CA1084791A

CA1084791A - Vaginal ring

Info

Publication number: CA1084791A
Application number: CA237,945A
Authority: CA
Inventors: Gisela Schopflin; Gerhard Laudahn; Barbara Muhe; Heidemarie Hartmann; Fred Windt
Original assignee: Schering AG
Current assignee: Bayer Pharma AG
Priority date: 1974-10-18
Filing date: 1975-10-20
Publication date: 1980-09-02

Abstract

ABSTRACT OF THE DISCLOSURE
A vaginal ring device includes a support ring formed of foamed silicone rubber and containing a recess in at least one of the inner and outer circumference, and a pharmaco-logically active substance-containing ring in said recess, the active substance-containing ring being formed of an LTV (low temperature vulcanizing)-silicone elastomer consisting, for example, of an organo-polysiloxane of the general formula

Description

This invention relates to a vaginal ring, which contains one or more pharmacologically active substances, more especially oestrogens and/or ges-tagens.
Vaginal rinys that contain gestagenically active steroid hormones or a combination of gestagenically and oestrogenically active medicaments and which prevent conception, with or wlthout inhibiting ovulation~ are used when pharmaceutical preparations `
for oral administration containing such active substances cannot be used for any of a very wide variety of reasons, for example, where the person concerned has an aversion to taking a tablet.
Vaginal rings also have the advantage that the woman is free from the necessity of having to take tablets daily. It is a ring-shaped structure simple to apply, which is introduced into the vagina and is well tolerated by women. As compared with the known intrauterine pessaries and capsules applied subcutaneously, they have the ~urther advantage that at any time they can be removed and reinserted by the woman.
Vaginal rings made ~rom synthetic plastic, especially those based on silicone elastomers Which are obtained from RTV-silicone rubber two-component compositions [Contraception 8 (1973) `
651] or which are based on silicone rubber hot vulcanizates [Steroids 21 (1973) 325] and which contain ~harmacologically act-ive substances such as, for example, steroid hormones, are known [Fertil.Steril. 21 (1970) 99; Amer.J.Obstet.Gynecol. 113 (1972) 927; Contraception 8 (6) (1973) 561; German Patent Publication No. 1,900,196]. The active substance is released ~rom the synthe-tic plastic carrier over a long period and is absorbed by the vaginal mucosa.
The steroid hormones contained in the hitherto known vaginal rings have;~been exclusively those having a gestagenic action. Depending on the rate o~ reIease o~ the active substance by the vaginal rings, their use provides protection against con- ~ `

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~ 38~79~

ception with or without inhibiting ovulation.
However, contraceptives in the'form of hi'therto known vaginal rings have disadvantages. Inter alia, they are based on RTV-silicone rubber two-component compositions which, as is known, have poor mechanical properties. The mechanical properties of RTV-silicone rubber vulcanizates must first be improved by the addition of fillers. The fillers, however, may impair the release of the active subs~ance from the vaginal ring. A few of the known vaginal rings are made by the vulcanization of suspensions of active substance in RTV (room temperature vulcanizing)-silicone rubber two-component compositions in the appropriate shapes. The active substances are released from this type of vaginal ring during the period of use inquantities that decrease considerably with time [Contraception 8 (1973) 561].
Considerable differences in the dosage of active sub-stance inevitably result in qualitative and quantitative differ-ences in the biological or contraceptive action, and in the~nature and magnitude of undesired side effects during the period of use of vaginal rings. Known vaginal rings, which contain the active ingredient homogeneously suspended in the synthetic plastic base, have a total weight of from around 6.0 to 15.0 g. If the active substance is to be released from the vaginal rings during the period of use in a ~uanti~y su~ficient for the desired action, they must contain from 5 to 50~ by weight of the active substance.
In relation to the quantity of active substance released during the period of use~/ this is an uneconomically high content of the substance in the device. ' Moreover, no method is yet known for regulating the rate'of release desired for a particular pharmacologically active "
substance from such vaginal rings based on silicone elastomer.
Some of the kno~n vaginal rings are based on synthetic plastics that are physiologically not entirely unobjectionable.

- 2 -. .

~ ~4'~1 Thus, for the manu~acture of some vaginal rings there have been used RTV-silicone rubber ~wo-component compositions aontaining tin compounds as vulcanization accelerators which have a toxic action on the living organism [Amer.~.Obstet.Gynecol. 113 (1972) 927].
There are also known vaginal rings which, like those for the treatment of prolapse, are provided with a metal spring.
The vaginal rings are relatively stiff and their use may lead to erosions of the mucous membrane in the region of the poster-lateral vault of the vagina ~Amer.Med.Ass. 208 (1969) 949].
British Patent No. 1,264,732 describes devices which consist of a medicament-containing capsule on a ring of silicone rubber.
However, because of their construction, such devices are` ill suited ~or mass production and lack practicability in use.
The problem with which the present invention is con-cerned is to provide a vaginal ring which contains pharmacologi-cally active substances, wherein the active substance or sub-stances are released over a period of at least three weeks, pre-~erably a longer period, in a regular and constant quantity nec-essary for producing the biological action desired, and whichavoid or minimize the above-mentioned disadvantages o~ known vaginal rings.
The present invention accoxdingly provides ~ vaginal ring device comprising a support ring, i~ desired, ~ormed with one or more recesses in which an elastomer material containing a pharm-cologically active substance is so located that the material ;
has an exposed surface, the elastomer material being an LTV (low temperature vulcanizing) silicone elastomer.
Advantageously the support ring is ~ormed from a synthetic ~-plastic mateiral, especially an LTV-silicone eLastomer.
A pre~erred construction of the vaginal ring device of the invention comprises a support ring having one or two pocket--i ;

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7~1 shap~d recesses ex-tendi.ng a:round it f~r r~ceiving suitable LTV-silicone elastomer rlngs con~aining a pharmacolog:ically ac-tive s~lbstance.
The preerred vaginal ring o the invention includes a support ring proper having one or two recesses, and an inner or outer ring member containing a pharmacologically active substance or two such active substance-containing rings together, which are fitted into the pocket-like recesses of the support ~ :
ring member.
10In a plane containing the axis of the support ring, that part of the active substance - containing ring member that ~.
lies on one side of the axis, may be a circle, in which case the ring member forms a complete ring, or a part of a circle in which case the ring member forms a segment of a ring.
The dimens.ions of the support ring and o~ the active substance-containing rings are so chosen that the lines of contact of the outer or inner edges of the support ring with the active substance-containing ring lie, in a radially outward direction beyond the centre line o~ the active substance-containing ring in the case of a circular ring, or in a radially outward direction beyond the curve on which lie the centres of the circles of which the cross-sections each form a part in the case of an active substance-containi.ng ri.ng having the shape o~ a segment of a circle. In this way, positive locat.ion of the active substance-containing rings in the pocket-shaped recesses of the support ring is achieved.
By a pharmacologically active substance is meant a substance capable of having an effect on a living organism. The pharmacologically active substance (also referred to herein simply as "the active substance") is preferably a medicament, the term medicament being understood to include not only substances capable of curing or preventing disease, but also ~ther substances capable ~4~

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beneficial effects in animal (including human~ organisms.
Examples of vaginal ring devices constructed in accord-ance with the invention are illustrated in the accompanying draw- `
ings in which~
Figures 1 - 3 are plan views of vaginal ring devices;
Figure 4 is a cross-sectional view taken along line 4-4 of Fig. l;
Figure 4a is a cross-sectional view taken along line 4a-4a of Fig. 4, on a larger scale and with parts omitted; ~ ~ ;
Figure 5 is a cross-sectional view o another form of vaginal ring device;
Figure 5a is a cross-sectional view along line 5a-Sa of Fig. 5, on a larger scale and with parts omitted;
Figure 6 is a cross-sectional view of yet another form of vaginal ring;
Figure 6a is a cross-sectional view along line 6a-6a of Fig. 6 on a larger scale and with a part omitted;
Figure 7 is a cross-sectional view taken along line 7-7 of Fig. 3;
Figure 7a is a cross-sectional view taken along line 7a-7a of Fig. 7, on a larger scale and with a part omitted;
Figure 8 is a schematic plan view of a vaginal ring device having inner and outer medicament-containing layers extend- i ng therearound;
Figure 8a is a cross-sectional view taken along line 8a-8a of Fig. 8, on a larger scale;
Figure 9 is a schematic plan view of a vaginal ring device having an outer medicament-containing layer extending therearound;
Figure 10 is a schematic p~an view of a vaginal ring ~ ~;
device with two sections of active substance-containing layers;
and -'' ' ' .

