CN108703364A - 脂肪酸代谢异常专用型临床营养配方及其制备方法 - Google Patents
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Abstract
本发明提供一种脂肪酸代谢异常专用型临床营养配方,其特征在于,包括如下组分及其重量份数:15‑28份蛋白质、8‑12份脂肪、48‑65份碳水化合物、3‑6份膳食纤维、0.6‑1.2份常量元素、0.01‑0.04份微量元素、0.005‑0.03份脂溶性维生素、0.008‑0.2份水溶性维生素、0.06‑2份药食同源成分、0.02‑3份天然植物化合物以及0.02‑2份新资源食品;本发明还提供上述临床营养配方的制备方法。本发明能够为脂肪酸代谢异常患者补充所需的营养,还能够改善多种脂代谢异常、促进脂代谢正常进行、缓解脂代谢异常症状、缓解患者病痛。
Description
技术领域
本发明涉及营养配方领域,尤其涉及一种脂肪酸代谢异常专用型临床营养配方及其制备方法。
背景技术
脂肪酸代谢异常(脂肪酸代谢障碍)是由于体内脂肪酸β-氧化酶或转运蛋白缺乏,导致脂肪酸分解和能量生成障碍,出现神经系统、骨骼肌、心、肝、肾、消化道等功能异常造成,其中以中链酰基辅酶A脱氢酶(MCAD)缺乏最为多见。该疾病是遗传性代谢病,主要累及婴儿和儿童,多数于出生后两年内起病,常有家族史。临床表现为慢性肌无力、肌痛或心肌病,也可表现为空腹昏迷和低血糖,发病期间常常没有症状,发病率和死亡率较高,故应及早诊断,及早治疗便可减少复发率。
脂肪酸代谢障碍主要分为以下几类:
1)脂肪酸和肉碱转运障碍:包括胞浆膜肉碱转运障碍(原发肉碱缺陷)、细胞摄取脂肪酸障碍、CPTⅠ缺陷、肉碱-CAT缺陷、CPTⅡ缺陷等;其中,CPTⅡ缺陷是脂肪酸代谢障碍中最常见的类型;
2)CoA脱氢酶(ACD)缺陷:包括极长链、中链、短链ACD缺陷,其多发人群、临床表现及基因突变各异;
3)线粒体基质β-氧化酶缺陷:包括长链、短链3-羟脂酰辅酶A脱氢酶(LCHAD,SCHAD)缺陷;其中,SCHAD缺陷较为罕见;
4)酮体生成障碍:指HGM-CoA(3-羟基-3-甲基戊二酸单酰辅酶A,亦参与亮氨酸代谢)功能障碍,表现为伴高血氨和酸中毒的低酮性低血糖;尿液中若发现强甲基戊二酸则具有诊断意义;
5)多重能量代谢缺陷:多重代谢缺陷可共同作用,使产能减少,且减少程度与临床症状的发展相一致,称为协同异质性。
一般根据含碳原子的多少,可将体内脂肪酸分为短链(2~6碳)、中链(8~12碳)、和长链(14碳以上)。脂肪酸β-氧化代谢是将二碳单位由长链脂肪酸上水解下来后进入三羧酸循环或酮体生成途径分解产能的过程。人体完成脂肪酸β-氧化代谢主要是通过线粒体和过氧化物酶。正常情况下,脂肪酸代谢大多由线粒体β-氧化完成,但在禁食延长的情况下,过氧化物酶可承担细胞内脂肪酸β-氧化总量的20%;此外,脂肪酸代谢尚可通过细胞质中的ω氧化途径,并可形成双羧酸,双羧酸大多发现于线粒体β-氧化超常情况下。当线粒体β-氧化受损害时,可由硫脂酶完成辅酶A脱肽基,并将肽基结合至甘氨酸和肉碱。上述脂肪酸氧化(FAO)途径中酶的先天性缺陷,将导致脂肪酸氧化障碍,从而引起一系列临床症状。
脂肪酸氧化缺陷主要引起心肌病,众多的证据均支持这样一个概念,即能量缺乏是心脏病变发生的机制之一,因此,对于心肌功能的改善以及调节心肌的能量底物代谢将有助于改善心脏的收缩功能障碍,预防心脏疾病的发生和发展。因此,中链脂肪酸(MCFAs)除了能够迅速提供能量,作为“代谢调节器”具有潜在的药理作用外,其对于心肌病的干预已被提议作为辅助疗法来治疗这些疾病;而且,MCFAs在遗传性LCFAβ-氧化缺陷心脏病的营养干预和管理上显示了一定的益处,而目前的研究结果从动物和人群研究上也证实LCFAs作为心肌收缩功能的决定因素,在梗死后或肥大的心脏心肌结构重建、线粒体能量代谢调节上并未起到有益的作用。
受遗传性脂肪酸氧化缺陷的影响,患者的临床表型是非常多样化的,但通常包括心肌病和/或心脏跳动紊乱。与LCFAs氧化缺陷相关的心脏疾病,主要是由于两方面原因:一是肉碱穿过线粒体膜运输的过程缺陷;二是LCFAs氧化需要的特定线粒体酶的缺陷。相反,MCFAs或短链脂肪酸氧化异常时,不存在上述两种原因。心脏代偿时,LCFAs通常是机体空腹或应激状态下的主要能源。对于LCFAs氧化缺陷的患者,给予含有MCT结合碳水化合物、肉碱的饮食(MCT的产热比为30%),同时减少LCT的摄入,可减轻心肌病的症状,并改善LCFAs氧化缺陷的体征。
患有不同临床表现的脂肪酸代谢异常患者应在确诊后进行营养治疗干预,PCD患者平时应注意预防低血糖、避免饥饿、多餐饮食、避免长时间运动,一般无特殊饮食要求。但有学者通过PCD动物模型研究发现,低脂饮食,尤其是限制长链脂肪酸摄入,有助于改善心肌肥厚。对于病情危重的PCD患者,还应积极对症支持治疗。
