Thiourea-containing dendrimer and thiourea-containing hyperbranched polymer as well as preparation methods thereof and applications thereof

Patent metadata

Field	Value
Publication number	US-10072125-B2
Application number	US-201515516378-A
Country	US
Kind code	B2
Filing date	Jan 30, 2015
Priority date	Oct 21, 2014
Publication date	Sep 11, 2018
Grant date	Sep 11, 2018

Abstract

The present invention discloses thiourea-containing dendrimers and thiourea-containing hyperbranched polymers, and respectively a preparation method for the thiourea-containing dendrimer and a preparation method for the thiourea-containing hyperbranched polymer, and a thiourea-containing dendrimer and a thiourea-containing hyperbranched polymer having increased water solubility prepared by using the thiourea-containing dendrimer and the thiourea-containing hyperbranched polymer as raw materials. Finally, disclosed are applications of the thiourea-containing dendrimers and the thiourea-containing hyperbranched polymers in the preparation of antitumor and antimicrobial drugs. The thiourea-containing dendrimer and the thiourea-containing hyperbranched polymer have a significant growth inhibitive effect on solid tumors and low toxicity to normal tissues, and thus can be used for preparing drugs for treating malignant tumors. The thiourea-containing dendrimer and the thiourea-containing hyperbranched polymer also have a good antimicrobial effect on various bacterial strains and thus can be used for preparing antiviral or antibacterial drugs.

First claim

The invention claimed is:

1. A thiourea-containing dendrimer characterized in that it is prepared by reacting an ABx-type monomer containing isothiocyanates and a CDy-type monomer containing amino groups, wherein said ABx-type monomer is 1-(2-hydroxy-3-diallylamino) propyl isothiocyanate or 2,2-bis (methacryloyloxymethyl) propionyl isothiocyanate, and the CDy-type monomer is cysteamine hydrochloride or cysteamine.

2. The thiourea-containing dendrimer according to claim 1 , wherein the thiourea-containing dendrimer has a number average molecular weight of 100 to 50000.

3. A method for producing a thiourea-containing dendrimer claim 1 , wherein the ABx-type monomer and the CDy-type monomer are prepared by stepwise reaction to obtain the thiourea-containing dendrimer, comprising the following steps:
(1) mixing polyamine with the ABx-type asymmetric monomer in an ice-water bath, stirring for 10 to 60 minutes, and then raising the temperature to from room temperature to about 60° C. for 2 to 12 hours, and then after further processing to obtain polythiourea dendrimers of a first generation;
(2) mixing the polythiourea dendrimers of the first generation obtained from the step (1), the CDy-type asymmetric monomer and a solvent, reacting under room temperature for 10 to 60 minutes or under ultraviolet radiation for 1 to 5 hours, and then after further processing to obtain an intermediate product;
(3) mixing the intermediate product obtained in step (2) with ABx-type asymmetric monomer, and the reaction is carried out at from room temperature to about 60° C., to obtain polythiourea dendrimers of a second generation;
repeating steps (2)-(3) 1 to N times, respectively, to prepare polythiourea dendrimers of a third generation to (N+2)th generation.

4. The method for producing a thiourea-containing dendrimer according to claim 3 , wherein the polyamine is ethylenediamine, 1,3-propanediamine, 1,4-butanediamine, 1,5-pentanediamine, 1,6-hexanediamine, 1,7-heptanediamine, 1,8-octanediamine, 1,9-nonanediamine, tris (2-aminoethyl) amine, tris (3-aminopropyl) amine or linear polyethyleneimine having a number average molecular weight of 100 to 40,000.

5. A thiourea-containing hyperbranched polymer characterized in that ABx-type monomers and CDy-type monomers are dissolved in an organic solvent and radiated by ultraviolet light for 1 to 5 hours or at from room temperature to about 60° C. for 2 to 12 hours, to obtain a thiourea-containing hyperbranched polymer, wherein said ABx-type monomer is 1-(2-hydroxy-3-diallylamino) propyl isothiocyanate or 2,2-bis (methacryloyloxymethyl) propionyl isothiocyanate, and the CDy-type monomer is cysteamine hydrochloride or cysteamine.

6. A thiourea-containing dendrimer with increased water solubility characterized in that it is obtained by reacting a dendrimer containing thiourea with a hydrophilic polymer, said hydrophilic polymer having a number average molecular weight of 200˜10,000 polyethylene glycol, wherein said ABx-type monomer is 1-(2-hydroxy-3-diallylamino) propyl isothiocyanate or 2,2-bis (methacryloyloxymethyl) propionyl isothiocyanate, and the CDy-type monomer is cysteamine hydrochloride or cysteamine.

7. A thiourea-containing hyperbranched polymer with increased water solubility characterized in that it is obtained by reacting a thiourea-containing hyperbranched polymer with a hydrophilic polymer having a number average molecular weight of 200˜10,000 polyethylene glycol, wherein said ABx-type monomer is 1-(2-hydroxy-3-diallylamino) propyl isothiocyanate or 2,2-bis (methacryloyloxymethyl) propionyl isothiocyanate, and the CDy-type monomer is cysteamine hydrochloride or cysteamine.

8. A method of preparing antitumor drugs, antiviral or antimicrobial agents comprising the step of utilizing the thiourea-containing dendrimers according to claim 1 .

9. A method of preparing antitumor drugs, antiviral or antimicrobial agents comprising the step of utilizing the water-soluble increased thiourea-containing dendrimer according to claim 6 .

10. A method of preparing antitumor drugs, antiviral or antimicrobial agents comprising the step of utilizing the thiourea-containing hyperbranched polymers according to claim 5 .

11. A method of preparing antitumor drugs, antiviral or antimicrobial agents comprising the step of utilizing the water-soluble increased thiourea-containing hyperbranched polymer according to claim 7 .

Assignees

• Univ Zhejiang

Inventors

• Shen Youqing
• Shao Shiqun
• Tang Jianbin
• Liu Xiangrui

Classifications

• C08G83/003 Primary

  Dendrimers · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• C08G18/32

  Polyhydroxy compounds; Polyamines; Hydroxyamines · CPC title

• C08G18/8108

  having only one isocyanate or isothiocyanate group · CPC title

• C08G83/004

  After treatment of dendrimers · CPC title