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Ginkgo biloba extract (Ginkgo biloba extract GBE) is based on traditional Chinese medicine Ginkgo biloba extract the active ingredients as the raw material. The main component of the total flavonoid glycosides and terpene lactones. Quercetin, kaempferol, isorhamnetin three of the flavonoid glycoside aglycone, scavenging oxygen free radicals have a significant effect on the cardiovascular and cerebrovascular diseases, high cholesterol, high blood pressure; including ginkgo terpene lactones lactone A, B, C, M, J and bilobalide, is a potent platelet activating factor (PAF) antagonists, can reduce blood viscosity, improve blood flow. Recent studies have shown, GBE can improve cognitive dysfunction and treatment of senile dementia. Senile dementia (senile dementia, SD) [3] refers to the old age of smart, in essence, continuing damage, which is caused by organic brain damage essentially irreversible lack of intelligent and social adaptation ability to reduce . Its pathogenesis is very complex, and may be provided with cholinergic, monoaminergic, neuropeptide can be a variety of neurotransmitters and modulation was dysfunction. GBE clinical route of administration is intravenous and oral formulations. Oral administration is convenient, but there is a serious first-pass effect, low bioavailability. Subcutaneous injection pain and should not be self-medication. Therefore, the development of an effective and convenient route of administration is to raise the concentration in the brain, to enhance the therapeutic effect of a selection. Intranasal administration in recent years, one of the most studied route of administration, not only has the advantage of rapid drug absorption, no first-pass effect, convenient administration, but also has the characteristics of drug delivery to the brain, which is expected to improve GBE brain concentration, and enhance the control effect on Alzheimer's. Modern forms of Chinese medicine for nasal administration is the main nasal drops, but due to the secretion of nasal mucus and cilia movement, so that drugs in the short residence time in the nasal cavity, reduce the bioavailability. Therefore, this project intends to GBE made nasal in situ gel was from body mucosal absorption and evaluation of its in vivo after administration of the pharmacokinetics of nature to provide an effective and convenient new agents for the clinical application of GBE. The main research contents: 1 GBE in vitro assay development HPLC-UV method for the determination of the content of GBE TFG. Agilent C18 column, mobile phase was methanol: 0.4% phosphoric acid (50:50, v / v); flow rate: 0.8 mL · min-1; detection wavelength: 360 nm; column temperature: 30 ° C: injection volume: 20 ul . HPLC-ELSD method for the determination of the GBE terpene lactone content. Elite C18 column, mobile phase: methanol: tetrahydrofuran: water (25:10:65, v / v); flow rate: 0.6 mL · min-1; flow rate of carrier gas (N2): 2.7L · min-1; column temperature: 35 ° C; drift tube temperature: 115 ° C. Ginkgo biloba nasal in situ gel prescription screening as an index to the viscosity of the adhesive force, Carbopol 934, HPMC as the carrier prepared in situ gel results in 0.8% Carbopol 934 and 1.5% HPMC. Ginkgo biloba extract is very slightly soluble in water. In this study, the phase solubility study GBE different volume fractions of HP-(?)-CD lower phase solubility. The remaining materials to nose ciliotoxicity small, does not affect the stability of the drug to the principle of prescription. Ginkgo biloba nasal Study on Preparation of in situ gel room temperature to take ginkgo biloba extract 4.5 g with double distilled water to dissolve the HP-(?)-CD solution, stirring constantly to dissolve, add the prescribed dose group minutes, stirring to dissolve, HPMC1.5 g, so that the hydration swelling, then Carbomer 9340.8 g dissolved therein was stirred for about 24 h, so that the full swelling. 1 mol · L-1 NaOH solution to adjust the pH to 4.3. Promote absorbent the GBE-ISG absorption of sheep nasal mucosa in vitro using Franz diffusion cell, select 1% Tween -80,0.5% borneol, 1% Azone, and then were intranasal absorption test. A result, the mucous membrane permeation rate of penetration enhancers: 1% Azone gt; 1% Tween gt; 0.5% borneol. With Azone increasing concentration, drug mucosal absorption gradual increase in the absorption process in line with the Weibull kinetic equation. 5 Ginkgo biloba nose with a safety evaluation of the in situ gel using toad palate model visits Ginkgo biloba nasal gel and accessories ciliary movement, to evaluate the nasal toxicity of the preparation. The results showed that no adverse effects of the Ginkgo biloba nasal gels and accessories. Ginkgo biloba nasal in situ gel preliminary preparation of Stability three batches of GbE-ISG preparation, preliminary stability test (heat test, light test, high humidity test), initially identified the product can be stored at room temperature . 7 Ginkgo biloba situ gel pharmacokinetic study in rabbits to establish a HPLC method for the determination of quercetin plasma concentration. Agilent C18 column (250 mmx4.6mm, 5μm); mobile phase was methanol -0.4% phosphoric acid (60:40, v / v); detection wavelength was 368 nm; injection volume of 20 ul. By the methodological evaluation, extraction recovery method recovery and precision measurement requirements are in line with biological samples. Determination of six rabbits with oral Ginkgo biloba and nasal administration GBE-ISG plasma concentration of quercetin, to calculate the pharmacokinetic parameters. A result, the the Ginkgo biloba nose situ gel and tablets process in vivo are in line with the single compartment model, Ginkgo biloba nasal in situ gel Tmax was approximately 1.22 h, Cmax is approximately 779.30μg · L-1; the control group Ginkgo biloba agent Tmax approximately 1.92h, Cmax is approximately 452.79μg L-1, the relative bioavailability of 77.52%. Conclusion: The Ginkgo biloba extract preparation nose pH-sensitive in situ gel formulation is reasonable, the process is feasible, facilitate quality control, release, good stability, small ciliotoxicity, fast absorption, reaches the purpose of the experimental design.
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