PCD患者对左旋肉碱治疗敏感,尤其在不可逆病变(如中枢神经系统损伤)发生之前应用,预后较好。经左旋肉碱治疗后,患者症状显著缓解,心功能迅速改善,心脏大小及心室壁厚度缩小,肌力及肌张力逐渐恢复,肝功能好转,肝脏缩小,智力、运动及生长发育正常。患者临床表现恢复所需的时间具有个体差异性,数周到数年均有报道。如报道,PCD患儿经过2个月的肉碱替代治疗,肝脏肿大、转氨酶水平及心脏功能均恢复正常。左旋肉碱的治疗剂量需根据个体血肉碱浓度变化和病情程度而进行调整:急性期,100~400mg/(kg·d),静脉滴注;稳定期,100~300mg/(kg·d),口服。一般分每日2~3次用药,以维持血肉碱水平的稳定。大剂量左旋肉碱治疗可能引起腹泻、恶心等胃肠道不适,可先减少剂量,待不良反应改善后再逐步增至治疗剂量。PCD患者需终身服用左旋肉碱,突然停药可使血浆肉碱浓度迅速下降,出现反复Reye综合征样发作、甚至猝死。对于无症状的PCD患者,补充左旋肉碱,可有效预防发病及猝死。目前,应用左旋肉碱治疗PCD杂合子还没有共识,但有研究发现心功能不全的杂合子补充肉碱后心脏情况得到改善。
MCADD患者第一次病情发作时,如得不到及时诊断和治疗,会导致神经系统后遗症。在明确诊断后,应积极补充高能量营养物质,不能口服或鼻饲的患儿静脉给予10%的葡萄糖。未有临床表现的患儿,注意如下事项可以预防疾病发作,明显改善预后:(1)避免空腹时间过长;(2)应激(发热、疫苗接种)时补充碳水化合物;(3)饮食中要提高碳水化合物和蛋白含量,减少脂肪含量(脂肪供给热量小于总供给热量的20%)。是否需要补充肉碱尚有争议。有的认为肉碱能结合毒性代谢产物,促进其排出体外。另一种观点认为不补充肉碱,仅补充能量,治疗效果也理想。对于慢性肌无力病人或重症病人可试用肉碱。
VLCAD缺陷症无特殊治疗,主要采用饮食疗法,高糖饮食辅以中链脂肪酸,限制长链脂肪酸的摄入,避免空腹,维持血糖稳定;补充肉毒碱,对长链脂肪酸代谢产物进行监测,以及进行相应的对症支持处理。进行体育活动前补充中链脂肪酸有助于控制发病。急性发作时可静脉输注100g/L葡萄糖。但值得注意的是,中链脂肪酸饮食疗法亦可引起内脏脂肪堆积、脂肪肝及组织脂肪构成的改变。基因治疗仍处于实验阶段。
线粒体基质β-氧化酶缺陷应补充中短链脂肪酸,改变膳食中脂肪酸链长度,避免饥饿、避免高脂肪饮食可以延缓和治疗本病。在发生能量危机时及时补充葡萄糖。长期的膳食治疗中还应注意患者生活管理,避免疲劳,预防急性发作。
对于这些症状的脂肪酸代谢异常目前市场上现有的产品比较少,只能通过医院营养科调配才能使用,不便于携带。
中国专利CN201410408121.X公开了一种脂肪酸代谢异常全营养配方食品,其依据“消中寓补”、“均衡营养”地传统中医的精髓理论,采用多种药食两用的中药提取物精华、多种益生菌、短肽为主要原料,调节脂代谢异常患者的营养状况,利用药食两用的中药中的功能因子调节身体机能等。但是,其并没有能够针对不同临床表现的脂代谢异常,深入了解不同临床表现的脂肪酸代谢异常患者的发病机理,综合研究后提供具有改善多种脂代谢异常、促进脂代谢正常进行、缓解脂代谢异常症状的营养配方。
因此研制一款针对脂肪酸代谢异常的便于服用和携带的临床营养产品,并能够改善多种脂代谢异常、促进脂代谢正常进行、缓解脂代谢异常症状、缓解患者病痛的脂肪酸代谢异常专用型临床营养配方显得尤为重要。
发明内容
本发明的目的在于克服现有技术中的缺陷,提供一种脂肪酸代谢异常专用型临床营养配方及其制备方法,既能够为脂肪酸代谢异常患者补充所需的营养,还能够改善多种脂代谢异常、促进脂代谢正常进行、缓解脂代谢异常症状、缓解患者病痛。
为实现上述目的,本发明采用如下技术方案:
本发明的第一个目的是提供一种脂肪酸代谢异常专用型临床营养配方,包括如下组分及其重量份数:15-28份蛋白质、8-12份脂肪、48-65份碳水化合物、3-6份膳食纤维、0.6-1.2份常量元素、0.01-0.04份微量元素、0.005-0.03份脂溶性维生素、0.008-0.2份水溶性维生素、0.06-2份药食同源成分、0.02-3份天然植物化合物以及0.02-2份新资源食品;
其中,所述新资源食品包括初乳碱性蛋白、γ-氨基丁酸、壳寡糖、杜仲雄花、竹叶黄酮、酪蛋白磷酸肽、燕麦β-葡聚糖、地龙蛋白、牡丹籽油、酵母β-葡聚糖、乳矿物盐、玛咖粉、刺梨、蛹虫草、低聚木糖中的至少一种;
其中,所述天然植物化合物包括左旋肉碱、氨基葡萄糖、低聚果糖、叶黄素、植物甾醇、番茄红素、白藜芦醇、大蒜素中的至少一种。
为了进一步优化上述技术方案,本发明所采取的技术措施还包括:
进一步地,所述营养配方中,蛋白质:脂肪:碳水化合物的产能比为15~20:20~25:55~65;更进一步地,蛋白质:脂肪:碳水化合物的产能比为16:24:60。
进一步地,所述蛋白质包括乳清蛋白粉、大豆分离蛋白、水解鱼胶原蛋白、全脂奶粉、脱脂奶粉、全蛋粉、乳铁蛋白、牛初乳、氨基酸、蛋白肽中的至少一种;其中,所述氨基酸包括L-赖氨酸-L-谷氨酸、L-谷氨酸、L-精氨酸、L-色氨酸、L-谷氨酰胺、牛磺酸、L-缬氨酸、L-异亮氨酸、L-亮氨酸中的至少一种,所述蛋白肽包括大豆低聚肽、小麦蛋白肽、蚕蛹蛋白肽、海洋鱼低聚肽粉、可乐肽、氨基肽、卵白蛋白肽中的至少一种;更进一步地,所述蛋白质为乳清蛋白粉、大豆分离蛋白、脱脂奶粉、牛初乳粉、海洋鱼低聚肽、牛磺酸。
进一步地,所述脂肪包括饱和脂肪酸、多不饱和脂肪酸、单不饱和脂肪酸、OPO结构脂、DHA、EPA、ARA、磷脂中的至少一种。
