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A kind of sialic acid modified composite nano drug delivery system and its preparation and application

A drug delivery system, sialic acid technology, applied in the field of sialic acid modified chitosan/hydroxyapatite nano drug delivery system and preparation, can solve the problem of insufficient joint function repair ability, difficult to cover lesion area, osteogenic bone loss and other problems, to achieve the effect of release, safe and efficient treatment, and recovery of joint function

Active Publication Date: 2021-01-08
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, rheumatoid arthritis is characterized by multiple joints and small joints, so nano-hydroxyapatite-based scaffolds are not only difficult to cover the entire lesion area, but also may further damage the joints during stent implantation
In addition, long-term inflammatory infiltration will cause loss of periarticular osteogenic bone and erosion of cartilage, and pure nano-hydroxyapatite has insufficient ability to repair joint function

Method used

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  • A kind of sialic acid modified composite nano drug delivery system and its preparation and application
  • A kind of sialic acid modified composite nano drug delivery system and its preparation and application
  • A kind of sialic acid modified composite nano drug delivery system and its preparation and application

Examples

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Effect test

Embodiment 1

[0022] Example 1 Preparation of sialic acid modified chitosan oligosaccharide / hydroxyapatite nano drug delivery system

[0023] The preparation of sialic acid modified chitosan oligosaccharide / hydroxyapatite nano drug delivery system is carried out in two steps, the first step is to synthesize sialic acid modified chitosan oligosaccharide graft. Take 50 mg of deoxycholic acid and 77 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in a round-bottomed flask, add 50 mL of ethanol for ultrasonic dissolution, stir at 60°C for 0.5 h, and then Add it into 50 mL of chitosan oligosaccharide (MW 5000 Da) aqueous solution with a concentration of 5 mg / mL that has been preheated at 60°C, and continue the reaction at 400 rpm for 24 hours. The reacted solution was transferred to a dialysis bag (MWCO 7.0 kDa), dialyzed with pure water for 48 h, the suspension was collected, centrifuged (6000 rpm, 15 min), and the supernatant was obtained by freeze-drying to obtain a chitosan...

Embodiment 2

[0031] The preparation of embodiment disialic acid modified chitosan oligosaccharide / hydroxyapatite nano drug delivery system

[0032] The preparation of sialic acid modified chitosan oligosaccharide / hydroxyapatite nano drug delivery system is carried out in two steps, the first step is to synthesize sialic acid modified chitosan oligosaccharide graft. Take 50 mg of deoxycholic acid and 77 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in a round-bottomed flask, add 50 mL of ethanol for ultrasonic dissolution, stir at 60°C for 0.5 h, and then Add it into 50 mL of chitosan oligosaccharide (MW 5000 Da) aqueous solution with a concentration of 5 mg / mL that has been preheated at 60°C, and continue the reaction at 400 rpm for 24 hours. The reacted solution was transferred to a dialysis bag (MWCO 7.0 kDa), dialyzed with pure water for 48 h, the suspension was collected, centrifuged (6000 rpm, 15 min), and the supernatant was obtained by freeze-drying to obtain a c...

Embodiment 3

[0040] The preparation of embodiment trisialic acid modified chitosan oligosaccharide / hydroxyapatite nano drug delivery system

[0041] The preparation of sialic acid modified chitosan oligosaccharide / hydroxyapatite nano drug delivery system is carried out in two steps, the first step is to synthesize sialic acid modified chitosan oligosaccharide graft. Take 80 mg of deoxycholic acid and 77 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in a round-bottomed flask, add 50 mL of ethanol for ultrasonic dissolution, stir at 60°C for 0.5 h, and then Add it into 50 mL of chitosan oligosaccharide (MW 30,000 Da) aqueous solution with a concentration of 5 mg / mL that has been preheated at 60° C., and continue the reaction at 400 rpm for 24 h. The reacted solution was transferred to a dialysis bag (MWCO 7.0 kDa), dialyzed with pure water for 48 h, the suspension was collected, centrifuged (6000 rpm, 15 min), and the supernatant was obtained by freeze-drying to obtain a ...

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Abstract

The invention provides a sialic acid-modified composite nano-drug delivery system and preparation and application thereof. Under the stabilization action of sialic acid-modified chitosan-deoxycholic acid graft micelle, hydroxyapatite nanoparticles are prepared by a hydrothermal method, thus enhancing stability of hydroxyapatite. Through the specific binding of sialic acid on the surface of the system to highly-expressed E-selectin on the surface of vascular endothelial cells in arthritic sites, targeted delivery and high accumulation of a drug on the arthritic sites are realized. Under the condition of low pH in the arthritic sites and cells, rapid release of the drug is achieved through the degradation of hydroxyapatite, which significantly improves the inhibitory effect and tolerance ofthe drug to inflammatory reactions and reduces the toxic and side effects of the drug. By promoting the synthesis and secretion of glycosaminoglycans by chondrocytes, cartilage repair is realized, andosteoblast mineralization is promoted. With the synergism of sialic acid's own bone repair ability, osteogenic repair and regeneration function is enhanced. The sialic acid-modified composite nano-drug delivery system can be applied to preparation of rheumatoid arthritis drugs.

Description

technical field [0001] The invention belongs to the preparation of a nano drug delivery system, and relates to a sialic acid modified composite nano drug delivery system, in particular to a sialic acid modified chitosan oligosaccharide / hydroxyapatite nano drug delivery system and a preparation method, and a sialic acid modified chitosan oligosaccharide Application of / hydroxyapatite nano drug delivery system in the preparation of rheumatoid arthritis drugs. Background technique [0002] Rheumatoid arthritis is a systemic autoimmune disease characterized by polyarticular synovial inflammation, often accompanied by extra-articular organ involvement and positive serum rheumatoid factor, which eventually leads to joint deformity and loss of function, with a high incidence in 30-50 years old In women, the incidence rate is increasing year by year. At present, the clinical treatment of rheumatoid arthritis is mainly based on drug therapy and surgical treatment, but surgical treat...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/107A61K31/519A61K31/7012A61K31/722A61K33/42A61K47/02A61K47/54A61K47/61A61P19/02A61P29/00
CPCA61K9/1075A61K31/519A61K31/7012A61K31/722A61K33/42A61K47/02A61K47/554A61K47/61A61P19/02A61P29/00A61K2300/00
Inventor 杜永忠徐晓玲应晓英
Owner ZHEJIANG UNIV
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