| Hypertrophic scar is a common disease after burn,operation and wound.Be in a bad way,it would not only affect the appearance of the body surface but also might lead to the body dysfunction and mental disorder.Modern treatment of hypertrophic scars often use hormone,laser,cryotherapy,surgery and so on,these therapies often accompanied by side effects.Traditional Chinese medicine has a long history on prevention and treatment of scar.However,there are many problems such as single route of administration,limited dosage forms and so on.If the traditional Chinese medicine is developed into modern preparation,it can provide a new way for the application of traditional Chinese medicine in the treatment of scar.Salvia miltiorrhiza and cortex moutan is a commonly used couplet medicines for promoting blood circulation and removing blood stasis,commonly known as "Shuangdan".Tanshinone ?A,Danshensu,paeonol are Shuangdanfang's main effective components which can inhibit the hypertrophic scar.In this paper,we design three effective components to prepare a new compound preparation,Shuangdan liposome gels.To make a new attempt for the development of traditional Chinese medicine prescription in treating scar.Objective To prepare the SD-Lip Gels,to optimize preparation process and investigate percutaneous permeability in vitro.to investigate transdermal penetration.To investigate the effect of anti rabbit ear hypertrophic scar and percutaneous pharmacokinetics.Method(1)To research on the pre-prescription study,such as determining the proportion of three prescription drugs,To establish a RP-HPLC method for determination the content of.DSS,DPF,DST and establish a method for determination of entrapment efficiency.(2)To prepare Shuangdan Lips was prepared by the ethanol injection method.The rate of phosphatidyl choline-drug(X1),PC-cholesterol(X2),PC-octadecylamine(X3),were observed.The encapsulation efficiency(EE)of tanshinol(Y1),the EE of panenol(Y2),and the EE of tanshinone?A(Y3)were evaluated.The SD-Lips was optimized by using Box-Behnken response surface methodology.To preparate the SD-Lip Gels,(3)To investigate the physical and chemical properties and quality of SD-Lip Gels,include the average particle size,Zeta potential,the the pH,viscosity,content and stability under high temperature and strong light were investigated.Develope transdermal test in vitro the transdermal rate,the amount of retained skin and the residual gel layer were compared between SD-Lip Gels and SD-Gels.(4)The model of hypertrophic scar of rabbit ears was established.After modeling 21 d,the drug was administered continuously for 42 d,the scar tissue specimens were collected for HE staining,histological observation was performed,and the proliferation index(HI)and fibroblast density(NA)were measured.Blood serum was collected from rabbits,and the content of TGF-?1 and IL-1? were measured.(5)Using microdialysis technique to develop percutaneous pharmacokinetic studies,Gain and Loss method were be used on recovery test in-vitro,the effects of different perfusion rate and drug concentration on the recovery rate of the probe were investigated,the recovery rate of the probe in vivo recovery was be corrected.Study on percutaneous pharmacokinetics of SD-Lip Gels and SD-Gels,Drawing the subcutaneous concentration-time curves,pharmacokinetic parameters of two formulations were compared.Results(1)A method for the determination of HPLC content and entrapment efficiency was established.(2)The optimal preparation process was as following: X1=13.8,X2=4.6,X3=13.3,X4=50?;The EE of tanshinol was(30.62±2.17)%,while panenol was(51.16±2.54)% and tanshinone was(80.47±3.24)%.(3)The average particle size of SD-Lips was 240.8nm,Zeta potential was +16.2mV.The pH of 6.48~6.62 of SD-Lip Gels,the viscosity is 23.9~24.8Pa·s,the total drug content was 2.12mg/g,The formulation is unstable under high temperature and strong light,so it need to avoid light and at room or low temperature storage.Compared with SD-Gels,the transdermal rate of SD-Lip Gels was decreased,the residual amount of gel layer was lower,and the amount of skin retention was significantly increased.(4)Compared with the model group,The scar fibroblasts of SD-Lip Gels group of were spindle shaped,slender slender,loosely arranged orderly,and the fibroblast density decreased significantly,the difference was statistically significant(P<0.05);after treatment,The content of TGF-?1 and IL-1? in rabbit serum were significant changes compared with before treatment,the difference was statistically significant(P<0.05).(5)Comparing the pharmacokinetic parameters of SD-Lip Gels and SD-Gels,the Tmax of the two preparations were close to 1hour,and the Cmax of SD-Gels was higher than SDLip Gels,the AUC area,MRT,and t1/2 was significantly lower than SD-Lip Gels.SD-Lip Gels can be sustained and stable release of drugs,drug retention time longer than SD-Gels,the total amount of transdermal drug was significantly higher than SD-Gels.Conclusion It is feasible to optimize the preparation process of SD-Lip Gels by BoxBehnken effect surface method.SD-Lip Gels has a slow release effect,which can increase the total amount of transdermal drug and skin volume,and reduce systemic absorption.SDLip Gels has a good therapeutic effect on hypertrophic scar of rabbit ears,and its mechanism may inhibit the formation of scar by regulating the expression of TGF-?1 and IL-1?. |
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