Study On Relationship Between Drug Property Characteristics And Penetrational Enhancing Effect Of Essential Oils From Pungent Herbals

Application of penetration enhancers(PE)is,so far,the most studied,the most common and the most convenient method for promote the bioavailability of transdermal drug delivery system.However,the existing PE can not fully meet the needs,and the synthesis of new varieties is more difficult and costly.Essential oils from herbs are a class of excellent PE,with the advantages of high safety,good promoting effect,synergies and so on.According to statistics,there are about 300 kinds of traditional Chinese medicine containing essential oils,of which about 130 are commonly used,and now there has been only 34 species used as PE,that is,essential oils have huge potentials of research and development.A systematic rule of penetration enhancement is required to guide the reasonable and efficient development of essential oils as PE.The Chinese literatures about penetration-enhancing effect of essential oils(as of June 2014)were systematically sorted and found that 34 kinds of essential oils were reported having the property of penetration enhancement.Through the literature research and data mining,a point was proposed for the first time:there exixts a relationship between drug property characteristics and penetrationenhancing effect of essential oils from herbs.The essential oils with the penetration enhancement were all from herbs with pungent flavor.Four natures and channel tropism have significant impacts on penetration enhancement(P=0.011 and 0.077),especially four natures.20 kinds of commonly used essential oils from pungent herbs were collected by using steam distillation method,and the physical properties were determined,and the component was analyzed using GC-MS.Then a data mining between component and drug properties was performed.The results showed that there was a positive correlation between bitter flavor and content of monoterpene,while sweet flavor positively correlated to sesquiterpenes and phthalates;From cold to hot,four natures have a positive correlation to aromatic components,and different meridian tropisms were also related to different component categories.With ibuprofen as a model drug,the Franz diffusion cell method was used to systematically investigate the penetration enhancement of 20 kinds of essential oils from pungent herbs.A stepwise regression analysis between component and promoting effect was performed,and essential oils of highly penetration enhancing effect were predicted from herbs of warm or hot nature、pungent(bitter)flavor and meridian tropism of spleen.Preliminary verification was then carried out with Evodia oil,and the results were basically the same.In addition,the relationship between penetration enhancing effect and coponents was analyzed.The results showed that the higher the content of sesquiterpene and monoterpene,the better the effect of promotion,while the content of aliphatic and fatty acids impeded promotion.With human skin keratinocytes HaCaT cells as a model,skin cytotoxicity of 20 kinds of essential oils from pungent herbs was systematically investigated on the same platform.The results showed that the skin cytotoxicity of essential oils was much lower than that of Azone.A stepwise regression analysis of essential oil cytotoxicity and drug properties was performed,and the results show that:essential oils from the herbs with the meridian tropism of heart,lung,or kidney with bladder had lower skin cytotoxicity.A verification was performed by using the essential oils of Ligustilide and frankincense,and the results were similar.9 oxygen-containing monoterpenes as penetration enhancement,5-fluorouracil,salicylic acid and ibuprofen as model drugs,the penetration enhancement of 9 oxygen-containing monoterpenes were investigated by using Franz diffusion cell method.The change of skin resistance before and after the treatment of oxygen-containing monoterpene solution was measured by cell resistance meter.By linear fitting between the effect of penetration enhancement and the change of skin resistance,it was found that the higher the fat solubility of the model drug,the better the linearity.Fourier transform infrared spectroscopy(FTIR)showed that the main mechanism of oxygen-containing monoterpenes penetration enhancers was to disturb the arrangement of stratum comeum(SC)lipid.The main mechanism of essential oils were consistent with that of oxygen-containing monoterpenes.It can be seen that the resistance method can be used to study the promoting effect of essential oils.