CA1037806A - Intra-uterine contraceptive device - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
An intra-uterine contraceptive device for human use includes a generally Y-shaped, synthetic plastic body formed of spheres interconnected by cylindrical rods, the body incorporating one or more pharmacologically active substances, e.g., metals, metal alloys, hormones, local anaesthetics and weakly basic buffer substances. The plastic may be, e.g., polyethylene or an ethylene/vinyl acetate copolymer, and the hormone may be, for example, progesterone, d-norgestrel, cyproterone, or mestranol.

Description

~037~0~
This invention relates to a medicament-containing intra-uterine contraceptive 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 that are required when the same medicaments are administered 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 long been proposed 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 preventinq 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, polyethylene and polyethylene/vinyl acetate, alone or with added barium sulphate, were used to form a very wide variety of contraceptives for intra-uterinal use, but they were very cumber-some and bulky for the uterine cavity. Examples of such devices are the MARGULIS Spiral (U.S. Patent No. 3,200,815; Federal German Patents Nos. 1,416,942 and 1,441,359), BIRNBERG's Bow (U.S. Patent No. 3,253,590), Saf-T-C~il (a trademark) (U.S. Patents Nos.
3,234,938 and 3,374,788) and LIPPES LOOP (a trademark) (U.S. Patent No. 3,250,271).
With the development of T-shaped contraceptives (U.S.
Patent No. 3,533,406), DALXON-Shield (a trademark) (German Offen-legungsschrift No. 1,956,701) and LIPPES LOOP D (a trademark), there became known contraceptives for intra-uterinal use made from synthetic plastic material and , - ~
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smaller in 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 plastic material. -There were dispersed as medicaments in the synthetic plastic material copper powder or steroid hormones having a gestagenic action. One construction of the DALKON Shield, for example, contain- -ed copper highly dispersed in the synthétic plastic carrier. The COPPER-T and COPPER-7 (U.S. Patent No. 3,563,235) were partially bound with copper wire, and the COPPER TCu 220 C (U.S. Patent No.
3,533,406) was partially covered with copper sleeves (U.S. Patent No. 3,563,235). The reliability in contraceptive action of the devices for intra-uterinal administration provided with copper ~ ;
on their surfaces was increased by the additional application of zinc or silver [see U.S. Patent No. 3,563,235; Zipper et al., Amer.J.Obst.Gynec. 105, 529-534 (1969); 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 plastic material and having connected thereto a capsule of silicone rubber containing medicament. Such combination-contraceptives are also intended for application in the cavum uteri lInt.J.Fert. 15 (1970) 210].
It has been fou~d, 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 lFORTIER et al., J.Amer.Obstet.Gynec. 115 (1973) 291; TATUM, contraception 6 (1972) 179; MISHELL et al., Amer.J.Obstet.Gynec.

116 (1973) 1092].

- 2 -Disadvantages of previously proposed contraceptives for intra-uterinal 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.Popul.Family Plan 4,6: (1973) 139]-The most frequent side effects of known contraceptivesfor intra-uterinal 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 DALKON-Shield (a trademark), T-shaped contraceptives or LIPPES LOOP D (a trademark).
Side effects, removals necessitated by side effects and expulsions of the intra-uterine contraceptives made of synthetic plastic materials do not, however, result solely from the unfavour-able shape and dimensions of the devices. Other important factors in this connection are the elasticity and hardness of the synthetic plastic material. Devices made of synthetic plastic material of too low an elasticity and of high hardness cause frequent pains and spasms. The devices must be made in different sizes to correspond to the dimensions of the cavum uteri. Contraceptives made of a synthetic plastic material that is too soft may twist within the uterus and are then often spontaneously expelled. Occasionally, they penetrate the uterine musculature. Fragments of such intra-uterinally used contradeptives and intact devices, if they have penetrated the wall of the uterus, enter the peritoneal cavity and there lead to further injuries or ligature the intestinal con-volutions.
Statistical studies have shown that, with the lessbulky intra-uterine contraceptives made of synthetic plastic material, the frequency of side effects and spontaneous expulsions is lower . .. . . . . , . ~ ~ , , ; . ..
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~,0*7~06 than for bulky contraceptive devices. The absolute number of undesired side effects and spontaneous explusions, however, is too high to be tolerable for either type of intra-uterine contra-ceptive device. Moreover, in the case of the less bulky intra-uterine contraceptives, there have been observed side effects such as the occurence of dysmenorrhoea, metromenorrhagia and leucorrhoea associated with continuous pain and occasionally convulsive pain [compare, for example, Ostergard et al., Contra-ception 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 Prodecures 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 5(2), 119-127 (1972), Baeyertz, Austr.N.Z.J. Obst.
Gynec. 11 117-121 (1971); Davis, Amer.J.Obst.Gynec. 114(1), 134-151 (1972)]. ~
Moreover, perforation of the wall of the uterus has 7" ' frequently been observed with this type of contraceptive (Buchmann, ;
Fert.Steril. 21(4), 348-355 (1973)].
Rigidly formed intra-uterine contraceptives may break ;
in the uterus because of the alternating bending stresses to which `
they are subjected. The broken pieces may be expelled spontan-eously without being noticed or, as in the case of undamaged devices, penetrate the wall of the uterus and enter the perintoneal cavity [Last, J.Obst.Gynec.Brit.Commonw. 79(2), 190-191 (1972); -Domany et al., Brit.Med.J. 1 549 (1973)].
The use of medicament-containing intra-uterine contrace- -ptives such as the TCu 200 or TCu 220C, the contraceptive contain-ing copper and zinc, or a device containing progesterone (German Patent Specification No. 2,247,949) or dl-11~-ethyl-17~-ethinyl-. ~ . . . ~:

17~-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 plastic material.
However, such medicament-containing intra-uterine contra-ceptives, like the similarly shaped devices free from medicament, lead during the period of use to undesired side effects such as haemorrhages and pains IFortier et al., J.Amer. Obst.Gynec. 115

