CN104546873A - 四羟基二苯乙烯苷在预防和治疗放射性损伤中的应用 - Google Patents
四羟基二苯乙烯苷在预防和治疗放射性损伤中的应用 Download PDFInfo
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Abstract
本发明公开了四羟基二苯乙烯苷或其药学上可接受的盐在制备预防和/或治疗放射性损伤药物中的应用。四羟基二苯乙烯苷毒性小，预防和治疗放射性损伤效果显著，尤其在与其它放射性损伤药物联合防治使用时，可用于协同治疗或降低其他疗法剂量和药物毒副作用，具有广泛的应用前景。
Description
技术领域
本发明涉及四羟基二苯乙烯苷及其药学上可接受的盐在预防和治疗辐射引起的放射性损伤中的应用，属于医药技术领域。
背景技术
众所周知，机体在接触辐射后，如防护措施不当，受照射的剂量超过一定限度，就会产生有害作用。辐射引起的放射性损伤疾病，为机体的全身性反应，几乎所有器官、系统均可发生病理改变，其中以神经系统、造血器官和消化系统的改变最为明显，具体临床表现为皮肤损伤、造血障碍、白细胞减少、生育力受损等，另外还可以致癌和引起胎儿的死亡和畸形。
在放射事故或辐射暴露环境作业时，辐射损伤防治药物是救治与防护最有效和最直接的手段之一。在接触放射前使用，能预防射线对人体的损伤；受到照射后使用，能减轻放射性损伤疾病的临床症状，促进早期恢复。所以，辐射防护药的开发也就成了放射医学研究领域中的重点和研究热点。目前，研究较多的辐射损伤防治药物主要包括含硫化合物(如氨磷汀WR-2721）、激素类、中药、细胞因子类等。寻求毒性低、疗效高的辐射防护与辐射治疗药物一直备受放射医学界的重视。
四羟基二苯乙烯苷是从何首乌、虎杖、珍珠菜等植物中提取的单体，其化学名为2，3，5，4’- 四羟基- 二苯乙烯-2-O-β-D- 葡萄糖苷。研究发现，四羟基二苯乙烯苷具有多种生理活性与药用价值，已在降血脂、抗衰老、抑制肿瘤、解酒保肝等方面发挥作用。目前，四羟基二苯乙烯苷已有多项医学应用专利，如中国专利99119853.0公开了二苯乙烯苷具有较强且广泛的心脑血管活性，可用于防治心脑血管疾病的药物和保健食品。中国专利200710178356.4公开了二苯乙烯苷或其衍生物能有效抑制α- 突触核蛋白的过度表达，可用于治疗或预防由α- 突触核蛋白过度表达所引起的帕金森病、路易体痴呆、单纯性自主神经功能障碍、多系统萎缩等多种神经系统疾病方面的用途。中国专利201110196199.6公开了二苯乙烯苷可用于治疗痴呆症、脑卒中、冠心病、心绞痛等方面的用途。因此，深入研究四羟基二苯乙烯苷及其药理作用，将有力地扩展其医学用途，推动其在医药学中的进一步应用。
发明内容
本发明的目的是提供四羟基二苯乙烯苷的一种新用途，即四羟基二苯乙烯苷预防和/或治疗放射性损伤的新应用，进一步的目的在于提供该化合物及其药学上可接受的盐在制备放射损伤预防与治疗药物或保健品中的用途。
本发明实现过程如下：
结构式（I）所示化合物或其药学上可接受的盐在预防和/或治疗放射性损伤中的应用，
所述药学上可接受的盐中阳离子为碱金属阳离子（如钠离子、钾离子），碱土金属阳离子（如钙离子、镁离子）或铵离子。
所述药学上可接受的盐制备方法为：以四羟基二苯乙烯苷为原料，经与碱金属氢氧化物、碱土金属氢氧化物或氨水在有机溶剂中反应得药学上可接受的盐，所述有机溶剂选自乙醇、甲醇、四氢呋喃、二氯甲烷、二氧六环。
四羟基二苯乙烯苷及其药学上可接受的盐作为活性成分，添加适当的药物载体（如生理盐水、注射用水、淀粉、糊精等）或赋形剂可制备得到不同剂型的药用组合物，如注射、口服、口腔、舌下、植入、局部用药或直肠给药的药用组合物，制备成多种药物剂型。所述载体包括药学领域常规的稀释剂、赋形剂、填充剂、粘合剂、湿润剂、崩解剂、吸收促进剂、表面活性剂、吸附载体、润滑剂等，必要时还可以加入甜味剂、香味剂等。本发明优选注射给药。
发明人研究发现，四羟基二苯乙烯苷及其药学上可接受的盐具有显著的预防和治疗放射损伤的作用，可应用于制备药物或保健品，预防和治疗放射性损伤疾病。四羟基二苯乙烯苷毒性小，预防和治疗放射性损伤效果显著，尤其在与其它放射性损伤药物联合防治使用时，可用于协同治疗或降低其他疗法剂量和药物毒副作用，具有广泛的应用前景。
具体实施方式
下面通过实施例对本发明作进一步描述，本发明范围不限于以下实例。
实施例1 对体外细胞增殖的影响
1、实验方法
选择人源性正常细胞株脐静脉血管内皮细胞（ECV-304）和肝细胞（L-02）。用 X线照射细胞建立辐射损伤模型，设立4组即预防对照组、预防组、治疗对照组，拟定合适的药物浓度进行防治实验。照射条件：美国RAD COURCE公司RS-2000型X线辐照器，剂量为6Gy。预防组和治疗组均给予6Gy照射，照后4天测定OD值并计算细胞存活率，通过比较各组存活率以测定四羟基二苯乙烯苷的辐射防治作用。
