CN1068777C - 5－羟甲基－2－糠醛的医药用途 - Google Patents
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Abstract
本发明公开了5-羟甲基糠醛在医药领域作为有效成分制备抗心肌缺血的心血管病药品的应用，其为首次从生脉散合煎剂中发现并被分离鉴定。
Description
本发明涉及5-羟甲基-2-糠醛(5-HMF)在医药领域的应用，尤其涉及5-HMF作为有效成分制备药品。
5-HMF在蔗糖生产、啤酒发酵以及各类含糖食品和药品的生产和贮存过程中作为糖的热降解产物而广泛存在，但至今未见对其药理活性的报道(参见袁建平等高效液相色谱法同时测定食品和药品中的糖及其降解产物5-羟甲基糠醛分析化学1996:24(1)57)。相反有一篇文献报道蜂蜜在长时间贮存或长时间高热条件下，产生5-HMF可引起动物横纹肌麻痹和内脏损害(参见苏孝礼等紫外分光光度法测定蜜丸中5-羟甲基糠醛的含量 中成药1994；16(2)12)。
本发明的目的在于发现5-HMF的药理活性，将其作为有效成份制备药品。
本发明的目的还在于发现5-HMF在中药配伍中，是否能降低或不产生上述毒副反应。
为了解决上述任务，本发明采用的技术方案是：5-羟甲基-2-糠醛在制备心血管病药品中的应用。
本发明的优选技术方案是5-羟甲基-2-糠醛在制备抗心肌缺血的心血管病药品中的应用。
本发明首次从中药古方生脉散合煎剂中发现并分离、鉴定了产生的新成分5-HMF，药效试验表明，5-HMF具有抗氧化作用，能降低心肌缺血小鼠血清中乳酸脱氢酶(LDH)活性，降低心肌缺血小鼠心肌组织中丙二醛(MDA)含量，其作用优于人参皂甙，表明其有抗心肌缺血作用，见下表及图1、图2。从德国默克公司购买的5-HMF同样具有下表及图1、图2表现的药理活性。
5-HMF和人参皂甙对异丙肾上腺素诱发小鼠心肌缺血时降低心肌MDA含量和降低血清LDH活性的比较组份 剂量(g/kg) n 心肌MDA 血清LDH
(nmol/g) (U/L)人参皂甙 0.2 10 29.28±10.25* 670.04±32.90
0.4 10 39.83±7.05 673.38±56.345-HMF 0.03 10 20.94±3.00*** 643.87±38.39*
0.06 10 34.49±4.55* 665.32±30.67正丁醇部位 5.5 10 30.19±7.89** 648.02±54.62
11.0 10 30.99±6.50** 631.65±36.15**正常组 - 10 22.64±2.35 641.21±23.66对照组 - 10 39.83±6.00### 687.83±49.88#
each value represents the mean±SD
*P＜0.05 **P＜0.01 ***P＜0.001 vs，对照组
#P＜0.05 ###P＜0.01 vs.正常组
生脉散由人参、麦冬、五味子三药组成，药理研究表明，三药共煎液的药效作用明显优于三药分煎液及其他各配伍组的提取液，化学研究表明，三药共煎液的化学成分并不等于各单味药的相加，在煎煮过程中，除了已报道的人参皂甙的种类有转化外，还有其他一些新的化合物产生。通过下述实验，分离鉴定了5-HMF。1 实验部份1.1 仪器与材料
岛津UV-2100紫外扫描仪；岛津IR-400红外分光光度计；MAT212型质谱仪；FT90Q型核磁共振仪；青岛海洋化工厂产柱层析、薄层层析用硅胶G、GF254；实验所用试剂均为分析纯。
方中红参(Panax ginseng C.A Mey)，麦冬(Ophipogon japonicus(L.f.)KerGawl)，北五味子(Schisandra chinensis(Turcz.)Baill)均购自南京市药材公司，经鉴定，符合1990年版中国药典规定；5-HMF对照品购自德国默克公司。1.2 实验方法和结果
根据生脉散配方比例(红参∶麦冬∶五味子=1∶3∶1.5)，分别取适量药材，10倍量水浸泡半小时，煎煮1.5小时，滤渣再用6倍量水，煎煮1小时，过滤，合并滤液，浓缩。
将生脉散水煎浓缩液用乙酸乙酯萃取，萃取液浓缩成浸膏，拌适量硅胶至流动性良好，干法上硅胶柱，以甲苯-乙酸乙酯梯度洗脱，薄层层析检查，收集且合并含5-HMF的流份，回收溶剂后，同法再上小柱分离纯化，最后用薄层制备色谱制得光谱样品。1.3 5-HMF的鉴定
