| Pulse drug delivery system is a new type of drug delivery system to quantificationally release effective dose drug, based on the principles of chronopharmacology and chronopharmacokinetic. In this system, drug can be quantificationally released at given time according to the biological rhythm characteristics of some diseases, and it can improve the patients' compliance. Compound Danshen tablet ( CDT ) , listed in the first section of the 2005's edition of "Pharmacopoeia of the People's Republic of China", consists of the extract of radix Salvia miltiorrhiza ( Bunge ) , root of Panax notoginseng ( Burk ), borneolum. It possesses the action and indication of activating blood stasis. It is primarily applied to the treatment of coronary artery disease, angina pectoris and myocardial infarcttion. The herbs in the recipe are precise, good curative effects and abundant source of raw materials, so CDT is selected as the model drug of Traditional Chinese Medicine compound pulse time-controlled release tablet. Compound Danshen pulse time-controlled release tablets ( CDPTCRT ) are prepared under the guidance of traditional Chinese medicine theory, combined with the characteristics of the disease, clinical study necessary and modern pharmaceutical formulations of the request, the use of modern science and technology. The extraction and purification, preparation process, quality control, and pharmacokinetics were studied in this thesis.1 Study on Extraction and Purification On the basis of the action indications, the character of the ingredients included in the herbs and pre-test results, the optimal extract conditions about water extraction and alcohol precipitation were selected. Orthogonal test method was used to target many general considerations. The optimal extraction process was as follows: adding ten times water and boiling extraction twice with 1.5 hours every time. The first time of alcohol precipitation's conditions were as follows: the relative density of liquid concentrated to 1.10, with 50% alcohol, keeping for 24h at 4℃; secondary alcohol precipitation's conditions were as follows: the relative density of liquid concentrated to 1.15, with 60% alcohol, keeping for 12h at 4℃. The extraction and purification process is stable and feasible. Borneol is synthetic materials with high purity. It is difficult to dissolve in water but is soluble in alcohol. It can be used as preparation materials after re-crystallization.2 Study on Preparation ProcessingCDPTCRT consist of coating layer and tablet core, which containing disintegrants and drugs. In point of tablet core preparation, some study has been done on disintegrants, fillers, lubricants, wetting agents. At last CMS-Na was used as disintegration agent. Wet granulating pressure method is used to preparation of tablets core weighing about 200mg. Targeting for the cumulative release percentage of Danshensu, a method to determine release in vitro was established. The effect of dissolution conditions to drug release has been investigated. In point of Outer coating layer prescription, some factors were studied, such as the viscosity and the amount of HPMC, the type and the amount of filler and the amount of coating layer. Based on it, the coating layer prescription with 40% HPMC ( 50mPa·s ) , 25% HPMC ( 15mPa·s ) , 10% lactose, 25% MCC has been gotten by the orthogonal design method. The outer coating layer weighs about 300mg. The results show that the lag-time of CDPTCRT is about 4 hours in vitro and release about 90% after taking it for 6 hours.3 Quality ControlDanshensu, ginsenosides Rg1, borneol were qualitatively identificated by TLC. The result showed that all separated spots were in a clear map, and negative control without interference. HPLC was used to determine the contents of Danshensu and ginsenosides Rg1. GC was used to determine the contents of borneol. The results showed that quantitative methods are accurate, simple, reliable and can be used for the contents of the corresponding components determination.4 Preliminary Study on Release in vivo and PharmacokineticsPharmacokinetics is to research speed rule of medicine process in vivo by applicating principle of dynamics and mathematical method. Using the pharmacokinetics principle and method to study the effect of Traditional Chinese Medicine process in vivo is of great significance for reasonable forms and processes selection, design of new drug delivery system of TCM, the correct evaluation of the quality of preparation, and clinical medicine. Pharmacokinetics is applied to evaluate the releasing process of pulse time-controlled release delivery systems in vivo. The releasing patterns, releasing time, releasing rate were studied, and the pharmacokinetics parameters was been gotten, which was used to evaluate the bioavailability. Compound Danshen aqueous extract preparation had been taken as the reference to establish a method to determine rabbit's serum concentration of Danshensu by HPLC. Comparing with the reference preparation, test preparation had a significant lag-time, and the result was the same with release in vitro. It achieved prospective purpose.
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