IE42319B1 - Intra-uterine gynacelogical device - Google Patents

Abstract

1495735 Intrauterine contraceptive SCHERING AG 6 Dec 1974 [6 Dec 1973 18 Jan 1974 1 June 1974] 52961/74 Headings A5B and A5R A Y-shaped intrauterine contraceptive is formed of synthetic plastics material and has a rounded head 5, 6 at the end of each of its branches 3, 4 respectively and a plurality of rounded enlargements 1, 10-13 spaced along its stem, the angle between the branches and that between each branch and the stem being obtuse and the resilience of the contraceptive being such that the branches can be brought into substantially axial alignment with the stem. The heads 5, 6 and enlargements 1, 10-13 may be substantially spherical. A pharmacologically active substance may be incorporated in or on the contraceptive for gradual release into the uterus. This substance may comprise a metal e.g. copper, silver or nickel, which may be applied as a coating to one or more of the spheres, and the coating may comprise a plurality of layers, successive layers being of different metals. Alternatively the metal may be in particulate form and distributed throughout a sphere. The substance may alternatively have a hormonal or gestagenic activity and may be a steroid. It may also have a local anaesthetic or weakly basic buffering action. The substance may be dispersed in the plastics or be included in a core member inserted in at least one sphere. The contraceptive may be inserted into the uterus using a tubular inserter 16 containing a rigid member 17 connected to an elongate member 14 at the base of the stem by a severable cord 18. A filament 19 for location in the cervical canal may be connected to member 14, which filament may also be provided with the pharmacologically active substance.

Description

The invention relates to intra-uterin contraceptives for human use.

Medicament-containing contraceptives for intra-uterine use have been proposed in an attempt to provide contraceptives which, without preventing ovulation, are reliable in action with smaller quantities of medicaments than are required when the same medicaments are adminiSr tered via the gastro-intestinal tract. The human organism can then be subjected to a reduced quantity of medicinal material with the result . that side effects should be reduced or eliminated.

It has been proposed for a long time to introduce into the uterus for preventing conception devices formed of a very wide variety of materials, having a variety of shapes and being designed to act in a variety of different ways. However, the mechanism of action of these previously proposed contraceptives for intra-uterinal use has not been definitively clarified.

A device capable of intra-uterinal use for preventing conception was developed in 1920 by Grafenberg. The device was made of a wire material consisting of an alloy of copper and silver.

Later on various synthetic plastics materials, such as nylon, poly20 ethylene and polyethylene/vinyl acetate, alone or with the addition of barium sulphate, were used to form a very wide variety of contraceptives for intra-uterinal use, but they were very cumbersome and bulky for the uterine cavity. Examples of such devices are the Margulis Spiral (U.S. Patent 3,200,815; Federal German Patents 1,416,942 and 1,441,359), Brinberg's Bow (U.S. Patent 3,253,590), Saf-T-Coil (Trade Mark) (U.S. Patents 3,234,938 and 3,374,788) and Lippes Loop (Trade Mark) (U.S. Patent 3,250,271).

Uith the development of T-shaped contraceptives (U.S. Patent 3,533,406), Daikon-Shield (Trade Mark) (German Offenlegung30 sschrift 1,956,701) and Lippes Loop D there became known contraceptives - 2 4231» for intra-uterinal use made from synthetic plastics material and smallerin linear dimension and volume than previously proposed devices. The , reliability in action of these contraceptives was increased by applying metallic copper to the surface of the device (compare Zipper, Amer. J. Obst. Gynec. 105, 1274—1278 (1969) and Jecht et al., Contraception, 7(5), 381 (1973) or by the incorporation of medicaments in the synthetic plastics material. There were dispersed as medicaments in the synthetic plastics material copper powder or steroid hormones having a gestagenic action. One construction of the Daikon Shield, for example, contained copper highly dispersed in the synthetic plastics carrier. The COPPER-. T and COPPER-7 (U.S. Patent 3,563,235) were partially bound round with copper wire, and the COPPER TCu 220 C (U.S. Patent 3,533,406) was partially covered with copper sleeves (U.S. Patent 3,563,235). The reliability in contraceptive action of the devices for intra-uterinal administration provided on the surface with copper was increased by the additional application of zinc or silver {see U.S. Patent 3,563,235; Zipper et al., Amer. J. Obst. Gynec. 105, 529—534 (1969a); Zipper et al., Human fertility control through the use of endouterine metal antagonism of trace elements in control of human fertility, Nobel 15, Almquist & Wiksell, Stockholm 1971, pp.199}.

There have also been proposed intra-uterine contraceptives consisting of a device formed of a synthetic plastics material and having connected thereto a capsule of silicone rubber containing medicament. Such combination-contraceptives are also intended for application in the cavum uteri (Int. J. Fert. 1£ (1970) 210).

It has been found, however, that previously proposed contraceptives containing medicaments for intra-uterinal use, and also similarly shaped devices free from medicament, lead during the period of use to undesired side effects such as haemorrhages and pains {Fortier et al., J. Amer. Obstet. Gynec. 115 (1973) 291; Tatum, Contraception £ (1972) 179; Mishell - 3 4 S3 19 et al., Amer. J. Obstet. Qynec. 116 (1973) 1092).

Disadvantages of previously proposed contraceptives for intrauterinal use are a risk that spontaneous expulsion will occur, a need to remove the contraceptive on medical grounds and the occurrence of pregnancies. A need to remove the contraceptive on account of side effects tends to occur especially at the beginning of the period of use {see Avery, Rep. Pop'ul. Family Plan 4,6: (1973) 139}.

The most frequent side effects of known contraceptives for intrauterinal use are haemorrhages and pains. The number of removals of intra-uterinally applied contraceptives necessitated by occurrence of these troubles is greater for the bulky devices formed of synthetic plastics than for the less bulky devices such as the Daikon-Shield, Tshaped contraceptives or Lippes Loop D.

Side effects and removals necessitated by side effects and also expulsions of the intra-uterine contraceptives made of synthetic plastics material do not, however, result solely from the unfavourable shape and dimensions of these devices. Further important factors in this connection are the elasticity and hardness of the synthetic plastics material. Devices made of synthetic plastics material of too low an elasticity and of high hardness cause frequent pains and spasms. These devices must be made in different sizes to correspond to the dimensions of the cavum uteri. Contraceptives made of synthetic plastics material that is too softmay twist within the uterus and are then often spontaneously expelled. Occasionally, they penetrate the uterine musculature. Frag25 ments of such intra-uterinally used contraceptives and intact devices, if these have penetrated the wall of the uterus, enter the peritoneal cavity and there lead to further injuries or ligature the intestinal convolutions.

Statistical studies have shown that, with the less bulky intra30 uterine contraceptives made of synthetic plastics material the frequency - 4 42319 of side effects and spontaneous expulsions is lower than for bulky contraceptive devices. The absolute number of undesired side effects and spontaneous expulsions, however, is too high to be tolerable for either type of intra-uterine contraceptive device. Also, in the case of the less bulky intra-uterine contraceptives there have been observed side effects such as the occurrence of dysmenorrhea, metro-menorrhagia and leucorrhea associated with continuous pain and occasionally convulsive pain {compare, for example, Ostergard et al., Contraception 4(5), 313—317 (1971); Portruff et al., Am. J. Obst. Gynec. 114 (7), 934— 937 (1972); Taylor et al., Obst. Gynec. 41, (3), 404—413 (1973); Buchmann, Fert. Steril. 21_ (4), 348—355 (1970)}. The pregnancy rate calculated by the life-table method {Tietze, Intra-Uterine Contraception, Recommended Procedures for Data Analysis Studies in Family Planning, No, 18 (Suppl,), The Population Council New York, 1967} when these contraceptives are used is such as to cast doubt on their reliability {Fuchs et al., Contraception £ (2), 119—127 (1972), Baeyertz, Austr. N. Z. J. Obst. Gynec.‘ jU, 117—121 (1971); Davis, Amer. 0. Obst. Gynec. 114 (1), 134—151 (1972)}.

Moreover, perforation of the wall of the uterus has frequently been observed with this type of contraceptive {Buchmann, Fert. Steril. (4), 348-355 (1973)}, Rigidly formed intra-uterine contraceptives may break in the uterus owing to the alternating bending stresses to which they are subjected.

The broken pieces may be expelled spontaneously without being noticed or, as in the case of undamaged devices, penetrate the wall of the uterus and enter the peritoneal cavity {Last, 0. Obst. Gynec. Brit. Commonw. (2), 190—191 (1972); Domany et al., Brit. Med. J. 1 549 (1973)}.

The use of medicament-containing intra-uterine contraceptives such as the TCu 200 or TCu 220 C, the contraceptive containing copper and zinc, or a device containing progesterone (German Patent Specification - 5 tu 42319 2,247,949) or dl - lie - ethyl - 17a - ethinyl - 17e - hydroxy - gon 4 - en - 3 - one, results in an observed reduction in the pregnancy rate as compared with intra-uterine contraceptives made only of synthetic plastics material.

