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Preparation method of insulin-supporting carboxymethyl chitosan/chitosan nanometer preparation

A carboxymethyl chitosan and chitosan nanotechnology, which is applied in the field of oral pharmaceutical preparations, can solve problems such as weak insulin protection, achieve good research and application prospects, protect biological activity, and have the effects of abundant raw materials

Inactive Publication Date: 2017-02-22
OCEAN UNIV OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, carboxymethyl chitosan is a water-soluble material and has a weak protective effect on insulin in the intestinal tract

Method used

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  • Preparation method of insulin-supporting carboxymethyl chitosan/chitosan nanometer preparation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0010] Dissolve carboxymethyl chitosan in water, insulin in 0.01 M hydrochloric acid solution, chitosan in 0.1 M acetic acid solution, the concentration of insulin, carboxymethyl chitosan and chitosan solution Both are 0.5 mg / mL; under the condition of stirring, add 1 mL insulin solution to 4 mL carboxymethyl chitosan solution, adjust the pH value to 4.5, continue stirring for 35 min, and drop 2 mL shell Adjust the pH value of the polysaccharide solution to 6, and continue to stir for 60 min; centrifuge the suspension at a high speed (12 000 r / min) for 30 min at 4°C to collect the precipitate; wash it with pure water three times, and freeze-dry it. Insulin was entrapped at 18%.

Embodiment 2

[0012] Dissolve carboxymethyl chitosan in water, insulin in 0.01 M hydrochloric acid solution, chitosan in 0.1 M acetic acid solution, the concentration of insulin, carboxymethyl chitosan and chitosan solution Both are 10 mg / mL; under the condition of stirring, add 1 mL insulin solution into 6 mL carboxymethyl chitosan solution, adjust the pH value to 3, continue stirring for 10 min, drop 4 mL shell Adjust the pH value of the polysaccharide solution to 7.5, and continue to stir for 35 min; centrifuge the suspension at a high speed (12 000 r / min) for 30 min at 4°C to collect the precipitate; wash it with pure water three times, and freeze-dry it. Insulin was entrapped at 23%.

Embodiment 3

[0014] Dissolve carboxymethyl chitosan in water, insulin in 0.01 M hydrochloric acid solution, chitosan in 0.1 M acetic acid solution, the concentration of insulin, carboxymethyl chitosan and chitosan solution Both are 10 mg / mL; under the condition of stirring, add 1 mL insulin solution into 2 mL carboxymethyl chitosan solution, adjust the pH value to 6, continue stirring for 35 min, and drop 6 mL shell Adjust the pH value of the polysaccharide solution to 4.5, and continue to stir for 10 min; centrifuge the suspension at a high speed (12 000 r / min) for 30 min at 4°C to collect the precipitate; wash it with pure water three times, and freeze-dry it. Insulin was entrapped at 14%.

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Abstract

The present invention relates to a preparation method of an oral insulin preparation insulin-supporting carboxymethyl chitosan / chitosan nanometer preparation. The preparation method comprises: 1) forming core nanoparticles from carboxymethyl chitosan and insulin; 2) adding chitosan to a core nanometer suspension, and forming the outer layer of the nanoparticles on the surface of the core nanoparticles through the chitosan and the part of the carboxymethyl chitosan; and 3) stirring the obtained mixture until completely performing the cross-linking, carrying out high speed centrifugal separation, and carrying out freeze-drying to obtain the insulin-supporting carboxymethyl chitosan / chitosan nanoparticles. According to the present invention, the preparation conditions are mild, such that the insulin can be effectively protected from the influence caused by the gastrointestinal tract acid environment and the protease; the chitosan and the carboxymethyl chitosan can further promote the intestinal epithelium to absorb the insulin; and the results of the in vivo tests using diabetes rats as model animals show that the insulin-supporting carboxymethyl chitosan / chitosan nanometer preparation can effectively reduce the blood glucose of the rats.

Description

technical field [0001] The invention belongs to the field of oral pharmaceutical preparations, and relates to a method for preparing insulin-loaded carboxymethyl chitosan / chitosan nano preparations. Background technique [0002] Insulin is the most effective drug for treating diabetes. However, since insulin is a protein drug, the current main method of administration is injection. During the course of treatment, multiple injections are prone to complications and patient compliance is low, such as Hypoglycemia, local infection, subcutaneous lipoatrophy, allergies and pain, etc. In contrast, oral administration is a good alternative delivery method, and oral administration of insulin pharmacokinetically mimics the secretion of physiological insulin, avoiding low compliance and complications caused by injection administration. However, the problem with the current oral drug delivery technology is the bioavailability of the drug, which cannot meet the clinically required hypog...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/61A61K38/28A61K9/14A61P3/10
Inventor 陈西广王娟冯超程晓杰孔明刘雅
Owner OCEAN UNIV OF CHINA
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