进一步地,所述脂肪包括中链甘油三酯,所述中链甘油三酯的重量份数为5-8份。
进一步地,所述脂肪包括亚油酸,所述亚油酸的重量份数为1-2份。
进一步地,所述碳水化合物包括果糖、冰糖、乳糖、麦芽糊精、木薯淀粉、抗性淀粉中的至少一种;更进一步地,所述碳水化合物为麦芽糊精。
进一步地,所述膳食纤维包括菊粉、魔芋粉、低聚半乳糖、低聚果糖、低聚异麦芽糖、大豆多糖、环糊精、抗性糊精、大豆纤维中的至少一种。
进一步地,所述常量元素包括柠檬酸钙、L-乳酸钙、磷酸氢钙、葡萄糖酸钙、柠檬酸钾、氯化钾、葡萄糖酸钾、氯化钠、柠檬酸钠、葡萄糖酸镁、碳酸镁、硫酸镁中的至少一种。
进一步地,所述微量元素包括葡萄糖酸亚铁、硫酸亚铁、碘化钾、柠檬酸锌、葡萄糖酸锌、亚硒酸钠、硫酸铜、葡萄糖酸铜、硫酸铬、氯化铬、葡萄糖酸锰、硫酸锰、钼酸钠中的至少一种。
进一步地,所述脂溶性维生素包括维生素A、β-胡萝卜素、维生素D3、维生素E、维生素K1中的至少一种。
进一步地,所述水溶性维生素包括维生素B1、维生素B2、维生素B6、维生素B12、维生素C、泛酸、叶酸、烟酸、胆碱、肌醇、生物素中的至少一种;更进一步地,所述水溶性维生素中维生素C的重量份数为0.15-0.17份;更进一步地,所述水溶性维生素中维生素C的重量份数为0.163份。
进一步地,所述药食同源成分的重量份数为0.06-0.6份。
进一步地,所述药食同源成分包括茯苓、枸杞、橘皮、鸡内金、芡实、山药、栀子、金银花、葛根、沙棘、桑叶、牡蛎、甘草中的至少一种;更进一步地,所述药食同源成分为茯苓、枸杞、橘皮、鸡内金、芡实、山药;其重量份数分别为:茯苓0.01-0.1份、枸杞0.01-0.1份、橘皮0.01-0.1份、鸡内金0.01-0.1份、芡实0.01-0.1份、山药0.01-0.1份。
进一步地,所述天然植物化合物为左旋肉碱;更进一步地,所述左旋肉碱的重量份数为0.04-0.64份。
进一步地,所述新资源食品的重量份数为0.02-0.2份。
进一步地,所述新资源食品包括γ-氨基丁酸和蛹虫草中的至少一种;更进一步地,所述新资源食品为γ-氨基丁酸和蛹虫草,其中,γ-氨基丁酸的重量份数为0.01-0.05份,蛹虫草的重量份数为0.01-0.1份。
本发明的第二个目的是提供一种上述脂肪酸代谢异常专用型临床营养配方的制备方法,包括如下步骤:
步骤1,制备脂肪粉末;
步骤2,制备药食同源成分粉末:采用粉碎机对预定重量份数的原料进行粉碎,将粉碎的原料置于容器中,加入重量为原料重量的3~8倍的水,浸泡3~4小时,然后对浸泡液煎煮30~60min,过滤去除原料,留取煎煮液,对煎煮液进行喷雾干燥,以60~80目筛分制备药食同源成分粉末;
步骤3,制备脂溶性维生素粉末和水溶性维生素粉末:将预定重量份数的脂溶性维生素作为芯材,选用卡拉胶、阿拉伯胶作为壁材,在高压下进行2次乳化均质处理,乳化均质时间为10~15min,然后进行喷雾瞬时干燥,以60~80目筛分制备脂溶性维生素粉末;将预定重量份数的水溶性维生素作为芯材,选用麦芽糊精、脂蛋白作为壁材,混合均匀,喷雾瞬时干燥,以60~80目筛分制备水溶性维生素粉末;
步骤4,将预定重量的蛋白质、碳水化合物、膳食纤维、常量元素、微量元素、天然植物化合物以及新资源食品分别制备成粒径为150~250μm的粉末;
步骤5,将步骤1~4所制得的粉末依次加入混合机混合均匀制得配方混合物,经过杀菌处理后备用;
步骤6,将所述配方混合物制备成营养粉、营养乳剂、胶囊剂、片剂、丸剂或口服液中的至少一种;
其中,步骤1~4的顺序可相互更换。
进一步地,所述步骤1中制备脂肪粉末具体包括如下步骤:
1)制备壁材水溶液:取麦芽糊精10g、大豆分离蛋白4g、脱脂乳粉11g、膳食纤维3g(抗性糊精)、菊粉0.5g、乳清蛋白粉5g、低聚异麦芽糖0.5g、阿拉伯胶0.2g、水50mL搅拌均匀;
2)将单甘酯取0.1g(总固形物浓度为0.2%)均匀溶于9mL混合植物油脂中;所述混合植物油脂由0.9mL橄榄油、1.4mL大豆油、0.9mL椰子油、0.2mL紫苏油、5.6mL中链甘油三酯组成;
3)将吐温80取0.1g(总固形物浓度为0.2%)均匀溶于所述壁材水溶液中;
4)将添加过乳化剂单甘酯的混合植物油脂与添加过乳化剂吐温80的壁材水溶液充分混合,得到混合溶液;
5)添加稳定剂琼脂0.1g(总固形物浓度为0.2%)于所述混合溶液后,用水定容至200mL(总固形物浓度为25%),20000r/min下高速分散2分钟,得到乳状液;
6)将所述乳状液在均质压力25MPa下,均质3次,每次5分钟,得到均质乳状液;
7)将所述均质乳状液进行喷雾干燥,进风温度为195℃,出风温度为80℃,收集得到脂肪粉末。
进一步地,所述步骤6中可选择性地增加适量的食品增稠剂和食品添加剂。其中,所述食品增稠剂包括瓜尔胶、黄原胶、槐豆胶、魔芋胶、果胶、卡拉胶、琼脂、明胶、阿拉伯胶中的至少一种,所述食品添加剂包括阿斯巴甜、食用香精香料、红糖中的至少一种。更优选为卡拉胶、阿拉伯胶、瓜尔胶、阿斯巴甜、食用香精香料。
进一步地,上述脂肪酸代谢异常专用型临床营养配方的制备方法的操作步骤均需在惰性气体的保护下进行,所使用的惰性气体为氮气、氩气、氦气等。在惰性气体的保护下进行上述操作步骤可以防止产生粉末爆炸的危险。
