Studies On Tongshuan Jiuxin Sustained-Released Pellets

Tongshuan Jiuxin capsule, based on the researches of modern pharmacology, consists of Cortex Moutan, Borneolum, Rhizoma Chuanxiong and Rhizoma Cyperi. It is primarily applied to treat chest distress, angina pectoris and myocardial infaction caused by coronary heart disease(CHD). In this dissertion, Tongshuan Jiuxin was selected as the model drug of traditional Chinese medicinal compound recipe (TCMCR). In order to make it possible that various components with great different properties in TCMCR are released synchronously, Tongshuan Jiuxin sustainesd-release capsules, which consists of three kinds of pH-dependent gradient-release pellets were investigated.TLC was developed to identify Rhizoma Chuanxiong and Rhizoma Cyperi in the preparation. HPLC for paeonol and GC for borneol were established to determine their contents in the preparation. The concentration of paeonol in intestine solution and in dogs' plasma were also assayed by HPLC.The preformulation studies showed that paeonol is slightly soluble in water or various physiological pH fluids. And its octanol/water partition coefficient is big(10 or so).The absorption sites and the absorption kinetics were studied in various intestinal segments ligated of rats by using in situ perfusion method. This study demonstrated that paeonol was absorbed well in intestine in general. And there is no notable difference among the absorption fraction and absorption rate constant of various segments. According to the experintal results of gastrointestinal absorption, the mechanism conjectured is that paeonol be transferred to cell via passive diffusion.The bata-CD inclusion complex of extraction of Cortex Moutan, Borneolum, Rhizoma Chuanxiong and Rhizoma Cyperi was formulated in order to increase the dissolution rate and prevent them from volatilizing.Tongshuan Jiuxin pellets with perfect shape and surface characteristics were prepared in a centrifugal granulator by using lactose as filler and 3%HPMC solution as adhesive agent under optimum condition. The dissolution rate of paeonol , ligustrazine and borneolum meet the demands of preparation and the yield of 18-24 mesh could reach to above 75%.A mini-fluidized bed spray coater was made for the coating pellcts.A pH-dependent gradient-release pellet system was investigated by using LE and vrious methacrylic acid copolymers as coating materials. In vitro experiment makes it clear that various components with different properties are released synchronously.The results of stability experiments showed that paeonol , ligustrazine and borneol in Tongshuan Jiuxin sustain-release coated pellets was stable in three months. It was verified that the stability problem of volatile components have been settled by the preparing technology applied in formulations.The plasma concentration of paeonol in dogs after a single oral administration of "Tongshuan Jiuxin sustain-released capsule(T)" was studied with "Tongshuan Jiuxin capsule(R)"as a reference preparation. Compare with R the plasma concentration of paeonol in T was steadier and its Cmax was lowered and the mean residence time was prolonged. A characteristic of gradient-release was showed in the concentration-time curves of paeonol of T.