CN1389202A - 盐酸左旋沙丁胺醇气雾剂及制备工艺 - Google Patents
盐酸左旋沙丁胺醇气雾剂及制备工艺 Download PDFInfo
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Abstract
本发明属药物制剂技术领域。本发明提供了盐酸左旋沙丁胺醇气雾剂及制备工艺。本发明的气雾剂在使用时能使肺部浓度迅速增高,起效快,使用方便,因体积小而携带方便,有较好的临床应用前景。
Description
技术领域
本发明属药物制剂技术领域。具体涉及盐酸左旋沙丁胺醇气雾剂及制备工艺。
背景技术
左旋沙丁胺醇为第三代β2受体激动剂，是哮喘治疗药物中第一个上市的具有光学活性的新药，由美国Sepracor公司(手性药物专业制造商)通过拆分消旋体沙丁胺醇而得。大量临床实验证明，左旋沙丁胺醇与消旋体相比有如下优点：
①药效强。文献报导左旋沙丁胺醇的药效是右旋体的64倍。临床实验证明，左旋体比消旋体药效至少强4-10倍。
②副作用小。右旋体体内代谢速度比左旋体慢10倍，而且右旋体会增加支气管的反应性。
此外，美国肺病协会及胸腔疾病学会大会提供的临床数据也表明，本品对患者肺功能的改善明显优于消旋体。
相关产品：
XopenexTM——盐酸左旋沙丁胺醇吸入剂，美国Sepracor公司生产，以雾化器给药。
发明内容
本发明所要解决的技术问题在于开发盐酸左旋沙丁胺醇的其它剂型，使其药效起效快，使用方便。
本发明提供了盐酸左旋沙丁胺醇气雾剂。该气雾剂是由按重量百分比含盐酸左旋沙丁胺醇为0.01-0.2％与含药用辅料为99.99-99.8％组成的。
上述药用辅料有：
表面活性剂用量范围0.01-0.5％(w/w)，如：
脱水山梨醇脂肪酸酯类，如：span20、span60、span65、span80、span85；
聚氧乙烯脱水山梨醇脂肪酸酯类，如：tween20、tween80；
聚氧乙烯脂肪酸酯类，如：Myrij；
聚氧乙烯脂肪醇醚类，如：Brij 30、Brij 35、Cetomacrogol、Peregol O；
聚氧乙烯聚氧丙烯共聚物，如：Pluronic F-68；
丙氧聚乙二醇类，如：Antarox 31R1；
聚乙二醇类，如：PEG 300；
磷脂类，如：大豆磷脂、卵磷脂等；
油酸；
甘露醇。
比重调节剂用量范围0.01-0.5％(w/w)，如：滑石粉、无水硫酸钠、氯化钠等。
抛射剂用量范围90-98％(w/w)，如：三氯一氟甲烷(F11)、二氯二氟甲烷(F12)、二氯四氟甲烷(F114)、四氟乙烷(F134a)、七氟丙烷(F227)二氯一氟乙烷(F141b)、一氯二氟乙烷(F142b)、二氟乙烷(F152a)等。
本发明的另一所要解决的技术问题是提供了盐酸左旋沙丁胺醇气雾剂的制备工艺，该方法包括下列步骤：
(1)将原辅料分别于真空干燥箱内干燥数小时，置干燥器内冷却至室温；
(2)将原辅料用气流粉碎机粉碎。微粉处理后的原辅料经400倍显微镜检查，合格后置干燥器内备用；
(3)按处方量称取将原辅料，置于特制的密封配料桶内，搅拌，做样品的中间体测定。测定合格后按规定的量灌入密闭容器内，再灌入抛射剂至规定量；
或者：
(1)将原辅料分别于真空干燥箱内干燥数小时，置干燥器内冷却至室温；
(2)将原辅料用气流粉碎机粉碎。微粉处理后的原辅料经400倍显微镜检查，合格后置干燥器内备用；
(3)按处方量称取将原辅料，置于特制的有压力的密封配料桶内，搅拌，做样品的中间体测定。测定合格后按规定的量灌入密闭容器内。
本发明的盐酸左旋沙丁胺醇气雾剂与盐酸左旋沙丁胺醇吸入剂比较，有如下优点：
(1)因其到达靶器官——肺部的浓度迅速增高，故与传统的片剂相比起效更快；
(2)与现有的雾化吸入剂相比，使用方便；
(3)体积小，携带方便。
沙丁胺醇(albuterol，salbutamol)，商品名舒喘宁，是广泛应用于治疗哮喘的β2受体激动剂。由于其疗效肯定，安全可靠，作用时间较长以及剂型齐全，曾进入世界十大畅销药的行列，1998年销售额仍达12亿美元。目前国内销售的是消旋体。临床试验表明，其左旋异构体(又称R-异构体)对病人肺功能的改善要明显优于消旋体。
具体实施方式
实施例1左旋沙丁胺醇 2.5mgSpan20 3mg滑石粉 4mg三氯一氟甲烷 加至足量
实施例2左旋沙丁胺醇 5mgtween80 6mg硫酸钠 7mg二氯二氟甲烷 加至足量
实施例3左旋沙丁胺醇 10mgBrij 35 12mg氯化钠 14mg四氟乙烷 加至足量
实施例4左旋沙丁胺醇 20mgPluronic F-68 25mg滑石粉 35mg七氟丙烷 加至足量
实施例5左旋沙丁胺醇 2.5mgPEG 300 3mg滑石粉 4mg二氯一氟乙烷 加至足量
