| Asthma is a common respiratory disease regarded as one of the four chronic diseases. It considered as a complex disorder characterized by airway inflammation, reversible airflow obstruction and bronchial hyper-responsiveness to various environmental stimuli. In clinic practice, therapy for asthma has the unique challenge of targeting the airways with topical drμgs. The two current areas of focus for treatment are anti-inflammatory agents (corticosteroids, anti-cytokines, anti-IgE, anti-adhesion molecules) and bronchodilators (selective b-2 agonists , anti-cholinergics, leukotriene modifiers, phosphodiesterase inhibitors) that interfere with smooth muscle contraction. Considering side effects of corticosteroids ,herbal preparations have been cited as the most popular complementary treatment modality by asthma sufferers.Xiao Qinglong decoction was first recorded in Shang HanLun written by Zhang Zhongjing, which is wildly used in clinical therapy. In the Pharmacopoeia of the People's Republic of China, it is recorded as a drug to treat asthma. A plenty of cases in clinical research demonstrate that Xiao Qinglong decoction can be antiasthmatic well. However, how to ensure its clinical medication reasonable, safe, effective, which must be based on the pharmacokinetics and pharmacology researches.The Purpose of this research is to study Pharmacokinetics and pharmacology of Xiao Qinglong Granule(XQL granule). XQL granule and Mahuang extracts were given to SD rats respectively, E and PE was determined by RP-HPLC assay in different time; Pharmacokinetics of E and PE in XQL granule and Mahuang extracts were investigated, and its difference was compared and analyzed; Groups of asthmatic SD rats were fed with DXM and different days'XQL granule. The pharmacodynamic actions of different groups were recorded and analysised.1 Literature ReviewWe had reviewed asthma-related and pharmacokinetic-related literature of in home and abroad, including the following aspects: general situation of anti-asthma by XQL granule; development of pharmacokinetic research of E and PE; development of the application of pharmacokinetic in TCM.2 Pharmacokinetic research2.1 Pharmacokinetics of Ephedrine and Pseudoephedrine in XQL granule by HPLCTo develop a HPLC method for the determination of ephedrine(E) and pseudoephdrine(PE) and to study the pharmacokinetics features of E and PE in SD rats. The plasma samples were extracted by ether. Phenylalanine hydrochloride (Phen) was used as the internal standard. The serum concentrations of E and PE were measured by HPLC. A good linearity was obtained in E from 0.008 to 0.985μg/mL and in PE from 0.004 to 0.492μg/mL.The limit of identification was 0.002μg/ml for E and 0.001μg/mL for PE. The recoveries were in the range of 93.1% to 102.6%and 110.4% to 95.37% for E and PE respectively. The interday RSD and intraday RSD of E and PE were both less than 8%. The E and PE plasma solution were steady within 60 days.SD rats were fed with XQL granule, plasma samples from rats were taken at 0.0 (before administration), 10min,20min,40min,1h,1.5h,2h,3h,4h,6h after the oral administration of XQL granule. The pharmacokinetic parameters were computed by using 3P97 . The main parameters were as follows. t1/2(ke) of E and PE were 1.41h and 1.27h; ke of E and PE were 0.49/h and 0.54/h; Vd of E and PE were 9.19 and 7.91(μg)/(μg/ml) respectively.2.2 Pharmacokinetics of Ephedrine and Pseudoephedrine in Mahuang extracts by HPLCSD rats were fed with Mahuang extracts, plasma samples from rats were taken at 0.0 (before administration), 10min,20min,40min,1h,1.5h,2h,3h,4h,6h after the oral administration of XQL granule. The pharmacokinetic parameters were computed by using 3P97 . The main parameters were as follows. t1/2(ke) of E and PE were 0.65h and 1.11h; ke of E and PE were 1.07/h and 0.62/h; Vd of E and PE were 8.75 and 11.48(μg)/(μg/ml) respectively.3 Pharmacology researches3.1 Effect of XQL granule on airway hyper-responsiveness in asthmatic animalSD rats were sensitized respectively by ovalbumin (OVA), before antigen challenge, rats in treatment groups were fed with Xiao Qinglong granule. To determine airway hyper-responsiveness Lung-function examinations were performed in asthmatic rats while latent period of asthma was observed in asthmatic guinea pigs. In asthmatic rats, airway hyper-responsiveness was seen with a significant increase in mean values of Ri, Re and decrease in mean values of Fev0.2/FVC compared with the control group and 10-days XQL granule improved these parameters obviously. These showed XQL granule had the DXM-like effect on changes of lung function and improves some symptom of asthma.3.2 Quantification of total serum IgE LevelsTo set up asthmatic model, rats were treated with a same method above. Total serum IgE levels were determined by RIA. Data showed total serum IgE levels in asthmatic rats were higher than control group. Rats treated with 10 days XQL granule showed lower IgE lever. The result indicated that XQL granule can inhibit the type I atopy by reducing the level of total serum IgE.3.3 Quantification of IL-4 Levels in BALFTo set up asthmatic model, rats were treated with a same method above. IL-4 levels in BALF were determined by RIA. Data showed IL-4 levels in asthmatic rats were higher compared with control group. Rats treated with XQL granule showed lower IgE lever. The result indicated that XQL granule can inhibit the type I atopy by reducing the level of IL-4 in BALF.In conclusion, Results of pharmacokinetics research about E and PE in XQL granule and Mahuang extracts show that TCM compatibility can change the pharmacokinetics courses of E and PE in SD rats.Pharmacology researches about different days XQL granule treatments on asthmatic model showed that 10 days XQL granule treatment on anti-asthma was similar with the group given DXM, and better than 5 days XQL granule treatment group. |
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