WO2000003682A2

WO2000003682A2 - Chemical composition having spermicidal, bactericidal and virucidal activity and apparatus for delivery into the vaginal canal

Info

Publication number: WO2000003682A2
Application number: PCT/US1999/016160
Authority: WO
Inventors: Alberto Haces
Original assignee: Gynetech
Priority date: 1998-07-17
Filing date: 1999-07-16
Publication date: 2000-01-27
Also published as: AU5001699A; EP1023031A1; BR9906695A; HUP0301790A2; WO2000003682A3; IL135137A0; CA2303946A1

Abstract

A chemical composition and vaginal sponge for introduction into the vaginal canal. The chemical composition has spermidicidal, bactericidal and virucidal activity, and when introduced into the vaginal canal, e.g. by a vaginal sponge, reduces or prevents the transmission of sexually transmitted diseases (STDs). Preferred compositions include nonoxynol-9 and polyethylene oxide; or, nonoxynol-9 and chlorhexidine digluconate; or, nonoxynol-9, chlorhexidine digluconate, and polyethylene oxide.

Description

Chemical Composition Having Spermicidal,

Bactericidal and Virucidal Activity and Apparatus for Delivery into the Vaginal Canal

Inventor: Dr. Alberto Haces

Related Applications

The present application claims the priority of U.S. Provisional Patent

Application No. 60/093,282 filed July 17, 1999 and of U.S. Provisional Patent

Application No. 60/098,046 filed August 27, 1998, the contents of which are fully

incorporated herein by reference.

Field of the Invention

The present invention relates to a chemical composition having spermicidal, bactericidal and virucidal activity and to an apparatus for delivery of the composition into the vaginal canal.

Background of the Invention

The term "Sexually Transmitted Disease" (STD) is a relatively new one that has gradually replaced the term "Venereal Disease." This terminology has expanded not only the awareness of infectious diseases transmitted through sexual contact, but now describes an expanded array of diseases. Venereal diseases originally encompassed five traditional infections: Gonorrhea, Syphilis, Chancroid, ymphogranuloma Venereum, and Granuloma Inguinale. The term STD today includes more than twenty specific organisms and syndromes, including HIV, Chlamydia Trachomatis, Genital Herpes, Genital Warts and Cervical Neoplasia. Thus, the use of the term STD has grown in its scope, and now encompasses a large number of sexually transmitted infections. These include Acquired Immunodeficiency Syndrome (AIDS), Acute Urethral Syndrome or Cystitis, Bacterial Vaginosis Vulvovaginitis, Candidiasis, Cervical Intraepithelial Neoplasia, Chancroid, Chlamydia, Cytomegalovirus infections, Enteric infections, Genital Warts, Gonorrhea, Granuloma Inguinale, Hepatitis B, Herpes Genitalis, Human Papillomavirus (HPV), Lymphogranuloma venereum (LGV), Molluscum Contagiosum, Mucopurulent Cervicitis, Nongonococcal Urethritis, Pediculosis Pubis, Pelvic Inflammatory Disease (PLD), Scabies, Syphilis, Trichomoniasis and Vulvovaginitis.

