Onoue Satomi, Yamada Shizuo, Yajima Takehiko
Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba 274-8510, Japan.
Peptides. 2007 Sep;28(9):1640-50. doi: 10.1016/j.peptides.2007.04.009. Epub 2007 Apr 22.
Vasoactive intestinal peptide (VIP) is one of the major peptide transmitters in the central and peripheral nervous systems, being involved in a wide range of biological functions. In an airway system where VIP-immunoreactive nerve fibers are present, VIP acts as neurotransmitter or neuromodulator of the inhibitory non-adrenergic and non-cholinergic airway nervous system and influences many aspects of pulmonary biology. A clinical application of VIP has been believed to offer potential benefits in the treatment of chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), however, its clinical application has been limited in the past for a number of reasons, including its extremely short plasma half-life after intravenous administration and difficulty in administration routes. The development of long-acting VIP analogues, in combination with appropriate drug delivery systems, may provide clinically useful agents for the treatment of asthma/COPD. In this review, development of efficacious VIP derivatives, drug delivery systems designed for VIPs and the potential application for asthma/COPD are discussed. We also include original data from our chemical modification experiments and formulation studies, which led to successful development of [R(15, 20, 21), L(17)]-VIP-GRR (IK312532), a potent VIP analogue, and a VIPs-based dry powder inhaler system.
血管活性肠肽（VIP）是中枢和外周神经系统中的主要肽类递质之一，参与广泛的生物学功能。在存在VIP免疫反应性神经纤维的气道系统中，VIP作为抑制性非肾上腺素能和非胆碱能气道神经系统的神经递质或神经调节剂，影响肺生物学的许多方面。人们认为VIP的临床应用在治疗慢性炎症性肺病如哮喘和慢性阻塞性肺疾病（COPD）方面具有潜在益处，然而，由于多种原因，其临床应用在过去受到限制，包括静脉给药后血浆半衰期极短以及给药途径困难。长效VIP类似物的开发，结合适当的药物递送系统，可能为哮喘/COPD的治疗提供临床上有用的药物。在这篇综述中，讨论了有效的VIP衍生物的开发、为VIP设计的药物递送系统以及对哮喘/COPD的潜在应用。我们还包括来自我们化学修饰实验和制剂研究的原始数据，这些研究成功开发了一种有效的VIP类似物[R(15, 20, 21), L(17)]-VIP-GRR（IK312532）和一种基于VIP的干粉吸入器系统。
