Preparation And Research On Berberine Hydrochloride-Phospholipid Complex

Phospholipid complex is a new drug delivery system in recent years. Many natural drugs, especially some types of flavonoids, may exhibit a marked affinity to phospholipids. The drug-phospholipid complex, so called phytosomes, may show some superior chemicophysical properties and enhance the absorption of drugs. Berberine hydoridrochle was discovered of its good function on cardiovascular disease, gastrointestinal neurosis and diabetes. Due to its bad liposolubility, which caused its low bioavailability, the new clinical application of Berberine hydoridrochle is severely effected. In this paper, Berberine hydrochloride-phospholipid complex was prepared to improve its oral absorption ability. The research focused on the pharmacokinetics of Berberine hydrochloride-phospholipid complex and its physicochemical and biological characteristics on the basis of optimizing the preparation conditions. The full work includes the following contents:1. Preparation of Berberine hydrochloride-phospholipid complex. The effect of factors such as solvent, reactive temperature, reactive time, concentration of reactants and the ratio of reactants on this reaction was investigated and the prescription composition was screened out by orthogonal design. The best conditions were obtained as follows: the solvent was 1,4- dioxane, the reactive temperature was 60℃, the reactive time was 3h, the concentration of reactants was 1.5mg·mL-1 and the ratio of Berberine hydrochloride to phospholipid was 1:1.2. The physicochemical characteristics, structure confirmation and formation mechanism of Berberine hydrochloride-phospholipid complex were researched. The complex was characterized by infrared spectrum and differential scanning calorimetry. A change in the transformation temperature was showed in DSC spectra. And there was a remarkable change in Infrared spectra of the complex. Particle analysis and morphologic observation showed that the complexes were spherical vesicles when dispersing in water. The solubilitys of the Berberine hydrochloride and Berberine hydrochloride-phospholipid complex were determined in water and n-octyl alcohol. The results showed that the solubility of the complex in n-octylalcohol is 11times than Berberine hydrochloride.3. Pharmacokinetics research on Berberine hydrochloride-phospholipid complex: An HPLC method for determination of the concentration of Berberine hydrochloride in rabbit plasma was established. Single oral dose pharmacokinetic parameters and relative bioavailability were evaluated in rabbit followed by double cycle crossover design. New Zealand rabbits were used as the tested animals and Berberine hydrochloride was used as control. Relative bioavailability was (248.4±3.4)% between Berberine hydrochloride-phospholipid complex and Berberine hydrochloride. The results showed that the complex promoted the absorption of Berberine hydrochloride and increased its oral bioavailability.