| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | May 16, 2000 |
| PATENT TITLE |
Cellulose sulfate for use as antimicrobial and contraceptive agent |
| PATENT ABSTRACT | The present invention relates to a method of reducing the risk of infections and the risk of conception. In particular, the invention relates to cellulose sulfate having contraceptive and anti-microbial properties. Cellulose sulfate may be administered in appropriate dosage forms to reduce the risk of infections or the risk of conception. It can also be used during sexual contact to concomitantly reduce the risk of conception and the risk of sexually transmitted diseases |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | September 29, 1995 |
| PATENT REFERENCES CITED |
Astrup, T. and Alkjaersig, N. (1950) Polysaccharide polysulphuric acids as antihyaluronidases. Nature 166: 568-569. Spensley, P.C. and Rogers, H.J. (1954) Enzyme Inhibition. Nature 173:1190. Doring, G.K. (1954) Practical experience with a new vaginal contraceptive. Int. J. Sexol. 8:93-94. Wood, S.G., Forrest M.E., John, B.A., Chasseaud, L.F. and van de Wiel, J.A.C. (1984) Extent of vaginal absorption of sulphated polysaccharide from A-gen 53 in the rabbit. Contraception 29: 375-383. Andolz, P., Palazon, X. and Bielsa, M.A. (1983) Estudio del efecto de una nueva asociacion contraceptiva sobre los expermatozozoides humanos. Gine-Dips 11: 1-14. Hildebrandt, A. (1956) Praktische erfahrungen mit einem fermentchemischen antikonzipiens. Medizinisch Klinik 51: 1192. Ziegeler, H. (1960) Geburtenkontrolle durch A-GEN 53. Med. Welt 41: 2181. Martinez-Sausor, V. and Royo A.P. (1984) Estudio de la eficacia y aceptabilldad de un spermicida espermostatico/vaginal en ovulos en portadoras de un disositivo intrauterino. El Medico 91: 82. Remington's Pharmaceutical Sciences 17.sup.th Ed 1985 p. 1158. Mizumoto et al. "Sulfated homopolysaccharides with immunomodulating activities are more potent anti-HTLV-III agents thatn sulfated heteropolysaccharides " vol. 58, No. 3, 1988. Yamamoto et al: "synthesis, structure and antiviral activity of sulfates of cellulose and its branched derivatives", vol. 14, No. 1, 1990, pp. 53-64, XP000160254. Rothschild et al: "endotoxin shock in dogs pretreated with cellulose sulfate" vol. 20, No. 1, 1967, pp. 77-78, XP000645736. Dunn et al: the reponse of the newborn rat to injury: vol. 116, No. 3, 1975, pp. 165-181, XP000645733. Zuffrey et al: "risques vrais et faux de la contraception locale" vol. 14, No. 3, 1985, pp. 359, 363, XP000645734. Zuffrey et al, 1985 J. Gynecol, Obstet Biol Reprod vol. 14 pp. 359-363. Polsly et al 1988, The Lancet, Jun. 25, p. 1456. Asculai et al, 1978, Antimicrobial Agent & Chemother vol. 13 (4) pp. 686-690. |
| PATENT CLAIMS |
What is claimed is: 1. A method of treating bacterial infection comprising administering an effective amount of cellulose sulfate to a patient in need of such treatment. 2. The method according to claim 1, wherein said bacterial infection is sexually transmitted. 3. The method according to claim 2, wherein said bacterial infection is caused by N.gonorrhea. 4. The method according to claim 1, wherein said cellulose sulfate is maximally sulfated. 5. The method according to claim 1, wherein said cellulose sulfate has a molecular weight of at least 500,000. 6. The method according to claim 1, wherein said cellulose sulfate is administered topically. 7. The method according to claim 1, wherein said cellulose sulfate is administered vaginally. 8. The method according to claim 1, wherein said cellulose sulfate is administered rectally. 9. A method according to claim 1 wherein said cellulose sulfate is administered in admixture with a pharmaceutically acceptable diluent or carrier. 10. A method of treating C. trachomatis infection comprising administering an effective amount of cellulose sulfate to a patient in need of such treatment. 11. The method according to claim 10, wherein said cellulose is maximally sulfated. 12. The method according to claim 10, wherein said cellulose sulfate has a molecular weight of at least 500,000. 13. The method according to claim 10, wherein said cellulose sulfate is administered topically. 14. The method according to claim 10, wherein said cellulose sulfate is administered vaginally. 15. The method according to claim 10, wherein said cellulose sulfate is administered rectally. 