Thermostable vaginal probiotic microbicide

耐热阴道益生菌杀菌剂

• 批准号: 8649506
• 负责人: Victor Bronshtein
• 金额: $ 51.71万
• 依托单位: UNIVERSAL STABILIZATION TECHNOLOGIES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8649506
• 关键词: AIDS prevention; Abstinence; Accounting; Acids; Adolescence; Adult; Africa South of the Sahara; Age-Years; Anaerobic Bacteria; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-inflammatory; Antiviral Agents; Bacteria; Bacterial Vaginosis; Biological; Biological Preservation; Cell Culture Techniques; Cells; Cervical; Clinical Research; Coitus; Cold Chains; Contracts; Development; Dosage Forms; Drug Formulations; Environment; Epidemic; Epithelium; Female; Feminization; Film; Freeze Drying; Goals; HIV; Individual; Infection; Intestines; Intravaginal Administration; Lactobacillus; Legal patent; Life; Local Microbicides; Mechanics; Methods; Modeling; National Institute of Allergy and Infectious Disease; Phase; Polymers; Powder dose form; Preparation; Prevention; Prevention strategy; Primates; Probability; Probiotics; Procedures; Production; Property; Recovery; Research Infrastructure; Risk; Sexually Transmitted Diseases; Suppositories; System; Tablets; Techniques; Technology; Temperature; Therapeutic; Time; Universities; Vagina; Washington; Water; Woman; aged; base; cold temperature; condoms; girls; improved; innovation; man; microbicide; particle; preference; prototype; public health relevance; safety testing; statistics; sugar; transmission process; user-friendly; vaginal microbicide; vaporization

DESCRIPTION (provided by applicant): Recently revised statistics show the number of individuals living with HIV at over 33 million worldwide, with 68% being in sub-Saharan Africa. Current HIV prevention methods, such as condom use, monogamy and abstinence, are not always feasible. The need for improved HIV preventative technologies remains urgent. The development of topical microbicides represents a new and exciting field in the prevention of sexually transmitted diseases. Of these, application of live probiotic bacterial microbicides (PBM) represents a promising preventative method. Our ultimate goal is to develop potent optimized multistrain thermostable and easily deliverable probiotic vaginal topical microbicides. To achieve this goal we will stabilize vaginal probiotics for long-term storage at high ambient temperatures and short term survival at temperatures required for quick dissolve film manufacturing (60¿C and above). The cornerstones of this proposal are: 1) Preservation by Vaporization" (PBV) - an innovative, patent pending method of dry-stabilizing probiotics bacteria and other fragile biologicals at high ambient temperatures, and 2) Quick-dissolve thin film technology that is being optimized to deliver conventional vaginal microbicides. The strategy can be described briefly as, to occupy the vaginal epithelium and provide a long lasting protective environment against HIV, BV, and STI acquisition small (10-50 ¿m) glassy sugar particles containing PBV vaginal probiotic bacteria will be formulated into thin films which utilize a water soluble polymer base. Thin films offer a unique delivery platform which has a number of advantages over other dosage forms. In a recent study comparing women's preference between films, tablets and ovules, the film dosage form was shown to have greatest acceptability among women studied. We believe that women will prefer using a vaginal film over other potential methods of probiotic microbicide delivery especially if a long-acting effect of the bacteria colonizing vaginal epithelium allows for less frequent use. Biologic properties of PBM after long-term storage at ambient temperatures will be characterized using cell culture models of vaginal and cervical epithelium.

描述(由申请人提供)：最近修订的统计数据显示，全球艾滋病毒携带者人数超过3300万，其中68%在撒哈拉以南非洲。目前的艾滋病毒预防方法，如使用避孕套、一夫一妻制和禁欲，并不总是可行的。仍然迫切需要改进艾滋病毒预防技术。局部杀微生物剂的发展代表了防止性传播疾病的一个新的令人兴奋的领域。其中，应用活的益生菌杀菌剂(PBM)是一种很有前途的预防方法。我们的最终目标是开发高效、优化、多菌种、耐热性和易于释放的益生菌阴道局部杀菌剂。为了实现这一目标，我们将稳定阴道益生菌，以便在环境温度较高的情况下长期储存，并在快速溶解薄膜制造所需的温度(60℃及以上)下短期存活。这项建议的基石是：1)蒸发保存“(PBV)--一种在高温下干燥稳定益生菌和其他脆弱生物制品的创新、正在申请专利的方法，以及2)正在优化的快速溶解薄膜技术，以提供传统的阴道杀菌剂。该策略可以简单地描述为，占据阴道上皮并提供针对HIV、BV和STI的持久保护环境。含有PBV阴道益生菌的小(10-50？m)玻璃糖颗粒将被配制成利用水溶性聚合物碱的薄膜。薄膜提供了一个独特的给药平台，与其他剂型相比具有许多优势。在最近的一项研究中，比较了女性对电影、片剂和胚珠的偏好，结果表明，在被研究的女性中，薄膜剂型的接受度最高。我们认为，与其他可能的益生菌杀菌剂输送方法相比，女性更喜欢使用阴道膜，特别是如果定植于阴道上皮的细菌的长效作用允许较少使用的话。PBM在常温下长期储存后，将使用阴道和宫颈上皮细胞培养模型来表征其生物学特性。