CN101724004A - 一种抗牛皮癣纯天然新药(11-羰基-β-乙酰乳香酸) - Google Patents
一种抗牛皮癣纯天然新药(11-羰基-β-乙酰乳香酸) Download PDFInfo
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Abstract
一种能够有效地抑制牛皮癣患者患病皮肤内核酸转录因子NF-kappa-B的过度活化，阻隔肿瘤坏死因子TNF-alpha的过量合成而治疗牛皮癣的纯天然新药。这种新药是一种天然提取物、生产成本低、药物疗效高而副作用小。
Description
所属技术领域
本发明涉及一种疗效好、安全性高的治疗牛皮癣的纯天然新药(11-羰基-β-乙酰乳香酸)。英文全名是：acetyl-11-keto-β-boswellic acid，简称：AKβBA(图1)。
背景技术
牛皮癣(Psoriasis)，是常见的慢性、复发性、炎症性的皮肤病。目前研究认为：牛皮癣是一种CD4+T细胞介导的自身免疫性疾病(Sano et al.，2005；Schon et al.，1997)。它的病因来自于遗传和环境两种因素，但到现在为止确切的发病原因还不清楚并且目前尚无根治的药物(Gottlieb and Bos，2002)。我国每年要花很多外汇用于进口治疗牛皮癣药物，尤其是科技含量高小分子蛋白。基于这一点，研究开发我国自主知识产权的治疗牛皮癣的新药势在必行。申请者的研究表明：与正常人的皮肤相比，牛皮癣患者的表皮和真皮内核酸转录因子NF-kappa-B过度活化导致肿瘤坏死因子TNF-alpha的大量释放，过量的肿瘤坏死因子TNF-alpha诱发了人类的牛皮癣。
目前，治疗牛皮癣的药物中有一种肿瘤坏死因子制剂Etanercept(依那西普)是美国FDA批准用于牛皮癣治疗的生物制剂。这种药物为人源化抗体，它的作用机理是阻隔肿瘤坏死因子的受体。由于肿瘤坏死因子在机体正常免疫反应中不可缺少，这种人源化抗体没有选择性地阻挡肿瘤坏死因子会导致用药后的副作用，甚至停药后疾病容易反弹。而且，由于这种药物是抗体、生产成本高、价格昂贵、普通病人很难能承受。
为了克服这种治疗牛皮癣药物生产成本高并且没有选择性的缺点，本发明提供一种生产成本低且有选择性地阻断核酸转录因子NF-kappa-B过度表达从而抑制肿瘤坏死因子的大量释放达到治疗效果的纯天然新药。
技术发现
本发明的技术发现是：首先观察到与对照正常人的皮肤相比，核酸转录因子NF-kappa-B被过度表达在牛皮癣患者的表皮和真皮内(图2A，B)。天然提取物11-羰基-β-乙酰乳香酸(AKβBA)能够特异地阻断核酸转录因子NF-kappa-B的活化，很大程度上降低肿瘤坏死因子TNF-alpha的表达量。用11-羰基-β-乙酰乳香酸治疗患有“牛皮癣”的小鼠35天后，“牛皮癣”小鼠被基本治愈(图3A，B)。在测试11-羰基-β-乙酰乳香酸对人类牛皮癣患者可能的治疗效果的体外实验中，11-羰基-β-乙酰乳香酸被发现能够特异地抑制牛皮癣患者真皮内核酸转录因子NF-kappa-B的活化，并且阻隔信号转导下游肿瘤坏死因子TNF-alpha的合成。对牛皮癣患者的小规模临床试验表明，11-羰基-β-乙酰乳香酸能够非常显著地改善牛皮癣患者的症状。鉴于以上科学实验的发现，申请11-羰基-β-乙酰乳香酸为治疗人类牛皮癣的新药。
本发明的有益效果是：11-羰基-β-乙酰乳香酸为天然提取物、生产成本低、能够特异阻隔肿瘤坏死因子TNF-alpha的过量合成、药物疗效高而副作用小。
附图说明
图1，acetyl-11-keto-β-boswellic acid分子结构图。
图2，与正常人的正常皮肤相比，牛皮癣患者的患病皮肤内核酸转录因子NF-kappa-B过度活化。图2A，正常人的正常皮肤中核酸转录因子NF-kappa-B活化的免疫荧光标记。图2B，牛皮癣患者的患病皮肤核酸转录因子NF-kappa-B活化的免疫荧光标记。
图3，11-羰基-β-乙酰乳香酸治愈了小鼠的“牛皮癣”。图3A，患“牛皮癣”的小鼠用11-羰基-β-乙酰乳香酸治疗前。图3B，患“牛皮癣”的小鼠用11-羰基-β-乙酰乳香酸治疗35天后。