16. A method according to claim 10, wherein said cellulose sulfate is administered in admixture with a pharmaceutically acceptable diluent or carrier. 17. A method of preventing bacterial infection comprising administering an effective amount of cellulose sulfate to a patient in need of such treatment. 18. The method according to claim 17, wherein said bacterial infection is sexually transmitted. 19. The method according to claim 18, wherein said bacterial infection is caused by N. gonorrhea. 20. The method according to claim 17, wherein said cellulose sulfate is maximally sulfated. 21. The method according to claim 17, wherein said cellulose sulfate has a molecular weight of at least 500,000. 22. The method according to claim 17, wherein said cellulose sulfate is administered topically. 23. The method according to claim 17, wherein said cellulose sulfate is administered vaginally. 24. The method according to claim 17, wherein said cellulose sulfate is administered rectally. 25. The method of claim 17, wherein said cellulose sulfate is administered in admixture with a pharmaceutically acceptable diluent or carrier. 26. A method of preventing C. trachomatis infection comprising administering an effective amount of cellulose sulfate to a patient in need of such treatment. 27. The method according to claim 26, wherein said cellulose is maximally sulfated. 28. The method according to claim 26, wherein said cellulose sulfate has a molecular weight of at least 500,000. 29. The method according to claim 26, wherein said cellulose sulfate is administered topically. 30. The method according to claim 26, wherein said cellulose sulfate is administered vaginally. 31. The method according to claim 26, wherein said cellulose sulfate is administered rectally. 32. The method according to claim 26, wherein said cellulose sulfate is administered in admixture with a pharmaceutically acceptable diluent or carrier. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
FIELD OF INVENTION The present invention relates to a pharmaceutical composition and method for reducing the risk of conception and transmission of infectious agents during sexual contact. In particular, it relates to a composition comprising cellulose sulfate having contraceptive and anti-microbial and anti-viral properties. BACKGROUND OF THE INVENTION Various contraceptive methods are known for reducing the risk of conception. The condom is a contraceptive method developed for use by men, and is known to reduce the risk of contracting sexually transmitted diseases. Presently, no contraceptive method for use by women is generally known to be effective in reducing the risk of contracting sexually transmitted diseases such as gonorrhea, herpes and more recently, AIDS. Contraceptive methods currently available to and under the control of women include oral contraceptives, diaphragm, intrauterine devices and vaginal foams, creams and suppositories. Each one of the vaginal formulations utilizes a cytotoxic agent, usually the detergent nonoxynol-9, as active ingredient. A vaginal suppository containing sulphuric acid ester of a polysaccharide (SAEP) in combination with nonoxynol-9 is also known. SAEP is a sulfated polysaccharide with a molecular weight of about 175,000. It inhibits hyaluronidase, an enzyme which is believed to have an indispensable role in fertilization. Nonoxynol-9, if used frequently causes irritation to the mucus membrane of the vagina, inactivates the natural protective vaginal flora and can cause lesions through which an infectious agent can invade and cause infection. Sexually transmitted diseases, and in particular, AIDS, caused by the Human Immunodeficiency Virus (HIV), present a serious health risk. It is therefore important to develop a method which avoids the vaginal irritation and the nonspecific inactivation of the naturally occurring vaginal microbes while providing protection against infectious microbes and unwanted pregnancies. Several such agents which are noncytotoxic or of low cytotoxicity are known to inhibit HIV infectivity in vitro, such as select sulfated polysaccharides including dextran sulfate and heparin sulfate. Some sulfated polysaccharides are also known to inhibit Herpes Simplex Virus (HSV), including dextran sulfate of relatively high molecular weight. As well, heparin sulfate has been shown to inhibit HSV infectivity. However, these sulfated polysaccharides shown to have anti-viral activity are not known to have contraceptive