Study On The Biopharmaceutics Classification And Absorption Mechanism Of Flavoniods Active Componetents Of Traditional Chinese Medicine

Oral administration of traditional Chinese medicine was the most convenient way which was widely used.It’s the most convenient and easily.The solubility and permeability is the core of an oral pharmaceutical.Solubility of most active ingredients of Traditional Chinese Medicine(TCM)is extremely small in water.Its bioavailability is low.The way which was used to analyse its druggability was needed in the early stages of drug discovery and drug development of TCM.Chinese medicine effective components monomer and effective parts were chosen.Referencing the scientific framework which has been widely accepted and plays an important role in chemical drugs-Biopharmaceutics Classification System(BCS).The physical and chemical properties of the active ingredients of TCM were researched about flavonoids which were Kaempferol,Liquiritin,Hesperidin,Apigenin,Genistein,Puerarin.The test which was simple,fast and low cost were used to evaluat the solubility and permeability of component.Conducting Biopharmaceutics Classification,as soon as possible to find and solve the solubility and permeability problems.Caco-2 cell model was used to research absorption mechanism of the active ingredients of traditional Chinese medicine.The possible transport mechanism of intestinal absorption was discussed.The druggability of biopharmaceutics was evaluated.In order to provide a theoretical basis for the evaluation method to build Chinese medicine effective components of the system and perfect the system of the TCM biopharmaceutics.Specific contents were shown as follows:1.The flavonoids Chinese medicine effective component classification method based on the BCS theory research:(1)The solubility of the active ingredients of traditional Chinese medicine flavonoids was determinated.Determination of the Solubility:Refer to "Chinese Pharmacopoeia"(2010 edition)Determination of Solubility:10mg drugs was precisionly weighed into stoppered centrifuge tube,5mL distilled water was added,the sample tube was placed at 37℃ water bath,shaking 30s every 5min.Dissolution was observated within 30min.Based on the approximate range of different solubilities,taking out part of the content solution was analyzed by HPLC.The solubility of Kaempferol was(0.16± 0.01)μg · mL-1;the solubility of Liquiritin was(157.98±0.52)μg · mL-1;the solubility of Hesperidin was(10.68 ± 0.25)μg · mL-1;the solubility of Apigenin was(0.15 ± 0.00)μg · mL-1;the solubility of Genistein was(3.07±0.01)μg· mL-1;the solubility of Puerarin was(5.93±0.11)mg · mL-1.The solubility of drugs were lower than 0.01 g · mL-1.The solubility of the drug was below the level of slightly soluble.The solubility.of six drugs were low.(2)The permeability of the active ingredients of TCM in flavonoids was determinated.Optimization in vitro cell culture method is adopted to establish the Caco-2 cell model,appropriate concentration of the drug was selected by the MTT method for cell transfer experiments,100μL of BL side drugs was drawn to determine its content in HPLC.Papp was calculated according to the result of cell transport experiment and permeability of drugs was determined,Papp of Kaempferol was(4.083±0.0147)*10-6 cm · s-1,which was a low permeability drug;Papp of Liquiritin was(0.5060 ± 0.0034)*10-6 cm · s-1,which was a low permeability drug.Papp of Hesperidin was(3.1548±0.0106)*10-6 cm·s-1,which was a low permeability drugs.Papp of Apigenin was(3.4375±0.0231)*10-6 cm·s-1,which was a low permeability drug;Papp of Genistein was(36.1607 ± 0.0243)*10-6 cm · s-1,which was a high permeability drug.Papp of Puerarin was(0.5208±0.0070)*10-6 cm · s-1,which was a low permeability drugs.From the above experiments,Kaempferol is the BCSⅣ drugs;Liquiritin is the BCSⅣ drugs;Hesperidin is BCSⅣdrugs;Apigenin was BCSⅣ drugs;Genistein is BCS Ⅱ drugs;Puerarin is BCSⅣ drugs.2.Caco-2 cell model of the absorption mechanism of TCM-based flavonoids active ingredient was studied:Three groups of drug which concentration were high,medium and low were choosed to do transport experiments.Volume of transfer which AP→BL and BL→AP side were measured by HPLC.At different time and different drug concentrations,both sides of the transfer traffic volume and Papp of the variation were investigated.Its absorption mechanism was analyzed.The experimental results show that:the absorption mechanism of Kaempferol is active transportation;the absorption mechanism of Liquiritin is passive transport;the absorptionn mechanism of Hesperidin is mainly passive transport;the absorption mechanism of Apigenin is passive transport;the absorption mechanism of Genistein is passive transport;the absorption mechanism of Puerarin is active transportation.