CN104857550B - Polylysine-p-hydroxyphenylpropionic acid antibacterial hydrogel dressing and preparation method thereof - Google Patents
Polylysine-p-hydroxyphenylpropionic acid antibacterial hydrogel dressing and preparation method thereof Download PDFInfo
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- CN104857550B CN104857550B CN201510289971.7A CN201510289971A CN104857550B CN 104857550 B CN104857550 B CN 104857550B CN 201510289971 A CN201510289971 A CN 201510289971A CN 104857550 B CN104857550 B CN 104857550B
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- polylysine
- propionic acid
- epsilon
- para hydroxybenzene
- hydroxybenzene propionic
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- 239000000017 hydrogel Substances 0.000 title claims abstract description 72
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 72
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- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
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- Materials For Medical Uses (AREA)
- Medicinal Preparation (AREA)
Abstract
A preparation method of a polylysine-p-hydroxyphenylpropionic acid antibacterial hydrogel dressing comprises the steps of dissolving p-hydroxyphenylpropionic acid in a blending solvent of an organic solvent and deionized water, and uniformly stirring and mixing; adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide into the obtained mixed system, and activating under the ice bath condition; adding polylysine dissolved by deionized water into the activated system, and reacting at room temperature; transferring the obtained system into a dialysis bag for dialysis; freeze-drying the purified solution after dialysis to obtain a polylysine-p-hydroxyphenylpropionic acid copolymer; and (3) respectively preparing a stock solution A and a stock solution B at normal temperature by using PBS buffer solution as a solvent, respectively adding the stock solutions A and B into an AB tube of a double-head injector, and slowly pushing out to obtain the uniform and transparent polylysine-p-hydroxyphenylpropionic acid antibacterial hydrogel dressing.
Description
Technical field
The invention belongs to medical material tech field, and in particular to a kind of epsilon-polylysine-para hydroxybenzene propionic acid hydrogel
And preparation method thereof.
Background technology
It is inevitable that people cause the various damages of human body skin in daily life and work.According to world health group
Knit statistics, lethal about 5,100,000 people of number of the various wounds in the nineteen ninety whole world, it is contemplated that the year two thousand twenty can increase to 8,400,000 people.According to national health
Portion counts, and wound is the 5th cause of the death in China city and rural area within 2005, accounts for the 6.17% of total death toll.Therefore, create
Wound is the very important disease of a class.Wound dressing is can to play temporary protection wound, prevent from polluting, promote the medical of healing
Material, is to carry out one of effective means of trauma care using wound dressing.
Preferably dressing should have the absorbable wound fluid, temperature and humidity that keep wound facing face, good
The advantages of gas permeability, anti-inflammation.Aerogel dressing is closer to the requirement of preferable dressing.Because hydrogel is high by hydrophily
Molecular compound is contained large quantity of moisture, there is three-dimensional netted knot by one kind that the crosslinking such as covalent bond, ionic bond or hydrogen bond is obtained
The swelling body of structure, possesses certain compression strength, and can provide the environment for moistening for wound, have preferable phase with biological tissue
Capacitive, thus greatly paid close attention in biomedical engineering fields such as medicine controlled releasing, tissue engineering bracket, wound dressings, have
Extremely good application prospect.
Although moist environment contributes to cell growth, promote the healing of wound, be simultaneously also beneficial to harmful microbe
Grow, therefore, the anti-harmful microorganism infection characterization of functional dressing is just particularly important.There are many researchs to report to pass through
Dipping, coating and chemically or physically the method such as modification improving the anti-harmful microorganism performance of dressing.Such as Radhakumary etc. with
The modified shitosan of poly-N-isopropyl acrylamide (NIPPA) is carrier, is mixed into Ciprofloxacin, is prepared for anti-microbial property
Thermo-responsive hydro gel dressing with medicament slow release effect.Silver system antiseptic dressing also more to be reported, and silver has efficient antibiotic property, and it can
By methods such as dipping, blendings, dressing antibacterial or bacteria resistance function is given, mitigate trauma surface infestation, promote wound healing.Chinese invention
A kind of preparation method of nano-silver functional hydrocolloid medical dressing is disclosed in patent CN102218155A, is by nano-silver powder
Body is added in macromolecule melt, but Nano Silver is reunited seriously, affects anti-microbial property.In Chinese invention patent CN102266583A
A kind of preparation method of Nano Silver hygrometric state dressing is disclosed, modified bacteria cellulose is immersed in nitrate solution, is contained
The bacteria cellulose of selective load silver ion, but formed dressing during application with the loss of silver ion, antibacterial
Effect weakens therewith.In addition, also adopting antibiotic, such as gentamicin, triclosan, BZK etc. are added in dressing
Play the report of antibacterial action.
