CN112773768A - 一种花生四烯酸乙醇胺颗粒 - Google Patents
一种花生四烯酸乙醇胺颗粒 Download PDFInfo
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- CN112773768A CN112773768A CN202110116225.3A CN202110116225A CN112773768A CN 112773768 A CN112773768 A CN 112773768A CN 202110116225 A CN202110116225 A CN 202110116225A CN 112773768 A CN112773768 A CN 112773768A
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- arachidonic acid
- acid ethanolamine
- ethanolamine
- emulsion
- antioxidant
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Abstract
本发明公开了一种花生四烯酸乙醇胺颗粒，其特征在于：本发明主要采用步骤一备料、步骤二乳化、步骤三均质化、步骤四灭菌制膏、步骤五造粒、步骤六冻干的造粒工艺，采用乳化剂包括辛烯基琥珀酸淀粉钠、酪蛋白酸钠、乳清蛋白、大豆蛋白、明胶、壳聚糖、磷脂等原料的一种或多种；增稠剂包括可得然胶、卡拉胶、结冷胶、黄原胶等；填充料包括麦芽糊精、葡萄糖浆及其他单糖或者寡糖、低聚糖等原料的一种或多种；抗氧化剂包括维生素C及制品，维生素E、迷迭香提取物及合成抗氧化剂等的一种或多种的辅助配料工艺。实现花生四烯酸乙醇胺能在水溶性产品中应用。合理有效地解决了现有技术的花生四烯酸乙醇胺的脂溶性应用难题。克服了现有技术的不足。
Description
技术领域
本发明涉及一种脂肪酸酰胺类化合物的合成纯化技术领域，尤其涉及一种花生四烯酸乙醇胺颗粒。
背景技术
花生四烯酸乙醇胺是人类发现的一种内源性大麻素，近年来，关于花生四烯酸乙醇酰胺(Arachidonoyl ethanolamide，AEA)是一种内源性脂质信号分子的大麻素类物质，具备调控食欲及脂质代谢，保护心脏及神经系统，改善血压及免疫功能等多种作用。
AEA在自然生物体组织内的浓度非常微小，化学结构不稳定，且从体内提取AEA过程复杂。大麻(Cannabis)是世界上历史悠久且被广泛应用的传统药物。早在4000多年前，我国就将大麻应用于日常生活和药物治疗。但因其在世界范围内的滥用而产生不良精神症状和成瘾性等特点，影响了对大麻药物进一步研究的热情。直到上世纪70年代确认并纯化了大麻的主要活性成分——四氢大麻酚(Δ9-tetrahydrocannabinol，Δ9-THC)，明确其在医学上的用途后，经历多次限制使用的大麻再次在美国部分州被合法使用，历史上出现了第一次研究大麻的热潮。
1992年，AEA被以色列科学家Devane等从猪脑组织中发现并分离鉴定。作为第一个被发现的内源性大麻素受体的配体物质，其具有与Δ9-THC极为相似的结构，在体内外实验中具有相似的生理作用。通常，AEA生理活性的发挥多与大麻素受体相关。
大麻素受体CB1型主要参与运动、记忆和情感等活动方面的调节，被用作肥胖、酒精依赖症、帕金森病等的主要药物靶点；大麻素受体CB2型与机体免疫调节有关，具有消炎镇痛等作用。除此之外，AEA还可通过作用于辣椒素受体的离子通道(TRPV1)，参与急性炎症疼痛信号的传导。故AEA在人体不同生理条件下发生的浓度适应性改变可能对人体具有保护意义。
神经退行性疾病是由大脑和脊髓细胞神经元丧失所致，会产生运动障碍和记忆缺失。AEA可以通过参与谷氨酸传递、氧化应激和炎性反应等过程发挥神经保护作用。Melis等还证实AEA可通过直接作用于经典核受体PPARα和PPARγ参与代谢及免疫炎性反应。脑室内注射AEA可引起脑水肿及记忆损失和CB1的选择性拮抗剂(SR141716A)可提高啮齿类动物的记忆功能等均表明AEA可影响学习记忆功能。因此，AEA可用作治疗中枢神经系统疾病的新靶点。
