CN105727104A - 一种消炎止咳的药物组合物及其制备方法 - Google Patents
一种消炎止咳的药物组合物及其制备方法 Download PDFInfo
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
本发明涉及一种消炎止咳的药物组合物及其制备方法,由以下重量份的成分制成:化橘红、百部、茯苓、半夏、白前、甘草、苦杏仁、五味子。该药物组合物由以下方法制备而成:化橘红、苦杏仁用水蒸气蒸馏;甘草、半夏加乙醇提取后加有机溶剂萃取;蜜制百部、茯苓、白前、五味子加水提取;合并提取物即得。本发明具有理气化痰,润肺止咳的功效,适用于痰浊阻肺所致的咳嗽、气喘、痰多;感冒、支气管炎、咽喉炎,经临床观察疗效确切,未发现毒副反应。
Description
技术领域
本发明涉及中医药领域,具体涉及一种消炎止咳的药物组合物及其制备方法。
背景技术
痰浊停留于肺,壅塞气道,临床以咳喘、胸闷、痰多痰鸣为主要表现的证。常见于咳嗽、喘、哮、肺胀、肺痈,以及西医的支气管炎、肺炎等疾病。痰浊阻肺的成因有内外两种:内因与脾有关,如饮食不节,劳倦伤脾,或七情过度,都可使脾虚失运,不能升清降浊,以致津液停聚,变为痰浊,上泛于肺,故有“脾为升痰之源,肺为贮痰之器”之说。外因则由风、热、燥等邪气犯肺,或风寒入里化热,灼液成痰,而成痰热壅阻于肺;或外感风寒之邪,引动痰饮内发,成为寒痰阻肺。
橘红痰咳液为《中华人民共和国药典》2010版第一部公开的复方,公开了处方组成及片剂、胶囊剂的制备方法。公开的提取方法如下:
化橘红、百部、茯苓、半夏、白前、甘草、苦杏仁、五味子等八味,化橘红、苦杏仁用水蒸气蒸馏,收集蒸馏液80ml,药渣与其余百部等六味,加水煎煮二次,每次2小时,合并煎液,滤过,滤液浓缩至80℃时相对密度为1.25-1.35的清膏,加乙醇使含醇量为75%-80%,静置24小时,取上清液,回收乙醇并浓缩至80℃时相对密度为1.18-1.20的清膏,加蔗糖400g、蜂蜜100g、苯甲酸钠3g、羟苯乙酯0.3g,搅拌使溶解,加入上述蒸馏液,混匀,滤过,放冷,加香精和薄荷脑适量,加水至1000ml,搅匀,即得。
由于中药材活性成分的性质各不相同,如采用上述方法先把化橘红、苦杏仁用水蒸气蒸馏,药渣并其余药材全部水提醇沉,最后合并提取液制成口服液,由于有效成分未经完全提取,在使用过程中药物未能发挥全部作用,从而影响药效。
因此,需要提供一种可以提高药品的活性成分提取率,以提高药品疗效的制备方法。
发明内容
本发明的目的是提供一种用于消炎止咳的药物组合物。
本发明的目的是提供一种用于消炎止咳的药物组合物的制备方法。
本发明提供的用于消炎止咳的药物组合物由以下重量份的成分制成:化橘红300份、蜜制百部30份、茯苓30份、制半夏30份、白前50份、甘草10份、苦杏仁100份、五味子20份,其特征在于,该药物组合物由以下方法制备而成:
1)化橘红、苦杏仁用水蒸气蒸馏,收集蒸馏液,药渣加乙醇提取,提取液过中性氧化铝,收集流出液,流出液过阳离子树脂,用水洗柱,弃去水洗液,用40%-90%乙醇洗脱,收集洗脱液,洗脱液过阴离子树脂,用水洗柱,弃去水洗液,用40%-90%乙醇洗脱,收集洗脱液,浓缩,得提取物A;
2)取甘草、半夏加乙醇提取,提取液滤过,滤液加3-10%碱液混匀,静置,过滤,弃去沉淀,滤液加有机溶剂萃取,收集碱水层,加2%酸调pH至3-4,加有机溶剂萃取,收集有机溶剂层,回收有机溶剂,得提取物B;
3)取蜜制百部、茯苓、白前、五味子加水浸泡后,煮沸提取,提取液过滤,滤液浓缩,得提取物C;
4)合并提取物A、B、C,干燥,即得。
优选地,所述步骤1)中碱液为:氢氧化钠、碳酸钾、碳酸氢钾、碳酸钠、碳酸氢钠、柠檬酸钠、柠檬酸钾、碳酸氢三钠、柠檬酸一钠中一种或几种。
优选地,所述步骤1)中酸为:枸橼酸、乳酸、磷酸、酒石酸、苹果酸、偏酒石酸、乙酸、盐酸、己二酸、富马酸中一种或几种。
优选地,所述步骤1)中阳离子树脂为:732强酸性苯乙烯系阳离子交换树脂、734强酸性苯乙烯系阳离子交换树脂、D254大孔强碱性季铵型阳离子交换树脂、D-61大孔强酸性苯乙烯系阳离子交换树脂中一种或几种。
优选地,所述步骤1)中阴离子树脂为:717强碱性苯乙烯系阴离子交换树脂、711强碱性苯乙烯系I型阴离子交换树脂、D311大孔丙烯酸系弱碱阴离子交换树脂、D318大孔丙烯酸系弱酸阴离子交换树脂中一种或几种。
优选地,所述步骤2)中有机溶剂为:乙酸乙酯、氯仿、正丁烷、二氯甲烷或***中一种或几种。
本发明提供了上述药物组合物的制备方法,具体包括以下步骤:
1)化橘红、苦杏仁用水蒸气蒸馏,收集蒸馏液,药渣加8-10倍药材重量50%-80%乙醇回流提取1-3次,每次1-3小时,合并提取液,提取液过中性氧化铝,收集流出液,流出液过阳离子树脂,用2倍树脂重量的水洗柱,弃去水洗液,继续用2倍树脂重量40%-90%乙醇洗脱,收集洗脱液,洗脱液继续过阴离子树脂,用2倍树脂重量的水洗柱,弃去水洗液,继续用2倍树脂重量40%-90%乙醇洗脱,收集洗脱液,浓缩至60-80℃时相对密度为1.1-1.2,得提取物A;
2)取甘草、半夏40%-90%的乙醇加热回流提取1-3次,每次加入药材重量6-10倍的乙醇,每次提取时间为1-3小时,滤过,合并滤液,滤液加浓度为3-10%的碳酸钠,静置,过滤,弃去沉淀,滤液加氯仿萃取3次,收集碱水层,碱水层加2%的盐酸调pH至3-4,氯仿萃取,收集氯仿层,回收氯仿,得提取物B;
3)取蜜百部、茯苓、白前、五味子加药材重量6-10倍的水浸泡60分钟后,煮沸提取1-3次,每次1-3小时,合并提取液,过滤,滤液浓缩至60-80℃时相对密度为1.1-1.2,得提取物C;
4)合并提取物A、B、C,真空干燥,即得。
本发明还提供了含上述药物组合物的制剂,该制剂由药物组合物单独制成或由药物组合物和药学上可接受的载体组成。
本发明还提供了上述药物组合物或制剂在制备消炎止咳的药物中的应用。
发明人对本发明中药组合物进行检测,发现使用本发明技术方案制备所得中药组合物柚皮苷、苦杏仁苷、甘草酸、半夏总酸含量很高,与现有提取工艺所得产品相比,两者有明显差异,检测结果从侧面表明了各组成分中某些有效成分的提取优于现有技术。由于每味中药材均含有诸多的活性成分,至少尚未有任何一味中药被完完全全地分析清楚所有成分,不同的中药合并在一起用不同提取方式提取时,由于溶剂、温度及不同成分之间的相互影响和作用,会产生极为复杂的化学反应。因此,上述有效成分只是中药提取物活性成分的一部分,对于整体药物的药效作用影响尚不明确。目前我们只能通过药效实验来对比不同提取方式在某个治疗用途方面的优劣,尚无法从部分有效成分的变化指标来判断复方中成药的疗效变化。因此,我们通过更实际动物药效学试验来观察工艺改变后药效发生的变化,实验结果证明,本发明技术方案制备的样品确实优于现有技术制备样品。
本发明提供的一种治疗***炎的药物组合物具有以下优点:
1、按本发明技术方案制备的实施例样品柚皮苷、苦杏仁苷、甘草酸、半夏总酸含量均显著高于对比例,实验结果提示采用本发明技术提取所得中药组合物中柚皮苷、苦杏仁苷、甘草酸、半夏总酸与现有技术相比,提取较完全。
2、药效学试验结果显示:按本发明技术方案制备的实施例样品可延长小鼠咳嗽潜伏期,减少3min内咳嗽次数,提示本发明提取技术方案优于现有技术,可能明显提高镇咳的疗效作用。
3、临床试验中未发现不良反应,安全性检测、疗效检验未发现与试验有关的新异常病例。
具体实施方式
以下实施例用于说明本发明,但不用来限制本发明的范围。
如无特殊说明,本发明中的乙醇浓度均为体积百分比。
实施例1:方案一提取
1)按以下份量称取原料:化橘红3kg、蜜制百部0.3kg、茯苓0.3kg、制半夏0.3kg、白前0.5kg、甘草0.1kg、苦杏仁1kg、五味子0.2kg。
2)化橘红、苦杏仁用水蒸气蒸馏,收集蒸馏液,药渣加10倍药材重量50%乙醇回流提取1次,提取3小时,过滤,提取液过中性氧化铝,收集流出液,流出液过732阳离子树脂,用2倍树脂重量的水洗柱,弃去水洗液,继续用2倍树脂重量40%乙醇洗脱,收集洗脱液,洗脱液继续过717阴离子树脂,用2倍树脂重量的水洗柱,弃去水洗液,继续用2倍树脂重量40%乙醇洗脱,收集洗脱液,浓缩至60℃时相对密度为1.1,得提取物A;
3)取甘草、半夏40%的乙醇加热回流提取1次,加入药材重量10倍的乙醇,提取时间为3小时,滤过,滤液加浓度为3%的碳酸钠,静置,过滤,弃去沉淀,滤液加氯仿萃取3次,收集碱水层,碱水层加2%的盐酸调pH至3.0,氯仿萃取,收集氯仿层,回收氯仿,得提取物B;
4)取蜜百部、茯苓、白前、五味子加药材重量10倍的水浸泡60分钟后,煮沸提取1次,3小时,过滤,滤液浓缩至60-80℃时相对密度为1.1,得提取物C;
4)合并提取物A、B、C,真空干燥,粉碎,加入适量的淀粉、羧甲基纤维素、微晶纤维素,制粒,干燥,整粒,压片,包衣,得片剂。
实施例2:
1)按以下份量称取原料:化橘红3kg、蜜制百部0.3kg、茯苓0.3kg、制半夏0.3kg、白前0.5kg、甘草0.1kg、苦杏仁1kg、五味子0.2kg。
2)化橘红、苦杏仁用水蒸气蒸馏,收集蒸馏液,药渣加8-10倍药材重量60%乙醇回流提取2次,每次2小时,合并提取液,提取液过中性氧化铝,收集流出液,流出液过734阳离子树脂,用2倍树脂重量的水洗柱,弃去水洗液,继续用2倍树脂重量60%乙醇洗脱,收集洗脱液,洗脱液继续过711阴离子树脂,用2倍树脂重量的水洗柱,弃去水洗液,继续用2倍树脂重量60%乙醇洗脱,收集洗脱液,浓缩至70℃时相对密度为1.15,得提取物A;
3)取甘草、半夏60%的乙醇加热回流提取2次,每次加入药材重量8倍的乙醇,每次提取时间为2小时,滤过,合并滤液,滤液加浓度为5%的碳酸氢钠,静置,过滤,弃去沉淀,滤液加***萃取3次,收集碱水层,碱水层加2%的柠檬酸调pH至3.5,***萃取,收集氯仿层,回收氯仿,得提取物B;
4)取蜜百部、茯苓、白前、五味子加药材重量8倍的水浸泡60分钟后,煮沸提取2次,每次2小时,合并提取液,过滤,滤液浓缩至70℃时相对密度为1.15,得提取物C;
5)合并提取物A、B、C,真空干燥,粉碎,加入适量的淀粉,制粒,干燥,整粒,装胶囊,得胶囊剂。
实施例3:
1)按以下份量称取原料:化橘红3kg、蜜制百部0.3kg、茯苓0.3kg、制半夏0.3kg、白前0.5kg、甘草0.1kg、苦杏仁1kg、五味子0.2kg。
2)化橘红、苦杏仁用水蒸气蒸馏,收集蒸馏液,药渣加8-10倍药材重量75%乙醇回流提取3次,每次提取1小时,合并提取液,提取液过中性氧化铝,收集流出液,流出液过D254阳离子树脂,用2倍树脂重量的水洗柱,弃去水洗液,继续用2倍树脂重量75%乙醇洗脱,收集洗脱液,洗脱液继续过D311阴离子树脂,用2倍树脂重量的水洗柱,弃去水洗液,继续用2倍树脂重量80%乙醇洗脱,收集洗脱液,浓缩至75℃时相对密度为1.2,得提取物A;
3)取甘草、半夏80%的乙醇加热回流提取3次,每次加入药材重量10倍的乙醇,每次提取时间为1小时,滤过,合并滤液,滤液加浓度为8%的碳酸钠,静置,过滤,弃去沉淀,滤液加乙酸乙酯萃取3次,收集碱水层,碱水层加2%的富马酸调pH至3.8,乙酸乙酯萃取,收集乙酸乙酯层,回收乙酸乙酯,得提取物B;
4)取蜜百部、茯苓、白前、五味子加药材重量10倍的水浸泡60分钟后,煮沸提取3次,每次1小时,合并提取液,过滤,滤液浓缩至75℃时相对密度为1.2,得提取物C;
5)合并提取物A、B、C,真空干燥,,粉碎,加入适量的淀粉,制粒,干燥,整粒,分装,得颗粒剂。
实施例4:
1)按以下份量称取原料:化橘红3kg、蜜制百部0.3kg、茯苓0.3kg、制半夏0.3kg、白前0.5kg、甘草0.1kg、苦杏仁1kg、五味子0.2kg。
2)化橘红、苦杏仁用水蒸气蒸馏,收集蒸馏液,药渣加10倍药材重量90%乙醇回流提取3次,每次提取1小时,合并提取液,提取液过中性氧化铝,收集流出液,流出液过D-61阳离子树脂,用2倍树脂重量的水洗柱,弃去水洗液,继续用2倍树脂重量95%乙醇洗脱,收集洗脱液,洗脱液继续过D318阴离子树脂,用2倍树脂重量的水洗柱,弃去水洗液,继续用2倍树脂重量90%乙醇洗脱,收集洗脱液,浓缩至80℃时相对密度为1.2,得提取物A;
3)取甘草、半夏90%的乙醇加热回流提取3次,每次加入药材重量10倍的乙醇,每次提取时间为1小时,滤过,合并滤液,滤液加浓度为10%的碳酸钠,静置,过滤,弃去沉淀,滤液加乙酸乙酯萃取3次,收集碱水层,碱水层加2%的富马酸调pH至4.0,乙酸乙酯萃取,收集乙酸乙酯层,回收乙酸乙酯,得提取物B;
4)取蜜百部、茯苓、白前、五味子加药材重量10倍的水浸泡60分钟后,煮沸提取3次,每次1小时,合并提取液,过滤,滤液浓缩至80℃时相对密度为1.2,得提取物C;
5)合并提取物A、B、C,混合,加入适量的蔗糖、纯化水、山梨酸钾,灌装,得口服液。
对比例1:
按以下份量称取原料:化橘红3kg、蜜制百部0.3kg、茯苓0.3kg、制半夏0.3kg、白前0.5kg、甘草0.1kg、苦杏仁1kg、五味子0.2kg。
以上八味,化橘红、苦杏仁用水蒸气蒸馏,收集蒸馏液80ml,药渣与其余百部等六味,加水煎煮二次,每次2小时,合并煎液,滤过,滤液浓缩至80℃时相对密度为1.25-1.35的清膏,加乙醇使含醇量为75%-80%,静置24小时,取上清液,回收乙醇并浓缩至80℃时相对密度为1.18-1.20的清膏,加蔗糖400g、蜂蜜100g、苯甲酸钠3g、羟苯乙酯0.3g,搅拌使溶解,加入上述蒸馏液,混匀,滤过,放冷,加香精和薄荷脑适量,加水至1000ml,搅匀,即得。
实验例1:不同制备方法所得样品含量测定的比较
