二妙丸、马钱子等中药超细粉体的药物动力学研究

【作者】 黄芳；

【导师】 郭立玮；

【作者基本信息】 南京中医药大学 ， 中药学， 2001， 硕士

【摘要】 超细粉体（superfine）技术是近几年来发展起来的一门新技术，它是借助于特殊的机械力、射流能力或物理、化学作用，使普通物质超细化，而不改变其化学组成，但能使物质的表面及界面发生奇特的变化，在使用时可取得普通粉末所无法达到的超常效果。 为了了解超细粉体的理化特性，我们利用扫描电子显微镜、生物显微鉴别、粒径、松密度和比表面积测定等方法对中药普通粉和超细粉体进行了表征。结果发现，中药材经超细粉碎后，颗粒大小均匀，球性度提高，松密度也明显提高，比表面积也大大提高，显微鉴定结果发现，超细粉体中大部分细胞已破碎，这样可使有效成分较好地暴露出来，而不再需要通过以往的透壁释放，从而使药物的生物利用度大大提高。 中药有效成分的溶出速度往往与药物的粉末细度有关，若能改善药物的粉末细度，提高中药有效成分的溶出速率，会大大提高临床疗效。为了探讨药材粉末的细度对丸剂的溶出度的影响，以及丸剂本身粒径的大小对溶出度的影响。本实验采用了分光光度法对自制的各种二妙丸的体外溶出度进行了测定比较。结果表明，超细粉的溶出速率明显快于普通粉，且丸剂粒径降低能提高体外的溶出速率，说明中药的超细粉碎技术可以用于中药丸剂以及微丸剂的制备。为剂改提供了一定的实验依据。 为探讨超细粉体技术对剧毒中药材毒性的影响。比较研究了普通马钱子粉与超细马钱子粉对小鼠的急性毒性实验，所得数据用“改良寇氏法”计算得：普通马钱子粉LD₅₀为223.95mg/kg，超细马钱子粉LD₅₀为198.09mg/kg。 用药物累积法测定普通马钱子粉与超细马钱子粉ig时的表观药动学参数。结果发现两种粉末均符合一室开放型模型，测得T_max分别为1.30h、0.31h；C_max分别为131.2mg·kg^-1、176.5mg·kg^-1；AUC分别为 南京中医药大学2001届硕士研究生毕业论文 1461．7mg·kg‘’h、702．！mg·kg”’·h，CL—0．1054mg’kg”’·卜‘、 0．ZI 08mg·kg＊·卜＊ 为了进一步考察两种粉末在体内的药动学参数，对小鼠单剂量给药 后，以士的宁为指标，用HPLC法测定在不同时间点的血药浓度。结果 发现马钱子粉在体内的吸收符合一室开放性模型，普通粉的主要药动学 参数为：＊－－o．36h，＊饲－二力9叩·m＊，＊＊＊－34＊9叩·m＊·h，＊卜2．883o n＊＠亚”＠h’0超细粉的主要药动学参数为：＊回孤一0．39h，＊－叫94n＊＠m卜， ＊＊＊－ic．56＊g·口匝·h，＊＊－9．4727＊g·亚＊·卜’。 结果表明，马钱子经超细粉碎后可增加其口服后毒性作用。超细粉 体技术既可加快、加大马钱子在体内的吸收，又可增加其在体内的清除 率。能大大提高药物的安全性。更多还原

【Abstract】 The technology of ultra powder turning up and developing in recent years, turns to special mechanical force, stream force, and physical or chemical action to ultra grind general substance. Not changing their chemical components, it changes their surface and interface to some fancy changes. When used, ultra powder can come into supernormal effects exceeding general powder. In order to know about physical and chemical character of ultra powder, we make use of scanning electron microscope, biological microscopic identification, granularity, bulk density, special surface area measurement and so on, to characterize the ultra powder and general powder of Chinese herbs. The results indicate that after Chinese herbs has been ultra ground, the sizes of grains are even, the bulk density increase notably, and the specific surface area are also greatly enhanced. By microscopic identification, most cells of samples are broken, and available composition can be exposed well without transmural release as usual, with greatly enhanced bioavailability. Solution speed of available composition of Chinese herbs, usually relates to the degree of fineness. If degree of fineness improved, and speed raised, clinical curative effects can be greatly enhanced. In order to study the effects of degree of fineness and granularity of pellets itself on solution speed of pellets, the test employ spectrophotometer to measure and compare solution speed of kinds of Ermiao Pellets in vitro. The result indicates that solution speed of ultra powder is quicker than of general powder, and with granularity decreasing the speed increases. So the technology of Chinese herbs ultra grind can be applied in preparation for Chinese herbs pellets and micropellet, which provides a certain basis for innovation of forms of drugs. In order to study the effect of the technology of superfine on toxicity of deadly poisoned Chinese herbs, acute toxicity tests of general and ultra powder Strychnos Nux-vomica power are studied and compared. LD~ of general powder and ultra powder were calculated by modified Kou抯 method, are respectively 223.95mg/kg, 198.05mg/kg. Apparent pharmacokinetics parameters of oral general powder and ultra powder are measured by drug’s accumulated method. The results indicate these two kinds of powders both conform to one compartment open model. T,,. are respectively l.30h, 0.33h; C,,are respectively 131.3mg ? 176.5mg g AUC are respectively 1461.7mg.kg?h, 702.lmg.kg?h ; CL are respectively 0.1054mg kg?Ii? 0.2108mg kg?If? In order to examine the parameters of the two kinds of powers in vivo, after one administration to mice, concentration of blood are measured at different times by HPLC, with the index of strychnine. The results indicate that the absorption of Strychnos Nux-vomica power conforms to one compartment open model. The main pharmacokinetics parameters of general powder :T,,~0.36h, C~=2.49ng mF? AUC34.69mg ml?h, CL CL=2.8830 ng kg?V?The main parameters of ultra powder: T.~0.39h, C=4.94ng?mF? AUC1O.56ng ml?h, CL=9.4727 ng kg~?If? It is concluded that oral toxicity of ultra powder of Strycbnos Nux- vomica is enhanced. The technology of superfine not only speeds up and enhances absorption of Strychos Nux-vomica, but also decreases its accumulation in body. And it can greatly enhance bioavailabiity.更多还原