CN112494450A - 化学药专用口腔崩解片包覆结构及其制备方法 - Google Patents
化学药专用口腔崩解片包覆结构及其制备方法 Download PDFInfo
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Abstract
本发明涉及医用敷料技术领域,尤其是化学药专用口腔崩解片包覆结构及其制备方法;它包括助咽层和被助咽层包裹在内的崩解层,所述助咽层包括氯化钠、L‑苹果酸、咖啡碱以及第一粘合剂,所述崩解层包括骨架支持剂、花椒麻素、第二粘合剂以及微胶囊,微胶囊内包裹有主药,主药可以是比沙可啶之类的难溶于水的化学药。药片入口后首先崩解助咽层,通过氯化钠、L‑苹果酸、咖啡碱的联合作用使得口腔分泌大量唾液,随后崩解层快速崩解,主药以微胶囊的形式悬浮在唾液中,而花椒麻素促使口腔出现振动的错觉,大幅度降低口腔感知微胶囊的异物感,于是在人体吞咽口水的过程中吞下主药。
Description
技术领域
本发明涉及医用敷料技术领域,尤其是化学药专用口腔崩解片包覆结构及其制备方法。
背景技术
对于难以吞咽常规药物的病人可采用口腔崩解片来用药。例如中国专利公开了一种镇痛药口腔崩解片及其制备方法,专利号201010523561.1,其中记载:主药5-90%、骨架支持剂3-60%、粘合剂5-65%。
该技术方案的不足在于:它仅仅适合用于可溶解于唾液并可被口腔快速吸收的化学药,例如吗啡,但不适用于难溶于水的其他化学药,例如比沙可啶。
发明内容
针对现有技术的不足,本发明提供一种适合难溶性化学药吞咽的口腔崩解片包覆结构。
本发明的技术方案为:
化学药专用口腔崩解片包覆结构,它包括助咽层和被助咽层包裹在内的崩解层,所述助咽层包括氯化钠、L-苹果酸、咖啡碱以及第一粘合剂,所述崩解层包括骨架支持剂、花椒麻素、第二粘合剂以及微胶囊,微胶囊内包裹有主药,主药可以是比沙可啶之类的难溶于水的化学药。
所述包覆结构各组分的重量份数为:
氯化钠10-20份、L-苹果酸5-10份、咖啡碱1-2份、第一粘合剂20-30份、骨架支持剂20-30份、花椒麻素5-10份、第二粘合剂20-30份、微胶囊30-50份。
在一个较优实施例中,所述包覆结构各组分的重量份数为:
氯化钠20份、L-苹果酸5份、咖啡碱1份、第一粘合剂20份、骨架支持剂30份、花椒麻素5份、第二粘合剂30份、微胶囊50份。
其中,骨架支持剂为甘氨酸,第一粘合剂为海藻酸钠,第二粘合剂为普鲁兰。
化学药专用口腔崩解片包覆结构的制备方法,它包括以下步骤:
步骤一,制备微胶囊;
步骤二,将骨架支持剂、花椒麻素、第二粘合剂以及微胶囊与清水混合成悬浊液,将悬浊液脱气并注入模具中,经过-150摄氏度预冷5分钟,转入冻干机,在8毫巴(mbar)压力下,-30摄氏度冷冻干燥5小时,得到崩解层;
步骤三,将氯化钠、L-苹果酸、咖啡碱以及第一粘合剂加清水混合得到包衣液,将崩解层放入包衣锅内,喷入适量包衣液,吹入干燥风,缓慢蒸发水分,重复若干次直至药片达到指定重量,而后转入冻干机,在8毫巴(mbar),-30摄氏度冷冻干燥5小时定型。
其中,所述步骤一中制备微胶囊的方法为:
S1在带搅拌叶的反应器中加入38份去离子水、2份酒精、1.5份海藻酸钠,以2000转每分钟搅拌一个小时;
S2往反应器投入0.08份聚山梨醇酯、2.5份碳酸氢钾和4份主药(例如比沙可啶);以3000转每分钟搅拌2小时并在搅拌过程中保持60摄氏度;
S3将步骤二得到的液体转移到可加压容器;该容器底部具有被40号金属网覆盖的筛板和搅拌桨叶的平底不锈钢槽,在这个不锈钢槽加入120份去离子水和6份氯化钙;
S4在2.1千克压力下通过使蒸汽通过不锈钢转移管的夹套使得上述液体加热到60摄氏度,通过两个直径为0.8毫米的尖端和分散器在端部以小液滴的形式加入到凝胶化介质中,通过反应器过滤得到微胶囊胚体,在搅拌中的0.1%海藻酸钠溶液中在悬浮30分钟,在流化床干燥得到成品微胶囊。
