CN110734556B - Preparation method of metal ion reinforced gamma-polyglutamic acid hydrogel - Google Patents

Preparation method of metal ion reinforced gamma-polyglutamic acid hydrogel Download PDF

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CN110734556B
CN110734556B CN201911111130.1A CN201911111130A CN110734556B CN 110734556 B CN110734556 B CN 110734556B CN 201911111130 A CN201911111130 A CN 201911111130A CN 110734556 B CN110734556 B CN 110734556B
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hydrogel
polyglutamic acid
metal ion
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CN110734556A (en
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高强
张晨阳
高春霞
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Yangzhou University
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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
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    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
    • C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
    • C08J3/075—Macromolecular gels
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2377/00—Characterised by the use of polyamides obtained by reactions forming a carboxylic amide link in the main chain; Derivatives of such polymers
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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
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    • C08K3/16—Halogen-containing compounds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00—Use of organic ingredients
    • C08K5/54—Silicon-containing compounds
    • C08K5/541—Silicon-containing compounds containing oxygen
    • C08K5/5435—Silicon-containing compounds containing oxygen containing oxygen in a ring

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Abstract

The invention discloses a method for strengthening gamma-polyglutamic acid hydrogel by metal ions. According to the method, water-soluble high-molecular gamma-polyglutamic acid is used as a monomer, gamma (2, 3-epoxypropoxy) propyl trimethoxy silane (GPTMS) is used as a cross-linking agent to prepare hydrogel, and trivalent metal cerium ions and lanthanum ions are used for carrying out chelation reaction with the hydrogel to prepare the hydrogel with better tensile strength. In the chelation reaction, the process is simple, the prepared hydrogel has good toughness and tensile strength, the tensile strength is improved by two orders of magnitude compared with that of the unreinforced hydrogel, and the obtained metal ion reinforced gamma-polyglutamic acid hydrogel can be applied to cartilage tissue repair, soft robots, biosensors and the like.

