CN116270457A - 一种用于药物临配的混合型液体药用辅料及其制备方法 - Google Patents
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Abstract
本发明设计一种用于药物临配的混合型液体药用辅料及其制备方法,所述药用辅料由以下原料组成:黄原胶0.1%‑0.8%(m/V);柠檬酸0.002%‑0.1%(m/V);高直链豌豆麦芽糊精0.0%‑0.2%(m/V);三氯蔗糖0.01%‑0.2%(m/V);木糖醇0.5%—1%(m/v);甘油5%‑15%(V/V);聚二甲基硅油0%‑0.005%(V/V);香精0.1%‑1.0%;纯化水90%‑98%。本发明可以有效达到矫味和难溶性药物分散均匀的效果,让药物临配操作更简洁方便。
Description
技术领域
本发明涉及一种用于药物临配的混合型液体药用辅料及其制备方法,具体用于药物临配、矫味、分剂量,属于药用辅料技术领域。
背景技术
现有专利国外有许多药物临配的案例,但因为既要达到矫味效果,又要达到药物混悬分散均匀效果,都要使用两款溶媒进行同时调配,操作步骤更繁琐。
部分现有专利配方包含山梨酸钾、羟苯甲酯、羟苯丙酯类防腐剂,在对儿童用药安全日趋严谨的当下,国家针对儿童用药的制剂都会建议防腐剂的减少或者甚至剔除。
部分现有专利包含色素(偶氮染料),CDE颁布的《儿童用药(化学药品)药学开发指导原则》中明确指出,用于儿童用药的制剂中,不建议添加偶氮染料。
部分现有专利虽然添加了消泡剂,但用于药物临配时,操作需要振摇混合,还是会产生气泡,对于服药分剂量准确容易产生误差。为此,设计一种用于药物临配的混合型液体药用辅料及其制备方法,以克服上述问题。
发明内容
本发明的目的是提供一种用于药物临配的混合型液体药用辅料及其制备方法,可以有效达到矫味和难溶性药物分散均匀的效果,让药物临配操作更简洁方便。对于吞咽苦难患者或儿童用药时,根据服用需求,将一定量的药物(如片剂、胶囊剂内容物、颗粒剂等)加入本发明药用辅料中形成药物液体制剂,摇晃分散均匀。按照药品说明书服用剂量或医嘱,服用对应毫升的制剂即可。本发明能够有效掩盖药物苦味,使吞咽困难性患者及儿童提供服药顺应性,和服药分剂量安全准确。
本发明是通过如下的技术方案予以实现的:一种用于药物临配的混合型液体药用辅料,所述药用辅料由以下原料组成:
黄原胶0.1%-0.8%(m/V);
柠檬酸0.002%-0.1%(m/V);
高直链豌豆麦芽糊精0.0%-0.2%(m/V);
三氯蔗糖0.01%-0.2%(m/V);
木糖醇0.5%—1%(m/v);
甘油5%-15%(V/V);
聚二甲基硅油0%-0.005%(V/V);
香精0.1%-1.0%;
纯化水90%-98%。
作为优选:所述香精为甜橙味香精或草莓味香精或柠檬草味香精或樱桃味香精或者其组合。
一种应用上述药用辅料的制备方法,所述方法包括如下步骤:
1)搅拌:取200ml的水加热,放入黄原胶,通过搅拌器搅拌均匀至肉眼可见无抱团颗粒。
2)乳化:另取一个不锈钢配制桶,倒入配方需求的聚二甲基硅油,用高速剪切机采用10000转/分钟的转速,缓慢倒入5倍的纯化水,使聚二甲基硅油充分乳化。搅拌15分钟后,倒入之前的已溶解黄原胶的搅拌罐中。
3)混合:另取200ml纯化水,往里依次加入三氯蔗糖、木糖醇、高直链豌豆麦芽糊精、甘油、香精,在加入每一辅料前,都要确保之前添加辅料已溶解完全,将溶解后物料一起倒入搅拌罐后,用纯化水定容至1000ml。
4)调PH:根据配方需求,缓慢加入柠檬酸,使得溶液整体PH在4.0-4.5范围之间。
5)灌装:配制好的溶液通过陶瓷泵抽至灌装机进行灌装。
6)灭菌:灌装好的溶液,采用巴氏灭菌法,推入灭菌柜进行高温灭菌。
7)包装:灭菌后的产品即可进行包装装箱。
作为优选:所述步骤1)搅拌具体为:取200ml的水,加热至75℃,放入黄原胶,以70转/分钟的速度用搅拌器搅拌均匀至肉眼可见无抱团颗粒。
作为优选:所述步骤5)灌装中的灌装速度为50分钟/瓶。
