Tumor vaccine based on injectable hydrogel as well as preparation method and application of tumor vaccine

A technology of tumor vaccine and injection water, which is applied in the field of biomedicine, can solve the problems of sudden drug release and non-solution, achieve long-term local sustained release, solve the effect of low utilization rate, and protect the activity

Pending Publication Date: 2021-11-19
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the release amount of tumor antigen and adjuvant exceeds 70% within 5 days, and the problem of drug burst release is still unsolved

Method used

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  • Tumor vaccine based on injectable hydrogel as well as preparation method and application of tumor vaccine
  • Tumor vaccine based on injectable hydrogel as well as preparation method and application of tumor vaccine
  • Tumor vaccine based on injectable hydrogel as well as preparation method and application of tumor vaccine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Preparation of polyaldehyde dextran

[0035] Dissolve 20g (0.50mmol) of dextran (DEX, with a molecular weight of 40000Da) in 300mL of water, stir and dissolve, add 8.6g (0.15mmol solution) of sodium periodate, seal, and at a temperature of 25°C, The reaction was stirred for 24h. After the reaction, it was dialyzed with deionized water for 3 days and freeze-dried to obtain polyaldehyde dextran.

Embodiment 2

[0037] Preparation of 4-arm hydroxylamine polyethylene glycol

[0038] Weigh the hydroxylated polyethylene glycol and dissolve it in toluene, heat and azeotrope to evaporate most of the toluene. Add tetrahydrofuran, N-hydroxyphthalimide (4.8mmol), and triphenylphosphine (4.8mmol), which have been dried with molecular sieves, and dissolve evenly. Under ice bath conditions, use a dropping funnel under N 2 Under protection, diisopropyl azodicarboxylate was slowly added dropwise within 30 minutes. Remove the ice bath, react at room temperature for 24 hours, and remove a large amount of tetrahydrofuran by rotary evaporation, and slowly add petroleum ether to precipitate a solid. The final product was obtained by repeated settling. The final product was dried in vacuo to give a pale yellow solid. Recorded on Bruker AV-500 NMR 1 H NMR spectrum and 13 C NMR Spectrum.

Embodiment 3

[0040] Preparation of 4-arm hydrazide polyethylene glycol

[0041] Fully dissolve 10 grams of hydroxylated polyethylene glycol in 90 mL of anhydrous toluene solution, add 17 mL of tert-butanol solution in which 1.8 grams of potassium tert-butoxide has been dissolved, and after fully mixing, nitrogen gas is passed for 20 minutes by bubbling method . Then, 3.2 mL of ethyl bromoacetate was added dropwise to the solution, and the drop was completed in about 30 minutes. After the reaction solution was stirred at room temperature for 4 hours, it was filtered to remove by-products; the resulting filtrate was concentrated and precipitated with a large amount of anhydrous ether. The resulting product was subjected to at least two CH 2 Cl 2 After dissolution and precipitation with a large amount of anhydrous ether, the bromine-containing impurities in the system can be removed to obtain a purer white product. The resulting PEG derivative was dissolved in methanol, and then a methano...

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Abstract

The invention provides a tumor vaccine based on injectable hydrogel as well as a preparation method and application of the tumor vaccine. The tumor vaccine is prepared from the following raw materials: a tumor antigen, an immunologic adjuvant, multi-arm polyethylene glycol and multi-aldehyde polysaccharide. The tumor vaccine can be constructed in a mild aqueous solution, can efficiently load tumor-associated antigens, adjuvants and the like, can protect the activity of the antigens, the adjuvants and the like, can maintain the stability of the antigens, the adjuvants and the like, realizes long-acting local slow release of the antigens and the adjuvants, and remarkably improves the immunostimulation effect.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to an injectable hydrogel-based tumor vaccine and its preparation method and application. Background technique [0002] Cancer therapy is rapidly entering the era of immunity, and representative immunotherapy methods, such as immune checkpoint inhibitors and CAR T cell therapy, have achieved great success in clinical practice, and more and more related products are entering the market. However, as the earliest and most promising means of tumor immunotherapy, tumor vaccines are developing slowly and are difficult to break through the bottleneck. Tumor vaccines are strategies to control or eliminate tumors by administering tumor-specific antigens to patients and artificially activating tumor-specific immune responses. However, since tumor antigens are difficult to effectively deliver to lymph nodes, the immunogenicity is low when used alone, and even if delivered to i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00A61K39/39A61K47/10A61K47/36A61K9/06A61K9/00A61P35/00
CPCA61K39/0011A61K39/39A61K47/10A61K47/36A61K9/0019A61K9/06A61P35/00A61K2039/54
Inventor 宋万通司星辉于镇滔徐玉笛汤朝晖陈学思
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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