CN105694030B - A kind of oligomeric amino acid and the compound hydridization anti-bacterial hydrogel of sodium alginate - Google Patents
A kind of oligomeric amino acid and the compound hydridization anti-bacterial hydrogel of sodium alginate Download PDFInfo
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- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
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Abstract
The invention discloses a kind of oligomeric amino acid and the compound hydridization anti-bacterial hydrogel of sodium alginate.Present invention firstly provides amphiphile, amphiphilic molecule based on oligomeric amino acid of the structural formula as shown in formula I or formula II, and provide the preparation method of the amphiphile, amphiphilic molecule based on oligomeric amino acid.Amphiphile, amphiphilic molecule provided by the invention based on polyaminoacid and the hybridized hydrogel of the compound preparation of sodium alginate have the characteristics that biocompatibility and biodegradability.The lysine residue of cation is introduced in polyaminoacid section, first, can mechanical strength compound with the carboxyl electrostatic on sodium alginate and crosslinking, improve hydrogel；Second, the lysine of cationic has bacteriostatic activity, assign hybridized hydrogel itself excellent anti-microbial property.And compared to other types of antibacterial hydrogel material, it has the advantages that preparation cost is cheap, preparation method is simple, short preparation period, the antibacterial activity for being easy to large-scale production and inherence, has high application prospect in biomedical materials field.
Description
Technical field
The present invention relates to a kind of oligomeric amino acid and the compound hydridization anti-bacterial hydrogel of sodium alginate, belong to biodegradable
Material and biomedical materials field.
Background technology
Hydrogel is a kind of gel rubber system using water as decentralized medium, and its water content can be more than 80%.Due to hydrogel
Advantageous property and feature, it is widely used in food engineering, environmental project and biomedicine field.Machine is formed according to it
System, hydrogel can be divided into chemical gel and physical gel.Chemical gel is formed by intermolecular chemical crosslinking, its mechanical property
It is excellent, stable performance.And physical gel is made by non-covalent bond (hydrogen bond, hydrophobe interaction and electrostatic interaction)
Firmly occurring what physical crosslinking was formed, reversible sol-gel transition can typically occur for this gellike, not be related to chemical reaction,
Preparation condition is gentle, is particluarly suitable for biomedical sector and is applied.
Natural polymer is widely used in preparing hydrogel, such as carboxymethyl cellulose, chitosan, gelatin and sodium alginate
Deng although above-mentioned hydrogel excellent in mechanical performance, its function is single, limits their applications in medical field.In recent years,
The research of polyaminoacid class hydrogel with multifunctionality receives much concern, and polyaminoacid hydrogel has inherent good
Biocompatibility, biodegradability and Bioabsorbable.Different amino acid residue sides carries different functional groups, it
Can assign material abundant feature, such as electropositive lysine can assign material good anti-microbial property.With good
The hydrogel of good anti-microbial property can greatly reduce the probability that injection site bacterium infection occurs.At present, usually through in hydrogel
Addition antiseptic assigns its anti-microbial property (physics cladded type anti-bacterial hydrogel), but such anti-bacterial hydrogel has bactericidal action
The shortcomings of time is short, adverse drug reaction, limits its application clinically.Therefore, exploitation one kind itself possesses antibiotic property
The hydrogel of energy is then particularly important.
The content of the invention
It is an object of the invention to provide a kind of oligomeric amino acid amphiphile, amphiphilic molecule containing lysine and sodium alginate complex
Into the stable hybridized hydrogel itself with anti-microbial property, the hybridized hydrogel can be achieved without additionally adding antiseptic
The anti-microbial property of itself, and can regulate and control the mechanical property of its hydrogel by changing molecular structural parameter and component ratio, this
Invention solves the problems, such as the anti-microbial property decline with antiseptic release of current physics cladded type anti-bacterial hydrogel.
Present invention firstly provides a kind of amphiphile, amphiphilic molecule based on oligomeric amino acid, its structural formula as shown in formula I or formula II,
In formula I and formula II, m is the natural number between 10~16, and n is the natural number between 2~20, between k is 1~5
Natural number, x are 1 or 2；
In formula I, y is the natural number between 2~6；
In formula II, z is the natural number between 1~3.
In formula I, m concretely 14, n concretely 3 or 4, x concretely 2, y concretely 3.