AEA通过中枢及外周神经途径可调节摄食行为、糖脂代谢及能量平衡。绝大多数肥胖患者存在内源配体和CB1受体障碍，而高营养饮食下的肥胖小鼠脑部伴有大麻系统的过度活化，下丘脑和肝脏CB1表达增加，加剧脂肪的生成和积累等。动物研究显示，阻断小鼠脂肪组织中CB1受体可诱导游离脂肪酸氧化，改善高血糖和高胰岛素血症。SR141716A的临床研究发现患者体质量、腰围和血脂血糖指标均明显改善。另外，AEA含量的变化还对妊娠过程具有重要的生理学意义。孕妇产前静脉血液中的AEA含量显著低于正常值，并在分娩过程中急剧升高，这可能与脂肪酸酰胺水解酶的调节作用或生成了对分娩有关键作用的前列腺素类物质有关。AEA与CB1间的反馈性调节可减少产妇因情绪等对宫缩的抑制作用。缺失CB1受体的怀孕大鼠导致早产的现象意味着大麻受体信号转导可能关乎人类早产。此外，AEA升高与孕妇产程间的相关性可作为调节胚胎植入窗口的一个因素。这为临床寻找应用于妇产科的大麻类新药物提供了新思路。
在实际的生产中，由于花生四烯酸乙醇胺合成的纯度不高及氧化的问题，会导致花生四烯酸乙醇胺在后期的应用效果不好，本发明主要是提出了多步分提及纯化花生四烯酸乙醇胺的技术。
在实际应用中，花生四烯酸乙醇胺是一种油溶性液体，在低温下处于膏状的产品，在常规使用中比较麻烦。
发明内容
本发明的目的在于提供一种花生四烯酸乙醇胺颗粒，合理有效地解决了现有技术的花生四烯酸乙醇胺的脂溶性应用难题、花生四烯酸乙醇胺不能在水溶性产品中应用的问题。
本发明采用如下技术方案：
一种花生四烯酸乙醇胺颗粒，其特征在于：花生四烯酸乙醇胺颗粒为水溶性物质，所述花生四烯酸乙醇胺的单剂含量可以控制在60％以内；所述花生四烯酸乙醇胺颗粒的制备方法包括以下步骤：
步骤一：备料
1.1、乳化剂包括辛烯基琥珀酸淀粉钠、酪蛋白酸钠、乳清蛋白、大豆蛋白、明胶、壳聚糖、磷脂等原料的一种或多种；
1.2、增稠剂包括可得然胶、卡拉胶、结冷胶、黄原胶等；
1.3、填充料包括麦芽糊精、葡萄糖浆及其他单糖或者寡糖、低聚糖等原料的一种或多种；
1.4抗氧化剂包括维生素C及制品，维生素E、迷迭香提取物及合成抗氧化剂等的一种或多种；
步骤二：乳化
将所述乳化剂、增稠剂、填充料、抗氧化剂按比例溶解到水中，缓慢加入花生四烯酸乙醇胺和抗氧化剂，将花生四烯酸乙醇胺与全部原料乳化均匀制备乳化液；所述乳化液中，固形物浓度不低于50％；
步骤三：均质化
将所述乳化液在20-80mpa的压力下进行均质，可以均质1～3遍，制备均匀乳化液；
步骤四：灭菌制膏
将所述均匀乳化液通过巴氏杀菌或者UHT高温灭菌后，降温到0～10℃，形成粘稠的膏状物，制备乳膏；
步骤五：造粒
将所述乳膏按照目标的粒度要求，采用造粒工艺挤压或者直接高压雾化、冷冻、剪切造粒成型；
步骤六：冻干、验收、包装，构成所述一种花生四烯酸乙醇胺颗粒。
进一步地，所述花生四烯酸乙醇胺颗粒包括单剂制剂和复方组合制剂。
进一步地，所述花生四烯酸乙醇胺颗粒中花生四烯酸乙醇胺的包埋率达到90％以上。
本发明的有益技术效果是:
本发明的目的在于提供一种花生四烯酸乙醇胺颗粒，合理有效地解决了现有技术的花生四烯酸乙醇胺的脂溶性应用难题、花生四烯酸乙醇胺不能在水溶性产品中应用的问题。
本发明主要采用步骤一备料、步骤二乳化、步骤三均质化、步骤四灭菌制膏、步骤五造粒、步骤六冻干、验收、包装的造粒工艺，采用乳化剂包括辛烯基琥珀酸淀粉钠、酪蛋白酸钠、乳清蛋白、大豆蛋白、明胶、壳聚糖、磷脂等原料的一种或多种；增稠剂包括可得然胶、卡拉胶、结冷胶、黄原胶等；填充料包括麦芽糊精、葡萄糖浆及其他单糖或者寡糖、低聚糖等原料的一种或多种；抗氧化剂包括维生素C及制品，维生素E、迷迭香提取物及合成抗氧化剂等的一种或多种的辅助配料工艺。实现花生四烯酸乙醇胺能在水溶性产品中应用。克服了现有技术的不足。
具体实施方式
通过下面对实施例的描述，将更加有助于公众理解本发明，但不能也不应当将申请人所给出的具体的实施例视为对本发明技术方案的限制，任何对部件或技术特征的定义进行改变和/或对整体结构作形式的而非实质的变换都应视为本发明的技术方案所限定的保护范围。
