread (3) to form a non-rigid structure of limited dimensions. The structure has a total surface area not exceeding 275 mm2. The length of the structure is less than 2.6 cm when the copper elements are closely approximated and not more than 3.0 cm when separated and its diameter is not more than 3.30 mm, preferably not more than 3.00 mm. The hollow elements have an inner diameter of at least 1.6 mm with a length equal or less than 8 mm. Optionally, the hollow elements are partially cut out or/and perforated.

Description

IMPROVEMENT TO INTRAUTERINE COPPER CONTRACEPTIVE DEVICES

FIELD AND BACKGROUND OF THE INVENTION

The invention relates to a new and improved "frameless" copper-releasing intrauterine contraceptive device (IUD).

These devices are remarkably well tolerated by any uterus due to the absence of a frame, which eliminates dimensional incompatibility with the uterine cavity.

Such a known device comprises copper cylinders and is very efficient as the inner surface of the copper cylinders is in contact with the uterine environment, thereby increasing the effective copper surface area.

The standard prior art "frameless" IUD (GyneFix) (US

4,708,134 or EP 0191747 incorporated herein by reference) with effective copper surface area of approximately 330 mm2 is a highly effective intrauterine contraceptive system. With this IUD, the effect on menstrual blood loss is reduced when compared with the larger, conventional copper-releasing IUDs.

An important drawback of IUDs is indeed their tendency to cause heavy, sometimes painful, menstrual bleeding. Heavy bleeding is the commonest cause for IUD discontinuation. Discontinuation rates for bleeding vary from 7.0 to 12.0 during the first year of use. In the USA, an estimate of 36% of IUD users terminate during the first year for reasons other than the desire for pregnancy, including heavy menstrual bleeding and pain. Heavy menstrual bleeding may have a deleterious effect on health among normally healthy women. This is especially the case in women living in deprived developing countries where increased menstrual blood loss may precipitate or aggravate iron deficiency anaemia. It has been reported that even minute increases in menstrual blood loss may adversely affect the health of women especially during long-term use of IUD contraception. Anaemia is common according to a recent report of the WHO (World Health Organization) report on the worldwide incidence of anaemia. According to this report, the incidence of anaemia in Western Europe and the USA is about 8%, in the older Eastern European countries about 20-30%, South America about 20-30%.

It has now been found that the use of a reduced size of the contraceptive device produces surprisingly even less impact on the amount of menstrual blood loss (MBL) . The smaller the surface area of the device, the less impact on menstrual blood loss. Research also found that a smaller nominal copper surface area reduces the effect on menstrual blood loss. The larger the nominal surface of copper the greater the amount of MBL.

It has therefore been found that reducing further the size of a device of the prior art results in an intrauterine device which is surprisingly still highly effective, due to its high effective copper surface area, and is well tolerated, with minimal effect on menstrual blood loss, because of its very small size.

Long duration of action is important for IUD users as it is economical and may reduce certain health risks related to frequent replacement. Additional in vitro research on GyneFix devices which were in place up to 12 years revealed the long duration of action of the GyneFix IUD. Previous dissolution studies of the GyneFix 330 IUD yielded a minimal dissolution rate, per copper tube, of 2.4 mg per year. This, in turn, confirms dissolution studies conducted with other copper IUDs which showed that copper is released constantly for long periods of time. These studies concluded that the estimation of the useful life-span of the IUD can be conducted on the basis of measurements of the copper weight, which is a linear, negative function of duration of use.

These studies concluded 1) that the copper release from the GyneFix IUD seems to be constant over a period up to 12 years; 2) that fragmentation of the copper tubes due to corrosion did not occur; 3) that the copper surface area did not decrease sufficiently to compromise contraceptive effectiveness; 4) that the "crimped" copper tubes last significantly longer than the "loose" copper tubes.

The study suggests that the GyneFix IUD has a useful life-span of at least 10 years. Fragmentation of copper is a major problem with copper IUDs which have a copper wire around the stem of the IUD. Due to corrosion, the wire can break and the copper can be lost resulting in absence or significant decreased pregnancy protection. Only in the case of sleeves is the risk of fragmentation of the copper and subsequent copper loss unlikely, even after long periods of time such as 12 years.

The purpose of the present invention is also to provide a frameless IUD which lasts for approximately years 25 years instead of 10 years. Due to the fact that the IUD consists of copper cylinders, the total weight of the copper can be increased thereby increasing the lifespan of the IUD by many years and at the same time reducing the risk of fragmentation of the copper which could increase the risk of pregnancy.

