Vasoactive Intestinal Peptide for the treatment of Female Sexual Arousal Disorder

血管活性肠肽治疗女性性唤起障碍

• 批准号: 8638840
• 负责人: Elijah M. Bolotin
• 金额: $ 22.5万
• 依托单位: PHARMAIN CORPORATION
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-15 至 2015-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8638840
• 关键词: Adverse effects; Age; Aging; Agonist; Animal Model; Arousal; Blood Pressure; Blood flow; Cardiovascular system; Clitoris; Development; Disease; Distress; Dopaminergic Agents; Dose; Drops; Drug Formulations; Drug Kinetics; Ensure; Esthesia; Etiology; Exhibits; Female; Female genitalia; Flushing; Gel; Half-Life; Hormones; Hour; Human; Inflammatory; Injectable; Injection of therapeutic agent; Intravaginal Administration; Lead; Length; Lubrication; Marketing; Modeling; Mus; Muscle relaxants; Muscle relaxation phase; Neprilysin; Nerve; Nerve Endings; Neuropeptides; Neurotransmitters; New Zealand; Operative Surgical Procedures; Oryctolagus cuniculus; Pelvis; Peptide Hydrolases; Peptides; Pharmaceutical Preparations; Phase; Physiological; Play; Polymers; Population; Postmenopause; Prevalence; Production; Property; Quality of life; Rattus; Role; Safety; Selective Serotonin Reuptake Inhibitor; Serum; Sexual Arousal; Sexual Arousal Disorder; Sexual Dysfunction; Smooth Muscle; Societies; Symptoms; Synthetic Prostaglandins; Technology; Temperature; Testing; Therapeutic; Topical application; Toxic effect; Trauma; Vagina; Vasoactive Intestinal Peptide; Vasodilation; Woman; aging population; alpha-adrenergic receptor; base; copolymer; efficacy testing; glucagon-like peptide 1; in vivo; inhibitor/antagonist; melanocortin receptor; nanocarrier; older women; phosphoric diester hydrolase; pressure; psychologic; public health relevance; research study; stability testing; success

DESCRIPTION (provided by applicant): Female sexual arousal disorder (FSAD), one of the conditions commonly described as Female sexual dysfunction (FSD) is common among older women and can be a significant reason for decreased quality of life in the aging population. FSAD is defined as the persistent or recurring inability to attain or maintain sufficient sexual excitement, causing personal distress. Disorders of arousal often include insufficient vaginal lubrication, decreased clitoral and labial sensation, decreased clitoral and labial engorgement and/or lack of vaginal smooth muscle relaxation. Often, physiological causes like previous pelvic trauma, pelvic surgery, decreased vaginal or clitoral blood flow (e.g. due to cardiovascular problems) or the side effects of certain medications, for example selective serotonin reuptake inhibitors, play an important role in the etiology of the condition. Vasoactive intestinal peptide s an important neurotransmitter in the female genitalia with smooth muscle relaxant and other pleiotropic functions. It has been shown that it can increase blood flow in female genitalia and also induce vaginal lubrication. These features make it a possible treatment for FSAD. However, given systemically it can lead to a dangerous drop in arterial blood pressure. Theses safety concerns and the pharmacokinetics profile of the free peptide require it being formulated in a way to overcome these problems before it can be used as human therapeutic. PharmaIN Corp. has succeeded in preliminary experiments with the development of an injectable, polymer-based VIP formulation called PGC-VIP. This formulation has been shown to be safe and biologically active in a model of an inflammatory disease. Additionally, it exhibits a massive increase in in-vivo half-life. This application proposes to test a topical PGC-VIP formulation for efficacy in a rat model of FSAD and to test shelf-stability of this formulation. During the Phase I of the project sufficient material to conduct the efficacy experiment as described in aim 2 of the proposal will be synthesized in aim 1. Before the start of aim 2, this material will be submitted t QC to ensure that it is of identical composition and properties as the PGC-VIP formulation used in the preliminary experiments. Aim 2 will test the efficacy of the formulation in a rat model of FSAD and in aim 3 we will conduct a stability study.

描述(由申请人提供)：女性性唤起障碍(FSAD)，通常被描述为女性性功能障碍(FSD)的条件之一，在老年女性中很常见，可能是老年人口生活质量下降的重要原因。FSAD被定义为持续或反复无法获得或维持足够的性兴奋，导致个人痛苦。唤醒障碍通常包括阴道润滑不足，阴蒂和嘴唇感觉减弱，阴蒂和嘴唇充血减少和/或阴道平滑肌松弛不足。通常，生理原因，如既往骨盆创伤、骨盆手术、阴道或阴蒂血流量减少(如心血管问题)或某些药物的副作用，如选择性5-羟色胺再摄取抑制剂，在该病的病因中起着重要作用。血管活性肠肽S是女性生殖器中重要的神经递质，具有平滑、松弛等多种功能。已经证明，它可以增加女性生殖器的血流量，也可以诱导阴道润滑。这些特点使其成为治疗FSAD的一种可能。然而，从系统角度来看，它可能会导致动脉血压危险的下降。这些安全问题和游离肽的药代动力学特征要求在将其用于人类治疗之前，以一种克服这些问题的方式来配制它。Pharmain公司开发了一种名为PGC-VIP的可注射聚合物VIP配方，并在初步试验中取得成功。在炎症性疾病的模型中，这种制剂已被证明是安全的和生物活性的。此外，它还显示出体内半衰期的大幅增加。本申请建议测试外用PGC-VIP配方在FSAD大鼠模型中的有效性，并测试该配方的货架稳定性。在第一阶段期间 在该项目中，将在目标1中合成足够的材料来进行提案目标2所述的功效实验。在目标2开始之前，该材料将提交给质量控制部门，以确保其成分和性能与初步实验中使用的PGC-VIP配方相同。目标2将在FSAD大鼠模型上测试该制剂的疗效，在目标3中，我们将进行稳定性研究。