SK107098A3 - Contraceptive release systems with antibacterial and/or antiviral effect - Google Patents

Abstract

The invention relates to the combination of at least one compound with contraceptive effect and/or one compound with antibacterial and/or antiviral effect for incorporation/application to an intravaginal, intrauterine or intracervical release system. The invention also relates to the use of said release system.

Description

? In IM

ANTI-CONCEPTION RELEASE SYSTEMS WITH ΑΝΤΙ BACTERIAL AND / OR ANTI-VIRUS EFFECTS AND THEIR USE

Technical field

The invention relates to the combination of at least one compound with (a) contraceptive action and / or one compound with (b) antibacterial and / or antiviral activity, wherein one compound may also have all three properties for incorporation / delivery on intravaginal, intrauterinal or intracervical release system.

BACKGROUND OF THE INVENTION

Sexually transmitted disease (STD) is a seriously increasing medical and sociological problem.

A large number of different diseases can be transmitted during intercourse. A distinction is made between bacterial diseases (chlamydia, gonorrhea, syphilis) and viral diseases (cytomegalvirus = CMV, genital herpes simplex = HSV, human papillomavirus = HPV and human immunodeficiency = HIV / AIDS).

In the US, about 12 million people aged 15 to 29 are affected by STD. Overall, 56 million Americans find some of the types of STD except AIDS or HIV. New WHO surveys have shown that under the term major reproductive health concerns, STD, with an estimated 315 million cases worldwide, is a major health problem. In particular, it represents an estimated 30 to 40 million HIV infections with an expected 12 to 18 million acquired immunodeficiency syndrome (AIDS) diseases by the year 2000 (Achieving Reproductive Health for AH. The role of WHO (WHO / FHE / 95.6, World Health Organization, Geneva, 1995)) is a serious threat to world health. In particular, the numbers of new infections in the countries of the less developed world should be mentioned in particular, with a sudden increase in infections, and a strong rise in infections in heterosexual populations must be expected in these countries. There are estimates suggesting that 60% of HIV infections worldwide are heterosexual. Also in the US there is an increasing number of HIV infections running heterosexually, with transmission in most cases from male to female.

In addition to condoms, various antibacterial and antiviral agents (tetracyclines, chlorhexidine, sulfonamides, interferons) have been available to prevent STD. For the treatment of HPV, ISIS2105 (antisense oligonucleotide) was recently tested in clinical trials. Nonoxynol-9 (N9) spermizide inhibits the transmission of Gonorrhea and Chlamydia. There are references that N9 inhibits HIV transmission. However, the data published on this topic are contradictory, with the help of N9, irritations of the vaginal epithelium may occur, which may improve STD transmission.

Furthermore, the use of so-called aminosterols, such as squalamine, for the treatment of STD (Aminosterol Antibiotics, Current Opin. Ther. Pat. 3, 1369-1370; Cohen J. Women: Absent Term in AIDS Research Equation, Science, 269, 777-780 (1995). Squalamine has a broad antibiotic activity (Moore K., Wehrli S. et al., Squalamine: An aminosterol antibiotic from the shark, Proc. Natl. Acad. Sci. 90, 13541358, 1992),

In most cases, these substances are used in the form of suppositories which are introduced into the vagina shortly before contact.

Another challenge is to influence the pH value in the vagina. Experiments have shown that HIV is inactivated in an acidic environment. In this deployment, the pH increasing during ejaculation is maintained in an acidic region. By inhibiting the exchange of sodium / hydrogen ions on the cell surface, the pH can be lowered. Thus, sodium / hydrogen ion exchange inhibitors would lead to a decrease in pH and prevent the possibility of HIV infection without damaging the vagina or reproductive tract cells.

j + es

Compounds that inhibit sodium / hydrogen ion exchange have been described in the literature as a possible therapy for the treatment of cardiovascular diseases (Scholz, Albus U. Potential of selective sodium-hydrogen exchange inhibitors in cardiovascular therapy, Cardiovasc. Res. 29, 184-188, 1995) . Compounds having this effect have been described in DE-4318756 (Schwark Jan-Robert), DE 93-120374 (Weichert A), EP 93-110195 (Weichert A) and US 4423069 (Zanverld L.).

