| Part I Clinical Study of Qingrun Yangmu Oral Liquid Objective :On the basis of previous studies,observe the clinical efficacy of Qingrun Yangmu oral liquid on dry eyes visual fatigue of liver and kidney yin deficiency type,and evaluate the clinical effects of three therapeutic methods,namely sodium hyaluronate eye drops,Qingrun Yangmu oral liquid and Qingrun Yangmu oral liquid combined with sodium hyaluronate eye drops,on dry eye visual fatigue of liver and kidney yin deficiency type,and provide patients with effective and appropriate treatment options.Method :(1)Multi-center observation of clinical research methods;(2)Grouping: Divided into3groups: sodium hyaluronate eye drops,Qingrun Yangmu oral liquid,and Qingrun Yangmu oral liquid combined with sodium hyaluronate eye drops;(3)Treatment: Give Qingrun Yangmu oral liquid(10ml,oral,3times/day)and artificial tears sodium hyaluronate eye drops(drops,1?2drops/time,4 times/day);(4)Observation time: Observations were made at the time of enrollment,on the 1st,11 th,and 21 st days after treatment,and relevant indicators were recorded;(5)Observed indicators: Subjective symptom scores,visual acuity,tear secretion(SIT),tear breakup time(BUT),corneal fluorescein sodium staining(CFS),Bright Visual Persistence(BVP),etc.finally,all data were statistically analyzed;(6)TCM symptom improvement.Result:(1)Subjective symptom score comparison: In terms of improving systemic symptoms,the systemic symptom scores in Sodium hyaluronate eye drops group did not change significantly before and after treatment(P>0.05).the systemic symptom scores of Qingrun Yangmu oral liquid combined with sodium hyaluronate eye drops and Qingrun Yangmu oral liquid group were signifi cantly lower than those before treatment at each observation time point(P<0.05).the systemic symptom scores in the Qingrun Yangmu oral liquid group,Qingrun Yangmu oral liquid combined with sodium hyaluronate eye drops group were significantly lower than sodium hyaluronate eye drops group at each observation time point(P<0.05).the systemic symptom scores in the Qingrun Yang mu oral liquid group were slightly lower than those in the Qingrun Yangmu oral liquid combined with sodium hyaluronate eye drops at each observation time point(P>0.05).it shows that Qingrun Yangmu oral liquid can effectively improve the systemic symptoms of patients.the improvement of ocular local symptoms,the scores of ocular symptoms after treatment in the three groups were significantly lower than before treatment(P<0.05).the ocular symptom scores in Qingrun Yangmu oral liquid combined with Sodium Hyaluronate eye drops group were lower than those in Qing run Yangmu oral liquid group at each observation time(P>0.05),but significantly lower than thosein sodium hyaluronate eye drops group(P<0.05).the scores of eye symp toms in Qingrun Yangmu oral liquid group were lower than those insodium hyaluronate eye drops group at each observation time point(P>0.05).the above results indicate that all three treatments can improve eyerelated symptoms.the effect of Qingrun Yangmu oral liquid combined with sodium hyaluronate eye drops is obviously better than that of sodium hyaluronate eye drops or Qingrun Yangmu oral liquid.from the long-term improvement of eye symptoms,Qingrun Yangmu oral liquid is better than sodium hyaluronate eye drops.(2)Visual acuity comparison: in improving vision,the visual acuity of Qingrun Yangmu oral liquid combined with Sodium Hyaluronate eye drops group was improved(P<0.05)on the 11 st day of treatment,and the visual acuity of Qingrun Yangmu oral liquid group and Sodium hyaluronate eye drops group was not significantly changed before treatment(P>0.05).at the 11 st and21st days of treatment,the average visual acuity of the three groups was not significantly different from that before treatment(P>0.05).there was no significant difference in the average visual acuity between the three groups at each observation time point(P>0.05).(3)Comparison of SIT and BUT: The SIT and BUT values of the three groups after treatment were all significantly higher than those before treatment(P<0.05),indicating that all three treatments can promote tear secretion and prolong BUT.the SIT and BUT values in Qingrun Yangmu oral liquid combined with Sodium Hyaluronate eye drops group and Qingrun Yangmu oral Liquid group were significantly higher than those in Sodium hyaluronate eye drops group at eachobservation time point(P<0.05),while the SIT and BUT values in Qingrun Yangmu oral liquid combined with Sodium Hyaluronate eye drops group were not significantly different from Qingrun Yangmu oral liquid group at each observation time point.the difference(P>0.05)indicates that Qingrun Yangmu oral liquid can promote tear secretion,prolong BUT,and have long-term effect.