1样品分组
实施例4、对比例1。
2对比项目
柚皮苷、苦杏仁苷、甘草酸、半夏总酸含量。
3实验结果,见表1
表1不同制备方法所得样品含量测定结果
表1结果显示:本发明实施例样品柚皮苷、苦杏仁苷、甘草酸、半夏总酸含量均显著高于对比例。实验结果提示采用本发明技术提取所得中药组合物中柚皮苷、苦杏仁苷、甘草酸、半夏总酸与现有技术相比,提取较完全。
药效学试验
对氨水致小鼠咳嗽的影响
1材料
1.1实验动物清洁级昆明种雄性小鼠50只,体质量18~22g,由广西医科大学动物中心提供。饲养环境:室温20—23℃,相对湿度45%~6o%,笼具用过氧乙酸溶液消毒,饮用水为净化水。
1.2药物及试剂
实施例1、实施例2、实施例3、实施例4、对比例1;氨水(分析纯)。
2方法
2.1分组与给药取昆明种雄性小鼠6O只,随机分为6组,每组各1O只,每组分别给予以下药物按0.2ml/10g灌胃给药,每日1次,连续7d:
空白对照组:等容积纯净水
实施例1、实施例2、实施例3、实施例4、对比例1:均相当于生药量4g/kg,相当于成人临床用量的8倍。
2.2操作末次给药后30min,分别将各组小鼠置于倒置的500mL烧杯中,内放一棉球,用1mL注射器吸取氨水,0.2mL注入棉球中,迅速倒置烧杯,以免气体泄漏,观察和记录小鼠咳嗽潜伏期及3min内咳嗽次数。
3结果各组小鼠咳嗽潜伏期及3min内咳嗽次数比较见表1。
表1各组小鼠咳嗽潜伏期及3min内咳嗽次数比较(x±s)
注:与空白对照组比较,*P<0.05,**P<0.01;与对比例1组比较,#P<0.05。
由表1可见,实施例1-4及对比例1片组与空白对照组相比,均可延长小鼠咳嗽潜伏期(P<0.05,P<0.01),减少3min内咳嗽次数(P<0.05,P<0.01);但实施例1-4组同时显著性优于对比例1组。提示本发明提取技术方案优于现有技术,可明显提高镇咳的疗效作用。
4结论
本发明是中药制剂,具有理气化痰,润肺止咳的功效,适用于痰浊阻肺所致的咳嗽、气喘、痰多;感冒、支气管炎、咽喉炎,经临床观察疗效确切,未发明毒副反应,是一种值得推广的中药新药。且本发明制备方法与现有技术相比,疗效有显著性差异。
虽然,上文中已经用一般性说明、具体实施方式及试验,对本发明作了详尽的描述,但在本发明基础上,可以对之作一些修改或改进,这对本领域技术人员而言是显而易见的。因此,在不偏离本发明精神的基础上所做的这些修改或改进,均属于本发明要求保护的范围。
Claims (8)
1.一种消炎止咳的药物组合物,由以下重量份的成分制成:化橘红300份、蜜制百部30份、茯苓30份、制半夏30份、白前50份、甘草10份、苦杏仁100份、五味子20份,其特征在于,该药物组合物由以下方法制备而成:
1)化橘红、苦杏仁用水蒸气蒸馏,收集蒸馏液,药渣加乙醇提取,提取液过中性氧化铝,收集流出液,流出液过阳离子树脂,用水洗柱,弃去水洗液,用40%-90%乙醇洗脱,收集洗脱液,洗脱液过阴离子树脂,用水洗柱,弃去水洗液,用40%-90%乙醇洗脱,收集洗脱液,浓缩,得提取物A;
2)取甘草、半夏加乙醇提取,提取液滤过,滤液加3-10%碱液混匀,静置,过滤,弃去沉淀,滤液加有机溶剂萃取,收集碱水层,加2%酸调pH至3-4,加有机溶剂萃取,收集有机溶剂层,回收有机溶剂,得提取物B;
3)取蜜制百部、茯苓、白前、五味子加水浸泡后,煮沸提取,提取液过滤,滤液浓缩,得提取物C;
