CN103497355B - Aminated compounds linking agent and the application in hydrogel preparation method thereof - Google Patents
Aminated compounds linking agent and the application in hydrogel preparation method thereof Download PDFInfo
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 66
- 238000002360 preparation method Methods 0.000 title claims abstract description 36
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- 239000002904 solvent Substances 0.000 claims abstract description 15
- 239000002131 composite material Chemical class 0.000 claims abstract description 7
- 238000004132 cross linking Methods 0.000 claims abstract description 7
- 238000006845 Michael addition reaction Methods 0.000 claims abstract description 4
- 230000007246 mechanism Effects 0.000 claims abstract description 3
- 229920000642 polymer Polymers 0.000 claims description 23
- 241001597008 Nomeidae Species 0.000 claims description 20
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 16
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- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical group C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 claims description 6
- 239000002994 raw material Substances 0.000 claims description 5
- 239000002798 polar solvent Substances 0.000 claims description 4
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims description 3
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- 230000004048 modification Effects 0.000 abstract description 7
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- 238000011065 in-situ storage Methods 0.000 description 14
- 239000000178 monomer Substances 0.000 description 13
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 239000002202 Polyethylene glycol Substances 0.000 description 8
- 229920001223 polyethylene glycol Polymers 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 6
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 6
- LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 description 5
- 229920002521 macromolecule Polymers 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 239000004254 Ammonium phosphate Substances 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 4
- 235000019289 ammonium phosphates Nutrition 0.000 description 4
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- 230000008569 process Effects 0.000 description 4
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 3
- 229920001661 Chitosan Polymers 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
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- 229920002451 polyvinyl alcohol Polymers 0.000 description 3
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 2
- 235000011130 ammonium sulphate Nutrition 0.000 description 2
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- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- QOLNPNNPYSZFGE-UHFFFAOYSA-N CC(C)[N+]([O-]C)=O Chemical compound CC(C)[N+]([O-]C)=O QOLNPNNPYSZFGE-UHFFFAOYSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
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- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
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- 230000018109 developmental process Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
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- 229960002989 glutamic acid Drugs 0.000 description 1
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Classifications
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- 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
- 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
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F222/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides, or nitriles thereof
- C08F222/36—Amides or imides
-
- 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
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L33/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- C08L33/24—Homopolymers or copolymers of amides or imides
- C08L33/26—Homopolymers or copolymers of acrylamide or methacrylamide
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L71/00—Compositions of polyethers obtained by reactions forming an ether link in the main chain; Compositions of derivatives of such polymers
- C08L71/02—Polyalkylene oxides
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- 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
- C08G2210/00—Compositions for preparing hydrogels
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- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2650/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G2650/28—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule characterised by the polymer type
- C08G2650/30—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule characterised by the polymer type branched
- C08G2650/32—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule characterised by the polymer type branched dendritic or similar
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- 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
- C08J2371/00—Characterised by the use of polyethers obtained by reactions forming an ether link in the main chain; Derivatives of such polymers
- C08J2371/02—Polyalkylene oxides
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Abstract
The invention provides a kind of aminated compounds linking agent and the application in hydrogel preparation method thereof.This aminated compounds linking agent comprises a kind of aminated compounds, or composite obtained by multiple aminated compounds.Adopt this aminated compounds linking agent, by novel Michael addition mechanism of crosslinking, make it be cross-linked into three-dimensional net structure, obtained hydrogel.By regulating the ratio of aminated compounds, polymkeric substance, solvent three, cross-linking density and the intensity of hydrogel can be changed, and then affect the swelling behavior of hydrogel.The hydrogel that the present invention obtains is harmless to health, to cytotoxic effect, can be widely used in biomedical sector, as cell cultures, organizational project, bioactivity surface modification etc.
Description
Technical field
The present invention relates to a kind of aminated compounds linking agent, relate to this application of aminated compounds linking agent in hydrogel preparation method simultaneously, belong to technical field of polymer materials.
Background technology
Hydrogel is a kind of macromolecule network system, and character is soft, can keep definite shape, only swellingly in water does not dissolve.Its chemical property and physical properties extremely similar to natural cellular environment, and good biocompatibility, has broad application prospects in fields such as medical science, biology, medicines.To absorb water high water-keeping material as height, hydrogel is widely used in multiple fields, as: wound auxiliary material, contact lens, pharmaceutical carrier etc., following have good development space in soft tissue repair, cardiac stent etc.
