CN1759834B - 黄连素或其与辛伐他汀联合在制备用于预防或治疗与血脂有关疾病或症状的产品中用途 - Google Patents

黄连素或其与辛伐他汀联合在制备用于预防或治疗与血脂有关疾病或症状的产品中用途 Download PDF

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CN1759834B
CN1759834B CN200410095066XA CN200410095066A CN1759834B CN 1759834 B CN1759834 B CN 1759834B CN 200410095066X A CN200410095066X A CN 200410095066XA CN 200410095066 A CN200410095066 A CN 200410095066A CN 1759834 B CN1759834 B CN 1759834B
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蒋建东
魏敬
刘静文
潘淮宁
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Priority to MX2007003023A priority patent/MX2007003023A/es
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Abstract

本发明涉及黄连素或其与辛伐他汀联合在制备用于预防和/或治疗与高血脂有关疾病或症状的产品中用途。本发明还涉及用于预防和/或治疗与血脂有关疾病或症状的产品，其包括黄连素或黄连素与辛伐他汀和/或赋形剂或载体。

Description

黄连素或其与辛伐他汀联合在制备用于预防或治疗与血脂有关疾病或症状的产品中用途
发明领域
本发明涉及黄连素或其与辛伐他汀联合在制备用于预防和/或治疗与高血脂有关疾病或症状的产品中用途。本发明还涉及用于预防和/或治疗与高血脂有关疾病或症状的产品，其包括黄连素、和/或辛伐他汀和/或赋形剂或载体。
背景技术
黄连素是一种已知化合物，其常作为抗菌素用于治疗肠道疾病或症状，如腹泻。
发明内容
本发明现出人意料地发现黄连素或其与辛伐他汀一起能增加低密度脂蛋白受体(LDLR)，进而降低人体中高血脂的水平，如降低胆固醇，甘油三酯和低密度脂蛋白的水平，从而可用于预防和/或治疗与高血脂有关的疾病或症状，本发明基于上述发现现已完成。
因此，本发明第一方面涉及黄连素或其与辛伐他汀联合在制备用于预防和/或治疗与高血脂有关疾病或症状的产品中用途。
本发明还涉及用于预防和/或治疗与高血脂有关疾病或症状的产品，其包括黄连素或其与辛伐他汀联合和/或赋形剂或载体。
本发明还涉及预防和/或治疗与高血脂有关疾病或症状的方法，其包括给与高血脂有关疾病或症状者服用黄连素或黄连素与辛伐他汀。换言之，本发明涉及预防和/或治疗与高血脂有关的疾病或症状的方法，其包括将有效量黄连素或黄连素与辛伐他汀给予高血脂者。
根据本发明，本发明中所用术语“与高血脂有关疾病或症状”通常是本领域已知的那些疾病或症状，如心脑血管疾病或症状，举例讲，如血压升高，冠心病，心肌梗塞，肥胖，中风等。
根据本发明，本发明中“产品”为药物或功能性食品，优选为药物。
根据本发明，本发明中“赋形剂或载体”为制药或食品领域中常用的赋形剂或载体，如稀释剂，崩解剂，润滑剂等。
根据本发明，本发明中的黄连素为市售或按已知方法制备的黄连素，本发明中黄连素还包括小檗碱或其药用盐、水合物或无水物。其中小檗碱药用盐包括：无机酸盐例如盐酸盐、氢溴酸盐、氢碘酸盐、硫酸盐、硝酸盐和磷酸盐；有机酸盐例如乙酸盐，苯甲酸盐，马来酸盐，富马酸盐，苹果酸盐，柠檬酸盐，草酸盐，乳酸盐，琥珀酸盐，酒石酸盐，烷基磺酸盐或芳基磺酸盐，半胱氨酸盐或其它氨基酸盐。还包括碱式盐如钠盐、钾盐和钙盐。
水合物包括含n个结晶水，n＝1-9。
根据本发明，本发明中所述黄连素的有效量可是目前黄连素应用领域中的常用量或剂量。根据本发明的黄连素可通过口服或注射形式使用。
附图说明
图1为肝细胞(人源)Bel-7402在经过黄连素处理后24小时表现出剂量相关高表达的LDLR。
图2为Bel-7402细胞在黄连素(15μg/ml)处理后24小时呈现出的表面LDLR蛋白表达情况。
具体实施方式
下面的实施例用来进一步描述本发明，但其不意味着对本发明的任何限制。
实施例1黄连素对高血脂中国仓鼠中的胆固醇，甘油三酯和低密度脂蛋白水平的影响
中国仓鼠(♀)购自国家疫苗与血清研究所(中国，北京)。仓鼠用高脂肪高胆固醇食物喂养2周后，形成高血脂中国仓鼠。然后腹腔注射或口服给予黄连素(剂量见表1)，持续给药25天，对照组用生理盐水注射。每组14只。给药25天后，取血测定胆固醇，甘油三酯和低密度脂蛋白的水平，并进行统计学处理。结果见表1和表2。
表1黄连素在高血脂中国仓鼠体内的抗血脂作用
Figure G200410095066XD00031
＊.p＜0.05；＊＊.p＜0.01；＊＊＊p＜0.001(与对照组相比较)
表2黄连素在高血脂病人体内的降血脂作用
＊＊＊p＜0.001，与治疗前相比较(配对t-检验)。
#血脂测定方法为医院常规化验方法。
实施例2黄连素对低密度脂蛋白受体(LDLR)的作用
2.1肝细胞(人源)Bel-7402在经过黄连素处理后24小时呈现出剂量相关高表达的LDLR，将黄连素处理的Bel-7402的细胞离心洗净后，提取其mRNA，用扫描定量RT-PCR的方法测定细胞中LDLRmRNA的量，结果见图1。黄连素明显增加了LDLR mRNA的表达，并呈剂量依赖性，5μg/ml的黄连素可增加LDLR mRNA表达2.3倍。
2.2Bel-7402细胞在黄连素(5μg/ml)处理后24小时，可以看到细胞表面LDLR蛋白表达明显增加。黄连素处理的Bel-7402细胞在离心洗净后，用抗LDLR的荧光标记抗体反应，于流式细胞仪上测定其LDLR表达的荧光强度，结果见图2。黄连素可以使LDLR在细胞表面的表达增加4倍。
讨论：
以上实验表明黄连素是通过增加LDLR表达的机理产生降血脂作用的，黄连素通过MEK/ERK信号途径使LDLR在细胞表面的表达明显增加，通过与载脂蛋白Apo IB的结合清除血清中的胆固醇和甘油三酯。
实施例3黄连素与辛伐他汀联合在仓鼠上的降血脂作用
表3黄连素与辛伐他汀在仓鼠联合使用的降血脂作用＊
Figure G200410095066XD00041
＊：中国仓鼠喂以高脂高胆固醇(HFHC)食物10天后，口服给予黄连素，或辛伐他汀，或联合使用。25天后测定血中总胆固醇、甘油三酯和低密度脂蛋白-C的水平。表中为平均值±标准差。给药方式：每日口服，共25天；每组动物数：n＝7。

