Nasocerebral administration of peptides for temporomandibular joint pain

肽鼻脑给药治疗颞下颌关节疼痛

• 批准号: 7536367
• 负责人: LAWRENCE R TOLL
• 金额: $ 22.61万
• 依托单位: TRIGEMINA, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7536367
• 关键词: Adverse effects; American; Analgesics; Area; Arthralgia; Behavioral; Blood; Blood - brain barrier anatomy; Blood Circulation; Brain; Bypass; Calcitonin; Cerebrum; Chronic; Clinic; Clinical Trials; Dental; Development; Disease; Drug Kinetics; Effectiveness; Enzymes; Future; Goals; Head; Headache; Health; Healthcare; Heart; Hepatic; Human; Inflammation; Inflammatory; Institutes; Intranasal Administration; Invasive; Laboratories; Literature; Liver; Migraine; Modeling; Morbidity - disease rate; Neuraxis; Nose; Octreotide; Orofacial Pain; Oxytocin; Pain; Pathway interactions; Peptides; Peripheral; Pharmaceutical Preparations; Pharmacodynamics; Phase; Public Health; Radioisotopes; Radiolabeled; Rattus; Research; Rodent Model; Route; Secondary to; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Spinal Cord; Standards of Weights and Measures; Technology; Temporomandibular Joint; Temporomandibular Joint Disorders; Testing; Therapeutic; Tissues; Trigeminal Neuralgia; Trigeminal System; Trigeminal nerve structure; United States; United States Food and Drug Administration; Woman; base; behavior test; blood filter; child bearing; craniofacial; disability; experience; inflammatory pain; men; new technology; novel; novel strategies; orofacial; radiotracer; research clinical testing; targeted delivery; uptake

DESCRIPTION (provided by applicant): This SBIR seeks to further the development of head pain treatment utilizing a newly emerging therapeutic delivery pathway to the trigeminal nerves and central nervous system - the final common pathway of most head and orofacial pain. The delivery pathway involves the intranasal administration of FDA approved analgesic peptides that are then transported directly to trigeminal pain targets, thus allowing for both delivery and targeting that was heretofore not attainable by standard routes due to obstacles of the GI/hepatic filters, blood borne enzymes, and the blood-brain barrier. The health implications of the proposal are its potential to mitigate the poorly treated morbidity of head and orofacial pain involving upwards of 45 million Americans. Using inflammatory temporomandibular joint pain as a model, the company seeks to explore the impact of analgesic peptides when delivered by this intranasal route. Specifically, the proposal seeks to explore the pharmacodynamics and pharmacokinetics of intranasally administered therapeutic peptides in order to demonstrate delivery, targeting and efficacy of the analgesic peptides at their targets in the central nervous system. Utilizing behavioral pain models and radiolabeled uptake and distribution studies, the company will assess the feasibility of these intranasal analgesic peptides for future human clinical testing. PUBLIC HEALTH RELEVANCE Orofacial and head pain represent one of the largest areas of morbidity in health care, involving upwards of 45 million Americans. One of the most prevalent and debilitating of these diseases is temporomandibular joint pain. Few options are available for those who suffer from these disorders, and disability as well as morbidity remains profound. This project explores a novel approach to treating this disorder by intranasally delivering appropriate drugs directly to their targets in the trigeminal nerves, brain and spinal cord, thus significantly increasing effectiveness while simultaneously reducing side effects.

描述(申请人提供)：这项SBIR旨在利用一种新出现的三叉神经和中枢神经系统的治疗途径-大多数头部和口面部疼痛的最终共同途径-进一步开发头痛治疗方法。给药途径涉及FDA批准的止痛肽的鼻腔给药，然后将这些止痛肽直接输送到三叉神经疼痛靶点，从而实现迄今为止由于GI/肝脏过滤器、血传酶和血脑屏障的障碍而无法通过标准路线实现的递送和靶向。该提案对健康的影响是，它有可能缓解超过4500万美国人头部和口腔面部疼痛治疗不当的发病率。该公司以炎症性颞下颌关节疼痛为模型，试图探索止痛肽通过这一鼻腔途径传递时的影响。具体地说，该提案旨在探索鼻内给药治疗多肽的药效学和药代动力学，以证明止痛肽在中枢神经系统靶点的递送、靶向和疗效。利用行为疼痛模型和放射性标记的摄取和分布研究，该公司将评估这些鼻内止痛肽用于未来人类临床测试的可行性。与公共健康相关的面部和头部疼痛是医疗保健中发病率最高的领域之一，涉及超过4500万美国人。这些疾病中最常见和最令人衰弱的是颞下颌关节痛。对于患有这些疾病的人来说，几乎没有什么选择，残疾和发病率仍然很高。该项目探索了一种治疗这种疾病的新方法，即通过鼻腔直接将适当的药物输送到三叉神经、大脑和脊髓的靶点，从而显著提高疗效，同时减少副作用。