WO2005025565A1

WO2005025565A1 - Microbicide composition comprising a minor groove binder optionally in combination with an anti-hiv compound and use thereof in the prevention of sexually transmitted diseases

Info

Publication number: WO2005025565A1
Application number: PCT/IB2004/002923
Authority: WO
Inventors: Fabrizio Marcucci
Original assignee: NEED PHARMACEUTICALS Srl
Current assignee: NEED PHARMACEUTICALS Srl
Priority date: 2003-09-12
Filing date: 2004-09-08
Publication date: 2005-03-24
Anticipated expiration: 2006-03-12
Also published as: ITMI20031754A1

Abstract

A microbicide composition and the use thereof in the prophylaxis of the sexually transmitted diseases.

Description

MICROBICIDE COMPOSITION COMPRISING A MINOR GROOVE BINDER OPTIONALLY IN COMBINATI ON WITH AN ANTI-HIV COMPOUND AND USE THEREOF IN THE PREVENTION OF SEXUALLY TRANS MITTED DISEASES ******** OBJECT OF THE INVENTION The object of the present invention is a microbicide composition and its use 5 in the prophylaxis of the sexually transmitted diseases. BACKGROUND OF THE ART It is known that the problem of sexually transmitted diseases is very felt and hard to be solved. In recent times, the problem has been made worse due to the HIV infection (human immunodeficiency virus), the sexual route being 10 one of the most dangerous and least easily controlled transmission means. The problem is felt worldwide, and is particularly serious in the underdeveloped countries, where an efficient campaign on safe sexual behaviour cannot be set up due to lack of sensitization, culture and also actual means. As a matter of fact, generally - and mainly in the 15 underdeveloped countries - condoms are not properly and continuously used, therefore they do not yield the desired outcome both in terms of prevention of the sexually transmitted diseases, and the concomitant contraceptive activity. Furthermore, condom use is often opposed to by male partners due to lack of culture or different reasons, whether religious or the like, and this contributes 20 to the spreading of sexually transmitted diseases. Studies and researches addressed to identify products being suitable to be used for the prophylaxis of the sexually transmitted diseases have been carried out for many years. These products might be used by vaginal or rectal application, upon or just before sexual contact, and should protect 25 against most of the so-called sexually transmitted diseases of viral origin, such as for example AIDS, herpes genitalis, of bacterial origin, such as gonorrhea, either or protozoan or fungine origine, such as trichomoniasis and candidiasis, respectively. To the purpose, products having antiviral activity are known for local topical 30 use, which are employed in the treatment of the sexually transmitted diseases of viral origin, limitedly to herpes genitalis and which are employed by application on external genitals. Products with antibacterial activity are also known, which are also used by local application and are active towards the sexually transmitted diseases of bacterial origin.

In any case, the products exhibited a good activity in the treatment of already existing infections, i.e. an activity that can be defined as being curative, but they cannot be used in the prevention of said sexually transmitted diseases.

Accordingly, the need for managing products capable of carrying out an a- priori antiviral/antibacterial activity (generally being defined as microbicide products), i.e. preventing the onset of the disease, is generally very felt. The microbicides currently studied and experimented for prophylactic use in the sexually transmitted diseases do not offer such a wide coverage as desired, and they further do not afford sufficient characteristics of safety, physical and chemical stability of the base product.

Therefore, the problem is that of identifying a class of microbicide products active as antivirals, antibacterials, antiprotozoans, and antifungals, such as to ensure a wide protection in the case of sexually transmitted diseases, which are stable, suitable to vaginal and/or rectal application, and can be also easily used by less culturally developed populations.

OBJECTS OF THE INVENTION The object of the present invention is to provide a composition having microbicide activity to be applied by vaginal and/or rectal route, which is stable over time and easy to use.

It is still an object of the present invention to provide a microbicide composition which is highly effective in terms of prophylaxis (i.e. preventive action against the onset of the infection) towards viruses, bacteria, fungus and protozoans.

