CN112807293A - 甲磺酸去铁胺在制备治疗中耳炎药物中的应用 - Google Patents

甲磺酸去铁胺在制备治疗中耳炎药物中的应用 Download PDF

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CN112807293A
CN112807293A CN202110226367.5A CN202110226367A CN112807293A CN 112807293 A CN112807293 A CN 112807293A CN 202110226367 A CN202110226367 A CN 202110226367A CN 112807293 A CN112807293 A CN 112807293A
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otitis media
deferoxamine mesylate
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treating otitis
preparing medicine
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CN112807293B (zh
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李博
郑庆印
颜斌
郑体花
谢道莉
张肖林
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Qingdao University
Binzhou Medical College
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract

本发明公开了甲磺酸去铁胺在制备治疗中耳炎药物中的应用，属于医药技术领域。甲磺酸去铁胺可减轻中耳炎的炎症反应，并且减轻中耳炎导致的听力损失，治疗效果显著。

Description

甲磺酸去铁胺在制备治疗中耳炎药物中的应用
技术领域
本发明涉及医药技术领域，更具体的说是涉及甲磺酸去铁胺在制备治疗中耳炎药物中的应用。
背景技术
中耳炎(Otitis medium,OM)是一种耳鼻喉科常见疾病；对于儿童患者来说，中耳炎是导致听力下降的原因之一，严重的会影响儿童的语言发育。对于有中重度耳痛和高烧的儿童，目前临床常见的治疗方法以抗生素消炎为主，该方法容易引起皮疹，腹泻等副作用，部分患者还会出现中耳炎长时间迁延不愈，转归为慢性中耳炎的情况。因此，寻找更加安全有效的治疗药物十分必要。
甲磺酸去铁胺(DFO)是一种铁死亡抑制剂，其可将游离铁与稳定复合物结合，来降低铁过载的毒性。甲磺酸去铁胺目前主要应用于输血依赖地中海贫血等疾病导致的铁超载的治疗，应用半个多世纪以来，安全性已经得到了充分的验证。目前尚无关于使用甲磺酸去铁胺治疗中耳炎的报道。
发明内容
有鉴于此，本发明首次提出了甲磺酸去铁胺在制备治疗中耳炎药物中的应用。
本发明通过在C57BL/6J小鼠中耳腔中接种链球菌肽聚糖多糖(PGPS)构建OM小鼠模型，使用了铁死亡抑制剂甲磺酸去铁胺(DFO)对小鼠进行治疗后，小鼠听力损失明显减轻，炎症反应显著减少。可见，调节细胞铁死亡可作为一种改善中耳炎的新的治疗方案。
进一步地，以甲磺酸去铁胺为药效成分制备治疗中耳炎的药物，还可添加药学上可接受的辅料。
有益效果：甲磺酸去铁胺作为治疗慢性铁过载和急性铁中毒的药物，已被证实安全性高、毒副作用小，本发明将其应用于治疗中耳炎，可减轻中耳炎炎症和听力损失，其作为治疗中耳炎的药物具有广阔应用前景。
附图说明
图1所示为各组ABR阈值；
图2所示为各组H&E染色图；
其中，下排图片为上排图片框内部分的局部放大图；
图3所示为各组H&E染色上皮局部图；
其中，框内部分为40μm宽上皮截面面积；
图4所示为图3框内部分上皮面积；
图5所示为各组炎症细胞覆盖面积示意图；
图6所示为各组小鼠中耳内炎症细胞相对覆盖面积。
具体实施方式
下面对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
实施例
1.OM小鼠模型构建与RPM治疗
取6–8周龄的C57BL/6J小鼠(来自杰克逊实验室)，测量其ABR阈值，选出25只ABR阈值正常的小鼠，包括10只雌性小鼠和15只雄性小鼠，将其随机分为五组。
用4％的水合氯醛麻醉各组小鼠，分别使用汉密尔顿注射器将如下药物通过鼓膜注入各组小鼠中耳腔：生理盐水(NS)、PGPS(100μg)、PGPS(100μg)+DFO(100μg)、PGPS(100μg)+DFO(200μg)、PGPS(100μg)+DFO(400μg)，药物均使用生理盐水溶解，注射量均为10μL。
2.听觉脑干反应(ABR)
注射PGPS之前和注射PGPS后第三天分别评估C57BL/6J小鼠的ABR阈值：
用4％的水合氯醛麻醉小鼠，并使其体温保持在37℃；将活动电极插入小鼠前额，参比电极插入右耳下方，接地电极插入左耳下方；分别用Click音和纯音8kHz、16kHz和32kHz引起的听觉脑干反应(ABR)；以Ⅱ波的消失为标准记录ABR阈值。
实验结果如图1所示，相较于NS组，PGPS组OM小鼠ABR阈值明显升高；而经DFO治疗后OM小鼠ABR阈值明显改善。
3.中耳组织学
注射PGPS后第三天处死小鼠，分离小鼠中耳和内耳；将整个中耳内耳浸入4％多聚甲醛(PFA)中固定24小时，然后用10％EDTA溶液脱钙3天，并包埋在石蜡中；石蜡组织切片(7μm)，用苏木精-伊红对组织切片染色，在光学显微镜下观察并使用LAS X软件(LeicaDM4500 B,leica Microsystems Inc,Bu ffalo Grove,IL,USA)进行分析。
结果如图2-6所示，相较于NS组，PGPS组OM小鼠表现出明显的炎症反应；而经DFO治疗后OM小鼠炎症反应明显改善。
本文中所定义的一般原理可以在不脱离本发明的精神或范围的情况下，在其它实施例中实现。因此，本发明将不会被限制于本文所示的这些实施例，而是要符合与本文所公开的原理和新颖特点相一致的最宽的范围。

Claims (3)

1.甲磺酸去铁胺在制备治疗中耳炎药物中的应用。
2.一种治疗中耳炎的药物，其特征在于，包括甲磺酸去铁胺。
3.根据权利要求2所述的一种治疗中耳炎的药物，其特征在于，还包括药学上可接受的辅料。
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102526005A (zh) * 2011-12-23 2012-07-04 苏州大学 甲磺酸去铁胺在制备治疗绝经后骨质疏松疾病药物中的用途
CN102905697A (zh) * 2010-03-22 2013-01-30 医疗研究局 靶向vegf和/或hif途径、用于治疗中耳炎的化合物如索拉非尼或瓦他拉尼
CN107184570A (zh) * 2017-06-02 2017-09-22 中国科学院遗传与发育生物学研究所 去铁胺在制备用于治疗非酒精性脂肪肝的药物中的应用

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102905697A (zh) * 2010-03-22 2013-01-30 医疗研究局 靶向vegf和/或hif途径、用于治疗中耳炎的化合物如索拉非尼或瓦他拉尼
CN102526005A (zh) * 2011-12-23 2012-07-04 苏州大学 甲磺酸去铁胺在制备治疗绝经后骨质疏松疾病药物中的用途
CN107184570A (zh) * 2017-06-02 2017-09-22 中国科学院遗传与发育生物学研究所 去铁胺在制备用于治疗非酒精性脂肪肝的药物中的应用

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ROBERT R. PARKS ET AL.: "Evidence of Oxygen Radical Injury in Experimental Otitis Media", 《LARYNGOSCOPE》 *
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