(3), 291-297 (1973); Tatum, Contraception 6(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 because of the tendency of synthetic plastics to acquire a permanent set, they cannot be sterilized in the 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, since the fold-up device and the upper edge of the insertion tube have sharp edges. The DALKON-Shield (a trade-mark) and the applicator developed for this device are so con-stituted 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 the contraceptive because of side effects, there are also spontan-eous 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)]. S~ontaneous expulsions have been observed with a few of these devices [DALKON Shield (a trademark); German Offen-legungsschrift No. 1,956,701; Ostergard et al., Obst.Gynec. 41(2), 257-2S8 (1973); T-shaped contraceptives, COPPER-7: Newton et al., Lancet 1972/II No. 7784, 951-954; Bernstein et al., Contraception 6(2), 99-107 lQ378Q6 (1972)], even through they are so shaped that they have abutments arranged to oppose the direction of expulsion. IJones et al., Brit.Med.J., 3, 143 (1973)1. In the DALKON Shield (a trademark) the abutments are fixed lateral projections in the form of fingers and prongs on a ring. Intra-uterine contraceptives thus formed -naturally have the risk of causing injuries to the uterus during application, during the period of use IKoetsawang, Contraception 7(4), 327-332 (1973); Johannisson, Contraception 8(2), 99-112 ~-(1973); Lehfeldt et al., Obst.Gynecol. 37(6), 826-831 (1971); ;
Brooks et al., Amer.J.Obst.Gynecol. 113(1), 104-106 (1972); Sprague et al., Obst.Gynecol. 41(1), 80-82 (1973); Rienprayura et al., Contraception 7(6), 515-521 (1973)] and during removal ISnowdon et al., Contraception 7(2), 91-104 (1973)]. KAMAL et al. [Fert.
Steril. _ (3), 165-169 (1973)] described 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 No. 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 re-sult of mechanical stress or become separated from the body of synthetic plastic 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 dis-advantages in that their total weight or the distribution of weight within the device tend to cause spontaneous expulsion. The COPPER-TCu 220 C weighs 612 mg, and one construction of the LIPPES LOOP

(a trademark) ',' ' ' ,: ' .. ~ ', . ~ . . ' . . .. ,' ' ' ' ~78~6 weighs 665 mg. Metal-containing intra-uterine contraceptives, such as that described in German Offenlegungsschrift No. 2,207,939, are easily expelled spontaneously (the metal rings all being fixed on the shaft of the synthetic plastic body).
Other contraceptives, for example, those proposed in German Patent Specification No. ~441,359 or German Offenlegungssch-rift No. 2,207,939, have an extension of the spiral to be applied intra-uterinally, which extension extends out of the cavum uteri through the cervical canal into the vagina. Such devices are made entirely of synthetic plastic material. However, the synthetic plastic suitable for forming the spiral is too rigid for the part located within the cervix and within the vagina. Therefore, with such 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 explusion and a subsequent pregnancy.
A further disadvantage of the known medicament-containing contraceptives is that the long term release of non-metallic 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 Sltudies 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 reliability in action as the known contraceptives administered ~ os, which contain hormones as medicinally active `~
substances [DAVIS, Amer.J.Obstet.Gynec. 114(1972) 134; FUCHS et al., Contraception 5(1972) 119].

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It is an object of the present invention to make it poss- -ible 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, nulligravidae, 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 explusions. 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 o 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 dilatation 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 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 ;
....

^` 103~7806 pregnancies duirng the period of use is as far as possible equal to zero.
According to the present invention there is provided 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 member, the stem of the Y being formed with a plurality of rounded enlarge-ment members 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 present invention substantially provides a con-traceptive consisting of round rods connecting a plurality of spheres of synthetic plastic of high elasticity, tensile strength and medium hardness having a maximum weight of 0.5 gram, and incorporating one or more pharmacologically active substances, and optionally having an intra cervical appendage of synthetic plastic, preferably LTV-silicone elastomer, in the form of a thread or filament.
The physical properties of the synthetic plastics material should be as follows:
Modulus of elasticity (ASTM D 747 RESP. 638):
900 to 2,900, preferably, 1,000 to 2,750, kilograms per squar~ centimetre.
, Tensile strength (ASTM D 638 RESP. 412):
50 to 120, preferably, 60 to 105, for silicone -elastomers and 150 to 550 kilograms per square _ centimetre for thermoplastics.
Shore hardness: A 35 to 85, preferably, 40 to 75, ~_9_ ' ;' A

-.
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-(DIN 53 505) for silicone elastomers, and D to 40 to 70, preferably, 45 to 60 (ASTM D 676) for thermoplastics.
J 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 two forms of device.
Referring to Fig. 1, the first form of device is generally Y-shaped and has a total length of 3 to 4 cm. Three roads 2, 3, and 4 extend outwardly from a central sphere 1 having a diameter of 2.5 to 3.0 mm. The rods 2, 3 and 4 terminate in spheres, and have different lengths and diameters of 1.0 to 1.5 mm. The length of the rod 3 is 0.8 to 1.2 cm, and the rod 4 is 0.5 - 0.8 cm long. The spheres 5 and 6 at the end of rods 3 and 4 have diameters of 4 to 5 mm and 1.5 - 2.0 mm, respective ly. The rods 3 and 4 are ~- -~ ~ .

