CN107072979B - 类黄酮化合物在制备伤口愈合组合物的用途 - Google Patents
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Abstract
本发明公开一种类黄酮化合物在制备伤口愈合组合物的用途,其中该化合物较佳为非糖基化黄酮。特定而言,本发明用途可用在治疗外伤、烧烫伤及慢性伤口的皮肤症状,尤指糖尿病患者伤口的愈合。
Description
技术领域
本发明公开一种化合物在制备伤口愈合组合物的新用途，具体而言，本发明涉及一种类黄酮化合物在制备伤口愈合组合物的新用途。
背景技术
类黄酮化合物(flavonoids)是泛指具两个含酚羟基的苯环，以中央三碳原子相互连接的一系列化合物，具通式I之结构：
通常见于水果、蔬菜、茶、葡萄酒、种子或是植物根等。虽非属维生素，被证实具抗氧化功能及抗发炎反应功效；也被验证具有抵抗或是减缓肿瘤的形成、止痛、减缓心血管疾病或失智症。
类黄酮化合物包含黄酮(flavone)及黄酮醇。黄酮又包括糖基化黄酮及非糖基化黄酮。
2002年10月29日核准公告之美國專利第6,471,973B2號，揭露類黄酮化合物可用在化粧品中，但未提及其他功效。又2002年9月17日核准公告之美國專利第6,451,837B1號，揭露類黄酮化合物的經保護功效。
发明内容
本发明的目的是提供类黄酮化合物(flavonoids)在制备伤口愈合组合物的新用途。
一方面，本发明提供一种化合物在制备伤口愈合组合物的用途，其中该化合物是具有下列通式I结构的化合物或其异构物：
其中A是氢原子、R或-OH；
n1及n2是相同或不同，是0至4的整數之一，其中n1及n2的總和至多為4；
n3及n4是相同或不同，是0至5的整數之一，其中n3及n4的總和至多為5；
其中R、R1、R2、R3或R4的定义是氢原子、含1-30个碳原子的烷基、含有1-30个碳原子的烷基的酰基、或含有1-30个碳原子的烃链；
或其医药可接受的酯或盐。
根据本发明，该伤口愈合组合物为用在伤口愈合是用在治疗外伤、烧烫伤及慢性伤口的皮肤症状愈合，尤指糖尿病患者伤口愈合。
根据本发明之一实例，其中该化合物为黄酮(flavone)，尤其是非糖基化黄酮(non-glycosylatedflavone)。
根据本发明的较佳实施例，其中该非糖基化黄酮化合物是滨蓟黄素(cirsimaritin)，具有下列结构：
本发明的该等及其它方面，可藉由以下的较佳具体实施例的描述以及图式，得以更为明晰；即便其中可能会有变化或修饰，但不背离本发明所揭露之新颖观念的精神及范畴。
具体实施方式
除非另有定义，所有本文所用的技术性及科学性术语，对于属于本发明领域的具有通常知识者而言，皆具有与其所习知者相同意义。
除非文中有清楚指明者，在本文中所使用的单数形式“一”、“一种”、及“该”之涵义均为包括“至少一种”的复数形式。因此，例如，当提及“一成分”时，包括复数个该等成分及对该领域具有通常知识者所知的同等物。
本发明提供一种化合物在制备伤口愈合组合物之用途，其中该化合物为具有下列通式I结构的化合物或其异构物：
其中A是氢原子、R或-OH；
n1及n2是相同或不同，是0至4的整數之一，其中n1及n2的總和至多為4；
n3及n4是相同或不同，是0至5的整數之一，其中n3及n4的總和至多為5；
其中R、R1、R2、R3或R4的定义是氢原子、含1-30个碳原子的烷基、含有1-30个碳原子的烷基的酰基、或含有1-30个碳原子的烃链；
或其医药可接受的酯或盐。
根据本发明，其中该化合物为黄酮(flavone)，尤指非糖基化黄酮(non-glycosylated flavone)。该非糖基化黄酮化合物是滨蓟黄素(cirsimaritin)，其具有下列结构：
根据本发明，其中该组合物包含一医药上可接受的载剂。
根据本发明，其中该组合物包含一适当赋形剂而制成外用药剂形式、化妆品形式或医药材料形式的组合物。
根据本发明，其中该组合物尚包含一治疗剂，例如其他抗发炎剂、抗菌剂或其他治疗药剂。
在本文中所使用的名词“皮肤症状”是包括伤口或疮，包括皮肤割伤、裂伤、刺伤、磨伤等皮肤伤害。根据本发明，该等化合物显示对于外伤、烧烫伤及慢性伤口的皮肤症状伤口具有愈合之效果，尤其是对糖尿病患者伤口特别有效，例如糖尿病患者的慢性伤口。
在本文中所使用的名词“治疗”，包括“处理”或“促进”之意，意指改善症状。
在本文中所使用的名词“患者”包含人类、及动物，特别是哺乳动物。
在本文中所使用的名词“医药上可接受的载剂”是指一般医药上常用的技术可用在制备医药组合物的稀释剂、赋形剂及其类似物。根据本发明，可调制成药品、化妆品或医药材料的型式。根据本发明，可制成局部方式涂敷的形式，例如，喷雾形式。喷雾形式包含喷剂及液剂；或半固体或固体形式，较佳是具有动态黏度大于水者的固体形式。适当配方包括但不限于悬浮液、乳化液、乳膏、软膏、擦剂等。较佳者，是呈软膏形式。本发明医药组合物不论呈何种形式，亦可含有润肤剂、香料或颜料，以提高其对于各种用途的可接受性。
在本文中所使用的名词“治疗有效量”，意指在症状处理上可有效治疗伤口的剂量。可依患者或伤口的需要，依一般医药上常用的技术或临床知识使用适当剂量，并可依照施予的方式及治疗的情况，包括年龄、体重、症状、治疗效果、施用方式及治疗时间调整。
