CN113273695B - 一种改善新生儿溶血性高胆红素血症的组合物 - Google Patents
一种改善新生儿溶血性高胆红素血症的组合物 Download PDFInfo
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Abstract
本发明公开了一种改善新生儿溶血性高胆红素血症的组合物，它由如下重量份的组分组成：人乳低聚糖500—1900，必需脂肪酸1000—4000，L‑抗坏血酸30—40，硫酸亚铁6—8，叶酸0.04—0.06，牛磺酸28—34。该组合物不属于药品，没有副作用，服用方便，并可以辅助改善溶血性高胆红素血症。
Description
技术领域
本发明属于食品技术领域，具体涉及一种改善新生儿溶血性高胆红素血症的组合物。
背景技术
新生儿高胆红素血症(NeonatalHyperbilirubinemia)，俗称黄疸，主要是由于胆红素代谢功能障碍引起，可致使患儿的皮肤或者其他器官发生黄染，由于未结合胆红素的神经毒性作用，处理不当可引起智力、听力及运动发育异常，甚至危及新生儿生命。
新生儿高胆红素血症可分为生理性和病理性，生理性高胆红素血症几乎所有新生儿均可发生，其原因在于新生儿的红细胞有相对较短的寿命，胆红素产生的速率比成人快，而新生儿清除胆红素的能力较成人低。结果，由于有易产生胆红素的倾向和有限的清除胆红素的能力，导致新生儿易患高胆红素血症。病理性高胆红素血症起因有很多，比如免疫或非免疫性溶血性贫血，6-磷酸葡萄糖脱氢酶缺陷，肝炎，胆道畸形等。
溶血性高胆红素血症是由于大量红细胞破坏，形成大量的非结合胆红素，超过肝细胞的摄取、结合与排泄的能力，另一方面，由于溶血造成的贫血、缺氧和红细胞破坏产物的毒性作用，削弱了肝细胞对胆红素的代谢功能，使非结合胆红素在血中潴留，超过正常的水平。
目前治疗新生儿黄疸的方法主要有：
1)血液交换疗法，该法可以减少溶血，去除患儿血液中的免疫抗体、致敏红细胞和红细胞血色素，从而降低血清中红细胞血色素水平；
2)光疗，蓝光与间接红细胞血色素发生光化学反应，增加水溶性，并通过胆汁和尿液排泄；
3)药物疗法，如服用茵栀黄或者皮下注射苯巴比妥。注射免疫球蛋白和白蛋白，后者可充当红细胞血色素的载体，降低血清中游离红细胞血色素水平，并达到治愈疾病的目的，通常是用于治疗溶血性疾病的有效药物。
但是，在上述现有方法中，血液交换疗法存在一定风险，严重时可能会导致死亡，此外，还存在低血钙、低血糖、体温过低、感染等风险，所以必须在换血前达到换血指征。而对于光疗，如果光照强度过大，照射的时间较长，或光线接近紫外线照射之后，新生儿体内的血小板将发生改变，姐妹染色体会进行交换，严重影响光疗的治疗效果。药物疗法则不能用于一些遗传病导致的新生儿黄疸病。
发明内容
本发明旨在克服现有技术的不足，提供一种改善新生儿溶血性高胆红素血症的组合物。
为了达到上述目的，本发明提供的技术方案为：
所述改善新生儿溶血性高胆红素血症的组合物由如下重量份的组分组成：人乳低聚糖500—1900，必需脂肪酸1000—4000，L-抗坏血酸30—40，硫酸亚铁6—8，叶酸0.04—0.06，牛磺酸28—34。
优选地，所述人乳低聚糖是中性人乳低聚糖和酸性人乳低聚糖的混合物。
更优选地，所述中性人乳低聚糖和酸性人乳低聚糖的混合物中，中性人乳低聚糖和酸性人乳低聚糖的质量比1:0.1至1:5。
优选地，所述中性人乳低聚糖包括2’-FL、3’-FL、LNT、LNnT、3’-GL、6’-GL、DFL中的至少一种。
优选地，所述酸性人乳低聚糖包括3’-SL、6’-SL、3’-NGL、6’-NGL中的至少一种。
优选地，所述必需脂肪酸是亚油酸和α-亚麻酸的混合物。
更优选地，所述亚油酸和α-亚麻酸的混合物中，亚油酸和α-亚麻酸的质量比为1:1至3:1。
以新生儿体重作为分母，以改善新生儿溶血性高胆红素血症的组合物用量为分子，改善新生儿溶血性高胆红素血症的组合物每天给新生儿的食用量为1—3g/kg。
本发明中所述的新生儿主要指足月的出生低体重儿，小于胎龄儿，早产儿等。
下面对本发明作进一步说明：
