The Absorption Kinetics of Main Constituents from Triptergium Wilfordii Hook.f
|School||Nanjing University of Traditional Chinese Medicine|
|Keywords||Tripterygium Triptolide Tripterine Rat in vitro everted gut sac model Rat intestinal perfusion model Liposomes|
Oral administration is the most commonly used clinical dose absorbed drugs play a role, and to produce a therapeutic effect or toxicity occurs premise and key, intestinal absorption characteristics of the study drug design, drug efficacy and toxicity of oral pharmaceutical dosage form having significance. Tripterygium drugs commonly used in clinical treatment of rheumatoid arthritis and other autoimmune diseases, Triptolide and tripterine the Tripterygium the main active ingredient, with a wide range of pharmacological activity for Tripterygium research focused on the pharmacological effect of the anti-inflammatory, anti-tumor mechanism, while rarely reported their process in vivo. Tripterygium wilfordii extract and its main ingredient intestinal absorption kinetics and to improve tripterine liposome technology of intestinal absorption, provide the basis for the rational use of drugs of the Tripterygium new dosage forms of research as well as clinical safety. 1 Tripterygium principal component in the physicochemical properties Tripterygium the diterpenoid active ingredients of the most representative Triptolide and triterpenoid active ingredient tripterine physicochemical properties by measuring their solubility and oil-water partition coefficient, visits solubility and membrane permeability, provide the basis for further experiments on the drug absorbed into the body to make a preliminary forecast. Results lower triptolide water-soluble, log P 0.58, good permeability, partition coefficient in the range of pH1.2-9.0 pH value, according to the \Road have good absorption; tripterine solubility and permeability are poor, is a Class IV drugs in the BCS classification criteria, speculated that the absorption in the body may be poor. Biological samples analysis methodology to establish establish Tripterygium extracts and monomer triptolide, the UPLC analysis method of tripterine valgus the gut sacs samples and intestinal perfusate samples by methodological study, specificity , linearity, recovery, precision and stability are in line with the requirements of The method is rapid, sensitive, accurate, and laid a foundation for these compounds in vitro and in vivo absorption experiments. Triptolide intestinal absorption kinetics study the establishment of isolated rat vitro everted gut sac model and rat intestinal perfusion model by in vitro method and the body wears, research and compare the monomer and extraction of triptolide The the matter two forms of administration under the intestinal absorption characteristics and differences. The results show that Triptolide each bowel in the rat have good absorption, the general trend of the duodenum, colon, jejunum and ileum order descending order, but no special absorption site; the test of time and concentration range within, in line with the zero-order absorption rate, possibly passive diffusion; Tripterygium extract other ingredients did not affect the intestinal absorption of Triptolide Triptolide absorption and monomer administered under the administration of the extract similar. 4 tripterine intestinal absorption kinetics by turning away from the in vitro intestinal sac model and in situ intestinal perfusion model to study and compare to Tripterygium red pigment in the monomer and extract these two forms of administration under the intestinal absorption characteristics differences. The results indicate that poor absorption in the intestine, tripterine between different bowel absorption performance, absorption absorption was significantly greater than in the duodenum and jejunum, ileum, colon, duodenum and jejunum obvious the difference between the rest of the bowel has significant difference; zero order absorption rate, within the test time and the concentration range likely to passive diffusion; other components in the extract has no effect on the intestinal absorption of tripterine with single body compared to extract tripterine intestinal absorption did not differ significantly. 5 of liposomes tripterine the preparation and its intestinal absorption kinetics of water solubility and poor permeability, tripterine poor intestinal absorption using liposome technology to improve tripterine intestinal absorption, establish tripterine liposome preparation method,, and pharmaceutics characterization of by liposomes tripterine intestinal absorption characteristics inspect. Liposome drug content determination method and the micro-column centrifugation method for determination of encapsulation efficiency; using ethanol injection prepared tripterine liposome encapsulation rate as the index of the prescription process single factor, orthogonal successfully tested to optimize the preparation process to determine the optimum process: soybean lecithin dosage 300mg tripterine dosage 30mg, cholesterol dosage 80mg, Twain the -80 concentration of 0.5 mg · mL-1, the volume of the water phase 40mL; prepared lipid lanes are not continuous spherical, uniform particle size, moderate potential, encapsulation efficiency and drug loading, stable nature; rat intestinal perfusion model investigated the tripterine liposomes intestinal absorption characteristics, the results between a different bowel uptake of liposomes in the same monomer prototype; the comparative monomer tripterine liposomes in each bowel absorption were significantly improved, effective improvement tripterine factors in intestinal absorption. To sum up Triptolide Tripterygium two main components, absorbed in the intestine is better, poor intestinal absorption of tripterine liposome technology, improved the tripterine intestinal absorption. Intestinal absorption kinetics study is the oral medicine formulations designed to provide a reliable basis.