Injection Research Renshensini Powder Injection

With the popularity of the traditional Chinese medicine （TCM） injection in clinical use, the problems associating with quality of the products and safety considerations become more and more obvious. The sterile powder of Renshensini for injection was mainly used for cardiovascular disease, which was the compound preparation made up of Licorice root, Aconite root, Zingiber and Red ginseng. Based on the Renshensini decoction, five intermediates were prepared, and the quality standard was established, respectively, with the assistance of new purification technology, such as organic solvent extraction, macroporous resin purification and recrystallization. The sterile powder of Renshensini for injection was successfully developed with better safety, efficiency and stability using the lyophilization technique, which can meet the requirements of the standard of sterile powder for TCM injection. The pharmacokinetic studies were separately carried out on mice analyzed by drug accumulation method（DAM） and wistar rats analyzed by blood drug level method（BDLM）, which can provide valuable information for clinical application.The analytical method was established for the quality control, taking the total alkaloid, ester-alkaloid, 6-gingerol, GA, Liquiritin and ginsenoside Rg1, Rb1, Re as index ingredients. The method of TLC was used to identify active components. The titrimetric method was developed to determine the total alkaloid. The method of UV was applied to determine the content of the total ginsenoside. The quantitative analysis of active ingredients and the limitation inspect of ester-alkaloid was completed with the method of HPLC. The method of GC was used to detect the residue of organic solvent.. All the methods had high sensitivity, good selectivity, precision and could be used to determine effective constituents.6-gingerol was separated from the ginger supercritical CO₂ extraction by column chromatography and preparative liquid chromatography. The structure of product was the same as that of 6-gingerol, affirmed by NMR, IR, MS, and identified by UV, TLC. The purity was above 98.5% analyzed by HPLC.Based on transfer rate of active substances, new extracting and separating techniques were applied in the preparation of injectable intermediates. The result indicated that the total transference rate were: 45%（GA）, 68%（L）, 70%（The total alkaloid）, 75%（6-Gingerol）, 73%（CAnsenoside Rg1）, 60%（Ginsenoside Re）, 57%（Ginsenoside Rb1）.Based on the intermediate, the freeze-drying technology was studied, including the screen of the prescription, the selection of the support agent and activated carbon, the method of preparing mixing physic liquor, the investigation of freeze-drying parameters and so on. The quality evaluation system was constructed, which include the character identification of TLC, the general examination（content uniformity, pH, water content, heavy metal）, safety test（stimulus, haemolyticus, anaphylaxis）. The product was examined according to the quality standard, and results showed that the process was stable, and can meet the request of injection preparation very well. The quality criterion of intermediate provided rules in future study. The content of active principles were: 0.11mg（Ginsenoside Rg1）/bottle, 0.04mg（Ginsenoside Re）/bottle, 0.12mg（Ginsenoside Rb1）/ bottle, 0.55mg（The total ginsenoside）/bottle, 0.47mg（6-Gingerol）/bottle, 2.49mg（GA）/bottle,.The pharmacokinetics of GA （single dose of GA and Renshensini decoction） in rats after i.v. was investigated by the method of blood drug level. The DAM was used to study the whole effect of compound preparation. The pharmacokinetics parameters of BDLM were as follows: AUC_{0â†'∞} was 424.2±94.3 mg·h·L^-1 and 728.1±149.5 mg·h·L^-1, MRT was 1.85±0.53 h and 2.00±0.46 h, Vss was 19.61±0.99 mL and 13.28±1.10 mL, CL was 11.23±2.79 mL·h^-1 and 6.90±1.45 mL·h^-1. The pharmacokinetics of mice and rats after i.v. fitted for two-compartment model. It distributed rapidly after entry into the body, and was also eliminated quickly from the plasma. The jump-points were both existed in the drug-time curves of Renshensini decoction. DAM was able to reflect the whole curative effect of compound preparation and provide actual value in clinical practice. It is suggested that we should pay attention to the influence of other ingredients on the main objective component in the study of pharmacokinetics of compound traditional Chinese drug.