CN102670529A - 注射用左旋泮托拉唑钠冻干粉组合物及其制备方法 - Google Patents
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Abstract
一种注射用左旋泮托拉唑钠冻干粉组合物及其制备方法，涉及医药领域，该组合物的主药为：左旋泮托拉唑钠和精氨酸，制备该冻干粉组合物的具体步骤为：将质量百分比为0.1%～99.9%的左旋泮托拉唑钠、99.9%～0.1%精氨酸，和主药5～10倍的甘露醇加到注射用水中；搅拌溶解后加入NaOH溶液调节pH值11.0；加入总体积0.1%的活性炭搅拌30分钟；滤除活性炭，药液再经0.45μm和0.22μm微孔滤膜过滤；罐装，送入冷冻干燥机中；降温至-40℃，保温2小时后，缓慢升温至-5℃～0℃升华干燥，再升温至35℃后，保温3小时；冷冻干燥结束，出箱，即得注射用左旋泮托拉唑钠冻干粉组合物。本发明的优点：液体加工方便，简化了无菌作业过程；提高了制剂的稳定性；无需经过热处理就能去除产品中的水分；增强了制剂的复水（溶解）性。
Description
技术领域：
本发明涉及医药领域，尤其涉及一种注射用左旋泮托拉唑钠冻干粉组合物及其制备方法。
背景技术：
胃溃疡是我国人群中常见病、多发病之一。其发生主要与胃十二指肠黏膜的损害因素和黏膜自身防御修复因素之间失平衡有关。幽门螺杆菌(H. pylori)感染、非甾体抗炎药(NSAID，如阿司匹林)、胃酸分泌异常是引起溃疡的常见病因。典型的溃疡疼痛具有长期性、周期性和节律性的特点。
胃腔内，胃酸和胃蛋白酶是胃液中重要的消化物质。胃酸为强酸性物质，具有较强的侵蚀性；胃蛋白酶具有水解蛋白质的作用，可破坏胃壁上的蛋白质，然而，在这些侵蚀因素的存在下，胃肠道仍能抵抗而维持黏膜的完整性及自身的功能，其主要是因为胃、十二指肠黏膜还具有一系列防御和修复机制。我们将胃酸及胃蛋白酶的有害侵蚀性称之为损伤机制，而将胃肠道自身具有的防御和修复机制称之为保护机制。目前认为，正常人的胃十二指肠黏膜的保护机制，足以抵抗胃酸及胃蛋白酶的侵蚀。但是，当某些因素损害了保护机制中的某个环节就可能发生胃酸及蛋白酶侵蚀自身黏膜而导致溃疡的形成。当过度胃酸分泌远远超过黏膜的防御和修复作用也可能导致溃疡发生。近年的研究已经表明，幽门螺杆菌和非甾体抗炎药是损害胃肠保护机制导致溃疡发病的最常见病因，胃酸在溃疡形成中起关键作用。此外，药物，应激，激素也可导致溃疡的产生，各种心理因素及不良的饮食生活习惯可诱发溃疡的出现。
发明内容：
本发明的目的在于提供一种注射用左旋泮托拉唑钠冻干粉组合物及其制备方法，该组合物在体内有协同作用，在临床上能治疗胃溃疡，修复溃疡伤口，治疗消化道溃疡，疗效迅速。
本发明的具体技术方案为：
一种注射用左旋泮托拉唑钠冻干粉组合物，其特征在于，该组合物的主药为：质量百分比，0.1%～99.9%的左旋泮托拉唑钠和99.9%～0.1%的精氨酸。
一种以上述组合物的主药制备注射用冻干粉针的方法，其特征在于，具体操作步骤为：
（1）将质量百分比为0.1%～99.9%的左旋泮托拉唑钠、99.9%～0.1%精氨酸，和主药5～10倍的甘露醇加到注射用水中；
（2）搅拌溶解后加入NaOH溶液调节pH值11.0；
（3）加入总体积0.1%的活性炭搅拌30分钟；
（4）滤除活性炭，药液再经0.45μm和0.22μm微孔滤膜过滤；
（5）罐装，送入冷冻干燥机中；
（6）降温至-40℃，保温2小时后，缓慢升温至-5℃～0℃升华干燥，再升温至35℃后，保温3小时；
（7）冷冻干燥结束，出箱，即得注射用左旋泮托拉唑钠冻干粉组合物。
左旋泮托拉唑钠作用于壁细胞胃酸分泌终末步骤中的关键酶H+-K+ATP酶，使其不可逆失活，抑酸作用更强且作用持久。左旋泮托拉唑钠促进溃疡愈合的速度较快、愈合率较高，适用于各种难治性溃疡或NSAID溃疡患者不能停用NSAID时的治疗，还可与抗生素的协同作用可用于根除幽门螺杆菌治疗，因此是胃溃疡的首选用药。
精氨酸 (Arg)为氨基酸类药，参与鸟氨酸循环，在肝精氨酸酶活力下促进氨转化为无毒的尿素由尿中排出，以降低血氨。主要用于血氨增高引起的肝昏迷及各类肝昏迷忌用谷氨酸钠的病人。新的药理研究发现: Arg是一氧化氮（NO）的生理性前提，经 NO合成酶 (NOS)作用后生成 NO。NO在体内具有多种生理活性作用:舒张血管，抗血小板聚集，抗血栓形成和抗血管平滑肌增生等。因而作为合成NO的底物，提供外源性的Arg，通过Arg-NO通路，促进体内NO浓度增加， Arg在临床中能起到加速溃疡伤口复原的作用。
单一的左旋泮托拉唑钠制剂只能起到治疗的作用，只能靠人体自身修复。单一的精氨酸却不能起到治疗的目的。所以将两者结合不仅治疗了胃溃疡，还能做到修复溃疡面积，从而提高治疗效果。