All the STD prevention applications described above serve only for temporary one-time protection, which is always used before sexual intercourse. As with any single application, administration errors and tolerability may occur. In this case, the risks of STD transmission and contraception remain. In purely contraceptive methods, long-acting methods such as IUDs, implants, vaginal rings and injectabiles are preferred for a large number of women. This is especially true for women in less developed countries.

Thus, there is a strong need to provide a system that would continuously provide combined protection against STD while providing safe contraceptive protection.

SUMMARY OF THE INVENTION It is therefore an object of the present invention to provide a system which at the same time provides contraceptive protection that continually protrudes for a long time from diseases transmitted by sexual intercourse and which is used by women.

SUMMARY OF THE INVENTION

It has now been found that a combination of a compound with (a) contraceptive action and / or a compound with (b) antibacterial effect and / or a compound with (c) antiviral effect, wherein one compound may also have all three properties, provides intravaginal, intrauterinal or intracervical release system

IC31 T ”contraceptive protection while preventing sexually transmitted diseases.

In a particularly preferred embodiment of the combination of the present invention, the compound with (a) the contraceptive effect is levonorgestrel and the compound with (b) the antibacterial effect and / or (c) the antiviral effect squalamine and the release system is IUD, intracervical system or vaginal ring.

Another embodiment of the present invention relates to the use of an intravaginal, intrauterine or intracervical release system comprising at least one compound with (a) contraceptive action and / or one compound with (b) antibacterial and / or (c) antiviral effect, to prevent disease sexually transmitted.

Possible release systems according to the present invention are IUDs (Figs. 1 and 2), vaginal rings (Fig. 3) and cervical systems (Fig. 4).

Intrauterine conceptions for preventing conception containing the active substance are dosing devices with a reservoir from which the active substance is released by diffusion. The devices comprise a core of solid or liquid carrier permeable to a lipophilic drug in which an excess of drug is dispersed and a polymer wall permeable to the drug surrounding the core. The wall is less well permeable to the drug than the carrier, so that the wall determines the rate of drug delivery to the environment in use. The hydrophilic active ingredient may be applied partially to the device as a mixture with a polar polymer to achieve the desired delivery rate, or the surface of the device may be partially coated in different layers of mixtures of hydrophilic drug and soluble polymers such as polyvinyl alcohol, polyethylene oxide, hydroxypropylmethylcellulose and / or carboxymethylcellulose, depending on the delivery value to be achieved. With the release systems described above, the drug substances contained are delivered at a substantially constant rate.

The use of intrauterine devices (IUDs) for contraception is described in the literature (Speroff L. and Darney P., The intrauterine device (IUD), Clinical Guide for Contraception, Eds. M. Fisher, Wiliams & Wilkins, Baltimore, Maryland, 157-185). , 1992). Also found are gestagens containing IUDs in some countries on the market (Luukkainen T., Allonen H., Haukkamaa M. et al., Five Year's Experience with Levonorgestrel Releasing lUDs, Contraception 33: 139-145, 1986). The contraceptive safety of IUDs is high. However, increased use of copper IUDs may result in increased menstrual blood loss. An increased risk of infection is also described in the literature (Buchan H., Villard Mackack L. et al., Epidermiology of Pelvic Inflammatory Disease in Parous Women with Special Reference to Intrauterine Device Use, Br. J. Obset. Gynacol. 97: 780-786, 1990) and the incidence of ectopic pregnancies. IUDs that are equipped with one progestogen appear to prevent and even significantly reduce menstrual blood loss; in addition, they combine mechanical contraception with hormonal (for example, thickening of the cervical mucus as a barrier to sperm), which enhances contraceptive protection (Speroff L. and Darney P., The intrauterine device (IUD), Clinical Guide for Contraception, Eds. M. Fisher, Wiliams &Amp; Vilkens, Baltimore, Maryland, 157-185,1992).

Possible antibacterial or antiviral compounds according to the invention are all compounds which can be used in the intravaginal, interuterine or intracervical release system and have an antibacterial or antiviral effect.

Preferably, in all embodiments, bacterial or antiviral compounds are selected from the group of the following compounds

Squalamine (33- [3 - [(4-aminobutyl) -amino] -propyl] -amino] -5α-cholestane-7α, 24-diol-24 sulfate),

3 »O31 T.

