CN113975379A - 羟氯喹与营养补充剂联用在制备改善妊娠期合并系统性红斑狼疮药物中的应用 - Google Patents

羟氯喹与营养补充剂联用在制备改善妊娠期合并系统性红斑狼疮药物中的应用 Download PDF

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CN113975379A
CN113975379A CN202111231614.7A CN202111231614A CN113975379A CN 113975379 A CN113975379 A CN 113975379A CN 202111231614 A CN202111231614 A CN 202111231614A CN 113975379 A CN113975379 A CN 113975379A
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邹爱标
王青鹏
吴海利
王华林
熊欢
王晓菲
邹勇
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Wuhan Inuling Biotechnology Co ltd
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Abstract

本发明公开了羟氯喹与营养补充剂联用在制备改善妊娠期合并系统性红斑狼疮药物中的应用。本发明配制的营养制剂，与羟氯喹联用增强改善妊娠期合并系统性红斑狼疮效果，并减小副作用，营养制剂对患者本身无副作用，可用于妊娠期合并系统性红斑狼疮患者的使用，同时对机体其他方面如抗疲劳、改善免疫等均有有益作用。

Description

羟氯喹与营养补充剂联用在制备改善妊娠期合并系统性红斑 狼疮药物中的应用
技术领域
本发明涉及羟氯喹与微生态补充剂、微量元素补充剂和抗氧化剂联用在制备改善妊娠期合并系统性红斑狼疮的药物中的应用。
背景技术
系统性红斑狼疮(SLE)是一种以分泌多种自身抗体及多脏器受累为主要特征的慢性自身免疫性疾病，其发病机制较为复杂，其中遗传、环境等因素改变可导致机体免疫功能紊乱，并引发自身免疫耐受紊乱，破坏免疫平衡。SLE病因复杂、起病急骤、病情发展快，近年研究表明，调节性T细胞数量减少或功能减退可能是导致SLE患者病情进展的主要原因。
女性发病率高于男性，通常在育龄期起病近年来，妊娠合并SLE患者生存率有所升高，但与正常妊娠比，其发生妊娠期并发症的风险仍处于较高水平。并且，SLE患者妊娠例数呈增加趋势，导致此类患者在围产期母儿发病和死亡的占比逐渐升高。目前，为兼顾母胎安全，SLE的孕期治疗仍十分受限。
SLE极易在妊娠期加重或复发，其原因可能如下：①妊娠机体免疫应答改变。正常妊娠导致孕妇体内多重免疫调节开启，其中最重要的是辅助性T细胞2(Th2)在母体免疫应答中发生极化改变，即Th2细胞数量相对增加。然而，SLE合并妊娠时，可能受体内低雌激素或孕激素水平影响，孕妇机体Th2极化改变缺失。②妊娠期全身各脏器负担加重，肾脏与心脏尤为显著妊娠期SLE复发的常见表现为疲倦、关节痛、皮疹和蛋白尿。
SLE患者妊娠期并发症的发病率高于正常女性20倍，主要包括高血压、子痫前期、流产、胎儿生长受限(FGR)、早产及新生儿狼疮综合征等。目前该类疾病常采用药物治疗，但药物的副作用几率大，危害性大。
非甾体类抗炎药(阿司匹林、布洛芬等可能导致胎儿动脉导管提前闭合以及羊水过少；糖皮质激素类(泼尼松等)，长期使用泼尼松与SLE活动及妊娠不良结局(高血压、糖尿病、先兆子痫、胎膜早破等)相关；硫唑嘌呤，动物研究发现有致畸作用。
SLE患者妊娠期服用羟氯喹，会导致胎儿自然流产(约21％)、早产(约20％)、不成功妊娠(约8％)的概率增加。
发明内容
本发明要解决的技术问题是克服现有技术的妊娠期合并系统性红斑狼疮药物副作用大的缺陷，提供一种羟氯喹与营养补充剂联用在制备改善妊娠期合并系统性红斑狼疮药物中的应用。
为了解决上述技术问题，本发明提供了如下的技术方案：
羟氯喹与营养补充剂联用在制备改善妊娠期合并系统性红斑狼疮药物中的应用，所述营养补充剂包括微生态补充剂、微量元素补充剂和抗氧化剂。
优选的，羟氯喹的用量为0.2～0.4g/天，微生态补充剂用量为20±2g/天、微量元素补充剂2g±0.2g/天和抗氧化剂1g±0.1g/天。
进一步的，所述的微生态补充剂包括以下重量份数的各组分：
低聚半乳糖200±20份、低聚果糖150±10份、多聚果糖200±20份、棉子糖200±20份、双歧杆菌100±10份和乳酸杆菌100±10份。
优选的，低聚半乳糖200份、低聚果糖150份、多聚果糖200份、棉子糖200份、双歧杆菌100份和乳酸杆菌100份。
肠道黏膜免疫反应是机体免疫系统的重要组成部分，其主要依靠黏膜内T、B细胞及分泌至肠腔中的sIgA等共同完成局部免疫功能。肠道菌群作为黏膜免疫重要参与者，通过影响黏膜免疫中特定的炎症因子发挥对机体免疫系统的整体调节作用。双歧杆菌、脆弱类拟杆菌可通过菌群本身及有效成分诱导Tregs产生，提示肠道菌群紊乱可能通过影响机体免疫细胞，尤其是Tregs，干扰免疫系统导致SLE发生发展。
进一步的，所述微量元素补充剂包括以下重量份数的各组分：
