Effect Of Borneol On Main Pharmacodynamic And Pharmacokinetics Of Ginkgo Biloba Extract And Its Application To Their Pharmaceutics Research

Based on the traditional Chinese medicine documents, Borneol given orally can improve concentration of the drugs used for central nervous system disease largely, the main purpose was going to investigate the impact of Borneol on Ginkgo biloba extract in this paper. We tested effects of Ginkgo biloba extract in the treatment of cerebral ischemia reperfusion injury in rats after being combined with different concentrations of borneol, and studied the impact of borneol on the bioavailability and brain distribution of the main active ingredient of Ginkgolide after oral administration once via rats pharmacokinetic model in vivo. And then, we analyzed pharmacokinetic parameters of four active ingredients using some software. End of the experiment, we filtered the best preparation conditions and evaluated in vitro and in vivo for this compound dropping pills.We explored effects of Ginkgo biloba extract in the treatment of cerebral ischemia reperfusion injury after being combined with different concentrations of Borneol by MACO in rats. Pharmacodynamic experiments showed that Ginkgo biloba extract could inhibit cerebral infarction rate and reduce cerebral index and brain water content of the tested rats to a certain extent after compatibled Borneol. In addition, we further understood that increase of pharmacodynamics depending on the content of Borneol. At the same time, results showed maximum daily dose of Ginkgo biloba extract were reduced in mice after compatibled Borneol which declined from 20.46 g·kg-1 to 15.03 g·kg-1.The impact of borneol on the bioavailability of main active ingredient of Ginkgolide after oral administration once via rats was conducted via rats pharmacokinetic model in vivo. Results detected by HPLC-MS/MS showed there were varying improvement to main ingredients as for AUC(0-∞), MRT(0-t)、t1/2, CLz/ Fand Cmax, especially for Ginkgolide B.It improved from 10855.79±2453.35 μg/L·h, 5.80±0.33 h,95.87±20.08 L/h/kg to 16294.98±3268.876 μg/L·h,6.66±0.35 h, 63.02±9.96 L/h/kg respectively for AUC(0-∞), MRT(0-t) and CLz/F for Ginkgolide B. It can be speculated the reason for improving bioavailability Ginkgolide after compatibled Borneol may be owing to reducing the metabolism mainly.After being detected with HPLC-MS/MS and being analyzed by t-test, it shows that Borneol had a conspicuous effect on Ginkgolide at the time of 120 min in the rat brain tissue, especially for the concentration increased of Ginkgolide B and Ginkgolide C. It might be related with opening the Blood-brain barrier temporarily to improving permeability of Blood-brain barrier to making Ginkgolide get into brain tissue.Later period of our work, we made the composition into dropping pills. Dropping pills were manufactured through orthogonal experiment. The dropping pills were made by solid dispersion technology with the carrier of PEG 4000 and PEG 6000, the coolant of methyl silicone,10±2℃ of the cooling temperature,1:4 of the rate of drug and carrier and 90℃ of liquid temperature. By the criterion of particle size, dropping pills weight, degree of circularity and dissolution rate, the amounts range of EGb and excipients were obtained through single factor experiment. An HPLC-ELSD method was established for the measurement of Ginkgolide in dropping pills. Means of FT-IR, DSC and XRD were utilized to evaluate characteristics of our dropping pills. With the result shown that drugs dispersed in carrier uniformly in form of fine crystal or molecular state. Furthermore, there was no chemical reaction appearance which guaranteed the purity of our drugs. In addition, bioavailability of dropping pills was taken into account through rats pharmacokinetic model in vivo. It shown that, compared with drug composition, the significantly enhancement for bioavailability just the Bilobalide were in Ginkgolide.