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".', ' '' . . " ' `' . ' `., ' ,., ; '. ' `~: , at an obtuse angle to the third rod 2. The stem of the Y is formed by the third rod 2 which continues into an assembly of three rods 7, 8, and 9 interconnecting four spheres 10, 11, 12 and 13 having a diameter of 2 to 3 mm, the stem terminating in a bean-like end-piece 14 having a length of 4 to 5 mm and a diameter of 2 to 3 mm. The piece 14 is provided with 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.
Moreover, 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 rods 2 and 3 is substantially equal to the angle between the axes of the rods 2 and 4.
The bore or eye 15 is provided for receiving a thread 18 of suitable material, for example, nylon or polyester. The thread 18 serves as an indicator thread for indicating in a simple manner the presence of the contraceptive device.
Figure 2 illustrates a second form of contraceptive device similar to the first form of device, except that another thread or filament 19 of synthetic plastic serves as an intra-cervical appendage which is passed through the central bore 15and secured to the end-piece 14, and also contains one or more pharmacologically active ingredients.
For making the synthetic plastic body for the contra-ceptive of the invention there may be used synthetic plastics, which release one or more pharmacologically active ingredients contained in admixture or conjunction with the synthetic plastic and have adequate mechanical properties such as, for example, tensile strength, elasticity and cold stretchability, and can eas-ily be formed into suitable shapes. Such plastics include, for example, polyethylene, ethylene/vinyl acetate copolymers, ionomeric resins derived from polyethylene, polyamides, polyether-ester elastomers on a terephthalate base, polyethylene terephtha]ate, ~ ;

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~037~06 and also silicone rubbers. The synthetic plastics may be usedsingly or in combination, for example, in layers. The pharma-cologically active ingredients incorporated in the intra-uterine contraceptive may be metals, metal alloys or non-metallic pharma-cologically 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.
Suitable metallic active ingredients include, for example, metals such as, for example, copper, silver, nickel, combinations of such metals with one another and mixtures of the pure metals with the corresponding metal alloys. The metal or metal alloys may be uniformly dispersed in the entire synthetic plastic 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 plastic bodies in known manner, 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 applied should be such that the metal does not become detached from the synthetic plastics body when the contracep-tive 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. The arrangement of metals on the different spheres may be in groups or alternating. Especially advantageous is an alternating arrangement of copper and nickel.

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The non-metallic pharmacologically active ingredients which may be used in contraceptives of the invention are preferably compounds having hormonal activity, local anaesthetics and weakly basic buffer substances. Such ingredients include, for example, ~4-pregnen-3,20-dione (Progesterone), d-13-ethyl-17~-ethinyl-17~-hydroxy-4-gonen-3-one (d-norgestrel) and esters thereof, 17~-ethinyl-19-nortestosterone (norethisterone) and esters thereof, 6-chloro-17-hydroxy-1~,2~-methylene-pregna-4,6-dien-3,20-dione (cyproterone) and esters thereof, 3-methoxy-19-nor-17~-pregna-1,3,5(10)-trien-20 -yn-17-ol (mestranol), 18-methyl-19-nor-~4-pregnen-17~-ol-3,20-dione, -17~-caproate, 3-hydroxy-1,3,5(10)-oestratien-17-one (oestrone), 17-acetoxy-6~,7~-epoxy-1~,2~-methylene-4-pregnen-3,20-dione,

4,6-dichloro-17-acetoxy-16a-methyl-4,6-pregnadien-3,20-dione, 17-hydroxy-6-methyl-pregna-4,6-dien-3,20-dione acetate (megestrol acetate), l9-nor-5~-pregnan-3,20-dione, 3~-hydroxy-19-nor-5~- ~
pregnan-20-one, l9-norhydroxyprogesterone and esters thereof, ;
6-chloro-17-hydroxy-pregna-4,5-dien-3,20-dione acetate (chloro-madinone acetate), 1,3,5tlO)-oestratrien-3,17~-diol (oestradiol), -.
1,3,5(10)-oestratrien-3,16a,17~-triol (oestriol), 17~-hydroxy-4-androsten-3-one (testosterone) and esters thereof, 21-hydroxy-5~
-pregnan-3,20-dione and esters thereof, 17~-acetoxy-6~-methyl- -progesterone (medroxy-progesterone acetate), 10~-pregna-4,6-dien -3,20-dione (dydrogesterone), 17~-oestradiol, and xylocaine, novocaine, triethanolamine, disodium ethylene diamine tetracetate and phosphate buffers of Sorensen.
The non-metallic pharmacologically active ingredients -~
may be in admixture or conjunction with the synthetic plastic body.
- For example, they may be dispersed homogeneously in the synthetic plastic body, if desired using auxiliary substances, or contained in separate parts of the contraceptive device in suitable quantities with or without the auxiliary substances for example, as a core in a part of the synthetic plastic body. Such auxiliary substances - . , : . . , . ... . , : ..

1~$7B06 may be, for example, tenside, highly dispersed silicon dioxide, anti-foaming agents, solubilisers, resorption retarders, X-ray contrast agents, and ferro-magnetic substances for assisting in ascertaining the location of the contraceptive device.
A preferred form of the contraceptive contains d-13-ethyl-17~-ethinyl-17~-nydroxy-4-gonen-3-one (d-norgestrel) homogeneously dispersed in a silicon rubber base that vulcanizes at a slightly elevated temperature, contains 5~ by weight of barium sulphate and is strengthened with highly dispersed silicon dioxide.
Another form of the contraceptive of the invention contains in the spheres 5, 6, 10, 11, 12 and 13 cores that consist of a mixture of 6-chloro-17-hydroxy-1~, 2~-methylene-pregna-4,6-dien-3, 20-dione acetate (cyproterone acetate) and lac~ose, the synthetic plastic body of this contraceptive consisting of an ethylene/vinyl acetate copolymer. The core members may have a cylindrical surface and end faces of which the radius of curvature is within the range of from the radius of the cylindrical surface (giving substantially spherical core members) to infinity (giving cylindrical core members).
The pharmacologically active ingredients contained in the thread-shaped appendage 19 are arranged to be released in a controlled manner from the carrier material of synthetic plastic at a given level within certain predetermined limits over a limited period, that is to say, in the first months of use of the contracep-tive, and subsequently the contraceptive action is derived from the contraceptive device, which, containing an active ingredient is also active on its own.
The appendage 19 can also be used with other contraceptive devices capable of intra-uterine use, which are suitable according to known practice for connection, for example, by knotting, adhesion or welding, to an intra-cervical thread-shaped medicament carrier.
There may be mentioned more especially contraceptives described in ~ .

