CN109481405B - 复方氨基酸颗粒(9aa)及其制备方法 - Google Patents
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Abstract
本发明涉及由异亮氨酸、亮氨酸、盐酸赖氨酸、甲硫氨酸、苯丙氨酸、苏氨酸、色氨酸、缬氨酸、盐酸组氨酸为有效成分的复方氨基酸颗粒(9AA)及其制备方法。本发明所述复方氨基酸颗粒(9AA)质量好、稳定性高、可溶性好,制备方法简单,质量可控。
Description
技术领域
本发明属于医药技术领域,涉及复方氨基酸颗粒(9AA)及其制备方法。
背景技术
复方氨基酸颗粒(9AA)有效成分为:异亮氨酸、亮氨酸、盐酸赖氨酸、甲硫氨酸、苯丙氨酸、苏氨酸、色氨酸、缬氨酸、盐酸组氨酸。
复方氨基酸颗粒(9AA)临床用于:非终末期慢性肾衰竭等。可补充体内必需氨基酸,使蛋白质合成显著增加而改善营养状况。慢性肾衰竭时,体内大多数必需氨基酸血浆浓度下降,而非必需氨基酸血浆浓度正常或升高,本品可使下降的必需氨基酸血浆浓度恢复。如同时供给足够能量,可加强同化作用,使蛋白质无须作为能源被分解利用,不产生或极少产生氮的终末代谢产物,有利减轻尿毒素症状。亦有降低血磷,纠正钙磷代谢紊乱作用。
因为复方氨基酸颗粒(9AA)的积极疗效,研究一种更加稳定的复方氨基酸颗粒(9AA)对于复方氨基酸颗粒(9AA)的应用有积极作用。本发明人在长期对复方氨基酸颗粒(9AA)的大量研究过程中获得了复方氨基酸颗粒(9AA)处方及其制备方法,处方简单、辅料用量少,制备的复方氨基酸颗粒(9AA)具有极高的质量及稳定性,增加了用药的安全性;同时因为主药极多成分复杂,现有技术生产的复方氨基酸颗粒往往溶化性较差,本发明和现有技术相比具有极好的溶化性,明显优于现有技术。
发明内容
本发明提供一种稳定的复方氨基酸颗粒(9AA)及其制备方法。
本发明提供的复方氨基酸颗粒(9AA)处方如下:
异亮氨酸:3.5 kg
亮氨酸:5.5 kg
盐酸赖氨酸:4.00 kg
甲硫氨酸:5.5 kg
苯丙氨酸:5.5 kg
苏氨酸:2.5 kg
色氨酸:1.25 kg
缬氨酸:4.06 kg
盐酸组氨酸:2.75 kg
蔗糖:110.40 kg
甜菊素:0.58 kg
95%乙醇:3.16 kg
纯化水:6.84 kg
制成:10000袋
本发明所述的复方氨基酸颗粒(9AA)制备方法包括如下步骤:
1、分别将蔗糖和盐酸组氨酸进行粉碎,过60目筛网;按处方量依次称量:蔗糖、异亮氨酸、亮氨酸、盐酸赖氨酸、甲硫氨酸、苯丙氨酸、苏氨酸、缬氨酸、色氨酸、盐酸组氨酸,待用;
2、黏合剂的配制:称取处方量95%乙醇中加入处方量的纯化水搅拌均匀制成溶液,待用;
3、将步骤1称量好的原辅料按照先后顺序置于湿法制粒机中,关闭锅盖,设置参数,桨叶转速设为140r~160r /min,切刀转速1800r~2000r/min,混合480S~500S;
4、往步骤3湿法制粒机中加入步骤2制备的黏合剂进行湿混,湿混桨叶转速设为140r~160r /min,切刀转速1800r~2000r/min,混合180 S~200S,出料;
5、制粒:将步骤4制备的物料用16目湿法造粒机制湿颗粒;
6、将步骤5制备的的湿颗粒均匀铺盘(厚度约8~12mm),送烘箱中烘干,温度设定为55±2℃,干燥2~3小时后将干燥后的颗粒用14目和40目振荡筛进行整理筛分,使成大小均一的颗粒;
7、将步骤6制备的颗粒置于料斗混合机中,加入处方量的甜菊素,设置转速5 r/min,混合5min出料,测定含量,按规格包装即得。
本发明处方采用蔗糖、甜菊素作为辅料起到调味剂的作用,同时该处方量的蔗糖和甜菊素能刚好保证本发明颗粒溶化性维持在极好水平,经过大量试验证实,改变蔗糖和甜菊素的用量将对溶化性产生不利的影响;本发明采用95%乙醇和纯化水作为黏合剂,该比例的黏合剂同样对制粒的效果和颗粒的溶化性起到了决定性的作用。