However, these medicament-containing intra-uterine contraceptives, like the similarly shaped devices free from medicament, lead during the period of use to undesired side effects such as haemorrhages and pains {Fortier et al., J. Amer. Obst. Gynec. 115 ( 3), 291—297 (1973); Tatum, Contraception £ (3), 179—189 (1972); Mishell et al., Amer. J. Obst.

Gynec. 116 (8), 1092—1096 (1973)}.

It is common to all T-shaped devices that owing to the tendency of the synthetic plastics to acquire a permanent set they cannot be sterilized while positioned in an applicator. Furthermore, it is hardly possible to insert the device in the applicator under aseptic conditions, because the device and applicator are not fitted together in a suitable manner.

The device and applicator together can cause injuries during application, as the folded-up device and the upper edge of the insertion tube have sharp edges. The Daikon-Shield and the applicator developed for this device are so constituted that it is only possible to introduce the contraceptive with considerable stretching of the cervical canal·.

In addition to the large number of enforced removals of this contraceptive owing to side effects there are also spontaneous expulsions {Fortier et al., Amer. J. Obst. Gynec. 115 (3), 291—297 (1973); Johannisson, Contraception 8 (2), 99—112 (1973); Snowden et al., Contraception 7 (2), 91—104 (1973); Horowitz, Contraception 7 (1), 1—10 (1973)}. Spontaneous expulsions have been observed with a few of these devices {Daikon Shield: German Offenlegungsschrift 1,956,701; Ostergard et al., Obst. Gynec. 41. (2), 257—258 (1973); T-shaped contraceptives, COPPER-7: Newton et al., Lancet 1972/11 No. 7784, 951—954; Bernstein - 6 43319 et al., Contraception (2), 99—107 (1972)}, even though they are so shaped that they have abutments so arranged as to oppose the direction of expulsion. {Jones et al., Brit. Med. J., 3 143 (1973)}. In the Daikon Shield these abutments are affixed laterial projections in the form of fingers and prongs on a ring. Intra-uterine contraceptives so formed naturally have the risk of causing injuries to the uterus during application, during the period of use {Koetsawang, Contraception 7 (4), 327—332 (1973); Johannisson, Contraception 8 ( 2), 99—112 (1973); Lehfeldt et al., Obst. Gynecol. 37 (6), 826—B31 (1971); Brooks et al., Amer. J. Obst. Gynecol. 113 (1), 104—106 (1972); Sprague et al., Obst. Gynecol. £[ (1), 80—82 (1973); Rienprayura et al., Contraception 7_ (6), 515—521 (1973)}' and during removal {Snowdon et al., Contraception 7 (2), 91—104 (1973)}. Kamel et al. {Fert. Steril. 24 (3), 165—169 (1973)} describe as trivial the injuries to the wall of the uterus caused by the two horizontal ends of the T-formed contraceptive device (U.S. Patent 3,533,406), which anchor the device in the wall of the uterus, and even as being favourable to the action and fixing of the contraceptive device.

In the case of intra-uterine contraceptives containing copper, such as the COPPER-T, the copper wire may break as a result of mechanical stress or become separated from the body of synthetic plastics material. The resulting fragments of copper wire may cause injuries. They may penetrate the wall of the uterus, pass into the peritoneal cavity and, being fragments, are difficult to locate. With the COPPER-TCu 220 C the risk of perforation of the wall of the uterus with subsequent separation of the copper cylinder and the copper cylinder remaining in the peritoneal cavity is especially great.

The hitherto proposed contraceptives also have disadvantages in that their total weight or the distribution of weight within the device tend to cause spontaneous expulsion. The COPPER-TCu 220 C weighs - 7 1» 612 mg, and one construction of the Lippes Loop weighs 665 mg. Metalcontaining intra-uterine contraceptives, such as that described in German Offenlegungsschrift 2,207,939, are easily expelled spontaneously (the metal rings all being fixed on the shaft of the synthetic plastics body) < Other contraceptivesj for example those proposed in German Patent Specification 1,441 ,359 or German Offenlegungsschrift 2,207,939, comprise a spiral having an extension of the spiral to be applied intrauterinally, which extension extends out of the cavum uteri through the cervical canal into the vagina. These devices are made entirely of synthetic plastics material. However, the synthetic plastics suitable for forming the spiral is too rigid for the part located within the cervix and within the vagina. Therefore, with these contraceptives which extend into the cervical canal very many side effects have been observed, such as spasmodic pain and haemorrhages {Willson, Amer. J. Obstet. Gynecol. 92 (1965) 62}. The consequence of spasms of the uterus is frequently an unnoticed spontaneous expulsion and a subsequent pregnancy.

A further disadvantage of the known medicament-containing contra20 ceptives is that the long term release of non-metallie active substances does not occur with the regularity necessary for maintaining the contraceptive action within certain predetermined limits. The large scale manufacture of contraceptives of this type is also technically difficult and necessitates the taking of many precautionary measures.

The pregnancy rate, which has been calculated by the life-table method {Tietze, Intra-Uterine Contraception, Recommended Proc. for Data Analyses Studies in Family Planning No. 18 (Suppl.), The Population Council, New York, 1967}, when the hitherto proposed intra-uterine contraceptives are used is such that they do not achieve as high a reliab30 ility in action as the known contraceptives administered per os, which - 8 42319 contain hormones as medicinally active substances {Davis, Amer. J.

Obstet. Gynec. 114 (1972) 134; Fuchs et al., Contraception 5. (1972) 119}, It is an object of the present invention to make it possible to provide a universal and uncomplicated medicament-containing contraceptive for human intra-uterinal use, which is reliable in action. The contraceptive should be capable of being used without risk continuously over a period of several years without physical or psychological injury for all expected dimensions of the cavum uteri in nulliparae, nuiligravidae, multiparae and multigravidae. It should also be so constituted that, during its period of use, it does not check or impair subsequent fertility. The use of the medicament-containing contraceptive should not entail the risk of undesired side effects such as dysfunctional haemorrhages, infections, spasmodic pain, translocations including perforations and migrations, and the risk of spontaneous expulsions. The intra-uterine contraceptive should be so shaped, while taking into account all expected dimensions of the cavum uteri, that it cannot twist in the uterus both at high motility of the uterus and in a small cavum uteri and cannot become undesirably placed, that its position can be simply and definitely ascertained if necessary by X-rays, and is so constituted with a sufficient degree of inherent stability and the flexibility necessary for application, use and extraction having regard to the form and the material used for its manufacture, that there is substantially no risk that mechanical injury to the uterus will occur. It should be possible to introduce the contraceptive under aseptic conditions into the uterus in a simple and painless manner without appreciable dilation of the cervical canal and without the use of further medicaments.

The applicator for the intra-uterine contraceptive should be so constituted and correlated to the device that the contraceptive can be administered under aseptic conditions.

Such medicament-containing contraceptives should be capable of - 9 -' 42319 being manufactured and sterilized in large numbers industrially in a simple and reliable manner. This type of contraceptive should, above all, be so constituted that the probability of undesired pregnancies during the period of use is as far as possible equal to zero.

The invention provides an intra-uterine contraceptive device which comprises a Y-shaped member formed of synthetic plastics material, the free end of each branch of the Y terminating in a rounded head, the stem of the Y being formed with a plurality of rounded enlargements which are spaced apart from one another along the length of the stem, the angle subtended between the branches of the Y and the angles subtended between the branches and the stem of the Y each being obtuse and the resilience of the Y-shaped member being such that the branches of the Y can be so resiliently deformed as to bring them into substantially axial alignment with the stem of the Y.

The physical properties of the synthetic plastics material may be as follows: Modulus of elasticity (ASTM D 747 RESP. 638): 900 to 2,900, preferably, 1,000 to 2,750, kilograms per square centimetre.

Tensile strength (ASTM 0 638 RESP. 412) 50 to 120, preferably, 60 to 105, for silicone elastomers and ISO to 550 kilograms -.per square centimetre for thermoplastics.

Shore hardness: A 35 to 85, preferably, 40 to 75, (DIN 53 505) for silicone elastomers, and D 40 to 70, preferably, 45 to 60 (ASTM D 676) for thermoplastics.

Advantageously, the stem of the Y comprises at least three rounded enlargements. Preferably, the stem of the Y comprises not more than seven rounded enlargements.

The invention also provides ah aseptic pack comprising a contraceptive device in accordance with the invention sealed within an envelope, bag or the like. - 10 42318 The invention also provides a method of contraception wherein a contraceptive device in accordance with the invention is fitted to a human female.

The invention further provides a contraceptive pack which comprises a contraceptive device in accordance with the invention and instructions for its use in fitting the device to a human female.

Several forms of intra-uterine contraceptive device constructed in accordance with the invention will now be described with reference to the accompanying drawings, in which Figures 1 and 2 are side views of a first and second form of device, respectively.