作为优选:所述步骤6)灭菌柜的温度为105℃,灭菌时间为30分钟。
本发明所设计的一种用于药物临配的混合型液体药用辅料,其只需要使用一款溶媒即可达到矫味和难溶性药物分散均匀的效果,让药物临配操作更简洁方便,本发明还具有以下有益效果:
1.本发明在配方上优化:增加了高直链豌豆麦芽糊精辅料,该辅料的加入能够大大提高对药物的矫味效果。另该辅料对非甾体抗炎药类的溶解度能够大大改善,使得这类药物在本发明中溶解度更大,分散更均匀,用药就会更安全。另外非甾体抗炎药包含:阿司匹林、布洛芬、双氯芬酸钠、对乙酰氨基酚等。这类药物都有解热镇痛抗炎等效果,是目前新冠感染者以及儿童常用的药物。
2.本发明在配方上优化:不添加防腐剂,不添加色素(偶氮染料),本发明在之前专利的基础上,删减了山梨酸钾、羟苯甲酯、羟苯丙酯防腐剂,在工艺上采用灌装后的巴氏灭菌法(105℃高温灭菌30分钟)。既能达到防腐效果又摒弃了防腐剂,使得儿童用药更安全。
3.本发明在配方上的优化:本发明在之前专利删减了山梨醇辅料。山梨醇可能会增加肠道渗透压,改变胃肠道中的水通量,影响药物穿过肠壁的转运速度,缩短药物吸收。另外山梨醇也会对药物产生相容性,举例如氯雷他定片,一种儿童常用的抗过敏药物,它会与山梨醇产生相容性,导致氯雷他定片在溶媒中会缓慢的产生降解杂质,缩短了氯雷他定片在溶媒中临配稳定性时间。本发明删减了该辅料,一方面能提供此类药物临配的药品制剂有效期,另一方面避免了儿童服药的药物吸收速度。
4.本发明在配方上的优化:之前专利甜味剂主要为糖精钠,糖精钠虽然在甜度上能够达到要求,但在矫味时,糖精钠自身带有的后苦现象,使得矫味效果并未达到最佳。本发明甜味剂采用了三氯蔗糖和木糖醇,三氯蔗糖的甜度和木糖醇甜味的清新,都使得矫味效果大大提升,且该两款甜味剂针对儿童都属于非常安全的甜味添加剂。
5.本发明在生产工艺上的优化:消泡剂的乳化,之前专利仅通过添加聚二甲基硅油来达到消泡效果,但因溶媒黏度较大,消泡效果不佳。本发明在工艺上添加消泡剂时,采用高速剪切机(也叫均质机)对消泡剂进行剪切乳化,再添加5倍的纯化水,乳化混合后再添加至产品中,消泡效果会大大提升,从而减少药物与本发明临配时,摇晃分散均匀会更快消除气泡,使得服药分剂量更准确。
附图说明
图1为本发明的整体操作流程图。
具体实施方式
为使本领域的普通技术人员更加清楚地理解本发明的目的、技术方案和优点,以下结合附图和实施例对本发明做进一步的阐述。
下面将结合附图对本发明作详细的介绍:如图1所示,一种用于药物临配的混合型液体药用辅料,所述药用辅料由以下原料组成:
黄原胶0.1%-0.8%(m/V);
柠檬酸0.002%-0.1%(m/V);
高直链豌豆麦芽糊精0.0%-0.2%(m/V);
三氯蔗糖0.01%-0.2%(m/V);
木糖醇0.5%—1%(m/v);
甘油5%-15%(V/V);
聚二甲基硅油0%-0.005%(V/V);
香精0.1%-1.0%;
纯化水90%-98%。
其中所述香精为甜橙味香精或草莓味香精或柠檬草味香精或樱桃味香精等或者其任意组合。
以下为配置1000ml本发明的示例:
一种应用上述药用辅料的制备方法,所述方法包括如下步骤:
1)搅拌:取200ml的水,加热至75℃左右,放入黄原胶,70转/分钟的速度用搅拌器搅拌均匀至肉眼可见无抱团颗粒。
2)乳化:另取一个不锈钢配制桶,倒入配方需求的聚二甲基硅油,用高速剪切机采用10000转/分钟的转速,缓慢倒入5倍的纯化水,使聚二甲基硅油充分乳化。搅拌15分钟后,倒入之前的已溶解黄原胶的搅拌罐中。
3)混合:另取200ml纯化水,往里依次加入三氯蔗糖、木糖醇、高直链豌豆麦芽糊精、甘油、香精,在加入每一辅料前,都要确保之前添加辅料已溶解完全,将溶解后物料一起倒入搅拌罐后,用纯化水定容至1000ml。
4)调PH:根据配方需求,缓慢加入柠檬酸,使得溶液整体PH在4.0-4.5范围之内。
5)灌装:配制好的溶液通过陶瓷泵抽至灌装机进行灌装,灌装速度为50分钟/瓶。
