CN102038644B - 叶黄素水溶性粉末及其制备工艺 - Google Patents
叶黄素水溶性粉末及其制备工艺 Download PDFInfo
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Abstract
本发明属于医药技术领域,涉及一种水溶性良好性质稳定且流动性优良的叶黄素水溶性粉末的制备工艺。本发明所述的叶黄素水溶性粉末的处方组成及重量比为叶黄素粉末:载体:附加剂=1:1-10:0-3。采用溶剂法制备叶黄素水溶性粉末,可制备成多种剂型或添加入各种功能食品中。该工艺制备的叶黄素水溶性粉末中叶黄素的溶出度可达96%,且水溶性良好,稳定性高,流动性好,休止角为34度,分散性好,可应用于食品、药品、化妆品等各个领域。
Description
技术领域
本发明属于医药技术领域,涉及一种叶黄素水溶性粉末及其制备工艺,具体涉及一种在水中速溶且稳定性好的叶黄素水溶性粉末及其制备工艺。
背景技术
叶黄素又名“植物黄体素”,在自然界中与玉米黄素共同存在。是构成玉米、蔬菜、水果、花卉等植物色素的主要组分,含于叶子的叶绿体中,可将吸收的光能传递给叶绿素a,推测对光氧化、光破坏具有保护作用。也是构成人眼视网膜黄斑区域的主要色素。医学实验证明植物中所含的天然叶黄素是一种性能优异的抗氧化剂,在食品中加入一定量的叶黄素可预防细胞衰老和机体器官衰老,同时还可预防老年性眼球视网膜黄斑退化引起的视力下降与失明,通过一系列的医学研究,叶黄素已被建议用作癌症预防剂,生命延长剂,溃疡抵制剂,心脏病发作与冠状动脉疾病的抵制剂.同时,叶黄素还可作为饲料添加剂用于家禽肉蛋的着色,同时也已在食品工业中用作着色与营养保健剂。
叶黄素对视网膜中的黄斑有重要保护作用,缺乏时易引黄斑退化和视力模糊。进而出现视力退化,近视等症状。叶黄素对眼睛的主要生理功能是作为抗氧化剂和光保护作用。叶黄素较强的氧化作用,能抑制活性氧自由基的活性,阻止活性氧自由基对正常细胞的破坏.有关实验证明,活性氧自由基可与DNA、蛋白质、脂类发生反应,削弱它们的生理功能,进而引发诸如癌症、动脉硬化,增龄性黄膜变性症等慢性病的发生。叶黄素可通过物理或化学淬灭作用灭活单线态氧,从而保护机体免受伤害,增强机体的免疫能力。白内障是世界范围内导致失明的主要眼疾,最新的研究证明通过增加叶黄素的摄入量可达到生率的目的,目前认为其机理为较低的黄斑色素密度与中老年人较高的晶状体视觉密度紧密关联,而较高的晶状体视觉密度被认为是白内障发病的明显特征。最近的研究结果表明,叶黄素对早期的动脉硬化进程有延缓作用。主要是动脉主干道血管内膜厚度的变化与血液中叶黄素含量之间的关系。血液中叶黄素含量较低,极易引起动脉血管壁增厚,随着叶黄素含量的逐渐增加,动脉壁增厚趋势降低,动脉栓塞也显著降低。同时,动脉壁细胞中的叶黄素还可降低LDL胆固醇的氧化性。多项研究表明,叶黄素对多种癌症有抑制作用,如乳腺癌、前列腺癌、直肠癌、皮肤癌等.根据纽约大学药物学院最近的研究,在降低乳腺癌的发病率与叶黄素摄入量间有很紧密的关系,调查发现叶黄素摄入量低的实验组的乳腺癌发病率是摄入量高组的(2.08~2.21)倍。这种作用可能涉及与其他器官组织协同的间接免疫调节作用.该项研究得出结论,在膳食中摄人叶黄素不仅能抑制肿瘤甚至可以起到预防肿瘤发生的作用。视网膜色素变性(RP)是一种慢性、进行性、遗传性、营养不良性视网膜色素病变。主要包括原发性视网膜色素变性,结晶性视网膜色素变性,白点状视网膜色素变性和无色素性视网膜色素变性。补充叶黄素可以增加视网膜色素密度,提高RP患者的视力,提高RP的治疗率。叶黄素、玉米黄素可以显著提高血管抵抗力,恢复血管内外渗透压失去的平衡,降低血管渗透性,抑制了血管中物质渗漏,保证眼睛血管的完整性,让眼睛得到充足的血液供应。同时可以防止自由基和眼睛胶原蛋白结合造成损害,加强视网膜胶原结构,从而提高各种视网膜疾病(如:糖尿病视网膜病,视网膜炎色素沉着,出血性和高血压视网膜病,以及黄斑退化等)的治疗率,改善、恢复因此导致的视力丧失。
