Zwitterionic polymer with reductive responding antitumor activity and synthesis thereof and application thereof as drug carrier

An anti-tumor activity, zwitterionic technology, applied in the preparation of anti-tumor drugs, in the field of zwitterionic polymers, to achieve the effects of reducing drug toxicity, good biocompatibility, and reducing damage

Inactive Publication Date: 2017-05-31
NORTHWEST NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, studies have found that PEG is flawed in its use

Method used

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  • Zwitterionic polymer with reductive responding antitumor activity and synthesis thereof and application thereof as drug carrier
  • Zwitterionic polymer with reductive responding antitumor activity and synthesis thereof and application thereof as drug carrier
  • Zwitterionic polymer with reductive responding antitumor activity and synthesis thereof and application thereof as drug carrier

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] (1) Preparation of the hydrophilic monomer CBB-tBu: Weigh 1.57 (10 mmol) dimethylaminoethyl methacrylate and dissolve it in 10 mL of acetone. Add 5 mL of acetone solution containing 2.93 (15 mmol) tert-butyl bromoacetate, react for 6 hours, then filter the filtrate after the reaction, wash it with anhydrous acetone several times, and dry it in vacuum at 25°C for 24 hours to obtain a white solid that is Water monomer CBB-tBu, labeled as compound , and the yield was 92.5%.

[0056] 1 H NMR (400 MHz, CDCl 3 ):δ6.13(s,1H,=C H H),5.67(s,1H,=CH H ),1.95(s,3H,-C H 3 ),4.74(t,2H,-OC H 2 CH 2 -),4.38(t,2H-OCH 2 C H 2 -),3.73(s,6H,-N(C H 3 ) 2 ),4.63(s,2H,-C H 2 -OOC),1.48(s,9H,-(C H 3 ) 3 ).

[0057] (2) Preparation of intermediate compounds: 0.42 g (2.7 mmol) bis(2-hydroxyethyl) disulfide, 0.5 g (1.35 mmol) RAFT reagent (2-(dodecyl trithiocarbonate group )-2-methylpropionic acid, 0.33g (2.7 mmol) 4-dimethylaminopyridine, dissolved in a round-bottomed flas...

Embodiment 2

[0067] (1) compound , compound , compound The preparation, with embodiment 1;

[0068] (2) of the compound Preparation: weigh 0.2g compound (0.2g, 0.04mmol), 0.18g (0.65mmol) compound , into a Shlenck bottle, add 2 mL of DMF, heat and stir to dissolve, add 0.025g (0.15mmol) azobisisobutyronitrile when cooled to room temperature, vacuumize and inflate with nitrogen for 3 times, seal and react at 60°C for 24 h, Precipitation with ether gave a white powdery solid. Dissolve the above white solid in 5 mL of dichloromethane, slowly drop trifluoroacetic acid into it for hydrolysis for 2 h, and precipitate with ether three times to obtain the compound . The yield was 76.8%.

[0069] 1 H NMR (600 MHz, CDCl 3 )(ppm):δ4.309(t,2H,-S-S-CH 2 CH 2 -OH), 1.365 (-OCH 2 CH 2 CH 2 CH 2 CH 2 COO-),1.623(-OCH 2 CH 2 CH 2 CH 2 CH 2 COO-),2.286(-OCH 2 CH 2 CH 2 CH 2 CH 2 COO-),4.041(-O CH 2 CH 2 CH 2 CH 2 CH 2 COO-),3.73(s,6H,-N(C H 3 ) 2...

Embodiment 3

[0072] (1) compound , compound The preparation, with embodiment 2;

[0073] (2) compound Preparation: Under nitrogen protection, 0.5g (1 mmol) of the compound , 0.002g (0.05mmol) stannous octoate, 6.8 g (60 mmol) ε-caprolactone, dissolved in 10 mL toluene, polymerized at 110°C for 24 h, added 10 mL dichloromethane to dilute after the reaction, and then Add dropwise to 200 mL of cold methanol for precipitation under stirring, and wash several times with 200 mL of cold methanol, filter and dry to obtain 6.5 g of white solid which is the compound , and the yield was 89%.

[0074] 1 H NMR (600 MHz, CDCl 3 ) (ppm): δ0.859(t,C H 3 (CH 2 ) 10 CH 2 -S-(C=S)-S-),1.237(m, 20H,

[0075] CH 3 (C H 2 ) 10 CH 2 -S-(C=S)-S-),4.346(t,2H,-(C=O)OC H 2 CH 2 -),2.908(t,2H,-COOCH 2 C H 2 -),3.251(t,2H,-S-S-C H 2 CH 2 -OH), 4.309(t,2H,-S-S-CH 2 CH 2 -OH)1.365(-OCH 2 CH 2 CH 2 CH 2 CH 2 COO-),1.623(-OCH 2 CH 2 CH 2 CH 2 CH 2 COO-),2.286(-O...

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Abstract

The invention provides a zwitterionic polymer with reductive responding antitumor activity. The zwitterionic polymer is an amphiphilic polymer formed by a disulfide bond-containing hydrophobic polycaprolactone and a hydrophilic polycarboxylic glycine betaine methacrylate. The amphiphilic polymer is self-assembled in water to form a micelle carrier of a core-shell structure, and through a physical embedding action, an antitumor drug is carried into a hydrophobic core of the nano micelle, so that the drug solubility is improved, the cycling time is prolonged, the vascular permeability synergistic effect is obtained, and the disulfide bond ruptures in a high reductive environment, so that the micelle structure is damaged so as to release adriamycin amycin, thereby further killing tumor cells; according to the polycarboxylic glycine betaine methacrylate monomer, a copolymer shows good biocompatibility, so that the toxicity of the antitumor drug is further reduced, and damage on normal tissues is reduced. An in-vitro simulative release experiment verifies that the zwitterionic polymer micelle as the drug carrier has a good release effect and is an antitumor active substance which has an application prospect.

Description

technical field [0001] The present invention relates to a zwitterionic polymer with anti-tumor activity, in particular to a zwitterionic polymer with reduction-responsive anti-tumor activity; the present invention also relates to the preparation method of the zwitterionic polymer and its use as a drug carrier in the preparation of anti-tumor The application in tumor medicine belongs to the fields of nanomaterial preparation and biomedicine. Background technique [0002] Nano-carriers have been widely used in the treatment of cancer. The surface of all nano-drug carriers requires a hydrophilic layer as a physical barrier to resist the interaction of the carrier with other tissues and various components in the blood before reaching the tumor tissue, especially The interaction with the protein in the blood, that is, the anti-protein non-specific adsorption material is needed to modify the surface of the nano-drug carrier. [0003] Anti-nonspecific protein adsorption (nonfoulin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08F283/02C08F220/36A61K9/107A61K47/32A61K31/704A61P35/00
CPCA61K9/1075A61K31/704A61K47/32C08F283/02C08F2438/03C08F220/365
Inventor 袁建超马敏苑莹芝张丹魏英英吴兴军
Owner NORTHWEST NORMAL UNIVERSITY
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