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Acid-sensitive nanometer protein gel based on cytochrome C as well as preparation method and application thereof

A technology of protein gel and cytochrome, which is applied in the field of biomedicine to achieve the effect of increasing the half-life of the body, prolonging the half-life of the drug, and improving the circulation time in the body

Inactive Publication Date: 2018-02-13
GUANGDONG MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But at the same time, positively charged nanogels are also easily recognized and eliminated by the mononuclear phagocyte system (MPS) in the blood, so the development of a method that can prevent nanogels from being cleared by the mononuclear phagocyte system (MPS) At the same time, a method to enable protein drugs to enter tumor cells is very necessary

Method used

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  • Acid-sensitive nanometer protein gel based on cytochrome C as well as preparation method and application thereof
  • Acid-sensitive nanometer protein gel based on cytochrome C as well as preparation method and application thereof
  • Acid-sensitive nanometer protein gel based on cytochrome C as well as preparation method and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Preparation of acid-sensitive nanoprotein gel

[0037] 1). Preparation of α-methoxy-ω-benzaldehyde polyethylene glycol: 1.75g ​​methoxypolyethylene glycol amine and 0.25g 4-formylbenzoic acid succinimide ester were dissolved in 18.5mL dimethyl In base formamide, and then stirred at 3°C ​​for 3h, a mixture A was formed, and the mixture A was slowly added dropwise to 137mL of frozen ether while keeping stirring, and after standing for 8h, a solid B was obtained, and the solid B was mixed with ether After washing twice, dissolve in 100 mL of isopropanol (Chengdu Jinshan Chemical Reagent Co., Ltd., analytically pure grade) at a temperature of 18°C ​​to obtain solution C, then lower the temperature of solution C to 3°C, and after standing for 3 hours , the solid D was precipitated, and the solid D was dried to obtain α-methoxy-ω-benzaldehyde polyethylene glycol (PEG-BzA);

[0038] 2). Preparation of nano-protein gel: 0.001 mol cytochrome C, 2.3 mol acrylamide, 0.5 mol N-(3-...

Embodiment 2

[0041] Preparation of acid-sensitive nanoprotein gel

[0042]1). Preparation of α-methoxy-ω-benzaldehyde polyethylene glycol: 2.25g methoxypolyethylene glycol amine and 0.25g 4-formylbenzoic acid succinimide ester were dissolved in 21mL dimethyl Formamide, then stirred at 5°C for 5 hours to form a mixture A, and slowly added the mixture A dropwise to 220 mL of frozen diethyl ether while keeping stirring, and after standing for 12 hours, a solid B was obtained, and the solid B was washed with diethyl ether After two times, it was dissolved in 100 mL of isopropanol (Chengdu Jinshan Chemical Reagent Co., Ltd., analytically pure grade) at a temperature of 25° C. to obtain solution C, and then the temperature of solution C was lowered to 5° C. After standing for 6 hours, The solid D was precipitated, and the solid D was dried to obtain α-methoxy-ω-benzaldehyde polyethylene glycol (PEG-BzA);

[0043] 2). Preparation of nano-protein gel: 0.001mol cytochrome C, 2.5mol acrylamide, 0.7...

Embodiment 3

[0046] Preparation of acid-sensitive nanoprotein gel

[0047] 1). Preparation of α-methoxy-ω-benzaldehyde polyethylene glycol: Dissolve 2g of methoxypolyethylene glycol amine and 0.25g of succinimide 4-formylbenzoate in 20mL of dimethyl formaldehyde amide, and then stirred at 4°C for 4 hours to form a mixture A, which was slowly added dropwise to 200 mL of frozen ether while maintaining stirring, and after standing for 10 hours, a solid B was obtained, and the solid B was washed with ether for two After three times, it was dissolved in 100mL of isopropanol (Chengdu Jinshan Chemical Reagent Co., Ltd., analytically pure grade) at a temperature of 23°C to obtain solution C, and then the temperature of solution C was lowered to 4°C, and after standing for 5h, precipitated Solid D, solid D was dried to obtain α-methoxy-ω-benzaldehyde polyethylene glycol (PEG-BzA);

[0048] 2). Preparation of nano-protein gel: 0.001 mol cytochrome C, 2.4 mol acrylamide, 0.6 mol N-(3-)methacrylamide...

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Abstract

The invention discloses an acid-sensitive nano-protein gel based on cytochrome C and its preparation method and application. The preparation method of the acid-sensitive nano-protein gel of the present invention comprises the following steps: 1) α-methoxy-ω-benzene Preparation of formaldehyde-polyethylene glycol; 2) preparation of nano-protein gel; 3) α-methoxy-ω-benzaldehyde-polyethylene glycol and nano-protein gel were mixed and reacted overnight. The acid-sensitive nano-protein gel of the present invention has good stability at physiological pH, and the benzimide bond is broken in acidic tumor tissue, and the exposed positively charged protein gel can enter tumor cells, and the Cytochrome C is released in a reducing environment and induces apoptosis. The preparation method of acid-sensitive nano-protein gel has the advantages of easy-to-obtain raw materials, simple process, warm reaction conditions, and low cost. The acid-sensitive nano-protein gel of the invention is applied to the targeted delivery, control and release of protein drugs, and enhances the anticancer effect of protein drugs.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to an acid-sensitive nano-protein gel based on cytochrome C and its preparation method and application. Background technique [0002] Cytochrome C (CytC for short) is a water-soluble protein located in the inner membrane of mitochondria and capable of inducing apoptosis. Studies have found that cytochrome C (CytC) can induce tumor cell apoptosis and play an anti-tumor effect. However, cytochrome C (CytC) cannot penetrate the cell membrane, so its clinical efficacy is greatly limited. Therefore, improving the cell delivery ability of cytochrome C (CytC) is its goal in tumor therapy. [0003] With the development of science and technology, the research of drug delivery system has attracted widespread attention. Nanoscale polymer drug delivery systems, such as nanogels, nanoparticles, nanomicelles, dendrimers, etc., have flexible molecular design, diverse synthesis methods, cont...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K38/41A61K47/10A61K47/32C08F289/00C08G12/22A61P35/00
CPCA61K9/06A61K38/415A61K47/10A61K47/32C08F289/00C08G12/22C08F220/56
Inventor 刘建强刘赣古楚莹李宝红罗志董刘伟聪郑明彬
Owner GUANGDONG MEDICAL UNIV
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