本发明的有益效果为:药片入口后首先崩解助咽层,通过氯化钠、L-苹果酸、咖啡碱的联合作用使得口腔分泌大量唾液,随后崩解层快速崩解,主药以微胶囊的形式悬浮在唾液中,而花椒麻素促使口腔出现振动的错觉,大幅度降低口腔感知微胶囊的异物感,于是在人体吞咽口水的过程中吞下主药。
具体实施方式
下面结合具体实施方式作进一步说明:
化学药专用口腔崩解片包覆结构,它包括助咽层和被助咽层包裹在内的崩解层,所述助咽层包括氯化钠、L-苹果酸、咖啡碱以及第一粘合剂,所述崩解层包括骨架支持剂、花椒麻素、第二粘合剂以及微胶囊,微胶囊内包裹有主药,主药可以是比沙可啶之类的难溶于水的化学药。
所述包覆结构各组分的重量份数为:
氯化钠10-20份、L-苹果酸5-10份、咖啡碱1-2份、第一粘合剂20-30份、骨架支持剂20-30份、花椒麻素5-10份、第二粘合剂20-30份、微胶囊30-50份。
在一个较优实施例中,所述包覆结构各组分的重量份数为:
氯化钠20份、L-苹果酸5份、咖啡碱1份、第一粘合剂20份、骨架支持剂30份、花椒麻素5份、第二粘合剂30份、微胶囊50份。
其中,骨架支持剂为甘氨酸,第一粘合剂为海藻酸钠,第二粘合剂为普鲁兰。
化学药专用口腔崩解片包覆结构的制备方法,它包括以下步骤:
步骤一,制备微胶囊;
步骤二,将骨架支持剂、花椒麻素、第二粘合剂以及微胶囊与清水混合成悬浊液,将悬浊液脱气并注入模具中,经过-150摄氏度预冷5分钟,转入冻干机,在8毫巴(mbar)压力下,-30摄氏度冷冻干燥5小时,得到崩解层;
步骤三,将氯化钠、L-苹果酸、咖啡碱以及第一粘合剂加清水混合得到包衣液,将崩解层放入包衣锅内,喷入适量包衣液,吹入干燥风,缓慢蒸发水分,重复若干次直至药片达到指定重量,而后转入冻干机,在8毫巴(mbar),-30摄氏度冷冻干燥5小时定型。
其中,所述步骤一中制备微胶囊的方法为:
S1在带搅拌叶的反应器中加入38份去离子水、2份酒精、1.5份海藻酸钠,以2000转每分钟搅拌一个小时;
S2往反应器投入0.08份聚山梨醇酯、2.5份碳酸氢钾和4份主药(例如比沙可啶);以3000转每分钟搅拌2小时并在搅拌过程中保持60摄氏度;
S3将步骤二得到的液体转移到可加压容器;该容器底部具有被40号金属网覆盖的筛板和搅拌桨叶的平底不锈钢槽,在这个不锈钢槽加入120份去离子水和6份氯化钙;
S4在2.1千克压力下通过使蒸汽通过不锈钢转移管的夹套使得上述液体加热到60摄氏度,通过两个直径为0.8毫米的尖端和分散器在端部以小液滴的形式加入到凝胶化介质中,通过反应器过滤得到微胶囊胚体,在搅拌中的0.1%海藻酸钠溶液中在悬浮30分钟,在流化床干燥得到成品微胶囊。
唾液分泌实验
为了验证本发明中氯化钠、L-苹果酸、咖啡碱对促进唾液分泌是有效的,本实验将设置5组志愿者(第一、二、三、四、五组),每组9人,均为成年人。第一组在口腔含0.1克氯化钠,保持一分钟,期间不吞咽口水,而后将口腔内所有口水导入量筒并统计该组志愿者的平均口水分泌量。第二组在口腔含0.1克L-苹果酸,保持一分钟,期间不吞咽口水,而后将口腔内所有口水导入量筒并统计该组志愿者的平均口水分泌量。第三组在口腔含0.1克咖啡碱,保持一分钟,期间不吞咽口水,而后将口腔内所有口水导入量筒并统计该组志愿者的平均口水分泌量。第四组在口腔含0.1克由氯化钠、L-苹果酸、咖啡碱按照重量份数20:5:1混合而成的混合物,保持一分钟,期间不吞咽口水,而后将口腔内所有口水导入量筒并统计该组志愿者的平均口水分泌量。第五组在口腔含0.1克直链淀粉,保持一分钟,期间不吞咽口水,而后将口腔内所有口水导入量筒并统计该组志愿者的平均口水分泌量。
统计结果如下表:
由此可见,氯化钠、L-苹果酸、咖啡碱单一成分含入口中与普通食物(直链淀粉)含入口中时促使口腔分泌的唾液量并没有明显区别,而将其混合后有意外的功效。