SUMMARY OF THE INVENTION

The primary aim of the present invention is to provide a copper IUD which has a smaller total surface area but a large effective copper surface area, when compared to the effective copper surface area of the high-load conventional copper IUDs, and of which the total surface area of the foreign body is at least two or three times smaller than that of conventional copper releasing IUDs in order to minimize the impact on menstrual blood loss.

The goals are reached, according to one aspect of the present invention, by devising an IUD of extremely small dimensions, wherein the active substance is preferably copper, and wherein the components are hollow and attached to each other one behind the other in a non-rigid assembly and wherein the such components, elements or members are sufficiently short allowing the inner surface of the cylinders to come into contact with the uterine environment.

According to another aspect of the invention, the total surface area of the IUD does not exceed 275 mm2. According to one embodiment it will not exceed 250 mm2.

According to an additional characteristic of the invention, the effective copper surface area equals the nominal copper surface area which should be at least 200 mm2.

According to yet another aspect of the invention, the components are copper cylinders and are not longer than 6 to 8 mm in order to allow easier direct contact between the inner surface of the cylinders and the uterine environment.

According to yet another characteristic of the invention, all copper cylinders are hollow and are kept in place by two small copper clips, one above and one below the copper cylinders, crimped or flattened onto the anchoring thread. The clips may be cylinders identical to the copper cylinders but which have been crimped. The design of the device and the manufacturing process may therefore be simplified.

According to another additional characteristic of the invention, the total length of the closely approximated copper elements of the IUD is not longer than 2.6 cm.

According to another additional characteristic of the invention, the total length of the IUD is not longer than 3.0 cm when the copper elements are separated.

According to yet another characteristic of the invention, the hollow elements are separated from each other by a small space to enhance the contact between the inner part of the cylinders and the uterine environment.

According to yet another characteristic of the invention, the hollow elements are not larger than 3.0 mm in diameter in order to allow easy insertion in the uterine cavity.

According to another characteristic of the invention, the inner diameter of the hollow elements is at least 1.6 mm in diameter to allow a high total (inner and outer) effective copper surface area similar to high-load copper IUDs.

According to yet another characteristic of the invention, the wall of the hollow elements is partly cut out to allow enhanced exchange between the inner surface area of the copper elements and the uterine environment.

According to an additional characteristic of the invention, the elements are provided with side holes to increase the contact between the inner surface of the elements and the uterine environment.

The goals in connection with lifetime of the device are also reached, according to the present invention, by creating an IUD of extremely small dimensions, consisting of hollow copper cylinders of which the wall thickness is increased to increase the copper load and consequently the lifespan of the device. The hollow, preferably but not necessarily copper, components are attached to each other one behind the other in a non-rigid assembly and of which the elements are sufficiently short allowing the inner surface of the cylinders to come into contact with the uterine environment. The preferred mode of realization is a frameless IUD consisting of 4 copper tubes, with outer diameter of 2.4 mm and an inner diameter of 1.6 mm, which are threaded on a length of suture material and of which the upper and lower copper tubes are crimped onto the thread to prevent sliding off the suture thread. The proximal end of the thread is provided with a knot which serves as retaining member to keep the device affixed to the uterine wall.

According to another characteristic of the invention, and contrary to prior art device such as disclosed in US 4,708,134, in which the copper cylinders are affixed to a thread which functions as a retaining member in the uterine tissue, the thread should have at least a 0-gauge size to maintain retention of the heavier IUD attached to the uterine wall . According to an additional characteristic of the invention, the outer diameter of the copper cylinders should not exceed 2.8 mm to allow easy insertion in the uterus.

According to an additional characteristic of the invention, the inner diameter of the copper cylinders should not be less than 1.6 mm to allow proper copper ion exchange with the uterine environment.

The number of elements may be between 2 and 10, preferably between 3 to 6. Particularly preferred is a structure comprising 4 cylindrical elements, each approximately 5 mm in length, in a row of which the first and last have been crimped onto the anchoring thread. The hollow elements are preferably made of copper.

The fixation means is an anchor made advantageously by heat-deformation of the end of a loop made in an anchoring (thermoplastic) thread whereby the end is essentially spherical and wherein one string is cut short to form a hook or appendix, adding to the functionality of the anchor.

The anchor may comprise a tubular metal element at the appendix fixedly attached to this appendix allowing better visibility of the anchor at examination by ultrasound.