3-acetyl-4-hydroxybenzoylguanidine, nonoxynol-9 cytokines such as interferons α, γ, β, and other peptide antibiotics such as:

magainin

PGLα (Gly-Met-Ala-Ser-Lys-Ala-Gly-Ala-Ile-Ala-Gly-Lys-Ile-Ala-Lys-ValAla-Leu-Lys-Ala-Leu-Nh ^), magain 2 and its analogs (Gly-Ile-Gly-Lys-Phe-Leu-His-Ser-Ala-Lys-Lys-Phe-Gly-Lys-Ala-Phe-ValGly-Glu-Ile-Met-Asn-Ser-Nbh),

1-aryl-imidazol-2-alkyl (thio) ether,

C31G (a mixture of alkyldimethylglycine and alkyldimethylamine oxide (US-P 5 314 917) and mixtures thereof.

Some of the above substances have a spermicidal effect in addition to an antibacterial and / or antiviral effect.

In a particular embodiment, the compound having antibacterial and / or antiviral activity is squalamine (33- [3 - [(4-aminobutyl) amino] propyl] amino] -5α-cholestane-7α, 24-diol-24 sulfate in an effective dose 0.01 to 1 g for the release system.

In another preferred embodiment, the compound having antibacterial and / or antiviral activity is inteferon β.

Suitable contraceptive agents are gestagens, antigestagens, and others, such as antiestrogens (raloxifene), aromatase inhibitors (fadrazole, atamestane), spermicides and cytokine antagonists (interleukins).

Preferably, in all embodiments of the embodiments of the present invention, a gestagen is selected from the group consisting of compounds 1031 T gestodene, progesterone.

levonorgestrel, cyproterone acetate, chlormadinoacetate, drospirenone (dihydrospirorenone), norethisterone, norethisterone acetate, norgestimat, desogestrel,

3-ketodesogestrel, or mixtures thereof.

In a particularly preferred embodiment, the gestagen is gestodene, levonorgestrel or 3-ketodesogestrel.

In another particularly preferred embodiment of the present invention, the gestagen levonorgestrel is at a dose of 0.01 g to 1.0 g for the release system.

As competitive progesterone antagonists according to the present invention, all compounds which themselves or their metabolic products block the action of progesterone at its receptors are suitable. Typical representatives of competitive progesterone antagonists include 17α-ethines 1-17β-hydroxy-11β- (4-methoxyphenyl) -estra-4,9-dien-3-one,

113- (4-acetylphenyl) -17β-hydroxy-17α- (1-propynyl) -estra-4,9-dien-3-one, (Z) -11β- (4-acetylphenyl) -17β-hydroxy-17a - (3-hydroxy-1-propenyl) -estra4,9-dien-3-one,

113 - [(4- (dimethylamino) phenyl) -173-hydroxy-17α- (1-propynyl) -estra-4,9-dien-3-one (RU 38 486), (Z) -9,11a-dihydro- 173-hydroxy-17- (3-hydroxy-1-propenyl) -6 '- (3-pyridinyl) -4'H-naphth [3', 2 ', 1': 10,9.11] -estra-4,9- (11 ) -diene-3-one,

8103 T · (Ζ) -113- [4- (dimethylamino) -phenyl] -17β-hydroxy-17α- (3-hydroxy-1-propenyl) estr-4-en-3-one,

4 ' ₁ 5'-dihydro-1β- [4- (dimethylamino) -phenyl] -6β-methylspiro- [estra-4,9-diene-17β, 2'(3'H) -furan] -3-one,

113- (4-acetylphenyl) -19,24-dinor-17,23-epoxy-17.alpha.-chola-9.4-20-trien-3-one,

4 ', 5'-dihydro-1β- [4- (dimethylamino) -phenyl] -7β-methylspiro- [estra-4,9-diene-17β, 2' (3'H) -furan] -3-one;

19.1 Ιβ-bridged steroids from EP-A 0 283 428 and ΙΟβ-Η-steroids from EP-A 0 404 283.

In a particularly preferred embodiment of the invention, the competitive progesterone antagonist is (Ζ) -11β- [4- (dimethylamino) -phenyl) -17β-hydroxy-17α- (3-hydroxy-1-propenyl) -estr-4-en-3-one or any of the compounds compatible with it.

This calculation is not limited, other competitive progesterone antagonists described in the publications as well as compounds from publications not mentioned herein are also suitable.

By combining the contraceptive active compound and / or the antibacterial active compound in the release system of the present invention, in addition to high contraceptive protection, the transmission of different SDS is effectively prevented, or both active components in the same form are released locally (uterus, cervix, vagina). required date range. Local application (IUD, vaginal rings, cervix system) produces a local effect in the endometrium.

