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用于溃疡性结肠炎治疗的热敏水凝胶的配方。

Formulation of a thermo-sensitive hydro-gel for ulcerative colitis treatment.

作者信息

Sathesh Deepa, Sathesh Kumar K, Devadasan Velmurugan, Kuppusamy Sujatha

机构信息

Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research (DU), Porur, Chennai, India.

Office of Dean Sponsored Research, Publications and Collaboration and Director R & D Cell, AMET University, Kanathur, ECR road, Chennai, Tamil Nadu, India.

出版信息

Bioinformation. 2022 Oct 31;18(10):925-937. doi: 10.6026/97320630018925. eCollection 2022.

DOI:10.6026/97320630018925
PMID:37654823
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10465774/
Abstract

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that causes chronic intestinal inflammation in gastrointestinal (GI) tract, mainly in innermost lining of colonic mucosa. In any of the UC drug therapy regimens, maintaining remission is challenging and about 20-40% of patients don't respond to conventional UC medications, namely, amino salicylates, steroids and immunosuppressive drugs. These agents can weaken the patient's immune system thus enhancing the risk of infectious diseases. Therefore, in our exploration we probed to test marine-derived anti-inflammatory compounds as potential agents to treat UC. Fucoidan, a complex fucose-rich sulphated polysaccharide originated in edible brown algae with known anti-inflammatory properties was isolated from Turbinaria ornate. Collagen (Achillis tendon) is another agent that may provide a beneficial effect in wound healing and tissue regeneration. Collagen was also reported to possess anti-UC properties. Collagen has a limitation of being in solution form even at high concentrations. We therefore formulated fucoidan with collagen that underwent a sol-gel transition and yielded a gel like consistency in situ. This formulation showed sustained release of fucoidan for about 12 hours. The fucoidan, collagen and the fucoidan-collagen formulation were tested in the dextran sodium sulfate (DSS) induced colitis model in mice. In comparison to the vehicle treated group, fucoidan-collagen hydrogel formulation led to significant reduction in the clinical scores and rectal bleeding, which was higher than the reference standard, mesalamine and those seen with fucoidan and collagen given alone.

摘要

溃疡性结肠炎(UC)是一种炎症性肠病(IBD),会导致胃肠道(GI)的慢性肠道炎症,主要发生在结肠黏膜的最内层。在任何UC药物治疗方案中,维持缓解都具有挑战性,约20%-40%的患者对传统的UC药物(即氨基水杨酸盐、类固醇和免疫抑制药物)没有反应。这些药物会削弱患者的免疫系统,从而增加感染性疾病的风险。因此,在我们的探索中,我们测试了海洋来源的抗炎化合物作为治疗UC的潜在药物。岩藻依聚糖是一种富含岩藻糖的复杂硫酸化多糖,源自具有已知抗炎特性的可食用褐藻,从石花菜中分离得到。胶原蛋白(跟腱)是另一种可能在伤口愈合和组织再生中发挥有益作用的物质。据报道,胶原蛋白也具有抗UC特性。胶原蛋白的一个局限性是即使在高浓度下也呈溶液形式。因此,我们将岩藻依聚糖与胶原蛋白配制成一种经历溶胶-凝胶转变并原位产生凝胶状稠度的制剂。该制剂显示岩藻依聚糖可持续释放约12小时。在葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎模型中对岩藻依聚糖、胶原蛋白和岩藻依聚糖-胶原蛋白制剂进行了测试。与载体处理组相比,岩藻依聚糖-胶原蛋白水凝胶制剂使临床评分和直肠出血显著降低,高于参考标准美沙拉嗪以及单独使用岩藻依聚糖和胶原蛋白时的效果。

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本文引用的文献

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Anti-Inflammatory Activity of Fucoidan Extracts In Vitro.体外岩藻聚糖硫酸酯提取物的抗炎活性。
Mar Drugs. 2021 Dec 11;19(12):702. doi: 10.3390/md19120702.
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Oral Single Dose Toxicity Study of Low Molecular Fucoidan in Mice.低分子岩藻聚糖对小鼠的口服单剂量毒性研究
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Fucoidan Extracts Ameliorate Acute Colitis.岩藻依聚糖提取物可改善急性结肠炎。
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