本发明中采用包括茯苓、枸杞、橘皮、鸡内金、芡实、山药的药食同源成分,上述成分配伍增效后具有提高机体免疫力、促进脂代谢、预防心脏疾病、缓解患者的病痛的功效。
茯苓及羧甲基茯苓多糖具有提高机体免疫力,抗菌,降糖等作用;同时土茯苓黄酮对小鼠肝脏中脂肪酸及胆固醇代谢的研究发现,土茯苓黄酮能够显著增加脂肪酸β-氧化酶活性,能够通过诱导增加脂肪分解代谢相关酶活性来促进脂肪分解;
枸杞的果、叶、柄中含有生物碱甜菜碱,甜菜碱是一种无毒的天然化合物,《甜菜碱对大鼠机体脂肪代谢的影响及肝脂代谢机制研究》对小鼠实验表明,甜菜碱能够增强血液中脂质的转运,高脂日粮组添加甜菜碱可增加肌肉组织内脂肪的含量,增强脂肪组织中的脂肪动员,显著降低肝脏中的脂肪堆积,增强肝脏内脂肪的氧化分解代谢;因此,脂代谢异常患者服用含有甜菜碱的枸杞能够促进脂代谢正常进行;
橘皮富含硒,硒对维持心肌纤维、血管的正常结构和功能发挥着重要作用,能够显著改善由于脂代谢异常引起的心肌病,有助于改善心脏的收缩功能障碍,预防心脏疾病的发生和发展,缓解患者的病痛;
鸡内金含有胃液素、胃蛋白酶、淀粉酶以及多种维生素;《鸡内金多糖对高脂血症大鼠血脂、血液流变学及氧化应激指标的影响》对大鼠实验表明,鸡内金多糖能够有效预防实验性高脂血症大鼠脂代谢紊乱,提高机体脂代谢能力,改善血液流变学指标异常,降低其氧化应激水平;
芡实含有丰富的淀粉,可为人体提供热能,并含有多种维生素和碳物质,保证体内营养所需成分;
山药具有滋补细胞、强化内分泌、补益强壮、增强机体造血功能等作用,可诱生干扰素,改善机体免疫功能,提高抗病能力等;国外研究表明,山药能促进大脑分泌脱氢表雄酮,脱氢表雄酮可使睡眠改善,心情愉快;山药含有的淀粉酶,能分解成维持人体生命的重要物质蛋白质和糖类,山药含有丰富的纤维素,具有降低胆固醇的作用;山药的重要成分之一——多巴胺,具有扩张血管、改善血液循环的功能,有助于心肌功能的改善以及调节心肌的能量底物代谢,预防心脏疾病的发生和发展,缓解患者的病痛。
本发明采用上述技术方案,与现有技术相比,具有如下技术效果:
1)本发明的脂肪酸代谢异常专用型临床营养配方采用15~20:20~25:55~65的蛋白质:脂肪:碳水化合物的供能比例,为患者提供均衡的营养补充。
2)本发明添加中链甘油三酯5-8份,研究表明,LCFAs氧化缺陷的基本病理生理机制一方面是由于LCFAs不能彻底氧化,产生过量的LCFAs衍生物,如长链酯酰辅酶A(LC-acyl-Co A)或肉毒碱,在患者体内储存,对患者产生毒性;另一方面是由于LCFAs不能彻底氧化,使患者不能得到足够的能源。使用MCT对LCFAs氧化缺陷的患者进行营养管理或疾病治疗,主要是由于MCFAs和它的主要代谢产物,不需要这些缺陷的酶的催化,即可产生能量,这个能量要优于机体碳水化合物提供的能量。如Schuler AM等用冷刺激LCFAs氧化缺陷的小鼠,给予富含MCT的膳食可迅速提供小鼠能量,而不是通过葡萄糖输液。此外,MCFAs还可减少体内有毒的LCFA衍生的代谢产物的积累,如以LCFA氧化缺陷的病人的成纤维细胞为研究对象进行实验,在这些细胞中,MCFAs被氧化,同时诱导减少了有毒的LCFA衍生物积累,纠正了LCFA的次生代谢紊乱。但具体的作用机制尚未阐明。然而,即使MCFA的利用在不同的酶缺陷个体中稍有不同,但MCT的补充对于LCFAs的氧化缺陷是有益的。
3)本发明添加维生素C 0.15-0.17份,维生素C能通过参与肉碱合成而间接促进脂质的代谢,从而增加脂质代谢和蛋白质的良性循环,改善能量代谢,当维生素C缺乏时,肉碱合成减少,以致脂肪的β-氧化减少。有研究探讨维生素C溶液浸泡对脂质合成代谢密切相关的脂肪酸合成酶(FAS)和乙酰辅酶A羧化酶(ACC),以及与脂质氧化分解密切相关的肉毒碱棕榈酰转移酶Ⅰ(CPTⅠ)的活性变化规律,结果发现维生素C组ACC、FAS和CPTⅠ比活力和全活力均高于对照组,其原因可能有2个:一是维生素C在脂质代谢中发挥了抗氧化功能,采用适宜浓度的维生素C溶液浸泡普安银鲫胚胎,降低了机体的损伤,提高了普安银鲫胚胎的免疫力,使其在抗氧化过程中维持维生素E和β-胡萝卜素的水平,阻断脂肪的氧化链,避免细胞膜遭受氧化损伤,同时保护脂质膜免受过氧化损害,防止脂肪酸过氧化,有利于免疫功能的发挥;二是维生素C参与肉碱合成间接促进了脂质代谢,诱导胚胎期ACC、FAS和CPTⅠ的分泌,导致维生素C溶液浸泡下的胚胎体内3种脂质代谢酶活性升高。上述结果表明适宜浓度的维生素C溶液对普安银胚胎发育过程中体内脂质代谢具有促进作用。