Referring to Fig. 1 of the accompanying drawings, the first.form of device is a generally Y-shaped synthetic plastics body and has a total length of 3 to 4 cm. Extending from a central sphere 1 having a diameter of 2.5 to 3.0 mm., are arranged three round rods 2—4 terminating in spheres and having different lengths and having diameters of 1.0 to 1.5 mm. The length of the rod 3 is within the range of from 0.8 to 1.2 cm and the length of the rod 4 is within the range of from 0.5 to 0.8 cm. The rods 3 and 4 terminate in spheres 5 and 6, respectively, having diameters of 4 to 5 mn. and 1.5—2.0 mm., respectively, and are arranged at an obtuse angle to the third rod 2, To form the stem of the Y, the third rod 2 continues into a three-rod assembly 7, 8, 9 connecting four spheres 10—13 having a diameter of 2 to 3 nm, and into a beam-shaped head 14 having a length of 4 to 5 mm. and a width of 2 to 3 mm. having a central bore 15 having a diameter of 0.5 to 1.5 mm. The angle between the axes of the rods 3 and 4 does not exceed 130° and preferably does not exceed 127°. Further, the angle between the axes of the rods 3 and 4 is advantageously at least 120° and preferably at least 121°. The angle between the axes of the rods 2 and 3 is substantially equal to the angle between the axes of the rods 2 and 4. - 11 42319 The bore is provided for fastening a thread 18 of suitable material, for example, nylon or polyester. This thread serves as an indicator thread for indicating in a simple manner the presence of the contraceptive device.

Referring to Figure 2 of the drawings, a second form of contraceptive device is similar to the first form of device except that a further thread or filament of synthetic plastics serves as an intra-cervical appendage 19 which is passed through the central bore 15 and secured to the end-piece 14 in addition to the indicator thread 18, and also con10 tains one or more pharmacologically active ingredients.

For making the. synthetic plastics body for the contraceptive of the invention there may be used synthetic plastics,which release one or more non-metallic pharmacologically active ingredients contained in admixture or conjunction with the synthetic plastics and have adequate mechanical properties such, for example, as tensile strength, elasticity and cold stretchability, and can easily be formed into suitable shapes.

As such there may be mentioned, for example, polyethylene, ethylene/ vinyl acetate copolymers, ionomeric resins derived from polyethylene, polyamides, polyether-ester elastomers on a terephthaiate base, poly20 ethylene terephthaiate, and also silicone rubbers. The synthetic plastics may be used singly or in combination, for example, by forming in layers. The pharmacologically active ingredients incorporated in the intra-uterine contraceptive may also be metals, metal alloys or nonmetallic pharmacologically active ingredients of natural or synthetic origin, which are located on the surface of the synthetic plastic body or contained in a synthetic plastics base.

As metallic active ingredients there may be mentioned, for example, metals such, for example, as copper, silver, nickel or combinations of these metals with one another and also.mixtures of the pure metals with alloys of those metals. The metal of metal alloys may be dispersed - 1Z 42319 uniformly in the entire synthetic plastics body or only in certain parts thereof or may be applied partially and/or in alternation to the surface of the contraceptive in a suitable manner.

The metallic pharmacologically active ingredients may be incorporated in or applied to the synthetic plastics bodies in a manner in itself known, for example, by electro-deposition, treatment with steam, reductive separation, optionally with the aid of an adhesive agent or by dispersing. In applying the metal or metals by electro-deposition the metal may separate in various forms and layers of different metals may be applied one upon another. The thickness of the layer of metal I applied should be such that the metal does not become detached from the synthetic plastics body when the contraceptive is subjected in the uterus to large alternating bending stresses.

In a preferred form of the contraceptive a metallic pharmacologically active ingredient is applied to the spheres 5, 6, 10, 11, 12 and 13, and the metal on different spheres may be the same or different. A given metal may be on a group of adjacent spheres or on alternate spheres. Especially advantageous is an alternating arrangement of copper and ni ckel.

The non-metallie pharmacologically active ingredients which may be contained in contraceptives of the invention are preferably compounds having hormonal activity, local anaesthetics and weakly basic buffer substances. There may be mentioned, for example, Δ1* - pregnen - 3,20 dione (Progesterone), d - 13 - ethyl - 17a - ethinyl 17β - hydroxy 4 - gonen - 3 - one (d - norgestrel) and esters thereof, 17a - ethinyl 19 - nortestosterone (norethisterone) and esters thereof, 6 - chloro 17 - hydroxy - Ια,2a - methylene - pregna - 4,6 - dien - 3,20 - dione (cyproterone) and esters thereof, 3 - methoxy - 19 - nor 17a - pregna 1,3,5(10) - trien - 20 - yn - 17 - ol (mestranol), 18 - methyl - 19 nor - δ 11 - pregnen - 17a - ol - 3,20 - dione - 17a - caproate, 3 - hy- 13 droxy - 1,3,5(10) - oestratrien - 17 - one (oestrone), 17 - acetoxy 60,70 - epoxy - Ια,2a - methylene - 4 - pregnen - 3,20 - dione, 4,6 dichloro - 17 - acetoxy - 16a - methyl - 4,6 - pregnadien - 3,20 dione, 17a - hydroxy - 6 - methyl - pregna - 4,6 - dien - 3,20 - dione acetate (megestrol acetate), 19 - nor - 5a.- pregnan - 3,20 - dione, - hydroxy - 19 - nor - 5a - pregnan - 20 - one, 19 - norhydroxyprogesterone and esters thereof, 6 - chloro - 17 - hydroxy - pregna 4,6 - dien - 3,20 - dione acetate (chiormadinone acetate), 1,3,5(10) oestratrien - 3,170 - diol (oestradiol), 1,3,5(10) - oestratrien 10 3,16a,17s - triol (oestriol), 170 - hydroxy - 4 - androsten - 3 - one (testosterone) and esters thereof, 21 -hydroxy - 5β - pregnan - 3,20 dione and esters thereof, 17a - acetoxy - 6a - methyl - progesterone (medroxy - progesterone acetate), 10a - pregna - 4,6 - dien - 3,20 dione (dydrogesterone), 170 - oestradiol, arid xylocaine, riovocaine, triethanolamine, disodium ethylene diamine tetracetate and phosphate buffers of Sorensen, or a mixture of any two or more of the above compounds.

The non-metal!ic pharmacologically active ingredients may be in admixture or conjunction with the synthetic plastics body. For example, they may be dispersed homogeneously in the synthetic plastics body, if desired with the use of auxiliary substances, or contained in separate parts of the contraceptive device in suitable quanitites with or without these auxiliary substances, for example, as a core member in a part of the synthetic plastics body. Such auxiliary substances may be, for example, tenside, highly dispersed silicon dioxide, anti-foaming agents, solubilisers, resorption retarders, X-ray contrast agents, and ferromagnetic substances for assisting in ascertaining the location of the contraceptive device.

A preferred form of the contraceptive contain d— 13 - ethyl - 17a 30 ethinyl - 170 - hydroxy - 4 - gonen - 3 - one (<[ - norgestrel) homo- 14 42319 geneously dispersed in a silicone rubber base that vulcanises at a slightly raised temperature, contains 5% by weight of barium sulphate and is strengthened with highly dispersed silicon dioxide.

A further form of the contraceptive of the invention contains in the spheres 5, 6, 10, 11, 12 and 13 core members that consist of a mixture of 6 - chloro - 17 - hydroxy - 1α,2α - methylene - pregna - 4,6 dien - 3,20 - dione acetate (cyproterone acetate) and lactose, the synthetic plastics body of this contraceptive consisting of an ethylene/ vinyl acetate copolymer. The core members may have a cylindrical surface and end surfaces of which the radius of curvature is within the range of from the radius of the cylindrical surface (giving substantially spherical core members when the length of the cylindrical surface is negligible) to infinity (giving cylindrical core members).

The pharmacologically active ingredients contained in the threadshaped appendage 19 are arranged to be released in a controlled manner from the carrier material of synthetic plastics at a given level within certain predetermined limits over a limited period, that is to say, in the first months of use of the contraceptive, and subsequently the contraceptive action is derived from the contraceptivedevice, which, containing an active ingredient is also active on its own.

The dimensions of the thread or filament that constitutes the appendage 19 are so chosen that the appendage can extend into the cervical canal, but not into the vagina. This thread or filament has a diameter of 0.2 to 1.0 mm. and a length of 1.0 to 5.0 cm. The thread or filament has a content of pharmacologically active ingredient of from 10% to 70%. Throughout the specification, all percentages are by weight.

The non-metallie medicaments present in the thread-shaped intracervical appendage are preferably compounds having hormonal activity.

