CN110558516A - 一种通过靶向补充bdnf、fto基因配体治疗肥胖的组合物及其制备方法和应用 - Google Patents
一种通过靶向补充bdnf、fto基因配体治疗肥胖的组合物及其制备方法和应用 Download PDFInfo
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Abstract
本发明提供了一种通过靶向补充BDNF、FTO基因配体治疗肥胖的组合物及其制备方法和应用,属于营养基因组学技术领域,所述组合物包括以下重量份的原料:车前子壳粉50~200份、燕麦粉50~200份、木瓜粉50~200份、菠萝粉50~200份、西兰花粉50~200份、蓝莓粉5~100份、甘油5~50份、低聚果糖10~30份、抗坏血酸10~40份和矿物质元素补充剂10~40份。本发明通过内源性生成IPA(吲哚丙酸)稳定脑源性神经营养因子BDNF和抑制FTO基因(α‑酮戊二酸依赖性双加氧酶)过度表达,靶向补充BDNF、FTO基因配体,从而通过靶向补充BDNF、FTO基因配体治疗肥胖。
Description
技术领域
本发明涉及营养基因组学技术领域,尤其涉及一种通过靶向补充BDNF、FTO基因配体治疗肥胖的组合物及其制备方法和应用。
背景技术
肥胖是指一定程度的明显超重与脂肪层过厚,是体内脂肪,尤其是甘油三酯积聚过多而导致的一种状态。肥胖在全球呈现上升趋势。约一半肥胖人群与遗传因素有关,另一半主要与营养素不均衡导致的基因组不稳定、表达异常有关。
目前市场上的减肥药物,如苯丙胺及其类似物,仅对于单纯性肥胖症效果较好,但不良反应较多。芬氟拉明、右芬氟拉明及其复方制剂,多项研究证实,此类药物可致心脏瓣膜损害、肺动脉高压和手指坏死等严重不良反应。吲哚类及其衍生物,如吗吲哚及环咪唑吲哚,以产热的形式“燃烧”多余脂肪,但该药可升高血压,不利于心血管疾病的肥胖患者使用。左旋肉碱等产品,可将脂肪转化为能量,配合运动可加速减肥,但部分人会出现晕旋、口渴、失眠症状。以上产品,还有一个普遍现象,就是具有依赖性,一但停止用药,会迅速出现反弹。
BDNF基因是脑源性神经营养因子,与神经性贪食症的易感性密切相关。BDNF基因发生变异或不能正常表达,神经元处于非稳态兴奋,会不断发出营养素需求信号,导致过量食物摄入。目前,国际上多数研究主要集中于内源性或外源性给予BDNF防止及治疗神经元损伤,尚无相关靶向药物或其它有效药物,对由于自身BDNF基因配体不足,导致基因毒性因子结合或过度甲基化、糖基化修饰等引起BDNF基因失活甚至出现沉默现象,进行有效调节,用于肥胖防治。
发明内容
本发明的目的在于提供一种通过靶向补充BDNF、FTO基因配体治疗肥胖的组合物及其制备方法和应用,该组合物能够通过靶向补充BDNF、FTO基因配体从而通过靶向补充BDNF、FTO基因配体治疗肥胖。
为了实现上述发明目的,本发明提供以下技术方案:
本发明提供了一种通过靶向补充BDNF、FTO基因配体治疗肥胖的组合物,包括以下重量份的原料:车前子壳粉50~200份、燕麦粉50~200份、木瓜粉50~200份、菠萝粉50~200份、西兰花粉50~200份、蓝莓粉5~100份、甘油5~50份、低聚果糖10~30份、抗坏血酸10~40份和矿物质元素补充剂10~40份;所述矿物质元素补充剂包括硫酸亚铁和葡萄糖酸锌;所述葡萄糖酸锌和硫酸亚铁的质量比为0.1~0.2:0.1~0.2。
优选的,所述组合物包括以下重量份的原料:车前子壳粉80~150份、燕麦粉80~150份、木瓜粉80~150份、菠萝粉80~150份、西兰花粉80~150份、蓝莓粉20~80份、甘油8~20份、低聚果糖15~25份、抗坏血酸12~20份和矿物质元素补充剂12~20份。
优选的,所述组合物包括以下重量份的原料:车前子壳粉100份、燕麦粉100份、木瓜粉100份、菠萝粉100份、西兰花粉100份、蓝莓粉50份、甘油10份、低聚果糖20份、抗坏血酸15份和矿物质元素补充剂15份。
