CN116889598A - 降脂平口服液制备方法及其产品、用途 - Google Patents
降脂平口服液制备方法及其产品、用途 Download PDFInfo
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Abstract
本发明涉及一种降脂平口服液制备方法及其产品、用途，属于中药领域。其包括：1)中药提取液的制备；2)向中药提取液中加入1％的木质素磺酸钠和海藻酸钠的水溶液；3)再向中药提取液中加入1％的壳聚糖季铵盐溶液；4)继续向中药提取液中加入纤维素酶和果胶酶，加入后搅拌均匀静置3‑5h；5)分离中药提取液和沉淀，向获得的中药提取液中加入蔗糖和山梨酸钾，灌装即得。本发明还提供了所述制备方法获得的产品及其用途。
Description
技术领域
本发明涉及一种降脂平口服液制备方法及其产品、用途，属于中药领域。
背景技术
降脂平口服液是吉林通化万通药业股份有限公司自主研发的一款中药口服制剂。其主要由何首乌、决明子、山楂、枸杞子、荷叶和人参制成；临床上用于治疗气血亏虚、肝肾不足引起的高脂血症，临床常伴有头晕耳鸣，心悸乏力，少寐多梦，腰膝酸软等症。其主要制备方法为：将人参用60-90％乙醇加热回流提取2-3次，每次6-10倍量提取1-3小时，合并醇提取液，滤过，滤液回收乙醇并浓缩至相对密度为1.20～1.25的清膏，备用；药渣与何首乌、决明子、山楂、枸杞子、荷叶，加水煎煮2-3次，每次8-10倍量，煎煮1-3小时，合并煎液，滤过，滤液浓缩至60℃时相对密度为1.13～1.15，加乙醇至含醇量为60-70％，静止24-48小时，取上清液滤过，滤液浓缩，备用，乙醇蒸馏回收；将上述药液合并，然后按常规工艺制成药剂学上可接受的口服液剂型。相关制备方法及质量标准参见部颁标准WS-10006(ZD-0006)-2005-2013Z。
中药口服液作为一种新型中药制剂，由于其具有服用剂量小、吸收快、适宜老年人和儿童服用等优点，目前已经广泛应用于临床中，但是由于口服液由复方组成，所含成分复杂多样，导致中药口服液存在混浊、澄清度低并且长时间放置容易产生沉淀等缺点。为了克服上述问题，本领域一般采用醇沉法、高速离心法、膜分离法、大孔树脂吸附法以及絮凝法等。
具体对于降脂平口服液来说，在目前标准中是采用醇沉法来保证口服液的澄清度及稳定性，但是醇沉法存在醇耗用量大并且成本高的缺点，更为重要的是醇沉法会导致中药复方中有效成分的大量损失，从而降低降脂平口服液的疗效。
中国专利CN100509016A公开了一种治疗高脂血症的药物及其制备方法，其采用乙醇沉淀使提取液澄清，并在1000ml口服液中加入400g蔗糖用于口味调节，但是如上所述，醇沉法澄清工艺会导致活性物质过量流失并且工艺较为复杂，另外，根据中国药典2020版通则相关规定，对于合剂，除另有规定外，含蔗糖量一般不高于20％(g/ml)。因此提供一种新的降脂平口服液的制备方法势在必行。
发明内容
本发明的第一方面是提供一种降脂平口服液的制备方法，其包括：
1)中药提取液的制备，所述中药包括30-85重量份人参、25-60重量份何首乌、25-60重量份决明子、400-750重量份山楂、110-250重量份枸杞子和60-150重量份荷叶；
2)向中药提取液中加入1％的木质素磺酸钠和海藻酸钠的水溶液，搅拌均匀后静置0.5-1h；其中，中药提取液与1％的木质素磺酸钠和海藻酸钠的水溶液的体积比为1000:0.5-6；
3)再向中药提取液中加入1％的壳聚糖季铵盐溶液，搅拌均匀后静置0.5-1h，其中，中药提取液与1％的壳聚糖季铵盐水溶液的体积比为1000:5-15；
4)继续向中药提取液中加入纤维素酶和果胶酶，其中每1000ml中药提取液中加入1-3g的纤维素酶和0.5-2g的果胶酶，加入后搅拌均匀静置3-5h；
5)分离中药提取液和沉淀，向获得的中药提取液中加入蔗糖和山梨酸钾，灌装即得。
在一种实施方案中，步骤1)的具体制备方法为：将30-85重量份人参用60-90％乙醇加热回流提取2-3次，每次6-10倍量提取1-3小时，合并醇提取液，滤过，滤液回收乙醇并浓缩至相对密度为1.20～1.25的清膏，备用；药渣与25-60重量份何首乌、25-60重量份决明子、400-750重量份山楂、110-250重量份枸杞子、60-150重量份荷叶，加水煎煮2-3次，每次8-10倍量，煎煮1-3小时，合并煎液，滤过，滤液浓缩至60℃时相对密度为1.13～1.15。
在另一种实施方案中，在步骤2)、3)和4)中，静置时需要对中药提取液进行保温，温度为40-60℃。优选的，在步骤2)、3)和4)中，静置温度为50℃.