本发明工艺中具体参数的设置对制粒的效果和颗粒的溶化性起到了决定性的作用。
以下试验用于说明本发明:
1、蔗糖及甜菊素用量的不同效果比较:
表1蔗糖及甜菊素用量比较试验结果
处方 | 1 | 2 | 3 | 4 | 5 |
蔗 糖(kg) | 110 | 110.4 | 110.4 | 110 | 112 |
甜菊素(kg) | 0.5 | 0.58 | 0.65 | 0.58 | 0.70 |
溶化时间(min) | 2 | 1 | 4 | 5 | 5 |
溶化状态 | 轻微浑浊 | 全部溶化 | 轻微浑浊 | 轻微浑浊 | 轻微浑浊 |
由表1的结果可以看出,在其他条件不变的情况下,即使极小的变化都会产生不同的效果,本发明处方量比例的蔗糖及甜菊素制备的复方氨基酸颗粒(9AA)的溶化性效果最好。
2、黏合剂用量的不同效果比较:
表2黏合剂用量比较试验结果
处方 | 1 | 2 | 3 | 4 | 5 |
95%乙醇(kg) | 2.50 | 3.00 | 3.16 | 3.30 | 3.50 |
纯化水(kg) | 7.50 | 7.00 | 6.84 | 6.70 | 6.50 |
颗粒状态 | 过硬,细粉多 | 过硬,细粉多 | 均匀,硬度适中 | 颗粒成型较差 | 颗粒成型差 |
溶化时间(min) | 3 | 2.5 | 1 | 3 | 3 |
溶化状态 | 轻微浑浊 | 轻微浑浊 | 全部溶化 | 轻微浑浊 | 轻微浑浊 |
由表2的结果可以看出,在其他条件不变的情况下,即使极小的变化都会产生不同的效果,本发明处方量比例的黏合剂制备的复方氨基酸颗粒(9AA)的颗粒性、溶化性效果最好。
本发明处方在制备颗粒的过程中,有十几个工序的具体参数控制,这些参数对维持本本发明颗粒质量的稳定性及溶化性也起到了至关重要的作用,在不同参数组合的过程中,本发明发明人通过大量的筛选终于确定了工艺各步骤中的具体参数,以下以步骤6中烘干温度及时间为例来说明参数变化对本发明技术效果的影响。
1、烘干温度不同效果比较:
表3烘干温度比较试验结果
温度(℃) | 48~52 | 53~57 | 58~62 |
时间(h) | 2~3 | 2~3 | 2~3 |
溶化时间(min) | / | 1 | 6 |
溶化状态 | 颗粒不成型 | 全部溶化 | 轻微浑浊 |
2、烘干温度不同效果比较:
表4 烘干时间比较试验结果
温度(℃) | 53~57 | 53~57 | 53~57 |
时间(h) | 1~1.5 | 2~3 | 3.5~5 |
溶化时间(min) | / | 1 | 5 |
溶化状态 | 颗粒不成型 | 全部溶化 | 轻微浑浊 |
由表3及表4的结果可以看出,烘干条件的些许变化都可以造成本发明技术效果的明显变化,本发明其他工艺参数的变化也会造成相同的结果。
由以上可以看出,本发明所述的复方氨基酸颗粒(9AA)及其制备方法是由特定的特殊的辅料配比及参数控制来意外取得了提溶化性等质量指标,并且在和上市品的质量对比中,质量各项指标优于上市品。
具体实施方式:
实施例1 复方氨基酸颗粒(9AA)的制备
处方:
异亮氨酸:3.5 kg
亮氨酸:5.5 kg
盐酸赖氨酸:4.00 kg
甲硫氨酸:5.5 kg
苯丙氨酸:5.5 kg
苏氨酸:2.5 kg
色氨酸:1.25 kg
缬氨酸:4.06 kg
盐酸组氨酸:2.75 kg
蔗糖:110.40 kg
甜菊素:0.58 kg
95%乙醇:3.16 kg
纯化水:6.84 kg
制成:10000袋
工艺:
1、分别将蔗糖和盐酸组氨酸进行粉碎,过60目筛网;按处方量依次称量:蔗糖、异亮氨酸、亮氨酸、盐酸赖氨酸、甲硫氨酸、苯丙氨酸、苏氨酸、缬氨酸、色氨酸、盐酸组氨酸,待用;