4)本发明添加左旋肉碱。长链脂肪酸是脂肪的主要成分,在人体内代谢时以甘油三酯的形式由淋巴管进入静脉,被输送并储存在人体各组织中,容易累积形成脂肪,而左旋肉碱在脂肪酸分解过程中起着关键性的作用,如果缺乏左旋肉碱,则脂肪酸的分解供能将会中断,生命活动将发生障碍;左旋肉碱主要的功能是作为载体以脂酰肉碱的形式将长链脂肪酸从线粒体膜外转运到膜内,在线粒体内进行β-氧化。促进三羧酸循环的正常进行,从而产生三磷酸腺苷功能,协助细胞完成正常的生理功能和能量代谢。在对小鼠给予高脂饲料喂养实验中,用剂量为予0、100、200、400mg/kg的左旋肉碱进行灌胃,并观察血脂的情况,发现200、400mg/kg左旋肉碱可有效促进脂肪酸代谢,减少体内脂肪的量,特别是能显著促进棕榈酸和C20H34O2等中长链脂肪酸的代谢,降低肥胖模型小鼠血清中甘油三酯、LDL-胆固醇,有效增加HDL-胆固醇含量。上述结果说明外援肉碱能加速脂肪酸的代谢,更多消耗脂肪酸,促使机体内储备的脂肪减少,引起机体的组成成分改变。其原因可能是外源L-肉碱的供给,直接提高机体L-肉碱水平,加速肉碱运输脂酰CoA进入线粒体内,增加脂肪酸氧化分解,最终导致体内储备脂肪减少。肉碱所在的运输系统酶由肉碱棕榈酰转移酶(CPT)Ⅰ、肉碱、乙酰肉碱移位酶、CPTⅡ组成,定位于不同的线粒体亚结构。在能量代谢中起重要作用的长链脂肪酸及其辅酶A只有通过该运输系统才能进入线粒体基质进行β氧化。CPTⅠ位于线粒体外膜上,催化长链脂酰CoA与肉碱合成脂酰肉碱,是线粒体脂肪酸氧化过程的第一个限速反应。肉碱剂量组小鼠较对照组棕榈酸的代谢显著增强,其原因可能是肉碱的丰富,增强了CPTⅠ的活性,从而对棕榈酸的优先运输作用在一定程度上增强。通过本实验看,左旋肉碱能有效促进肥胖小鼠体内脂肪酸代谢,降低血脂。
5)本发明添加γ-氨基丁酸0.01-0.0.05份。γ-氨基丁酸(GABA)又称氨酪酸,是一种非蛋白质组成的天然氨基酸,分布非常广泛,在动物、植物和微生物中均有GABA存在。GABA是哺乳动物、甲壳类动物昆虫和某些寄生蠕虫中枢神经系统中最重要的抑制性神经递质,介导了40%以上的抑制性神经传导,具有突触后抑制作用,可通过突触后膜超极化,减少离子内流,降低细胞代谢及氧消耗等机制,使突触后神经元处于保护性抑制状态,并可通过突触前抑制减少谷氨酸的释放,从而减少灌注区神经元的死亡。GABA这种递质的异常是诱发多种神经系统疾病,如兴奋性毒性反应、癫痫、失眠等。脂肪酸代谢异常是由于体内脂肪酸β-氧化酶或转运蛋白缺乏,导致脂肪酸分解和能量生成障碍,出现神经系统、骨骼肌、心肝肾等功能异常,而癫痫的发作和中枢神经递质之间有密切关系。癫痫是中枢神经系统的常见疾病,发病率0.5%~1.5%,是大脑功能失调引起的一种临床综合症。患者脑脊髓中GABA较正常人明显降低,且其程度与发病类型有关,其表明GABA可提高抗惊厥阈值,是治疗顽固性癫痫的特效生化药物。
6)本发明添加蛹虫草0.01-0.1份。蛹虫草又称蛹草、北虫草、北冬虫夏草,与冬虫夏草同属异种,蛹虫草含有丰富的维生素,具有调节神经系统的作用,对植物神经系统具有外周抗胆碱作用,能降低副交感神经兴奋性,使蛹虫草具有镇静作用,并且对心悸、失眠有较好的治疗作用。实验结果显示蛹虫草能明显减少小鼠自主活动,能对抗戊四氮诱发小鼠惊厥并且在一定程度上协同戊巴比妥钠诱发小鼠睡眠,作用强度与冬虫夏草相似,表明蛹虫草具有镇静催眠作用,但其作用机制是否与GABA递质释放有关尚有待于进一步研究。脂肪酸代谢异常是由于体内脂肪酸β-氧化酶或转运蛋白缺乏,导致脂肪酸分解和能量生成障碍,出现神经系统、骨骼肌、心肝肾等功能异常。桂宝等对蛹虫草水煎液的药理作用进行了研究,结果显示蛹虫草具有明显的镇静、增强戊巴比妥的睡眠作用。
7)亚油酸是天然存在的十八碳-9,12-二烯酸(顺,顺),其主要存在于植物油中,具有多种生物活性,包括降血脂,促进细胞生长,减肥,免疫调节等。亚油酸对高脂小鼠脂代谢的影响极其机制研究中发现,亚油酸能够作为PPARs的配体的激活或抑制PPARs的活性,从而在脂代谢中发挥调节作用。其原因是,脂蛋白脂酶能将甘油三酯降解为甘油和游离脂肪酸,是脂质代谢过程中的关键酶,而亚油酸能够通过改变脂蛋白脂酶的活性来调节脂质代谢的平衡。因而,亚油酸对于脂肪酸代谢异常患者具有改善脂代谢异常、促进脂代谢正常进行的功能。
本发明通过选用合理配比的基础营养素,同时添加具有提高机体免疫力、促进脂代谢、预防心脏疾病、缓解患者病痛、改善LCFAs氧化缺陷、治疗神经系统疾病的膳食纤维、药食同源成分、天然植物化合物和新资源食品等特殊营养物质,并调整其配比与基础营养素进行配伍增效,使的本发明的脂肪酸代谢异常专用型临床营养配方既能够为脂肪酸代谢异常患者补充均衡全面的营养,还能够改善多种脂代谢异常、促进脂代谢正常进行、缓解脂代谢异常症状、缓解患者病痛。
具体实施方式
本发明提供了一种脂肪酸代谢异常专用型临床营养配方,包括如下组分及其重量份数:15-28份蛋白质、8-12份脂肪、48-65份碳水化合物、3-6份膳食纤维、0.6-1.2份常量元素、0.01-0.04份微量元素、0.005-0.03份脂溶性维生素、0.008-0.2份水溶性维生素、0.06-2份药食同源成分、0.02-3份天然植物化合物以及0.02-2份新资源食品;
其中,所述新资源食品包括γ-氨基丁酸和蛹虫草中的至少一种;
其中,所述天然植物化合物包括左旋肉碱、氨基葡萄糖、低聚果糖、叶黄素、植物甾醇、番茄红素、白藜芦醇、大蒜素中的至少一种。
下面通过具体实施例对本发明进行详细和具体的介绍,以使更好的理解本发明,但是下述实施例并不限制本发明范围。
实施例1