For example, there may be mentioned Δ1* - pregnen - 3,20 - dione (pro- 15 42319 gesterone), cl - 13 - ethyl - 17a - ethinyl - 17β - hydroxy - 4 - gonen 3 - one (d - norgestrel) and esters thereof, 17a - ethinyl - 19 - nortestosterone (norethisterone) and esters thereof, 6 - chloro - 17 hydroxy - Ια,2a - methylene - pregna - 4,6 - dien - 3,20 - dione (cypro5 terone) and esters thereof, 3 - methoxy - 19 - nor - 17a - pregna 1,3,5(10) - trien - 20 - yn - 17 - ol (itiestranol), 18 - methyl - 19 nor - a1* - pregnen - 17a - ol - 3,20 - dione - 17a - caproate, 3 hydroxy - 1,3,5(10)oestratrien - 17 - one (oestrone), 17 - acetoxy 6g,7e - epoxy - Ια,2a - methylene - 4 - pregnen - 3,20 - dione, 4,6 10 dichloro - 17 - acetoxy - 16a - methyl - 4,6- pregnadien -3,20 - dione, 17o - hydroxy - 6 - methyl - pregna - 4,6 - dien - 3,20 - dione acetate (megestrol acetate), 19 - nor - 5a - pregnan - 3,20 - dione, 3$ - hydroxy 19 - nor - 5a - pregnan - 20 - one, - 19 - norhydroxy - progesterone and esters thereof, 6 - chloro - 17 - hydroxy - pregna - 4,6 - dien 15 3,20 - dione - acetate (chlormadinone - acetate), 15,16a - and 15,16g methylene - 176 - hydroxy - 18 - methyl - 17a - ethinyl - 4 - oestren 3 - one, 176 - hydroxy - 4 - androsten - 3 - one (testosterone) and esters thereof, 21-hydroxy - 5β - pregnan - 3,20 - dione and esters thereof, 17a - acetoxy - 6a - methyl - progesterone (medroxy - proges20 terone acetate), and 10a - pregna - 4,6 - dien - 3,20 - dione (dydrogesterone), or a mixture of any two or more of such compounds.

There are preferred steroid hormones having a gestagenic activity, such as d - norgestrel and progesterone, norethisterone, cyproterone acetate, norhydroxyprogesterone, 15,16a - and 15,163 - methylene -^25 norgestrel.

The non-metallic pharmacologically active ingredients in the thread or filament are dispersed homogeneously therein, if desired with the addition of auxiliary substances. Such auxiliary substances may be, for example, tenside, anti-foaming agents, solubilisers and resorption retarders such, for example, as highly dispersed silicon dioxide. - 16 42319 As synthetic plastics for making the medicament-containing appendage 19 there may be used, more especially, LTV-silicone rubber twocomponent compositions such as can be prepared, for example, by the process of U.S.. Patent 2,823,218 (see also the article by W. Noll, Chemie and Techno!ogie der Silicone, 1968, page 341, and ChemikerZeitung 97 (1973), pages 176 et seq.) Especially suitable are those compositions, that contain from 895! to 91% of linear dimethyl - polysiloxane containing a maximum of 0.5 mol % of methyl - vinyl - siloxane units and 9—11% of dimethyl polysiloxane containing Si-H-bonds and having a molecular weight of 500 to 1000, which may contain up to three Si-H-bonds and are catalysed with platinum or platinum compounds such, for example, as hexachloroplatinic acid, or one which contains 85—89% of dimethyl - polysiloxane having a maximum of 0.5 mol % of methyl vinyl - siloxane units, 5—6% of dimethyl polysiloxane containing Si-Hbonds, and 5—10% of a cross-linking and strengthening dimethyl - polysiloxane resin having a maximum of 1.2 mol % methyl - vinyl - siloxane units, and which is catalysed with a platinum - ethanol complex compound.

The contraceptives of the invention are superior to the known contraceptives in their long-term action as their pregnancy rate during application, determined on the basis of the life-table method, is markedly lower and fewer spontaneous expulsions and other side effects occur.

The expulsion rate of the contraceptives of the invention is extraordinarily low, although the devices contain no abutments acting against expulsive movement and their shape does not permit of anchoring in the mucous membrane or muscalature of the uterus. In contradistinction to intra-uterine contraceptives free from pharmacologically active ingredients a large surface of contact between the device and the endometrium can be dispensed with without impairing activity, because a better activity is obtained by the addition of one or more active ingredients, - 17 42319 By the use of synthetic plastics in themselves known, but not hitherto usual for making intra-uterine contraceptives, it is possible to produce, for example, gestagen-containing contraceptives, which over periods from months to years have a rate of release of medicament at a dosage within the limits required for intra-uterine contraception.

These contraceptives, independently of the size of the cavum uteri, are capable of universal use. The devices are so constructed that they do not penetrate the musculature of the uterus or even push or cut into it.

An advantage of the contraceptive device of the invention having 10 filamentary appendage containing a substance having gestagenic activity is that the tranquillising action of gestagens has a favourable effect on the uterus (UFER, J., Hormontherapie in der Frauenhei1kunde, Verlag Walter De Gruyter Berlin, 1972, p. 124). The physiological increase in the motility of the musculature of the uterus that occurs after in15 serting a foreign body is in this way reduced. Also, in this way, the rate of early expulsions is lowered and, as a result of this, the number of pregnancies that occur is also reduced. Thus, the disadvantage hitherto associated with all intra-uterine contraceptives of a high failure rate in the first few months of use is eliminated, that is to say, the first critical phase in the use of intra-uterine pessaries can be bridged.

The intra-uterine contraceptive devices of the invention are formed in a manner favourable for application. For application there may be used suitable known insertion tubes 16 having, for example, an internal diameter of 3.5 mm. and a wall thickness of 0.5 mm., and formed of highpressure polyethylene or other suitable synthetic plastics. The contraceptive is inserted under aseptic conditions up to the point of connection of the sphere 5 with the indicator thread 18 fastened in the eye 15 and the pull and push rod 17 connected thereto. Thus, aseptic conditions can be maintained because the contraceptive device can be inserted into the applicator tube by pulling the rod 17 and without removing the bag in which the device and applicator have been stored and without touching the device itself. The sphere 5 of the device forms a ball closure for the application unit consisting of the contraceptive and applicator. As the edge of the insertion tube 16 is covered, primary injuries during application are eliminated. Moreover, the ball-shaped end having a diameter of 4 to 5 mm. prevents the fundus uteri from being cut into. The application of the contraceptive device can easily be carried out by a professional person. It can be carried out under aseptic conditions without anaesthesia or the use of further medicaments or dilation of the cervical canal without causing spasmodic pain, even in the case of wdmen who have not given birth.

The following Examples illustrate the invention: Example 1 An intra-uterine contraceptive device comprising a synthetic plastics bocty consisting of a thermoplastic polyether-ester elastomer sprayed onto a therephthalate base and having the outline shown in Figure 1 has the following dimensions: Total length 3.6 cm, diameter of the sphere 5 4.8 mm, diameter of the sphere 6 1.5 mm., diameter of each of the spheres 1 and 10 to 13 2.8 mm., diameter of the round rod 4 1.3 mm., diameters of the round rods 2, 3 and 7 to 9 1.5 nm. lengths of the round rods 3 and 4, 0.85 cm and 0.65 cm, respectively, length and diameter of the end piece 14 4.5 mm. and 2.8 mm., respectively, and total weight of the synthetic plastics body 220 mg. The angle between the axes of the rods 3 and 4 is 123°. The angle between the axis of the rod 2 and the axis of the rod 3 and the angle between the axis of the rod 2 and the axis of the rod 4 are equal.

The physical properties of the device are as follows: Elongation at break: 200% Tensile strength: 365 kilograms per square centimetre. - 19 19 Shore hardness: D 55 Modulus of elasticity: 1410 kilograms per square centimetre.

Coefficient of restitution: 55%.

Flexural modulus: 2100 kilograms per square centimetre.

The surfaces of the spheres of the synthetic plastics body are electroplated with the aid of an adhesive underlayer. The spheres 5, 6, 10, 11, 12 and 13 are galvanically coated with nickel having a layer thickness of 100 pm and the spheres 5, 11 and 13 are in addition galvanically co'ated with copper having a layer thickness of 100 pm.

Example 2 A synthetic plastics body having the dimensions given in Example 1 is formed from a thermoplastic synthetic plastics material derived from polyethylene, which material contains carboxyl groups connected by copolymerisation to the chain molecules of the polymer and is cross-linked with sodium ions. The spheres 5, 6 and 10 to 13 of the synthetic plastics body are chemically coppered on the Surface, the layer thickness being about 0.5 pm, with the interposition of an adhesive underlayer of highly dispersed iron. Nickel is'electro-deposited, the layer thickness being 80 pm, on the chemically deposited copper layer. The spheres 5, 11 and 13 are in addition galvanically coated with copper having a layer thickness of 60 pm.

