Fully-dissociable type polyethylene glycol-poly(L-glutamate-gamma-benzyl ester)-polyethyleneimine copolymer as well as synthesizing method and application thereof

A polyethyleneimine copolymer and polyethyleneimine technology are applied in the field of completely dissociable polyethylene glycol-polyethyleneimine copolymer and its synthesis, which can solve the problem of repeated medication and inability to combine , patient troubles and other problems, to achieve the effect of increasing the effective concentration of drugs, reducing toxic and side effects, and promoting escape

Inactive Publication Date: 2014-09-10
XI AN JIAOTONG UNIV
View PDF3 Cites 11 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these imine bonds cannot guarantee the stability of the gene carrier, and may have been dissociated before reaching the tumor tissue and entering the cells, making it difficult to guarantee the transfection effect
[0004] Sequential combination therapy is often used in clinical malignant tumors to overcome the unsatisfactory therapeutic effect of single agents
However, this combination therapy cannot achieve combination at the microscopic level, and requires repeated medications, which brings unnecessary troubles to patients.
At the same time, this combined treatment method is difficult to ensure the combined drug at the same site, the effect of synergistic anti-tumor treatment is not easy to reflect, and the clinical efficacy is not satisfactory.

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
  • Fully-dissociable type polyethylene glycol-poly(L-glutamate-gamma-benzyl ester)-polyethyleneimine copolymer as well as synthesizing method and application thereof
  • Fully-dissociable type polyethylene glycol-poly(L-glutamate-gamma-benzyl ester)-polyethyleneimine copolymer as well as synthesizing method and application thereof
  • Fully-dissociable type polyethylene glycol-poly(L-glutamate-gamma-benzyl ester)-polyethyleneimine copolymer as well as synthesizing method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] 1) Synthesis of cystaminated methoxypolyethylene glycol (mPEG):

[0047] 1.1) Dissolve dry methoxy-terminated polyethylene glycol with a molecular weight of 4000Da, dibutyltin dilaurate and 2,2'-dithiodiethylisocyanate in anhydrous toluene, and store at 85°C under a nitrogen atmosphere. After reacting for 48 hours, the resulting reaction system was precipitated three times in anhydrous n-hexane, and the precipitate was collected and dried in vacuo to obtain mPEG modified with 2,2'-dithiodiethylisocyanate; The molar ratio of polyethylene glycol, dibutyltin dilaurate and 2,2'-dithiodiethylisocyanate is 1:0.06:8; dissolve 5g of methoxy-terminated polyethylene glycol per 100ml of anhydrous toluene alcohol;

[0048] 1.2) Dissolve 2,2'-dithiodiethylisocyanate-modified mPEG in distilled water and react at 60°C for 6 hours. The reaction system is dialyzed in distilled water and freeze-dried to obtain white powder cystaminated endoform Oxypolyethylene glycol; Dissolve 5g of 2,...

Embodiment 2

[0064] 1) Synthesis of cystaminated methoxypolyethylene glycol:

[0065] 1.1) Dissolve dry methoxy-terminated polyethylene glycol with a molecular weight of 1200Da, dibutyltin dilaurate and 2,2'-dithiodiethylisocyanate in anhydrous toluene, and react at 85°C under a nitrogen atmosphere After 48 hours, the resulting reaction system was precipitated three times in anhydrous n-hexane, and the precipitate was collected and dried in vacuo to obtain 2,2'-dithiodiethylisocyanate-modified mPEG; wherein, the methoxy-terminated poly The molar ratio of ethylene glycol, dibutyltin dilaurate and 2,2'-dithiodiethylisocyanate is 1:0.04:5, and 25g of methoxy-terminated polyethylene glycol is dissolved in 100ml of anhydrous toluene ;

[0066] 1.2) Dissolve 2,2'-dithiodiethylisocyanate-modified mPEG in distilled water and react at 60°C for 6 hours. The reaction system is dialyzed in distilled water and freeze-dried to obtain white powder cystaminated endoform Oxy-polyethylene glycol; wherein,...

Embodiment 3

[0076] 1) Synthesis of cystaminated methoxypolyethylene glycol:

[0077] 1.1) Dissolve dry methoxy-terminated polyethylene glycol with a molecular weight of 2000Da, dibutyltin dilaurate and 2,2'-dithiodiethylisocyanate in anhydrous toluene, and react at 85°C under a nitrogen atmosphere After 48 hours, the resulting reaction system was precipitated three times in anhydrous n-hexane, and the precipitate was collected and dried in vacuo to obtain 2,2'-dithiodiethylisocyanate-modified mPEG; wherein, the methoxy-terminated poly The molar ratio of ethylene glycol, dibutyltin dilaurate and 2,2'-dithiodiethylisocyanate is 1:0.02:3, and 10g of methoxy-terminated polyethylene glycol is dissolved in 100ml of anhydrous toluene ;

[0078] 1.2) Dissolve 2,2'-dithiodiethylisocyanate-modified mPEG in distilled water and react at 60°C for 6 hours. The reaction system is dialyzed in distilled water and freeze-dried to obtain white powder cystaminated endoform Oxy-polyethylene glycol; wherein,...

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 provides a fully-dissociable type polyethylene glycol-poly(L-glutamate-gamma-benzyl ester)-polyethyleneimine copolymer as well as a synthesizing method and application thereof. The method comprises the following steps: performing cystamine modification on terminated methoxy polyethylene glycol; initiating a ring-opening polymerization of gamma-benzyl ester-L-glutamate-N-carboxyanhydride by utilizing the terminated amine of the terminated methoxy polyethylene glycol; connecting the product in the ring-opening polymerization and polyethyleneimine by utilizing 2,2'-dithio-diethyl isocyanate by virtue of an addition reaction to obtain the target product. According to the method, the synthesized copolymer is amphipathic, can be self-assembled to form nano-particles; chemotherapeutic medicines and genetic medicines can be simultaneously loaded to the copolymer when the copolymer is used as a medical vector; the copolymer can be completely dissociated and disintegrated by responding glutathione and other reductive substances, so that the vector can escape from endosome to cytoplasm, medicines can be quickly released, and the treatment effect can be improved. The method can be used for controlling the molecular weight and length of each fragment in the segmented copolymer, is mild in reaction condition, and is suitable for more medicine types.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and in particular relates to a completely dissociable polyethylene glycol-poly(L-glutamic acid-γ-benzyl ester)-polyethyleneimine copolymer and its synthesis method and application. Background technique [0002] Malignant tumor is one of the main threats to human health, and its treatment is a worldwide problem. Chemotherapy, like surgery and radiotherapy, is currently the mainstay of cancer treatment. Chemotherapy is a method that uses cytotoxic drugs to kill tumor cells for therapeutic purposes. However, cytotoxic drugs, such as doxorubicin, paclitaxel, epirubicin, and docetaxel, are usually poorly water-soluble and non-selective, with low bioavailability, which can cause serious side effects. Moreover, tumor cells are prone to multidrug resistance during chemotherapy, and the curative effect is not ideal. According to the American Cancer Society estimates, more than 90% of cancer patients...

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 Applications(China)
IPC IPC(8): C08G81/00C08G69/48C08G69/40C08G65/48A61K47/48A61K48/00A61P35/00A61K31/704A61K31/337A61K31/4745A61K47/34A61K47/59
Inventor 钱军民徐明辉胥伟军刘茸茸王红洁
Owner XI AN JIAOTONG UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap