Preparation, Characterization Evaluation On Murraya Exotica L. Leaves Flavones-hydroxypropyl-β-cyclodextrin Inclusion Complex

Murraya exotica L. leaves flavones are active compounds extracted and separated from traditional Chinese medicine named murraya exotica L. leaves. The content of total flavones is more than 90%, and they have significant treatment effect on acute myocardial infarction and diabetes. However, the low polar as well as poor water solubility seriously influence the in vivo absorption of murraya exotica L. leaves flavones, which limit its clinical application.Cyclodextrins (CDs) has hollow cylindrical structure and can include some small molecule drugs in its special cavity. For the exterior hydrophilic surface of CDs, inclusion complexes can have a good wettability, which will improve the water solubility of the poorly soluble drugs. The most often used as solubility increaser is hydroxypropyl-β-cyclodextrin (HP-β-CD), which has features of good water solubility, good thermal stability and low toxicity. It will improve guest's water solubility, dissolution velocity and bioavailability.At home and abroad there is no research report relate to murraya exotica L. leaves flavones-hydroxypropyl-β-cyclodextrin inclusion complex. In this thesis, the JK-HP-P-CD inclusion complex was prepared with solution-agitating method. The primary experiments and results were listed below. (1) The impact factors of inclusion reaction have been investigested and the main factors were identified. The preparation procedure was optimized by orthogonal design. The results showed that the best reaction conditions for inclusion are:the ratio of host/ guest molecules was 1:1, inclusion temperature was 25℃, inclusion time was 2h. The inclusion complex was identified by differential scanning calorimetry, X-ray diffraction and infrared spectrometry, respectively.(2) It was also comfirmed by phase solubility method that a 1:1 molar ratio inclusion complex of JK with HP-β-CD could be formed, and the phase diagram was AL type. The water solubility of JK-HP-β-CD increased 43.9 times compared to that of the free drug. According to the rotating basket method described in ChP 2005, the in vitro dissolution of three physical state with 0.2% SDS as dissolution medium was determined. The results demonstrated that dissolution velocity of inclusion complex was significantly faster than that of both physical mixture and free drug. The drug conatined in inclusion complex could release completely within 15 minutes.(3) Methods are established to determine the concentration of JK in plasma with HPLC, and the pharmacokinetics of JK and JK-HP-β-CD inclusion complex in rats through oral administration were studied. It was found that the concentration of JK in plasma and bioavailability of inclusion complex was significantly improved compared to that of free drug.