赵金华

发布时间:2020-10-14 浏览次数:

出生年月:1965年9月

民族:汉

职称:教授(二级)、博士生导师

学科专业:药理学/药物化学

研究方向:天然产物心血管药理学与新药研发

电子邮箱:zhaojinhua@mail.kib.ac.cn


工作经历

2015.8,中南民族大学药学院药理学研究所,教授(二级)、博士生导师;

2010.4~2018.10,中国科学院昆明植物研究所,研究员(二级)、博士生导师;

1999.6~2010.4,深圳海王集团技术中心,资深研究员;

1984.6~1993.8,安徽省无为县太平初级中学,教师。


学习经历

1996.6~1999.6,中山大学生命科学学院,动物学(天然产物药学方向)博士;

1993.9~1996.6,中山大学生命科学学院,生理学(心血管药理学方向)硕士;

1988.9~1990.6,安徽教育学院生物系,进修;

1981.9~1984.6,安徽省无为师范学校,中师。


学术与应用研究:

从事天然产物心血管药理学活性与机制研究。重点方向是具有心血管药理活性并具有重复结构单元的天然产物多糖的化学结构、结构修饰、药效活性、药理机制及构效关系研究。

岩藻糖化糖胺聚糖(fucosylated glycosaminoglycan, FG)结构研究方面,基于“bottom up”策略,通过建立糖苷键选择性解聚技术及寡糖纯化与波谱学结构解析技术,阐明了一系列不同物种来源的天然FG的确切结构;获得一系列用于药理学活性与机制研究的、具有特殊端基结构的纯品FG寡糖及其结构修饰产物。

系统研究了FG及其解聚产物、纯品寡糖的抗凝抗血栓活性及其药理学机制特点,重点研究了FG寡糖选择性抑制内源性因子X酶(Tenase, Xase)构效关系、必须结构、酶学动力学特点与机制、靶蛋白相互作用的动力学过程与机制。

基于天然FG结构修饰,研制选择性抑制内源性Xase的新靶点抗凝抗血栓新药LFG-53(First In Class,获FDA临床许可),系列专利获得国内、美、日等国授权,已实现知识产权及关键技术的企业技术转移。

海王集团国家级企业技术中心工作期间,组建药物研发实验研究平台,主管创新药物研发。其代表性工作包括:立项并研发中药天然药物1类新药虎杖苷注射液(临床批件(现已取得FDA临床许可))、5类中药新药艾心酮片(临床批件)、中药大品种改进药物鼻渊软胶囊(上市许可)等。

PNASJBCCarbohydr PolymThromb HaemostPharmacol ResEur J Med ChemThromb ResInt J Biol MacromolMar DrugsBBAAngew ChemChem Eur J等国内外学术期刊上发表论文百余篇;申请国内及PCT发明专利70余件,已获中、美、日、澳、等国授权的发明专利60余件。

先后主持国家、科学院及省级课题二十余项,包括国家新药重大专项项目、863课题及引导项目、发改委重大专项、自然科学基金项目、科技部技术创新基金项目、科学院创新药物项目、科学院天然产物应用转化项目、粤港关键领域重点突破项目、深港创新圈项目、广东省教育部产学研结合项目、云南省应用基础研究计划重点项目、云南省重点新产品项目等。


近年发表的部分学术论文:

Li XM, Li SN, Liu J, Lin LS, Sun HF, Yang WJ, Cai Y, Gao N, Zhou LT, Qin HB*, Yin RH*, Zhao JH*. A regular fucan sulfate fromStichopus herrmanniand its peroxide depolymerization: Structure and anticoagulant activity.Carbohyd Polym.2021; 256: 117513.

Li SN, Zhong W, Pan Y, Lin LS, Cai Y, Mao H, Zhang TC, Li SJ, Chen R, Zhou LT, Wang WL, Cui QH*, Yin RH*, Huang SX*, Zhao JH*. Structural characterization and anticoagulant analysis of the novel branched fucosylated glycosaminoglycan from sea cucumberHolothuria nobilis.Carbohyd Polym.2021; 269: 118290.

Zhou LT, Yin RH, Gao N, Sun HF, Chen DY, Cai Y, Ren L, Yang L, Zuo ZL*, Zhang HB*, Zhao JH*. Oligosaccharides from fucosylated glycosaminoglycan prevent breast cancer metastasis in mice by inhibiting heparanase activity and angiogenesis.Pharmacol Res. 2021; 166: 105527.