It is also an object of the present invention to provide a microbicide composition for use in the prophylaxis of the sexually transmitted diseases.

It is still an object of the present invention to provide a microbicide pharmaceutical composition for use in the prophylaxis of the sexually transmitted diseases. DESCRIPTION

These and other objects, as well as the advantages thereof, which will be better understood from the description below are achieved by means of a composition comprising at least one "Minor Groove Binder" (MGB) compound and at least one anti-HIV compound.

By "Minor Groove Binder" (MGB) is meant a compound that is able to bind (through a non-covalent binding) to the DNA at the minor groove. Particularly, said "Minor Groove Binder" (MGB) compound is selected from, though not being limited to: Distamycin A, Mithramycin, Congocidine, Hoechst 33258, Pentamidine, Furamidine, analogues of bis-distamycin and bis-netropsine, diarylamidine and diarylamidossime, such as DB-2898. Still according to the present invention, said anti-HIV compound is selected from, though not being limited to: surfactant agents such as Nonoxynol-9, sodium dodecyl-sulphate, C31G, benzalconium chloride, antibiotics such as magainin, protegrin, oxidizing agents such as chlorhexidine, hydrogen peroxide, anti-HIV and anti-CD4 antibodies, reverse transcriptase inhibitors such as Tenofovir, UC781 , Nevirapine etc., inhibitors of HIV attack and/or fusion to cells such as Suradista analogues, anionic polymers (PRO 2000), Carragenin, Polystyrene Sulfonate, Cyanovirin. The products described in Antiviral Research, 27 (1995 ) 335-354 belong for example to the Suradista class.

More particularly, in a preferred embodiment of the invention, said MGB compound is Distamycin A , whereas said anti-HIV compound is comprised among the products belonging to the Suradista class. Distamycin A is a natural product having antibiotic activity, particularly a fungicide activity for application in the agricultural or veterinary field, obtained from Streptomyces distallicus such as described in US 3,190,801. Said anti-HIV compound belonging to the Suradista class is a compound similar to the above Distamycin, for use as a drug for the treatment of AIDS, Acquired ImmunoDeficiency Syndrome caused by HIV virus type 1 and 2, such as described in Drug Data Report, Vol.20, No.9, 1995-1999 (Prous Science) with code NSC-651016.

In both cases, the activity of each component is recognized for the treatment of an already existing disease, when the infection has already developed and is symptomatic, both in the case of the antibiotic and AIDS. Both products exhibit their known antibiotic and antiviral activity, though not preventively but only after the onset of the disease, and cause the regress of the latter mainly in the case of Distamycin A antibiotic, as well as a partial deactivation of the virus or inhibition of the viral activity in the case of those compounds belonging to the Suradista class. It has been surprisingly observed that the composition according to the invention has a microbicide activity; it is particularly active towards viruses, bacteria, protozoans, fungus and is advantageously employed as a microbicide in the prophylaxis of the sexually transmitted diseases, such as for example those due to: Herpes simplex virus (HSVI II), hepatitis B and^: C virus , Papilloma virus, Trichomonas vaginalis, Treponema pallidum, Neisseria gonorrheae, Chlamydia trachomatis, Candida albicans, human immunodeficiency virus (HIV) type 1 and 2.

Surprisingly, the composition according to the invention is effective in preventing those sexually transmitted diseases which are generally caused by the above mentioned organisms and is thus employed in the prophylaxis, i.e. at a preventive stage before the onset of the disease. Surprisingly, the composition is sinergically active in the prevention of the sexually transmitted pathologies caused indifferently by viruses, bacteria, protozoans, fungus. Practically, the composition according to the invention is suitable to be administered by vaginal and/or rectal route prior to sexual contact and carries out its protective function by countering the initial action of viruses, bacteria and other microrganisms responsible for the major sexually transmitted diseases thus allowing to counter the onset of the disease. The most appreciable advantage is thus due to the fact that said compositions are not used after the emergence of the pathology but, as stated above, at a preventive stage, and inhibit the onset thereof.

