CN107334754A - 一种清开灵雾化吸入用溶液制剂及其制备方法 - Google Patents
一种清开灵雾化吸入用溶液制剂及其制备方法 Download PDFInfo
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- CN107334754A CN107334754A CN201610023853.6A CN201610023853A CN107334754A CN 107334754 A CN107334754 A CN 107334754A CN 201610023853 A CN201610023853 A CN 201610023853A CN 107334754 A CN107334754 A CN 107334754A
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Abstract
本发明涉及一种清开灵雾化吸入用溶液制剂，属于制剂学领域。一种清开灵的雾化吸入用溶液制剂，包括(1)清开灵有效成分；(2)等渗剂及溶剂，还可以包括缓冲液。本发明制备的溶液制剂弥补了目前国内市场上的空白，而且本发明制备的溶液制剂是专为雾化吸入用患者设计，与雾化器配套使用，使用过程便捷，与清开灵注射液相比，给药途径不同，使用剂量减少，安全性提高。
Description
技术领域
本发明涉及一种清开灵雾化吸入用溶液制剂及其制备方法，属于制剂学领域。
背景技术
清开灵注射液是在安宫牛黄丸古方的基础上研制而成，主要成分有水牛角、珍珠母、板蓝根等，具有清热解毒，镇静安神之功效。主治外感风热时毒，火毒内盛所致的高热不退，烦躁不安，咽喉肿痛，舌质红绛，苔黄，脉数者；上呼吸道感染，病毒性感冒，急性化脓性扁桃体炎，急性咽炎，急性气管炎，高热等病症属于上述证候者。
近年来随着临床用药人群的增加，其不良反应报道也日益增多，主要表现在过敏性休克、过敏性哮喘等严重不良反应。因此，亟待开发一种更为安全的剂型，减少不良反应，提高临床用药安全。
发明内容
本发明主要解决的技术问题是提供一种安全、有效、质量优异的清开灵雾化吸入用溶液制剂；本发明还提供了该制剂的制备方法。
本发明是通过以下技术方案实现的：
一种清开灵雾化吸入用溶液制剂，包括：
(1)清开灵有效成分；
(2)等渗剂及溶剂；
还可以加入缓冲液。
其中，有效成分与等渗剂的质量比为1∶1-1∶5。
有效成分是这样制备得到的：
胆酸10-20份、珍珠母50-300份、猪去氧胆酸10-25份、栀子50-500份、水牛角50-500份、板蓝根500-2000份、黄芩苷5-50份、金银花50-4000份
按照上述重量份称取八味药，板蓝根加水煎煮二次，每次1小时，合并煎液，滤过，滤液浓缩至适量，加乙醇使含醇量达60％，冷藏，滤过，滤液回收乙醇，加水，冷藏备用；栀子加水煎煮二次，第一次1小时，第二次0.5小时，合并煎液，滤过，滤液浓缩至适量，加乙醇使含醇量达60％，冷藏，滤过，滤液回收乙醇，加水，冷藏备用；金银花加水煎煮二次，每次0.5小时，合并煎液，滤过，滤液浓缩至适量，加乙醇使含醇量达75％，滤过，滤液调节pH值至8.0，冷藏，回收乙醇，再加乙醇使含醇量达85％，冷藏，滤过，滤液回收乙醇，加水，冷藏备用；水牛角粉用氢氧化钡溶液、珍珠母粉用硫酸分别水解7-9小时，滤过，合并滤液，调节pH值至3.5-4.0，滤过，滤液加乙醇使含醇量达60％，冷藏，滤过，滤液回收乙醇，加水，冷藏备用；将栀子液、板蓝根液和水牛角、珍珠母水解混合液合并后，加到胆酸、猪去氧胆酸的75％乙醇溶液中，混匀，加乙醇使含醇量达75％，调节pH值至7.0，冷藏，滤过，滤液回收乙醇，加水，冷藏备用；黄芩苷用注射用水溶解，调pH值至7.5，加入金银花提取液，混匀，与上述各备用液合并，混匀，浓缩至适量，得到本发明的有效成分。
等渗剂为氯化钠、氯化钾、氯化镁、氯化钙、葡萄糖、木糖醇、山梨醇中的一种。