S1~7806 U.S. Patent No. 3,533,406, German Offenlegungsschrift No. 1,956,701, U.S. Patent No. 3,563,235 and German Offenlegungsschrift No.
2,207,939.
The dimensions of the thread or filament are so chosen that the thread can extend into the cervical canal, but not into é
the vagina. The 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 pharmacologically active ingredient content of from 10 to 70~. ~
The non-metallic medicaments present in the thread-shaped --10intra-cervical appendage are preferably compounds having hormonal activity, for example, A4-pregnen-3,20-dione (progesterone), d-13-ethyl-17a-ethinyl-17~-hydroxy-4-gonen-3-one (d-norgestrel) and esters thereof, 17a-ethinyl-19-nortestosterone (norethisterone) and esters thereof, 6-chloro-17-hydroxy-la, 2a-methylene-pregna-4,6- - ~
dien-3,20-dione (cyproterone) and esters thereof, 3-methoxy-19-nor - --l7a-pregna-l~3~5(lo)-trien-2o-yn-l7-ol (mestranol), 18-methyl-19-nor-~4-pregnen-17a-ol-3,20-dione-17a-caproate, 3-hydroxy-1,3,5(10) oestratrien-17-one (oestrone), 17-acetoxy-6~,7~-epoxy-la,2a-methy-lene-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), l9-nor-5a-pregnan-3,20-dione, 3~-hydroxy-19-nor-5a-pregnan-20-one, l9-norhydroxy-progesterone and esters thereof, 6-chloro-17-hydroxy-pregna-4,6-dien-3,20-dione acetate(chlormadinone-acetate), 15, 16a- and 15,16~-methylene-17~-hydroxy-18-methyl-17a-ethinyl-4-oestren-3-one, 17~-hydroxy-4-androsten-3-one (testosterone) and esters thereof, 21-hydroxy-5~- -pregnan-3,20-dione and eslters thereof, 17a-acetoxy-6a-methyl-progesterone (medroxy-progesterone acetate and 10a-pregna-4,6- `
dien-3,20-dione (dydrogesterone).
Preferred are steroid hormones having a gestagenic activity, -such as d-norgestrel and progesterone, norethisterone, cyproterone acetate, norhydroxyprogesterone, and 15,16a- and 15,16~-methylene-~137~Q~
d-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 resor~tion retarders such, for example, as highly dispersed silicon dioxide.
As synthetic plastics for making the medicament-containing appendage 19 there may be used, more especially, LTV-silicone rubber two-component compositions such as can be prepared, for example, by the process of U.S. Patent No. 2,823,218 [see also the article by W. Noll, Chemie and Technologie der Silicone, 1968, page 341, and Chemiker-Zeitung 97 ~1973), pages 176 et seq].
Especially suitable are those compositions which contain from 89%
to 91% of linear dimethyl-polysiloxane containing a maximum of 0.5 mol% of methyl-vinyl-siloxane units and g - 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 catalyzed with platinum or platinum compounds such as, for example, -hexachloroplatinic acid (elastomer composition I), 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-H bonds, 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 catalyzed -~-with a platinum-ethanol complex compound (elastomer composition II).
The contraceptives of the invention are superior to the known contraceptives in their long-term action since their pregnancy rate during application, determined on the basis of the life-table method, is markedly lower and fewer spontaneous explusions and other side effects occur.
. ' 378~6 The expulsion rate of the contraceptives of the invention is extraordinarily low, although the devices contain no abutments acting against explusive movement and their shape does not permit anchoring in the mucous membrane or musculature 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.
By the use of known synthetic plastics 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. The contraceptives, independently of the size of the cavum uteri, are capable of universal use. The devices are so constructed that they do not penetrate or even push or cut into the musculature of the uterus.
An advantage of the contraceptive device of the invention ~ -having filamentary appendage containing a substance having gesta-genic activity is that the tranquillizing action of gestagens has a favourable effect on the uterus tUFER, J., Hormontherapie in der Frauenheilkunde, Verlag Walter De Gruyter Berlin, 1972, p. 124).
The physiological increase in the motility of the musculature of the uterus that occurs after inserting a foreign body is in this way reduced. Also, in thlis way, the rate of early explusions 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. ;

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378l~6 The intra-uterine contraceptive devices of the invention are formed in a manner favourable for application. One form of suitable applicator is the known insertion tube 16 having an internal diameter of 3.5 mm and a wall thickness of 0.5 mm, and ~ - -:. .. .
formed of high-pressure polyethylene or another suitable synthetic plastic. 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 has been stored or touching the device itself. The sphere

5 of the device forms a ball closure for the application unit consisting of the contraceptive and applicator. Since 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.
Application of the contraceptive device can easily be carried out by a professional person. It can be carried out under aseptic cand~-tions without anaèsthesia or the use af further medicaments or dilat-ion of the cervical canal without causing spasmodic pain, even in the case of women who have not given birth.
The following examples illustrate the invention.
Example 1 An intra-uterine contraceptive device including a synthetic plastic body consisting of a thermoplastic polyether-ester elastomer sprayed onto a terephthallate base and having the structure 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 and 3 and 7 to 9-1.5 mm, lengths of the round rods 3 and 4-0.85 cm and 0.65 cm, .. : .

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1~7~0t:~
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 axes of the rods 2 and 3, and the angle between the axes of the rods 2 and 4 are equal.
The physical properties of the device are as follows:
Elongation at break : 200~.
Tensile strength : 365 kilograms per square centimetre.
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 plastic body are electroplated with the aid of an adhesive underlayer. The spheres 5, 6, 7, 10, 11, 12 and 13 are galvanically coated with nickel having a layer thickness of 100 ~m, and the spheres 5, 11 and 13 are in addition galvanically coated with copper having a layer of 100 ~m.
Example 2 A synthetic plastic body having the dimensions given in Example 1 is formed from a thermoplastic synthetic plastic ;
material derived from polyethylene, which material contains carboxyl groups connected by copolymerization 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 plastic body are chemically coppered on the surface, the layer thickness being about 0.5 ~m, with the interposition of an adhesive underlayer of highly dispersed iron. Nickel is electro-deposited, the layer thickness being 80 ~m, 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 ~m.