STDs are getting worse both in magnitude and severity. A large and growing number of pathogens have been implicated as causative agents. To name a few of the causative agents currently known, Acquired Immunodeficiency Syndrome is caused by Human Immunodeficiency Virus (HIV). Acute Urethral Syndrome is caused by E. coli, C. trachomatis, N. gonorrhea and other gram- negative bacteria. Cervical Intraepithelial Neoplasia (CIN) has been associated with human papilloma virus (HPV), and the Herpes Simplex Virus. Chancroid is caused by Hemophilus Ducreyi. Chlamydia, one of the most common bacterial STD infections in the United States, is caused by Chlamydia trachomatis. Cytomegalovirus infections are caused by a DNA virus of the Herpes virus group. Enteric infections, which are outside, but are related to STDs, are caused by many sexually transmissible bacteria, viruses and protozoa, and by other organisms that produce disease, and are carried in the gastrointestinal tract. Genital Warts are caused by the human papillomavirus (HPV), a small DNA virus belong to the papillomavirus group. Gonorrhea is caused by Neisseria Gonorrhea, a gram- negative diplococcus. Granuloma Inguinale is caused by the gram-negative bacteria calymmato-bacterium granulomatis. Hepatitis B is caused by Hepatatis B virus (HBV), a DNA virus with multiple antigenic components. Herpes Genitalis is caused by the Herpes Simplex II virus (HSV). Lymphogranuloma venereum (LGV) is caused by immuno-types L I, L II, or L III of Chlamydia Trachomatis. Molluscum Contagiosum is caused by the Molluscum Contagiosum virus, the largest DNA virus of the poxvirus group. Mucopurulent Cervicitis is caused by Chlamydia and Gonorrhea. Nongonococcal Urethritis (NGU) is caused by Chlamydia of the D to K immunotypes. Pediculosis Pubis, which, strictly speaking is not a true sexually transmitted disease, is caused by a pubic or crab louse, an ectoparasite. Pelvic Inflammatory Disease (PID) is caused by Gonorrhea, Chlamydia, and other anaerobic bacteria and gram-negative rods, such as E. coli and mycoplasma homines. Scabies is caused by Sarcoptes scabies, a female mite approximately 0.4 mm long. (Although not a true STD disease it is commonly found among those with other STD infections). Syphilis is caused by Treponema Pallidum, a spirochete. Vulvovaginitis is caused by Trichomonas Vaginalis.

As can be seen from the foregoing, a broad variety of microorganisms can potentially enter the vaginal tract through sexual intercourse, and result in a sexually transmitted disease. These microorganisms include bacteria, viruses, fungi, protozoa, and yeasts, among others. The health consequences which can result from the contraction of a sexually transmitted disease can be severe and extremely debilitating. The risk of contracting AIDS through sexual intercourse, for example, is a major concern for many individuals.

The epidemic proportions that some sexually transmitted diseases have reached, as well as the need to prevent unwanted pregnancies, especially among adolescents, has created an urgent need to develop methods to deliver spermicidal, bactericidal and/or virucidal compounds into the vaginal cavity with a high degree of bioavailability. This bioavailability can be in the form of a slow and sustained release, or in the form of "release on demand". A suitable device which fulfills the latter type of release profiles is a chemically inert, pre-cured, reticulated sponge loaded with the desired biocides of the appropriate rheological properties.

A spermicidal sponge device under the trade name, the Today Sponge, was previously released and withdrawn from the market on grounds of manufacturing problems. Such a sponge was made from polyurethane pre-polymers (not cured) and thus not reticulated. In addition, it contained its active ingredient, nonoxynol-9, as one of the components used to make the sponge itself (i.e. this active ingredient was part of the sponge matrix). This made it impossible to remove from it a carcinogenic by-product, 2,4-diaminotoluene, which was present as part of the manufacturing process, without also removing the active ingredient. Also, the inclusion of nonoxynol-9 in the sponge matrix made the sponge brittle and easy to tear (low tensile and tear strength).

The sponge in this application is a completely cured, non-water foamed (such step produces 2,4-diaminotoluene), totally-reticulated, polyurethane sponge. This sponge is prewashed to remove any possible contaminants before it is filled with the active formulation. There are several advantages in this type of device: (1) A precise manufacturing control can be established in its production; (2) the loading and nature of formulation can be optimized for maximum bioavailability; and (3) by its reticulated nature, it can absorb a significant amount of formulation which can be released by the mechanical action of the vaginal muscles or by the thrusting action of the male partner at the time when it is needed most.

Summary of the Invention

The present invention relates to a chemical composition having spermicidal, bactericidal and virucidal activity for intravaginal administration to act as a contraceptive and to prevent the transmission of sexually transmitted diseases. The invention also relates to an apparatus, namely an intravaginal contraceptive sponge, for delivery of the chemical composition into the vaginal canal.