Invention further provides the preparation method of the amphiphile, amphiphilic molecule based on oligomeric amino acid formula I Suo Shi, including it is as follows
Step：
(1) γ-benzyl-Pidolidone ester is reacted to obtain the N- carboxylics of γ-benzyl-Pidolidone with phosgene or triphosgene
Base-ring inner-acid anhydride compound；
(2) ε-benzyloxycarbonyl group -1B is reacted to obtain ε-benzyloxycarbonyl group -1B with phosgene or triphosgene
N- carboxyls-ring inner-acid anhydride compound；
(3) under the initiation of alkyl chain primary amine, N- carboxyls-ring inner-acid anhydride chemical combination of the γ-benzyl-Pidolidone
N- carboxyls-ring inner-acid anhydride compound of thing and the ε-benzyloxycarbonyl group -1B through ring-opening copolymerization react to obtain alkyl chain -
Poly- (γ-benzyl-Pidolidone ester)-co- is poly- (ε-benzyloxycarbonyl group -1B)；
(4) alkyl chain-poly- (γ-benzyl-Pidolidone ester)-co- poly- (ε-benzyloxycarbonyl group -1B) and hydramine
Class compound carries out aminolysis reaction, obtains alkyl chain-polyglutamic acid alcohol amine amide-co- poly- (ε-benzyloxycarbonyl group -1B)；
(5) under HBr catalysis, the alkyl chain-polyglutamic acid alcohol amine amide-co- is poly-, and (ε-benzyloxycarbonyl group-L- relies ammonia
Acid) through deprotection reaction, that is, obtain the amphiphile, amphiphilic molecule based on oligomeric amino acid shown in formula I.
The present invention still further provides the preparation method of the amphiphile, amphiphilic molecule based on oligomeric amino acid shown in formula II, including such as
Lower step：
(1) β-benzyl-L-aspartate ester is reacted to obtain the N- of β-benzyl-L-aspartate with phosgene or triphosgene
Carboxyl-ring inner-acid anhydride compound；
(2) ε-benzyloxycarbonyl group-lysine is reacted to obtain the N- of ε-benzyloxycarbonyl group -1B with phosgene or triphosgene
Carboxyl-ring inner-acid anhydride compound；
(3) under the initiation of alkyl chain primary amine, N- carboxyls-ring inner-acid anhydride of the β-benzyl-L-aspartate
N- carboxyls-ring inner-acid anhydride compound of compound and the ε-benzyloxycarbonyl group -1B reacts to obtain alkyl through ring-opening copolymerization
Chain-poly- (β-benzyl-L-aspartate ester)-co- is poly- (ε-benzyloxycarbonyl group -1B)；
(4) alkyl chain-poly- (β-benzyl-L-aspartate ester)-co- poly- (ε-benzyloxycarbonyl group -1B) and alcohol
Aminated compounds carries out aminolysis reaction, and obtaining alkyl chain-poly-aspartate alcohol amine amide-co-, poly- (ε-benzyloxycarbonyl group-L- relies ammonia
Acid)；
(5) under HBr catalysis, the alkyl chain-poly-aspartate alcohol amine amide-co- is poly-, and (ε-benzyloxycarbonyl group-L- relies
Propylhomoserin) through deprotection reaction, that is, obtain the amphiphile, amphiphilic molecule based on oligomeric amino acid shown in formula II.
In above-mentioned preparation method, in step (1) and (2), the solvent of the reaction can be tetrahydrofuran, ethyl acetate or
Dichloromethane；
The temperature of the reaction can be 40 DEG C~60 DEG C, concretely 50 DEG C；
The time of the reaction can be 3~5 hours, concretely 4 hours；
The reaction is carried out under atmosphere of inert gases, such as argon gas or nitrogen.
In above-mentioned preparation method, in step (3), the alkyl chain primary amine can be lauryl amine, tetradecy lamine, cetylamine or ten
Eight amine；
The solvent of the ring-opening polymerization can be dimethylformamide, dimethyl acetamide, dimethyl sulfoxide (DMSO), tetrahydrochysene furan
At least one of mutter with dioxane；
N- carboxyl-ring inner-acid anhydride compound and the ε-benzyl of the alkyl chain primary amine with the γ-benzyl-Pidolidone
The mol ratio of the integral molar quantity of the N- carboxyls of oxygen carbonyl -1B-ring inner-acid anhydride compound can be 1：2~20, concretely
1：5；
N- carboxyls-ring inner-acid anhydride the compound and the ε of the alkyl chain primary amine and the β-benzyl-L-aspartate-
The mol ratio of the integral molar quantity of the N- carboxyls of benzyloxycarbonyl group -1B-ring inner-acid anhydride compound can be 1：2~20, specifically may be used
For 1：5；
The alkyl chain primary amine and mole of N- carboxyls-ring inner-acid anhydride compound of the ε-benzyloxycarbonyl group -1B
Than that can be 1：1~5, concretely 1：1 or 1：2；
The temperature of the ring-opening copolymerization reaction can be 20 DEG C~50 DEG C, concretely 40 DEG C；
The time of the ring-opening copolymerization reaction can be 8 hours~36 hours, concretely 12 hours；
The ring-opening copolymerization reaction can be carried out under an inert gas, such as argon gas or nitrogen.