优选的,所述车前子壳粉、燕麦粉、木瓜粉、菠萝粉、西兰花粉和蓝莓粉的粒径独立为60~100目。
优选的,所述组合物还包括辅料;所述辅料包括芦荟凝胶粉。
优选的,所述组合物的剂型包括果冻、粉剂和口服液。
优选的:将所述车前子壳粉、燕麦粉、木瓜粉、菠萝粉、西兰花粉、蓝莓粉、甘油、抗坏血酸和矿物质元素补充剂混合,进行灭菌,得到组合物。
本发明还提供了上述方案所述组合物在制备通过靶向补充BDNF、FTO基因配体治疗肥胖的食品或保健品中的应用。
本发明的有益效果:本发明提供了一种通过靶向补充BDNF、FTO基因配体治疗肥胖的组合物,包括以下重量份的原料:车前子壳粉50~200份、燕麦粉50~200份、木瓜粉50~200份、菠萝粉50~200份、西兰花粉50~200份、蓝莓粉5~100份、甘油5~50份、低聚果糖10~30份、抗坏血酸10~40份和矿物质元素补充剂10~40份;所述矿物质元素补充剂包括硫酸亚铁和葡萄糖酸锌;所述硫酸亚铁和葡萄糖酸锌的质量比为0.1~0.2:0.1~0.2。
本发明利用营养基因组学与分子营养学原理,通过内源性生成IPA(吲哚丙酸)稳定脑源性神经营养因子BDNF和α-酮戊二酸依赖性双加氧酶FTO基因的表达,靶向补充BDNF、FTO基因配体,从而通过靶向补充BDNF、FTO基因配体治疗肥胖。
BDNF基因存在一个重要配体IPA(吲哚丙酸Indole propionic acid),可以稳定BDNF基因表达,帮助肥胖患者有效控制贪食行为。与此同时,IPA还可以通过调节BDNF基因,减弱肝脏促炎细胞因子的释放,诱导肝脏合成游离脂肪酸,有效干预非酒精性脂肪肝的发展,同时,还能影响胰腺β细胞功能,促进胰岛素分泌,预防2型糖尿病。
本发明的组合物包含车前子壳粉、燕麦粉、木瓜粉、菠萝粉、西兰花粉和蓝莓粉等特定的膳食纤维成分,由肠道菌群代谢这些特定的植物膳食纤维和低聚果糖产生吲哚丙酸(IPA)物质,能够为BDNF基因提供稳定配体,稳定BDNF基因在海马,杏仁核,大脑皮质和小脑中的表达,平衡调节激活磷脂酶C活性、脑源性神经营养因子受体信号通路、细胞信号、神经侧枝发芽、肌管分化的负调控、神经营养因子TRK受体信号通路、脑源性神经营养因子受体信号通路的正调控、受体结合的正调控以及蛋白质定位到细胞表面的调节,帮助肥胖患者有效控制贪食行为。
FTO(α-酮戊二酸依赖性双加氧酶)基因是蛋白质编码基因,在脑组织,尤其是在控制食欲的下丘脑中高表达。FTO基因与体重指数,肥胖风险和2型糖尿病密切相关。另外,FTO基因的失活或表达不足,也影响ghrelin的表达水平,ghrelin是胃内产生的一种多肽,能够增强食欲、促进摄食,减弱了人的餐后饱腹感,进而导致了肥胖。
本发明所述组合物中西兰花粉协同甘油、抗坏血酸和矿物质元素补充剂,能够稳定FTO基因表达,进而预防由于FTO基因元件供体不足,导致基因不稳定而产生等位基因变异,从而实现肥胖防治。
具体实施方式
本发明提供了一种通过靶向补充BDNF、FTO基因配体治疗肥胖的组合物,包括以下重量份的原料:车前子壳粉50~200份、燕麦粉50~200份、木瓜粉50~200份、菠萝粉50~200份、西兰花粉50~200份、蓝莓粉5~100份、甘油5~50份、低聚果糖10~30份抗坏血酸10~40份和矿物质元素补充剂10~40份;所述矿物质元素补充剂包括硫酸亚铁和葡萄糖酸锌;所述硫酸亚铁和葡萄糖酸锌的质量比为0.1~0.2:0.1~0.2。
本发明中,所述组合物包括车前子壳粉50~200份,优选为80~150份,更优选为100份;所述车前子壳粉的粒径优选为60~100目,更优选为80目;所述车前子壳粉来源于常规市售,本发明具体实施过程中,所述车前子壳粉来源于广东大时代健康产业园有限公司。
本发明中,所述组合物包括燕麦粉50~200份,优选为80~150份,更优选为100份;所述燕麦粉的粒径优选为60~100目,更优选为80目;所述燕麦粉来源于常规市售,本发明具体实施过程中,所述燕麦粉来源于广东大时代健康产业园有限公司。