上述实施例和说明书中描述的只是说明本发明的原理和最佳实施例,在不脱离本发明精神和范围的前提下,本发明还会有各种变化和改进,这些变化和改进都落入要求保护的本发明范围内。
Claims (6)
1.化学药专用口腔崩解片包覆结构,其特征在于:它包括助咽层和被助咽层包裹在内的崩解层,所述助咽层包括氯化钠、L-苹果酸、咖啡碱以及第一粘合剂,所述崩解层包括骨架支持剂、花椒麻素、第二粘合剂以及微胶囊,微胶囊内包裹有主药。
2.根据权利要求1所述的化学药专用口腔崩解片包覆结构,其特征在于:所述包覆结构各组分的重量份数为:
氯化钠10-20份、L-苹果酸5-10份、咖啡碱1-2份、第一粘合剂20-30份、骨架支持剂20-30份、花椒麻素5-10份、第二粘合剂20-30份、微胶囊30-50份。
3.根据权利要求2所述的化学药专用口腔崩解片包覆结构,其特征在于:所述包覆结构各组分的重量份数为:
氯化钠20份、L-苹果酸5份、咖啡碱1份、第一粘合剂20份、骨架支持剂30份、花椒麻素5份、第二粘合剂30份、微胶囊50份。
4.根据权利要求1所述的化学药专用口腔崩解片包覆结构,其特征在于:骨架支持剂为甘氨酸,第一粘合剂为海藻酸钠,第二粘合剂为普鲁兰。
5.化学药专用口腔崩解片包覆结构的制备方法,其特征在于:它包括以下步骤:
步骤一,制备微胶囊;
步骤二,将骨架支持剂、花椒麻素、第二粘合剂以及微胶囊与清水混合成悬浊液,将悬浊液脱气并注入模具中,经过-150摄氏度预冷5分钟,转入冻干机,在8毫巴压力下,-30摄氏度冷冻干燥5小时,得到崩解层;
步骤三,将氯化钠、L-苹果酸、咖啡碱以及第一粘合剂加清水混合得到包衣液,将崩解层放入包衣锅内,喷入适量包衣液,吹入干燥风,缓慢蒸发水分,重复若干次直至药片达到指定重量,而后转入冻干机,在8毫巴,-30摄氏度冷冻干燥5小时定型。
6.根据权利要求5所述的化学药专用口腔崩解片包覆结构的制备方法,其特征在于:所述步骤一中制备微胶囊的方法为:
S1在带搅拌叶的反应器中加入38份去离子水、2份酒精、1.5份海藻酸钠,以2000转每分钟搅拌一个小时;
S2往反应器投入0.08份聚山梨醇酯、2.5份碳酸氢钾和4份主药;以3000转每分钟搅拌2小时并在搅拌过程中保持60摄氏度;
S3将步骤二得到的液体转移到可加压容器;该容器底部具有被40号金属网覆盖的筛板和搅拌桨叶的平底不锈钢槽,在这个不锈钢槽加入120份去离子水和6份氯化钙;
S4在2.1千克压力下通过使蒸汽通过不锈钢转移管的夹套使得上述液体加热到60摄氏度,通过两个直径为0.8毫米的尖端和分散器在端部以小液滴的形式加入到凝胶化介质中,通过反应器过滤得到微胶囊胚体,在搅拌中的0.1%海藻酸钠溶液中在悬浮30分钟,在流化床干燥得到成品微胶囊。
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Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090124701A1 (en) * | 2007-11-08 | 2009-05-14 | Symrise Gmbh & Co. Kg | Use of alkamides for masking an unpleasant flavor |
JP2012044918A (ja) * | 2010-08-26 | 2012-03-08 | Japan Health Science Foundation | 容器詰飲料 |
CN102451164A (zh) * | 2010-10-22 | 2012-05-16 | 量子高科(北京)研究院有限公司 | 一种镇痛药口腔崩解片及其制备方法 |
CN102525970A (zh) * | 2010-12-31 | 2012-07-04 | 量子高科(北京)研究院有限公司 | 一种抗痴呆药物口腔崩解片及其制备方法 |
