CN105920020A - 一种治疗肺部疾病的药物组合物及其制备方法和用途 - Google Patents
一种治疗肺部疾病的药物组合物及其制备方法和用途 Download PDFInfo
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Abstract
本发明公开的一种药物组合物及其制备方法和用途,按照过碳酰胺:醋酸可的松:地塞米松:N‑乙酰半胱氨酸:肝素钠:失水山梨醇三油酸酯:1,1,1,2‑四氟乙烷:尼泊金甲酯=1:1~4:1~3:2:2:1:5:1的比例制备药物混合物,装入有定量气雾剂阀门的气雾罐制成喷雾剂;药物组合物有效成分首先进行冷冻干燥处理,再采用高能球磨机或者气流粉碎机技术进行微粉化处理,后装入定量气雾剂阀门释药范围为30μl~250μl的气雾罐制成气雾剂。药物通过肺部直接给药,提高了药物的利用率,具有消炎抗病毒的功效,同时提高了病人对氧气的吸收量。
Description
技术领域
本发明涉及药物技术领域,尤其涉及一种治疗肺部疾病的药物组合物及其制备方法和用途。
背景技术
慢性阻塞性肺疾病是一种重要的慢性呼吸系统疾病,患病人数多,病死率高。患者在急性发作期过后,临床症状虽有所缓解,但其肺功能仍在继续恶化,并且由于自身防御和免疫功能的降低以及外界各种有害因素的影响,经常反复发作,而逐渐产生各种心肺并发症。一般认为与支气管阻塞以及蛋白酶-抗蛋白酶失衡有关。在感染等情况下,体内蛋白酶活性增高。α1抗胰蛋白酶缺乏者对蛋白酶的抑制能力减弱,故更易发生肺气肿。肺气肿是指终末细支气管远端的气道弹性减退,过度膨胀、充气和肺容积增大或同时伴有气道壁破坏的病理状态。按其发病原因肺气肿有如下几种类型:老年性肺气肿、代偿性肺气肿、间质性肺气肿、灶性肺气肿、旁间隔性肺气肿、阻塞性肺气肿。一般认为与支气管阻塞以及蛋白酶-抗蛋白酶失衡有关。肺心病主要是由于支气管-肺组织或肺动脉血管病变所致肺动脉高压引起的心脏病。慢阻肺经过10~20年的时间里可发展成慢性肺心病,导致严重的心、肺功能障碍,严重者会夺去患者生命,肺气肿的危害是多方面的,常见肺气肿病人稍一活动就气喘如牛,紧接着又些人还会拼命咳嗽。由于吸氧和呼出二氧化碳很困难,造成缺氧和二氧化碳在血液内积蓄,造成心脏、大脑、肝脏、肾脏、胃肠道功能损害,尤其对心脏影响最大,会引起肺心病。最后导致呼吸衰竭和心力衰竭甚至死亡。目前,对于肺部疾病的治疗,临床上一般采用消炎抗感染、调节蛋白酶-抗蛋白酶平衡联合治疗的方法,也有采用药物增氧化剂对重症病人进行急救的措施。
过碳酰胺是一种效果良好的药物增氧化剂,在水中分解为尿素、H2O2和原子氧,并缓慢放出O2,具有使用浓度低,不留残毒等优点,还可抑制细菌与霉菌生长,残留无刺激;也可以在癌症治疗中用于抗肝腹水等。醋酸可的松、地塞米松,是肾上腺皮质激素类药,具有抗炎、抗过敏、抗风湿、免疫抑制作用,降低免疫复核物通过基底膜,并能减少补体成分及免疫球蛋白的溶度,是应用广泛的蛋白酶-抗蛋白酶剂。N-乙酰半胱氨酸适用于大量粘痰阻塞引起的呼吸困难,如手术后的咯痰困难、急性和慢性支气管炎、支气管扩张、肺结核、肺炎、肺气肿等引起的痰液粘稠、咯痰困难、痰阻气管等。肝素除具有抗凝血作用外,还具有其他多种生物活性和临床用途,包括降血脂作用、抗中膜平滑肌细胞(SMC)增生、促进纤维蛋白溶解等作用,是治疗肺心病的首选药物。
肺部存在丰富的毛细血管,其内皮直接紧贴于肺泡上皮,对药物吸收屏障极薄,药物的生物利用度较高,且对药物的代谢活性也低,因此,肺部吸入给药具有极好的前景。但由于目前临床上所用药品,大多从单一的治疗角度出发,没有考虑到增大氧气的吸收量对肺病病人病情的积极意义,故药物对肺部疾病的治疗效果会受到很大的影响。
发明内容
本发明为了解决上述不足,提供一种通过肺部给药治疗肺部疾病的药物组合物及其制备方法和用途。
