利福昔明子宫注入剂稳定性及其对家兔阴道黏膜刺激性研究

doi:10.16431/j.cnki.1671-7236.2019.09.036

Abstract

Abstract: In order to study the stability of the rifaximin uterine injection,and initially determined its quality guarantee period,three batches of rifaximin were used to test the stability of uterine injectors,including the influencing factors test,the high temperature accelerated test and long term stability test,the content of rifaximin and its related substances were determined by high performance liquid chromatography (HPLC).Thus,the quality guarantee period of rifaximin uterine injection was preliminarily determined.Referring to the relevant technical specifications,rabbit vaginal mucous membrane irritation test was studied.The results showed that the contents of the related substances were not more than 3% according to the area normalization method,the properties,sedimentation and particle size of the injector did not change significantly,and the change of the content of rifaximin in the principal component was 90.0% to 110.0%,the validity of this product was determined to be two years.In rabbit vaginal mucous membrane irritation test,the results showed that erythema and edema were not been found on rifaximin uterus implants administration site skin and saline control site skin,and the score was 0 point.In the vaginal mucous membrane irritation test,leukocyte infiltration,hyperemia and edema were not found in vaginal mucosa of test and control groups,vaginal mucous membrane irritation index was 0.25.So,rifaximin uterus injection had no irritation on rabbit vaginal mucous membrane.This product had good clinical safety and could be further promoted and used.

Key words: uterine injection of rifaximin; stability test; rabbit; vaginal mucous membrane irritation

CLC Number:

S859.79⁺6

XU Fei, LIU Jing, HUANG Huili, CHEN Xiaojie, LI Xiubo. Study on the Stability of Rifaximin Uterine Infection and Its Stimulation to Vaginal Mucosa in Rabbits[J]. China Animal Husbandry and Veterinary Medicine, 2019, 46(9): 2795-2802.

References

[1] 李世宏,杨国林,杨锐乐,等.奶牛子宫内膜炎研究进展[J].中国奶牛,2007,1:34-38. LI S H,YANG G L,YANG R L,et al. Research progress of cow endometritis[J].China Dairy Cattle,2007,1:34-38.(in Chinese)
[2] WILLIAMS E J,FISCHER D P,NOAKES D E,et al.The relationship between uterine pathogen growth density and ovarian function in the postpartum dairy cow[J].Theriogenology,2007,68(4):549-559.
[3] PISTIKI A,GALANI I,PYLERIS E,et al.In vitro activity of rifaximin against isolates from patients with small intestinal bacterial over growth[J].International Journal of Antimicrobial Agents,2014,43(3):236-241.
[4] 叶院宁,毛华,汪芳裕.利福昔明在消化道疾病中的应用进展[J].胃肠病学和肝病学杂志,2018,27(2):212-215. YE Y N,MAO H,WANG F Y.Progress in the application of rifaximin in digestive tract diseases[J].Chinese Journal of Gastroenterology and Hepatology,2018,27(2):212-215.(in Chinese)
[5] GILLIS J C,BROGDEN R N.Rifaximin a review of its antibacterial activity,pharmacokinetic properties and therapeutic potential in conditions mediated by gastrointestinal bacteria[J].Drugs,1995,49(3):467-484.
[6] GASZTONY I B,HUNYADY B.Clinical and pharmacological as pects of rifaximin,local antibiotic therapy in intestinal disorders[J].Orvosi Hetilap,2004,145(43):2177-2181.
[7] 孙雷,李丹,毕言锋,等.牛奶中利福昔明残留消除规律研究[J].中国兽药杂志,2013,47(9):27-30. SUN L,LI D,BI Y F,et al.Study on the depletion of rifaximin residue in milk[J]. Chinese Journal of Veterinary Drug,2013,47(9):27-30.(in Chinese)
[8] DUPONT H L.Biologic properties and clinical uses of rifaximin[J].Expert Opinion on Pharmacotherapy,2011,12(2):293-302.
[9] 帅海涛,刘艳飞,彭东明,等.利福昔明合成工艺的研究[J].应用化工,2013,42(10):1801-1803. SHUAI H T,LIU Y F,PENG D M,et al.Study on the synthesis process of rifaximin[J].Applied Chemical Industry,2013,42(10):1801-1803.(in Chinese)
[10] 王佩,李玉珍.利福昔明的药理作用和临床应用[J].药物不良反应杂志,2005,5:382-385. WANG P,LI Y Z. Pharmacological actions and clinical applications of rifaximin[J].Adverse Drug Reactions Journal,2005,5:382-385.(in Chinese)
[11] 边益庆,高娴.复方利福昔明纳米乳的制备及质量评价[J].畜牧与饲料科学,2018,39(4):1-4. BIAN Y Q,GAO X.Preparation and quality evaluation of compound rifaximin nano-milk[J].Animal Husbandry and Feed Science,2018,39(4):1-4.(in Chinese)
[12] 黄慧丽,徐飞,张道康,等.奶牛用利福昔明子宫注入剂有关物质反相高效液相色谱检测方法的建立及应用[J].中国畜牧兽医,2017,44(4):1211-1218. HUANG H L,XU F,ZHANG D K,et al.Establishment and application of reversed-phase high performance liquid chromatography method for detection of related substances of rifaximin uterine infusion in dairy cows[J].China Animal Husbandry & Veterinary Medicine,2017,44(4):1211-1218.(in Chinese)
[13] PIGANNELLI S,SHURDHI A.Short communication:In vitro activity of rifaximin against Chlamydia suis[J].Veterinary Record,2011,169(22):584.
[14] 余祖功,李晶,张海彬,等.家畜用利福昔明阴道栓剂及其制备方法[P].CN201110425645.6.2013. YU Z G,LI J,ZHANG H B,et al.Rifaximin vaginal thrombosis for domestic animals and its preparation method[P].CN201110425645.6.2013.(in Chinese)
[15] 余祖功,周振雷,刘永旺,等.一种防治家畜子宫内膜炎用复方利福昔明干混悬剂及其制备方法[P].CN102512417 B.2013. YU Z G,ZHOU Z L,LIU Y W,et al.A compound rifaximin dry suspension for preventing and treating endometritis of livestock and its preparation method[P].CN102512417 B.2013.(in Chinese)
[16] 李晶.利福昔明阴道栓和缓释阴道泡腾片的研制及评价[D].南京:南京农业大学,2011. LI J.Development and evaluation of the vaginal thrombolysis and slow release vaginal effervescent tablets[D].Nanjing:Nanjing Agricultural University,2011.(in Chinese)
[17] 汤秀梅,杨燕,丁江生,等.灯盏花素口崩片的稳定性[J].中成药,2019,41(2):416-419. TANG X M,YANG Y,DING J S,et al.Stability of Breviscapine mouth disintegrating tablets[J].Chinese Traditional Patent Medicine,2019,41(2):416-419.(in Chinese)
[18] 吴嘉玲.药物稳定性的试验方法及统计处理[J].生物化工,2018,4(1):105-107. WU J L.Test method for drug stability and statistical treatment[J].Biochemical Engineering,2018,4(1):105-107.(in Chinese)
[19] 初香芝,刘丽娜.药物制剂稳定性的影响因素及优化策略分析[J].心理月刊,2019,14(5):124. CHU X Z,LIU L N.Analysis of influencing factors and optimization strategy of drug preparation stability[J].Psychologies,2019,14(5):124.(in Chinese)
[20] 陶春,吴博,黄爱文,等.复方酮康唑软膏的制备与稳定性考察[J].药学实践杂志,2017,35(6):535-538. TAO C,WU B,HUANG A W,et al.Development and stability test of compound ketoconazole ointment[J].Journal of Pharmaceutical Practice,2017,35(6):535-538.(in Chinese)
[21] 林树乾,宋敏训,赵增成,等.西地碘粉的加速与长期稳定性研究[J].家禽科学,2018,8:3-5. LIN S Q,SONG M X,ZHAO Z C,et al.Study on the acceleration and long-term stability of Xidi iodine powder[J].Poultry Science,2018,8:3-5.(in Chinese)
[22] 何宁,孙贺春,代苗苗,等.初均速加速试验法研究温度和湿度对药物稳定性的影响[J].中南大学学报(医学版),2014,39(5):501-510. HE N,SUN H C,DAI M M,et al.The effect of temperature and humidity on drug stability was studied by means of initial average speed acceleration test[J].Journal of Central South University (Medical Science),2014,39(5):501-510.(in Chinese)
[23] 杜欢欢,管庆霞,朱婷,等.提高水溶性药物稳定性的新型技术研究进展[J].中国药房,2017,28(7):994-997. DU H H,GUAN Q X,ZHU T,et al.Advances in the study of new technologies for improving the stability of water-soluble drugs[J].China Pharmacy,2017,28(7):994-997.(in Chinese)
[24] 黄慧丽,徐飞,刘义明,等.利福昔明的药理作用及其在奶牛疾病防治中应用的研究进展[J].中国畜牧兽医,2015,42(12):3358-3363. HUANG H L,XU F,LIU Y M,et al.Pharmacological effects of rifampicin and its application in the prevention and treatment of cow diseases[J].China Animal Husbandry & Veterinary Medicine,2015,42(12):3358-3363.(in Chinese)
[25] 蒋玲玉,黄慧丽,李秀波,等.利福昔明子宫注入剂含量测定及方法耐用性试验研究[J].中国兽药杂志,2018,52(8):25-31. JIANG L Y,HUANG H L,LI X B,et al.Study on the content and durability ofrifaximin in uterus injection[J].Chinese Journal of Veterinary Drug,2018,52(8):25-31.(in Chinese)
[26] 王建,程雪娇,焦晓军,等.利福昔明乳房注入剂的局部刺激性与过敏性试验研究[J].天津农业科学,2016,22(6):23-27. WANG J,CHENG X J,JIAO X J,et al.Study on local irritation and hypersensitivity of rifampicin breast injector[J].Tianjin Agricultural Sciences,2016,22(6):23-27.(in Chinese)
[27] 国家食品药品监督管理局.药物刺激性、过敏性和溶血性研究技术指导原则[Z].2014. STATE FOOD AND DRUG ADMINISTRATION.Technical guidelines for drug irritancy,allergies and hemolysis[Z].2014.(in Chinese)
[28] 中华人民共和国农业部.农业部公告(1247号).兽药临床前毒理学评价试验指导原则[Z].2009. MINISTRY OF AGRICULTURE.Announcement of the Ministry of Agriculture (1247).Guiding principles for pre-clinical toxicological assessment of veterinary drugs[Z].2009.(in Chinese)

Study on the Stability of Rifaximin Uterine Infection and Its Stimulation to Vaginal Mucosa in Rabbits

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