DE19606355A1 - Contraceptive release systems with antiviral and / or antibacterial effects - 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

The present invention relates to the combination of at least one compound with (a) contraceptive effect and / or a compound with (b) antibacterial and / or (c) antiviral activity, one compound also having all three properties may have, for incorporation / application to an intravaginal, intrauterine or intracervical delivery system.

Sexually transmitted disease (STD) represent a serious medical and socio-economic problem.

A large number of different diseases can occur during the Sexual intercourse. A distinction is made between bacterial (Chlamydia, Gonorrhea, Syphilis) and viral (cytomegalovirus = CMV, genital herpes Simplex = HSV, Human Papillomavirus = HPV and Human Immunodeficiency HIV / AIDS) diseases.

In the U.S., approximately 12 million people ages 15-29 are affected by STDs. In total, there are some types of STDs in 56 million Americans except AIDS and HIV. New WHO research shows that under the term "major reproductive health concerns", STDs with worldwide esteemed Cases of 315 million pose a significant health problem. In particular, the estimated 30-40 million HIV infections are expected 12-18 million AIDS (acquired immunodeficiency syndrome) diseases by Year 2000 (Achieving Reproductive Health for All. The role of WHO (WHO / FHE / 95.6, World Health Organization, Geneva, 1995)) a serious threat to the World health. Here, in particular, the skyrocketing numbers are new HIV infections in countries of the less developed world, with in these countries a sharp increase in heterosexual infections Population can be observed. There are estimates that suggest that 60% of the HIV infections occur worldwide through heteresexual transmission. Even in the USA there is a growing number of HIV infections that are heterosexual in most cases, the transfer is from man to woman.

In addition to condoms, there have been various preventive measures for STDs antibacterial and antiviral substances (tetracyclines, chlorhexidine, sulfonamides,  Interferons). For the treatment of HPV ISIS2105 (a Antisense oligonucleotide) tested in clinical studies. The spermicide Nonoxynol-9 (N9) inhibits the transmission of gonorrhea and chlamydia. It gives indications that N9 inhibits the transmission of HIV. The one about this The subject of published data is contradictory, however, through N9 it can Irritation of the vaginal epithelium is coming, this could be the transmission of STDs favor.

Furthermore, the use of so-called aminosterols such as Squalamine described for the treatment of STDs (Aminosterol antibiotics, Current Opin. Ther. Pat. 3, 1369-1370, 1993; Cohen J. Women: Absent Term in the AIDS Research Equation. Science, 269, 777-780, 1995). Squalamine is broad antibiotic activity (Moore K, Wehrli S et al. Squalamine: An aminosterol antibiotic from the shark. Proc. Natl. Acad. Sci. 90, 1354-1358, 1992).

In most cases, these substances are in the form just before traffic of suppositories that are inserted into the vagina.

Another approach is based on influencing the pH in the vagina. Studies have shown that HIV is inactivated in an acidic environment. At In this approach, the pH increases during acid ejaculation Level maintained. By inhibiting the sodium / hydrogen ion exchange the pH of the cell surface can be lowered. Inhibitors of Na / H Ion exchange would thus lead to a drop in pH and that Prevent HIV infection without the vagina or cells of the Reproductive tract. Compounds that contain the sodium / hydrogen Inhibiting ion exchange are considered a possible therapy for the treatment of cardiovascular diseases have been described in the literature (Scholz, Albus U. Potential of selective sodium-hydrogen exchange inhibitors in cardiovascular therapy. Cardiovasc. Res. 29, 184-188, 1995). Substances that have this effect have in DE 93-43 18 756 (Schwark Jan-Robert), DE 93-1 20 374 (Weichert A), EP 93-110195 (Weichert A) and US4423069 (Zanverld L).

All of the previously described applications for the prevention of STDs only offer temporary one-time protection, each against intercourse is to be applied. As with any single-use application, revenue errors and Compliance issues arise. In such a case, the risks of STD Transmission and contraception exist. With purely contraceptive  Methods are therefore permanent methods - such as B. IUDs, Implants, vaginal rings, injectables - by a large number of women prefers. This is especially true for women in the less developed countries.

