CN109125257B - 氨酚愈创肾素口服液及其制备方法 - Google Patents
氨酚愈创肾素口服液及其制备方法 Download PDFInfo
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Abstract
本发明氨酚愈创肾素口服液及其制备方法，其目的是提供一种能够缓解或治疗感冒和流感引起的鼻塞、头痛及轻微的疼痛、鼻窦充血和压力、退热、通窍、改善鼻腔通气，促进鼻窦引流、化痰、镇咳作用的氨酚愈创肾素口服液，该口服液适合于12岁以上人群服用，具有水果味，易于服用。本发明的另一个目的是提供氨酚愈创肾素口服液的制备方法，该方法操作简单，无污染，生产成本低，适合于产业化生产。
Description
技术领域
本发明属药物研发技术领域，具体涉及氨酚愈创肾素口服液及其制备方法。
背景技术
感冒主要是由于体虚和抗病毒能力减弱引起的，主要表现为鼻塞、打喷嚏、流鼻涕、咳嗽、咳痰、头疼、厌食或发热等症状。
流行性感冒(简称流感)是流感病毒引起的急性呼吸道感染，也是一种传染性强、传播速度快的疾病。其主要通过空气中的飞沫、人与人之间的接触或与被污染物品的接触传播。
现在治疗感冒的药物有很多，大多为口服药物，以冲剂、片剂和胶囊剂居多，但是现大多数感冒药在用法用量上都没有对年龄上的限制，导致乱服感冒药现象，特别是不少家长将成人感冒药减半给孩子服用，这样就会有损于儿童健康。服用剂量过大、无服用年龄限制、规格不齐以及服药口感不好，是我国感冒药现存的极其严重的问题。
发明内容
本发明的目的是提供一种能够缓解或治疗感冒和流感引起的鼻塞、头痛及轻微的疼痛、鼻窦充血和压力、退热、通窍、改善鼻腔通气，促进鼻窦引流、化痰、镇咳作用的氨酚愈创肾素口服液，该口服液适合于12岁以上人群服用，具有水果味，易于服用。
本发明的另一个目的是提供氨酚愈创肾素口服液的制备方法，该方法操作简单，无污染，生产成本低，适合于产业化生产。
本发明的技术方案如下：
处方：
(1)每1000ml中含：
对乙酰氨基酚32.5g、愈创木酚甘油醚20.0g、盐酸去氧肾上腺素0.5g、黄原胶5-2.0g、丙二醇100.0-500.0g、甘油100.0-300.0g、没食子酸丙酯0.5-5.0g、依地酸二钠0.1-1.0g、无水柠檬酸0.5-3.0g、苯甲酸钠1.0-4.0g、山梨醇50.0-200.0-5.0g、三氯蔗糖0.5-5.0g、柠檬酸三钠0.5-3.0g、色素10.0-30.0mg、香精0.5-5.0ml。纯化水适量。
(2)还可以是，每1000ml中含对乙酰氨基酚32.5g、愈创木酚甘油醚20.0g、盐酸去氧肾上腺素0.5g、黄原胶0.95g、丙二醇300.0g、甘油200.0g、没食子酸丙酯2.0g、依地酸二钠 0.5g、无水柠檬酸1.9g、苯甲酸钠2.0g、山梨醇100.0g、三氯蔗糖2.5g、柠檬酸三钠1.0g、色素28.5mg、香精2.5ml。纯化水适量。
(3)优选地，每1000ml中含对乙酰氨基酚32.5g、愈创木酚甘油醚20.0g、盐酸去氧肾上腺素0.5g、黄原胶1.0g、丙二醇250.0g、甘油200g、没食子酸丙酯2.0g、依地酸二钠0.5g、无水柠檬酸1.9g、苯甲酸钠2.3g、山梨醇100g、三氯蔗糖2.5g、柠檬酸三钠2.2g、色素2.0 mg、香精2.5ml。纯化水适量。
