CN106074542A - 一种阿齐沙坦酯钾盐软胶囊的制备方法 - Google Patents
一种阿齐沙坦酯钾盐软胶囊的制备方法 Download PDFInfo
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- CN106074542A CN106074542A CN201610759552.XA CN201610759552A CN106074542A CN 106074542 A CN106074542 A CN 106074542A CN 201610759552 A CN201610759552 A CN 201610759552A CN 106074542 A CN106074542 A CN 106074542A
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- potassium salt
- soft capsule
- acid
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- 239000009637 wintergreen oil Substances 0.000 description 1
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 1
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Abstract
本发明涉及一种阿齐沙坦酯钾盐软胶囊的制备方法。步骤：以明胶、硬酯酸、大豆蛋白、甘油和纯水为囊体原料，制作得到囊体；根据处方得到混合均匀的内容物；将内容物及囊体经过压丸、定型、洗丸、干燥、拣丸和分装步骤，制备得到软胶囊。本发明的治疗高血压的药物组合，配比合理，可以快速释放药物，对所述病症能产生很好的疗效。
Description
技术领域
本发明属于医药技术领域，具体涉及一种阿齐沙坦酯钾盐软胶囊的制备方法。
背景技术
阿齐沙坦酯钾盐(azilsartan medoxomil)是日本武田研发。阿齐沙坦的一种前药，在胃肠道吸收期间被水解为阿齐沙坦。2011年2月22日在FDA批准上市，商品名：Edarbi，规格为40mg、80mg。2012年4月阿齐沙坦在日本上市，商品名：Azilva,规格：20mg、40mg。阿齐沙坦酯是一种选择性AT1亚型血管紧张素II受体拮抗剂。阿齐沙坦选择性阻断血管紧张素Ⅱ与AT1 受体结合（阿齐沙坦对AT1受体的亲和力高出AT2受体的10000倍以上），从而阻断血管紧张素Ⅱ引起的血管收缩，醛固酮分泌等升血压效应。其作用不依赖于血管紧张素Ⅱ合成途径，故避免了ACEI对缓激肽水平的影响。与血管紧张素转化酶抑制剂（ACEI）类降压药物相比，单独或联合用药均具有平稳降压、不会引起干咳的优点，平稳持久降血压作用。还能通过部分激活过氧化物酶体增殖物激活受体-γ（PPAR-γ）而对糖尿病患者产生潜在的保护作用，相关临床试验结果表明其临床效果要优于现在临床广泛使用的奥美沙坦酯和缬沙坦。2012年3月5日，Edarbi被全球著名的药品与医疗研究/顾问公司-DecisionResources公司确认为降压药评价的黄金标准，到2020年，没有药物可能会替代Edarbi的这一黄金标准地位。虽然当前某些新兴的降压药具有一定的潜力，但其自身在有效性、安全性与耐受性、及/或给药方法上的缺陷可能会其无法取代Edarbi。 【知识产权情况】化合物专利（CN1946717） 2025年2月22日到期。
发明内容
本发明的目的是：提供一种稳定性好的阿齐沙坦酯钾盐软胶囊的制备方法，主要是通过加入稳定性组分来实现上述目的。
技术方案是：
一种阿齐沙坦酯钾盐软胶囊的制备方法，包括如下步骤：