本发明中，人乳低聚糖是人类母乳中仅次于乳糖和脂肪的第三大固体成分，具有重要的生理功能，新生儿肠道菌群未建立，不能将结合胆红素还原成尿胆素原，这会使游离胆红素产生并经肝肠循环再吸收。人乳低聚糖可起到促进婴儿肠道微生态平衡，促进肠道内有益菌的增殖、调节免疫系统的作用，同时起到协助胆红素代谢的功能。
必需脂肪酸是指对维持机体功能不可缺少、但机体不能合成、必须由食物提供的脂肪酸，可以起到保护肝脏，减少炎症的作用。
L-抗坏血酸起到抗氧化，减少红细胞破坏的作用。硫酸亚铁和叶酸起到进一步减少红细胞破坏的作用。牛磺酸则能调节细胞活化、增殖、免疫清除、凋亡、衰老、自噬、抗氧化应激、减少氧自由基介导的肝损伤。
本发明所述的可以改善新生儿溶血性高胆红素血症的组合物不属于药品，其组分均是营养物质，各组分之间相辅相成，共同维持人体正常生理活动，对人体没有副作用，服用方便，并可以辅助改善溶血性高胆红素血症。
附图说明
图1为大鼠肝UDP-葡萄糖醛酸转移酶活性实验结果图；
图2为大鼠血清总胆红素含量实验结果图；
图3为大鼠血清直接胆红素含量实验结果图；
图4为大鼠血清间接胆红素含量实验结果图；
图5为大鼠血清谷丙转氨酶含量实验结果图；
图6为大鼠血清谷草转氨酶含量实验结果图。
具体实施方式
实施例1至3以及对比例1至4的具体组成如表1所示，表1中的比例均为质量比：
表1
案例中使用的中性人乳低聚糖为2-岩藻糖基乳糖标准品(2’-FL),酸性人乳低聚糖为6-唾液酸乳糖标准品(6’-SL)，购于sigma。
亚油酸、α-亚麻酸、L-抗坏血酸、硫酸亚铁、叶酸、牛磺酸均可通过市售购买得到。
使用时，组合物按比例加入到常规食品(包括婴儿配方奶粉以及特殊医学用途婴儿配方食品，以新生儿体重作为分母，以改善新生儿溶血性高胆红素血症的组合物用量为分子，改善新生儿溶血性高胆红素血症的组合物每天给新生儿的食用量为1—3g/kg)中，混合均匀即可。
功效验证：
动物实验：
实验方案：SD大鼠雄性，SPF级，11-12W龄，250-300g，135只，实验期间给予普通饲料，自由采食饮水。
适应性喂养7天后，随机分为9组，每组15只：空白对照组、模型对照组、对比例1组，对比例2组，对比例3组，对比例4组，实施例1组，实施例2组，实施例3组。除正常组外，其余各组大鼠腹腔注射乙酰苯肼(APH)150mg/kg，用药3d后，对比组1至4和实验组1至3从第4天开始灌胃给予相应受试物(10g/kg/d)，同时空白组和模型组每天给予生理盐水灌胃。连续给样7d后，乙醚麻醉大鼠，摘眼球取血，室温静置30min后3 000r/min离心15min取血清，检测其总胆红素、直接胆红素、谷丙转氨酶、谷草转氨酶含量，并计算间接胆红素含量(间接胆红素＝总胆红素-直接胆红素)。
大鼠死后，摘取肝脏检测其肝UDP-葡萄糖醛酸转移酶活性。单位以每分钟每克肝匀浆蛋白催化生成的结合胆红素的μmol数表示(μmol/gprotein/min)。
实验结果：
1、大鼠肝UDP-葡萄糖醛酸转移酶活性(见图1)：
UDP-葡萄糖醛酸转移酶，即尿苷二磷酸葡醛酸转移酶，是位于内质网腔侧面的一类微粒体糖蛋白，该蛋白能够催化内源性物质、药物等与尿苷二磷酸葡糖醛酸(UridineDiphosphate Glucuronic Acid,UDPGA)结合，使其水溶性增加，能有效地从尿或胆汁中排出，是机体的一个重要的解毒机制。胆红素(bilirubin)是从衰老的红细胞的血红蛋白中代谢的产物，主要在肝脏由UDP-葡萄糖醛酸转移酶催化，生成结合胆红素，使其成为水溶性，利于排泄。因此肝UDP-葡萄糖醛酸转移酶活性可以反映机体代谢胆红素的能力。从实验结果可以看出，与正常组相比，模型组大鼠的肝UDP-葡萄糖醛酸转移酶显著降低，说明造模成功。对比组2和对比组1,3,4相比差异极显著(P<0.01),说明人乳低聚糖、牛磺酸、L-抗坏血酸、硫酸亚铁、叶酸等成分对于肝UDP-葡萄糖醛酸转移酶活性提升有一定影响，但亚油酸与亚麻酸混合物对于肝UDP-葡萄糖醛酸转移酶活性有显著提升作用，对比组4与对比组1相比差异显著(P<0.05),而与对比组3相比差异不显著，说明亚油酸与亚麻酸混合物如果不是按照本发明的必需脂肪酸比例配比，所起的效果也不显著。实验组1至3之间效果差异不显著，而实验组1与对比组1至4相比效果极显著，说明只有本发明的组合配比才能极大提升肝UDP-葡萄糖醛酸转移酶活性，从而利于降低胆红素。
2、大鼠血清总胆红素含量(见图2)：
实验结果表明，对比组1至4与模型组相比，血清总胆红素下降，但是实验组1至3的降幅更大。对比组1与对比组2差异不显著，而对比组1和2分别与对比组3、4相比差异极显著(P<0.01),说明缺乏人乳低聚糖或者必需脂肪酸组合物，都会影响降低血清总胆红素的效果。但当人乳低聚糖中中性低聚糖与酸性低聚糖比例比例或者必需脂肪酸中亚油酸和α-亚麻酸比例不是本发明的比例时，降低总胆红素的效果也不如本发明组合物的效果好。
3、大鼠血清直接胆红素含量(见图3)：
测定直接、间接胆红素可以鉴别诊断溶血性、肝细胞性和梗阻性黄疸。当肝脏受损，肝细胞处理胆红素后的排出发生障碍时，直接胆红素明显升高。对比组1和2与模型组相比，直接胆红素含量差异不显著，说明缺乏人乳低聚糖和必需脂肪酸，均不能提升肝细胞处理胆红素的能力。对比组3和4虽然都含有人乳低聚糖和必需脂肪酸，但是其降低直接胆红素的效果不及本发明组合物，说明中/酸性人乳低聚糖的比例，以及必需脂肪酸中亚油酸与α-亚麻酸的比例同样很重要。
4、大鼠血清间接胆红素含量(见图4)：
APH(乙酰苯肼)是强氧化剂，通过干扰还原型谷胱甘肽的生成使红细胞膜的稳定性遭到破坏致溶血性黄疸，是诱导的大鼠溶血性黄疸是常见的造模方法。当发生溶血性黄疸时，间接胆红素明显升高。本实验中，总胆红素的升高是以间接胆红素升高为主引起的，符合溶血性高胆红素血症的特征。对比组1/2的效果比对比组3/4的效果差，说明需要人乳低聚糖和必需脂肪酸联合使用，才能起到抗氧化，保护红细胞膜的稳定性，减少胆红素的产生的作用。但适宜的中/酸性人乳低聚糖的比例，以及亚油酸/α-亚麻酸比例，能发挥更好的作用降低间接胆红素含量。
5、大鼠血清谷丙转氨酶含量(见图5)：
在各种急性病毒性肝炎、药物引起急性肝细胞损伤时，谷丙转氨酶升高最明显、最敏感，在临床症状如黄疸出现前就急剧升高，对早期发现某些疾病有重要意义。实验结果表明，缺少人乳低聚糖(对比例1)或者必需脂肪酸(对比例2)都不能保护肝脏，而中/酸性人乳低聚糖的比例，以及亚油酸/α-亚麻酸比例不在本专利配方内的，也不能显著的降低谷丙转氨酶含量。
6、大鼠血清谷草转氨酶含量(见图6)：
谷丙转氨酶和谷草转氨酶是肝细胞受损的指标，实验结果表明人乳低聚糖与必需脂肪酸联合作用，可以保护肝损伤，但需要有合适的中/酸性人乳低聚糖的比例，以及亚油酸/α-亚麻酸比例，才能更好的保护肝细胞。
Claims (4)
1.一种改善新生儿溶血性高胆红素血症的组合物，其特征在于，所述组合物由如下重量份的组分组成：人乳低聚糖500—1900，必需脂肪酸1000—4000，L-抗坏血酸30—40，硫酸亚铁6—8，叶酸0.04—0.06，牛磺酸28—34；所述人乳低聚糖是中性人乳低聚糖和酸性人乳低聚糖的混合物，所述中性人乳低聚糖和酸性人乳低聚糖的混合物中，中性人乳低聚糖和酸性人乳低聚糖的质量比1:0.1至1:5；所述必需脂肪酸是亚油酸和α-亚麻酸的混合物，所述亚油酸和α-亚麻酸的混合物中，亚油酸和α-亚麻酸的质量比为1:1至3:1。
2.如权利要求1所述的改善新生儿溶血性高胆红素血症的组合物，其特征在于，所述中性人乳低聚糖包括2’-FL、3’-FL、LNT、LNnT、3’-GL、6’-GL、DFL中的至少一种。
3.如权利要求1所述的改善新生儿溶血性高胆红素血症的组合物，其特征在于，所述酸性人乳低聚糖包括3’-SL、6’-SL、3’-NGL、6’-NGL中的至少一种。
4.如权利要求1至3任一项所述的改善新生儿溶血性高胆红素血症的组合物，其特征在于，以新生儿体重作为分母，以改善新生儿溶血性高胆红素血症的组合物用量为分子，改善新生儿溶血性高胆红素血症的组合物每天给新生儿的食用量为1—3 g/ kg。
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