CN113599479A - 一种降低同型半胱氨酸的组合物及其应用 - Google Patents
一种降低同型半胱氨酸的组合物及其应用 Download PDFInfo
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- CN113599479A CN113599479A CN202110881791.3A CN202110881791A CN113599479A CN 113599479 A CN113599479 A CN 113599479A CN 202110881791 A CN202110881791 A CN 202110881791A CN 113599479 A CN113599479 A CN 113599479A
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- choline
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Abstract
本发明提供一种含胆碱类化合物和姜黄提取物的组合物及其在降低同型半胱氨酸的应用。
Description
技术领域
本发明涉及一种组合物,特别涉及一种种降低同型半胱氨酸的组合物及其应用。
背景技术
同型半胱氨酸是人体中常见的一种氨基酸。随着科学研究的加深,人们发现高同型半胱酸与心血管疾病,中风,癌症,糖尿病,老年痴呆有着密切的联系。同型半胱氨酸值是除了血糖,血脂,血压外的第四种基础健康指标,应当被给与足够的关注和重视。
因此,具有降低同型半胱氨酸效果的组合物,是很需要的;尤其是既能够用于药物、辅助药物治疗,又能够用作膳食补充剂,比如在体检发现同型半胱酸指标异常后,可以作为膳食补充剂进行调节该指标,以避免更大的健康风险出现。
发明内容
本发明的目的在于针对现有技术的不足之处,提供一种降低同型半胱氨酸的组合物。
组合物包括胆碱类化合物和姜黄提取物;
胆碱类化合物包括:卵磷脂,胞磷二胆碱,酒石酸氢胆碱,氯化胆碱,甘油磷酰胆碱及他们的酸,盐,酯,螯合物,异构体及异构体的酸,盐,脂,螯合物。
姜黄提取物包括:一个或两种以上的姜黄素类化合物;姜黄素类化合物包括:姜黄素,二氢姜黄素,四氢姜黄素,六氢姜黄素脱甲氧基姜黄素,脱二甲氧基姜黄素)及他们的酸,盐,酯,螯合物,异构体及异构体的酸,盐,脂,螯合物。
进一步的,胆碱类化合物为0.05-50份,姜黄提取物为0.1-20份;优选的,胆碱类化合物为2.5份,姜黄提取物为1份;优选的,胆碱类化合物为0.1-20份,姜黄提取物为0.5-10份;优选的,胆碱类化合物为1-8份,姜黄提取物为0.5-5份;优选的,胆碱类化合物为8份,姜黄提取物为0.8份。
在另一个实施方案中,胆碱类化合物折算为胆碱的量为0.05-50份,姜黄提取物为0.1-20份;优选的,胆碱类化合物折算为胆碱的量为2.5份,姜黄提取物为1份;优选的,胆碱类化合物折算为胆碱的量为0.1-20份,姜黄提取物为0.5-10份;优选的,胆碱类化合物折算为胆碱的量为1-8份,姜黄提取物为0.5-5份;优选的,胆碱类化合物折算为胆碱的量为2.5份,姜黄提取物为1份。
优选的,胆碱类化合物折算为胆碱的量0.01mg-50g/天,姜黄提取物为0.01mg-50g/天;优选的,胆碱类化合物折算为胆碱的量0.1mg-1g/天,姜黄提取物为0.1mg-1g/天;优选的,胆碱类化合物折算为胆碱的量250mg/天,姜黄提取物为100mg/天;
