CN101914106B - 头孢孟多酯钠水合物及其制备方法 - Google Patents
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Abstract
本发明涉及一种头孢孟多酯钠的水合物，其分子式为C19H17N6NaO6S2·5H2O。本发明的头孢孟多酯钠水合物制备方法如下：头孢孟多酯钠原料药用水溶解，放入结晶器中，加入5～15份的溶析剂，冷却到2～8℃，待固体析出，过滤，固体物用溶析剂润洗，在通风或真空条件下干燥，干燥时间3～5小时，干燥温度10～50℃，得头孢孟多酯钠水合物。本发明还提供了注射用头孢孟多酯钠，由上述的头孢孟多酯钠的水合物为原料药制得。本发明所得的头孢孟多酯钠水合物，表面光洁，稳定性好，在水中的溶解速度快。而且溶解于水以后，其作用机理和临床疗效和现有工艺制得的头孢孟多酯钠一样。
Description
技术领域
本发明涉及一种头孢孟多酯钠的水合物，涉及该水合物的制备方法及其在医学上的用途，属于医药技术领域。
技术背景
头孢孟多酯钠化学式为7-D-(2-甲酰氧苯乙酰胺)-3[(1-甲基-1H-四唑-5基)巯甲基]-3头孢烯-4-羧酸钠盐，分子式为C19H17N6NaO6S2，为第二代头孢菌素，应用于敏感的革兰阴性菌所致的呼吸道、泌尿生殖系、皮肤和软组织、骨和关节、咽耳鼻喉等部位感染以及腹膜炎、败血症等。对胆道和肠道感染有较好疗效。
目前，头孢孟多酯钠多为注射用粉针制剂，含有少量的头孢孟多，由于头孢孟多在水中溶解度较小，需要在制剂中加入碳酸钠作为助溶剂，配制注射液时会产生大量的二氧化碳，给使用带来不方便。
本发明得到的头孢孟多酯钠水合物，具有特定的晶型，含5个结晶水，头孢孟多酯钠水合物稳定性好，易溶解，而且溶解于水以后，其作用机理和临床疗效和现有工艺制得的头孢孟多酯钠一样。
发明内容
本发明的目的是提供头孢孟多酯钠水合物及其制备方法，得到的头孢孟多酯钠水合物易溶解且稳定性好。
本发明提供的技术方案是：头孢孟多酯钠水合物(也可称为头孢孟多酯钠五水合物)，其分子式为C19H17N6NaO6S2·5H2O。
本发明的头孢孟多酯钠水合物制备方法如下：
头孢孟多酯钠原料药用水溶解，放入结晶器中，加入5～15份的溶析剂，冷却到2～8℃，待固体析出，过滤，固体物用溶析剂润洗，在通风或真空条件下干燥，干燥时间3～5小时，干燥温度10～50℃，得头孢孟多酯钠水合物。
所述的溶析剂为丙酮、二氯甲烷、三氯甲烷、乙醇、异丙醇、正丙醇、乙醚、乙酸甲酯、乙酸乙酯、乙酸丁酯的一种或几种(二种以上的组合物)。
本发明还提供了注射用头孢孟多酯钠，由上述的头孢孟多酯钠的水合物为原料药制得。
本发明所得的头孢孟多酯钠水合物，表面光洁，稳定性好，在水中的溶解速度快。而且溶解于水以后，其作用机理和临床疗效和现有工艺制得的头孢孟多酯钠一样。
具体实施方式
实施案例1
称取头孢孟多酯钠原料200g，置于500ml烧杯中，加入50ml水溶解。缓慢加入(半小时内加完)丙酮200ml，边加边搅拌，控制温度至2～8℃，恒温3小时。
抽滤，用乙醇洗涤滤饼，50℃减压干燥4小时，得头孢孟多酯钠五水合物。
实施案例2
称取头孢孟多酯钠原料200g，置于500ml烧杯中，加入50ml水溶解。缓慢加入(半小时内加完)溶析剂200ml，边加边搅拌，溶析剂为乙醇50ml、乙酸乙酯150ml，控制温度至2～8℃，恒温3小时。
抽滤，用乙醇洗涤滤饼，50℃减压干燥4小时，得头孢孟多酯钠五水合物。
实施案例3
称取头孢孟多酯钠原料2000g，置于5000ml烧杯中，加入500ml水溶解。缓慢加入(40分钟内加完)溶析剂2000ml，边加边搅拌，溶析剂为二氯甲烷500ml、乙酸乙酯1500ml，控制温度至2～8℃，恒温3小时。
抽滤，用乙醇洗涤滤饼，50℃减压干燥4小时，得头孢孟多酯钠五水合物。
头孢孟多酯钠水合物的有关特性研究：
1、元素分析
取以上制备的头孢孟多酯钠水合物进行元素分析，结果：C 37.88％；H 4.50％；N 13.87％，与头孢孟多酯钠五水合物理论值相符(理论值：C 37.84％；H 4.48％；N 13.94％)
2、差热分析
取以上制备的头孢孟多酯钠水合物进行差热分析，市购原料药做对照。结果表明：本品在100℃～115℃之间有吸收峰，说明样品中含有结晶水或结晶溶剂，而对照品没有吸收峰，说明样品中无结晶水或结晶溶剂。
3、干燥失重及水分分析
将以上制备的头孢孟多酯钠水合物在105℃干燥至恒重，减少重量为15.17％；另按卡氏水分测定法测定其中的水分，结果为15.25％，两种结果一致。这表明样品中只含有水，不含其它溶剂。
综合元素分析、差热分析、干燥失重及水分分析结果，可以证明样品中含有5分子的结晶水。
4、稳定性分析
取以上制备的头孢孟多酯钠水合物进行高湿试验，市购头孢孟多酯钠原料药做对照，于25℃下置相对湿度为75％的恒温恒湿箱中，放置10天，分别于第2、4、6、8、10天取样检定，结果与0天样品检验结果比较。结果见表1
表1在40℃，75％条件下的稳定性试验结果
结果表明：头孢孟多酯钠水合物具有较好的稳定性和较低的吸潮性。
5、溶解性分析
取以上制备的头孢孟多酯钠水合物与原料药对照，比较二者在水中的溶解速度，结果如表2
表2溶解速度比较
| 溶解速度 | |
| 本专利制备样品 | 1min |
| 市售原料药 | 大于30min |
本发明制备的头孢孟多酯钠冻干粉针原料药的溶解性明显提高。
实施案例4
取上述制备的头孢孟多酯钠水合物，按装量要求进行无菌分装，即得药品注射用头孢孟多酯钠。装量可以是但不仅仅是0.5g、1g、2g每瓶。
Claims (2)