In above-mentioned preparation method, in step (4), the aminolysis reaction is carried out under the conditions of existing for catalyst, described
Catalyst can be 2 hydroxy pyrimidine；
The alcamine compound can be the alcohol amine compounds of linear paraffin hydramine, branching type hydramine and the class containing oligomeric ethylene glycol
At least one of thing；
The linear paraffin hydramine can be at least one of monoethanolamine, Propanolamine, butanolamine, amylalcohol amine and hexanol amine；
The branching type hydramine can be at least one of isopropanolamine, isobutyl hydramine and isoamyl hydramine；
The alcohol amine compound of the class containing oligomeric ethylene glycol can be diethyleneglycolamin and/or triethylene glycol amine；
Repeated in the alkyl chain-poly- (γ-benzyl-Pidolidone ester)-co- poly- (ε-benzyloxycarbonyl group -1B) single
The mol ratio of first glutamic acid and the alcamine compound can be 1：5~30, concretely 1：10；
Repeated in the alkyl chain-poly- (γ-benzyl-Pidolidone ester)-co- poly- (ε-benzyloxycarbonyl group -1B) single
The mol ratio of first amino acid and the 2 hydroxy pyrimidine can be 1：1~10；
Repeated in the alkyl chain-poly- (β-benzyl-L-aspartate ester)-co- poly- (ε-benzyloxycarbonyl group -1B) single
The mol ratio of first aspartic acid and the alcamine compound can be 1：5~30, concretely 1：10；
Repeated in the alkyl chain-poly- (β-benzyl-L-aspartate ester)-co- poly- (ε-benzyloxycarbonyl group -1B) single
The mol ratio of repeat unit amino acid and the 2 hydroxy pyrimidine can be 1 in member：1~10；
The temperature of the aminolysis reaction can be 40 DEG C~60 DEG C, concretely 45 DEG C；
The time of the aminolysis reaction can be 24 hours~72 hours, concretely 72 hours；
The aminolysis reaction can be carried out under atmosphere of inert gases, such as argon gas or nitrogen.
In above-mentioned preparation method, in step (5), the deprotection reaction can be carried out in trifluoroacetic acid；
Repeat unit relies ammonia in the alkyl chain-polyglutamic acid alcohol amine amide-co- poly- (ε-benzyloxycarbonyl group -1B)
The sour and mol ratio of the HBr can be 1：1.5~3；
Repeated in the alkyl chain-poly-aspartate alcohol amine amide-co- poly- (ε-benzyloxycarbonyl group -1B) single
First lysine and the HBr mol ratio can be 1：1.5~3；
The temperature of the deprotection reaction can be 0 DEG C~25 DEG C, concretely 25 DEG C；
The time of the deprotection reaction can be 20 minutes~60 minutes, concretely 30 minutes.
Amphiphile, amphiphilic molecule based on oligomeric amino acid shown in formula I or formula II provided by the present invention can be used for preparing antibacterial water-setting
Glue.
Invention also provides a kind of anti-bacterial hydrogel, its shown in formula I and/or formula II based on oligomeric amino acid two
Affinity molecule and sodium alginate form with decentralized medium；
The decentralized medium can be the aqueous solution of water or salt；
The aqueous solution of the salt can be one kind in physiological saline, various types of cells culture medium solution etc..
In the anti-bacterial hydrogel, the quality percentage of the amphiphile, amphiphilic molecule based on oligomeric amino acid contains shown in formula I and/or formula II
Measure as 0.5%~10%, concretely 1%~2%, 1% or 2%；
The weight/mass percentage composition of the sodium alginate is 0.5%~10%, concretely 0.2%,
The molecular weight of the sodium alginate can be 5kDa~500kDa.