CN104244927A (zh) * | 2012-03-20 | 2014-12-24 | 莱博瑞特瑞欧斯巴戈公司 | 通过离子凝胶化生产包含双氯酚酸或其一种盐的肠溶海藻酸盐微胶囊的方法以及包含该微胶囊的多颗粒药物组合物 |
CN104382869A (zh) * | 2014-10-23 | 2015-03-04 | 温州芳植生物科技有限公司 | 一种麻痹口腔掩味的口崩片及其制备方法 |
CN105147646A (zh) * | 2015-09-30 | 2015-12-16 | 合肥华方医药科技有限公司 | 一种苯巴比妥口腔速溶膜剂及其制备方法 |
CN109966271A (zh) * | 2019-04-22 | 2019-07-05 | 上海昊海生物科技股份有限公司 | 一种盐酸莫西沙星膜剂及其制备方法 |
CN110548010A (zh) * | 2019-04-02 | 2019-12-10 | 海南海神同洲制药有限公司 | 一种罗红霉素分散片制备方法 |
-
2020
- 2020-12-12 CN CN202011453862.1A patent/CN112494450A/zh active Pending
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090124701A1 (en) * | 2007-11-08 | 2009-05-14 | Symrise Gmbh & Co. Kg | Use of alkamides for masking an unpleasant flavor |
JP2012044918A (ja) * | 2010-08-26 | 2012-03-08 | Japan Health Science Foundation | 容器詰飲料 |
CN102451164A (zh) * | 2010-10-22 | 2012-05-16 | 量子高科(北京)研究院有限公司 | 一种镇痛药口腔崩解片及其制备方法 |
CN102525970A (zh) * | 2010-12-31 | 2012-07-04 | 量子高科(北京)研究院有限公司 | 一种抗痴呆药物口腔崩解片及其制备方法 |
CN104244927A (zh) * | 2012-03-20 | 2014-12-24 | 莱博瑞特瑞欧斯巴戈公司 | 通过离子凝胶化生产包含双氯酚酸或其一种盐的肠溶海藻酸盐微胶囊的方法以及包含该微胶囊的多颗粒药物组合物 |
CN104382869A (zh) * | 2014-10-23 | 2015-03-04 | 温州芳植生物科技有限公司 | 一种麻痹口腔掩味的口崩片及其制备方法 |
CN105147646A (zh) * | 2015-09-30 | 2015-12-16 | 合肥华方医药科技有限公司 | 一种苯巴比妥口腔速溶膜剂及其制备方法 |
CN110548010A (zh) * | 2019-04-02 | 2019-12-10 | 海南海神同洲制药有限公司 | 一种罗红霉素分散片制备方法 |
CN109966271A (zh) * | 2019-04-22 | 2019-07-05 | 上海昊海生物科技股份有限公司 | 一种盐酸莫西沙星膜剂及其制备方法 |
Non-Patent Citations (3)
Title |
---|
T NAGARAJU,等: "Comprehensive review on oral disintegrating films", 《CURRENT DRUG DELIVERY》 * |
彭红,等: "尼麦角林口腔崩解片的研制", 《江西中医学院学报》 * |
郭长江,等: "《现代营养治疗》", 31 August 2016, 中国医药科技出版社 * |
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