CN1096266C - 抗菌组合药物 - Google Patents

抗菌组合药物 Download PDF

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CN1096266C
CN1096266C CN98113282A CN98113282A CN1096266C CN 1096266 C CN1096266 C CN 1096266C CN 98113282 A CN98113282 A CN 98113282A CN 98113282 A CN98113282 A CN 98113282A CN 1096266 C CN1096266 C CN 1096266C
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ceftazidime
beta
tazobactam
sulbactam
alkali metal
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CN1214246A (zh
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吕华冲
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Xiangbei Welman Pharmaceutical Co Ltd
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Wei'erman Pharmaceutic Co Ltd Guangzhou
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Abstract

本发明涉及一种抗菌组合药物。它由头孢他啶与β-内酰胺酶抑制剂混合而成，头孢他啶与β-内酰胺酶的重量百分比为1∶2至10∶1(含端点)。头孢他啶为头孢他啶游离酸、头孢他啶五水合物、头孢他啶的碱金属盐以及头孢他啶游离酸的水合和非水合物加用碳酸钠或碳酸氢钠的形式，β-内酰胺酶抑制剂为棒酸及其衍生物，舒巴坦及其衍生物以及他佐巴坦及其衍生物。该产品不仅对敏感菌，而且对产酶菌有较好作用，其抗菌谱更广、抗菌作用更强。

Description

一种抗菌组合药物
本发明涉及一种头孢他啶(Ceftazidime)与β-内酰胺酶抑制剂组成的抗菌组合药物。
头孢他啶的抗菌谱广，抗菌作用强，对绿脓杆菌具有高度活性，其对金葡菌、A组溶血性链球菌、无乳链球菌、肺炎球菌、大肠杆菌、肺炎杆菌、奇异变形杆菌、普通变形杆菌、流感杆菌、百日咳杆菌、淋球菌与脑膜炎球菌等均有效。
到目前为止，头孢他啶通常仅以单一药物形式使用。然而，近来临床上发现，许多革兰氏阳性菌和阴性菌对头孢他啶形成耐药，许多重要病原菌中产生β-内酰胺酶的菌株明显增加，已引起人们关注。在大多数情况下，细菌耐药是由于其所产的β-内酰胺酶对抗生素的水解作用所致。因而使用头孢他啶时，加用一种能有效地抑制β-内酰胺酶作用的β-内酰胺酶抑制剂，更有利于头孢他啶稳定地发挥其抗菌作用，尤其对产β-内酰胺酶的病原体而言更是如此。因此，头孢他啶与β-内酰胺酶抑制剂组成的组合药物不仅对敏感菌，而且对产酶菌均有较好作用，其抗菌谱更广、抗菌作用更强。
本发明的目的在于提供一种抗菌谱更广、抗菌作用更强的头孢他啶与β-内酰胺酶抑制剂组成的抗菌组合药物。
本发明是这样实现的，它由头孢他啶和β-内酰胺酶抑制剂混合而成，头孢他啶与β-内酰胺酶抑制剂的重量比为1∶2至10∶1(含端点)。其中头孢他啶可以为头孢他啶游离酸、头孢他啶五水合物、头孢他啶的碱金属盐以及头孢他啶游离酸的水合和非水合物加用碳酸钠或碳酸氢钠的形式。β-内酰胺酶抑制剂为棒酸(Clavulanicacid)及其衍生物，舒巴坦(Sulbactam)及其衍生物以及他佐巴坦(Tazobactam)及其衍生物。而棒酸衍生物有棒酸的碱金属盐例如棒酸钾，舒巴坦有舒巴坦的碱金属盐例如舒巴坦钠；他佐巴坦衍生物有他佐巴坦的碱金属盐例如他佐巴坦钠。
本发明的粉针剂或冻干粉针剂可用于治疗细菌感染例如呼吸道感染、肝胆系统感染、腹腔内感染、盆腔感染和其他妇科感染、败血症、脑膜炎、皮肤软组织感染、骨髓炎。本发明的粉针剂或冻干粉针剂通常适用于治疗对β-内酰胺类抗生素敏感的微生物感染，也对一些耐青霉素微生物有效。
下面结合实施例对本发明作进一步详述。
实施例1：头孢他啶组合药物由头孢他啶1克与棒酸钾0.5克制成组合制剂，按粉针剂制备工艺程序操作进行。
实施例2：头孢他啶组合药物由头孢他啶1克与棒酸钾0.5克制成组合制剂，按冻干粉针制剂工艺程序进行。
实施例3：头孢他啶组合药物由头孢他啶1克与棒酸钾0.25克制成组合制剂，按粉针剂制备工艺程序操作进行。
实施例4：头孢他啶组合药物由头孢他啶1克与棒酸钾0.25克制成组合制剂，按冻干粉针剂制备工艺程序操作。
实施例5：头孢他啶组合药物由头孢他啶1克与舒巴坦钠1克制成组合制剂，按粉针剂制备工艺程序操作。
实施例6：头孢他啶组合药物由头孢他啶1克与舒巴坦钠1克制成组合制剂，按冻干粉针剂制备工艺程序操作。
实施例7，头孢他啶组合药物由头孢他啶0.5克与舒巴坦钠1克制成组合制剂，按粉针剂制备工艺程序操作。
实施例8，头孢他啶组合药物由头孢他啶1克与舒巴坦钠0.5克制成组合制剂，按冻干粉针剂制备工艺程序进行。
实施例9，头孢他啶组合药物由头孢他啶1克与他佐巴坦钠0.25克制成组合制剂，按粉针剂制备程序进行。
实施例10，头孢他啶组合药物由头孢他啶1克与他佐巴坦钠0.125克制成组合制剂，按冻干粉针剂制备工艺程序操作。
实施例11，头孢他啶组合药物由头孢他啶1克与他佐巴坦钠0.125克制成组合制剂，按粉针剂制备工艺程序进行。
实施例12，头孢他啶组合药物由头孢他啶1克与他佐巴坦钠0.125克制成组合制剂，按冻干粉针剂制备工艺程序进行。
本发明不限于以上所述的实施例。
本发明的组合制剂经体外试验证明，其抗菌活性及抗菌谱比头孢他啶应用时作用更强。
表1  头孢他啶与头孢他啶/棒酸的抗菌作用(MIC mg/L)
细菌 株数 头孢他啶 头孢他啶/棒酸(1∶4)
大肠杆菌 14 32 0.25
阴沟肠杆菌 22 128 16
克雷伯氏肺炎杆菌 10 8 0.125
绿脓杆菌 6 25.6 16
粘氏沙雷氏菌 14 4 0.125
金黄色葡萄球菌 18 16 0.5
表皮葡萄球菌 4 128 16
溶血链球菌 26 32 0.25
表2  头孢他啶与头孢他啶舒巴坦的抗菌作用(MIC mg/L)
细菌 株数 头孢他啶   头孢他啶/棒酸(1∶1)
金黄色葡萄球菌 14 16   1
溶血链球菌 20 64   4
肺炎球菌 10 2   0.125
大肠杆菌 18 16   0.125
粘氏沙雷菌 12 4   0.25
绿脓杆菌 8 256   32
克雷伯氏肺炎杆菌 8 16   0.5
氟氏拘橼酸杆菌 20 128   32
奇异变形杆菌 16 8   0.125
表3  头孢他啶与头孢他啶/他佐巴坦的抗菌作用(MIC mg/L)
细菌 株数 头孢他啶  头孢他啶/他佐马坦(4∶1)
大肠杆菌 16 16  2
阴沟肠杆菌 18 128  8
氟氏枸橼酸杆菌 16 128  16
绿脓杆菌 10 256  8
金黄色葡萄球菌 14 32  2
溶血性链球菌 20 32  0.5
粘氏沙雷氏菌 24 4  0.125
本发明的粉针剂或冻干粉针剂通常适用于治疗对β-内酰胺酶敏感的微生物感染，也对一些耐青霉素微生物有效，可用于治疗细菌感染例如呼吸道感染，肝胆系统感染，腹腔内感染，盆腔感染和其他妇科感染、败血症、脑膜炎，皮肤软组织感染和骨髓炎。并适用于由上述常见病原体引起的动物的感染，因而也可用于兽类感染疾病的治疗。
本发明药物的单位剂量通常为注射给药，可作静脉推注，快速静脉滴入或肌肉注射。头孢他啶每日适当的总剂量为1500-6000毫克，每日三次给药。
综上所述，按照本发明的药物，β-内酰胺酶抑制剂与头孢他啶间具有显著的协同作用，能明显地增强头孢他啶的抗菌活性和抗菌谱。从而有效地解决细菌越来越多的对头孢他啶耐药问题，增强药物的临床疗效。