There is therefore an urgent need to provide a system which continuously provides combined protection against STDs and one at the same time offers safe contraceptive protection.

The object of the present invention is to provide a system which offers contraceptive protection, transmitted through sexual intercourse Diseases continuously prevented over a long period of time and by women is applied.

It has now been found that the combination of a compound with (a) contraceptive effect and / or a compound with (b) antibacterial and / or (c) Antiviral activity, one compound also has all three properties may have, for incorporation / application to an intravaginal, intrauterine or intercervical delivery system provides contraceptive protection and at the same time prevents diseases transmitted through sexual intercourse.

In a particularly preferred embodiment of the invention Combination is the compound (a) with contraceptive action and levonorgestrel the combination with (b) antibacterial and / or (c) antiviral action squalamine and the delivery system is an IUD, an intracervical system, or a Vaginal ring.

In a further embodiment, the invention relates to the use of a containing intravaginal, interauterine or intracervical release system at least one contraceptive compound and / or compound with antibacterial and / or antiviral effect to prevent by the Sexually transmitted diseases.

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

Intrauterine contraceptives containing active ingredients are delivery devices with a reservoir from which active ingredients are released by diffusion. The Devices include a core of a lipophilic drug  permeable solid or liquid carrier in which an excess of drug is dispersed, and a drug-permeable polymeric wall that this Core surrounds. The wall is less permeable to the drug than the carrier, so that the wall contributes to the rate of release of the drug to the environment the application. A hydrophilic active ingredient can be mixed with a polar polymer are partially applied to the device so as to to achieve desired release rates, or the surface of the device is with a mixture of the hydrophilic drug and soluble polymers, such as. B. Polyvinyl alcohol, polyethylene oxide, hydroxypropyl methyl cellulose and / or Carboxymethyl cellulose, partially coated in different layers, depending on what delivery rate to achieve. By such as described above Release systems, the drugs contained are essentially with given constant speed.

The use of intrauterine devices (IUDs) for contraception is in the Literature described (Speroff L and Darney P. The intrauterine device (IUD). In a Clinical Guide for Contraception. Eds. M. Fisher, Wiliams & Wilkins, Baltimore, Maryland p157-185, 1992). There are also gestagen-containing IUDs in some Countries already on the market (Luukkainen T, Allonen H, Haukkamaa M et al. Five years ′ experience with levonorgestrel-releasing IUDs. Contraception 33: 139-145, 1986). The contraceptive security of IUDs is high. However, it can Use of copper IUDs lead to increased menstrual blood loss. There is also an increased risk of infection (Buchan H, Villard-Mackintosh L et al. Epidemiology of pelvic inflammatory disease in parous women with special reference to intrauterine device use. Br. J. Obset. Gynecol. 97: 780-786, 1990) and that Occurrence of ectopic pregnancies described in the literature. IUDs, who are loaded with a progestin appear to be the increased menstrual Prevent and even significantly reduce blood loss; combine as well mechanical contraception with hormonal (e.g. thickening of the cervical mucus as a barrier to sperm) which is the contraceptive protection increased (Speroff L and Darney P. The intrauterine Device (IUD). In a Clinical Guide for Contraception. Eds. M. Fisher, Wiliams & Wilkins, Baltimore, Maryland p 157-185, 1992).

As antibacterial or antiviral compounds come according to of the present invention all compounds in question in an intravaginal,  interauterine or intracervical delivery system can be used and have antibacterial or antiviral effects.

In all embodiments of the invention, the antibacterial or antiviral compound from the group of the following compounds is preferred
Squalamine (3β- [3 - [(4-aminobutyl) amino] propyl] amino] -5α-cholestan-7α, 24-diol-24-sulfate)
3-acetyl-4-hydroxybenzoylguanidine
Nonoxynol-9
Cytokines such as the interferons α, γ, β and others.