Description

Preparation method of metal ion reinforced gamma-polyglutamic acid hydrogel
Technical Field
The invention belongs to a preparation method of hydrogel, and particularly relates to a preparation method of reinforced hydrogel.
Background
Hydrogels are a class of materials consisting of three-dimensional polymer networks that are capable of absorbing large amounts of water. Biodegradable hydrogel is a typical soft material, and has been applied to various biomedical fields, such as tissue engineering scaffolds, drug carriers, and the like. Polyglutamic acid (gamma-PGA), also called natto gum and polyglutamic acid, is a biological polymer which is water-soluble, biodegradable and nontoxic and is prepared by using a microbial fermentation method.
The gamma-polyglutamic acid hydrogel has the characteristics of good biocompatibility, pH response and the like, and is a biological high molecular material with very high application potential because of the excellent characteristics of the gamma-polyglutamic acid hydrogel. However, there are some disadvantages such as a decrease in mechanical strength at a higher water content, resulting in a great limitation in application thereof, and thus it is critical to improve the strength of the gamma-polyglutamic acid hydrogel.
Relevant patents at home and abroad are searched, and no relevant report about metal ion reinforced gamma-polyglutamic acid hydrogel is provided.
Disclosure of Invention
The invention aims to provide a preparation method of metal ion reinforced gamma polyglutamic acid hydrogel, which solves the technical problem that the mechanical strength of the existing gamma polyglutamic acid hydrogel is reduced at higher water content.
Therefore, the preparation method of the metal ion reinforced gamma polyglutamic acid hydrogel provided by the invention comprises the following steps:
(1) dissolving gamma-polyglutamic acid (gamma-PGA) in water and uniformly stirring until the gamma-polyglutamic acid is completely dissolved to obtain a gamma-polyglutamic acid aqueous solution serving as a first reaction solution;
(2) slowly adding gamma- (2, 3-epoxypropoxy) propyl trimethoxy silane (GPTMS) into the first reaction solution while stirring, and uniformly stirring;
(3) taking out the uniformly stirred solution, and putting the solution into an oven to stand for 6 to 12 hours at the temperature of between 35 and 38 ℃ to obtain gamma-polyglutamic acid hydrogel;
(4) and (3) immersing the prepared hydrogel into a trivalent metal ion solution for chelation reaction to obtain the metal ion-reinforced gamma-polyglutamic acid hydrogel, wherein the trivalent metal ion is cerium ion or lanthanum ion.
Furthermore, the molecular weight of the selected gamma-polyglutamic acid is 20-200 ten thousand units. The gamma-polyglutamic acid with the molecular weight of 20-200 ten thousand units has good hydrophilicity and water retention capacity and is easy to dissolve in water.
Further, the mass concentration of the gamma-polyglutamic acid is 5-20 wt%. The gamma-polyglutamic acid in this concentration range is more likely to form a gel.
Preferably, the mass ratio of the gamma- (2, 3-epoxypropoxy) propyl trimethoxy silane to the first reaction liquid is 1: (9-11). Gamma- (2, 3-epoxy propoxy) propyl trimethoxy silane as a cross-linking agent is in cross-linking reaction with gamma-polyglutamic acid, and forms hydrogel after standing in a solution environment.
In a preferred embodiment of the present invention, the concentration of cerium ions or lanthanum ions in the trivalent metal ion solution is 0.02 to 0.2M.
As a preferential scheme of the invention, the time for immersing the hydrogel into the trivalent metal ion solution is 14-18 h; the drying time is 30-45 min.
Compared with the prior art, the invention has the beneficial effects that:
(1) the gamma-polyglutamic acid hydrogel prepared by using gamma-polyglutamic acid which is nontoxic to human bodies as a reaction monomer and using an inorganic silane gamma- (2.3 epoxypropoxy) propyltrimethoxysilane (GPTMS) which is favorable for the growth of osteoblasts as a reaction cross-linking agent adopts the chelation reaction of metal ions by using cheap trivalent metal chloride hydrate as a source for chelating the metal ions in the hydrogel, and has the advantages of low reaction temperature, simple process and low implementation cost.
(2) The reinforced hydrogel prepared by the method has good toughness, can finish chelation reaction in a short time to form chelate with uniform strength, and is small in swelling coefficient and suitable for later-stage application.
(3) The reinforced hydrogel prepared by the method has higher tensile strength when being subjected to a tensile experiment, compared with gamma-polyglutamic acid hydrogel which is not chelated, the strength of the hydrogel prepared by 0.02M/L of cerium ion solution is the best, the Young modulus is improved by 661 times, the tensile strength is improved by 53 times, the strength of the hydrogel prepared by 0.15M/L of lanthanum ion solution is the best under different concentrations of lanthanum ion chelated hydrogel, the Young modulus is improved by 960 times, the tensile strength is improved by 118 times, and the mechanical strength of the hydrogel is greatly improved.
(4) The reinforced hydrogel prepared by the method can be used for cartilage tissue repair, soft robots, biosensors and the like.
Drawings
FIG. 1 is Ce3+At different concentrationsTensile strength phase diagram of the chelated hydrogel.
FIG. 2 is Ce3+Phase diagram of elongation at break for chelating hydrogels at different concentrations.
FIG. 3 is Ce3+Young's modulus of the chelated hydrogel at different concentrations.
FIG. 4 is Ce3+Schematic representation of the principle of chelating hydrogels.
FIG. 5 is La3+Phase diagram of tensile strength of chelated hydrogels at different concentrations.
FIG. 6 is La3+Phase diagram of elongation at break for chelated hydrogels at different concentrations.
FIG. 7 is La3+Young's modulus of the chelated hydrogel at different concentrations.
FIG. 8 shows the hydrogel and La of example 13+Scanning electron microscope pictures of the ion-enhanced hydrogel.
Detailed Description
The present invention will be described in more detail with reference to the following examples and the accompanying drawings.
