The Absorption Kinetics Of Main Constituents From Triptergium Wilfordii Hook.f

Oral administration is the most common clinical drug delivery. Absorption is the prerequisite for drugs to exert therapeutic or toxic effects. Intestinal absorption research is important for dosage form design, efficacy and toxicity study of oral drugs. Triptergium wilfordii Hook.f (TwHf) is used as an herbal remedy to treat arthritis and other autoimmune deseases. Triptolide and tripterine are the major components in TwHf, which possess extensive pharmacological activitities. Currently, the research mostly focuses on the anti-inflammatory and antitumor efficacy mechanism, while their ADME process study is rarely reported. Therefore, the absorption kinetics of main components from TwHf is studied, and the tripterine liposome is prepared to improve the intestinal absorption. It can provide the basis to design new dosage forms and derect safe and reasonable clinical application of TwHf.1 Physical and chemical properties of main components from TwHfThe physical and chemical properties of triptolide and tripterine, which are the most representative active components of diterpenes and triterpenoids, are studied. The solubility and membrane permeability are determined to provide the basis for further experiments, and their intracorporal absorption are predicted. Triptolide is low water-solubility, but has well membrane permeability with log P of 0.58 in octanol/water system and the pH of buffer solution had no influence to its distribution coefficient. It is speculated that triptolide could be well absorbed in general intestinal according to the "Five Rules". Tripterine has poor solubility and permeability, belonging to class IV of the BCS, which might be poor absorbed in vivo.2 Establishment of biological sample analytical methodsThe analytical methods for triptolide, tripterine and TwHf extracts in biological samples were established. The specialization, linearity, recovery, precision and stability are investigated and results are satisfactory. The methods are rapid, sensitive and accurate, which meet the requirement of the following experiments.3 The absorption kinetics of triptolideThe in vitro everted rat gut scas model and in situ perfused rat intestinal model are established. The absorption mechanism of triptolide and its in extract is studied and their differences are compared through in vitro and in situ experiments. The results show that triptolide could be well absorbed in general intestinal tract. The absorption tends to be decreased in the order of duodenum, colon, jejunum and ileum, but without specific absorption site. The absorption of triptolide conforms to the zero order rate process and displays the passive diffusion mechanism in the test of time and concentration range. There are no obvious differences between triptolide and its in extract. Other components in the extract of TwHf have no effect on the absorption of triptolide.4 The absorption kinetics of tripterineThe absorption mechanism of tripterine and its in extract is studied and their differences are compared using everted gut scas model and perfused rat intestinal model. The results show that tripterine is rarely absorbed in the intestine. The absorption in duodenum and jejunum is significantly larger than that in ileum and colon. There are no significant difference between duodenum and jejunum, while other segments of intestine were significant different. The absorption of tripterine conforms to the zero order rate process and displays the passive diffusion mechanism in the test of time and concentration range. There are no obvious differences between tripterine and its in extract. Other components in the extract of TwHf have no effect on the absorption of tripterine.5 Study of tripterine liposome and its intestinal absorption kineticsAs the poor solubility and permeability, the intestinal absorption of tripterine is poor. We use liposome technology to improve the absoption of tripterine. Tripterine liposome is prepared, and the properies are verified. Finally, the absorption of tripterine liposome is investigated. The method for content determination is established and minicolum centrifugation method is employed to determine the entrapment efficiency. Tripterine liposome is prepared by ethanol injection method with encapsulation efficiency as index. After screened by orthogonal experimental design, the optimized formula is as the follows: 300mg of soybean phosopholipids,30mg of tripterine,80mg of cholesterol, 0.5mg·mL-1 of Tween-80, and 40mL of water. The tripterine liposome is intact spherical or oval shaped ball vesicle, with uniform particle size and moderate potential. The encapsulation efficiency and drug loading of the optimized liposome are high. We use in situ perfused rat intestinal model to study the absorption mechanism of tripterine liposome. Results show that the absorption differences in four intestinal segments of liposome are same as that of tripterine. Compared with tripterine, the absorption of liposome in intestines is significant increased. Tripterine liposome effectively improves tripterine absorption in the intestine.In conclusion, triptolide is well absorbed in intestine, while of tripterine, the absorption is poor. The absorption is significantly improved by liposome technology. Intestinal absorption kinetics can porvide a method for profound study on new dosage forms.