| Guanxin Suhe Wan, listed in first section of the 2000's edition of "Pharmacopeia of the People's Republic of China" consists of Styrax, Borneolum, Olbanum, Radix aristolochiae and Lignum santali albi. It is primarily applied to the treatment of chest distress, angina pectoris and myocardial infarction caused by coronary heart. In this thesis, Guanxin Suhe Wan 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, Guanxin Suhe delayed-release capsules, which consists of three kinds of pH-dependent gradient-release pellets were investigated. TLC methods were used to identify Styrax, Olibanum. HPLC method for cinnamic acid, GC method for bomeol were developed to determine their contents in preparations. The concentration of cinnamic acid in human plasma was assayed by HPLC method with IJV detector. The index of pharmacodynamics was adopted to research three kinds of preparation techniques of fine intermediate product: (1) Radix aristolochiae was extracted with 80% alcohol, the spray drying technique was used to dry extract of Radix aristolochiae in liquid state; Water steam distillation was applied to extract the Santal oil and Olibanum oil; The beta-cyclodextrin inclusion of Borneol and Styrax were formulated; (2) The preparation of Styrax, Bomeol, Radix aristolochiae and Lignum santali albi were the same as above, Olibanum was comminuted without extracting at super low temperature; (3) The preparation of Styrax, Bomeol were the same as above, Radix aristolochiae, Olibanum and Lignum santali albi were mixed and extracted together. The results showed that the third technique was best. The beta-cyclodextrin inclusion of Olibanum oil was formulated and optimized by uniform design. Compared with mixture, the solubility and the dissolution rate of inclusion complexes were remarkably increased. The Guanxin Suhe pellets were prepared in a centrifugal granulator by using starch as filler and 3% HPMC solution as adhesive agent. The added speed of adhesive agent and powder feeding rate were found to have significant influences on palletizing process. Under the optimum conditions, the pellets prepared have perfect shape and surface characteristics and the yield of 1 &"0 mesh pellets could reach to above 80%. A self-designed mini-fluidized bed spray coater was made for the coating pellets. A pH-dependent delayed-release pellet system was parepared by coating with LE, HPMCP55 and Endragit II as coating material. The above three kinds of coating pellets were designed to release drug in stomach, duodenum and jejunum or ileum, respectively. The results of stability experiments showed that cirmamic acid and borneol in Guanxin Suhe pH-dependent delayed-release coated pellets toward heat, humidity and light were stable. It was verified that the stability problems of volatile components have been settled by the preparing technology applied in formulations. The plasma concentration of cinnamic acid in three healthy volunteers after a single oral administration of "Guanxin Suhe delayed-release capsule" was studied with "Guanxin Suhe Wan"as a reference preparation. The concentration-time curves of cinnamic acid of "Guanxin Suhe Wan"fit in two-compartment model. Cmax, Tmax of "Guanxin Suhe delayed-release capsule"were 88.20 ng/nil, 0.25 hr, respectively. Compared with... |
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