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Figure 11 is a schematic plan view of a vaginal ring device haviny an active substance-containing layer extending around only a park of the outer circumference thereof.
Referring to Figs. 1, 4 and 4a, one form of vaginal ring device in accordance with the present invention includes a support -ring 1, having annular grooves 2 and 3 in its outer and inner peri-pheries, respectively. The grooves 2 and 3 are of semicircular ;~
cross-sectional configuration for receiving external and internal active substance-containing rings 4 and 5 respectively. The in-ternal active substance-containing ring 5 can be omitted (Fig. 2) or the external ring 4 can be omitted (Fig.3.) The cross-sectional configuration in the peripheries of the support ring 1 and of the active substance-containing rings can be varied. As shown in Figs 5, 5a, and 6 and 6a an outer groove 7 having a cross-sectional configuration in the form of a section o~ a circle, and an active substance-containing ring 8 of semicircular cross-sectional configuration can be employed.
The ring 8 can be used in conjunction with the internal ring 5 of circular cross-sectional configuration (Figs. 5 and 5a) or alone (Figs. 6 and 6a). By the same token, the internal ring 5 of cir-cular cross-sectional configuration can be used alone (Figs. 3, 7 and 7a), or the external ring ~ can be used alone ~Fig. 2)~
From the foregoing, it will be appreciated that the shapes of the grooves in the support ring 1 and of the active substance-containing rings can be varied and still fall within the teachings of the present invention. -~
The support ring 1 of Figs. 1 to 7a may consist of any physiologically tolerable synthetic plastic material, provided that it has suPfi~ient strength and elasticity. Suitable synthetic plastics include organo-polysiloxane elastomers such as LTV-di-methyl-polysiloxane elastomer, heat-vulcanized dimethyl-polysilo-xane eIastomers, polyamides, natural and synthetic rubber, poly-79~

esters, polytetrafluorethylene and polyethylenes, which may beworked up in known manner into moulded bodies, for example, by injection moulding or casting.
As shown in Figs. 8 to 10, another preferred construc-tion of the invention is one in which rings based on LTV-sili-cone elastomer which contain a pharmacologically active sub-stance are vulcanized onto a support ring 1 of LTV-silicone elas-tomer.
The construction includes a support ring proper having one or two layers containing a pharmacologically active substance and which are vulcanized onto the inner and/or outer edge of the support ring. In the device of Figs. 8 and 8a, active substance-containing layers 9 and 10 are vulcanized onto the outer and inner peripheries, respectively of the support ring 1, and, in the de-vice of Fig. 9, only one active substance-containing layer 9 is provided on the outer periphery of the support rin~ 1. The a~tive substance-containing layer can be in two sections 11 and 12 (Fig. ~ ~' 10) on the outer periphery of the support ring 1, or be in the form of a section 13 (Fig. 11) covering a portion only of the outer periphery of the support ring 1.
The active substance-containing layers form a part of an annulus. The dimensions of the support rin~ and the vulcanized outer and inner active substancercontaining rings are so chosen that the outer and inner vulcanized active substance- i containing rin~s, respectively, of the support ring do not make ;`'~
contact with each other. The layers containing a pharmacologically active substance ma~,extend around the whole support rin~ or may be vulcanized ln preferably circumferentially extending sections. ~ ' The vaginal ring devices of the invention have an average size (external diameter of the device) of 0.5 to 20 cm, the size ' depending on the purpose for which they are to be used. In the ,~
case of the smaller ~ammels, such as dogs, the size of the ring ,~

is smaller than in the case of larger mammals, such as horses and cows. In the case of vaginal ring devices for women the external diameter may be about 5 to 10 cm, and, in the case o~
rhesus apes, it is about 2 to 3 cm. The diameter of the cross-section of the ring may be about 5 to 15 mm, and preferably 7 to 10 mm.
The support ring and the activ~ substance-containing rings or vulcanized layers may be made from known ~TV-silicone elastomers. Silicone elastomers of the LTV-type and organopoly-siloxane two-component moulding compositions of the LTV-type used in preparing such elastomers and constituents of such compositions are known, for example, ~rom German Patent No. 1,171,641 and 1,900,969, German Patent Publication No. 1,940,12~ and U.S. Patent Nos. 2,371,362; 2,823,218; 2,970,150; 3,159,601; 3,159,662 and 3,220,972.
There are suitable, for example, LTV-silicone elastomer two-component compositions which consist of 89-91% of linear di-methyl-polysiloxane containing a maximum of 0.5 mol% of methyl-vinyl-siloxane units and 9-11~ of dimethyl-polysiloxane containing SiH-bonds, and having amolecule weight of 500 to 1,000, which con-tain up to 3 SiH-bonds, and which are vulcanized in the presence of platinum or a platinum compound as catalyst, such as, for ex-ample, hexachloroplatinic acid, (LTV-silicone elastomer ~); LTV-silicone elastomer two-component compositions which contain 85 to 89% of dimethyl-polysiloxane having a maximum of 0.5 mol~ of methyl-vinyl-siloxane units, 5-6% o~ dimethyl-polysiloxane con-taining Si~I-bonds, 5-10% of a dimethyl-polysiloxane resin having a cross-linking and reinforcing action and containing a maximum ~ -of 1.2 mol% o~ methyl-vinyl-siloxane units, and which are vul-canized, ~or example, with a platinum compound as catalyst (LTV- `
silicone elastomer B~; and LTV-silicone elastomer two-component moulding compositions containing dimethyl-polysiloxane copolymer - 8 ~
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(LTV-sillcone elastomer C).
The LTV-silicone elastomer C i5 preferably used in the case of pharmacologically active substances having one or more unsa~urated groups in the molecule and includes~
I. 20 - 100 parts by weight of an organo-polysiloxane having a viscosity of 500 - 200,000 cSt (at 25C) and :~
the general formula:
lo t t R R R
n in which R represents an alkyl (preferably methyl) and/
or aryl group, and n represents an integer of 200 to 1,600.
II. 1 - 50 parts, preferably 10 - 35 parts, by weight of an organo-polysiloxane copolymer including ~
(a) (R')3SiOo 5-units ` -:
(b) (R')2(vi) sioo 5-units and (c) SiO2-units, ;~
in which R' represents a monovalent saturated organic group and at least 50~ of R' are methyl groups, and the ~ :
ratio a-~b/c is 0.4 - 1.5 (pre~erably 0.6 - 1.0) and the b/c is 0.02 - 0.5 (preerably 0.05 - 0.15). ~ ~ ;
III. 5 - 1.5 parts by weight of an organo-hydrogen-polysiloxane :~
of the general formula `; `