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Example 3 75.0 g 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 g of highly dispersed copper powder and 12.5 g of highly dispersed nickel powder. From the above mixture, there is formed a contraceptive device having the shape, dimensions and physical properties specified in Example l. -Example 4 60.0 g of a catalyzed silicone rubber two-component mixture of low temperature vulcanizing type (LTV) are mixed with 40.0 g of highly dispersed silicon dioxide. From the suspension, there is produced, by vulcanizing the moulded mass for one hour at ll~qC 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: D40.
Coefficient of restitution: 45%
In the manner described in Example 2, the synthetic ~ ;
plastic bodies are partially and in alternation galvanically surface coated with copper and nickel. -Example 5 An intra-uterine contraceptive device, which includes surfaces partially and in alternating order copper and silver coated, is produced in the following manner:
From high pressure polyethylene, synthetic plastic bodies are formed having the structure shown in Figure 1 and the following 30 dimensions: total length 3.4 cm, diameter of sphere 5-4.6 mm, dia-meter of 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, length of the rod 3-0.9 cm, length of the rod 4-0.7 cm, length of the end-piece 14-4.5 mm and diameter of - 19-- ' ' ' ' 7bl06 the end-piece 14-2.6 mm.
On the spherical parts 5, 6 and 10 to 13 of the synthetic plastic body silver is deposited by reduction, the layer thickness being about l~m. On the silver layer, copper is electro-deposited, the layer thickness being about 90 ~m, and the surface of each of the spheres 5, 11 and 13 is also galvanically coated with silver, the layer thickness being 70 ~m.
Example 6 A synthetic plastic body having the dimensions given in Example 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 structure shown in Figure 1 and the physical properties given in Example 1 is formed by injection moulding a thermoplastic poly-ether-ester elastomer based on a terephthalate base. The partial metal coating of the synthetic plastic body with 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 hauing a thickness of 100 ~m, and the spheres 5, 11 and 13 are additionally coated, on top of the 100 ~m copper `
layer, with a layer of silver having a thickness of 75 ~m.
Example 7 A synthetic plastic body of thermoplastic polyether-ester elastomer based on terephthalate is formed with the outline shown in Figure 1 and the dimehsions 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 thick-ness of 10 ~m, with nickel in a layer thickness of 90 ~m. The 30 spheres 5, 11 and 13 are also coated, over a layer of conductive silver lacquer having a thickness of about 10 ~m, with silver having a layer thickness of 80 ~m.

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Example 8 35.0 g of micronized d-13-ethyl-17~-ethinyl-17~-hydroxy-4-gonen-3-one and 5.0 g of highly dispersed barium sulphate are uniformly mixed with 60.0 g of very finely granulated high pressure polyethylene having a particle size of about 500 ~m. From the mixture, there is formed an intra-uterine contraceptive device having the structure given in Figure 1 and the dimensions mentioned in Example 5. ~
Example 9 ~ -30.0 g of micronized d-13-ethyl-17~-ethinyl-17~-hydroxy-4-gonen-3-one (d-Norgestrel) are incorporated in a mixture of 5.0 g of highly dispersed barium sulphate, 20.0 g of highly dispersed silicon dioxide and 45.0 g of catalyzed LTV-silicone rubber two-component composition. The suspension is shaped and vulcanized for one hour at 110C to form d-norgestrel- containing synthetic plastic bodies having the outline shown in Figure 1 and the dim-ensions 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 g of micronized progesterone and ~ ~ ;
49.1 g of lactose with the addition of 0.1 g of lubricant, there are made by injection moulding 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 palrts 5 and 10 to 13 of an intra-uterine ;
contraceptive device, of which the structure 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 g of barium sulphate, 35.0 g of highly dispersed silicon dioxide and 60.0 g of catalyzed LTV-silicone rubber two-, l037~aG
component composition by vulcanization for one hour at a temp-erature of 100C in conjunction with moulding. The physical properties of the device are as specified in Example 4.
Example 11 A homogeneous mixture of 40.0 g of 6-chloro-17-hydroxy-la,2~-methylene-pregna-4,6-dien-3,20-dione acetate with 59.8 g of lactose and 0.2 g 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.
The 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 spec-ified 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 100C a medicament-contain-ing synthetic plastic 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 minuies an intra-uterine contraceptive device of which the core of the synthetic plastic body is enriched with _-norgestrel. The physical properties x of the device and the angle between the axes of the rods 3 and 4 are as specified in Example 4. ~
Example 13 ~ -50.0 g of micronized 17~-ethinyl-19-nortestosterone-oenanthate are homogeneously mixed with 10.0 g of highly dispersed silicon dioxide, 5.0 g of barium sulphate and 35.0 g of catalyzed 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 60C, and serves as the core member of an intra-uterine contraceptive ` ~

-22- ~ -device having the outline shown in Figure 1. The 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 ~ -30.0 g of d-13-ethyl-17~-ethinyl-17~-hydroxy-4-gonen-3-one are mixed with 10.0 g of barium sulphate and 60.0 g 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. The medicament-containing body is encased with a mixture consisting of 45.0 g of highly dispersed silicon oxide, 10.0 g of barium sulphate and 45.0 g of catalyzed LTV-silicone 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 hQating at 100C. ' 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 centi-metre.
Example 15 A synthetic pl~stic body injection moulded from thermo-plastic polyether-ester elastomer based on terephthalate has the structure shown in Figure 1 and the following dimensions: `~
total length 3.6 cm, diameter of the sphere 5-4.8 mm, diameter of ~-30 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 the rods 3 and 4-0.85 cm ,_ . . . - . . . . . . . .. . .

