CN107375393B - 一种金银花有机酸类成分微丸包衣颗粒及其制备方法 - Google Patents
一种金银花有机酸类成分微丸包衣颗粒及其制备方法 Download PDFInfo
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61K2236/50—Methods involving additional extraction steps
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Abstract
本发明公开了一种金银花有机酸类成分微丸包衣颗粒及其制备方法，该包衣颗粒由载药微丸及包衣层组成，所述的载药微丸由金银花有机酸提取物、蔗糖粉、糊精、亚硫酸氢钠、乙二胺四乙酸二钠、枸橼酸、3％羟丙基甲基纤维素及直径为0.3‑1mm的蔗糖空白丸芯制备组成；所述的包衣层由尤特奇EPO、十二烷基硫酸钠、硬脂酸、滑石粉、二氧化钛制备组成。本发明通过合理的原料配比以及工艺的改进优化，显著提供了所得颗粒中绿原酸及总有机酸的稳定性，从而保证了药剂的质量及临床疗效。
Description
技术领域
本发明涉及中药制剂领域，具体涉及一种金银花有机酸类成分微丸包衣颗粒及其制备方法。
背景技术
金银花为忍冬科植物忍冬(Lonicera japonica Thunb)的干燥花蕾或带初开的花，具有清热解毒、疏散风热、抗菌消炎的功效，药理研究表明，其主要抗菌成分为有机酸类化合物，包括咖啡酸、绿原酸、异绿原酸等，这类化合物分子骨架中具有酯键、不饱和双键或多元酚结构，该类成分酯键水解及多元酚氧化是导致其不稳定的主要因素。由于该类成分稳定性差，外界条件(如温度、湿度、光线等)对其稳定性影响较大，因此金银花制剂中往往规定其含量限度范围进行质量控制，无法建立严格的质量标准。绿原酸在金银花有机酸类化合物中含量较高，药理活性显著，常作为含金银花的中药成方制剂指标性成分进行质量控制，临床上应用的金银花颗粒、金银花胶囊及复方对乙酰氨基酚金银花注射液均将绿原酸作为指标性成分之一。金银花颗粒标准规定每袋颗粒(10g)按绿原酸含量计算不低于12mg；复方对乙酰氨基酚金银花注射液规定绿原酸每mL含绿原酸0.68-0.82mg，可见此类制剂质量标准的制定考虑到了有机酸类成分的不稳定性，难以制定严格的含量控制指标，然而，此类制剂中有机酸类成分因氧化、水解等造成的含量变化必将影响制剂质量及临床疗效，因此提高金银花有机酸类成分稳定性对提高金银花制剂的质量稳定性、促使建立严格的含量控制指标具有重要意义。
发明内容
为解决上述问题，本发明提供了一种质量稳定的金银花有机酸类成分微丸包衣颗粒及其制备方法。
为实现上述目的，本发明采取的技术方案为：
一种金银花有机酸类成分微丸包衣颗粒，由载药微丸及包衣层组成，所述的载药微丸由金银花有机酸提取物、蔗糖粉、糊精、亚硫酸氢钠、乙二胺四乙酸二钠、枸橼酸、3％羟丙基甲基纤维素及直径为0.3-1mm的蔗糖空白丸芯制备组成；所述的包衣层由尤特奇EPO、十二烷基硫酸钠、硬脂酸、滑石粉、二氧化钛制备组成。
其中，所述金银花有机酸提取物通过以下步骤制备所得：
取金银花粉碎，加8倍量水回流煎煮3次，每次2h，滤过，合并3次煎煮液，浓缩至相对密度1.1的浸膏，加入95％乙醇至含醇量为70％，静置24h，滤过，取续滤液减压浓缩得粗提液，粗提液调节pH至3.0，经大孔吸附树脂吸附，先后经7倍柱体积水及10倍柱体积75％乙醇洗脱，收集乙醇洗脱液，减压浓缩，真空干燥，粉碎，即得金银花有机酸提取物。
本发明还提供了上述一种金银花有机酸类成分微丸包衣颗粒的制备方法，包括如下步骤：
S1、制备载药微丸：