The preparation method of amphiphile, amphiphilic molecule provided by the invention based on oligomeric amino acid, its raw material sources is extensive, is
Commercially produced product, cheap, synthetic method is simple and easy, and synthesis cycle is short；It is provided by the invention based on polyaminoacid two
Hybridized hydrogel obtained by affinity molecule and sodium alginate are compound, its polyaminoacid block is Poly-L-glutamic acid or poly- L- asparagus ferns ammonia
Acid and poly-L-Lysine, wherein poly-L-Lysine is antibacterial unit, must be contained
Because polyaminoacid has good biocompatibility and biodegradability, and the alkyl short chain after degrading also may be used
Directly it is excluded in vitro by renal metabolism approach without causing bio-toxicity.And sodium alginate is a kind of natural polysaccharide,
It equally has good biocompatibility and biodegradability.Therefore, the amphiphilic provided by the invention based on polyaminoacid
Molecule and the hybridized hydrogel of the compound preparation of sodium alginate have the characteristics that biocompatibility and biodegradability.In poly- amino
Sour section introduces the lysine residue of cation, when can be compound with the carboxyl electrostatic on sodium alginate and crosslink, improve water
The mechanical strength of gel；Second, the lysine of cationic has bacteriostatic activity, assign hybridized hydrogel itself excellent antibacterial
Performance.And it has and prepares that cost is cheap, preparation method is simple, prepares week compared to other types of antibacterial hydrogel material
Phase is short, is easy to large-scale production and the advantages that inherent antibacterial activity, has high application in biomedical materials field
Prospect.
Brief description of the drawings
Fig. 1 is the amphiphile, amphiphilic molecule based on polyaminoacid shown in formula III1H-NMR spectrum.
Fig. 2 is the amphiphile, amphiphilic molecule based on polyaminoacid shown in formula IV1H-NMR spectrum.
Fig. 3 is in the water-setting with the compound front and rear formation of sodium alginate shown in formula III and formula IV based on polyaminoacid amphiphile, amphiphilic molecule
The mechanical strength of glue material.
Fig. 4 is the anti-of the hybridized hydrogel that the amphiphile, amphiphilic molecule shown in formula III based on polyaminoacid is compounded to form with sodium alginate
Bacterium test experiments result.
Embodiment
Experimental method used in following embodiments is conventional method unless otherwise specified.
Material used, reagent etc., unless otherwise specified, are commercially obtained in following embodiments.
The preparation of amphiphile, amphiphilic molecule and its hybridized hydrogel based on polyaminoacid shown in embodiment 1, formula III
(1) take 10g γ-benzyl-Pidolidone esters and 5g triphosgenes to add in reaction bulb, used under nitrogen protective condition
200ml tetrahydrofuran dissolves both, is warming up to 50 DEG C and reacts 4 hours, and system is become by muddiness to be clarified, and is drained solvent, is obtained light
Yellow solid, it is recrystallized three times with tetrahydrofuran and n-hexane, obtain white needle-like crystals γ-benzyl-Pidolidone
N- carboxyls-ring inner-acid anhydride compound (BLG-NCA) 8.93g, yield 80.47%.Same method prepares ε-benzyloxycarbonyl group-bad ammonia
N- carboxyls-ring inner-acid anhydride compound (ZLL-NCA) of acid.
(2) carried out in the reaction bulb of the polymerisation of the step under nitrogen protection：Take 5.26g in step (1)
(20mmol) BLG-NCA and 1.53g (5mmol) ZLL-NCA, is dissolved in 60ml tetrahydrofurans.Rapidly join 1.205g (5mmol)
Cetylamine.In the system, step (1) obtains the molar fraction of BLG-NCA, ZLL-NCA and lauryl amine respectively than for 4:1、1:
1.Then the system is reacted 12 hours at 40 DEG C.After reaction terminates, reaction solution is transferred in single port bottle, uses Rotary Evaporators
Remove most of solvent.Reaction solution is added in substantial amounts of n-hexane, white solid is obtained by centrifugation.Product quality
4.98g, yield 72.22%.
Its average degree of polymerization i.e. Amino Acid Unit number is calculated as 5, the wherein average degree of polymerization of lysine according to NMR spectra
For 1.
(3) carried out in the reaction bulb of the reaction of the step under nitrogen protection：Take the white of 2.76g (2mmol) step (2)
Product, it is dissolved in 20 milliliters of DMF solvents.Add 6g (80mmol) Propanolamines and 2.28g (24mmol) 2- hydroxyls
Yl pyridines.In this system, the molfraction ratio of glutamic acid units, monoethanolamine and 2 hydroxy pyrimidine is 1:10:3 (i.e. amino acid lists
Member and the mol ratio of 2 hydroxy pyrimidine are 1:8).This system reacts 72h at 45 DEG C, after completion of the reaction, concentration of reaction solution, with big
The ether precipitation of amount, obtains yellow oily liquid.This yellow oily liquid is soluble in water, and dialyse 24h, freezes, obtains white solid
Product.Product quality 1.57g, yield 63%.