本发明所述的脂肪酸代谢异常专用型临床营养配方包括乳清蛋白粉10.9g、大豆分离蛋白3.6g、脱脂奶粉11.02g、牛初乳粉0.1g、海洋鱼低聚肽0.1g、牛磺酸0.12g;橄榄油0.8g、大豆油1.3g、椰子油0.8g、紫苏油0.18g、中链甘油三酯5g;麦芽糊精48.97g;膳食纤维4g;常量元素中钙0.44g、磷0.2g、钾0.1g、钠0.3g、镁0.15g;微量元素中铁0.01g、锌0.007g;维生素A0.0007g、β-胡萝卜素0.017g、维生素D3 0.000001g、维生素E 0.009g;维生素B10.001g、维生素B2 0.001g、维生素B6 0.001g、维生素B12 0.000005g、维生素C 0.163g、泛酸0.003g、叶酸0.00013g、烟酸0.0124g;茯苓0.1g、枸杞0.1g、橘皮0.1g、鸡内金0.1g、芡实0.1g、山药0.1g;γ-氨基丁酸0.1g、蛹虫草0.1g、左旋肉碱0.64g。
实施例2
本发明所述的脂肪酸代谢异常专用型临床营养配方包括乳清蛋白粉10.9g、大豆分离蛋白3.6g、脱脂奶粉11.02g、牛初乳粉0.1g、海洋鱼低聚肽0.1g、牛磺酸0.12g;橄榄油0.8g、大豆油1.3g、椰子油0.8g、紫苏油0.18g、中链甘油三酯5g;麦芽糊精48.97g;膳食纤维4g;常量元素中钙0.44g、磷0.2g、钾0.1g、钠0.3g、镁0.15g;微量元素中铁0.01g、锌0.007g;维生素A0.0007g、β-胡萝卜素0.017g、维生素D3 0.000001g、维生素E 0.009g;维生素B10.001g、维生素B2 0.001g、维生素B6 0.001g、维生素B12 0.000005g、维生素C 0.163g、泛酸0.003g、叶酸0.00013g、烟酸0.0124g;茯苓0.1g、枸杞0.1g、橘皮0.1g、鸡内金0.1g、芡实0.1g、山药0.1g;初乳碱性蛋白0.1g、燕麦β-葡聚糖0.1g、左旋肉碱0.64g。
实施例3
本发明所述的脂肪酸代谢异常专用型临床营养配方包括乳清蛋白粉10.9g、大豆分离蛋白3.6g、脱脂奶粉11.02g、牛初乳粉0.1g、海洋鱼低聚肽0.1g、牛磺酸0.12g;橄榄油0.8g、大豆油1.3g、椰子油0.8g、紫苏油0.18g、中链甘油三酯5g、亚油酸1g;麦芽糊精48.97g;膳食纤维4g;常量元素中钙0.44g、磷0.2g、钾0.1g、钠0.3g、镁0.15g;微量元素中铁0.01g、锌0.007g;维生素A0.0007g、β-胡萝卜素0.017g、维生素D3 0.000001g、维生素E0.009g;维生素B1 0.001g、维生素B2 0.001g、维生素B6 0.001g、维生素B12 0.000005g、维生素C 0.163g、泛酸0.003g、叶酸0.00013g、烟酸0.0124g;茯苓0.1g、枸杞0.1g、橘皮0.1g、鸡内金0.1g、芡实0.1g、山药0.1g;γ-氨基丁酸0.1g、蛹虫草0.1g、左旋肉碱0.64g。
实施例4
本发明所述的脂肪酸代谢异常专用型临床营养配方包括乳清蛋白粉10.9g、大豆分离蛋白3.6g、脱脂奶粉11.02g、牛初乳粉0.1g、海洋鱼低聚肽0.1g、牛磺酸0.12g;橄榄油0.8g、大豆油1.3g、椰子油0.8g、紫苏油0.18g、中链甘油三酯5g;麦芽糊精48.97g;膳食纤维4g;常量元素中钙0.44g、磷0.2g、钾0.1g、钠0.3g、镁0.15g;微量元素中铁0.01g、锌0.007g;维生素A0.0007g、β-胡萝卜素0.017g、维生素D3 0.000001g、维生素E 0.009g;维生素B10.001g、维生素B2 0.001g、维生素B6 0.001g、维生素B12 0.000005g、维生素C 0.163g、泛酸0.003g、叶酸0.00013g、烟酸0.0124g;茯苓0.01g、枸杞0.01g、橘皮0.01g、鸡内金0.01g、芡实0.01g、山药0.01g;γ-氨基丁酸0.1g、蛹虫草0.1g;左旋肉碱0.64g。
实施例5
本发明所述的脂肪酸代谢异常专用型临床营养配方包括乳清蛋白粉10.9g、大豆分离蛋白3.6g、脱脂奶粉11.02g、牛初乳粉0.1g、海洋鱼低聚肽0.1g、牛磺酸0.12g;橄榄油0.8g、大豆油1.3g、椰子油0.8g、紫苏油0.18g、中链甘油三酯5g;麦芽糊精48.97g;膳食纤维4g;常量元素中钙0.44g、磷0.2g、钾0.1g、钠0.3g、镁0.15g;微量元素中铁0.01g、锌0.007g;维生素A0.0007g、β-胡萝卜素0.017g、维生素D3 0.000001g、维生素E 0.009g;维生素B10.001g、维生素B2 0.001g、维生素B6 0.001g、维生素B12 0.000005g、维生素C 0.163g、泛酸0.003g、叶酸0.00013g、烟酸0.0124g;茯苓0.01g、枸杞0.01g、橘皮0.01g、鸡内金0.01g、芡实0.01g、山药0.01g;γ-氨基丁酸0.01g、蛹虫草0.01g;左旋肉碱0.04g。
实施例6
一种如实施例1~实施例5所述的脂肪酸代谢异常专用型临床营养配方的制备方法如下:
1)制备粉末油脂(粉末脂肪):