The active ingredients of the sponge are nonoxynol-9 ("N-9") and chlorhexidine digluconate in an acetate buffered aqueous solution of polyethylene oxide (PEO). Nonoxynol-9 is the most commonly used spermicide in the United States and was the only active ingredient of the Today sponge. Chlorhexidine digluconate is also a spermicide, but is less potent than N-9. However, it has the advantage over N-9 that it can immobilize sperm in cervical mucus, whereas N-9 is ineffective in this medium. Thus, chlorhexidine immobilizes sperm at the point of entry to the uterus where it counts the most. In addition, chlorhexidine is a strong bactericide/virucide with a broad spectrum of action. Thus, it not only serves as a preservative, but is also believed to potentially act as an anti-sexually transmitted diseases agent since its spectrum of activity includes some of the most common venereal disease causing bacteria as well as some genital viruses. Chlorhexidine is already used in vaginal products such as K-Y^® (Ortho), Surgilube^® (E. Fougera), as well as in mouthwash products such as Peridex^® (Procter & Gamble). Its efficacy as a safe topical microbiocide which is not absorbed through the skin has been documented for the last 40 years (see e.g. Graham W. Denton, cited below). As described below, it is preferred herein for chronic use as a spermicide/bactericide for use in the vaginal canal, with the preferred method of delivery being a vaginal sponge to provide a well controlled bioavailability of the active ingredients with minimal or no irritation to the user.

In a further embodiment of the invention, the active ingredients of the sponge are nonoxynol-9 ("N-9") and polyethylene oxide (PEO). In this embodiment, the PEO and N-9 act together to produce a synergistic effect and highly effective results, and possibly even superior results to those obtained using chlorhexidine, as described above.

In a preferred embodiment of the invention a vaginal sponge is utilized, which is manufactured as set forth below. Alternatively, another vaginal sponge device or other delivery method or system can be utilized as well.

Brief Description of the Figures

Figure 1 illustrates the chemical formulas and structures of the ingredients and the sponge of the present invention.

Figure 2 illustrates the process for preparation of the polyurethane sponge of the present invention.

Detailed Description of the Invention and the Preferred Embodiments In accordance with the present invention, a chemical composition is provided having spermicidal, bactericidal and virucidal activity for intravaginal administration to act as a contraceptive and to prevent the transmission of sexually transmitted diseases. As detailed below, in one embodiment of the invention, the active ingredients of the sponge are nonoxynol-9 ("N-9") and chlorhexidine digluconate in an acetate buffered aqueous solution of polyethylene oxide (PEO). In an alternative embodiment of the invention, the active ingredients of the sponge are nonoxynol-9 ("N-9") and polyethylene oxide (PEO). In this alternative embodiment, the PEO and N-9 act produce a synergistic effect which can potentially produce even better results than those obtained using chlorhexidine.

In a further preferred embodiment of the invention the chemical composition is delivered to the vaginal canal using a vaginal sponge is utilized, although, alternatively, other delivery methods or system can be utilized, as well.

I. Structural and Chemical Names (USAN)

The structural and chemical names of the major components referred to in the present application are as follows:

1) Polyurethane foam (See Figure la).

2) Alpha-(p-nonylphenyl-w-hydroxyona(oxyethylene),USP. Common name: Nonoxynol-9 (See Figure lb).

3) l,l-hexamethylenebis[5-(4-chlorophenyl)biguanide] di D-gluconate, Ph.Eur.. Common name: chlorhexidine digluconate. (See Figure lc)

4) Polyethylene oxide, NF

Trade name: Polyethylene oxide, WSR-301 (See Figure Id)

5) Sodium acetate buffer, 1M, pH = 5.00 (See Figure le).

II. Polyurethane Sponge

In the preferred embodiment of the present invention, the chemical composition disclosed herein is delivered using an intravaginal contraceptive sponge. It is preferred that the sponge be manufactured of a polyurethane foam. The general scheme to make to foam is shown in Figure 2.

The sponge, which is fully reticulated, is commercially available from Crest Foam Industries, Inc., 100 Carol Place, Moonachie, New Jersey 07074. This sponge is highly regular in cell size and is basically a void space encased by a polyurethane framework or scaffold. The foam is then mechanically cut into small sponges.