本发明用冻干工艺生产注射用左旋泮托拉唑钠冻干粉组合物有以下优点：1）液体加工方便，简化了无菌作业过程；2）提高了制剂的稳定性；3）无需经过热处理就能去除产品中的水分；4）增强了制剂的复水（溶解）性。
具体实施方式：
为了使本发明实现的技术手段、创作特征、达成目的与功效易于明白了解，下面结合具体实施例，进一步阐述本发明。
实施例一、注射用左旋泮托拉唑钠组合物冻干粉针的制备，以1000支计
1.处方
2.制备工艺
将处方量的的左旋泮托拉唑钠、精氨酸和甘露醇加到注射用水中，搅拌溶解后加入NaOH溶液调节pH值11.0，加入0.1%的活性炭搅拌30分钟，滤除活性炭，药液再经0.45μm和0.22μm微孔滤膜过滤，罐装，送入冷冻干燥机中，降温至-40℃，保温2小时后，缓慢升温至-5℃～0℃升华干燥，再升温至35℃后，保温3小时，冷冻干燥结束，出箱。
实施例二、注射用左旋泮托拉唑钠组合物冻干粉针的制备，以1000支计
1.处方
2.制备工艺
将处方量的的左旋泮托拉唑钠、精氨酸和甘露醇加到注射用水中，搅拌溶解后加入NaOH溶液调节pH值11.0，加入0.1%的活性炭搅拌30分钟，滤除活性炭，药液再经0.45μm和0.22μm微孔滤膜过滤，罐装，送入冷冻干燥机中，降温至-40℃，保温2小时后，缓慢升温至-5℃～0℃升华干燥，再升温至35℃后，保温3小时，冷冻干燥结束，出箱。
实施例三、注射用左旋泮托拉唑钠组合物冻干粉针的制备，以1000支计
1.处方
2.制备工艺
将处方量的的左旋泮托拉唑钠、精氨酸和甘露醇加到注射用水中，搅拌溶解后加入NaOH溶液调节pH值11.0，加入0.1%的活性炭搅拌30分钟，滤除活性炭，药液再经0.45μm和0.22μm微孔滤膜过滤，罐装，送入冷冻干燥机中，降温至-40℃，保温2小时后，缓慢升温至-5℃～0℃升华干燥，再升温至35℃后，保温3小时，冷冻干燥结束，出箱。
实验资料
SD大白鼠50只。试验前禁食24h。在乙醚麻醉下打开腹腔，将内径5mm、长30mm的玻璃管垂直放置于胃体部浆膜面上，向管腔内加入冰醋酸0. 2ml，1.5min后用棉签蘸出冰醋酸，缝合手术切口。术后正常饮食，第二天将动物随机分为5组: 对照组1( 蒸馏水)，对照组2( 注射用左旋泮托拉唑钠)，治疗组1(实施例一)、治疗组2(实施例二)、治疗组3(实施例三)；连续给药15d。解剖取出胃，并用甲醛固定，沿胃大弯剖开胃，平展在玻璃板上，测量溃疡横竖径d1、d2。用公式S=π×(d1/2)×(d2/2)计算溃疡面积S( mm2) 作为溃疡指数， 并计算溃疡愈合率和溃疡抑制率。结果见下表
通过实验资料表明，实施例一、二、三均对溃疡有良好的治疗作用，治疗组1、2、3的治愈率比单用左旋泮托拉唑钠（对照组2）高，对胃溃疡有良好的治疗效果，并且能修复溃疡面积。
以上显示和描述了本发明的基本原理、主要特征以及本发明的优点。本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的只是说明本发明的原理，在不脱离本发明精神和范围的前提下，本发明还会有各种变化和改进，这些变化和改进都落入要求保护的本发明范围内。本发明要求保护范围由所附的权利要求书及其等效物界定。
Claims (2)
1.一种注射用左旋泮托拉唑钠冻干粉组合物，其特征在于，该组合物的主药为：质量百分比，0.1%～99.9%的左旋泮托拉唑钠和99.9%～0.1%的精氨酸。
2.一种以权利要求1所述组合物的主药制备注射用冻干粉针的方法，其特征在于，具体操作步骤为：
（1）将质量百分比为0.1%～99.9%的左旋泮托拉唑钠、99.9%～0.1%精氨酸，和主药5～10倍的甘露醇加到注射用水中；
（2）搅拌溶解后加入NaOH溶液调节pH值11.0；
（3）加入总体积0.1%的活性炭搅拌30分钟；
（4）滤除活性炭，药液再经0.45μm和0.22μm微孔滤膜过滤；
（5）罐装，送入冷冻干燥机中；
（6）降温至-40℃，保温2小时后，缓慢升温至-5℃～0℃升华干燥，再升温至35℃后，保温3小时；
（7）冷冻干燥结束，出箱，即得注射用左旋泮托拉唑钠冻干粉组合物。
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| CN115444826A (zh) * | 2022-10-14 | 2022-12-09 | 海南锦瑞制药有限公司 | 注射用泮托拉唑钠的制备方法 |
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| CN115444826B (zh) * | 2022-10-14 | 2023-07-21 | 海南锦瑞制药有限公司 | 注射用泮托拉唑钠的制备方法 |
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