Chen R, Yin RH, Li SN, Pan Y, Mao H, Cai Y, Lin LS, Wang WL, Zhang TC, Zhou LT, Gao N*, Luo XD*, Zhao JH*. Structural characterization of oligosaccharides from free radical depolymerized fucosylated glycosaminoglycan and suggested mechanism of depolymerization.Carbohyd Polym.2021; 270: 118368.

Yin RH, Zhou LT, Gao N, Lin LS, Sun HF, Chen DY, Cai Y, Zuo ZL, Hu KF, Huang SX*, Liu JK*, Zhao JH*. Unveiling thedisaccharide-branched glycosaminoglycan and anti-coagulant potential of its derivatives.Biomacromolecules. 2021; 22(3): 1244-55.

Ma Y, Gao N, Zuo ZC, Li SN, Zheng WQ, Shi X, Liu QP, Ma T, Yin RH*, Li X*, Zhao JH*. Five distinct fucan sulfates from sea cucumberPattalus mollis: Purification, structural characterisation and anticoagulant activities.Int J Biol Macromol. 2021; 186: 535.

Shi X#, Guan RW#, Zhou LT, Zuo ZC, Tao XL, Wang P, Zhou YR, Yin RH, Zhao LY*, Gao N*, Zhao JH. Structuralcharacterization and heparanase inhibitory activity of fucosylated glycosaminoglycan fromHolothuria floridana.Mar Drugs. 2021; 19(3): 162.

Liu S#, Zhang TC#, Sun HF, Lin LS, Gao N, Wang WL, Li SJ, Zhao JH *. Pharmacokinetics and pharmacodynamics of a depolymerized glycosaminoglycan fromHolothuria fuscopunctata, anovel anticoagulant candidate, in rats by bioanalytical methods.Mar Drugs.2021; 19: 212.

Lisha Lin, Sujuan Li, Na Gao, Weili Wang, Taocui Zhang, Lian Yang, Xingzhi Yang, Dan Luo, Xu Ji*, Jinhua Zhao*. Thetoxicology of native fucosylated glycosaminoglycans and the safety of their depolymerized products as anticoagulants.Mar Drugs. 2021; 19(9): 487-499.

Lin LS, Yang L, Chen J, Zhou LT, Li SJ, Gao N, Zhao JH*. High-molecular-weight fucosylated glycosaminoglycan induces human platelet aggregation depending on αIIbβ3 and platelet secretion.Platelets. 2021; 32(7): 975.

Mao H#, Cai Y#, Li SN, Sun HF, Lin LS, Pan Y, Yang WJ, He ZC, Chen R, Zhou LT, Wang WL, Yin RH*, Zhao JH*. A new fucosylated glycosaminoglycan containing disaccharide branches fromAcaudina molpadioides: Unusual structure and anti-intrinsic tenase activity.Carbohyd Polym. 2020; 245: 116503-12.

Yang WJ#, Chen DY#, He ZC, Zhou LT, Cai Y, Mao H, Gao N*, Zuo ZL*, Yin RH*, Zhao JH. NMR characterization and anticoagulant activity of the oligosaccharides from the fucosylated glycosaminoglycan isolated fromHolothuria coluber.Carbohyd Polym. 2020; 233: 115844-52.

Lin LS, Zhao LY, Gao N, Yin RH, Li SJ, Sun HF, Zhou LT, Zhao GL, Purcelle SW, Zhao JH*. From multi-target anticoagulants to DOACs, and intrinsic coagulation factor inhibitors.Blood Reviews. 2020; 39: 100615.

Gao N, Chen R, Mou RR, Xiang JY, Zhou K, Li Z, Zhao JH*. Purification, structural characterization and anticoagulant activities of four sulfated polysaccharides from sea cucumberHolothuria fuscopunctata.Int J Biol Macromol. 2020; 164: 3421–3428.

Sun HF#, Gao N#, Ren L, Liu S, Lin LS, Zheng WQ, Zhou LT, Yin RH, Zhao JH*. The components and activities analysis of a novel anticoagulant candidate dHG-5.Eur J Med Chem. 2020: 112796-801.