Example 1
Weighing 1g of gamma-PGA powder with the molecular weight of 20-200 ten thousand units, dissolving the gamma-PGA powder in 10ml of deionized water, stirring the mixture for 2-3 hours by using magnetic force to completely dissolve the gamma-PGA powder, adding 1ml of GPTMS serving as a cross-linking agent, stirring the mixture for 4-5 hours by using magnetic force to perform cross-linking reaction on the gamma-PGA and the GPTMS, pouring the liquid polymer solution into a mold, placing the mold into a drying oven at 37 ℃ to stand for 8-12 hours until the gel is formed, taking out the gel to obtain gamma-PGA hydrogel, and cutting the hydrogel into strip samples with basically the same length and width.
Example 2
Further, 0.373g, 1.118g, 1.863g, 2.795g, 3.726g CeCl were weighed respectively3·7H2O was dissolved in 50ml of ultrapure water to prepare 0.02M (mol/L), 0.06M, 0.1M, 0.15M, 0.2M Ce3+Aqueous solution of concentration the hydrogel specimens prepared in example 1 were immersed in different Ce solutions3+And (3) taking out the solution with the concentration for 16h, and drying for 30-45min to obtain the metal ion reinforced gamma-PGA hydrogel.
Measured by tensile test with Ce3+Gamma-PGA hydrogel undergoing chelation reactionTensile strength of (1) and (2) Ce in FIGS. 1 and 23+The comparative graphs of the tensile strength and the elongation at break of the chelating hydrogel under different ion concentrations respectively correspond to the non-soaked Ce3+Ionic gamma-PGA hydrogel samples and 0.02M (mol/L), 0.06M, 0.1M, 0.15M, 0.2M Ce3+The test result of the sample soaked by the aqueous solution with the concentration shows that: passing through Ce compared to tensile strength of gamma-PGA hydrogel3+The tensile strength of the hydrogel after the ion chelation reaction is improved by 53 times to the maximum extent, the elongation at break is slightly reduced, but the tensile strength is obviously improved. FIG. 3 is Ce3+The Young's modulus of the chelating hydrogel under different ion concentrations is compared with the tensile strength of the gamma-PGA hydrogel through Ce3+The Young modulus of the hydrogel after chelation reaction is improved by 661 times at most. The mechanical strength of the hydrogel is obviously improved. FIG. 4 is a schematic diagram illustrating the principle of the chelating reaction between γ -PGA hydrogel and trivalent metal ions, wherein γ -polyglutamic acid is reacted with γ - (2, 3-epoxypropoxy) propyltrimethoxysilane (GPTMS) to form a cyclic γ -polyglutamic acid hydrogel having Si-O-Si structure, and the resulting γ -polyglutamic acid hydrogel is immersed in CeCl3In solution, hydrogel with Ce3+Ions generate chelation reaction to generate the hydrogel crosslinked by the physical and chemical network double networks.
Example 3
0.258g, 0.775g, 1.293g, 1.938g and 2.584g of CeCl were weighed respectively3·7H2Dissolving O in 50ml ultrapure water to obtain 0.02M (mol/L), 0.06M, 0.1M, 0.15M, 0.2M La3+Aqueous solution of concentration the hydrogel specimens prepared in example 1 were immersed in different La solutions3+And (4) taking out the solution with the concentration for drying for 30-45min to obtain the metal ion reinforced gamma-PGA hydrogel.
Determined by tensile test and La3+Tensile strength of the chelate-reacted γ -PGA hydrogel, and La is shown in FIGS. 5 and 63+Comparative phase diagram of tensile Strength and elongation at Break of chelating hydrogels at different concentrations, compared to tensile Strength of γ -PGA hydrogels over La3+The tensile strength of the hydrogel after the chelation reaction is improved by 118 times to the maximum, the elongation at break is slightly reduced, but the tensile strength is obviously improvedFIG. 7 is La3+The Young's modulus of the chelating hydrogel at different concentrations is compared with the tensile strength of the gamma-PGA hydrogel through La3+The Young modulus of the hydrogel after chelation reaction is improved by 960 times to the maximum. The mechanical strength of the hydrogel is obviously improved.
Example 4
A preparation method of metal ion reinforced gamma polyglutamic acid hydrogel comprises the following steps:
(1) dissolving gamma-polyglutamic acid with the molecular weight of 20-200 million units in water, and uniformly stirring until the gamma-polyglutamic acid is completely dissolved to obtain a gamma-polyglutamic acid aqueous solution serving as a first reaction solution, wherein the mass concentration of the gamma-polyglutamic acid in the first reaction solution is 5-20 wt%;
(2) slowly adding gamma- (2, 3-epoxypropoxy) propyl trimethoxy silane into the first reaction liquid while stirring, and uniformly stirring; the mass ratio of the gamma- (2, 3-epoxy propoxy) propyl trimethoxy silane to the first reaction liquid is 1: (9-11);
(3) taking out the uniformly stirred solution, and putting the solution into an oven to stand for 6 to 12 hours at the temperature of between 35 and 38 ℃ to obtain gamma polyglutamic acid hydrogel;
(4) immersing the prepared solution into a trivalent lanthanum ion solution for 14-18h, carrying out chelation reaction, taking out hydrogel, and drying for 30-45mi to obtain reinforced hydrogel, namely the metal ion reinforced gamma polyglutamic acid hydrogel, wherein the concentration of lanthanum ions is 0.02-0.2M.
The obtained metal ion reinforced gamma polyglutamic acid hydrogel has high tensile strength, and the mechanical strength of the hydrogel is obviously improved.
The γ -PGA hydrogel obtained in example 1 and La of this example3+The chelated hydrogel was freeze-dried and SEM photographed to obtain fig. 8, in which it was clearly seen that the hydrogel had a significantly reduced pore size and was more dense.
The trivalent lanthanum ion solution can be replaced by trivalent cerium ion solution, and the aim of improving the strength of the hydrogel can be achieved.
The present invention is not limited to the above embodiments, and based on the technical solutions disclosed in the present invention, those skilled in the art can make some substitutions and modifications to some technical features without creative efforts based on the disclosed technical contents, and these substitutions and modifications are all within the protection scope of the present invention.