S11、称取
S12、将称取的金银花有机酸提取物、糖粉、糊精、亚硫酸氢钠、乙二胺四乙酸二钠及枸橼酸混合均匀后，置于包衣造粒机的饲料室中，将蔗糖空白丸芯置离心造粒机滚转锅内，以3％羟丙基甲基纤维素为黏合剂，开动机器，采用粉末层积法制备载药微丸，待载药微丸为24目～30目时，开启出料口，取出成品，40℃烘干，用标准筛筛分，收取24目～30目微丸，备用；
S2、制备金银花有机酸类成分微丸包衣颗粒
S21、称取
S22、将称取的十二烷基硫酸钠、癸二酸二丁酯、尤特奇EPO加入400ml水中，搅拌均匀，加入滑石粉和二氧化钛，高剪切乳化剂乳化均匀得包衣液，包衣过程持续搅拌；
S23、称取500g所得的载药微丸，40℃预热微丸3min，置于流化床包衣机内，采用底喷式，喷液速度为4.0～5.0mL/min，入风频率为30～40Hz，流化床包衣机内的温度始终维持30～40℃，包衣结束，包衣微丸继续在流化床内干燥一段时间取出，即得。
本发明具有以下有益效果：
通过合理的原料配比以及工艺的改进优化，显著提供了所得颗粒中绿原酸及总有机酸的稳定性，从而保证了药剂的质量及临床疗效。
具体实施方式
为了使本发明的目的及优点更加清楚明白，以下结合实施例对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅仅用以解释本发明，并不用于限定本发明。
实施例1
制备金银花有机酸类成分微丸包衣颗粒
S1、金银花有机酸提取物的制备
取金银花粉碎，加8倍量水回流煎煮3次，每次2h，滤过，合并3次煎煮液，浓缩至相对密度1.1的浸膏，加入95％乙醇至含醇量为70％，静置24h，滤过，取续滤液减压浓缩得粗提液，粗提液调节pH至3.0，经大孔吸附树脂吸附，先后经7倍柱体积水及10倍柱体积75％乙醇洗脱，收集乙醇洗脱液，减压浓缩，真空干燥，粉碎即得有机酸类提取物。
S2、金银花有机酸提取物载药微丸的制备
S21、按载药微丸处方称取：
S22、将称取的金银花有机酸提取物、糖粉、糊精、亚硫酸氢钠、乙二胺四乙酸二钠及枸橼酸混合均匀，置于包衣造粒机的饲料室中，蔗糖空白丸芯置离心造粒机滚转锅内，以3％羟丙基甲基纤维素为黏合剂，开动机器，采用粉末层积法制备金银花有机酸载药微丸，待含药微丸长大约24目～30目开启出料口，取出成品，40℃烘干，用标准筛筛分，收取24目～30目微丸，备用。
S3、金银花有机酸提取物包衣微丸的制备
S31、按包衣液处方称取：
S32、将称取的十二烷基硫酸钠、癸二酸二丁酯、尤特奇EPO加入400ml水中，搅拌均匀，加入滑石粉和二氧化钛，高剪切乳化剂乳化均匀得包衣液，包衣过程持续搅拌。称取500g载药微丸，40℃预热微丸3min，置于流化床包衣机内，采用底喷式，喷液速度为4.0～5.0mL/min，入风频率为30～40Hz，流化床包衣机内的温度始终维持30～40℃，包衣结束，包衣微丸继续在流化床内干燥一段时间取出，即得金银花有机酸包衣微丸。
金银花有机酸包衣微丸稳定性试验
1.总有机酸含量测定方法
(1)对照品溶液的配制
精密称取绿原酸、咖啡酸、3，4-二咖啡酰奎宁酸、3，5-二咖啡酰奎宁酸和4，5-二咖啡酰奎宁酸对照品适量，加50％甲醇制成浓度分别为40μg/mL、40μg/mL、15μg/mL、20μg/mL、20μg/mL的混合液，10℃以下保存备用。
(2)供试品溶液的制备
取金银花有机酸包衣微丸适量，研细，精密称定置具塞锥形瓶中，精密加入50％甲醇50ml，称定重量，超声处理(功率250W，频率35kHz)30分钟，放冷，再称定重量，用50％甲醇补足减失的重量，摇匀，滤过，精密量取续滤液5ml，置25ml棕色量瓶中，加50％甲醇至刻度，摇匀，即得。