缓冲液为柠檬酸-柠檬酸钠、柠檬酸-磷酸氢二钠、磷酸二氢钾-磷酸氢二钠、柠檬酸-氢氧化钠、枸橼酸-磷酸氢二钠中的一种。
雾化吸入溶液的pH值是3.0-8.5；优选pH值是4.0-7.0。
雾化吸入溶液的用量是清开灵注射液用量的0.1-0.8倍；优选用量是清开灵注射液用量的0.3-0.6倍。
本发明所述的清开灵雾化吸入用溶液制剂可以用于治疗上呼吸道感染、病毒性感冒、急性化脓性扁桃体炎、急性咽炎、急性气管炎等。
本发明的优点是提供了一种优于清开灵注射液的新剂型，该制剂直接由呼吸道吸入，在局部聚集成较高浓度，并直接作用于气道表面的感受器或靶受体而发挥作用，且可从气道黏膜和肺部直接吸收，该给药方式可以将药效成分直接递送至病灶，安全有效，生物利用度高，能够实现低剂量而快速有效的治疗，因而具有明显优势。
本发明制备的溶液制剂弥补了目前国内市场上的空白，可以杜绝因缺乏吸入治疗专用的制剂药物，使用清开灵注射液替代用于吸入治疗而产生的安全性隐患。而且本发明制备的溶液制剂是专为雾化吸入用患者设计，与雾化器配套使用，使用过程便捷，与清开灵注射液相比，给药途径不同，使用剂量减少，安全性提高。
以下通过试验例进一步说明本发明的有益效果：
制备上呼吸道感染大鼠模型60只，随机分为正常对照组、阳性对照组、药物组一、药物组二、药物组三、药物组四，每组10只，其中，正常对照组给予等量生理盐水静脉注射；阳性对照组给予清开灵注射液静脉注射；药物组一、二、三、四分别给予清开灵雾化吸入溶液(用量分别为清开灵注射液的0.1倍、0.3倍、0.6倍、0.8倍)，连续给药3天，观察经过治疗后，各组的治愈率、不良反应发生率，以及末次给药后肺组织和血液中的药峰浓度。具体见下表：
表 各组治疗后的情况
由此可以看出，各药物组对上呼吸道感染大鼠均有较好的治疗作用，其中药物组二、三、四的治疗效果明显优于阳性对照组，且没有不良反应发生。
综上可知，药物组用药剂量小，不良反应少，且药物主要在肺部聚集成较高浓度，有利于药效成分直接作用于病灶，生物利用度高，实现了低剂量而快速有效的治疗，因而具有明显优势。
同样，药物组在治疗病毒性感冒、急性化脓性扁桃体炎、急性咽炎、急性气管炎等的效果也明显优于清开灵注射液。
本发明清开灵雾化吸入溶液的治疗效果明显优于清开灵注射液，填补了目前国内市场上的清开灵专用雾化吸入溶液的空白，与清开灵注射液相比，使用剂量大大减少，是清开灵注射液的0.1-0.8倍，优选为0.3-0.6倍，同时改变了给药途径，减少不良反应的发生，因此，本发明具备创造性和突出的实质性特点及显著的进步。
具体实施方式
以下药物制剂实施例的制剂过程和制剂所用物质或制剂所用物质的用量不限于文字表述，凡含有本发明提供的药物组合物的制剂方法，均属于本发明的保护范围。
实施例1
(1)有效成分的制备：
胆酸10-20份、珍珠母50-300份、猪去氧胆酸10-25份、栀子50-500份、水牛角50-500份、板蓝根500-2000份、黄芩苷5-50份、金银花50-4000份
按照上述重量份称取八味药，板蓝根加水煎煮二次，每次1小时，合并煎液，滤过，滤液浓缩至适量，加乙醇使含醇量达60％，冷藏，滤过，滤液回收乙醇，加水，冷藏备用；栀子加水煎煮二次，第一次1小时，第二次0.5小时，合并煎液，滤过，滤液浓缩至适量，加乙醇使含醇量达60％，冷藏，滤过，滤液回收乙醇，加水，冷藏备用；金银花加水煎煮二次，每次0.5小时，合并煎液，滤过，滤液浓缩至适量，加乙醇使含醇量达75％，滤过，滤液调节pH值至8.0，冷藏，回收乙醇，再加乙醇使含醇量达85％，冷藏，滤过，滤液回收乙醇，加水，冷藏备用；水牛角粉用氢氧化钡溶液、珍珠母粉用硫酸分别水解7-9小时，滤过，合并滤液，调节pH值至3.5-4.0，滤过，滤液加乙醇使含醇量达60％，冷藏，滤过，滤液回收乙醇，加水，冷藏备用；将栀子液、板蓝根液和水牛角、珍珠母水解混合液合并后，加到胆酸、猪去氧胆酸的75％乙醇溶液中，混匀，加乙醇使含醇量达75％，调节pH值至7.0，冷藏，滤过，滤液回收乙醇，加水，冷藏备用；黄芩苷用注射用水溶解，调pH值至7.5，加入金银花提取液，混匀，与上述各备用液合并，混匀，浓缩至适量，得到本发明的有效成分。