在又一种实施方案中，在步骤2)中，中药提取液与1％的木质素磺酸钠和海藻酸钠的水溶液的体积比为1000:1-3，在1％的木质素磺酸钠和海藻酸钠的水溶液中，木质素磺酸钠和海藻酸钠的重量比为1:3。
在又一种实施方案中，在步骤3)中，中药提取液与1％的壳聚糖季铵盐水溶液的体积比为1000:7-10。
在又一种实施方案中，在步骤5)中，中药提取液和沉淀的分离方式为过滤或离心。
本发明的第二方面是提供所述制备方法制备的降脂平口服液。
本发明的第三方面是提供所述降脂平口服液在制备治疗高脂血症药物中的应用。
本发明通过2步澄清工艺替代原有醇沉澄清工艺，在提高澄清度的基础上也较高的保留口服液中的活性成分，尤其是纤维素酶和果胶酶的使用，在促进提高澄清度的同时，极大的改善了降脂平口服液原有工艺中容易出现瓶底沉淀的问题，并且在降低蔗糖使用量的同时也使口服液的口感没有明显降低，使降脂平口服液的蔗糖含量也符合最新的中国药典规定。
下面通过实施例，对本发明的技术方案做进一步的详细描述。
具体实施方式
下面对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
实施例1降脂平口服液的制备
1)将56g人参用70％乙醇加热回流提取2次，每次8倍量提取1.5小时，合并醇提取液，滤过，滤液回收乙醇并浓缩至60℃时相对密度为1.20～1.25的清膏，备用；药渣与44g何首乌、44g决明子、667g山楂、167g枸杞子、132g荷叶，加水煎煮3次，每次10倍量，煎煮2小时，合并煎液，滤过，滤液浓缩至60℃时相对密度为1.13～1.15。
2)向每1000ml中药提取液中加入2ml的1％(w/v)的木质素磺酸钠和海藻酸钠的水溶液，搅拌均匀后，50℃静置1h；在1％的木质素磺酸钠和海藻酸钠的水溶液中，木质素磺酸钠和海藻酸钠的重量比为1:3。
3)再向每1000ml中药提取液中加入8ml的1％(w/v)的壳聚糖季铵盐溶液，50℃静置1h；
4)继续向中药提取液中加入纤维素酶和果胶酶，其中每1000ml中药提取液中加入2g的纤维素酶和1g的果胶酶，加入后搅拌均匀静置4h；
5)过滤分离中药提取液和沉淀，将获得的中药提取液用去离子水调节至总体积1000ml，然后加入200g蔗糖和2.4g山梨酸钾，灌装即得。
实施例2降脂平口服液的澄清工艺考察
以透光率和人参皂苷Rg1含量(HPLC法)为考察标准，分别考察步骤2、3和4中所使用澄清剂的合适种类及用量。
1)步骤2中澄清剂考察
分别使用不同的澄清剂组成，考察所获得降脂平口服液的透光率和人参皂苷含量，各组使用的原始中药提取液均来自同一批提取物，澄清剂用量及其他制备方法同实施例1，澄清剂具体分组如下：
结果如下：
| 透光率(％) | 人参皂苷Rg1含量 | |
| 组1 | 72.1 | 0.11mg/ml |
| 组2 | 83.6 | 0.06mg/ml |
| 组3 | 88.5 | 0.15mg/ml |
| 组4 | 93.2 | 0.37mg/ml |
| 组5 | 85.3 | 0.26mg/ml |
以上结果表明，在步骤2中，木质磺酸钠与海藻酸钠混合澄清剂的效果明显优于单一澄清剂的效果，并且木质磺酸钠与海藻酸钠的重量配比在1:3时效果最佳。
另外，在获得澄清剂最佳重量配比后，对澄清剂添加量进行了考察，具体结果如下：
| 添加量 | 透光率(％) | 人参皂苷Rg1含量 | |
| 组1 | 1ml | 82.7 | 0.34mg/ml |
