VAGINAL BIOPROTECTION BY CONTROLLED ACIDIFICATION

BIOTEK建议研究新的生物保护制剂，通过将阴道酸化与壬苯醇醚-9的浓度相结合，保护精子和性病病原体，比目前阴道避孕药中使用的浓度低得多，刺激性可能更小。这样的杀精-杀菌组合应该得到广泛的接受。第一阶段将研究阴道凝胶，旨在保持pH值在2和3之间，并含有几毫克/毫升的壬苯醇醚-9。使用的酸化剂包括难溶的强酸和强酸性缓冲剂。BIOTEK使用人类精液和FDA避孕产品测试指南进行的广泛的初步研究表明，pH值为2至3可能不会使精子丧失活性，但在这种酸性制剂中加入1至2 mg/ml的壬苯醇醚-9可产生完全杀精子的产品。I期体外研究将包括粘度、粘性稳定性、平衡pH值和缓冲能力;体内研究将包括家兔阴道刺激和绵羊阴道pH值。微生物学研究将用于测试对乳酸杆菌、人类精子和重要性病病原体的影响。第二阶段将表征GMP凝胶，制备并提交IND，并进行FDA批准的人体临床研究。拟议的商业应用：最近的一项调查显示，由于不使用避孕套的伴侣会带来怀孕和疾病的风险，妇女会欢迎一种不引人注目的提供单方面保护的阴道产品。具有杀菌和杀精子特性的凝胶应该进入阴道避孕药的现有市场，并促进用于其他适应症的阴道凝胶的开发。

BIOTEK proposes to investigate new bioprotective formulations which protect against sperm and STD pathogens by combining vaginal acidification with concentrations of nonoxynol-9 much lower, and potentially less irritating, than those used in current vaginal contraceptives. Such a combined spermicide-germicide should achieve widespread acceptance. Phase I will study vaginal gels designed to keep the pH between 2 and 3, and containing a few mg/ml of nonoxynol-9. Acidifying agents to be used include a strong sparingly soluble acid and a powerful acidic buffer. Extensive preliminary work by BIOTEK, using human semen and the FDA Testing Guidelines for Contraceptive Products, has shown that pH values of 2 to 3 may not disable sperm, but that introducing as little as l to 2 mg/ml of nonoxynol-9 to such an acidic preparation produces a fully spermicidal product. Phase I in vitro studies will include viscosity, viscous stability, equilibrium pH, and buffering capacity; in vivo studies will include vaginal irritation in rabbits and vaginal pH in sheep. Microbiological studies will be employed to test the effects on lactobacilli, human sperm, and important STD pathogens. Phase II will characterize a GMP gel, prepare and submit an IND, and proceed to an FDA-approved human clinical study. PROPOSED COMMERCIAL APPLICATIONS: A recent survey showed that, because of the risk of pregnancy and disease posed by partners who do not use condoms, women would welcome an unobtrusive vaginal product offering unilateral protection. A gel with both germicidal and spermicidal properties should tap into the existing market for vaginal contraceptives and facilitate development of vaginal gels for other indications.