R'laHbsiO4-a b in which R'' represents a monovalent saturated group ~
and the ratio a:b:is 0.5 - 10 (preferably 1.0 - 5) and - ~:

the sum a+b is 1 to 2.5, and there being present, per . . ~ ..

molecule, at least three hydroge~ atoms bound to different Si-atoms, which contains 50 - lQ0 mol% of the unsaturated groups present in components ~I) and (II) on Si-H-bonds, and IV. a catalytic quantity of platinum o~ a platinum compound.
The alkyl and/or aryl groups R present in component I
may contain up to 10 carbon atoms, and include methyl, ethyl, propyl, isopropyl~ butyl, octyl, t-amyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tolyl, xylyl, benzyl, chlorophenyl, cyanomethyl and 3,3,3,-tribluoropropyl radicals.
The groups R' and R'' present in components (I) and (II) are the same or different, and represent alkyl radicals containing up to 8 carbon atoms, and preferably those containing up to 3 carbon atoms including the methyl, ethy]. and n-propyl groups.
The constituents I, II and IV form one component of the LTV-organo-polysiloxane two-component moulding composition and constituent III is the second component having a cross-linking action. ;~
~or the purpose o~ retarding hardening at room temper-ature, component I or the mixture of components I, II and IV or I, II, III and IV may contain metal ions, ~or example, copper(II) ions, in a quantity of from 2.00 to 75 parts by weight oE metal ions ~or each part by weight o~ platinum.
Although the vulcanization of the organo-polysiloxane moulding compositions in the presence of noble metal catalysts can also be carried out at room temperature or body temperature, it is especially advantageous to carry out the vulcanization at a temperature within the range of from 40 to 120C. The vul-canization time of the catalyzed mixture is 1 to 6 hours at a ;~
temperature o~ 60 to 120C. ~or pre-vulcanization the mixture may be heated at a higher temperature ~or a shbrt time, for example, ~ - 10 -up to 150~ for l to lO minutes, but a maximum of 15 minutes.
The pla-tinum component IV of the moulding composition may be used in one of the forms which are described in the lit-erature for catlyzing the reactionbetween silicon-bound hydro-gen residues and silicon-bound vlnyl residues, including metallic platinum or platinum on a carrier substance, such as silica gel or carbon powder, or hexachloroplatinic acid and platinum salts such as platinum carbonyl dichloride PtCOC12 and platinum dicarbonyl dichloride Pt(CO)2C12. A11 such platinum compounds can be used as vulcanization catalysts. However, pure hexachloroplatinic acid has the disadvantage that it is relatively difficult to dis-solve in organo-silicon compounds that contain silane groupings.
Platinum compounds that are used as catalysts in solid form cause the cross-linking reaction to proceed very slowly and in a manner ;`
difficult to regulate, and the reaction itself can be more easily interrupted than is to be expected when comparable catalysts are used in solution. Hexachloroplatinic acid used as catalyst is therefore preferably dissolved in isopropanol, and PtCOCl2 and -Pt(CO)2Cl2 are dissolved in a vinyl group-containing diorganopoly-siloxane containing lO to 15 mol% of vinyl groups. There must be used at least 0.1 part by weight of platinum per million parts by ;~
weight of components I and II. Since impurities in the moulding compositions can poison such small amounts of catalyst, there ~;
are preferably used lO to 40 parts per million of platinum. Larger quantities of platinum do not impair the reaction.
In a special construction of the vaginal ring device of the invention, there is used the same ~TV-silicone elastomer both for the support ring and for the pharmacologically active substance- ~ -containing ring.
In a special construction of the support ring, the support ring comprises a foamed silicone rubber having closed pores. For such purpose, there is added to the vulcanizing mixture in a finely - 11 ~

~ 34'~

divided form an agent that evaporates during the vulcanization such as a hydrocarbon for example, pentane or heptane and a halo-genated hydrocarbon, for example, methylene chloride, monofluoro-dichloromethane, dichlorofluoromethane or trichIorotrifluoroethane.
The vulcanizates obtained from the organo-polysiloxane two-component moulding compositions are inactive towards non- ;
ionic lipophilic medicaments, and physiologically tolerable to the living organism and not absorbed thereby. ~`
The pharmacologically active substances present in the elastomer material, for example, elastomer rings, are preferably active substances having a hormonal activity such as oestrogens and gestagens, inclllding 3-methoxy-17~-ethinyl-1,3,5(10)-oestra-trine-17-ol (mestranol), 3-hydroxy-1,3,5(10)-oestratrien-17-one (oestrone), 17~-oestradiol,oestriol and ethinyl-oestradiol and also 4-pregnen-3/20-dione (progesterone), d-13-ethyl-17~-ethinyl-17~-hydroxy-4-gonen-3-one (d-norgestrel) and esters thereof, 17~-ethinyl-l9-nortestosterone (norethisterone) and esters thereo~, 6-chloro-17-hydroxy-1~-2~-methylene-pregna-4,6-dien-3,20-dione (cyproterone) and esters thereof, l9-nor-hydroxyprogesterone and esters thereo~, 6-chloro-17-acetoxy-pregna-4,6-dien-3,20-dione (chloromadinone acetate), 15,16~-methylene- and 1~,16~-methylene-17~-hydroxy-18-methyl-17a-ethinyl-4-oestren-3-one, 17~-acetoxy-6~-methyl-progesterone ~medroxy-progesterone acetate) and 9~,10~-pregna-4,6-dien-3,20-dione (dydrogesterone).
As pharmacologically active substances there come into consideration all such substances, especially those which are non-ionic and lipophilic. Thus, there are also suitable neuro-leptics such as butyrophenone derivatives, for example, haloper-idol or bacteriostatics and fungistatics such as nystatin or metronidazole, for incorporation in the silicone elastomer.
The quantity of ph~armacologically active substance incorporated in the LTV-silicone elastomer may be from 10 to 60 ~\

by weight and in each particular case depends on the specific active substance or combination of active substances. The fol-lowing are examples of suitable total aosages:
Cyproterone acetate: 200 to 1,000 mg D-norgestrel: 100 to 500 mg Ethinyl-oestradiol: 20 to 100 mg Oestradiol: 20 to 90 mg Mestranol: 50 to 100 mg Ehtinyl-nort~stoesterone acetate: 150 to 950 mg ;~, Oestrone: 10 to 80 mg Oestriol: 15 to 70 mg Progesterone: 250 to 900 mg Norethisterone: 100 to 600 mg Cyproterone: 100 to !900 mg Norhydroxyprogesterone: 250 to 950 mg Chloromadionone acetate: 170 to 850 mg 15,16~-methylene- and 15,16~-methylene ~7~-hydroxy 18-methyl-17~-ethinyl-~
oestren-3-one: 50 to 750 mg Dydrogesterone: 100 to 550 mg Metronidazole: 300 to 950 mg Thus, it is possible for the outer elastomer section or ring to contain only a gestagen and the inner section or ring an oestrogen, or vice versa. Gestagens or estrogens may be used, for example in combination with bactericides.
The total quantity o~ active substance in the LTV-sili- -cone elastomer is so chosen that during the desired period a predetermined constant ~uantity i5 released per day. Examples are as follows: ' Cyprotone acetate: 3aa to 1,000 ~gm/d D-norgestrel: 30 to 250 ~gm/d Ethinyl-oestradiol: 30 to 60 ~gm/d ..