4)合并提取物A、B、C,干燥,即得。
2.根据权利要求1所述的药物组合物,其特征在于,所述步骤1)中碱液为:氢氧化钠、碳酸钾、碳酸氢钾、碳酸钠、碳酸氢钠、柠檬酸钠、柠檬酸钾、碳酸氢三钠、柠檬酸一钠中任一种或几种。
3.根据权利要求1所述的药物组合物,其特征在于,所述步骤1)中加酸调pH,其中酸为:枸橼酸、乳酸、磷酸、酒石酸、苹果酸、偏酒石酸、乙酸、盐酸、己二酸、富马酸中任一种或几种。
4.根据权利要求1所述的药物组合物,其特征在于,所述步骤1)中阳离子树脂为:732强酸性苯乙烯系阳离子交换树脂、734强酸性苯乙烯系阳离子交换树脂、D254大孔强碱性季铵型阳离子交换树脂、D-61大孔强酸性苯乙烯系阳离子交换树脂中任一种或几种。
5.根据权利要求1所述的药物组合物,其特征在于,所述步骤1)中阴离子树脂为:717强碱性苯乙烯系阴离子交换树脂、711强碱性苯乙烯系I型阴离子交换树脂、D311大孔丙烯酸系弱碱阴离子交换树脂、D318大孔丙烯酸系弱酸阴离子交换树脂中一种或几种。
6.根据权利要求1所述的药物组合物,其特征在于,所述步骤2)中有机溶剂为:乙酸乙酯、氯仿、正丁烷、二氯甲烷或***中任一种或几种。
7.根据权利要求1所述的药物组合物,其特征在于该药物组合物由以下步骤制备而成:
1)化橘红、苦杏仁用水蒸气蒸馏,收集蒸馏液,药渣加8-10倍药材重量50%-80%乙醇回流提取1-3次,每次1-3小时,合并提取液,提取液过中性氧化铝,收集流出液,流出液过阳离子树脂,用2倍树脂重量的水洗柱,弃去水洗液,继续用2倍树脂重量40%-90%乙醇洗脱,收集洗脱液,洗脱液继续过阴离子树脂,用2倍树脂重量的水洗柱,弃去水洗液,继续用2倍树脂重量40%-90%乙醇洗脱,收集洗脱液,浓缩至60-80℃时相对密度为1.1-1.2,得提取物A;
2)取甘草、半夏40%-90%的乙醇加热回流提取1-3次,每次加入药材重量6-10倍的乙醇,每次提取时间为1-3小时,滤过,合并滤液,滤液加浓度为3-10%的碳酸钠,静置,过滤,弃去沉淀,滤液加氯仿萃取3次,收集碱水层,碱水层加2%的盐酸调pH至3-4,氯仿萃取,收集氯仿层,回收氯仿,得提取物B;
3)取蜜百部、茯苓、白前、五味子加药材重量6-10倍的水浸泡60分钟后,煮沸提取1-3次,每次1-3小时,合并提取液,过滤,滤液浓缩至60-80℃时相对密度为1.1-1.2,得提取物C;
4)合并提取物A、B、C,真空干燥,即得。
8.含权利要求1-6任一项所述药物组合物的制剂,其特征在于,该制剂由权利要求1-6任一项所述药物组合物单独制成或由药物组合物和药学上可接受的载体组成。
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CN101181563A (zh) * | 2006-06-16 | 2008-05-21 | 贵州益佰制药股份有限公司 | 橘红痰咳制剂及制备方法和质量控制方法 |
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WO2023273558A1 (zh) * | 2021-06-30 | 2023-01-05 | 广州白云山星群(药业)股份有限公司 | 橘红痰咳浸膏在制备抑制人冠状病毒感染的药物中的用途 |
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