Zhou LT#, Gao N#, Sun HF, Xiao C, Yang L, Lin LS, Yin GH, Li Z, Zhang HB*, Ji X*, Zhao JH*. Effects of native fucosylated glycosaminoglycan, its depolymerized derivatives on intrinsic factor Xase, coagulation, thrombosis, and hemorrhagic risk.Thromb Haemost. 2020, 120(4):607-619.

Liu XX, Zhang ZX, Mao H, Wang P, Zuo ZC, Gao L, Shi X, Yin RH, Gao N*, Zhao JH*. Characterization of the hydrolysis kinetics of fucosylated glycosaminoglycan in mild acid and structure of the resulting oligosaccharides.Mar Drugs.2020; 18: 286-302.

Luo D, Xu JP, Chen XJ, Zhu X, Liu S, Li J, Xu XT, Ma X*, Zhao JH*, Ji X*. EGCG attenuates salt-induced hypertension and renal injury in Dahl salt-sensitive rats.Sci Rep.2020, 10: 4783-93.

Cai Y#, Yang WJ#, Li XM, Zhou LT, Wang ZJ, Lin LS, Chen DY, Zhao LY, Li ZK, Liu SB, Yin RH*, Zuo ZL*, Gao N*, Zhao JH. Precise structures and anti-intrinsic tenase complex activity of three fucosylated glycosaminoglycans and their fragments.Carbohyd Polym, 2019; 224:115146.

He ZC, Zhou LT, Lin LS, Yin RH*, Zhao JH*. Structure and heparanase inhibitory activity of a new glycosaminoglycan from the slugLimacus flavus.Carbohyd Polym, 2019; 220:176–184.

Yang WJ#, Cai Y#, Yin RH, Lin LS, Li ZK*, Wu MY*, Zhao JH*. Structural analysis and anticoagulant activities of two sulfated polysaccharides from the sea cucumberHolothuria coluber.Int J Biol Macromol. 2018; 115: 1055-1062.

Xiao C, Zhao LY, Gao N, Wu MY, Zhao JH*. Nonasaccharide inhibits intrinsic factor Xase complex by binding to factor IXa and disrupting factor IXa-Factor VIIIa interactions.Thromb Haemost. 2019; 19: 705–715.

Luo D, Chen X, Zhu X, Liu S, Li J, Xu J, Zhao JH*, Ji X*. Pu-Erh tea relaxes the thoracic aorta of rats by reducing intracellular calcium.Front Pharmacol. 2019, 10:1-13.

Zheng WQ, Zhou LT, Lin LS, Cai Y, Sun HF, Zhao LY, Gao N, Yin RH*, Zhao JH*. Physicochemical characteristics and anticoagulant activities of the polysaccharides from sea cucumberPattalus mollis.Mar Drugs. 2019;17(4): 198.

Guan RW, Peng Y, Zhou LT, Zheng WQ, Liu XX, Wang P, Yuan QX, Gao N, Zhao LY*, Zhao JH*. Precise structure and anticoagulant activity of fucosylated glycosaminoglycan fromApostichopus japonicus:Analysis of its depolymerized fragments.Mar Drugs. 2019; 17(4): 195.

Lin LS, Xu L, Xiao C, Zhou LT, Gao N, Wu MY, Zhao JH*. Plasma contact activation by a fucosylated chondroitin sulfate and its structure–activity relationship study.Glycobiol, 2018; 8(10): 754.

He HQ, Chen D, Li XM, Li CJ, Zhao JH *, Qin HB *. Synthesis of trisaccharide repeating unit of fucosylated chondroitin sulfate.Org Biomol Chem,2019, 17, 2877.

Yin RH, Zhou LT, Gao N, Li Z, Zhao LY, Shang FN, Wu MY*, Zhao JH*. Oligosaccharides from depolymerized fucosylated glycosaminoglycan: Structures and minimum size for intrinsic factor Xase complex inhibition.J Biol Chem,2018; 293(36): 14089.

Shang FN#, Mou RR#, Zhang ZD#, Gao N, Lin LS, Li ZK, Wu MY*, Zhao JH*. Structural analysis and anticoagulant activities of three highly regular fucan sulfates as novel intrinsic factor Xase inhibitors.Carbohyd Polym.2018; 195: 257-266.

