| Puerarin (4', 7-dihydroxy-8-C-β-D-gluco-isoflavone) is one of the important active components of pueraria lobato (Wild) Ohwi. Some research shows that puerarin has a variety of pharmacological activities, such as reducing vascular resistance, improving circulation of brain and coronary artery, reducing myocardial oxygen demand, regulating the activity of NOS, antioxidation, anticancer and inducing cancer cell differentiation. Moreover, it has the advantages of small toxicity and quick metabolism and so on.However, the isoflavones'own structural characteristics causes puerarin has the bad water-solubility and liposolubility, and its poor bioavailability. So the clinical application is restricted.To improve the above-mentioned shortcomings, we selected puerarin as the lead compound and the acylation synthetic process to prepare Lactic Acid puerarin according to the reagent's structure and the reaction of acylation characteristics. Then we confirmed the derivates'structure by using UV, IR and NMR.In the process optimization aspect, finally, we determined the optimum conditions: The preparation of raw materials molar ratio is 1.4:1; The reaction temperature is 20℃; The reaction time is 100 min and the solvent dosage of Pyr. is 1.0 ml.We carried on the preliminary study on the physico-chemical property and stability of puerarin derivatives. We chose the appearance, TLC, HPLC and moisture absorption as evaluation index on the stability aspect. In the physico-chemical property study, we observated the effects of temperature, humidity, light, oxygen in the air and pH etc for puerarin derivatives. The results indicated that the derivatives were instable in the high temperature, high humidity and highlight. They were sensitive about the atmosphere. They were instable under the alkaline condition, too. When we acylated the 4'-phenolic hydroxyl group in the molecular structure of puerarin, the derivatives'physico-chemical properties had some changes. Their melting point was degraded, and the optical activity was increased by comparing with puerarin. But all of them were d-isomers. The solubility in water to some extent boosted; their lipoids/water distribution coefficient increased, and pKa had some change. Compared with puerain, it was demonstrated that water-solubility and liposolubility of the derivatives which had processed structural modification was improved in some extent.The Anti-myocardial ischemia animal experiments indicated that the derivatives can obviously antagonize the myocardial ischemia of rats caused by hypophysin. The derivatives can resist arrhythmia of mice induced by chloroform in the anti-arrhythmia animal experiments. In addition, it could apparently improve the hemorheological correlated index of acute hyperlipemia rats in the research about the hemorheology of hyperlipemia rats. All of the researches showed that the effects of the derivatives were more conspicuous than puerarin.The acute toxicity testing finding showed that after the mice were lavaged with maximum concentration and maximum capacity of lactic acid puerarin's thick liquor, lactic acid puerarin didn't have conspicuous toxic reaction.In summary, the properties of the derivatives which were synthesized based on the puerarin's molecular structure, such as, physico-chemical properties and biological activity , and so on, have been improved. So they can improve their bioavailability and enhance pharmacological activity. At the same time, this paper also provides theoretical basis and useful data for praeparatum development and clinical application in future.
|
PDF Full Text Request