Studies On The Preparation And Pharmacodynamics Of Xionggui Cataplasm

Ligusticum chuanxiong and Angelica sinensis are popular traditional Chinese medicinal herbs,which can be used to promot blood flow and activate meridians to relieve pain and usually used for the treatment of dysmenorrhea,amenorrhea and irregular menses.But the common dosage forms,as pilulae and granule,are retarded in effects,inconvenience in taking and poor in compliance.The major advantages of cataplasm include avoiding drug degradation in liver and gastrointestinal tract,increasing the drug concentration in local position,reducing administration frequency and predetermining releasing rate and blood level.A Thin-layer Chromatography Assay method was established to investigate the influence of different extract mehtods on the yield of ferulic acid,the main active component both in Ligusticum chuanxiong and Angelica sinensis.Orthogonal test was designed and carried out to investigate the influence on the yield of ferulic acid with various amount and velocity of percolate and aether,and time of extraction.The total amount of extract and the content of ferulic acid in the Ligusticum chuanxiong and Angelica sinensis(ELCAS) were used as evaluation indexes.The optimal extract method is that 15 Kg of Ligusticum chuanxiong and Angelica sinensis each were respectively weighed and comminuted into coarse powder,then immersed in 95%alcohol for 24 hours.The 60000 mL percolate were collected,at the rate of 3～5 mL·min^-1,then concentrated solution of 1.20～1.25 relative density was obtained by reclaiming alcohol.The percolate was extracted 4 times by 1000 mL aether each time and extract was obtained by reclaiming aether at 50℃water-bath and reduced pressure.A rapid and sensitive High Performance Liquid Chromatography assay method was established to determine the content of ferulic acid in releasing sample and permeating sample in vitro.The solubility of ferulic acid in phosphate buffer saline(PBS) is 1302.9250±1.0932μg·mL^-1(n=5),which is approximated three times of that in water.So phosphate buffer saline of pH 7.4 was selected as receiver medium in permeation test in vitro.To study the effect of Ligusticum chuanxiong and Angelica sinensis(ELCAS) and different concentration of water-soluble azone(WSA) on the permeation of ferulic acid in vitro, excised mouse abdominal skin was pretreated with penetration enhancers.The study indicated that both ELCAS and WSA showed significant enhancement effects on the permeability of ferulic acid compared with blank skin.ELCAS showed much higher permeation enhancing effects than those of WSA,which was mainly contributed by components existed in the extract.The combined application of 100 g·L^-1 ELCAS and 30 g·L^-1WSA exhibited the greatest permeation enhancing effects and the permeation flux was 99.0970±5.1367μg·cm^-2·h^-1(n=6) and the enhancement ratio(ER) was 54.0804.The effects on the physical property of cataplasm of water-soluble high molecular polymer,cross-linking agent,cross-linking agent moderator and humectant were investigated on the basis of definitive extract technology and permeation test of ferulic acid in vitro.The optimal proportion of matrix formulation of Xionggui cataplasm was selected by uniform design,and the tacking strength,cohesive strength were used as evaluation indexes.The optimal proportions of matrix formulation of Xionggui cataplasm are water-soluble high molecular polymer:cross-linking agent:cross-linking agent moderator:humectant = 1.0: 0.02:0.01:2.5.The experiments of retest indicated that the results of uniform design were reliable.The releasing test according with 2005 edition Pharmacopoeia of the People's Republic of China showed the ferulic acid release pattern in Xionggui Cataplasm following Higuchi equation.The permeation tests through mouse skin in vitro demonstrated that ferulic acid exhibited zero-order kinetics.The permeation flux of ferulic acid was 3.3022μg·cm^-2·h^-1 and the accumulate release percent was 11.37%within 24 hours.The appearance,characteristics and ferulic acid content of Xionggui Cataplasm were stable in six months.The irritation and allergia tests showed that Xionggui Cataplasm had a good compliance and with no irritation and allergia on the volunteer skin. The dysmenorrhea models intrduced by oxytocin and body-twisting models introduced by acetic acid were used to study Xionggui Cataplasm's effects on dysmenorrhea.The results showed that Xionggui Cataplasm evidently inhibited the body-twisting reactions caused by oxytocin and acetic acid.