甘草总黄酮混悬乳房注射剂对奶牛乳房炎治疗效果研究

发布时间：2018-04-11 19:36

本文选题：乳房炎 + 中药混悬液　；参考：《黑龙江八一农垦大学》2015年硕士论文

【摘要】：甘草总黄酮混悬乳房注射剂是由吉林大学药理实验室自主研发的一种用来治疗奶牛乳房炎的纯中药制剂，并经全面质量考察表明该制剂符合甘草总黄酮混悬液的质量标准草案。本研究旨在证明甘草总黄酮混悬乳房注射剂临床用药安全，并且能够有效治疗奶牛临床型乳房炎。本研究主要内容包括：通过试管二倍稀释法观察中药混悬液对乳房炎主要致病菌体外抑菌效果；通过家兔热原试验、家兔皮肤过敏性试验及肌肉刺激性试验、溶血与凝集检查、健康奶牛乳房刺激性试验、小鼠急性毒性试验，观察甘草总黄酮混悬乳房注射剂临床用药安全性；通过对选取的80头患有临床型乳房炎奶牛，，按中药低、中、高剂量组，抗生素对照组进行1d一次，连用5d的治疗方式，然后对各组治愈率、有效率进行对比来确定混悬液临床用药剂量；通过采用中药临床确定剂量进行临床治疗扩大试验，对60头临床型乳房炎奶牛进行治疗，以抗生素组、健康组为对照，对治愈率、有效率进行统计，并对治疗前后乳汁SCC数、泌乳量，乳清中NAGase（N-乙酰基-β-D-氨基葡萄糖苷酶）、SA（乳清白蛋白）、LDH（乳酸脱氢酶）这些指标的升降趋势，以及血清及乳清中SOD（超氧化物歧化酶）、GSH-PX（谷胱甘肽过氧化物酶）、MDA（丙二醛）、NO（一氧化氮）给药前后这些指标的活性变化进行检测，全面了解中药混悬液的药效。体外药敏研究说明：甘草总黄酮混悬液对无乳链球菌的最低抑菌浓度（MIC）、最低杀菌浓度（MBC）为4.88μg／mL，对金黄色葡萄球菌的MIC、MBC为19.53μg／mL，对大肠杆菌的MIC为625.00μg／mL。安全性试验结果表明：该中药制剂热原性符合药典规定；该中药注射剂无溶血性；不会引起皮肤过敏反应，是弱致敏物；对家兔腿部肌肉刺激级数小于2，可用于肌肉注射；对小鼠急性毒性属于基本无毒物质；对健康奶牛乳房刺激效果与注射用生理盐水无差异（P0.05），以上结果证明甘草总黄酮混悬乳房注射剂符合临床用药安全性。用药剂量筛选试验结果表明：中药治疗组中，20ml/乳区组、40ml/乳区组、抗生素组治愈率能高达86.00%、89.36%、86.54%，并且三组之间治愈率差异性均不显著（P＞0.05），有效率高达90.00%、93.62%、94.23%，差异不显著（P＞0.05）；治疗后发现由金黄色葡萄球菌、无乳链球菌及大肠杆菌和混合菌引发的患病乳区在中药治疗后转阴率分别是70.00%、100.00%、28.57%、50.00%，病原菌总转阴率高达69.04%，与抗生素组相比差异性不显著（P＞0.05）。临床疗效扩大试验结果表明：中药组和抗生素组治疗60头患病奶牛，治愈率分别为87.17%、86.84%，有效率高达97.44%、93.42%；在最后一次给药后，与健康奶牛乳汁体细胞数相比，中药组与抗生素组体细胞均恢复到正常范围SCC＜50万，但是抗生素组仍显著高于健康值（P＜0.05）；患病奶牛经过5d治疗后，中药组泌乳量恢复到正常值（P0.05）;患病奶牛治愈后乳清及血清中谷胱甘肽过氧化物酶、超氧化物歧化酶的活性明显恢复（P＜0.05），一氧化氮、丙二醛含量明显降低（P＜0.05或P0.01），与正常值相比无差异，乳清中乳清白蛋白、乳酸脱氢酶、N-乙酰基-β-D-氨基葡萄糖苷酶含量显著降低（P＜0.05或P0.01）。以上研究结果表明，甘草总黄酮混悬乳房注射剂临床用药安全，能够有效修复受损的乳腺组织，治疗奶牛临床型乳房炎效果良好，为新兽药的研发提供可靠的实践及理论依据。
[Abstract]:Total flavonoids of Glycyrrhiza suspension injection is used in treating breast mastitis of pure Chinese medicine by the Jilin University Laboratory of pharmacology of independent research and development, and the comprehensive quality inspection showed that the quality standard draft of the preparation with total flavonoids of Glycyrrhiza suspension. The purpose of this study is to prove the TFG suspension injection breast clinical medication safety, and can effective treatment of clinical mastitis.
The main contents of this research include: the suspension of the main pathogenic bacteria of mastitis in vitro antibacterial effect through the tube two times dilution method to observe the traditional Chinese medicine; through the pyrogen test, allergic test and muscle of rabbit skin irritation test, hemolysis and agglutination test, healthy cow breast irritation test, acute toxicity test of mice, observe the total flavonoids of Glycyrrhiza mixture suspension injection breast clinical drug safety; through the 80 head selection with clinical mastitis, according to traditional Chinese medicine low, high dose group, antibiotic group 1D once and for 5D treatment, and the cure rate of each group, the efficiency were compared to determine the suspension through clinical dosage; the use of Chinese medicine to determine the clinical dose for clinical treatment of expanded testing, treatment of 60 clinical mastitis, antibiotic group, normal control group, the cure rate and effective rate. For statistics, before and after treatment SCC number of lactation, milk, whey (NAGase N- acetyl beta -D- Glucosaminidase (SA), whey albumin), LDH (lactate dehydrogenase) rise trend of these indexes, and serum and whey SOD (superoxide dismutase, glutathione (GSH-PX) peroxidase), MDA (malondialdehyde), NO (nitric oxide) before and after the administration activity changes of these indexes were detected, a comprehensive understanding of traditional Chinese medicine drug suspension.