(4)还可以是每1000ml中含对乙酰氨基酚32.5g、愈创木酚甘油醚20.0g、盐酸去氧肾上腺素0.5g、黄原胶0.95g、丙二醇300g、甘油200g、没食子酸丙酯2.0g、依地酸二钠0.5g、无水柠檬酸1.9g、苯甲酸钠2.3g、山梨醇100g、三氯蔗糖0.73g、柠檬酸三钠2.2g、色素28.5mg、香精2.5ml。纯化水适量。
制备方法
制备方法1：可以取上述(1)-(4)任一处方，
1、称取处方量黄原胶、丙二醇至洁净的容器中，搅拌使之分散均匀，得药液1，备用；
2、称取处方量的没食子酸丙酯、依地酸二钠、无水柠檬酸、苯甲酸钠、山梨醇、柠檬酸三钠、三氯蔗糖置洁净容器中，搅拌使溶解或均匀分散，加入上述药液1中，继续搅拌，使之溶解或分散均匀，得药液2，备用；
3、称取处方量的甘油，加少量的水稀释后，加入上述药液2中，搅拌状态下，依次加入处方量的对乙酰氨基酚、愈创木酚甘油醚、盐酸去氧肾上腺素，搅拌使全部溶解后，依次加入处方量的色素、香精，加水至配制量，搅拌均匀，过滤，脱气，装，即得。
制备方法2：可以取上述(1)-(4)任一处方，
1、称取处方量的黄原胶于洁净容器中，加入一定量的水使之溶胀，静止12-15h，得药液1，备用；
2、称取处方量的甘油、丙二醇，加入上述药液1中，搅拌使之溶解或分散，得药液2，备用；
3、另称取处方量对乙酰氨基酚、愈创木酚甘油醚、盐酸去氧肾上腺素、没食子酸丙酯、依地酸二钠、无水柠檬酸、苯甲酸钠、山梨醇、柠檬酸三钠和三氯蔗糖，加入上述药液2中，搅拌，使其溶解，在依次加入处方量的色素、香精，加水至配制量，搅拌使其全部溶解，过滤，脱气，灌装，即得。
制备方法3：可以取上述(1)-(4)任一处方，
1、称取处方量的对乙酰氨基酚、愈创木酚甘油醚、盐酸去氧肾上腺素、没食子酸丙酯、依地酸二钠、无水柠檬酸、苯甲酸钠、山梨醇、柠檬酸三钠和三氯蔗糖于配液罐中，混合均匀，得药物混合物，备用；
2、称取处方量甘油、丙二醇，用少量水稀释后，加入上述药物混合物中，搅拌，使其溶解，加入处方量的色素、香精，加水至配制量，搅拌使其全部溶解后，过滤，脱气，灌装，即得。
制备方法4：可以取上述(1)-(4)任一处方，
1、称取处方量黄原胶加入处方量的丙二醇中，搅拌使其溶解或分散后，加入处方量的甘油，继续搅拌使其溶解，得药液1，备用；
2、药液1中依次加入对乙酰氨基酚、愈创木酚甘油醚、盐酸去氧肾上腺素，搅拌使溶解得药液2，备用；
3、另分别称取处方量的没食子酸丙酯、依地酸二钠、无水柠檬酸、苯甲酸钠、山梨醇、柠檬酸三钠和三氯蔗糖，加入少量温度为50-75℃水，搅拌使其溶解后，加入上述药液2中，在依次加入处方量的色素、香精，加水至配制量，搅拌，使其全部溶解后，过滤，脱气，灌装，即得。
所述香精，是指菠萝香精或苹果香精或橘子香精或山楂香精一种或一种以上的混合物；
所述色素，是指亮蓝或诱惑红其中的一种。
所述过滤，是指用0.35-0.60μm微孔滤膜过滤；
所述脱气，是指将药液用减压方法脱气10-60min。
本发明具有缓解或治疗感冒和流感引起的鼻塞、头痛及轻微的疼痛、鼻窦充血和压力、退热、通窍、改善鼻腔通气，促进鼻窦引流、化痰、镇咳等作用。
本发明适合于12岁以上人群服用，水果味。
有益效果
本发明氨酚愈创肾素口服液及其制备方法，提供一种能够缓解或治疗感冒和流感引起的鼻塞、头痛及轻微的疼痛、鼻窦充血和压力、退热、通窍、改善鼻腔通气，促进鼻窦引流、化痰、镇咳药物，该发明适合于12岁以上人群服用，水果味，易于服用。