2、实验结果
体外辐射预防与治疗评价实验结果表明，四羟基二苯乙烯苷在细胞水平具有辐射预防与治疗作用，X线6Gy照射后与对照组相比，其细胞存活率明显降低了50%以下，表明细胞放射损伤模型成功，而给予四羟基二苯乙烯苷5-500 μmol/L浓度预防和治疗时，500 μmol/L组对ECV-304细胞具有预防与治疗作用(表1)，对L-02细胞具有明显治疗作用（表2）。
实施例2 对辐射损伤动物生存率的影响
1、实验方法
选择体重20g左右雄性小鼠。采用X线全身照射，设立4组即照射组、预防组、治疗组，各组按药物浓度又分为若干小组。照射条件：美国RAD COURCE公司RS-2000型X线辐照器，小鼠放入30×30cm2浅底(10cm深)有机玻璃照射盒内，小鼠在盒内呈自由状态，射源距小鼠40cm，射野为30×30cm2，剂量率为1.414Gy/min，剂量为6Gy，一次性全身照射。药物用生理盐水稀释，小鼠用药量5mg/ml·d，腹腔注射0.2 ml，1/d，预防从照前4天开始给予，在给药第4天时给药后立刻照射，照后停止用药，治疗从照射后立刻给药，连续5天用药。预防组和治疗组均给予6Gy照射，照后1-30天观察存活只数和死亡率，通过比较各组存活率以测定四羟基二苯乙烯苷的辐射防治作用。
2、实验结果
动物体内辐射预防与治疗评价实验结果表明， 6Gy照射时预防组和治疗组死亡率均低于照射组，而且四羟基二苯乙烯苷治疗组死亡率明显低于预防组(表3)。体内外研究表明，四羟基二苯乙烯苷具有显著的辐射防治作用，可用于相关疾病的预防与治疗。
Claims (3)
1.结构式（I）所示化合物或其药学上可接受的盐在制备预防和/或治疗放射性损伤药物或保健品中的应用，
。
2.根据权利要求1所述应用，所述药学上可接受的盐中阳离子为碱金属阳离子、碱土金属阳离子或铵离子。
3.根据权利要求2所述应用，其特征在于药学上可接受的盐制备方法为：以四羟基二苯乙烯苷为原料，经与碱金属氢氧化物、碱土金属氢氧化物或氨水在有机溶剂中反应得药学上可接受的盐，所述有机溶剂选自乙醇、甲醇、四氢呋喃、二氯甲烷、二氧六环。
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| CN107441182A (zh) * | 2016-05-30 | 2017-12-08 | 中国人民解放军第三〇二医院 | 何首乌提取物的制备方法及其制剂和应用 |
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| EP1013260A2 (fr) * | 1998-12-22 | 2000-06-28 | L'oreal | Utilisation d'hydroxystilbènes pour la teinture, composition prête à l'emploi les contenant et procédé de teinture |
| CN102060889A (zh) * | 2007-02-27 | 2011-05-18 | 江苏正大天晴药业股份有限公司 | 二苯乙烯苷衍生物 |
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| EP1013260A2 (fr) * | 1998-12-22 | 2000-06-28 | L'oreal | Utilisation d'hydroxystilbènes pour la teinture, composition prête à l'emploi les contenant et procédé de teinture |
| CN102060889A (zh) * | 2007-02-27 | 2011-05-18 | 江苏正大天晴药业股份有限公司 | 二苯乙烯苷衍生物 |
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| 廖勇 等: "何首乌二苯乙烯苷抑制长波紫外线诱导的HaCaT细胞氧化损伤", 《中国皮肤性病学杂志》 * |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107441182A (zh) * | 2016-05-30 | 2017-12-08 | 中国人民解放军第三〇二医院 | 何首乌提取物的制备方法及其制剂和应用 |
| CN107441182B (zh) * | 2016-05-30 | 2021-08-10 | 中国人民解放军第三〇二医院 | 何首乌提取物的制备方法及其制剂和应用 |
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