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pH sensitive hydrogel as well as preparation method and application thereof

A hydrogel, sensitive technology, applied in the directions of application, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., to achieve the effects of easy industrial production, overcoming potential safety hazards, and controllable slow-release effect

Active Publication Date: 2017-11-07
THE SECOND PEOPLES HOSPITAL OF SHENZHEN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It has been reported in the literature that gels and microgels composed of phenylboronic acid and poly(N-isopropylacrylamide) (PNIPAM) can swell and release insulin in the presence of glucose, but these materials can only be used above the pKa of phenylboronic acid. It has glucose responsiveness only at pH 9 and higher glucose concentration (20g / L), which limits its application under physiological conditions (pH 7.4, glucose concentration 1-3g / L) (Synthesis and Volume Phase Transitions of Glucose-Sensitive Microgels, Biomacromolecules 2006, 7, 3196-3201, Phenylboronic acid-based glucose-responsive polymeric nanoparticles: synthesis and applications in drug delivery, Polym.Chem., 2014, 5, 1503-1518)

Method used

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  • pH sensitive hydrogel as well as preparation method and application thereof
  • pH sensitive hydrogel as well as preparation method and application thereof
  • pH sensitive hydrogel as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Weigh an appropriate amount of sodium hyaluronate with a number average molecular weight of 15KDa and dissolve it in water, add excess sodium periodate, stir and react for 2 hours at room temperature in the dark, add appropriate amount of ethylene glycol, continue stirring for 15 minutes, and transfer the reaction mixture to the intercepting Dialyze in deionized water for 72 hours in a dialysis bag with a molecular weight of 0.6 kDa, changing the water every four hours. The dialyzed sample was freeze-dried to obtain a white powder product, ie, formylated sodium hyaluronate, with a formylation rate of 5%.

[0038] Add 5g of formylated sodium hyaluronate (formylation rate of 5%) and 1g of four-arm amino-modified polyethylene glycol (Laysan) with a number average molecular weight of 600KDa, add 14g of sterile deionized water, and shake and mix rapidly at 37°C Evenly, after 22 seconds, 20 g of a transparent and uniform pH-sensitive hydrogel was obtained.

[0039] The scann...

Embodiment 2

[0041] Weigh an appropriate amount of sodium hyaluronate with a number average molecular weight of 300KDa and dissolve it in water, add excess sodium periodate, and stir for 2 hours in the dark at room temperature, add an appropriate amount of ethylene glycol, continue stirring for 15 minutes, and transfer the reaction mixture to the intercepting Dialyze in deionized water for 72 hours in a dialysis bag with a molecular weight of 0.6 kDa, changing the water every four hours. The dialyzed sample was freeze-dried to obtain a white powder product, ie, formylated sodium hyaluronate, with a formylation rate of 5%.

[0042] Add 10g of formylated sodium hyaluronate (formylation rate of 5%) and 1g of polyethylene glycol (Laysan) modified with amino groups at the four-arm end of =6.5), at 37° C., oscillated rapidly and mixed evenly, and after 25 seconds, 55 g of a transparent and uniform pH-sensitive hydrogel was obtained.

[0043] The scanning electron microscope images of the pH-sen...

Embodiment 3

[0045] Weigh an appropriate amount of sodium hyaluronate with a number-average molecular weight of 700KDa and dissolve it in water, add excess sodium periodate, stir and react for 2 hours in the dark at room temperature, add appropriate amount of ethylene glycol, continue stirring for 15 minutes, and transfer the reaction mixture to the intercepting Dialyze in deionized water for 72 hours in a dialysis bag with a molecular weight of 0.6 kDa, changing the water every four hours. The dialyzed sample was freeze-dried to obtain a white powder product, ie, formylated sodium hyaluronate, with a formylation rate of 5%.

[0046] Add 0.1g of formylated sodium hyaluronate (formylation rate of 5%) and 1g of four-arm amino-modified polyethylene glycol (Laysan) with a number average molecular weight of 800KDa to add 9.9g of disodium hydrogen phosphate-sodium dihydrogen phosphate The buffer solution (pH=7.4) was shaken and mixed rapidly at 37° C., and after 30 seconds, 11 g of a transparent...

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Abstract

The invention discloses pH sensitive hydrogel as well as a preparation method and an application thereof. The pH sensitive hydrogel is prepared from a raw material A, a raw material B and a gelling solution, the sum of the mass of the raw material A and the mass of the raw material B is 10%-60% of the mass of the hydrogel, wherein the raw material A is aldehyde sodium hyaluronate, the raw material B is polyethylene glycol modified with amino groups at four arms; the pH sensitive hydrogel is mainly obtained through imide dynamic bonds formed by amino groups of polyethylene glycol modified with amino groups at four arms and aldehyde groups of aldehyde sodium hyaluronate or aldehyde glucan. The pH sensitive hydrogel can be used as a drug carrier, an embolization material or a tissue engineering material. The preparation method of the pH sensitive hydrogel comprises the steps as follows: the raw material A, the raw material B and the gelling solution are uniformly mixed to form the pH sensitive hydrogel. The preparation method has the advantages that the preparation process is simple, convenient and quick and mass production is facilitated.

Description

technical field [0001] The invention belongs to the technical field of biomolecular medicine, and in particular relates to a pH-sensitive hydrogel and its preparation and application. Background technique [0002] Hydrogel is a three-dimensional network structure cross-linked by polymers, and has a wide range of applications in biomedical fields such as drug release, tissue engineering, and biosensing. Stimuli-responsive hydrogels, that is, smart hydrogels, can be constructed by introducing groups or chemical structures that are sensitive to physiological environments into polymer chains. The ability of smart hydrogels to respond to environmental stimuli, such as pH, temperature, ionic strength, biochemical signals, and magnetic fields, has drawn increasing interest from researchers. In the human body, the physiological microenvironment of some organelles and lesion sites will be different from that of normal tissues, such as lysosomes, endosomes, inflammatory sites and tum...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/075C08J3/24C08B37/08A61K9/06A61K31/704A61K47/36A61P35/00A61L27/18A61L27/20A61L27/52A61L27/58A61L27/50A61L24/08A61L24/04C08L71/02C08L5/08
CPCA61K9/06A61K31/704A61K47/36A61L24/001A61L24/0031A61L24/0042A61L24/046A61L24/08A61L27/18A61L27/20A61L27/50A61L27/52A61L27/58A61L2400/06C08B37/0072C08J3/075C08J3/246C08J2305/08C08J2371/02C08J2405/08C08J2471/02C08L71/02C08L5/08
Inventor 谭回李维平黄贤键黄国栋刘文兰
Owner THE SECOND PEOPLES HOSPITAL OF SHENZHEN
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