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Preparation method of injection type pH and glucose sensitive hydrogel

A glucose-sensitive, hydrogel technology, applied in non-active ingredient medical preparations, medical preparations containing active ingredients, pharmaceutical formulations, etc., can solve the problem of non-biodegradable, unfavorable ionic strength, biocompatibility of drug activity, Reduce biocompatibility and other problems, achieve the effect of maintaining activity, good biocompatibility and biodegradability, and simple and convenient preparation method

Active Publication Date: 2007-05-02
INST OF PROCESS ENG CHINESE ACAD OF SCI
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  • Abstract
  • Description
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AI Technical Summary

Problems solved by technology

The disadvantage is that the system needs to use a large amount of sodium glycerophosphate to achieve solution-gel transition at body temperature, and too high ionic strength is not conducive to the activity of the encapsulated drug and the biocompatibility of the dosage form
The disadvantage is that the required gelling temperature is 47°C, which is far higher than the normal temperature of the human body, which is not conducive to the application in the human body, and its drug release rate is relatively fast, and the embedded drug is basically released within 10 hours
The system can gel at 37°C, but the disadvantage is that glyoxal has certain cytotoxicity, even if the concentration is very low, it will reduce the biocompatibility of the system
This system can undergo solution-gel transition at 37°C, but the disadvantage is that the preparation steps are cumbersome, and PEG or chitosan needs to be activated for cross-linking reaction; and organic solvents or toxic Reagents, need to be removed by filtration or dialysis etc.
Their disadvantage is that the first two systems need to use exogenous proteins, which will trigger the body's immune response, and need to be separated from the human body environment with a semi-permeable membrane or other materials; surgically implanted

Method used

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  • Preparation method of injection type pH and glucose sensitive hydrogel
  • Preparation method of injection type pH and glucose sensitive hydrogel
  • Preparation method of injection type pH and glucose sensitive hydrogel

Examples

Experimental program
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preparation example Construction

[0031] (1) Preparation of chitosan quaternary ammonium salt

[0032] Disperse chitosan and 2,3-epoxypropyltrimethylammonium chloride with a molar ratio of 1:2-1:8 in water or isopropanol, heat to a reaction temperature of 60-90°C, Reaction 2-12h. The reaction solution is poured into acetone for precipitation, washed, and dried to obtain chitosan quaternary ammonium salt.

[0033] The molecular weight range of chitosan is 5-2 million, and the degree of deacetylation is 65%-100%.

[0034] (2) Preparation of polyethylene glycol cross-linked chitosan quaternary ammonium hydrogel

[0035] The chitosan quaternary ammonium salt that above-mentioned step (1) gained is dissolved in the acidic solution of pH2.0-6.0 and obtains the chitosan quaternary ammonium salt solution of 1.0-10.0wt.%, and acidic solution comprises acetic acid, hydrochloric acid, lactic acid, Citric Acid, Ascorbic Acid, Formic Acid. Adding polyethylene glycol with a molecular weight range of 200-25000 in the chi...

Embodiment 1

[0040] Disperse 3.0g of chitosan in 20mL of water and stir at 80°C for 1h. 16.94g of 2,3-epoxypropyltrimethylammonium chloride was dissolved in 40mL of water, and added to the chitosan dispersion. After stirring and reacting at 80° C. for 10 h, the reaction solution was poured into acetone to precipitate, stirred and washed overnight in a refrigerator, and then dried to obtain a white loose product. Characterized by infrared spectroscopy, see Figure 1, 1597cm after quaternization -1 The amino stretching vibration peak at 1481cm -1 appear-CH 3 The strong absorption peak of the C-H bending vibration of C-H proves that the quaternary ammonium group is substituted on the chitosan chain to generate the chitosan quaternary ammonium salt.

Embodiment 2

[0042] Dissolve 0.50 g of chitosan quaternary ammonium salt and 0.72 g of PEG8000 prepared in Example 1 in 8 mL of 0.1 mol / L lactic acid solution, add 2 mL of 0.125 g / mL beta-glycerophosphate sodium solution dropwise under stirring, and fully stir Mix it well. The pH of the resulting solution was 7.4. The mixed solution was heated to 37°C and kept for 60 minutes to fully gel the system. The system is stable at 4°C.

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Abstract

An injection of aquatic gel sensitive to pH value and glucose for controlling the release of the medicine wrapped by it is prepared through preparing the quaternary ammonium salt of chitosan, dissolving it along with polyethanediol in acid solution, adding the solution of glycerin phosphate, stirring, and gelatinizing.

Description

technical field [0001] The invention relates to a method for preparing a drug controlled release system, more precisely, relates to a method for preparing an injectable pH- and glucose-sensitive hydrogel, and belongs to the field of pharmaceutical preparations in medical engineering. Background technique [0002] Chitosan is a linear polysaccharide composed of β(1→4)-bonded D-glucosamine residues and N-acetylglucosamine with different numbers and random distribution. As a natural cationic biopolymer, chitosan has a wide range of sources, non-toxic, odorless, antithrombotic, antistatic, alkali resistance, film forming, bioadhesion, biocompatibility and biodegradability, and its The degradation products are non-toxic, non-immunogenic and non-carcinogenic. These characteristics make chitosan a biomedical carrier with broad application prospects. In the article written by Chenite et al. (A.Chenite, C.Chaput, D.Wang, C.Combes, M.D.Buschmann, C.D.Hoemann, J.C Leroux, B.L.Atkinso...

Claims

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Application Information

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IPC IPC(8): A61K31/7004A61K9/00A61K47/36A61P3/00A61P43/00
Inventor 马光辉苏志国吴颉
Owner INST OF PROCESS ENG CHINESE ACAD OF SCI
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