CN103497330A - Amphiphilic molecule hydrogel based on polyamino acid - Google Patents
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Abstract
The invention discloses an amphiphilic molecule hydrogel based on polyamino acid. The structural formula of the amphiphilic molecule hydrogel based on the polyamino acid is as shown in a formula I, wherein x in the formula is a natural number in the range from 4-16, and n is a natural number in the range of 10-50. A preparation method of the amphiphilic molecule hydrogel based on the polyamino acid provided by the invention and shown in the formula I comprises the following steps: (1) reacting glutamic acid with 2-(2-Methoxyethoxy)ethanol under the action of an acid catalyst so as to obtain an amino acid compound, the lateral chain of which has the 2-(2-Methoxyethoxy)ethanol; (2) reacting the amino acid compound, the lateral chain of which has the 2-(2-Methoxyethoxy)ethanol, with triphosgene so as to obtain an N-carboxyanhydride compound; and (3) carrying out ring-opening polymerization reaction on the N-carboxyanhydride compound under the triggering action of alkyl chain primary amine, thus obtaining the amphiphilic molecule hydrogel based on polyamino acid. The amphiphilic molecule hydrogel based on the polyamino acid has biocompatibility, biodegradability and other properties. Compared with other polyamino acid-based hydrogel, the amphiphilic molecule hydrogel has the advantages of low cost and easiness in realization of large-scale production and a very wide application prospect in the field of biological materials.
Description
Technical field
The present invention relates to a kind of amphiphile, amphiphilic molecule hydrogel based on polyamino acid, relate to Biodegradable material and medicine and control the release field.
Background technology
The purpose that delivery formulations is controlled in research is to seek a kind ofly can keep pharmaceutical activity, can in the administration process, in affected part, maintain for a long time effective drug level again, and make the Plasma Concentration of other parts of human body drop to minimum method.Hydrogel be exactly a kind of very effectively and application system very widely, can be used for the carrier as drug molecule and active biomolecule.Organizational engineering is principle and the method for application cell biology and engineering science, from being familiar with the relation of normal and Pathological structure and function. research and development biological substitution product, to recover, to maintain or improve the morphology and function of damaged tissue and organ, reach the purpose of reconstruction.One of gordian technique of organizational engineering is the cytoskeleton that preparation has biocompatibility and degradable absorption.A large class material as tissue engineering cell scaffold is hydrogel, and during according to its gel, the crosslinking method difference, can be divided into chemically crosslinked and physical crosslinking.Physical crosslinking has good reversibility and lower gel strength than chemically crosslinked.Aspect physical gel, oligomer based on natural amino acid and polymkeric substance due to its unique physicochemical property, can form stable hydrogen bond between Amino Acid Unit simultaneously, and there is different secondary structures, can under different conditions, form multiple aquogel system.In addition, but the hydrogel based on polyamino acid has good biocompatibility, degradability and bioresorbable, becomes the focus of hydrogel area research.Be the focus of studying in the world utilizing amino acid to construct hydrogel always, have every year many relevant patents and article to deliver.So far having delivered several pieces at international top publications such as Science as the Stupp of Northwestern Univ USA teach problem group from calendar year 2001 is alkyl chain about hydrophobic section, the article of the amphipathic molecule hydrogel that hydrophilic section is polypeptide chain; The Bing Xu of Hong Kong University of Science and Thchnology teach problem group has been delivered the article of tens of pieces of writing about the micromolecule polypeptide hydrogel on the publications such as JACS, they utilize amino acid progressively the method for condensation synthesized 2-3 amino acid whose polypeptide chain, this small molecules also can form gel under certain condition in water.Although, but the oligomerization amino acid that Patents and article are reported can form hydrogel preferably, all molecules are all with the progressively method acquisition of condensation of solid phase synthesis, genetic expression or amino acid.And the aminoacid sequence that these methods obtain does not have universality, and cost is higher can't realize scale operation.Especially the process that this small molecules amino acid prepares hydrogel is more complicated, needs a plurality of steps of experience can form hydrogel.In addition on the one hand, research finds that the block polyamino acid obtained by ring-opening polymerization also can form hydrogel.Deming seminar has reported how by ring-opening polymerization, to prepare amphipathic block polyamino acid copolymerization peptide on the Nature of 2002, and prove that this two block polyamino acid can directly form hydrogel in water and buffered soln, and the intensity of gel and gel strength can be regulated by changing polymerizing condition and molecular weight easily.Yet the harsher use transition metal initiators that needs of this two block polyamino acid polymerizing conditions, need the molecular weight of polyamino acid also larger, and require hydrophilic segment to be necessary for polyelectrolyte, thereby just have certain limitation in practical application.
