CN113583256B - Preparation method of cationic hydrogel material - Google Patents

Preparation method of cationic hydrogel material Download PDF

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CN113583256B
CN113583256B CN202110756740.8A CN202110756740A CN113583256B CN 113583256 B CN113583256 B CN 113583256B CN 202110756740 A CN202110756740 A CN 202110756740A CN 113583256 B CN113583256 B CN 113583256B
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hydrogel material
gel
compound
cationic hydrogel
cationic
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CN113583256A (en
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董伟
黄怡静
谢阿明
程思瑶
王浩
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Nanjing University of Science and Technology
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    • 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
    • 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
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
    • C08G73/02—Polyamines
    • 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
    • C08J2379/00—Characterised by the use of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing nitrogen with or without oxygen, or carbon only, not provided for in groups C08J2361/00 - C08J2377/00
    • C08J2379/02—Polyamines

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Abstract

The invention discloses a preparation method of a cationic hydrogel material, belonging to the technical field of hydrogel materials, and the preparation method comprises the following steps: dispersing the diamido compound into a sodium hydroxide solution, uniformly stirring, dropwise adding the dibromo compound into the mixed solution, uniformly stirring, pouring into a gel mold, standing at 30-70 ℃ to form gel, dialyzing a gel crude product to remove impurities, and freeze-drying to obtain the cationic hydrogel material. The reaction condition is mild, the reaction time is short, various hydrogel materials can be prepared by changing the types and the proportions of the diamino compound and the dibromo compound, and the obtained hydrogel materials have no cytotoxicity and contain a large number of hydrophilic groups and a large number of tertiary amino groups, so that the hydrogel materials have excellent water absorption performance and good antibacterial capacity, and have good prospects in application of biological materials.

