CN109453147B - 脂溶性维生素组合物及其应用 - Google Patents
脂溶性维生素组合物及其应用 Download PDFInfo
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- CN109453147B CN109453147B CN201811471362.3A CN201811471362A CN109453147B CN 109453147 B CN109453147 B CN 109453147B CN 201811471362 A CN201811471362 A CN 201811471362A CN 109453147 B CN109453147 B CN 109453147B
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- iron
- vitamin
- fat
- liver
- group
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/07—Retinol compounds, e.g. vitamin A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
本发明公开了一种脂溶性维生素组合物及其应用，所述的脂溶性维生素组合物，包括如下重量百分比的组份：维生素A 1％～30％，维生素D 1％～20％，维生素E 20％～60％，维生素K 3％～30％，动物试验证明，本发明的脂溶性维生素组合物对于促进肝脏储存铁的转化具有显著的作用，可以用于制备促进体内肝脏储存铁的转化利用的药物，从而使补铁更有效,降低高铁对肝脏的损伤。本发明可在口腔内吸收，通过口腔黏膜进入血液，不仅起效快，首过效应小，解决了因缺乏脂肪而无法吸收的问题，还可以促进体内肝脏储存铁的转化利用，从而使补铁更有效。本发明产品同时还具有抗氧化、抗衰老、促智力、防治眼睛疾病，促进骨骼生长等作用。
Description
技术领域
本发明涉及一种维生素组合物。
背景技术
铁是人体必需的重要营养元素。缺铁或铁利用不良将导致氧的运输、贮存、二氧化碳的运输及氧化还原等代谢过程的紊乱，影响生长发育，甚至贫血等各种疾病。机体若贮存铁不足或摄入铁不足，则会出现缺铁性贫血(Iron Deficiency Anemia,IDA)。IDA是指体内可用来制造血红蛋白的储存铁已被用尽或体内储存的铁不能正常被利用，红细胞生成障碍时所发生的贫血，是发病率最高的营养缺乏性疾病之一，且多见于儿童、妊娠妇女、哺乳妇女和慢性病患者。据WHO的报告，全世界有10％～30％的人群存在不同程度的缺铁，男性发病率为约10％，女性发病率则大于20％。据调查，我国患有不同程度的贫血症状的人群高达3800万。
目前缺铁性贫血的防治主要通过补铁剂来实现。常见补铁剂包括硫酸亚铁、氯化亚铁、葡萄糖酸亚铁、乳酸亚铁、琥珀酸亚铁和富马酸亚铁等。这些铁剂虽然含铁量高，但他们在体内的利用度低。要想达到理想的补铁效果，都是短期内大量服用补铁剂，从而出现恶心、胃胀、消化器官障碍、腹泻、便秘等症状。补铁的同时补充维生素C可促进铁的吸收是目前主要的方式，其机理是提高二价铁的稳定性，避免其在胃肠道被氧化成三价铁，从而失去补铁作用。但维生素C只能从源头加强铁的稳定性，却不能将摄入且储存在肝脏内的铁有效利用。
发明内容
本发明的目的是提供一种脂溶性维生素组合物及其应用，以克服现有技术存在的缺陷。
所述的脂溶性维生素组合物，包括如下重量百分比的组份：
优选的，包括如下重量百分比的组份：
优选的：
所述的维生素A选自醋酸视黄酯、棕榈酸视黄酯或β-胡萝卜素；
需要说明的是，在2016年第205号公告附件1(保健食品原料目录) 中，已经有明确的规定，所述的醋酸视黄酯、棕榈酸视黄酯和β-胡萝卜素为维生素A的来源物质。
所述的维生素D选自维生素D2或维生素D3，优选维生素D3；
所述的维生素E选自D-α生育酚、D-α醋酸生育酚、D-α琥珀酸生育酚、dl-α生育酚、dl-α醋酸生育酚或维生素E琥珀酸钙；
所述的维生素K选自维生素K1或维生素K2，优选维生素K2；
动物试验证明，本发明的脂溶性维生素组合物对于促进肝脏储存铁的转化具有显著的作用，可以用于制备促进体内肝脏储存铁的转化利用的药物，从而使补铁更有效。
本发明可以以制剂的形式，施加于需要治疗的患者。