Thus, the combination of the present invention provides effective protection against pregnancy and STD transmission that operates continuously at the desired site of action over a period of time.

The invention is illustrated by the following non-limiting examples.

DETAILED DESCRIPTION OF THE INVENTION

The relative proportions of the active ingredient and the polymeric carrier in the devices 1, 2 and 3 can vary within wide limits, depending on the effectiveness of the active ingredient and the rate at which they are to be released from the device and the release time. The devices of the present invention are therefore equipped to release one or more active ingredients over a prolonged period of time, so the proportion of active ingredient (s) is generally considerable, i.e. approximately 40 to 70% by volume of the carrier / active ingredient mixture.

Example 1

T-shaped IUDs (Figure 2)

A device for releasing two medicaments of the type shown in FIG. 1, according to the present invention, is produced as follows:

0.075 g of levonorgestrel is treated with a silicone-based polymer by extrusion so that the active ingredient is embedded in a plastic material and both form the core of the device. The ratio of levonorgestrol to silicone polymer in the blend is 70:30. In the next step, the core is coated with a silicone-based polymer wall and poured into a known T-form. 0.1 g of squaiamine is mixed as a mixture with 0.05 g of polyacrylate-based polymer at a ratio of 40:60 in a partial manner onto the rod-shaped base body T. The proportion of polymer in the mixture is determined by the release value achieved.

Surprisingly, such a tabular container has a diameter of several millimeters and a length of several centimeters.

Example 2

IUD in the form of a spherical stick

All intrauterine T-shaped contraceptives can lead to undesirable side effects such as bleeding and pain during the period of use. A device which provides the possibility of avoiding these risk factors is described in DE-OS 24 02 882.

The device consists of a rod-like array of several plastic balls with high elasticity, crack resistance and medium hardness with a maximum weight of 0.5 g. It may contain one or more active substances.

With respect to this baseline, a device is made in a modified form which, in addition to a lipophilic drug, preferably a gestagen hormone, comprises a hydrophilic drug with an antiviral effect.

An embodiment of the contraceptive according to the present invention and the applicator are shown in FIG. 1. Here is a plan view similar to the letter Z with a total length of 3 to 4 cm. Starting from a central ball 1 having a diameter of 2.5 to 3.0 mm, there are arranged three ball-shaped rods having a circular cross-section 2, 3 and 4 of different lengths with a diameter of 1.0 to 1.5 mm. Rods with a circular diameter of 3 and 4 end at a length of 0.8 to 1.2 cm (3) or 0.5 to 0.8 cm (4) in balls 5 and 6 with a diameter of 4 to 5 mm (5) or 1.5 to 2.0 mm (6) and are arranged in blunt angles of a third rod having a circular cross-section 2. The third rod 2 continues as three rod connectors 7, 8 and 9 of balls 10, 11, 12 and 13 with a diameter of 2 to 3 mm into a bean-shaped end piece 14 having a length of 4-5 mm and a diameter of 2-3 mm with a central opening 15 having a diameter of 0.5-1.5 mm. The opening is intended for fastening a fiber of a suitable material, such as nylon or polyester. This fiber serves as a display fiber for easy testing of the presence of a contraceptive.

For the manufacture of the plastic body for the contraceptive according to the present invention, known plastics are used which, on the one hand, re-disperse the dispersed medicament, and on the other hand have sufficient mechanical properties such as crack resistance, elasticity and cold ductility is easy to form. As such, polyethylene, polyethylene / vinyl acetate, ionomeric resin derived from polyethylene, polyamides, polyether-ester terephthalate-based elastomers, polyethylene glycol terephthalate, and silicone rubber may also be mentioned. The plastics can be used singly or in combination, for example produced by layer molding.

The medicaments comprised in the intrauterine-useful contraceptives of the present invention contain the medicaments in a plastic base (lipophilic substances, for example levonorgestrel), or fixed on the surface of the plastic body (hydrophilic substances, for example squalamine).

Lipophilic drugs may be dispersed homogeneously in the plastic body, optionally with the addition of excipients, or may be contained in appropriate amounts in individual portions of the contraceptive with or without such excipients, for example as a core in a single piece of plastic body. Excipients are, for example, surfactants, highly dispersed silica, antifoams, solubilizers and resorption agents.