本发明中所述的组合物的产品可以为各种剂型,包括也不局限于药品常见剂型,如粉剂、凝胶、口服液、硬胶囊、软胶囊,也可以为保健食品和膳食补充剂的常见剂型,如饮料、固体饮料、软饮料、硬胶囊、软胶囊、多层硬胶囊、溶豆、冻干粉、奶豆、巧克力、夹心软糖、夹心巧克力、茶饮料、冷萃咖啡,营养棒。
本发明还提供了一种降低同型半胱氨酸的组合物的制备方法,包括将胆碱类化合物和姜黄提取物混合,进一步的,胆碱类化合物为0.05-50份,姜黄提取物为0.1-20份;优选的,胆碱类化合物为2.5份,姜黄提取物为1份;优选的,胆碱类化合物为0.1-20份,姜黄提取物为0.5-10份;优选的,胆碱类化合物为1-8份,姜黄提取物为0.5-5份;优选的,胆碱类化合物为8份,姜黄提取物为0.8份。
在另一个实施方案中,胆碱类化合物折算为胆碱的量为0.05-50份,姜黄提取物为0.1-20份;优选的,胆碱类化合物折算为胆碱的量为2.5份,姜黄提取物为1份;优选的,胆碱类化合物折算为胆碱的量为0.1-20份,姜黄提取物为0.5-10份;优选的,胆碱类化合物折算为胆碱的量为1-8份,姜黄提取物为0.5-5份;优选的,胆碱类化合物折算为胆碱的量为2.5份,姜黄提取物为1份。
优选的,胆碱类化合物折算为胆碱的量0.01mg-50g/天,姜黄提取物为0.01mg-50g/天;优选的,胆碱类化合物折算为胆碱的量0.1mg-10g/天,姜黄提取物为0.1mg-1g/天;优选的,胆碱类化合物折算为胆碱的量2500mg/天,姜黄提取物为1000mg/天。
本发明还提供了一种降低同型半胱氨酸的方法,包括添加胆碱类化合物和姜黄提取物。优选的,胆碱类化合物折算为胆碱的量0.01mg-50g/天,姜黄提取物为0.01mg-50g/天;优选的,胆碱类化合物折算为胆碱的量0.1mg-10g/天,姜黄提取物为0.1mg-10g/天;优选的,胆碱类化合物折算为胆碱的量2500mg/天,姜黄提取物为1000mg/天。
本发明还提供了一种胆碱类化合物和姜黄提取物组合使用在制备降低同型半胱氨酸的产品中的用途,组合物包括胆碱类化合物和姜黄提取物;本发明还提供了一种胆碱类化合物和姜黄提取物组合使用在制备预防、控制、治疗阿尔茨海默病的产品中的用途,组合物包括胆碱类化合物和姜黄提取物;本发明还提供了一种胆碱类化合物和姜黄提取物组合使用在制备预防、控制、治疗老年痴呆相关疾病的产品中的用途,组合物包括胆碱类化合物和姜黄提取物。
胆碱类化合物包括:卵磷脂,胞磷二胆碱,酒石酸氢胆碱,氯化胆碱,甘油磷酰胆碱)及他们的酸,盐,酯,螯合物,异构体及异构体的酸,盐,脂,螯合物。
姜黄提取物包括:一个或两种以上的姜黄素类化合物;姜黄素类化合物包括:姜黄素,二氢姜黄素,四氢姜黄素,六氢姜黄素脱甲氧基姜黄素,脱二甲氧基姜黄素)及他们的酸,盐,酯,螯合物,异构体及异构体的酸,盐,脂,螯合物。
进一步的,胆碱类化合物为0.05-50份,姜黄提取物为0.1-20份;优选的,胆碱类化合物为2.5份,姜黄提取物为1份;优选的,胆碱类化合物为0.1-20份,姜黄提取物为0.5-10份;优选的,胆碱类化合物为1-8份,姜黄提取物为0.5-5份;优选的,胆碱类化合物为8份,姜黄提取物为0.8份。
在另一个实施方案中,胆碱类化合物折算为胆碱的量为0.05-50份,姜黄提取物为0.1-20份;优选的,胆碱类化合物折算为胆碱的量为2.5份,姜黄提取物为1份;优选的,胆碱类化合物折算为胆碱的量为0.1-20份,姜黄提取物为0.5-10份;优选的,胆碱类化合物折算为胆碱的量为1-8份,姜黄提取物为0.5-5份;优选的,胆碱类化合物折算为胆碱的量为2.5份,姜黄提取物为1份。
