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Anti-human progastrin polypeptide immune composition

An immune composition and peptide-mimicking technology, applied in hormone peptides, drug combinations, gastrin/cholecystokinin, etc., can solve the problem of not being able to capture gastrin

Active Publication Date: 2013-11-20
戚胜美
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Thus, antibodies induced by G17DT capture only the G17 and C-terminal extended forms, but not the unprocessed or partially processed gastrin (progastrin), which is abundant in the circulation of gastrointestinal patients

Method used

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  • Anti-human progastrin polypeptide immune composition
  • Anti-human progastrin polypeptide immune composition
  • Anti-human progastrin polypeptide immune composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Peptides were synthesized using standard solid-phase synthesis methods. The amino acid content and purity of each polypeptide were identified using methods commonly used in the art.

[0016] Synthesize a polypeptide with the following amino acid sequence:

[0017] The amino acid sequence of peptide: 1) Cys-pro-Pro-Pro-Pro-Ser-Ser-Gly-Trp-Met-Asp-Phe-Gly-Arg-Arg-Ser-Ala-Glu-Asp-Glu-Asn (SEQ ID NO.: 1) (G-21); 2) pGlu-Gly-Pro-Trp-βLeu-Glu-Glu-Glu-Glu-Glu-Ala-Ser-Ser-Pro-Pro-Pro-Pro-pro-Cys( SEQ ID NO.: 2) (G-18); 3) (hu G17 homologue) pGlu-Gly-Pro-Trp-βLeu-Glu-Glu-Glu-Glu-Glu-Ala-Ser-Ser-Pro- Pro-Pro-pro-Cys (SEQ ID NO.: 3) (G-18LV); 4) pGlu-Gly-Pro-Trp-Ile-Glu-Glu-Glu-Glu-Glu-Ala-Ser-Ser-Pro - Pro-Pro-pro-Cys (SEQ ID NO.4) (G18LI); 5) Cys-pro-Pro-Pro-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly -Trp-Met-Asp-Phe-Gly; (SEQ ID No.5)(G-20a); 6) Cys-pro-Pro-Pro-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu- Ala-pNO 2 -Phe-Gly-Trp-Met-Asp-Phe-Gly; (SEQ ID No.6)(G-20b); 7) Ser-Ser-Pro-P...

Embodiment 2

[0025]The polypeptide-TT cross-linked product in Example 1 was emulsified for immunization, and the preparation method of the emulsion was as follows: the concentration of the cross-linked product and adjuvant in the aqueous phase was twice the concentration in the final emulsion. , the cross-linked product was dissolved in PBS with a pH of 6.5-8 to make a final concentration of 5-12 mg / ml. The aqueous and oily media were mixed 1:1 (v / v) to form an emulsion containing the final immunogen. Various types of oily media known to those skilled in the art can be used. One of the oil phase medium is composed of 20-60 parts of squalene, 70-30 parts of squalane, 2-12 parts of Span 80, 0.6-2 parts of lead monostearate, 0.1-1 part of Tween 80 and 0.2-1.2 parts Tween 40 mixed. The aqueous and oily phases can be mixed by any means known to those skilled in the art to form an emulsifying mixture. The emulsifier must be stable during storage (e.g. no significant separation of the oil and ...

Embodiment 3

[0028] As described in Examples 1 and 2, we used the peptides G18 and G21 in Example 1 to link with TT and DT, respectively, to construct conjugates, and then immunogen with peptide G18 ( Figure 1A , 1B) and peptide G21 immunogen ( Figure 1C , 1D) Six mice were immunized respectively.

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Abstract

Immunogens against human extended-progastrin species comprise (A) a mimetic peptide comprised of (i) the amino acid sequence of a progastrin or a N- and / or C-terminal processed species of a progastrin joined to (ii) a 7 amino-acid spacer coupled to (B) an immunogenic carrier. Illustrative of the mimetic peptide / spacer combination are a 21 amino-acid peptide (SEQ ID NO.: 1) and other, related polypeptides (SEQ ID NOs.: 2-5). Pharmaceutical compositions containing such an immunogen display improved immunological properties, including the induction of effective antibody levels shortly after the administration of an initial course of immunogen. Levels of antibody thus elicited stay elevated for several months and readily elevate to higher levels upon subsequent boosting by a single injection of immunogen.

Description

technical field [0001] The present invention relates to an improved anti-human extended gastrin immune composition. Background technique [0002] Gastrointestinal tumors are the most common tumors in humans, and they are also the diseases that cause the highest mortality in many countries in the world. Many growth factors are known to affect the proliferation of malignant gastrointestinal cells, especially the family of peptide hormones produced during the processing of progastrin. The maturation of progastrin in normal tissues involves multiple processing steps of progastrin intermediates, which eventually form amidated forms of gastrin in the peripheral circulation, namely gastrin G34 and gastrin G17, and gastrin G17. They are called "big" gastrin and "little" gastrin, respectively. These hormones are known to regulate the proliferation of mucosal cells and the secretion of gastric acid after eating (postprandial). It has been reported that progastrin, gastrin especiall...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K39/385A61K47/42A61P1/00A61P35/00C07K14/595C07K7/08C07K7/06
CPCA61K39/0005C07K14/595A61K47/4833A61K47/48338A61K47/646A61K47/65A61P1/00A61P35/00A61P37/00A61P37/04A61K38/16A61K38/1703
Inventor 戚胜美理查德·阿斯旺王宾
Owner 戚胜美