Hydrogel of a great variety, the hydrogel being applied to biomedical sector can be divided into natural polymer hydrogel and synthesis macromolecule hydrogel substantially.Natural macromolecule hydrogel comprises polyose (starch, Lalgine, hyaluronic acid, chitosan etc.) and polypeptide class (collagen, polylysine, L-glutamic acid etc.).The macromolecule hydrogel of synthesis mainly comprises polyoxyethylene glycol and derivative, poly(lactic acid), polycaprolactone, polyacrylamide, polyacrylic acid etc.
Hydrogel is generally by physics or the crosslinked preparation of chemical mode.In the past in 30 years, develop the hydrogel that many crosslinking methods are different.Wherein more traditional hydrogel formation method is progressively polymerized, particularly Michael's conjugate addition method.In recent years, people have studied the formation of hydrogel by progressively polymerization mechanism.Wherein, the Michael addition chemistry between sulfydryl and acrylate-based or vinyl sulfuryl applies method very widely, and it can be utilized to prepare the hydrogel of original position.Such as, Hubbell equals 2003 have successfully obtained PEG base when sulfydryl and acrylate-based mol ratio are 1:1 hydrogel by this cross-linking method, and open source literature is see Vernon, B.; Tirelli, N.; Bachi, T.; Haldimann, D.; Hubbell, J.A.Water-borne, in situ crosslinked biomaterialsfrom phase-segregated precursors.J.Biomed.Mater.Res.A2003,64,447.Such as, but this method existing defects, in synthesis, sulfydryl has niff, and functionalization step is more consuming time, and the sulfide being connected with biomolecules has the possibility of sex change, and lacks the control to the room and time of network structure.
The most frequently used polymkeric substance doing hydrogel has polyoxyethylene glycol, polyvinyl alcohol etc.Wherein polyoxyethylene glycol (PEG) is as a kind of raw material of synthesis type hydrogel, good biocompatibility, and due to its simply submissive structure, PEG has natural biologically inert to cell adhesion and identification.PEG by the certification of FDA Food and Drug Administration (FDA), has a wide range of applications at biology, medical science, medicine etc.Commercial polyoxyethylene glycol has different molecular weight, and its structure can be linear or multi-arm star-shaped structure, and different groups can be modified in its molecular chain two ends, as end group connects dissimilar double bond, is cross-linked by free radical or Michael addition.
Summary of the invention
Primary technical problem to be solved by this invention is to provide a kind of novel aminated compounds linking agent.
Another technical problem to be solved by this invention is to provide a kind of method utilizing aminated compounds linking agent to carry out hydrogel to prepare.
For realizing above-mentioned goal of the invention, the invention provides following technical scheme:
A kind of aminated compounds linking agent, comprises a kind of aminated compounds, or composite obtained by multiple aminated compounds.
Described aminated compounds has following general formula:
Wherein R can be:
in one or more.
Wherein more preferably, described aminated compounds linking agent, composite obtained by ammoniacal liquor and other aminated compounds.
Wherein more preferably, described aminated compounds is selected from Secondary ammonium phosphate, primary ammonium phosphate, ammonium phosphate, ammoniacal liquor, ammonium sulfate, ammonium nitrate, ammonium chloride, volatile salt, bicarbonate of ammonia.
The application of above-mentioned aminated compounds linking agent in hydrogel preparation method.
A kind of hydrogel using above-mentioned aminated compounds linking agent to prepare.
A kind of hydrogel preparation method take end group as the polymer derivant of unsaturated double-bond is raw material, adds solvent and above-mentioned aminated compounds linking agent, obtained hydrogel.
Wherein more preferably, described polymer derivant is water-soluble polymers.
Wherein more preferably, the end group of described polymer derivant is selected from the unsaturated double-bonds such as vinyl sulphone, acrylamide, vinyl cyanide.
Wherein more preferably, described solvent is polar solvent.
Wherein more preferably, the mass ratio of described polymer derivant and described solvent is between 2:1 to 1:20; The mass ratio of described polymer derivant and described aminated compounds linking agent is between 100:1 to 1:5.
Aminated compounds linking agent provided by the invention, is selected from cheap aminated compounds, better economy.Meanwhile, in the process preparing hydrogel, this aminated compounds can decompose and can not produce toxic gas, and the feature of environmental protection is better.