However, the current anti-harmful microorganism medical dressing of report or application, on the one hand most using modified chitin or
Nano Silver system, not only expensive, and also antimicrobial action is slow, and effect is also unsatisfactory；On the other hand, much using having
Machine small molecule antiseptic, for example adjacent hydroxycyclopent alkene diketone etc., quaternary ammonium salt, season biguanides antiseptic etc., with sterilized fast, antibacterial
The advantages of scope is wide, but antiseptic is simply added in dressing using the method for blending or dipping, and the antiseptic for oozing out is not
Only possible can be detrimental to health, and Long-Time Service also results in the formation of drug resistance pathogen, so as to substantially reduce medicine
Anti-infection ability.
Epsilon-polylysine (EPL) is the 1B either homopolymers that a kind of degree of polymerization by Microbe synthesis is 25-35,
Have broad-spectrum antiseptic (having antibacterial action to gram-negative bacteria, gram positive bacteria, fungi and fractionated viral etc.), safety non-toxic,
The advantages of good water solubility and high heat endurance, it is widely used in food antiseptic field, as its structure is rich in cation amino, this
Body possesses antibacterial ability, is not required in addition add small molecule antibacterials, and is easy to modification, is the ideal for preparing anti-biotic material
Select.
The preparation method of hydrogel mainly has chemical method, radiation method etc..Chemical method needs to add during preparing hydrogel
A certain amount of crosslinking agent, is to prepare the more conventional method of hydrogel, the hydrogel properties of generation by cross-linking monomer, crosslinking agent and
The impact of reaction condition, and these monomers and crosslinking agent often have toxicity, can cause the poor biocompatibility of material.Radiation method
Cause crosslinking that hydrogel is obtained by high-energy radiation, its process is not required to add chemical cross-linking agent and initiator etc., and product is pure, and
Can carry out at room temperature, reaction condition is gentle, can pass through to control the control properties of product such as dose of radiation, at the same gel-forming with
Sterilization synchronously can be carried out.But generally mechanical strength is less for hydrogel prepared by radiation method, very high to equipment requirement, makes
Popularity is restricted.
To sum up, antibacterial wound aerogel dressing has various aspects in the preparation method of anti-biotic material and hydrogel
Deficiency, or poor biocompatibility, or antibiotic property difference etc..
Content of the invention
It is contemplated that abandoning the biography for adding the chemical reagent such as antibiotic, small-molecule drug in wound dressing preparation process
A kind of system technique, there is provided aerogel dressing with intrinsic antibacterial effect, and with good biocompatibility and biodegradable
Property.
Another object of the present invention is to providing a kind of preparation method of polylysine hydrogel antimicrobial dressing, the method is adopted
Prepared with the method for enzyme situ-gel, with the polylysine anti-bacterial hydrogel gelation time of the method acquisition, mechanical performance, degraded
Property is controllable, with more preferable biocompatibility.
For realizing the object of the invention to solve the technical problems, employ the following technical solutions：
A kind of preparation method of epsilon-polylysine-para hydroxybenzene propionic acid anti-bacterial hydrogel dressing, it comprises the steps：
(1) preparation of epsilon-polylysine-para hydroxybenzene propionic acid copolymer (EPL-HPA)：
(1a) para hydroxybenzene propionic acid (HPA) is dissolved in the blend solvent of organic solvent and deionized water, stirring mixing
Uniformly；
(1b) 1- (3- dimethylamino-propyls) -3- ethyl carbodiimide salt is added in the mixed system obtained to step (1a)
Hydrochlorate (EDC) and N-hydroxy-succinamide (NHS), activate 2～8h under condition of ice bath；
(1c) epsilon-polylysine of deionized water dissolving is added in the system after step (1b) activation, under room temperature condition
10～20h of reaction；
(1d) system that step (1c) is obtained is transferred in bag filter, is placed in deionized water and dialyses 3～7 days；
(1e) the purification solution freeze-drying after step (1d) dialysis is obtained epsilon-polylysine-para hydroxybenzene propionic acid copolymerization
Thing；
(2) using PBS as solvent, A stostes and B stostes are prepared at normal temperatures respectively：
A stostes solute is epsilon-polylysine-para hydroxybenzene propionic acid copolymer and horseradish peroxidase (HRP)；
B stostes solute is epsilon-polylysine-para hydroxybenzene propionic acid copolymer (EPL-HPA copolymers) and hydrogen peroxide
(H2O2)；
(3) the A stostes and B stostes for obtaining step (2) is separately added in the AB pipes of dual-head injector, and slow release obtains
The epsilon-polylysine of homogeneous transparent-para hydroxybenzene propionic acid anti-bacterial hydrogel dressing.