本发明的另一个目的是提供一种氨酚愈创肾素口服液的制备方法，该方法操作简单，无污染，生产成本低，适合于产业化生产。
具体实施例
实施例1(按1000ml配制量配制)
1、称取黄原胶0.5g、丙二醇100g置洁净的容器中，搅拌使之分散均匀，得药液1，备用；
2、称取没食子酸丙酯0.5g、依地酸二钠0.1g、无水柠檬酸0.5g、苯甲酸钠1.0g、山梨醇 50.0g、柠檬酸三钠0.5g、三氯蔗糖0.5置洁净容器中，搅拌使溶解或均匀分散，加入上述药液1中，继续搅拌，使之溶解或分散均匀，得药液2，备用；
3、称取甘油100g，加少量的水稀释后，加入上述药液2中，搅拌状态下，依次加入处方量的对乙酰氨基酚32.5g、愈创木酚甘油醚20.0g、盐酸去氧肾上腺素0.5g，搅拌使全部溶解后，在依次加入亮蓝10mg、菠萝香精0.5ml，加水至1000ml，搅拌均匀，用0.35μm微孔滤膜过滤过滤，减压脱气50min，灌装，即得。
实施例2(按1000ml配制量配制)
1、称取黄原胶0.95g，丙二醇300.0g置洁净的容器中，搅拌使之分散均匀，得药液1，备用；
2、称取没食子酸丙酯2.0g、依地酸二钠0.5g、无水柠檬酸1.9g、苯甲酸钠2.0g、山梨醇 100.0g、柠檬酸三钠1.0g和三氯蔗糖2.5g置洁净容器中，搅拌使溶解或均匀分散，加入上述药液1中，继续搅拌，使之溶解或分散均匀，得药液2，备用；
3、称取甘油200.0g，加少量的水稀释后，加入上述药液2中，搅拌状态下，依次加入处方量的对乙酰氨基酚32.5g、愈创木酚甘油醚20.0g、盐酸去氧肾上腺素0.5g，搅拌使全部溶解后在依次加入处方量的亮蓝28.5mg、苹果香精2.5ml，加水至配制量，搅拌均匀，用0.45μm 微孔滤膜过滤，减压脱气30min，灌装，即得。
实施例3(按1000ml配制量配制)
1、称取黄原胶1.0g于配液罐中，加入一定量的水使之溶胀，静止12-15h，得药液1，备用；
2、称取甘油200g、丙二醇250g，加入上述药液1中，搅拌使之溶解或分散，得药液2，备用；
3、另称取对乙酰氨基酚32.5g、愈创木酚甘油醚20.0g、盐酸去氧肾上腺素0.5g、没食子酸丙酯2.0g、依地酸二钠0.5g、无水柠檬酸1.9g、苯甲酸钠2.3g、山梨醇100g、柠檬酸三钠 2.2g和三氯蔗糖2.5g，加入上述药液2中，搅拌，使其溶解，在依次加入诱惑红2.0mg、橘子香精2.5ml，加水至配制量，搅拌使其全部溶解，用0.45μm微孔滤膜过滤，减压脱气60min，灌装，即得。
实施例4(按1000ml配制量配制)
1、称取对乙酰氨基酚32.5g、愈创木酚甘油醚20.0g、盐酸去氧肾上腺素0.5g、没食子酸丙酯2.0g、依地酸二钠0.5g、无水柠檬酸1.9g、苯甲酸钠2.3g、山梨醇100g、柠檬酸三钠2.2g 和三氯蔗糖0.73g于配液罐中，混合均匀，得药物混合物，备用；
2、称取甘油200g、丙二醇300g，用少量水稀释后，加入上述药物混合物中，搅拌，使其溶解，加入亮蓝28.5mg、菠萝香精2.5ml，加水至配制量，搅拌使其全部溶解后，用0.56μm微孔滤膜过滤，减压脱气40min，灌装，即得。
实施例5(按1000ml配制量配制)
1、称取黄原胶0.95g、丙二醇300g至洁净的容器中，搅拌使之分散均匀，得药液1，备用；