但叶黄素是一种水不溶且稳定性差的物质,其水不溶性和稳定性差限制了其在各个领域的应用,使这样一种具有较好预防和治疗效果的物质的使用受到了限制,因此如何改善其水溶性和稳定性,扩大其使用范围是本领域技术人员一直在努力的。
公开号CN101177540A 描述了一种食品级叶黄素水溶性干粉的制备方法。先将叶黄素用丙酮、乙酸乙酯等有机溶剂溶解后,与变性淀粉、葡萄糖的水溶液混合得乳化后的混合液,再通过高压乳匀机乳化,最后用喷雾干燥法或喷雾-淀粉流化床干燥法除掉乳液中水份,得干粉。这一工艺较复杂,且需高压乳匀及喷雾干燥设备。
公开号CN1757315A涉及了一种叶黄素酯改性为水溶性叶黄素的工艺技术、配方。采用化学法和物理法改性工艺技术,对叶黄素酯加热液化后皂化乳化,然后经过高压匀质后真空脱气,最后灭菌灌装。这一工艺先进行皂化,然后乳化,过程复杂。对压力要求较多,先进性高压匀质,然后真空脱气,对设备要求高。
公开号CN101433528A描述了一种从叶黄素晶体制备稳定水分散的叶黄素微胶囊的方法。采用瞬时高温60-150℃熔融法对叶黄素晶体进行溶解,添加乳化基质进行乳化,经高压均质机将活性化合物均质,制备成纳米级叶黄素溶液,采用流化床制粒包衣,将囊材通过雾滴表面吸附并冷凝成型,过筛,包装。这一工艺对叶黄素纯度要求高,不适于叶黄素粗品。常压高温60-150℃不能保证叶黄素晶体熔融,且叶黄素性质不稳定,加热过程中可能发生变质。
总之,上述这些已知技术揭示的叶黄素水溶性制剂的制备方法中操作条件要求较高,操作过程复杂,工业化生产较难。本发明的操作过程简单,对设备要求较少,利于工业化生产。
发明内容
本发明的目的是提供一种水溶性良好且性质稳定的叶黄素水溶性粉末制备工艺。
本发明的是通过如下方案实现的:
本发明所述的叶黄素水溶性粉末的处方组成及重量比为叶黄素:载体:附加剂为1:1-10:0-3。
其中所述的叶黄素为叶黄素含量至少50%的叶黄素粉末或叶黄素晶体;
其中所述的载体为:
A. 聚维酮为C15、C30、K-25、K29/32、K90、K90D中的任意一种或它们的任意比混合物;
B. 聚乙二醇为聚乙二醇1500、聚乙二醇2000、聚乙二醇3000、聚乙二醇4000、聚乙二醇6000、聚乙二醇8000中的任意一种或它们的任意比混合物;
C. 甘露糖、半乳糖、胆酸中的任意一种或它们的任意比混合物。
其中所述附加剂为:
A. 聚山梨酯为吐温60、吐温61、吐温65、吐温80、吐温81、吐温85中的任意一种或它们的任意比混合物;
B. 山梨醇脂肪酸酯为司盘60、司盘65、司盘80、司盘83、司盘85中的任意一种或它们的任意比混合物;
C. 脂肪酸蔗糖酯为SE12、SE13、SE14、SE15中的任意一种或它们的任意比混合物;
D. 生育酚、抗坏血酸、叔丁基羟苯基甲醚中的一种或它们的任意比混合物。
本发明按下述方法制备:
将叶黄素、载体材料和附加剂中至少两种混合后,加入有机溶剂搅拌溶解,加热温度为20-50℃,保温时间为5-30分钟,而后在温度30-85℃,真空度为0-1兆帕条件下蒸干,粉碎,即得。
整个制备过程在避光条件下进行。
其中所述的溶剂为:丙酮、无水乙醇、95乙醇、乙酸乙酯中的一种或它们的任意比混合物。
本发明制备的叶黄素水溶性粉末,和药学上接受的载体混合,可制成片剂、胶囊、散剂或制成速释制剂,或任一形式的功能食品。