In step (1a), described organic solvent is DMF (DMF), dimethyl sulfoxide (DMSO) or acetic acid second
Ester, preferably DMF (DMF).The volume ratio of organic solvent and deionized water (RO water) is 1：1～5.
In step (1a), the consumption of para hydroxybenzene propionic acid is 1g/100mL blend solvents.
In step (1b), 1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides and N-hydroxy-succinamide
Mol ratio be 3.5～1:1, preferably 1:1；1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides and para hydroxybenzene
The mol ratio of propionic acid is 5～1:1, preferably 3:1.
In step (1c), described epsilon-polylysine is prepared by microbe fermentation method；Molecular weight is 2000～5500
Dalton.
In step (1c), the amino in epsilon-polylysine is 1 with the mol ratio of para hydroxybenzene propionic acid:1～5, preferably 1:3.
In step (2), described PBS is the PBS of 0.01～0.05mol/L, and preferably 0.01M PBS delay
Rush liquid.
In step (2), in A stostes, the concentration of solute epsilon-polylysine-para hydroxybenzene propionic acid copolymer is 4～20wt%,
It is preferred that 10wt%；The concentration of solute horseradish peroxidase is 0.02～0.1mg/mL, preferably 0.05mg/mL；In B stostes, molten
The concentration of matter epsilon-polylysine-para hydroxybenzene propionic acid copolymer is 4～20wt%, preferably 20wt%；Solute concentration of hydrogen peroxide
For 0.04～0.12wt%, preferably 0.12wt%.
In step (3), A stostes and B stostes equal-volume release mixing.
The epsilon-polylysine that above-mentioned preparation method is prepared-para hydroxybenzene propionic acid anti-bacterial hydrogel dressing is also in the present invention
Protection domain within.
Beneficial effect：The antibacterial hydrogel material source is native biopolymer polylysine, in situ using enzymatic
The method of gel is obtained under normal atmosphere temperature neutral, and preparation process does not contain any chemical cross-linking agent.Antibacterial water obtained in of the invention
Gel dressing is respectively provided with excellent inhibitory action to Escherichia coli and staphylococcus aureus, can effectively prevent wound infection, and
There is excellent biocompatibility and biodegradability.
Description of the drawings
Fig. 1 is the reaction principle schematic diagram of the present invention；
Fig. 2 for polylysine-para hydroxybenzene propionic acid proton nmr spectra (1H-NMR), solvent is D2O；
Fig. 3 is gelation time of the hydrogel under the polymer and enzyme-catalyzed reaction condition of variable concentrations；
Fig. 4 be hydrogel in different hydrogen peroxide (H2O2) elastic modelling quantity under concentration；
Scanning electron microscopic picture (SEM) of the Fig. 5 for polylysine hydrogel；
Fig. 6 be polylysine hydrogel antimicrobial dressing to Escherichia coli (E.coli) and staphylococcus aureus
(S.aureus) qualitative (Bactericidal test) and the antibacterial effect of variable concentrations EPL-HPA.
Specific embodiment
Below by embodiment, the present invention is further illustrated, its purpose be only that be better understood from the present invention rather than
Limit the scope of protection of the invention.
Following examples agents useful for same source is as follows：
Epsilon-polylysine：It is purchased from Nanjing Shinekingbiotech, Ltd.；2000～5500Da of molecular weight.
PBS (PBS), HPA (para hydroxybenzene propionic acid), EDC (1- (3- dimethylaminopropyls) -3- ethyls
Carbodiimide), NHS (N-hydroxy-succinamide), HRP (horseradish peroxidase), H2O2(hydrogen peroxide) is purchased from Sigma-
Aldrich.
Following examples device therefor source is as follows：
Magnetic stirring apparatus：Model 85-2C, Shanghai turn round boat experimental instruments and equipment limited.
Freeze drier：Model FD-1C-50, Beijing Bo Yikang laboratory apparatus Co., Ltd.
Vacuum drying chamber：Model YZG-600, Nanjing Yan Tai heating equipments Co., Ltd.
NMR：Model AVANCE AV-500, Bruker Daltonics companies of the U.S..
SEM：Model JEOL, JSM-6380, NEC (JEOL).
Embodiment 1
The blend solvent that para hydroxybenzene propionic acid is dissolved in N,N-dimethylformamide (DMF) and deionized water (RO water)
In, DMF is 1 with the volume ratio of RO water：3, the consumption of para hydroxybenzene propionic acid is 1g/100mL blend solvents, is uniformly mixed.
