| Breviscapine is an active extract of traditional Chinese medicine Erigeron breviscapus (Vant). Its preparations have been extensively used in clinic to treat cerebral insufficiency and peripheral circulatory problems. In recent years, study on its clinic effects has been full-scaled acquainted. In its preparation aspect, besides of tablet and injection, new dosage forms such as capsule, pill, infusion solution and so on have been explored. But the oral dosage forms of Breviscapine are poorly absorbed in body, and they have low absolute bioavailability. The new dosage form of Breviscapine needs to be enhanced. In this work, in order to improve Breviscapine 's ig. bioavailability and to get a convenient preparation, the dry suspension of Breviscapine was explored; and its pharmacodynamics has been evaluated. The main results are as follows:The preparation of Breviscapine dry suspensionThe key to preparation is to improve Breviscapine 's bioavailability by adding phosphatidylcholine. On study of the oxidated degree during the preparation process and the change of the main medicine mixed with the auxiliaries, the preparation techinics and the sort of auxiliaries have been decided. According to dispersion time, ratio of subsided volume and re-dispersion time, the kind and dosage of suspending agent have been found. The best prescription is breviscapine 2g, phosphatidylcholine 3.4g, carboxyl-methyl cellulose sodium 3.2g, mannitol 8g, lactose 16g, which dispersed into 1000mL suspension when using. The characteristic absorption of breviscapine in the suspension has not changed; its hydrodynamics behavior is similar to shear thinning liquid; its Zeta potention is –41.8mV; and the dry suspention's critical relative humidity is 60%.The quantitative analysis of breviscapine dry suspension and experiment on its effective factorsThe method of quantitative analysis on breviscapine dry suspension by HPLC has been built. And through this method, three batches of samples have been quantitatively analysed. One batch of them has been put in 60℃, relative humidity of 75%, illuminated at 4500Lx respectively for 5d and 10d, and then, the relative substance and content in the samples have been determined. It indicated that the analytical method is convenient to operate; the results are veracious and believable. The effective factor experiments indicated that breviscapine dry suspension must avoid high temperature, high humidity during preparation, preservation and transportation.The absorption of breviscapine dry suspension in vitro evaginated small intestines of ratThe model of vitro evaginated small intestines and the method of quantitative analysis of intestines juice containing breviscapine with HPLC have been built. The absorption of breviscapine in different small intestine segments has been investigated, and then the best absorptive part has been confirmed. The absorption of breviscapine dry suspension in the best absorptive part was compared with breviscapine and breviscapine- phosphatidylcholine mixture. The result showed that: in the experiment of vitro small intestines absorption, there is significant difference (P<0.05) among different parts of the small intestine. The best absorptive part is the duodenum; breviscapine- phosphatidylcholine mixture and breviscapine dry suspension can observably improve absorption of breviscapine in vitro small intestine; compared with breviscapine, both groups showed significant difference (P<0.05); but between these two groups there is no significant difference (P>0.05). Which indicated that phosphatidylcholine can improve the absorption of breviscapine vitro small intestine.The pharmacokinetics of breviscapine dry suspensionThe quantitative analysis method of plasma containing breviscapine has been built. Breviscapine,breviscapine-phosphatidylcholine mixture and breviscapine dry suspension are respectively given to rat (100mg/kg, account as breviscapine, ig), and analyzed the plasma samples from 0.33h to12h, then drew the concentration-time curves, finally, these cur... |
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