~03~06 and 0.65 cm, respectively, length of the end-piece 14-4.5 mm, diameter of the end-piece 14-2.8 mm, and total weight of the syn-thetic plastic body 220 mg. The angle between the rods 3 and 4 is 123 and the physical properties of the device are as specified in Example 1.
The surfaces of the spheres of the synthetic plastic 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 ~m and the spheres 6, 10 and 12 are gal-vanically coated, in addition, with copper having a layer thicknessof 100 ~m.
Example 16 ` In order to form an intra-uterine contraceptive device, a synthetic plastic body having the dimensions specified in Example 1 is formed from a thermoplastic synthetic plastic material derived from polyethylene, which material contains carboxyl groups connected by copolymerization 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 plastic body are coppered chemically -~
with the interposition of an adhesive underlayer containing highly , ~ , .
dispersed iron (layer thickness about 0.5 ~m). Onto the chemically deposited copper layer, silver is electro-deposited to a thickness -of 80 ~m. The spheres 6, 10 and 12 are galvanically coated, in addition, with copper having a layer thickness of 80 ~m.
Example 17 ; 75.0 g of ther~oplastic polyether-ester elastomer based :; :
~ on terephthalate in the form of a very fine granulate are uniformly ~
~;,i :
mixed with 12.5 g of highly dispersed copper powder and 12.5 g of highly dispersed silver powder. The mixture is formed into an intra-uterine contraceptive device having the dimensions and physical properties specified in Example 1.

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Example 18 60.0 g of a catalyzed silicone rubber two-component mixture of the low temperature vulcanizing type (LTV) are mixed with 40.0 g of highly dispersed silicon dioxide. Synthetic plastic 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 110C. The physical properties of the device are as specified in Example 4.
In the manner described in Example 2, the synthetic plastic bodies are partially and in alternation galvanically coated on the surface with copper and silver.
' -,.'~, Example 19 An intra-uterine contraceptive device, which contains on the surface partially and in alternating order copper and silver, is made as follows:
, Synthetic plastic 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 end-piece 14-4.5 mm and diameter of the end-piece 14-2.6 mm. -On the spheres 5, 6 and 10 to 13 of the synthetic plastic body, the surface of thelsynthetic plastic material is activated -~
by treatment with an ionic solution of palladium. Upon the activat-ed surface, copper is chemically deposited to a layer thickness of about 1 - 2 ~m. Silver is then electro-deposited by a customary process of galvanizing synthetic plastic to a layer thickness of about 80 ~m on the spheres 6, 10 and 12, in addition, 100 ~m of copper.
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Example 20 A synthetic plastic 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 in-jection moulding a thermoplastic polyether-ester elastomer based on terephthalate. The synthetic plastic body is partially coated with metal consisting of copper and silver in alternating order, as described in Example 19, by chemical and electrolytic deposition on the surfaces, which have previously been activiated with ionic palladium solution, of the spheres 5, 6 and 10 to 13. The elec-trolytically deposited silver layer has a layer thickness of about 90 ~m, and the electrolytically deposited copper layer has a thick-ness of about 60 ~m. The device has the physical properties spec-ified in Example 1.
Example 21 A synthetic plastic body consisting of thermoplastic polyether-ester elastomer based on terephthalate partially met-. ~., allized with copper and silver in alternating order and having theoutline shown in Figure 1 and the dimensions given in Example 1, is, after activation of the synthetic plastic surface with ionic 20 pa~ladium solution, chemically coppered to a layer thickness of r'' about 1 to 2 ~m. There are then electro-deposited, in succession, 100 ~m of silver and 80 ~m 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 metallization of the spheres 5, 11 and 13 remaining :' I . ..
complete and that of the spheres 6, 10 and 12 being retained with the exception of the 80 ~m copper layer. The physical properties - of the device are as specified in Example 1.
Example 22 ;~

30.0 g of micronized _-13-ethyl-17~-ethinyl-17~-hydroxy- - -4-gonen-3-one ~d-norgestrel) and 70.0 g of LTV-silicone rubber two-- component composition (elastomer type I) are worked up into a `~: . ' 10;17~6 suspension free from air bubbles. The suspension is passed through a jet to form a filament and vulcanized by being heated at a temp-erature of 100C 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 similar 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 17~-acetoxy-17-ethinyl-4-oestren-3-one (norethisterone acetate), and may be 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 micronized progesterone which is mixed with -60 parts by weight of catalyzed LTV-silicone rubber two-component composition (elastomer composition II), by shaping the progesterone suspension and then heating for one hour at 100C. The thread is ~-2.5 cm in length and has a diameter of 0.5 mm. It may be attached ~
to an intra-uterine contraceptive device as shown in Figure 2.
Example 25 In a manner similar 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 17-hydroxy-19-norpregn-4-en-3,20- ;~ , dione (norhydroxy-progesterone). It may be attached to an intra-uterine coneraceptive device as shown in Figure 2.
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Claims (108)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. An intra-uterine contraceptive device which com-prises a Y-shaped member formed of synthetic plastics material, the free end of each branch of the Y terminating in a rounded head member, the stem of the Y being formed with a plurality of rounded enlargement members 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.

2. A device according to claim 1, wherein the modulus of elasticity of the synthetic plastic material is from 900 to 2,900 kilograms per square centimetre.

3. A device according to claim 2, wherein the modulus of elasticity of the synthetic plastic material is from 1,000 to 2,750 kilograms per square centimetre.

4. A device according to claim 3, wherein the tensile strength of the synthetic plastic material is within the range of from 50 to 550 kilograms per square centimetre.

5. A device according to claim 1, 2 or 3, wherein the synthetic plastic material is a silicone elastomer having a tensile strength of from 50 to 120 kilograms per square centimetre.

6. A device according to claim 1, 2 or 3, wherein the synthetic plastic material is a silicone elastomer having a tensile strength of from 60 to 105 kilograms per square centimetre.

7. A device according to claim 1, 2 or 3, wherein the synthetic plastic material is a thermoplastic material having a tensile strength within the range of from 150 to 550 kilograms per square centimetre.

8. A device according to claim 4, wherein the Shore hardness of the synthetic plastic material is within from 35 to 85.

9. A device according to claim 8, wherein the synthetic plastic material is a silicone elastomer.

10. A device according to claim 9, wherein the Shore hardness of the synthetic plastic material is from 40 to 75.

11. A device according to claim 8, wherein the synthetic plastic material is a thermoplastic material having a Shore hardness of from 40 to 70.

12. A device according to claim 11, wherein the synthetic plastic material has a Shore hardness within the range of from 45 to 60.

