| The natural medicine—Puerarin which have extensive curative effect in cardiovascular disease were choosed in this dissertation as the research object and the synthesizing approach of Sulfonic Acid Sodium is adopted to modify its structure to improve it's physical and chemical performance such as solubility,and fundamentally solve the problem of low bioavailability caused by poor water. Crystalline forms with better drug eddect will screened through the preliminary study of its crystalline forms. Meanwhile, through promoting this research,the advantage of Puerarin resource in Chongqing can turn into the economic advantage with bring about an advance in social economy of Chongqing.To improve the poor solubility, low oral bioavailability and restriction in the clinical application of Puerarin, utilizing the theoretical ground of the synthesizing approach of Sulfonic Acid Sodium, two process of Sulfonation reaction and salt-forming reaction were adopted to modify its structure. The derivative of Puerarin was separated and purified with TLC and silica gel column chromatography. Through synthesized structure analysis of spectroscopy methods such as U.V.,I.R.,1HNMR,13CNMR,element-analysis,the derivative was confirmed as a innovative compound that not been reported before.Aiming at product receiving ratio, through orthogonal tests and single-factor experiment design, we got the best conditions of synthesize: reaction temperature was 40℃, reaction time was 1h, the mol ratio of Puerarin and oil of vitriol was 1:1.4. The derivative of Puerarin from the reacting was separated and purified with silica gel column chromatography and TLC and the condition of separating and purifying was investigated.By investgating physical and chemical performance of the derivative, the following results were obtained: compared to Puerarin, the melting point of the derivative was decreased to 183.2±1.5℃result from the introduction of Sulfonic Acid Sodium at the ortho positions of 4'location;alcohol solubility of the derivative is much lower than Puerarin( a decrease of 85.4%,97.8% and 99.6% for methanol, ethanol and normal butyl alcohol respectively, compared to Puerarin,but increased as much as 2.9 times in Banana Liquid),and water solubility is much higher than Puerarin( as much as 159.2 times than Puerarin); pKa value of the derivative is 7.72,exbiting alkalescence and comply with fundamentality of drug compounds;oil/water distribution coefficient of the derivative (P)is smaller, showing that its water solubility is better than alcohol solubility; from the value transformation trend of P, it can be concluded that the distribution behavior of the drug can be changed by adjusting its pH; under the experimental condition, the stability of the derivative is poorer than Puerarin, resulting from the deliquescence of the derivative which is caused by water adsorption in air, so airproof keeping is needed; rotary power of both Puerarin and its derivative are similar, and both are dextrorotation with 0.190 and 0.182 respectively, predicting Glicosyl group existing in the derivative, because all the five chiral carbon atoms are all in the Glicosyl group.Primary study for crystal structure is presented, and we obtained three types crystal structure: amorphous, acicula and irregular hexahedron with diagonal, providing a reference for the sceening of more efficient drug.The derivative prepared in this paper has better water solubility compared to Puerarin. Therefor, by the structure modifying from sulfonation reaction,we can improve the physical and chemical performance of the Puerarin such as water solubility, which is propitious to enhancing its bioavailability and convenient for continuous drug development. |
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