注射型盐酸益母草碱穴位埋植凝胶的制备及其含量测定

Preparation and content determination of hydrochloric leonurineacupoint injection in-situ gel

制备注射型盐酸益母草碱穴位埋植凝胶,建立其药物含量测定方法。以聚乳酸-羟基乙酸共聚物(PLGA)为主要凝胶载体材料,利用高效液相色谱法(HPLC),色谱柱为Eclipse Plus C18分析柱(4.6 mm×250 mm,5μm),流动相0.4%辛烷磺酸钠的0.1%磷酸溶液-乙腈(76∶24),流速1.0 mL/min,检测波长277 nm,柱温30℃,建立药物含量测定方法。通过凝胶粘度、通针阻力及体外释放度测定评价凝胶处方。结果表明,所建立的HPLC方法,盐酸益母草碱在2.02~101μg/mL范围内线性良好;平均回收率为104.05%。注射型穴位埋植凝胶的最佳方案为3%盐酸益母草碱,20%PLGA,15%PEG400,60%甘油缩甲醛,2%HPMC,凝胶25℃粘度为193.7 mPa·s,37℃粘度为148.0 mPa·s,粘度流变为205 mPa·s;1 mL通针阻力为1.81 N,5 mL通针阻力为1.95 N;体外释放率在1 d时约达到64.50%,5 d时为91.02%。说明注射型盐酸益母草碱穴位埋植凝胶制备成功,所建立的HPLC方法可用于盐酸益母草碱埋植凝胶的质量控制。

To prepare and establish the method for content determination of hydrochloric leonurineacupoint injection in situ gel.Poly(lactic-co-glycolic acid)was main composition used to prepare the in-situ gel.High performance liquid chromatography(HPLC)method was established to determine the content of hydrochloric leonurine in the gel.The separation was performed on an Eclipse plus C18 analytical column(4.6 mm×250 mm,5μm)and the mobile phase consisted of 0.4%sodium 1-octanesulfonate and 0.1%phosphoric acid-acetonitrile in the ratio of 76∶24(V∶V).The UV detector wavelength was set at 277 nm with flow rate of 1.0 mL·min^-1 and column temperature was 30℃.For evaluation of gel formula,the viscosity and resistance in syringe needle of the gel,and in vitro release curve were examined.The peak area and the concentration were used as the standard curve,and the linear regression equation was y=0.2997 x-0.9126,the correlation coefficient R^2=0.9941.The linearity was good in the range of 2.02μg·mL^-1~101μg·mL^-1.The average recovery was 104.05%.The optimal formula is 3%hydrochloric leonurine,20%PLGA,15%PEG400,60%Glicerinformal,2%HPMC.The viscosity of the gel at 25℃was 193.7 mPa·s and at 37℃was 148.0 m Pa·s,the rheological property is 205 mPa·s;the resistance of the gel in 1 mL syringe needle was 1.81 N and in 5 mL syringe needle was 1.95 N,the release rate in vitro of the hydrochloric leonurine was 64.5%at 1 d,91.02%at 5 d.The results showed the acupoint injection in-situ gel of hydrochloric leonurine was successfully prepared,and the HPLC method can be used for determine the content of leonurine hydrochloride and control the quality of the drug in acupoint injection in situ gel.