CN105079009B - 预防和/或治疗心脑血管疾病的组合物 - Google Patents
预防和/或治疗心脑血管疾病的组合物 Download PDFInfo
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Abstract
本发明涉及一种预防和/或治疗心脑血管疾病的组合物,具体涉及一种具有预防和/或治疗心脑血管疾病的组合物及其制备方法和用途,其中,所述组合物包含二十二碳六烯酸或其酯、辅酶Q10、硫辛酸和磷脂中的至少两种,本发明的组合物相较于单一组分的应用,取得了预料不到的协同作用,作为膳食补充剂或药物组合物在防治心脑血管疾病方面均具有良好的应用前景。
Description
技术领域
本发明涉及医药和保健食品领域,具体涉及预防和/或治疗心脑血管疾病的组合物。
背景技术
心脑血管疾病是心脏血管和脑血管的疾病统称,泛指由于高脂血症、血液黏稠、动脉粥样硬化、高血压等所导致的心脏、大脑及全身组织发生缺血性或出血性疾病,是一种严重威胁人类,特别是50岁以上中老年人健康的常见病,即使应用目前最先进、完善的治疗手段,仍有50%以上的心脑血管意外幸存者生活不能完全自理,全世界每年死于心脑血管疾病的人数高达1500万人,居各种死因首位。
目前心脑血管疾病仍然是以预防为主,主要手段是控制危险因素和抗栓。心脑血管疾病发生的危险因素分为两大类,即可以处理的危险因素,如高血压、血脂紊乱、糖尿病、吸烟等,另一类是不可处理的危险因素,如年龄、性别和遗传。已经证明,控制血压在正常范围、治疗糖尿病、戒烟和治疗血脂紊乱可以明显降低心脑血管事件的发生。
现有技术已经公开了多种物质对于预防和治疗心脑血管疾病具有一定作用,但从未揭示何种组合会表现出协同作用。
发明内容
本发明的发明人经过不断实验,令人惊喜的发现了一系列对心脑血管具有保护作用的成分的组合,其在预防和/或治疗心脑血管疾病方面产生了预料不到的协同效应,本发明即是基于以上发现而完成。
本发明的第一方面提供一种组合物,其包含二十二碳六烯酸或其酯、辅酶Q10、硫辛酸和磷脂中的至少两种,例如两种、三种或四种。
在本发明的一个实施方案中,所述组合物包含选自以下的组合:二十二碳六烯酸或其酯以及辅酶Q10,二十二碳六烯酸或其酯以及硫辛酸,二十二碳六烯酸或其酯以及磷脂,辅酶Q10和硫辛酸,辅酶Q10和磷脂,硫辛酸和磷脂,二十二碳六烯酸或其酯、辅酶Q10和硫辛酸,二十二碳六烯酸或其酯、辅酶Q10和磷脂,二十二碳六烯酸或其酯、硫辛酸和磷脂,辅酶Q10、硫辛酸和磷脂,或者二十二碳六烯酸或其酯、辅酶Q10、硫辛酸和磷脂的组合;优选地,所述组合物为二十二碳六烯酸或其酯以及辅酶Q10的组合;更优选地,所述组合物为二十二碳六烯酸或其酯、辅酶Q10、硫辛酸和磷脂的组合。
根据本发明第一方面任一项所述的组合物,其按重量百分比计算包含0.5~80%的二十二碳六烯酸或其酯,例如5~80%,例如5~60%,例如5~57%,例如5~40%,例如5~30%,例如5~25%,例如5~10%,例如10~57%,例如10~40%,例如10~30%,例如10~25%,例如10~20%,例如20~57%,例如20~40%,例如20~30%,例如20~25%,例如30~57%,例如30~40%,例如40~57%。
在本发明的实施方案中,所述二十二碳六烯酸或其酯为微生物发酵提取物;优选地,所述微生物选自双鞭甲藻、裂殖壶菌、隐甲藻、硅藻和小球藻。
在本发明的实施方案中,所述二十二碳六烯酸的酯选自二十二碳六烯酸甲酯、二十二碳六烯酸乙酯、二十二碳六烯酸甘油酯、二十二碳六烯酸异丙酯和二十二碳六烯酸磷脂中的一种或多种。