In the preferred embodiment, the cured foam is cut into small blocks for quality control purposes. These blocks are checked for tensile strength, percentage elongation, die cut profile, tear and color. Upon passing the quality control tests, the foam is mechanically cut into sponges. The sponges are then washed with water at room temperature and dried. A formulation, whose chemical composition is provided below, is then infused into the sponges. The sponge is then packaged. III. Analysis of the sponge for the presence of residual methylene chloride and tin catalyst

For quality control purposes, to confirm that no undesirable residues are present in the sponge, an analysis of the sponge can be performed as follows:

Sample sponges are washed by submersion in 45 ml of water at room temperature (23 °C) and at 37 °C, and mechanically compressed/depressed for 30 min. The water extracts, along with a sample of blank water and unwashed sponges, are then tested or sent to an appropriate laboratory for testing (e.g. Quantitative Technologies, Inc. of Whitehouse, NJ) for tin and methylene chloride residue analyses. In prior tests of the invention, the analyses have showed that no tin above 0.15 ppm was present in the water extract and no methylene chloride was present in the unwashed sponges at 0.15 ppm or above.

Washing and recovery of the residue from the sponge.

The cut sponges are submersed in warm water at 50 °C and mechanically compressed/depressed for 30 min. The water is squeezed out, and the water rinse is repeated twice more. The sponges are then air dried. The water extract is evaporated on a rotary evaporator at 80 °C under vacuum and an oily residue is obtained.

Analysis of the residue

The residue can be analyzed by thin layer chromatography (TLC) for the presence of 2,4-and 2,6- diaminotoluene, which are the possible by-products from the sponge manufacturing process assuming that the excess polyether diol did not completely react with the limiting reagents 2-4 and 2,6- toluenediisooyanates. Additionally, the Fourier transform infrared (FT-IR) and hydrogen nuclear magnetic resonance (H-NMR) spectra of the residue can be obtained and compared against spectra 2,4 and 2,6- diaminotoluene. None of these potential impurities should be detected with these techniques, nor have been detected in prior studies. In prior studies, it was established with the latter techniques that the residue is composed mainly of the non-hazardous polyether diol, Multranol 7159.

IV Chemical Composition For Delivery into the Vaginal Canal

In accordance with the present invention, a chemical composition is also provided for administration into the vaginal canal. The composition is suitable for contraceptive use and for prevention of the transmission of sexually transmitted diseases, due to its spermicidal, bactericidal and virucidal activity.

The composition consists of a mixture of Nonoxynol-9, Chlorhexidine Digluconate, Polyethylene Oxide, Sodium Acetate and Acetic Acid. Such compounds can be obtained from the following sources, although other manufacturers and sources of ingredient having the same or substantially equivalent activity and purity may be utilized, as well.

Ingredient Manufacturer Cat. No. IP method

Nonoxynol-9 Rhone Poulenc, USA IGEPAL CO 630 Infrared spectrum SPECIAL, USP HPLC (USP

Mono)

Chlorhexidine MediChem, Spain Same as name.Eur P. Infrared spectrum Digluconate (George Uhe,

USA) (Free base),

HPLC

Polyethylene Oxide Union Carbide WSR-301, NF Infrared spectrum Sodium acetate Mallinckrodt, USA 7364 USP Monograph

Acetic Acid Aldrich, USA 10,908- USP Monograph

All active ingredients as well as the polyethylene oxide have their certificates of analyses per USP and/or Ph.Eur or BP, as applicable. Drug Master Files of these ingredients filed by the manufacturers are available as well, the contents of which are incorporated herein by reference.

Protocol

Equipment: Mettler-Toledo analytical balance, AG-104, self calibrating with internal weights, serial number: 1116391267; Gilmont falling ball viscometer, GV-2300; magnetic stirrer; pH meter Mettler-Toledo MP-220, serial number: 037482. Calibration buffer pH = 7.00; chronometer; 1ml Gilson or Eppendorff pipettor.

Preparation of IM acetate buffer. pH = 5.00 Calibrated pH meter at pH = 7.00

A mixture of 9.4800g (0.0069 moles) of sodium acetate trihydrate and 1.8357g (0.0030 moles) of glacial acetic acid in 100 ml of final water solution give IM, pH = 5.00 acetate buffer solution.