(4)CFS comparison: The CFS scores of the three groups after treatment were significantly lower at each observation time point than those before treatment(P<0.05).it was shown that all three treatments can improve Corneal fluorescein staining and promote corneal epithelial repair.on the 1st day of treatment,the CFS scores in Qingrun Yangmu oral liquid combined with Sodium Hyaluronate eye drops group were significantly lower than those in Qingrun Yangmu oral liquid group and Sodium hyaluronate eye drops group(P<0.05),while the CFS scores in Qingrun Yang mu oral liquid group were slightly higher than those in Sodium hyaluronate eye drops group(P>0.05).on the 11 st and 21 st days of treatment,the CFS scores in Qingrun Yangmu oral liquid combined with Sodium Hyaluronate eye drops group and Qingrun Yangmu oral liquid group were significantly lower than those in Sodium hyaluronate eye drops group(P<0.05).The CFS scores in Qingrun Yangmu oral liquid combined with Sodium Hyaluronate eye drops group were lower than those in Sodium hyaluronate eye drops group(P>0.05).it was shown that the effect of Qing run Yangmu oral liquid combined with sodium hyaluronate eye drops on reduced CFS scores was significantly better than that of sodium hyaluronate eye drops or Qingrun Yangmu oral Liquid alo-ne.the Qingrun Yangmu oral liquid in the short term to improve corneal fluorescein staining is not as good as sodium hyaluronate eye drops,from the longterm effect of Qingrun Yangmu oral liquid is better than sodium hyaluronate eye drops.(5)Comparison of BVP: The BVP values of three groups after treatment were significantly higher than those before treatment(P<0.05).It shows that the three treatments can extend the duration of vision,increase the BVP value,and relieve the symptoms of visual fatigue.the BVP value of Qingrun Yangmu oral liquid combined with Sodium Hyaluronate eye drops group was significantly higher than that of Sodium hyaluronate eye drops group and Qingrun Yangmu oral liquid group at each observation time point(P<0.05),while the BVP value of Qingrun Yangmu oral liquid group was slightly lower than the artificial tear group at the 1st day(P>0.05).the BVP values were higher on the 11 st and 21 st days of treatment than in the artificial tear group(P>0.05).the results showed that the combination of Qingrun Yangmu oral liquid and sodium hyaluronate eye drops in the improvement of patients with BVP,relieve visual fatigue than the effect of sodium hyaluronate eye drops or Qingrun Yangmu oral Liquid.(6)Comparison of curative effects: The total effective rates of the three groups after treatment were: 65.0% in Sodium hyaluronate eye drops group,70.0% in Qingrun Yangmu oral Liquid group,and 78.9% in Qingrun Yangmu oral Liquid combined with Sodium Hyaluronate eye drops group.after comparison,the efficacy of Qingrun Yangmu oral liquid Combined with Sodium Hyaluronate eye drops group was significantly better than that of the other two groups(P<0.05),while Qingrun Yangmu oral Liquid group was slightly better than Sodium hyaluronate eye drops group(P>0.05).(7)Drug side effects: During the treatment period,there were 2 cases in the Qingrun Yangmu oral Liquid group,3 cases in the Qingrun Yangmu oral Liquid combined with sodium hyaluronate eye drops,and gastric upset,heartburn,and pantothenic acid after taking the Qingrun Yangmu oral Liquid.Such as unwell symptoms,or make the symptoms worse.Conclusion(1)Qingrun Yangmu oral Liquid has good clinical curative effect on dry eye visual fatigue of liver and kidney yin deficiency type.(2)Qingrun Yangmu oral liquid combined with sodium hyaluronate eye drops for treatment of dry eye visual fatigue,better than the simple application Qingrun yangmu oral liquid or sodium hyaluronate eye drops.(3)Qingrun Yangmu oral liquid in some patients have some medical side effects.Part II Pharmaceutical Study of Qingrun Yangmu Oral LiquidObjective: The possible mechanism of Qingrun Yangmu oral liquid treatment was explored by thin layer chromatographic identification,decoction,and determination of polysaccharides in samples of Qingrun Yangmu oral liquid.Method: According to the preparation of the reference drug solution,the preparation of the test solution,and the preparation of the negative sample solution,a thin-layer chromatographic identification method was established,the deployment system was adjusted,the thin-layer chromatography conditions were established,and the thin-layer chromatographic identification of the medicinal material was performed.Preparation of the standard solution,preparation of the test solution,establish a standard curve of the polysaccharide and absorbance values,using sulfuric acidfluorenone spectrophotometric determination of absorbance at 572 nm,calculate the content of