本发明解决上述问题所采用的技术方案是:一种治疗肺部疾病的药物组合物及其方法和用途,其特征在于,所述药物组合物为过碳酰胺、醋酸可的松、地塞米松、N-乙酰半胱氨酸、肝素钠、抛射剂、表面活性剂、防腐剂所组成的混合物装入有定量气雾剂阀门的气雾罐制成喷雾剂,所述药物组合物按照质量分比为过碳酰胺:醋酸可的松:地塞米松:N-乙酰半胱氨酸:肝素钠:表面活性剂:抛射剂:防腐剂=1:1~4:1~3:2:2:1:5:1的比例制备。
优选的,一种药物组合物及其制备方法和用途中所述药物组合物为一种气雾化的颗粒药物组合物,所述颗粒药物组合物中的微粉粒度具有0.1μm~5μm的平均粒度。
优选的,一种药物组合物及其制备方法和用途中所述药物组合物中抛射剂为1,1,1,2-四氟乙烷(HFA134a),所述表面活性剂为失水山梨醇三油酸酯,所述防腐剂为尼泊金甲酯。
优选的,一种药物组合物及其制备方法和用途中所述药物组合物首先进行冷冻干燥处理,使其含水量小于1%,于-10℃条件下保存。
优选的,一种药物组合物及其制备方法和用途中所述药物组合物按照处方量,将过碳酰胺、醋酸可的松、地塞米松、N-乙酰半胱氨酸、肝素钠、失水山梨醇三油酸酯、1,1,1,2-四氟乙烷(HFA134a)、尼泊金甲酯冷却至-30℃以下加入同一容器中,搅拌,混悬均匀,灌装入气雾剂罐中,加盖拧紧。
优选的,一种药物组合物及其制备方法和用途中所述药物组合物灌装的气雾罐选择定量气雾剂阀门释药范围为30μl~250μl。
本发明的优点是:
本发明公开的一种药物组合物及其制备方法和用途,通过肺部直接给药,提高了药物的利用率,药物可在肺部直接起效;可将药物导入肺泡细胞内,对于肺部细胞内感染的防治尤其有意义;还可以将药物高效、快速地转运入全身循环;药物组方具有消炎抗感染、调节蛋白酶-抗蛋白酶平衡的功效,同时提高了病人对氧气的吸收量。
具体实施方式
以下给出本发明的具体实施例,用来对本发明作进一步详细说明。
下述实施例中的实验方法,如无特殊说明,均为常规方法。下述实施例中所用的药材原料、试剂材料等,如无特殊说明,均为市售购买产品。
实施例1
一种治疗肺部疾病的药物组合物的制备方法
(1)称取过碳酰胺0.15g,醋酸可的松0.15g,地塞米松0.15g,N-乙酰半胱氨酸0.3g,肝素钠0.3g进行冷冻干燥处理,使其含水量小于1%。
(2)将过碳酰胺、醋酸可的松、地塞米松、N-乙酰半胱氨酸、肝素钠采用气流粉碎机技术进行微粉化处理,使其微粉粒度分布在0.1μm~5μm范围内,于-10℃条件下保存。
(3)将失水山梨醇三油酸酯0.3g,1,1,1,2-四氟乙烷(HFA134a)0.75g,尼泊金甲酯0.15g与微粉化的药物混合物混合均匀。
(4)将药物组合物冷却至-30℃以下加入同一容器中,搅拌,分别装入10个气雾剂阀门释药范围为30μl~250μl的气雾剂罐中,加盖拧紧,即得气雾剂10罐。
实施例2
一种治疗肺部疾病的药物组合物的制备方法
(1)按照质量分比为过碳酰胺0.2g,醋酸可的松0.8g,地塞米松0.6g,N-乙酰半胱氨酸0.4g,肝素钠0.4g,进行冷冻干燥处理,使其含水量小于1%。
(2)将过碳酰胺、醋酸可的松、地塞米松、N-乙酰半胱氨酸、肝素钠采用气流粉碎机技术进行微粉化处理,使其微粉粒度分布在0.1μm~5μm范围内,于-10℃条件下保存。
(3)将失水山梨醇三油酸酯0.2g,1,1,1,2-四氟乙烷(HFA134a)1.0g,尼泊金甲酯0.2g与微粉化的药物混合物混合均匀。
(4)将药物组合物冷却至-30℃以下加入同一容器中,搅拌,分别装入20个气雾剂阀门释药范围为30μl~250μl的气雾剂罐中,加盖拧紧,即得气雾剂20罐。
实施例3
一种治疗肺部疾病的药物组合物的制备方法
(1)按照过碳酰胺0.3g,醋酸可的松0.3g,地塞米松0.3g,N-乙酰半胱氨酸0.6g,肝素钠0.6g进行冷冻干燥处理,使其含水量小于1%。
(2)将过碳酰胺、醋酸可的松、地塞米松、N-乙酰半胱氨酸、肝素钠采用气流粉碎机技术进行微粉化处理,使其微粉粒度分布在0.1μm~5μm范围内,于-10℃条件下保存。