Peptide antibiotics such as Magainin:
PGLa (Gly-Met-Ala-Ser-Lys-Ala-Gly-Ala-Ile-Ala-Gly-Lys-Ile-Ala- Lys-Val-Ala-Leu-Lys-Ala-Leu-NH₂)
Magainin 2 and its analogues:
(Gly-Ile-Gly-Lys-Phe-Leu-His-Ser-Ala-Lys-Lys-Phe-Gly-Lys-Ala- Phe-Val-Gly-Glu-Ile-Met-Asn-Ser-NH₂)
1-aryl-2-imidazolyl-alkyl (thio) ether
C31G (mixture of alkyldimethylglycine and alkyldimethylamine oxide (US Pat. No. 5,314,917))
or a mixture of these.

Some of the substances mentioned have antibacterial and / or antiviral effect also a spermicidal effect.

In a special embodiment, the compound is antibacterial and / or antiviral activity: squalamine (3β- [3 - [(4-aminobutyl) amino] propyl] amino] - 5α-cholestan-7α, 24-diol-24-sulfate) in an effective dosage of 0.01-1 g per release system.

In a further preferred embodiment, the connection is with  antibacterial and / or antiviral effect interferon β.

Gestagens, antigestagens and others such as B. antiestrogens (raloxifene), aromatase inhibitors (fadrozole, Atamestane), spermicides and cytokine antagonists (interleukins) in question.

In all embodiments of the invention, the gestagen is preferably selected from the group of compounds
Gestoden,
Progesterone,
Levonorgestrel,
Cyproterone acetate,
Chlormadinone acetate;
Drospirenone (dihydrospirorenone),
Norethisterone,
Norethisterone acetate,
Norgestimate
Desogestrel
3-ketodesogestrel
or a mixture of these.

In a particularly preferred embodiment, the gestagen is:
Gestoden, Levonorgestrel or 3-Ketodesogestrel.

In another particularly preferred embodiment, the gestagen is Levonorgestrel in a dose of 0.01 g-1.0 g per release system.

All compounds which themselves or their metabolic products block the action of the progesterone at its receptor are suitable as competitive progesterone antagonists according to the present invention. Typical competitive progesterone antagonists are mentioned here
17 a-ethynyl-17β-hydroxy-11β- (4-methoxyphenyl) 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) estra-4,9-dien-3-one
11β- [4- (dimethylamino) phenyl] -17β-hydroxy-17α- (1-propynyl) estra-4,9-dien-3-one (RU 38 486)
(Z) -9,11α-dihydro-17β-hydroxy-17α- (3-hydroxy-1-propenyl) -6 ′ - (3-pyridinyl) -4′H- naphth [3 ′, 2 ′, 1 ′: 10,9,11] 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-11β- [4- (dimethylamino) phenyl] -6β-methylspiro [estra-4,9-diene-17β, 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-11β- [4- (dimethylamino) phenyl] -7β-methylspiro [estra-4,9-diene-17β, 2 ′ (3′H) -furan] -3-one
such as
19, 11β-bridged steroids from EP-A-0 283 428 and
10β-H steroids from EP-A-0 404 283.

In a particularly preferred embodiment of the invention, the is competitive Progesterone antagonist is the compound (Z) -11β- [4- (dimethylamino) phenyl] -17β- hydroxy-17α- (3-hydroxy-1-propenyl) estr-4-en-3-one or one in their profile comparable connection.

This list is not exhaustive; also others in the above Publications described competitive progesterone antagonists and such from publications not mentioned here are suitable.

Through the combination of a contraceptive compound according to the invention and / or an antiviral and / or antibacterial compound in one Release system is next to a maximum of contraceptive protection at the same time effectively prevents the transmission of different STDs, as both Active components uniformly in a desired dose over a desired one Period locally (uterus, cervix, vagina) are released. By local  Administration (IUD, vaginal ring, cervix system) is a local effect in the Endometrium reached.

The inventive combination thus provides effective protection against Pregnancy and the transmission of STDs are available, which acts continuously at the desired site of action over a certain period of time.  