Zhang X, Liu H, Lin L, Yao W, Zhao JH, Wu MY*, Li ZJ*. Synthesis of fucosylated chondroitin sulfate nonasaccharide as a novel anticoagulant targeting intrinsic factor Xase complex.Angew Chem Int Ed.2018; 57(39): 12880.

Zhao LY, Qin YJ, Guan RW, Zheng WQ, Liu JK,Zhao JH*. Digestibility of fucosylated glycosaminoglycan from sea cucumber and its effects on digestive enzymes under simulated salivary and gastrointestinal conditions.Carbohyd Polym.2018; 186: 217-225.

Liu J, Zhou LT, He ZC, Gao N, Shang FN, Xu JP, Li Z, Yang ZM, Wu MY*, Zhao JH*. Structural analysis and biological activity of a highly regular glycosaminoglycan fromAchatina fulica.Carbohyd Polym.2018; 181: 433-441.

Xu L#, Gao N#, Xiao C, Lin LS, Purcell SW, Wu MY*, Zhao JH*. Modulating the degree of fucosylation of fucosylated chondroitin sulfate enhances heparin cofactor II-dependent thrombin inhibition.Eur J Med Chem. 2018; 154:133-143.

Shang FN#, Gao N#, Yin RH, Lin LS, Xiao C, Zhou LT, Li Z, Purcell SW, Wu MY*, Zhao JH*. Precise structures of fucosylated glycosaminoglycan and its oligosaccharides as novel intrinsic factor Xase inhibitors.Eur J Med Chem.2018; 148: 423.

Zhang X, Yao W, Xu XJ, Sun HF, Zhao JH, Meng XB, Wu MY, Li ZJ*. Synthesis of fucosylated chondroitin sulfate glycoclusters: a robust route to new anticoagulant agents.Chem.-Eur J. 2018; 24(7): 1694-1700.

Qin YJ, Yuan QX, Zhang YX, Li JL, Zhu XJ, Zhao LL, Wen J, Liu JK, Zhao LY,* Zhao JH*. Enzyme-assisted extraction optimization, characterization and antioxidant activity of polysaccharides from sea cucumberPhyllophorus proteus.Molecules.2018; 23: 590.

Cai Y, Yang WJ, Yin RH, Zhou LT, Li ZK, Wu MY*, Zhao JH*. An anticoagulant fucan sulfate with hexasaccharide repeating units from the sea cucumberHolothuria albiventer.Carbohyd Res, 2018; 464: 12.

Li XM, Luo L, Cai Y, Yang WJ, Lin LS, Li Z, Gao N, Purcell SW, Wu MY*, Zhao JH*. Structural elucidation and biological activity of a highly regular fucosylated glycosaminoglycan from the edible sea cucumberStichopus herrmanni.J Agric Food Chem. 2017; 65(42): 9315-9323.

Xiao C, Lian W, Zhou LT, Gao N, Xu L, Chen J, Wu MY*, Peng WL*, Zhao JH*. Interactions between depolymerized fucosylated glycosaminoglycan and coagulation proteases or inhibitors,Thromb Res. 2016; 146: 59-68.

Zhao LY#, Wu MY#, Xiao C, Yang L, Zhou LT, Gao N, Li Z, Chen J, Chen JC, Liu JK*, Qin HB*, Zhao JH*. Discovery of an intrinsic tenase inhibitor, pure nonasaccharide from fucosylated glycosamino-glycan.PNAS. 2015; 112: 8284-8289.

Gao N#, Lu F#, Xiao C, Yang L, Chen J, Zhou K, Wen DD, Li Z, Wu MY, Jiang JM, Liu GM*, Zhao JH*. β-Eliminative depolymerization of the fucosylated chondroitin sulfate and anticoagulant activities of resulting fragments.Carbohyd Polym. 2015; 127(3): 427–437.

Wu MY#, Wen DD#, Gao N, Xiao C, Yang L, Xu L, Lian W, Peng WL, Jiang JM*, Zhao JH*, Anticoagulant and antithrombotic evaluation of native fucosylated chondroitin sulfates and their derivatives as selective inhibitors of intrinsic factor Xase.Eur J Med Chem.2015; 92: 257-269.