13. A device according to claim 1, 4 or 8, wherein the weight of the device does not exceed 0.5 gram.

14. A device according to claim 1, 4 or 8, wherein the rounded members are formed of the same synthetic plastic material as rods forming the branches and stem.

15, A device according to claim 1, 2 or 3, wherein the rounded members, except where they adjoin a rod forming a branch or stem, are substantially spherical.

16. A device according to claim 1, 4 or 8, wherein the outer surfaces of rods forming the branches or stem are rounded.

17. A device according to claim 1, 4 or 8, wherein rods forming the branches or stems are of substantially circular section.

18. A device according to claim 1, 4 or 8, wherein rods forming the branches or stem are substantially straight.

19. A device according to claim 1, 4 or 8, wherein the total length of the device does not exceed 4 centimetres.

20. A device according to claim 1, 4 or 8, wherein the total length of the device is at least 3 centimetres.

21. A device according to claim 1, 4 or 8, wherein the diameter of each of the rounded members does not exceed 5 millimetres.

22. A device according to claim 1, 4 or 8, wherein the diameter of each of the rounded members is at least 1.5 millimetres.

23. A device according to claim 1, 4 or 8, wherein the length of each of the rods forming the branches and stem does not exceed 1.2 centimetres.

24. A device according to claim 1, 4 or 8, wherein the length of each of the rods forming the branches and stem is at least 0.5 centimetre.

25. A device according to claim 1, 4 or 8, wherein each rod forming the branches and stem terminates at each end in one of the said rounded members in a rounded end piece.

26. A device according to claim 1, wherein the angle between the two branches of the Y is from 120 to 130°.

27. A device according to claim 1, wherein the angle between the branches of the Y is from 121 to 127°.

28. A device according to claim 1, 26 or 27 wherein the angle between one branch of the Y and the stem of the Y is substantially equal to the angle between the other branch of the Y and the stem of the Y.

29. A device according to claim 1, wherein the two branches of the Y are of different lengths and, when the two branches of the Y are brought together by flexing, 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 member which terminates the end of the longer of the two branches of the Y that is remote from the stem of the Y.

30. A device according to claim 29, wherein each branch of the Y comprises only a single rod and each rod termin-ates at the end remote from the stem of the Y 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 the end remote from the stem of the Y being less than the length of the rod forming the longer 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 the end remote from the stem of the Y 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 the end remote from the stem of the Y.

31. A device according to claim 30, wherein the length of the rod forming the shorter of the two branches of the Y is from 0.5 to 0.8 centimetre, the length of the rod forming the longer of the two branches of the Y is from 0.8 to 1.2 centimetres, the diameters of the rods forming the two branches of the Y being 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 the end remote from the stem of the Y is 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 the end remote from the stem of the Y is from 4 to 5 millimetres.

32. A device according to claim 1, 26 and 27 wherein there is a rounded member where the branches of the Y join the stem of the Y.

33. A device according to claim 27, wherein the stem of the Y comprises a plurality of rods and rounded members arranged alternately.

34. A device according to claim 33, wherein the stem of the Y comprises at least three rounded members.

35. A device according to claim 34, wherein the stem of the Y comprises not more than seven rounded members.

36. A device according to claim 34, wherein the stem of the Y comprises five rounded members.

37. A device according to claim 33, wherein the rounded members in the stem of the Y are each substantially spherical.

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

39. A device according to claim 33, wherein in addition to the said rounded members, the stem of the Y termin-ates at the end remote from the branches of the Y in a rounded end-piece formed with an aperture.

40. A device according to claim 39, wherein the rounded end-piece has a width within the range of from 2 to 3 millimetres and a length within the range of from 4 to 5 millimetres.

41. A device according to claim 39, wherein the rounded end-piece is formed with a transverse aperture or bore.

42. A device according to claim 41, wherein the diameter of the aperture or bore is within the range of from 0.5 to 1.5 millimetres.

43. A device according to claim 40, having an indicator thread secured through the aperture or bore in the rounded end-piece.

44. A device according to claim 1 or 33 wherein the stem of the Y is substantially straight.

45. A device according to claim 1 in combination with an applicator comprising a generally tubular member, the stem of the Y and overlapping portions of the branches of the Y being within the applicator tube.

46. A device according to claim 45, wherein the maximum lateral dimension of the rounded member in which a longer branch of the Y terminates at the end remote from the stem of the Y is too great to permit that member to enter the applicator tube.

47. A device according to claim 45, wherein the arrangement is such that, during the insertion of the device into the human body, the rounded member in which a 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 according to claim 45, 46 or 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. A device according to claim 1, wherein the device incorporates a pharmacologically active substance.

50. A device according to claim 49, wherein the pharmacologically active substance is a substance having a contraceptive action.

51. A device according to claim 49, wherein the pharmacologically active substance is or includes a metal.

52, A device according to claim 51, wherein the metal is copper, silver or nickel.

53. A device according to claim 52, wherein the device incorporates another metal or metals selected from the group consisting of copper, silver and nickel.

54. A device according to claim 51, wherein the metal or metlas is or are incorporated with one or more of the rounded members.

55. A device according to claim 54, wherein substant-ially no metal is incorporated with the rods as a coating.

56. A device according to claim 54, wherein the device is Y-shaped, there is provided a rounded member where the branches of the Y join the stem of the Y and substantially no metal is incorporated with that rounded member as a coating.

57. A device according to claim 51, wherein the metal, or at least one of the metals is in particulate form and is distributed throughout at least one of the rounded members.

58. A device according to claim 57, wherein the rounded members are formed of a synthetic plastic material for releasing the particulate metal in a controlled manner.

59. A device according to claim 52, wherein the metal is applied as a coating to one or more of the rounded members.

60. A device according to claim 59, wherein at least one of the rounded members is coated with copper.

61. A device according to claim 60, wherein the copper is applied chemically.

62. A device according to claim 61, wherein the copper is applied chemically to an underlayer of dispersed iron.

63. A device according to claim 61, wherein the surface of the plastic material to be chemically coated with copper is first activated by treatment with palladium ions.

