CN102872137A - Houttuynoid B在治疗***药物中的应用 - Google Patents

Houttuynoid B在治疗***药物中的应用 Download PDF

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CN102872137A
CN102872137A CN2012104195739A CN201210419573A CN102872137A CN 102872137 A CN102872137 A CN 102872137A CN 2012104195739 A CN2012104195739 A CN 2012104195739A CN 201210419573 A CN201210419573 A CN 201210419573A CN 102872137 A CN102872137 A CN 102872137A
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houttuynoid
cervical cancer
drug
human cervical
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CN102872137B (zh
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黄晨
吴俊艺
吴俊华
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Abstract

本发明公开了Houttuynoid B在制备治疗人***药物中的应用,属于药物新用途技术领域。本发明通过体外MTT抗肿瘤活性评价发现,Houttuynoid B对人***细胞株HeLa、HeLa229、HCE1和CaSKi的生长也具有显著的抑制作用。因此,Houttuynoid B能用于制备抗***药物,具有良好的开发应用前景。对于本发明涉及的Houttuynoid B在制备治疗人***药物中的用途属于首次公开,由于骨架类型属于全新的骨架类型,而且其对于人***细胞的抑制活性强得意想不到。

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Houttuynoid B在治疗***药物中的应用
技术领域
本发明涉及化合物Houttuynoid B的新用途,尤其涉及Houttuynoid B在制备抗***药物中的应用。 
技术背景
癌症是对人类生命健康危害最大的疾病之一,每年都有大量的人死于癌症。抗癌药物的研发一直是药学研究的热点。抗肿瘤药物中有74%是天然产物或其衍生物,如紫杉醇及其衍生物就是目前临床上应用效果比较好的抗肿瘤药物。因此,从天然产物中寻找抗癌化合物或先导化合物具有重要的意义。 
本发明涉及的化合物Houttuynoid B是一个2012年发表(Chen, S. D. et al., 2012. Houttuynoid B_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772–1775.)的新骨架化合物,该化合物拥有全新的骨架类型,目前的用途仅仅涉及抗单纯疱疹病毒活性(Chen, S. D. et al., 2012. Houttuynoid B_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772–1775.),对于本发明涉及的Houttuynoid B在制备治疗***药物中的用途属于首次公开,由于骨架类型属于全新的骨架类型,而且其对于***细胞的抑制活性强得意想不到,不存在由其他化合物给出任何启示的可能,具备突出的实质性特点,同时用于***的防治显然具有显著的进步。 
发明内容
本发明提供化合物Houttuynoid B在制备抗肿瘤药物中的应用。 
本发明采用如下技术方案:Houttuynoid B在制备抗***药物中的应用,Houttuynoid B的结构式如式(Ⅰ)所示: 
Figure BDA0000231836751
本发明通过体外MTT抗肿瘤活性评价发现,Houttuynoid B对人***细胞株HeLa、HeLa229、HCE1和CaSKi的生长也具有显著的抑制作用,抑制这4株细胞生长的IC50值分别为0.13±0.02μM、0.18±0.03μM、0.25±0.07μM和0.19±0.06μM。因此,Houttuynoid B能用于制备抗***药物,具有良好的开发应用前景。 
本发明涉及的Houttuynoid B在制备治疗***药物中的用途属于首次公开,由于骨架类型属于全新的骨架类型,而且其对于***细胞的抑制活性强得意想不到,不存在由其他化合物给出任何启示的可能,具备突出的实质性特点,同时用于***的防治显然具有显著的进步。 
以下通过实施例对本发明作进一步详细的说明,但本发明的保护范围不受具体实施例的任何限制,而是由权利要求加以限定。 
具体实施方式
本发明所涉及化合物Houttuynoid B的制备方法参见文献(Chen, S. D. et al., 2012.  Houttuynoid B_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772–1775.)。 
以下通过实施例对本发明作进一步详细的说明,但本发明的保护范围不受具体实施例的任何限制,而是由权利要求加以限定。 
实施例1:本发明所涉及化合物Houttuynoid B片剂的制备: 
取20克化合物Houttuynoid B,加入制备片剂的常规辅料180克,混匀,常规压片机制成1000片。 
实施例2:本发明所涉及化合物Houttuynoid B胶囊剂的制备: 
取20克化合物Houttuynoid B,加入制备胶囊剂的常规辅料如淀粉180克,混匀,装胶囊制成1000片。 
下面通过药效学实验来进一步说明其药物活性。 
实验例:采用MTT法评价化合物Houttuynoid B对人***细胞株的生长抑制作用 
1.方法:处于生长对数期的细胞:人***细胞株HeLa、HeLa229、HCE1和CaSKi(购买自中国科学院细胞库)以1.5×104浓度种于96孔板中。细胞培养24 h贴壁后吸去原来的培养基。试验分为空白对照组、药物处理组。空白组更换含10%胎牛血清的1640培养基;药物处理组更换含浓度为100 μM,50 μM,10 μM,1 μM,0.1 μM,0.01 μM和0.001 μM的Houttuynoid B的培养基。培养48 h后,加入浓度5 mg/mL的MTT,继续放于CO2培养箱培养4 h,然后沿着培养液上部吸去100 μL上清,加入100 μL DMSO,暗处放置10 min,利用酶标仪(Sunrise公司产品)测定吸光值(波长570nm),并根据吸光值计算细胞存活情况,每个处理设6个重复孔。细胞存活率(%)=ΔOD药物处理/ΔOD空白对照×100。 
2. 结果:Houttuynoid B对人***细胞株HeLa、HeLa229、HCE1和CaSKi的生长具有显著的抑制作用。该化合物抑制人***细胞株HeLa、HeLa229、HCE1和CaSKi生长的IC50值分别为:0.13±0.02μM、0.18±0.03μM、0.25±0.07μM和0.19±0.06μM。 
由上述实施例表明,本发明的Houttuynoid B对人***细胞株HeLa、HeLa229、HCE1和CaSKi的生长具有很好的抑制作用。由此证明,本发明的Houttuynoid B具有抗***活性,能用于制备抗***药物。 

