CN113951517A - 一种具有减肥降脂作用的海洋活性蛋白组合物及其制备方法 - Google Patents
一种具有减肥降脂作用的海洋活性蛋白组合物及其制备方法 Download PDFInfo
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- A—HUMAN NECESSITIES
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- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
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Abstract
本发明涉及一种天然海洋来源活性蛋白组合物及其制备方法,组合物包括藻红蛋白、磷虾油和岩藻黄素。以此组合物辅以其他辅料可以制备含该组合物的片剂、胶囊剂、口服液、颗粒剂、丸剂或粉剂等。本发明组合物以天然海洋来源食物为原料提取,安全性高,具有显著降低体重,调节血脂的作用,能明显预防、治疗高血脂症,预防肥胖,减轻体重,调节血脂,预防心血管相关疾病等作用。
Description
技术领域
本发明涉及药物技术领域,具体涉及一种具有减肥降脂作用的海洋活性蛋白组合物及其制备方法。
背景技术
现代医学证明,过度肥胖可导致高血脂、高血糖和高血压等心血管疾病,以及胆囊炎等消化系统疾病,甚至会导致乳腺癌和结肠癌等肿瘤在内的相关疾病。随着生活水平的不断提高,人们的饮食结构偏向高脂高糖,导致肥胖症的发病率越来越高,与肥胖相关的一些疾病的死亡率也越来越高。因此,肥胖及与之相关的疾病对人们的健康带来了严重影响。过于肥胖的人往往伴有血脂异常相关的疾病,血脂异常是指血液中总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)和低密度脂蛋白(LDL-C)等血液指标中的一种或几种超出正常血液中浓度,一般称为高血脂症。该疾病发病时无明显症状,对身体的损害是渐进式的,但危害性极大,后期会导致动脉粥样硬化、脂肪肝、肾衰竭、脑卒中、冠心病和心卒死等相关疾病,严重危害人们的生命健康。
现有的减肥药物或者保健品大多通过控制饮食或腹泻等方法达到目的,甚至有些还添加违禁药品,有很大的副作用,服用后会对人体健康产生不良影响。针对高血脂症往往也是采用化学药物进行治疗,不可避免的会产生副作用,如果停药就会造成病情反弹,如果长期服药就会对身体造成损害。此外,药物治疗肥胖症和高血脂症只针对其中一种病症进行治疗,未将两者综合治疗。因此,针对肥胖并发高血脂症患者需要一种能够长期服用的兼具减肥和降脂作用的产品,此产品既能减轻体重,又能调节血脂异常,还不会影响人们的正常饮食。
海洋中有100多万种动植物和上亿种微生物,由于其特殊的环境,海洋生物拥有有别于陆地生物独特的基因体系,产生了结构奇特新颖的分子,具有各种生物活性,为相关产品开发提供了独有的海洋资源。随着海洋生物技术的发展,人们对海洋生物资源的认识和利用正在逐步深入。“海藻”是海带、紫菜、裙带菜、石花菜等海洋藻类的总称,是生长在海洋中的藻类,是人类非常重要的可食用资源,并且含有丰富的生物活性物质。藻红蛋白是一种存在于海藻中的天然水溶性色素蛋白,具有抗氧化和抗肿瘤作用,常作为荧光检测试剂使用。