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Application of heterocyclic compound containing at least two sulfur atoms to preparation of nano vaccine and prepared nano vaccine

A nano-vaccine and compound technology, applied in medical preparations containing active ingredients, medical preparations with non-active ingredients, nanotechnology, etc., can solve the problem of reducing cross-presentation of antigens, inability to avoid enzymatic degradation in lysosomes, Reduce stimulation and activation-promoting effects, achieve high-efficiency immune activation and immune regulation, prevent tumor cell proliferation and virus infection, and improve cross-presentation effects

Pending Publication Date: 2021-10-26
苏州维益生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Existing nano-vaccine mainly enters dendritic cells through the endocytosis-lysosome pathway, that is, after being endocytized by dendritic cells, it will form endocytic bodies or vesicles, and then fuse with intracellular lysosomes. The nuclease or proteolytic enzyme in the lysosome will cut or hydrolyze the nucleic acid adjuvant or antigenic peptide released by the nano-vaccine, reduce the stimulation and activation of dendritic cells by the nucleic acid adjuvant, and affect its effect on the antigenic peptide. Cross-presentation, activation and proliferation of immature T lymphocytes, weakens the body's cellular immune response to antigenic peptides, resulting in poor efficacy of tumor immunotherapy
[0004] In recent years, although liposome mRNA or peptide vaccines developed based on liposome embedding technology can reduce the degradation of their active ingredients by endolysosomes to a certain extent, they still rely on endocytosis-lysosome pathway uptake. Into lymphocytes, unable to avoid the degradation of enzymes in lysosomes; and because polyethylene glycol on the surface of liposomes can effectively resist or hinder the endocytosis of lymphocytes such as macrophages, thereby reducing the uptake efficiency of antigens and the activation ratio of lymphocytes, thereby reducing the cross-presentation of antigens

Method used

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  • Application of heterocyclic compound containing at least two sulfur atoms to preparation of nano vaccine and prepared nano vaccine
  • Application of heterocyclic compound containing at least two sulfur atoms to preparation of nano vaccine and prepared nano vaccine
  • Application of heterocyclic compound containing at least two sulfur atoms to preparation of nano vaccine and prepared nano vaccine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0080] Compound 1: Synthesized in Example 1;

Embodiment 2

[0081] Compound 2: Synthesized in Example 2;

[0082] Compound 3: purchased from McLean Biochemical Technology Co., Ltd.

[0083] Below in conjunction with embodiment, further set forth the present invention:

[0084] Example 1

[0085] The dichloromethane solution containing N,N'-carbonyldiimidazole and lipoic acid was gradually dropped into the dichloromethane of ethylenediamine at 0°C, stirred at 0°C for 1h and at room temperature for another 1h, and washed with anhydrous Sodium sulfate was used to remove water, and then concentrated under reduced pressure to obtain an oily substance. Dissolve the oil in a dichloromethane solution containing 1H-pyrazole-1-carboxamidine hydrochloride, stir, distill under reduced pressure, dissolve the obtained precipitate in methanol, wash the precipitate with ether, and finally obtain Compound 1.

[0086]

[0087] Example 2

[0088]

[0089] Molecule 1 of anhydrous CH 2 Cl 2 Add 1,1-carbonyldiimidazole (CDI) to the solution...

Embodiment 3

[0091] Nano vaccine preparation method: the compound 1 (concentration is 146.2mM) that embodiment 1 makes, the nucleic acid adjuvant (CpG-ODN) of 100mM, the polypeptide antigen of 2.5mg / mL (mouse liver cancer cell H22 polypeptide antigen, amino acid sequence It is HTDAHAQAFAALFDSMH, the N-terminal is connected with Cy3 label, and the isoelectric point is 5.71) mixed according to the volume ratio of 1:1:1, and put into the TM buffer buffer solution (pH 7.4) of 60-70 times the total volume, at 37 Mix and stir for 15 minutes at ℃, and dialyze in deionized water for 24 hours to remove unloaded nucleic acid adjuvant or polypeptide antigen, and finally obtain the nano-vaccine.

[0092] After the nano-vaccine was prepared by shock dialysis, the particle size was measured and the scanning electron microscope was used to characterize the successful preparation of the nano-vaccine. The results show that CpG-ODN, polypeptide antigen and compound 1 can form a spherical nano-vaccine in TM ...

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Abstract

The invention relates to the technical field of immunotherapy or vaccine prevention and treatment, in particular to a heterocyclic compound containing two or more sulfur atoms and an application of the heterocyclic compound to preparation of a nano vaccine. The invention provides an application of the heterocyclic compound which contains at least two sulfur atoms and can be covalently or non-covalently connected with polypeptide to preparation of the nano vaccine. Nanoparticles prepared by self-assembly of the compound and an antigen can enter dendritic cytoplasm in a transmembrane mode, and the uptake efficiency of the antigen and an immunologic adjuvant is improved. In the process of entering the cells, biodegradation of an enzyme body in lysosome on antigens or nucleic acid adjuvants can be effectively avoided or reduced, so that the nano vaccine disclosed by the invention can efficiently activate the dendritic cells and improve the cross presentation effect on the antigens, further CD8 + T cells can be effectively activated, and proliferation of the T cells can be promoted. Therefore, the nano vaccine provided by the invention can prevent tumor cell proliferation and virus infection by utilizing efficient immune activation and immune regulation effects.

Description

technical field [0001] The invention relates to the technical field of immunotherapy or vaccine prevention and control, in particular to the application of heterocyclic compounds containing two or more sulfur atoms in the preparation of nano vaccines and the prepared nano vaccines. Background technique [0002] In recent years, the research and development of immune vaccines has made significant progress in the comprehensive prevention and treatment of cancer and viral infections, and has high clinical application value in anti-tumor or anti-viral infections. At present, countries have successively developed various anti-tumor or anti-viral vaccines for disease prevention or treatment and have entered clinical phase I and II, and some have been approved for clinical use in the United States and Europe. However, such vaccines still face some challenges in stimulating the maturation of antigen-presenting cells and enhancing cross-presentation. After entering intracellular lys...

Claims

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Application Information

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IPC IPC(8): A61K39/385A61K39/39A61K47/22A61K47/54A61P31/12A61P35/00B82Y5/00
CPCA61K39/385A61K39/39A61P35/00A61P31/12A61K2039/55561A61K39/0011A61P31/04A61K2039/60A61K2039/627B82Y5/00Y02A50/30A61K2039/55555A61K39/12C12N2770/20034A61P31/14A61K2039/5154A61K47/6455A61K47/6929A61K47/545A61K2039/844A61K39/215B82Y40/00C07D339/04C12N7/00
Inventor 杨黄浩李娟张达刘小龙
Owner 苏州维益生物科技有限公司
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