本发明操作简便,制得的叶黄素水溶性粉末水溶性良好、稳定性高且流动性好,溶出率可达96%以上,可应用于各种剂型或以食品添加剂的形式加入到各种食品中。亦可制成任意形式的药品或功能食品。
本发明的优点:
1. 本发明制得的叶黄素水溶性粉末使其水溶性大大提高,改变叶黄素的溶解性,扩大叶黄素的应用范围。
2. 增加了叶黄素的稳定性。优良的流动性使其可以用于压片,装胶囊,或添加入各种功能食品中。
3. 本发明制得的叶黄素水溶性粉末可加入饮料,乳制品,口服液中。
附图说明:
图1为叶黄素水溶性粉末溶出曲线:
具体实施方式:
下面的示例有助于我们进一步详细阐述本发明,而不应被解释为限制本发明的范围。
本发明中叶黄素的吸光度检测方法是紫外可见光光度法,空白液为纯化水,检测波长为446nm。
体外溶出度试验按中国药典2010版附录中第三法(小杯法)测定药物体外溶出度。介质为30%乙醇溶液,转速50rpm,温度为37±0.5℃。
实施例1
取5g高纯度叶黄素晶体、5g聚维酮K90、2.5g吐温70,50毫升丙酮搅拌5分钟后充分溶解,常压水浴60℃蒸干。待脆化后,取出粉碎过80目筛即得。
实施例2
取10g80%叶黄素、20g聚乙二醇2000、10g吐温65,60毫升乙酸乙酯,搅拌10分钟后充分溶解,真空度0.7兆帕水浴30℃蒸干。待脆化后,取出粉碎过80目筛即得。
实施例3
取15g70%叶黄素、45g 聚维酮K29和10g脂肪酸蔗糖酯SE15,100毫升无水乙醇,搅拌20分钟后充分溶解,真空度0.9兆帕水浴35℃蒸干。待脆化后,取出粉碎过80目筛即得
实施例4
取20g60%叶黄素、100g聚维酮K30和10g司盘75,200毫升95乙醇,搅拌30分钟后充分溶解,真空度1兆帕水浴35℃蒸干。待脆化后,取出粉碎过80目筛即得。
实施例5
取15g70%叶黄素、105g聚乙二醇4000 、5g十聚甘油硬脂酸酯和9g抗坏100毫升乙酸乙酯,搅拌10分钟后充分溶解,真空度0.7兆帕水浴30℃蒸干。待脆化后,取出粉碎过80目筛即得。
实施例6
取20g60%叶黄素、200g半乳糖、5g司盘20、5g吐温70和30gα—生育酚150毫升95乙醇,搅拌25分钟后充分溶解,真空度1兆帕水浴35℃蒸干。待脆化后,取出粉碎过80目筛即得。
溶解度试验:
取实施例1制得的叶黄素水溶性粉末20g,采用溶质质量法测定其溶解度。称取100g水于250ml烧杯中,加入水溶性叶黄素20g,20℃水浴不断搅拌。多余粉末较长时间(5min)不再溶解,则得到叶黄素水溶性粉末的饱和溶液。通过加热蒸发、称量,得到其中溶质质量为11.5g。计算得溶解度为11.5g,其中含叶黄素4.6g。由此可得叶黄素水溶性粉末为易溶,并将叶黄素由不溶提高至溶解。
S=溶质质量(g)/溶剂质量(g)×100g
溶出度试验:
取实施例2制得的叶黄素水溶性粉末100g,平均分成两份。一份W1用1000ml人工胃液完全溶解,放于37℃±0.5℃水浴中静置30min,取样,滤过,用紫外分光光度计于446nm处测定其吸光度E值。另一份W2用37℃±0.5℃的人工胃液1000ml 加搅拌桨溶解,每隔5分钟取样,测其吸光度Ei,计算其百分溶出量。结果见表1及图1
百分溶出量=W1×Ei/W2×E
取实施例5制得的叶黄素水溶性粉末100g,及同批次的叶黄素晶体原料100g,按照光照影响因素,高温影响因素试验做稳定性考察。
光照影响因素试验:
取上述样品各10g,分成若干份,置于4500LX灯箱中,分别于0时,1时,2时,4时,8时,12时,24时,48时取样测定叶黄素的吸光度值,计算保存率。
保存率=(测定吸光度/初始吸光度)×100%
结果见表2。
高温影响试验:
取上述样品各10g,分成若干份,置于70℃恒温箱中,分别于0时,1时,2时,4时,8时,12时,24时,48时取样测定叶黄素的吸光度值,计算保存率。