根据本发明第一方面任一项所述的组合物,其按重量百分比包含0.5~60%的辅酶Q10,例如5~60%,5~55%,例如5~40%,例如5~30%,例如5~20%,例如5~10%,例如10~55%,例如10~40%,例如10~30%,例如10~20%,例如20~55%,例如20~40%,例如20~30%,例如30~55%,例如30~40%,例如40~55%,。
在本发明的实施方案中,所述辅酶Q10为微生物发酵提取物;优选地,所述微生物选自深红红螺菌、沼泽红假单胞菌、类球红细菌、嗜硫小红卵菌和荚膜红假单胞菌。
在本发明的实施方案中,所述辅酶Q10选自氧化型辅酶Q10和还原型辅酶Q10中的一种或两种。
根据本发明第一方面任一项所述的组合物,其按重量百分比包含0.5~60%的硫辛酸,例如5~60%,例如5~50%,例如5~40%,例如5~30%,例如5~20%,例如5~10%,例如10~50%,例如10~40%,例如10~30%,例如10~20%,例如20~50%,例如20~40%,例如20~30%,例如30~50%,例如30~40%,例如40~50%。
在本发明的实施方案中,所述硫辛酸选自氧化型硫辛酸和还原型硫辛酸中的一种或两种;优选地,所述还原型硫辛酸为二氢硫辛酸。
根据本发明第一方面任一项所述的组合物,其按重量百分比包含0.1~60%的磷脂,例如2~50%,例如2%~35%,例如2~30%,例如2~15%,例如2~10%,例如10~35%,例如10~30%,例如10~20%,例如20~35%,例如20~30%,例如30~35%,例如5%,例如20%。
在本发明的实施方案中,所述磷脂选自羟化磷脂、磷脂酰胆碱、磷脂酰乙醇胺、磷脂酰丝氨酸、磷脂酰甘油、二磷脂酰甘油、磷脂酰肌醇、鞘磷脂等中的一种或几种;优选地,所述磷脂选自羟化卵磷脂和磷脂酰丝氨酸。
在本发明的一个实施方案中,所述磷脂为天然大豆提取物。
根据本发明第一方面任一项所述的组合物,其还包含选自以下的一种或多种(例如两种,三种,四种或五种):原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖。
在本发明的一个实施方案中,所述组合物还包含选自以下的组合:原花青素和大豆异黄酮,原花青素和叶黄素,原花青素和三七总皂苷,原花青素和β-葡聚糖,大豆异黄酮和叶黄素,大豆异黄酮和三七总皂苷,大豆异黄酮和β-葡聚糖,叶黄素和三七总皂苷,叶黄素和β-葡聚糖,或者三七总皂苷和β-葡聚糖;优选地,其还包含原花青素和大豆异黄酮,大豆异黄酮和叶黄素,叶黄素和三七总皂苷,三七总皂苷和β-葡聚糖,原花青素、大豆异黄酮和叶黄素,原花青素、大豆异黄酮和三七总皂苷,原花青素、大豆异黄酮和β-葡聚糖,原花青素、叶黄素和三七总皂苷,原花青素、叶黄素和β-葡聚糖,原花青素、三七总皂苷和β-葡聚糖,大豆异黄酮、叶黄素和三七总皂苷,大豆异黄酮、叶黄素和β-葡聚糖,或者大豆异黄酮、三七总皂苷和β-葡聚糖的组合;进一步优选地,其还包含原花青素、大豆异黄酮和叶黄素,大豆异黄酮、叶黄素和三七总皂苷,叶黄素、三七总皂苷和β-葡聚糖,原花青素、大豆异黄酮、叶黄素和三七总皂苷,原花青素、大豆异黄酮、叶黄素和β-葡聚糖,原花青素、叶黄素、三七总皂苷和β-葡聚糖,或者大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖,更进一步优选地,其还包含原花青素、大豆异黄酮、叶黄素和三七总皂苷,或者大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖,或者原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖,此时各组分的质量比为(1~400):(2~250):(1~200):(5~20):(2~5):1:(2~5):(0.1~5):(0.1~5)。
根据本发明第一方面任一项所述的组合物,其按重量百分比包含0.1~15%的原花青素,例如0.1~11%,例如0.1~1%,例如1~11%。