Summary of the invention
The purpose of this invention is to provide a kind of amphiphile, amphiphilic molecule based on polyamino acid with good biocompatibility, can form stable hydrogel, the synthetic difficulty of hydrogel that solves current amino acids is large, cost is high and be not easy to realize the problem such as scale operation.
A kind of amphiphile, amphiphilic molecule based on polyamino acid provided by the present invention, its structural formula is suc as formula shown in I,
In the formula I, x is the natural number between 4～16, and n is the natural number between 10～50.
In amphiphile, amphiphilic molecule based on polyamino acid provided by the invention, x specifically can be 4～10,4,10 or 14; N specifically can be 10～15,10,15 or 50.
The present invention further provides the preparation method of the amphiphile, amphiphilic molecule based on polyamino acid shown in the formula I, comprised the steps:
(1) L-glutamic acid and diethylene glycol monomethyl ether react the amino-acid compound that obtains side chain band diethylene glycol monomethyl ether under an acidic catalyst;
(2) amino-acid compound of described side chain band diethylene glycol monomethyl ether is reacted with triphosgene and is obtained N-carboxyl-ring inner-acid anhydride compound;
(3) described N-carboxyl-ring inner-acid anhydride compound carries out ring-opening polymerization and obtains the described amphiphile, amphiphilic molecule based on polyamino acid under the initiation of alkyl chain primary amine.
In above-mentioned preparation method, in step (1), described an acidic catalyst can be the vitriol oil, anhydrous hydrogen chloride or trimethylchlorosilane;
The ratio of quality and the number of copies of described L-glutamic acid and described diethylene glycol monomethyl ether can be 1:4～8, specifically can be 1:6;
The ratio of quality and the number of copies of described L-glutamic acid and described an acidic catalyst can be 1:0.5～2, specifically can be 1:1.1.
In above-mentioned preparation method, in step (1), the temperature of described reaction can be 20 ℃～30 ℃, specifically can be 20 ℃; The time of described reaction can be 8 hours～and 48 hours, specifically can be 48 hours.
In above-mentioned preparation method, in step (2), the glutamic acid compounds of described side chain band Diethylene Glycol can be 1:0.30～0.50 with the molfraction ratio of described triphosgene, specifically can be 1:0.40;
Described reaction can be carried out under rare gas element, as nitrogen or argon gas.
In above-mentioned preparation method, in step (2), the solvent of described reaction can be tetrahydrofuran (THF), ethyl acetate or methylene dichloride;
The temperature of described reaction is 35 ℃～55 ℃, specifically can be 55 ℃; The time of described reaction can be 4 hours～and 6 hours, specifically can be 4 hours.
In above-mentioned preparation method, in step (3), described alkyl chain primary amine can be normal hexyl Amine, amino dodecane, cetylamine or stearylamine;
The solvent of described ring-opening polymerization can be at least one in dimethyl formamide, N,N-DIMETHYLACETAMIDE, dimethyl sulfoxide (DMSO), tetrahydrofuran (THF) and dioxane.
In above-mentioned preparation method, in step (3), described alkyl chain primary amine can be 1:10～50 with the molfraction ratio of described N-carboxyl-ring inner-acid anhydride compound, specifically can be 1:20;
The temperature of described ring-opening polymerization can be 20 ℃～50 ℃, specifically can be 25 ℃; The time of described polyreaction can be 24 hours～and 36 hours, specifically can be 24 hours.
It is a kind of based on the amphiphile, amphiphilic molecule hydrogel based on polyamino acid shown in the formula I that the present invention also provides, it is comprised of amphiphile, amphiphilic molecule and the water based on polyamino acid shown in the formula I, wherein, the mass fraction of amphiphile, amphiphilic molecule based on polyamino acid shown in the formula I in described water can be 1%～10%, as 2%, 3% or 4%.This hydrogel can be dissolved in water and be obtained by the amphiphile, amphiphilic molecule based on polyamino acid shown in the formula I.