In vitro drug sensitivity study showed that the minimum inhibitory concentration (MIC) of licorice flavonoids suspension against Streptococcus lactis was lowest (MBC), and the minimum bactericidal concentration (MBC) was 4.88 g / mL. The MIC and MBC for Staphylococcus aureus were 19.53 g / mL, and the MIC for E. coli was 625 g / mL..
Safety test results show that the traditional Chinese medicine preparation pyretogen accords with the Chinese Pharmacopoeia; the traditional Chinese medicine injection had no hemolysis; do not cause skin allergic reactions, is a weak sensitizer; on rabbit leg muscle stimulation series is less than 2, can be used for intramuscular injection; belong to non-toxic substances on the acute toxicity of mice; no difference of healthy cows breast stimulation the effect of injection with saline (P0.05), the results show that the total flavonoids of Glycyrrhiza suspension injection breast with clinical medication safety.
Dose screening test results show that the Chinese medicine treatment group, 20ml/ 40ml/ group in dairy, dairy group, antibiotics group, the cure rate can be as high as 86%, 89.36%, 86.54%, and the cure rate are not significantly difference between the three groups (P > 0.05), efficiency is as high as 90%, 93.62%, 94.23%, the difference is not significant (P > 0.05); after the treatment by Staphylococcus aureus, Streptococcus agalactiae and no milk in Escherichia coli and mixed bacteria caused in traditional Chinese medicine after treatment negative rate were 70%, 100%, 28.57%, 50%, total bacteria negative rate as high as 69.04%, compared with the antibiotic group difference significant (P > 0.05).
The clinical curative effect of expanding test results show that: Traditional Chinese medicine group and the antibiotic treatment group 60 head sick cows, the cure rate was 87.17%, 86.84%, the efficiency was up to 97.44%, 93.42%; after the final dose, compared with healthy milk somatic cell counts, somatic medicine group and the antibiotic group were restored to the normal range of SCC < 500 thousand, but still the antibiotic group was significantly higher than that of healthy values (P < 0.05); the prevalence of dairy cows after 5D treatment, traditional Chinese medicine group lactation returned to normal value (P0.05); sick cows were cured after whey and serum enzyme glutathione peroxidase, superoxide dismutase activity significantly (P < 0.05), nitric oxide, MDA content decreased significantly (P < 0.05 or P0.01), compared with the normal value of no difference in WHEY WHEY albumin, lactate dehydrogenase, N- acetyl beta -D- Glucosaminidase were significantly lower (P < 0.05 or P0.01).
The above research results indicate that licorice total flavonoids suspension breast injections are safe and effective in repairing damaged mammary tissues, which is effective in treating clinical mastitis in dairy cows, providing reliable practice and theoretical basis for the development of new veterinary drugs.

【学位授予单位】：黑龙江八一农垦大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：S858.23

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