本发明中,所述组合物包括木瓜粉50~200份,优选为80~150份,更优选为100份;所述木瓜粉的粒径优选为60~100目,更优选为80目;所述木瓜粉来源于常规市售,本发明具体实施过程中,所述木瓜粉来源于广东大时代健康产业园有限公司。
本发明中,所述组合物包括菠萝粉50~200份,优选为80~150份,更优选为100份;所述菠萝粉的粒径优选为60~100目,更优选为80目;所述菠萝粉来源于常规市售,本发明具体实施过程中,所述菠萝粉来源于广东大时代健康产业园有限公司。
本发明中,所述组合物包括西兰花粉50~200份,优选为80~150份,更优选为100份;所述西兰花粉的粒径优选为60~100目,更优选为80目;所述西兰花粉优选的包含甘氨酸;所述甘氨酸占西兰花粉的质量百分含量优选为0.1%~1%,更优选为0.2%~0.8%,最优选为0.5%;本发明中,所述西兰花粉富含甘氨酸成分,与甘油和Zn2+协同作用为FTO提供稳定的双加氧酶底物组件,每个亚基绑定1个Fe2+离子的同时被抗坏血酸激活,并可被N-草酰甘氨酸,富马酸盐和琥珀酸盐抑制;所述西兰花粉来源于常规市售,本发明具体实施过程中,所述西兰花粉来源于陕西森弗天然制品有限公司。
本发明中,所述组合物包括蓝莓粉5~100份,优选为20~80份,更优选为50份;所述蓝莓粉的粒径优选为60~100目,更优选为80目;所述蓝莓粉优选的包含花青素;所述花青素占蓝莓粉的质量百分含量优选为1%~50%,更优选为5%~40%,最优选为10%~20%;所述蓝莓粉来源于常规市售,本发明具体实施过程中,所述蓝莓粉大兴安岭林格贝寒带生物科技股份有限公司。
本发明所述组合物包括车前子壳粉、燕麦粉、木瓜粉、菠萝粉、西兰花粉和蓝莓粉等特定的膳食纤维成分,由肠道菌群代谢这些特定的植物膳食纤维和低聚果糖产生吲哚丙酸(IPA)物质,能够为BDNF基因提供稳定配体,稳定BDNF基因在海马,杏仁核,大脑皮质和小脑中的表达,平衡调节激活磷脂酶C活性、脑源性神经营养因子受体信号通路、细胞信号、神经侧枝发芽、肌管分化的负调控、神经营养因子TRK受体信号通路、脑源性神经营养因子受体信号通路的正调控、受体结合的正调控以及蛋白质定位到细胞表面的调节,帮助肥胖患者有效控制贪食行为。
本发明中,所述组合物中的膳食纤维包括但不仅限于车前子壳粉、燕麦粉、木瓜粉、菠萝粉、西兰花粉和蓝莓粉,优选的还包括草莓粉和蔓越莓粉。
本发明中,所述组合物包括甘油5~50份,优选为8~20份,更优选为10份;所述甘油来源于常规市售。
本发明中,所述组合物包括低聚果糖10~30粉,优选为15~25份,更优选为20份;所述低聚果糖来源于常规市售。
本发明中,所述组合物包括抗坏血酸10~40份,优选为12~20份,更优选为15份;所述抗坏血酸来源于常规市售,本发明具体实施过程中,所述抗坏血酸购自于郑州瑞普生物工程有限公司。
本发明中,所述组合物包括矿物质元素补充剂10~40份,优选为12~20份,更优选为15份;所述矿物质元素补充剂包括硫酸亚铁和葡萄糖酸锌;所述葡萄糖酸锌和硫酸亚铁的质量比为0.1~0.2:0.1~0.2。,优选为0.15~0.2:0.15~0.2,最优选为0.18~0.2:0.18~0.2;所述葡萄糖酸锌和硫酸亚铁优选的购自于郑州瑞普生物工程有限公司。
本发明中,所述组合物优选的还包括辅料;所述辅料优选的包括芦荟凝胶粉;所述芦荟凝胶粉优选为库拉索芦荟凝胶粉,来源于常规市售。
本发明中,所述组合物的剂型优选的包括果冻、粉剂和口服液。
本发明还提供了上述方案所述组合物的制备方法,包括以下步骤:将所述车前子壳粉、燕麦粉、木瓜粉、菠萝粉、西兰花粉、蓝莓粉、甘油、抗坏血酸和矿物质元素补充剂混合,按植物饮料加工工艺进行灭菌,得到组合物;本发明对所述混合、灭菌的方式、时间和温度没有特殊限制,采用本领域常规方法即可。
本发明还提供了上述方案所述组合物在制备通过靶向补充BDNF、FTO基因配体治疗肥胖的食品或保健品中的应用。
