Intravaginal treatment of vaginal infections with buffered metronidazole compositions
Patent 5840744 Issued on November 24, 1998. Estimated Expiration Date: July 15, 2016. Estimated Expiration Date is calculated based on simple USPTO term provisions. It does not account for terminal disclaimers, term adjustments, failure to pay maintenance fees, or other factors which might affect the term of a patent.
A non-flowing composition and method for treatment of bacterial vaginosis are disclosed. An afflicted vagina is treated with a therapeutically effective but relatively low dose of metronidazole in a composition that includes a buffer system maintaining the composition at a pH value in the range of about 3.75 to about 4.25. The composition can also be used for prophylactic purposes.
Other References
Amsel R. et al. "Comparison of metronidazole, ampicillin, and amoxicillin for treatment of bacterial vaginosis (nonspecific vaginitis): possible explanation for the greater efficacy of metronidazole." In proceedings of the First U.S. Metronidazole Conference: pp. 225-242. Edited by Finegold S.M, George W.L., and Rolfe R.D. N.Y.: Biomedical Information Corporation (1982)
Balsdon M.J. et al., "Corynebacterium vaginale and vaginitis: a controlled trial of treatment." Lancet 1:501 (1980)
Barlett J.G. et al. Bacterial flora of the vagina: quantitative study. Rev. Infect. Dis. (Suppl 1) 6:S67-S72 (1984)
Bistoletti P. et al. "Comparison of oral and vaginal metronidazole therapy for nonspecific bacterial vaginosis." Gyencol. Obstet. Invest., 21:144-149 (1986)
Brenner W.E. et al., "Metronidazole-containing vaginal sponges for the treatment of bacterial vaginosis," Adv. Contracept. 2:363-369 (1986)
Charles D. et al. Antimicrobial treatment of infectious vaginopathies. The Female Patient 10:25-42 (1985)
Davis B. et al. Analysis of metronidazole penetration into vaginal fluid by reversed-phased high-performance liquid chromatography. Am. J. Obstet. Gynec. 149:802-803 (1984)
Edelman D.A. et al., "Treatment of bacterial vaginosis with intravaginal sponges containing metronidazole," J. Reprod. Medicine 34(5):341-344 (1989)
Eschenbach D.A. et al. "A dose-duration study of metronidazole for the treatment of nonspecific vaginosis." Scand. J. Infect. Dis. (Suppl) 40:73-80 (1983)
Eschenbach D.A. et al. Diagnosis and clinical manifestations of bacterial vaginosis. Am. J. of Obstet. & Gynecol. 158:819-829 (1988)
Eschenbach D.A. et al. Prevalence of Hydrogen Peroxide-Producing Lactobacillus Species in Normal Women and Women Bacterial Vaginosis. J. Clin. Microbiology 27(2):251-256 (1989)
Fouts A.C. et al. Trichomonas vaginalis: reevaluation of its clinical presentation and laboratory diagnosis. J. Infect. Diseases 141:137-143 (1980)
Hager W.D. et al. Metronidazole for vaginal trichomoniasis. Seven-day vs Single-dose regimens. J.A.M.A. 244:1219-1220 (1980)
Hagstrom B. et al. "Comparison of two different regimens of metronidazole in the treatment of nonspecific vaginitis." Scand. J. Infect. Dis. (Suppl) 40:95-96 (1983)
Hill, L.V.H. et al. Vaginitis: current microbiological & clinical concepts. Can. Med. Assoc. J. 134:321-331 (1986)
Hillier S.L. et al., "Efficacy of Metronidazole-Containing Sponges for the Treatment of Bacterial Vaginosis." ICAAC Abstract No. 1056, p. 281 (1989)
Larsen B. et al. Vaginal microbial flora: composition and influence of host physiology. Ann. Intern. Med. 96:926-930 (1982)
Malouf M. et al., Dube J-L. "Treatment of Hemophilus vaginalis vaginitis." Obstet. Gynecol. 57(6):711-714 (1981)
Mardh P. et al. In vitro interactions between Lactobacilli and other microorganisms occurring in the vaginal flora. Scand. J. Infect. Dis, (Suppl) 40:47-51 (1983)
McCue J.D. Evaluation and management of vaginitis. Arch. Intern. Med. 149:565-568 (1989)
Mollgaard B. et al. Vehicle effect on topical drug delivery. II. Concurrent skin transport of drugs and vehicle components. Acta Pharm. Succ. 20: 443-450 (1983)
Moorman C.N. et al. Impact of site release of vaginal pH buffer cream on introital colonization by gram-negative bacilli. J. Urology 147: 1576-1578 (1992)
Nielsen P.G. Treatment of rosacea with 1% metronidazole cream. A double-blind study. Br. J. Dermatol. 108: 327-332 (1983)
Nielsen P.G. A double-blind study of 1% metronidazole cream versus systemic oxytretracycline therapy for rosacea. Br. J. Dermatol. 109: 63-65 (1983)
Peeters M. et al. Adhesion of Garnerella vaginalis to vaginal epithelial cells: variables affecting adhesion and inhibition by metronidazole. Genitourin Med. 61:391-395 (1985)
Pheifer T.A. et al. "Nonspecific vaginitis: role of Haemophilus vaginalis and treatment with metronidazole." New Eng. J. Med. 298(26):1429-1434 (1978)
Purdon A. et al. An evaluation of single dose metronidazole treatment for Gardnerella vaginalis vaginitis. Obstet. Gynecol. 64:271 (1984)
Rein M.F. Vulvovaginitis and cervicitis, in Mandell G. L., Douglas R.G., Bennett T.E. (eds). Principles and Practice of Infectious Diseases, Edition 2, New York, John Wiley & Sons Inc., pp. 729-738 (1984)
Robie M.O. et al. Metronidazole use in obstretrics and gynecology: A review. Am. J. Obstet. Gynecol. 145: 865-879 (1983)
Skavin A. et al. Vaginal Lactobacilli inhibiting growth of Gardnerella vaginalis, mobiluncus and other bacterial species cultured from vaginal content of women with bacterial vaginosis. Acta. Path. Microbiol. Immunol. Scand., Section B, 94:399-403 (1986)
Staerfelt F. et al. A survey of genital infections in patients attending a clinic for sexually transmitted diseases. Scand. J Infect. Dis. 40:53-57 (1983)
Swedberg J. et al. "Comparison of single dose versus one week course of metronidazole for symptomatic bacterial vaginosis." JAMA, 258(8):1046-1049 (1985)
Totten P.A. et al. Selective differential human blood filagen media for isolation of Gardnerella vaginalis. J. Clin. Microbiol. 15:141-147 (1982)