CN110522736A - 一种改善睡眠、美容的双层控释片及制备方法 - Google Patents
一种改善睡眠、美容的双层控释片及制备方法 Download PDFInfo
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Abstract
本发明提供了一种具有改善睡眠和美容功效的保健品双层控释片,它包括速释层和缓释层,速释层包括GABA、透明质酸钠,缓释层包括GABA、含镁化合物、酸枣仁提取物、透明质酸钠。速释层与缓释层中的GABA重量比为(0.3‑3):1,透明质酸钠重量比为(0.6‑3):1;速释层中的透明质酸钠分子量为(0.2‑0.6)×106 Da,缓释层中的透明质酸钠分子量为(1.2‑2.5)×106 Da。本发明的双层控释片将GABA、含镁化合物、酸枣仁提取物、透明质酸钠作为有效成分,能够起到控制释放改善睡眠成分物质的良好功效。通过调节各有效成分在不同层的比例、含量或种类,达到了既能快速起到改善睡眠效果,又能够延长作用时间的效果,使服用次数减少。
Description
技术领域
本发明属于食品领域,涉及一种双层控释片及制备方法。
背景技术
失眠又称为睡眠障碍,是指睡眠的始发和睡眠维持发生障碍,致使睡眠质量不能满足个体生理需要而明显影响患者白天活动的一种睡眠障碍综合征。睡眠不足所带来的害处有精力不济、反应迟钝、记忆力衰退、免疫力降低,甚至使机体过早的衰老。皮肤是人体最大的器官,参与吸收、排泄、防护、各种物质的代谢,人表皮细胞活跃代谢时间为凌晨至次日2点,这个时间段皮肤的胶原蛋白和角蛋白不断更新,如果处于失眠状态,会减慢皮肤新陈代谢、皮肤锁水功能下降,从而引起面部干燥缺水、皮肤弹力下降,细纹增多。
γ-氨基丁酸(GABA)又称氨酪酸,是一种非蛋白质组成的天然氨基酸,为哺乳动物中枢神经系统一种主要的抑制性神经递质,介导40%以上的抑制性神经传导。大量研究报道GABA具有改善睡眠的作用,小鼠实验表明,口服GABA后可以延长睡眠时间、增加阈下剂量入睡动物数。另外,日本学者研究表明GABA具有美容功效。
酸枣仁为鼠李科植物酸枣的干燥成熟种子,是中医安神之要药,对于虚烦、失眠、心悸、体虚多汗等症状有明显疗效,而且具有补肝、宁心、敛汗、生津的作用。大量药理研究和临床用药结果表明,酸枣仁可以有效延长睡眠的时间,与戊巴比妥等镇静催眠药物有良好协同作用,对于入睡困难、睡眠易醒的人群都有良好的疗效。
镁是人体细胞内的主要阳离子,浓集于线粒体中,仅次于钾和磷,参与生物体正常生命活动及新陈代谢。镁缺乏在临床上主要表现为情绪不安、易激动、手足抽搐、反射亢进等。口服镁补充剂影响老年人的睡眠内分泌功能,硫酸镁对健康男性的睡眠具有GABA激动作用。较高含量的镁进入消化道,肠胃只能吸收有限的镁,多余的镁会被排出,从而造成浪费;另一方面,体内镁过多会使机体镁贮存体系饱和,损伤机体,有研究报道服用硫酸镁过量会在机体内存在蓄积中毒等并发症。
透明质酸(HA)是由N-乙酰氨基葡糖和D-葡糖醛酸双糖重复单位构成的无分支高分子糖胺聚糖,存在于动物组织细胞间质中,以皮肤、关节腔、眼等器官中含量较高。HA通过口服经消化吸收,增加体内HA合成的前体,使皮肤和其他组织中HA合成量增加,从而提高皮肤的保水性能,使皮肤富有弹性,皱纹减少。另外,一定高分子量的透明质酸钠不仅具有改善皮肤水分作用,而且能够缓慢释放药物发挥作用;低分子量的透明质酸钠易于被人体快速吸收,起到快速补充皮肤水分、增加皮肤弹性效果。