实施例1：
分别称取辛烯基琥珀酸淀粉钠60g，可得然胶10g，麦芽糊精25.6g、抗坏血酸钠4g，加入150g去离子水，用剪切机混合均匀，并升温到60℃；
称取100g花生四烯酸乙醇胺，含量为73.5％，加入0.4g的抗氧化剂TBHQ,混合均匀后，将花生四烯酸乙醇胺缓慢加入乳化液中，使用剪切机高速搅拌，是花生四烯酸乙醇胺和乳化液混合均匀并乳化完全。
将乳化液静置，除去气泡，在实验室用均质机均质，均质机压力50MPa,均质3次，得到花生四烯酸乙醇胺的均质液；
将均质液降温到3℃±1℃，形成粘稠的膏状物，通过挤压制粒设备，将物料挤压成40目的物料，并在液氮中快速冷冻成型；
将冷冻成型的物料，转入冻干设备中进行冻干，得到生四烯酸乙醇胺颗粒。
通过检测，花生四烯酸乙醇胺颗粒中的花生四烯酸乙醇胺含量为36.5％，包埋率为95.4％。
实施例2：
分别称取酪蛋白酸钠16g，结冷胶12g，麦芽糊精40g、葡萄糖21g，抗坏血酸钠10g，加入100mg去离子水，用剪切机混合均匀，并升温到70℃；
称取110g花生四烯酸乙醇胺，含量为85.4％，加入0.4g的抗坏血酸棕榈酸酯、0.2g维生素E、0.4g迷迭香提取物的抗氧化剂,混合均匀后，将花生四烯酸乙醇胺缓慢加入乳化液中，使用剪切机高速搅拌，是花生四烯酸乙醇胺和乳化液混合均匀并乳化完全。
将乳化液静置，除去气泡，在实验室用均质机均质，均质3次，均质机压力分别为40MPa、50MPa和60MPa,得到花生四烯酸乙醇胺的均质液；
将均质液降温到5℃±1℃，形成粘稠的膏状物，通过挤压制粒设备，将物料挤压成20目的颗粒，并在液氮中快速冷冻成型；
将冷冻成型的物料，转入冻干设备中进行冻干，干燥的物料通过粉碎，得到生四烯酸乙醇胺颗粒。
通过检测，花生四烯酸乙醇胺颗粒中的花生四烯酸乙醇胺含量为46.6％，包埋率为96.3％。
实施例3：
分别称取浓缩乳清蛋白50g，黄原胶2g，淀粉7.2g、蔗糖20g，乳糖40g，加入130g去离子水，用剪切机混合均匀，并升温到80℃，使淀粉糊化；
称取80g花生四烯酸乙醇胺，含量为93.2％，加入0.4g的TBHQ、0.4gHBA,混合均匀后，将花生四烯酸乙醇胺缓慢加入乳化液中，使用剪切机高速搅拌，是花生四烯酸乙醇胺和乳化液混合均匀并乳化完全。
将乳化液静置，除去气泡，在实验室用均质机均质，均质3次，均质机压力为40MPa、40MPa和60MPa,得到花生四烯酸乙醇胺的均质液；
将均质液降温到8℃±1℃，形成粘稠的膏状物，通过挤压制粒设备，将物料10目的颗粒，并在液氮中快速冷冻成型；
将冷冻成型的物料，转入冻干设备中进行冻干，干燥的物料通过粉碎，得到花生四烯酸乙醇胺颗粒。
通过检测，花生四烯酸乙醇胺颗粒中的花生四烯酸乙醇胺含量为37.4％，包埋率为95.1％。
实施例4：
分别称取酪蛋白酸钠30kg，明胶30g，卡拉胶15kg、葡萄糖浆30kg，低聚果糖粉6kg，抗坏血酸钠9kg，加入到150kg去离子水中，用剪切机混合均匀，并升温到75℃；
称取240kg花生四烯酸乙醇胺，含量为93.2％，加入0.6kg的抗坏血酸棕榈酸酯、0.3kg天然维生素E,混合均匀后，用泵将花生四烯酸乙醇胺缓慢加入乳化液中，使用剪切机高速搅拌，是花生四烯酸乙醇胺和乳化液混合均匀并乳化完全。
将乳化液静置，除去气泡，通过均质机均质，均质机压力为65MPa,得到花生四烯酸乙醇胺的均质液；
将均质液缓慢降温降温到9℃±1℃，通过高压雾化技术，将料液雾化，在-40℃的料仓内快速冷冻成型；
将冷冻成型的物料，转入冻干设备中进行冻干，得到80～50目范围的花生四烯酸乙醇胺颗粒。
通过检测，花生四烯酸乙醇胺颗粒中的花生四烯酸乙醇胺含量为55.5％，包埋率为90.1％。
实施例5：
分别称取大豆蛋白138kg，壳聚糖27.5kg，卡拉胶16.5kg、淀粉11kg，麦芽糊精138kg，低聚半乳糖24kg，加入到300kg去离子水中，用剪切机混合均匀，并升温到85℃，使淀粉糊化；
称取193kg花生四烯酸乙醇胺，含量为93.2％，加入1.1kg的迷迭香提取物、1.1kgTBHQ,1.1kgHBA混合均匀后，用泵将花生四烯酸乙醇胺缓慢加入乳化液中，使用剪切机高速搅拌，是花生四烯酸乙醇胺和乳化液混合均匀并乳化完全。
