| Total glucosides of paeonia(TGP) is the active extracts extracted from the dry root of Radix paeoniae alba, including paeoniflorin、albiflorin、hydroxy-paeoniflorin、 benzoylpaeoniflorin、paeonin, and so on. Paeoniflorin, which is the most content of TGP,is sensitive to Heat、light、acid and alkali,may reduced the content easily.TGP is often used for chronic hepatitis,rheumatoid arthritis and the prevent of aged diseases. In Present, conventional dosage forms of TGP are tablet、capsule、sustained release pellet, which have low bioavailability.In this research,we investigated the oil-water partition coefficients in different dissolvants; investigated the prescription and prepara-tion of TGP liposome; optimized the prescription by Box-Bhenken-Response-surface Methods; established quality standard of TGP liposome;also did the study of medicine dynamics in mice after intravenous injection.In this study,we established the method for the determination of Paeoniflorin in TGP liposome, investigated the oil-water partition coefficients in different dissolva-nts,and determined the aqueous phase; separated liposome from free drugs using dialysis method; chosed methanol as the demulsifier of TGP liposome.The preparation prescription and technological factors to elevate the bruclne concentration in liposomes were investigated.In order to determine the formulation and process conditions.the factors such as organic solvent type and dosage, phospho-lipids and the proportion of cholesterol, hydrated medium varieties and dosage, lipids and drug scale, water bath temperature, hydrated time were studied by using single factorexperiments. We fixed reverse evaporation method as the preparating method of TGP liposome.In this part of study, we come to the conclusion that the lipid and drug scale, hydrated medium consumption, lecithin and cholesterol proportion are the bigg-est influence factors which influence the encapsulation efficiency.We used Box-Bhenken-Response Surface Methods to optimize the prescription of TGP liposome, R2=0.9731, Adj R2=0.9386, indicates the model fitting good.We conclued the optimum prescription is:lipid5g (including lecithin and cholesterol ratio is2.5), the dosage of TGP is0.18g/5ml, torganic solvent ethyl ether1000ml, water bath temperature45℃, ultrasonic2min, hydrated dosage530ml. Three groups of verification tests the encapsulation efficiency and predicted values are not signifi-cant, is-1.09%, shows good repeatabilityThe form and particle size of liposomes were observed by transmission electron microscopy. The result showed that the particle size was498nm,with the entrapment efficiency more than70%.The leak sealing rate of TGPliposomes in continued seven days in was19.4%at room temperature while12.9%at4℃,it indicates that the TGP liposomes in4℃under a stable storage.The average spectrophotometry in534nm of TGP liposome is0.0117using malondialdehyde method indicates the low oxidation degree. The dialysis experiments shows that liposome has certain slow-release effect,and it’s drug release in vitro fits Higuchi equation.The pharmacokinetic characteristics of a single dose intravenous injection of TGP liposomes in rats were investigated compared with that of TGP solution, and the data were calculated by means of3p87. Accofding to companment-model fitting results, TGP liposomes was fitted with two companment-model with the weigllt of1/C;TGP solution was fitted with three san companment-model with the weigllt of1/C2.T1/2of TGP liposomes and solution was61.9034min and25.3284min respect-ively, and the clearance rate was0.5188ml/min and1.268ml/min.The result suggests that the TGP liposomes can slow the rate of clearing. |
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