The anchor may also comprise a thin tube which is threaded onto the anchoring thread up to the body of the anchor to allow the anchor to be inserted with a forceps into the musculature of the uterine fundus. The hollow elements are preferably made of copper or of biocompatible stainless steel.

However, according to a particular aspect of embodiment of the invention, in addition to the spermicidal action of copper, gold is added. It has indeed been shown that copper and gold (or silver) enter into a electrochemical reaction. The alloy of copper and noble metal (silver, gold) creates a multitude of local tiny galvanic (alkaline) batteries when in contact with the uterine environment (which serves as an electrolyte) . Copper act as an anode, while the noble metals (Ag, Au) serve as cathode. The resulting weak electrical activity has a negative effect on sperm cell motility, capacitation and survival, while the foreign body reaction, also stimulated electrically, increases leucocyte infiltration in the endometrium and further increases the number of macrophages in the uterine cavity (enhanced spermicidal effect) . Silver and gold ions, dissolved in trace quantities, exhibit in situ bactericidal and fungicidal effects (oligodynamic effects), which are expected to lessen the risk of pelvic inflammatory disease (infection) .

In view of the above considerations, practically, gold tubes with length varying between 1.6 and 2.0 mm are added between the copper tubes of the small IUD (GyneFix type) at three possible locations : first, below the first "crimped" copper tube; second, between the "loose" copper tubes; and thirdly above the lower "crimped" copper tube.

Another mode of realization (also preferred) is to crimp onto the suture thread one short 2.5-3.0 mm gold tube above and one below the 4 copper tubes DESCRIPTION OF THE DRAWINGS

These and other characteristics of the invention will be more readily understood when referring to the description as well as the accompanying drawings which represent, merely by way of examples, several embodiments of the invention, and in which:

FIG. 1 is a schematic cross sectional view of the uterus with a preferred embodiment of an IUD according to the invention,

FIG. 2 represents a view of a preferred embodiment of an IUD according to the invention, compared with a conventional copper-T IUD, showing the significant difference in size between the two IUDs,

FIG. 3 is a transversal sectional view of an element of the invention,

FIG. 4 is another view of an embodiment according to the invention of which the elements are separated from each other to enhance the contact between the inner surface of the hollow cylinders and the uterine fluid,

FIG. 5 represents another view of embodiments according to the invention of which the elements are cut out longitudinally or laterally to enhance the contact with the uterine environment. FIG. 6 represents another view of an embodiment according to the invention of which the elements are perforated to enhance the contact with the uterine environment .

FIG. 7 represents another view of an embodiment wherein the elements are perforated and comprise a cut out .

FIG.8 is an enlarged view of the thread anchor provided with a thin tube which is threaded just below the anchoring knot.

FIG. 9 represents the anchor as in Fig. 8 provided with an additional tube which is threaded onto the appendix of the anchor.

DETAILED DESCRIPTION

Referring now particularly to FIG. 1, an IUD is made of a material which is physiologically active in the uterine cavity, consisting of 4 hollow longitudinal members, 2 open at both ends, and arranged in a sequence in order to form a longitudinal flexiblebody . The elements are threaded on a length of thread, for example a polypropylene suture material. The sleeve members or elements (2) are prevented from sliding off the material by the upper and lower sleeves which are at least partially crimped onto the thread. The proximal end of the thread is provided with a fixing means 5 to secure the IUD in the fundal part of the uterine cavity 1 and prevent expulsion. This device has no rigid plastic body, making it a completely flexible unit.

The IUD is made of hollow elements of which the total surface area is at least two times smaller when compared with a well-known conventional IUD (TCu380A ) as shown in FIG . 2 .

FIG. 3 is a transversal sectional view of an element of the invention, showing the possibility of exchange of contact between the inner surface of the hollow cylinders and the uterine fluid.

As shown in FIG. 4, which is a cross sectional view according to one embodiment with a retaining member 5 at the upper end of the thread, the hollow elements, open at both ends, are separated from each other by a spacer 4 being provided crimped or not onto the thread, in order to enhance the contact with the uterine environment.

FIG. 5A and 5B are sectional views illustrating a particular embodiment of the hollow elements 52 being provided with cut outs 56, 57 (longitudinal or transversal) to enhance the contact with the uterine environment

FIG. 6 and FIG. 7 show other embodiments of a hollow element 62 which is perforated and another element which is provided with holes and is also partly cut out 72,78 to enhance the contact with the uterine environment 11. FIG. 8 show an embodiment of the anchoring means different from the one illustrated in Fig. 4. The enlarged detail shows a knot 80, a loop 81, an appendix 82 and a tube 83 narrowly threaded on the thread 3 of the device.