岩藻黄素也是一种存在于海带等食用海藻中的一种活性物质,现代药理学证明其具有减肥功能[Diabetes,Obesity and Metabolism 12:72–81,2010]。磷虾油是一种从南极磷虾中提取出来的含有多种DHA、EPA不饱和脂肪酸和磷脂等成分的油状物,是制备食品和保健品的优质原料。如CN107987948A采用磷虾油、植物甾醇、玉米油复配,制备一种调节血脂的南极磷虾油制剂,可以调节血脂;专利CN108552325A公开了一种磷虾油、紫苏籽油和葡萄籽油的组合物,制备成各种制剂,具有降脂作用。藻红蛋白、磷虾油和岩藻黄素的制备原料为海洋来源可食用的天然食品,安全性高,长期食用不会造成损害。因此,以藻红蛋白、磷虾油和岩藻黄素为主要活性物质开发减肥降脂功能品具有非常好的应用前景。
现有技术中没有本发明提供的藻红蛋白、磷虾油和岩藻黄素组合协同联用的报道。因此,本发明将天然来源的藻红蛋白、磷虾油和岩藻黄素进行功能组合,三种物质在减肥和降脂等方面协同增效,长期服用有减轻体重和降低血脂的良好作用,并且具有很好的安全性。
发明内容
针对目前具有协同减肥降脂作用产品的缺失,本发明的目的在于提供一种具有减肥降脂作用的海洋活性蛋白组合物,该组合物具有协同减肥降脂功效,安全性好,可长期服用。
为了实现上述目的,本发明采用的技术方案如下:
一种具有减肥降脂作用的海洋活性蛋白组合物,由以下重量份的组分制成:藻红蛋白0.1-5份、磷虾油0.5-10份和岩藻黄素0.05-1.0份。
优选范围为包括以下原料(重量份计):藻红蛋白1-5份、磷虾油1-7份和岩藻黄素0.5-1.0份。
所述藻红蛋白从可食用含藻红蛋白海藻经细胞破碎,盐析,柱层析获得经测定含藻红蛋白纯度大于0.7为食品级藻红蛋白;所述磷虾油从南极磷虾经乙醇提取,含磷脂≥50%、EPA≥10%、DHA≥5%、虾青素≥0.08‰;所述岩藻黄素由含岩藻黄素海藻经乙醇提取柱层析纯化获得经测定纯度大于90%。
所述可食用含藻红蛋白海藻是指紫菜、龙须菜、多管藻、红毛菜、顶丝藻、石花菜、鸡毛菜、叉枝藻、江蓠、凹顶藻、珊瑚藻、蜈蚣藻等海藻中的一种或两种以上;含岩藻黄素海藻是指海带、三角褐指藻、羊栖菜、铜藻、裙带菜等海藻中的一种或两种以上,但不限于以上含岩藻黄素的海藻。
其中所述藻红蛋白的制备方法包括以下步骤:
含藻红蛋白的海藻加入去离子水破壁粉碎,放入-20℃冰箱反复冻融3次,粗提液过滤后加入70%硫酸铵固体盐析,取析出物后透析、透析后溶液在6000-7000rpm、4-5℃,超滤20-25min,超滤后溶液真空冷冻干燥,即得纯度为食品级藻胆蛋白。
其中所述磷虾油的制备方法包括以下步骤:
将南极磷虾粉碎,加入95%以上的乙醇在4-30℃下浸泡2-3h;然后搅拌,分离提取液,再提取并分离提取液3次;将提取液合并并用旋蒸真空蒸发除去提取液中乙醇得到南极磷虾油粗提液,然后进一步精制得食品级磷虾油。
其中所述岩藻黄素的制备方法包括以下步骤:
将含岩藻黄素的海藻粉碎,然后加入无水乙醇在50℃提取3次,合并提取液,30-40℃减压浓缩得岩藻黄素粗品浸膏,然后两次硅胶柱层析分离得岩藻黄素。
其中一种具有减肥降脂作用的海洋活性蛋白组合物的制备方法包括以下步骤:
分别称取上述中的配方量的藻红蛋白、磷虾油和岩藻黄素,分别研磨,过100目筛,混合均匀,加入质量比为10%-95%相应辅料(羟丙甲基纤维素E5:微晶纤维素MCC102:硬脂酸镁:8%聚维酮K30(15-20:15-20:2-3:0.1-0.5)或含质量浓度10%-20%单糖浆和0.1%-1%苯甲酸钠的蒸馏水或药用淀粉:葡萄糖:水解明胶:甘氨酸(10-30:5-15:0.5-1:0.5-1)或吐温80:丙二醇:环糊精:乳糖(1-2:2-5:3-5:10-15)),按常规工艺,制成相应剂型。
本发明提供一种具有减肥降脂作用的海洋活性蛋白组合物的制剂以方便患者服用,优选地,所述组合物的制剂为口服制剂。所述的口服制剂包括但不局限于颗粒剂、口服液、片剂、胶囊剂、丸剂或粉剂,但不局限于以上剂型。
本发明还提供上述组合物在制备减肥作用相关药物和/或食品/或保健品中的应用。
本发明还提供上述组合物在制备降脂作用相关药物和/或食品/或保健品中的应用。
本发明相对现有技术,本发明的具有以下优点:
1、现有的减肥降脂药物或者保健品大多副作用大,长期服用对人体健康产生不良影响,不能长期服用。本发明提供一种海洋活性蛋白组合物,所使用的原料均为海洋来源可食用的天然食品,安全性高,不会对身体产生副作用,长期食用不会造成损害。
2、本发明根据传统经典古书和现代营养科学为依据,将海洋天然来源的藻红蛋白、磷虾油和岩藻黄素进行复配,各活性成分协同增效,动物功效实验证明具有明显的减肥降脂效果,与阳性对照药奥利司他相当。
3、本发明提供的以食品级藻胆蛋白、岩藻黄素和磷虾油为主要原料制备的组合物,采用常规方法制备,生产成本低,市场潜力大,前景广。
现有技术中没有本发明提供的提供的藻红蛋白、磷虾油和岩藻黄素组合协同联用的报道。本发明将天然来源的藻红蛋白、磷虾油和岩藻黄素进行功能组合,三种物质在减肥和降脂等方面协同增效,长期服用有减轻体重和降低血脂的良好作用,并且具有很好的安全性,具有推广应用价值。
具体实施方式
为了更好地理解本发明的实质,下面将用本发明的实施例来说明提供的一种海洋活性蛋白组合物及其制备方法,但不以此实施例来限定本发明。
实施例1:一种海洋活性蛋白组合物片剂
(1)紫菜加入去离子水破壁粉碎,放入-20℃冰箱反复冻融3次,粗提液过滤后加入70%硫酸铵固体盐析,取析出物后透析、透析后溶液在6000rpm、4℃,超滤20min,超滤后溶液真空冷冻干燥,即得纯度为食品级藻胆蛋白;
(2)将南极磷虾粉碎,加入95%乙醇在4-30℃下浸泡2h;然后搅拌,分离提取液,再将滤渣提取3次;将提取液合并,并用旋蒸真空在55℃下除去提取液中乙醇,得到南极磷虾油粗提液,然后进一步用活性碳精制得食品级磷虾油。
(3)将海带粉碎,然后加入无水乙醇在50℃提取3次,合并提取液,40℃真空浓缩得岩藻黄素粗品浸膏,然后硅胶柱层析分离得岩藻黄素。
(4)将步骤(1)-(3)分别得到的藻红蛋白、磷虾油和岩藻黄素按照5:10:1复配,作为主要原料占比80%,然后加入赋形剂(羟丙甲基纤维素E5:微晶纤维素MCC102:硬脂酸镁:(8%聚维酮K30)=15:15:2:0.1)占比20%,研磨,过100目筛,混合均匀,压片制成片剂。
实施例2:一种海洋活性蛋白组合物口服液
将按照实施例1中步骤(1)-(3)得到的藻红蛋白、磷虾油和岩藻黄素按照2:10:1复配,然后加入到含质量浓度20%单糖浆和0.1%苯甲酸钠的蒸馏水中,按常规口服液制法制成50毫升、100毫升和200毫升不同规格口服液。
实施例3:一种海洋活性蛋白组合物胶囊剂