Description

Preparation method of cationic hydrogel material
Technical Field
The invention relates to the technical field of hydrogel material preparation, in particular to a preparation method of a cationic hydrogel material.
Background
With the rapid advance of science and technology, modern medicine also revolutionized. Wound dressings for wound care have been developed from conventional gauze, bandages and the like to the present new bioactive dressings. Currently, the biological auxiliary materials required in the medical field are mainly hydrogel materials, the adopted hydrogel materials need to have good moisture retention and antibacterial property and good biocompatibility, and the gel materials and wounds keep a complete stripping state so as to reduce the damage to the wound surfaces during replacement.
Currently, most hydrogel materials are loaded with antimicrobial agents and drugs through physical encapsulation, which is prone to drug burst release. For example, hydrogel containing zinc oxide or silver particles may cause local excessive concentration due to release of nanoparticles or ions at the initial stage of use, generate excessive toxicity, and eventually the gel may lose antibacterial ability with sustained release of the drug.
Based on this, there is a strong need for a hydrogel material that has good moisture retention and antibacterial properties and does not cause the problem of burst release of the drug.
Disclosure of Invention
The present invention is directed to solve the problems of the prior art, and provides a method for preparing a cationic hydrogel material, wherein the method is simple, the cationic hydrogel material can be produced in large quantities, and the prepared hydrogel material has excellent moisture retention, antibacterial property and biocompatibility, and has no drug burst release problem.
Technical scheme
A preparation method of a cationic hydrogel material comprises the following steps:
(1) Dispersing the diamino compound into a sodium hydroxide solution, and uniformly stirring to obtain a mixed solution;
(2) Dropwise adding a dibromo compound into the mixed solution in the step (1), uniformly stirring, pouring into a gel mold, and standing at 30-70 ℃ to form gel to obtain a gel crude product;
(3) And dialyzing the gel crude product, and freeze-drying to obtain the cationic hydrogel material.
In the step (2), the dibromo compound is selected from any one of 1, 3-dibromo-2-propanol, 1, 3-propanedibromo, 1, 4-butanedibromo, 1, 6-hexandibromo, 1, 7-heptadibromo and 1, 8-octadibromo.
Further, in the step (1), the diamino compound is selected from any one of 1, 3-diamino-2-propanol, 1, 3-propanediamine, 1, 4-butanediamine, 1, 6-hexanediamine, 1, 7-heptanediamine, 1, 8-octanediamine or trans-1, 4-cyclohexanediamine, and more preferably 1, 6-hexanediamine, because the carbon skeleton is long, but has good biocompatibility and water solubility, and a large amount of tertiary amine can be obtained by the reaction.
Further, in the step (2), the dibromo compound is 1, 3-dibromo-2-propanol.
Further, in the step (2), the molar ratio of the diamino compound to the dibromo compound is (0.1 to 1.5): 1.
further, in the step (2), the molar ratio of the sodium hydroxide to the dibromo compound is (1-8): 1.
the invention has the beneficial effects that: the invention provides a preparation method of a cationic hydrogel material, which has mild reaction conditions and short reaction time, and can prepare various hydrogel materials by changing the types and the proportions of a diamino compound and a dibromo compound.
Drawings
FIG. 1 shows the results of cytotoxicity tests on cationic hydrogel materials prepared in examples 1 to 6;
FIG. 2 shows the results of the test of the sterilization efficiency of the cationic hydrogel materials prepared in examples 1 to 6 on Escherichia coli;
FIG. 3 shows the results of the measurement of the antibacterial activity of the cationic hydrogel material prepared in example 4 against E.coli.
Detailed Description
In order to make the technical means, the characteristics, the objectives and the functions of the present invention easy to understand, the present invention will be further described with reference to the following embodiments.
Example 1
A preparation method of a cationic hydrogel material comprises the following steps:
(1) Dispersing 1, 3-diamino-2-propanol (0.0249 mol) into sodium hydroxide aqueous solution (1 g/4 mL), and stirring uniformly to obtain mixed solution;
(2) Dropwise adding 1, 3-dibromo-2-propanol (0.0166 mol) into the mixed solution in the step (1), stirring for 30min, pouring into a gel mold, and standing in a water bath kettle at 40 ℃ to form gel to obtain a crude gel product;
(3) And (3) dialyzing the gel crude product by using deionized water to remove impurities, and then freezing and drying to obtain the cationic hydrogel material.
The reaction equation for this example is as follows:
Figure BDA0003147952100000031
example 2
A method for preparing a cationic hydrogel material, comprising the following steps:
(1) Dispersing 1, 3-propane diamine (0.0166 mol) into a sodium hydroxide aqueous solution (2 g/4 mL), and uniformly stirring to obtain a mixed solution;
(2) Dropwise adding 1, 3-dibromo-2-propanol (0.0166 mol) into the mixed solution obtained in the step (1), stirring for 30min, pouring into a gel mold, and standing in a water bath kettle at 30 ℃ to form gel to obtain a crude gel product;
(3) And (3) dialyzing the gel crude product by using deionized water to remove impurities, and then freezing and drying to obtain the cationic hydrogel material.
The structural formula of the cationic hydrogel material prepared in this example is as follows:
Figure BDA0003147952100000032
example 3
A preparation method of a cationic hydrogel material comprises the following steps:
(1) Dispersing 1, 4-butanediamine (0.0249 mol) into a sodium hydroxide aqueous solution (1 g/4 mL), and uniformly stirring to obtain a mixed solution;
(2) Dropwise adding 1, 3-dibromo-2-propanol (0.0166 mol) into the mixed solution obtained in the step (1), stirring for 30min, pouring into a gel mold, and standing in a water bath kettle at 40 ℃ to form gel to obtain a crude gel product;
(3) And (3) dialyzing the gel crude product by using deionized water to remove impurities, and then freeze-drying to obtain the cationic hydrogel material.
The structural formula of the cationic hydrogel material prepared in this example is as follows:
Figure BDA0003147952100000041
example 4
A preparation method of a cationic hydrogel material comprises the following steps:
(1) Dispersing 1, 6-hexamethylene diamine (0.0166 mol) into a sodium hydroxide aqueous solution (2 g/4 mL), and uniformly stirring to obtain a mixed solution;
(2) Dropwise adding 1, 3-dibromo-2-propanol (0.0166 mol) into the mixed solution obtained in the step (1), stirring for 30min, pouring into a gel mold, and standing in a water bath kettle at 50 ℃ to form gel to obtain a crude gel product;
(3) And (3) dialyzing the gel crude product by using deionized water to remove impurities, and then freeze-drying to obtain the cationic hydrogel material.
The structural formula of the cationic hydrogel material prepared in this example is as follows:
Figure BDA0003147952100000051
example 5
A method for preparing a cationic hydrogel material, comprising the following steps:
(1) Dispersing 1, 7-heptanediamine (0.0133 mol) into a sodium hydroxide aqueous solution (1 g/4 mL), and uniformly stirring to obtain a mixed solution;
(2) Dropwise adding 1, 3-dibromo-2-propanol (0.0166 mol) into the mixed solution in the step (1), stirring for 30min, pouring into a gel mold, and standing in a water bath kettle at 60 ℃ to form gel to obtain a crude gel product;
(3) And (3) dialyzing the gel crude product by using deionized water to remove impurities, and then freeze-drying to obtain the cationic hydrogel material.
The structural formula of the cationic hydrogel material prepared in this example is as follows:
Figure BDA0003147952100000052
example 6
A preparation method of a cationic hydrogel material comprises the following steps:
(1) Dispersing 1, 8-octanediamine (0.0166 mol) into a sodium hydroxide aqueous solution (1 g/4 mL), and uniformly stirring to obtain a mixed solution;
(2) Dropwise adding 1, 3-dibromo-2-propanol (0.0166 mol) into the mixed solution obtained in the step (1), stirring for 30min, pouring into a gel mold, and standing in a water bath kettle at 70 ℃ to form gel to obtain a crude gel product;
(3) And (3) dialyzing the gel crude product by using deionized water to remove impurities, and then freeze-drying to obtain the cationic hydrogel material.
The structural formula of the cationic hydrogel material prepared in this example is as follows:
Figure BDA0003147952100000061
example 7
A preparation method of a cationic hydrogel material comprises the following steps:
(1) Dispersing trans-1, 4-cyclohexanediamine (0.0166 mol) into a sodium hydroxide aqueous solution (1 g/4 mL), and uniformly stirring to obtain a mixed solution;
(2) Dropwise adding 1, 3-dibromo-2-propanol (0.0166 mol) into the mixed solution in the step (1), stirring for 30min, pouring into a gel mold, and standing in a water bath kettle at 70 ℃ to form gel to obtain a crude gel product;
(3) And (3) dialyzing the gel crude product by using deionized water to remove impurities, and then freeze-drying to obtain the cationic hydrogel material.
The structural formula of the cationic hydrogel material prepared in this example is as follows:
Figure BDA0003147952100000071
and (3) performance testing:
1. cytotoxicity test (MTT method)
The cationic hydrogel materials prepared in examples 1-6 were subjected to cytotoxicity tests, which were carried out according to the following procedure:
(1) Log phase L929 cells were collected, cell suspension concentration was adjusted, 100u1 was added per well, and test cells were plated to 5000-10000 cells/well (marginal wells filled with sterile PBS).
(2)5％CO 2 Incubate at 37 ℃ until the cell monolayer is confluent at the bottom of the well (96-well flat bottom plate), add concentration gradient drug (1 mg/mL,5mg/mL,10mg/mL,15mg/mL,20mg/mL,30mg/mL,50 mg/mL), add the drug the next day in the morning, 100ul per well, and set 5 replicates.
(3)5％CO 2 Incubated at 37 ℃ for 48h and observed under an inverted microscope.
(4) 20ul of MTT solution (5 mg/ml, i.e.0.5% MTT) was added per well and the incubation was continued for 4h.
(5) The culture was terminated and the culture medium in the wells was carefully aspirated.
(6) Adding 150u1 dimethyl sulfoxide into each hole, and placing on a shaking table to shake at low speed for 10min to fully dissolve crystals. The absorbance of each well was measured at OD 490nm in an enzyme-linked rabbit disease detector.
The results of cytotoxicity test at a dosing concentration of 20mg/mL are shown in FIG. 1, and it can be seen that the cell survival rate exceeds 80% in the presence of the cationic hydrogel materials prepared in examples 1-6, which indicates that the cationic hydrogel materials prepared in examples 1-6 of the present invention have low cytotoxicity and good biocompatibility.
2. Sterilization Rate test (bacteria OD test)
(1) Preparing bacterial liquid: inoculating Escherichia coli on common agar plate, culturing at 37 deg.C for 24 hr, transferring the strain to 4ml culture medium tube with inoculating loop, culturing for 6-8 hr, adding 0.1ml bacterial liquid into 100ml liquid culture medium, and diluting by 1000 times.
(2) Set experimental and control groups (set one parallel group):
experimental groups 1ml of LB medium +4ml of cationic hydrogel material,
control group, 1ml LB medium +4ml physiological saline.
(3) 0.1ml of 2 bacterial solutions (experimental group and control group) diluted 1000 times were added to each test tube, cultured for 4 hours, and the OD value at 600nm was measured.
The results of the sterilization rate test are shown in FIG. 2, and it can be seen from FIG. 2 that the cationic hydrogel materials prepared in examples 1-6 all have a sterilization capability of 80% or more on Escherichia coli, and have excellent sterilization capability.
3. Antibacterial experiments
(1) First, 30. Mu.L of E.coli cells were mixed with 2.97mL of LB medium and incubated at 37 ℃ and 250rpm for 6 hours. Then, the concentration was 1X 10 by dilution 6 Colony forming units/mL (CFU/mL) of bacterial suspension.
(2) The hydrogel materials prepared in example 4 (0 mg, 0.25mg, 0.5mg and 1.0 mg) were placed in 1.5mL centrifuge tubes, 100. Mu.L of the bacterial suspension obtained in step (1) was added, mixed, 20. Mu.L of the bacterial suspension was taken out, dropped on an agar plate, dispersed uniformly, incubated at 37 ℃ for 12h, and E.coli was collected.
FIG. 3 shows the result of the antibacterial test, wherein (a) is the experimental control group, the hydrogel material is added in an amount of 0, (b) the corresponding hydrogel material is added in an amount of 0.25mg, (c) the corresponding hydrogel material is added in an amount of 0.5mg, and (d) the corresponding hydrogel material is added in an amount of 1.0mg, which shows that the hydrogel prepared in example 4 has excellent antibacterial performance against Escherichia coli.

