Study On In Vitro Transdermal Absorption And Quality Standard Improvement Of Compound Nanxing Acesodyne Plaster

Compound Nanxing Acesodyne Plaster consists of twelve Chinese medicines,including Arisaematis Rhizoma,Aconiti Radix,Caryophylli Flos,Cinnamomi Cortex,Angelicae Dahuricae Radix,Asari Radix Et Rhizoma,Chuanxiong Rhizoma,Cynanchi Paniculati Radix Et Rhizoma,Olibanum,Myrrha,Camphor,Borneol and Isoborneol.It has the effects of dispersing cold and removing dampness,activating blood circulation and relieving pain,and is widely used in the treatment of osteoarthritis and rheumatoid arthritis caused by cold and dampness,including joint pain,muscle swelling,etc.Its curative effect is exact and its application is extensive.Since it was developed than 20 years ago,it has gradually developed as the clinical first-line drugs for osteoarthritis and rheumatoid arthritis.Because of its good curative effect,it has been widely recognized by doctors and patients in clinical practice.Moreover,it has entered the national essential drugs list with good clinical advantages and market prospects.At present,the research of Compound Nanxing Acesodyne Plaster mainly focuses on quality control,pharmacological effects and clinical efficacy,etc.And there are few researches on the material basis of its efficacy.With the development of analytical techniques,the quality control standards of the preparations can no longer meet the technical requirements of the comprehensive controllable,environmentally friendly,scientific targets.Therefore,it is necessary to adopt a more advanced technology and more suitable evaluation index to carry out research on the quality standard improvement of Compound Nanxing Acesodyne Plaster to better control the stability and uniformity of product quality.The chemical components and in vitro transdermal components of Compound Nanxing Acesodyne Plaster are analyzed by the UPLC-Q-TQF-MS/MS and GC-MS.Basised on this,the quality standard of Compound Nanxing Acesodyne Plaster is improved to combine the selection of index components with drug efficacy,and improving the quality control level of the product.The main contents are as follows:1.Study on the Chemical Components and Transdermal Absorption Spectrum of Compound Nanxing Acesodyne PlasterThe experiment used UPLC-Q-TQF-MS/MS and GC-MS to identify the chemical components of Compound Nanxing Acesodyne Plaster.A total of 115 compounds were identified by both methods.Sixty compounds are identified by UPLC-Q-TQF-MS/MS,including 6 amino acid compounds,10 phenolic acids,17 alkaloids,8 flavonoids,4 Chuanxiong lactones,7 coumarins,2 phenylpropanoids,and 6 other compounds,12 of which have been confirmed by comparison of the reference substances.Fifty-five compounds were identified by GC-MS,including 7 monoterpenes and their oxygen-containing derivatives,24 sesquiterpenoids and their oxygen-containing derivatives,16 aromatic compounds,8 organo alkanes,alcohols and esters,7 of which compounds have been confirmed by comparison with the controls.This study improved the chemical composition spectrum information of the preparation from the two aspects of non-volatile components and volatile components,and provided the basis for the quality control and the pharmacodynamic materials.In vitro ransdermal absorption model was used to investigate the possible transdermal absorption components of Compound Nanxing Acesodyne Plaster.We firstly investigated and determined the composition of the transdermal receiving solution and the sample pretreatment method,and then we used UPLC-Q-TOF-MS/MS to qualitatively analyze the receiving liquid of the in vitro transdermal absorption.A total of 22 transdermal components were identified by comparison with the blank matrices and chemical composition profiles,including 11 volatile components,4 lactones,4 coumarins and 3 diesters of aconitum alkaloids.They are all identified in their chemical composition spectrum,suggesting that transdermal absorption may be the material basis for the efficacy of Compound Nanxing Acesodyne Plaster.2.Study on Quality Standard Improvement of Compound Nanxing Acesodyne PlasterBased on the results of chemical composition spectrum and in vitro transdermal absorption research,the quality standards of Compound Nanxing Acesodyne Plaster are comprehensively improved.The experiment firstly increased the TLC identification of the 2 medicinal materials of Angelicas Dahuricae Radix and Chuanxiong Rhizoma,the determination of the multi-index content of volatile components and the limit examination of aristolochic acid I.We also optimized the GC identification of volatile components,the determination of the content of hypaconitine,and the routine inspection method of the preparation,in order to effectively control the quality of the product and ensure the quality.Technical support was provided for inter-batch consistency.At the same time,in order to further improve the quality control level of the product,focusing on the micro-toxic components in the preparation,namely 3 diesters of aconitum alkaloids(mesaconitine,aconitine and hypaconitine),a multicomponent simultaneous determination has been established.The two-dimensional ultra-efficient liquid chromatography(2D-UPLC)for online center cutting,and verified by systematic method,proving the feasibility of the method.This method provides a useful reference for the quality control of the trace components in complex systems of traditional Chinese medicines.