The preparation method of the amphiphile, amphiphilic molecule based on polyamino acid provided by the invention, its raw material sources are extensive, can obtain from existing commercial sources, and with low cost, synthetic method is simple; Amphiphile, amphiphilic molecule hydrogel based on polyamino acid provided by the invention, the L-glutamic acid that its polyamino acid section is modification, because L-glutamic acid is one of 20 kinds of common alpha amino acids that form human body protein, so there is good biocompatibility and energy biological degradation, and after degraded, the alkyl short chain that is connected on L-glutamic acid also can directly excrete and can not cause toxicity by kidney, so amphiphile, amphiphilic molecule hydrogel based on polyamino acid provided by the invention has the character such as biocompatibility and biodegradable; And have with low costly than other polyamino acid class hydrogel, be easy to realize the advantage of scale operation to there is high application prospect in technical field of biological material.
The accompanying drawing explanation
Fig. 1 is the amphiphile, amphiphilic molecule based on polyamino acid shown in the formula II
1h NMR spectrogram.
Fig. 2 is the amphiphile, amphiphilic molecule based on polyamino acid shown in the formula III
1h NMR spectrogram.
Fig. 3 is the amphiphile, amphiphilic molecule based on polyamino acid shown in the formula IV
1h NMR spectrogram.
Fig. 4 is that the amphiphile, amphiphilic molecule hydrogel storage modulus based on polyamino acid shown in the formula II is with the graphic representation of change in concentration.
Fig. 5 is that the amphiphile, amphiphilic molecule hydrogel storage modulus based on polyamino acid shown in the formula III is with the graphic representation of change in concentration.
Fig. 6 is that the amphiphile, amphiphilic molecule hydrogel storage modulus based on polyamino acid shown in the formula IV is with the graphic representation of change in concentration.
Embodiment
The experimental technique used in following embodiment if no special instructions, is ordinary method.
In following embodiment, material used, reagent etc., if no special instructions, all can obtain from commercial channels.
Amphiphile, amphiphilic molecule based on polyamino acid shown in embodiment 1, formula II and the preparation of hydrogel thereof
(1) at first in round-bottomed flask, add 90 milliliters of diethylene glycol monomethyl ethers, and add 15 gram L-glutamic acid, the ratio of quality and the number of copies of this system Glutamic Acid and diethylene glycol monomethyl ether is 1:6, suspension liquid is placed in to ice-water bath, wait to be chilled to 0 ℃, slowly splash into 10 milliliters of vitriol oils (wherein, the ratio of quality and the number of copies of L-glutamic acid and the vitriol oil is 1:1.1), be back to 20 ℃ after dripping off, treat to react 48 hours under 20 ℃.Clear soln is poured in the mixing solutions (volume ratio is 1:10) of triethylamine and Virahol, produced white precipitate.Centrifugal, obtain white solid 15.5 grams, productive rate is 61.0%;
Nucleus magnetic hydrogen spectrum
1h NMR (400MHz, D
2o): δ 4.31-4.22 (t, 2H), 3.82-3.72 (m, 3H), 3.72-3.64 (m, 2H), 3.63-3.56 (m, 2H), 3.39-3.32 (s, 3H), 2.66-2.49 (m, 2H), 2.25-2.07 (m, 2H); Nuclear-magnetism carbon spectrum
13c NMR (400MHz, D
2o): δ 174.6,173.9, and 70.9,69.5,68.4,64.1,58.1,53.9,29.8,25.4; High resolution mass spectrum HRMS-ESI (m/z) [M+H]
+calcd C
10h
19nO
6, 250.1291; Found250.1291.
(2) white solid 3 grams that step (1) obtained and 1.5 gram triphosgene are mixed (wherein; this white solid is 1:0.40 with the molfraction ratio of triphosgene), under nitrogen protection, add 150 milliliters of tetrahydrofuran (THF)s; under 55 ℃, reaction is 4 hours; reaction is drained solvent after finishing, and obtains yellow oily liquid; column chromatography (ethyl acetate: normal hexane=1:1; v/v), obtain colourless oil liquid 2.13 grams, productive rate is 75.2%.
