Preparation And Pharmacodynamics Of Coreopsis Tinctoria Nutt.gel

Objective:Preparation and quality evaluation of Coreopsis tinctoria Nutt.gel which can be used externally for skin.Study the transdermal release rule and mechanism of Coreopsis tinctoria Nutt.gel in vitro,as well as its retention characteristics on the skin.In addition,the pharmacodynamic effect of Coreopsis tinctoria Nutt.gel against skin photoaging is studied.Methods:The appearance traits,uniformity,spreadability,viscosity,moisture retention and water loss of the gel agents were taken as the evaluation index.The matrices,humectants,and transdermal absorption enhancers of the screened gel were determined by single factor method,and the optimized prescription process was performed by using orthogonal tests.The appearance traits,viscosity,p H,centrifugation stability,high temperature stability,low temperature stability and content of Coreopsis tinctoria Nutt.gel were used as the investigation indexes to evaluate the quality.High performance liquid chromatography（HPLC）was used to determine the content of marein in transdermal solution,and equation fitting was performed to investigate the release characteristics of Coreopsis tinctoria Nutt.gel in vitro.Skin elasticity,skin thickness,and skin water content of photoaged mouse skin were examined.The histopathological structure of the skin was evaluated by HE staining and Masson’s trichrome staining,while the ameliorative effect of Coreopsis tinctoria Nutt.gel on skin photodamage and the inhibitory effect of tyrosinase activity were evaluated by measuring superoxide dismutase（SOD）activity,malondialdehyde（MDA）content,hydroxyproline（HYP）content as well as tyrosinase（TYR）activity.The safety of Coreopsis tinctoria Nutt.gel was evaluated by skin irritation test in rats and active allergy test in guinea pigs.The retention of gels was studied using fluorescence imaging.Results:The best prescription for preparing 100g of Coreopsis tinctoria Nutt.gel is as follows:the dosage of Coreopsis tinctoria Nutt.is 10%.The dosage of CP940 is 1.1 g.The dosage of propylene glycol is 7.5 m L.The dosage of glycerol is 7.5m L.The dosage of triethanolamine is 1.2 m L.The dosage of ethylparaben is 0.1 g.The dosage of absolute ethanol is 3 m L.The dosage of pure water is appropriate.The appearance of Coreopsis tinctoria Nutt.gel agent is brownish yellow,uniform texture,delicate semi-solid gel,its surface has luster,easy to evenly coat,and the viscosity is suitable.After high-speed centrifugation,it is relatively stable,the p H range is 6.33～6.50,the Coreopsis tinctoria Nutt.gel is relatively stable in a short period of high temperature and low temperature environment,the content of marein in the Coreopsis tinctoria Nutt.gel is 6245.99±94.67μg·g^-1,and the finished quality of the Coreopsis tinctoria Nutt.gel is stable.The in vitro release equation of Coreopsis tinctoria Nutt.gel is Q=192.42t(1-e^0.07t),which conforms to the first-order release rule.The absorption of drugs increases with the increase of adsorption time,which can avoid the burst release phenomenon.In the macroscopic evaluation of mouse skin,the skin of mice in the dosing group relative to the model group recovered to the original state less time-consuming,indicating better skin elasticity in the administration group.Relative to the model group,the skin thickness of mice in the low-dose group is highly significant different（P<0.01）,and the medium and high-dose groups are significant different（P<0.05）.HE staining results indicated that the skin structure of Coreopsis tinctoria Nutt.gel administered group is intact,with no inflammatory cell infiltration and no fibroproliferation.Masson’s staining results showed that the morphology of collagen fibers in Coreopsis tinctoria Nutt.gel agent administered group is more regular and orderly arranged,whose morphology is similar to the control group.The SOD activity of the skin of the middle and high doses group of Coreopsis tinctoria Nutt.gel agents is higher than that of the model group,all of which are highly significant difference（P<0.01）.The content of MDA in the middle and high dose groups of Coreopsis tinctoria Nutt.gel is highly significant lower than that in the model group（P<0.01）.The HYP content of model dose group and high dose group of Coreopsis tinctoria Nutt.gel is highly significant higher than that of the model group（P<0.01）.The Tyr activity in the model and high dose groups of Coreopsis tinctoria Nutt.gel is significantly lower than that in the model group（P<0.05）.Coreopsis tinctoria Nutt.gel has no irritation to the intact or damaged skin of rats,and no allergy to the skin of guinea pigs.Coreopsis tinctoria Nutt.gel has strong retention and adhesion on skin within 8.0 h.The preparation of liquid preparation into gel for external use on skin can prolong the stay time of Coreopsis tinctoria Nutt.gel on the skin,which is conducive to absorption.Conclusion:The Coreopsis tinctoria Nutt.gel developed in this project has reliable preparation process and stable quality of the finished product.The in vitro release of Coreopsis tinctoria Nutt.gel conforms to the first-order release rule,and the release mechanism is skeleton dissolution.Coreopsis tinctoria Nutt.gel is able to improve the condition of photoaged mouse skin,and shows good antioxidant activity and inhibition of tyrosinase in photoaged skin.It has the effect of improving skin photoaging damage as well as abnormal skin pigmentation.Relative to liquid formulations,the skin retention time of gels is prolonged,it is easy to play the advantages of gels,and the application prospect is wide.