Example 3 \ 75.0 grams of a thermoplastic polyether - ester elastomer on a terephthalate base present in the form of a very fine granulate are uniformly mixed with 12.5 grams of highly dispersed copper powder and 12.5 grams of highly dispersed nickel powder. From this mixture there is formed a contraceptive device having the shape, dimensions and physical properties specified in Example 1. - 20 48319 Example 4 60.0 grams of a catalysed silicone rubber two-component mixture of low temperature vulcanizing type (LTV) are mixed with 40.0 grams of highly dispersed silicon dioxide. From the suspension there is pro5 duced, by vulcanizing the moulded mass for one hour at 110°C., a contraceptive device having the dimensions given in Example 1, except that the angle between the axes of the rods 3 and 4 is 125°.

The physical properties of the device are as follows: Elongation at break: 290% Tensile strength: 70 kilograms per square centimetre.

Shore hardness: 0 40.

Coefficient of restitution: 45% In the manner described in Example 2 the synthetic plastics bodies are partially and in alternation galvanically coated on the surface with copper and nickel.

Example 5 An intra-uterine contraceptive device is produced in the following manner: There are formed from high pressure polyethylene synthetic plastics bodies having the outline shown in Figure 1 and the following dimensions: Total length 3.4 cm., diameter of sphere 5 4.6 mm., diameter of sphere 6 1.6 mm., diameter of each of the spheres 1 and 10—13 2,6 mm., diameter of the rod 4 1.2 mm., diameter of each of the rods 2, 3 and 7 to 9 1.6 mm., length of the rods 3 0.9 cm, length of the rod 4 0.7 cm, length of the end-piece 14 4.5 mm. and width of the end-piece 14 2.6 mm.

On the spherical parts 5, 6 and 10 to 13 of the synthetic plastics body silver is deposited by reduction, the layer thickness being about 1 pm. On this silver layer copper is electro-deposited, the layer thickness being about 90 pm, and the surface of each of the spheres 5, - 21 42319 Π and 13 is galvanically coated in addition with silver, the layer thickness being 70 pm.

Example 6 A synthetic plastics body having the dimensions given in Example 5 5 (the angle between the axes of the rods 3 and 4 being 123° and the angle between the axes of the rods 2 and 3 being equal to the angle between the axes of the rods 3 and 4), the outline shown in Figure 1 and the physical properties given in Example 1, is formed by injection moulding a thermoplastic polyether-ester elastomer based on a tereph10 thalate base. A partial metal coating of the synthetic plastics body, consisting of copper and silver in alternating order, is applied, using the procedure described in Example 2, with the aid of an adhesive underlayer and subsequent electro-deposition. The spheres 5, 6 and 10 to 13 are coated with a layer of copper having a thickness of 100 pm, and the spheres 5, 11 and 13 are additionally coated, on top of the 100 pm copper layer with a layer of silver having a thickness of 75 pm.

Example 7 A synthetic plastics body of thermoplastic polyether-ester elastomer based on terephthalate is formed having the outline shown in Figure 1 and the dimensions and physical properties given in Example 1. The spheres 6, 10 and 12 are galvanically coated, after applying a conductive silver lacquer having a layer thickness of 10 pm, with nickel, the layer thickness being 90 pm. The spheres 5, 11 and 13 are coated, also over a layer of conductive silver lacquer having a thickness of about pm, with silver having a layer thickness of 80 pm.

Example 8 .0 grams of micronised d - 13 - ethyl - 17a - ethinyl - 17$ hydroxy - 4 - gonen - 3 - one and 5.0 grams of highly dispersed barium sulphate are uniformly mixed with 60.0 grams of very finely granulated - 22 42319 high pressure polyethylene having a particle size of about 500 pm. From this mixture there is formed an intra-uterine contraceptive device having the outline given in Figure 1 and the dimensions mentioned in Example 5.

Example 9 .0 grams of micronised d. - 13 - ethyl - 17a- ethinyl - 17g hydroxy - 4 - gonen - 3 - one (d - Norgestrel) are incorporated in a mixture of 5.0 grams of highly dispersed barium sulphate, 20.0 grams of highly dispersed silicon dioxide and 45.0 grams of catalysed LTVsilicone rubber two-component composition. The suspension is shaped and vulcanized for one hour at 110°C to form d - norgestrel-containing synthetic plastics bodies having the outline shown in Figure 1 and the dimensions specified in Example 1 except that the angle between the axes of the rods 3 and 4 is 125°. The physical properties of the device are as specified in Example 4.

Example 10 From a mixture of 50.0 grams of micronised progesterone and 49.1 grams of lactose with the addition of 0.1 gram of lubricant there are made by injection molding generally cylindrical mouldings of 2 mm. diameter, the end faces being convex and having a radius of curvature of 3 mm. The progesterone mouldings are inserted as cores in the spherical parts 5 and 10 to 13 of an intra-uterine contraceptive device of which the outline is as shown in Figure 1 and the dimensions are as specified in Example 5 except that the angle between the axes of the rods 3 and 4 is 125°. Apart from the mouldings already referred to, the device is made from a mixture of 5.0 grams of barium sulphate, 35.0 grams of highly dispersed silicon dioxide and 60.0 grams of catalysed LTV-silicone rubber two-component composition by vulcanization for one hour at a temperature of 100°C in conjunction with moulding. The physical properties of the device are as specified in Example 4.

Example 11 A homogeneous mixture of 40.0 grams of 6 - chloro - 17 - hydroxy 1α,2α - methylene - pregna - 4,6 - dien - 3,20 - dione acetate with 59.8 grams of lactose and 0.2 gram of a lubricant mixture is moulded under pressure to form generally cylindrical mouldings having a diameter of 2 mm., the end faces being convex and having radius of curvature of 3 mm. These mouldings are incorporated as cores in the spheres 5 and 10 to 13 of an intra-uterine contraceptive device, of which the body has the outline shown in Figure 1 and which has the dimensions specified in Example 5, and which is made of high pressure polyethylene with the addition of 5% of barium sulphate.

Example 12 With the mixture described in Example 9 there is made by moulding and vulcanizing for 2 hours at 100°C a medicament-containing synthetic plastics body, from which is made by extraction in succession with 10 ml of ethanol of 96% strength for 90 minutes and ethanol of 70, 50, 30 and 10% strength for 30 minutes an intra-uterine contraceptive device of which the core of the synthetic plastics body is enriched with d - nor20 gestrel. The physical properties and the angle between the axes of the rods 3 and 4 of the device are as specified in Example 4.

Example 13 50.0 grams of micronised 17a - ethinyl - 19 - nortestosterone oenanthate are homogeneously mixed with 10.0 grams of highly dispersed silicon dioxide, 5.0 grams of barium sulphate and 35.0 grams of catalysed LTV-silicone rubber two-component composition. The mixture is moulded to form a Y-shaped body having a rod diameter of 1 mm. and a total length of 3 cm, and is vulcanized for 10 hours at 60°C., and serves as the core member of an intra-uterine contraceptive device having the outline shown - 24 <231 in Figure 1. This medicament-containing body is encased with high pressure polyethylene in such a manner that a contraceptive having the dimensions specified in Example 5 is obtained. The angle between the axes of the rods 3 and 4 is 125°. The physical properties of the device are as specified in Example 4.

Example 14 .0 grams of d - 13 - ethyl - 17<* - ethinyl - 17g - hydroxy - 4 gonen - 3 - one are mixed with 10.0 grams of barium sulphate and 60.0 grams of a very finely granulated copolymer of ethylene and vinyl acetate and the mixture is shaped to form a Y-shaped body having a rod diameter of 1 mm, and a total length of 3 cm. This medicament-containing body is encased with a mixture consisting of 45.0 grams of highly dispersed silicon oxide, 10.0 grams of barium sulphate and 45.0 grams of catalysed LTV-silicon rubber two-component composition so as to have the dimensions given in Example 1, except that the angle between the axes of the rods 3 and 4 is 126°, and the outline shown in Figure 1, and is vulcanized for one hour by heating at 100°C.

The physical properties of the device are as follows: Elongation at break: 600%.

Tensile strength: 211 kilograms per square centimetre.

Shore hardness: D 35.

Modulus of elasticity: 1 ,270 kilograms per square centimetre.

Example 15 A synthetic plastics body injection moulded from thermoplastic polyether-ester elastomer based on terephthalate has the outline shown in Figure 1 and the following dimensions: total length 3.6 cm. diameter of the sphere 5 4.8 mm., diameter of the sphere 6 1.5 mm., diameters of each of the spheres 1 and 10 to 13 2.8 mm., diameter of the rod 4 1.3 mm., diameter of each of the rods 2, 3 and 7 to 9 1,5 mm., lengths of - 25 42319 the rods 3 and 4 0.85 cm and 0.55 cm, respectively, length of the endpiece 14 4.5 mm. width of the end-piece 14 2.8 nm.; and total weight of the synthetic plastics body 220 mg. The angle between the rods 3 and 4 is 123° and the physical properties of the device are as speci5 fied in Example 1.