Nucleus magnetic hydrogen spectrum
1h NMR (400MHz, CDCl
3): δ 7.30-7.17 (br, 1H), 4.48-4.36 (t; 1H), 4.35-4.13 (m, 2H); (3.76-3.65 m, 2H), 3.65-3.56 (m; 2H), 3.56-3.46 (m, 2H); (3.39-3.25 s, 3H), 2.62-3.39 (m; 2H), 2.34-2.01 (m, 2H); Nuclear-magnetism carbon spectrum
13c NMR (400MHz, CDCl
3): δ 172.1,170.1, and 152.1,71.7,70.2,68.7,63.7,58.9,57.0,29.9,26.9; Infrared spectra FTIR (THF): 2921,1854,1786,1735,1690,1451,1107,922cm
-1.
(3) polyreaction of this step is to carry out in the reaction flask of nitrogen protection: during the colourless oil liquid that step (2) is obtained is dissolved in dimethyl formamide; be made into the solution of 100 mg/ml and get 10 milliliters; join rapidly (molfraction of the colourless oil liquid that normal hexyl Amine and step (2) obtain is than being 1:20) in the tetrahydrofuran solution (20 mg/ml) that is placed with 0.9 milliliter of normal hexyl Amine, under 25 ℃, reaction is 24 hours.Reaction joins solution in a large amount of ether after finishing, and by the centrifugal white solid that obtains, is the amphiphile, amphiphilic molecule based on polyamino acid shown in formula II.
Nucleus magnetic hydrogen spectrum (as shown in Figure 1)
1h NMR (400MHz, CDCl
3/ CF
3cO
2d (v:v=1:1)): δ 4.76-4.59 (br, 1H), 4.46-4.23 (br, 2H), (4.01-3.87 br, 4H), 3.87-3.76 (br, 2H), (3.62-3.50 br, 3H), 2.73-2.47 (br, 2H), 2.31-1.95 (br, 2H), (1.70-1.51 br, 3H), 1.30-1.18 (br, 8H), 0.94-0.71 (br, 2H).
Show that according to nucleus magnetic hydrogen spectrum its molecular weight is 11000, the polymerization degree is 50, and n is 50.
(4) white solid step (3) obtained is soluble in water with 2% massfraction, through the placements of six hours, obtains stable hydrogel.
The storage modulus of the amphiphile, amphiphilic molecule hydrogel based on polyamino acid shown in formula II with the graphic representation of change in concentration as shown in Figure 4, by figure, can be learnt, concentration along with the amphiphile, amphiphilic molecule based on polyamino acid in water increases, gel-strength also increases gradually, illustrates that the intensity of hydrogel can be regulated and controled by the amphiphile, amphiphilic molecule concentration changed based on polyamino acid.
Amphiphile, amphiphilic molecule based on polyamino acid shown in embodiment 2, formula III and the preparation of hydrogel thereof
(1) at first in round-bottomed flask, add 90 milliliters of diethylene glycol monomethyl ethers, and add 15 gram L-glutamic acid, the ratio of quality and the number of copies of this system Glutamic Acid and diethylene glycol monomethyl ether is 1:6, suspension liquid is placed in to ice-water bath, wait to be chilled to 0 ℃, slowly splash into 10 milliliters of vitriol oils (wherein, the ratio of quality and the number of copies of L-glutamic acid and the vitriol oil is 1:1.1), be back to 20 ℃ after dripping off, treat to react 48 hours under 20 ℃.Clear soln is poured in the mixing solutions (volume ratio is 1:10) of triethylamine and Virahol, produced white precipitate.Centrifugal, obtain white solid 15.5 grams, productive rate is 61.0%.
Nucleus magnetic hydrogen spectrum
1h NMR (400MHz, D
2o): δ 4.31-4.22 (t, 2H), 3.82-3.72 (m, 3H), 3.72-3.64 (m, 2H), 3.63-3.56 (m, 2H), 3.39-3.32 (s, 3H), 2.66-2.49 (m, 2H), 2.25-2.07 (m, 2H); Nuclear-magnetism carbon spectrum
13c NMR (400MHz, D
2o): δ 174.6,173.9, and 70.9,69.5,68.4,64.1,58.1,53.9,29.8,25.4; High resolution mass spectrum HRMS-ESI (m/z) [M+H]
+calcd C
10h
19nO
6, 250.1291; Found250.1291.
(2) white solid 3 grams that step (1) obtained and 1.5 gram triphosgene are mixed (wherein; this white solid is 1:0.40 with the molfraction ratio of triphosgene), under nitrogen protection, add 150 milliliters of ethyl acetate; under 55 ℃, reaction is 4 hours; reaction is drained solvent after finishing, and obtains yellow oily liquid; column chromatography (ethyl acetate: normal hexane=1:1; v/v), obtain colourless oil liquid 2.02 grams, productive rate is 65.8%.
