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Long-acting nanometer composite peptide resistant to II-type diabetes and preparing method and application of long-acting nanometer composite peptide

A nano-composite, diabetes technology, applied in the directions of non-active ingredients medical preparations, medical preparations containing active ingredients, metabolic diseases, etc., can solve the problems of prolonging the half-life of active polypeptide drugs, reducing bioavailability, and small molecular weight, etc. Achieve the effect of improving in vivo half-life and bioavailability, significant curative effect, protecting and restoring β-cell function

Active Publication Date: 2014-11-12
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] VPAC2 receptor-specific agonist active peptides have good glucose-dependent hypoglycemic effect, but often have a small molecular weight, short half-life in vivo, and reduced bioavailability. The biological role of polypeptides, coupling these active polypeptides with chitosan-modified nanocarrier particles as a new drug system can effectively improve the water solubility and in vivo stability of polypeptide drugs, control the release of drugs in vivo and target selectivity, Effectively prolong the half-life of active peptide drugs, which has important medicinal value

Method used

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  • Long-acting nanometer composite peptide resistant to II-type diabetes and preparing method and application of long-acting nanometer composite peptide
  • Long-acting nanometer composite peptide resistant to II-type diabetes and preparing method and application of long-acting nanometer composite peptide
  • Long-acting nanometer composite peptide resistant to II-type diabetes and preparing method and application of long-acting nanometer composite peptide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Preparation of nanocomposite peptides DBAYL-CS-SeNPs and BAY55-9837-CS-SeNPs

[0043] The amino acid sequence of DBAYL is:

[0044] MHSDAVFTDQYTRLRKQLAAKKYLQSLKQKRY;

[0045] The amino acid sequence of BAY55-9837 is:

[0046] HSDAVFTDNYTRLRKQVAAKKYLQSIKNKRY;

[0047] Under normal temperature and pressure, weigh 8.7mg Na 2 SeO 3 Dissolve in double-distilled water, and dilute to 10mL to obtain 5mM Na 2 SeO 3 solution; weigh 35.2mg of ascorbic acid (Vc), dissolve it in double-distilled water, and set the volume to 10mL to obtain a 20mM Vc solution; weigh 8mg of chitosan, dissolve it in double-distilled water, and set the volume to 10mL to obtain 0.8 mg / mL chitosan solution. Draw 1mL of the prepared Vc solution into a small beaker, add 1mL of Na 2 SeO 3 Shake the solution evenly while adding it, and when the color no longer deepens, transfer to a low temperature (0-4° C.) for reaction for 4 hours to obtain a crude nano-selenium particle solution.

[0048] Weigh 1 ...

Embodiment 2

[0051] Transmission electron microscopy (TEM) detection of prepared nanocomposite peptides DBAYL-CS-SeNPs and BAY55-9837-CS-SeNPs

[0052] The morphology of the nanocomposite peptides DBAYL-CS-SeNPs and BAY55-9837-CS-SeNPs was observed with a TECNAI-10 transmission electron microscope (Philips): the nanocomposite peptides were evenly dispersed, and the samples were dipped with a copper grid to determine the obtained sample The size, shape and uniformity of the particles, and take representative electron micrographs.

[0053] Experimental results such as figure 2 , the prepared nanocomposite peptide DBAYL-CS-SeNPs ( figure 2 A) and BAY55-9837-CS-SeNPs ( figure 2 B), has good dispersibility, the particle size is about 100nm, the particle shape is spherical, and the uniformity is good.

Embodiment 3

[0055] Zeta potential and Fourier transform infrared spectroscopy (FT-IR) detection of prepared nanocomposite peptides DBAYL-CS-SeNPs and BAY55-9837-CS-SeNPs

[0056] The Zeta potentials of SeNPs, SeNPs-CS and two nanocomposite peptides DBAYL-CS-SeNPs and BAY55-9837-CS-SeNPs were measured by Nano-ZS (Malvern Instruments Limited), and the differences between them were compared. Experimental results such as image 3 As shown, the zeta potential of SeNPs is -8.5mV, that of SeNPs-CS is 47.5mV, that of DBAYL-CS-SeNPs is 34.9mV, and that of BAY55-9837-CS-SeNPs is 29.8mV.

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Abstract

The invention discloses a long-acting nanometer composite peptide resistant to II-type diabetes and a preparing method and application of the long-acting nanometer composite peptide. Nano-selenium serves as a carrier, chitosan performs a connection function, and accordingly covalent binding of active polypeptides and nano-selenium particles is achieved. The prepared nanometer composite peptide has the functions of carrying, protecting and slowly releasing therapeutic polypeptides and effectively prolonging the half-life period of the therapeutic polypeptides in the physiological environment. Effective dosage of the peptide with a therapeutic effect can be obviously lower than dosage of the therapeutic polypeptides which are used separately, and the biological functions of medicine slow releasing and long-acting treatment can be performed. The defect that when used separately, the therapeutic polypeptides are prone to being quickly metabolized and removed in the body due to the fact that the molecular weight of the therapeutic polypeptides is small is overcome, and the half-life period and bioavailability of the small-molecule therapeutic polypeptides in the body can be effectively improved. The nanometer composite peptide can be used for preparing medicines for treating the following diseases of diabetes and hyperglycemia. The preparing method is high in efficiency and low in cost and the application prospect is wide.

Description

technical field [0001] The invention belongs to the field of nano-biotechnology, and in particular relates to a long-acting nano-composite peptide for anti-type 2 diabetes and its preparation method and application. Background technique [0002] Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide with important biological functions discovered in 1990 and secreted by the pituitary gland. It is a new member of the secretin / glucagon / VIP family. PACAP exists in two forms: PACAP38, which consists of 38 amino acids; PACAP27, which consists of 27 amino acids at the N-terminal of PACAP38. PACAP exerts extensive and important biological functions by activating its specific G protein-coupled receptors and increasing the concentration of second messengers such as cAMP in target cells. PACAP has three types of G protein-coupled receptors: PAC1, VPAC1 and VPAC2; the three types of receptors have different distributions in organisms and play different roles. Among t...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K38/00A61P3/10
Inventor 马义洪岸陈填烽
Owner JINAN UNIVERSITY
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