1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides (EDC), N-hydroxy-succinamide (NHS) is added, in ice bath
Under the conditions of activate 5h.Water-soluble for RO epsilon-polylysine is added in the system after activation, 15h under room temperature condition, is reacted.Respectively
The mol ratio of material is as follows：EPL(NH2):HPA=1:1, EDC:HPA=1:1,EDC:NHS=1:1.Reacted solution is turned
Move in bag filter, be placed in RO water and dialyse 5 days.Purification solution freeze-drying after the dialysis for obtaining is obtained EPL-HPA altogether
Polymers, yield are 45%.
Embodiment 2
The blend solvent that para hydroxybenzene propionic acid is dissolved in N,N-dimethylformamide (DMF) and deionized water (RO water)
In, DMF is 1 with the volume ratio of RO water：3, the consumption of para hydroxybenzene propionic acid is 1g/100mL blend solvents, is uniformly mixed.
1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides (EDC), N-hydroxy-succinamide (NHS) is added, in ice bath
Under the conditions of activate 5h.Water-soluble for RO polylysine is added in the system after activation, 15h under room temperature condition, is reacted.Each thing
The mol ratio of matter is as follows：EPL(NH2):HPA=1:3, EDC:HPA=1:1,EDC:NHS=1:1.Reacted solution is shifted
Into bag filter, it is placed in RO water and dialyses 5 days.Purification solution freeze-drying after the dialysis for obtaining is obtained EPL-HPA copolymerization
Thing, yield are 87%.
Embodiment 3
The blend solvent that para hydroxybenzene propionic acid is dissolved in N,N-dimethylformamide (DMF) and deionized water (RO water)
In, DMF is 1 with the volume ratio of RO water：3, the consumption of para hydroxybenzene propionic acid is 1g/100mL blend solvents, is uniformly mixed.
1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides (EDC), N-hydroxy-succinamide (NHS) is added, in ice bath
Under the conditions of activate 5h.Water-soluble for RO polylysine is added in the system after activation, 15h under room temperature condition, is reacted.Each thing
The mol ratio of matter is as follows：EPL(NH2):HPA=1:5, EDC:HPA=1:1,EDC:NHS=1:1.Reacted solution is shifted
Into bag filter, it is placed in RO water and dialyses 5 days.Purification solution freeze-drying after the dialysis for obtaining is obtained EPL-HPA copolymerization
Thing, yield are 63%.
Embodiment 4
The blend solvent that para hydroxybenzene propionic acid is dissolved in N,N-dimethylformamide (DMF) and deionized water (RO water)
In, DMF is 1 with the volume ratio of RO water：3, the consumption of para hydroxybenzene propionic acid is 1g/100mL blend solvents, is uniformly mixed.
1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides (EDC), N-hydroxy-succinamide (NHS) is added, in ice bath
Under the conditions of activate 5h.Water-soluble for RO polylysine is added in the system after activation, 15h under room temperature condition, is reacted.Each thing
The mol ratio of matter is as follows：EPL(NH2):HPA=1:3, EDC:HPA=3:1,EDC:NHS=1:1.Reacted solution is shifted
Into bag filter, it is placed in RO water and dialyses 5 days.Purification solution freeze-drying after the dialysis for obtaining is obtained EPL-HPA copolymerization
Thing, yield are 90%.And nucleus magnetic hydrogen spectrum sign is carried out to product, as a result as shown in Fig. 2 the nucleus magnetic hydrogen spectrum of product EPL-HPA exists
There is the characteristic peak of HPA in 6.8ppm and 7.0ppm, show that HPA is successfully grafted EPL.
Embodiment 5
The blend solvent that para hydroxybenzene propionic acid is dissolved in N,N-dimethylformamide (DMF) and deionized water (RO water)
In, DMF is 1 with the volume ratio of RO water：3, the consumption of para hydroxybenzene propionic acid is 1g/100mL blend solvents, is uniformly mixed.
1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides (EDC), N-hydroxy-succinamide (NHS) is added, in ice bath
Under the conditions of activate 5h.Water-soluble for RO polylysine is added in the system after activation, 15h under room temperature condition, is reacted.Each thing
The mol ratio of matter is as follows：EPL(NH2):HPA=1:3, EDC:HPA=5:1,EDC:NHS=1:1.Reacted solution is shifted
Into bag filter, it is placed in RO water and dialyses 5 days.Purification solution freeze-drying after the dialysis for obtaining is obtained EPL-HPA copolymerization
Thing, yield are 85%.
Embodiment 6
The blend solvent that para hydroxybenzene propionic acid is dissolved in N,N-dimethylformamide (DMF) and deionized water (RO water)
In, DMF is 1 with the volume ratio of RO water：3, the consumption of para hydroxybenzene propionic acid is 1g/100mL blend solvents, is uniformly mixed.