Known insertion tubes of suitable plastics are useful for the application of these contraceptives. The contraceptive is introduced up to the bead extension 5 by means of a filament 18 fastened in the opening 15 and the associated pulling and shifting bars 17 associated therewith under aseptic conditions. In this case, the device ball 5 forms a spherical end for the application unit, consisting of a contraceptive and an applicator. Since the edge of the insertion tube is covered, primary application damage is excluded. Furthermore, a spherical end with a diameter of 4 to 5 mm prevents the fundus uteri from breaking when applied. The application of the contraceptive is readily practicable to those skilled in the art. It can be performed under aseptic conditions without anesthesia or the use of other drugs or dilatation of the cervical canal and induction of convulsion-like pain even in women who have not yet given birth.

Example 2.1

From a mixture of 50.0 g of micronized levonorgestrel and 49.1 g of milk sugar with the addition of 0.1 g of lubricant, molded bodies with a diameter of 2 mm with a convex radius of 3 mm are pressed. Levonorgestrel shaped bodies are used as cores in the spherical portion 5 and alternatively in the beads 10-13 of the contraceptive intrauterine device, the basic shape and dimensions of which are shown in FIG. 1 and which is prepared from a mixture of 5.0 g of barium sulfate, 35.0 g of highly dispersed silica and 60.0 g of catalysed low temperature vulcanized type (LTV) two-component silicone rubber by single-stage vulcanization at 100 ° C following shaping.

The surface of the beads of the plastic body is coated with 0.1 g of squalamine and 0.05 g of polyacrylate-based polymer (alternately filled with levonorgestrel shaped bodies) with the aid of an adhesive base to achieve the desired release values for these drugs.

Example 2.2.

The apparatus is manufactured as described in Example 2.1.

The bead surface is coated with a mixture of 0.1 g squalamine and 0.06 g hydroxypropylcellulose / carboxymethylcellulose in different layers to achieve the necessary drug release value.

The polymers used are in solid form before use and dissolve only at body temperature and humidity, releasing the active ingredient at the desired time and dose.

Example 3

Vaginal ring (fig. 3)

S10S1 T

Another variant is a vaginal ring which is also modified as shown in FIG. 3. The vaginal ring consists of a carrier ring 1 without active ingredient, layer 2, which contains a lipophilic active ingredient, for example a steroid hormone, and which is inserted into a continuous groove of the carrier ring. This layer 2 is coated with an active substance-free layer 3. All components are preferably manufactured on a silicone basis. The ratio of the thickness of the active ingredient layer 2 to the non-active layer thickness 3 is approximately 5 to 50: 1. As a result, long-term uniform release values for lipophilic drugs can be achieved. This provides the advantage of the vaginal ring of the present invention over the vaginal rings known to those skilled in the art.

The hydrophilic drug can be applied as a mixture with a relatively polar polymer to the layer 3, partially as layer 4.

Example 3.1.

For the production of the support ring 1, the following components are properly mixed:

232.6 g vinyldimethoxysiloxane, molecular weight M = 5854 17.4 g tetramethyltetravinylcyclotetrasiloxane 25.0 mg platinum (mixture A1)

193.8 g vinyl polydimethylsiloxane a

56.2 g of polydiethylhydrosiloxane (mixture B1).

Both mixtures A1 and B1 are homogenized in a static mixer, introduced into an injection molding machine and cured for 60 s at 100 [deg.] C. into rings with a circular cross-section. The hardness is 45 and the elongation at break is 50%.

The following components are intensively mixed to produce the layer 2 containing the lipophilic drug:

49.9 g vinyl polydimethylsiloxane, M = 8170

0.1 g of tetramethyltetravinylcyclotetrasiloxane

31031 T14

5.0 mg platinum (mixture A1)

0.05 g levonorgestrel (mixture A2)

48.6 g vinyl polydimethylsiloxane, M = 8170

1.4 g of polydimethylhydrosiloxane and

0.05 g levonorgestrel (mixture B2)

The two mixtures A2 and B2 are homogenized in a static mixer, introduced into an injection molding machine comprising a support ring I and vulcanized at the outer edge of the support ring 1 at 100 ° C for 60 s.

The vaginal rings thus produced are sprayed with a silicone-elastomer-based layer 3 in the region of the layer 2 containing the lipophilic drug. The thickness of layer 3 is about 200 µm. This layer forms a mixed vulcanizate with layer 2 which is located below it.