(3)将失水山梨醇三油酸酯0.3g,1,1,1,2-四氟乙烷(HFA134a)1.5g,尼泊金甲酯0.3g与微粉化的药物混合物混合均匀。
(4)将药物组合物冷却至-30℃以下加入同一容器中,搅拌,分别装入30个气雾剂阀门释药范围为30μl~250μl的气雾剂罐中,加盖拧紧,即得气雾剂30罐。
实施例4
一种治疗肺部疾病的药物组合物
药物组合物的成分按照质量分比为过碳酰胺:醋酸可的松:地塞米松:N-乙酰半胱氨酸:肝素钠:表面活性剂:抛射剂:防腐剂=1:1:1:2:2:1:5:1。
实施例5
一种治疗肺部疾病的药物组合物
药物组合物按照质量分比为过碳酰胺:醋酸可的松:地塞米松:N-乙酰半胱氨酸:肝素钠:表面活性剂:抛射剂:防腐剂=1:4:3:2:2:1:5:1。
实施例6
一种治疗肺部疾病的药物组合物
药物组合物按照质量分比为过碳酰胺:醋酸可的松:地塞米松:N-乙酰半胱氨酸:肝素钠:表面活性剂:抛射剂:防腐剂=1:2.5:2:2:2:1:5:1。
实施例7
一种治疗肺部疾病的药物组合物的应用
本发明治疗肺部疾病的药物组合物可用于慢性阻塞性肺疾病的治疗。
实施例8
一种治疗肺部疾病的药物组合物的应用
本发明治疗肺部疾病的药物组合物可用于肺气肿的治疗。
实施例9
一种治疗肺部疾病的药物组合物的应用
本发明治疗肺部疾病的药物组合物可用于肺心病的治疗。
实施例10
一种治疗肺部疾病的药物组合物的应用
本发明治疗肺部疾病的药物组合物可用于慢性阻塞性肺疾病和肺气肿和肺心病联合症状的治疗。
以下实施例11为本发明提供的药物组合物喷雾剂(以实施例2方案制备的药物组合物为例)的药效学试验,其中:
受试样品:按照实施例2制备的药物组合物喷雾剂;
空白对照药物:0.9%氯化钠灭菌注射液(规格:250ml/瓶,物理性状:无色透明液体),购自西安京西双鹤药业有限公司,国药准字H20023017,生产批号2014011。
细菌悬液:将肺炎球菌于肉汤培养基培养18小时后,取100μl均匀涂布于平板上,37℃培养18小时后刮取菌苔,溶于灭菌生理盐水中,2500r·min-1离心20min,连续三次后将细菌沉淀溶解于灭菌生理盐水,制成106CFU·ml-1细菌悬液。
受试动物为健康昆明系小鼠(体重18~42g),均购自西安交大医学院试验动物中心,使用许可证号SYXK(陕)2009-004。给药前后,自由饮水,室温20℃~25℃,实验室相对湿度50%~70%。
试验时,控制室温:20~22℃,相对湿度:60%~70%。
试剂盒:TNF-α购自上海西唐生物科技有限公司;NAGase购自南京建成生物工程研究所。
实施例11本发明药物组合物的抗菌作用
本实施例考察了实施例2制备的药物组合物对细菌所致小鼠肺部炎症的治疗作用。
将45只分娩后哺乳期第10天的小鼠随机分成5组,每组9只。第一组为模型组,前5天不作任何处理,第6天每只小鼠鼻腔导入0.05ml浓度为106CFU·ml-1肺炎病毒悬液;第二组为治疗组,每只小鼠喷用实施例1制备的药物组合物气雾剂,每日2次,每次0.3ml/10g,连续给药5天,第6天每只小鼠鼻腔导入0.05ml浓度为106CFU·ml-1肺炎病毒悬液。第三组为空白对照组,不做任何处理。
随后小鼠处死,打开腹腔,分离肺部感染区组织,将感染区组织用10%中性福尔马林固定,用于病理切片;并将感染区组织称重,按1:9(W/V)加入生理盐水,冰浴匀浆,无菌取部分10%匀浆液做细菌计数,另取部分匀浆液2500r·min-1离心40min,上清液用生理盐水稀释成1%匀浆液,用试剂盒测定TNF-α含量和NAGase活力。
表1 各组小鼠治愈率、有效率、无效率和死亡率(%)
注:**代表与模型组比较,差异极显著,p<0.01。
表1可以看出,治疗组有效率为89%,治愈率为78%,与模型组相较具有极显著的差异性。
表2 感染区组织和血清中TNF-α含量(x±SD)
注:与空白对照组小鼠相比,**代表差异极显著,p<0.01;与模型组小鼠相比,b代表差异极显著,p<0.01。