lV1~ 31 Oestradiol: 20~.to 150 ~gm/d Mestranol: 20 ta 100 ~gm/d Ethinyl-nortestosterone acetate: 300 to 1,000 ~gm/d.
One construction of the vaginal ring deviee of the invention is for use in preventing conception. A contraceptive effect based on inhibiting ovulation may be achieved within the period of use of the vaginal ring of the invention when it re-leases 130 to 250 ~gm of d-norgestrel and 30 to 50 ~gm of ethinyl-oestradiol or 800 to 1,000 ~gm of cyproterone acetate and 30 to 50 ~m of ethinyl-oestradiol daily. Vaginal rings that contain, in the active substance-containing inner and outer sections or rings, agents that are active against protozoa such as metjrone-idazole and optionally oestrogens, are especially suitable for of trichomoniasis. The active substanee is incorporated in the LTV-silicone rubber base used for making the ring containing the active substance. For such purpose, the active substance is :
disintegrated or finely ground, optionally micronized, mixed with an LTV-silieone rubber two-component compos*iion to form a sus-pension free from air bubbles, moulded into rings, and vulcanized ;.
by heating~, preferably at 40 - 120C. . .
The active substance-eontaining rings have, in the ease ;~
of the outer ring, a diameter of 0.5 to 8.0 mm, preferably 1.5 to 5.0 mm and, in the case of the inner ring, a diameter of:0.3 to 2.0 mm, preferably 0.4 to 1.6 mm.
The aetive substanee-containing rings may be built up wholly or partially on the matrix prineiple. However, the aetive substanee-containing rings may instead consist of a core eontaining an active substance and an outer sheath of silieone elastomer of any desired layer thiekness ~hich is free from active substance .
or lower in eoncentration of the aetive substance than is the core, or, conversely, it may eonsist of an enelosing layer of eIastomer and a core member low in medicament. Sueh a sheath whieh is lower ' ~ - 14 -. . ~ . , : .

'79~ ~:

in concentration of the active substance over a core higher in ~;
concentration of active substance in which the active substance is preponderantly in suspension is obtained, for example, by sub-jecting a preparation built up on the matrlx principle to an ex~
traction for a short time with a suitable solvent, such as a 1~
ethanol~water mixture (vol/vol). :
The se~ments or complete rings containing the active -~ :
substance are inserted in the pocket-shaped recesses in the support ring, and, if desired, adhesively secured in the recesses ... ~ ..
by the use of a catalyzed LTV-silicone elastomer two component composition and subse~uent vulcanization, or moulded on the ".
prevulcanized support ring and vulcanized with the support ring.~
The support ring and the acti~e substance-containing outer and~or .:
inner ring or segmentr joined or adhesively secured together, ~ :;
form the vaginal ring device proper.
For producing a coating or layer containing a pharma- `
cologically active substance on the support ring the active sub-stance is likewise incorporated in the LTV~sllicone elastomer base. For this purpose the active substance is finely ground, ~20 if desired, micronized, mixed with an LTV-silicone elastomer two~
component composition to form a suspension, applied as a layer using the multi~colour injection moulding techni~ue to the pre-vulcanized support ring, and vulcanized by heating, preferably at 40 - 120C.
It may also be of advantage to add to the suspension containing the acti~e substance and silicone elastomer an aux-iliary substance 5uch as tenside, an anti-Eoaming agent, a solub- :
ilizer or an absorption retarder, or a mixture of any two or more of such substances, .in order to impart the desired physical pro- : :
perties to the moulded body. Moreover, inert auxiliary substances such as highly dlspersed sllicon dioxide may be added to ~ive the ~;

ring the desired mechanical properties. ~
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Advantageously the active substance~containing~coatings, when vulcanized onto the outside o~ the support ring, have a thick- '' ness of 0.1 to 5.0 mm, and preferably 0.5 to 3.0 mm, and, when vulcanized onto the inside of the support ring, a thl'ckness of 0.1 to 3.0 mm,and preferably O.S to 2.0 mm.
The active substance-containing c~atings are built up wholly or partially on the matrix principle.
Since, during the vulcanization of the LTV-silicone ;
elastomer two-component composition, no by-products are formed a subsequent heat treatment of the hardened product ls unnecessary.
The vaginal ring devices of the invention have the ad- --vantage that the pharmacologically active substance or substances are released therefrom regularly and in constant amounts over a ' long period wi~hin the limits of the dosage necessary for the de-sired biological action, ~or example, for inhibiting ovulation. ' They have a further advantage that the quantity of the active '' substance that has to be incorporated in a single such contracep- ;
tive can be much smaller than in the case of the known vaginal rlngs .
The vaginal rings of the invention based on LTV-silicone elastomer have a materially reduced tendency to crumble under ' mechanical stress. When introduced into the body they are not as easily damaged as vaginal rings based on ~TV-elastomers, which contain, For improving the mechanical properties, more or less de~ined mixtures of active fillers~havingknown disadvantageous properties towards the pharmacologically active substance. ;
With the vayinal ring device of the invention, there :
can successfully be used many active substances that could not be used success~ully"with hitherto known and usual carrier materials in known vaginal rings~
The vaginal ring devices made in accordance with the invention can be sterilized in saturated, superheated steam at ~' '; ' "' "' - 16 - ~
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120~c, without undergoing undesired changes.
The following examples illustrate the invention:
Example 1 A support ring 1 (Figs. 1, 4 and 4a~ intended to receive two rings 4 and 5 containing pharmacologically active substances is injection moulded from polyethylene vinyl acetate copolymer (ALATHON ~ E/VA 3170/Du Pont & De Nemours) with the following dimensions: the external diameter of the support ring 1 is 6 cm, the internal diameter of the support ring is 4.2 cm and the distance from the pocket-shaped recess 2 for the outer ring 4 to the pocket-shaped recess 3 for the inner ring 5 (that is to say, ;;~
the shortest distance between the recess 2 of the outer ring 4 and the recess 3 of the inner ring 5) is 5.5 mm. The active substance- - ~
containing outer ring 4 has a diameter of 4 mm, and the active ~ ;
substance-containing inner ring 5 has a diameter of 0.5 mm. The cross-section of the vaginal ring has a diameter of 10.1 mm. !. ' ; .', ' :' ~
The active substance-containing outer ring 4 ha~ing a diameter of 4 mm is moulded from a homogeneous suspension of 15.0 g of D-norgestrel in 85.0 g of LTV-organo-polysiloxane two-com-ponent moulding composition,I, and is vulcanized by heating for2 hours at 110C. The ~TV-organo-pol~siloxane two-component moulding composition Cl consists of 75 parts by weight of a poly-dimethylsiloxane vinyl-terminally blocked at both ends and having ;;
a viscosity of 50,000 cSt at 25C, and 25 parts by weight of a copolymer having the following composition: 40 mol~ of SiO2-units 45 mol% of ~CH3)Sioo 5-units, 15 mol~ of Vi~CH3)25iOo 5-units, 8 parts by weight of an Si-H-~omponent consisting of: 16.6 mol~ of (CH3)3SiOo 5-units, 33.4 mol~ of (CH3~2SiO-units, 50 mol~ of CH3HSiO-units and la ppm of platinum (calculated on the total mixture inthe form of a solution of 2~ strength of H2PtC16 in isopropanol~. The active substance-containing inner ring 5 is made from a homogeneous suspension of 58.0 g of ethinyl-oestradiol , ~ :
, . .. .. . . .. .. . . . ....

