【作者】 刘红宁；

【导师】 罗杰英；

【作者基本信息】 湖南中医药大学 ， 中医内科学， 2006， 博士

【摘要】 首次系统开展了彭泽贝母的化学成分、药效物质基础及主要活性单体作用机理的研究、彭泽贝母采收时间与干燥工艺的研究,制备了以彭泽贝母为主药的“贝杏甘”双层含片。为阐明彭泽贝母的药效物质基础,合理利用药用资源,完整地评价彭泽贝母的药材质量奠定了科学基础,为彭泽贝母的开发利用、新药创制提供了依据。对彭泽贝母活性部位的化学成分进行了系统分离,从中获得26个化合物,鉴定了其中的20个成分,包括10个生物碱类化合物,7个二萜类化合物,3个其他类化合物。其中7个是新化合物,17个为首次从该植物中获得。基本阐明了彭泽贝母的物质基础。对有效部位(总生物碱、总皂苷等)进行了祛痰止咳作用的评价,开展了浙贝甲素、贝母辛舒张支气管平滑肌的作用机理研究。表明总提取物、总生物碱、总皂苷均具有止咳、平喘、祛痰作用;首次阐明了贝母辛松弛气管平滑肌的作用是通过作用于气管平滑肌M受体,从而抑制乙酰胆碱引起的平滑肌收缩。为彭泽贝母的质量标准中活性指标确定提供了依据。建立了同时测定彭泽贝母中浙贝甲素、浙贝乙素含量的方法(HPLC-ELSD);采用指纹图谱的方法,对不同生长年限对彭泽贝母中活性成分的积累进行了初步研究,表明彭泽贝母的最佳采收时间为4年生较好。探索了彭泽贝母的干燥方法,为彭泽贝母产地初加工方法的确定奠定了基础。以“贝母丸”处方为模型复方,将其剂型改进为口含片,重点研究了不同矫味剂,不同工艺对贝母等苦味中药的矫味作用,表明采用矫味剂和甜味剂适当配比,制备双层含片的工艺,能够较好地改善口感,掩盖苦味在口腔中长久滞留等问题,为苦味中药的口含片制备提供了示范。更多还原

【Abstract】 Objective: To study some key factors on developing Fritillaria monantha Migo ,such as effective components,collecting time& dry process of crude bulbs, quality control method and pharmaceutiacl way of covering bitter taste.Methods: （1）The chemical constituents of Fritillaria monatha Migo have been studied systematically by chromatography method and spectroscopy analysis;（2） In vitro trachea strips model has been established and applied to study the mechanism of some active compounds of Fritillaria monatha Migo; （3） The method of HPLC-ELSD has been developed to determinate peimisine and peminine simultaneously; Initial studies have been conducted on collecting time of Fritillaria monantha Migo bulb by HPLC-ELSD fingerprint technique. （4）Different sweeters and preparetion process has been applied to make buccal tablet.Results:（1） twenty-six compounds are seperated from Fritillaria monantha Migo bulbs, among them twenty compounds having been dentified. They are determined as peimisine（FA₁）,peminine（FA₂）,peimine（FA₃）,pengbeisineA（FA₄）,pengbeisineB（FA₅）,pengbei mineA（FA₆）,pengbeimineB（FA₇）,pengbeimineC（FA₈）,ent-kauran-15-en-17-ol（FD₁）,campesterol（FD₂）,stearicacid（FD₃）,ent-kauran-16β, 17-diol（FD₄）,ent-16,17-epoxy-kauran-3β-ol（FD₅）,daucosterol（FD₆）,pengbeimine（FD₇）,isoverticine(FD₁₀),fritillaziebinol(FD₁₂),ent-kaurane-3β, 16β, 17-triol·H₂O (FD₁₃),ent-16α-methoxy-kauran-17-ol (FD₁₄)、ent-kauran-15-en-6α,17-dio (FD₇).The compounds pengbeisine A, pengbeisine B, pengbeimine A, pengbeimine B, pengbeimine C, pengbeimine D, and ent-16,17-epoxy-kauran-3β-ol are seven new compounds. （2）The results of pharmacological experiments show that the EtOH extracts can control the rat’s cough from ammonia, and can increase the quantity of FenHong in the rat’s trachea. In the mean while, the CHC1₃Ⅱextracts can control the rat’s cough from ammonia, and the BuOH extracts can increase the quantity of FenHong in the rat’s trachea. Pharmacological studies further reveal that peimisine and peminine can release the tracheal smooth muscle contraction caused by Ach through reaction on M receptor. This result demonstrates that peminine can be selected as index to control the quality of crude Fritillaria monantha Migo bulb and Chinese patent medicine which contain Fritillaria monantha Migo bulb.（3） The best collecing time of Fritillaria monantha Migo bulb is of 4. Dry process of Fritillaria monantha Migo bulb also been researched ,reletively better dry conditions are established.（4）Beixinggan double-deck buccal tablet has been prepared.Conclusions: Fritillaria monatha Migo bulbs contain chemical components which can relieve cough and antiasthma, Peimisine and Peimine are two main active ingredients. Peimine can be choosed as quality control ingredient and can be assaied by HPLC-ELSD. It is demenstrated that taking double-deck buccal tablet process can effectively cover bitter taste of Chinese patent medicine.The thesis get the financial supports from the National Natural Science Foundation of China（30160097）.更多还原