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Compound micelle-based nano-vector, and preparation method and application thereof

A technology of compound micelles and nanocarriers, which can be applied in preparations for in vivo experiments, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problem of the restriction of the application range of anti-tumor antibiotics, multi-drug resistance Drugs, anti-tumor antibiotics strong cytotoxicity and other issues, to overcome multi-drug resistance, good stability, good biocompatibility and biodegradability effect

Inactive Publication Date: 2014-03-26
SHENZHEN INST OF ADVANCED TECH
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  • Claims
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Problems solved by technology

[0003] But at the same time, antitumor antibiotics also have strong cytotoxicity, which can produce a wide range of biochemical effects on the body.
In addition, it also presents defects such as multi-drug resistance in clinical application, for example, doxorubicin can be cross-resistant with daunorubicin, etc., so the application range of anti-tumor antibiotics is greatly restricted

Method used

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  • Compound micelle-based nano-vector, and preparation method and application thereof
  • Compound micelle-based nano-vector, and preparation method and application thereof

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preparation example Construction

[0037] In a more specific embodiment of the present invention, the preparation method may include the following steps:

[0038] ① Prepare dextran-4-nitro-p-benzochloroformate (DEX-PNC) by precipitation washing and vacuum drying, the purpose is to introduce acid chloride on dextran;

[0039] ② DEX-PNC and cystamine hydrochloride dissolved in water were obtained by dialysis to obtain DEX-SS-NH 2 polymer;

[0040] ③ Active components activated by succinic anhydride and DEX-SS-NH 2 The reduction-responsive dextran-loaded active component is obtained by dialysis, and the reduction-responsive dextran-loaded active component is combined with water-soluble vitamin E to obtain a composite micelle by dialysis.

[0041] Among them, dithiodianhydride can also be used instead of cystamine hydrochloride to obtain reduction-sensitive bonds.

[0042] Moreover, in the present invention, multidrug resistance can be overcome to the greatest extent by adjusting the dosage of water-soluble vita...

Embodiment 1

[0055] Example 1: Preparation of dextran-4-nitro-p-benzochloroformate (DEX-PNC)

[0056]Dissolve 0.3 g of dextran with a molecular weight of 40,000 in 40 mL of dimethyl sulfoxide and pyridine (1:1 by volume) solution, add 0.62 g of 4-dimethylaminopyridine and 0.04 g of 4-nitroparaben chloroformate , react in ice bath for 4h, after the reaction, sink into 10 times the mixture of ethanol and ether (v / v=1 / 1), wash the precipitate, and dry it in vacuum to obtain DEX-PNC polymer. Dissolve 1.6g of cystamine hydrochloride into 30mL of dimethyl sulfoxide solution, react with the DEX-PNC polymer obtained above for 24h at room temperature, and then dialyze to obtain DEX-SS-NH 2 Polymer, the obtained product was reacted with succinic anhydride-activated doxorubicin to obtain DEX-SS-DOX micelles.

Embodiment 2

[0057] Embodiment 2: the preparation of DEX-SS-DOX and TPGS

[0058] The above-mentioned product DEX-SS-DOX and the natural water-soluble vitamin E of 5% by mass ratio obtain composite micelles by the method of dialysis, and its structure can refer to figure 1 .

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Abstract

The invention discloses a compound micelle-based nano-vector, and a preparation method and application thereof. The nano-vector comprises a compound micelle which is mainly formed by glucan, an active component combined with glucan through a reduction-sensitive bond, and water-soluble vitamin E (such as TPGS, namely tocopherol polyethylene glycol succinate), wherein the casing of the compound micelle is mainly formed by glucan and the hydrophyllic terminal of the water soluble vitamin E, and the core is mainly formed by the active component and the hydrophobic terminal of the water soluble vitamin E; the reduction-sensitive bond is preferably disulfide bond, and the active component can be adriamycin. The preparation method comprises the step of dialyzing the glucan-active component micelle and the water soluble vitamin E to form the compound micelle. The nano-vector can effectively realize targeted release of anti-tumor antibiotics and other active components in a physiological environment, and reduces the side effect and drug resistance; the preparation method is simple and feasible, low in cost and convenient to popularize, and is applicable to application of targeted drug vectors, genetic vectors or bio-probe vectors.

Description

technical field [0001] The invention relates to a drug carrier and a preparation process thereof, in particular to a composite micelle-based nano drug carrier and a preparation method thereof. Background technique [0002] Antitumor antibiotics, such as doxorubicin, can inhibit the synthesis of RNA and DNA, have a broad antitumor spectrum, and have effects on a variety of tumors. They are cycle non-specific drugs that can kill tumor cells in various growth cycles . [0003] But at the same time, antitumor antibiotics also have strong cytotoxicity and can produce a wide range of biochemical effects on the body. In addition, it also presents defects such as multi-drug resistance in clinical application. For example, doxorubicin can be cross-resistant with daunorubicin, etc., which greatly restricts the application range of anti-tumor antibiotics. Contents of the invention [0004] An object of the present invention is to provide a nanocarrier based on complex micelles, whi...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K9/107A61K48/00A61K49/00A61P35/00A61K31/704A61K47/54A61K47/61
Inventor 蔡林涛王碧刘朋丁泽轩
Owner SHENZHEN INST OF ADVANCED TECH
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