Claims (1)

1.Houttuynoid B在治疗***药物中的应用,所述化合物Houttuynoid B结构如式(Ⅰ)所示:
式(Ⅰ)。
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Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
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SHAO-DAN CHEN等: "Houttuynoids A-E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata", 《ORGANIC LETTERS》 *

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Assignee: NANTONG YUQI METAL PRODUCTS Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048459

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231129

Application publication date: 20130116

Assignee: NANTONG KYLIN MACHINERY LTD.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048456

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231129

Application publication date: 20130116

Assignee: NANTONG LILIAN MACHINE TOOL MANUFACTURING CO.,LTD.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048450

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231129

Application publication date: 20130116

Assignee: Nantong Yuma Electromechanical Manufacturing Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048446

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231129

Application publication date: 20130116

Assignee: Nantong Dongdong Steel Structure Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048444

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231129

Application publication date: 20130116

Assignee: Nantong Huaxin Price Evaluation Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048443

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231129

Application publication date: 20130116

Assignee: Nantong Yaocheng mechanical equipment manufacturing Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048440

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231129

Application publication date: 20130116

Assignee: Nantong Xinxin Pharmaceutical Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048425

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231129

EE01 Entry into force of recordation of patent licensing contract

Application publication date: 20130116

Assignee: Nantong Yijialai Woolen Knitting Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980049377

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231203

Application publication date: 20130116

Assignee: NANTONG BEITE PHARMACEUTICAL MACHINERY Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980049199

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231203

Application publication date: 20130116

Assignee: NANTONG HAIGUO MACHINERY Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980049196

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231203

Application publication date: 20130116

Assignee: Nantong Qiaojiang packaging materials Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980049191

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231203

Application publication date: 20130116

Assignee: Nantong Bairun Catering Management Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980049185

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231203

Application publication date: 20130116

Assignee: Nantong Nongchaoer Food Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048976

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231203

Application publication date: 20130116

Assignee: Xingren Tank Farm of Nantong Xinhai Liquefied Gas Service Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048969

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231203

Application publication date: 20130116

Assignee: NANTONG SHUANGHE FOOD Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048967

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231203

Application publication date: 20130116

Assignee: Jiangsu guanan electromechanical Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048961

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231203

Application publication date: 20130116

Assignee: Nantong Runyuan structural parts Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048952

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231203

Application publication date: 20130116

Assignee: Nantong Jinbao Machinery Manufacturing Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048947

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231202

Application publication date: 20130116

Assignee: Nantong Juntai motor vehicle testing Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048942

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231202

Application publication date: 20130116

Assignee: Honglei mechanical equipment (Nantong) Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048782

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231202

Application publication date: 20130116

Assignee: American Antelope Home Textile (Nantong) Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048774

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231202

Application publication date: 20130116

Assignee: Nantong Ansheng Textile Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048765

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231130

Application publication date: 20130116

Assignee: NANTONG YA TAI CANDLE ARTS & CRAFTS Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048764

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231130

Application publication date: 20130116

Assignee: Nantong Jianwei Metal Technology Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048759

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231202

Application publication date: 20130116

Assignee: JIANGSU YATAI FITNESS CO.,LTD.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980048748

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231202

EE01 Entry into force of recordation of patent licensing contract
EE01 Entry into force of recordation of patent licensing contract

Application publication date: 20130116

Assignee: Nantong Zhili Machinery Technology Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2023980049698

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20231205

EE01 Entry into force of recordation of patent licensing contract
OL01 Intention to license declared
OL01 Intention to license declared
EE01 Entry into force of recordation of patent licensing contract

Application publication date: 20130116

Assignee: JIANGSU HAOHAN INFORMATION TECHNOLOGY Co.,Ltd.

Assignor: Nantong San Intellectual Property Service Co.,Ltd.

Contract record no.: X2024980003183

Denomination of invention: Application of Houttuynoid B in the preparation of drugs for the treatment of cervical cancer

Granted publication date: 20130717

License type: Common License

Record date: 20240322

EE01 Entry into force of recordation of patent licensing contract