论文总字数：14850字

摘 要

目的：通过微泵连续7天每天静脉注射头孢哌酮钠他唑巴坦钠（4：1），并通过7天的恢复期，测试新西兰兔潜在的血管刺激。观察、评估血管刺激的可逆性，并与商业上可用的对照进行比较，为临床实验提供参考。方法10只新西兰兔子（5只雌性和5只雄性）被选中。在测试组中使用了新西兰兔（3公2雄）和控制新西兰兔（2母3雄）。试验组左耳给出了试验样品，临床浓度为12.9毫克/毫升，给药量为10毫升/千克，右耳给出了相同剂量的0.9%氯化钠注射液，对照组左耳给药量为10毫升/千克。给予右耳的参考物质量与同体积相同。一整天，连续7天，微注射泵静脉注射。在最后一次给药后，有6只动物（3只雌性和3只雄性）在腹腔内注射。用20%的乌来糖溶液进行了深度麻醉，麻醉后牺牲了颈动脉。其余4只动物（雌性2只，雄性2只）在观测7天后被牺牲。兔子的耳朵被送去做常规取样、脱水、包埋、染色和光学显微镜检查。结果：病理检查表明，在给药期间，各家兔耳朵的左、右血管壁都没有破损，每一层组织都没有出现异常。没有出现充血、肿胀、出血等现象。在恢复期内，试验组和对照组的左、右兔耳均未观察到延迟毒性。结论：本实验在GLP规定的实验室内，在12.9 mg/ml浓度下，注射用头孢哌酮钠他唑巴坦钠（4：1）对供试品和对照品均未引起注射处局部血管刺激性病理学反应。

关键词：注射用头孢哌酮钠他唑巴坦钠（4：1） 兔耳耳缘恒流泵静脉注射 血管刺激性试验

Cefoperazone Sodium Tazobactam Sodium Injection (4:1) Comparison of Vascular Irritation Tests

Abstract

OBJECTIVE: To test the potential vascular irritation of New Zealand rabbits by injecting Cefoperazone Sodium Tazobactam Sodium (4:1) intravenously into a New Zealand rabbit once a day for 7 consecutive days with a microinjection pump, and through a 7-day recovery period. Observation, assessment of reversibility of vascular irritation, and comparison with commercially available controls provide a reference for clinical trials. Methods: Ten New Zealand rabbits (5 females and 5 males) were selected. New Zealand rabbits (3 males and 2 males) and control New Zealand rabbits (2 females and 3 males) were used in the test group. The test group left ear gave the test sample, the clinical concentration was 12.9mg/ml, the administration volume was 10ml/kg, the right ear gave the same amount of 0.9% sodium chloride injection, and the control group left ear gave the test article The volume of administration is 10ml/kg. The same amount of reference substance is given to the right ear as the same volume. Once through the day, 7 consecutive days, the microinjection pump is injected intravenously. After the last administration, 6 animals (3 females and 3 males) are injected intraperitoneally. A deep anesthesia was performed with a 20% solution of ulaurose, and the carotid artery was sacrificed after anesthesia. The remaining 4 animals (2 females and 2 males) were sacrificed 7 days after the observation. Rabbit ears were sent for routine sampling, dehydration, embedding, staining, and light microscopy. RESULTS: Pathologic examination showed that the left and right blood vessel walls of each rabbit's ear were not damaged during the administration of the drug, and there was no abnormality in each layer of tissue. There was no congestion, swelling, bleeding and other phenomena. No delayed toxicity was observed in the left and right rabbit ears of the test group and control group during the convalescence period. CONCLUSIONS: In the laboratory prescribed by GLP, at a concentration of 12.9 mg/ml, cefpiperidone sodium telazobatam sodium(4:1) for injection did not cause local vascular irritation at the injection site. Pathological response.

Key words: Cefoperazone Sodium Tazobactam Sodium for Injection (4:1)；Rabbit ear ear constant flow pump intravenous injection；Vascular irritation test

目录

摘要 I

Abstract II

第一章 文献综述 1

1.1 头孢哌酮钠他唑巴坦钠介绍 1

1.2 头孢哌酮钠他唑巴坦钠药动学相关知识 1

1.3 头孢哌酮钠他唑巴坦钠临床应用 1

1.4 头孢哌酮钠他唑巴坦钠（4：1）血管刺激性试验研究^[15-19] 2

1.4.1 实验动物的选择 2

1.4.2 实验方法 2

1.4.3 病理取材方法 2

1.4.4 病理观察 3

1.5 研究的问题与方法 3

1.5.1 研究的问题 3

1.5.2 研究方法 3

第二章 试验材料 4

2.1 仪器 4

2.2 试剂 4

2.3.1 供试品 4

2.2.2对照品 5

2.2.3溶媒对照 5

2.2.4麻醉剂 5

2.3 实验系统 6

2.3.1 实验动物 6

2.3.2 实验系统的选择理由 6

2.3.3 饲养标识和动物识别 6

2.3.4 实验动物的饲养管理^[30] 7

2.3.5 试验后动物处死和尸体的处理 8

第三章 注射用头孢哌酮钠他唑巴坦钠（4：1）血管刺激性试验研究 9

3.1 实验设计 9

3.1.1 给药剂量及选择理由 9

3.1.2 动物分组 9

3.2 供试品和对照品的配制 9

3.3 供试品溶液采集和分析 10

3.3.1 样品采集计划 10

3.3.2供试品制剂浓度检测 10

3.3.3供试品制剂稳定性检测 10

3.3.4供试品制剂均一性检测 10

3.3.5分析方法 11

3.4 给药方案 11

3.4.1 供试品和对照品给药方法 11

3.4.2 供试品和对照品的给药体积 11

3.4.3 给药方式的选择 11

3.5 实验过程 11

3.5.1 实验方法 11

3.5.2 临床观察 12

3.5.3 血管注射部位肉眼观察和评价 12

3.5.4 体重 12

3.6 结果 13

3.6.1 制剂分析 13

3.6.2 给药结束 13

3.6.3 恢复期 14

3.6.4 病理检查图片 17

3.7 讨论 19

第四章 总结 20

参考文献 21

致谢 24

1. 文献综述

1.1 头孢哌酮钠他唑巴坦钠介绍

头孢哌酮钠他唑巴坦钠属于复合药物，是第三代头孢菌素，主要成分为他唑巴坦以及头孢哌酮钠^[1]。英文化学名称为Cefoperagone Sodium and Tazobactam Sodium for lnjection。

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