复方苦参注射液醇沉工艺优化及醇沉颗粒沉降过程研究

Alcohol-purification technology and its particle sedimentation process in manufactory of Fufang Kushen injection

目的:以复方苦参注射液为模型药物,对其醇沉工艺进行优化,并对醇沉过程中颗粒沉降过程及其特点进行研究,掌握其沉降机制和过程变化规律,探讨过程控制模式在中药生产中的可行性。方法:以复方苦参注射液为研究对象,以生物碱及大泽米苷成分的保留量为评价指标,优化醇沉工艺,同时结合对醇沉过程中形成的沉淀颗粒的数量、密度、沉降速度等参数的测定确定醇沉时间,理解工艺过程。结果:优选出的醇沉工艺为醇沉2次,乙醇浓度依次为60%,80%～90%。该过程随着沉降时间的延长,生物碱类成分有一定的下降,一次醇沉36 h,二次醇沉6 h即可满足生产要求。10μm及25μm颗粒在第1次醇沉过程中完全沉降所需时间分别为157.7,25.2 h;在第2次醇沉过程中完全沉降所需时间分别为84.2,13.5 h。结论:优化后的醇沉工艺能够更好地保留指标成分,节约时间,减少能耗。同时也证实了中药注射剂的生产质量是可以控制和把握的,但过程控制模式应在充分理解过程的变化规律的基础上制定。

Objective： Fufang Kushen injection was selected as the model drug,to optimize its alcohol-purification process and understand the characteristics of particle sedimentation process,and to investigate the feasibility of using process analytical technology（PAT） on traditional Chinese medicine（TCM） manufacturing.Method：Total alkaloids（calculated by matrine,oxymatrine,sophoridine and oxysophoridine） and macrozamin were selected as quality evaluation markers to optimize the process of Fufang Kushen injection purification with alcohol.Process parameters of particulate formed in the alcohol-purification,such as the number,density and sedimentation velocity,were also determined to define the sedimentation time and well understand the process.Result： The purification process was optimized as that alcohol is added to the concentrated extract solution（drug material） to certain concentration for 2 times and deposited the alcohol-solution containing drug-material to sediment for some time,i.e.60% alcohol deposited for 36 hours,filter and then 80%-90% alcohol deposited for 6 hours in turn.The content of total alkaloids was decreased a little during the depositing process.The average settling time of particles with the diameters of 10,25 μm were 157.7,25.2 h in the first alcohol-purified process,and 84.2,13.5 h in the second alcohol-purified process,respectively.Conclusion： The optimized alcohol-purification process remains the marker compositions better and compared with the initial process,it′s time saving and much economy.The manufacturing quality of TCM-injection can be controlled by process.PAT pattern must be designed under the well understanding of process of TCM production.