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Study on the Preparation of Chrysophanol-Hydroxypropyl-β-Cyclodextr in Inclusion Complex and Its Pharmacokinetics

Author: ZhengXiaoXia
Tutor: ZhangDanCan
School: Hebei North University
Course: Pharmacology
Keywords: Chrysophanol - hydroxypropyl -β- cyclodextrin - Inclusion Orthogonal Stability Dissolution Pharmacokinetics
CLC: R285
Type: Master's thesis
Year: 2010
Downloads: 411
Quote: 0
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Abstract

Rhubarb phenol (Chrysophanol, Chry) is the rhubarb, Polygonum cuspidatum, Polygonum multiflorum, etc. Polygonaceae Branch plants in the one kinds effective monomer, belonging to anthracene-quinone class of compound, a has antibacterial, hemostasis, anticancer, cough, diuretic, etc. pharmacological effects. According to the literature reports, the rhubarb phenol but also to eliminate in vivo free radicals, there are obvious anti-aging and the promotion of learning and memory role. Chrysophanol belong to liposoluble compounds, easily soluble in methanol, ethanol, acetone and other organic solvents. Since chrysophanol solubility in water is extremely small, bioavailability is not high, limiting the rhubarb phenol in the clinical in the application of. Therefore, in order broaden the rhubarb phenol the application range of, for the clinical medication to provide selectable Application of formulations, the subject studied the rhubarb phenol of the package co-technologies. Packet an aggregate technology because of can greatly improve the poorly soluble Xing drug solubility, while the widely used in poorly soluble Xing drugs dosage forms research field. This topic Select the hydroxypropyl-β-cyclodextrin for the package an aggregate materials, adopt the best preparation method and process will be rhubarb phenol made of clathrate, order to increase its the solubility in water, and examine chrysophanol Inclusion Compound of stability of the, in vitro dissolution degrees. While observing the chrysophanol Inclusion Complex in the animal vivo's pharmacokinetic characteristics, get pharmacokinetic parameters, in order to rhubarb phenol Inclusion Complex injectable agent for developed by provide the basis for. Chrysophanol clathrate preparation methods and process Study: in order to rhubarb phenol - hydroxypropyl-β-Cyclodextrin Inclusion Complex packet combined rate with the the closing too rate as the index, in the same process conditions, under, comparative stirring method, grinding Legalist with the ultrasonic method of the package co-effect, in order to determine more appropriate for the of the preparation method thereof. Adopt orthogonal test pairs of the Preparation of main craft conditions of carry on screening, investigating rhubarb phenols with hydroxypropyl-β-cyclodextrin mass ratio, solvent concentration, the package an aggregate time and temperature and other factors on package an aggregate process the impact of, optimizing the hydroxypropoxyl yl-β-cyclodextrin inclusion chrysophanol the conditions for. The same time using ultraviolet spectrophotometry, thin layer chromatography Method and Phase solubility method verify the Inclusion Complex formation. The results Showing: Rhubarb phenol and hydroxypropyl-β-cyclodextrin optimum packet bonding process is: That the rhubarb phenol and hydroxypropyl-β-cyclodextrin mass ratio of 1:60, the solvent ethanol concentration of 50% , inclusion time 2h, inclusion temperature yes 30 ℃, rhubarb phenol - hydroxypropyl-β-cyclodextrin inclusion compound packet an aggregate rate of up to 64.11%. Phase solubility curve for the AL-type. When the HP-β-CD's mass fraction was 20%, the can make Chry increased solubility 102.66 fold. Chrysophanol Inclusion Complex stability of the and in vitro Dissolution degrees research: To compare the rhubarb phenol with rhubarb phenol Inclusion Complex light stability, thermal stability and wet stability. Adopt Dynamic Dialysis technology research rhubarb phenol Inclusion Complexes in vitro dissolution degrees, the observe its drug release performance. The results Display: In the light, heat and Wetland the factors that under the influence of, rhubarb phenol clathrate the stability of the representing an monomer drugs have improved significantly. Chrysophanol Inclusion Complexes in vitro dissolution performance is good, showing that the a certain degree of sustained release characteristics of. Animal in vivo pharmacokinetic Study: selection of two kinds animal, respectively, expedition rhubarb phenol formulations the pharmacokinetics of, to give rabbit ear edge of the intravenous injection of rhubarb phenol solution or an rhubarb phenol inclusion compound aqueous solution, continuous determination of at each time point plasma drug content, the analyze pharmacokinetic parameters of and septal compartment model. Mice were given tail intravenous injection of rhubarb phenol solution or an rhubarb phenol inclusion compound aqueous solution, at different time point determination mouse plasma, heart, liver, brain, spleen, lung, kidney middle content of chrysophanol, research rhubarb phenols and rhubarb phenol package adduct in the mouse vivo's tissue distribution characteristics of. The results Display: rhubarb-phenols and Inclusion Complex in rabbits in vivo pharmacokinetic process are in line with two-compartment model, both of which, the average elimination half-life (t1/2β) respectively for the 9.093h and 13.075h, speculated that clathrate's elimination process the larger yellow phenol slightly slower. Adopt two sample t test pairs of rhubarb-phenols and Inclusion Complex in mouse vivo various organization's content of were statistically analyzed, intravenous injection in mice Inclusion Complex with injecting chrysophanol comparison, in the blood, liver and the the brain drug content there is was significantly Xing difference (p lt; 0.05). Summary, the use optimized process conditions for Preparation of rhubarb phenol - hydroxypropyl-β-cyclodextrin inclusion compound, the package an aggregate rate is high, craft stability, simple operation. Chrysophanol is suitable to use hydroxypropyl-β-cyclodextrin inclusion, solubilization effect is obvious. Rhubarb phenol clathrate significantly improves the the stability of drugs and in vitro dissolution degrees. Rhubarb phenol inclusion compound in rabbits in vivo's The pharmacokinetic process for the two-compartment model. Chrysophanol made of clathrate after the can significantly improve the mouse brain's drug content.

Study on the Preparation of Chrysophanol-Hydroxypropyl-β-Cyclodextr in Inclusion Complex and Its Pharmacokinetics

Abstract

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