优选的,胆碱类化合物折算为胆碱的量0.01mg-50g/天,姜黄提取物为0.01mg-50g/天;优选的,胆碱类化合物折算为胆碱的量0.1mg-10g/天,姜黄提取物为0.1mg-1g/天;优选的,胆碱类化合物折算为胆碱的量2500mg/天,姜黄提取物为1000mg/天;
本发明中所述的组合物的产品可以为各种剂型,包括也不局限于药品常见剂型,如粉剂、凝胶、口服液、硬胶囊、软胶囊,也可以为保健食品和膳食补充剂的常见剂型,如饮料、固体饮料、软饮料、硬胶囊、软胶囊、多层硬胶囊、溶豆、冻干粉、奶豆、巧克力、夹心软糖、夹心巧克力、茶饮料、冷萃咖啡,营养棒。
发明人发现,胆碱类化合物和姜黄提取物的组合能够显著降低同型半胱氨酸。
现有技术中有提及到姜黄素能够降低同型半胱氨酸,但并没有给出具体的机理解释。现有技术中有胆碱类化合物降低同型半胱氨酸的机理解释,该解释有所争议,但被大多数学者认可。胆碱类化合物在胆碱氧化酶的作用下,在体内二次氧化,然后在甜菜碱-同型半胱氨酸甲基转移酶的作用下,参与蛋氨酸循环,为同型半胱氨酸提供甲基,使其转化为蛋氨酸,因此降低体内同型半胱氨酸的含量。
本发明中所述的包括胆碱类化合物和姜黄提取物的组合物的产品的各种剂型可以按照药品、保健食品、普通食品、日化、饲料、添加剂等的常规生产制备方法制备。将该组分中的一种或者多种载体混合,然后制成所需的剂型。
本发明还提供一种包括胆碱类化合物和姜黄提取物的组合物的产品的制备方法,包括将胆碱类化合物和姜黄提取物混合,灌装。
在一个实施方式中,本发明中所述的产品制备方法是:可选择的将需要控制水分指标的物料制粒或不制粒后至生产所需水分指标,将胆碱类化合物和姜黄提取物混合,可选择的加入物料所需流动剂后进行胶囊灌装,可选择的将灌装好的胶囊挑选出不合格的后进行包衣(肠溶包衣)或不包衣,可选择的将包衣后的胶囊根据包装所需规格数量灌装至内包材即可。
在一个实施方式中,本发明中所述的产品制备方法是:将胆碱类化合物和姜黄提取物混合制备芯材,可选择性的芯材加入甜味剂和/或食用胶,尤其是吸水性高的食用胶,并采用食用胶制备为壁材,可选择的加入物料所需流动剂和/或增稠剂后制备为夹心糖果或软胶囊。
在一个实施方式中,本发明中所述的产品制备方法是:将胆碱类化合物和姜黄提取物混合,溶于溶剂,该溶液可以是水溶液、盐溶液、果汁等呈现出液体状态的溶剂,然后灌装成品。
具体实施方式
为了便于本领域技术人员的理解,下面结合实施例对本发明作进一步的说明,实施方式提及的内容并非对本发明的限定。
实施例1
一种组合物,包括胞磷二胆碱和姜黄素,胞磷二胆碱为8份,姜黄素为0.8份。
实施例2
一种组合物,包括胞磷二胆碱和姜黄素,胞磷二胆碱为0.5份,姜黄素为1份。
实施例3
一种组合物,包括胞磷二胆碱和姜黄素,胞磷二胆碱为2.5份,姜黄素为1份。
实施例4
一种组合物,包括卵磷脂和姜黄素,卵磷脂为2.5份,姜黄素为1份。
实施例5
一种组合物,包括卵磷脂和姜黄素,卵磷脂为8份,姜黄素为1份。
实施例6
一种组合物,包括卵磷脂和姜黄素,卵磷脂为0.5份,姜黄素为1份。
实施例7
一种组合物,包括卵磷脂和姜黄提取物,卵磷脂为8份,姜黄提取物为1份,姜黄提取物95%以上为姜黄素类化合物。
实施例8
一种组合物,包括卵磷脂和姜黄提取物,卵磷脂为50份,姜黄提取物为1份,姜黄提取物95%以上为姜黄素类化合物。
实施例9
一种组合物,包括卵磷脂和姜黄提取物,卵磷脂为2.5份,姜黄提取物为10份,姜黄提取物95%以上为姜黄素类化合物。