Examples

The invention is illustrated by the following non-limiting examples:
The relative proportions of active ingredient and polymer carrier in devices 1, 2 and 3 can vary within wide limits, depending on the effectiveness of the active ingredients and the speed at which they are released from the device and the duration of the release. The devices according to the invention are intended to release one or more active substances over a long period of time, therefore the proportion of active substance or active substances is generally considerable, ie it makes up approximately 40 to 70% by volume of the mixtures of carrier and active substance.

example 1 T-shaped IUD ( Fig. 2)

A dispenser for two drugs of the type shown in Figure 1 is made as follows:
0.075 g of levonorgestrel are processed with a silicone-based polymer by extrusion in such a way that the active ingredient is embedded in the plastic material and both form the core of the device. The levonorgestrel to silicone polymer mixture used is 70:30. In a further step, the core is coated with a silicone-based polymer wall and poured into the known T-shape. 0.1 g of squalamine is partially applied to the rod-shaped base body ( 1 ) as a mixture with 0.05 g of a polyacrylate-based polymer in a ratio of 40:60. The proportion of the polymer in the mixture is defined by the release rates to be achieved.

Such a tubular container usually has a diameter of a few Millimeters and a length of a few centimeters.

Example 2 Ball-shaped IUD

All T-shaped intrauterine contraceptives can be used in Period of application for undesirable side effects such as bleeding and  Cause pain. A device that has the ability to avoid this Risk factors offers is described in laid-open specification No. 24 02 882.

The device consists of a round rod assembly of several balls Plastic with high elasticity, tear resistance and medium hardness with one Maximum weight of 0.5g. It can contain one or more drugs.

Based on this basic idea, devices have been modified prepared in addition to a lipophilic drug, preferably a hormone gestagen effect contain a hydrophilic drug with an antiviral effect.

The application form of the contraceptive according to the invention and the applicator are shown in Fig. 1. With a total length of 3 to 4 cm, it shows a Y-like plan. Starting from a central ball ( 1 ) with a diameter of 2.5 to 3.0 mm, three round rods ( 2-4 ) of different lengths with a diameter of 1.0 to 1.5 mm are arranged which run into balls. The round rods ( 3 ) and ( 4 ) end at a length of 0.8 to 1.2 cm ( 3 ) and 0.5 to 0.8 cm ( 4 ) in the balls ( 5 ) and ( 6 ) of 4 up to 5 mm ( 5 ) diameter or 1.5 to 2.0 mm ( 6 ) diameter and are arranged at an obtuse angle to the third round rod ( 2 ). The third round rod ( 2 ) sits in the triple round rod assembly ( 7 , 8 , 9 ) of balls ( 10-13 ) with a diameter of 2 to 3 mm in a bean-like end piece ( 14 ) of 4 to 5 mm in length and 2 to 3 mm diameter with a central bore ( 15 ) from 0.5 to 1.5 mm in diameter. The eyelet is provided for fastening a thread ( 18 ) made of a suitable material, such as. B. nylon or polyester. This thread serves as an indicator thread for easy checking for the presence of the contraceptive.

To produce the plastic body for the invention Contraceptives are used plastics known per se, which are used for dispense a dispersed drug and on the other hand sufficient mechanical properties such as tensile strength, elasticity and cold stretchability have and can be easily brought into suitable shapes. As such for example called polyethylene, polyethylene / vinyl acetate, from polyethylene derived ionomer resins, polyamides, polyether ester elastomers Terephthalate base, polyethylene glycol terephthalate and silicone rubber. The Plastics can be used individually or in combination, e.g. B. by layering be used.  

The contraceptive agent which can be used in the intrauterine device according to the invention Medicinal substances included are contained in the plastic base (lipophilic, e.g. Levonorgestrel) or fixed on the surface of the plastic body (hydrophilic, e.g. B. squalamine).

