Self-assembled collagen-stimulated microsphere with naturally constituted shell-core structure and preparation method thereof

A core structure, self-assembly technology, applied in tissue regeneration, medical science, prosthesis, etc., can solve the problems of reducing the initial high molecular weight HA, reducing the viscosity of high molecular weight HA, etc., to solve the problem of high viscosity, reduce viscosity, technical route Environmentally friendly effect

Active Publication Date: 2019-01-18
SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In order to reduce the viscosity of high molecular weight HA, the common method is to dissolve HA in alkaline solution, but this is only applicable to the cross-linking reaction under alkaline conditions, and the cross-linking agent is generally divinyl sulfone, 1,4-butyl Toxic chemical reagents such as diol diglycidyl ether (Chinese patent CN103333351B; CN102942699B)
Therefore, how to reduce the viscosity of the initial high molecular weight HA by a simple and non-toxic method, and prepare HA microspheres that meet the product requirements, has great practical application value, and has not been reported yet.

Method used

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  • Self-assembled collagen-stimulated microsphere with naturally constituted shell-core structure and preparation method thereof
  • Self-assembled collagen-stimulated microsphere with naturally constituted shell-core structure and preparation method thereof
  • Self-assembled collagen-stimulated microsphere with naturally constituted shell-core structure and preparation method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Sodium hyaluronate (HA) dry powder with a molecular weight of 1.3 million Daltons was weighed, dissolved in a phosphate buffered saline solution (PBS) with a pH of 7.2, and fully dissolved to prepare a 1.2 wt% HA solution. Weigh ε-polylysine dry powder and add it into HA solution, the molar ratio of ε-polylysine to HA is 1:1, stir well to form emulsion. Add the formed emulsion into the mixed solution of liquid paraffin and Span80, the mass ratio of emulsion: liquid paraffin: Span80 is 1:0.1:10, and stir at 800 rpm for 2 hours after adding. Then add the mixed solution of ε-polylysine and 4-methylmorpholine hydrochloride (DMTMM) in the emulsification system, ε-polylysine: DMTMM: the mol ratio of the HA in the system is 0.5:0.2: 1. Continue stirring for 18 hours to allow the microspheres to settle. The obtained precipitate was suction filtered to remove the oil phase, washed with acetone, and sieved for particle size.

[0033] The particle size and particle size distribu...

Embodiment 2

[0035] Sodium hyaluronate (HA) dry powder with a molecular weight of 1 million Daltons was weighed, dissolved in a phosphate buffered saline solution (PBS) with a pH of 7.2, and fully dissolved to prepare a 1.5 wt% HA solution. Weigh ε-polylysine dry powder and add it into HA solution, the molar ratio of ε-polylysine to HA is 1.3:1, stir well to form emulsion. Add eosin dye dropwise to the emulsion and mix well. Add the formed emulsion to the mixed solution of liquid paraffin and Span80, the mass ratio of emulsion: liquid paraffin: Span80 is 2:0.1:10, and stir at 600 rpm for 1 hour after adding. Then add the mixed solution of ε-polylysine and 4-methylmorpholine hydrochloride (DMTMM) to the emulsification system, drop toluidine blue dye in the mixed solution, ε-polylysine: DMTMM: in the system The molar ratio of HA was 1:0.2:1 and stirring was continued for 24 h to allow the microspheres to settle. The resulting precipitate was filtered off with suction to remove the oily pha...

Embodiment 3

[0038] Sodium hyaluronate (HA) dry powder with a molecular weight of 1.5 million Daltons was weighed, dissolved in 0.9 wt% sodium chloride solution, fully dissolved, and prepared into a 1.8 wt% HA solution. Weigh ε-polylysine dry powder and add it into HA solution, the molar ratio of ε-polylysine to HA is 0.8:1, stir well to form emulsion. Add the formed emulsion into the mixed solution of silicone oil and Span80, the mass ratio of emulsion: silicone oil: Span80 is 2:0.4:10, and stir at 800 rpm for 2 hours after adding. Then add the mixed solution of ε-polylysine and 4-methylmorpholine hydrochloride (DMTMM) in the emulsification system, ε-polylysine: DMTMM: the mol ratio of the HA in the system is 2:1: 1. Continue stirring for 24 hours to allow the microspheres to settle. The obtained precipitate was suction filtered to remove the oil phase, washed with acetone, and sieved for particle size. Then soak the obtained microspheres in 0.9wt% sodium chloride solution for 24 hours,...

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Abstract

The invention discloses a self-assembled collagen-stimulated microsphere with a naturally constituted shell-core structure and a preparation method thereof. The electrostatic interaction between polycationic polymers and sodium hyaluronate (HA) is used to change the conformation of HA molecule and reduce the viscosity of HA neutral solution. The formation of micron-sized HA microspheres in emulsion system is promoted. The precipitation of microspheres is promoted by the electrostatic interaction between polycationic natural polymers and HA and by the condensation crosslinking reaction of amines and acids. The method skillfully solves the problem of high viscosity of high molecular weight HA neutral solution, and has the advantages of simple procedure and environmental protection. The prepared collagen-stimulated microspheres have a shell. The self-assembled structure of the nucleus is composed of natural macromolecules, which can be rapidly degraded by specific biological enzymes whenside reactions occur, thus ensuring the safety of injection products. At the same time, the microspheres have good mechanical strength and long degradation time, can effectively stimulate the secretion of collagen for a long time, and have good application prospects in the field of soft tissue filling, especially in the field of medical cosmetic filling.

Description

technical field [0001] The invention belongs to the field of biomedical polymer materials, and in particular relates to a naturally composed self-assembled collagen stimulation microsphere with a shell-core structure and a preparation method thereof, which are mainly used in soft tissue filling, especially medical cosmetic filling. Background technique [0002] With the continuous improvement of people's aesthetic requirements, the medical beauty industry has developed rapidly around the world. There are a variety of filling materials on the market that have been applied to the field of cosmetic injections. Among them, sodium hyaluronate (HA) is one of the most important components in the dermal tissue of human skin. It is non-immunogenic, non-carcinogenic, and non-teratogenic. With many advantages, it has been favored by the industry and consumers since it was approved by the FDA to enter the plastic surgery market in 2003. It is the main ingredient of most injection fillin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/18A61L27/20A61L27/50A61L27/58
CPCA61L27/18A61L27/20A61L27/50A61L27/58A61L2430/34C08L5/08C08L77/04
Inventor 魏长征王晓彤周琳耀
Owner SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD
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