Claims (3)
1.11-羰基-β-乙酰乳香酸为天然提取物，要求保护的权利范围为：“治疗牛皮癣的纯天然新药”。这种纯天然新药能够特异地抑制牛皮癣患者真皮内核酸转录因子NF-kappa-B的过度活化，并且阻隔信号转导下游肿瘤坏死因子TNF-alpha的过量合成。
2.根据权利要求1所述的纯天然抗牛皮癣新药，其特征是：抑制牛皮癣患者真皮内核酸转录因子NF-kappa-B的过度活化，阻隔肿瘤坏死因子TNF-alpha的过量合成。要求将此特征归为权利保护范围。
3.根据权利要求1所述的纯天然抗牛皮癣新药，其特征是：这种纯天然新药可以产生疗效高而副作用小的治疗牛皮癣的效果。要求将此特征归为权利保护范围。
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| CN200810201526A CN101724004A (zh) | 2008-10-22 | 2008-10-22 | 一种抗牛皮癣纯天然新药(11-羰基-β-乙酰乳香酸) |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103897010A (zh) * | 2012-12-25 | 2014-07-02 | 苏州博创园生物医药科技有限公司 | 一种用于治疗银屑病的组合物及制备方法 |
| CN104672293A (zh) * | 2013-11-30 | 2015-06-03 | 苏州博创园生物医药科技有限公司 | 一种五环三萜结构修饰化合物及其制备方法和应用 |
| CN108888618A (zh) * | 2018-06-21 | 2018-11-27 | 上海交通大学医学院 | 治疗银屑病的新型药物及其应用 |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103897010A (zh) * | 2012-12-25 | 2014-07-02 | 苏州博创园生物医药科技有限公司 | 一种用于治疗银屑病的组合物及制备方法 |
| CN103897010B (zh) * | 2012-12-25 | 2017-07-11 | 苏州博创园生物医药科技有限公司 | 一种用于治疗银屑病的组合物及制备方法 |
| CN104672293A (zh) * | 2013-11-30 | 2015-06-03 | 苏州博创园生物医药科技有限公司 | 一种五环三萜结构修饰化合物及其制备方法和应用 |
| WO2015078321A1 (zh) * | 2013-11-30 | 2015-06-04 | 苏州博创园生物医药科技有限公司 | 一种五环三萜结构修饰化合物及其制备方法和应用 |
| CN105814072A (zh) * | 2013-11-30 | 2016-07-27 | 苏州博创园生物医药科技有限公司 | 一种五环三萜结构修饰化合物及其制备方法和应用 |
| JP2016538346A (ja) * | 2013-11-30 | 2016-12-08 | ▲蘇▼州博▲創▼▲園▼生物医▲薬▼科技有限公司 | 五環トリテルペン構造修飾化合物とその調製方法及び応用 |
| CN104672293B (zh) * | 2013-11-30 | 2017-01-18 | 苏州博创园生物医药科技有限公司 | 一种五环三萜结构修饰化合物及其制备方法和应用 |
| US9725482B2 (en) | 2013-11-30 | 2017-08-08 | Suzhou Botany Biomedical Co., Ltd. | Pentacyclic triterpenoid compound with modified structure and preparation method and use thereof |
| CN108888618A (zh) * | 2018-06-21 | 2018-11-27 | 上海交通大学医学院 | 治疗银屑病的新型药物及其应用 |
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