FIG. 9 is a similar view with an additional tube 94 threaded and fixed to the appendix to facilitate detection by ultrasound techniques.

It will be appreciated that the new advantageous embodiments illustrated in Figs. 8 and 9 are applicable separately and are applicable also to any intra-uterine device requiring anchoring means to the fundus or device similar to but having not the dimensional features of the present claim 1. Therefore, the invention concerns also an intrauterine contraceptive device (IUD) comprising: a plurality of hollow, metabolically active elements, open at both ends and arranged longitudinally onto a thread 3, one end of which comprises an anchoring means, with a knot in said thread, to retain to the fundal part of the uterine cavity, such device forming a non-rigid structure of limited dimensions, wherein there is provided a further crimped hollow member or thin tube which is threaded just below the anchoring knot and/or there is provided a further crimped hollow member at the appendix of the anchoring means.

The invention has been described and illustrated merely by way of examples which are in no way restrictive. Numerous changes in its conception may be made without departing from the spirit of the invention.

Claims

Claims :

1. An intrauterine contraceptive device (IUD) comprising: a plurality of elongated hollow, metabolically active members (2), open at both ends and arranged longitudinally onto a thread (3), one end of which comprises an anchoring means (5, 25) to retain to the fundal part of the uterine cavity (1), such device forming a non-rigid structure of limited dimensions, characterised in that: the structure has a total surface area not exceeding 275 mm2 ; the length of the structure , when the hollow members are closely approximated is less than 2.6 cm, and not more than 3.0 cm when the members are freely separated along said thread, and its diameter is not more than 3.30 mm, preferably not more than 3.00 mm; and the hollow members have an inner diameter of at least 1.6 mm but less than 2.5 mm.

2. An IUD according to claim 1 wherein the hollow members (2) are hollow cylinders or sleeves, the length thereof being equal to or less than 8 mm.

3. An IUD according to any of the previous claims, characterized in that the wall of the hollow members 2 is partially cut out or perforated.

4. An IUD according to any of the previous claims, characterized in that the hollow members are made of copper,

5. An IUD according to any of the claims 1-3, characterized in that one or some of the hollow members (2) are made of copper and the other (s) of gold and/or silver.

6. An IUD according to any of the previous claims, characterized in that the hollow members 2 are kept in place by two small crimped clips (2' ) , one above and one below the hollow elements (2) .

7. An IUD according to any of the previous claims wherein the clips (2^?) are also hollow elements (2), possibly of shorther length, having been crimped or flattened onto the thread (3) .

8. An IUD according to any of the previous claims wherein the number of members 2 is between 3 to 8, preferably around 4.

9. An intrauterine contraceptive device for insertion in the uterus comprising: a plurality of hollow, metabolically active elements (2), arranged longitudinally to form a non-rigid structure of limited dimensions; a structure of which the elements are copper cylinders are at least 2.4 mm in diameter and maximum 2.8 mm in length; a structure of which the wall thickness of each or part of the copper cylinders is at least 0.4 mm.

10. An IUD according to claim 1, characterized in that the total copper load is minimally 350 mg.

11. An IUD according to to any of the previous claims , characterized in that the retaining thread 3 is made of polypropylene and/or has at least 0-gauge size US.

12. An IUD according to to any of the previous claims , characterized in that the total length of the hollow members (2) does not exceed 2.5 cm.

13. An IUD according to to any of the previous claims , characterized in that the effective copper surface area is between 220 mm² and 280 mm².

14. An IUD according to any of the previous claims , characterized in that there is provided a hollow member or thin tube (83) which is threaded just below the anchoring knot (80) .

15. An IUD according to the previous claim wherein the hollow member (83) is made of copper and has a length between 1 and 9 mm and a diameter which is between 0.1 and 0.3 mm larger than the size of the suture thread (3) on which the tiny metal tube (83) is threaded.

16. An IUD according to any of the previous claims , characterized in that there is provided a further crimped hollow member (94) at an appendix (82) of the anchoring means (80) .

17. An IUD according to any of the claims 1 to 8 wherein the hollow members 2 are copper cylinders and the wall thickness of each or part of the copper cylinders is at least 0.4 mm.