CN113209169A - 一种参附雾化吸入用溶液制剂及其制备方法 - Google Patents
一种参附雾化吸入用溶液制剂及其制备方法 Download PDFInfo
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- 241000208340 Araliaceae Species 0.000 title claims abstract description 69
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 title claims abstract description 69
- 235000003140 Panax quinquefolius Nutrition 0.000 title claims abstract description 69
- 235000008434 ginseng Nutrition 0.000 title claims abstract description 69
- 241000173529 Aconitum napellus Species 0.000 title claims abstract description 26
- 229940023019 aconite Drugs 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- 229940041682 inhalant solution Drugs 0.000 title claims abstract description 13
- 239000000443 aerosol Substances 0.000 title claims description 8
- 239000000243 solution Substances 0.000 claims abstract description 105
- 238000002347 injection Methods 0.000 claims abstract description 24
- 239000007924 injection Substances 0.000 claims abstract description 24
- 239000007951 isotonicity adjuster Substances 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 474
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 107
- 238000001914 filtration Methods 0.000 claims description 78
- 239000000284 extract Substances 0.000 claims description 75
- 239000000706 filtrate Substances 0.000 claims description 66
- 238000002156 mixing Methods 0.000 claims description 41
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 36
- 238000001035 drying Methods 0.000 claims description 36
- 239000011347 resin Substances 0.000 claims description 33
- 229920005989 resin Polymers 0.000 claims description 33
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 13
- 241000227129 Aconitum Species 0.000 claims description 10
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 10
- 238000009472 formulation Methods 0.000 claims description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
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- CBMPTFJVXNIWHP-UHFFFAOYSA-L disodium;hydrogen phosphate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].OP([O-])([O-])=O.OC(=O)CC(O)(C(O)=O)CC(O)=O CBMPTFJVXNIWHP-UHFFFAOYSA-L 0.000 claims description 4
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- BUCIWTBCUUHRHZ-UHFFFAOYSA-K potassium;disodium;dihydrogen phosphate;hydrogen phosphate Chemical compound [Na+].[Na+].[K+].OP(O)([O-])=O.OP([O-])([O-])=O BUCIWTBCUUHRHZ-UHFFFAOYSA-K 0.000 claims description 2
- IGHGOYDCVRUTSU-UHFFFAOYSA-M sodium;2-hydroxypropane-1,2,3-tricarboxylic acid;hydroxide Chemical compound [OH-].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O IGHGOYDCVRUTSU-UHFFFAOYSA-M 0.000 claims description 2
- XPFJYKARVSSRHE-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O XPFJYKARVSSRHE-UHFFFAOYSA-K 0.000 claims description 2
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- -1 compound disodium hydrogen phosphate Chemical class 0.000 description 9
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- 229940079593 drug Drugs 0.000 description 9