在本发明的一个实施方案中,所述原花青素来自葡萄籽提取物。
根据本发明第一方面任一项所述的组合物,其按重量百分比包含0.1~8%的大豆异黄酮,例如0.1~5.5%。
在本发明的一个实施方案中,所述大豆异黄酮来自大豆胚芽提取物。
根据本发明第一方面任一项所述的组合物,其按重量百分比包含0.1~10%的叶黄素,例如0.1~1%,例如1~10%,例如0.5~10%,例如0.5~5%。
在本发明的一个实施方案中,所述叶黄素来自万寿菊提取物。
根据本发明第一方面任一项所述的组合物,其按重量百分比包含0.1~8%的三七总皂苷,例如0.1~6%,例如0.1~1%,例如0.1~3%,例如1~6%。
在本发明的一个实施方案中,所述三七总皂苷来自三七提取物。
根据本发明第一方面任一项所述的组合物,其按重量百分比包含0.1~8%的β-葡聚糖,例如0.1~6%,例如0.1~1%,例如0.1~3%,例如1~6%。
在本发明的一个实施方案中,所述β-葡聚糖为燕麦提取物。
根据本发明第一方面任一项所述的组合物,余量为载体油。
在本发明的实施方案中,所述载体油选自天然植物油脂、天然动物油脂和人工合成油脂中的一种或几种,其选自大豆油、菜籽油、橄榄油、芝麻油、玉米油、棕榈油、葵花油、芥子油、米糠油、椰子油、亚麻籽油、月见草油、大蒜油、荷荷巴油、猪油、牛脂、鱼油、黄油和中链甘油三酯中的一种或几种,优选地,所述中链甘油三酯选自饱和辛酸甘油三酯和饱和癸酸甘油三酯中的一种或两种。
根据本发明第一方面任一项所述的组合物,其为油剂或混悬剂或与辅料制成软胶囊、硬胶囊、微胶囊、片剂、散剂、丸剂、乳剂和混悬剂等剂型。
本发明第二方面提供本发明第一方面任一项的组合物的制备方法,其包含以下步骤:
称取各组分,混合即得所述组合物;优选地,混合后还包括过滤的步骤;更优选地,混合后还包括脱除气泡的步骤。
在本发明的实施方案中,所述混合可采用常规搅拌、剪切乳化和高压均质中的至少一种方法;优选地,所述混合在30~80℃下进行,优选50~70℃,例如60℃;优选地,所述混合在真空或惰性气体环境中进行。
本发明第三方面提供本发明第一方面任一项的组合物用于制备膳食补充剂或保健食品中的用途。
本发明的第四方面提供本发明第一方面任一项的组合物在制备预防和/或治疗血脂异常或心脑血管疾病的药物中的用途。
在本发明的实施方案中,所述血脂异常包括高血脂症(例如高胆固醇血症和/或高甘油三酯血症),或者选自血中的总胆固醇升高、低密度脂蛋白胆固醇升高、甘油三酯升高和高密度脂蛋白胆固醇降低中的一项或多项。
在本发明的实施方案中,所述心脑血管疾病选自动脉硬化、高血压、高血脂、脑梗塞、脑出血、冠心病、心绞痛、心肌缺血、心肌梗塞、心力衰竭和心律失常。
下面对本发明的各个方面和特点作进一步的描述。
本发明使用的各种术语和短语具有本领域技术人员公知的一般含义,即便如此,本发明仍然希望再次对这些术语和短语更详尽的说明和解释,提及的术语和短语如有与公知含义不一致的,以本发明所表述的含义为准。
本发明中使用的术语“二十二碳六烯酸”即为DHA。
本发明所述的“提取物”为市售可得的或采用本领域公知的提取方法制备得到,所述提取物的来源不构成对本发明组合物各组成成分的限制。
本发明中使用的术语“磷脂”,其包括磷脂酰胆碱、磷脂酰乙醇胺、磷脂酰丝氨酸、磷脂酰甘油、二磷脂酰甘油及磷脂酰肌醇和鞘磷脂等。
本发明中使用的术语“辅酶Q10”,其包括氧化型和还原型,是一种脂溶性抗氧化剂。
本发明中使用的术语“硫辛酸”为一种含硫八碳脂肪酸,是一种存在于线粒体的酶,在哺乳动物细胞内可以转化为还原型的二氢硫辛酸。
本发明中使用的术语“葡萄籽提取物”是从天然葡萄籽中提取的有效活性营养成份,富含原花青素和多酚。所述原花青素,简称OPC,是目前国际上公认的清除人体内自由基最有效的天然抗氧化剂。
