| Ginkgo biloba Extracts (GBE) are thought to have two groups of effective compounds: flavonoids and triterpene lactones,which have many pharmacological activities,including inhibitation of platelet aggregation, expand blood vessel, hypotensive, antioxidant and so on, have wide prospect in application of cardiovascular and cerebrovascular diseases.The oral absorption were limited because the bad hydrophilicity and lipophilicity of Ginkgo biloba flavonoids.The phospholipid complex is a preparation technique which can improve the drug bioavailability in recent years, so in this study Ginkgo Biloba extract was taken as a model drug and total flavonoids was taken as index, Ginkgo Biloba extract phospholipid complex was prepared to improve the affinity for cellular membrane, multivariant-phospholipid complex was prepared through adding another water-soluble carrier-poloxamer 188 on the basis of phospholipid complex to acceletate the dissolution speed and rate by using solvent evaporation method to improve its oral absorption and bioavailability.In this paper, the physico-chemical property of Ginkgo biloba flavonoids, preparation technology of phospholipid complex and multivariant-phospholipid complex and its pharmacokinetic were studied systematically and deeply, which could provide reference for the research of Ginkgo biloba Extracts preparation. The paper include several sections as below:1. The preformulation study of Ginkgo biloba flavonoids:(1).To establish accurate, high-performance method to determine the concentration of Ginkgo biloba total flavonoids of Ginkgo Biloba Extracts, chromatographic condition is:column; Hedera ODS-2 column (250 mm×4.6 mm i.d., particle size 5μm), mobile phase; methanol-0.4%phosphoric acid (60:40, v/v), flow rate; 1.0ml/min, detector wave length; 370nm, sample size; 10μl, number of theoretical plates can't be lower than 2500(calculated by quercetin). The method have strong specificity, is convenient and accurate.(2).Physical-chemical properties in vitro studies:The dissolution of Ginkgo biloba total flavonoids is 219.6μg/ml in water, it showed that it belong to the drugs that extreme slightly dissolve in water. The oil-water partition coefficient of the total flavonoids in water is 1.23. In gastrointestinal tract environment, it's stable, almost don't degrade after 24h.2. The research on technology of phospholipid complex, exosyndrome and the physicochemical characteristics(1). Optimize of the preparation technology of phospholipid complexA reasonable criterion of accurate evaluation-complexing rate was established during preparation of phospholipid complex, and the reaction solvent, temperature, time,the ratio of phospholipid/GBE and the concentration of GBE were examined. On the base of investigate single fator,we choose the ratio of phospholipid/GBE, the concentration of GBE and reaction time as variables, which influence notable of complexing rate.The preparation was optimized by central composite design methodology. The best preparing conditions of phospholipid complex: take dehydrated alcohol as reaction solvent at 25℃, the concentration of GBE is 10mg·ml-1, reaction time is 2h, phospholipid and GBE reaction ratio is 1:1.(2). Exosyndrome and the physicochemical characteristics of phospholipid complex.Use XRD, DSC,oil-water partion coefficient and dissolution to inspect the exosyndrome and physicochemical characteristics of phospholipid complex.The results showed that phospholipid complex was prepared successfully, the endothermic peaks and character of crystal of GBE disappeared and changed into amorphism form. Compared with GBE, the liposoluble of total flavonoids was enhanced distinctly and the dissolution was also improved, but need to improve further.3. The research on technology of multivariant-phospholipid complex, exosyndrome and the physicochemical characteristics(1).On the base of phospholipid complex, add anther water solubility carrier to improve the dissolution. Multivariant-phospholipid complex was prepared by using solvent evaporation method with dehydrated alcohol, investigated different carrier, ration and method. Poloxamer 188 was the best carrier to prepared multivariant-phospholipid complex.(2). Exosyndrome and the physicochemical characteristics of multivariant-phospholipid complex.Use XRD, DSC,oil-water partion coefficient and dissolution to inspect the exosyndrome and physicochemical characteristics of multivariant-phospholipid complex.The results showed that multivariant-phospholipid complex was prepared successfully, the the endothermic peaks and character of crystal of GBE disappeared and changed into amorphism form. Compared with GBE, the liposoluble and the dissolution of total flavonoids were enhanced distinctly at the same time.4. The research on absorption pharmacokinetics of GBE, phospholipid complex, multivariant-phospholipid complex and solid dispersion in rats(1). Establish accurate, high-performance and simple method to determine the concentration of Ginkgo biloba flavonoids in rats'plasma, chromatographic condition is:column; Hedera ODS-2 column (250 mm×4.6 mm i.d., particle size 5μm), mobile phase; methanol-0.4% phosphoric acid (60:40, v/v), flow rate; 1.Oml/min, detector wave length; 370nm, sample size; 20μl. (2). The rats were divided into four groups at random, and they were dosaged GBE, phospholipid complex, multivariant-phospholipid complex and solid dispersion, respectively.The blood concentration at different intervals was tested by high performance liquid chromatography (HPLC). The parameters of pharmacokinetics were calculated by 3P97 software.The result showed that compared with GBE, the bioavailability of Ginkgo biloba flavonoids of GBS, GBP, MGBP increased 1.69,2.25,3.05 times, respectively. It demonstrated that durg absorpotion are closely related to the hydrophilicity and lipophilicity.
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