Claims (6)

1.一种抗菌组合药物，其特征在于：它由头孢他啶与β-内酰胺酶抑制剂混合而成，头孢他啶与β-内酰胺酶抑制剂的重量百分比为1∶2至10∶1。
2.根据权利要求1所述的抗菌组合药物，其特征在于：头孢他啶为头孢他啶游离酸、头孢他啶五水合物、头孢他啶的碱金属盐以及头孢他啶游离酸的水合和非水合物加用碳酸钠或碳酸氢钠的形式。
3.权利要求1所述的抗菌组合药物，其特征在于：β-内酰胺酶抑制剂为棒酸及其衍生物，舒巴坦及其衍生物以及他佐巴坦及其衍生物；而棒酸衍生物有棒酸的碱金属盐，舒巴坦衍生物有舒巴坦的碱金属盐，他佐巴坦衍生物有他佐巴坦的碱金属盐。
4.根据权利要求3所述的抗菌组合药物，其特征在于棒酸的碱金属盐为棒酸钾。
5.根据权利要求3所述的抗菌组合药物，其特征在于舒巴坦的碱金属盐为舒巴坦钠。
6.根据权利要求3所述的抗菌组合药物，其特征在于他佐巴坦的碱金属盐为他佐巴坦钠。
CN98113282A 1998-07-15 1998-07-15 抗菌组合药物 Ceased CN1096266C (zh)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100384857C (zh) * 2003-11-28 2008-04-30 浙江永宁制药厂 耐β-内酰胺酶的头孢菌素酯化合物及其盐

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1321183C (zh) * 2004-11-25 2007-06-13 上海医药工业研究院 具有抑制β－内酰胺酶抑制活性的多肽及编码的DNA
CN101849949B (zh) * 2010-06-17 2012-05-23 深圳市新泰医药有限公司 一种头孢匹林钠和舒巴坦钠的组合物及其配比
CN104147013A (zh) * 2013-09-09 2014-11-19 海南康芝药业股份有限公司 一种抗耐药菌组合物及其制法
CN111658642A (zh) * 2019-03-05 2020-09-15 广州新创忆药物临床研究有限公司 一种治疗耐碳青霉烯类抗生素鲍曼不动杆菌感染的组合物

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
《中国抗生素杂志》,22(5) 1997.10.1 凌保东等，"氯唑西大对阴沟杆菌B-内酰胺酶的抑制及其与头孢他啶的协同抗菌作用" *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100384857C (zh) * 2003-11-28 2008-04-30 浙江永宁制药厂 耐β-内酰胺酶的头孢菌素酯化合物及其盐

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