| Objective 1.Prepare different Liuwei Dihuang Pill formulations in accordance with the relevant quality standards:water-bindered pill,big honeyed pill,little honeyed pill,condensed pill,water pill,paste pill,wax-wrapped pill.2.To develop a quantitative HPLC method for simultaneous analysis of paeonol and loganin in Liuwei Dihuang Pill and study the release property of paeonol and loganin in different Liuwei Dihuang Pill formulations3.Study the materiomic release kinetics characteristics of different types of Liuwei Dihuang Pill,evaluate its similarity and difference visually.4.Using the Liuwei Dihuang Pill(Honeyed Pill)as an example,by studying the influences of Pieces' different grinding degree and herbal powder wall-breaking rate,honey refining degree,dosage and temperature,pill size,the dry degree on materiomic dissolution/release kinetics characteristics,the theory composed of drug release characterization of traditional Chinese medicine pills(Liuwei Dihuang Pill)could be analyzed.To provide a new model for qualitative evaluation and control of Liuwei Dihuang Pills(Chinese medicine pills),to provide evaluative methods and standards for upgrading formulations and processing transformations of Liuwei Dihuang Pills(Chinese medicine pills),and to provide basis for clinical reasonable selection and application of Liuwei Dihuang PillsMethods 1.Prepare different Liuwei Dihuang Pill formulations and do the related quality test according to the "Chinese Pharmacopoeia"(2010 edition)2.The active components of Liuwei Dihuang Pill that including paeonol and loganin were analyzed by HPLC at 237nm(0?17min)?274nm(18?43 min)with mobile phase of acetonitrile-water.The paddle method was adopted,the speed was 75 rpm.Determined the contents of index components in four different dissolution mediums(Degassing of pure water,pH1.2 HCl solution,pH4.5 acetate buffer,pH6.8 phosphate buffer),drew release curve and fit the kinetic equations3.Use the ultraviolet absorption spectrometry combined with Kalman filter method to set up a Methodology to determine the materiomic release of Liuwei Dihuang Pills,determine the materiomic release of different Liuwei Dihuang Pill types,get the materiomic release and draw the release cruves;the Matlab software is used to change the materiomic release date into material related to the concentration of colour information.And evaluating the materiomic release characteristics of different type Liuwei Dihuang Pills visually.4.Preparation medicinal powder with different crushing degree,use Comus officinalis as an example,applied cell counting method,establish a methodology to determine the powder cell wall-broken rate of Liuwei Dihuang Pills.Determine the wall-broken rate and particle size distribution of fine powder?impalpable powder and micro powder respectively,prepare Honeyed Pill;respectively refine three honey called tender honey,refined honey and old honey,determine their density,humidity,viscosity and other relevant index respectively;Prepare series of Honeyed Pills using different refinied degree honey,different amount of refined honey,different temperature of honey;Prepare honey pill with different pill size and humidity;use a plurality of solubility curves to compare the Release kinetics equation,calculate Ts0 and Td,through analysis of variance to compare the influence of those factors on materiomic dissolution/release kinetics characteristicsResults 1.7 types of Liuwei Dihuang Pills'appearance inspection,moisture content,weight difference,soluble time,are matched with "Chinese Pharmacopoeia"(2010 edition)2.To establish a method for separation and determination of paeonol and loganin by HPLC,which are index components of Liuwei Dihuang Pill.The results of the linear relationship was good,and the correlation coefficient was all more than 0.999.The recoveries were 98.79%for loganin,103.07%for paeonol,respectively The rative standard deviations were 1.38%,1.05%,respectively(n=6).Repeatability,precision and stability of the method were in conformity with the requirements.In four kinds of release medium,the release of paeonol and loganin in different types of Liuwei Dihuang Pill had bigger difference.The release of water-bindered pill,little honeyed pill,paste pill were matched with Peppas dynamic