包合技术概述 ●包合物( inclusion complexes)系指 种药物分子结构被全部或部分包含入 另一种物质的分子腔中而形成独特形式 的络合物 主分子( host molecules, 客分子( guest molecules)
包合技术概述 包合物（inclusion complexes） 系指 一种药物分子结构被全部或部分包含入 另一种物质的分子腔中而形成独特形式 的络合物。 主分子（host molecules） 客分子（guest molecules） 复旦大学药剂学精品课程版权所有
包合物的分类 (1)多分子包合物主分子由氢键相连,按 定方向松散地排列形成晶格洞穴,客分子包 嵌入内,包合材料有尿素、去氧胆酸、硫脲等。 (2)单分子包合物单个主分子空穴包含单 个客分子,包合材料有环糊精类。 (3)大分子包合物由天然或人工大分子化 合物形成的多孔结构,可容纳一定大小的客分 子,如葡聚糖凝胶、纤维素等
包合物的分类 （1）多分子包合物 主分子由氢键相连，按 一定方向松散地排列形成晶格洞穴，客分子包 嵌入内，包合材料有尿素、去氧胆酸、硫脲等。 （2）单分子包合物 单个主分子空穴包含单 个客分子，包合材料有环糊精类。 （3）大分子包合物 由天然或人工大分子化 合物形成的多孔结构，可容纳一定大小的客分 子，如葡聚糖凝胶、纤维素等。 复旦大学药剂学精品课程版权所有
几何形状分类 a b C a:笼状包合物b:管状包合物c:层状包合物
几何形状分类 a b c a: 笼状包合物 b: 管状包合物 c: 层状包合物 复旦大学药剂学精品课程版权所有
包合材料 环糊精 胆酸 ●淀粉 ●纤维素 蛋白质 ●核酸
包合材料 环糊精 胆酸 淀粉 纤维素 蛋白质 核酸 复旦大学药剂学精品课程版权所有
Cyclodextrins and the development of carbohydrate chemistry Year Event l808 Malus develops plane polarized light and observes optical rotation by carbohydrat Acid-hydrolyzed starch is shown to produce sweet crystalline sugar. 1821 Production of dex trins by heating starch is discovered 1838 The sugar from honey. grapes, starch and cellulose is found to be identical and is called glucose by Dumas 1858 The empirical formula of glucose is determined to be C6H12O6 1870 Bayer and Fittig propose that the formula of glucose is HO-CH2-CH(OH-CH(OH)-CH(OH)-CH(OH)-CHO 1888 Glucose is shown to be a six-carbon polyhydroxy aldehyde 1888-1891 Fisher determines the structure of several carbohydrates, including glucose fructose, mannose and arabinose 1891 Villiers publishes his discovery of cellulosine(cyclodextrin) Schardinger publishes his first paper on ae- and B-dextrins (cyclodextrins) 1920-1930 English carbohydrate research group, lead by Norman Haworth, definitely demonstrate the size of carbohydrate rings to be 1924 发现 imary six-membered pyranoses and propose a six-membered hexagon to represent the carbohydrates different grades of methylated cyclodextrins ater both Freudenberg and Meyer-Delius(1938)and Szejtli(1980)prepared Methylation of cyclodextrins first described 1928-1932 The ability of cyclodex trins to form complexes with vanous organic compounds discovered 1935 Freudenberg and Jacobi discover y-cyclodextrin 1938-1952 The chemical structure of a-, B- and y-cyclodextrin elucidated by Freudenberg. Cramer. Borchert, French and Rundle 1948-1951 Formation and structure of cyclodextrin inclusion complexes discovered 1953 研究 The first cyclodex trin patent entitled"Method for preparation of inclusion compounds of physiologically active organic compounds"was issued in Germany to Freudenberg. Cramer and Plieninger 1954 Cramer's book on inclusion complexes(Einschlussverbindungen) published 1957-1965 French describes the existence of large natural cyclodextrins with up to 12 glucose units 1965 Higuchi and Connors publish their article on classification of complexes based on their phase- solubility profiles 1976 The parent a- and B-cyclodex trin officially approved as food additives in Japan 1976 The worlds first pharmaceutical product, prostaglandin E2/B-cyclodextrin( Prostarmon EM sublingual tablets), marketed in 利用 Japan by Ono Pharmaceutical Co 1981 The first International Symposium on Cyclodextrins was organized and held in Budapest by Szejtli. 1983-1985 Brauns and Muller( Europe)and Pitha(USA)file for patents on 2-hydroxypropyl-B-cyclodextrin 1988 Piroxicam/B-cyclodextrin tablets (Brexin )marketed by Chiesi Farmaceutici (Italy) 1990 Stella and Rajewski file for a patent on sulfobutyl ether B-cyclodextrin T Loftsson, D Duch ene/Int J Pharm 329(2007)1-11
发现 研究 利用 Cyclodextrins and the development of carbohydrate chemistry 复旦大学药剂学精品课程版权所有 T. Loftsson, D. Duchˆene / Int J Pharm 329 (2007) 1–11