(2)清开灵雾化吸入用溶液的制备：
按处方量称取有效成分，加入适量注射用水，搅拌均匀，得溶液1；取氯化钠和柠檬酸，加入适量注射用水，搅拌使溶解，得溶液2；将溶液1与溶液2合并，搅拌均匀，得溶液3；另取磷酸氢二钠适量，加适量注射用水配制成0.4mol/L的溶液，搅拌缓慢加入到溶液3中，调节pH值至5.0-7.0，加注射用水1000ml，灌装、封口，即得。
实施例2
(1)有效成分的制备：同实施例1。
(2)清开灵雾化吸入用溶液的制备：
按处方量称取有效成分，加入适量注射用水，搅拌均匀，得溶液1；取氯化钠，加入适量注射用水，搅拌使溶解，得溶液2；将溶液1与溶液2合并，搅拌均匀，得溶液3；另取磷酸氢二钠适量，加适量注射用水配制成0.4mol/L的溶液，搅拌缓慢加入到溶液3中，调节pH值至4.0-7.0，加注射用水1000ml，灌装、封口，即得。
实施例3
(1)有效成分的制备：同实施例1。
(2)清开灵雾化吸入用溶液的制备：
按处方量称取有效成分，加入适量注射用水，搅拌均匀，得溶液1；取氯化镁和柠檬酸，加入适量注射用水，搅拌使溶解，得溶液2；将溶液1与溶液2合并，搅拌均匀，得溶液3；另取磷酸氢二钠适量，加适量注射用水配制成0.2mol/L的溶液，搅拌缓慢加入到溶液3中，调节pH值至5.0-6.0，加注射用水1000ml，灌装、封口，即得。
实施例4
(1)有效成分的制备：同实施例1。
(2)清开灵雾化吸入用溶液的制备：
按处方量称取有效成分，加入适量注射用水，搅拌均匀，得溶液1；取氯化钙和柠檬酸，加入适量注射用水，搅拌使溶解，得溶液2；将溶液1与溶液2合并，搅拌均匀，得溶液3；另取磷酸氢二钠适量，加适量注射用水配制成0.4mo1/L的溶液，搅拌缓慢加入到溶液3中，调节pH值至5.0-6.5，加注射用水1000ml，灌装、封口，即得。
实施例5
(1)有效成分的制备：同实施例1。
(2)清开灵雾化吸入用溶液的制备：
按处方量称取有效成分，加入适量注射用水，搅拌均匀，得溶液1；取氯化钠和柠檬酸，加入适量注射用水，搅拌使溶解，得溶液2；将溶液1与溶液2合并，搅拌均匀，得溶液3；另取柠檬酸钠适量，加适量注射用水配制成0.4mol/L的溶液，搅拌缓慢加入到溶液3中，调节pH值至6.0-7.0，加注射用水1000ml，灌装、封口，即得。
实施例6
(1)有效成分的制备：同实施例1。
(2)清开灵雾化吸入用溶液的制备：
按处方量称取有效成分，加入适量注射用水，搅拌均匀，得溶液1；取葡萄糖和柠檬酸，加入适量注射用水，搅拌使溶解，得溶液2；将溶液1与溶液2合并，搅拌均匀，得溶液3；另取磷酸氢二钠适量，加适量注射用水配制成0.4mol/L的溶液，搅拌缓慢加入到溶液3中，调节pH值至4.5-5.5，加注射用水1000ml，灌装、封口，即得。
实施例7
(1)有效成分的制备：同实施例1。
(2)清开灵雾化吸入用溶液的制备：
按处方量称取有效成分，加入适量注射用水，搅拌均匀，得溶液1；取木糖醇和柠檬酸，加入适量注射用水，搅拌使溶解，得溶液2；将溶液1与溶液2合并，搅拌均匀，得溶液3；另取氢氧化钠适量，加适量注射用水配制成0.1mol/L的溶液，搅拌缓慢加入到溶液3中，调节pH值至3.0-5.0，加注射用水1000ml，灌装、封口，即得。
实施例8
(1)有效成分的制备：制备方法同实施例1。
(2)清开灵雾化吸入用溶液的制备：
按处方量称取有效成分，加入适量注射用水，搅拌均匀，得溶液1；取氯化钠和磷酸二氢钾，加入适量注射用水，搅拌使溶解，得溶液2；将溶液1与溶液2合并，搅拌均匀，得溶液3；另取磷酸氢二钠适量，加适量注射用水配制成0.4mol/L的溶液，搅拌缓慢加入到溶液3中，调节pH值至7.5-8.5，加注射用水1000ml，灌装、封口，即得。
实施例9
(1)有效成分的制备：制备方法同实施例1。
(2)清开灵雾化吸入用溶液的制备：