维生素C 200±20份、维生素A 10±0.1份、维生素E 10±0.1份、维生素D 5±0.05份、维生素B25±0.05份、维生素B65±0.05份、维生素B12±0.05份、硫酸铁100±10份、葡萄糖酸锌100±10份和富硒酵母50±5份。
优选的，所述微量元素补充剂包括以下重量份数的各组分：维生素C 200份、维生素A10份、维生素E10份、维生素D 5份、维生素B25份、维生素B65份、维生素B125份、硫酸铁100份、葡萄糖酸锌100份和富硒酵母50份。
摄入足量维生素、微量元素并注重发挥其协同作用。机体在应激和高代谢状态下维生素、矿物质损耗增加，需求增加。尤其儿童、孕妇微量营养素的储备低需求大，比成人更易缺乏。此外，鉴于维生素A、E、C，微量元素锌、硒等营养元素对人体免疫功能的调节作用，在此例患者的营养支持过程中，保证了患者每日维生素、微量元素的有效摄入，提升了治疗功效。
进一步的，所述的抗氧化剂包括以下重量份数的各组分：
超氧化物歧化酶SOD 100±10份、叶黄素50±5份、甘露醇50±5份、乳铁蛋白50±5份和辅酶Q1010±0.1份；优选的，所述的抗氧化剂包括以下重量份数的各组分：超氧化物歧化酶SOD 100份、叶黄素50份、甘露醇50份和乳铁蛋白50份和辅酶Q1010份。
在SLE的氧化损伤病因中除自由基产生增多外，自由基清除剂的缺乏也是原因之一，在研究中已发现红细胞内超氧化物歧化酶(SOD)减少。因此补充抗氧化剂将对系统性红斑狼疮具有较好的改善效果。
有益效果：
本发明配制的营养制剂，与羟氯喹联用增强改善妊娠期合并系统性红斑狼疮效果，并减小副作用。营养制剂对患者本身无副作用，可用于妊娠期合并系统性红斑狼疮患者的使用，同时对机体其他方面如抗疲劳、改善免疫等均有有益作用。
具体实施方式
以下对本发明的优选实施例进行说明，应当理解，此处所描述的优选实施例仅用于说明和解释本发明，并不用于限定本发明。
实施例
羟氯喹与营养补充剂联用在制备改善妊娠期合并系统性红斑狼疮药物中的应用，所述营养补充剂包括微生态补充剂、微量元素补充剂和抗氧化剂。
羟氯喹的用量为0.3g/天，微生态补充剂用量为20g/天、微量元素补充剂2g/天和抗氧化剂1g/天。
所述的微生态补充剂包括以下重量份数的各组分：低聚半乳糖200份、低聚果糖150份、多聚果糖200份、棉子糖200份、双歧杆菌100份和乳酸杆菌100份。
所述微量元素补充剂包括以下重量份数的各组分：维生素C 200份、维生素A10份、维生素E10份、维生素D 5份、维生素B25份、维生素B65份、维生素B125份、硫酸铁100份、葡萄糖酸锌100份和富硒酵母50份。
所述的抗氧化剂包括以下重量份数的各组分：超氧化物歧化酶SOD 100份、叶黄素50份、甘露醇50份和乳铁蛋白50份和辅酶Q1010份。
实验过程
选取70名初诊SLE患者。纳入标准：①年龄18～35岁；②符合美国风湿病学会1982年诊断标准，确诊为SLE。排除标准：①近4周内曾应用抗生素或微生物制剂；②近期有肠道手术史；③药物依从性差及不配合患者。其中女58例，年龄19～35岁、中位年龄26岁。
对照组：羟氯喹0.3g/d。
实施例一：羟氯喹0.3g/d，微生态制剂20g。
实施例二：羟氯喹0.3g/d，微量元素补充剂2g。
实施例三：羟氯喹0.3g/d，抗氧化剂1g。
实施例四：羟氯喹0.3g/d，微生态制剂20g，微量元素补充剂2g。
实施例五：羟氯喹0.3g/d，微生态制剂20g，抗氧化剂1g。
实施例六：羟氯喹0.3g/d，微量元素补充剂2g，抗氧化剂1g。
实施例七：羟氯喹0.3g/d，微生态制剂20g，微量元素补充剂2g，抗氧化剂1g。
分别收集SLE组患者在治疗前及治疗后的粪便标本，40min内保存于-80℃冰箱。称取中段200mg便样，严格按照粪便基因组DNA提取试剂盒操作说明操作，对所提取DNA进行浓度及纯度检测。
Figure BDA0003316172150000051
从肠道菌群检测数据可以得知，使用羟氯喹会导致肠道菌群变化，益生菌数量减少。通过微生态制剂干预，可以有效改变对肠道菌群的影响。加入微量元素补充剂，与微生态制剂发挥协同作用，增强肠道菌群的改善效果。
Figure BDA0003316172150000061
Figure BDA0003316172150000071
从血清氧化应激指标检测数据可以得知，微生态制剂可以与抗氧化剂发挥协同作用，增强抗氧化能力，清除体内自由基。
Figure BDA0003316172150000072
从该组数据分析，可以得知通过多种营养组分的加入，有利于药物对红斑狼疮的控制作用。
本技术方案中新加入的产品原辅料均来源于食品，对患者本身无副作用，可用于妊娠期合并系统性红斑狼疮患者的使用。该技术方案的推广有利于改变目前SLE的孕期治疗仍受限的现状。
最后应说明的是：以上所述仅为本发明的优选实施例而已，并不用于限制本发明，尽管参照前述实施例对本发明进行了详细的说明，对于本领域的技术人员来说，其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分技术特征进行等同替换。凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。