(4) white solid product of 1.25g (1mmol) step (3) is taken, is dissolved in 10ml trifluoroacetic acids, is added appropriate
Hydrobromic acid (hydrobromic acid：Lysine=1.5：1, mol ratio) catalysis, the reaction 30 minutes of 25 DEG C of room temperature, revolving removes after reaction terminates
Solvent, it is dissolved in water, dialyse 48h, freezes, obtains white solid product, i.e. formula III, product quality 0.8g, yield 72%, its1H-
NMR nucleus magnetic hydrogen spectrum spectrograms are as shown in Figure 1.
It will be dissolved in formula III manufactured in the present embodiment Suo Shi based on the amphiphile, amphiphilic molecule of polyaminoacid with 1% mass fraction
Water, the hydrogel that can be stablized by the standing of 12 hours.
It will be dissolved in formula III manufactured in the present embodiment Suo Shi based on the amphiphile, amphiphilic molecule of polyaminoacid with 1% mass fraction
Water, and dissolve mass fraction be 0.2% sodium alginate (molecular weight 5000Da) with wherein, by the standing of 12 hours
The hybridized hydrogel stablized.
The power of the hydrogel (with sodium alginate before compound) and hybridized hydrogel (with sodium alginate after compound) of above-mentioned preparation
Intensity is learned as shown in figure 3, as seen from Figure 3, having with the mechanical strength of the compound hydrogel formed afterwards of sodium alginate bright
Aobvious lifting.
The method of testing of mechanical strength：Using AR2000ex rotational rheometers, angle is 1 °, a diameter of 40mm, spacing are
31 μm of cone-plate mould test, angular frequency 6rad/s, strain γ are 0.4%
The preparation of amphiphile, amphiphilic molecule and hybridized hydrogel based on polyaminoacid shown in embodiment 2, formula IV
(1) take 10g γ-benzyl-Pidolidone esters and 5g triphosgenes to add in reaction bulb, used under nitrogen protective condition
200ml tetrahydrofuran dissolves both, is warming up to 50 DEG C and reacts 4 hours, and system is become by muddiness to be clarified, and is drained solvent, is obtained light
Yellow solid, it is recrystallized three times with tetrahydrofuran and n-hexane, obtain white needle-like crystals γ-benzyl-Pidolidone
N- carboxyls-ring inner-acid anhydride compound (BLG-NCA) 8.93g, yield 80.47%.Same method prepares ε-benzyloxycarbonyl group-bad ammonia
N- carboxyls-ring inner-acid anhydride compound (ZLL-NCA) of acid.
(2) carried out in the reaction bulb of the polymerisation of the step under nitrogen protection：Take 3.95g in step (1)
(15mmol) BLG-NCA and 3.06g (10mmol) ZLL-NCA, is dissolved in 60ml tetrahydrofurans.Rapidly join 1.205g
The cetylamine of (5mmol).In the system, step (1) obtain the molar fraction of BLG-NCA, ZLL-NCA and lauryl amine respectively than for
3:1、2:1.Then the system is reacted 12 hours at 40 DEG C.After reaction terminates, reaction solution is transferred in single port bottle, with rotation
Evaporimeter removes most of solvent.Reaction solution is added in substantial amounts of n-hexane, white solid is obtained by centrifugation.Product matter
Measure 4.9g, yield 69%.
Its average degree of polymerization i.e. Amino Acid Unit number is calculated as 5, the wherein average degree of polymerization of lysine according to NMR spectra
For 2.
(3) carried out in the reaction bulb of the reaction of the step under nitrogen protection：Take the white of 2.84g (2mmol) step (2)
Product, it is dissolved in 20 milliliters of DMF solvents.Add 4.5g (60mmol) Propanolamines and 1.71g (18mmol) 2-
Pyridone.In this system, the molfraction ratio of glutamic acid units, monoethanolamine and 2 hydroxy pyrimidine is 1:10:3 (i.e. amino acid
Unit number and the mol ratio of 2 hydroxy pyrimidine are 1:7.5).This system reacts 72h at 45 DEG C, after completion of the reaction, concentration reaction
Liquid, precipitated with substantial amounts of ether, obtain yellow oily liquid.This yellow oily liquid is soluble in water, and dialyse 24h, freezes, obtains white
Color solid product.Product quality 1.96g, yield 74.3%.