实施例10
一种组合物,包括卵磷脂和姜黄提取物,卵磷脂为2.5份,姜黄提取物为1份,姜黄提取物90%以上为姜黄素类化合物。
实施例11
一种组合物,包括卵磷脂和姜黄提取物,卵磷脂折算为胆碱的量为2.5份,姜黄提取物为1份,姜黄提取物90%以上为姜黄素类化合物。
实施例12
一种组合物,包括卵磷脂和姜黄提取物,卵磷脂折算为胆碱的量为10份,姜黄提取物为1份,姜黄提取物90%以上为姜黄素类化合物。
实施例13
一种组合物,包括卵磷脂和姜黄提取物,卵磷脂折算为胆碱的量为50份,姜黄提取物为1份,姜黄提取物90%以上为姜黄素类化合物。
实施例14
一种组合物,包括卵磷脂和姜黄提取物,卵磷脂折算为胆碱的量为50份,姜黄提取物为15份,姜黄提取物95%以上为姜黄素类化合物。
实施例15
一种组合物,包括卵磷脂和姜黄提取物,卵磷脂折算为胆碱的量为8份,姜黄提取物为6份,姜黄提取物95%以上为姜黄素类化合物。
实施例16
一种组合物,包括卵磷脂和二氢姜黄素,卵磷脂折算为胆碱的量为2.5份,二氢姜黄素为1份。
实施例17
一种组合物,包括卵磷脂和四氢姜黄素,卵磷脂折算为胆碱的量为2.5份,四氢姜黄素为1份。
实施例18
一种组合物,包括卵磷脂和六氢姜黄素,卵磷脂折算为胆碱的量为2.5份,六氢姜黄素为1份。
实施例19
一种组合物,包括卵磷脂和脱甲氧基姜黄素,卵磷脂折算为胆碱的量为2.5份,脱甲氧基姜黄素为1份。
实施例20
一种组合物,包括卵磷脂和脱二甲氧基姜黄素,卵磷脂折算为胆碱的量为2.5份,脱二甲氧基姜黄素为1份。
实施例21
一种组合物,包括氯化胆碱和姜黄素,氯化胆碱为2.5份,姜黄素为1份。
实施例22
一种组合物,包括甘油磷酰胆碱和姜黄素,甘油磷酰胆碱为2.5份,姜黄素为1份。
实施例23
一种组合物,包括氯化胆碱钠和姜黄素,氯化胆碱钠为2.5份,姜黄素为1份。
实施例24
一种组合物,包括甘油磷酰胆碱酯和姜黄素,甘油磷酰胆碱酯为2.5份,姜黄素为1份。
实施例25
一种组合物,包括甘油磷酰胆碱钙和姜黄素,甘油磷酰胆碱钙为2.5份,姜黄素为1份。
实施例26
一种降低同型半胱氨酸的组合物的制备方法,包括将胆碱类化合物和姜黄提取物混合,包括氯化胆碱钠和姜黄素,氯化胆碱钠为2.5份,姜黄素为1份。
实施例27
一种降低同型半胱氨酸的方法,包括添加胆碱类化合物和姜黄提取物。包括氯化胆碱钠和姜黄素,胆碱类化合物折算为胆碱的量2500mg/天,姜黄提取物为1000mg/天。
实施例28
一种胆碱类化合物和姜黄提取物组合使用在制备降低同型半胱氨酸的产品中的用途,组合物包括胆碱类化合物和姜黄提取物;包括氯化胆碱钠和姜黄素,胆碱类化合物折算为胆碱的量2500mg/天,姜黄提取物为1000mg/天。
实施例29
一种包括胆碱类化合物和姜黄提取物的组合物的产品的制备方法,包括将胆碱类化合物和姜黄提取物混合,灌装。包括卵磷脂和姜黄素,氯化胆碱钠为2.5份,姜黄素为1份。
实施例30
一种包括胆碱类化合物和姜黄提取物的组合物的软胶囊的制备方法,包括将胆碱类化合物和姜黄提取物混合,灌装。包括卵磷脂和姜黄素,氯化胆碱钠为2.5份,姜黄素为1份。
实验例
选取大鼠180g~200g,大鼠在20~25摄氏度条件下喂养,给予日常鼠粮和蒸馏水饲养,不限制进食量及饮水量。分成4组,每组10只雌雄各半。
人工光照周期下动物房内,喂食和喂水8周,测试血液中同型半胱氨酸的含量。
喂食饲料如下:
1.控制组:大鼠饲料