Accordingly, those subject having risky or however unprotected sexual intercourses and are therefore more exposed to contracting sexually transmitted diseases, does not fall ill, i.e. they do not develop any pathology among those indicated above. The composition according to the invention does not represent a cure, it is rather a preventive treatment, a prophylaxis which prevents contracting the disease and avoids that a subject may fall ill and need to be cured.

Another advantage deriving from the use of the microbicide composition according to the present invention, is that the female partner is able to autonomously select and use the product prior to sexual intercourse. In this case, above all in the underdeveloped countries, the problem of a poor, if any, condom use by the male partner would be obviated.

The composition according to the invention can also provide adding at least a further component having contraceptive activity, thereby allowing to achieve two targets: carrying out a preventive prophylactic activity towards the sexually transmitted diseases and at the same time performing a contraceptive activity, even a partial one, if desired.

Also objects of the present invention are the pharmaceutical compositions comprising a therapeutically and/or prophylactically effective dose of a microbicide composition comprising at least a "Minor Groove Binder" (MGB) compound and at least an anti HIV compound, in admixture with pharmaceutically acceptable carriers and/or excipients.

Said pharmaceutical compositions are advantageously prepared in the form of cream, gel, tablets, bougies or other system suitable for vaginal and/or rectal application and are employed in the prophylaxis of the sexually transmitted diseases.

The compositions according to the invention are not noxious for the organism, do not cause lactobacilli growth inhibition within the vaginal tract, which are responsible for the preservation of the proper acid level in the vagina, and represent a valid defence against the sexually transmitted diseases such as, as stated above, those due to: herpes virus, hepatitis B and C virus , Papilloma virus, Trichomonas vaginalis, Treponema pallidum, Neisseria gonorrheae, Chlamydia trachomatis, Candida albicans, human immunodeficiency virus (HIV) of type 1 and 2. Still according to the present invention, a pharmaceutical composition with microbicide activity comprises a "Minor Groove Binder" (MGB) such as Distamycin A as the active ingredient. Said composition exhibits a surprising microbicide action and is advantageously employed in the prophylactic treatment of sexually transmitted diseases, particularly those due to: Herpes simplex virus, hepatitis B and C virus , Papilloma virus, Trichomonas vaginalis, Treponema pallidum, Neisseria gonorrheae, Chlamydia trachomatis, Candida albicans, human immunodeficiency virus (HIV) of type 1 and 2. Also in this case, there are prepared pharmaceutical compositions comprising a therapeutically and/or prophylactically effective dose of Distamycin A as the active ingredient, in admixture with pharmaceutically acceptable carriers and/or excipients.

Said pharmaceutical compositions are advantageously prepared in the form of cream, gel, tablets, bougies or other system suitable for vaginal and/or rectal application and are used in the prophylaxis of sexually transmitted diseases. Particularly, they are employed prior to the onset of the pathology and therefore they carry on a preventive action by countering and preventing the onset of the pathology, rather than a therapeutic activity towards an already existing and emerged pathology. Several pharmaceutical compositions according to the invention, which are given by way of non-limiting examples, are described below. EXAMPLE 1

Activity of Distamycin A in combination with Suradista towards HSV-1. The activity of Distamycin towards HSV-1 and 2 is discussed for example in Antiviral Chemistry & Chemotherapy. 1997: 8(3):243-254 and in Anti-cancer Drug Design. 1986: 1 : 235-244. The antiviral activity of Distamycin A whether alone or in combination with Suradista assayed towards HSV-1 until the maximum concentration of 100 μM for both compounds has been determined by using a culture of the virus HSV-1 strain HF in HEp-2 cells (epithelial cells derived from human laryngeal cancer). The cells are infected with 1000 DI₅₀ (1 Dl₅₀ corresponding to the Dose Infecting 50% of cells after 72 hour incubation at 37°C). The antiviral activity is determined after 72 hour incubation of the infected cells (2 x 10⁵ cells/mL) with various concentrations of Distamycin A either alone or in combination with Suradista by microscopic observation of the cytopathic effect being induced by HSV-1. The Clso, i.e. the concentration inhibiting the viral cytopathic effect by 50% is obtained by correlating the compound concentration to the corresponding measure of the cytopathic effect. The CI₅₀ obtained with Distamycin A was 11.7 μM. The addition of Suradista until a concentration of 100 μM has not affected the activity of Distamycin A (CI₅₀: 12.1 μM in the presence of 100μM Suradista). Activity of Distamycin A in combination with Suradista towards HSV-2.