下面结合实施例对本发明提供的技术方案进行详细的说明,但是不能把它们理解为对本发明保护范围的限定。
实施例1一种通过靶向补充BDNF、FTO基因配体治疗肥胖的果冻
所述果冻的活性组分和含量如表1所示,辅料为库拉索芦荟凝胶。
表1活性组合物果冻制剂成分
组分 | 每100g溶液的含量 |
车前子壳粉 | 9g |
燕麦粉 | 9g |
木瓜粉 | 9g |
菠萝粉 | 9g |
西兰花粉 | 9g |
蓝莓粉 | 1g |
锌(Zn) | 2mg |
铁(Fe) | 2mg |
甘油 | 30mg |
抗坏血酸 | 30mg |
低聚果糖 | 5g |
库拉索芦荟凝胶 | 5g |
果冻制备方法
流程:原料混合—煮胶—调配—灌装—封口—杀菌—冷却—包装—成品。
1、原料混合:先将车前子壳粉、燕麦粉、木瓜粉、菠萝粉、西兰花粉、蓝莓粉、库拉索芦荟凝胶按以上以配方比例,根据所需份数调配粉果冻粉,然后按果蔬粉总用量3%~5%,加水,搅拌。
2、煮胶:在搅拌状态下加入,加热溶解(90~100℃,保持10min);
3、调配:依次加入锌、铁、甘油、低聚果糖;
4、过滤:100~150目粗滤,再精滤(原水最好经过系统处理),到过度桶(缸)保温、暂存;
5、灌装、封口;
6、常压杀菌,温度80~85℃,时间10~15min,杀菌后用冷水喷淋,使果冻表面迅速降温到35度左右(凝胶温度),最后用50度左右的热风吹干;
7、冷却、包装、成品。
实施例2一种通过靶向补充BDNF、FTO基因配体治疗肥胖的粉末冲剂所述粉末冲剂活性组分和含量如表2所示,辅料为库拉索芦荟凝胶粉剂。
表2活性组合物粉末冲剂成分
粉末冲剂制备流程
流程:原料验收—领料—去外衣—消毒—预处理—称料—混和—填充—包装打码—金属探测—热收缩—成品
具体制备方法,按《植物饮料》GB/T 31326-2014国家标准进行。
实施例3一种通过靶向补充BDNF、FTO基因配体治疗肥胖的口服液
所述口服液活性组分和含量如表3所示,辅料为库拉索芦荟凝胶。
表3活性组合物口服液成分
组分 | 每100ml溶液的含量 |
车前子壳粉 | 9g |
燕麦粉 | 9g |
木瓜粉 | 9g |
菠萝粉 | 9g |
西兰花粉 | 9g |
蓝莓粉 | 1g |
锌(Zn) | 2mg |
铁(Fe) | 2mg |
甘油 | 20mg |
抗坏血酸 | 50mg |
低聚果糖 | 5g |
库拉索芦荟凝胶 | 1g |
口服液生产工艺流程
原料净化—混和—配制—过滤—精制—洗瓶—灌封—灭菌—检漏—贴签—装盒
具体制备方法,按《植物饮料》GB/T 31326-2014国家标准进行。
实施例4
与深圳第一健康医学检验中心连锁、深圳靶向基因研发中心、修曼基因、康美汇健康管理连锁、细胞云等机构等合作,对广东、北京、河北、天津、河南、黑龙江、内蒙古、江苏、四川、中国香港、澳大利亚悉尼等地BMI指数≥26的超重及肥胖者,采用以上方案进行试用,对日常饮食、运动时间及强度未提出任何改变,半个月左右,819位肥胖者体重平均下降4.5公斤。干预一个月后,其中有5位中度脂肪肝肥胖者进行医学检验数据对比,脂肪肝普遍由中度转为轻度,血液低密度胆固醇、甘油三酯标准区间值以上的超区间值部分,平均下降60%,平均体重下降6公斤以上,体重下降最显著的,一个月达到15公斤,具体结果参见表1。
95%以上受试者在食用本发明活性组合物3天后,陆续都感觉有饱腹感,食量明显得到控制,对平日喜欢的肉食与高油脂食物的兴趣明显下降。
表1受试者在食用本发明活性组合物15天河30天对应的身体情况
编号 | 主要对照项目 | 15天 | 30天 |
1 | BMI指数下降1个点以上 | 60% | 100% |
2 | 平均减重 | 4.5kg | 6.6kg |
3 | 肉食及高油偏食倾向 | 明显减弱 | 主动控制 |
4 | 主食量 | 减少1/3有饱腹感 | 减少1/2有饱腹感 |
