| Background,Objective and Research SignificanceWei Nai An (WNA) capsules has good effect on gastric mucosa damage disease (such as peptic ulcer and chronic gastric)and great economic and social profits,which was recognised as one of the national protected trad-itional medicines, Guangdong top brand. WNA capsules consists of Astragalu s, Panax notoginseng, Red ginseng, Pearl layer powder, Artificial bezoar. The preparation process of WNA capsules is water extract-ion Astragalus and milling panax notoginseng, red ginseng, which increases clinical sulfate Meanwhile,the basic research of pharmacody-namics and mechanism of the preparation need studying more deeply. In order to adapt new situation of consumers’requirements to the Chinese patent drug and upgrading andvanced production technology,it is necesscery to re-development the WNA capsules. The extraction seprapation process of Astragalus, Panax notoginseng, Red ginseng and resistence gastric mucosa damage mechanism of the WNA praprat-ion by polyamineand free radical were investigated, so the new extraction separation process shceme and pharmacological scientific proof to the re-development of WNA capsules will be applied.The research contents of the paper involves optimazating the extracti-on separation process of San-Yao.which consists of Astragalus, Panax notoginseng, Red ginseng accorded to 756:76:25 ratio, and studing resiste-nce gastric mucosa damage of WNA preparation. In order to advance techno-logy content of process and reduce clinical sulfate, screening extraction solvent, optimazating the extraction and three separation processes (alcohol-precipation, resin adsorption, membrane separation),selecting the preferred separation process and evaluating the new extraction separa-tion process by pilot study were be done one by one. To verify the mecha-nism and scientifically instruct clinical practice of WNA preparation, the pharmacodynamic effects of resistence gastric mucosa damage and mecha-nism of influencing polyamine and radical of it will be investigated.Methods1. Screening extraction solvent of San-Yao was carried out between water and ethanol by Acute gastric ulcer models with hydrochloric acid ethanol.2. According to the chemical composition yield and dry paste rate as the chief indexes, the extracting time, solvent ratio, extracting times were optimazated by orthogonal test after the extracting time, solvent ratio were determined by single factor test.Then the curative effects of the new extraction process was investigated compared with WNA capsules by Acute gastric ulcer models with hydrochloric acid ethanol and chronic ulc er model with acetic acid.3. According to the chemical composition yield and total solid removal rate as the chief indexes,the technological parameter of alcohol-precipat-ion, resin adsorption, membrane separation were optimazated separately gui ded by Acute gastric ulcer models with hydrochloric acid ethanol.Then the processes were screened parallelly guided by Acute gastric ulcer models with hydrochloric acid ethanol and cost estimation.4. According to the chemical composition yield, total solid removal rate and membrane flux as the chief indexes, two pilot studies were carrie-d out to investigate the stability of process.Meanwhile, the curative eff-ects of the processwere inspected by Acute gastric ulcer models with hydrochloric acid ethanol, Acute gastric ulcer models with Indomethacin and acute gastric lesions with NaOH5. After the new WNA preparation was compounded by mixing the thick paste of second pilot study with Pearl layer powder and Artificial bezoar according to former prescription proportion, pharmacodynamic effect of resistence gastric mucosa damage were evaluated through perusal, macroscop-ic observation and transmission electron microscope by chronic gastritis model with odoacetamide and actue gastric ulcer model with water resident stress.The contents of polyamine and free radical were detected, the corre-lation between them was analysised to proclaim the mechanism of resisten-ce gastric mucosa damage.Results1. The ulcer inhibition rate of water-soluble (44.28%)of San-Yao was more than the ethanol-solube (33.86%).2. The solvent ratio (6、8、10)and extracting time(1.5、2、2.5 hours) ensure the chemical composition yield maximum. According to the results of orthogonal test,the optimizated proposal was determined as 6 of solvent ratio,1.5 hours of extracting time and three extracting times. After optim-izating the extracting times, the wight of third extraction grade was 15.72%.The ulcer inhibition rate of mixture extraction of these three mat-erials(36.92%) was more than single extraction (30.70%) in the Acute gastric ulcer models with hydrochloric acid ethanol.The ulcer inhibition rate and ulcer healing rate of the extraction preparation(84.22%,66.67%) were more than the WNA capsules (44.03%,44.44%) in the chronic gastric ulcer models with hydrochloric acid ethanol. The ulcer inhibition rate of the extraction preparation and WNA capsules were 75.77% and 65.19% respec-tively in the Acute gastric ulcer models with hydrochloric acid ethanol.3. The best alcohol-precipitation procedure was determined as 0.857 (g/mL)of drug density and 50% alcohol, which ensure the chemical composit-ion yield and dry paste rate maximum and the ulcer inhibition rate (80.74%) more than other procedures. The best membrane separation procedure was determined as screen filtering with 400 mesh,200 nm of membrane aper ture,41.45HZ of frequency,2.0 bar of pressure,65 (gcm2·h)of LMP,25 to 50 of temperature range.The Composite grade of membrane separation and alcohol-precipitation were 61.75 and 58.15 respectively, which consists of the chemical composition yield, total solid removal rate and pharmacody-namic effects.The economic cost grade of the membrane separation, alcohol-precipitation and resin adsorption were 24.13,25.20,and 13.14, respectiv-ely.4. The varation trendency and chemical composition yield of the first and second pilot study was very similar.The dry paste rate of two pilot studies were 23.44%,23.19% separately, the reduce rate of solids of them were 28.01%,26.74% respectively. The ulcer inhibition rate of the new WNA preparation were 82.42%,81.72%,75.17% separately among Acute gastric ulcer models with hydrochloric acid ethanol,Acute gastric ulcer models with Indomethacin and acute gastric lesions with NaOH, which were more than the ulcer inhibition rate of WNA capsules5. The damage grade of the two models were reduced by perusal and mac-roscopic observation (P<0.05, contrast to model group) after adminis trati-on,the highest dosage group reversed the damage change of gastric mucosa ultrastructure. After administration, the contents of SOD and polyamine increased significantly,while MDA was reduced markedly, there were dose-response relationship between the contents and new preparation. The conte-nts of MDA had little to do with polyamine in the two models. There was bigger correlation between SOD and polyamine (P<0.05) in the chronic gastr-itis model, while there was little correlation in the gastric ulcer model with water resident stress.Conclusion1. The best extraction separation procedure of WNA new preparation was determined.Compared to the extisting technology, the new extraction seprapation process had great stability, reduced dosage and enhanced thera-peutic efficacy, which was value for development and suitable for factory production2. The new WNA preparation had good effects of resistence gastric muc-osa damage, increasing polyamine and reducing radical were regarded as the mechanism. Polyamine eliminated free radical through increasing SOD in the chronic gastritis models, while polyamine had little to do with free radical, they may played a role through different pathway respectively.3. Combined with prescription and medicinal materials characteristics , the three materials (Astragalus, Panax notoginseng, Red ginseng)were mixed and taken as a whole in the same proportion under the premise of original prescription. The optimizated extraction separation process was guided by combined organically efficacy with chemical composition yield, then two pilot studies were conducted to verify the stability and effecti-veness of the process. The new WNA preparation was preparated and invest-igated the mechanism of resistence gastric mucosa damage, which was prove-d to act through the pathway of polyamine and free radical inititally for the first time. In the paper, the content is full and systematic which contains laboratory screening, pilot study and mechanism proved prelimin-arily, the research method is innovative simultaneously, there is an instr-ucting significance in the research results of the paper.So that our work will provide reliable science data for clinical application of the new preparation and bring forward a referenced idea for re-development of patent medicine. |
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