(4) white solid product of 1.32g (1mmol) step (3) is taken, is dissolved in 10ml trifluoroacetic acids, is added appropriate
Hydrobromic acid (hydrobromic acid：Lysine=2：1, mol ratio) catalysis, the reaction 30 minutes of 25 DEG C of room temperature, revolving removes molten after reaction terminates
Agent, it is dissolved in water, dialyse 48h, freezes, obtains white solid product, i.e. formula IV, product quality 0.84g, yield 79.6%, its1H-
NMR nucleus magnetic hydrogen spectrum spectrograms are as shown in Figure 2.
It will be dissolved in formula IV manufactured in the present embodiment Suo Shi based on the amphiphile, amphiphilic molecule of polyaminoacid with 2% mass fraction
Water, the hydrogel that can be stablized by the standing of 12 hours.
It will be dissolved in formula IV manufactured in the present embodiment Suo Shi based on the amphiphile, amphiphilic molecule of polyaminoacid with 2% mass fraction
Water, and dissolve mass fraction be 0.2% sodium alginate (molecular weight 5000Da) with wherein, by the standing of 12 hours
The hybridized hydrogel stablized.
The power of the hydrogel (with sodium alginate before compound) and hybridized hydrogel (with sodium alginate after compound) of above-mentioned preparation
Intensity is learned as shown in figure 3, as seen from Figure 3, having with the mechanical strength of the compound hydrogel formed afterwards of sodium alginate bright
Aobvious lifting.
The method of testing of mechanical strength：Using AR2000ex rotational rheometers, angle is 1 °, a diameter of 40mm, spacing are
31 μm of cone-plate mould test, angular frequency 6rad/s, strain γ are 0.4%.
The anti-microbial property of amphiphile, amphiphilic molecule and sodium alginate hybridized hydrogel shown in embodiment 3, formula III based on polyaminoacid
Test
(1) among pure water being dissolved in based on the amphiphile, amphiphilic molecule of polyaminoacid with 1% mass fraction formula III Suo Shi, and add
Enter the sodium alginate (molecular weight 5000Da) that mass fraction is 0.2%, both is sufficiently mixed dissolving, obtain both mixing
The thing aqueous solution；
(2) mixture aqueous solution obtained by, which is added in culture dish, to be stored at room temperature 12 hours, you can spontaneously forms one layer of water
Gel thin-layer；
(3) concentration is separately added into as 10 in hydrogel surface obtained above4CFU/ml、105CFU/ml、106CFU/ml and
107CFU/ml E. coli broth, cultivate 24 hours (condition of culture：37 DEG C, 180rpm), draw upper strata Bacteria Culture
Liquid, the OD of respective sample is tested by ultraviolet specrophotometer600nmValue characterizes large intestine bar of the hydrogel sample to 4 kinds of density
Bacterium inhibiting rate, as shown in figure 4, as seen from Figure 4, amphiphile, amphiphilic molecule of the present invention based on polyaminoacid and sodium alginate hydridization water
Gel has good anti-microbial property.
Claims (3)
1. the preparation method of the amphiphile, amphiphilic molecule based on oligomeric amino acid, comprises the following steps shown in formula I：
(1) γ-benzyl-Pidolidone ester and phosgene or triphosgene reacted to obtain the N- carboxyls of γ-benzyl-Pidolidone-
Ring inner-acid anhydride compound；
The solvent of the reaction is tetrahydrofuran, ethyl acetate or dichloromethane；
The temperature of the reaction is 40 DEG C~60 DEG C；
The time of the reaction is 3~5 hours；
The reaction is carried out under atmosphere of inert gases；
(2) ε-benzyloxycarbonyl group -1B is reacted to obtain the N- carboxylics of ε-benzyloxycarbonyl group -1B with phosgene or triphosgene
Base-ring inner-acid anhydride compound；
The solvent of the reaction is tetrahydrofuran, ethyl acetate or dichloromethane；