所述的制剂，包括治疗有效量的所述的脂溶性维生素组合物和药学上可接受的载体，如甘露糖醇、乳糖、交联羧甲基纤维素钠、聚维酮；
剂量一般为80mg～300mg/天。
所述的脂溶性维生素组合物的制备方法如下：
将维生素A、维生素D、维生素E、维生素K和载体辅混合，采用本领域公知的方法，压片，获得所述的制剂。
其中载体的重量百分比含量为40～90％；
本发明可在口腔内吸收，通过口腔黏膜进入血液，不仅起效快，首过效应小，解决了因缺乏脂肪而无法吸收的问题，还可以促进体内肝脏储存铁的转化利用，从而使补铁更有效。本发明产品同时还具有抗氧化、抗衰老、促智力、防治眼睛疾病，促进骨骼生长等作用。
具体实施方式
实施例1
以重量计：维生素为28％，载体为72％；
以维生素总重量为基准，各个维生素的重量百分比如下：
以载体的总重量计：
甘露糖醇 99.3％
硬脂酸镁 余量
维生素A为β-胡萝卜素；
维生素D为维生素D3；
维生素E为D-α生育酚；
维生素K为维生素K2；
维生素A(20％)，其中，(20％)指的是有效成分含量；
维生素D(100000IU)，其中，(100000IU)指的是有效成分含量；维生素E(50％)，其中，(50％)指的是有效成分含量；
维生素K(4500ppm)，其中，(4500ppm)指的是有效成分含量；
制作方法：
1.除硬脂酸镁外，其他物料称量、混合、过20目筛后混合15min；
2.硬脂酸镁过40目筛后，与步骤1的产物混合5min；
3.将步骤2的混合粉压片，每片120mg。
实施例2
以重量计：维生素为19.5％，载体为80.5％；
以维生素总重量为基准，的重量百分比如下：
载体
甘露糖醇 99.4％
硬脂酸镁 余量
维生素A选自棕榈酸视黄酯；
维生素D选自维生素D3
维生素E选自D-α生育酚；
维生素K选自维生素K2；
制作方法：
1.除硬脂酸镁外，其他物料称量、混合、过20目筛后混合15min；
2.在步骤1的基础上添加硬脂酸镁，混合5min；
3.将2的混合粉压片，每片120mg。
实施例3
1.动物实验
(1)实验原理：建立缺铁性贫血模型，再给予受试样品，观察其对血液细胞学、血液生化学等指标的影响，可判定该受试样品对改善动物缺铁性贫血的作用。
(2)实验动物SD大鼠100只，雌性，体重40-60g，购浙江省实验动物中心，生产许可证号：SCXK(浙)2008-0033，质量合格证号：0014189；使用许可证号：SYXK(苏)2013-0037。
(3)低铁饲料
配方如下：
混合矿物盐配方:
混合维生素配方：
饲料配好后测定其铁元素的含量，结果为8.51mg/kg，符合实验要求。
(4)剂量分组及受试样品给予时间
分4组，每组大鼠16只；一个低铁空白对照组、一个硫酸亚铁组，一个实施例 1+硫酸亚铁组、一个实施例2+硫酸亚铁组，
(4)实验步骤
建立缺铁性贫血大鼠模型
健康断乳大鼠在实验环境下适应3天后饲予低铁饲料及去离子水，采用不锈钢笼及食罐，同时，采用剪尾取血法放血，5天一次，每次0.3－0.5ml。实验过程中避免铁污染。自第3周开始每周选取部分大鼠采尾血测Hb，第4周后多数动物Hb低于100g/L 时，测定全部大鼠的体重及Hb。
选取Hb<100g/L的大鼠48只作为实验动物，根据贫血大鼠Hb水平和体重将其随机分为低铁对照组、硫酸亚铁组和实施例1+硫酸亚铁组、实施例2+硫酸亚铁组，每组 12只，各组均继续饲予低铁饲料，空白对照组和实验组分别给予不同剂量的受试样品，具体如下：
低铁对照组给予的0.5％CMC-Na溶液(用蒸馏水配制)；
硫酸亚铁组：实际用品为七水合硫酸亚铁(铁含量为20.1％)，取0.149g样品，加90ml 0.5％CMC-Na溶液溶解，冰箱冷藏，备用。
实施例1+硫酸亚铁组：样品配置方法：取实施例11片，加20ml 0.5％CMC-Na 溶液溶解，冰箱冷藏，备用；
实施例2+硫酸亚铁组：样品配置方法：取实施例21片，加20ml 0.5％CMC-Na 溶液溶解，冰箱冷藏，备用；
受试样品给予时间45天，测定体重，采尾血测定Hb，股动脉放血取血致死，测定
血红细胞计数(RBC)、血清中铁含量，取肝脏测定肝脏中铁及各项血液学指标。
(5)观察指标
体重、血红蛋白、血清铁含量、肝脏铁含量
(6)数据统计处理方法
实验所得数值变量资料用SAS软件中的单因素方差分析进行多组间的比较，各
样品组与对照组两两之间的比较采用Student-Newman-Keuls检验。
2结果
2.1试验期间各组动物体重的变化见表1-1、1-2。