由表2结果可见,模型组与空白对照组相比较,小鼠感染区组织中的TNF-α水平显著提高(p<0.01),说明感染区组织细菌感染引起感染的肺部组织中TNF-α水平显著升高,而血清中的TNF-α水平略有升高。治疗组与模型组比较,感染区组织中的TNF-α水平明显降低(p<0.01),血清中的TNF-α水平略有降低,接近空白对照组。可见本发明的药物组合物可以有效逆转因细菌感染引起的TNF-α水平的改变,从而可以抑制感染的感染区组织的炎症反应,减少渗出。
表3 肺部组织和血清中NAGase活力(x±SD)
注:与对照组小鼠相比,**代表差异极显著,p<0.01;与模型组小鼠相比,b代表差异极显著,p<0.01。
由表3结果可见,模型组与空白对照组相比较,小鼠感染区组织和血清中的NAGase活力都具有极显著差异性(p<0.01),说明感染区组织细菌感染引起感染的感染区组织中NAGase活力的显著升高,而血清中的NAGase活力降低。治疗组与模型组比较,感染区组织中的NAGase活力明显降低(p<0.01),血清中的NAGase活力明显升高(p<0.01)。可见本发明的药物组合物可以有效逆转因细菌感染引起的NAGase活力的改变。
综合表1~3结果可见,本发明所述的药物组合物可有效降低因细菌感染引起的小鼠肺部感染区组织中的NAGase活力和TNF-α水平,对于肺部感染区组织中的炎症反应具有较好的治疗效果。
以上仅为本发明的优选实施例而已,并不用于限制本发明,对于本领域的技术人员来说,本发明可以有各种更改和变化。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 (8)
1.一种药物组合物,其特征在于,所述药物组合物为过碳酰胺、醋酸可的松、地塞米松、N-乙酰半胱氨酸、肝素钠、抛射剂、表面活性剂、防腐剂所组成,所述药物组合物按照质量分比为过碳酰胺:醋酸可的松:地塞米松:N-乙酰半胱氨酸:肝素钠:表面活性剂:抛射剂:防腐剂=1:1~4:1~3:2:2:1:5:1的比例制备。
2.根据权利要求1所述的药物组合物,其特征在于,所述药物组合物为一种气雾化的颗粒药物组合物,所述颗粒药物组合物中的微粉粒度具有0.1μm~5μm的平均粒度。
3.根据权利要求1所述的药物组合物,其特征在于所述药物组合物中抛射剂为1,1,1,2-四氟乙烷(HFA134a),所述表面活性剂为失水山梨醇三油酸酯,所述防腐剂为尼泊金甲酯。
4.一种如权利要求1~4任一项所述的药物组合物的制备方法,其特征在于,包括以下步骤:首先对过碳酰胺、醋酸可的松、地塞米松、N-乙酰半胱氨酸、肝素钠进行冷冻干燥处理,使其含水量小于1%,于-10℃条件下保存。
5.根据权利要求4所述的制备方法,其特征在于,进一步包括:所述药物组合物的混合物用冷灌法装入有定量气雾剂阀门的气雾罐制成喷雾剂。
6.根据权利要求5所述的制备方法,其特征在于,所述药物组合物冷灌法的灌装流程为:按照处方量将过碳酰胺、醋酸可的松、地塞米松、N-乙酰半胱氨酸、肝素钠、失水山梨醇三油酸酯、1,1,1,2-四氟乙烷(HFA134a)、尼泊金甲酯冷却至-30℃以下加入同一容器中,搅拌,混悬均匀,灌装入气雾剂罐中,加盖拧紧。
7.根据权利要求6所述的的制备方法,其特征在于,所述药物组合物灌装的气雾罐选择定量气雾剂阀门,定量气雾剂阀门释药范围为30μl~250μl。
8.一种如权利要求1~3任一项所述的药物组合物的应用,其特征在于,在制备治疗慢性阻塞性肺疾病和/或肺气肿和/或肺心病药物中的应用。
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JP2020500945A (ja) * | 2016-12-11 | 2020-01-16 | シナジー・ダーマトロジー・リミテッド | 硫酸化多糖を含む組成物 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1440268A (zh) * | 2000-06-30 | 2003-09-03 | 宝洁公司 | 促进全身健康 |