按处方量称取有效成分，加入适量注射用水，搅拌均匀，得溶液1；取山梨醇和柠檬酸，加入适量注射用水，搅拌使溶解，得溶液2；将溶液1与溶液2合并，搅拌均匀，得溶液3；另取磷酸氢二钠适量，加适量注射用水配制成0.2mo1/L的溶液，搅拌缓慢加入到溶液3中，调节pH值至5.0-6.0，加注射用水1000ml，灌装、封口，即得。
实施例10
(1)有效成分的制备：制备方法同实施例1。
(2)清开灵雾化吸入用溶液的制备：
按处方量称取有效成分，加入适量注射用水，搅拌均匀，得溶液1；取氯化钠和枸橼酸，加入适量注射用水，搅拌使溶解，得溶液2；将溶液1与溶液2合并，搅拌均匀，得溶液3；另取磷酸氢二钠适量，加适量注射用水配制成0.2mol/L的溶液，搅拌缓慢加入到溶液3中，调节pH值至5.0-6.5，加注射用水1000ml，灌装、封口，即得。
实施例11
(1)有效成分的制备：制备方法同实施例1。
(2)清开灵雾化吸入用溶液的制备：
按处方量称取有效成分，加入适量注射用水，搅拌均匀，得溶液1；取氯化镁，加入适量注射用水，搅拌使溶解，得溶液2；将溶液1与溶液2合并，搅拌均匀，得溶液3；另取磷酸氢二钠适量，加适量注射用水配制成0.4mol/L的溶液，搅拌缓慢加入到溶液3中，调节pH值至6.5-8.5，加注射用水1000ml，灌装、封口，即得。
Claims (9)
1.一种清开灵雾化吸入用溶液制剂，其特征在于，包括(1)清开灵有效成分；(2)等渗剂及溶剂；
其中，有效成分与等渗剂的质量比为1∶1-1∶5。
2.根据权利要求1所述的制剂，其特征在于，有效成分是这样制备得到的：
胆酸10-20份、珍珠母50-300份、猪去氧胆酸10-25份、栀子50-500份、水牛角50-500份、板蓝根500-2000份、黄芩苷5-50份、金银花50-4000份
按照上述重量份称取八味药，板蓝根加水煎煮二次，每次1小时，合并煎液，滤过，滤液浓缩至适量，加乙醇使含醇量达60％，冷藏，滤过，滤液回收乙醇，加水，冷藏备用；栀子加水煎煮二次，第一次1小时，第二次0.5小时，合并煎液，滤过，滤液浓缩至适量，加乙醇使含醇量达60％，冷藏，滤过，滤液回收乙醇，加水，冷藏备用；金银花加水煎煮二次，每次0.5小时，合并煎液，滤过，滤液浓缩至适量，加乙醇使含醇量达75％，滤过，滤液调节pH值至8.0，冷藏，回收乙醇，再加乙醇使含醇量达85％，冷藏，滤过，滤液回收乙醇，加水，冷藏备用；水牛角粉用氢氧化钡溶液、珍珠母粉用硫酸分别水解7-9小时，滤过，合并滤液，调节pH值至3.5-4.0，滤过，滤液加乙醇使含醇量达60％，冷藏，滤过，滤液回收乙醇，加水，冷藏备用；将栀子液、板蓝根液和水牛角、珍珠母水解混合液合并后，加到胆酸、猪去氧胆酸的75％乙醇溶液中，混匀，加乙醇使含醇量达75％，调节pH值至7.0，冷藏，滤过，滤液回收乙醇，加水，冷藏备用；黄芩苷用注射用水溶解，调pH值至7.5，加入金银花提取液，混匀，与上述各备用液合并，混匀，浓缩至适量，得到本发明的有效成分。
3.根据权利要求1所述的制剂，其特征在于，所述的等渗剂为氯化钠、氯化钾、氯化镁、氯化钙、葡萄糖、木糖醇、山梨醇中的一种。
4.根据权利要求1所述的制剂，其特征在于，该制剂中还包括缓冲液。
5.根据权利要求4所述的制剂，其特征在于，所述的缓冲液为柠檬酸-柠檬酸钠、柠檬酸-磷酸氢二钠、磷酸二氢钾-磷酸氢二钠、柠檬酸-氢氧化钠、枸橼酸-磷酸氢二钠中的一种。
6.根据权利要求1所述的制剂，其特征在于，雾化吸入用溶液的pH值是3.0-8.5。
7.根据权利要求7所述的制剂，其特征在于，雾化吸入用溶液的pH值是4.0-7.0。
8.根据权利要求1所述的制剂，其特征在于，雾化吸入用溶液的用量是清开灵注射液用量的0.1-0.8倍。
9.根据权利要求8所述的制剂，其特征在于，雾化吸入用溶液的用量是清开灵注射液用量的0.3-0.6倍。
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