2、称取没食子酸丙酯2.0g、依地酸二钠0.5g、无水柠檬酸1.9g、苯甲酸钠2.3g、山梨醇 100g、柠檬酸三钠2.2g和三氯蔗糖0.73g置洁净容器中，搅拌使溶解或均匀分散后，加入上述药液1中，继续搅拌，使之溶解或分散均匀，得药液2，备用；
3、称取甘油200g，加少量的水稀释后，加入上述药液2中，搅拌状态下，依次加入对乙酰氨基酚32.5g、愈创木酚甘油醚20g、盐酸去氧肾上腺素0.5，搅拌使全部溶解后在依次加入亮蓝28.5mg、苹果香精2.0ml，加水至配制量，搅拌均匀，用0.45μm微孔滤膜过滤，减压脱气20min，灌装，即得。
实施例6(按1000ml配制量配制)
每1000ml中含：
1、称取对乙酰氨基酚32.5g、愈创木酚甘油醚20.0g、盐酸去氧肾上腺素0.5g、没食子酸丙酯5.0g、依地酸二钠1.0g、无水柠檬酸3.0g、苯甲酸钠4.0g、山梨醇100.0g、柠檬酸三钠 3.0g和三氯蔗糖5.0g于洁净容器中，混合均匀，得药物混合物，备用；
2、称取甘油300.0g、丙二醇200g，用少量水稀释后，加入上述药物混合物中，搅拌，使其溶解，加入处方量的亮蓝30mg、橘子香精5.0ml，加水至配制量，搅拌使其全部溶解后，用 0.45μm微孔滤膜过滤，减压脱气30min，灌装，即得。
实施例7(按1000ml配制量配制)
1、称取黄原胶0.7g置洁净容器中，加入一定量的水使之溶胀，静止12-15h，得药液1，备用；
2、称取甘油200.0g、丙二醇150.0g，加入上述药液1中，搅拌使之溶解或分散，得药液2，备用；
3、另称取对乙酰氨基酚32.5g、愈创木酚甘油醚20.0g、盐酸去氧肾上腺素0.5g、没食子酸丙酯0.8g、依地酸二钠0.8g、无水柠檬酸2.0g、苯甲酸钠3.0g、山梨醇100g、柠檬酸三钠 2.0g和三氯蔗糖3.0g，加入上述药液2中，搅拌，使其溶解，在依次加入诱惑红2.5mg、山楂香精5.0ml，加水至配制量，搅拌使其全部溶解，用0.35μm微孔滤膜过滤，减压脱气30min，灌装，即得。
实施例8
对上述实施例1至实施例7进行稳定性试验，考察药液的澄清度：
试验方法：取上述实施例1至实施例7制备的药液各10支，每支10ml，放置37℃恒温箱中，每月检查一次，共检查12个月，每个实施例中如果发现一支有轻微浑浊或浑浊或严重浑浊，就可以按规定进行判断。(检查结果见下表)。
澄清用“-”表示，轻微浑浊用“+”表示；浑浊用“++”表示；严重浑浊用“+++”表示。
检查方法：
澄清：将样品倒置在阳光下观察，无小颗粒或浑浊现象；
轻微浑浊：将样品倒置在阳光下观察，有小颗粒或药液稍有不透明感；
浑浊：将样品倒置在阳光下观察，颗粒数增加，瓶底有少量的沉淀，药液不透明；
严重浑浊：将样品倒置在阳光下观察。瓶底有大量沉淀产生，轻摇沉淀不挥散，药液无透明感。
结论：经稳定性试验考察，实施例3从第1个月至第12个月，药液始终保持澄清状态，其他实施例都有不同程度的浑浊或轻微浑浊，所以，实施例3为优选制备方案。
实施例9
考察：氨酚愈创肾素口服液对小鼠醋酸扭体的抑制作用，阐述其镇痛作用。
试验用药物：氨酚愈创肾素口服液
阴性对照：生理盐水；湖南金建药业有限公司生产，批号为180101
阳性对照：罗通定片：四川迪菲特药业有限公司生产，批号为180403
