Check patentability & draft patents in minutes with Patsnap Eureka AI!

Macromolecule vinblastine conjugate adopting amino acids or oligopeptides as connexons

A conjugate and macromolecular technology, applied in the field of macromolecules-vinblastine conjugates with amino acids or oligopeptides as linkers, can solve the problem of large adverse reactions

Inactive Publication Date: 2014-03-26
INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Although vinblastine drugs are widely used clinically, as cytotoxic antineoplastic drugs, these drugs have side effects such as bone marrow suppression and gastrointestinal reactions, and the adverse reactions are large.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Macromolecule vinblastine conjugate adopting amino acids or oligopeptides as connexons
  • Macromolecule vinblastine conjugate adopting amino acids or oligopeptides as connexons
  • Macromolecule vinblastine conjugate adopting amino acids or oligopeptides as connexons

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0109] Embodiment 1 monomethoxypolyethylene glycol 10kD -[4-O-(leucyl)-desacetylvinblastine]-conjugate (m-PEG 10kD -OCH 2 CH 2 CONH-Leu-CO-des-vinblastine, I 1 ) preparation

[0110] 1.1 Synthesis of 4-deacetylvinblastine (des-vinblastine)

[0111] Put 875ml of anhydrous methanol in a 3000ml three-necked flask, put it in an ice-salt bath, and pass through dry hydrogen chloride gas for 4 hours continuously to prepare a saturated hydrogen chloride methanol solution (0°C). Add 8g of vinblastine sulfate, continue to feed hydrogen chloride gas, react at low temperature, the reaction solution first becomes turbid and then clarifies, TLC detects the degree of progress of the reaction (developing agent DCM:CH 3 OH=15:1,R f =0.45), the reaction was carried out for 72h, and the reaction was stopped. Concentrate under reduced pressure to remove the solvent, leaving a viscous solid, dissolve it in water, add crushed ice, and then adjust the pH with ammonia water until no more preci...

Embodiment 2

[0117] Embodiment 2 monomethoxypolyethylene glycol 10kD -[4-O-(leucyl)-desacetylvincristine] conjugate (m-PEG 10kD -OCH 2 CH 2 CONH-Leu-CO-des-vincristine, I 2 ) preparation

[0118] 2.1 Synthesis of 4-deacetyl vincristine (des-vincristine)

[0119] Put 875ml of anhydrous methanol in a 3000ml three-necked flask, put it in an ice-salt bath, and pass through dry hydrogen chloride gas for 4 hours continuously to prepare a saturated hydrogen chloride methanol solution (0°C). Add 8g of vincristine, continue to feed hydrogen chloride gas, react at low temperature, the reaction solution first becomes turbid and then clarifies, TLC detects the degree of progress of the reaction (developing agent DCM:CH 3 OH=15:1, R f =0.45), the reaction was carried out for 72h, and the reaction was stopped. Concentrate under reduced pressure to remove the solvent, leaving a viscous solid, dissolve it in water, add crushed ice, and then adjust the pH with ammonia water until no more precipitates ...

Embodiment 3

[0125] Embodiment 3 monomethoxypolyethylene glycol 10kD -[4-O-(leucyl)-deacetylvinorelbine] conjugate (m-PEG 10kD -OCH 2 CH 2 CONH-Leu-CO-des-vinorelbine, I 3 ) preparation

[0126] 3.1 Synthesis of 4-deacetyl Vinorelbine (des-vinorelbine)

[0127] Put 875ml of anhydrous methanol in a 3000ml three-necked flask, put it in an ice-salt bath, and pass through dry hydrogen chloride gas for 4 hours continuously to prepare a saturated hydrogen chloride methanol solution (0°C). Add 8g Vinorelbine, continue to pass into hydrogen chloride gas, react at low temperature, the reaction solution first becomes turbid and then clarifies, TLC detects the degree of progress of the reaction (developing agent DCM:CH 3 OH=15:1,R f =0.45), the reaction was carried out for 72h, and the reaction was stopped. Concentrate under reduced pressure to remove the solvent, leaving a viscous solid, dissolve it in water, add crushed ice, and then adjust the pH with ammonia water until no more precipitate...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to a macromolecule vinblastine conjugate adopting amino acids or oligopeptides as connexons. Specifically, the invention relates to a conjugate represented by a formula I, or pharmaceutically-acceptable salts thereof. The conjugate is prepared by conjugating a biocompatible macromolecule and vinblastine through amino acids or oligopeptides, wherein each symbol in the formula I is described in an instruction. The invention further relates to a method for preparing the conjugate or the pharmaceutically-acceptable salts thereof, drug combinations combined through the conjugate and the pharmaceutically-acceptable salts thereof, application in medicine for treating and / or preventing proliferative disease, neoplastic disease or carcinoma disease. According to the present invention, hydroxy group on C-4 of the vinblastine or the hydroxy group on the deacetylated C-4 of derivatives is adopted as a cross-linked group, and is conjugated with the macromolecule through the amino acids or the oligopeptides to obtain an effective conjugate of the vinblastine with novel characteristic.

Description

technical field [0001] The invention relates to a conjugate formed by a biocompatible macromolecule through an amino acid or an oligopeptide and a vinblastine drug and a non-toxic pharmaceutically acceptable salt thereof, wherein the vinblastine drug is vinblastine, vincristine, and vindesine , Vinrelbine and Vinflunine. Background technique [0002] Vinblastine drugs are the most commonly used antineoplastic drugs clinically, including vinblastine, vincristine, vindesine, vinorelbine and vinflunine. The chemical structures of vinblastine drugs are shown below: [0003] [0004] [0005] Vinblastine antineoplastic drugs can not only bind to tubulin and inhibit the polymerization of tubulin double microsomes into microtubules; Cancer cells divide and multiply. Vinblastine is a representative of vinblastine drugs, mainly effective for lymphoma, choriocarcinoma and testicular tumors, and also effective for other cancers such as lung cancer, breast cancer, ovarian cance...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/48A61K47/34A61K31/475A61P35/00A61K47/10A61K47/59A61K47/60
Inventor 仲伯华张爱红王永广何新华史卫国张振清谢剑炜
Owner INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com