The drug-free silicone-elastomer mixture consists of:

42.5 g vinyl polydimethylsiloxane, M = 4561

5.7 g of polydimethylhydrosiloxane

1.8 g of tetramethyltetravinylcyclotetrasiloxane and

5.0 ppm platinum.

To produce a layer 4 that contains a hydrophilic drug, the following components are intensively mixed and sprayed partially onto layer 3:

0.05 g of polyacrylate polymer a

0.1 g squalamine.

Example 3.2.

The vaginal ring is made as described in Example 3.1.

Apply layer 4, which is made from a mixture of squalamine and hydroxypropyimethylcellulose / carboxymethylcellulose with the following composition:

 mas: t

0.06 g 0.06 G hydroxypropylmethylcellulose / carboxymethylcellulose and 0.1 g squalamine.

Example 4

Cervical delivery system (Fig. 4)

It is a two-layer mucosal adhesive system (see Fig. 4), which controls the lipophilic drug from the core 7 and delivers the hydrophilic drug from the outer layer 2.

To this end, a core is produced by extrusion of a mixture of 0.025 g of microsonized levonorgestrel and a silicone-based polymer. The weight ratio of levonorgestrel to silicone polymer is 50:50.

In a further work step, a mixture of 0.1 g squalamine and 0.05 g mucoadhesive polymer blend based on carboxymethylcellulose / polyacrylate or hydroxypropylcellulose / carboxyvinyl polymer and other polymers as a second layer is partially applied using the adhesive base to achieve the desired release values for these drugs for a desired period of time. Such a container has a diameter of a few millimeters and a length of 1 to 2 centimeters.

Claims (14)

