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）：女性性唤醒疾病（FSAD），通常被描述为女性性功能障碍（FSD）的疾病之一在老年妇女中很常见，可能是老年人口中降低生活质量的重要原因。 FSAD被定义为持续或无力实现或保持足够的性兴奋，从而造成个人困扰。唤醒的疾病通常包括阴道润滑不足，阴蒂降低和唇唇感，阴蒂和唇部发挥作用和/或缺乏阴道平滑肌松弛。通常，诸如先前的骨盆创伤，骨盆手术，阴道或阴蒂血液流动（例如，由于心血管疾病引起的）或某些药物的副作用（例如选择性5-羟色胺再摄取抑制剂）等生理原因，在这种情况的病因学中起重要作用。血管活性肠肽是女性生殖器中具有平滑肌松弛剂和其他多效性功能的重要神经递质。已经表明，它可以增加雌性生殖器的血流并诱导阴道润滑。这些功能使FSAD成为可能的治疗方法。但是，鉴于系统地，它可能导致动脉血压下降。自由肽的安全性问题和药代动力学概况要求它以一种克服这些问题的方式制定，然后才能用作人类治疗。 Pharmain Corp.成功地进行了初步实验，并开发了可注射的，基于聚合物的VIP配方，称为PGC-VIP。在炎症性疾病模型中，该公式已被证明是安全且具有生物学活性的。此外，它显示出体内半衰期的大量增加。该应用建议测试局部PGC-VIP公式，以在FSAD的大鼠模型中测试该公式的固定稳定性。在第一阶段 在AIM 1中，将合成该项目的足够材料来进行疗效实验。 AIM 2将测试配方在FSAD大鼠模型中的功效，在AIM 3中，我们将进行稳定研究。