Claims (2)

1.黄连素与辛伐他汀联合在制备用于预防和/或治疗与高血脂有关的疾病或症状的药物中用途。
2.用于预防和/或治疗与高血脂有关的疾病或症状的产品，其包括黄连素和辛伐他汀以及任选的赋形剂或载体。
CN200410095066XA 2004-09-17 2004-11-23 黄连素或其与辛伐他汀联合在制备用于预防或治疗与血脂有关疾病或症状的产品中用途 Active CN1759834B (zh)

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Application Number Priority Date Filing Date Title
CN200410095066XA CN1759834B (zh) 2004-09-17 2004-11-23 黄连素或其与辛伐他汀联合在制备用于预防或治疗与血脂有关疾病或症状的产品中用途
US11/229,339 US20060223838A1 (en) 2004-09-17 2005-09-16 Methods and compositions for the treatment of hyperlipidemia
EP05791957A EP1796666A4 (en) 2004-09-17 2005-09-19 METHOD AND COMPOSITIONS FOR TREATING HYPERLIPIDEMIA
EP10195408A EP2361625A1 (en) 2004-09-17 2005-09-19 Methods and compositions for the treatment of hyperlipidemia
BRPI0515393-0A BRPI0515393A (pt) 2004-09-17 2005-09-19 métodos para prevenir ou tratar hiperlipidemia e um ou mais sintomas de uma doença cardiovascular ou condição causada por hiperlipidemia em um indivìduo mamìfero, para controlar hiperlipidemia em um indivìduo mamìfero, para tratar um ou mais sintomas de doença cardiovascular, para modular a expressão de ldlr em um indivìduo mamìfero e para modular a expressão de ldlr em um indivìduo mamìfero e a ativação de erk em um indivìduo mamìfero e para reduzir colesterol em um indivìduo mamìfero, composições para prevenir ou aliviar hiperlipidemia, para tratar ou prevenir hiperlipidemia em um indivìduo mamìfero para aumentar expressão de ldlr em um indivìduo mamìfero, e em uma célula de mamìfero, tecido, órgão, ou indivìduo, aumentar a estabilidade de ldlr em uma célula, tecido, órgão ou indivìduo mamìfero e para aumentar a estabilidade de ldlr em uma célula, tecido, órgão ou indivìduo mamìfero
NZ554475A NZ554475A (en) 2004-09-17 2005-09-19 Methods and compositions for the treatment of hyperlipidemia
AU2005284528A AU2005284528A1 (en) 2004-09-17 2005-09-19 Methods and compositions for the treatment of hyperlipidemia
JP2007531572A JP2008513382A (ja) 2004-09-17 2005-09-19 高脂血症を治療する方法及び組成物
PCT/CN2005/001489 WO2006029577A1 (en) 2004-09-17 2005-09-19 Methods and compositions for the treatment of hyperlipidemia
RU2007114290/14A RU2007114290A (ru) 2004-09-17 2005-09-19 Способы и композиции для лечения гиперлипидемии
CA002620208A CA2620208A1 (en) 2004-09-17 2005-09-19 Methods and compositions for the treatment of hyperlipidemia
MX2007003023A MX2007003023A (es) 2004-09-17 2005-09-19 Metodos y composiciones para el tratamiento de la hiperlipidemia.
KR1020077008761A KR20070095279A (ko) 2004-09-17 2005-09-19 고지혈증 치료 방법 및 조성물
IL181896A IL181896A0 (en) 2004-09-17 2007-03-13 Methods and compositions for the treatment of hyperlipidemia
US11/784,294 US20080081781A1 (en) 2004-09-17 2007-04-06 Methods and compositions for the treatment of metabolic syndrome
NO20071930A NO20071930L (no) 2004-09-17 2007-04-16 t4Metoder og sammensetninger til behandling av hyperlipidemi.
US12/330,447 US20110158932A1 (en) 2004-09-17 2008-12-08 Methods And Compositions For The Treatment of Hyperlipidemia

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