The antiviral activity of Distamycin A either alone or in combination with Suradista assayed until the maximum concentration of 100 μM for both compounds towards HSV-2 has been determined by using a culture of HSV- 2 virus isolated from pathologic material and grown in human fibroblasts. The cells (2 x 10⁵ celIs/mL in 6-well plates; 1 mL/well) are infected with such viral concentrations as to cause the formation of 20-30 plaques of cytopathic activity per each well. The antiviral activity is determined after 72 hour incubation of the infected cells (2 x 10⁵ cells/mL) with various concentrations of Distamycin A either alone or in combination with Suradista by microscope observation of the cytopathic effect being induced by HSV-2. The Cl₅₀, i.e. the concentration inhibiting the viral cytopathic effect by 50% is determined by correlating the compound concentration with the corresponding measure of the cytopathic effect. The CI₅₀ obtained with Distamycin A was 35 μM. The addition of Suradista to a concentration of 100 μM has not affected the activity of Distamycin A (CI₅₀: 41 μM in the presence of 100μM Suradista). EXAMPLE 2 Activity of Distamycin A on various species of bacteria, fungus, protozoans, and viruses. The minimum inhibiting concentration (MIC) of Distamycin A on bacteria and fungus has been determined according to the procedures of National Committee for Clinical Laboratory Standards (NCCLS), Documents M7-A4 (1997), M11-A4 (1997), M27-T (1995). The tested microrganisms included: Staphylococcus aureus, S.epidermidis, Streptococcus pyogenes, Escherichia coli, Enterococcus faecalis, E. faecium, Neisseria gonorrheae, Candida albicans, Chlamydia trachomatis, Ureoplasma urealyticum. Distamycin A (Table 1 ) is active towards those bacteria and fungus mostly involved in the sexually transmitted pathologies, such as Neisseria gonorrheae (CIM= 8 mg/L), Chlamidia trachomatis (CIM=16 mg/L), Ureoplasma urealyticum (CIM: 16 mg/L), Candida albicans (CIM= 16 mg/L).

The activity of Distamycin A towards the motility of Trichomonas vaginalis has been determined in Loche medium additioned with 10% bovine serum. Distamycin A at a concentration of 10 mg/L inhibits the motility of the protozoan after 4 hour contact.

EXAMPLE 3

Activity of Distamycin A in combination with Suradista towards bacteria, fungus, protozoans and viruses. The presence of Suradista at a concentration of 512 mg/L does not interfere with the exhibited activity of Distamycin A towards bacteria, fungus protozooms and viruses being described in Example 2 (Table 1).

EXAMPLE 4

Activity of Suradista in combination with Distamycin A towards HIV-1 and 2. The Suradista activity towards HIV 1 and 2 is described in J. Med. Chem,

1998, 41 :2184. The interaction of Distamycin A with the antiviral activity of

Suradista has been determined by measuring the viral replication of HIV-1

RF strain in CEM-SS lymphocytic cells, according to the protocol described in

J. Med. Chem, 1998, 41:2184. The Suradista concentration inhibiting viral replication by 50% was 2.3 μM. This value in the presence of 1 mM

Distamycin A was 2.7 μM. Distamycin A, until a concentration of 1 mM, does not interfere with the Suradista anti-HIV activity.