Lipophilic drugs can be homogeneous in the plastic body, if necessary also with the aid of auxiliaries, dispersed or in individual parts of the Contraceptive with or without these adjuvants, e.g. B. as the centerpiece in part of the plastic body, be contained in a suitable amount. Auxiliaries Examples are surfactants, highly disperse silicon dioxide, anti-foaming agents, Solubilizers, absorption retarders.

For the application of these contraceptives, known insertion tubes made of suitable plastics can be used. The contraceptive is inserted under aseptic conditions up to the ball ( 5 ) with the thread ( 18 ) fastened in the eyelet ( 15 ) and the associated pull and push rod ( 17 ). The ball ( 5 ) of the device forms a ball end for the application unit consisting of contraceptive and applicator. Since the edge of the insertion tube is covered, primary injuries during application are excluded. Furthermore, the spherical end with a diameter of 4 to 5 mm prevents the fundus uteri from being pierced during application. The application of the contraceptive is easy for the person skilled in the art to carry out. It can be performed under aseptic conditions without anesthesia or with the use of other drugs or dilation of the cervical canal, even in women who have not yet given birth, without triggering cramp-like pain.

Example 2.1

From a mixture of 50.0 g of micronized levonorgestrel and 49.1 g of milk sugar with 0.1 g of lubricant additive, pressed articles with a diameter of 2 mm and a radius of curvature of 3 mm are pressed. The levonorgestrel compacts are placed as cores in the spherical parts ( 5 ) and alternately in the balls ( 10-13 ) of an intrauterine contraceptive, the basic body and dimensions of which are as in
Fig. 1 look and which consists of a mixture of 5.0 g of barium sulfate, 35.0 g of highly disperse silicon dioxide and 60.0 g of catalyzed low temperature vulcanizing-type (LTV) silicone rubber two-component mass by vulcanizing at 100 ° C for one hour afterwards to the molding.

The surface of the balls of the plastic body is made with the help of a Partially and alternately with a mixture of 0.1g squalamine and 0.05g of a polyacrylate-based polymer coated (alternating with the load with Levonorgestrel compacts) in order to obtain the desired release rates for this To achieve drug.

Example 2.2

The device is manufactured as in Example 2.1.

The surface of the balls is covered with a mixture of 0.1g squalamine and 0.06g Hydroxypropyl cellulose / carboxymethyl cellulose in different layers coated to achieve the required release rate for the drug.

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

Example 3 Vaginal ring ( Fig. 3)

Another variant is the vaginal ring, which is also modified, as shown in Fig. 3. The vaginal ring consists of a supporting ring 1 without an active ingredient, a layer 2 which contains a lipophilic active ingredient, e.g. B. a steroid hormone, and is placed in a continuous groove of the supporting ring. This layer 2 is made with an active substance-free 3rd Layer coated. All components are preferably made on a silicone basis. The ratio of the layer thicknesses of active substance-containing layer 2 to active substance-free layer 3 is approximately 5-50: 1. As a result, a long-lasting uniform release rate for the lipophilic drug can be achieved. This offers an advantage of the vaginal ring according to the invention over vaginal rings known to the person skilled in the art.

A hydrophilic drug can be mixed as a mixture with a relatively polar polymer on the layer 3 partially as 4 . Layer can be applied.

Example 3.1

The following components are mixed thoroughly to produce the supporting ring 1 :

232.6 g vinyl polydimethylsiloxane, molecular weight M = 5854
17.4 g of tetramethyltetravinylcyclotetrasiloxane
25.0 mg platinum (mixture A1)
193.8 g vinyl polydimethylsiloxane
56.2 g polydimethylhydrosiloxane (mixture B1).

The two mixes A1 and B1 are in a static mixer homogenized, placed in an injection molding machine and over a period of 60s vulcanized at 100 ° C into rings with a circular cross section. The hardness is 45 and the elongation to break 50%.

