烟碱龙胆酸盐的制备、表征和缓释性能研究

  目的  为了研发适用于新型烟草制品，具有缓释烟碱效果的烟碱有机酸盐，  方法  在可与烟碱成盐的有机酸中，以pKa < 4.5（优选pKa < 3.5）、含有羧基和羟基、可作为食品添加剂等为原则，结合分子对接模拟（YASARA）软件，筛选出烟碱龙胆酸盐。利用X-射线单晶衍射技术解析其晶体结构。以离体猪口腔颊黏膜为跨膜载体，通过药物透皮扩散体外模拟实验，研究对比了不同pH下烟碱及烟碱龙胆酸盐的跨膜扩散行为。  结果  （1）烟碱龙胆酸盐相对分子质量为316.35，晶体密度为1.342 mg/m3，属单斜晶系，空间群为P2₁。（2）烟碱龙胆酸盐在低pH介质中具有相对偏慢的渗透速率，跨膜扩散慢。（3）在相同pH条件下，表现出初始浓度越高，稳态渗透速率越大，即跨膜扩散越快。  结论  总体而言，烟碱龙胆酸盐具有明显的缓释扩散特性，且在低pH介质中缓释效果更为显著，可用于新型烟草制品开发。 

Preparation,characterization and sustained-release properties of nicotinic gentisate

This study aims to develop sustained-release nicotinic organic acids for new tobacco products.Since organic acids(PKa<4.5(preferably pKa<3.5))containing carboxyl and hydroxyl groups can be used as food additives,YASARA software was used for screening nicotinic gentiate.The structure of nicotine gentisate crystal was characterized with single crystal X-ray diffraction technique.Using buccal mucosa as the transmembrane carrier,the diffusion behaviors of nicotinic acid and nicotinic gentisate at different pH condition were compared through the simulation experiment of drug transdermal diffusion in vitro.The results indicated that the relative molecular weight of the compound was 316.35,the crystal density was 1.342 mg/m^3,the crystal belonged to monoclinic crystal system and the spatial group was P21.Nicotinic gentiate had relatively slow permeation rate and slow transmembrane diffusion in low pH medium.Under the same pH condition,the higher the initial concentration,the higher the steady permeability rate,that is,the faster the transmembrane diffusion.In general,nicotinic gentiate has obvious slow-release diffusion characteristics,and the slow-release effect is more significant in low pH medium,so it can be used in the development of new tobacco products.