Claims (8)

1.羟氯喹与营养补充剂联用在制备改善妊娠期合并系统性红斑狼疮药物中的应用，所述营养补充剂包括微生态补充剂、微量元素补充剂和抗氧化剂。
2.如权利要求1所述的应用，其特征在于，羟氯喹的用量为0.2～0.4g/天，微生态补充剂用量为20±2g/天、微量元素补充剂2g±0.2g/天和抗氧化剂1g±0.1g/天。
3.如权利要求1或2所述的应用，其特征在于，所述的微生态补充剂包括以下重量份数的各组分：
低聚半乳糖200±20份、低聚果糖150±10份、多聚果糖200±20份、棉子糖200±20份、双歧杆菌100±10份和乳酸杆菌100±10份。
4.如权利要求3所述的应用，其特征在于，所述的微生态补充剂包括以下重量份数的各组分：
低聚半乳糖200份、低聚果糖150份、多聚果糖200份、棉子糖200份、双歧杆菌100份和乳酸杆菌100份。
5.如权利要求1或2所述的应用，其特征在于，所述微量元素补充剂包括以下重量份数的各组分：
维生素C 200±20份、维生素A 10±0.1份、维生素E 10±0.1份、维生素D 5±0.05份、维生素B25±0.05份、维生素B65±0.05份、维生素B12±0.05份、硫酸铁100±10份、葡萄糖酸锌100±10份和富硒酵母50±5份。
6.如权利要5所述的应用，其特征在于，所述微量元素补充剂包括以下重量份数的各组分：
维生素C 200份、维生素A 10份、维生素E 10份、维生素D 5份、维生素B25份、维生素B65份、维生素B125份、硫酸铁100份、葡萄糖酸锌100份和富硒酵母50份。
7.如权利要求1或2所述的应用，其特征在于，所述的抗氧化剂包括以下重量份数的各组分：
超氧化物歧化酶SOD 100±10份、叶黄素50±5份、甘露醇50±5份、乳铁蛋白50±5份和辅酶Q1010±0.1份。
8.如权利要求7所述的应用，其特征在于，所述的抗氧化剂包括以下重量份数的各组分：
超氧化物歧化酶SOD 100份、叶黄素50份、甘露醇50份和乳铁蛋白50份和辅酶Q1010份。
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