以上实验获得的纯品，经紫外、红外、质谱、氢谱、碳谱鉴定分析确定为5-羟甲基-2-糠醛(简称5-HMF)。其结构式为：
5-HMF为棕色油状物。分子式C6H6O3。UVλmaxnm:280。IR(KBr)cm-1:3395(OH),3134(C=C),2932,2843,1682(C=O),1581,1521,1390,1367,1334,1281,1188,1068,1020,990,971,814,773。EI-MS(70ev)m/z:127[M+1]+(9),126[M]+(60),109[M-OH]+(12),97[M-CHO]+(100),69(84)。HNMR(CDCl3,300MHz)δppm:2.45(brs,醇OH),4.72(2H,S,CH2OH),6.52(1H,d,J=3.5Hz,4-H),7.22(1H,d,J=3.5Hz,3-H),9.58(1H,s,醛基H)。13CNMR(CDCl3)δppm:57.61(CH2OH),109.93(C-4),122.60(C-3),152.41(C-2),177.64(醛基C)，以上数据与已知物5-羟甲基-2-糠醛UV、IR、MS、1HNMR、13CNMR标准图谱核对均一致，故推断为5-羟甲基-2-糠醛。
研究表明，单味人参、麦冬、五味子在煎煮前均不含5-HMF，单味五味子水煎后能产生少量的5-HMF，人参、麦冬的水煎液中均未发现5-HMF的存在，生脉散全方及麦冬与五味子配伍的水煎液中5-HMF的含量显著增高，由此推断，5-HMF的形成可能与五味子的酸性有关，而其含量主要受麦冬的影响。
本发明首次证明5-HMF具有抗氧化、降低心肌缺血小鼠血清中LDH活性及降低心肌缺血小鼠心肌组织中MDA含量的药理活性，可用于制备治心血管病的药品，尤适用于制备抗心肌缺血的心血管病药品。心肌缺血的临床症状表现为冠心病、心绞痛及扩张型心肌病等。
本发明首次从麦冬和五味子合煎剂中发现5-HMF，在生脉散复方制剂中从未发现有5-HMF单独使用时产生的毒性，表明5-HMF与中药配伍可减少毒副作用(参见严永清等，生脉散口服液de综合研究，中国医药科技出版1990年)。
图面说明：
图1：5-HMF和人参皂甙对异丙肾上腺素诱发小鼠心肌缺血时降低心肌MDA含量的比较图。
图2：5-HMF和人参皂甙对异丙肾上腺素诱发小鼠心肌缺血时降低血清LDH活性的比较图。
实施例1
称人参1.0002g，麦冬3.0008g，五味子1.4999g，加水55ml，水煎90分钟，过滤，再加水28ml，煎煮60分钟，过滤，合并二次滤液，按常规方法制成口服液，用HPLC按前述方法测定，其5-HMF含量为276.5mg。
Claims (2)
1．5-羟甲基-2-糠醛在制备治心血管病药品中的应用。
2．根据权利要求1 5-羟甲基-2-糠醛在制备药品中的应用，其特征在于：5-羟甲基-2糠醛在制备抗心肌缺血的心血管病药品中的应用。
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| CN100574813C (zh) * | 2004-06-17 | 2009-12-30 | 甘布罗伦迪亚股份公司 | 用于医疗装置的洛克溶液及其用途 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1790013B (zh) * | 2004-12-16 | 2010-06-16 | 雅安三九药业有限公司 | 一种同时测定生脉注射液中原儿茶酸和5-羟甲基糠醛含量的方法 |
| CN101116661B (zh) * | 2007-06-06 | 2010-05-19 | 南京中医药大学 | 5-羟甲基糠醛在制备保护血管内皮细胞药物中的应用 |
| CN104292191B (zh) * | 2014-09-09 | 2016-09-14 | 浙江工业大学 | 一种从生脉方中分离制备5-羟甲基糠醛的方法 |
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| CN100574813C (zh) * | 2004-06-17 | 2009-12-30 | 甘布罗伦迪亚股份公司 | 用于医疗装置的洛克溶液及其用途 |
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