Compound for enhancing immune response

A technology for enhancing immunity and amino compounds, which is applied in the field of complexes for enhancing immune response, which can solve the problems of insufficient safety and effectiveness data, large side effects, and poor effect, and achieve the effect of convenient pharmaceutical preparation, easy absorption, and enhanced immune response

Active Publication Date: 2018-12-25
XINFU BEIJING MEDICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In August 2012, Hemispherx biopharmaceutical company submitted further original clinical research data, but it was rejected by the US Food and Drug Administration (FDA) due to insufficient safety and efficacy data
[0007] It can be seen that s

Method used

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  • Compound for enhancing immune response
  • Compound for enhancing immune response
  • Compound for enhancing immune response

Examples

Experimental program
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preparation example Construction

[0159] According to one aspect of the present invention, the present invention also relates to a method for preparing a compound for enhancing immune response, comprising:

[0160] contacting polyinosinocytes, at least one cationic stabilizer, and a soluble calcium salt in a liquid reaction system;

[0161] The cationic stabilizer is a water-soluble non-antibiotic amino compound with a molecular weight of ≤5kDa, or the water-soluble non-antibiotic amino compound mixed with polyethylene glycol monomethyl ether, polyethylene glycol, polyethyleneimine, folic acid, galactose One or more of the formed grafts.

[0162] In some embodiments, the polyinosinic acid is prepared by base pairing reaction of polycytidylic acid and polyinosinic acid.

[0163] In some embodiments, the molecular weight of the polycytidylic acid and polyinosinic acid is greater than 23,000 Daltons.

[0164] In some embodiments, the polycytidylic acid has a molecular weight ranging from 66,000 Daltons to 660,0...

Embodiment 1

[0191] The preparation of embodiment 1 pamica

[0192] 1. Preparation of Pamika Complex

[0193] 1. Prepare PBS solution (pH7.2):

[0194] 1.1 Prepare sodium chloride solution (0.85%, 1500ml): weigh 12.75g of sodium chloride, put it into a 2000ml measuring cylinder, and dilute to 1500ml with water;

[0195] 1.2 Prepare disodium hydrogen phosphate solution (0.006mol / L, 500ml): weigh disodium hydrogen phosphate 0.006×0.5×141.96=0.4259g, put it into a 500ml volumetric flask, and dilute to 500ml with 0.85% normal saline;

[0196] 1.3 Prepare sodium dihydrogen phosphate solution (0.006mol / L, 500ml): weigh sodium dihydrogen phosphate 0.006×0.5×137.99=0.4140g, put it into a 500ml volumetric flask, and dilute to 500ml with 0.85% normal saline;

[0197] 1.4 Prepare a PBS solution with a pH value of 7.2: take 273.6ml of "1.2 solution" + 126.4ml of "1.3 solution".

[0198] 2. Prepare PIC solution (2.0mg / ml, 100ml):

[0199] 2.1 Weigh PI 2.0mg / ml*100ml*【1.04 / (1.04+1)】 / 91.5% / (1-2.7%)=1...

Embodiment 2

[0279] Embodiment 2 Pamika combined with PEI increases the solubility test

[0280]Refer to the preparation method of "Pamica combined with PEG" (i.e. Example 1) for preparation. After increasing the amount of COS in Pamica, precipitation occurs, which affects the uniformity of its administration. After adding PEI, precipitation can be avoided and COS can be increased. The dosage can further enhance its immune effect.

[0281]

[0282] The test clearly showed that after pamicha combined with PEI, the solubility of COS in PIC was increased from 1.6mg / ml to 6.4mg / ml, at least 4 times.

[0283] CN105396130A patent application literature discloses a "calcium dermamine adjuvant and a vaccine containing calcium dermamine adjuvant", and discloses that the non-antibiotic amino compound can be selected as chitosan.

[0284] In this comparative example, water-soluble chitosan (chitosan hydrochloride, referred to as CS) was used to replace the chitosan oligosaccharide in Example 1, s...

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Abstract

The invention relates to a novel compound, and researches the preparation, application and other aspects of the compound. The compound is prepared from at least the following components under suitableconditions: polyinosinic cells, cationic stabilizers and soluble calcium salts, wherein, the cationic stabilizer is a non-antibiotic amino compound with a molecular weight less than or equal to 5 kilodalton or a graft formed by the non-antibiotic amino compound and one or more of polyethylene glycol monomethyl ether, polyethylene glycol, polyethyleneimine, folic acid and galactose. The compound has moderate viscosity and molecular mass, convenient pharmacy, stable chemical properties, difficult degradation during long-term storage and safe use. The compound can significantly enhance the nonspecific immune response of the body when the compound is used alone to achieve the purpose of preventing and treating diseases, and has better anti-tumor, anti-virus and anti (super) bacteria functionswhen the compound is used in combination with other medicines and is easy to be absorbed by patients.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a complex for enhancing immune response. Background technique [0002] Double-stranded RNA (dsRNA) adjuvants are generally considered to include PIC (polyriboinosinic-polyribocytoidylic acid), PICLC (PIC with poly-L-lysine andcarboxymethylcellulose), PIC 12 U(PIC with uridylic acid in specific interval, trade name Ampligen) and PICKCa((PIC-kanamycin-CaCl 2 ), which are ligands of various membrane recognition receptors (PRRs), enhance the immune response on the one hand, and change the type of immunity on the other hand, making it possible for preventive vaccines to become therapeutic vaccines. [0003] PIC (polyinocyte) was developed by Merck in the 1960s. In mice, PIC is an inducer of IFN-α and has antiviral activity. PIC protects mice from lethal nasal and lung infections. However, due to the degradation of PIC by primate and human serum nucleases, the stability of PIC structure ...

Claims

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Application Information

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IPC IPC(8): A61K39/39A61K33/14A61P37/04A61K31/722A61K31/713
CPCA61K31/713A61K31/722A61K33/14A61K39/39A61K2039/55505A61K2039/55583A61P37/04A61K2300/00Y02A50/30
Inventor 林海洋刘芳查力
Owner XINFU BEIJING MEDICAL TECH CO LTD
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