EXAMPLE 5

Distamycin A and Suradista, either alone or in combination, do not exhibit any direct antibacterial activity towards Lattobacillus acidophylus.

The MIC of Distamycin A and Suradista, being determined according to the procedures of National Committee for Clinical Laboratory Standards

(NCCLS), Documents M7-A4 (1997), were both > 256 mg/L. This value means that the Lattobacilli, which are part of the normal vaginal flora and contribute both to preserve the acidity of the vaginal mucosa and to the defence against agents responsible for sexually transmitted diseases, are not inhibited by Distamycin A and Suradista.

EXAMPLE 6

Cytotoxic activity of Distamycin A and Suradista towards cell lines of human origin.

Cytotoxicity measure is indicative of the tolerability and toxicity of compounds designated as microbicide in the prevention of sexually transmitted diseases. The cytotoxic activity of Distamycin A and Suradista, either alone or in combination, has been determined by using the following human cell lines: HepG2 (hepatocellular carcinoma) e HeLa (cervix epithelioid carcinoma), according to MTT method. Both compounds, whether tested alone or in combination, at 1 mM maximum concentration have not induced any cytotoxicity after 24 hour incubation (IC₅₀: > 1 mM). EXAMPLE 7 Distamycin A in gel form The composition contains Distamycin A at the possible concentrations ranging from 0.01 to 4 %. The formulation contains for example a gelling agent, a preserving agent, a wetting agent. For example, gelling agents and their concentrations thereof are: Carbomer 934P (0.5-2%), cetostearic alcohol (10%), hydroxyethylcellulose (0.1-0.5%), hydroxymethylcellulose, polyoxymethylene- or polyoxypropylene-based copolymer (15-50%), sodium carboxymethylcellulose (4-6%). For example, wetting agents and their concentrations thereof are: propylene glycol (15%), glycerine (10-20%), sorbitol (3-15%). For example, preserving agents and their concentrations thereof are: methyl parabenzoate (0.1-0.2%), propyl parabenzoate (0.02- 0.1 %), propylene glycol (5-80%).

Combination of Distamycin + Suradista in the form of gel The composition contains Distamycin A in combination with Suradista at the possible respective concentrations ranging from 0.01 and 4 %. In this composition, the ratio of Distamycin A and Suradista can range between 1 :5 e 5%, preferably between 1 :2 and 2:1 , preferably about 1 :1. The formulation contains the same ingredients as the composition with Distamycin A alone. EXAMPLE 8

Distamycin A in the form of a cream The composition contains Distamycin A at the possible concentrations ranging from 0.01 and 4 %. The formulation contains for example an emulsifying agent, a preserving agent, an aqueous base. For example, emulsifying agents and their concentrations thereof are: cetyl stearyl alcohol (2-5%), cetyl alcohol (2-5%), polyethylenglycol (...), polysorbate 60 (1-10%). For example, preserving agents and their concentrations thereof are: methyl parabenzoate (0.1-0.2%), propyl parabenzoate (0.02-0.1%), propylene glycol (5-80), benzyl alcohol (1%). For example aqueous bases are: spermaceti, stearic acid (1-20%).

Combination of Distamycin + Suradista in the form of a cream The composition contains Distamycin A in combination with Suradista at the respective possible concentrations ranging from 0.01 to 4 %. In this composition, the ratio of Distamycin A and Suradista can range between 1 :5 and 5%, preferably between 1 :2 and 2:1 , preferably about 1 :1. The formulation contains the same ingredients as the composition with Distamycin A alone. EXAMPLE 9 Distamycin A in the form of tablets/capsules

The composition contains Distamycin A at the possible concentrations ranging from 0.01 and 4 %. The formulation contains for example: cellulose (0-100%), hydroxypropylmethylcellulose (2-10%), methylcellulose (2-10%), crospovidone (2-5%), magnesium stearate (0,25-5%), corn starch (5-25%), lactic acid (0.05-6%), colloidal silicon dioxide (2-10%),

Combination of Distamycin + Suradista in the form of tablets/capsules The composition contains Distamycin A in combination with Suradista at the respective possible concentrations ranging between 0.01 and 4 %. In this composition, the ratio of Distamycin A and Suradista can be between 1 :5 and 5%, preferably between 1 :2 and 2:1 , preferably about 1 :1. The formulation contains the same ingredients of the composition with Distamycin A alone.