Wu MY, Xu L, Zhao LY, Xiao C, Gao N, Luo L, Yang L, Li Z, Chen LY,* Zhao JH*. Structural analysis and anticoagulant activities of the novel sulfated fucan possessing a regular well-defined repeating unit from sea cucumber.Mar Drugs.2015; 13: 2063-2084.

Lian W, Huang N, Li Z, Zheng YT*, Peng WL*, Zhao JH*. Anti-HIV-1 activity and structure-activity-relationship study of a fucosylated glycosaminoglycan from an echinoderm by targeting the conserved CD4 induced epitope.Biochim Biophys Acta. 2013; 1830: 4681-4691.

Zhao LY#, Lai SS#, Huang R, Wu MY, Gao N, Xu L, Qin HB*, Peng WL*, Zhao JH. Structure and anticoagulant activity of fucosylated glycosaminoglycan degraded by deaminative cleavage.Carbohyd Polym. 2013; 98(2): 1514-1523.

Luo L, Wu MY, Xu L, Lian W, Xiang JY, Lu F, Gao N, Zhao JH*. Comparison of physicochemical characteristics and anticoagulant activities of polysaccharides from three sea cucumbers.Mar Drugs. 2013; 11: 399-417.

Huang N, Wu MY, Zheng CB, Zhu L, Zhao JH*, Zheng YT*. The depolymerized fucosylated chondroitin sulfate from sea cucumber potently inhibits HIV replication via interfering with virus entry.Carbohyd Res. 2013; 380: 64-69.


近年获得授权的发明专利

Zhao JH, Li ZG, Gao Na, Wu MY, Chen YM, Zhao LY, Wu YS, Li Z, Xiao C, Zheng SL, Nan ZY, Zhou JB, Xu JP, Zhou LT, Guo YF, Qin HB, Liu JK. Oligosaccharide compound for inhibiting endogenous coagulation factor X-enzyme complex, and preparation method therefor and uses thereof.特许6980018 [日本授权2021-11-18]

赵金华,尹荣华,高娜,周路坦,刘吉开.一种寡糖化合物及其药学上可接受的盐、制备方法及应用. CN 111423523 B [授权2021-10-26]

Zhao JH, Wu MY, Gao N, Li Z, Lai SS, Zhao LY. Low-molecular-weight glycosaminoglycan derivative containing terminal 2, 5-anhydrated talose or derivative thereof. CA2908959 [加拿大授权2020-10-6]

Zhao JH, Liu JK, Wu MY, Gao N, Lu F, Li Z. Low molecular weight glycosaminoglycan derivative, pharmaceutical composition thereof, preparation method therefor and use thereof. CA2907887 [加拿大授权2020-10-6]

Zhao JH, Liu JK, Wu MY, Gao N, Lu F, Li Z. Low molecular weight glycosaminoglycan derivative, pharmaceutical composition thereof, preparation method therefor and use thereof. EP2980103 [欧洲授权2020-11-4]

Zhao JH, He JX, Wu MY, Liu ZW, Gao N, Zhao LY, Li Z, Lu F, Xu L. Fuc3S4S substituted oligoglycosaminoglycan and preparation method thereof. IN349399 [印度授权2020-10-6]

Zhao JH, Liu JK, Wu MY, Gao N, Lu F, Li Z. Low molecular weight glycosaminoglycan derivative, pharmaceutical composition thereof, preparation method therefor and use thereof.US 9896517b2[美国授权2018-02-20]

Zhao JH, Liu JK, Wu MY, Gao N, Lu F, Li Z. Low-molecular-weight-glycosaminoglycan derivative, pharmaceutical composition thereof, preparation method therefor and use thereof.特许6293862[日本授权2018-02-23]

Zhao JH, Wu MY, Gao N, Li Z, Lai SS, Zhao LY. Low-molecular-weight-glycosaminoglycan derivative containing terminal 2,5-anhydrated talose or derivate thereof特许6248179[日本授权2017-11-24]

Zhao JH, Kang H, Wu MY, Zeng WZ, Li Z, Gao Y, Cui J, Wang ZG, Feng HL, Yu, L. Depolymerized glycosaminoglycan from Thelenota ananas and preparation method thereof.AUS 2010324437[澳大利亚授权2015-04-02]

赵金华,刘吉开,吴明一,高娜,卢锋,李姿. 一种低分子量糖胺聚糖衍生物及其药物组合物和其制备方法与应用.ZL 201310099800.9[授权2015-09-16]