第1步，制作囊体：按重量份计，以明胶15～25份、硬酯酸3～6份、大豆蛋白2～3份、甘油10～25份和纯水10～15份为囊体原料，将甘油和纯水注入溶胶罐内，加热搅拌，再加入明胶、硬酯酸和大豆蛋白，继续搅拌均匀后真空脱泡，制作得到囊体；
第2步：配制内容物：按重量份计，将大豆油30～90份、不饱和脂肪酸4～9份、阿齐沙坦酯钾盐20～50份及甘油5～20份进行混合，过胶体磨，得到混合均匀的内容物；
第3步：将第2步得到的内容物及第1步得到囊体经过压丸、定型、洗丸、干燥、拣丸和分装步骤，制备得到阿齐沙坦酯钾盐软胶囊。
所述的第1步中，搅拌加热的温度是60～70℃。
所述的第2步中，不饱和脂肪酸选自二十二碳六烯酸、二十碳五烯酸、鱼油、亚麻籽油、琉璃苣油、α-亚麻酸、γ-亚麻酸、共轭亚油酸或者锯叶棕提取物。
所述的第2步中，混合时的温度50～70℃，混合时间20～40min，过胶体磨的次数是1～3次。
本发明制备得到的阿齐沙坦酯钾盐软胶囊具有稳定性好，性状稳定的优点。
具体实施方式:
本发明的软胶囊的内容物，除了上述的成分之外，根据实际的应用需要，还可以包含其它的添加物组分，所述的添加物组分可以包含一种或多种适合食物的其他组分。这些包括抗氧化剂、乳化剂、防腐剂、甜味剂、香精、pH调节剂等。添加物组分在与组合物混合后的混合物所占的重量百分比范围可以为最大89wt%，例如10～89wt%，更优选是20～75wt%。
抗氧化剂的可以采用生育酚类如α-生育酚、α-生育酚棕榈酸酯、α-生育酚乙酸酯，叔丁基羟基甲苯，叔丁基羟基茴香醚，抗坏血酸、其盐和酯，例如抗坏血酸钠、抗坏血酸钙、抗坏血酰磷酸酯、抗坏血酸的脂肪酸酯如抗坏血酰硬脂酸酯和抗坏血酰棕榈酸酯以及乙氧基喹。
乳化剂的实例尤其是亲油性分散剂，例如是抗坏血酸的脂肪酸酯如抗坏血酰棕榈酸酯，聚甘油脂肪酸酯如聚甘油-3-聚蓖麻醇酸酯，脱水山梨醇脂肪酸酯，尤其是脱水山梨醇C10～C28脂肪酸酯。
作为pH调节剂，可被包括在本发明的制剂组合物中以提高或降低本发明的制剂组合物的pH。所述制剂组合物的pH可被降低或提高，用于感官觉察的作用，或者用于改善理化特性，例如增加溶解的化合物的溶解度。pH调节剂可以是指酸化剂或碱化剂。例如，乳酸、柠檬酸、苹果酸、氢氧化钾、氢氧化钙和氢氧化镁。
防腐剂，可任选地包括在本发明的制剂组合物中的防腐剂的非限定性实例包括：醋酸、柠檬酸、苯甲酸、山梨酸、二氧化硫、苯甲酸钾、山梨酸钾。
作为香精，优选使用1种或2种以上天然香精、合成香精等油脂香精和粉末香精，但并无特别限定。例如，冬青油、肉桂油、薄荷醇油、绿薄荷油、酸橙油、薰衣草油、草莓油、香兰酮。
作为甜味剂，优选常用甜味剂，例如从麦芽糖醇、蔗糖、葡萄糖、葡聚糖选出的至少1种。
实施例1
阿齐沙坦酯钾盐软胶囊的制备方法，步骤：
第1步，制作囊体：按重量份计，以明胶15份、硬酯酸3份、大豆蛋白2份、甘油10份和纯水10份为囊体原料，将甘油和纯水注入溶胶罐内，60℃加热搅拌，再加入明胶、硬酯酸和大豆蛋白，继续搅拌均匀后真空脱泡，制作得到囊体；
第2步：配制内容物：按重量份计，将大豆油85份、γ-亚麻酸4份、阿齐沙坦酯钾盐20份、及甘油20份在50℃下进行混合，混合时间20min，过胶体磨3次，得到混合均匀的内容物；
第3步：将第2步得到的内容物及第1步得到囊体经过压丸、定型、洗丸、干燥、拣丸和分装步骤，制备得到阿齐沙坦酯钾盐软胶囊。
实施例2
阿齐沙坦酯钾盐软胶囊的制备方法，步骤：
第1步，制作囊体：按重量份计，以明胶25份、硬酯酸6份、大豆蛋白3份、甘油25份和纯水15份为囊体原料，将甘油和纯水注入溶胶罐内，70℃加热搅拌，再加入明胶、硬酯酸和大豆蛋白，继续搅拌均匀后真空脱泡，制作得到囊体；
