【作者】 姚新成；

【导师】 陈文；

【作者基本信息】 石河子大学 ， 药理学， 2005， 硕士

【摘要】 本实验通过利用新疆特色植物药资源甘草的水解提取产物甘草次酸,以及具有抗过敏功效的经典药物盐酸苯海拉明为原料,在实验室制备新的复合物:甘草次酸-苯海拉明复盐。目的:使甘草次酸和苯海拉明复合后改善甘草次酸的溶解性、吸收性或使两种药物药理作用协同;同时将该药物制成软膏剂,研究其初步抗炎的药效学功效。本实验通过以下两方面试验进行: 1 制备工艺和产物的鉴定:通过对制备产物的物理性质(外观、熔点、不同溶剂中的溶解度、晶形、稳定性试验)、结构鉴定(TLC、UV、IR、X-衍射、元素分析、DSC)、杂质检查(TLC、HPLC)、含量测定(滴定法、HPLC法)等试验结果综合分析,结果如下:复合物外观:白色、类晶型粉末;晶形:类雪状、粉末状晶体;熔点:m.p.=87～95℃;溶解度:在甲醇、乙醇、丙酮、氯仿中易溶,在水中微溶。常温下20%乙醇中溶解度为80.2μg/ml;50%乙醇中为2059μg/ml;10%甘油中为316μg/ml。结构鉴定:TLC、UV、IR、X-衍射数据、元素分析及DSC对照图谱均说明制各产物结构与原料药不同。杂质检查:TLC杂质检查杂质限量<1.0%;HPLC杂质限量<1.0%。含量测定:滴定法测定产物含量为:102.3%;HPLC法测定含量为:102.7%。结论:制备得到了甘草次酸-苯海拉明复盐。 2 药物软膏剂的初步研究:根据实验方案制备含药软膏并对软膏质量评价如下:外观性状:白色细腻膏状半固体,涂布于皮肤上细腻、无颗粒感;软膏的黏度:9100 mPa.s;稳定性实验:离心法和耐热、耐寒试验均未发生油水分离或分层情况,制剂较稳定;皮肤、结膜刺激性实验:软膏对家兔皮肤和眼结膜均无刺激性或刺激性很小;皮肤局部过敏实验:空白基质和含药软膏均无致敏性;软膏的含药量测定:HPLC法测定含量为68.62%;1%含药软膏的药物透皮吸收释放实验:经HPLC法测定,药物累积溶出量(Q)与溶出时间(t)呈直线关系;回归方程为:Q=0.0811t+0.0157 R=0.9991,说明含药软膏是以恒速方式进行释药的。小鼠抗炎实验:由统计结果进行t检验:空白基质组:1%含药组之间有显著性差异;空白基质组:2%含药组之间也有显著性差异:而1%含药组:2%含药组之间无显著性差异。说明1%含药软膏具有显著的抗炎作用。更多还原

【Abstract】 Abstract: this study is to use the glycyrrhetic acid GTA and the diphenhydramin hydrochloric BHCL as two material for preparing a new anti-allergic compound salt drug :GTA - B. The GTA which come from the hydrolysis extracted from glycyrrhiza glabra, which is a special botanicals in xinjang indigenous plant. The BHCL is a classical anti-allergic medicine and is frequently employed in hospital. Purpose: this new prepared compound salt could modify the solubility of GTA or alter it’s absorption properties or cooperate with two raw material drug pharmacological properties. We will make this new compound salt into ointment and study it’s anti-inflammatory effect. This study has been done in two aspects with trial. The examination process as fellows:1 Preparing process and new compound salt identification. The new compound salt was investigated by using follow methods: First, the physic properties. for example, appearance, melting point m.p., solubility in different solvent ,crystal form and stability test; Second, structure identification: with thin layer chromatography TLC, ultra-violet spectrum UV, infra-red spectrum IR, element analysis and differential scanning calormetry DSC; Third, impurity check: with TLC, high performance liquid chromatography HPLC; Finally, content assay: with titrational and HPLC method. conclusion: the prepared compound salt is white, likes snow and as similar to crystal powder. m.p.=87~95℃;it can easy solved in methanol MeOH, ethanol EtOH, acetone and chloroform but solve in water less. At normal temperature , the new drug’s solubility as follows : 80.2 μ g/ml in 20% EtOH, 2059 μ g/ml in 50% EtOH, 316 μ g/ml in 10% glycerin solution. Structure identification: with TLC;UV;IR;X-ray; element analysis and DSC date all have demonstrated that prepared compound salt structure is a new one. This result compared with the raw material structure. Impurity check conclusion: the impurity limit L<l%with TLC or HPLC method. Content assay conclusion: 102.3% in titration method and 102.7% in HPLC method. Result: prepared a new compound salt :GTA - B.2 Medicinal ointment preparation and preliminary research on it’s preparation. With preparation process, we prepared a medicinal ointment and estimated it’s quality as follows: white, slender, semisolid appearance, it did not have particle on skin when it was daubed. The ointment viscosity is 9100 mPa.s; it didn’t case oil or water delamination when using centrifugal machine and high or low temperature accelerate method. Ointment didn’t stimulate rabbit’s skin and eye conjunctiva. The blank bases and medicinal ointment didn’t case allergic effect in topical rabbit’s skin. Content assay: the drug in ointment is 68.62% with HPLC detector method. Skin permeation experiments were carried out suing excised abdominal rat skin with 1% ointment, the conclusion is: the drug cumulative quantity(Q) is linear to release time, the regression equation is : Q = 0.0811t + 0.0157 R = 0.9991, it also shows the release ratio of medicinal ointment is constant. The rat anti- inflammatory test conclusion through t-test shows: blank bases compared with 1% or 2% ointment has prominent difference. But 1% versus 2% hasn’t. Result: 1% ointment has prominent anti-inflammatory effect.更多还原