Nucleus magnetic hydrogen spectrum
1h NMR (400MHz, CDCl
3): δ 7.30-7.17 (br, 1H), 4.48-4.36 (t; 1H), 4.35-4.13 (m, 2H); (3.76-3.65 m, 2H), 3.65-3.56 (m; 2H), 3.56-3.46 (m, 2H); (3.39-3.25 s, 3H), 2.62-3.39 (m; 2H), 2.34-2.01 (m, 2H); Nuclear-magnetism carbon spectrum
13c NMR (400MHz, CDCl
3): δ 172.1,170.1, and 152.1,71.7,70.2,68.7,63.7,58.9,57.0,29.9,26.9; Infrared spectra FTIR (THF): 2921,1854,1786,1735,1690,1451,1107,922cm
-1.
(3) polyreaction of this step is to carry out in the reaction flask of nitrogen or argon shield: during the colourless oil liquid that step (2) is obtained is dissolved in dimethyl formamide; be made into the solution of 100 mg/ml and get 10 milliliters; join rapidly (molfraction of the colourless oil liquid that amino dodecane and step (2) obtain is than being 1:20) in the tetrahydrofuran solution (20 mg/ml) that is placed with 1.5 milliliters of amino dodecanes, under 25 ℃, reaction is 24 hours.Reaction joins solution in a large amount of ether after finishing, and centrifuging obtains white solid, is the amphiphile, amphiphilic molecule based on polyamino acid shown in the formula III.
Nucleus magnetic hydrogen spectrum (as shown in Figure 2)
1h NMR (400MHz, CDCl
3/ CF
3cO
2d (v:v=1:1)): δ 4.76-4.59 (br, 1H), 4.46-4.23 (br, 2H), (4.01-3.87 br, 4H), 3.87-3.76 (br, 2H), (3.62-3.50 br, 3H), 2.73-2.47 (br, 2H), 2.31-1.95 (br, 2H), (1.70-1.48 br, 3H), 1.40-1.13(br, 16H), 0.94-0.71 (br, 6H).
Show that according to nucleus magnetic hydrogen spectrum its molecular weight is 3650, the polymerization degree is 15, and n is 15.
(4) white solid step (3) obtained is soluble in water with 2% massfraction, through halfhour placement, obtains stable hydrogel.
Amphiphile, amphiphilic molecule hydrogel storage modulus based on polyamino acid shown in the formula III with the graphic representation of change in concentration as shown in Figure 5, by figure, can be learnt, concentration along with the amphiphile, amphiphilic molecule based on polyamino acid in water increases, gel-strength also increases gradually, illustrates that the intensity of hydrogel can be regulated and controled by the amphiphile, amphiphilic molecule concentration changed based on polyamino acid.
The preparation of the amphiphile, amphiphilic molecule based on polyamino acid shown in embodiment 3, formula IV
(1) at first in round-bottomed flask, add 90 milliliters of diethylene glycol monomethyl ethers, and add 15 gram L-glutamic acid, the ratio of quality and the number of copies of this system Glutamic Acid and diethylene glycol monomethyl ether is 1:6, suspension liquid is placed in to ice-water bath, wait to be chilled to 0 ℃, slowly splash into 10 milliliters of vitriol oils (wherein, the ratio of quality and the number of copies of L-glutamic acid and the vitriol oil is 1:1.1), be back to 20 ℃ after dripping off, treat to react 48 hours under 20 ℃.Clear soln is poured in the mixing solutions (volume ratio is 1:10) of triethylamine and Virahol, produced white precipitate.Centrifugal, obtain white solid 15.5 grams, productive rate is 61.0%.
Nucleus magnetic hydrogen spectrum
1h NMR (400MHz, D
2o): δ 4.31-4.22 (t, 2H), 3.82-3.72 (m, 3H), 3.72-3.64 (m, 2H), 3.63-3.56 (m, 2H), 3.39-3.32 (s, 3H), 2.66-2.49 (m, 2H), 2.25-2.07 (m, 2H); Nuclear-magnetism carbon spectrum
13c NMR (400MHz, D
2o): δ 174.6,173.9, and 70.9,69.5,68.4,64.1,58.1,53.9,29.8,25.4; High resolution mass spectrum HRMS-ESI (m/z) [M+H]
+calcd C
10h
19nO
6, 250.1291; Found250.1291.