第2步：配制内容物：按重量份计，将大豆油85份、γ-亚麻酸4份、阿齐沙坦酯钾盐40份、及甘油20份在50℃下进行混合，混合时间20min，过胶体磨3次，得到混合均匀的内容物；
第3步：将第2步得到的内容物及第1步得到囊体经过压丸、定型、洗丸、干燥、拣丸和分装步骤，制备得到阿齐沙坦酯钾盐软胶囊。
实施例3
阿齐沙坦酯钾盐软胶囊的制备方法，步骤：
第1步，制作囊体：按重量份计，以明胶20份、硬酯酸5份、大豆蛋白3份、甘油20份和纯水12份为囊体原料，将甘油和纯水注入溶胶罐内，65℃加热搅拌，再加入明胶、硬酯酸和大豆蛋白，继续搅拌均匀后真空脱泡，制作得到囊体；
第2步：配制内容物：按重量份计，将大豆油90份、γ-亚麻酸4份、阿齐沙坦酯钾盐80份、及甘油15份在50℃下进行混合，混合时间20min，过胶体磨3次，得到混合均匀的内容物；
第3步：将第2步得到的内容物及第1步得到囊体经过压丸、定型、洗丸、干燥、拣丸和分装步骤，制备得到阿齐沙坦酯钾盐软胶囊。
实施例4
阿齐沙坦酯钾盐软胶囊的制备方法，步骤：
第1步，制作囊体：按重量份计，以明胶20份、硬酯酸5份、大豆蛋白3份、甘油20份和纯水12份为囊体原料，将甘油和纯水注入溶胶罐内，65℃加热搅拌，再加入明胶、硬酯酸和大豆蛋白，继续搅拌均匀后真空脱泡，制作得到囊体；
第2步：配制内容物：按重量份计，将大豆油90份、γ-亚麻酸4份、阿齐沙坦酯钾盐60份、及甘油15份在50℃下进行混合，混合时间20min，过胶体磨3次，得到混合均匀的内容物；
第3步：将第2步得到的内容物及第1步得到囊体经过压丸、定型、洗丸、干燥、拣丸和分装步骤，制备得到阿齐沙坦酯钾盐软胶囊。
Claims (4)
1.一种阿齐沙坦酯钾盐软胶囊的制备方法，其特征在于，包括如下步骤：
第1步，制作囊体：按重量份计，以明胶15～25份、硬酯酸0～6份、大豆蛋白0～3份、甘油10～25份和纯水10～15份为囊体原料，将甘油和纯水注入溶胶罐内，加热搅拌，再加入明胶、硬酯酸和大豆蛋白，继续搅拌均匀后真空脱泡，制作得到囊体；
第2步：按重量份计，将大豆油30～90份、不饱和脂肪酸4～9份、阿齐沙坦酯钾盐20～50份及甘油5～20份进行混合，过胶体磨，得到混合均匀的内容物；
第3步：将第2步得到的内容物及第1步得到囊体经过压丸、定型、洗丸、干燥、拣丸和分装步骤，制备得到阿齐沙坦酯钾盐软胶囊。
2.根据权利要求1所述的阿齐沙坦酯钾盐软胶囊的制备方法，其特征在于：所述的第1步中，搅拌加热的温度是60～70℃。
3.根据权利要求1所述的阿齐沙坦酯钾盐软胶囊的制备方法，其特征在于：所述的第2步中，不饱和脂肪酸选自二十二碳六烯酸、二十碳五烯酸、鱼油、亚麻籽油、琉璃苣油、α-亚麻酸、γ-亚麻酸、共轭亚油酸或者锯叶棕提取物。
4.根据权利要求1所述的阿齐沙坦酯钾盐软胶囊的制备方法，其特征在于：所述的第2步中，混合时的温度50～70℃，混合时间20～40min，过胶体磨的次数是1～3次。
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| CN105476011A (zh) * | 2015-12-27 | 2016-04-13 | 刘家容 | 一种番茄红素软胶囊的制备方法 |
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| CN102711735A (zh) * | 2009-11-20 | 2012-10-03 | Gp制药股份公司 | 治疗心血管疾病的、活性药物成分与多不饱和脂肪酸酯的胶囊 |
| CN102342944A (zh) * | 2011-07-14 | 2012-02-08 | 丁尧 | 一种治疗高血压病的药物组合物 |
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