| 组2 | 2ml | 93.2 | 0.37mg/ml |
| 组3 | 4ml | 94.1 | 0.21mg/ml |
2)步骤3中澄清剂考察
分别使用不同的澄清剂组成，考察所获得降脂平口服液的透光率和人参皂苷含量，各组使用的原始中药提取液均来自同一批提取物，澄清剂用量及其他步骤制备方法同实施例1，澄清剂具体分组如下：
| 澄清剂组成及重量配比(w/v) | |
| 组1 | 1％壳聚糖季铵盐水溶液 |
| 组2 | 1％羧甲基壳聚糖水溶液 |
| 组3 | 1％壳聚糖水溶液 |
结果如下：
| 透光率(％) | 人参皂苷Rg1含量 | |
| 组1 | 93.2 | 0.37mg/ml |
| 组2 | 90.1 | 0.17mg/ml |
| 组3 | 81.6 | 0.23mg/ml |
以上结果表明，在步骤3中，壳聚糖季铵盐的澄清效果最佳，并且活性成分保留率较高。而羧甲基壳聚糖澄清效果较好，但活性成分保留率太差，壳聚糖澄清效果不佳，活性成分保留率较羧甲基壳聚糖好。
实施例3降脂平口服液的果胶酶和纤维素酶作用考察
1)纤维素酶和果胶酶对口服液澄清度的影响
分别使用不同的澄清剂组成，考察所获得降脂平口服液的透光率和人参皂苷含量，各组使用的原始中药提取液均来自同一批提取物，澄清剂用量及其他制备方法同实施例1，澄清剂具体分组如下：
结果如下：
| 透光率(％) | 人参皂苷Rg1含量 | |
| 组1 | 83.9 | 0.27mg/ml |
| 组2 | 87.3 | 0.29mg/ml |
| 组3 | 84.4 | 0.26mg/ml |
| 组4 | 90.1 | 0.31mg/ml |
| 组5 | 93.2 | 0.37mg/ml |
以上结果表明，纤维素酶和果胶酶对口服液澄清度和活性成分保留率均有一定的促进作用。
2)纤维素酶和果胶酶对口服液稳定性影响
将上述组1、2、3和5制备的口服液置于45℃，相对湿度75％的环境中；在0天、15天和30天取样本进行主药含量检测、透光率检测和瓶底沉淀量检测。
沉淀量检测方法为：对口服液样本在1000rpm下离心10min，然后取出上清液，对沉淀进行烘干称重。
从上述结果可以看出，添加纤维素酶和果胶酶后可以大幅提高降脂平口服液的稳定性，在加速稳定性试验中，未添加纤维素酶和果胶酶的组1中，澄清度明显降低，瓶底沉淀量较多，并且活性成分含量随时间下降较快，这说明经过木质磺酸钠、海藻酸钠和壳聚糖季铵盐处理后的降脂平口服液虽然获得了较高的澄清度和活性成分，但是稳定性不佳，而添加纤维素酶和果胶酶后较好的解决了这一问题并进一步提高了的澄清度。
对比例1
1)将56g人参用70％乙醇加热回流提取2次，每次8倍量提取1.5小时，合并醇提取液，滤过，滤液回收乙醇并浓缩至60℃时相对密度为1.20～1.25的清膏，备用；药渣与44g何首乌、44g决明子、667g山楂、167g枸杞子、132g荷叶，加水煎煮3次，每次10倍量，煎煮2小时，合并煎液，滤过，滤液浓缩至60℃时相对密度为1.13～1.15。
2)向每1000ml中药提取液中加入2ml的1％(w/v)海藻酸丙二醇酯、3海藻酸钠和膨润土的水溶液(重量配比为：37％海藻酸丙二醇酯、35％海藻酸钠、28％膨润土)，搅拌均匀后，50℃静置数分钟；
3)再向每1000ml中药提取液中加入8ml的1％(w/v)的壳聚糖和卡拉胶的醋酸水溶液(重量配比为：：65％壳聚糖、35％卡拉胶)，50℃静置6h；
4)过滤分离中药提取液和沉淀，将获得的中药提取液用去离子水调节至总体积1000ml，然后加入200g蔗糖和2.4g山梨酸钾，灌装即得。