2.卵磷脂组:大鼠饲料中混入液体卵磷脂8.3g/kg/day(含有胆碱约250mg/kg/day)
3.姜黄组:大鼠饲料中混入姜黄100mg/kg/day(95%姜黄素类化合物)
4.混合组:大鼠饲料中混入8.3g/kg/day液体卵磷脂+100mg/kg/day姜黄。
同型半胱氨酸的测量:100μL的待测血样和30μL硼氢化钠,5μL正辛醇混合。N-乙酰半胱氨酸作为内部标准。在血样混合液中加入100μL 0.6M/L的高氯酸,并使其含有1mM/L的乙二胺四乙酸(EDTA),然后在15000g的条件下离心分离10分钟,去除沉淀的蛋白质。取50μL上层澄清液,和10μL 1.55M/L的氢氧化钠溶液及125μL 0.125M/L的硼酸-EDTA缓冲液(46.67g硼酸,1L 4M/L EDTA-2Na溶液)混合,在含有50μL,1.0g/L,SBD-F的硼酸-EDTA缓冲液中,60摄氏度的黑暗条件下培养1小时。过程结束后,待测样在黑暗环境中冷却。进样40μL至液相中测试,C18 HPLC(5um,3.9*150mm)。在2%的甲醇0.08M/L醋酸溶液(pH=4)中等度洗脱,流速0.8mL/min,12分钟,用荧光检测器检测(Excitation 390nm,Emission 470nm)
表1血液中同型半胱氨酸浓度(μM/L)
Hcy | 控制组 | 胆碱组 | 姜黄组 | 混合组 |
Mean | 2.24±0.58 | 1.95±0.47 | 2.04±0.52 | 1.62±0.41 |
p | N/A | <0.05 | <0.05 | <0.05 |
相对于控制组,胆碱组同型半胱氨酸减少13%,p<0.05,与控制组相比差异显著。相对于控制组,姜黄组同型半胱氨酸减少9%,p<0.05,与控制组相比差异显著。相对于控制组,混合组同型半胱氨酸减少28%,p<0.05,与控制组相比差异显著。
现有技术中从未有人将胆碱类化合物和姜黄提取物的组合用于降低同型半胱氨酸。申请人发现,胆碱类化合物和姜黄提取物的组合用于降低同型半胱氨酸,能够起到协同降低同型半胱氨酸的作用。因为胆碱类化合物在降低体内同型半胱氨酸时,需要多种酶的协调参与;申请人预测,姜黄素会影响其中的某一种酶或者某几种酶的活力或者酶量,促进了胆碱降低同型半胱氨酸的效果,进而显示出协同降低同型半胱氨酸的效果。
本技术领域技术人员可以理解,除非另外定义,这里使用的所有术语(包括技术术语和科学术语),具有与本发明所属领域中的普通技术人员的一般理解相同的意义。还应该理解的是,诸如通用字典中定义的那些术语,应该被理解为具有与现有技术的上下文中的意义一致的意义,并且除非像这里一样被特定定义,否则不会用理想化或过于正式的含义来解释。
应当理解,以上借助优选实施例对本发明的技术方案进行的详细说明是示意性的而非限制性的。本领域的普通技术人员在阅读本发明说明书的基础上可以对各实施例所记载的技术方案进行修改,或者对其中部分技术特征进行等同替换;而这些修改或者替换,并不使相应技术方案的本质脱离本发明各实施例技术方案的精神和范围。
Claims (9)
1.一种组合物,其特征在于,包含胆碱类化合物和姜黄提取物。
2.根据权利要求1所述的组合物,其特征在于,胆碱类化合物包括:卵磷脂,胞磷二胆碱,酒石酸氢胆碱,氯化胆碱,甘油磷酰胆碱及他们的酸,盐,酯,螯合物,异构体及异构体的酸,盐,脂,螯合物的一种或两种以上组合;
和/或
姜黄提取物包括:姜黄素,二氢姜黄素,四氢姜黄素,六氢姜黄素脱甲氧基姜黄素,脱二甲氧基姜黄素,及他们的酸,盐,酯,螯合物,异构体及异构体的酸,盐,脂,螯合物的一种或两种以上组合。