-?9~

in 42.0 g of LTV-organo-polysiloxane two-component moulding compostiion C2 by moulding and vulcanizing for two hours at 105C.
The LTV-organo-polysiloxane two-component moulding composition C2 consists of 85 parts by weight of a polydimethylsiloxane vinyl-terminally blocked at both ends and having a viscosity of 1,000 cSt at 25C~ and 15 parts by weight of a copolymer of the com-position: 40 mol~ of SiO2-units, 45 mol% of (CH3)3SiOo 5-units 15 mol% of vi(cH3)2sioo 5-units, 4.5 parts by weight of an Si-H-component consistins Of: 38 mol% of SiO2-units, 29 mol% of (CH3)3SiOo 5-units, 33 mol% of (CH3)2HSiOo 5-units and 10 ppm platinum (calculated on the total mixture in the form of a solution of 2% strength of H2PtC16 in isopropanol).
Example 2 From a dimethyl-polysiloxane moulding composition (SILASTIC ~ 4600/Dow Corning), is made by moulding, pre-vulcan-ization for 5 minutes at 150C and vulcanization for one hour at 120C a support ring 1 (Figs. 1, 4 and 4a) having the fol-lowing dimensions: an external diameter of 6 cm, an internal diameter of 4.2 cm and a distance of 5.3 mm from the pocket-shaped recess 2 for the outer ring 4 to the pocket-shaped recess 3 for the inner ring 5. In such support ring 1, are inserted a D-norgestrel-containing outer ring 4 of 4 mm diameter and a mestranol-contain-ing inner ring 5 of 1 mm diameter.
The D-norgestrel-containing outer ring 4 is made from a suspension of 20.0 g of D-norgestrel and 18.0 of highly dispersed silicon dioxide in 62.0 g of LTV-organo-polysiloxane two-component moulding composition C3 by moulding and vulcanization for two hours at 100C. The LTV-organo-polysiloxane two-component moulding composition C3 has the follcwing composition: 75 parts by weight of a poly-dimethylsiloxane vinyl-terminally blocked at both ends and having a viscosity of 1,000 cSt at 25C, and 25 parts by weight of a copolymer having the composition: 40 mol% of SiO2-units, :

45 mol~ of (CH3)2SiOo 5-units, 15 mol~ of Vi(CH3~2Sioo 5-units, 8 parts by weight of an Si-H-component consisting of 16.6 mol% of (CH3)3SiOo 5-units, 33.4 mol~ of (CH3~2SiO-units, 50.0 mol~ of CH3HSiO-units and 30 ppm platinum (calculated on the total mix-ture in the form of a solution of 1~ strength of Pt(CO)2C12 in an open-chained vinyl group-containing dimethylpolysiloxane con-taining 12 mol% of vinyl groups) and 5 parts by weight of Cu(II)-ions, calculated on ~he parts by weight of platinum.
The mestranol-containing inner ring 5 is made from a ~;
homogeneous suspension of 60.0 g of mestranol in 40.0 g of LTV-organo-polysiloxane two-component moulding composition C4 by moulding and vulcanization for 90 minutes at 110C. The LTV-. :
organo-polysiloxane two-component moulding composition C4 consists ~`
of 75 parts by weight o~ a poly-dimethylsiloxane vinyl-terminally blocked at both ends and having a viscosity of 1,000 cSt at 25C, `
25 parts by weight of a copolymer having the composition: 40 mol%
of SiO2-unitsr 45 mol~ of (CH3)2SiOo 5-units, 15 mol% of Vi(CH3)2SiOo 5-units, 8 parts by weight of an Si-H-component con-sisting of 16.6 mol% of (CH3)3SiOo 5-units, 33.4 mol~ of (CH3)2SiO-units, 50.0 mol~ of CH3HSiO-units, and 10 ppm platinum (calculated on the total mixture in the form of a solution of 2 stxength of H2PtC16 in isopropanol).
Example_3 From a homogeneous mixture of 35.0 g of highly dispersed silicon dioxide and 65.0 g of resin-reinformed dimethyl-polysiloxane moulding composition (SIL GEL ~ 2001/Wacker Chemi) are made sup-port rings 1 (Figs. 1, 4 and 4a) having the dimensions given in .Example 2 by the method described in that example. `
The vaginal ring devices are made using such support rings by adhesively uniting therewith the active substance-contain-ing inner and outer rings 4 and 5, respectiveIy having the dimen- `~
sions described in Example`2.

.

For the adhesive union, there is used the above-men-tioned catalyzed t~o-component composition. The active substance-containing outer ring 4 is made from a suspension of 25.0 g of micronized cyproterone acetate and 15.0 g of highly dispersed silicon dioxide in 60.0 g of LTV-organo-polysiloxane two-compon-ent moulding composition C5 by moulding and vulcanization for two hours at 115C. The LTV-organo-polysiloxane two-component moulding composition C5 consists of 75 parts by weight of a poly-dimethyl-siloxane vinyl-terminally blocked at both ends and having a vis-cosity of 50,000 cSt at 25C, 25 parts by weight of a copolymer having the composition: 40 mol% of SiO2-units, 45 mol% of (CH3)3SiOo 5-units, 15 mol% of Vi(CH3)2SiOo 5-units, 8 parts by weight of an Si-H-component consisting of 16.6 mol% of (CH3)3SiOo 5-units, 33.4 mol% of (CH3~2SiO-units, 50 mol% of CH3HSiO-units and 35 ppm platinum (calculated on the total mixture in the form of a solution of 1.5% strength of Pt(CO)2C12 dissolved in a vinyl group-containing dimethylpolysiloxane con- ~ `
taining 15 mol% of vinyl groups).
The active substance-containing inner ring 5 is made from a suspension of 20.0 g of oestradiol in LTV-organo-polysil-oxane two-component moulding composition C6 by mouLding and vul-canization at 110C for 2 hours.
The LTV-organo~polysiloxane two-component moulding com-position C6 has the ~ ~ ng composition: 75 parts by weight of a polydimethylsiloxane vinyl-terminally blocked at both ends and having a viscosity of 50,000 cSt at 25C, 25 parts by weight of a copolymer of the composition: 40 mol% of SiO2-units, 45 mol%
of (CH3) SiOo 5-unitsr 15 mol% Vi~CH3)2SiOo 5-units, 8 parts by weight of an Si-H-component consisting of: 16.6 mol% of (CH3~3Sioo 5-units, 33.4`mol% of (CH3~2SiO-units, 50 mol% of ;~
CH3HSiO-units and 25 ppm platinum (calculated on the total mixture in the form of a solution of 2% strength of PttCO)2C12 ~L~8~ 7a3 dissolve~ in a ~inyl group-containing dimethylpolysiloxane con-taining 10 mol% o~ vinyl groupsl.
Example 4 , Support rings 1 (Figs. 1, 4 and 4a~ having a diameter of 9 mm and a distance of 5.3 mm from the pocket~shaped recess 2 ~
for receiving the active substance-containing outer ring 4 to ;
the pocket-shaped recess 3 for the active substance-containing -inner ring 5 are each made from a homogeneous mixture of 30.0 g of highly dispersed silicon dioxide in a catalysed LTV-silicone elastomer base in the form of a dimethyl-pol~siloxane casting ;
composition (SILOP~EN ~ 0228/Bayer) by moulding, pre-vulcan-ization for 5 minutes at 140C and vulcanization at 120C for 120 minutes. The support rings 1 are designed to receive a D-norges-txel-containing outer ring 4 of 3.0 mm diameter and an oestradiol-containing inner ring 5 of 1.0 mm diameter. The cross-section of the vaginal ring has a diameter of 10.3 mm. The D-norgestrel-containing outer ring ~ is made from a suspension of 15.0 g of micronized D-norgestrel and 20.0 g of highly dispersed silicon dioxide in 65.0 g of the LTV-organo-polysiloxane two-component moulding composition C4, such as described in Example 2, by mould- -, ing and vulcanization at 110C for 2 hours. The vulcanizates are extracted at room temperature in succession for 90 minutes with ethanol of 96% strength, again for 30 minutes with ethanol of 96% strength, for 60 minutes with ethanol of 70% strength and for 30 minutes with ethanol of 50~ strength, and are then dried in air.
There are obtained D-norgestrel-containing rings having a sheath low in D-norgestrel on a core rich in D-norgestrel. The oestradiol containing inner ring 5 is moulded ~rom a suspension of 35.0 g o~ micronized oestradiol in 65.0 g of the LTV-organo-polysiloxane two component moulding compositlon C3 described in Example 2, and vulcanized by being hèated for 2 hours at 100C.