表1-1各实验组对大鼠体重(g)的影响(均值)
注：a与低铁对照组比较有显著性差异，p<0.05。
表1-2各实验组对大鼠体重(g)的影响(均值)(续)
注：a与低铁对照组比较有显著性差异，p<0.05；
经单因素方差分析，从第14天开始，各组大鼠体重的均值差异均有显著性(F＝2.41，P<0.05；F＝5.04，P<0.01；F＝7.06，P<0.01；F＝9.46，P<0.01；F＝12.73， P<0.01；F＝12.67，P<0.01)。经SNK检验，第14天实施例1+硫酸亚铁组、实施例2+硫酸亚铁组大鼠体重均值与低铁对照组比较差异均有显著性(P<0.05)；从第21天开始，硫酸亚铁阳性对照组大鼠体重均值与低铁对照组比较差异均有显著性(P<0.05)。
2.2试验期间各组动物体重增重的情况见表2-1、2-2。
经单因素方差分析，实验各周及最后3天，各组大鼠体重增重的均值差异均有显著性(F＝15.99，P<0.01；F＝14.89，P<0.01；F＝10.91，P<0.01；F＝6.83，P<0.01； F＝6.24，P<0.01；F＝8.41，P<0.01；F＝3.08，P<0.01)。
表2-1各实验组对大鼠体重增重(g)的影响(均值)
注：a与低铁对照组比较有显著性差异，p<0.05；
e与硫酸亚铁阳性对照组比较有显著性差异，p<0.05。
表2-2各实验组对大鼠体重增重(g)的影响(均值)(续)
注：a与低铁对照组比较有显著性差异，p＜0.05；
经单因素方差分析，实验前后各组大鼠体重增重的均值差异有显著性(F＝25.48，P<0.01)。经SNK检验，实验前后实施例1+硫酸亚铁组、实施例2+硫酸亚铁组、硫酸亚铁组大鼠体重增重均值与低铁对照组比较差异均有显著性(P<0.05)。
2.3大鼠Hb的影响
试验期间各组动物Hb的变化见表3。
表3各实验组对大鼠Hb(g/L)的影响(均值)
注：a与低铁对照组比较有显著性差异，p＜0.05；b与硫酸亚铁对照组有显著性差异，p<0.05
经单因素方差分析，实验前各组大鼠Hb的均值差异无显著性(F＝0.03， P>0.05)。
经单因素方差分析，实验第30天、第45天各组大鼠Hb的均值差异有显著性(F ＝6.46，P<0.01)。经SNK检验，实验第30天实施例1+硫酸亚铁组、实施例2+硫酸亚铁组、硫酸亚铁阳性对照组大鼠Hb均值与低铁对照组比较差异均有显著性(P<0.05)；实验第30天实施例2+硫酸亚铁组组与硫酸亚铁阳性对照组比较差异均有显著性(P<0.05)；实验第45天实施例1+硫酸亚铁、实施例2+硫酸亚铁与硫酸亚铁阳性对照组比较差异有显著性 (P<0.05)。
2.5大鼠血清铁含量、肝脏铁含量的影响
试验期结束时各组动物血清铁含量、肝脏铁含量的情况见表4。
表4各实验组对大鼠血清铁、肝脏铁含量的影响(均值)
注：a与低铁对照组比较有显著性差异，p＜0.05；b与硫酸亚铁阳性对照组比较有显著性差异，p＜0.05。
经单因素方差分析，实验结束时实施例组与硫酸亚铁对照组在大鼠血清铁含量方面的均值差异无显著性(F＝2.03，P>0.05)，但实施例组的血清铁含量稍高于硫酸亚铁组。
经单因素方差分析，实验结束时实施例组大鼠肝脏铁含量的均值差异无显著性，硫酸有显著性(F＝60.21，P<0.01)。经SNK检验，实验结束时实施例1+硫酸亚铁组、实施例2+硫酸亚铁组、硫酸亚铁阳性对照组大鼠肝脏铁含量均值与低铁对照组比较差异均有显著性(P<0.05)；实验结束时实施例1+硫酸亚铁组、实施例2+硫酸亚铁组大鼠肝脏铁含量均值与硫酸亚铁阳性对照组比较差异均有显著性(P<0.05)，说明实施例组可明显改善肝脏铁沉积问题。
Claims (3)
1.脂溶性维生素组合物在制备促进体内肝脏储存铁的转化利用药物中的应用，所述脂溶性维生素组合物，由如下重量百分比的组份组成：
2.根据权利要求1所述的应用，其特征在于，所述的维生素A选自醋酸视黄酯、棕榈酸视黄酯或β-胡萝卜素；
所述的维生素D选自维生素D2或维生素D3；
所述的维生素E选自D-α生育酚、D-α醋酸生育酚、D-α琥珀酸生育酚、dl-α生育酚、dl-α醋酸生育酚或维生素E琥珀酸钙；
所述的维生素K选自维生素K1或维生素K2。
3.根据权利要求2所述的应用，其特征在于，所述的维生素K为维生素K2；所述的维生素D为维生素D3。
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