CN102205128B - 抗菌肽保存试剂和含该试剂的抗菌肽制剂及制剂制备方法 - Google Patents
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Abstract
本发明公开了一种抗菌肽保存试剂和含该试剂的抗菌肽制剂及制剂制备方法，属于药物制剂领域。其中，抗菌肽保存试剂包含缓冲液、氨基酸、稳定剂和抗氧化剂。抗菌肽制剂中包含抗菌肽、缓冲液、氨基酸、稳定剂和抗氧化剂。抗菌肽制剂的制备方法为：将抗菌肽、缓冲液、氨基酸、稳定剂、抗氧化剂以及注射用水混合均匀；将PH值调至8.0-10.5。其中，缓冲液为Tris盐缓冲液。氨基酸为精氨酸、赖氨酸或谷氨酸。稳定剂为吐温-80、Pluronic F68或Pluronic F88。抗氧化剂为甲硫氨酸。本发明实施例提供的技术方案带来的有益效果是：能够使抗菌肽长期保存而生物活性不会降低，且制备工艺简单，适合于工业化生产。
Description
技术领域
本发明涉及药物制剂领域，特别涉及一种抗菌肽保存试剂和含该试剂的抗菌肽制剂及制剂制备方法。
背景技术
抗菌肽(Antibacterial peptide，ABP)又叫抗微生物肽(Antimicrobialpeptide)、抗生素肽(Antibiotics peptide)，是生物体经诱导产生的一类具有多种生物活性的小分子多肽，是宿主免疫防御***的一个重要组成部分，具有广谱抗菌、无耐药性及毒副作用等优点。目前，抗菌肽已成为生命科学研究领域的热点，国内外科学家从细菌、真菌、两栖类、水生生物、高等植物、哺乳动物乃至人类中分离得到了抗菌肽，同时用人工合成的方法得到了许多抗菌活性强于天然产物的抗菌肽，在研究它们的生物特性和空间结构的基础上，采用分子生物学和基因工程技术，将抗菌肽基因重组到微生物体内进行表达，可望成为新一代抗生素的来源。
抗菌肽作为多肽，也存在多肽药物常见的在液体制剂中不稳定和药物利用度降低的难题。药物制剂中危害多肽活性和药效的物理不稳定性包括：变性和可溶及不可溶凝聚体的形成。而化学不稳定性包括水解、生成亚胺、氧化、外消旋和脱酰胺。已知这些变化中一些可以导致药物活性降低或者消失。特别是这些降解产物可能存在潜在的不良副反应。
发明内容
为了延长抗菌肽的保存期且不影响其生物活性，本发明实施例提供了一种抗菌肽保存试剂和含该试剂的抗菌肽制剂及制剂制备方法。
为了实现上述发明目的，本发明提供了一种抗菌肽保存试剂，其中，所述试剂包含缓冲液、氨基酸、稳定剂和抗氧化剂。
所述缓冲液的浓度为5-500mmol/L，所述氨基酸的浓度为1-100mg/ml，所述抗氧化剂的浓度为0.01-5.0mg/ml，所述稳定剂的浓度为20-120ml/L。
所述缓冲液的浓度为20mmol/L，所述氨基酸的浓度为21.5mg/ml，所述抗氧化剂的浓度为0.1mg/ml，所述稳定剂的浓度为50ml/L。
所述缓冲液为Tris盐缓冲液。
所述氨基酸为精氨酸、赖氨酸或谷氨酸。
所述稳定剂为吐温-80、Pluronic F68或Pluronic F88。
所述抗氧化剂为甲硫氨酸。
为了实现上述发明目的，本发明又提供了一种抗菌肽保存试剂的抗菌肽制剂，其中，所述制剂中含有抗菌肽。
所述抗菌肽的浓度为1-100μg/ml。
为了实现上述发明目的，本发明还提供了一种抗菌肽制剂的制备方法，其中，其制备方法为：将抗菌肽1-100mg、缓冲液5-500mmol、氨基酸1-100g、稳定剂20-120ml、抗氧化剂0.01-5.0g以及注射用水1000ml混合均匀；将PH值调至8.0-10.5。
本发明实施例提供的技术方案带来的有益效果是：由于抗菌肽一般富含阳离子多肽，偏碱性，本发明制剂中的缓冲液能够控制制剂的pH在抗菌肽接受的范围内，避免其变性和生物学活性丧失；氨基酸能保护抗菌肽对抗各种应力(包括热、pH、搅拌、冷冻或解冻等)的作用，从而提高或维持抗菌肽的稳定性；吐温-80作为稳定剂，具有安全性高、分散性好等优点，且具有多种生物学和药理学活性；抗氧化剂作为辅料，能够最大程度的减少抗菌肽接触氧或存在自由基时所发生的氧化过程，延长制剂保存期；因此，上述组合能够使抗菌肽长期保存而生物活性不会降低，且制备工艺简单，适合于工业化生产。
