| Chrysophanol (Chrysophanol, Chry) is one of the main anthraquinone components in rhubarb, which belongs to hydroxyanthraquinone. The experiments proved that chrysophanol could significantly inhibit the generation of lipid peroxide in rat liver and brain tissue, and could obviously reduce the content of malondialdehyde in tissue, with the correlation to the doses. In addition, chrysophanol had the obvious anti-hypoxia ability, strengthening the body’s immune function and antioxidant capacity, and improved memory disorders. As chrysophanol had a very small solubility in water, its absorption was poor, and the bioavailability was lower and stimulating effect on gastrointestine was serious, its clinical application was limited. It is urgent to prepare a new chrysophanol dosage form to enhance its medicinal value. At present, in the pharmacodynamics, the effect of single and preparation of chrysophanol on anti-aging and promoting intelligence have been studied in our department. The three formulations were prepared:nanocapsules loading with chrysophanol by polybutylcyanoacrylate (Chry-PBCA-NC), chrysophanol-hydroxypropyl-β-cyclodextrin inclusion complex (Chry-HP-β-CD) and chrysophanol liposomes (Chry liposomes). But in the pharmacokinetic, only the single and preparation of chrysophanol were studied in mice and rabbits. There was no pharmacokinetic comparison among these three chrysophanol preparations. In this topic, the release, stability and pharmacokinetic parameters of the three kinds of formulations at different dose groups in vitro were compared. The changing process of the three preparations was detected, so as to choose the optimal dosage forms, and expand the clinical application of chrysophanol preparation. Stability study:The equal doses of Chry-PBCA-NC, Chry-HP-β-CD and Chry liposomes were put in the stability tester and illumination incubator. Within10days, the thermal stability, wet stability and light stability were determined accordingly, then the appearances of extracted samples were observed and the contents were measured on0,2,5,8,10d. The stability strength of three preparations was judged by the degradation rate. The results showed as follows:The degradation rates were86.7%±0.5%,90.7%±1.3%,89.9%±0.6%respectively, when three preparations were kept for10days under the temperature of60℃, and the degradation rates were86.9%±1.0%,90.7%±1.3%,90.3%±3.1%at the humidity rate of75%. After ten days’illumination under the intensity of3000lx, the degradation rates of Chry-PBCA-NC, Chry-HP-β-CD, Chry liposomes were72.4%±1.8%,87.0%±1.1%,70.5%±2.3%respectively. After ten days, compared between three preparations, the stability of Chry-PBCA-NC was inferior to Chry-HP-β-CD and Chry liposomes.External dissolution study:The technology of dynamic dialysis was adopted to observe the external dissolution of three chrysophanol preparations by sampling after0.5,1,2,4,6,8,12,24,36,48,60,72h. The drug content was measured by high performance liquid chromatography (HPLC) method, and fitted by cumulative release percentage of drug. The results showed as follows:the sequence of the dissolution rate of three preparations was:Chry liposomes> Chry-HP-β-CD> Chry-PBCA-NC. The external release of Chry-PBCA-NC was rarely slow and its accumulated dissolution was less than20%after72h. The dissolution of chry-HP-P-CD and Chry liposomes began to rise sharply after12h, and the cumulative dissolution reached56.2%and96.1%respectively after72h. The external dissolution models of three preparations were fitted by the curve estimation function of SPSS17.0software. According to the principle, the closer R2tended to1, the more accurate results would be gotten. The results showed that triple models were the best among all kinds of curve models.Pharmacokinetics study:Three preparations were divided into three dose groups (9,3,1mg·kg-1), and administered intravenously to rabbits. HPLC method was adopted to measure the chrysophanol density of blood plasma at the time point of0.5,1,2,3,4,6,8,10h, and then the pharmacokinetic parameters were calculated and the compartment model was estimated at the same time. The results showed as follows:The change process of three chrysophanol preparations in rabbits was complied with two-compartment model. With the increase in dose, the area under concentration-time curve and half-life for elimination phase of three chrysophanol preparations were increased at the spots of doses (9,3,1mg·kg-1), their elimination process was complied with the feature of nonlinearity dynamics. Besides, the half-life for elimination phase, compared with the other two preparations, Chry-PBCA-NC had significant difference at the spots of doses (9,3mg-kg-1)(P<0.05). On the contrary, there was no significant difference between Chry liposomes and Chry-HP-β-CD at half-life for elimination phase (P>0.05). By comparison, the elimination process of Chry-PBCA-NC was slowest. |
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