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Multi-responsive smart hydrogel for colon targeting and preparation method thereof

A colon-targeting and responsive technology, used in emulsion delivery, aerosol delivery, liquid delivery, etc., can solve the problem that glutaraldehyde and CMCS aqueous solution are difficult to mix evenly, the gel uniformity is deteriorated, and it is prone to breakage. and other problems, to achieve the effect of increasing treatment efficiency, reducing degradation, and reducing drug toxicity and side effects

Inactive Publication Date: 2018-07-27
WUHAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are three defects in this method: one, because the cross-linking reaction between glutaraldehyde and the amino groups on CMCS is extremely rapid, it is difficult to mix the glutaraldehyde and CMCS aqueous solution evenly
Second, due to the high viscosity of the solution, it is difficult to remove a large number of air bubbles in the solution before the crosslinking reaction of the system occurs, resulting in a large number of pores in the gel, the uniformity of the gel becomes poor, and it is easy to break during the swelling process.
Third, during the drug-loaded molding process, glutaraldehyde is very easy to react with the amino groups on the drug (such as enzymes, polypeptides, etc.) molecules, resulting in drug inactivation

Method used

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  • Multi-responsive smart hydrogel for colon targeting and preparation method thereof
  • Multi-responsive smart hydrogel for colon targeting and preparation method thereof
  • Multi-responsive smart hydrogel for colon targeting and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] (1) Preparation of carboxymethyl chitosan:

[0031] Add 100mL isopropanol (analytically pure) in 250mL there-necked flask, weigh 10g chitosan and add wherein, after stirring at room temperature for 6h, filter, take out the filter residue and import it into a beaker, then add 60g of NaOH solution (50wt%) in the beaker , Stir well, put it in the refrigerator overnight, take it out the next day and wait for it to melt naturally, transfer it to a 500mL three-neck bottle, add 100mL isopropanol, and stir evenly. Get 30g of isopropanol solution (50wt%) of chloroacetic acid and add it dropwise in the three-necked flask, and the dripping is completed in about 2 hours. At this time, the three-necked bottle is in a white emulsified state, and the stirring reaction is continued for 20 hours. The reaction is carried out in an ice bath, and the reaction temperature is controlled. Below 10°C, filter, dissolve the filter cake in 250mL deionized water, then centrifuge to remove insolubl...

Embodiment 2

[0037] (1) Preparation of carboxymethyl chitosan:

[0038] Add 100mL isopropanol (analytically pure) in 250mL there-necked flask, weigh 10g chitosan and add wherein, after stirring at room temperature for 6h, filter, take out the filter residue and import it into a beaker, then add 60g of NaOH solution (50wt%) in the beaker , Stir well, put it in the refrigerator overnight, take it out the next day and wait for it to melt naturally, transfer it to a 500mL three-neck bottle, add 100mL isopropanol, and stir evenly. Get 30g of isopropanol solution (50wt%) of chloroacetic acid and add it dropwise in the three-necked flask, and the dripping is completed in about 2 hours. At this time, the three-necked bottle is in a white emulsified state, and the stirring reaction is continued for 20 hours. The reaction is carried out in an ice bath, and the reaction temperature is controlled. Below 10°C, filter, dissolve the filter cake in 250mL deionized water, then centrifuge to remove insolubl...

Embodiment 3

[0044] (1) Preparation of carboxymethyl chitosan:

[0045] Add 100mL isopropanol (analytically pure) to a 250mL three-necked flask, weigh 10g of chitosan with a deacetylation degree of 75%, add it, stir at room temperature for 6h, filter, take out the filter residue and introduce it into a beaker, then add 60g of NaOH to the beaker Solution (50wt%), fully stirred evenly, put it in the refrigerator overnight, took it out the next day and waited for natural melting, transferred to a 500mL three-necked bottle, added 100mL isopropanol, and stirred evenly. Get 30g of isopropanol solution (50wt%) of chloroacetic acid and add it dropwise in the three-necked flask, and the dripping is completed in about 2 hours. At this time, the three-necked bottle is in a white emulsified state, and the stirring reaction is continued for 20 hours. The reaction is carried out in an ice bath, and the reaction temperature is controlled. Below 10°C, filter, dissolve the filter cake in 250mL deionized wa...

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Abstract

The invention relates to a multi-responsive smart hydrogel for colon targeting and a preparation method thereof. An effective component of the hydrogel is a disulfide bond cross-linked carboxymethyl chitosan derivant. The preparation method of the multi-responsive smart hydrogel for colon targeting comprises the following steps of performing a reaction on a raw material carboxymethyl chitosan andmercaptobenzoic acid activated by EDC so as to prepare thiolated carboxymethyl chitosan, and then oxidizing thiol of the water solution of thiolated carboxymethyl chitosan by using air at room temperature and cross linking to form the multi-responsive smart hydrogel. The method has mild reaction conditions, no cross-linking agent was needed, and the prepared smart hydrogel has unique pH sensitivity, enzyme sensitivity and reduction sensitivity and has a potential application value in the field of transfer of colon targeted drugs.

Description

technical field [0001] The invention relates to a colon-targeted drug delivery carrier, in particular to a colon-targeted multi-responsive intelligent hydrogel and a preparation method thereof. Background technique [0002] Oral colon-targeted drug delivery system has been attracting much attention in the medical field. The main reason is that it can deliver the drug target to the colon to improve the treatment rate of colon diseases and reduce the toxic and side effects of drugs; the second is that it is poorly absorbed in the upper gastrointestinal tract The delivery of easily degradable peptide and protein drugs to the colon can promote their better absorption and improve their bioavailability. Among the methods currently used in the design of colon-targeted drug delivery systems, most of the pH-sensitive hydrogels based on the pH changes in the gastrointestinal tract can only deliver drugs to the small intestine; the designed microbial enzymes can degrade water by utiliz...

Claims

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Application Information

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IPC IPC(8): A61K9/06A61K47/36
CPCA61K9/06A61K47/36
Inventor 殷以华杨梦丹潘茜郑丽敏吴杰
Owner WUHAN UNIV OF TECH
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