model.The release of big honeyed pill was matched with zero oeder dynamic model.And The release of wax-wrapped pill was matched with Higuchi dynamic model.T50 of water-bindered pill,big honeyed pill,little honeyed pill,condensed pill,water pill,paste pill,wax-wrapped pill for loganin were 71,386,30,1,2,56,880min(in degassed water),58,366,23,3,5,54,709min(in pH1.2 HCl solution),65?523,32,1,2,55,890min(in pH4.5 acetate buffer),61,397,28,1,6,60,776min(in pH6.8 phosphate buffer),all had significant difference;Td were 117,588,54,6,24,92,1508min(in degassed water),94,558,39,6,9,89,1177min(in pH1.2 HCl solution),115,828,59,3,4,95,1550min(in pH4.5 acetate buffer),108,609,57,5,12,99,1377min(in pH6.8 phosphate buffer),all had significant difference.T50 for paeonol were 231,558,91,1,2,153,1152(in degassed water),179,691,98,2,8,136,1177min(in pH1.2 HCl solution),200,900,82,1,11,144,1346min(in pH4.5 acetate buffer),207,657,82,2,6,131,1356min(in pH6.8 phosphate buffer),all had significant difference;Td were 367,847,161,2,8,255,2216min(in degassed water),288,1085,201,9,97,236,2277min(in pH1.2 HCl solution),319,1462,156,5,61,249,2663min(in pH4.5 acetate buffer),332,1095,170,4,89,234,2298min(in pH6.8 phosphate buffer),all had significant difference.3.The methodology that determine the materiomic release of liuwei dihuang pill in four release mediators was set up by the ultraviolet absorption spectrometry combined with Kalman filter method,the linear relations were fine,precision and stability all meet the requirements.The release of paeonol and loganin in different types of Liuwei Dihuang Pill had bigger difference,and calculate T50 and Td.T50 of water-hindered pill,big honeyed pill,little honeyed pill,condensed pill,water pill,paste pill,wax-wrapped pill were 102,754,46,3,2,83,1164min(in degassed water),108,850,43,3,4,87,1073min(in pH1.2 HCl solution),90,1022,52,6,10,79,1535min(in pH4.5 acetate buffer),96,844,56,5,8,68,702min(in pH6.8 phosphate buffer),all had significant difference;Td were 171,1290,76,8,5,130,2393min(in degassed water),194,1443,71,7,11,128,2083min(in pH1.2 HCl solution),144,1733,86,15,24,117,3204min(in pH4.5 acetate buffer),178,1427,88,11,20,104,1421min(in pH6.8 phosphate buffer),all had significant difference.Visual evalution can directly display similarity and difference of various Liuwei Dihuang Pills' release characteristics:water pill and condensed pill release fast and full.Water-bindered pill,little honeyed pill and paste pill release were slower,but completely last.Big honeyed pill and wax-wrapped pill were release slow and not complete4.Wall-broken rate on asiatic comelian cherry fruit micropowder is 86.04%,96.63%.There is a certain influence on the release kinetics characteristics of Liuwei Dihuang Pill when pieces'grinding degree,powder wall-breaking rate,honey refining degree,dosage and temperature,pill size and the dry degree were different.Conclusion 1.Homemade Liuwei Dihuang Pill matched"Chinese Pharmacopoeia"(2010 edition).It can be used for subsequent experimental study.2.HPLC method was of high sensitivity and specificity,which was suitable for the determination of paeonol and loganin in Liuwei Dihuang Pill.In four kinds of release medium,the release of paeonol and loganin in different types of Liuwei Dihuang Pill had bigger difference.Basically in agreement with the saying the "water pills from the facilitation,pill take the slow,paste pill from the late of,wax-wrapped pill take the difficult"3.The methodology to determine the materiomic release of Liuwei Dihuang Pills established by this research is accurate and reliable,and It was more convenient and direct when combined with visual evaluation.There is a great difference between different Liuwei Dihuang Pill types,water-honeyed pill,big honeyed pill,water pill,paste pill and wax-wrapped pill have sustained release characteristics4.The pieces' grinding degree and powder wall-breaking rate,honey refinied degree,temperature and dosage,pill size and the dry degree were the important factors to influence the whole release kinetics characteristics of Liuwei Dihuang Pill(Honeyed Pill).Among them,pill size and the pieces' grinding degree and powder wall-breaking rate were the two biggest influence. |
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