Claims (5)

1. A preparation method of a cationic hydrogel material is characterized by comprising the following steps:
(1) Dispersing the diamido compound into a sodium hydroxide solution, and uniformly stirring to obtain a mixed solution;
(2) Dropwise adding a dibromo compound into the mixed solution in the step (1), uniformly stirring, pouring into a gel mold, and standing at 30-70 ℃ to form gel to obtain a gel crude product;
(3) Dialyzing the gel crude product, and then freeze-drying to obtain a cationic hydrogel material;
the dibromo compound is 1, 3-dibromo-2-propanol.
2. The method for preparing the cationic hydrogel material according to claim 1, wherein in the step (1), the diamine compound is any one selected from 1, 3-diamino-2-propanol, 1, 3-propanediamine, 1, 4-butanediamine, 1, 6-hexanediamine, 1, 7-heptanediamine, 1, 8-octanediamine and trans-1, 4-cyclohexanediamine.
3. The method of preparing the cationic hydrogel material of claim 2, wherein the diamino compound is 1, 6-hexanediamine.
4. The method for preparing the cationic hydrogel material according to claim 1, wherein in the step (2), the molar ratio of the diamino compound to the dibromo compound is (0.1 to 1.5): 1.
5. the method for preparing the cationic hydrogel material according to any one of claims 1 to 4, wherein in the step (2), the molar ratio of the sodium hydroxide to the dibromo compound is (1-8): 1.
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