Aminated compounds linking agent provided by the invention can be used for preparing hydrogel.Adopt aminated compounds of the present invention as linking agent, by novel Michael reaction, make it be cross-linked into three-dimensional net structure, obtained hydrogel.By regulating the ratio of aminated compounds, polymkeric substance, solvent three, cross-linking density and the intensity of hydrogel can be changed, and then affect the swelling behavior of hydrogel.
The mechanical property of the hydrogel obtained by above-mentioned preparation method is controlled, has the functional group that can modify in a large number.This hydrogel is harmless to health, to cytotoxic effect, without immune response.Therefore, the hydrogel obtained by the present invention has important application by biomedical sector, such as, for cell cultures, organizational project, bioactivity surface modification, intraocular lens etc.
Embodiment
Below aminated compounds linking agent provided by the invention and the application in hydrogel preparation method thereof are described in detail.
Aminated compounds linking agent provided by the present invention, comprises a kind of aminated compounds, or composite obtained by multiple different aminated compounds.Above-mentioned aminated compounds can be selected from ammoniacal liquor and ammonium salt thereof, such as be selected from Secondary ammonium phosphate, primary ammonium phosphate, ammonium phosphate, ammoniacal liquor, ammonium sulfate, ammonium nitrate, ammonium chloride, volatile salt, bicarbonate of ammonia any one, can be various water miscible inorganic or organic amine compounds and their mixture.More preferably, aminated compounds linking agent, can be composite obtained by ammoniacal liquor and other aminated compounds.When multiple aminated compounds is composite, the part by weight of various aminated compounds is unrestricted, and the ammonium ion total mainly through it is had an effect.When preparing hydrogel, multiple aminated compounds can mix in advance, also can add to respectively in the mixing solutions for the preparation of hydrogel.
Aminated compounds linking agent provided by the invention has the structure shown in general structure [1]:
Wherein, R can be:
in any one or multiple.
Aminated compounds linking agent provided by the invention, is selected from cheap aminated compounds, better economy.Meanwhile, this aminated compounds can decompose in the process preparing hydrogel, can not produce toxic gas, and the feature of environmental protection is also better.By the aminated compounds of selecting one or more common as the linking agent preparing hydrogel, the preparation system of hydrogel is made to have the feature of cheap environmental protection.
Meanwhile, the invention provides the application of above-mentioned aminated compounds linking agent in hydrogel preparation method.
This hydrogel preparation method take end group as the polymer derivant of unsaturated double-bond is raw material, adds solvent and above-mentioned aminated compounds linking agent, obtained hydrogel.
In this hydrogel preparation method, the end group of polymer derivant can be selected from the activation double bond functional groups such as vinyl sulphone, vinyl cyanide, acrylamide, also can be selected from and have the end group of general structure [2] to the unsaturated double-bond structure shown in [4]:
In this hydrogel preparation method, the structure of the polymer derivant of use can be any one in linear structure, branched structure or multi-arm structure.This polymer derivant can be water miscible complete same, same, a random compound.Polymer derivant can be selected from the polyoxyethylene glycol of molecular weight between 500-100000, polyacrylamide, polyvinyl alcohol, polysiloxane-based etc. and all water-soluble natural or synthesising macromolecule copolymers well such as hyaluronic acid, chitosan, Mierocrystalline cellulose.The general structure of common water-soluble polymers has:
Polyoxyethylene glycol:
Polyvinyl alcohol
Polysiloxane-based:
Hyaluronic acid:
Chitosan
Mierocrystalline cellulose etc.
In this hydrogel preparation method, the solvent of use can be selected from methyl alcohol, ethanol, water, dimethyl sulfoxide (DMSO), dimethyl formamide polar solvent.
In this hydrogel preparation method, use above-mentioned polymer derivant, aminated compounds linking agent, solvent, Homogeneous phase mixing obtains hydrogel.Wherein, the mass ratio of polymer derivant and solvent is between 2:1 to 1:20; The mass ratio of polymer derivant and aminated compounds linking agent is between 100:1 to 1:5.It is the polymer derivant of unsaturated double-bond that this hydrogel synthesis system comprises a certain amount of water miscible end group, various organic or inorganic amino derivative and their mixture, ethanol or water polar solvent, after Homogeneous phase mixing, wait for certain hour, spontaneous in-situ cross-linked formation hydrogel.In the process forming in-situ hydrogel, can by heating or increasing stirring velocity, accelerated reaction process.But the formation of in-situ hydrogel does not also rely on the temperature of heating or the speed of stirring, after the solution mixed at room temperature is left standstill for some time, also acquisition in-situ hydrogel can be observed.