Formulation mixture

In the preferred embodiment, the composition of the chemical agents added to the sponge is as follows:

Ingredient Weight g(+/-0.0001g) %Weight Nonoxynol-9, USP 2.0006 3.06 Chlorhexidine 13.7800 21.20 (4.00% dry weight) digluconate (20% w/v),BP

Polyethylene oxide NF 0.4550 0.70

Wsr-301

Acetated buffer, IM 0.5140 0.79 (0.008% dry weight) pH = 5.00

Water, USP 48.2625 74.25

Total 65.0121 100.00

With respect to the preferred ranges of each of the above components, in alternative embodiments of the invention, the N-9 can range from 0.5% to 20%, the chlorhexidine digluconate can range from 0.1% to 4% (dry weight), and the polyethylene oxide (PEO) can range from 0.4-4%. Higher percentages of the N-9 and the chlorhexidine digluconate can be used as well, however, such ranges are not preferred due to the fact that above the upper limits of the preferred ranges these two chemical agents will act as irritants. The PEO can range from 300,000 to 7,000,000 in molecular weight, although in the preferred embodiment it ranges from 4 to 5 million in molecular weight. The preferred pH range is from 5-8.

In a further preferred embodiment of the invention, the PEO and N-9 are used together as the active ingredients, without the chlorhexidine. It has been found that the PEO and N-9 produce a synergistic effect, and can produce highly favorable results. In this embodiment of the invention, the preferred range of the PEO component is 0.05-5%, and the preferred range of the N-9 component is 0.1-20%. It is believed that, in this embodiment, the PEO and N-9 may potentially produce results which are superior even to those obtained using the chlorhexidine formulation described above. Preferably, formulation of the mixture is conducted as follows:

1) The N-9/water mixture is stirred at room temperature until homogenous

2) The chlorhexadine digluconate is weighed and added to the mixture's container. This step is optional and is only used in those embodiments using chlorhexidine as an active ingredient. In embodiments utilizing N-9 and PEO only, this step is skipped.

3) With a vortex forming stirring speed, the polyethylene oxide (PEO) is weighed and added to the mixture's container. This addition is done as evenly and as fast as the PEO can be dispersed into the solution's body. Too slow addition will impede the dissolution of additional PEO, and too fast addition might produce clumps which are gelatinous on the surface and dry- in the inside. These clumps might never dissolve. Once dissolved, the speed is lowered to approximately 50-60 rpm.

4) The pH meter is inserted into the solution, and the buffer acetate solution is added and the entire solution stirred until homogeneous. The pH should be checked during the addition. If 5.50 or less, the addition should be stopped.

5) The pH should be checked, and should be 5.50 + /-0.05.

Viscosity determination

In addition to the above, the viscosity of the composition should be checked. This can be conducted as follows: 1) The density of the solution should be determined by weighing a 1ml volume of the solution using a 1ml Gilson pipetor (+ /-0.002ml).

2) The viscometer should then be placed on a vertical position. If necessary, it should be clamped to a universal stand.

3) The viscometer should be filled all the way to the top and the glass ball dropped gently in the solution.

4) The viscosity should be calculated with the following equation: μ = K (p_t * p_s)t where t = time in minutes , K = 35 constant for the instrument, p_g = density of glass (2.53g/ml), and p_s = density of the solution.

In the preferred embodiment, the viscosity should be 180 +/- 10 cps. An acceptable range for the viscosity, however, is from 10-500 cps (centipoises).

In accordance with the above, chemical compositions are provided which have significant contraceptive activity, and which protect against sexually transmitted diseases.

References

The following references, cited above, are fully incorporated herein by reference: 1. Chijioke P.C., Zaman S. and Pearson R.M. Contraception 1986, 34:207-211.

Comparison of the potency of d-propanolol, chlorhexidine and Nonoxynol-9 in the Sander-Cramer test. 2. Sharman D., Chantler E., Dukes M., Hutchinson F.G. and Elstein M., Fertil. Sterl. 1986, 45:259-264. Comparison of the action of Nonoxynol-9 and Chlorhexidine on Sperm.

3. Graham W. Denton, Disinfection, Sterilization and Preservation (Fourth edition), Seymour S. Block Editor, Lea & Febiger Publishers, Philadelphia, 1991, p. 274-289.

