Title:
CABAZITAXEL-FATTY ALCOHOL SMALL MOLECULE PRODRUG AND CONSTRUCTION OF SELF-ASSEMBLED NANOPARTICLE THEREOF
Document Type and Number:
WIPO Patent Application WO/2022/227555
Kind Code:
A1
Abstract:
The present invention relates to a cabazitaxel-fatty alcohol prodrug and the construction of a self-assembled nanoparticle thereof, and specifically relates to a disulfide bond-bridged redox dual-sensitive cabazitaxel-fatty alcohol prodrug and the construction of a self-assembled nanoparticle thereof, and the use thereof in the preparation of a drug delivery system. The prodrug is prepared by means of introducing a long-chain fatty alcohol structure into a cabazitaxel molecule, and connecting the long-chain fatty alcohol structure with the cabazitaxel molecule by means of a redox dual-sensitive disulfide bond, so that the prodrug is activated in a high-redox micro-environment in a tumor cell, and the technical concentrate is released quickly. The structure of the prodrug is as follows, wherein R and n are as described in the claims and the description. In addition, by means of the introduction of the long-chain fatty alcohol structure, the hydrophobicity of the cabazitaxel is increased, thus same is endowed with the self-assembly capability, and can self-assemble to form a nanoparticle. The cabazitaxel-fatty alcohol prodrug and the self-assembled nanoparticle thereof can significantly improve the anti-tumor effect of the cabazitaxel, reduce the toxicity thereof and improve the bioavailability of a drug.
Inventors:
LUO CONG (CN)
WANG YONGJUN (CN)
YANG JINCHENG (CN)
MA HONGDA (CN)
SUN JIN (CN)
HE ZHONGGUI (CN)
FENG YAO (CN)
MA ZHI NING (CN)
WANG YONGJUN (CN)
YANG JINCHENG (CN)
MA HONGDA (CN)
SUN JIN (CN)
HE ZHONGGUI (CN)
FENG YAO (CN)
MA ZHI NING (CN)
Application Number:
PCT/CN2021/133827
Publication Date:
November 03, 2022
Filing Date:
November 29, 2021
Export Citation:
Assignee:
SUZHOU YUTAI PHARMACEUTICAL TECH CO LTD (CN)
International Classes:
A61K47/54; A61K9/51; A61K31/337; A61K45/06; A61K47/10; A61K47/60; A61K47/69; A61K49/00; A61P35/00; C07D305/14
Foreign References:
| CN113398277A | 2021-09-17 | |||
| CN105884719A | 2016-08-24 | |||
| CN108478803A | 2018-09-04 | |||
| CN109350748A | 2019-02-19 | |||
| CN111116521A | 2020-05-08 | |||
| CN112604002A | 2021-04-06 |
Other References:
XUE PENG, LIU DAN, WANG JING, ZHANG NA, ZHOU JIAHUA, LI LIN, GUO WEILING, SUN MENGCHI, HAN XIANGFEI, WANG YONGJUN: "Redox-Sensitive Citronellol–Cabazitaxel Conjugate: Maintained in Vitro Cytotoxicity and Self-Assembled as Multifunctional Nanomedicine", BIOCONJUGATE CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 27, no. 5, 18 May 2016 (2016-05-18), US , pages 1360 - 1372, XP055981503, ISSN: 1043-1802, DOI: 10.1021/acs.bioconjchem.6b00155
JIANG YAN, WANG XIUZHEN, LIU XIN, LV WEI, ZHANG HONGJUAN, ZHANG MINGWAN, LI XINRUI, XIN HONGLIANG, XU QUNWEI: "Enhanced Antiglioma Efficacy of Ultrahigh Loading Capacity Paclitaxel Prodrug Conjugate Self-Assembled Targeted Nanoparticles", APPLIED MATERIALS & INTERFACES, AMERICAN CHEMICAL SOCIETY, US, vol. 9, no. 1, 11 January 2017 (2017-01-11), US , pages 211 - 217, XP055981508, ISSN: 1944-8244, DOI: 10.1021/acsami.6b13805
KANG TIANYI, LI YANG, WANG YONG, ZHU JIAO, YANG LING, HUANG YULAN, XIONG MEIMEI, LIU JINLU, WANG SHUAI, HUANG MEIJUAN, WEI XIAWEI,: "Modular Engineering of Targeted Dual-Drug Nanoassemblies for Cancer Chemoimmunotherapy", APPLIED MATERIALS & INTERFACES, AMERICAN CHEMICAL SOCIETY, US, vol. 11, no. 40, 9 October 2019 (2019-10-09), US , pages 36371 - 36382, XP055981510, ISSN: 1944-8244, DOI: 10.1021/acsami.9b11881
SUN BINGJUN, LUO CONG, YU HAN, ZHANG XUANBO, CHEN QIN, YANG WENQIAN, WANG MENGLIN, KAN QIMING, ZHANG HAOTIAN, WANG YONGJUN, HE ZHO: "Disulfide Bond-Driven Oxidation- and Reduction-Responsive Prodrug Nanoassemblies for Cancer Therapy", NANO LETTERS, AMERICAN CHEMICAL SOCIETY, US, vol. 18, no. 6, 13 June 2018 (2018-06-13), US , pages 3643 - 3650, XP055981522, ISSN: 1530-6984, DOI: 10.1021/acs.nanolett.8b00737
JIANG YAN, WANG XIUZHEN, LIU XIN, LV WEI, ZHANG HONGJUAN, ZHANG MINGWAN, LI XINRUI, XIN HONGLIANG, XU QUNWEI: "Enhanced Antiglioma Efficacy of Ultrahigh Loading Capacity Paclitaxel Prodrug Conjugate Self-Assembled Targeted Nanoparticles", APPLIED MATERIALS & INTERFACES, AMERICAN CHEMICAL SOCIETY, US, vol. 9, no. 1, 11 January 2017 (2017-01-11), US , pages 211 - 217, XP055981508, ISSN: 1944-8244, DOI: 10.1021/acsami.6b13805
KANG TIANYI, LI YANG, WANG YONG, ZHU JIAO, YANG LING, HUANG YULAN, XIONG MEIMEI, LIU JINLU, WANG SHUAI, HUANG MEIJUAN, WEI XIAWEI,: "Modular Engineering of Targeted Dual-Drug Nanoassemblies for Cancer Chemoimmunotherapy", APPLIED MATERIALS & INTERFACES, AMERICAN CHEMICAL SOCIETY, US, vol. 11, no. 40, 9 October 2019 (2019-10-09), US , pages 36371 - 36382, XP055981510, ISSN: 1944-8244, DOI: 10.1021/acsami.9b11881
SUN BINGJUN, LUO CONG, YU HAN, ZHANG XUANBO, CHEN QIN, YANG WENQIAN, WANG MENGLIN, KAN QIMING, ZHANG HAOTIAN, WANG YONGJUN, HE ZHO: "Disulfide Bond-Driven Oxidation- and Reduction-Responsive Prodrug Nanoassemblies for Cancer Therapy", NANO LETTERS, AMERICAN CHEMICAL SOCIETY, US, vol. 18, no. 6, 13 June 2018 (2018-06-13), US , pages 3643 - 3650, XP055981522, ISSN: 1530-6984, DOI: 10.1021/acs.nanolett.8b00737
Attorney, Agent or Firm:
SHENYANG FEIYANG LINGRUI INTELLECTUAL PROPERTY AGENCY (GENERAL PARTNERSHIP) (CN)
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