1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides (EDC), N-hydroxy-succinamide (NHS) is added, in ice bath
Under the conditions of activate 5h.Water-soluble for RO polylysine is added in the system after activation, 15h under room temperature condition, is reacted.Each thing
The mol ratio of matter is as follows：EPL(NH2):HPA=1:3, EDC:HPA=3:1,EDC:NHS=2:1.Reacted solution is shifted
Into bag filter, it is placed in RO water and dialyses 5 days.Purification solution freeze-drying after the dialysis for obtaining is obtained EPL-HPA copolymerization
Thing, yield are 79%.
Embodiment 7
The blend solvent that para hydroxybenzene propionic acid is dissolved in N,N-dimethylformamide (DMF) and deionized water (RO water)
In, DMF is 1 with the volume ratio of RO water：3, the consumption of para hydroxybenzene propionic acid is 1g/100mL blend solvents, is uniformly mixed.
1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides (EDC), N-hydroxy-succinamide (NHS) is added, in ice bath
Under the conditions of activate 5h.Water-soluble for RO polylysine is added in the system after activation, 15h under room temperature condition, is reacted.Each thing
The mol ratio of matter is as follows：EPL(NH2):HPA=1:3, EDC:HPA=3:1,EDC:NHS=3.5:1.Reacted solution is turned
Move in bag filter, be placed in RO water and dialyse 5 days.Purification solution freeze-drying after the dialysis for obtaining is obtained EPL-HPA altogether
Polymers, yield are 86%.
Embodiment 8
The blend solvent that para hydroxybenzene propionic acid is dissolved in N,N-dimethylformamide (DMF) and deionized water (RO water)
In, DMF is 1 with the volume ratio of RO water：3, the consumption of para hydroxybenzene propionic acid is 1g/100mL blend solvents, is uniformly mixed.
1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides (EDC), N-hydroxy-succinamide (NHS) is added, in ice bath
Under the conditions of activate 2h.Water-soluble for RO polylysine is added in the system after activation, 15h under room temperature condition, is reacted.Each thing
The mol ratio of matter is as follows：EPL(NH2):HPA=1:3, EDC:HPA=3:1,EDC:NHS=1:1.Reacted solution is shifted
Into bag filter, it is placed in RO water and dialyses 5 days.Purification solution freeze-drying after the dialysis for obtaining is obtained EPL-HPA copolymerization
Thing, yield are 54%.
Embodiment 9
The blend solvent that para hydroxybenzene propionic acid is dissolved in N,N-dimethylformamide (DMF) and deionized water (RO water)
In, DMF is 1 with the volume ratio of RO water：3, the consumption of para hydroxybenzene propionic acid is 1g/100mL blend solvents, is uniformly mixed.
1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides (EDC), N-hydroxy-succinamide (NHS) is added, in ice bath
Under the conditions of activate 8h.Water-soluble for RO polylysine is added in the system after activation, 15h under room temperature condition, is reacted.Each thing
The mol ratio of matter is as follows：EPL(NH2):HPA=1:3, EDC:HPA=3:1,EDC:NHS=1:1.Reacted solution is shifted
Into bag filter, it is placed in RO water and dialyses 5 days.Purification solution freeze-drying after the dialysis for obtaining is obtained EPL-HPA copolymerization
Thing, yield are 82%.
Embodiment 10
The blend solvent that para hydroxybenzene propionic acid is dissolved in N,N-dimethylformamide (DMF) and deionized water (RO water)
In, DMF is 1 with the volume ratio of RO water：3, the consumption of para hydroxybenzene propionic acid is 1g/100mL blend solvents, is uniformly mixed.
1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides (EDC), N-hydroxy-succinamide (NHS) is added, in ice bath
Under the conditions of activate 5h.Water-soluble for RO polylysine is added in the system after activation, 10h under room temperature condition, is reacted.Each thing
The mol ratio of matter is as follows：EPL(NH2):HPA=1:3, EDC:HPA=3:1,EDC:NHS=1:1.Reacted solution is shifted
Into bag filter, it is placed in RO water and dialyses 5 days.Purification solution freeze-drying after the dialysis for obtaining is obtained EPL-HPA copolymerization
Thing, yield are 84%.
Embodiment 11
The blend solvent that para hydroxybenzene propionic acid is dissolved in N,N-dimethylformamide (DMF) and deionized water (RO water)
In, DMF is 1 with the volume ratio of RO water：3, the consumption of para hydroxybenzene propionic acid is 1g/100mL blend solvents, is uniformly mixed.
1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides (EDC), N-hydroxy-succinamide (NHS) is added, in ice bath
Under the conditions of activate 5h.Water-soluble for RO polylysine is added in the system after activation, 20h under room temperature condition, is reacted.Each thing
The mol ratio of matter is as follows：EPL(NH2):HPA=1:3, EDC:HPA=3:1,EDC:NHS=1:1.Reacted solution is shifted
Into bag filter, it is placed in RO water and dialyses 5 days.Purification solution freeze-drying after the dialysis for obtaining is obtained EPL-HPA copolymerization
Thing, yield are 89%.