Combination of at least one compound with (a) contraceptive action and / or compound with (b) antibacterial effect and / or compound with (c) antiviral effect, wherein one compound may also have all three properties for incorporation / application on intravaginal, intrauterine or intracervical release system. Combination of at least one compound with (a) contraceptive action and compound with (b) antibacterial and / or compound with (c) antiviral effect for incorporation / delivery onto an intravaginal, intrauterine or intracervical release system. The combination of claim 1, wherein the release system is an IUD, an intracervical system, or a vaginal ring. The combination according to claim 1, characterized in that the contraceptive compound is a gestagen and / or a competitive progesterone antagonist. The combination according to claim 4, wherein the contraceptive compound is a gestagen selected from the group consisting of gestodene, progesterone, levonorgestrel, cyproterone acetate, chlormadinoacetate, drospirenone (dihydrospirorenone), norethisterone, norethisterone acetate, norgestimat, desogestrel, 3-ketodesogestrel, or mixtures thereof, and competitive progesterone antagonists are selected from the group consisting of: 17.alpha.-ethynyl-17.beta.-hydroxy-113- (4-methoxy-phenyl) estra-4,9-dien-3-one, 11β- (4-acetylphenyl) -17β-hydroxy-17α- (1-propynyl) -estra-4,9-dien-3-one, (Z) -11β- (4-acetylphenyl) -17β-hydroxy- 17α- (3-hydroxy-1-propenyl) -estra4,9-dien-3-one, 113 - [(4- (dimethylamino) phenyl) -173-hydroxy-17α- (1-propynyl) -estra-4,9-dien-3-one (RU 38 486), (Z) -9,11 α-dihydro -17β-hydroxy-17α- (3-hydroxy-1-propenyl) -6 '- (3-pyridinyl) -4'H-naphth [3', 2110,9,11] -estra-4,9- (11 (1) -113- [4- (dimethylamino) -phenyl] -17β-hydroxy-17α- (3-hydroxy-1-propenyl) estr-4-en-3-one; 4 ', 5'-dihydro-113- [4- (dimethylamino) phenyl] -6?-Methyl spiro [4,9-dién17p, 2' (3 'H) -furan] -3-one, 11β- (4-acetylphenyl) -19,24-dinor-17,23-epoxy-17α-chola-4,9,20-trien-3-one, 4 ', 5'-dihydro-1β- [4- (dimethylamino) -phenyl] -73-methylspiro- [estra-4,9-diene173,2' (3'H) -furan] -3-one, or their mixture. Combination according to claim 1, characterized in that the compound with an antibacterial and / or antiviral effect is selected from the group consisting of squalamine (3β- [3 - [(4-aminobutyl) amino] -propyl] -amino] -5a- cholestane-7a, 24-diol-24-sulfate), 3-acetyl-4-hydroxybenzoylguanidine, nonoxynol-9 They are r-cytokines peptide antibiotics 1-aryl-imidazol-2-alkyl (thio) ether, C31G (a mixture of alkyldimethylglycine and alkyldimethylamine oxide (US-P 5 314 917) and mixtures thereof. Combination according to claim 1, characterized in that the compound with (a) contraceptive effect is levonorgestrel and the compound with (b) antibacterial effect and / or the compound with (c) antiviral effect is squalamine (33- [3 - [(4) (aminobutyl) -amino] -propyl] -amino] -5α-cholestane (24-diol-24-sulfate), and the release system is an IUD, cervical system or vaginal ring. Use of an intravaginal, intrauterine or intracervical release system comprising at least one compound with (a) contraceptive action and / or one compound with (b) antibacterial and / or (c) antiviral activity, wherein one compound may have all three properties, to prevent sexually transmitted diseases. Use of an intravaginal, intrauterine or intracervical release system comprising at least one compound with (a) contraceptive effect in combination with one compound with (b) an antibacterial and / or (c) antiviral effect, to protect against sexually transmitted diseases. The use of claim 8, wherein the release system is an IUD, a cervical system or a vaginal ring. Use according to claim 8, wherein the contraceptive compound is a gestagen and / or a competitive progesterone antagonist. The use of claim 8, wherein the contraceptive compound is a gestagen selected from the group consisting of gestodene, progesterone, levonorgestrel, cyproterone acetate, chlormadinoacetate, drospirenone (dihydrospirorenone), norethisterone, norethisterone acetate, norgestimat, desogestrel, 3-ketodesogestrel, or mixtures thereof, and competitive progesterone antagonists are selected from the group consisting of: 17α-ethynyl-17β-hydroxy-11β- (4-methoxyphenyl) -estra-4,9-dien-3-one, 1β- (4-acetylphenyl) -17β-hydroxy-17α- (1-propynyl) -estra-4,9-dien-3-one, (Z) -11β- (4-acetylphenyl) -17β-hydroxy-17α- (3-hydroxy-1-propenyl) -estra4,9-dien-3-one, 11 P - [(4- (dimethylamino) -phenyl] -17β-hydroxy-17α- (1-propynyl) -estra-4,9-dien-3-one (RU 38 486), (Z) -9,11 α- dihydro-17β-hydroxy-17α- (3-hydroxy-1-propenyl) -6 '- (3-pyridinyl) -4'H-naphth [3', 2 ', 110,9,11] -estra-4,9- (11) -dien-3-one, (Z) -11β- [4- (dimethylamino) -phenyl] -17β-hydroxy-17α- (3-hydroxy-1-propenyl) estr-4-en-3- one, 4 ', 5'-dihydro-1ip- [4- (dimethylamino) phenyl] -6?-Methyl spiro [4,9-dién17p, 2' (3 'H) -furan] -3-one, 11β- (4-acetylphenyl) -19,24-dinor-17,23-epoxy-17α-chola-4,9,20-trien-3-one, 4 ', 5'-dihydro-1β- [4- (dimethylamino) -phenyl] -7β-methylspiro- [estra-4,9-diene-17β, 2' (3'H) -furan] -3-one, or their mixture. ., 3-1031 T Combination according to claim 8, characterized in that the compound having an antibacterial and / or antiviral effect is a compound selected from the group consisting of squalamine (33- [3 - [(4-aminobutyl) amino] -propyl] -amino] - 5a-cholestane-7a, 24-diol-24 sulfate), 3-acetyl-4-hydroxybenzoylguanidine, nonoxynol-9 cytokines peptide antibiotics 1-Aryl-2-imidazole-alkyl (thio) ether C31G (a mixture of alkyldimethylglycine and alkyldimethylamine oxide (US-P 5 314 917) and mixtures thereof. Combination according to claim 8, characterized in that the compound with (a) the contraceptive effect is levonorgestrel and the compound with (b) the antibacterial effect and / or (c) the antiviral effect is squalamine 4 - [3 - [(4-aminobutyl) (-amino) -propyl] -amino] -5α-cholestane-7α, 24-diol-24-sulfate) and the release system is an IUD or vaginal ring.