(3)测定法
以绿原酸、咖啡酸、3，4-二咖啡酰奎宁酸、3，5-二咖啡酰奎宁酸和4，5-二咖啡酰奎宁酸含量的总和作为总有机酸含量。
分别精密吸取对照品溶液与供试品溶液各10μl，注入液相色谱仪，测定，按外标法分别计算绿原酸及总有机酸含量。
2.稳定性试验
以实施例1中金银花有机酸包衣微丸颗粒为例验证本发明专利效果，以市售金银花颗粒作为对照进行稳定性试验，主要考察颗粒外观、绿原酸、总有机酸含量变化情况。
高温试验条件如下：供试品开口置适宜的密封洁净容器中，40℃(RH75％)条件下放置3个月，于第0月、1月、三月取样，观察颗粒外观，测定绿原酸及总有机酸含量变化情况，结果表明，市售颗粒1月、2月、3月均有不同程度的结块现象，实施例1中金银花颗粒未见外观明显改变。绿原酸及总有机酸含量变化见表1。
表1.实施例1金银花颗粒与市售金银花颗粒不同时间绿原酸与总有机酸含量
由表中数据可知实施例1中绿原酸及总有机酸稳定性明显增强
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以作出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。
Claims (1)
1.一种金银花有机酸类成分微丸包衣颗粒，其特征在于，微丸包衣颗粒由载药微丸及包衣层制成，所述的载药微丸由金银花有机酸提取物、蔗糖粉、糊精、亚硫酸氢钠、乙二胺四乙酸二钠、枸橼酸、3%羟丙基甲基纤维素及直径为0.3-0.5mm的蔗糖空白丸芯制成；所述的包衣层由尤特奇EPO、十二烷基硫酸钠、硬脂酸、滑石粉、二氧化钛制成；
所述金银花有机酸提取物，通过以下步骤制备得到：
取金银花粉碎，加8倍量水回流煎煮3次，每次2h，滤过，合并3次煎煮液，浓缩至相对密度为1.1的浸膏，加入95%乙醇至浸膏含醇量为70%，静置24h，滤过，取续滤液减压浓缩得粗提液，粗提液调节pH至3.0，经大孔吸附树脂吸附，先后经7倍柱体积水及10倍柱体积75%乙醇洗脱，收集乙醇洗脱液，减压浓缩，真空干燥，粉碎，即得金银花有机酸提取物；
所述金银花有机酸类成分微丸包衣颗粒的制备方法，包括如下步骤：
S1、制备载药微丸：
S11、称取
金银花有机酸提取物 2.5g
蔗糖粉 50g
糊精 250g
亚硫酸氢钠 0.6g
乙二胺四乙酸二钠 0.6g
枸橼酸 1.5g
3%羟丙基甲基纤维素 适量
直径为0.3-0.5mm的蔗糖空白丸芯 200g
S12、将称取的金银花有机酸提取物、蔗糖粉、糊精、亚硫酸氢钠、乙二胺四乙酸二钠及枸橼酸混合均匀后，置于包衣造粒机的饲料室中，将蔗糖空白丸芯置离心造粒机滚转锅内，以3%羟丙基甲基纤维素为黏合剂，开动机器，采用粉末层积法制备载药微丸，待载药微丸为24目～30目时，开启出料口，取出成品，40℃烘干，用标准筛筛分，收取24目～30目微丸，备用；
S2、制备金银花有机酸类成分微丸包衣颗粒
S21、称取
尤特奇EPO 50g
十二烷基硫酸钠 3.5g
硬脂酸 5.5g
滑石粉 200g
二氧化钛 20g
S22、将称取的十二烷基硫酸钠、硬脂酸、尤特奇EPO加入400ml水中，搅拌均匀，加入滑石粉和二氧化钛，高剪切乳化机乳化均匀得包衣液，包衣过程持续搅拌；
S23、称取500g 所得的载药微丸，40℃预热微丸3min，置于流化床包衣机内，采用底喷式，喷液速度为4.0～5.0mL/min，入风频率为30～40 Hz，流化床包衣机内的温度始终维持30～40 ℃，包衣结束，包衣微丸继续在流化床内干燥一段时间取出，即得。
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