properties. Accordingly, there is a need for a contraceptive for use by women, and as an alternative to the use of the condom, which also reduces the risk of contraction of sexually transmitted diseases. SUMMARY OF THE INVENTION According to an aspect of the present invention, there is provided a method for at least one of reducing the risk of infections and treating infections comprising administering an effective amount of cellulose sulfate. There is also provided a method for concomitantly reducing the risk of conception and at least one of reducing the risk of infections and treating infections comprising administering an effective amount of cellulose sulfate. Yet in another aspect of the invention, there is provided a method for reducing the risk of conception comprising administering an effective amount of cellulose sulfate, with a molecular weight of at least 500,000. In another aspect of the invention, there is provided a method for at least one of reducing risk of infections and treating infections comprising administering a pharmaceutical composition said composition comprising an effective amount of cellulose sulfate. There is also provided a method for concomitantly reducing risk of conception and at least one of reducing risk of infections and treating infections comprising administering a pharmaceutical composition said composition comprising an effective amount of cellulose sulfate. In another aspect of the invention, there is provided a method for reducing risk of conception comprising administering a pharmaceutical composition said composition comprising an effective amount of cellulose sulfate, with a molecular weight of at least 500,000. Yet in another aspect of the invention, there is provided a cellulose sulfate for use in at least one of reducing risk of infections and treating infections. There is also provided a cellulose sulfate for use in concomitantly reducing risk of conception and at least one of reducing risk of infections and treating infections. There is provided a cellulose sulfate for use in reducing risk of conception wherein said cellulose sulfate has a molecular weight of at least 500,000. In another aspect of the invention, there is provided a pharmaceutical composition comprising an effective amount of cellulose sulfate for use in at least one of reducing the risk of infections and treating infections. Yet in another aspect of the invention, there is provided a pharmaceutical composition comprising an effective amount of cellulose sulfate for use in concomitantly reducing the risk of conception and at least one of reducing the risk of infections and treating infections. There is also provided a pharmaceutical composition comprising an effective amount of cellulose sulfate for use in reducing the risk of conception wherein said cellulose sulfate has a molecular weight of at least 500,000. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a table showing fertilization outcome after artificial insemination of spermatozoa pretreated with different polysaccharides. FIG. 2 is a table showing the contraceptive efficacy of cellulose sulfate when applied vaginally. FIG. 3 is a table providing the results of cervical mucus penetration experiments. FIG. 4 is a table illustrating the influence of cellulose sulfate on acrosome reaction of human spermatozoa. FIG. 5 is a table illustrating the results of HIV inhibition assay experiments. FIG. 6 is a table providing the results of HSV infectivity experiments. FIG. 7 is a table illustrating the effects of cellulose sulfate on the infectivity of N. gonorrhea. FIG. 8 is a table illustrating the effects of cellulose sulfate on the growth of Lactobacilli. FIG. 9 is a table illustrating anti-chlamydial effects of cellulose sulfate . DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Cellulose sulfate of the present invention has preferably a molecular weight of at least 500,000 and is maximally sulfated (about 17% by weight). It has been found that cellulose sulfate is effective in reducing the risk of conception. Upon vaginal application, or upon pre-treatment of spermatozoa preparations, cellulose sulfate inhibits conception in rabbits. It has also been found that cellulose sulfate is effective in reducing the risk of the infection of human cells growing in vitro by various viruses. It can also be used to inhibit replication of bacteria which are foreign to the normal vaginal flora. Therefore, the