a)制备壁材水溶液:取麦芽糊精10g、大豆分离蛋白4g、脱脂乳粉11g、膳食纤维3g(抗性糊精)、菊粉0.5g、乳清蛋白粉5g、低聚异麦芽糖0.5g克、阿拉伯胶0.2g、水50mL搅拌均匀(有条件边加热边搅拌至60℃,保持30分钟后冷却至室温)。
b)将单甘酯取0.1g(总固形物浓度为0.2%)均匀溶于9mL油脂中(橄榄油0.9mL、大豆油1.4mL、椰子油0.9mL、紫苏油0.2mL、中链甘油三酯5.6mL)。
c)将吐温80取0.1g(总固形物浓度为0.2%)均匀溶于壁材水溶液中。
d)将添加过乳化剂单甘酯的混合植物油脂与添加过乳化剂吐温80的壁材水溶液充分混合。
e)添加稳定剂琼脂取0.1g(总固形物浓度为0.2%)进混合溶液后,用水定容至200mL(总固形物浓度为25%),20000r/min下高速分散2分钟。
f)均质压力为25MPa,均质3次(每次5分钟),制得均质乳状液。
g)将制得的乳状液进行喷雾干燥,进风温度为195℃,出风温度为80℃。收集粉末油脂(粉末脂肪)。
2)制备药食同源成分粉末:采用粉碎机对预定重量份数的原料进行粉碎,将粉碎的原料置于容器中,加入重量为原料重量的3~8倍的水,进行浸泡3~4小时,然后对浸泡液进行煎煮30~60min,过滤去除原料,留取煎煮液,对煎煮液进行喷雾干燥,以60~80目筛分制备药食同源成分粉末;
3)制备维生素粉末:将预定重量份数的脂溶性维生素作为芯材,选用卡拉胶、阿拉伯胶作为壁材,在高压下进行2次乳化均质处理,乳化均质时间为10~15min,然后进行喷雾瞬时干燥,以60~80目筛分制备脂溶性维生素粉末;将预定重量份数的水溶性维生素作为芯材,选用麦芽糊精、脂蛋白作为壁材,混合均匀,喷雾瞬时干燥,以60~80目筛分制备水溶性维生素粉末;
4)将预定重量的蛋白质和氨基酸、核苷酸、碳水化合物、膳食纤维、常量元素、微量元素、天然植物化合物以及新资源食品分别制备成粒径为150~250μm的粉末;
5)将步骤1)~步骤4)所制得的粉末依次加入锥形混合机或其他形式的混合机混合均匀制得配方混合物,经过杀菌处理后,备用;
6)根据常规技术手段将步骤5)中的配方混合物制备成营养粉、营养乳剂、胶囊剂、片剂、丸剂或口服液中的至少一种。
在步骤6)中,可选择性地增加适量的食品增稠剂和食品添加剂。所述食品增稠剂为瓜尔胶、黄原胶、槐豆胶、魔芋胶、果胶、卡拉胶、琼脂、明胶、阿拉伯胶中的至少一种,所述食品添加剂为阿斯巴甜、食用香精香料、红糖中的至少一种;更优选卡拉胶、阿拉伯胶、瓜尔胶、阿斯巴甜、食用香精香料。
上述操作步骤均需在惰性气体的保护下进行,比如氮气、氩气、氦气等,以防止产生粉末爆炸的危险。
按照所述配方可制备成粉状、颗粒状、胶囊状、片剂状、饮料等类别。
实施例7
本实施例为验证实施例。
本实验证实施例验证本发明所述的脂肪酸代谢异常专用型临床营养配方对脂肪酸代谢异常患者的影响。本实施例采用实施例1、2和3的配方制备的营养粉以及下述对比例:
本实施例采用实施例1、2和3的配方制备的营养粉以及下述对比例:
对照组:采用市售脱脂奶粉;
实验组1:采用实施例1的营养配方制备的营养粉;
实验组2:采用实施例2的营养配方制备的营养粉;
实验组3:采用实施例3的营养配方制备的营养粉;
实验组4:采用实施例1的营养配方中删除新资源食品制备的营养粉;
实验组5:采用实施例1的营养配方中删除天然植物化合物制备的营养粉;
实验组6:采用实施例1的营养配方中删除亚油酸制备的营养粉;
以上每组选用自愿服用相应营养粉的脂肪酸代谢异常患者30名,各组患者均进行常规护理。根据患者的正常营养摄入量,在正常摄食时间给予本发明的营养粉,冲服,每日早晚1次,2个月后进行以下指标的测量及结果统计,
测量指标:
1、血糖:测量前禁食12个小时,静脉取血3ml,室温静置1小时以上,离心,取上清,使用罗氏COBAS-ⅠⅠ全自动生化仪测量血糖值;
2、血浆游离脂肪酸浓度:动脉取血3ml,室温静置1小时以上,于4℃离心,取上清,按试剂盒说明书操作测量游离脂肪酸;
实验结果如下表所示:
血糖(mmol/L) | FFA(c/mmol/L) | |
对照组 | 12.19±3.26 | 41.35±0.51 |
实验组1 | 25.26±3.21 | 57.41±0.92 |
实验组2 | 26.12±2.59 | 52.84±1.36 |
实验组3 | 28.21±3.29 | 59.33±0.62 |
实验组4 | 21.49±1.26 | 48.54±0.55 |
实验组5 | 21.59±3.64 | 46.35±0.61 |
实验组6 | 22.25±3.23 | 52.72±0.58 |
由上表1可知,本发明的脂肪酸代谢异常专用型临床营养配方能够有效改善脂肪酸代谢异常患者的低血糖症状;研究表明低血糖是氨基酸及脂肪酸代谢过程中酶的缺陷主要临床表现,本发明的专用型临床营养配方能够增强脂肪酸代谢过程中酶的活性,进而有效改善脂肪酸代谢异常患者的低血糖症状。同时由上表可知,食用了本发明所述的专用型临床营养配方,患者游离脂肪酸(FFA)浓度有所上升,说明本发明有助于促进脂代谢正常进行。