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- 206010033557 Palpitations Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
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- 238000002664 inhalation therapy Methods 0.000 description 2
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- 239000000463 material Substances 0.000 description 2
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- 208000006820 Arthralgia Diseases 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 239000009798 Shen-Fu Substances 0.000 description 1
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- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
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Abstract
本发明涉及一种参附雾化吸入用溶液制剂,属于制剂学领域。一种参附的雾化吸入用溶液制剂,包括(1)参附有效成分;(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,与参附注射液相比,给药途径不同,使用剂量减少,安全性提高。
Description
本发明是申请号为201610112699.X,申请日为2016年03月01日,发明名称为“一种参附雾化吸入用溶液制剂及其制备方法”的中国发明专利申请的分案申请,其内容通过引用并入本文。
技术领域
本发明涉及一种参附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
参附注射液具有回阳救逆、益气固脱的功效,主要用于阳气暴脱的厥脱症(感染性、失血性、失液性休克等),也可用于阳虚(气虚)所致的惊悸、怔忡、喘咳、胃疼、泄泻、痹症等。但是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,因此,研究开发疗效确切、作用迅速的新型药物具有重要实际意义。
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、质量优异的参附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:
一种参附雾化吸入用溶液制剂,包括:
(1)参附有效成分;
(2)等渗剂及溶剂;
还可以加入缓冲液。
其中,参附有效成分是指红参提取物和附子提取物的混合物;
参附有效成分与等渗剂的质量比为1:1-1:5。
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参附注射液用量的0.1-0.8倍;优选用量是参附注射液用量的0.3-0.6倍。
本发明中红参提取物是通过以下任意一种方法制备得到的:
(1)将红参50-200重量份用4-12倍量50-90%乙醇提取1-4次,每次1-3小时,滤过,合并滤液,滤液加乙醇使含醇量达70-90%,静置,滤过,滤液回收乙醇,加适量水溶解,超滤,收集超滤液,用乙醚萃取2-4次,收集水相,水相加正丁醇萃取2-7次,收集正丁醇液,脱水,回收正丁醇,干燥,得红参提取物;
(2)将红参50-200重量份加4-12倍量50-90%乙醇回流提取1-4次,每次1-3小时,滤过,合并滤液,回收乙醇至无醇味,上大孔树脂柱吸附,用碱化的10-50%乙醇溶液洗涤树脂,并用纯化水洗至中性,用50-90%乙醇洗脱,收集乙醇洗脱液,回收乙醇,加适量水溶解,超滤,收集超滤液,加正丁醇萃取2-7次,收集正丁醇液,脱水,回收正丁醇,干燥,得红参提取物;
(3)将红参50-200重量份加4-12倍量50-90%乙醇回流提取1-4次,每次1-3小时,滤过,合并滤液,回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得红参提取物;
(4)将红参50-200重量份加4-12倍量50-90%乙醇超声提取1-4次,每次10-50分钟,滤过,合并滤液,回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得红参提取物;
(5)将红参50-200重量份加4-12倍量水超声提取1-4次,每次10-50分钟,滤过,合并滤液,适当浓缩,加入乙醇使含醇量达60-80%,冷藏,滤过,回收乙醇至无醇味,加入乙醇使含醇量达70-90%,冷藏,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得红参提取物;
(6)将红参50-200重量份加4-12倍量水回流提取1-4次,每次1-3小时,滤过,合并滤液,适当浓缩,加入乙醇使含醇量达60-80%,冷藏,滤过,回收乙醇至无醇味,加入乙醇使含醇量达70-90%,冷藏,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得红参提取物。
附子提取物是通过以下任意一种方法制备得到的:
(1)将附子100-400重量份加4-12倍量水提取1-4次,每次1-3小时,滤过,合并滤液,滤液适当浓缩,加入乙醇使含醇量达60-80%,静置,取上清液回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物;
(2)将附子100-400重量份加4-12倍量50-90%乙醇提取1-4次,每次1-3小时,滤过,合并滤液,回收乙醇至无醇味,适当浓缩后离心,取上清液过大孔树脂柱,用4-6倍柱体积的水洗脱,再用1-10倍柱体积50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物;
(3)将附子100-400重量份加4-12倍量50-90%乙醇超声提取1-4次,每次10-50分钟,滤过,合并滤液,回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物;
(4)将附子100-400重量份加4-12倍量水或酸水超声提取1-4次,每次10-50分钟,滤过,合并滤液,适当浓缩,加入乙醇使含醇量达60-80%,冷藏,滤过,回收乙醇至无醇味,加入乙醇使含醇量达70-90%,冷藏,滤过,减压回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物;
(5)将附子100-400重量份加4-12倍量50-90%乙醇回流提取1-4次,每次1-3小时,滤过,合并滤液,回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物;
