The Effect Of Papaverine Hydrochloride Lecithin Micro Emulsion On Survival Of Dorsal Random Skin Flap In Rats

Skin flap is the most important method for repairing of tissue defects and deformities and reconstruction of organs, for the advantages of self-blood supplying and better recovery of functions and appearances, in contract with free skin graft. Survival of flaps is influenced by many factors, and the most important factor is promptly reestablishment of available blood circulation with recipient bed and wound edge.Papaverine Hydrochloride is commonly used in skin flap grafting, for its effect of expansion of vascular smooth muscle and improving blood supply of skin. Injection, main administration method of Papaverine Hydrochloride currently, has a lot of systematic side reactions. Regional external application has never been generally applied. However, regional application has the advantages of high drug concentration in regions, convenient application and fewer systematic side reactions; it has satisfactory adaptivity in skin flap grafting, a regional surgery.With small molecular weight, strong pharmacology actions, good curative effects, sparingly soluble in water, PH of saturated water solution ranging from 3. 0 to 4. 0, without sensitization and stimulus, consistent with requirements of drug for Cutaneous penetration, Papaverine Hydrochloride suits to be prepared into Cutaneous penetration preparation.Micro Emulsion is an important carrying agent for cutaneous penetration; it is an isotropic, clearing and heat-stable disperse system which is mixed by water, oil, surface acting agent and co-surfactant according to appreciable proportion. Micro Emulsion is small in grain size; it's capable of elevating dispersity of drug, changing lipidic and polar pathway in drug transport though skin, so that increase diosmosis of drug. There are few reports of research in Papaverine Hydrochloride Micro Emulsion all over the world.In this experimental research, we prepared Papaverine Hydrochloride Lecithin Micro Emulsion with Phosphatidyocholine (PC>99%, surface acting agent), isopropyl myristate (oil), alcohol (co-surfactant), water and Papaverine Hydrochloride according to optimize prescription, and make dorsal skin flap in rats to invest Papaverine Hydrochloride Lecithin Micro Emulsion's influences on survival of skin flap, targeting at offer references and evidences in exploitation and clinical application of Papaverine Hydrochloride cutaneous penetration praeparatum.Objective:This study was instituted to prepare Papaverine Hydrochloride lecithin micro emulsion and investigate in a rat model the effect of Papaverine hydrochloride lecithin micro emulsion on survival of dorsal random flap.Methods:1. Preparing and quality evaluation of Papaverine Hydrochloride Lecithin Micro Emulsion: The Papaverine Hydrochloride Lecithin Micro Emulsion was prepared with lecithin, isopropyl myristate, ethyl alcohol, water, Papaverine Hydrochloride by using shah method.2. 40 rats were divided into 4 groups: the external application group, the injection group, the wet compress group, and the control group. All rats were operated on back and made ischemic dorsal random flap, with treatment of Papaverine Hydrochloride Lecithin Micro Emulsion ad hibeo, Papaverine Hydrochloride IM, wet compress with Papaverine Hydrochloride aq sol on experimental groups. Rats in control group were injected with Sodium Chloride.3. The blood flow, microvessel density, and survival rate of the flaps were measured to inspect therapeutic effects.Results:1. 60ml of pallide-flavens settled pellucid adqulis liquid was made. Quality evaluations show ME with high quality and high stability.2. Operations in rats were successfully performed, with little hemorrhage and no infection. All operations were performed by myself.3. There is no obvious difference in the blood flow of all groups before and instantly after operation (P>0.05). After treatment, the blood flow of the external application group was higher than other groups gradually (P<0.01).4. The detection of microvessel density shows that: the external application group> the injection group>the wet compress group and the control group.5. The detection of survival rates shows that: the external application group> the injection group>the wet compress group and the control group.Conclusions:1. Preparing of Papaverine hydrochloride lecithin micro emulsion is convenient and effective, with low requirements for instrumentations and environments.2. The results of blood flow detection show that Papaverine hydrochloride lecithin micro emulsion is effective in reconstruction of blood circulation in the early stage of flap operation, for its effect of releasing vasospasm and increasing blood flow. The Papaverine hydrochloride lecithin micro emulsion has stronger effect than Papaverine Hydrochloride Injection in increasing blood flow. Papaverine water solution has no obvious effect in improving blood circulation, from which we can see that the Papaverine hydrochloride lecithin micro emulsion is capable of enhancing dissolubility of papaverine hydrochloride in water and its cutaneous penetration.3. With the results of microvessel density detection we consider that improvement of regional blood flow causes microvessel enhancement and construction of collateral circulation.4. Instead of the traditional one, we invented a new method of survival rate detection, which is more convenient and more effective.In conclusion, the Papaverine Hydrochloride Lecithin Micro Emulsion Papaverine can effectively permeate through skin and expand local vessels in local tissue, thus increase the blood flow and promote survival of flaps.