PEG modifying PHPMA material and preparation method thereof

A modified and hydroxyl technology, applied in the field of PEG modified PHPMA material and its preparation, can solve the problems of wide molecular weight distribution, no prevention, uncontrollable molecular weight of the carrier, etc., to achieve high targeting, good biocompatibility, The effect of preventing non-specific adsorption of proteins

Inactive Publication Date: 2008-09-17
INST OF CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the PHPMA carrier also has obvious deficiencies, such as single function, lack of ability to prevent non-specific adsorption of proteins, etc., resulting in the adsorption and accumulation of PHPMA drug carriers in non-lesional sites during blood circulation.
More importantly, since the preparation of the current PHPMA carrier adopts a common free radical polymerization method, the molecular weight of the obtained carrier is uncontrollable and the molecular weight distribution is very wide, which seriously affects the EPR effect and pharmacokinetics of the polymer carrier, thereby further affect the therapeutic effect of the drug

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] The preparation of embodiment 1, PEG-b-PHPMA

[0037] Dissolve 2.4 g of single-terminal hydroxyl PEG with a number average molecular weight of 2000 in 40 mL of toluene, add 0.68 g of 4-dithiobenzoate-4-cyanovaleric acid (CPAD), 4-dimethylaminopyridine (DMAP ) 0.041g, after being completely dissolved, add 0.74g of N,N'-dicyclohexylcarbodiimide (DCC), and react for 90 hours under stirring at room temperature. Suction filtration, pour the filtrate into excess diethyl ether, suction filtration, the resulting precipitate was dissolved in a small amount of toluene, and then precipitated with diethyl ether, and this was repeated three times. The precipitate was vacuum-dried at 40° C. for 24 hours, and the obtained product was a macromolecular chain transfer agent of PEG.

[0038] Take 0.13g of this chain transfer agent, 0.716g of HPMA, 5mg of 4,4'-azobis(4-cyanovaleric acid) and 6mL of pure water, put it in a vacuum reaction tube, vacuumize it under refrigeration, and then re...

Embodiment 2

[0040] The preparation of embodiment 2, PHPMA-b-PEG-b-PHPMA

[0041] The preparation method of this three-block copolymer is basically the same as that of Example 1, except that the single-end hydroxyl or amino PEG with a number average molecular weight of 2000 is replaced with a double-end hydroxyl or amino PEG with a number average molecular weight of 2000. The amount of double-terminal hydroxyl or amino group is changed to 1.2g in this embodiment, and the amount of macromolecular chain transfer agent is changed to 0.065g. When the reaction was terminated, the reaction tube was quickly put into liquid nitrogen, and then the small molecules were removed by dialysis, and finally the solvent was evaporated to dryness to obtain the desired product. The composition and molecular weight of the product can be determined by aqueous GPC and 1 H NMR for co-confirmation.

[0042] Different reaction times can obtain products with different compositions and molecular weights. When the...

Embodiment 3、 3

[0043] Embodiment 3, preparation 1 of triblock PEG-b-PHPMA-b-PX

[0044] In this example, PX is polyglycine dipeptide methacrylamide. Take 0.10 g of PEG-b-PHPMA with a number average molecular weight of 10,000 synthesized in Example 1, 0.20 g of glycine dipeptide methacrylamide, and 2 mg of 4,4'-azobis(4-cyanovaleric acid), Put 3 mL of acetic acid-sodium acetate buffer solution in a vacuum reaction tube (the concentration of acetic acid in the acetic acid-sodium acetate buffer solution is 0.27moL / L, the concentration of sodium acetate is 0.73moL / L, pH=5.2), vacuumize under freezing, and then return to room temperature , filled with argon, and this freezing-thawing-argon filling process was repeated three times. Under the protection of argon, the reaction tube was placed in a 70°C oil bath for reaction. When the reaction was terminated, the reaction tube was quickly put into liquid nitrogen, and then the small molecules were removed by dialysis, and finally the solvent was ev...

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PUM

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Abstract

The invention discloses a PEG modified PHPMA material and a preparation method thereof. The PEG modified PHPMA material which is provided by the invention is N-(2'-hydroxyl) propyl methyl acrylamide (HPMA) and/or a copolymer of the derivative of the N-(2'-hydroxyl) propyl methyl acrylamide and polyethylene glycol (PEG). The PEG modified PHPMA material of the invention is a polymer which is formed by the copolymerization of the polyethylene glycol (PEG), poly-N-(2'-hydroxyl) propyl methyl acrylamide (PHPMA) and the derivative of the PHPMA, the copolymer can be obtained by adopting the reversible addition-fragmentation chain transfer (RAFT), the composition and the molecular weight are controllable, and the molecular weight distribution is narrow (the molecular weight distribution d is less than 1, 4). Such polymers can be applied in the targeting drug delivery, which can not only have high targeting property and good biocompatibility, but can also have the function of preventing the protein non-specific absorption after the PEG modification, so the PEG modified PHPMA material is a good drug targeting carrier with the good performance, in particular to the drug targeting carrier of an anti-tumor drug.

Description

technical field [0001] The invention relates to a modified polymer material, in particular to a PEG modified PHPMA material and a preparation method thereof. Background technique [0002] Tumor is the second largest disease that threatens human health at present, with high mortality rate, low cure rate and poor prognosis. At present, there are three main types of treatment methods for tumors: surgery, chemotherapy and radiotherapy. Generally speaking, chemotherapy and radiotherapy are combined with surgery to kill residual and metastatic tumor cells after surgery. [0003] Although chemotherapy and radiotherapy have significant curative effects in tumor treatment, there are still many problems. For chemotherapy, while the drugs kill tumor cells, they also non-selectively kill normal cells, causing considerable systemic side effects in patients, seriously affecting the recovery of the patient's body and the enthusiasm of the patient to cooperate with the treatment. For rad...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G81/02
Inventor 魏振柯甘志华
Owner INST OF CHEM CHINESE ACAD OF SCI
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