近些年研制开发的改善睡眠的保健食品种类繁多,如专利CN104758397A公开了一种改善睡眠的组合物及其制备方法,所述组合物由苹果干细胞冻干粉、酸枣仁提取物和γ-氨基丁酸制成;所述苹果干细胞冻干粉、酸枣仁提取物和γ-氨基丁酸的质量比为25:25:13。CN103784611A公开了一种具有改善睡眠帮助缓解压力的组合物及其应用,所述组合物由玫瑰花、酸枣仁、γ-氨基丁酸(GABA)、茶叶、西番莲、桑椹、甘氨酸、L-色氨酸、维生素B6组成。CN103110709A公开了一种改善睡眠的组合物及其制备方法,该组合物为片剂,由以下重量份的原料制成:γ-氨基丁酸50-200份、酸枣仁提取物50-200份、镁50-300、维生素B6 0.5-20份。上述专利中γ-氨基丁酸和酸枣仁提取物均被用于常规剂型中,所有的GABA均一次性摄入体内,会造成部分GABA未能与GABA受体结合而排出体外,从而造成浪费;并且一般GABA在体内4h即代谢完全,普通片剂不能达到长久起效的作用。
因此,需要开发一种各功效成分可以循序渐进发挥作用,进而达到充分利用、服用次数少、功效作用时间长、副作用低的改善睡眠和美容的保健食品。
发明内容
针对目前含GABA和镁离子产品释放过快的问题,本发明提供一种改善睡眠、美容的双层控释片,起效迅速、作用时间长,同时具有改善睡眠和美容效果。
本发明的另一目的是提供一种上述双层控释片的制备方法。
为实现上述目的,本发明采用如下技术方案。
一种改善睡眠、美容的双层控释片,由速释层和缓释层组成;所述速释层的有效成分为GABA和透明质酸钠;所述缓释层的有效成分为GABA、含镁化合物、酸枣仁提取物和透明质酸钠。
所述速释层与缓释层中的GABA重量比为(0.3-3):1。
所述速释层中的透明质酸钠分子量为(0.2-0.6)×106 Da;所述缓释层中的透明质酸钠分子量为(1.2-2.5)×106 Da;所述速释层与缓释层中的透明质酸钠重量比为(0.6-3):1。
双层控释片中,GABA、透明质酸钠、含镁化合物(以镁计)、酸枣仁提取物的质量百分含量分别是10%-15%、7%-11%、0.5%-7%、2-4%。
所述含镁化合物为硫酸镁、L-苏糖酸镁、氯化镁、氧化镁、碳酸氢镁、碳酸镁、甘氨酸镁和乳酸镁中的一种或几种;优选为L-苏糖酸镁。
上述改善睡眠、美容的双层控释片还包括辅料,如崩解剂、填充剂、润滑剂、缓释剂、成膜剂等。优选的,辅料至少包括崩解剂和缓释剂;所述崩解剂在速释层中;所述缓释剂在缓释层中。
优选的,上述改善睡眠、美容的双层控释片包括以下原料:
速释层:GABA,透明质酸钠,崩解剂,填充剂,润滑剂;
缓释层:GABA,含镁化合物,酸枣仁提取物,透明质酸钠,缓释剂,填充剂,润滑剂。
所述崩解剂为羧甲淀粉钠、交联聚维酮、低取代羟丙纤维素、交联羧甲基纤维素钠中的一种或几种。
所述缓释剂为海藻酸钠、预胶化淀粉、甲基纤维素、乙基纤维素、羟丙甲纤维素、羟甲基纤维素、壳聚糖和聚乙烯基吡咯烷酮中的一种或几种。
所述润滑剂为硬脂酸镁、二氧化硅、微粉硅胶、滑石粉、聚乙二醇和十二烷基硫酸钠中的一种或几种。
所述填充剂为微晶纤维素、乳糖、糊精、β-环糊精、淀粉、可胶化淀粉和糖粉中的一种或几种。
所述粘合剂为聚维酮、淀粉浆、羧甲基纤维素钠和糖浆中的一种或几种。
上述改善睡眠、美容的双层控释片可以采用常规的制备方法制备获得,如分别将速释层或缓释层的原料按比例混合进行湿法造粒,将得到的速释层颗粒和缓释层颗粒整粒后压片即可得到。
本发明的协同作用如下:
速释层中的GABA可快速释放,达到有效浓度起到改善睡眠的作用;缓释层中的GABA释放速度慢,可以保持较长时间的有效浓度,以达到延长作用时间效果。由于酸枣仁提取物需要分解为小分子后,作用于GABA受体发挥改善睡眠作用,放于缓释层中,能在GABA发挥作用后继续起到改善睡眠效果,总体延长作用时间。位于缓释层的含镁化合物,释放量比较均一、缓慢,可以有效防止过量镁蓄积中毒引起的不良反应。透明质酸钠具有美容功效,同时由于其具有粘性,在湿法制粒时可起到粘结作用,促进制粒效果,降低粘合剂使用量;通过将高分子量的透明质酸钠放于缓释层中还能起到缓释剂的作用。
本发明具有以下优点:
本发明的双层控释片将GABA、含镁化合物、酸枣仁提取物、透明质酸钠作为有效成分,能够起到控制释放改善睡眠成分物质的良好作用。通过调节各有效成分在不同层的比例、含量或种类,达到了既能快速改善睡眠,又能够延长作用时间的效果,使服用次数减少。
附图说明
图1是实施例1中的改善睡眠双层控释片的制备工艺流程示意图。