Having described this invention with regard to specific embodiments, it is to be understood that the description is not meant as a limitation since further embodiments, modifications and variations may be apparent or may suggest themselves to those skilled in the art. It is intended that the present application cover all such embodiments, modifications and variations.

Claims

ClaimsWhat is claimed is:

1. A chemical composition, comprising: nonoxynol-9; and, polyethylene oxide.

2. A chemical composition as claimed in Claim 1, wherein said nonoxynol-9 comprises 0.1% - 20% of said chemical composition.

3. A chemical composition as claimed in Claim 1, wherein said polyethylene oxide comprises 0.5-5% of said chemical composition.

4. A chemical composition as claimed in Claim 1, wherein said nonoxynol-9 comprises 0.1% - 20% of said chemical composition, and said polyethylene oxide comprises 0.5-5% of said chemical composition.

5. A chemical composition as claimed in Claim 1, wherein said nonoxynol-9 comprises approximately 3% of said chemical composition.

6. A chemical composition as claimed in Claim 1, wherein said polyethylene oxide comprises approximately 0.7% of said chemical composition.

7. A chemical composition as claimed in Claim 1, wherein said nonoxynol-9 comprises approximately 3% of said chemical composition and said polyethylene oxide comprises approximately 0.7% of said chemical composition.

8. A chemical composition as claimed in Claim 1, further comprising a buffer solution.

9. A chemical composition as claimed in Claim 6, wherein said buffer is an acetate buffer.

10. A chemical composition, comprising: nonoxynol-9; and chlorhexidine digluconate.

11. A chemical composition as claimed in Claim 10, wherein said nonoxynol-9 comprises 0.5% - 20% of said chemical composition.

12. A chemical composition as claimed in Claim 10, wherein said chlorhexidine digluconate comprises 0.1% to 4% (dry weight) of said chemical composition.

13. A chemical composition as claimed in Claim 10, wherein said nonoxynol-9 comprises 0.5% - 20% of said chemical composition and said chlorhexidine digluconate comprises 0.1% to 4% (dry weight) of said chemical composition.

14. A chemical composition as claimed in Claim 10, wherein said nonoxynol-9 comprises approximately 3% of said chemical composition.

15. A chemical composition as claimed in Claim 10, wherein said chlorhexidine digluconate comprises approximately 20% or 4% dry weight of said chemical composition.

16. A chemical composition as claimed in Claim 10, wherein said nonoxynol-9 comprises approximately 3% of said chemical composition and said chlorhexidine digluconate comprises approximately 20% (or 4% dry weight) of said chemical composition.

17. A chemical composition as claimed in Claim 10, further comprising a buffer solution.

18. A chemical composition as claimed in Claim 17, wherein said buffer is an acetate buffer.

19. A chemical composition, comprising: nonoxynol-9; chlorhexidine digluconate; and, polyethylene oxide.

20. A chemical composition as claimed in Claim 19, wherein said nonoxynol-9 comprises 0.5% - 20% of said chemical composition.

21. A chemical composition as claimed in Claim 19, wherein said chlorhexidine digluconate comprises 0.1% to 4% (dry weight) of said chemical composition.

22. A chemical composition as claimed in Claim 19, wherein said polyethylene oxide comprises 0.4-4% of said chemical composition.

23. A chemical composition as claimed in Claim 19, wherein said nonoxynol-9 comprises 0.5% - 20% of said chemical composition, said chlorhexidine digluconate comprises 0.1% to 4% (dry weight) of said chemical composition, and said polyethylene oxide comprises 0.4-4% of said chemical composition.

24. A chemical composition as claimed in Claim 19, wherein said nonoxynol-9 comprises approximately 3% of said chemical composition.

25. A chemical composition as claimed in Claim 19, wherein said chlorhexidine digluconate comprises approximately 20% or 4% dry weight of said chemical composition.

26. A chemical composition as claimed in Claim 19, wherein said polyethylene oxide comprises approximately 0.7% of said chemical composition.

27. A chemical composition as claimed in Claim 19, wherein said nonoxynol-9 comprises approximately 3% of said chemical composition, said chlorhexidine digluconate comprises approximately 20% or 4% dry weight of said chemical composition, and said polyethylene oxide comprises approximately 0.7% of said chemical composition.