.

-" ~.(.)~9R'~ffl~

Example 5 Support rings 1 (Figs. 1, 4 and 4ai having the dimen-sions yiven in Example 1 are made from a dimethylpolysiloxane moulding composition ~SILASTIC ~ 4600/Dow Corning)~ as given in Example 2. Vaginal rings are made from the support rings 1 and the active substance-containing outer and inner rings 4 and 5, respectively of Example 1, whlch are inserted in the support rings 1. .

Example 6 ' Support rings 1 (Figs. 1, 4 and 4a) having the dimen-sions given in ~xample 1 are injection moulded from a thermo- . :
plastic polyether-ester-elastomer based on terephthalate. The support rings 1 are intended to receive D-norgestrel- containing outer ring 4, such as is described in Example 2, and an ethinyl-oestradiol-containing inner ring 5 such as is described in Example 1. The active substance-containing outer and inner rings 4 and 5, respectively are inserted in the support ring 1.
Example 7 Support rings 1 (Figs. 1, 4 and 4a) having the dimen-sions given in Example 4 are made by the method given in thatexample from a suspension of 32.0 g of highly dispersed silicon dioxide in the LTV-organo-polysiloxane two-component moulding composition C4 described in detail in Example 3.
The active substance~containing outer rings 4 are made .:
from a suspensoin of 35.0 g of micronized ethinyl-nortestosterone acetate and 15.0 g of silicon dioxide, highly dispersed and ren-dered hydrophobic, in 50.0 g o~ LTV-organo-polysiloxane two-component moulding composition C3, such.as is described in Example .-2, by moulding and vulcanization for 2 hours at 100 C. The active ~;
substance-containing inner rings 5 have the composition of the ~ .

inner rings 4 described in Example 3 and are made in an analogous manner. The support ring 1 and the active substance-containing outer and inner rings 4 and 5, respectively are united to form ' a vaginal ring device.
Example 8 Support rings 1 (Figs. 5 and 5a) having a cross-section-al diameter of 9 mm and a distance of 6.2 mm between the pocket- -~
shaped recesses 3 and 7 to receive the active substance-containing outer and inner ring 8 and 5, respectively are made from a sus-pension of 28.0 g of highly dispersed silicon dioxide and 5.0 g of barium sulphate in 67.0 g of catalyzed LTV-silicone rubber ,~
two-component composition (SILOPREN ~ 0839/Bayer) in accordance with the method given in Example 4. The support rings are des-igned to receive a D-norgestrel-containing outer ring 8 with a cross-sectional coniguration in the form of a section of a cir-cle having a diameter of 2.5 mm and an ethinyl-oeskradiol-con-taining inner ring 5 having a diameter of 0.5 mm.
The D-norgestrel-containing outer ring 8 is made from a suspension of 40.0 g of D-norgestrel in 60.0 g of LTV-organo- ;
poLysiloxane two-component moulding composition Cl, such as is described in Example 1, by moulding and vulcanization for 90 minutes at 110C.
The ethinyl-oestradiol-containing inner rings 5 are made from 55.0 g of ethinyl-oestradiol and ~5.0 g of LTV-organo-polysiloxane two-component moulding composition C3, such as is described in Example 2, after preparing a suspension free from air bubbles, by moulding and vulcanization for three hours at 90C.
Example` 9 Support rings 1 as shown in Figures 5 and 5a having the dimensions given in Example 8 are injection moulded from thermoplastic polyether-ester elastomers based on terephthalate.
By inserting the active substance-containing inner and outer rings 5 and 8, respectively described in Example 8 the support rings 1 ' .

. ~ ~

are made up into vaginal ring ~evices of which the cross-section has a diameter of 10.2 mm.
Example 10 A support ring 1 as shown in Figures 1, 4 and 4a design-ed to receive two active substance-containing rings 4 and 5, is made, as described in Example 2, from dimethyl-polysiloxane mould-ing composition (SILASTIC ~ 4600/Dow Corning) having an external diameter of 3 cm and an internal diameter of 2 cm. The distance between the pocket-shaped recesses 2 and 3 of the support ring is 3.1 mm from the outer ring 4 to the inner ring 5. The active substance-containing outer ring 4 has a diameter of 2mm and is made, as described in Example 1, from a D-norgestrel suspension ~ `
in LTV-organo-polysiloxane two-component moulding composition Cl.
The active substance-containing inner ring 5 has a diameter of 0.5 mm and is made, as described in Example 9, from an ethinyl-oestradiol suspension in LTV-organo-polysiloxane two-component moulding composition C3 as described in Example 2. The active substance-containing rings 4 and 5 are inserted in the support ring 1 and all three rings together form a vaginal ring device for use in an animal.
Example 11 Support rings 1 as shown in Figures 1, 4 and 4a having an external diameter of 4.2 cm and an internal diameter of 3.0 cm having two pocket-shaped recesses 2`and 3 for receiving the active substance-containing outer ring 4 having a diameter of 2.5 mm and the active substance~containing inner ring 5 having a diameter of 0.5 mm and a distance of 3.8 mm between the pocket-shaped recesses 2 and 3 are moulded from a homogeneous mixture of 31.0 g of highly dispersed silicon dioxide in catalysed LTV-silicone elastomer base A, and pre-vulcanized for 5 minutes at 130C. The active substance-containing vaginal ring is made by moulding on the pre-vulcanized support ring in a second stage of the process the outer ring 4 '7~

containin~ D-nor~estrel in the LTV-organo-polysiloxane two-component moulding composition Cl (as described in Example 1) and the inner ring 5 containing ethinyl-oestradiol in the LT~-organo-polysiloxane two-component moulding composition C2 (as described in Example 1), and pre-vulcanizing them by heat for 5 minutes at 120C.. To comple-te the vulcanization,:the assembly of support ring and active substance-containing rings is heated for 2 hours at 110C.. The vulcanizate is sterilized by heating for 30 minutes in superheated steam, and is then packed sterile.
Examplè 12 There is made from dimethyl-polysiloxane moulding composition (SILASTIC ~ 4600/Dow Corning) by moulding, pre-vulcanizing for 5 minutes at 150C and vulcanizing at 120C for 1.5 hours a support ring 1 as shown in Figures 1, ~ and 4a having the following dimensions: external diameter 6 cm, internal diameter .