To produce layer 2 , which contains the lipophilic drug, the following components are mixed intensively:

49.9 g vinyl polydimethylsiloxane, M = 8170
0.1 g tetramethyltetravinylcyclotetrasiloxane
5.0 mg platinum
0.05 g levonorgestrel (mixture A2)
48.6 g vinyl polydimethylsiloxane, M = 8170
1.4 g polydimethylhydrosiloxane
0.05 g levonorgestrel (mixture B2).

The two mixtures A2 and B2 are homogenized in a static mixer, placed in an injection molding machine which contains the supporting ring 1 and vulcanized over a period of 60 s at 100 ° C. on the outer edge of the supporting ring 1 .

The vaginal rings thus produced are sprayed in the region of layer 2 , which contains the lipophilic drug, with a layer 3 based on silicone elastomers. The layer thickness of layer 3 is approximately 200 μm. This layer forms a mixed vulcanizate with layer 2 , which is arranged below it.

The drug-free silicone elastomer mixture consists of:

42.5 g vinyl polydimethylsiloxane, M = 4561
5.7 g polydimethylhydrosiloxane
1.8g tetramethyltetravinylcyclotetrasiloxane
50 ppm platinum.

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

0.05g polyacrylate polymer
0.1g squalamine

Example 3.2

The vaginal ring is made as in Example 3.1.

The 4th layer is made from a mixture of squalamine and Hydroxypropylmethylcellulose / Carboxymethylcellulose manufactured and applied.

0.06g hydroxypropylmethyl cellulose / carboxymethyl cellulose
0.1g squalamine

Example 4 Cervical application system ( Fig. 4)

It is a two-layer mucous membrane-adhering system (see Fig. 4) that delivers a lipophilic drug from the core ( 1 ) and a hydrophilic drug from the outer layer ( 2 ).

For this purpose, a mixture of 0.025 g micronized levonorgestrel and one Silicone based polymer made by extruding a core. The used The mixture of levonorgestrel and silicone polymer is 50:50.

In a further work step, with the help of a primer, is partial a mixture of 0.1g Sqalamin and 0.05g of a mucoadhesive Polymer mixture based on carboxymethyl cellulose / polyacrylate or Hydroxypropyl cellulose / carboxy vinyl polymer and other polymers second Layer applied in such a way that the desired release rates for this Drugs can be achieved over the desired period. Such a container has a diameter of a few millimeters and a length of 1-2 Centimeters.

Claims (14)