Claims (4)

1. A preparation method of metal ion reinforced gamma-polyglutamic acid hydrogel is characterized by comprising the following steps:
dissolving gamma-polyglutamic acid in water and uniformly stirring until the gamma-polyglutamic acid is completely dissolved to obtain a gamma-polyglutamic acid aqueous solution serving as a first reaction solution; in the first reaction liquid, the mass concentration of the gamma-polyglutamic acid is 9-11 wt%; the molecular weight of the selected gamma-polyglutamic acid is 20-200 ten thousand units;
slowly adding gamma- (2, 3-epoxypropoxy) propyl trimethoxy silane into the first reaction liquid while stirring, and uniformly stirring; the mass ratio of the gamma- (2, 3-epoxypropoxy) propyl trimethoxy silane to the first reaction liquid is 1: (9-11);
taking out the uniformly stirred solution, and putting the solution into an oven to stand for 6 to 12 hours at the temperature of between 35 and 38 ℃ to obtain gamma-polyglutamic acid hydrogel;
and (2) immersing the prepared gamma-polyglutamic acid hydrogel into a trivalent metal ion solution for carrying out chelation reaction, taking out the hydrogel and drying to obtain the metal ion reinforced gamma-polyglutamic acid hydrogel, wherein the trivalent metal ion is cerium ion or lanthanum ion, and the concentration of the cerium ion or lanthanum ion in the trivalent metal ion solution is 0.02-0.2M.
2. The method of claim 1, wherein the concentration of trivalent metal ions is in the range of 0.02 to 0.15M.
3. The method for preparing a metal ion-reinforced gamma-polyglutamic acid hydrogel according to claim 1, wherein the time for immersing the hydrogel in the solution of trivalent metal ions is 14-18 h.
4. The method for preparing metal ion-reinforced gamma-polyglutamic acid hydrogel according to claim 1, wherein the drying time is 30-45 min.
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CN106589409A (en) * 2016-11-28 2017-04-26 上海大学 Polyglutamic acid/sodium alginate adhesive hydrogel and preparation method thereof
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