(2) white solid 3 grams that step (1) obtained and 1.5 gram triphosgene are mixed (wherein; this white solid is 1:0.40 with the molfraction ratio of triphosgene), under nitrogen protection, add 150 milliliters of methylene dichloride; under 55 ℃, reaction is 4 hours; reaction is drained solvent after finishing, and obtains yellow oily liquid; column chromatography (ethyl acetate: normal hexane=1:1; v/v), obtain colourless oil liquid 2.40 grams, productive rate is 78.1%.
Nucleus magnetic hydrogen spectrum
1h NMR (400MHz, CDCl
3): δ 7.30-7.17 (br, 1H), 4.48-4.36 (t; 1H), 4.35-4.13 (m, 2H); (3.76-3.65 m, 2H), 3.65-3.56 (m; 2H), 3.56-3.46 (m, 2H); (3.39-3.25 s, 3H), 2.62-3.39 (m; 2H), 2.34-2.01 (m, 2H); Nuclear-magnetism carbon spectrum
13c NMR (400MHz, CDCl
3): δ 172.1,170.1, and 152.1,71.7,70.2,68.7,63.7,58.9,57.0,29.9,26.9; Infrared spectra FTIR (THF): 2921,1854,1786,1735,1690,1451,1107,922cm
-1.
(3) polyreaction of this step is to carry out in the reaction flask of nitrogen or argon shield: during the colourless oil liquid that step (2) is obtained is dissolved in dimethyl sulfoxide (DMSO); be made into the solution of 100 mg/ml and get 10 milliliters; join rapidly (molfraction of the colourless oil liquid that cetylamine and step (2) obtain is than being 1:20) in the tetrahydrofuran solution (20 mg/ml) that is placed with 2.2 milliliters of cetylamines, under 25 ℃, reaction is 24 hours.Reaction joins solution in a large amount of ether after finishing, and centrifuging obtains white solid, is the amphiphile, amphiphilic molecule based on polyamino acid shown in the formula IV.
Nucleus magnetic hydrogen spectrum (as shown in Figure 3)
1h NMR (400MHz, CDCl
3/ CF
3cO
2d (v:v=1:1)): δ 4.76-4.59 (br, 1H), 4.46-4.23 (br, 2H), (4.01-3.87 br, 4H), 3.87-3.76 (br, 2H), (3.62-3.50 br, 3H), 2.73-2.47 (br, 2H), 2.31-1.95 (br, 2H), (1.73-1.52 br, 3H), 1.40-1.10(br, 24H), 0.94-0.71 (br, 6H).
Show that according to nucleus magnetic hydrogen spectrum its molecular weight is 2550, the polymerization degree is 10, and n is 10.
(4) white solid step (3) obtained is soluble in water with 2% massfraction, through the placements of ten minutes, obtains stable hydrogel.
Amphiphile, amphiphilic molecule hydrogel storage modulus based on polyamino acid shown in the formula IV with the graphic representation of change in concentration as shown in Figure 6, by figure, can be learnt, concentration along with the amphiphile, amphiphilic molecule based on polyamino acid in water increases, gel-strength also increases gradually, illustrates that the intensity of hydrogel can be regulated and controled by the amphiphile, amphiphilic molecule concentration changed based on polyamino acid.
Claims (10)
1. the amphiphile, amphiphilic molecule based on polyamino acid, its structural formula is suc as formula shown in I,
In the formula I, x is the natural number between 4～16, and n is the natural number between 10～50.
2. the preparation method of the amphiphile, amphiphilic molecule based on polyamino acid shown in the formula I, comprise the steps:
(1) L-glutamic acid and diethylene glycol monomethyl ether react the amino-acid compound that obtains side chain band diethylene glycol monomethyl ether under an acidic catalyst;
(2) amino-acid compound of described side chain band diethylene glycol monomethyl ether is reacted with triphosgene and is obtained N-carboxyl-ring inner-acid anhydride compound;
(3) described N-carboxyl-ring inner-acid anhydride compound carries out ring-opening polymerization and obtains the described amphiphile, amphiphilic molecule based on polyamino acid under the initiation of alkyl chain primary amine.