present invention provides a contraceptive which also reduces the risk of transmission of infectious agents during sexual contact. The present invention may be administered in an effective amount in suitable dosage forms such as vaginal or rectal gels, foams, creams, suppositories or aerosols. Cellulose sulfate of the present invention may also be administered in combination with a known spermicide such as nonoxynol-9. Suitable carriers, diluents and other non-active ingredients generally known to those skilled in the relevant art may also be combined with cellulose sulfate or cellulose sulfate and nonoxynol-9. Contraceptive Effect: FIG. 1 illustrates the antifertility effect of cellulose sulfate on rabbit spermatozoa at a concentration as low as 0.1%. Pre-treatment of spermatozoa with 1% cellulose sulfate effectively prevented conception in rabbits inseminated with treated spermatozoa. On the other hand, treating spermatozoa with heparin or dextran sulfate showed little or no anti-fertility effect. Referring to FIG. 2, a 5% cellulose sulfate formulation when applied intra-vaginally in rabbits reduces the risk of conception. A comparison of the percentage of fertilized oocytes observed from rabbits treated with 5% cellulose sulfate and 2.2% commercial preparation of nonoxynol-9 indicates that cellulose sulfate of the present invention is as effective or more effective than nonoxynol-9 in reducing the risks of conception when applied intravaginally. Cellulose sulfate, when administered vaginally to rabbits, causes minimal vaginal irritation. When applied in combination with nonoxynol-9, cellulose sulfate of the present invention does not cause an increase in the vaginal irritation of nonoxynol-9. Referring to FIG. 3, experimental results indicate that at 1% concentration, cellulose sulfate impedes penetration by spermatozoa into the cervical mucus membrane in vitro, and to a significantly greater extent than dextran sulfate at the same concentration. With reference to FIG. 4, cellulose sulfate of the present invention also induces acrosomal loss in human spermatozoa, and to a significantly greater extent than heparin or dextran sulfate. Acrosome refers to the anterior organelle of the sperm head necessary for fertilization of an egg by the sperm. From the foregoing results, as described in FIGS. 1-4, it will be apparent to one skilled in the art that cellulose sulfate of the present invention, in effective amounts, can be used to reduce the risk of conception in humans. Anti-viral and Anti-microbial Effects: Referring to FIG. 5, the experimental results indicate that cellulose sulfate at concentration of 0.005% inhibits the binding of HIV to human cells in vitro. FIG. 6 illustrates that at concentration as low as 0.00001%, cellulose sulfate of the present invention inhibits infection of human cells by HSV in vitro. With reference to FIG. 7, the experimental results indicate that, cellulose sulfate at a concentration of at least 0.01% can completely kill the bacteria N. gonorrhea. Moreover, cellulose sulfate of the present invention at 1.8% has no effect on normal vaginal flora, namely Lactobacilli (FIG. 8). FIG. 9 illustrates anti-chlamydial effect of cellulose sulfate. At a concentration of 100 .mu.g/ml, cellulose sulfate inhibits chlamydial infection of HeLa cells by 91%. The forgoing results, as described in FIGS. 5 and 6, indicate that the addition of cellulose sulfate in a concentration as low as 0.00001% is effective in inhibiting the infection of human cells by viral pathogens in vitro. Furthermore, the forgoing results, as described in FIGS. 7-9, indicate that cellulose sulfate can inhibit infection caused by bacteria which are foreign to normal vaginal flora. Accordingly, it will be apparent to one skilled in the art that cellulose sulfate in effective amounts can be used in humans to reduce the risk of or treat viral and microbial infections. In particular, cellulose sulfate of the present invention will be useful as vaginal, rectal and other topical (including dermatological) applications. The forgoing detailed description is for the purposes of illustration only and is not intended as limiting the scope of the invention. Persons skilled in the art will appreciate the nature and the scope of the invention including all of its practical applications. |
| PATENT PHOTOCOPY | Available on request |
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