Be described using above-mentioned aminated compounds linking agent to carry out method prepared by hydrogel below by specific embodiment.Be necessary to herein means out; following examples are only for the present invention is described further; can not be interpreted as limiting the scope of the invention, the professional and technical personnel in this field makes some nonessential improvement and adjustment according to the content in embodiment, still belongs to protection scope of the present invention.
Embodiment 1: the preparation of novel hydrogels
In 4ml test tube, add the multi-arm polyethylene glycol monomer that 300mg is acrylate modified respectively, 200mg water and 50mg amine compound.Wherein, amine compound is the mixture of Secondary ammonium phosphate and ammoniacal liquor, and the mass ratio of Secondary ammonium phosphate and ammoniacal liquor is 20:100.
Secondary ammonium phosphate and ammoniacal liquor are added respectively in the aqueous solution of acrylic amide modified multi-arm polyethylene glycol monomer successively, it is fully dissolved.At 30 ~ 50 DEG C, magneton stirs, and reacts 5 ~ 30 minutes, obtained in-situ hydrogel.
Embodiment 2: the preparation of novel hydrogels
Adopt and prepare hydrogel with different types of polymer derivant in embodiment 1.
In 4ml test tube, add the water soluble silicones monomer of 300mg vinyl sulphone modification respectively, 200mg water, 50mg amine compound.Wherein, amine compound is primary ammonium phosphate/ammoniacal liquor, and mass ratio is 10:100.First primary ammonium phosphate is mixed with ammoniacal liquor, obtained aminated compounds linking agent, then this linking agent is added in the aqueous solution of water soluble silicones monomer of vinyl sulphone modification, it is fully dissolved, at 30 ~ 50 DEG C, magneton stirs, and reacts 5 ~ 30 minutes, obtained in-situ hydrogel.
Embodiment 3: the preparation of novel hydrogels
Adopt and prepare hydrogel with different types of aminated compounds in embodiment 1.
In 4ml test tube, add the multi-arm polyethylene glycol monomer that 300mg is acrylic amide modified respectively, 200mg water, 50mg amine compound, wherein, amine compound is bicarbonate of ammonia/ammoniacal liquor, and mass ratio is 5:100.After abundant dissolving, at 30 ~ 50 DEG C, magneton stirs, and reacts 5 ~ 30 minutes, obtained in-situ hydrogel.
Embodiment 4: the preparation of novel hydrogels
Adopt and prepare hydrogel with different kinds of liquid solvents in embodiment 1.
In 4ml test tube, add the multi-arm polyethylene glycol monomer that 300mg is acrylic amide modified respectively, 200mg ethanol, 60mg amine compound, wherein, amine compound is Secondary ammonium phosphate/ammoniacal liquor, and mass ratio is 10:100.At 30 ~ 50 DEG C, magneton stirs, and reacts 5 ~ 30 minutes, obtained in-situ hydrogel.
Embodiment 5: the preparation of novel hydrogels
Adopt the solvent with different ratios in embodiment 1.
In 4ml test tube, add the multi-arm polyethylene glycol monomer that 300mg is acrylic amide modified respectively, 400mg water, 60mg amine compound, wherein, amine compound is primary ammonium phosphate/ammoniacal liquor, and mass ratio is 5:100.At 30 ~ 50 DEG C, magneton stirs, and reacts 5 ~ 30 minutes, obtained in-situ hydrogel.
Embodiment 6: the preparation of novel hydrogels
Adopt and prepare hydrogel with the polymer monomer of different structure in embodiment 1.
In 4ml test tube, add the linear polyethylene glycol monomer of 300mg vinyl sulphone modification respectively, 200mg water, 60mg amine compound, wherein amine compound is ammonium phosphate/ammoniacal liquor, and mass ratio is 2.5:100.At 30 ~ 50 DEG C, magneton stirs, and reacts 5 ~ 30 minutes, obtained in-situ hydrogel.
Embodiment 7: the preparation of novel hydrogels
Adopt and prepare hydrogel with the polymer monomer of different end group in embodiment 1.
In 4ml test tube, add the multi-arm polyethylene glycol monomer that 300mg is acrylic amide modified respectively, 200mg water, 60mg amine compound, wherein amine compound is Secondary ammonium phosphate/ammoniacal liquor, and mass ratio is 10:100.At 30 ~ 50 DEG C, magneton stirs, and reacts 5 ~ 30 minutes, obtained in-situ hydrogel.