Embodiment 12
A, B stoste that hydrogel is prepared under normal temperature condition respectively with 0.01mol/L PBSs, A solutes are：EPL-
HPA copolymers (embodiment 4 be obtained), horseradish peroxidase (HRP), B solutes are：EPL-HPA copolymers, hydrogen peroxide
(H2O2).In A stostes, EPL-HPA concentration is 4wt%, and HRP concentration is 0.1mg/mL.In B stostes, EPL-HPA concentration is 4wt%,
H2O2Concentration is 0.12wt%.AB stostes are separately added in the AB pipes of dual-head injector, slow release obtain homogeneous transparent can
Injection-type EPL-HPA anti-bacterial hydrogels.The gelation time of hydrogel is 11s, as shown in Figure 3.Can be obtained by Fig. 3 results, dense in HRP
On the premise of degree is fixed, the concentration of the gelation time of EPL-HPA hydrogels and EPL-HPA materials into positive correlation, meanwhile, in EPL-
On the premise of HPA material concentrations are fixed, with HRP concentration into positive correlation.
Embodiment 13
A, B stoste that hydrogel is prepared under normal temperature condition respectively with 0.01mol/L PBSs, A solutes are：EPL-
HPA copolymers (embodiment 4 be obtained), horseradish peroxidase (HRP), B solutes are：EPL-HPA copolymers, hydrogen peroxide
(H2O2).In A stostes, EPL-HPA concentration is 5wt%, and HRP concentration is 0.1mg/mL.In B stostes, EPL-HPA concentration is 5wt%,
H2O2Concentration is 0.12wt%.AB stostes are separately added in the AB pipes of dual-head injector, equal-volume is slowly released and obtained uniformly thoroughly
Bright injectable type EPL-HPA anti-bacterial hydrogels.The gelation time of hydrogel is 7s, as shown in Figure 3.
Embodiment 14
A, B stoste that hydrogel is prepared under normal temperature condition respectively with 0.01mol/L PBSs, A solutes are：EPL-
HPA copolymers (embodiment 4 be obtained), horseradish peroxidase (HRP), B solutes are：EPL-HPA copolymers, hydrogen peroxide
(H2O2).In A stostes, EPL-HPA concentration is 10wt%, and HRP concentration is 0.1mg/mL.In B stostes, EPL-HPA concentration is
10wt%, H2O2Concentration is 0.12wt%.AB stostes are separately added in the AB pipes of dual-head injector, equal-volume is slowly released
Injectable type EPL-HPA anti-bacterial hydrogels to homogeneous transparent.The gelation time of hydrogel is 3s, as shown in Figure 3.
Embodiment 15
A, B stoste that hydrogel is prepared under normal temperature condition respectively with 0.01mol/L PBSs, A solutes are：EPL-
HPA copolymers (embodiment 4 be obtained), horseradish peroxidase (HRP), B solutes are：EPL-HPA copolymers, hydrogen peroxide
(H2O2).In A stostes, EPL-HPA concentration is 10wt%, and HRP concentration is 0.02mg/mL.In B stostes, EPL-HPA concentration is
10wt%, H2O2Concentration is 0.12wt%.AB stostes are separately added in the AB pipes of dual-head injector, equal-volume is slowly released
Injectable type EPL-HPA anti-bacterial hydrogels to homogeneous transparent.The gelation time of hydrogel is 231s, as shown in Figure 3.
Embodiment 16
A, B stoste that hydrogel is prepared under normal temperature condition respectively with 0.01mol/L PBSs, A solutes are：EPL-
HPA copolymers (embodiment 4 be obtained), horseradish peroxidase (HRP), B solutes are：EPL-HPA copolymers, hydrogen peroxide
(H2O2).In A stostes, EPL-HPA concentration is 10wt%, and HRP concentration is 0.06mg/mL.In B stostes, EPL-HPA concentration is
10wt%, H2O2Concentration is 0.12wt%.AB stostes are separately added in the AB pipes of dual-head injector, equal-volume is slowly released
Injectable type EPL-HPA anti-bacterial hydrogels to homogeneous transparent.The gelation time of hydrogel is 32s, as shown in Figure 3.
