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ph responsiveness protein-macromolecule combination and preparing and assembling method thereof

A responsive, high-molecular technology, applied in the direction of non-active components of high-molecular compounds, can solve the problems that are rarely transformed into clinical and put into the market, and the controllability of the size and shape of nanocarriers limits the development, etc., to achieve a good pH Responsiveness, low toxicity, and high production yield

Inactive Publication Date: 2015-09-16
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] So far, significant progress has been made in the design of nanocarriers, which can effectively improve the therapeutic effect of therapeutic agents, but most of them are still in the experimental stage, and few of them are transformed into clinical practice and put into the market, and further efforts of scientists are still needed
At the same time, due to reasons such as preparation technology, the controllability of the size and shape of nanocarriers is also an important reason that limits its development.

Method used

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  • ph responsiveness protein-macromolecule combination and preparing and assembling method thereof
  • ph responsiveness protein-macromolecule combination and preparing and assembling method thereof
  • ph responsiveness protein-macromolecule combination and preparing and assembling method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Synthesis of Bovine Serum Albumin (BSA) Macromolecular ATRP Initiator.

[0054] ① Disperse 30g of maleic anhydride in 150ml of toluene, stir and heat in an oil bath to 80°C, slowly inject 33.3ml of furan with a syringe, condense and reflux for 6 hours. After the reaction was completed, it was lowered to room temperature, allowed to stand for 1 h, filtered under reduced pressure, washed 3 times with petroleum ether, and a white product A was obtained.

[0055] ②Take 10g of product A, disperse it in 100ml of methanol, stir and cool in an ice bath to 0°C, slowly add 3.6ml of ethanolamine dropwise to the above solution, stir at 0°C for 20min, then stir at room temperature for 35min, and reflux in a stirring oil bath at 80°C 24h. After the reaction, cooling and recrystallization, filtration under reduced pressure, white crystal B was obtained.

[0056] ③ Take 3g of product B and 2.16ml of triethylamine, add it to 170ml of THF at 0°C, dissolve 1.89ml of 2-bromoisobutyryl br...

Embodiment 2

[0061] Synthesis of Bovine Serum Albumin (BSA) Macromolecular ATRP Initiator.

[0062] ① Disperse 40g of maleic anhydride in 180ml of toluene, stir and heat in an oil bath to 90°C, slowly inject 44.4ml of furan with a syringe, condense and reflux for 8 hours. After the reaction was completed, it was lowered to room temperature, allowed to stand for 2 hours, filtered under reduced pressure, washed twice with petroleum ether, and a white product A was obtained.

[0063] ②Take 20g of product A, disperse it in 80ml of methanol, stir and cool in an ice bath to 0°C, slowly add 7.2ml of ethanolamine to the above solution dropwise, stir at 0°C for 15min, then stir at room temperature for 40min, and reflux in a stirring oil bath at 90°C 36h. After the reaction, cooling and recrystallization, filtration under reduced pressure, white crystal B was obtained.

[0064] ③ Take 6g of product B and 4.32ml of triethylamine, add it to 170ml of THF at 0°C, dissolve 3.78ml of 2-bromoisobutyryl b...

Embodiment 3

[0068] Synthesis of Bovine Serum Albumin (BSA) Macromolecular ATRP Initiator.

[0069] ① Disperse 20g of maleic anhydride in 120ml of toluene, stir and heat in an oil bath to 100°C, slowly inject 22.2ml of furan with a syringe, condense and reflux for 7 hours. After the reaction was completed, it was lowered to room temperature, allowed to stand for 3 hours, filtered under reduced pressure, washed 3 times with petroleum ether, and a white product A was obtained.

[0070] ②Take 15g of product A, disperse it in 90ml of methanol, stir and cool in an ice bath to 0°C, slowly add 5.4ml of ethanolamine dropwise to the above solution, stir at 0°C for 25min, then stir at room temperature for 30min, and reflux in a stirring oil bath at 100°C 48h. After the reaction, cooling and recrystallization, filtration under reduced pressure, white crystal B was obtained.

[0071] ③Take 4g of product B and 2.88ml of triethylamine, add it to 150ml THF at 0°C, dissolve 2.52ml of 2-bromoisobutyryl b...

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Abstract

The invention relates to a pH responsiveness protein-macromolecule combination and a preparing and assembling method thereof. A bovine serum albumin macromolecule atom transfer radical polymerization initiator is synthesized; ATRP polymerization of methacrylic acid diisopropyl amino ethyl ester monomers is triggered; and the pH responsiveness bovine serum albumin-polymethylacrylic acid diisopropyl amino ethyl ester amphipathicity combination is prepared. BSA exists as a hydrophilic part and gives great biocompatibility to the combination. A hydrophobic end PDPA introduced by controllable living polymerization improves the stability of the BSA, so that the protein-macromolecule combination has amphipathicity and pH responsiveness. Self assembling is carried out; pH mediating treating medicine loading is carried out. Under an environment with a low pH value in a tumor microenvironment or a cell endosome, strong protonation happens to the PDPA; loaded medicine is released; the treating effect is effectively improved. The preparing method can achieve PDPA fixed point combination and number controlling.

Description

technical field [0001] The invention relates to a stimulus-responsive protein-macromolecule combination and its preparation and assembly method, belonging to the technical field of drug carrier material preparation. Background technique [0002] The carefully designed nano-drug carrier can embed or dissolve the drug inside the nano-particle, and can also be adsorbed or coupled on its surface. The nanocarriers are modified with targeting agents, and the targeting ligands are connected to the surface of the nanoparticles. Through the specific recognition of the ligands on the receptors on the cell membrane, the modified drug-loaded nanoparticles can be targeted to cancer cells and enter Cells release drugs to achieve targeted delivery of drugs, and at the same time have the advantages of sustained release, protection of drugs, improvement of efficacy, and reduction of toxic and side effects. [0003] After the nanoparticles enter the cells, only when the therapeutic agent is ...

Claims

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Application Information

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IPC IPC(8): A61K47/42
Inventor 常津房蕾刘中云宫晓群杨文涛
Owner TIANJIN UNIV
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