本发明中使用的术语“万寿菊提取物”,其富含叶黄素和玉米黄质。所述叶黄素,别名类胡萝卜素、胡萝卜醇、植物黄体素、核黄体、万寿菊花素及植物叶黄素等,英文名为Lutein。
本发明中使用的术语“大豆异黄酮”是大豆生长中形成的一类次级代谢产物。
本发明中使用的术语“三七提取物”,其富含三七总皂苷。
本发明中使用的术语“燕麦提取物”,其富含β-葡聚糖。
本发明中使用的术语“膳食补充剂”(dietary supplement)又称营养补充剂、营养补充品、营养剂、饮食补充剂等,是作为饮食的辅助手段,用来补充人体所需的氨基酸、微量元素、维生素、矿物质等,达到提高机体健康水平和降低疾病风险的目的。
本发明的组合物可以以已知的任何方式给药,如口服、肌肉、皮下等,给药剂型例如片剂(例如口含片、咀嚼片)、胶囊(例如软胶囊、硬胶囊、微胶囊)、油剂、散剂、丸剂、乳剂和混悬剂、酏剂、透皮剂、微囊包埋剂、埋植剂、糖浆剂等。可以是普通制剂、缓释制剂、控释制剂及各种微粒给药系统。各种剂型的制备可参考本领域教科书教导制备,为了将单位给药剂型制成片剂,可以广泛使用本领域公知的各种生物可降解的或生物相容载体。本发明的组合物中含有的药用载体包括但不局限于:离子交换剂,氧化铝,硬脂酸铝,卵磷脂,血清蛋白如人血清蛋白,缓冲物质如磷酸盐,甘油,山梨酸,山梨酸钾,饱和植物脂肪酸的部分甘油酯混合物,水,盐或电解质,如硫酸鱼精蛋白,磷酸氢二钠,磷酸氢钾,氯化钠,锌盐,胶态氧化硅,三硅酸镁,聚乙烯吡咯烷酮,纤维素物质,聚乙二醇,羧甲基纤维素钩,聚丙烯酸酯,蜂蜡,羊毛醋等。载体在药物组合物中的含量可以是1重量%~98重量%,通常大约占到80重量%,为方便起见,局部麻醉剂,防腐剂,缓冲剂等可直接溶于载体中。
本发明所述组合物的给药剂量取决于许多因素,例如所要预防或治疗疾病的性质和严重程度,患者或动物的性别、年龄、体重,敏感性及个体反应,所用的具体化合物,给药途径,给药次数以及所希望达到的治疗效果等。上述剂量可以单一剂量形式或分成几个,例如二、三、四个剂量形式给药。单个最大剂量一般不超过30mg/Kg体重,例如0.001~30mg/Kg,优选0.01~5mg/Kg,较佳剂量范围为0.5~2mg/Kg体重。但是,在某些情况下,也可能使用30mg/Kg体重以上或者0.001mg/Kg以下的单个剂量。
发明的有益效果
本发明提供了一系列具有心脑血管保护作用的成分的组合,其在预防和/或治疗心脑血管疾病方面取得了预料不到的协同作用。在脂代谢紊乱动物模型中,本发明的组合物能有效降低大鼠血清中总胆固醇(TC)、甘油三酯(TG)水平并能显著提高高密度脂蛋白胆固醇(HDL-C)水平,相较于单一组分的应用,具有明显的协同作用。
具体实施方式
下面将结合实施例对本发明的实施方案进行详细描述,但是本领域技术人员将会理解,下列实施例仅用于说明本发明,而不应视为限定本发明的范围。实施例中未注明具体条件者,按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者,均为可以通过市购获得的常规产品。
实施例1-37所用原料均为市场购得,为食品级或医药级,主要原料的规格如表1所示,组合物配方如表2所示。
表1 主要原料规格表
原料名称 | 规格 |
二十二碳六烯酸藻油 | 二十二碳六烯酸含量为55% |
氧化型辅酶Q10 | 氧化型辅酶Q10含量为98% |
还原型辅酶Q10 | 还原型辅酶Q10含量为98% |
氧化型硫辛酸 | 氧化型硫辛酸含量为99% |
二氢硫辛酸 | 二氢硫辛酸含量为99% |
大豆磷脂 | 总磷含量为60% |
磷脂酰丝氨酸 | 磷脂酰丝氨酸含量为98% |
改性磷脂 | 羟化卵磷脂含量为60% |
葡萄籽提取物 | 原花青素含量为99% |
大豆胚芽提取物 | 大豆异黄酮含量为80% |
