VAGINAL BIOPROTECTION BY CONTROLLED ACIDIFICATION

Biotek建议研究新的生物保护配方，通过将阴道酸化与非氧合酚-9的浓度结合在一起来保护精子和性病病原体，这些浓度比目前阴道避孕药中使用的浓度低得多，而且刺激性更小。这种杀精剂和杀菌剂的组合应该会得到广泛的接受。第一阶段将研究阴道凝胶，旨在将PH值保持在2到3之间，并含有几毫克/毫升的非氧合酚-9。使用的酸化剂包括一种难溶的强酸和一种强酸缓冲剂。Biotek使用人类精液和美国食品和药物管理局的避孕产品测试指南进行了广泛的初步工作，结果表明，pH值为2至3可能不会使精子失效，但在这种酸性制剂中加入低至2毫克/毫升的非氧合酚-9可以产生完全杀精的产品。第一阶段的体外研究将包括粘度、粘性稳定性、平衡pH值和缓冲能力；体内研究将包括对兔的阴道刺激性和对绵羊的阴道pH值。微生物学研究将被用来测试对乳杆菌、人类精子和重要的性病病原体的影响。第二阶段将确定GMP凝胶的特征，准备并提交IND，并进行FDA批准的人类临床研究。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，女性会欢迎一种提供单边保护的不引人注目的阴道产品。一种兼具杀菌和杀精作用的凝胶应能打入现有的阴道避孕药市场，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.