Claims

CLAIMS 1. A composition comprising at least a "Minor Groove Binder" (MGB) compound and at least an anti- HIV compound.

2. The composition according to claim 1 , characterized in that said "Minor Groove Binder" (MGB) compound is selected from, though not being limited to: Distamycin A, Mithramycin, Congocidine, Hoechst 33258, Pentamidine, Furamidine, analogues of bis-distamycin and bis- netropsine, diarylamidine and diarylamidossime, such as DB-2898.

3. The composition according to claim 1 , characterized in that said anti- HIV compound is selected from, though not being limited to: agenti surfattanti such as surfactant agents such as Nonoxynol-9, sodium dodecyl-sulphate, C31 G, benzalconium chloride, antibiotics such as magainin, protegrin, oxiding agents such as chlorhexidine, hydrogen peroxide, anti-HIV and anti-CD4 antibodies, reverse transcriptase inhibitors such as Tenofovir, UC781 , Nevirapine etc., inhibitors of HIV attack and/or fusion to cells such as Suradista analogues, anionic polymers (PRO 2000), Carragenin, Polystyrene Sulfonate, Cyanovirin.

4. The composition according to claim 1 , characterized in that said "Minor Groove Binder" (MGB) compound is Distamycin A.

5. The composition according to claim 1 , characterized in that said anti- HIV compound belongs to the Suradista class.

6. The composition according to claim 1 , characterized in that said compound "Minor Groove Binder" (MGB) is Distamycin A and said anti-HIV compound belongs to the Suradista class.

7. Use of the composition of claim 1 as a microbicide.

8. Use of the composition of claim 1 in the prophylaxis of the sexually transmitted diseases.

9. Use according to claim 8 wherein said sexually transmitted diseases are due to: Herpes simplex virus (HSV II), hepatitis B and C virus, Papilloma virus, Trichomonas vaginalis, Treponema pallidum, Neisseria gonorrheae, Chlamydia trachomatis, Candida albicans, human immunodeficiency virus (HIV) of type 1 and 2.

10. A pharmaceutical composition comprising at least one "Minor Groove Binder" (MGB) compound and at least a HIV compound according to claim 1 as the active ingredient, in admixture with pharmaceutically acceptable carriers and/or excipients.

11. The pharmaceutical composition according to claim 10, characterized in that said "Minor Groove Binder" (MGB) compound is selected from, though not being limited to: Distamycin A, Mithramycin, Congocidine, Hoechst 33258, Pentamidine, Furamidine, analogues of bis- distamycin and bis-netropsine, diarylamidine and diarylamidossime, such as DB-2898.

12. The pharmaceutical composition according to claim 10, characterized in that said anti-HIV compound is selected from, though not being limited to: surfactant agents such as Nonoxynol-9, sodium dodecyl- sulphate, C31 G, benzalconium chloride, antibiotics such as magainin, protegrin, oxidizing agents such as chlorhexidine, hydrogen peroxide, anti-HIV and anti-CD4 antibodies, reverse transcriptase inhibitors such as Tenofovir, UC781 , Nevirapine, inhibitors of HIV attack and/or fusion to cells such as Suradista analogues, anionic polymers (PRO 2000), Carragenin, Polystyrene Sulfonate, Cyanovirin.

13. The pharmaceutical composition according to claim 10, characterized in that said Minor Groove Binder" (MGB) compound is Distamycin A .

14. The pharmaceutical composition according to claim 10, characterized in that said anti-HIV compound belongs to the Suradista class.

15. The pharmaceutical composition according to claim 10, characterized in that said "Minor Groove Binder" (MGB) compound is Distamycin A and said anti-HIV compound belongs to the Suradista class.

