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Osteoprotegerin supported sustained release nanoparticle, and preparation method and application thereof

An osteoprotegerin and nanoparticle technology, applied in the field of biomedicine, can solve the problems of short half-life, difficulty, poor stability, etc., and achieve the effect of avoiding protease hydrolysis, strong anti-calcification effect, and improving bioavailability.

Inactive Publication Date: 2018-09-07
THE SECOND AFFILIATED HOSPITAL TO NANCHANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, since free OPG is easily degraded by protease in the body, has poor stability and short half-life, it is difficult to achieve a therapeutic concentration locally.

Method used

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  • Osteoprotegerin supported sustained release nanoparticle, and preparation method and application thereof
  • Osteoprotegerin supported sustained release nanoparticle, and preparation method and application thereof
  • Osteoprotegerin supported sustained release nanoparticle, and preparation method and application thereof

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preparation example Construction

[0078] The present invention provides a preparation method of osteoprotegerin, which comprises the following steps: forming osteoprotegerin, maleimide-polyethylene glycol-polycaprolactone, polycaprolactone and an organic solvent The mixture is used as the oil phase, and the aqueous solution of the water-soluble polymer is used as the water phase, and is obtained by ultrasonic treatment.

[0079] In a preferred embodiment of the present invention, the present invention provides a preparation method of sustained-release nanoparticles loaded with osteoprotegerin, which comprises the following steps:

[0080] (1) Osteoprotegerin and phospholipids are mixed to obtain osteoprotegerin-phospholipid complexes;

[0081] (2) The mixture formed by osteoprotegerin-phospholipid complex, maleimide-polyethylene glycol-polycaprolactone and polycaprolactone and organic solvent is used as oil phase, and the aqueous solution of water-soluble polymer is used as The aqueous phase was obtained by u...

Embodiment 1

[0125] 1. Preparation of OPG-loaded nanoparticles

[0126] (1) Preparation of osteoprotegerin (OPG)-phospholipid complex

[0127] Dissolve 1ugOPG in sterile three-distilled water and adjust the concentration to 1ug / ml, accurately weigh 10mg soybean lecithin and dissolve it in 1ml tert-butanol, then mix 1ml 1ug / ml OPG aqueous solution and 1ml 10mg / ml soybean lecithin / tert-butanol The solution was blown evenly with a pipette, pre-frozen in a freeze dryer at -60°C for 2 hours, and then vacuum-dried for 22 hours to obtain the OPG-phospholipid complex.

[0128] (2) Preparation of loaded OPG nanoparticles

[0129] OPG-loaded nanoparticles were prepared by emulsification solvent evaporation method. Accurately weigh 4mg maleimide-polyethylene glycol-polycaprolactone (MAL-PEG-PCL) and 12mg polycaprolactone (PCL) and dissolve in 1.5ml methylene chloride, then step (1 ) The prepared OPG-phospholipid complex is dissolved therein to form an oil phase (O), 6ml of 2% PVA aqueous solution ...

Embodiment 2

[0163] 1. Preparation of OPG-loaded nanoparticles

[0164] (1) Preparation of osteoprotegerin (OPG)-phospholipid complex

[0165] Dissolve 0.5ugOPG in sterile three-distilled water and adjust the concentration to 1ug / ml, accurately weigh 5mg soybean lecithin and dissolve it in 0.5ml tert-butanol, then mix 1ml 1ug / ml OPG aqueous solution and 1ml 10mg / ml soybean lecithin / tert-butyl The alcohol solution was blown evenly with a pipette, pre-frozen in a freeze dryer at -55°C for 1 hour, and then vacuum-dried for 20 hours to obtain the OPG-phospholipid complex.

[0166] (2) Preparation of loaded OPG nanoparticles

[0167] OPG-loaded nanoparticles were prepared by emulsification solvent evaporation method. Accurately weigh 6mg of maleimide-polyethylene glycol-polycaprolactone (MAL-PEG-PCL) and 15mg of polycaprolactone (PCL) and dissolve them in 1ml of dichloromethane, and then add step (1) The prepared OPG-phospholipid complex is dissolved therein to form an oil phase (O), and 5ml...

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Abstract

The invention relates to the field of biomedical science, and concretely relates to an osteoprotegerin supported sustained release nanoparticle, and a preparation method and an application thereof. The osteoprotegerin supported sustained release nanoparticle is prepared from osteoprotegerin, maleimide-polyethylene glycol-polycaprolactone and polycaprolactone. The invention also provides the preparation method of the osteoprotegerin supported sustained release nanoparticle. The osteoprotegerin supported sustained release nanoparticle is prepared through performing ultrasonic treatment with a mixture formed by the osteoprotegerin, maleimide-polyethylene glycol-polycaprolactone, polycaprolactone and an organic solvent as an oil phase and an aqueous solution of a water-soluble polymer as an aqueous phase. The osteoprotegerin is encapsulated in a nanoparticle to construct a nano-drug supported controlled release system to make the osteoprotegerin slowly released locally from the nanoparticle at a certain rate, so therapeutic concentration is achieved, the osteoprotegerin is prevented from being hydrolyzed by proteases in vivo, and the bioavailability is increased.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a sustained-release nanoparticle loaded with osteoprotegerin, a preparation method and application thereof. Background technique [0002] The incidence of calcific aortic valve disease (Calcific aortic valve disease, CAVD) presents an increasing trend year by year in the elderly population. At present, the main treatment method is aortic valve replacement surgery, but there are bleeding, Calcification decline, poor durability and other issues. With the deepening of research on the pathogenesis of CAVD, studies have shown that CAVD is an active disease process involving inflammation, lipid metabolism, cell differentiation, matrix remodeling and other pathological changes, and it also provides a new treatment for the treatment of CAVD target. [0003] Osteoprotegerin (Osteoprotegerin, OPG) is a soluble secreted glycoprotein and a member of the tumor necrosis factor receptor superfamily...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61K9/50A61K47/34A61P9/00
CPCA61K9/5031A61K38/177A61P9/00
Inventor 周建良李杨丁静丽刘季春徐建军易应萍高日峰朱志刚樊虎熊许伟长
Owner THE SECOND AFFILIATED HOSPITAL TO NANCHANG UNIV
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