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Hyaluronic acid-hydroxyapatite nano composite sphere and preparation method

A technology of hydroxyapatite and hyaluronic acid, which is used in the preparation of microspheres, gene therapy, pharmaceutical formulations, etc., can solve the problem that hydroxyapatite nanoparticles lack biological targeting, hydroxyapatite particles are easy to agglomerate, and phase stability, poor dispersion, etc., to achieve good biocompatibility, environmental friendliness, and mild reaction conditions.

Inactive Publication Date: 2009-10-21
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the above research has achieved certain results, the problems of easy agglomeration, uneven size distribution, and poor dispersion in the aqueous phase of the prepared hydroxyapatite particles have not been effectively solved, and the obtained hydroxyapatite nanoparticles generally lack specific properties. biological targeting

Method used

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  • Hyaluronic acid-hydroxyapatite nano composite sphere and preparation method
  • Hyaluronic acid-hydroxyapatite nano composite sphere and preparation method
  • Hyaluronic acid-hydroxyapatite nano composite sphere and preparation method

Examples

Experimental program
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Effect test

Embodiment 1

[0030] In this example, the process steps for preparing hyaluronic acid-hydroxyapatite nanocomposite spheres are as follows:

[0031] (1) Preparation of hyaluronic acid solution

[0032] Add 0.01g of hyaluronic acid with a molecular weight of 6 million to a reaction vessel containing 50mL of deionized water at normal pressure and room temperature, and dissolve the hyaluronic acid completely under stirring;

[0033] (2) Reaction synthesis

[0034]Under stirring, add Ca(NO 3 ) 2 4H 2 O aqueous solution, Na with a concentration of 0.05mol / L 2 HPO 4 12H 2 Each 1.5mL of O aqueous solution, the molar ratio of Ca / P in the reaction system is 1.2: 1;

[0035] Subsequently, adjust the pH value of the reaction system with a NaOH aqueous solution with a concentration of 0.1 mol / L and HCl of 0.1 mol / L to stabilize the pH value of the reaction system at 9, and then age at normal pressure and room temperature for 48 hours;

[0036] (3) Product collection and drying

[0037] After ag...

Embodiment 2

[0040] In this example, the process steps for preparing hyaluronic acid-hydroxyapatite nanocomposite spheres are as follows:

[0041] (1) Preparation of Hyaluronic Sodium Hyaluronate Solution

[0042] Add 0.1 g of sodium hyaluronate with a molecular weight of 1.8 million to a reaction vessel containing 60 mL of deionized water at normal pressure and room temperature, and completely dissolve the sodium hyaluronate under stirring;

[0043] (2) Reaction synthesis

[0044] Add CaCl with a concentration of 0.39mol / L to the sodium hyaluronate aqueous solution prepared in step (1) under stirring. 2 Aqueous solution, concentration 0.3mol / L (NH 4 ) 2 HPO 4 2H 2 Each 10mL of O aqueous solution, the mol ratio of Ca / P in the reaction system is 1.3: 1;

[0045] Subsequently, adjust the pH value of the reaction system with ammonia solution with a concentration of 0.2 mol / L and HCl with a concentration of 0.2 mol / L to stabilize the pH value of the reaction system at 10, and then age at...

Embodiment 3

[0050] In this example, the process steps for preparing hyaluronic acid-hydroxyapatite nanocomposite spheres are as follows:

[0051] (1) Preparation of Potassium Hyaluronate Solution

[0052] Add 1.0kg of potassium hyaluronate with a molecular weight of 1.18 million to a reaction vessel containing 70L of deionized water at normal pressure and room temperature, and dissolve the potassium hyaluronate completely under stirring;

[0053] (2) Reaction synthesis

[0054] Add Ca(OH) with a concentration of 0.45mol / L to the potassium hyaluronate aqueous solution prepared in step (1) under stirring. 2 Aqueous solution, NaH concentration 0.3mol / L 2 PO 4 2H 2 Each 20L of O aqueous solution, the mol ratio of Ca / P in the reaction system is 1.5: 1;

[0055] Subsequently, adjust the pH value of the reaction system with ammonia solution with a concentration of 0.5 mol / L and HCl with a concentration of 0.5 mol / L to stabilize the pH value of the reaction system at 10, and then age at norm...

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Abstract

The invention relates to a hyaluronic acid-hydroxyapatite nano composite sphere. The nano composite sphere comprises 93 to 98.7 mass percent of hydroxyapatite and 1.3 to 7.0 mass percent of hyaluronicacid, and has a spherical shape and the grain size of 20 to 200 nm. A preparation method for the hyaluronic acid-hydroxyapatite nano composite sphere comprises the following process steps: (1) preparation of a hyaluronic acid saccharoid solution; (2) reaction and synthesis: adding an aqueous solution of calcium salt and an aqueous solution of phosphate into the hyaluronic acid saccharoid solutionprepared in step (1) with agitating, then regulating the pH value of a reaction system to make the pH value stabilize from 9 to 11, and carrying out the aging for at least 48 hours at the room temperature and normal pressure; and (3) product collection and drying. The nano composite sphere has the unique targeting characteristics (CD44 receptor) in vivo, and has good application prospect in the field of medicine and gene targeting transportation.

Description

technical field [0001] The invention belongs to the field of hydroxyapatite nanocomposite materials, in particular to a hyaluronic acid-hydroxyapatite nanocomposite ball and a preparation method thereof. Background technique [0002] Because hydroxyapatite is basically the same as the inorganic components of human bones and teeth, it has good biocompatibility and bioactivity, making it a research hotspot in the field of biomaterials. In the research on hydroxyapatite, nano-hydroxyapatite has attracted extensive attention because of its great application potential in the fields of drug controlled release, gene carrier, drug-loaded tissue engineering scaffold, and micro-nano biomaterial processing. Known as the most promising second-generation nonviral vector in gene therapy (Maitra A, Calcium phosphate nanoparticles: second-generation nonviral vectors in gene therapy, Expert.Rev.Mol.Diagn., 2005, 5(6), 893-905 ; Sokolova V, Epple M, Inorganic nanoparticles as carriers of nuc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/42A61K9/16A61K47/36A61K48/00B01J13/02A61L27/12A61L27/20
Inventor 李旭东陈震华王彩红周慧慧桑琳
Owner SICHUAN UNIV
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