Evaluation Of Enhancing Penetration Activity And Irritating Of O-acyl Terpineol

Objectives The research of Percutaneous preparation-third generation has become a hot spot, while it exists difficulties in drug penetration into the skin because of natural barrier function of keratoderm, therefore researching ways of more efficient penetration drugs is an problem urgently to be solved in transdermal drug delivery. Chemical promote infiltration method, used the most widely, is one of effective methods of drug transdermal.The accelerator become the focus of research, but ideal accelerator is rare. Terpenoids from natural, have advantages of high activity and low toxicity, have imperfections of Low melting point, volatile which bring inconvenience for percutaneous preparation production and storage. The research is to find out safer, more efficient, less volatile promoter than before through structure transformation of terpineol with analogy in menthol way of transformation.Methods Terpineol ester derivatives is the synthesis of terpineol and different fatty acid,the structures are determined by 1HNMR and MS. Select isosorbide dinitrate, ibuprofen,meloxicam as the model drugs, terpineol ester derivatives as the patch penetration, evaluate liquid environment and the penetration efficient of patch preparations, filter them which have the notable penetration efficient. Evaluate this type of patch preparations in safety respect through skin stimulative experiment.Results 1 Compound eight terpineol ester derivatives with terpineol and different fatty acid as raw materials: T-OA, T-BUT, T-HEX, T-HEP, T-DEC, T-DOD, T-TET, T-STE,the structures are determined by 1HNMR and MS. 2 Terpineol derivatives of ISDN and ibuprofen promoting effect is remarkable, on the contrary is the effct of meloxicam nonsignificant in IPM penetration system. 3 Part of terpineol derivatives of ISDN and ibuprofen still has a good promoting effect, the T- TET is best. 4 The skin stimulative experimental results show that T-TET as PE has no skin irritation, Terpineol ' s skin irritation is greater than T-TET.Conclusions The promoting effect of terpineol ester derivatives is closely related to the solubility of drugs. It can promote percutaneous absorption of ISDN and ibuprofen of the solubility of drugs, for small solubility meloxicam, do not show significant promoting effect. Terpineol ester derivatives as PE have the optimal length of hydrophobic chain,they have optimal effect with 14 tail chain length in IPM solution and Patches of straightchain terpineol ester experiment. The skin stimulative experimental results show that terpineol ester derivatives as PE has no skin irritation, safer than terpineol.