The temperature of the reaction is 40 DEG C~60 DEG C；
The time of the reaction is 3~5 hours；
The reaction is carried out under atmosphere of inert gases；
(3) under the initiation of alkyl chain primary amine, N- carboxyls-ring inner-acid anhydride compound of the γ-benzyl-Pidolidone with
N- carboxyls-ring inner-acid anhydride compound of the ε-benzyloxycarbonyl group -1B reacts to obtain alkyl chain-poly- through ring-opening copolymerization
(γ-benzyl-Pidolidone ester)-co- poly- (ε-benzyloxycarbonyl group -1B)；
The alkyl chain primary amine is lauryl amine, tetradecy lamine, cetylamine or octadecylamine；
The solvent of ring-opening copolymerization reaction is dimethylformamide, dimethyl acetamide, dimethyl sulfoxide (DMSO), tetrahydrofuran and
At least one of dioxane；
N- carboxyls-ring inner-acid anhydride the compound and the ε-benzyloxy carbonyl of the alkyl chain primary amine and the γ-benzyl-Pidolidone
The mol ratio of the integral molar quantity of the N- carboxyls of base -1B-ring inner-acid anhydride compound is：1：2~20；
The alkyl chain primary amine and the mol ratio of N- carboxyls-ring inner-acid anhydride compound of the ε-benzyloxycarbonyl group -1B are
1：1~5；
The temperature of the ring-opening copolymerization reaction is 20 DEG C~50 DEG C；
The time of the ring-opening copolymerization reaction is 8 hours~36 hours；
The ring-opening copolymerization reaction is carried out under an inert gas；
(4) alkyl chain-poly- (γ-benzyl-Pidolidone ester)-co- poly- (ε-benzyloxycarbonyl group -1B) and alcamines
Compound carries out aminolysis reaction, obtains alkyl chain-polyglutamic acid alcohol amine amide-co- poly- (ε-benzyloxycarbonyl group-lysine)；
The alcamine compound for linear paraffin hydramine, branching type hydramine and the class containing oligomeric ethylene glycol alcohol amine compound in extremely
Few one kind；
The linear paraffin hydramine is at least one of monoethanolamine, Propanolamine, butanolamine, amylalcohol amine and hexanol amine；
The branching type hydramine is at least one of isopropanolamine, isobutyl hydramine and isoamyl hydramine；
The alcohol amine compound of the class containing oligomeric ethylene glycol is diethyleneglycolamin and/or triethylene glycol amine；
Repeat unit paddy in the alkyl chain-poly- (γ-benzyl-Pidolidone ester)-co- poly- (ε-benzyloxycarbonyl group -1B)
The mol ratio of propylhomoserin and the alcamine compound is 1：5~30；
For the aminolysis reaction under the conditions of existing for catalyst, the catalyst is 2 hydroxy pyrimidine；
Repeat unit ammonia in the alkyl chain-poly- (γ-benzyl-Pidolidone ester)-co- poly- (ε-benzyloxycarbonyl group -1B)
Base is sour and the mol ratio of the 2 hydroxy pyrimidine is 1：1~10；
The temperature of the aminolysis reaction is 40 DEG C~60 DEG C；
The time of the aminolysis reaction is 24 hours~72 hours；
The aminolysis reaction is carried out under atmosphere of inert gases；
(5) under HBr catalysis, the alkyl chain-polyglutamic acid alcohol amine amide-co- poly- (ε-benzyloxycarbonyl group -1B) warps
Deprotection reaction, that is, obtain the amphiphile, amphiphilic molecule based on oligomeric amino acid shown in formula I；
The deprotection reaction is carried out in trifluoroacetic acid；
In the alkyl chain-polyglutamic acid alcohol amine amide-co- poly- (ε-benzyloxycarbonyl group -1B) repeat unit lysine with
The mol ratio of the HBr is 1：1.5~3；
The temperature of the deprotection reaction is 0 DEG C~25 DEG C；
The time of the deprotection reaction is 20 minutes~60 minutes；
In formula I, m be 10~16 between natural number, n be 2~20 between natural number, k be 1~5 between natural number, x 1
Or 2, y are the natural number between 2~6.