万寿菊提取物 | 叶黄素含量为90% |
三七提取物 | 三七总皂苷含量为80% |
燕麦提取物 | β-葡聚糖含量为75% |
实施例38 降低血脂功能测试
1 原理
用高胆固醇和脂类饲料喂养动物可形成脂代谢紊乱动物模型,再给予动物受试样品,可检测受试样品对高血脂症的影响,并可判定受试样品对脂质的吸收、脂蛋白的形成、脂质的降解或排泄产生的影响。
2 仪器及试剂
解剖器械,分光光度计,自动生化分析仪,胆固醇,胆盐,血清总胆固醇(TC),甘油三酯(TG),高密度脂蛋白(HDL-C)测定试剂盒。
3 动物选择及饲料
选取健康成年雄性SD大鼠,体重为150~200g,每组10只。
高脂饲料:78.8%基础饲料,1%胆固醇、10%蛋黄粉、10%猪油、0.2%胆盐。
标准饲料:基础饲料。
4 方法
试验设39个组,第1组为高脂饮食的对照组(给予高脂饲料),第2组为标准饮食组(给予标准饲料),其余各组分别每天给予高脂饮食的同时经口灌胃给予实施例1~37制备的的受试样品,每次2ml,每天3次,试验时间为30天。
5 试验步骤
在实验环境下对大鼠饲喂基础饲料观察10天,然后取尾血,测定血清总胆固醇(TC),甘油三酯(TG),高密度脂蛋白胆固醇(HDL-C)水平。根据TC水平,随机分成39组,按上述4中所述方法进行饲养,定期称量体重,于试验结束禁食16小时,测血清TC,TG,HDL-C水平。结果如表3-5所示:
表3 血清总胆固醇(TC)测试结果
表4 血清甘油三酯(TG)测试结果
表5 血清高密度脂蛋白胆固醇(HDL-C)测试结果
上述试验结果证明了本发明的组合物与它们的单一成分相比具有预料不到的协同效应。
实施例39 制备软胶囊制剂
制备软胶囊内容物:取实施例30的营养组合物作为软胶囊的内容物。
软胶囊的胶皮的制备方法为:称取明胶150g、甘油90g、纯化水180g、焦糖色10g、辣椒红2g、二氧化钛1.5g,将甘油、纯化水投入溶胶罐中,加热至60℃,投入明胶继续加热至65℃使其溶解,再将已经溶解混匀并过滤后的焦糖色、辣椒红、二氧化钛投入溶胶罐内,搅拌25min后抽真空脱尽气泡,制得胶皮溶液,60℃保温,备用。
将上述的制备得到的软胶囊内容物与胶皮溶液经过压丸、定型、干燥、拣丸和包装步骤,即得规格为450mg/粒的软胶囊。
尽管本发明的具体实施方式已经得到详细的描述,本领域技术人员将会理解。根据已经公开的所有教导,可以对那些细节进行各种修改和替换,这些改变均在本发明的保护范围之内。本发明的全部范围由所附权利要求及其任何等同物给出。
Claims (31)
1.组合物,其包含:
二十二碳六烯酸或其酯、辅酶Q10、硫辛酸、磷脂、原花青素、大豆异黄酮、叶黄素、三七总皂苷和β-葡聚糖。
2.根据权利要求1所述的组合物,其特征在于选自以下的一项或多项:
1)所述二十二碳六烯酸或其酯的含量按重量百分比计算为0.5~80%;
2)所述辅酶Q10的含量按重量百分比计算为0.5~60%;
3)所述硫辛酸的含量按重量百分比计算为0.5~60%;和
4)所述磷脂的含量按重量百分比计算为0.1~60%。
3.根据权利要求1所述的组合物,其特征在于选自以下的一项或多项:
1)所述二十二碳六烯酸或其酯的含量按重量百分比计算为5~60%;
2)所述辅酶Q10的含量按重量百分比计算为5~55%;
3)所述硫辛酸的含量按重量百分比计算为5~50%;和
4)所述磷脂的含量按重量百分比计算为2~35%。
4.根据权利要求1所述的组合物,其中,所述二十二碳六烯酸的酯选自二十二碳六烯酸甲酯、二十二碳六烯酸乙酯、二十二碳六烯酸甘油酯、二十二碳六烯酸异丙酯和二十二碳六烯酸磷脂中的一种或多种。
5.根据权利要求1所述的组合物,其中,所述辅酶Q10选自氧化型辅酶Q10和还原型辅酶Q10中的一种或两种。
6.根据权利要求1所述的组合物,其中,所述硫辛酸选自氧化型硫辛酸和还原型硫辛酸中的一种或两种。