将藻红蛋白、磷虾油和岩藻黄素按照2:3:1复配,作为主要原料占比75%,然后加入赋形剂(药用淀粉:葡萄糖:水解明胶:甘氨酸=30:10:1:1)占比25%,混合均匀,按常规胶囊剂制法制成胶囊。
实施例4:一种海洋活性蛋白组合物粉剂
将按照实施例1中步骤(1)-(3)得到的藻红蛋白、磷虾油和岩藻黄素按照5:5:1复配,作为主要原料占比90%,然后加入赋形剂(吐温80:丙二醇:环糊精:乳糖=1:2:4:12)占比10%,混合均匀,按常规粉剂制法制成粉剂。
功效评价实验例:
组合物减肥降脂功效动物评价实验参照减肥和降脂保健品功能评价方法进行功能评价,具体如下:
1、实验目的
观察本实验发明组合物的减肥降脂功效
2、实验仪器及试剂
解剖器械、分光光度计,胆固醇、胆酸钠、血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C),高密度脂蛋白胆固醇(HDL-C)测定试剂盒。
3、实验动物
健康成年雄性SD大鼠,适应期结束时,体重150±20g,每组8-12只。
4、模型饲料
在维持饲料中添加20.0%蔗糖、15%猪油、1.2%胆固醇、0.2%胆酸钠,适量的酪蛋白、磷酸氢钙、石粉等。除了粗脂肪外,模型饲料的水分、粗蛋白、粗脂肪、粗纤维、粗灰分、钙、磷、钙:磷均要达到维持饲料的国家标准。
5、造模期
按体重随机分成2组,10只大鼠给予维持饲料作为空白对照组,其余给予模型饲料作为模型组。每周称量体重1次,每周记录摄食量。
模型组给予模型饲料4周后,空白对照组和模型对照组大鼠不禁食采血(眼内眦或尾部),采血后尽快分离血清,测定血清TC、TG、LDL-C、HDL-C水平。根据TC水平将模型组随机分成8组。
6、剂量分组及受试样品给予时间
实验设5个受试药物组,空白对照组和模型对照组,对照组和模型组给予0.5%的CMC-Na,以奥利司他为阳性对照组,受试样品给予时间为6周。
组别 | 实验药物及剂量 |
空白组 | 0.5%的CMC-Na:1÷150×体重(mL) |
模型组 | 0.5%的CMC-Na:1÷150×体重(mL) |
阳性对照组 | 奥利司他:20mg/kg/天 |
藻红蛋白组 | 藻红蛋白:100mg/kg/天 |
磷虾油组 | 磷虾油:200mg/kg/天 |
岩藻黄素组 | 盐藻黄素:20mg/kg/天 |
组合物实验1组 | 组合物(藻胆蛋白:磷虾油:盐藻黄素=5:10:1):160mg/kg/天 |
组合物实验2组 | 组合物(藻胆蛋白:磷虾油:盐藻黄素=1:20:0.1):320mg/kg/天 |
7、受试样品给予
分组后,每天经-口给予受试样品,空白对照组和模型对照组同时给予同体积的相应溶剂,空白对照组继续给予维持饲料,模型对照组、阳性对照及受试药物组继续给予模型饲料,并定期称量体重,于实验结束时不禁食采血,采血后尽快分离血清,测定血清TC、TG、LDL-C、HDL-C水平。取大鼠肾周围、睾丸周围脂肪垫称重,取肝、肾组织称重。
8、观察指标
大鼠体重、摄食量、脂肪湿重等;血清指标:TC、TG、LDL-C、HDL-C。
9、实验结果
(1)受试样品对体重、脂肪指数、肝指数和肾指数的影响
与模型组和其他组别比较,组合物实验1组减轻动物体重效果明显,组合物实验1组的脂肪指数与模型组比较减小且具有显著性差异,并且与阳性对照药效果相当。
表1不同组别体重、脂肪指数、肝指数和肾指数的比较
注:肝指数=肝重/体重*100;脂肪指数=脂肪湿重/体重*100;肾指数=肾重/体重*100。**p<0.01vs.对照组,#p<0.05vs.模型组