具体实施方式
针对延长抗菌肽的保存期且不降低其生物活性，本发明提供了一种抗菌肽保存试剂，其中，试剂包含缓冲液、氨基酸、稳定剂和抗氧化剂。
其中，缓冲液为Tris盐缓冲液且浓度为20mmol/L，氨基酸为精氨酸且浓度为21.5mg/ml，抗氧化剂为甲硫氨酸且浓度为0.1mg/ml，稳定剂为吐温-80且浓度为50ml/L。
为了实现上述发明目的，本发明又提供了一种抗菌肽保存试剂的抗菌肽制剂，其中，制剂中含有抗菌肽、缓冲液、氨基酸、稳定剂和抗氧化剂。
其中，缓冲液为Tris盐缓冲液且浓度为20mmol，氨基酸为精氨酸且浓度为21.5g，抗氧化剂为甲硫氨酸且浓度为0.1g，稳定剂为吐温-80且浓度为50ml，抗菌肽的浓度为10mg。
为了实现上述发明目的，本发明还提供了一种抗菌肽制剂的制备方法，其中，其制备方法为：将抗菌肽10mg、缓冲液20mmol、氨基酸21.5g、稳定剂50ml、抗氧化剂0.1g以及注射用水1000ml混合均匀；将PH值调至8.0-9。
其中，缓冲液为Tris盐缓冲液，氨基酸为精氨酸，抗氧化剂为甲硫氨酸，稳定剂为吐温-80。
对比试验
试验组：按上述比例制备抗菌肽液体制剂，滤菌后分装至10ml安剖瓶，压盖，20℃保存。同时设立对照组：将抗菌肽10mg溶入1000ml注射用水中，滤菌后分装至10ml安剖瓶，压盖，20℃保存。每隔1个月取样检测制剂外观性状和抑菌活性，连取6个月。抑菌活性采用标准琼脂孔穴扩散法，以金黄色葡萄球菌Cowanl为试验菌株，青霉素作为对照。试验结果如下：
表1 抗菌肽液体制剂20℃保存条件下的变化
由表1能够看到，试验组与对照组相比，四个月时对照组就出现浑浊，抑菌活性降低，试验组则保存半年未见变化，说明试验组能够使抗菌肽保存更长时间而生物活性不会降低。
以上所述仅为本发明的较佳实施例，并不用以限制本发明，凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。
Claims (3)
1.一种抗菌肽保存试剂，其特征在于，所述试剂包含缓冲液、氨基酸、稳定剂和抗氧化剂；
所述缓冲液的浓度为5-500mmol/L，所述氨基酸的浓度为1-100mg/ml，所述抗氧化剂的浓度为0.01-5.0mg/ml，所述稳定剂的浓度为20-120ml/L；
所述缓冲液为Tris盐缓冲液；
所述氨基酸为精氨酸或赖氨酸；
所述稳定剂为吐温-80；
所述抗氧化剂为甲硫氨酸。
2.一种含有权利要求1所述的抗菌肽保存试剂的抗菌肽制剂，其特征在于，所述制剂中含有抗菌肽。
3.根据权利要求2所述的抗菌肽制剂，其特征在于，所述抗菌肽的浓度为1-100μg/ml。
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| CN1249175A (zh) * | 1999-09-10 | 2000-04-05 | 广州市华桑生物工程有限公司 | 新型护肤化妆品 |
| CN1528138A (zh) * | 2003-10-16 | 2004-09-15 | 上海高科生物工程有限公司 | 一种足部消毒剂 |
| CN101766805A (zh) * | 2009-12-24 | 2010-07-07 | 深圳市圣西马生物技术有限公司 | 稳定化的抗菌肽制剂及其制备方法 |
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| CN1249175A (zh) * | 1999-09-10 | 2000-04-05 | 广州市华桑生物工程有限公司 | 新型护肤化妆品 |
| CN1528138A (zh) * | 2003-10-16 | 2004-09-15 | 上海高科生物工程有限公司 | 一种足部消毒剂 |
| CN101766805A (zh) * | 2009-12-24 | 2010-07-07 | 深圳市圣西马生物技术有限公司 | 稳定化的抗菌肽制剂及其制备方法 |
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