6)灭菌:灌装好的溶液,采用巴氏灭菌法,推入灭菌柜进行高温灭菌,105℃高温灭菌30分钟。
7)包装:灭菌后的产品即可进行包装装箱。
为了方便理解,对本发明的每个原料的功能和作用进行详细阐述,其中:
三氯蔗糖、木糖醇、甘油:作为甜味剂可以很好的掩盖住药物的难闻性,尝起来可以更顺滑、更甜一些,使儿童能更好的服用;
香精:作为矫味剂的一种,有着可以吸引人的作用,能掩盖具有气味的药物(如卡托普利片的蒜臭味),能提高儿童服药顺应性;
高直链豌豆麦芽糊精:作为矫味剂和助溶剂,高直链豌豆麦芽糊精的分子结构具有包合空间,可以很好的包裹住一些苦涩难喝的药物,起到矫味效果;高直链豌豆麦芽糊精的分子包合空间恰好对应6-8个葡萄糖,能够有效改善非甾体抗炎药类的溶解度。
柠檬酸:作为酸味调节剂将pH调节至4.0-4.5范围之内,达到一定的抑菌效果和人体能接受的PH范围;
黄原胶:作为增稠剂,使液体黏度达到所需范围可以更好的将难溶性药物进行分散;
聚二甲基硅油:作为消泡剂可以使配置溶媒中的气泡。
对于吞咽苦难患者或儿童用药时,根据服用需求,将一定量的药物(如片剂、胶囊剂内容物、颗粒剂等)加入本发明药用辅料中形成药物液体制剂,摇晃分散均匀。按照药品说明书服用剂量或医嘱,服用对应毫升的制剂即可,本发明能够有效掩盖药物苦味,使吞咽困难性患者及儿童提供服药顺应性,和服药分剂量安全准确。
本发明所设计的一种用于药物临配的混合型液体药用辅料及其制备方法,其只需要使用一款溶媒即可达到矫味和难溶性药物分散均匀的效果,让药物临配操作更简洁方便,本发明还具有以下有益效果:
1.本发明在配方上优化:增加了高直链豌豆麦芽糊精辅料,该辅料的加入能够大大提高对药物的矫味效果。另该辅料对非甾体抗炎药类的溶解度能够大大改善,使得这类药物在本发明中溶解度更大,分散更均匀,用药就会更安全。另外非甾体抗炎药包含:阿司匹林、布洛芬、双氯芬酸钠、对乙酰氨基酚等。这类药物都有解热镇痛抗炎等效果,是目前新冠感染者以及儿童常用的药物。
2.本发明在配方上优化:不添加防腐剂,不添加色素(偶氮染料),本发明在之前专利的基础上,删减了山梨酸钾、羟苯甲酯、羟苯丙酯防腐剂,在工艺上采用灌装后的巴氏灭菌法(105℃高温灭菌30分钟)。既能达到防腐效果又摒弃了防腐剂,使得儿童用药更安全。
3.本发明在配方上的优化:本发明在之前专利删减了山梨醇辅料。山梨醇可能会增加肠道渗透压,改变胃肠道中的水通量,影响药物穿过肠壁的转运速度,缩短药物吸收。另外山梨醇也会对药物产生相容性,举例如氯雷他定片,一种儿童常用的抗过敏药物,它会与山梨醇产生相容性,导致氯雷他定片在溶媒中会缓慢的产生降解杂质,缩短了氯雷他定片在溶媒中临配稳定性时间。本发明删减了该辅料,一方面能提供此类药物临配的药品制剂有效期,另一方面避免了儿童服药的药物吸收速度。
4.本发明在配方上的优化:之前专利甜味剂主要为糖精钠,糖精钠虽然在甜度上能够达到要求,但在矫味时,糖精钠自身带有的后苦现象,使得矫味效果并未达到最佳。本发明甜味剂采用了三氯蔗糖和木糖醇,三氯蔗糖的甜度和木糖醇甜味的清新,都使得矫味效果大大提升,且该两款甜味剂针对儿童都属于非常安全的甜味添加剂。
5.本发明在生产工艺上的优化:消泡剂的乳化,之前专利仅通过添加聚二甲基硅油来达到消泡效果,但因溶媒黏度较大,消泡效果不佳。本发明在工艺上添加消泡剂时,采用高速剪切机(也叫均质机)对消泡剂进行剪切乳化,再添加5倍的纯化水,乳化混合后再添加至产品中,消泡效果会大大提升,从而减少药物与本发明临配时,摇晃分散均匀会更快消除气泡,使得服药分剂量更准确。
以上所述,仅为本发明较佳的具体实施方式,但本发明的保护范围并不局限于此,任何熟悉本技术领域的技术人员在本发明揭露的技术范围内,可轻易想到的变化或替换,都应涵盖在本发明的保护范围内。
Claims (6)
1.一种用于药物临配的混合型液体药用辅料,其特征在于:所述药用辅料由以下原料组成:
黄原胶0.1%-0.8%(m/V);
柠檬酸0.002%-0.1%(m/V);
高直链豌豆麦芽糊精0.0%-0.2%(m/V);
三氯蔗糖0.01%-0.2%(m/V);