4.2 cm and a distance of 5.3 mm between the pocket-shaped recesses 2 and 3 for receiving the active substance-containing outer and inner ring 4 and 5, respecti~ely.
In this support ring 1 are inserted an outer ring 4 hav-ing a diameter of 4 mm containing metronidazole and nystatin andan inner ring 5 having a diameter of 1 mm containing oestriol.
The outer ring 4 can easily be removed by the patient from the application unit after usiny the vaginal ring for one week. The remaining oestriol-containing vaginal ring is intended for use over several weeks.
The active substance-containing outer ring is moulded from a homogeneous mixture of 30.0 g of micronized l~-thydroxy-ethyl)-2-methyl-5-nitro-imidazole (metronidazole), 30.0 g of micronized nystatin, 2.0 g of silicon dioxide highly dispersed and rendered hydrophobic and 38.0 g of LTV-organo-polysiloxane two-component moulding composition C4 as described in Example 2. :

.

The vulcanization of this ring is carried out first for 5 minutes at 100C and then for ~ hours at 80C..
The active substance-containing inner ring 5 is moulded from a suspension of ~5.0 g of micronized oestriol in 45.0 g of LTV-organo-polysiloxane two-component moulding composition C3, as described in Example 2, and vulcanized by heating for 3 hours at 95C..
The vaginal ring device is intended for the treatment of trichomoniasis.
Example 13 From dimethyl-polysiloxane moulding composition (SILASTIC ~ 4600/Dow Corning) there is obtained by moulding, -pre-vulcanizing for 5 minutes at 150C and vulcanizing for 1.5 -~
hours at 120C a support ring 1 as shown in Figures 1, ~ and 4a having the following dimensions: external diameter 6 cm, internal diameter 4.2 cm and a distance of 5.6 mm between the pocket-shaped recesses 2 and 3 for receiving the D-norgestrel-containing outer and inner rings 4 and 5, respectively.
D-norgestreI-containing rings having a diameter of 4 mm (outer ring) and 1 mm (inner ring), respectively, are moulded from a suspension of 25.0 g of micronized D-norgestrel, 12.0 g o~ highly dispersed silicon dioxide in 63.0 g o~ LTV-organo-polysiloxane two-component moulding composition C~, as described in Example 2, pre-vulcanized by being heated for 10 minutes at 115C and then vulcanized by heating for 3 hours at 100C. The vulcanizates are e~tracted at room temperature in succession for 90 minutes with ethanol of 96% strength, again for 30 minutes ~
with ethanol of 96% strength, for 60 minutes with ethanol of 70% `
. ~ . . .
strength and for 30 minutes with ethanol of 50% strength, and then air-dried. The D-norgestreI-containing rings consisting of an envelope low in D-norgestrel on a core rich in D-norgestrel, are inserted in the support ring 1 to form the` vaginal ring. ~ ;

i .~ .. . .. . , . , , , . ~ . . . .. . .. . . . . . .

~38~;~

Example 14 From dimethyl-polysiloxane moulding composition (SILASTIC ~ 4600/Dow Corning), a support ring 1 as shown in Figures 1, 4 and 4a is made as described in Example 13 and having the same dimensions. Oestriol-containing outer and inner rings 4 and 5, respectively are made from a suspension of 20.0 g of micronised oestriol, 15.0 g of highIy dispersed silicon dioxide in the LTV-organo-polysiloxane two-component moulding compos-ition C4 described in Example 2 by the method given in Example 13, and partially extracted with ethanol in the same manner. The oestriol-containing outer ring 4 and inner ring 5 are inserted in the support ring 1 and provide a vaginal ring device of whish the cross-section has a diameter of 10.3 mm.
Example 15 From dimethyl-polysiloxane moulding composition SILASTIC ~ 4600/Dow Corning) there is made by moulding, pre-vulcanizing for 5 minutes at 150C and vulcanizing for one hour at 120C a support ring 1 as shown in Figures 6 and 6a having the following dimensions: external diameter 6 cm, internal diameter 4.2 cm and a pocket-shaped recess 7 for the outer ring spaced 6.5 mm from the inner edge of the support ring.
In the support ring 1 is inserted an outer ring 4 con-taining D-norgestrel and having a cross-sectional configuration in the form of a section of a circle having a diameter of 2O5 mm.
The outer ring 4 containing D-norgestrel is made from a suspension of 20.0 g of D-norgestrel and 18.0 g of highly dis-persed silicon dioxide in 62.0 g of LTV-organo-polysiloxane two-component moulding composition C3 by moulding and vulcanizing for 2 hours at 100C.. The composition of the LTV-organo-polysiloxane two-component moulding composition C~ is given in Example 2.
Example 16 From dimethyl-polysiloxane moulding eomposition r8~

(SILASTIC ~ 4600/Dow Corning) there is made by mo~lding, pre-vulcanizing for 5 minutes at 150C and vulcanizing for 1.5 hours at 120C a support ring 1 as shown in Figures 7 and 7a having the following dimensions: outer diameter 6 cm, inner diameter 4.2 cm and a distance o~ 8.1 mm from the pocket-shaped recess 3 for receiving the active substance-containing inner ring 5 to the outer edge of the support ring. : ;
An inner ring 5, containing oestriol and having a dia- .
meter of 1.5 mm is inserted in the recess 3.
The active substance-containing inner ring 5 is moulded from a suspension of 55.0 g of micronized oestriol in ~5.0 g of LTV-organo-polysiloxane two-component moulding composition C3, as described in Example 2, and vulcaniæed at 95C. by heating for 3 hours. :
Example 17 ; `.
A D-norgestreI- and ethinyl-oestradiol-containing vaginal ring device as shown in Figures 8 and 8a, having an .
external diameter of 60 mm and an internal diameter of 42 mm, is made using the multi-colour injection moulding technique from three components in the form of a compound vulcanizate, which is vulcanized at 100C for one hour. Component I is a homogeneous mixture of 26 parts by weight of highly dispersed silicon dioxide, 3 parts by weight of highly dispe~sed magnesium oxide and 71 parts by weight of catalyzed ~TV-silicone elastomer base (SILOPREN
3008/Bayer). :~
Component II consists of a mixture o~ 24 parts by weight o~ highly dispersed silicon dioxide, 8 parts b~ weight o~ micronized :.. . .
D-norgestrel and 68 parts by weight of catalyzed LTV-silicone .. .:~
elastomer base (SILOPREN ~ 3008/Bayer).
Component III contains in 100 parts by weight 10 parts .

by weight of micronized ethinyl-oestradiol and 21 parts by weight of highIy dispersed siIicon dioxide in addition to 69 parts by ~, .