The surfaces of the spheres of the synthetic plastics body are electroplated with the aid of an adhesive ground layer. The spheres 5, 6 and 10 to 13 are galvanically coated with silver having a layer thickness of 100 pm and the spheres 6, 10 and 12 are galvanically coated in addition with copper having a layer thickness of 100 pm.

Example 16 In order to form an intra-uterine contraceptive device, a synthetic plastics body having the dimensions specified in Example 1 is formed from a thermoplastic synthetic plastics material derived from poly15 ethylene, which material contains carboxyl groups connected by copolymerisation to the chain molecules of the polymer and is cross-linked with sodium ions. The surfaces of the spheres 5, 6 and 10 to 13 of the synthetic plastics body are coppered chemically with the interposition of an adhesive underlayer containing highly dispersed iron (layer thick20 ness about 0,5 pm). Onto the chemically deposited copper layer silver is electro-deposited to a thickness of 80 pm. The spheres 6, 10 and 12 are galvanically coated in addition with copper having a layer thickness of 80 pm.

Example 17 75.0 grams of thermoplastic polyether-ester elastomer based on terephthalate in the form of a very fine granulate are uniformly mixed with 12.5 grams of highly dispersed copper powder and 12.5 grams of highly dispersed silver powder. The mixture is formed into an intrauterine contraceptive device having the dimensions and physical properties - 26 42319 specified in Example 1.

Example 18 60.0 grams of a catalysed silicone rubber two-component mixture of the low temperature vulcanizing type (LTV) are mixed with 40.0 grams of highly dispersed silicon dioxide. Synthetic plastics bodies having the dimensions given in Example 1, except that the angle between the axes of the rods 3 and 4 is 125°, are made with the suspension by vulcanizing the shaped mass for one hour at a temperature of 1l0°C. The physical properties of the device are as specified in Example 4.

In the manner described in Example 2 the synthetic plastics bodies are partially and in alternation galvanically coated on the surface with copper and silver.

Example 19 An intra-uterine contraceptive device is made as follows: Synthetic plastics bodies of high pressure polyethylene are formed having the outline shown in Figure 1 and the following dimensions: Total length 3.4 cm, diameter of the sphere 5 4.6 mm,, diameter of the sphere 6 1.6 mm., diameter of each of the spheres 1 and 10 to 13 2.6 mm., diameter of the rod 4 1.2 mm., diameter of each of the rods 2, 3 and 7 to 9 1.6 mm., lengths of the round rods 3 and 4 0.9 cm and 0.7 cm, respectively, length of the endpiece 14 4.5 mm. and width of the end-piece 14 2.6 mm.

On the spheres 5, 6 and 10 to 13 of the synthetic plastics body the surface of the synthetic plastics material is activated by treat25 ment with an ionic solution of palladium. Upon this activated surface copper is chemically deposited to a layer thickness of about 1—2 pm. Silver is then electro-deposited by a customary process of galvanizing synthetic plastics to a layer thickness of about 80 pm on the spheres 6, 10 and 12 in addition 100 pm of copper. - 27 42319 Example 20 A synthetic plastics body having the dimensions given in Example 5, except that the angle between the axes of the rods 3 and 4 is 123°, and the outline shown in Figure 1, is made by injection moulding a thermo plastic polyether-ester elastomer based on terephthalate. The synthetic plastics body is partially coated with copper and silver as described in Example 19, by chemical and electrolytic deposition on the surfaces, which have previously been activated with ionic palladium solution, of the spheres 5, 6 and 10 to 13. The electrolytically deposited silver layer has a layer thickness of about 90 pm, and the electrolytically deposited copper layer has a thickness of about 60 pm. The device has the physical properties specified in Example 1.

Example 21 A synthetic plastics body consisting of thermoplastic polyether15 ester elastomer based on terephthalate partially metallised with copper and silver in alternating order and having the outline shown in Figure 1 and the dimensions given in Example 1, is, after activation of the synthetic plastics surface with ionic palladium solution, chemically coppered to a layer thickness of about 1 to 2 pm. There are then electro-deposited in succession 100 pm of silver and 80 pm of copper.

With the aid of a suitable screening lacquer the metal coating of all the round rods, of the end-piece 14 and of the central sphere 1 is removed in a two-stage process, the metallisation of the spheres 5, 11 and 13 remaining complete and that of the spheres 6, 10 and 12 being re25 tained with the exception of the 80 pm-copper layer. The physical properties of the device are as specified in Example 1.

Example 22 .0 grams of micronised ^-13- ethyl - 17« - ethinyl - 17β hydroxy - 4 - gonen - 3 - one (d - norgestrel) and 70,0 grams of LTV30 silicone rubber two-component composition (elastomer type I) are worked - 28 42319 up into a suspension free from air bubbles. The suspension is passed through a jet to form a filament and vulcanized by being heated at a temperature of 100°C. for two hours. A filament having a diameter of 0.5 mm. is obtained and is cut into lengths of 4 cm, one of which, after attachment to an intra-uterine contraceptive as shown in Figure 2, leaves a free length of 2 cm. The filament together with the contraceptive is sterilized in superheated steam for 30 minutes and packed sterile.

Example 23 In a manner analogous to that specified in Example 22, a filament having the dimensions specified in that Example is made. The filament contains as a gestagenically active steroid hormone 25% of 173-acetoxy 17a - ethinyl - 4 - oestren - 3 - one (norethisterone acetate), and is attached to an intra-uterine contraceptive device as shown in Figure 2.

Example 24 An intra-cervical filament is made using 40 parts by weight of very finely micronised progesterone which is mixed with 60 parts by weight of catalysed LTV-silicone rubber two-component composition (elastomer composition II), by shaping the progesterone suspension and then heating for one hour at !00°C. The thread is 2.5 cm in length and has a diameter of 0.5 mm. It is attached to an intra-uterine contraceptive device as shown in Figure 2.

Example 25 In a manner analogous to that described in Example 22 a filament is made having the length specified in that Example but a diameter of 0.4 mm. The filament contains as a gestagenically active steroid hormone 30% of 17a - hydroxy - 19 - norpregn - 4 - en - 3,20 - dione (norhydroxy-progesterone). It is attached to an intra-uterine contraceptive device as shown in Figure 2.

Claims (121)

1. WHAT WE CLAIM IS:1. An intra-uterine contraceptive device which comprises a Yshaped member formed of synthetic plastics material, the free end of each branch of the Y terminating in a rounded head, the stem of the Y 5 being formed with a plurality of rounded enlargements which are spaced apart from one another along the length of the stem, the angle subtended between the branches of the Y and the angles subtended between the branches and the stem of the Y each being obtuse and the resilience of the Y-shaped member being such that the branches of the Y can be so 10 resiliently deformed as to bring them into substantially axial alignment with the stem of the Y.

2. A device as claimed in claim 1, wherein the modulus of elasticity of the synthetic plastics material is within the range of from 900 to 2,900 kilograms per square centimetre. 15

3. A device as claimed in claim 2, wherein the modulus of elasticity of the synthetic plastics material is within the range of from 1,000 to 2,750 kilograms per square centimetre.

4. A device as claimed in any one of claims 1 to 3, wherein the tensile strength of the synthetic plastics material is within the range 20 of from 50 to 550 kilograms per square centimetre.

5. A device as claimed in claim 4, wherein the synthetic plastics material is a silicone elastomer having a tensile strength within the range of from 50 to 120 kilograms per square centimetre.

6. A device as claimed in claim 5, wherein the tensile strength of 25 the synthetic plastics material is within the range of from 50 to 105 kilograms per square centimetre.

7. A device as claimed in claim 4, wherein the synthetic plastics material is a thermoplastic material having a tensile strength within the range of from 150 to 550 kilograms per square centimetre,

8. A device as claimed in any one of claims 1 to 7, wherein the - 30 42319 shore hardness of the synthetic plastics material is within the range of from 35 to 85.

9. A device as claimed in claim 8, wherein the synthetic plastics material is a silicone elastomer.

10. A device as claimed in claim 9, wherein the shore hardness of the synthetic plastics material is within the range of from 40 to 75.

11. A device as claimed in claim 8, wherein the synthetic plastics material is a thermoplastic material having a shore hardness within the range of from 40 to 70.

12. A device as claimed in claim 11, wherein the synthetic plastics material has a shore hardness within the range of from 45 to 60.

13. A device as claimed in any one of claims 1 to 12, wherein the weight of the device does not exceed 0.5 gram.

14. A device as claimed in any one of claims 1 to 3, wherein the rounded heads and enlargements are interconnected by rods,

15. A device as claimed in any one of claims 1 to 14, wherein the rounded heads and enlargements, except where they adjoin another part of the Y-shaped member, are substantially spherical.

16. A device as claimed in claim 14, wherein the outer surfaces of the rods are rounded.

17. A device as claimed in claim 16, wherein the rods are of substantially circular section.

18. A device as claimed in any one of claims 14, 16 and 17, wherein the rods are substantially straight.

19. A device as claimed in any one of claims 1 to 18, wherein the total length of the device does not exceed 4 centimetres.

