CN110787171A - 槐糖在预防和治疗炎症性肠病产品中的应用及对应产品 - Google Patents
槐糖在预防和治疗炎症性肠病产品中的应用及对应产品 Download PDFInfo
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Abstract
本发明公开了槐糖在制备用于预防和治疗炎症性肠病产品中的应用。本发明还公开了其对应产品。本发明通过研究结果证明槐糖能够一定程度上减少炎症性肠病模型大鼠的炎症因子水平，其可以作为药物治疗炎症性肠病，也可以作为日常饮食的一部分预防炎症性肠病，这种调控作用比较温和，作用效果较好，相比于其他药物不具有副作用。
Description
技术领域
本发明涉及预防和治疗炎症性肠病技术领域，具体涉及槐糖在预防和治疗炎症性肠病产品中的应用及对应产品。
背景技术
槐糖是一种由两个葡萄糖通过β-1,2-糖苷键连接形成的二糖，价格昂贵，仅试剂级，未见工业生产。因槐糖生产量少，价格昂贵，无法广泛应用研究，现主要用于诱导曲霉属或者木霉属等生产纤维素酶，其诱导作用是乳糖等其他诱导化合物的几十到几千倍，是一种强诱导剂。甜菊糖苷的分子量为804.9，其C13位上的槐糖基占了整个分子质量的42％，由此可见在甜菊糖苷中，槐糖质量占比很高，根据已有专利的制备方法，回收率高到80％，大大地提高了槐糖的产量，给槐糖的应用研究提供了原料保障。
炎症性肠病(Inflammatory bowel disease，IBD)是一种慢性非特异性肠道疾病，具有终生复发的倾向。通常认为IBD是由遗传缺陷导致肠上皮屏障的改变引起粘膜免疫系统暴露于肠道菌群，触发微生物异常免疫反应。IBD包括一系列慢性、进行性和致残性胃肠道炎症性疾病，如克罗恩病(Crohn Disease，CD)和溃疡性结肠炎(ulcerative colitis，UC)，IBD治疗方案包括一般治疗、药物治疗、手术治疗。
饮食是正常肠道微环境的关键参与者，影响肠道微生物的组成、功能、肠道屏障和宿主免疫力。从以植物为基础的饮食转变为以动物为基础的饮食，从根本上改变了菌群分类和代谢，导致胆汁酸和硫化物代谢的改变，两者可能在IBD中起作用。饮食疗法对IBD的可能作用主要体现在CD中。但饮食疗法需要排除普通餐桌饮食。
当前IBD药物治疗方案包括非特性抗炎药物(如氨基水杨酸类、糖皮质激素免疫调节剂)和针对炎症的靶点生物制剂。IBD新的靶向药物治疗主要集中在新的小分子抑制剂、新的单克隆抗体和基因治疗(反义核苷酸片段、基因修饰)方面。靶向药物通过阻断免疫炎症过程中的不同环节发挥作用。尤其是TNF抑制剂的应用，是IBD治疗最重要的进展之一。1998年，Centocor公司上市了英夫利昔单抗(Infliximab，商品名Remicade)用于治疗CD，2005年扩大到UC的治疗，目前也用于类风湿性关节炎、强直性脊柱炎及银屑病关节炎等其它自身免疫性疾病的治疗。除了英夫利昔单抗外，还有三种其他抗TNF-α单克隆抗体用于IBD的治疗：阿达木单抗、塞妥单抗和戈利木单抗。尽管目前还没有比较研究，但英夫利昔单抗、阿达木单抗和塞妥珠单抗似乎在CD中具有较好的疗效，特别是在维持缓解方面。然而，高达30％的患者对抗TNF药物的初始治疗无反应。白细胞介素(IL)类也是IBD治疗常用的细胞因子靶标。2016年，FDA批准抗IL-12/IL-23人单克隆抗体Ustekinumab(Stelara)作为首个具有CD治疗作用机制的生物制剂。但白细胞介素类成本较高。