~.

weight of LTV-organo-polysiloxane moulding composition consisting of 75 parts by weight of a poly-dimethylsiloxane vinyl-terminally blocked at both ends and having a viscosity of 1000 cSt at 25C., 25 parts by weight of a copolymer having the composition: 40 mol ~
of SiO2-units, 45 mol ~ of (CH3)2Sio~ 5-units, 15 mol % of Vi(CH3)2 SiOo 5-units, 8 parts by weight of an Si-H-component consisting if 16.6 mol % of (CH3)3Sioo 5-units, 33.4 mol % of (CH3)2SiO-units, 50.0 mol ~ of CH3HSiO-units and 10 ppm platinum (calaulated on the total mixture in the form of a solution of 2% strength of H2PtC16 in isopropanol).
The compound vulcanizate component I forms a ring having an eIlipsoidal aross-sectional configuration and the active sub-stance-containing components II and III are vulcanized onto the outer and inner edges in a manner such that the vaginal ring as a whole has a circular cross-sectional configuration having a radius of curvature of ~.5 mm at its outer edge. Component II
has a maximum layer thickness of 2 mm and is vulcanized onto an arcuate section of 2.5 mm in a ring-enclosing manner. Com-ponent III is vulcanized in a ring-enclosing manner with a maximum layer thickness of 1.5 mm and a.spread of 1.5 mm.
Example 18 A vaginal ring device as shown in Figures 8 and 8a is made from the three components I, II and III desaribed in Example 17 in the form of a compound vulcanizate having the same dimensions, but ethylene chloride is added to the active substanae-free com-ponent I so that evaporation occurs in component I during the in- :
jection moulding and the vulcanization process, and it forms a foamed rubber having closed pores.
Example 19 A vaginal ring device as shown in Figure 10 having the dimensions given in Example 17 is made of three components in the form o~ a compound vulcan`iza~e`using the multi-colour:. .`
,.
.
, -:, :

~ ~ 8 ~

injection moulding technique. Component I consists of a mixture of 24 parts by weight of highly dispersed silicon dioxide and 73 parts by weight o~ LTV-silicorle elaskomer composition (SILOPREN ~ 0028/Bayer).
Component II consists of a mixture of 4.8 parts by weight of micronized D-norgestrel, and 22.4 parts by weight of highly dispersed silicon dioxide and 72.8 parts by weight of organo-polysiloxane two-component moulding composition as describ-ed in Example 17.
Component III contains 10 parts by weight of micronized ethinyl-oestradiol and 22 parts by weight of highly dispersed silicon dioxide in 68 parts by weight of an LTV-organo-polysiloxane two-component moulding composition consisting of 75 parts by weight of a poly-dimethylsiloxane vinyl-terminally blocked at both ends and having a viscosity of 1,000 cSt at 25C, 25 parts by `
weight of a copolymer of the composition: 40 mol ~ of SiO2-units, 45 mol % of (CE3)2Sioo 5-units, 15 mol % of Vi(CH3)2SiOo 5-units, 8 parts by weight of an Si-H-component consisting of 16.6 mol % of (CH3)3SiOo 5-units, 33.4 mol % (CH3)2SiO-units, 50.0 mol % of CH3 HSiO-units and 30 ppm of platinum ~calculated on the total mixture in the form of a solution of 1~ strength of Pt!~CO)2C12 dissolved in an open-chained vinyl group-containing dimethylpolysiloxane ~' containing 12 mol % of vinyl groups) and 5 parts by weight o~ Cu (II) ions, calculated on the parts by weight of platinum.
From the three components, the compound vulcanizate in the form of rings lying one upon another is made by vulcanization for 75 minutes at 120C.. In the compound, vulcanizate component I is shape-determining and has an approximately circular cross-sectional configuration. On the flattened outer edge of the ring, consisiting of active substance-free component I, are vulcanized component II in a width of 3 mm at a maximum layer thickness of 2.0 mm over 120 mm of the outer edge of the ring and component III

4~

in a width of 2 mm at a maximum layer thickness of 2.5 mm over the remainder of the length of the outer edge.
Example 20 ~;
A vaginal ring device as shown in Figure 9 in the form of a compound vulcanizate is made in a manner similar to that described in Example 19. The D-norgestrel-containing component II is applied round the outer edge of component I in a width of 2.5 mm and a maximum layer thickness of 3 mm.
Example 21 `
A vaginal ring device as shown in Figures 8 and 8a containing ethinyl-oestradiol and D-norgestrel is made in a multi-colour injection moulding apparatus from components I, II
and III described in detail in Example 19 by compound vulcanization at 120C. The resulting compound vulcanizate having a circular cross-sectional configuration has the D-norgestrel-containing component extending around the outer edge in a maximum layer thickness of 2.0 mm and a width of 2.5 mm. On the inner side of the ring, is fixed the ethinyl-oestradiol-containing component III extending over a length of 30 mm and having a width of 2.0 mm and a thickness of about 2.5 mm.

': :

,,, ~:"

Claims

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

1. A vaginal ring device which comprises a support-ring and at least one ring member, extending circumferentially round at least a part of the support-ring and incorporating a pharmacologically active substance, each ring member being compos-ed of an LTV-silicone elastomer material and being so located that the material has an exposed surface.

2. A device according to claim 1, wherein said each ring member is a complete ring extending circumferentially wholly around said support ring.

3. A device according to claim 1, wherein said support ring includes an inner ring member, extending around the interior circumference thereof incorporating an inner active substance ring of said elastomer material, and an outer ring member extend-ing around the exterior circumference thereof incorporating an outer active substance-ring of said elastomer material.

4. A device according to claim 2 or 3, wherein each said active substance-containing ring member has a circular cross-sectional configuration.

5. A device according to claim 2 or 3, wherein each said active substance-containing ring member has a semi-circular cross-sectional configuration.

6. A device according to claim 1, 2 or 3, wherein the silicone elastomer material is vulcanized onto the support ring.

7. A device according to claim 1, 2 or 3, wherein the LTV-silicone elastomer comprises:
(I) 20 - 100 parts by weight of an organo-polysiloxane having a viscosity of 500 - 200,000 cSt (at 25°C) and the general formula:

in which R represents an alkyl or aryl group, and n represents an integer of 200 to 1,600, (II) l - 50 Parts by weight of an organio-polysiloxane co-polymer comprising:
(a) (R') 3Si00.5-units (b) (R')2(vi)Si00.5-units and (c) Si02-units, in which R' represents a monovalent organic group containing no unsaturated groups and at least 50% of R' are methyl group, and the ratio a+b/c is 0.4 - 1.5 and the ratio b/c is 0.02 - 0.5, (III) 5 - 15 Parts by weight of an organo-hydrogen-polysil-oxane of the general formula in which R'' represents a monovalent group containing no unsat-urated groups and the ratio a:b has a value 0.5 - 10 and the sum a+b is equal to 1 to 2.5, and there being present, per molecule, at least three hydrogen atoms bound to different Si-atoms, which contains 50 - 500 mol % of the unsaturated groups present in components (I) and (II) on Si-H-bonds, and (IV) a catalytic quantity of platinum or a platinum compound.

8. A device according to claim 1, 2 or 3, wherein the pharmacologically active substance is a compound containing one or more unsaturated bonds in the molecule.

9. A device according to claim l, 2 or 3, wherein the pharmacologically active substance is a non-ionic lipoid soluble substance.

10. A device according to claim 1, 2 or 3, wherein the pharmacologically active substance is a steroid hormone.

11. A device according to claim 1, 2 or 3, wherein the support ring is formed of a synthetic plastic material.

12. A device according to claim 1, 2 or 3, wherein the support ring is formed of an LTV-silicone elastomer.

13. A device according to claim 1, 2 or 3, wherein said support ring is formed from the same LTV-silicone elastomer as the material containing a pharmacologically active substance

14. A device according to claim 1, 2 or 3, wherein the pharmacologically active substance is a contraceptive.

15. A device according to claim 1, 2 or 3, wherein the pharmacologically active substance is D-norgestrel.

16. A device according to claim 3, wherein one of said rings contains a compound having gestagenic activity and the other ring contains a compound having oestrogenic activity.

17. A device according to claim 16 wherein said inner ring contains a compound having estrogenic activity and said outer ring contains a compound having gestagenic activity.

18. A device according to claim 1, wherein an LTV-silicone elastomer layer containing a pharmacologically active substance occupies only a section of the outer edge of the support ring.

19. A device according to claim 1, 2 or 3, wherein the support ring is formed of a foamed silicone rubber having closed pores.