20. A device as claimed in any one of claims 1 to 19, wherein the total length of the device is at least 3 centimetres.

21. A device as claimed in any one of claims 1 to 20, wherein the diameter of each of the rounded heads and rounded enlargements does not - 31 2319 exceed 5 millimetres.

22. A device as claimed in any one of claims 1 to 21, wherein the diameter of each of the rounded heads and rounded enlargements is at least 1.5 millimetres.

23. A device as claimed in both claim 14 and any one of claims 15 to 22, wherein the length of each of the rods does not exceed 1.2 centimetres.

24. A device as claimed in both claim 14 and any one of claims 15 to 23, wherein the length of each of the rods is at least 0.5 centimetre,

25. A device as claimed in any one of claims 1 to 24, wherein the stem of the Y terminates at its free end in a rounded head.

26. A device as claimed in any one of claims 1 to 25, wherein the angle included between the two branches of the Y is within the range of from 120° to 130°.

27. A device as claimed in claim 26, wherein the angle included between the branches of the Y is within the range of from 121° to 127°.

28. A device as claimed in any one of claims 1 to 27, wherein the angle included between one branch of the Y and the stem of the Y is substantially equal to the angle included between the other branch of the Y and the stem of the Y.

29. A device as claimed in any one of claims 1 to 28, wherein the two branches of the Y are of different lengths and, when the two branches of the Y are brought together by flexing so that they are in substantially axial alignment with the stem of the Y, the maximum transverse dimension of the overlapping portions of the branches of the Y and the maximum transverse dimension of the stem of the Y are less than the maximum transverse dimension of the rounded head in which there terminates the free end of the longer of the two branches of the Y.

30. A device as claimed in both claim 14 and claim 29, wherein each branch of the Y comprises only a single rod and each rod terminates at - 32 42319 its free end in a sphere, the length of the rod forming the shorter of the two branches of the Y plus the diameter of the sphere in which that rod terminates at its free end being less than the length of the rod forming the longer of the two branches of the Y, and the diameter of the sphere in which the rod forming the shorter of the two branches of the Y terminates at its free end plus the diameter of the rod that forms the longer of the two branches of the Y being less than the diameter of the sphere in which the rod forming the longer of the two branches of the Y terminates at its free end.

31. A device as claimed in claim 30, wherein the length of the rod forming the shorter of the two branches of the Y is within the range of from 0.5 to 0.8 centimetre, the length of the rod forming the longer of the two branches of the Y is within the range of from 0.8 to 1.2 centimetres, the diameters of the rods forming the two branches of the Y is within the range of from 1.0 to 1.5 millimetres, the diameter of the sphere in which the rod forming the shorter branch of the Y terminates at its free end is within the range of from 1.5 to 2.0 millimetres, and the diameter of the sphere in which the rod forming the longer branch of the Y terminates at its free end is within the range of from 4 to 5 millimetres.

32. A device as claimed in any one of claims 1 to 31, wherein there is a rounded enlargement where the branches of the Y join the stem of the Y.

33. A device as claimed in any one of claims 1 to 32, wherein the stem of the Y comprises a plurality of rods and rounded enlargements arranged alternately.

34. A device as claimed in claim 33, wherein the stem of the Y comprises at least three rounded enlargements.

35. A device as claimed in claim 33 or claim 34, wherein the stem of the Y comprises not more than seven rounded enlargements. - 33 42319

36. A device as claimed in claim 35, wherein the stem of the Y comprises five rounded enlargements.

37. A device as claimed in any one of claims 33 to 36, wherein the rounded enlargements in the stem of the Y are each, except where they 5 adjoin rods, substantially spherical.

38. A device as claimed in claim 37, wherein the diameter of each of the substantially spherical enlargements in the stem of the Y is within the range of from 2 to 3 millimetres.

39. A device as claimed in any one of claims 33 to 38, wherein, in 10 addition to the said rounded enlargements, the stem of the Y terminates at its free end in a rounded head formed with an aperture.

40. A device as claimed in claim 39, wherein the rounded head in which the stem of the Y terminates at its free end has a width within the range of from 2 to 3 millimetres and a length in the direction in 15 which the stem of the Y extends within the range of from 4 to 5 millimetres .

41. A device as claimed in claim 39 or claim 40, wherein the said aperture in the rounded head extends transversely with respect to the stem of the Y. 20

42. A device as claimed in claim 41, wherein the diameter of the aperture is within the range of from 0.5 to 1.5 millimetres.

43. A device as claimed in any one of claims 40 to 42, having an indicator thread secured through the aperture in the rounded head.

44. A device as claimed in any one of claims 1 to 43, wherein the 25 axis of the stem of the Y is substantially straight.

45. A device as claimed in any one of claims 1 to 44 in combination with an applicator tube, the stem of the Y and at least the shorter of the branches, if they are of different lengths, or both overlapping portions of branches of the Y, if they are of the same length, being 30 within the applicator tube. - 34 42319

46. A device in combination with an applicator as claimed in claim 45, wherein the maximum lateral dimension of the rounded head in which the longer branch of the Y terminates at its free end is too great to permit that rounded head to enter the applicator tube.

47. A device in combination with an applicator as claimed in claim 46, wherein the arrangement is such that, during the insertion of the device into the human body, the rounded member in which the longer branch of the Y terminates at the end remote from the stem of the Y protects the body from the adjacent end of the applicator tube.

48. A device in combination with an applicator as claimed in any one of claims 45 to 47, wherein the applicator also comprises a rod movable axially within the applicator tube and secured to the device by means of a severable indicator thread.

49. An aseptic pack comprising a device in combination with an applicator as claimed in any one of claims 45 to 48 sealed within an envelope, bag or the like.

50. A device as claimed in any one of claims 1 to 44, wherein the device incorporates one or more pharmacologically active substances.

51. A device as claimed in claim 50, wherein the pharmacologically active substance is a substance having a contraceptive action.

52. A device as claimed in claim 50 or claim 51, wherein the pharmacologically active substance is or includes a metal.

53. A device as claimed in claim 52, wherein the metal is copper, silver or nickel.

54. A device as claimed in claim 53, wherein the device also incorporates another metal or metals selected from copper, silver and nickel.

55. A device as claimed in any one of claims 52 to 54, wherein the metal or metals is or are incorporated with one or more of the rounded enlargements or heads. - 35 42319

56. A device as claimed in both claim 14 and claim 55, wherein substantially no metal is incorporated with the rods as a coating.

57. A device as claimed in claim 55 or claim 56, wherein there is provided a rounded enlargement where the branches of the Y join the stem 5 of the Y and substantially no metal is incorporated with that rounded enlargement as a coating.

58. A device as claimed in any one of claims 52 to 57, wherein at least a part of the metal, or of at least one of the metals, is in particulate form and is distributed throughout at least one of the 10 rounded enlargements or heads.

59. '. A device as claimed in claim 58, wherein the plastics material of which the rounded enlargements and heads are made is such as to release the particulate metal in a controlled manner.

60. A device as claimed in any one of claims 52 to 56, 57 and 59, 15 wherein at least a part of the metal, or of at least one of the metals, is applied as a coating to one or more of the rounded enlargements or heads.

61. A device as claimed in claim 60, wherein at least one of the rounded enlargements or heads is coated with copper. 20

62. A device as claimed in claim 61, wherein the copper coating has been applied chemically.

63. A device as claimed in claim 62, wherein the surface of the plastics material to which the copper coating has been applied chemically was first activated by treatment.with palladium ions. 25

64. A device as claimed in claim 61, wherein the copper coating has been applied galvanically.

65. A device as claimed in claim 64, wherein the copper coating has been applied to a-coating of nickel.

66. A device as claimed in any one of claims 60 to 65, wherein at 30 least one of the rounded enlargements or heads is coated with nickel. - 36 42319

67. A device as claimed in claim 66, wherein the nickel coating has been applied galvanically,

68. A device as claimed in claim 67, wherein the nickel coating has been applied galvanically to a coating of copper.

69. A device as claimed in any one of claims 60 to 68, wherein at least one of the rounded enlargements or heads is coated with silver.

70. A device as claimed in claim 69, wherein the silver coating has been formed by reduction.

71. A device as claimed in claim 69, wherein the silver coating has been applied galvanically.

72. A device as claimed in any one of claims 60 to 71, wherein a metal coating, comprising one or more metal layers, has been applied to the device, a screening layer having been applied to that part of the coating that was to be retained and the part of the coating that was not covered by the screening layer having been removed,

73. A device as claimed in claim 72, wherein the said metal coating comprises two or more metal layers superimposed on one another, a screening layer having been applied to that part of the coating that was to be retained intact, the part of the coating that was not covered by the screening layer having been removed, a part of the screening layer having thereafter been removed and the outer layer of the part of the coating that was then not covered by the screening layer having been removed.

