| The total flavonoes of Hippophae rhamnoides (TFH) was extracted from the efficacious parts of the natural officinal plant called Hippophae Rhamnoides L., contains isorhamnetin (Isor), quercetin (Quer), isorhanmetin-3-β-D-glucoside ect. The TFH can depress the hypertension placidly, has a good curative effect in coronary heart disease and angina, and decrease side effect. But there are lots of resinic matter in its raw material, the total flavonoes are contained only 19% about, which is disadvantageous to make a good sustained-release preparation.Cyclodextrin (CD) is cyclic oligosaccharides consisting of 6～12 glucoses units , mostlyα,βandγ-cyclodextrins (including 6,7 and 8 glucose units respectively). They have unique characteristics and include a variety of substances to form inclusion complexes. Properties of CD inclusion complexes may be changed,so they can be applied to a variety of fields.Inclusion compound of TFH Withβ-CD making use of structure properties ofβ-cyclodextrin was studied. With the new developmental supramolecular chemistry, which is formed by host molecular and guest molecular, a guest molecular is fully or partly included in the structure space of a host molecular. With CD supramolecular theory,β-CD can extract active constituents of TFH.Using the methodology to establish two methods to determine the content of total flavones with UV spectrophotometry and the content of the Isor and the Quer with RP-HPLC. A good line a relationship in the range of 2～10μg/ml (r = 0.9999) was obtained for determining total flavones by UV spectrophotometry, The average recovery was 92.85%. A good line relationship in the range of 2～10μg/ml (r = 0.9991) was obtained for determining the Isor and 1.6～8.0μg/ml (r = 0.9993 ) was obtained for determining the Quer by RP-HPLC.Three methods of ultrasonic, solution and trituration were adopted in this Paper. The yield of inclusion and inclusion rate of TFH was used as a criterion in the study. The method of solution is obviously much better than other methods. The uniform design method was used to establish the optimum prepared conditions for inclusion, as follows : mole ratio of TFH toβ-cyclodextrin to be l:4, heating temperature 60℃and stirring 3 hours. The inclusion rate reached 30.86% .The formation of inclusion compound of TFH withβ-cyclodextrin was demonstrated by TLC, microscopic pictures, and polarimetry.The active constituents of TFH have been isolated from the TFH withβ-cyclodextrin, the content reached 42.3%. With the result of identifying by TLC, indicating that the property of the Isor and Quer has no change. And the content of the Isor and Quer in TFH increased largely with RP-HPLC.Using the pure TFH to prepare TFH sustained-release tablet, designing and optimizing the prescription. Choosing Hydroxypropyl Methyl Cellulose(HPMC)as framework materials,lactose as diluents and binders. The TFH sustained-release tablet can constantly sustained release lasting 12 hours in vitro. The determination method of the dissolve dose of TFH sustained-release tablet was set up and evaluated by UV method. The rotation basket method was used in vitro dissolution determination. The solvent was 0.5% Tween-80 solution and the temperature was constant 37±0.5℃, stirring rate was 100r/min.Take out samples at different times, calculate the accumulative dissolution. The accumulative dissolve dose of TFH sustained-release tablet is 92.2±1.59% within 12h. The release law of TFH sustained-release tablet in vitro was studied initially. The drug release pattern is in accord with Zero-order and Ritger-Peppas model. The quality evaluation study of TFH sustained-release tablet was studied.A HPLC method for determinating the TFH concentration in the dog plasma was established while the method was suited for studying pharmacokinetics in dog. The TFH general tablet was used as the reference preparation, the pharmacokinetics study of TFH sustained-release tablet in the dog was made after oraling the TFH general tablet and the TFH sustained-release tablet.The study indicates that a new extracting method of CD-Supramolecular extracting chemical constituents in TFH has been established, which is reliably feasibility and simplified. This inclusion suppies a theory base for the research of Traditional Chinese medicine -CD supramolecular. |
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