Mitochondria-targeted anti-inflammatory polypeptide nano-drug as well as preparation method and application thereof

A nano-drug and mitochondrial technology, applied in the field of medicine, can solve problems such as low bioavailability, and achieve the effects of low cost, improved targeting effect, and simple preparation method.

Active Publication Date: 2021-09-03
ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, because peptide drugs are prone to degradation in the in vivo environment, their bioavailability is low

Method used

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  • Mitochondria-targeted anti-inflammatory polypeptide nano-drug as well as preparation method and application thereof
  • Mitochondria-targeted anti-inflammatory polypeptide nano-drug as well as preparation method and application thereof
  • Mitochondria-targeted anti-inflammatory polypeptide nano-drug as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036]Dissolve 6mg of lecithin, 9mg of polyethylene glycol-distearoylphosphatidylethanolamine solution and 15mg of cetylbromotriphenylphosphine in 15mL of water, heat at 65°C for 30min to obtain the aqueous phase; 30mg of active Oxygen-responsive and scavenging-capable carrier material TPCD (β-cyclodextrin with imidazolecarbonyloxy-2,2,6,6-tetramethylpiperidine nitroxide and 4-imidazolecarbonyloxy-phenylboronic acid pinacol (obtained by ester reaction) was dissolved in 5 mL of methanol to obtain an organic phase; then the organic phase was slowly added dropwise to the cooled water phase, magnetically stirred at 25°C for 120 min, centrifuged, and freeze-dried to obtain mitochondria-targeted nano The drug TTPCD NP has a particle size of 105 nm.

Embodiment 2

[0038] Dissolve 6mg of lecithin, 9mg of polyethylene glycol-distearoylphosphatidylethanolamine solution in 15mL of water, and dissolve by heating at 65°C for 30min to obtain the aqueous phase; The carrier material with scavenging ability is TPCD (β-cyclodextrin reacted with imidazole carbonyloxy-2,2,6,6-tetramethylpiperidine nitroxide and 4-imidazole carbonyloxy-phenylboronic acid pinacol ester ) was dissolved in 5mL methanol to obtain an organic phase; then the organic phase was slowly added dropwise to the cooled water phase, magnetically stirred at 30°C for 120min, centrifuged, and freeze-dried to obtain the anti-inflammatory polypeptide nano drug A-TPCD NP with a particle size of 104nm.

Embodiment 3

[0040] Dissolve 6mg of lecithin, 9mg of polyethylene glycol-distearoylphosphatidylethanolamine solution and 15mg of cetylbromotriphenylphosphine in 15mL of water, and heat at 65°C for 30min to obtain the aqueous phase; mg polypeptide drug Ac2-26 and 30 mg active oxygen response and scavenging capacity of the carrier material TPCD (β-cyclodextrin with imidazole carbonyloxy-2,2,6,6-tetramethylpiperidine nitrogen oxide and 4-imidazole carbonyloxy-phenylboronic acid pinacol ester reaction) was dissolved in 5mL methanol / DMSO to obtain an organic phase; then the organic phase was slowly added dropwise to the cooled water phase, magnetically stirred at 25°C for 120min, and centrifuged. After freeze-drying, the mitochondria-targeted anti-inflammatory polypeptide nano drug A-TTPCD NP can be obtained, with a particle size of 109 nm.

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Abstract

The invention discloses a mitochondria-targeted anti-inflammatory polypeptide nano-drug as well as a preparation method and application thereof. The mitochondria-targeted anti-inflammatory polypeptide nano-drug is composed of a carrier material with active oxygen response and removal capacity, a mitochondria-targeted unit and anti-inflammatory polypeptide, and the mass ratio of the mitochondria-targeted unit to the carrier material with the active oxygen response and removal capacity ranges from 1: 0.2 to 1: 350. The mass ratio of the anti-inflammatory polypeptide to the carrier material with the active oxygen response and removal capability is (1: 0.3)-(1: 300), and the particle size of the nano-drug is 10-500nm. The medicine disclosed by the invention can be applied to preparation of medicines for preventing and treating various acute and chronic inflammations or oxidative stress related diseases, and the administration modes comprise oral administration, intravenous injection, subcutaneous injection, intramuscular injection and any combination of the modes. The nano-drug has remarkable prevention and treatment effects on asthma, heart failure, myocardial ischemia / reperfusion injury, cerebral arterial thrombosis, inflammatory enteritis and atherosclerosis.

Description

technical field [0001] The invention relates to the field of medicine, in particular to the composition and preparation method of a mitochondria-targeted anti-inflammatory polypeptide nano drug and its application in the prevention and treatment of diseases related to inflammation and oxidative stress. Background technique [0002] Mitochondria are essential organelles in all cells except for a few mammalian cells. They participate in many important processes of cells, especially play a huge role in cell redox / oxidation balance, and are closely related to cell growth and apoptosis. 1-3 . Mitochondrial reactive oxygen species are metabolic byproducts of normal and functionally active mitochondria due to electron leakage during oxidative phosphorylation and molecular oxygen reduction, mainly including superoxide anion, hydroxyl radicals, hydrogen peroxide and singlet oxygen, etc. 4,5 . Excess reactive oxygen species can damage mitochondrial function, induce cell death, cause...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/61A61K47/54A61K47/64A61K47/69A61K38/06A61K38/08A61K38/17A61P29/00A61P39/06A61P31/04A61P31/12A61P11/06A61P9/04A61P9/10A61P1/00
CPCA61K47/61A61K47/54A61K47/545A61K47/64A61K47/6939A61K38/06A61K38/08A61K38/1709A61P29/00A61P39/06A61P31/04A61P31/12A61P11/06A61P9/04A61P9/10A61P1/00
Inventor 张建祥李兰兰刘超胡厚源马永昌李沉纹
Owner ARMY MEDICAL UNIV
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