16. The pharmaceutical composition according to claim 10, characterized in that it comprises: Distamycin A in combination with 0.01 to 4 % Suradista.

17. The pharmaceutical composition according to claim 10, characterized in that it comprises at least a compound having contraceptive activity.

18. The pharmaceutical composition according to claim 10, characterized in that it is suitable to vaginal or rectal local application.

19. The pharmaceutical composition according to claim 10, characterized in that it is in the form of cream, gel, bougies, tablets.

20. Use of the pharmaceutical composition of claim 10 as a microbicide.

21. Use of the pharmaceutical composition of claim 10 in the prophylaxis of the sexually transmitted diseases.

22. Use according to claim 21 wherein said sexually transmitted diseases are due to: herpes virus, hepatitis B and C virus, Papilloma virus, Trichomonas vaginalis, Treponema pallidum, Neisseria gonorrheae, Chlamydia trachomatis, Candida albicans, human immunodeficiency virus HIV of type 1 and 2.

23. A method for the prophylaxis of the sexually transmitted diseases comprising the use of said pharmaceutical composition of claim 10.

24. A composition comprising at least one "Minor Groove Binder" (MGB) compound.

25. The composition according to claim 24, characterized in that said compound "Minor Groove Bindef (MGB) is selected from, though not being limited to: Distamycin A, Mithramycin, Congocidine, Hoechst 33258, Pentamidine, Furamidine, analogues of bis-distamycin and bis- netropsine, diarylamidine and diarylamidossime, such as DB-2898.

26. The composition according to claim 24, characterized in that said "Minor Groove Bindef (MGB) compound is Distamycin A .

27. The composition according to claim 24, characterized in that it comprises: 0.01 to 4 % Distamycin A

28. The composition according to claim 24, characterized in that it comprises at least one compound having contraceptive activity.

29. Use of the composition of claim 24 as a microbicide.

30. Use of the composition of claim 24 in the prophylaxis of the sexually transmitted diseases.

31. Use according to claim 30 wherein said sexually transmitted diseases are due to: herpes virus, hepatitis B and C virus, Papilloma virus, Trichomonas vaginalis, Treponema pallidum, Neisseria gonorrheae, Chlamydia, Candida albicans, human immunodeficiency virus HIV of type 1 and 2.

32. A pharmaceutical composition comprising at least one "Minor Groove Binder" (MGB) compound of claim 24 as the active ingredient, in admixture with pharmaceutically acceptable carriers and/or excipients.

33. The pharmaceutical composition according to claim 32, characterized in that said "Minor Groove Binder" (MGB) compound is selected from, though not being limited to: Distamycin A, Mithramycin, Congocidine, Hoechst 33258, Pentamidine, Furamidine, analogues of bis- distamycin and bis-netropsine, diarylamidine and diarylamidossime, such as DB-2898.

34. The pharmaceutical composition according to claim 32, characterized in that said "Minor Groove Binder" (MGB) compound is Distamycin A .

35. The pharmaceutical composition according to claim 32, characterized in that it is suitable for vaginal or rectal local application.

36. The pharmaceutical composition according to claim 32, characterized in that it is in the form of cream, gel, bougies, tablets.

37. The pharmaceutical composition according to claim 32, characterized in that it comprises at least one compound having contraceptive activity.

38. Use of the pharmaceutical composition of claim 32 as a microbicide.

39. Use of the pharmaceutical composition of claim 32 in the prophylaxis of the sexually transmitted diseases.

40. Use according to claim 39 wherein said sexually transmitted diseases are due to: herpes virus, hepatitis B and C virus, Papilloma virus, Trichomonas vaginalis, Treponema pallidum, Neisseria gonorrheae, Chlamydia, Candida albicans, human immunodeficiency virus HIV di tipo 1 and 2.

41. A method for the prophylaxis of the sexually transmitted diseases comprising the use of said pharmaceutical composition of claim 32.