3.根据权利要求1所述的组合物,其特征在于,胆碱类化合物为0.05-50份,姜黄提取物为0.1-20份;优选的,胆碱类化合物为2.5份,姜黄提取物为1份;优选的,胆碱类化合物为0.1-20份,姜黄提取物为0.5-10份;优选的,胆碱类化合物为1-8份,姜黄提取物为0.5-5份;优选的,胆碱类化合物为8份,姜黄提取物为0.8份。
4.根据权利要求1所述的组合物,其特征在于,胆碱类化合物折算为胆碱的量为0.05-50份,姜黄提取物为0.1-20份;优选的,胆碱类化合物折算为胆碱的量为2.5份,姜黄提取物为1份;优选的,胆碱类化合物折算为胆碱的量为0.1-20份,姜黄提取物为0.5-10份;优选的,胆碱类化合物折算为胆碱的量为1-8份,姜黄提取物为0.5-5份;优选的,胆碱类化合物折算为胆碱的量为2.5份,姜黄提取物为1份。
5.一种降低同型半胱氨酸的组合物的制备方法,其特征在于,包括将胆碱类化合物和姜黄提取物混合,进一步的,胆碱类化合物为0.05-50份,姜黄提取物为0.1-20份;优选的,胆碱类化合物为2.5份,姜黄提取物为1份;优选的,胆碱类化合物为0.1-20份,姜黄提取物为0.5-10份;优选的,胆碱类化合物为1-8份,姜黄提取物为0.5-5份;优选的,胆碱类化合物为8份,姜黄提取物为0.8份。
6.一种降低同型半胱氨酸的组合物的制备方法,其特征在于,包括将胆碱类化合物和姜黄提取物混合,进一步的,胆碱类化合物折算为胆碱的量为0.05-50份,姜黄提取物为0.1-20份;优选的,胆碱类化合物折算为胆碱的量为2.5份,姜黄提取物为1份;优选的,胆碱类化合物折算为胆碱的量为0.1-20份,姜黄提取物为0.5-10份;优选的,胆碱类化合物折算为胆碱的量为1-8份,姜黄提取物为0.5-5份;优选的,胆碱类化合物折算为胆碱的量为2.5份,姜黄提取物为1份。
7.根据权利要求5或6的方法,其特征在于,胆碱类化合物包括:卵磷脂,胞磷二胆碱,酒石酸氢胆碱,氯化胆碱,甘油磷酰胆碱及他们的酸,盐,酯,螯合物,异构体及异构体的酸,盐,脂,螯合物的一种或两种以上组合;
和/或
姜黄提取物包括:姜黄素,二氢姜黄素,四氢姜黄素,六氢姜黄素脱甲氧基姜黄素,脱二甲氧基姜黄素,及他们的酸,盐,酯,螯合物,异构体及异构体的酸,盐,脂,螯合物的一种或两种以上组合。
8.一种胆碱类化合物和姜黄提取物组合使用在制备降低同型半胱氨酸的产品中的用途,组合物包括胆碱类化合物和姜黄提取物;
进一步的,胆碱类化合物为0.05-50份,姜黄提取物为0.1-20份;优选的,胆碱类化合物为2.5份,姜黄提取物为1份;优选的,胆碱类化合物为0.1-20份,姜黄提取物为0.5-10份;优选的,胆碱类化合物为1-8份,姜黄提取物为0.5-5份;优选的,胆碱类化合物为8份,姜黄提取物为0.8份;
和/或
进一步的,胆碱类化合物折算为胆碱的量为0.05-50份,姜黄提取物为0.1-20份;优选的,胆碱类化合物折算为胆碱的量为2.5份,姜黄提取物为1份;优选的,胆碱类化合物折算为胆碱的量为0.1-20份,姜黄提取物为0.5-10份;优选的,胆碱类化合物折算为胆碱的量为1-8份,姜黄提取物为0.5-5份;优选的,胆碱类化合物折算为胆碱的量为2.5份,姜黄提取物为1份。
9.一种产品,其特征在于,包含权利要求1-4之一的组合物,所述产品为降低同型半胱氨酸的药物、保健品、普通食品、化妆品。
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