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: 8054563
• 负责人: LAWRENCE R TOLL
• 金额: $ 6.12万
• 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/8054563
• 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; Development; Disease; Drug Kinetics; Effectiveness; Enzymes; FDA approved; Future; Goals; Head; Headache; Health; Healthcare; Heart; Hepatic; Human; Inflammation; Inflammatory; Intranasal Administration; Laboratories; Literature; Liver; Migraine; Modeling; Morbidity - disease rate; National Institute of Dental and Craniofacial Research; Neuraxis; Nose; Octreotide; Orofacial Pain; Oxytocin; Pain; Pathway interactions; Peptides; Peripheral; Pharmaceutical Preparations; Pharmacodynamics; Phase; Radioisotopes; Radiolabeled; Rattus; Research; Rodent Model; Route; Secondary to; Small Business Innovation Research Grant; Spinal Cord; Technology; Temporomandibular Joint; Temporomandibular Joint Disorders; Therapeutic; Tissues; Trigeminal Neuralgia; Trigeminal System; Trigeminal nerve structure; United States; Woman; base; behavior test; blood filter; child bearing; disability; efficacy testing; experience; inflammatory pain; men; new technology; novel; novel strategies; orofacial; public health relevance; 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（由申请人提供）：本 SBIR 旨在利用新出现的三叉神经和中枢神经系统治疗传递途径（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。递送途径涉及鼻内施用 FDA 批准的镇痛肽，然后将其直接转运至三叉神经疼痛靶点，从而实现迄今为止由于胃肠道/肝过滤器、血源性酶和血脑屏障的障碍而通过标准途径无法实现的递送和靶向。该提案对健康的影响在于，它有可能减轻 4500 万美国人因治疗不当而导致的头部和口面部疼痛的发病率。该公司以炎症性颞下颌关节疼痛为模型，试图探索通过这种鼻内途径输送镇痛肽的影响。具体来说，该提案旨在探索鼻内给药的治疗肽的药效学和药代动力学，以证明镇痛肽在中枢神经系统中的靶标的递送、靶向和功效。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镇痛肽用于未来人体临床测试的可行性。公共卫生相关性 口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。这些疾病中最普遍和最使人衰弱的疾病之一是颞下颌关节疼痛。患有这些疾病的人几乎没有什么选择，而且残疾和发病率仍然很严重。该项目探索了一种治疗这种疾病的新方法，通过鼻内将适当的药物直接输送到三叉神经、大脑和脊髓的靶点，从而显着提高疗效，同时减少副作用。