具体实施方式
下面结合实施例和附图对本发明做进一步说明,但本发明不受下述实施例的限制。
实施例1 改善睡眠、美容的双层控释片的制备(每片1000mg)
表1 各样品S1-3和对照品C2-5的双层控释片的重量 (1片,1000mg)
表2 各有效成分在速释层和缓释层中的含量与比例
注:含量指的是在整个双层控释片中的质量百分比。
按照表1重量称取各原料,按照以下方法进行片剂制备:
(1)取酸枣仁提取物、GABA、透明质酸钠、含镁化合物、崩解剂、填充剂、润滑剂过80目筛,备用;
(2)速释层制备:称取GABA、透明质酸钠、崩解剂、填充剂、润滑剂混合均匀,加入适量粘合剂溶液制软材,过20目筛后,于40-60℃烘箱中干燥4小时后,过18目筛整粒,得速释层颗粒;
(3)缓释层制备:称取GABA、含镁化合物、酸枣仁提取物、透明质酸钠、填充剂、润滑剂,混合均匀,加入适量粘合剂溶液制软材,过20目筛后,于40-60℃烘箱中干燥4小时后,过18目筛整粒,得缓释层颗粒;
(4)取缓释层颗粒,加入少量润滑剂,混合均匀;取速释层颗粒,加入少量润滑剂,混合均匀;将两种混合料分别置于双层压片机的两个料斗中,压片。
对比例1 改善睡眠、美容的片剂的制备
按照实施例1中样品1的原料使用量直接混合后压片,获得对照品C1。
实施例2 释放度测定
参照药典2015版第二部附录XD第一法,取实施例与对比例得到的双层控释片各6片,分别加入1000ml 0.1mol/L盐酸溶液,离心,转速100r/min,在2小时、4小时、8小时、12小时、18小时分别取出溶液10mL,滤过,并及时在操作容器中补充0.1mol/L盐酸溶液10mL。取滤液按《保健食品功效成分检测方法》(白鸿. 中国中医药出版社, 2011)中γ-氨基丁酸的高效液相色谱测定法规定的方法测定GABA含量,计算GABA累计释放百分率,结果如表3所示。
表3 不同片剂的累计释放百分率
由表3可知:4小时时,缓释片S1-S3中,速释层GABA释放完全,缓释层GABA已开始释放;缓释片S1-S3的缓释效果较好,达90%释放率的时间都在12h以上。普通片剂C1在4小时内的释放量就达到了95%以上,GABA释放速度快,基本无缓释效果。与S1相比,对照品C2中速释层透明质酸钠分子量高于0.6×106Da,缓释层中的透明质酸钠分子量低于1.2×106Da,在8h内释放率达到了90%以上,缓释效果差,说明缓释层中透明质酸钠的分子量对释放速度有着重要影响,并非任何分子量的透明质酸钠在缓释层中都能够发挥缓释作用。对照品C3中缓释层透明质酸钠与速释层中透明质酸钠的质量比为2:1,缓释层中透明质酸钠含量较高,会延缓GABA的释放,导致速释层中GABA释放完全后,缓释层中的GABA还未开始释放,从而导致无法连续释放GABA的作用。对照品C4速释层中透明质酸钠与缓释层中GABA的质量比为3.5:1,虽然和S1缓释效果一致,但是由于缓释层中GABA含量较低,缓释时间仅达到12小时,低于S1的18小时缓释时间。对照品C5将缓释层中具有缓释效果的透明质酸钠替换为海藻酸钠。与缓释片S1相比,前期释放量大,释放时间短。
实施例3 产品安全性验证
1. 材料与方法
1.1 受试对象
选取400名存在经常失眠、易醒、失眠情况、皮肤干燥(皮肤水分≤10)、面色蜡黄的志愿者作为试验对象,男女各半,年龄35-60岁。
受试者排除标准:
(1)妊娠或哺乳期妇女,过敏体质及对本保健食品过敏者;
(2)合并有心脑血管、肝、肾、造血系统性疾病和精神病史者;
(3)短期内服用与受试功能有关的物品,影响到对结果的判断者;
(4)未按试验要求服用受试样品,无法判定功效或资料不全影响疗效或安全性判断者。
表4 受试对象分组情况(均值±标准差)
1.2 试验方法
将400名受试者随机分为8组,3组实验组和5组对照组,实验组每天服用样品S1、S2、S3产品一片,5组对照组分别每天服用对照品C1、对照品C2、对照品C3、对照品C4、对照品C5各一片,连续服用15天。