以上述发明说明以及下列实施例说明本发明，但并非用以限制本发明的范围。
实施例1：动物试验模式建立
大鼠体重达300g后以链脲菌素(Streptozotocin(STZ))进行高血糖的诱导(65mg/kg，ip给药)。选择诱导成功的高血糖动物(300mg/DL)，该等高血糖动物在产生高血糖症状两个月后进行糖尿病伤口愈合试验。淘汰体重低于300克的高血糖动物，进行随机分组。将动物以戊巴比妥(pentobarbital)麻醉后在其背部进行剃毛、消毒。在动物背部正上方，距两肩胛骨中点4、6、8公分处以直径1公分钻孔圆刀取下3块动物表皮(full thickness)。
每只动物伤口涂上测试药物，实验结束后取下新生表皮进行检测。
每只大鼠背上三个伤口经image pro分析面积后以第零天的面积为原始伤口面积。将原始伤口面积减去各时间点的伤口面积再除以原始伤口面积的数值当成伤口愈合百分率。将每只大鼠三个伤口愈合百分率平均值，当成每只大鼠当成各伤口愈合程度。每次试验每组大鼠只数6只。数据以平均值(mean)±标准误差(SEM)表示。测试结果以对照组t-test来计算P value，P＜0.05表示有显著差异，以*表示。
0.5％滨蓟黄素组合物制成软膏形式，处理经其上述处理的老鼠，实验结果如下，施用后的第9、11、13、15天与未处理的对照组伤口愈合百分率比较如下，愈合效果均达显著差异。进一步计算伤口愈合一半所需天数(CT50值)亦显示具显著差异。
％：伤口愈合百分率
CT50：伤口愈合一半所需天数(wound half-closure time)
*：p＜0.05
动物只数：n＝6
由实验结果可知本发明化合物中以滨蓟黄素为例，对于糖尿病患者的慢性伤口愈合具有治疗效果。
Claims (3)
1.一种化合物在制备供慢性伤口的愈合的组合物的用途,其中该化合物为具有下列结构的化合物:
2.如权利要求1所述的用途,其中该慢性伤口是糖尿病患者的慢性伤口。
3.如权利要求1所述的用途,其中该化合物包含一适当赋形剂而制成外用药剂形式、化妆品形式或医药材料形式的组合物。
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| US6066642A (en) * | 1996-01-29 | 2000-05-23 | The United States Of America As Represented By The Department Of Health And Human Services | Dihydropyridine-, pyridine-, benzopyran-4-one- and triazoloquinazoline derivative, their preparation and their use as adenosine receptor antagonists |
| KR100447918B1 (ko) * | 1996-07-25 | 2005-09-28 | 동아제약주식회사 | 대장을포함한위장관보호작용을갖는플라본및플라바논화합물 |
| US8449924B2 (en) * | 2007-08-29 | 2013-05-28 | Development Center For Biotechnology | Process for the preparation of plant extracts for treating skin disorders and enhancing healing of wounds |
| AU2010286318A1 (en) * | 2009-08-24 | 2012-04-05 | Wound Management Pty Ltd | Purine-targeted diagnosis and therapy of wounds |
| TWI501772B (zh) * | 2011-11-22 | 2015-10-01 | Oneness Biotech Co | 具抗關節炎活性的到手香精萃物 |
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| Publication number | Publication date |
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| EP3189837B1 (en) | 2023-11-15 |
| EP3189837A4 (en) | 2018-01-17 |
| CN107072979A (zh) | 2017-08-18 |
| WO2016033802A1 (zh) | 2016-03-10 |
| EP3189837A1 (en) | 2017-07-12 |
| US10376488B2 (en) | 2019-08-13 |
| US20170273938A1 (en) | 2017-09-28 |
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