Embodiment 17
A, B stoste that hydrogel is prepared under normal temperature condition respectively with 0.01mol/L PBSs, A solutes are：EPL-
HPA copolymers (embodiment 4 be obtained), horseradish peroxidase (HRP), B solutes are：EPL-HPA copolymers, hydrogen peroxide
(H2O2).In A stostes, EPL-HPA concentration is 10wt%, and HRP concentration is 0.06mg/mL.In B stostes, EPL-HPA concentration is
10wt%, H2O2Concentration is 0.12wt%.AB stostes are separately added in the AB pipes of dual-head injector, equal-volume is slowly released
Injectable type EPL-HPA anti-bacterial hydrogels to homogeneous transparent.The gelation time of hydrogel is 32s.The hydrogel for obtaining is entered
After row freeze-drying process, metal spraying is scanned Electronic Speculum sign, as a result shows that EPL-HPA hydrogels are tied for stereoscopic three-dimensional network
Structure, as shown in Figure 4.
Embodiment 18
A, B stoste that hydrogel is prepared under normal temperature condition respectively with 0.01mol/L PBSs, A solutes are：EPL-
HPA copolymers (embodiment 4 be obtained), horseradish peroxidase (HRP), B solutes are：EPL-HPA copolymers, hydrogen peroxide
(H2O2).In A stostes, EPL-HPA concentration is 10wt%, and HRP concentration is 0.1mg/mL.In B stostes, EPL-HPA concentration is
10wt%, H2O2Concentration is 0.12wt%.AB stostes are separately added in the AB pipes of dual-head injector, equal-volume is slowly released
Injectable type EPL-HPA anti-bacterial hydrogels to homogeneous transparent.The elastic modelling quantity of hydrogel is 1634Pa.As shown in Figure 5.By scheming
5 results can be obtained, and on the premise of EPL-HPA copolymers and HRP concentration are fixed, the elastic modelling quantity of hydrogel is dense with hydrogen peroxide
Spend into positive correlation.
Embodiment 19
A, B stoste that hydrogel is prepared under normal temperature condition respectively with 0.01mol/L PBSs, A solutes are：EPL-
HPA copolymers (embodiment 4 be obtained), horseradish peroxidase (HRP), B solutes are：EPL-HPA copolymers, hydrogen peroxide
(H2O2).In A stostes, EPL-HPA concentration is 10wt%, and HRP concentration is 0.1mg/mL.In B stostes, EPL-HPA concentration is
10wt%, H2O2Concentration is 0.08wt%.AB stostes are separately added in the AB pipes of dual-head injector, equal-volume is slowly released
Injectable type EPL-HPA anti-bacterial hydrogels to homogeneous transparent.The elastic modelling quantity of hydrogel is 1385Pa.As shown in Figure 5.
Embodiment 20
A, B stoste that hydrogel is prepared under normal temperature condition respectively with 0.01mol/L PBSs, A solutes are：EPL-
HPA copolymers (embodiment 4 be obtained), horseradish peroxidase (HRP), B solutes are：EPL-HPA copolymers, hydrogen peroxide
(H2O2).In A stostes, EPL-HPA concentration is 10wt%, and HRP concentration is 0.1mg/mL.In B stostes, EPL-HPA concentration is
10wt%, H2O2 concentration is 0.04wt%.AB stostes are separately added in the AB pipes of dual-head injector, equal-volume is slowly released
Injectable type EPL-HPA anti-bacterial hydrogels to homogeneous transparent.The elastic modelling quantity of hydrogel is 772Pa.As shown in Figure 5.
Embodiment 21：The anti-microbial property test of hydrogel
Qualitative experiment：LB solid culture wares are prepared, and the column type for diameter 2cm being dug out in the centre of solid culture ware respectively coagulates
Glue, fills polylysine hydrogel prepared by this patent in cylinder type hollow position, is coated with solid culture primary surface a certain amount of
Then culture medium is placed in 37 DEG C of incubator culture 24h by Escherichia coli or staphylococcus aureus, observes inhibition zone after taking-up
Size.
Quantitative experiment：Prepare the EPL-HPA hydrogels (being obtained according to embodiment 4) of variable concentrations respectively, and be placed on
In the bacterium solution of Escherichia coli and staphylococcus aureus, the OD values of routine test bacterium solution calculate the antimicrobial efficiency of hydrogel.
As a result as shown in fig. 6, the concentration that abscissa A, B, C represent polymer EPL-HPA in hydrogel respectively is respectively
2.wt%, 5.wt%, 10.wt%, have figure to understand that hydrogel is to Gram-negative bacteria (Escherichia coli) and gram-positive bacteria
(staphylococcus aureus) is respectively provided with obvious fungistatic effect, and fungistatic effect is with the increasing of hydrogel EPL-HPA material concentrations
Greatly (A to C increases successively for EPL-HPA concentration) and increase, control group TCTP be blank, Survival probability of bacteria is 100%, is
Fungistatic effect.