3. method according to claim 2, it is characterized in that: in step (1), described an acidic catalyst is the vitriol oil, anhydrous hydrogen chloride or trimethylchlorosilane;
The ratio of quality and the number of copies of described L-glutamic acid and described diethylene glycol monomethyl ether is 1:4～8;
The ratio of quality and the number of copies of described L-glutamic acid and described an acidic catalyst is 1:0.5～2.
4. according to the method in claim 2 or 3, it is characterized in that: in step (1), the temperature of described reaction is 20 ℃～30 ℃; The time of described reaction is 8 hours～48 hours.
5. according to the described method of any one in claim 2-4, it is characterized in that: in step (2), the glutamic acid compounds of described side chain band Diethylene Glycol is 1:0.30～0.50 with the molfraction of described triphosgene ratio;
Described reaction is carried out under rare gas element.
6. according to the described method of any one in claim 2-5, it is characterized in that: in step (2), the solvent of described reaction is tetrahydrofuran (THF), ethyl acetate or methylene dichloride;
The temperature of described reaction is 35 ℃～55 ℃; The time of described reaction is 4 hours～6 hours.
7. according to the described method of any one in claim 2-6, it is characterized in that: in step (3), described alkyl chain primary amine is normal hexyl Amine, amino dodecane, cetylamine or stearylamine;
The solvent of described ring-opening polymerization is at least one in dimethyl formamide, N,N-DIMETHYLACETAMIDE, dimethyl sulfoxide (DMSO), tetrahydrofuran (THF) and dioxane.
8. according to the described method of any one in claim 2-7, it is characterized in that: in step (3), described alkyl chain primary amine is 1:10～50 with the molfraction ratio of described N-carboxyl-ring inner-acid anhydride compound;
The temperature of described ring-opening polymerization is 20 ℃～50 ℃; The time of described polyreaction is 24 hours～36 hours.
9. a hydrogel, it is characterized in that: described hydrogel is comprised of amphiphile, amphiphilic molecule and the water based on polyamino acid shown in the formula I.
10. hydrogel according to claim 9, it is characterized in that: the mass fraction of the amphiphile, amphiphilic molecule based on polyamino acid shown in the formula I in described water is 1%～10%.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104761721A (en) * | 2015-03-31 | 2015-07-08 | 青岛科技大学 | Amphipathic molecule injectable and non-ionic super water gel based on oligomeric amino acid |
| CN104784103A (en) * | 2015-03-31 | 2015-07-22 | 青岛科技大学 | Injectable antibacterial hydrogel based on amphiphilic molecules of oligomeric amino acid |
| CN104817688A (en) * | 2015-04-17 | 2015-08-05 | 中国科学院长春应用化学研究所 | Convertible surface charge nano-gel, preparation method thereof and convertible surface charge nano-gel drug-loaded particle |
| CN105418861A (en) * | 2015-12-10 | 2016-03-23 | 宁波大学 | Crosslinking hydrogel based on polyamino acid molecules and preparation method thereof |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104761721A (en) * | 2015-03-31 | 2015-07-08 | 青岛科技大学 | Amphipathic molecule injectable and non-ionic super water gel based on oligomeric amino acid |
| CN104784103A (en) * | 2015-03-31 | 2015-07-22 | 青岛科技大学 | Injectable antibacterial hydrogel based on amphiphilic molecules of oligomeric amino acid |
| CN104784103B (en) * | 2015-03-31 | 2017-09-05 | 青岛科技大学 | Based on oligomeric amino acid amphiphile, amphiphilic molecule injectable anti-bacterial hydrogel |
| CN104817688A (en) * | 2015-04-17 | 2015-08-05 | 中国科学院长春应用化学研究所 | Convertible surface charge nano-gel, preparation method thereof and convertible surface charge nano-gel drug-loaded particle |
| CN104817688B (en) * | 2015-04-17 | 2016-07-06 | 中国科学院长春应用化学研究所 | A kind of reversible nanogel of surface charge and preparation method thereof and a kind of reversible nanogel medicine carrying granule of surface charge |
| CN105418861A (en) * | 2015-12-10 | 2016-03-23 | 宁波大学 | Crosslinking hydrogel based on polyamino acid molecules and preparation method thereof |
| CN105418861B (en) * | 2015-12-10 | 2018-02-13 | 宁波大学 | One kind is based on polyaminoacid molecule cross-link hydrogel and preparation method thereof |
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