2、黏合剂的配制:称取处方量95%乙醇中加入处方量的纯化水搅拌均匀制成溶液,待用;
3、将步骤1称量好的原辅料按照先后顺序置于湿法制粒机中,关闭锅盖,设置参数,桨叶转速设为140r /min,切刀转速1800r/min,混合480秒秒;
4、往步骤3湿法制粒机中加入步骤2制备的黏合剂进行湿混,湿混桨叶转速设为140r/min,切刀转速1800r/min,混合180秒,出料;
5、制粒:将步骤4制备的物料用16目湿法造粒机制湿颗粒;
6、将步骤5制备的的湿颗粒均匀铺盘(厚度约8mm),送烘箱中烘干,温度设定为53℃,干燥2小时后将干燥后的颗粒用14目和40目振荡筛进行整理筛分,使成大小均一的颗粒;
7、将步骤6制备的颗粒置于料斗混合机中,加入处方量的甜菊素,设置转速5 r/min,混合5min出料,测定含量,按规格包装即得。
实施例2复方氨基酸颗粒(9AA)的制备
处方:
异亮氨酸:3.5 kg
亮氨酸:5.5 kg
盐酸赖氨酸:4.00 kg
甲硫氨酸:5.5 kg
苯丙氨酸:5.5 kg
苏氨酸:2.5 kg
色氨酸:1.25 kg
缬氨酸:4.06 kg
盐酸组氨酸:2.75 kg
蔗糖:110.40 kg
甜菊素:0.58 kg
95%乙醇:3.16 kg
纯化水:6.84 kg
制成:10000袋
工艺:
1、分别将蔗糖和盐酸组氨酸进行粉碎,过60目筛网;按处方量依次称量:蔗糖、异亮氨酸、亮氨酸、盐酸赖氨酸、甲硫氨酸、苯丙氨酸、苏氨酸、缬氨酸、色氨酸、盐酸组氨酸,待用;
2、黏合剂的配制:称取处方量95%乙醇中加入处方量的纯化水搅拌均匀制成溶液,待用;
3、将步骤1称量好的原辅料按照先后顺序置于湿法制粒机中,关闭锅盖,设置参数,桨叶转速设为160r /min,切刀转速2000r/min,混合500秒;
4、往步骤3湿法制粒机中加入步骤2制备的黏合剂进行湿混,湿混桨叶转速设为160r /min,切刀转速2000r/min,混合200秒,出料;
5、制粒:将步骤4制备的物料用16目湿法造粒机制湿颗粒;
6、将步骤5制备的的湿颗粒均匀铺盘(厚度约12mm),送烘箱中烘干,温度设定为57℃,干燥3小时后将干燥后的颗粒用14目和40目振荡筛进行整理筛分,使成大小均一的颗粒;
7、将步骤6制备的颗粒置于料斗混合机中,加入处方量的甜菊素,设置转速5 r/min,混合5min出料,测定含量,按规格包装即得。
实施例3复方氨基酸颗粒(9AA)的制备
处方:
异亮氨酸:3.5 kg
亮氨酸:5.5 kg
盐酸赖氨酸:4.00 kg
甲硫氨酸:5.5 kg
苯丙氨酸:5.5 kg
苏氨酸:2.5 kg
色氨酸:1.25 kg
缬氨酸:4.06 kg
盐酸组氨酸:2.75 kg
蔗糖:110.40 kg
甜菊素:0.58 kg
95%乙醇:3.16 kg
纯化水:6.84 kg
制成:10000袋
工艺:
1、分别将蔗糖和盐酸组氨酸进行粉碎,过60目筛网;按处方量依次称量:蔗糖、异亮氨酸、亮氨酸、盐酸赖氨酸、甲硫氨酸、苯丙氨酸、苏氨酸、缬氨酸、色氨酸、盐酸组氨酸,待用;
2、黏合剂的配制:称取处方量95%乙醇中加入处方量的纯化水搅拌均匀制成溶液,待用;
3、将步骤1称量好的原辅料按照先后顺序置于湿法制粒机中,关闭锅盖,设置参数,桨叶转速设为150r /min,切刀转速1900r/min,混合490秒;
4、往步骤3湿法制粒机中加入步骤2制备的黏合剂进行湿混,湿混桨叶转速设为150r /min,切刀转速1900r/min,混合190秒,出料;
5、制粒:将步骤4制备的物料用16目湿法造粒机制湿颗粒;
6、将步骤5制备的的湿颗粒均匀铺盘(厚度约10mm),送烘箱中烘干,温度设定为55℃,干燥2.5小时后将干燥后的颗粒用14目和40目振荡筛进行整理筛分,使成大小均一的颗粒;
7、将步骤6制备的颗粒置于料斗混合机中,加入处方量的甜菊素,设置转速5 r/min,混合5min出料,测定含量,按规格包装即得。