1. Combination of at least one compound with (a) contraceptive effect and / or a compound with (b) antibacterial and / or (c) antiviral activity, a connection can also have all three properties, for Incorporation / application to an intravaginal, intrauterine or intracervical Release system. 2. Combination of at least one compound with (a) contraceptive effect and a compound with (b) antibacterial and / or (c) antiviral activity for Incorporation / application to an intravaginal, intrauterine or intracervical Release system. 3. The combination of claim 1, wherein the release system is an IUD intracervical system or a vaginal ring. 4. Combination according to claim 1, in which the connection with contraceptive Effect is a progestogen and / or a competitive progesterone antagonist. 5. A combination according to claim 4, in which the contraceptive compound is a progestogen from the group of compounds
Gestoden,
Progesterone,
Levonorgestrel,
Cyproterone acetate,
Chlormadinone acetate,
Drospirenone (dihydrospirorenone),
Norethisterone,
Norethisterone acetate,
Norgestimate,
Desogestrel,
3-ketodesogestrel
or a mixture thereof is selected and
the competitive progesterone antagonist from the group of compounds:
17α-ethynyl-17β-hydroxy-11β- (4-methoxyphenyl) 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) estra-4,9-dien-3-one
11β- [4- (dimethylamino) phenyl] -17β-hydroxy-17α- (1-propynyl) estra-4,9-dien-3-one (RU 38 486)
(Z) -9,11α-dihydro-17β-hydroxy-17α- (3-hydroxy-1-propenyl) -6 ′ - (3-pyridinyl) -4′H- naphth [3 ′, 2 ′, 1 ′: 10,9,11] 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-11β- [4- (dimethylamino) phenyl] -6β-methylspiro [estra-4,9-diene-17β, 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-11β- [4- (dimethylamino) phenyl] -7β-methylspiro [estra-4,9-diene-17β, 2 ′ (3′H) -furan] -3-one
or a mixture thereof is selected. 6. Combination according to claim 1, in which the compound having antibacterial and / or antiviral activity from the group of the compounds:
Squalamine ( 3 β- [3 - [(4-aminobutyl) amino] propyl] amino] -5α-cholestan-7α, 24-diol-24-sulfate)
3-acetyl-4-hydroxybenzoylguanidine
Nonoxynol-9
Cytokines
Peptide antibiotics
1-aryl-2-imidazolyl-alkyl (thio) ether
C31G (mixture of alkyldimethylglycine and alkyldimethylamine oxide
or a mixture thereof is selected. 7. Combination according to claim 1, in which the compound (a) with contraceptive Effect is levonorgestrel and the connection with (b) antibacterial and / or (c) viral action squalamine (3β- [3 - [(4-aminobutyl) amino] propyl] amino] -5α-cholestan- 7α, 24-diol-24-sulfate) -7 and the release system is an IUD, a cervical System or a vaginal ring. 8. Use of an intravaginal, intrauterine or intracervical Release system containing at least one compound with (a) contraceptive Effect and / or with (b) antibacterial and / or (c) antiviral effect, wherein one Compound can also have all three properties to prevent sexually transmitted diseases. 9. Use of an intravaginal, intrauterine or intracervical Release system containing at least one compound with (a) contraceptive Effect in combination with a compound with (b) antibacterial and / or (c) antiviral effect to prevent sexually transmitted diseases. 10. Use according to claim 8, in which the release system is an IUD cervical system or a vaginal ring. 11. Use according to claim 8, in which the connection with contraceptive Effect is a progestogen and / or a competitive progesterone antagonist. 12. Use according to claim 8, in which the contraceptive compound is a progestogen from the group of compounds
Gestoden,
Progesterone,
Levonorgestrel,
Cyproterone acetate,
Chlormadinone acetate,
Drospirenone (dihydrospirorenone),
Norethisterone,
Norethisterone acetate,
Norgestimate,
Desogestrel,
3-ketodesogestrel
or a mixture thereof is selected and
the competitive progesterone antagonist from the group of compounds:
17α-ethynyl-17β-hydroxy-11β- (4-methoxyphenyl) 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) estra-4,9-dien-3-one
11β- [4- (dimethylamino) phenyl] -17β-hydroxy-17α- (1-propynyl) estra-4,9-dien-3-one (RU 38 486)
(Z) -9,11α-dihydro-17β-hydroxy-17α- (3-hydroxy-1-propenyl) -6 ′ - (3-pyridinyl) -4′H- naphth [3 ′, 2 ′, 1 ′: 10,9,11] 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-11β- [4- (dimethylamino) phenyl] -6β-methylspiro [estra-4,9-diene-17β, 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-11β- [4- (dimethylamino) phenyl] -7β-methylspiro [estra-4,9-diene-17β, 2 ′ (3′H) -furan] -3-one
or a mixture thereof is selected. 13. Combination according to claim 8, in which the compound having antibacterial and / or antiviral activity from the group of the compounds:
Squalamine (3β- [3 - [(4-aminobutyl) amino] propyl] amino] -5α-cholestan-7α, 24-diol-24-sulfate)
3-acetyl-4-hydroxybenzoylguanidine
Nonoxynol-9
Cytokines
Peptide antibiotics
1-aryl-2-imidazolyl-alkyl (thio) ether
C31G (mixture of alkyldimethylglycine and alkyldimethylamine oxide
or a mixture thereof is selected. 14. Combination according to claim 8, in which the compound (a) with contraceptive Effect is levonorgestrel and the connection with (b) antibacterial and / or (c) viral action squalamine (3β- [3 - [(4-aminobutyl) amino] propyl] amino] -5α-cholestan- 7α, 24-diol-24-sulfate) and the delivery system is an IUD or a vaginal ring.