1.头孢孟多酯钠的水合物，其分子式为C19H17N6NaO6S2·5H2O。
2.权利要求1所述头孢孟多酯钠水合物的制备方法，包括以下步骤：将头孢孟多酯钠用水溶解，放入结晶器中，加入5～15份重量的溶析剂，冷却到2～8℃，待固体析出，过滤，固体物用溶析剂润洗，在通风或真空条件下干燥，干燥时间3～5小时，干燥温度10～50℃，得权利要求1所述头孢孟多酯钠水合物；溶析剂为丙酮、二氯甲烷、三氯甲烷、乙醇、异丙醇、正丙醇、乙醚、乙酸甲酯、乙酸乙酯、乙酸丁酯中的一种或几种。
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| CN105037391B (zh) * | 2015-07-07 | 2017-09-29 | 山东罗欣药业集团股份有限公司 | 一种头孢孟多酯钠化合物及其制剂 |
| CN106831821B (zh) * | 2017-01-04 | 2019-05-10 | 海南灵康制药有限公司 | 1/4水头孢孟多酯钠化合物 |
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Application publication date: 20101215 Assignee: Hunan Kelun Pharmaceutical Co., Ltd. Assignor: Hubei Neo-Treation Pharmaceutical Co., Ltd. Contract record no.: 2014420000020 Denomination of invention: Cefamandole nafate hydrate and preparation method thereof Granted publication date: 20121219 License type: Exclusive License Record date: 20140324 |
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Owner name: HUBEI MERRYCLIN PHARMACEUTICALS CO., LTD. Free format text: FORMER OWNER: HUBEI NEO-TREATION PHARMACEUTICAL CO., LTD. Effective date: 20150209 |
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Free format text: CORRECT: ADDRESS; FROM: 430014 WUHAN, HUBEI PROVINCE TO: 432500 XIAOGAN, HUBEI PROVINCE |
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Effective date of registration: 20150209 Address after: 432500 Yunmeng Economic Development Zone, Hubei, Xiaogan Patentee after: Hubei Merryclin Pharmaceutical Co., Ltd. Address before: 430014, B2B5, room 15, Zhenghe Plaza, 707 Zhongshan Avenue, Jiang'an District, Hubei, Wuhan Patentee before: Hubei Neo-Treation Pharmaceutical Co., Ltd. |
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Effective date of registration: 20171207 Address after: 432800 Xiaogan City, Hubei Province town of Chengguan Dawu County Han market No. 126 Patentee after: Hubei Yuan Yuan medical science and Technology Co., Ltd. Address before: 432500 Yunmeng Economic Development Zone, Hubei, Xiaogan Patentee before: Hubei Merryclin Pharmaceutical Co., Ltd. |
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Effective date of registration: 20181107 Address after: 432500 Yunmeng County Economic Development Zone, Xiaogan, Hubei Patentee after: Hubei Merryclin Pharmaceutical Co., Ltd. Address before: 432800 126, Han Da market, Chengguan Town, Dawu County, Xiaogan, Hubei Patentee before: Hubei Yuan Yuan medical science and Technology Co., Ltd. |