将乳化液静置，除去气泡，通过均质机均质，均质机压力为55MPa,得到花生四烯酸乙醇胺的均质液；
将均质液缓慢降温降温到8℃±1℃，通过高压雾化技术，将料液雾化，在-40℃的料仓内快速冷冻成型；
将冷冻成型的物料，转入冻干设备中进行冻干，得到80～40目的花生四烯酸乙醇胺颗粒。
通过检测，花生四烯酸乙醇胺颗粒中的花生四烯酸乙醇胺含量为32.5％，包埋率为97.6％。
进一步地，所述花生四烯酸乙醇胺的含量可以控制在60％以内。
进一步地，所述花生四烯酸乙醇胺颗粒中花生四烯酸乙醇胺的包埋率达到90％以上。完成所述一种花生四烯酸乙醇胺颗粒的实施。
当然，本发明还可以有其他多种实施例，在不背离本发明精神及其实质的情况下，熟悉本领域的技术人员可以根据本发明做出各种相应的改变和变形，但这些相应的改变和变形都应属于本发明所附的权利要求的保护范围。
Claims (3)
1.一种花生四烯酸乙醇胺颗粒，其特征在于：花生四烯酸乙醇胺颗粒为水溶性物质，所述花生四烯酸乙醇胺的单剂含量可以控制在60％以内；所述花生四烯酸乙醇胺颗粒的制备方法包括以下步骤：
步骤一：备料
1.1、乳化剂包括辛烯基琥珀酸淀粉钠、酪蛋白酸钠、乳清蛋白、大豆蛋白、明胶、壳聚糖、磷脂等原料的一种或多种；
1.2、增稠剂包括可得然胶、卡拉胶、结冷胶、黄原胶等；
1.3、填充料包括麦芽糊精、葡萄糖浆及其他单糖或者寡糖、低聚糖等原料的一种或多种；
1.4抗氧化剂包括维生素C及制品，维生素E、迷迭香提取物及合成抗氧化剂等的一种或多种；
步骤二：乳化
将所述乳化剂、增稠剂、填充料、抗氧化剂按比例溶解到水中，缓慢加入花生四烯酸乙醇胺和抗氧化剂，将花生四烯酸乙醇胺与全部原料乳化均匀制备乳化液；所述乳化液中，固形物浓度不低于50％；
步骤三：均质化
将所述乳化液在20-80mpa的压力下进行均质，可以均质1～3遍，制备均匀乳化液；
步骤四：灭菌制膏
将所述均匀乳化液通过巴氏杀菌或者UHT高温灭菌后，降温到0～10℃，形成粘稠的膏状物，制备乳膏；
步骤五：造粒
将所述乳膏按照目标的粒度要求，采用造粒工艺挤压或者直接高压雾化、冷冻、剪切造粒成型；
步骤六：冻干、验收、包装，构成所述一种花生四烯酸乙醇胺颗粒。
2.根据权利要求1所述一种花生四烯酸乙醇胺颗粒，其特征在于，所述花生四烯酸乙醇胺颗粒包括单剂制剂和复方组合制剂。
3.根据权利要求1所述一种花生四烯酸乙醇胺颗粒，其特征在于，所述花生四烯酸乙醇胺颗粒中花生四烯酸乙醇胺的包埋率达到90％以上。
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| CN114621818A (zh) * | 2022-03-09 | 2022-06-14 | 山东省食品发酵工业研究设计院 | 一种卷烟滤棒用纳米香精颗粒及其制备方法 |
| CN115531245A (zh) * | 2022-05-25 | 2022-12-30 | 上海拜思丽实业有限公司 | 一种抗炎修复纳米组合物及其制备方法和应用 |
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| WO2016022936A1 (en) * | 2014-08-07 | 2016-02-11 | Murty Pharmaceuticals, Inc. | An improved oral gastrointestinal dosage form delivery system of cannabinoids and/or standardized marijuana extracts |
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| CN114621818A (zh) * | 2022-03-09 | 2022-06-14 | 山东省食品发酵工业研究设计院 | 一种卷烟滤棒用纳米香精颗粒及其制备方法 |
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