2. 观察指标
2.1 安全性指标
(1)一般状况 包括精神、睡眠、饮食、血压等;
(2)血、尿、便常规检查
(3)肝、肾功能检查
(4)胸透、心电图、腹部B超检查
2.2 改善睡眠指标观察
疗效情况判定标准:参照《中医新药临床研究指导原则》拟定。显效:入睡时间<30min,夜间不苏醒;有效:入睡时间<2h,夜间苏醒1-2次;无效:入睡时间>2h,夜间苏醒>2次。
2.3 改善皮肤水分指标观察
测试前额眉间皮肤的水分:在宽敞、通风条件良好,温度、湿度等空间环境稳定的检查室进行。在安静状态下用洁净棉球蘸蒸馏水清洁被测部位,擦干后15分钟进行水分的测定,试食前后测定工作由同一台仪器、同一人操作。按照以下标准判断:
有效:水分得到改善;
无效:水分没有得到显著改善。
3. 结果
3.1 安全性检测结果
服用本发明产品前后,受试者的心率、血压均无显著变化,血常规、肝肾功能、大小便各项检测标准及胸透、心电图、B超检查均在正常范围,说明本发明双层控释片对机体健康无明显影响,见表5。
表5 试用前后安全指标变化比较(均值±标准差)
3.2 皮肤水分功效结果
服用15天时各组受试者改善睡眠的显效、无效例数和百分比结果如表6所示。
表6 受试者皮肤改善效果比较
结果如表6所示,从中可知,C1组和其它对照组相比,显效率最低,说明具有缓释功能的片剂改善睡眠和皮肤水分效果优于普通片剂;三个样品组的显效率分别为66%、70%和68%,显著高于其余5个对照组,说明样品组改善皮肤水分效果显著优于其它对照组。
3.4 睡眠改善结果
服用15天时各组受试者改善睡眠的显效、有效、无效例数和百分比结果如表7所示。
表7 受试者治疗效果比较
受试者改善睡眠治疗效果如表7所示,从表中可看出,C1组的显效率低于其它对照组,无效率高于其余对照组,说明普通片剂改善睡眠效果与双层控释片相比较差;S1、S2和S3组显效率和有效率分别为44%和46%、50%和42%以及46%和48%,无效率分别仅为10%、8%和6%,显效率和有效率明显高于C1-C5组,无效率显著低于C1-C5组,从而可见实验组患者的治疗结果明显优于对照组。说明本发明所得产品对改善睡眠有显著疗效。
由安全性、改善睡眠、改善皮肤水分功能的试验结果得出,试验结束时受试者的体检结果和各项安全性指标未见异常,表明本发明对人体无不良影响,服用安全。试食者皮肤水分和睡眠与试验初期以及对照组相比,效果改善均比较显著,说明本发明双层控释片同时具有改善皮肤水分和睡眠功能,具有实际的临床价值。
Claims (8)
1.一种改善睡眠、美容的双层控释片,其特征在于,由速释层和缓释层组成,所述速释层的有效成分为GABA和透明质酸钠;所述缓释层的有效成分为GABA、含镁化合物、酸枣仁提取物和透明质酸钠。
2.根据权利要求1所述的双层控释片,其特征在于,所述速释层与缓释层中的透明质酸钠重量比为(0.6-3):1。
3.根据权利要求2所述的双层控释片,其特征在于,所述速释层中的透明质酸钠分子量为(0.2-0.6)×106 Da;所述缓释层中的透明质酸钠分子量为(1.2-2.5)×106 Da。
4.根据权利要求1所述的双层控释片,其特征在于,所述速释层与缓释层中的GABA重量比为(0.3-3):1。
5.根据权利要求1所述的双层控释片,其特征在于,双层控释片中,GABA、透明质酸钠、含镁化合物(以镁计)、酸枣仁提取物的质量百分含量分别是10%-15%,7%-11%,0.5%-7%和2-4%。
6.根据权利要求1所述的双层控释片,其特征在于,所述含镁化合物为硫酸镁、L-苏糖酸镁、氯化镁、氧化镁、碳酸氢镁、碳酸镁、甘氨酸镁和乳酸镁中的一种或几种。
7.根据权利要求1所述的双层控释片,其特征在于,所述含镁化合物为L-苏糖酸镁。
8.根据权利要求1所述的双层控释片,其特征在于,双层控释片中还包括崩解剂和缓释剂;所述崩解剂在速释层中;所述缓释剂在缓释层中。
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