Effect On Material Properties Of Tongmai Pill Strychnine And Brucine In Vivo Release

Objective: In vitro dissolution and pharmacokinetic studies as means of releasing toxic ingredients tongmai pill study and determine the impact of the dissolution of the material properties of pills, provide a scientific basis for medicine pills attenuated research, also for the final development tongmai pill become a safe and effective drug and lay a good foundation.Methods: Under the guidance of Chinese medicine theory, based on the "medicine auxiliary unified" theory, taking tongmai pill party as a model of prescription,To conduct the research specific research methods are as follows:(1)Preparation of model drugs: The tongmai pill prescription formulation of materials into fiber, starch, fats and oils and resins four different types of traditional Chinese medicine materials, According to different grinding ratio of prescription, Pan for preparation of 7 batches of water pills(which the 1 batch of the original prescription pill),(which a grant is original prescription water pills), And general inspection for each batch of pill.(2)Indicators measuring liquid ingredients dissolution: Select paddle method and 900 ml ultrapure water ultrasounded 30 min as the dissolution medium, Speed is set to 100 r ?min-1, adjusting the temperature to 37±0.5 ℃, insulation 30 min. Taking the size of uniform tongmai pill 15 g in dissolution cup, In the 2,5,10,20,30,40,60,120,240,1440 min sample 2ml after dosing, Stripping liquid after the centrifugation HPLC.Chromatographic conditions : Waters Acquity UPLC BEH C18 column(2.1mm×100mm,1.7μm), mobile phase of acetonitrile- acidic water(17:83), acidic water for 0.02 mol ? L-1potassium dihydrogen phosphate and 0.0148 mol ? L-1 heptane solution by mixing equal amounts of sodium, with 10% phosphoric acid system PH adjusted to 2.8, the flow rate was 0.3ml ? min-1,check the wavelength 260 nm, the column temperature was 30 ℃, the injection volume 5μL,determine the content of strychnine and brucine.(3)Determination of ingredients in rat plasma:The pill respectively three prescription into small particles, Gavage after suspension with water, take 0.5ml blood from the bottoms of the rat`s eyes before dosing and after dosing 10, 20,30, 40, 60, 90, 120, 180, 300, 480, 600, 720 min, placed the blood in a centrifuge tube anticoagulant, 4000 min centrifugal 10 min, The upper plasma under alkaline conditions by methyl tert butyl ether extraction for two times. And then injected into the ultra high performance liquid chromatography. Chromatographic conditions : Waters Acquity UPLC BEH C18 column(2.1×100mm, 1.7μm); mobile phase: acetonitrile- acidic water(17:83), acidic water: 0.02 mol ?L-1 potassium dihydrogen phosphate and 0.0148 mol ? L-1 sodium equal mixture of heptane and adjusted with 10% phosphoric acid of p H 2.8; flow rate of 0.3m L ? min-1; detection wavelength260nm; column temperature was 30 ℃; injection volume 2μL. Determine the content of strychnine and brucine in the blood of the rats.Results: Through experiments, the following results are obtained:(1) There is a relationship between material properties and dissolution parameters-- Y20min=0.529 + 0.182A- 0.106B-0.133 C + 0.57AD(Where Y represents 20 min preparation time for each prescription Strychnine dissolution percentage, A is the ratio of fats and oils extracted material; B is the ratio of starch extracted material; C for extraction ratio of fiber materials; extraction ratio D resin materials). It can be seen, fiber and starch material dissolution rather ingredient disabilities promoted contrary,fats and oils and resins to inhibit the dissolution of strychnine effect.(2)tongmai pill formulations in three different models, prescription2,4,5 the average strychnine plasma concentration of prescription2, 4, 5 is about 30 min, 40 min and 60 min, the metabolic rate of the three groups of rats had significant differences and consistent with the in vitro dissolution rate of speed in the rate of prescription2 faster than prescription 4, prescription 4 is greater than prescription 5.Conclusion: Through experiments and analysis, preliminary conclusions are as follows:(1)Between material properties and dissolution parameters medicine quantitative relationship,consistent with Our previous findings. Where the fiber material and starch material on the toxic components of strychnine and brucine promoted dissolution, while fats and oils and resin materials to both inhibit the dissolution of the toxic components of the role.(2)Material properties in the release rate of toxic components has a decisive influence, so the attenuation mechanism tongmai pill formulation studies further elucidate the mechanism of the material properties of attenuated forms, also proved the medicine auxiliary unified theory.