(2)受试样品对血清中不同指标的影响
与模型组比较,在实验剂量下磷虾油组和岩藻黄素组可以降低甘油大鼠血清甘油三酯含量,组合物实验1组可以降低大鼠血清中甘油三酯和低密度脂蛋白含量且具有显著性差异,并且与阳性对照药效果相当。
表2不同组别血清中总胆固醇、甘油三酯、低密度脂蛋白和高密度脂蛋白的比较
*p<0.05,**p<0.01vs.对照组,#p<0.05vs.模型组
10、结论
减肥降脂动物功效实验结果表明,藻红蛋白、磷虾油和岩藻黄素在实验剂量下表现出一定程度的减轻体重和降低血脂功效。将三者剂量减半按重量比5:10:1(藻胆蛋白:50mg/kg、磷虾油100mg/kg、盐藻黄素:10mg/kg)组合后,在此剂量下可显著降低大鼠身体中脂肪重量,减轻体重,并能显著降低大鼠血清中甘油三酯和低密度脂蛋白含量,效果与阳性对照药奥利司他相当。
综上,实验结果表明本发明组合物具有协同减肥降脂功效,参照减肥降脂功效动物评价实验评价标准,可以确认组合物具有协同减肥降脂功效。
Claims (8)
1.一种减肥降脂海洋活性蛋白组合物,其特征在于:包括以下原料(重量份计):藻红蛋白0.1-5份、磷虾油0.5-10份和岩藻黄素0.05-1.0份。
2.按照权利要求1所述的一种海洋活性蛋白组合物,其特征在于,包括以下原料(重量份计):藻红蛋白1-5份、磷虾油1-7份和岩藻黄素0.5-1.0份。
3.按照权利要求1所述的一种海洋活性蛋白组合物,其特征在于,所述藻红蛋白从可食用含藻红蛋白海藻经细胞破碎,盐析,柱层析获得经测定含藻红蛋白纯度大于0.7为食品级藻红蛋白;所述磷虾油从南极磷虾经乙醇提取,含磷脂≥50%、EPA≥10%、DHA≥5%、虾青素≥0.08‰;所述岩藻黄素由含岩藻黄素海藻经乙醇提取柱层析纯化获得经测定纯度大于90%。
4.按照权利要求2所述的一种海洋活性蛋白组合物,其特征在于,所述可食用含藻红蛋白海藻是指紫菜、龙须菜、多管藻、红毛菜、顶丝藻、石花菜、鸡毛菜、叉枝藻、江蓠、凹顶藻、珊瑚藻、蜈蚣藻等海藻中的一种或两种以上;含岩藻黄素海藻是指海带、三角褐指藻、羊栖菜、铜藻、裙带菜等海藻中的一种或两种以上,但不限于以上含岩藻黄素的海藻。
5.一种权利要求1-2所述的具有减肥降脂作用的组合物的制备方法,其特征在于,包括以下步骤:
分别称取权利要求1中的配方量的藻红蛋白、磷虾油和岩藻黄素,分别研磨,过100目筛,混合均匀,加入质量比为10%-95%相应辅料(羟丙甲基纤维素E5:微晶纤维素MCC102:硬脂酸镁:8%聚维酮K30(15-20:15-20:2-3:0.1-0.5)或含质量浓度10%-20%单糖浆和0.1%-1%苯甲酸钠的蒸馏水或药用淀粉:葡萄糖:水解明胶:甘氨酸(10-30:5-15:0.5-1:0.5-1)或吐温80:丙二醇:环糊精:乳糖(1-2:2-5:3-5:10-15)),按常规工艺,制成相应剂型。
6.按照权利要求5所述的制备方法,其特征在于:所述的剂型为片剂、胶囊剂、口服液、颗粒剂、丸剂或粉剂,但不局限于以上剂型。
7.一种权利1或2所述的组合物在制备减肥作用相关药物和/或食品/或保健品中的应用。
8.一种权利1或2所述的组合物在制备降脂作用相关药物和/或食品/或保健品中的应用。
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