Result of the test shows：The epsilon-polylysine aerogel dressing of the present invention has controllable gelation time and three-dimensional netted
Structure, and with good antibacterial effect, have a extensive future in medical anti-infectious Material Field.
Although, above the present invention is described in detail with a general description of the specific embodiments,
On the basis of the present invention, some modification and improvement can be made to it, this will be apparent to those skilled in the art.Cause
This, these modification and improvement that is done without departing from theon the basis of the spirit of the present invention belong to the scope of protection of present invention.
Claims (10)
1. the preparation method of a kind of epsilon-polylysine-para hydroxybenzene propionic acid anti-bacterial hydrogel dressing, it is characterised in that it include as
Lower step：
(1) preparation of epsilon-polylysine-para hydroxybenzene propionic acid copolymer：
(1a) para hydroxybenzene propionic acid is dissolved in the blend solvent of organic solvent and deionized water, is uniformly mixed；
(1b) 1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides are added in the mixed system obtained to step (1a)
And N-hydroxy-succinamide, 2～8h is activated under condition of ice bath；
(1c) epsilon-polylysine of deionized water dissolving is added in the system after step (1b) activation, is reacted under room temperature condition
10～20h；
(1d) system that step (1c) is obtained is transferred in bag filter, is placed in deionized water and dialyses 3～7 days；
(1e) the purification solution freeze-drying after step (1d) dialysis is obtained epsilon-polylysine-para hydroxybenzene propionic acid copolymer；
(2) using PBS as solvent, A stostes and B stostes are prepared at normal temperatures respectively：
A stostes solute is epsilon-polylysine-para hydroxybenzene propionic acid copolymer and horseradish peroxidase；
B stostes solute is epsilon-polylysine-para hydroxybenzene propionic acid copolymer and hydrogen peroxide；
(3) the A stostes and B stostes for obtaining step (2) is separately added in the AB pipes of dual-head injector, and slow release obtains uniformly
Transparent epsilon-polylysine-para hydroxybenzene propionic acid anti-bacterial hydrogel dressing.
2. the preparation method of epsilon-polylysine according to claim 1-para hydroxybenzene propionic acid anti-bacterial hydrogel dressing, its are special
Levy and be, in step (1a), described organic solvent is DMF, dimethyl sulfoxide (DMSO) or ethyl acetate, organic
The volume ratio of solvent and deionized water is 1：1～5.
3. the preparation method of epsilon-polylysine according to claim 1-para hydroxybenzene propionic acid anti-bacterial hydrogel dressing, its are special
Levy and be, in step (1a), the consumption of para hydroxybenzene propionic acid is 1g/100mL blend solvents.
4. the preparation method of epsilon-polylysine according to claim 1-para hydroxybenzene propionic acid anti-bacterial hydrogel dressing, its are special
Levy and be, in step (1b), 1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides and N-hydroxy-succinamide
Mol ratio is 3.5～1:1；1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides and para hydroxybenzene propionic acid mole
Than for 5～1:1.
5. the preparation method of epsilon-polylysine according to claim 1-para hydroxybenzene propionic acid anti-bacterial hydrogel dressing, its are special
Levy and be, in step (1c), described epsilon-polylysine is prepared by microbe fermentation method；Molecular weight is 2000～5500 roads
Er Dun.
6. the preparation method of epsilon-polylysine according to claim 1-para hydroxybenzene propionic acid anti-bacterial hydrogel dressing, its are special
Levy and be, in step (1c), the amino in epsilon-polylysine is 1 with the mol ratio of para hydroxybenzene propionic acid:1～5.
7. the preparation method of epsilon-polylysine according to claim 1-para hydroxybenzene propionic acid anti-bacterial hydrogel dressing, its are special
Levy and be, in step (2), described PBS is the PBS of 0.01～0.05mol/L.
8. the preparation method of epsilon-polylysine according to claim 1-para hydroxybenzene propionic acid anti-bacterial hydrogel dressing, its are special
Levy and be, in step (2), in A stostes, the concentration of solute epsilon-polylysine-para hydroxybenzene propionic acid copolymer is 4～20wt%；
The concentration of solute horseradish peroxidase is 0.02～0.1mg/mL；In B stostes, solute epsilon-polylysine-para hydroxybenzene propionic acid
The concentration of copolymer is 4～20wt%；Solute concentration of hydrogen peroxide is 0.04～0.12wt%.
9. the preparation method of epsilon-polylysine according to claim 1-para hydroxybenzene propionic acid anti-bacterial hydrogel dressing, its are special
Levy and be, in step (3), A stostes and B stostes equal-volume release mixing.
10. the epsilon-polylysine that any one preparation method is prepared in claim 1～9-para hydroxybenzene propionic acid antibacterial water
Gel dressing.
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