CN1471923A (zh) * | 2003-06-24 | 2004-02-04 | 凌沛学 | 一种治疗哮喘的喷雾剂及其制备工艺 |
CN1778291A (zh) * | 2004-11-25 | 2006-05-31 | 张玲 | 口服过碳酰胺给氧剂及制备方法 |
WO2006060027A2 (en) * | 2004-09-20 | 2006-06-08 | Corus Pharma, Inc. | A method for improvement of tolerance for therapeutically effective agents delivered by inhalation |
CN1874757A (zh) * | 2003-09-15 | 2006-12-06 | 维克特拉有限公司 | 治疗肺病的粘液活性剂 |
CN101897719A (zh) * | 2010-08-04 | 2010-12-01 | 中国人民解放军第三军医大学 | 一种用于治疗烟雾吸入性肺损伤的药物组合物 |
-
2016
- 2016-06-23 CN CN201610486640.7A patent/CN105920020B/zh active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1440268A (zh) * | 2000-06-30 | 2003-09-03 | 宝洁公司 | 促进全身健康 |
CN1471923A (zh) * | 2003-06-24 | 2004-02-04 | 凌沛学 | 一种治疗哮喘的喷雾剂及其制备工艺 |
CN1874757A (zh) * | 2003-09-15 | 2006-12-06 | 维克特拉有限公司 | 治疗肺病的粘液活性剂 |
WO2006060027A2 (en) * | 2004-09-20 | 2006-06-08 | Corus Pharma, Inc. | A method for improvement of tolerance for therapeutically effective agents delivered by inhalation |
CN1778291A (zh) * | 2004-11-25 | 2006-05-31 | 张玲 | 口服过碳酰胺给氧剂及制备方法 |
CN101897719A (zh) * | 2010-08-04 | 2010-12-01 | 中国人民解放军第三军医大学 | 一种用于治疗烟雾吸入性肺损伤的药物组合物 |
Non-Patent Citations (1)
Title |
---|
詹益兴 主编: "《精细化工新产品》", 31 October 2007, 科学技术文献出版社 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020500945A (ja) * | 2016-12-11 | 2020-01-16 | シナジー・ダーマトロジー・リミテッド | 硫酸化多糖を含む組成物 |
JP7253494B2 (ja) | 2016-12-11 | 2023-04-06 | シナジー・ダーマトロジー・リミテッド | 硫酸化多糖を含む組成物 |
AU2017372976B2 (en) * | 2016-12-11 | 2023-12-07 | Seanergy Dermatology Ltd. | Compositions comprising sulfated polysaccharides |
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