木糖醇0.5%—1%(m/v);
甘油5%-15%(V/V);
聚二甲基硅油0%-0.005%(V/V);
香精0.1%-1.0%;
纯化水90%-98%。
2.根据权利要求1所述的用于药物临配的混合型液体药用辅料,其特征在于:所述香精为甜橙味香精或草莓味香精或柠檬草味香精或樱桃味香精或者其组合。
3.一种根据权利要求1-2任一一项所述的药用辅料的制备方法,其特征在于:所述制备方法包括如下步骤:
1)搅拌:取200ml的水加热,放入黄原胶,通过搅拌器搅拌均匀至肉眼可见无抱团颗粒;
2)乳化:另取一个不锈钢配制桶,倒入配方需求的聚二甲基硅油,用高速剪切机采用10000转/分钟的转速,缓慢倒入5倍的纯化水,使聚二甲基硅油充分乳化,搅拌15分钟后,倒入上述的已溶解黄原胶的搅拌罐中;
3)混合:另取200ml纯化水,往里依次加入三氯蔗糖、木糖醇、高直链豌豆麦芽糊精、甘油、香精,在加入每一辅料前,都要确保之前添加辅料已溶解完全,将溶解后物料一起倒入搅拌罐后,用纯化水定容至1000ml;
4)调PH:根据配方需求,缓慢加入柠檬酸,使得溶液整体PH在4.0-4.5;
5)灌装:配制好的溶液通过陶瓷泵抽至灌装机进行灌装;
6)灭菌:灌装好的溶液,采用巴氏灭菌法,推入灭菌柜进行高温灭菌;
7)包装:灭菌后的产品即可进行包装装箱。
4.根据权利要求3所述的制备方法,其特征在于:所述步骤1)搅拌具体为:取200ml的水,加热至75℃,放入黄原胶,以70转/分钟的速度用搅拌器搅拌均匀至肉眼可见无抱团颗粒。
5.根据权利要求3所述的制备方法,其特征在于:所述步骤5)灌装中的灌装速度为50分钟/瓶。
6.根据权利要求3所述的制备方法,其特征在于:所述步骤6)灭菌柜的温度为105℃,灭菌时间为30分钟。
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CN103622905A (zh) * | 2013-12-17 | 2014-03-12 | 中山大学 | 一种矫味柚皮苷口服溶液及其制备方法 |
CN106236697A (zh) * | 2016-08-08 | 2016-12-21 | 王春艳 | 改善口服药物制剂时不适口感的矫味糖浆剂及其制备方法 |
CN114931552A (zh) * | 2021-02-12 | 2022-08-23 | 浙江贝灵生物医药有限公司 | 一种口服碱性溶媒组合物及其制备方法与应用 |
CN115634198A (zh) * | 2021-07-20 | 2023-01-24 | 浙江贝灵生物医药有限公司 | 用于水难溶性物质的溶媒组合物及其制备方法与应用 |
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US5272137A (en) * | 1992-02-14 | 1993-12-21 | Mcneil-Pfc, Inc. | Aqueous pharmaceutical suspension for pharmaceutical actives |
CN103622905A (zh) * | 2013-12-17 | 2014-03-12 | 中山大学 | 一种矫味柚皮苷口服溶液及其制备方法 |
CN106236697A (zh) * | 2016-08-08 | 2016-12-21 | 王春艳 | 改善口服药物制剂时不适口感的矫味糖浆剂及其制备方法 |
CN114931552A (zh) * | 2021-02-12 | 2022-08-23 | 浙江贝灵生物医药有限公司 | 一种口服碱性溶媒组合物及其制备方法与应用 |
CN115634198A (zh) * | 2021-07-20 | 2023-01-24 | 浙江贝灵生物医药有限公司 | 用于水难溶性物质的溶媒组合物及其制备方法与应用 |
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