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Anti-inflammatory polypeptide nano drug and preparation method thereof

A nano-drug and responsive technology, applied in anti-inflammatory agents, drug combinations, pharmaceutical formulations, etc., can solve the problems of short half-life of polypeptide drugs, limited clinical application, and inability to take oral administration, etc., and achieves easy large-scale preparation and low price , good in vivo and in vitro safety effects

Inactive Publication Date: 2019-10-08
ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, peptide drugs have problems such as short half-life, poor stability, and inability to be administered orally, which limit their further clinical application

Method used

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  • Anti-inflammatory polypeptide nano drug and preparation method thereof
  • Anti-inflammatory polypeptide nano drug and preparation method thereof
  • Anti-inflammatory polypeptide nano drug and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0040] First, 2mg lecithin and 15mg polyethylene glycol-distearoylphosphatidylethanolamine (the molecular weight of polyethylene glycol is 2000Da) are dissolved in 2mL deionized water under the condition of constant temperature magnetic stirring at 65℃. Dissolve completely, let it cool to room temperature. 50 mg of acetalized α-cyclodextrin was dissolved in 4 mL of methanol. 1 mg Ac2-26 was dissolved in 100 μL of deionized water and added to the above organic phase. Then, while stirring, the organic phase was slowly added dropwise to the water phase (1 mL / min). After the addition is complete, continue stirring at 25°C for 3 hours. After centrifugal separation, washing with deionized water, and freeze-drying, the pH-responsive nanomedicine of the present invention can be obtained. The particle size of nano-medicine is between 100-200nm.

Embodiment 2

[0042] First, 1mg lecithin and 5mg polyethylene glycol-distearoylphosphatidylethanolamine (the molecular weight of polyethylene glycol is 2000Da) are dissolved in 2mL deionized water under the condition of constant temperature magnetic stirring at 65℃. Dissolve and leave to cool to room temperature. 30 mg of acetalized β-cyclodextrin was dissolved in 3 mL of methanol / acetonitrile. 1 mg Ac2-26 was dissolved in 100 μL of deionized water and added to the above organic phase. Then, while stirring, the organic phase was slowly added dropwise to the water phase (1 mL / min). After the addition is complete, continue stirring at 35°C for 4 hours. After centrifugal separation, washing with deionized water, and freeze-drying, the pH-responsive nanomedicine of the present invention can be obtained. The particle size of nanomedicine is between 20-150nm.

Embodiment 3

[0044] First, 0.5 mg of lecithin and 5 mg of polyethylene glycol-distearoyl phosphatidyl ethanolamine (the molecular weight of polyethylene glycol is 2000 Da) are dissolved in 2 mL of deionized water under the condition of constant temperature magnetic stirring at 65°C. Dissolve and leave to cool to room temperature. 40 mg of acetalized γ-cyclodextrin was dissolved in 5 mL methanol / tetrahydrofuran. 1 mg Ac2-26 was dissolved in 100 μL of deionized water and added to the above organic phase. Then, while stirring, the organic phase was slowly added dropwise to the water phase (1 mL / min). After the addition is complete, continue stirring at 45°C for 1 hour. After centrifugal separation, washing with deionized water, and freeze-drying, the pH-responsive nanomedicine of the present invention can be obtained. The particle size of nanomedicine is between 50-250nm.

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Abstract

The invention discloses an anti-inflammatory polypeptide nano drug and a preparation method thereof. The anti-inflammatory polypeptide nano drug comprises anti-inflammatory polypeptides, a pH or reactive oxygen responsive material, phospholipids and polyethylene glycol-distearoyl phosphatidylethanolamine, wherein the anti-inflammatory polypeptide comprises the active N-terminal peptide Ac2-26 of annexin A1 and the tissue protective polypeptide ARA290; the mass ratio of the anti-inflammatory polypeptide to the pH or active oxygen responsive material is 0.01:1 and 2:1, the mass ratio of polyethylene glycol-distearoyl phosphatidylethanolamine to the pH or reactive oxygen responsive material is 0.02:1 and 2.5:1, and the mass ratio of polyethylene glycol-distearoyl phosphatidylethanolamine to phospholipid is 0.01:1 and 1:0.01. The drug can be used in preparation of preventive and therapeutic drugs for acute and chronic inflammation-related diseases. An administration method includes oral administration, intravenous injection, subcutaneous injection, intramuscular injection, and any combination of the above MODEs, and the product has obvious prevention and treatment effects on acute andchronic inflammation-related diseases such as inflammatory bowel disease, peritonitis and atherosclerosis.

Description

Technical field [0001] The present invention relates to a nano-medicine that targets the inflammatory microenvironment of slightly acidic and oxidative stress to exert an anti-inflammatory effect, in particular to a class of inflammatory bowel disease, peritonitis, arterial disease, and inflammatory bowel disease by responding to local low pH or reactive oxygen microenvironment of the lesion. The composition and preparation method of targeted anti-inflammatory polypeptide nanomedicine for atherosclerosis and other acute and chronic inflammation-related diseases, and its application in the prevention and treatment of inflammatory bowel disease, peritonitis, atherosclerosis and other acute and chronic inflammation-related diseases. Background technique [0002] Inflammation is an adaptive response caused by harmful stimuli and conditions, such as infection and tissue damage. Persistent inflammation has become the key pathological basis of many diseases, including arthritis, inflamm...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/24A61K47/40A61K38/02A61P29/00A61P1/00A61P9/10
CPCA61K9/5123A61K9/5146A61K9/5161A61K38/02A61P1/00A61P9/10A61P29/00
Inventor 张建祥李沉纹靳涛涛李兰兰胡厚源郭嘉伟窦寅
Owner ARMY MEDICAL UNIV
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