polysaccharides(in glucose)in the pieces and samples.Result:(1)Thin layer chromatography: Wolfberry:in the chromatogram of the test sample,there is a fluorescent spot of the same color at the position corresponding to the chromatogram of the standard reference drug material.chrysanthemum: for the test solution and the mixed standard working solution,peaks at the same retention time,and the maximum absorption wavelength of the chromatographic peaks is the same;the negative sample has a peak at the same retention time as the chlorogenic acid standard and the maximum absorption wavelength is the same.Negative samples showed interference,so they were not used as qualitative identification peaks.Luteolin,3,5-O-biscaffeoylquinic acid was used as a qualitative characteristic peak.That is,in the chromatogram of the test sample,a chromatographic peak with the same retention time appears in the position corresponding to the chromatogram of the reference substance of luteolin and 3,5-O-dicacylquinic acid.(2)The average polysaccharide content in the 2batches of Qingrun Yangmu oral liquid was 162.92 mg/ml.(3)The polysaccharide content of the herbs used in the Qingrun Yangmu oral liquid was 81.48% of wolfberry fruit,40.06% of the processed huangjing,16.08 % of the chrysanthemum,and 20.15% of North Adenophora.Conclusion:(1)Identification by thin-layer chromatography of drugs,Qingrun Yangmu oral Liquid of Chinese wolfberry,chrysanthemum thin layer identification method is stable,reproducible and specific properties are good,can effectively control product quality.(2)In Qingrun Yangmu oral liquid,the contents of Polysaccharides of Gardenia jasminoides and Polygonatum sibiricum are high,and that of ginseng and chrysanthemum is also polysaccharides,further evidence that the polysaccharide may be the main component of Qingrun Yangmu oral liquid,the therapeutic mechanism may be related to the efficacy of these high levels of polysaccharides in the drug.Part III Toxicology Study of Qingrun Yangmu Oral LiquidObjective: Through toxicological studies on the Qingrun Yangmu oral liquid,the toxic and toxic effects and dose-response relationship were studied to evaluate its safety to humans and eyes.Method: Through acute oral toxicity test,genotoxicity test and chronic oral toxicity test of rats and mice,the maximum drug-resistance dose,genotoxicity,animal behavior and weight of the animal fed with Qingrun Yangmu oral liquid were observed.Hematology,blood biochemistry,ratio of body mass,histopathological changes,and other changes of the animal to Qingrun Yang mu oral liquid,were evaluated to evaluate their safety to humans and eyes.Result:(1)Acute oral toxicity test:The acute oral oral toxicity test of Qingrun Yangmu oral liquid confirmed that the maximum tolerated dose value was greater than 180g/kg.BW.(2)Genetic toxicity test.Ames test: In Qingrun Yangmu oral Liquid with or without S9 mix,the number of reverted colonies against Salmonella typhimurium(TA97a,TA98,TA100,and TA102)did not increase to twice that of the untreated control group or More than twice.Micronucleus test of bone marrow polychromatic erythrocytes in mice: there was no significant difference in the micronu-cleus rate between the three dose groups of Qingrun Yangmu oral liquid and the negative control group(P>0.05),while the frequency of micronucleus in the positive control group was significan tly higher than that in the negative control group(P<0.05).the PCE/RBC ratios of the three dose groups were not statistically different from those of the negative control group(P>0.05),and were not less than 20% of the solvent control group.Mouse sperm deformity test:there was no significant difference in the rate of sperm abnormality between three dose groups of Qingrun Yangmu oral liquid(P>0.05),and the sperm abnormality rate in the positive control group was significantly higher than that in the negative control group(P<0.01).(3)Chronic toxicity test Rats in each dose group of Qingrun Yangmu oral liquid had normal growth and no poisoning and death occurred.there were no significant differences between the results of body weight and body weight gain,food intake and food utilization,hematology,organ weight,blood biochemistry,and visceral body ratio,etc,compared with the negative control group(P>0.05).Gross anatomy and histopathological examination of rats,Qingrun Yangmu oral liquid showed no obvious toxic damage to the eyeball,optic nerve,liver,spleen,kidney,testis,ovary,and gastrointestinal tract of the examined organs.Conclusion Qingrun Yangmu Oral Liquid has no acute toxicity,genetic toxicity and sub-chronic toxicity,no target tissues or target organs,no dose-effect relationship,and no toxicity to humans and eyes. |
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