刘吉开,郑永唐,赵金华,吴明一,黄宁,李姿,高娜,文丹丹,连武,何江波.低分子量岩藻糖化糖胺聚糖的羧基还原衍生物及其制备方法与用途.ZL 201110435559.3[授权2013-10-02]

赵金华,吴明一,高娜,文丹丹,连武,李姿.一种岩藻糖化糖胺聚糖衍生物及其制备方法.ZL 2011 10318704. [授权2014- 04-09]

赵金华,吴明一,高娜,李姿,赖森森,赵龙岩.一种含末端2,5-脱水塔罗糖或其衍生物的低分子量糖胺聚糖衍生物. ZL 201310127447.0[授权2015-11-04]

赵金华,何金星,吴明一,刘峙汶,高娜,赵龙岩,李姿,卢锋,徐丽. Fuc3S4S取代的低聚糖胺聚糖及其制备方法.CN 201410007855.7[授权2016-08-31]

吴滨,孙文武,曹沛,赵金华,杨莲. N-喹啉基取代的β-内酰胺类化合物及其药物组合物和合成方法与应用. ZL 201310428596 [授权2016-03-02]

赵金华,吴明一,李姿.一种抗消化性溃疡的组合物及其应用.ZL 201310680958.5[授权2016- 04-06]

赵金华,吴明一,李姿.一种含石斛多糖和苍术硬脂的组合物及其应用.ZL 20131068 0378.6 [授权2016-03-30]

赵金华,何金星,吴明一,赵龙岩,刘峙汶,杨莲,李姿,高娜,肖创,徐丽,陈钧,周路坦.一种抑制内源性因子X酶活性的寡糖类化合物及其药物组合物.ZL 201410549676.6[授权2017-12-01]


主持承担的部分课题项目:

国家新药重大专项:LFG-53新药临床前研究(2017~2020)

国家发改委企业技术中心重大项目:①天然药物创新能力建设(2008~2012);

②创新海洋药物研究开发中心建设(2004~2008)

863课题:①牡蛎生物活性成分的提取及应用研究(1999 ~2001);

②中药1类新药虎杖苷注射液(2005~2008)

自然基金面上项目:①P-选择素抑制剂发现及其抗血栓活性研究(2021~2025)

②FG寡糖抑制Xase药理机制(2017~2021);

②FGAG纯化结构序列及其对血栓形成与止血功能的影响(2013~2017)

科技部科技型中小企业技术创新基金:降血脂药蔗烷醇胶囊研制(2008~2010);

科学院技术百人项目:天然产物成药性研究技术平台建设(2011~2013);

科学院创新药物研究院新药项目:新靶点抗血栓药物LFG研究(2015~2018);

科学院天然产物应用转化项目:P-选择素抑制剂发现与转化(2016~2018)

科学院自主部署项目:①活性天然多糖药代、安全性与应用转化(2015~2019);

②基于天然产物及其片段的创新药物研发能力建设(2010 ~ 2013)

云南省高端人才项目:基于天然产物及其结构片段的创新药物研发(2010~ 2016)

云南省基础研究计划重点项目:①LFG组分及其抗凝抗血栓活性(2016~2019);

②抑制因子X酶的FG衍生物的构效关系及应用价值评价(2013~2016)

广东省教育部产学研结合项目:虎杖苷注射液治疗脑卒中适应症研究(2009~2011)

云南省科技计划项目:抗艾新药注射用DT-8临床前预研究(2012~2015)

云南省创新团队项目:活性天然产物发现与生物合成(2017~2020年)

粤港关键领域重点突破项目:中药1类新药虎杖苷注射液(2006 ~ 2009年)

深港创新圈计划项目:中药一类创新药物虎杖苷注射液(2006 ~ 2009年)


获奖与荣誉

2008年,入选“改革开放三十年广东省医药行业杰出科技人才”

2010年,入选“云南省引进高端人才计划”;

2011年,入选中国科学院人才计划

2015年,F.Xase抑制剂学术研究入选昆明植物研究所年度“十大进展”;

2016年,LFG新药技术转移入选昆明植物研究所年度“十大进展(第一位)”;

2017年,入选云南省政府“享受政府特殊津贴人员”

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