实施例6左旋沙丁胺醇 5mg卵磷脂 6mg硫酸钠 7mg一氯二氟乙烷 加至足量
实施例7左旋沙丁胺醇 10mg油酸 12mg氯化钠 14mg四氟乙烷 加至足量
实施例8左旋沙丁胺醇 20mg甘露醇 25mg氯化钠 35mg二氟乙烷 加至足量
Claims (3)
1.一种盐酸左旋沙丁胺醇气雾剂，其特征在于该气雾剂是由按重量百分比含盐酸左旋沙丁胺醇为0.01-0.2％与含药用辅料为99.99-99.8％组成的。
2.根据权利要求1所述的一种盐酸左旋沙丁胺醇气雾剂，其特征在于其中所述的药用辅料为：
表面活性剂用量范围0.01-0.5％(w/w)，如：
脱水山梨醇脂肪酸酯类，如：span20、span60、span65、span80、span85；
聚氧乙烯脱水山梨醇脂肪酸酯类，如：tween20、tween80；
聚氧乙烯脂肪酸酯类，如：Myrij；
聚氧乙烯脂肪醇醚类，如：Brij30、Brij35、Cetomacrogol、Peregol O；
聚氧乙烯聚氧丙烯共聚物，如：Pluronic F-68；
丙氧聚乙二醇类，如：Antarox 31R1；
聚乙二醇类，如：PEG 300；
磷脂类，如：大豆磷脂、卵磷脂等；
油酸；
甘露醇；
比重调节剂用量范围0.01-0.5％(w/w)，如：滑石粉、硫酸钠、氯化钠等；
抛射剂用量范围90-98％(w/w)，如：三氯一氟甲烷(F11)、二氯二氟甲烷(F12)、二氯四氟甲烷(F114)、四氟乙烷(F134a)、七氟丙烷(F227)二氯一氟乙烷(F141b)、一氯二氟乙烷(F142b)、二氟乙烷(F152a)等。
3.一种盐酸左旋沙丁胺醇气雾剂的制备工艺，其特征在于该方法包括下列步骤：
(1)将原辅料分别于真空干燥箱内干燥数小时，置干燥器内冷却至室温；
(2)将原辅料用气流粉碎机粉碎，微粉处理后的原辅料经400倍显微镜检查，合格后置干燥器内备用；
(3)按处方量称取将原辅料，置于特制的密封配料桶内，搅拌，做样品的中间体测定，测定合格后按规定的量灌入密闭容器内，再灌入抛射剂至规定量；
或者：
(1)将原辅料分别于真空干燥箱内干燥数小时，置干燥器内冷却至室温；
(2)将原辅料用气流粉碎机粉碎，微粉处理后的原辅料经400倍显微镜检查，合格后置干燥器内备用；
(3)按处方量称取将原辅料，置于特制的有压力的密封配料桶内，搅拌，做样品的中间体测定，测定合格后按规定的量灌入密闭容器内。
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| CN 02111473 CN1216600C (zh) | 2002-04-24 | 2002-04-24 | 盐酸左旋沙丁胺醇气雾剂及制备工艺 |
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| CN 02111473 CN1216600C (zh) | 2002-04-24 | 2002-04-24 | 盐酸左旋沙丁胺醇气雾剂及制备工艺 |
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| CN1389202A true CN1389202A (zh) | 2003-01-08 |
| CN1216600C CN1216600C (zh) | 2005-08-31 |
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| WO2007020204A3 (en) * | 2005-08-12 | 2007-06-07 | Boehringer Ingelheim Pharma | Hfc solution formulations for inhalation containing salbutamol hydrochloride or salbutamol citrate |
| CN101849928A (zh) * | 2009-03-30 | 2010-10-06 | 北京利乐生制药科技有限公司 | 一种治疗哮喘的吸入制剂及其制备方法、用途 |
| CN102871967A (zh) * | 2012-09-18 | 2013-01-16 | 刘晓忠 | 左旋沙丁胺醇与中药单体成盐的药物颗粒的制备及该颗粒吸入式气雾剂的制备 |
| CN101889993B (zh) * | 2009-05-19 | 2013-03-27 | 扬州市三药制药有限公司 | 表面修饰的沙丁胺醇混悬型非氟利昂吸入气雾剂及制法 |
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