7.根据权利要求6所述的组合物,其中,所述还原型硫辛酸为二氢硫辛酸。
8.根据权利要求1所述的组合物,其中,所述磷脂选自羟化磷脂、磷脂酰胆碱、磷脂酰乙醇胺、磷脂酰丝氨酸、磷脂酰甘油、二磷脂酰甘油、磷脂酰肌醇和鞘磷脂中的一种或多种。
9.根据权利要求1所述的组合物,其中,所述磷脂选自羟化卵磷脂和磷脂酰丝氨酸。
10.根据权利要求1所述的组合物,其特征在于选自以下的一项或多项:
(1)所述原花青素的含量按重量百分比计算为0.1~15%;
(2)所述大豆异黄酮的含量按重量百分比计算为0.1~8%;
(3)所述叶黄素的含量按重量百分比计算为0.1~10%;
(4)所述三七总皂苷的含量按重量百分比计算为0.1~8%;和
(5)所述β-葡聚糖的含量按重量百分比计算为0.1~8%。
11.根据权利要求1所述的组合物,其特征在于选自以下的一项或多项:
(1)所述原花青素的含量按重量百分比计算为0.1~11%;
(2)所述大豆异黄酮的含量按重量百分比计算为0.1~5.5%;
(3)所述叶黄素的含量按重量百分比计算为0.5~10%;
(4)所述三七总皂苷的含量按重量百分比计算为0.1~6%;和
(5)所述β-葡聚糖的含量按重量百分比计算为0.1~6%。
12.根据权利要求1所述的组合物,其余量为载体油。
13.根据权利要求12所述的组合物,其中,所述载体油选自天然植物油脂、天然动物油脂和人工合成油脂中的一种或多种。
14.根据权利要求12所述的组合物,其中,所述载体油选自大豆油、菜籽油、橄榄油、芝麻油、玉米油、棕榈油、葵花油、芥子油、米糠油、椰子油、亚麻籽油、月见草油、大蒜油、荷荷巴油、猪油、牛脂、鱼油、黄油和中链甘油三酯中的一种或多种。
15.根据权利要求14所述的组合物,其中,所述中链甘油三酯选自饱和辛酸甘油三酯和饱和癸酸甘油三酯中的一种或两种。
16.根据权利要求1~15中任一权利要求所述的组合物,其为油剂或混悬剂。
17.根据权利要求1~15中任一权利要求所述的组合物,其与辅料制成软胶囊、硬胶囊、微胶囊、片剂、散剂、丸剂、乳剂或混悬剂。
18.制备权利要求1~16中任一权利要求所述的组合物的方法,其包含以下步骤:
称取各组分,混合,得到所述组合物。
19.根据权利要求18所述的制备方法,其中,还包括在混合之后过滤的步骤。
20.根据权利要求18所述的制备方法,其中,还包括在混合之后脱除气泡的步骤。
21.根据权利要求18所述的制备方法,其中,所述混合采用常规搅拌、剪切乳化和高压均质中的至少一种方法。
22.根据权利要求18所述的制备方法,其中,所述混合在30~80℃下进行。
23.根据权利要求18所述的制备方法,其中,所述混合在50~70℃下进行。
24.根据权利要求18所述的制备方法,其中,所述混合在60℃下进行。
25.根据权利要求18所述的制备方法,其中,所述混合在真空或惰性气体环境中进行。
26.权利要求1~17中任一权利要求所述的组合物用于制备膳食补充剂或保健食品的用途。
27.权利要求1~17中任一权利要求所述的组合物在制备预防和/或治疗血脂异常或心脑血管疾病的药物中的用途。
28.根据权利要求27所述的用途,其中,所述血脂异常为高脂血症。
29.根据权利要求28所述的用途,其中,所述高脂血症为高胆固醇血症和/或高甘油三酯血症。
30.根据权利要求28所述的用途,其中,所述血脂异常选自血中的总胆固醇升高、低密度脂蛋白胆固醇升高、甘油三酯升高和高密度脂蛋白胆固醇降低中一项或多项。
31.根据权利要求27所述的用途,其中,所述心脑血管疾病选自动脉粥样硬化、高血压、高血脂、脑梗塞、脑出血、冠心病、心绞痛、心肌缺血、心肌梗塞、心力衰竭和心律失常。
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