Cationic poly-prodrug polymer as well as preparation method and application thereof

A technology of cationic polymers and polymers, which is applied in the direction of nano-drugs, pharmaceutical formulations, drug combinations, etc., can solve the problems of low drug-loading rate of carriers, obstacles in practical application, and increase the metabolic burden of patients, so as to achieve simple components and improve drug-loading. rate, the effect of reducing the metabolic burden

Inactive Publication Date: 2020-04-10
INST OF PROCESS ENG CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in tri-block polymers, most of the materials are inert materials, resulting in low drug loading rate of the carrier and increasing the metabolic burden of patients, which brings great obstacles to practical application.

Method used

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  • Cationic poly-prodrug polymer as well as preparation method and application thereof
  • Cationic poly-prodrug polymer as well as preparation method and application thereof
  • Cationic poly-prodrug polymer as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0052] When X of PCB-L-X is a small molecule drug containing hydroxyl or amino group (X-NH 2 , X-OH), when L is a single bond, the preparation method comprises the steps:

[0053] Add PCB to the first organic solvent, then add catalyst and X, stir and react to obtain a mixed solution containing polymer PCB-L-X;

[0054] Carrying out the first dialysis on the mixed solution containing the polymer PCB-L-X, and freeze-drying to obtain the PCB-L-X polymer;

[0055] When X of PCB-L-X is a small molecule drug (X-COOH) containing a carboxyl group, and L is a connecting molecule containing a bifunctional group, the preparation method includes the following steps:

[0056] Add X to the first organic solvent, then add catalyst and PCB-L, stir and react to obtain a mixed solution containing polymer PCB-L-X;

[0057] Perform the first dialysis on the mixed solution containing the polymer PCB-L-X, and freeze-dry to obtain the PCB-L-X polymer.

[0058] In the embodiment of the present in...

Embodiment 1

[0093] Example 1: Preparation of gene therapy drug and small molecule drug camptothecin combined delivery carrier

[0094] Dissolve 6mg of cyanoisopropyl dithiobenzoate, 311.1mg of carboxybetaine methacrylate (CB), and 1.5mg of azobisisobutyronitrile in methanol, remove the oxygen in the reaction flask and the mixed solution, and place in nitrogen Under protection, the reaction was stirred at 60°C for 24h. Carry out dialysis 24 hours with water as external phase, freeze-dry to obtain the polycarboxybetaine methacrylate (PCB) that theoretical polymerization degree is 50 50 ).

[0095] 40mg of polycarboxybetaine methacrylate (PCB) with a degree of polymerization of 50 50 ), 255.8 mg of 4-dimethylaminopyridine and 481.8 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride were dissolved in dimethylsulfoxide. After dissolving 303.8 mg of camptothecin (CPT) in dimethyl sulfoxide, the mixture was added dropwise, and stirred for 48 hours at 25°C. The product was dialyz...

Embodiment 2

[0097] Example 2: Preparation of gene therapy drug and small molecule drug simvastatin combined delivery carrier

[0098] Adopt the preparation PCB method described in embodiment 1 to prepare the polycarboxybetaine methacrylate (PCB) that theoretical polymerization degree is 50 50 ).

[0099] 400mg of polycarboxybetaine methacrylate (PCB) with a degree of polymerization of 50 50 ), 255.8 mg of 4-dimethylaminopyridine and 518.5 mg of dicyclohexylcarbodiimide were dissolved in dimethylsulfoxide. 730.2mg simvastatin (SIM 30 ) was dissolved in dimethyl sulfoxide, and the mixture was added dropwise, and stirred and reacted for 48 hours at 25°C. The product was dialyzed for 24 hours with dimethyl sulfoxide and water as the external aqueous phase, and freeze-dried for 48 hours to obtain the final PCB 20 -SIM 30 product.

[0100] At 25°C, the cationic polyprodrug polymer molecule PCB 20 - Simvastatin (SIM 30 ) was dissolved in dimethyl sulfoxide at a concentration of 1 mg / mL. ...

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Abstract

The invention discloses a cationic poly-prodrug polymer as well as a preparation method and an application thereof. The preparation method of the cationic poly-prodrug polymer PCB-L-X comprises the following steps: bonding PCB and a small molecular drug X through a single bond or a connecting molecule containing a bifunctional group to obtain the small molecular drug-loaded PCB-L-X. The PCB-L-X has positive charges, can be loaded with a gene therapy drug to form a combined delivery carrier, realizes common loading of the gene therapy drug and a small molecule drug, and is used for preparing asynergistic therapy drug for related diseases caused by abnormal expression of genes. The PCB-L-X effectively reduces the use of cationic polymers and hydrophobic polymers, can effectively improve thedrug loading rate of the combined delivery carrier, reduces the metabolic burden of patients, and is high in safety.

Description

technical field [0001] The invention relates to the technical field of a drug-loaded polymer molecule, in particular to a cationic polyprodrug polymer molecule, its preparation method and application. Background technique [0002] In the treatment of genetic diseases, malignant tumors, neurodegenerative diseases, cardiovascular diseases or infectious diseases, the efficacy of single drug therapy is not very satisfactory. Therefore, combined administration is mostly used in clinical practice, such as combining gene therapy drugs and small molecule drugs targeting different targets, to exert a synergistic effect to treat diseases. However, the shortcomings of the two drugs seriously limit their application. Among them, small molecule drugs have short blood half-life and poor tissue selectivity; gene therapy drugs usually have poor stability, short blood half-life, poor tissue selectivity and poor cell entry ability. The combined delivery carrier simultaneously packs two drugs...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/58A61K45/00A61K31/4745A61K31/366A61K31/203A61P35/00C08F8/10C08F8/32C08F122/18B82Y5/00
CPCA61K31/203A61K31/366A61K31/4745A61K45/00A61K47/58A61P35/00B82Y5/00C08F8/10C08F8/32C08F122/18
Inventor 张欣李燕籍伟红刘霖颖彭欢
Owner INST OF PROCESS ENG CHINESE ACAD OF SCI
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