(6)将附子100-400重量份加4-12倍量水或酸水回流提取1-4次,每次1-3小时,滤过,合并滤液,适当浓缩,加入乙醇使含醇量达60-80%,冷藏,滤过,回收乙醇至无醇味,加入乙醇使含醇量达70-90%,冷藏,滤过,回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物。
本发明所述的参附雾化吸入用溶液制剂可以用于治疗阳气暴脱的厥脱症(感染性、失血性、失液性休克等),也可用于阳虚(气虚)所致的惊悸、怔忡、喘咳、胃疼、泄泻、痹症等。
本发明的优点是提供了一种优于参附注射液的新剂型,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,使用参附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,与参附注射液相比,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:
制备喘咳大鼠模型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;阳性对照组给予参附注射液静脉注射;药物组一、二、三、四分别给予参附雾化吸入溶液(用量分别为参附注射液的0.1倍、0.3倍、0.6倍、0.8倍),连续给药5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,各药物组对喘咳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,药物组在治疗其他适应症的效果也明显优于参附注射液。
本发明参附雾化吸入溶液的治疗效果明显优于参附注射液,填补了目前国内市场上的参附专用雾化吸入溶液的空白,与参附注射液相比,使用剂量大大减少,是参附注射液的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
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,加注射用水适量,灌装、封口,即得。
实施例2
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,加注射用水适量,灌装、封口,即得。
实施例3
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,加注射用水适量,灌装、封口,即得。
实施例4
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0.4mol/L的溶液,搅拌缓慢加入到溶液3中,调节pH值至5.0-6.5,加注射用水适量,灌装、封口,即得。
实施例5
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,加注射用水适量,灌装、封口,即得。
实施例6
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,加注射用水适量,灌装、封口,即得。
实施例7
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,加注射用水适量,灌装、封口,即得。
实施例8
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,加注射用水适量,灌装、封口,即得。
实施例9
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0.2mol/L的溶液,搅拌缓慢加入到溶液3中,调节pH值至5.0-6.0,加注射用水适量,灌装、封口,即得。
实施例10
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,加注射用水适量,灌装、封口,即得。
实施例11
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,加注射用水适量,灌装、封口,即得。
以上实施例1-11中有效成分是指红参提取物和附子提取物的混合物;
其中红参提取物是通过以下任意一种方法制备得到的:
(1)将红参50-200重量份用4-12倍量50-90%乙醇提取1-4次,每次1-3小时,滤过,合并滤液,滤液加乙醇使含醇量达70-90%,静置,滤过,滤液回收乙醇,加适量水溶解,超滤,收集超滤液,用乙醚萃取2-4次,收集水相,水相加正丁醇萃取2-7次,收集正丁醇液,脱水,回收正丁醇,干燥,得红参提取物;
(2)将红参50-200重量份加4-12倍量50-90%乙醇回流提取1-4次,每次1-3小时,滤过,合并滤液,回收乙醇至无醇味,上大孔树脂柱吸附,用碱化的10-50%乙醇溶液洗涤树脂,并用纯化水洗至中性,用50-90%乙醇洗脱,收集乙醇洗脱液,回收乙醇,加适量水溶解,超滤,收集超滤液,加正丁醇萃取2-7次,收集正丁醇液,脱水,回收正丁醇,干燥,得红参提取物;
(3)将红参50-200重量份加4-12倍量50-90%乙醇回流提取1-4次,每次1-3小时,滤过,合并滤液,回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得红参提取物;
(4)将红参50-200重量份加4-12倍量50-90%乙醇超声提取1-4次,每次10-50分钟,滤过,合并滤液,回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得红参提取物;
(5)将红参50-200重量份加4-12倍量水超声提取1-4次,每次10-50分钟,滤过,合并滤液,适当浓缩,加入乙醇使含醇量达60-80%,冷藏,滤过,回收乙醇至无醇味,加入乙醇使含醇量达70-90%,冷藏,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得红参提取物;
(6)将红参50-200重量份加4-12倍量水回流提取1-4次,每次1-3小时,滤过,合并滤液,适当浓缩,加入乙醇使含醇量达60-80%,冷藏,滤过,回收乙醇至无醇味,加入乙醇使含醇量达70-90%,冷藏,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得红参提取物。
附子提取物是通过以下任意一种方法制备得到的:
(1)将附子100-400重量份加4-12倍量水提取1-4次,每次1-3小时,滤过,合并滤液,滤液适当浓缩,加入乙醇使含醇量达60-80%,静置,取上清液回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物;
(2)将附子100-400重量份加4-12倍量50-90%乙醇提取1-4次,每次1-3小时,滤过,合并滤液,回收乙醇至无醇味,适当浓缩后离心,取上清液过大孔树脂柱,用4-6倍柱体积的水洗脱,再用1-10倍柱体积50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物;
(3)将附子100-400重量份加4-12倍量50-90%乙醇超声提取1-4次,每次10-50分钟,滤过,合并滤液,回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物;
(4)将附子100-400重量份加4-12倍量水或酸水超声提取1-4次,每次10-50分钟,滤过,合并滤液,适当浓缩,加入乙醇使含醇量达60-80%,冷藏,滤过,回收乙醇至无醇味,加入乙醇使含醇量达70-90%,冷藏,滤过,减压回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物;
(5)将附子100-400重量份加4-12倍量50-90%乙醇回流提取1-4次,每次1-3小时,滤过,合并滤液,回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物;
(6)将附子100-400重量份加4-12倍量水或酸水回流提取1-4次,每次1-3小时,滤过,合并滤液,适当浓缩,加入乙醇使含醇量达60-80%,冷藏,滤过,回收乙醇至无醇味,加入乙醇使含醇量达70-90%,冷藏,滤过,回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物。
Claims (10)
1.一种参附雾化吸入用溶液制剂,其特征在于,包括(1)参附有效成分;(2)等渗剂及溶剂;
其中,参附有效成分是指红参提取物和附子提取物的混合物;
参附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,红参提取物是通过以下任意一种方法制备得到的:
(1)将红参50-200重量份用4-12倍量50-90%乙醇提取1-4次,每次1-3小时,滤过,合并滤液,滤液加乙醇使含醇量达70-90%,静置,滤过,滤液回收乙醇,加适量水溶解,超滤,收集超滤液,用乙醚萃取2-4次,收集水相,水相加正丁醇萃取2-7次,收集正丁醇液,脱水,回收正丁醇,干燥,得红参提取物;
(2)将红参50-200重量份加4-12倍量50-90%乙醇回流提取1-4次,每次1-3小时,滤过,合并滤液,回收乙醇至无醇味,上大孔树脂柱吸附,用碱化的10-50%乙醇溶液洗涤树脂,并用纯化水洗至中性,用50-90%乙醇洗脱,收集乙醇洗脱液,回收乙醇,加适量水溶解,超滤,收集超滤液,加正丁醇萃取2-7次,收集正丁醇液,脱水,回收正丁醇,干燥,得红参提取物;
(3)将红参50-200重量份加4-12倍量50-90%乙醇回流提取1-4次,每次1-3小时,滤过,合并滤液,回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得红参提取物;
(4)将红参50-200重量份加4-12倍量50-90%乙醇超声提取1-4次,每次10-50分钟,滤过,合并滤液,回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得红参提取物;
(5)将红参50-200重量份加4-12倍量水超声提取1-4次,每次10-50分钟,滤过,合并滤液,适当浓缩,加入乙醇使含醇量达60-80%,冷藏,滤过,回收乙醇至无醇味,加入乙醇使含醇量达70-90%,冷藏,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得红参提取物;
(6)将红参50-200重量份加4-12倍量水回流提取1-4次,每次1-3小时,滤过,合并滤液,适当浓缩,加入乙醇使含醇量达60-80%,冷藏,滤过,回收乙醇至无醇味,加入乙醇使含醇量达70-90%,冷藏,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得红参提取物。
3.根据权利要求1所述的制剂,其特征在于,附子提取物是通过以下任意一种方法制备得到的:
(1)将附子100-400重量份加4-12倍量水提取1-4次,每次1-3小时,滤过,合并滤液,滤液适当浓缩,加入乙醇使含醇量达60-80%,静置,取上清液回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物;
(2)将附子100-400重量份加4-12倍量50-90%乙醇提取1-4次,每次1-3小时,滤过,合并滤液,回收乙醇至无醇味,适当浓缩后离心,取上清液过大孔树脂柱,用4-6倍柱体积的水洗脱,再用1-10倍柱体积50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物;
(3)将附子100-400重量份加4-12倍量50-90%乙醇超声提取1-4次,每次10-50分钟,滤过,合并滤液,回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物;
(4)将附子100-400重量份加4-12倍量水或酸水超声提取1-4次,每次10-50分钟,滤过,合并滤液,适当浓缩,加入乙醇使含醇量达60-80%,冷藏,滤过,回收乙醇至无醇味,加入乙醇使含醇量达70-90%,冷藏,滤过,减压回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物;
(5)将附子100-400重量份加4-12倍量50-90%乙醇回流提取1-4次,每次1-3小时,滤过,合并滤液,回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物;
(6)将附子100-400重量份加4-12倍量水或酸水回流提取1-4次,每次1-3小时,滤过,合并滤液,适当浓缩,加入乙醇使含醇量达60-80%,冷藏,滤过,回收乙醇至无醇味,加入乙醇使含醇量达70-90%,冷藏,滤过,回收乙醇至无醇味,滤过,滤液通过大孔树脂柱,先用4-6倍量水或20%以下浓度的乙醇洗脱,洗脱液弃去,再用1-10倍量50-90%乙醇洗脱,收集洗脱液,回收乙醇至无醇味,浓缩至稠膏,干燥,得附子提取物。
4.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。
5.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。
6.根据权利要求5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。
7.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。
8.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。
9.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参附注射液用量的0.1-0.8倍。
10.根据权利要求9所述的制剂,其特征在于,雾化吸入用溶液的用量是参附注射液用量的0.3-0.6倍。
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