2. the preparation method of the amphiphile, amphiphilic molecule based on oligomeric amino acid, comprises the following steps shown in formula II：
(1) β-benzyl-L-aspartate ester is reacted to obtain the N- carboxylics of β-benzyl-L-aspartate with phosgene or triphosgene
Base-ring inner-acid anhydride compound；
The solvent of the reaction is tetrahydrofuran, ethyl acetate or dichloromethane；
The temperature of the reaction is 40 DEG C~60 DEG C；
The time of the reaction is 3~5 hours；
The reaction is carried out under atmosphere of inert gases；
(2) ε-benzyloxycarbonyl group -1B is reacted to obtain the N- carboxylics of ε-benzyloxycarbonyl group -1B with phosgene or triphosgene
Base-ring inner-acid anhydride compound；
The solvent of the reaction is tetrahydrofuran, ethyl acetate or dichloromethane；
The temperature of the reaction is 40 DEG C~60 DEG C；
The time of the reaction is 3~5 hours；
The reaction is carried out under atmosphere of inert gases；
(3) under the initiation of alkyl chain primary amine, N- carboxyls-ring inner-acid anhydride compound of the β-benzyl-L-aspartate
React to obtain alkyl chain-poly- through ring-opening copolymerization with N- carboxyls-ring inner-acid anhydride compound of the ε-benzyloxycarbonyl group -1B
(β-benzyl-L-aspartate ester)-co- poly- (ε-benzyloxycarbonyl group -1B)；
The alkyl chain primary amine is lauryl amine, tetradecy lamine, cetylamine or octadecylamine；
The solvent of ring-opening copolymerization reaction is dimethylformamide, dimethyl acetamide, dimethyl sulfoxide (DMSO), tetrahydrofuran and
At least one of dioxane；
N- carboxyl-ring inner-acid anhydride compound and the ε-benzyloxy of the alkyl chain primary amine with the β-benzyl-L-aspartate
The mol ratio of the integral molar quantity of the N- carboxyls of carbonyl -1B-ring inner-acid anhydride compound is：1：2~20；
The alkyl chain primary amine and the mol ratio of N- carboxyls-ring inner-acid anhydride compound of the ε-benzyloxycarbonyl group -1B are
1：1~5；
The temperature of the ring-opening copolymerization reaction is 20 DEG C~50 DEG C；
The time of the ring-opening copolymerization reaction is 8 hours~36 hours；
The ring-opening copolymerization reaction is carried out under an inert gas；
(4) alkyl chain-poly- (β-benzyl-L-aspartate ester)-co- poly- (ε-benzyloxycarbonyl group -1B) and alcamines
Compound carries out aminolysis reaction, obtains alkyl chain-poly-aspartate alcohol amine amide-co- poly- (ε-benzyloxycarbonyl group -1B)；
The alcamine compound for linear paraffin hydramine, branching type hydramine and the class containing oligomeric ethylene glycol alcohol amine compound in extremely
Few one kind；
The linear paraffin hydramine is at least one of monoethanolamine, Propanolamine, butanolamine, amylalcohol amine and hexanol amine；
The branching type hydramine is at least one of isopropanolamine, isobutyl hydramine and isoamyl hydramine；
The alcohol amine compound of the class containing oligomeric ethylene glycol is diethyleneglycolamin and/or triethylene glycol amine；
For the aminolysis reaction under the conditions of existing for catalyst, the catalyst is 2 hydroxy pyrimidine；
Repeat unit day in the alkyl chain-poly- (β-benzyl-L-aspartate ester)-co- poly- (ε-benzyloxycarbonyl group -1B)
The mol ratio of winter propylhomoserin and the alcamine compound is 1：5~30；
In the alkyl chain-poly- (β-benzyl-L-aspartate ester)-co- poly- (ε-benzyloxycarbonyl group -1B) in repeat unit
The mol ratio of repeat unit amino acid and the 2 hydroxy pyrimidine is 1：1~10；
The temperature of the aminolysis reaction is 40 DEG C~60 DEG C；
The time of the aminolysis reaction is 24 hours~72 hours；
The aminolysis reaction is carried out under atmosphere of inert gases；
(5) under HBr catalysis, the alkyl chain-poly-aspartate alcohol amine amide-co- poly- (ε-benzyloxycarbonyl group -1B)
Through deprotection reaction, that is, obtain the amphiphile, amphiphilic molecule based on oligomeric amino acid shown in formula II；
The deprotection reaction is carried out in trifluoroacetic acid；
Repeat unit relies in the alkyl chain-poly-aspartate alcohol amine amide-co- poly- (ε-benzyloxycarbonyl group -1B)
Propylhomoserin and the HBr mol ratio are 1：1.5~3；
The temperature of the deprotection reaction is 0 DEG C~25 DEG C；
The time of the deprotection reaction is 20 minutes~60 minutes；
In formula II, m is the natural number between 10~16, and n is the natural number between 2~20, and k is the natural number between 1~5, and x is
1 or 2, z be 1~3 between natural number.
3. a kind of anti-bacterial hydrogel, its amphiphile, amphiphilic molecule and sodium alginate based on oligomeric amino acid shown in formula I and/or formula II
Formed with decentralized medium；
The decentralized medium is the aqueous solution of water or salt；
In the anti-bacterial hydrogel, the weight/mass percentage composition of the amphiphile, amphiphilic molecule based on oligomeric amino acid is shown in formula I and/or formula II
0.5%~10%；
The weight/mass percentage composition of the sodium alginate is 0.5%~10%；
In formula I and formula II, m is the natural number between 10~16, and n is the natural number between 2~20, and k is the nature between 1~5
Number, x are 1 or 2；
In formula I, y is the natural number between 2~6；
In formula II, z is the natural number between 1~3.
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