28. A chemical composition as claimed in Claim 19, further comprising a buffer solution.

29. A chemical composition as claimed in Claim 28, wherein said buffer is an acetate buffer.

30. A vaginal sponge, comprising: nonoxynol-9; and, polyethylene oxide.

31. A vaginal sponge as claimed in Claim 30, wherein said nonoxynol-9 comprises 0.1%

- 20% of said vaginal sponge.

32. A vaginal sponge as claimed in Claim 30, wherein said polyethylene oxide comprises 0.5-5% of said vaginal sponge.

33. A vaginal sponge as claimed in Claim 30, wherein said nonoxynol-9 comprises 0.1%

- 20% of said vaginal sponge, and said polyethylene oxide comprises 0.5-5% of said vaginal sponge.

34. A vaginal sponge as claimed in Claim 30, wherein said nonoxynol-9 comprises approximately 3% of said vaginal sponge.

35. A vaginal sponge as claimed in Claim 30, wherein said polyethylene oxide comprises approximately 0.7% of said vaginal sponge.

36. A vaginal sponge as claimed in Claim 30, wherein said nonoxynol-9 comprises approximately 3% of said vaginal sponge and said polyethylene oxide comprises approximately 0.7% of said vaginal sponge.

37. A vaginal sponge, comprising: nonoxynol-9; and chlorhexidine digluconate.

38. A vaginal sponge as claimed in Claim 37, wherein said nonoxynol-9 comprises 0.5%

- 20% of said vaginal sponge.

39. A vaginal sponge as claimed in Claim 37, wherein said chlorhexidine digluconate comprises 0.1% to 4% (dry weight) of said vaginal sponge.

40. A vaginal sponge as claimed in Claim 37, wherein said nonoxynol-9 comprises 0.5%

- 20% of said vaginal sponge and said chlorhexidine digluconate comprises 0.1% to 4% (dry weight) of said vaginal sponge.

41. A vaginal sponge as claimed in Claim 37, wherein said nonoxynol-9 comprises approximately 3% of said vaginal sponge.

42. A vaginal sponge as claimed in Claim 37, wherein said chlorhexidine digluconate comprises approximately 20% or 4% dry weight of said vaginal sponge.

43. A vaginal sponge as claimed in Claim 37, wherein said nonoxynol-9 comprises approximately 3% of said vaginal sponge and said chlorhexidine digluconate comprises approximately 20% (or 4% dry weight) of said vaginal sponge.

44. A vaginal sponge, comprising: nonoxynol-9; chlorhexidine digluconate; and, polyethylene oxide.

45. A vaginal sponge as claimed in Claim 44, wherein said nonoxynol-9 comprises 0.5%

- 20% of said vaginal sponge.

46. A vaginal sponge as claimed in Claim 44, wherein said chlorhexidine digluconate comprises 0.1% to 4% (dry weight) of said vaginal sponge.

47. A vaginal sponge as claimed in Claim 44, wherein said polyethylene oxide comprises 0.4-4% of said vaginal sponge.

48. A vaginal sponge as claimed in Claim 44, wherein said nonoxynol-9 comprises 0.5% - 20% of said vaginal sponge, said chlorhexidine digluconate comprises 0.1% to 4% (dry weight) of said vaginal sponge, and said polyethylene oxide comprises 0.4-4% of said vaginal sponge.

49. A vaginal sponge as claimed in Claim 44, wherein said nonoxynol-9 comprises approximately 3% of said vaginal sponge.

50. A vaginal sponge as claimed in Claim 44, wherein said chlorhexidine digluconate comprises approximately 20% or 4% dry weight of said vaginal sponge.

51. A vaginal sponge as claimed in Claim 44, wherein said polyethylene oxide comprises approximately 0.7% of said vaginal sponge.

52. A vaginal sponge as claimed in Claim 44, wherein said nonoxynol-9 comprises approximately 3% of said vaginal sponge, said chlorhexidine digluconate comprises approximately 20% or 4% dry weight of said vaginal sponge, and said polyethylene oxide comprises approximately 0.7% of said vaginal sponge.