对比例2
参见中国专利CN100509016A说明书第7页倒数最后一段和第8页第一段，具体为：将56g人参用70％乙醇加热回流提取2次，每次8倍量提取1.5小时，合并醇提取液，滤过，滤液回收乙醇并浓缩至60℃时相对密度为1.20～1.25的清膏，备用；药渣与44g何首乌、44g决明子、667g山楂、167g枸杞子、132g荷叶，加水煎煮3次，每次10倍量，煎煮2小时，合并煎液，滤过，滤液浓缩至60℃时相对密度为1.13～1.15，加乙醇至含醇量为70％，静置24小时，取上清液滤过，滤液浓缩备用，乙醇蒸馏回收，取蔗糖400g制成单糖浆，与上述药液合并，加入山梨酸钾1000ml含2.4g，调整总量至1000ml，搅拌，滤过，灌装即得。
对比例1和对比例2所获得的口服液透光率和人参皂苷Rg1含量结果如下：
Claims (9)
1.一种降脂平口服液的制备方法，其包括：
1)中药提取液的制备，所述中药包括30-85重量份人参、25-60重量份何首乌、25-60重量份决明子、400-750重量份山楂、110-250重量份枸杞子和60-150重量份荷叶；
2)向中药提取液中加入1％的木质素磺酸钠和海藻酸钠的水溶液，搅拌均匀后静置0.5-1h；其中，中药提取液与1％的木质素磺酸钠和海藻酸钠的水溶液的体积比为1000:0.5-6；
3)再向中药提取液中加入1％的壳聚糖季铵盐溶液，搅拌均匀后静置0.5-1h，其中，中药提取液与1％的壳聚糖季铵盐水溶液的体积比为1000:5-15；
4)继续向中药提取液中加入纤维素酶和果胶酶，其中每1000ml中药提取液中加入1-3g的纤维素酶和0.5-2g的果胶酶，加入后搅拌均匀静置3-5h；
5)分离中药提取液和沉淀，向获得的中药提取液中加入蔗糖和山梨酸钾，灌装即得。
2.如权利要求1所述的制备方法，其特征在于，步骤1)的具体制备方法为：将30-85重量份人参用60-90％乙醇加热回流提取2-3次，每次6-10倍量提取1-3小时，合并醇提取液，滤过，滤液回收乙醇并浓缩至相对密度为1.20～1.25的清膏，备用；药渣与25-60重量份何首乌、25-60重量份决明子、400-750重量份山楂、110-250重量份枸杞子、60-150重量份荷叶，加水煎煮2-3次，每次8-10倍量，煎煮1-3小时，合并煎液，滤过，滤液浓缩至60℃时相对密度为1.13～1.15。
3.如权利要求1所述的制备方法，其特征在于，在步骤2)、3)和4)中，静置时需要对中药提取液进行保温，温度为40-60℃。
4.如权利要求1所述的制备方法，其特征在于，在步骤2)中，中药提取液与1％的木质素磺酸钠和海藻酸钠的水溶液的体积比为1000:1-3，在1％的木质素磺酸钠和海藻酸钠的水溶液中，木质素磺酸钠和海藻酸钠的重量比为1:3。
5.如权利要求1所述的制备方法，其特征在于，在步骤3)中，中药提取液与1％的壳聚糖季铵盐水溶液的体积比为1000:7-10。
6.如权利要求1所述的制备方法，其特征在于，在步骤5)中，中药提取液和沉淀的分离方式为过滤或离心。
7.如权利要求3所述的制备方法，其特征在于，在步骤2)、3)和4)中，静置时需要对中药提取液进行保温，温度为50℃。
8.如权利要求1-7任一项所述的降脂平口服液制备方法制备的口服液。
9.如权利要求8所述的降脂平口服液在制备治疗高脂血症药物中的应用。
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