Study On Preparation,Quality Control And Anti-myocardial Ischemia Effect Of Danhong Core Component Dripping Pills

Herb-pair “Danshen-Honghua” is a typical herb pair for promoting blood circulation and removing blood stasis,which plays an important role in the treatment of cardiovascular and cerebrovascular diseases.Nevertheless,there are still many challenges in quality control and pharmacological mechanism study due to its complex Chemical constituentst,which restrict its development.According to our previous study on metabolism in vivo and literature tracing,it was found that there were Danshensu,Salvianolic acid A and five other core components of activating blood circulation and removing blood stasis in herbpair “Danshen-Honghua”.In this thesis,with the advantages of rapid effect and high bioavailability of dropping pills,these seven core components were prepared into dropping pills.Subsequently,the quality standard and effect of anti-myocardial ischemia(MI)in rats were studied,which will provide reference for the development of safe and effective new cardiovascular drugs based on herb-pair “Danshen-Honghua”.The main contents of this paper were as follows:1.Single factor test and orthogonal test were used to investigate the prescription and preparation process of Danhong core component dripping pills.It was found that the optimal prescription contained: the dosage of PEG 4000 was 62.5%,the dosage of PEG6000 was 20.83%,and the drug loading was 16.67%.The optimum dropping conditions were:(1)Drip system temperature: 65℃.(2)coolant: dimethyl silicone oil.(3)cooling temperature: 10 ～15℃.(4)cooling column length: 45 cm.(5)drop distance: 6 cm.(6)drop rate: 10 drops /min.Three batches of validation tests showed that the dropping pills had good formability;average weight of the pills were 49.6 mg;the coefficient of variation of pill weight(cv)and the dissolution time limit met the requirements of the Chinese Pharmacopoeia(2020 edition);indicating that the preparation process was stable and reliable.2.According to the requirements of dropping pills in the 2020 edition of Chinese Pharmacopoeia,the quality standard of Danhong core component dripping pills was studied.The inspection items included identification,dissolution time limit,content determination,and content uniformity.Three batches of dripping pills were determined,and the results showed that:(1)Dissolution time limit was ≤ 15min;(2)The content of each drug ingredient is 90%-110% of the labeled amount;(3)The content uniformity was in accordance with the Chinese Pharmacopoeia(2020 edition).The results showed that the preparation method of Danhong core component dropping pills was reasonable and feasible,and the quality of them was reliable,indicating that thy could be used for the following research.3.The acute MI rat model was established by tail-vein injection of pituitrin.The anti-MI effect and mechanism of Danhong core component dropping pills were studied.The results showed that Danhong core component dropping pills had equivalent anti-MI effect to that of DHI,and both of them can stabilize the electrophysiology of cardiomyocytes,protect the structure of cardiomyocytes,reduce cardiomyocyte injury,improve myocardial metabolism,and resist reactive oxygen species(ROS)and lipid peroxidation.