本发明提供以下试验及对比结果:
样品1:本发明实施例1制备复方氨基酸颗粒(9AA)
样品2:市售的复方氨基酸颗粒(9AA)
将样品1~2进行加速稳定性考察(40℃±2℃,RH 75%±5%),结果见表5~6。
表5复方氨基酸颗粒(9AA)加速试验结果
表6复方氨基酸颗粒(9AA)加速试验氨基酸含量结果
由表5~6的结果可以看出,本发明制备的复方氨基酸颗粒(9AA)稳定性好,溶化性好跟现有技术相比具有明显的优势。本发明其他实施例制备的复方氨基酸颗粒(9AA)也进行了相同的试验,得到了相似的结果。
Claims (2)
1.一种复方氨基酸颗粒(9AA),其特征在于,所述的复方氨基酸颗粒(9AA)的处方为每10000袋由:3.5 kg的异亮氨酸、5.5 kg的亮氨酸、4.00 kg的盐酸赖氨酸、5.5 kg的甲硫氨酸、5.5 kg的苯丙氨酸、2.5 kg的苏氨酸、1.25 kg的色氨酸、4.06 kg的缬氨酸、2.75 kg的盐酸组氨酸、110.40 kg的蔗糖、0.58 kg的甜菊素、3.16 kg的95%乙醇、6.84 kg的纯化水按以下方法制备而成:
(1)分别将蔗糖和盐酸组氨酸进行粉碎,过60目筛网;按处方量依次称量:蔗糖、异亮氨酸、亮氨酸、盐酸赖氨酸、甲硫氨酸、苯丙氨酸、苏氨酸、缬氨酸、色氨酸、盐酸组氨酸,待用;
(2)黏合剂的配制:称取处方量95%乙醇中加入处方量的纯化水搅拌均匀制成溶液,待用;
(3)将步骤(1)称量好的原辅料按照先后顺序置于湿法制粒机中,关闭锅盖,设置参数,桨叶转速设为140r~160r /min,切刀转速1800r~2000r/min,混合480S~500S;
(4)往步骤(3)湿法制粒机中加入步骤(2)制备的黏合剂进行湿混,湿混桨叶转速设为140r~160r /min,切刀转速1800r~2000r/min,混合180 S~200S,出料;
(5)制粒:将步骤(4)制备的物料用16目湿法造粒机制湿颗粒;
(6)将步骤(5)制备的的湿颗粒均匀铺盘,厚度8~12mm,送烘箱中烘干,温度设定为55±2℃,干燥2~3小时后将干燥后的颗粒用14目和40目振荡筛进行整理筛分,使成大小均一的颗粒;
(7)将步骤(6)制备的颗粒置于料斗混合机中,加入处方量的甜菊素,设置转速5 r/min,混合5min出料,测定含量,按规格包装即得复方氨基酸颗粒(9AA)。
2.权利要求1所述的复方氨基酸颗粒(9AA)的制备方法包括以下步骤:
(1)分别将蔗糖和盐酸组氨酸进行粉碎,过60目筛网;按处方量依次称量:蔗糖、异亮氨酸、亮氨酸、盐酸赖氨酸、甲硫氨酸、苯丙氨酸、苏氨酸、缬氨酸、色氨酸、盐酸组氨酸,待用;
(2)黏合剂的配制:称取处方量95%乙醇中加入处方量的纯化水搅拌均匀制成溶液,待用;
(3)将步骤(1)称量好的原辅料按照先后顺序置于湿法制粒机中,关闭锅盖,设置参数,桨叶转速设为140r~160r /min,切刀转速1800r~2000r/min,混合480S~500S;
(4)往步骤(3)湿法制粒机中加入步骤(2)制备的黏合剂进行湿混,湿混桨叶转速设为140r~160r /min,切刀转速1800r~2000r/min,混合180 S~200S,出料;
(5)制粒:将步骤(4)制备的物料用16目湿法造粒机制湿颗粒;
(6)将步骤(5)制备的的湿颗粒均匀铺盘,厚度8~12mm,送烘箱中烘干,温度设定为55±2℃,干燥2~3小时后将干燥后的颗粒用14目和40目振荡筛进行整理筛分,使成大小均一的颗粒;
(7)将步骤(6)制备的颗粒置于料斗混合机中,加入处方量的甜菊素,设置转速5 r/min,混合5min出料,测定含量,按规格包装即得复方氨基酸颗粒(9AA)。
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