64. A device according to claim 60, wherein the copper coating is applied galvanically.

65. A device according to claim 64, wherein the copper coating is applied to a coating of nickel.

66. A device according to claim 59, wherein at least one of the rounded members is coated with nickel.

67. A device according to claim 66, wherein the nickel is applied galvanically.

68. A device according to claim 67, wherein the nickel is applied galvanically to a coating of copper.

69. A device according to claim 59, wherein at least one of rounded members is coated with silver.

70. A device according to claim 69, wherein the silver is applied by reduction.

71. A device according to claim 69, wherein the silver is applied galvanically.

72. A device according to claim 59, wherein a metal coating, comprising one or more metal layers, is applied to the device, a screening layer is applied to that part of the coating that is to be retained and the part of the coating that is not covered by the screening layer is removed.

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

74. A device according to claim 3, wherein the metal coating is formed by coating the whole device, excluding through-out 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 device that is not covered with said layer of material resistant to electroplating, thereafter removing the metal coating from those parts of the device that are not to have a metal coating, and removing the layer of material that is resistant to electroplating.

75. A device according to claim 59, wherein the rounded members, other than any rounded member at the junction of branches of the device, are so coated with two or more metals that the outer surfaces of alternate rounded members are formed of the same metal.

76. A device according to claim 75, wherein the outer surface of the rounded member in which a longer branch of the Y
terminates at the end remote from the stem of the Y is formed of a first metal, the outer surface of the rounded member in which a shorter branch of the Y terminates and the outer surface of the rounded member in the stem next to a rounded member at the junction between the branches and the stem are formed of a second metal, and the outer surfaces of the remaining rounded members in the stem are formed alternately of the first and second metals.

77. A device according to claim 1, wherein the centres of the rounded members and the axes of the rods are substantially coplanar.

78. A device according to claim 49, wherein at least one of the pharmacologically active substances is a substance having hormonal activity.

79. A device according to claim 78, wherein the substance having hormonal activity is a steroid.

80. A device according to claim 78 or 79, wherein the substance having hormonal activity is one having gestagenic activity.

81. A device according to claim 79, wherein the steroid is d-norgestrel, progesterone, norethisterone, cyproterone acetate, norhydroxyprogesterone, 15,16.alpha.-methylene-d-norgestrel or 15,16.beta.-methylene-d-norgestrel, or a mixture of two or more of such compounds.

82. A device according to claim 79, wherein the substance having hormonal activity is a mixture of cyproterone acetate and lactose.

83. A device according to claim 49, wherein the pharmalogically active substance is a substance having a local anaesthetic action.

84. A device according to claim 83, wherein the substance having a local anaesthetic action is xylocaine or novocaine.

85. A device as claimed in claim 49, wherein the pharmacologically active substance is a substance having a weakly basic buffering action.

86. A device according to claim 85, wherein the substance having a weakly basic buffering action is triethanol-amine, disodium ethylenediaminetetracetate or a phosphate buffer of Sorensen.

87. A device according to claim 1, which also com-prises an intra-cervical filament.

88. A device according to claim 77, wherein the filament incorporates one or more pharmacologically active substances.

89. A device according to claim 88, wherein at least one of the pharmacologically active substances is a substance having hormonal activity.

90. A device according to claim 89, wherein the substance having hormonal activity is a steroid.

91. A device according to claim 89, wherein the substance having hormonal activity is one having a gestagenic activity.

92. A device according to claim 90, wherein the steroid is d-norgestrel, progesterone, norethisterone, cyproterone acetate, norhydroxyprogesterone, 15,16.alpha.-methylene-d-norgestrel or 15,16.beta.-methylene-d-norgestrel, or a mixture of two or more of such compounds.

93. A device according to claim 49 or 78 wherein the pharmacologically active substance is non-metallic and is dispersed in the synthetic plastic material.

94. A device according to claim 49 or 78, wherein the pharmacologically active substance is non-metallic and is included in or as a core member in a part of the synthetic plastic body.

95. A device according to claim 49, which also contains an auxiliary substance.

96. A device according to claim 95, 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.

97. A device according to claim 1, wherein the synthetic plastic material is polyethylene, an ionomeric resin derived from polyethylene, a copolymer of ethylene and vinyl acetate, a polyethylene containing carboxyl groups connected by copolymerization to the chain molecules and cross-linked by sodium ions, a polyamide, a polyether-ester elastomer on a terephthalate base, or a silicone rubber, or any two or more of such compounds.

98. A device according to claim 97, wherein the synthetic plastic body is formed in layers of the same or different plastic material.

99. A device according to claim 97, wherein the silicone rubber is a silicone rubber of the LTV-type.

100. A device according to claim 99, wherein the silicone rubber is lone that contains from 89 to 91% of linear dimethyl-polysiloxane 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 Si=H-bonds and are catalyzed with platinum or a platinum compound.

101. A device according to claim 99, wherein the silicone rubber is one that contains from 85 to 89% of dimethyl-polysiloxane having a maximum of 0.5 mol per cent of methyl-vinyl-siloxane units, 5 to 6% of dimethyl-polysiloxane contain-ing 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 is catalyzed with a platinum-ethanol complex compound.

102. A device according to claim 87, 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.

103. A device according to claim 102, wherein the filament is composed of a synthetic plastics material.

104. A device according to claim 103, wherein the synthetic plastics material is a silicone rubber of the LTV-type.

105. A device according to claim 87, wherein the filament contains from 10 to 70 per cent by weight of one or more pharmacologically active substances.

106. A device according to claim 50, which contains d-norgestrel homogeneously dispersed in a silicone rubber base that vulcanizes at a slightly raised temperature, and also con-tains barium sulphate and highly dispersed silicon dioxide.

107, A device according to claim 50, which contains, as the pharmacologically active substance or one of the active substances, nuclear particles consisting of a mixture of cyproterone acetate and lactose, and contains a copolymer of ethylene and vinyl acetate as the material of the synthetic plastics body.

108. A device according to claim 79, wherein the synthetic plastic body contains from 25% to 50% by weight of one or more steroids having a contraceptive action.