5 | 高血脂超出标准区间值部分 | 平均下降35% | 平均下降60% |
实施例5
北京从事金融工作的王先生,应用实施例一、二制备得到的果冻和粉剂进行分子营养干预共两个月,每天早晚各一个果冻,晚上一杯粉末冲剂,不但减重8公斤,身上两个脂肪瘤,直径约2公分,有一个彻底消失,另一个明显缩为扁平,难以用手感触。
实施例6
本发明人与东莞赛尔生物科技有限公司合作干细胞营养项目,对重度肥胖人士,应用实施例一、二制备得到的果冻和粉剂进行分子营养干预,每天早晚各一个果冻,早晚各一杯粉末冲剂,效果非常显著。
王先生为赛尔干细胞某代理机构总经理,在使用多种减肥方案遇到体重控制瓶颈难以突破的情况下,采用本发明活性组合物半个月,减重3.5公斤,一个月减重8.5公斤。
实施例7
广东汕尾某房地产开发商卓先生,中心性肥胖,高血糖(长期餐前7~9mmol/L)、高尿酸(参与营养干预前体验,达594umo1/L),经常感觉疲劳、倦怠。应用实施例一、二制备得到的粉剂进行分子营养干预三个月,每天早晚各一杯粉末冲剂,体重降5公斤,血糖一直稳定在5.3~5.9之间,尿酸首月即将至430umo1/L,明显感觉有精气神。
实施例8
蔡某,供职于深圳某房地产公司,中心性肥胖,经常舒张压90~100(mmHg),收缩压150~180(mmHg)之间,餐前血糖在8~10mmol/L之间波动,头晕眼花,并伴焦虑情绪。应用实施例一、二制备得到的果冻和粉剂进行分子营养干预三个月,每天早晚各一个果冻,早晚各一杯粉末冲剂,体重减少9.5kg,餐前血糖稳定在6.0mmol/L以内,血压稳定在收缩压:100~130(mmHg),舒张压:80~89(mmHg)。随访两年,只有在处理公司危机事务过程中,血压再度升高过一次,经过一个多月的实施例一、二分子营养方案调理,恢复稳定。
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
Claims (8)
1.一种通过靶向补充BDNF、FTO基因配体治疗肥胖的组合物,包括以下重量份的原料:车前子壳粉50~200份、燕麦粉50~200份、木瓜粉50~200份、菠萝粉50~200份、西兰花粉50~200份、蓝莓粉5~100份、甘油5~50份、低聚果糖10~30份、抗坏血酸10~40份和矿物质元素补充剂10~40份,所述矿物质元素补充剂包括硫酸亚铁和葡萄糖酸锌;所述葡萄糖酸锌和硫酸亚铁的质量比为0.1~0.2:0.1~0.2。
2.根据权利要求1所述的组合物,其特征在于,所述组合物包括以下重量份的原料:车前子壳粉80~150份、燕麦粉80~150份、木瓜粉80~150份、菠萝粉80~150份、西兰花粉80~150份、蓝莓粉20~80份、甘油8~20份、低聚果糖15~25份、抗坏血酸12~20份和矿物质元素补充剂12~20份。
3.根据权利要求2所述的组合物,其特征在于,所述组合物包括以下重量份的原料:车前子壳粉100份、燕麦粉100份、木瓜粉100份、菠萝粉100份、西兰花粉100份、蓝莓粉50份、甘油10份、低聚果糖20份、抗坏血酸15份和矿物质元素补充剂15份。
4.根据权利要求1~3任意一项所述的组合物,其特征在于,所述车前子壳粉、燕麦粉、木瓜粉、菠萝粉、西兰花粉和蓝莓粉的粒径独立为60~100目。
5.根据权利要求1~3任意一项所述的组合物,其特征在于,所述组合物还包括辅料;所述辅料包括芦荟凝胶粉。
6.根据权利要求1~3任意一项所述的组合物,其特征在于,所述组合物的剂型包括果冻、粉剂和口服液。
7.权利要求1~6任意一项所述组合物的制备方法,包括以下步骤:将所述车前子壳粉、燕麦粉、木瓜粉、菠萝粉、西兰花粉、蓝莓粉、甘油、抗坏血酸和矿物质元素补充剂混合,进行灭菌,得到组合物。
8.权利要求1~6任意一项所述组合物在制备通过靶向补充BDNF、FTO基因配体治疗肥胖的食品或保健品中的应用。
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