通过上述实施例可知,本发明所述的脂肪酸代谢异常专用型临床营养配方能够为脂肪酸代谢异常患者补充所需的营养,还能够改善多种脂代谢异常、促进脂代谢正常进行、缓解脂代谢异常症状、缓解患者病痛。本发明采用的药食同源成分配伍增效后具有提高机体免疫力、促进脂代谢、预防心脏疾病、缓解患者的病痛的功效。
以上对本发明的具体实施例进行了详细描述,但其只是作为范例,本发明并不限制于以上描述的具体实施例。对于本领域技术人员而言,任何对本发明进行的等同修改和替代也都在本发明的范畴之中。因此,在不脱离本发明的精神和范围下所作的均等变换和修改,都应涵盖在本发明的范围内。
Claims (10)
1.一种脂肪酸代谢异常专用型临床营养配方,其特征在于,包括如下组分及其重量份数:15-28份蛋白质、8-12份脂肪、48-65份碳水化合物、3-6份膳食纤维、0.6-1.2份常量元素、0.01-0.04份微量元素、0.005-0.03份脂溶性维生素、0.008-0.2份水溶性维生素、0.06-2份药食同源成分、0.02-3份天然植物化合物以及0.04-2份新资源食品;
其中,所述新资源食品包括初乳碱性蛋白、γ-氨基丁酸、壳寡糖、杜仲雄花、竹叶黄酮、酪蛋白磷酸肽、燕麦β-葡聚糖、地龙蛋白、牡丹籽油、酵母β-葡聚糖、乳矿物盐、玛咖粉、刺梨、蛹虫草、低聚木糖中的至少一种;
其中,所述天然植物化合物包括左旋肉碱、氨基葡萄糖、低聚果糖、叶黄素、植物甾醇、番茄红素、白藜芦醇、大蒜素中的至少一种。
2.根据权利要求1所述的一种脂肪酸代谢异常专用型临床营养配方,其特征在于,所述营养配方中,蛋白质:脂肪:碳水化合物的产能比为15~20:20~25:55~65。
3.根据权利要求1所述的一种脂肪酸代谢异常专用型临床营养配方,其特征在于,所述脂肪包括5-8份的中链甘油三酯。
4.根据权利要求3所述的一种脂肪酸代谢异常专用型临床营养配方,其特征在于,所述脂肪包括1-2份的亚油酸。
5.根据权利要求1所述的一种脂肪酸代谢异常专用型临床营养配方,其特征在于,所述水溶性维生素包括0.15-0.17份的维生素C。
6.根据权利要求1所述的一种脂肪酸代谢异常专用型临床营养配方,其特征在于,所述天然植物化合物为左旋肉碱。
7.根据权利要求1所述的一种脂肪酸代谢异常专用型临床营养配方,其特征在于,所述新资源食品包括γ-氨基丁酸和蛹虫草中的至少一种。
8.根据权利要求7所述的一种脂肪酸代谢异常专用型临床营养配方,其特征在于,所述新资源食品为γ-氨基丁酸和蛹虫草,其中,γ-氨基丁酸的重量份数为0.01-0.05份,蛹虫草的重量份数为0.01-0.1份。
9.根据权利要求1-8中任一项所述的脂肪酸代谢异常专用型临床营养配方的制备方法,其特征在于,包括如下步骤:
步骤1,制备脂肪粉末;
步骤2,制备药食同源成分粉末:采用粉碎机对预定重量份数的原料进行粉碎,将粉碎的原料置于容器中,加入重量为原料重量的3~8倍的水,浸泡3~4小时,然后对浸泡液煎煮30~60min,过滤去除原料,留取煎煮液,对煎煮液进行喷雾干燥,以60~80目筛分制备药食同源成分粉末;
步骤3,制备脂溶性维生素粉末和水溶性维生素粉末:将预定重量份数的脂溶性维生素作为芯材,选用卡拉胶、阿拉伯胶作为壁材,在高压下进行2次乳化均质处理,乳化均质时间为10~15min,然后进行喷雾瞬时干燥,以60~80目筛分制备脂溶性维生素粉末;将预定重量份数的水溶性维生素作为芯材,选用麦芽糊精、脂蛋白作为壁材,混合均匀,喷雾瞬时干燥,以60~80目筛分制备水溶性维生素粉末;
步骤4,将预定重量的蛋白质、碳水化合物、膳食纤维、常量元素、微量元素、天然植物化合物以及新资源食品分别制备成粒径为150~250μm的粉末;
步骤5,将步骤1~4所制得的粉末依次加入混合机混合均匀制得配方混合物,经过杀菌处理后备用;
步骤6,将所述配方混合物制备成营养粉、营养乳剂、胶囊剂、片剂、丸剂或口服液中的至少一种;
其中,步骤1~4的顺序可相互更换。
10.根据权利要求9所述的制备方法,其特征在于,所述步骤1中制备脂肪粉末具体包括如下步骤:
1)制备壁材水溶液:取麦芽糊精10g、大豆分离蛋白4g、脱脂乳粉11g、膳食纤维3g(抗性糊精)、菊粉0.5g、乳清蛋白粉5g、低聚异麦芽糖0.5g、阿拉伯胶0.2g、水50mL搅拌均匀;
2)将单甘酯取0.1g(总固形物浓度为0.2%)均匀溶于9mL混合植物油脂中;所述混合植物油脂由0.9mL橄榄油、1.4mL大豆油、0.9mL椰子油、0.2mL紫苏油、5.6mL中链甘油三酯组成;
3)将吐温80取0.1g(总固形物浓度为0.2%)均匀溶于所述壁材水溶液中;
4)将添加过乳化剂单甘酯的混合植物油脂与添加过乳化剂吐温80的壁材水溶液充分混合,得到混合溶液;
5)添加稳定剂琼脂0.1g(总固形物浓度为0.2%)于所述混合溶液后,用水定容至200mL(总固形物浓度为25%),20000r/min下高速分散2分钟,得到乳状液;
6)将所述乳状液在均质压力25MPa下,均质3次,每次5分钟,得到均质乳状液;
7)将所述均质乳状液进行喷雾干燥,进风温度为195℃,出风温度为80℃,收集得到脂肪粉末。
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