74. A device as claimed in claim 60, wherein the metal coating has been formed by coating the whole Y-shaped member of synthetic plastics material, excluding any thread or filament, with a metal-containing adhesive layer, thereafter coating the entire device with a layer of copper applied galvanically, coating a part only of the surface of the layer of copper with a layer of a material resistant to electroplating, thereafter electroplating with silver that part of the surface of the - 37 42319 device that was not covered with the said layer of material resistant to electroplating, thereafter removing the metal coating, and removing the layer of material that was resistant to electroplating.

75. A device as claimed in any one of claims 60 to 74, wherein the 5 rounded enlargements and heads, other than any rounded enlargement at the junction of the branches of the device, have been so coated with two or more metals that the outer surfaces of alternate rounded heads or enlargements are formed of the same metal.

76. A device as claimed in both claim 30 and claim 75, wherein the 10 outer surface of the rounded head in which the longer branch of the Yterminates at its free end is formed of a first metal, the outer surface of the rounded head in which the shorter branch of the Y terminates at its free end and the outer surface of the rounded enlargement in the stem next to the rounded enlargement at the junction between the branches 15 and the stem are formed of a second metal, and the outer surfaces of the remaining rounded enlargements in the stem are formed alternately of the first and second metals.

77. A device as claimed in any one of claims 1 to 44 and 50 to 76, wherein the centres of the rounded heads and enlargements and the axes 20 of the branches and stem of the Y are substantially coplanar.

78. A device as claimed in claim 50 or claim 51, wherein one or more of the pharmacologically active substances is a substance having hormonal activity.

79. A device as claimed in claim 78, wherein the substance having 25 hormonal activity is a steroid.

80. A device as claimed in claim 78 or claim 79, wherein the substance having hormonal activity is one having gestagenic activity.

81. A device as claimed in claim 79, wherein the steroid is d^ - norgestrel, progesterone, norethisterone, cyproterone acetate, norhydroxy30 progesterone, 15,16a - methylene - d^ - norgestrel or 15,16p - methylene - 38 42319 ii - norgestrel, or a mixture of two or more of such compounds.

82. A device as claimed in claim 79, wherein the steroid is any one or more of the steroid compounds specifically mentioned herein, other than a compound mentioned in claim 81.

83. A device as claimed in claim 78, wherein there is used a mixture of cyproterone acetate and lactose.

84. A device as claimed in any one of claims 50, 51 and 78 to 83, wherein one or more of the pharmacologically active substances is a substance having a local anaesthetic action.

85. A device as claimed in claim 84, wherein the substance having a local anaesthetic action is xylocaine or novocaine.

86. A device as claimed in any one of claims 50, 51 and 78 to 85, wherein at least one of the pharmacologically active substances is a substance having a weakly basic buffering action.

87. A device as claimed in claim 86, wherein the substance having a weakly basic buffering action is triethanolamine, disodium ethylene diamine tetracetate, or a phosphate buffer of Sorensen.

88. A device as claimed in any one of claims 1 to 87, which also comprises an intra-cervical filament.

89. A device as claimed in claim 88, wherein the filament incorporates one or more pharmacologically active substances.

90. A device as claimed in claim 89, wherein at least one of the pharmacologically active substances is a substance having hormonal activity.

91. A device as claimed in claim 90, wherein the substance having hormonal activity is a steroid.

92. A device as claimed in claim 90, wherein the substance having hormonal activity is one having a gestagenic activity.

93. A device as claimed in claim 91, wherein the steroid is d - norgestrel, progesterone, norethisterone, cyproterone acetate, norhydroxy- 39 42319 progesterone, 15,Τ6α - methylene - d - norgestrel or 15,16β - methylene d - norgestrel, or a mixture of two or more of such compounds.

94. A device as claimed in claim 91, wherein the steroid is any one or more of the steroid compounds specifically mentioned herein, 5 other than a compound mentioned in claim 93.

95. A device as claimed in any one of claims 50, 51 and 78 to 94, wherein the pharmacologically active substance is non-metallic and is dispersed in the synthetic plastics material.

96. A device as claimed in any one of claims 50, 51 and 78 to 94, 10 wherein the pharmacologically active substance is non-metallic and is included in or as a core member in a part of the synthetic plastics member.

97. A device as claimed in any one of claims 50, 51 and 78 to 96, which also contains an auxiliary substance. 15

98. A device as claimed in claim 97, wherein the auxiliary substance is tenside, silicon dioxide, an anti-foaming agent, a solubiliser, a resorption retarder, an X-ray contrast agent or a ferro-magnetic material.

99. A device as claimed in any one of claims 1 to 98, wherein the synthetic plastics material is polyethylene, an ionomeric resin derived 20 from polyethylene, a copolymer of ethylene and vinyl acetate, a polyethylene containing carboxyl groups connected by copolymerisation to the chain molecules and cross-linked by sodium ions, a polyamide, a polyether-ester elastomer on a terephthaiate base, or a silicone rubber, or any two or more of such compounds. 25

100. A device as claimed in claim 99, wherein the synthetic plastics body is formed of layers of the same plastics material or of different plastics materials.

101. A device as claimed in claim 99 or claim 100, wherein the silicone rubber is a silicone rubber of the LTV-type. 30

102. A device as claimed in claim 101, wherein the silicone rubber - 40 42319 of the LTV-type is one that is obtainable by the process described in U.S. Patent No. 2,823,218.

103. A device as claimed in claim 99, wherein the silicone rubber is one that contains from 89 to 91% of linear dimethyl - polysiloxane 5 containing a maximum of 0.5 mol per cent of methyl - vinyl - siloxane units and 9 to 11% of dimethyl - polysiloxane containing Si-H-bonds and having a molecular weight of 500 to 1000, which may contain up to 3 SiH-bonds and are catalysed with platinum or a platinum compound.

104. A device as claimed in claim 101, wherein the silicone rubber 10 is one that contains from 85 to 89% of dimethyl - polysiloxane having a maximum of 0.5 mol percent of methyl - vinyl - siloxane units, 5 to 6% of dimethyl - polysiloxane containing Si - H - bonds, and 5 to 10% of a cross-linking and strengthening dimethyl - polysiloxane resin having a maximum of 1.2 mol % methyl - vinyl - siloxane units, and which 15 is catalysed with a platinum - ethanol complex compound.

105. A device as claimed in any one of claims 88 to 104, wherein the intra-cervical filament has a diameter of 0.2 to 1.0 mm. and a length of 1.0 to 5.0 cm.

106. A device as claimed in claim 105, wherein the filament is com20 posed of a synthetic plastics material.

107. A device as claimed in claim 106, wherein the synthetic plastics material is a silicone rubber of the LTV-type.

108. A device as claimed in claim 107, wherein the silicone rubber is as specified in claim 102 or claim 103. 25

109. A device as claimed in any one of claims 88 to 108, wherein the filament contains from 10 to 70 per cent by weight of one or more pharmacologically active substances.

110. A device as claimed in claim 51, which contains - norgestrel homogeneously dispersed in a silicone rubber base that vulcanises at a 30 slightly raised temperature, and also contains barium sulphate and highly - 41 4 2 319 dispersed silicone dioxide.

111. A device as claimed in claim 51, which contains, as the pharmacologically active substance or one of the active substances, nuclear particles consisting of a mixture of cyproterone acetate and lactose, 5 and contains a copolymer of ethylene and vinyl acetate as the material of the synthetic plastics member.

112. A device as claimed in any one of claims 79 to 111, wherein the synthetic plastics member contains from 25« to 50% by weight of one or more steroids having a contraceptive action. 10

113. An intra-uterine contraceptive device as claimed in claim 1, substantially as described in any one of Examples 1 to 7 and 15 to 21 herein.

114. An intra-uterine contraceptive device as claimed in claim 1, substantially as described in any one of Examples 8 to 14 and 22 to 25 15 herein.

115. A method of contraception, wherein a device as claimed in any one of claims 1 to 48 and 50 to 114 is fitted to a human female.

116. A contraceptive pack which comprises an intra-uterine contraceptive device as claimed in any one of claims 1 to 48 and 50 to 114 20 and instructions for its use in fitting the device to a human female.

117. A contraceptive pack as claimed in claim 116, which also contains an applicator.

118. A contraceptive pack as claimed in claim 116 or 117, wherein the device and applicator are aseptically sealed within an envelope, bag 25 or tube.

119. A contraceptive pack as claimed in any one of claims T16 to 118, which also comprises an intra-cervical filament as specified in any One of claims 90 to 94 and 105 to 109.

120. An intra-uterine contraceptive device substantially as herein30 before described with reference to, and as shown in, Fig. 1 of the - 42 42319 accompanying drawings.

121. An intra-uterine contraceptive device substantially as hereinbefore described with reference to, and as shown in, Fig. 2 of the accompany!ng drawi ngs.