实验方法：取昆明种小鼠50只，体重18-22g，随机分为5组，单次灌胃给予剂量低剂量1.3 ml/kg，中剂量2.6ml/kg，高剂量5.2ml/kg，阴性对照为生理盐水，阳性对照为罗通定0.03g/kg，给药后1h，腹腔注射0.7％醋酸10ml/kg，同时用秒表计时，立即观察小鼠出现第一次扭体时间(扭体潜伏期)和15min内扭体次数。各给药组与对照组比较，统计数据以X±S表示。
药物镇痛百分率(％)＝[(对照组扭体次数-给药组扭体次数)/对照组扭体次数]*100％
表1：氨酚愈创肾素口服液对冰醋酸致通小鼠的镇痛作用(X±S)
| 组别 | 潜伏期t/min | 15min内扭体次数 | 镇痛率(％) |
| 生理盐水 | 6.23±2.31 | 12.35±6.33 | |
| 罗通定 | 1.23±4.54<sup>#</sup> | 0.79±3.02<sup>#</sup> | 93.60 |
| 低剂量 | 4.23±2.32 | 6.24±6.55<sup>*</sup> | 49.47 |
| 中剂量 | 2.86±2.75<sup>*</sup> | 4.23±5.31<sup>#</sup> | 65.75 |
| 高剂量 | 2.78±2.24<sup>*</sup> | 3.14±8.31<sup>#</sup> | 74.57 |
与生理盐水组比较，*p＜0.05，#p＜0.01
结果表明，本品中剂量和高剂量组与阳性药物均能有效延长冰醋酸致小鼠疼痛潜伏期，并能显著减少小鼠扭体次数，对小鼠醋酸扭体有较强的抑制作用，具有一定的镇痛效果。
Claims (1)
1.一种氨酚愈创肾素口服液，其特征在于按照如下方法制备得到：1）、称取黄原胶1.0g于配液罐中，加入一定量的水使之溶胀，静止12-15h，得药液1，备用；2）、称取甘油200g、丙二醇250g，加入上述药液1中，搅拌使之溶解或分散，得药液2，备用；3）、另称取对乙酰氨基酚32.5g、愈创木酚甘油醚20.0g、盐酸去氧肾上腺素0.5g、没食子酸丙酯2.0g、依地酸二钠0.5g、无水柠檬酸1.9g、苯甲酸钠2.3g、山梨醇100g、柠檬酸三钠 2.2g和三氯蔗糖2.5g，加入上述药液2中，搅拌，使其溶解，在依次加入诱惑红2.0mg、橘子香精2.5ml，加水至配制量，搅拌使其全部溶解，用0.45μm微孔滤膜过滤，减压脱气60min，灌装，即得。
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| CN108187054A (zh) * | 2013-02-28 | 2018-06-22 | 辉瑞公司 | 新液体组合物的增强的稳定性 |
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| Bioavailability of paracetamol, phenylephrine hydrochloride and guaifenesin in a fixed-combination syrup versus an oral reference product;Annick Janin等;《Journal of INTERNATIONAL MEDICAL RESEARCH》;20141231;第42卷(第2期);第347-358页 * |
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