Cisplatin polymer micelle preparation method and use thereof

A polymer glue and polymer technology, applied in the field of biomedical technology and nanomedicine, can solve the problems of strong toxic and side effects, low oral activity, poor water solubility, etc., and achieve low toxicity, good chemotherapeutic effect, and good passive targeting. Effect

Inactive Publication Date: 2009-06-17
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Cis-dichlorodiamminoplatinum(II) (cisplatin, CDDP) is a broad-spectrum antitumor chemotherapy drug, which is effective for ovarian cancer, cervical cancer, testicular cancer, breast cancer, esophageal cancer, non-small cell lung cancer and gastric cancer. It has the characteristics of definite curative effect and high anticancer activity, but its water solubility is poor, oral activity is low, the remission period is short, and the toxic and side effects are strong. Large doses or continuous medication can cause severe and long-lasting nephrotoxicity and auditory attenuation.

Method used

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  • Cisplatin polymer micelle preparation method and use thereof
  • Cisplatin polymer micelle preparation method and use thereof
  • Cisplatin polymer micelle preparation method and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] (a) Synthesis of polyethylene glycol-g-polyaspartimide (mPEG-g-PSI)

[0029] 10g mPEG 5000 -NH 2 Dissolve in 20mL DMF, add dropwise 20mL DMF solution containing 1g polyaspartimide, in N 2 Under protection, heat in an oil bath at 70°C and react for 24h. After reprecipitation with ether and drying in a vacuum, the product polyethylene glycol-g-polyaspartimide can be obtained with a yield of 94%.

[0030] (b) Synthesis of polyethylene glycol-g-polyaspartic acid derivatives (mPEG-g-α, β-Poly[(N-amino acidyl)-DL-aspartamide])

[0031] 2 g of aspartic acid and 1 g of polyethylene glycol-g-polyaspartimide were dissolved in a mixed solvent of 100 mL of water and 20 mL of triethylamine, and reacted at room temperature for 24 hours. The reaction mixture solution was concentrated to 10 mL, adjusted to pH 2 with hydrochloric acid, stirred for 4 hours, dialyzed for 3 days, and freeze-dried to obtain polyethylene glycol-g-polyaspartic acid derivative with a yield of 76%.

[0032] (c) Pre...

Embodiment 2

[0036] (a) Synthesis of polyethylene glycol-g-polyaspartimide (mPEG-g-PSI)

[0037] 4g mPEG 2000 -NH 2 Dissolve in 10mL DMF, add dropwise 20mL DMF solution containing 1g polyaspartimide, in N 2 Under protection, heat in an oil bath at 70°C and react for 24h. The product polyethylene glycol-g-polyaspartimide can be obtained by reprecipitation with ether and drying in a vacuum with a yield of 90%.

[0038] (b) Synthesis of polyethylene glycol-g-polyaspartic acid derivatives (mPEG-g-α, β-Poly[(N-amino acidyl)-DL-aspartamide])

[0039] 4g glutamic acid and 1g polyethylene glycol-g-polyaspartimide were dissolved in a mixed solvent of 80mL water and 10mL triethylamine, and reacted at room temperature for 24h. The reaction mixture solution was concentrated to 10 mL, adjusted to pH 2 with hydrochloric acid, stirred for 4 hours, dialyzed for 3 days, and freeze-dried to obtain polyethylene glycol-g-polyaspartic acid derivative with a yield of 70%.

[0040] (c) Preparation of cisplatin polym...

Embodiment 3

[0044] (a) Synthesis of polyethylene glycol-g-polyaspartimide (mPEG-g-PSI)

[0045] 5g mPEG 2000 -NH 2 Dissolve in 20mL DMF, add dropwise to 10mL DMF solution containing 1g polyaspartimide, in N 2 Under protection, heat in an oil bath at 70°C and react for 24h. The product polyethylene glycol-g-polyaspartimide can be obtained by reprecipitating with ether and drying in a vacuum with a yield of 93%.

[0046] (b) Synthesis of polyethylene glycol-g-polyaspartic acid derivatives (mPEG-g-α, β-Poly[(N-amino acidyl)-DL-aspartamide])

[0047] Dissolve 5 g of aspartic acid and 1 g of polyethylene glycol-g-polyaspartimide in a mixed solvent of 80 mL of water and 10 mL of triethylamine, and react for 24 hours at room temperature. The reaction mixture solution was concentrated to 10 mL, adjusted to pH 2 with hydrochloric acid, stirred for 4 hours, dialyzed for 3 days, and freeze-dried to obtain polyethylene glycol-g-polyaspartic acid derivative with a yield of 73%.

[0048] (c) Preparation of c...

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Abstract

The invention discloses a method for preparing cisplatin polymer micelles and application of the cisplatin polymer micelles. The method comprises: grafting poly asparagus imide with amino polyethylene glycol monomethyl ether to obtain polyethylene glycol-g-poly asparagus imide; dissolving the polyethylene glycol-g-poly asparagus imide product into a mixed system of triethylamine and water, and opening loop by glutamic acid or aspartic acid, so as to obtain polyethylene glycol-g-poly(aspartic acid) amino acid derivatives; and dissolving the derivatives and cisplatin into an aqueous-phase system, and obtaining the cisplatin polymer micelles through complexation of carboxyl groups and metals. The cisplatin polymer micelles are applied to treatment of oophoroma, cervical cancer, testis cancer, breast cancer, esophagus cancer, non-small cell lung cancer and gastric cancer. The obtained cisplatin polymer micelles have the particle diameter which can be controlled to be between 80 and 200 nanometers, and have good passive targeting property. Compared with cisplatin micromolecular anticarcinogen, the cisplatin polymer micelles have better chemotherapy effect and low toxicity.

Description

Technical field [0001] The invention relates to the fields of biomedicine technology and nanomedicine, in particular to a polyethylene glycol grafted polyaspartic acid amino acid derivative (mPEG-g-α, β-Poly [(N-aminoacidyl)-DL-aspartamide] ) And the controllable preparation and application of anticancer drug cisplatin nanomicelles using it as a polymer carrier. Background technique [0002] In recent years, polymer micelles have received widespread attention as an effective drug carrier. The nano-scale particle size and the hydrophilic effect of the micelle shell make the polymer micelles difficult to be swallowed by the reticuloendothelial system, and can prevent the adsorption of proteins and cells, so they can circulate in the blood for a long time and remain stable, so that they can Stay at the target site (such as tumor tissue, inflammatory tissue) for a long time, and achieve passive targeting by enhancing penetration and EPR effect. In the preparation process of drug-load...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/34A61K9/00A61K33/24A61P35/00C08G81/00
Inventor 余家会王成运刘顺英罗淑芳
Owner EAST CHINA NORMAL UNIV
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