公开号为CN103030687A的专利中公开了SN1能够治疗与TNF-α相关的疾病，还公开了其能够治疗结肠炎并给出了葡聚糖硫酸钠诱导的小鼠结肠炎模型，但原公开SN1(22AA)靶点不专一，可以与TNF-α、TNFR1以及TNFR2结合，与TNFR1的结合能力最大，约为32μM；而SN10(10AA)靶点特异，具有选择性，只与TNFR1结合，而不与TNF-α、TNFR2结合；与TNFR1结合能力约为2.8μM，并能竞争性抑制TNFR1与TNF-α的结合。
公开号为CN102526030A的专利公开了一类可以有效保护机体免受自由基损伤，从而阻断炎症性肠病发作的小分子药物，具体涉及到3,3’-二吲哚甲烷(DIM)及其水溶液注射制剂以及母体化合物吲哚-3-甲醇(I3C)在炎症性肠病中的治疗，但此类药物的安全性仍存在不足。
发明内容
本发明的目的是提供槐糖在预防和治疗炎症性肠病产品中的应用及对应产品，以解决现有技术的不足。
本发明采用以下技术方案：
本发明一方面提供了槐糖在制备用于预防和治疗炎症性肠病产品中的应用。
进一步地，所述产品为食品或保健品或药品。
本发明另一方面提供了一种用于预防和治疗炎症性肠病的产品，包括槐糖。
进一步地，所述产品为食品或保健品或药品。
进一步地，所述产品用法为口服。
与现有技术相比，本发明具有如下优势：
1、细胞因子(cytokkines，CK)是免疫效应细胞间的信息传递中介，主要由活化的T细胞产生，与IBD发病有关的CK包括有IL-1、IL-2、IL-4、IL-6、IL-8、IL-10、IL-11、IFN-γ、TNF-α等。CK既可以使大量的T细胞，尤其是CD4+T细胞迅速分裂、增殖，形成致敏淋巴细胞，又可以活化粒细胞、增强NK细胞和LAK细胞的杀伤力，并诱导粘附分子表达及肥大细胞脱颗粒，以增进炎症反应。而本发明通过灌胃槐糖后，炎症性肠病模型大鼠体内血清中IL-2、IL-6、TNF-α含量显著降低，在一定程度起到预防或治疗炎症性肠病的有益效果。
2、本发明通过研究结果证明槐糖能够一定程度上减少炎症性肠病模型大鼠的炎症因子水平，其可以作为药物治疗炎症性肠病，也可以作为日常饮食的一部分预防炎症性肠病，这种调控作用比较温和，作用效果较好，相比于其他药物不具有副作用。
附图说明
图1为本发明的实施例1自制槐糖的色谱图。
图2为本发明的动物实验中槐糖对大鼠血清中IL-2浓度的影响示意图。
图3为本发明的动物实验中槐糖对大鼠血清中IL-6浓度的影响示意图。
图4为本发明的动物实验中槐糖对大鼠血清中TNF-α浓度的影响示意图。
具体实施方式
为了使本发明所要解决的技术问题、技术方案及有益效果更加清楚明白，以下结合附图及实施例，对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅仅用以解释本发明，并不用于限定本发明。
实施例1
1.槐糖的制备
以下实施例涉及的槐糖可购买或自制，自制时可通过如下方法制备：将10g甜菊糖苷(98％)溶解于20mL～80mL甲酸溶液中，在80℃，搅拌反应30min～40min，真空旋蒸除去反应溶剂，得到的沉淀用100mL超纯水洗涤，抽滤，弃沉淀，再次旋蒸，用100mL超纯水溶解，保留上清液。将得到溶液用硅藻-活性碳层析柱分离，依次用超纯水、5v/v％～30v/v％乙醇溶液梯度洗脱，得到的溶液用HPLC检测。溶液分别过0.22μm滤膜，色谱条件：色谱柱：BioRadHPX-87H(300mm*7.5mm)，检测器：示差折光检测器，温度：55℃，流动相：5mM硫酸，流速：0.4mL/min，进样体积：20μL。如图1所示，第一个正峰为洗脱液乙醇的峰，倒峰为该色谱条件下每个样都带有的峰，第二个正峰为槐糖的峰。
2.动物实验