微粉的流动性试验:
取适量实施例6值得的叶黄素水溶性粉末,将4×1×1厘米的矩形盒装满,其松实程度适宜,将盒子逐步倾斜至叶黄素水溶性粉末开始流出为止。盒子倾斜的角度为休止角。平行测定3次,35度、34度、34度,平均得叶黄素固体分散体的休止角为34度,可以满足工业生产的流动性需求。
结果见表3。
表1叶黄素水溶性粉末中叶黄素的溶出度测定数据及计算结果(E=0.51)
取样时间(min) | 吸光度Ei | 百分溶出量(%) | 残留待溶量(%) |
0 | 0.0617 | 12.1 | 87.9 |
5 | 0.1237 | 24.25 | 75.75 |
10 | 0.2809 | 55.08 | 44.92 |
15 | 0.3701 | 72.57 | 27.43 |
20 | 0.4552 | 89.25 | 10.75 |
25 | 0.4889 | 95.86 | 4.14 |
30 | 0.4909 | 96.25 | 3.75 |
35 | 0.501 | 98.23 | 1.77 |
40 | 0.5061 | 99.23 | 0.77 |
45 | 05073 | 99.47 | 0.53 |
表2光照(4500LX)对叶黄素稳定性的影响:
时间 | 样品 | 保存率 |
0时 | 叶黄素晶体 | 100% |
叶黄素水溶性粉末 | 100% | |
1时 | 叶黄素晶体 | 63% |
叶黄素水溶性粉末 | 98% | |
2时 | 叶黄素晶体 | 52% |
叶黄素水溶性粉末 | 96% | |
4时 | 叶黄素晶体 | 36% |
叶黄素水溶性粉末 | 96% | |
8时 | 叶黄素晶体 | 23% |
叶黄素水溶性粉末 | 95% | |
12时 | 叶黄素晶体 | 7% |
叶黄素水溶性粉末 | 95% | |
24时 | 叶黄素晶体 | 0% |
叶黄素水溶性粉末 | 94% | |
48时 | 叶黄素晶体 | 0% |
叶黄素水溶性粉末 | 94% |
表3 高温对叶黄素稳定性的影响:
时间 | 样品 | 保存率 |
0时 | 叶黄素晶体 | 100% |
叶黄素水溶性粉末 | 100% | |
1时 | 叶黄素晶体 | 61% |
叶黄素水溶性粉末 | 98% | |
2时 | 叶黄素晶体 | 50% |
叶黄素水溶性粉末 | 97% | |
4时 | 叶黄素晶体 | 32% |
叶黄素水溶性粉末 | 95% | |
8时 | 叶黄素晶体 | 18% |
叶黄素水溶性粉末 | 93% | |
12时 | 叶黄素晶体 | 0% |
叶黄素水溶性粉末 | 93% | |
24时 | 叶黄素晶体 | 0% |
叶黄素水溶性粉末 | 91% | |
48时 | 叶黄素晶体 | 0% |
叶黄素水溶性粉末 | 91% |
Claims (3)
1.叶黄素水溶性粉末,其特征在于,取5g高纯度叶黄素晶体、5g聚维酮K90、2.5g吐温70,50毫升丙酮搅拌5分钟后充分溶解,常压水浴60℃蒸干,待脆化后,取出粉碎过80目筛即得。
2.叶黄素水溶性粉末,其特征在于,取10g80%叶黄素、20g聚乙二醇2000、10g吐温65,60毫升乙酸乙酯,搅拌10分钟后充分溶解,真空度0.7兆帕水浴30℃蒸干,待脆化后,取出粉碎过80目筛即得。
3.叶黄素水溶性粉末,其特征在于,取15g70%叶黄素、105g聚乙二醇4000 、5g十聚甘油硬脂酸酯和9g抗坏血酸,100毫升乙酸乙酯,搅拌10分钟后充分溶解,真空度0.7兆帕水浴30℃蒸干,待脆化后,取出粉碎过80目筛即得。
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