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Novel diagnosis and treatment integrated hybridization micelle and preparation method thereof

A hybrid and micelle technology, which is applied in the field of new hybrid micelles for the integration of diagnosis and treatment and its preparation, can solve the problems of inability to effectively and clearly track and observe the therapeutic effects of drugs, the inability to organically combine cancer diagnosis and treatment, and drug leakage. To achieve the effect of flexible and easy control, superior performance and strong repeatability

Inactive Publication Date: 2013-07-24
TONGJI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to provide a novel hybrid micelle for diagnosis and treatment and its preparation method in order to overcome the above-mentioned defects in the prior art. The drug rate is low, the drug leaks, the cancer diagnosis and treatment cannot be organically combined, and the drug treatment effect cannot be effectively and clearly tracked, and it can prolong the half-life of the drug in the body, improve the distribution of the drug in the body, and reduce the elimination of the drug by the kidney or liver , to protect the drug from degradation

Method used

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  • Novel diagnosis and treatment integrated hybridization micelle and preparation method thereof
  • Novel diagnosis and treatment integrated hybridization micelle and preparation method thereof
  • Novel diagnosis and treatment integrated hybridization micelle and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0041] (1) Preparation of mPEG-COOH (Mn: 2000)

[0042]In 50 mL of anhydrous 1,4-dioxane solution, 2 g, 1 mmol mPEG (Mn: 2000), and 0.25 g, 2.5 mmol succinic anhydride were added, and 0.125 g, 1 mmol DMAP was added as a catalyst. The mixture was reacted at room temperature for 24 h under nitrogen protection; after the reaction was completed, the reaction solvent was removed by rotary evaporation. Then the reactant was dissolved in a small amount of dichloromethane, extracted and purified three times in a saturated solution of NaCl, and the organic phase was collected; the collected product was precipitated in ether, filtered, and the solid phase precipitate was collected, repeated twice, and dried in vacuo The final white powdery solid is mPEG-COOH.

[0043] (2) mPEG-S-S-NH 2 preparation

[0044] Under the protection of nitrogen, 0.62mmol EDC·HCl, 0.23mmol NHS were added to the dichloromethane solution dissolved in 0.4g, 0.2mmol mPEG-COOH, stirred for 5h; 0.15g, 1mmol desal...

Embodiment 2

[0048] (1) Preparation of mPEG-COOH (Mn: 5000)

[0049] In 50 mL of anhydrous 1,4-dioxane solution, 2 g, 0.4 mmol mPEG (Mn: 5000), and 0.1 g, 1 mmol succinic anhydride were added, and 0.05 g, 0.4 mmol DMAP was added as a catalyst. The mixture was reacted at room temperature for 24 h under nitrogen protection; after the reaction was completed, the reaction solvent was removed by rotary evaporation. Then the reactant was dissolved in a small amount of dichloromethane, extracted and purified three times in a saturated solution of NaCl, and the organic phase was collected; the collected product was precipitated in ether, filtered, and the solid phase precipitate was collected, repeated twice, and dried in vacuo The final white powdery solid is mPEG-COOH.

[0050] (2) mPEG-S-S-NH 2 preparation

[0051] Under the protection of nitrogen, 0.62mmol EDC·HCl, 0.23mmol NHS were added to the dichloromethane solution dissolved in 1g, 0.2mmol mPEG-COOH, stirred for 5h; 0.15g, 1mmol desalt...

Embodiment 3

[0056] Self-assembly of polymer complex micelles

[0057] Take 30mg of mPEG-S-S-MTX (Mn: 2000), 20mg of Pal-AAAAHHHD in a sample bottle, add 10ml of deionized water and sonicate for 2 hours to self-assemble to form polymer composite micelles, and dialyze with a dialysis bag with a cut-off of 1000 for 24 hours, Change the water every 6 hours to remove uncomplexed micelles.

[0058] Preparation of drug-loaded magnetic composite micelles by co-precipitation

[0059] Add the configured Fe to the complex micellar solution under the protection of nitrogen 3+ , Fe 2+ , the iron salt solution with a molar ratio of 2:3 was vigorously stirred at room temperature for 0.5 h, then the temperature was raised to 80°C under vigorous stirring, and ammonia water was slowly added to react for 1 h, and the magnetic balls were prepared by co-precipitation method.

[0060] The particle size of the obtained polymer composite micelles is as follows image 3 As shown, the transmission electron mic...

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Abstract

The invention relates to a novel diagnosis and treatment integrated hybridization micelle and a preparation method thereof. The hybridization micelle is a compound micelle which is self-assembled of two segmented copolymers through a dewatering effect. During preparation, the central nucleus of the compound micelle self-assembled of the two segmented copolymers through the dewatering effect is composed of an amphiphilic polymer hydrophobic chain segment and a hydrophobic medicine, a shell layer is a polymer hydrophilic chain segment, and special groups on the chain segment are used for generating magnetic nanoparticles on the shell layer in situ by a chemical coprecipitation method. Compared with the prior art, the preparation method has the advantages of being mild in preparation conditions and being simple, convenient and easy to carry out. The prepared micelle is stable in structure, has very good biocompatibility and biodegradability and can rapidly release medicine in a tumor environment, thus having the diagnosis-treatment integrated application potentiality.

Description

technical field [0001] The invention belongs to the field of macromolecule nano biomedical materials, and in particular relates to a novel hybrid micelle integrating diagnosis and treatment and a preparation method thereof. Background technique [0002] Cancer is a major disease that endangers human health. Chemotherapy is the basic method of cancer treatment. Chemotherapy is of great significance for the treatment of cancer and the control of metastasis of cancer cells. However, chemotherapy also faces many unsolved problems. For example, the side effects of the drug are large, the solubility is low, the circulation time is short, there is no targeting, and the utilization rate of the drug is low. The development of new multifunctional nano-drug delivery systems is the main way to solve such problems, so it has attracted extensive attention of many researchers. [0003] Polymer micelles are a common nano-drug delivery system. How to selectively release drugs at lesion site...

Claims

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Application Information

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IPC IPC(8): A61K9/107A61K47/42A61K47/34A61K49/14A61K49/12
Inventor 李永勇马俊平董海青吴畏时东陆
Owner TONGJI UNIV
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