动物造模方法：将大鼠禁食24小时后麻醉，用长约15cm，直径2mm的硅胶管(或聚乙烯导管)由肛门轻缓插入8cm处的肠腔内，快速(5s内)注入50mg/kg～150mg/kg的30％～50％TNBS乙醇溶液。造模1d后出现竖毛、懒动、厌食、大便次数增多，稀便，夹杂黏液或脓点等症状，3d后达到高峰；1w后大鼠出现大便隐血阳性及便血，肉眼可见组织黏膜水肿；2w后组织黏膜出现坏死溃疡，随后出现组织增生，肠壁增厚，肠腔变小，病变可持续8w左右，呈现慢性的炎症变化。该模型中TNBS的用量及浓度决定模型病变的轻重，一般以100mg/kg为造模的最佳剂量。
体重200g±20g的雄性SD大鼠30只，普通饲料(按照GB14924.3-2010制作的基础饲料)适应性喂养一周后，其中20只SD大鼠通过TNBS乙醇溶液建模后分为MC模型对照组(代号*)、PC实验组(代号#)，另外10只未建模大鼠为C对照组。C、MC组每天早上九点灌胃3ml生理盐水，PC组灌胃0.1339g/kg BW槐糖(换算到人体为1.5g/d剂量)，光照黑暗每12h交替，自由采食和饮水，总共饲养五周，五周后取大鼠全血测试白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、肿瘤坏死因子(TNF-α)指标。
通过各指标结果图，如图2至图4所示，图中，*与C组相比，p<0.05；#与MC组相比，p<0.05，可以发现PC组大鼠相对于MC组，血清中IL-2、IL-6、TNF-α含量显著降低，说明通过每日灌胃0.1339g/kg BW槐糖后，可以有效降低炎症性肠病大鼠体内的炎性因子水平，从而一定程度的预防/治疗炎症性肠病大鼠的炎症情况。
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等，均应包含在本发明的保护范围之内。
Claims (5)
1.槐糖在制备用于预防和治疗炎症性肠病产品中的应用。
2.如权利要求1所述的应用，其特征在于，所述产品为食品或保健品或药品。
3.一种用于预防和治疗炎症性肠病的产品，其特征在于，包括槐糖。
4.如权利要求3所述的用于预防和治疗炎症性肠病的产品，其特征在于，所述产品为食品或保健品或药品。
5.如权利要求4所述的用于预防和治疗炎症性肠病的产品，其特征在于，所述产品用法为口服。
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| CN107771083A (zh) * | 2015-04-23 | 2018-03-06 | 卡莱多生物科技有限公司 | 聚糖治疗剂和治疗方法 |
| CN109497555A (zh) * | 2018-11-27 | 2019-03-22 | 浙江华康药业股份有限公司 | 一种槐糖微胶囊及其制备方法和应用 |
| US20190290675A1 (en) * | 2016-12-06 | 2019-09-26 | Kaleido Biosciences, Inc. | Glycan polymers and related methods thereof |
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| CN107771083A (zh) * | 2015-04-23 | 2018-03-06 | 卡莱多生物科技有限公司 | 聚糖治疗剂和治疗方法 |
| US20190290675A1 (en) * | 2016-12-06 | 2019-09-26 | Kaleido Biosciences, Inc. | Glycan polymers and related methods thereof |
| CN109497555A (zh) * | 2018-11-27 | 2019-03-22 | 浙江华康药业股份有限公司 | 一种槐糖微胶囊及其制备方法和应用 |
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