Chitosan microspheres as well as preparation method and application thereof

A technology of chitosan microspheres and chitosan derivatives is applied in pharmaceutical formulations, medical preparations with inactive ingredients, and medical preparations containing active ingredients, which can solve the problems of short degradation cycle and frequent injections, etc. To achieve the effects of mild preparation process, improved drug loading capacity, uniform and controllable particle size

Pending Publication Date: 2022-04-26
SUZHOU HAOWEI MEDICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are also problems such as the short degradation cycle and the need for frequent injections.

Method used

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  • Chitosan microspheres as well as preparation method and application thereof
  • Chitosan microspheres as well as preparation method and application thereof
  • Chitosan microspheres as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] (1) Weigh 6g of carboxymethyl chitosan and add it to 100ml of deionized water, then add 10mL of sodium hydroxide solution with a mass concentration of 20%, stir evenly, cool down to -5°C to 10°C, and then add 2g After the dropwise addition of acryloyl chloride, react for another 0.5 h, then use deionized water to dialyze to remove impurities, and then freeze-dry to obtain an acryloyl chitosan intermediate.

[0046] (2) Dissolve 5g of acryloyl chitosan intermediate in 20ml of deionized water, then add 0.1g of N,N'-methylenebisacrylamide, 0.5g of (2-aminoethyl) allyl carbamate hydrochloride Salt, 0.01g potassium persulfate to prepare a polymer monomer solution; 5g Span 80 was added to 200mL liquid paraffin to form an oil phase mixture; the polymer monomer solution was added to the oil phase mixture, dispersed by mechanical stirring, Control the temperature at 50°C, then add 0.1g of tetramethylethylenediamine to initiate the polymerization reaction for 6 hours, and generat...

Embodiment 2

[0049] (1) Weigh 1.0g of hydroxypropyl chitosan and add it to 100ml of deionized water, then add 10mL of 1% pyridine solution, stir evenly, cool down to -5°C to 10°C, and then add 0.1g After the dropwise addition of methacryloyl chloride, react for another 0.5 h, then use deionized water to dialyze to remove impurities, and freeze-dry to obtain the acryloyl chitosan intermediate.

[0050] (2) Dissolve 1.0g of acryloyl chitosan intermediate in 10ml of deionized water, then add 0.1g of polyethylene glycol dimethacrylate, 0.1g of sodium 2-acrylamide-2-methylpropanesulfonate , 0.01g sodium persulfate to prepare a polymer monomer solution; 1g of polyoxyethylene fatty alcohol ether was added to 100mL of n-hexane to form an oil phase mixture; the polymer monomer solution was added to the oil phase mixture, and stirred by mechanical Disperse, control the temperature at 50°C, then add 0.05g of tetramethylethylenediamine to initiate the polymerization reaction for 6 hours, and generate ...

Embodiment 3

[0053] (1) Weigh 10g of hydroxyethyl chitosan and add it to 100ml of deionized water, then add 20mL of triethylamine solution with a mass concentration of 20%, stir evenly, cool down to -5°C to 10°C, and then add 5g Ethacryloyl chloride, after the dropwise addition, was reacted for 1.0 h, and then was dialyzed with deionized water to remove impurities, and then freeze-dried to obtain an acryloyl chitosan intermediate.

[0054] (2) Dissolve 10g of acryloyl chitosan intermediate in 20ml of deionized water, then add 1.0g of hydroxyethyl methacrylate, 2.0g of 2-(diethylamino)ethyl methacrylate, 0.05g of persulfuric acid ammonium to prepare a polymer monomer solution; add 20g ABIL EM 90 to 250mL petroleum ether to form an oil phase mixture; add the polymer monomer solution to the oil phase mixture, disperse by mechanical stirring, control the temperature at 50 ° C, and then Add 0.5g tetramethylethylenediamine to initiate the polymerization reaction for 6h to generate porous chitosa...

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Abstract

The invention discloses a chitosan microsphere, which is formed by polymerizing an acryloylated chitosan intermediate through a cross-linking agent and a charge modifier, and is prepared by the following steps: (1) dissolving a chitosan derivative in water, adding an acid-binding agent, and reacting with an acryloyl chloride compound to obtain the acryloylated chitosan intermediate; (2) dissolving the acryloylated chitosan intermediate in water, and adding a cross-linking agent, a charge modifier and persulfate to obtain a polymer monomer solution; and adding the polymer monomer solution into the oil phase mixture, and adding an initiator to carry out polymerization reaction to obtain the porous chitosan microspheres. Through water-in-oil reverse phase polymerization reaction, the degradation period of the chitosan microspheres is prolonged and can reach 1-12 months, meanwhile, groups capable of loading different kinds of charge drugs are introduced into the microspheres, the drug loading capacity of the microspheres is improved, and meanwhile the drug loading range of the microspheres is expanded.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and relates to the application technology of polymer materials, in particular to a chitosan microsphere, a preparation method and an application thereof. Background technique [0002] Chitosan (Chitosan), the chemical name is β-(1,4)-2-amino-2-deoxy-D-glucan, is a linear polymerization product of chitin deacetylation, and also exists in the biological world The only alkaline amino polysaccharide. Chitosan forms various intramolecular and intermolecular hydrogen bonds through the interaction of hydroxyl groups and amino groups distributed on the macromolecular chain, and easily forms crystallization regions, resulting in chitosan being insoluble in water, alkaline solutions and general oil phase solvents. Soluble in dilute acid solution, which greatly limits the modification application of chitosan. [0003] Carboxymethyl chitosan is the product of carboxymethylation of chitosan. Du...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/722A61K9/16A61K47/61A61K47/69A61P19/02A61P29/00A61K31/196A61K31/573A61K31/704
CPCA61K31/722A61K9/16A61P19/02A61P29/00A61K47/61A61K47/6941A61K31/704A61K31/196A61K31/573A61K2300/00
Inventor 郭平
Owner SUZHOU HAOWEI MEDICAL TECH CO LTD
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