Embodiment 8: the preparation of novel hydrogels
Adopt and prepare hydrogel with the polymer monomer of different types of aminated compounds in embodiment 1 and different end group.
In 4ml test tube, add the multi-arm polyethylene glycol monomer that 300mg is acrylic amide modified respectively, 200mg water, 30mg ammonium phosphate, fully dissolves it.At 30 ~ 50 DEG C, magneton stirs, reaction 0.5-1h, obtained in-situ hydrogel.
Measure the in-situ hydrogel obtained in embodiment 1 ~ embodiment 8, the physicochemical property obtaining this novel hydrogels is as follows:
1. outward appearance: transparent, colourless hydrogel;
2.PH value: 7.0 ~ 11;
3. thermostability: 120 DEG C keep stable;
4. multi-functional can modification group residue;
5. excellent mechanical property.
The above is to aminated compounds linking agent provided by the present invention and the application in hydrogel preparation thereof, and the detailed introduction of the hydrogel obtained.The purposes of the hydrogel that the present invention obtains, is mainly used in biomedical sector.The application of aminated compounds linking agent provided by the present invention in hydrogel preparation method is Late Cambrian, and this linking agent has abundant raw material source, cheap, the feature that production cost is low, makes the preparation of hydrogel simple.Further, by regulating the consumption of aminated compounds, can control the forming process of hydrogel, gelation time, mechanical property, can rhetorical function etc.In hydrogel preparation method provided by the present invention, by regulating the ratio of aminated compounds, polymkeric substance, solvent three, cross-linking density and the intensity of hydrogel can be changed, and then affect the swelling behavior of hydrogel.The hydrogel that the present invention obtains is harmless to health, to cytotoxic effect, can be widely used in biomedical sector, such as cell cultures, organizational project, bioactivity surface modification, intraocular lens etc.
Above aminated compounds linking agent provided by the present invention and the application in hydrogel preparation method thereof are described in detail.To those skilled in the art, to any apparent change that it does under the prerequisite not deviating from connotation of the present invention, all by formation to infringement of patent right of the present invention, corresponding legal obligation will be born.
Claims (8)
1. the purposes in hydrogel prepared by aminated compounds linking agent, and wherein, the general structure of described aminated compounds linking agent is as follows:
Wherein, R is
in any one or multiple.
2. the purposes in hydrogel prepared by aminated compounds linking agent as claimed in claim 1, and wherein, described aminated compounds linking agent is composite obtained by ammoniacal liquor and other aminated compounds.
3. a hydrogel preparation method, is characterized in that:
Take end group as the polymer derivant of unsaturated double-bond be raw material, add solvent and aminated compounds linking agent, by Michael addition mechanism of crosslinking, obtained hydrogel,
Wherein, the general structure of described aminated compounds linking agent is as follows:
Wherein, R is
in any one or multiple.。
4. hydrogel preparation method as claimed in claim 3, is characterized in that:
Described polymer derivant is water-soluble polymers.
5. hydrogel preparation method as claimed in claim 3, is characterized in that:
The end group of described polymer derivant is selected from vinyl sulphone, vinyl cyanide, acrylamide.
6. hydrogel preparation method as claimed in claim 3, is characterized in that:
Described solvent is polar solvent.
7. hydrogel preparation method as claimed in claim 3, is characterized in that:
The mass ratio of described polymer derivant and described solvent is between 2:1 to 1:20; The mass ratio of described polymer derivant and described aminated compounds linking agent is between 100:1 to 1:5.
8. the hydrogel using the hydrogel preparation method according to any one of claim 3 to 7 to prepare.
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| CN107003266B (en) | 2014-06-11 | 2020-06-23 | 帕克-汉尼芬公司 | Indicator electrode and pH sensing device comprising same |
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| CN101338036A (en) * | 2007-07-06 | 2009-01-07 | 舒晓正 | Biocompatible quick-gelatinizing hydrogels and method for preparing spray thereof |
| CN101781796A (en) * | 2009-01-15 | 2010-07-21 | 河南师范大学 | Simple method for preparing hydroxyapatite nanocrystals |
| CN101671362A (en) * | 2009-09-28 | 2010-03-17 | 南京第一农药集团有限公司 | Process for preparing N-(phosphonomethyl) iminodiacetic acid by hydroxyacetonitrile continuous method |
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