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CN109758618A - A kind of antibacterial hydrogel with controllable release of nano silver ions and preparation method thereof - Google Patents

A kind of antibacterial hydrogel with controllable release of nano silver ions and preparation method thereof Download PDF

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Publication number
CN109758618A
CN109758618A CN201811531940.8A CN201811531940A CN109758618A CN 109758618 A CN109758618 A CN 109758618A CN 201811531940 A CN201811531940 A CN 201811531940A CN 109758618 A CN109758618 A CN 109758618A
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preparation
nano silver
nano
silver particles
solution
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Inventor
肖文谦
李克江
曲晓航
刘爽
李波
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Chongqing University of Science and Technology
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Chongqing University of Science and Technology
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Priority to CN201811531940.8A priority Critical patent/CN109758618A/en
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Abstract

The present invention provides a kind of anti-bacterial hydrogels and preparation method thereof of controllable nano silver particles release, the preparation method includes the following steps: that the silver-colored microballoon of modified Nano load, modified gelatin solution 1) are mixed to form pre-polymer solution, photoinitiator is added into pre-polymer solution, and is uniformly mixed;2) it takes step 1) acquired solution in mold, photo-crosslinking plastic is carried out under ultraviolet source, obtains anti-bacterial hydrogel.The hydrogel of prepared achievable nano silver particles controlled release can effectively improve nano silver particles to histiocytic toxic effect, long acting antibiotic, bacteria resistance function be realized, so that promotion group casts off reparation and regeneration.

Description

A kind of anti-bacterial hydrogel and preparation method thereof of nano-silver ionic controllability release
Technical field
The invention belongs to biomedical engineering composite biological material fields, and in particular to a kind of nano-silver ionic controllability is released Anti-bacterial hydrogel put and preparation method thereof.
Background technique
Currently, some physicochemical properties are superior, the preferable biomaterial of biocompatibility is widely used in clinical medicine, and make The main reason for about biomaterial develops is the infection (BCI) centered on biomaterial, the infection centered on biomaterial (BCI) it is serious problems clinically adjoint using biomaterial, operative failure is resulted even in, to the therapeutic effect structure of patient At significant impact.Bacterium in the sticking of biomaterial surface, breed and form the main reason for bacterial biof iotalm is BCI.
Due to the bacterium in biomembrane morphosis, physicochemical property, Antibiotic Sensitivity and in terms of with Commonly the bacterium of planktonic growth has dramatically different, and existing medical technology becomes extremely difficult to the treatment of BCI, often finally must not Do not take out implantation material.
The appearance of antibacterial biological material, it is more likely that solve the problems, such as this, ideal antibacterial biological material should have efficiently, It is long-acting, wide spectrum, non-toxic and safe, the conditions such as nonirritant.It has recently been demonstrated that nano silver particles to Escherichia coli, gonococcus, The tens of kinds of pathogenic microorganisms such as chlamydia trachomatis have strong inhibition and killing effect, and have strong bactericidal, permeability By force, many advantages such as promotion tissue repair regenerates, antibacterial is lasting, has no drug resistance, therefore nano silver particles are introduced into biomaterial Implant realizes the extensive attention and concern of antibacterial or bacteriostasis to implant site by researcher.
Traditional method is mostly by nano silver particles and implant direct combination, to assign the function that implant has antibacterial Energy.By taking hydrogel material as an example, after nano-silver ionic and hydrogel material direct combination, nano silver particles and tissue or cell There are reciprocations, but when the concentration of nano silver particles is more than a certain range, can generate certain toxicity to cell and tissue, By penetrating or being deposited on cell wall, it will affect the transport of electrolyte and metabolin, cause the interaction with memebrane protein, swash Signal path living, inhibits cell Proliferation and contraction.Be mainly shown as: cell adheres to paramophia, cell membrane fluidity declines, thin After birth integrality is destroyed.And the concentration of influence and nano silver particles of the nano silver particles to cell this several respect is at non-linear Relationship.At the same time, since the hole of hydrogel belongs to micron or sub-micron rank more, Nano silver grain readily penetrates through this some holes And the outside of timbering material is quickly escaped into, cause implantation material to can not achieve long-term antibacterial or antibacterial effect.
Therefore, how to realize that long-term slow release of the nano silver particles in implant is to realize that tissue is successfully repaired and again The technique direction that the key and this field built need constant quest to study.
Summary of the invention
In view of this, it is an object of that present invention to provide the anti-bacterial hydrogels and its system of a kind of release of nano-silver ionic controllability Preparation Method.
The specific technical proposal is:
1, a kind of preparation method of the anti-bacterial hydrogel of controllable nano silver particles release, includes the following steps:
1) the silver-colored microballoon of modified Nano load, modified gelatin solution are mixed to form pre-polymer solution, added into pre-polymer solution Enter photoinitiator, and is uniformly mixed;
2) it takes step 1) acquired solution in mold, photo-crosslinking plastic is carried out under ultraviolet source, obtains anti-bacterial hydrogel.
Further, the modified Nano carries the method preparation as described below of silver-colored microballoon:
1) preparation of nano silver-carrying microballoon:
S1. the beaker that volume is 200ml is placed on magnetic stirring apparatus, takes 75ml deionized water, 0.75ml ammonium hydroxide, 15ml Ethyl alcohol is placed in a beaker uniformly mixed, and 0.24g cetyl trimethylammonium bromide is then added and stirs to being completely dissolved;
S2. under stirring condition, the mixed solution of 1.5ml ethyl orthosilicate and 30ml ethyl alcohol is equal with 0.1g silver nitrate simultaneously Even to be slowly added in step 1) acquired solution, room temperature sealing reaction 24 hours, revolving speed was 360rmp during sealing reaction, will be reacted Solution is successively filtered afterwards, washes to obtain solid;
S3. solid sample is mixed with secondary water by mass volume ratio (g/ml) 1:500 again, is then standing and soaking 48 Hour, it filters again, washes to obtain solid sample;
S4. sample obtained by S3 is put into 60 DEG C of drying boxes to be dried, thoroughly takes out and is put into Muffle furnace by pre- after drying If temperature is sintered, muffle furnace program setting are as follows: the temperature rising stage is 110 DEG C/h, constant temperature after temperature rises to 550 DEG C 5 hours, setting decrease speed was 150 DEG C/h, takes out sample after muffle furnace drops to room temperature, nano silver-carrying can be obtained Microballoon;
2) modified Nano carries the preparation of silver-colored microballoon:
Take nano silver-carrying microballoon obtained by 0.04g step 1) and 10ml methanol, 3- (trimethoxy silane) propyl third of 1.2ml Diluted acid at the uniform velocity stirs 5 hours at room temperature, and gained sample with methanol eccentric cleaning 3 times, wash rear sample and be placed in ventilation certainly by collection So silver-colored microballoon is carried up to modified Nano after drying.
Further, the step 1) modified Nano carries silver-colored microballoon, the mass ratio of modified gelatin solution is 1:20-240, described The quality volume fraction of modified gelatin solution is 5%-10%.
Further, the step 1) photoinitiator is -4 ˊ of 2- hydroxyl-(2- hydroxy ethoxy) -2- methyl phenyl ketone, added light The mass volume ratio (g/ml) of initiator and pre-polymer solution is 0.5%-1.5%.
Further, the step 2) mold is diameter 0.8cm, the cylinder type of height 0.3cm.
Further, step 2) the ultraviolet source wavelength: 320-480nm, ultraviolet point light source power: 7.0mW/cm2, light Crosslinking time is 30 seconds.
2, according to the anti-bacterial hydrogel of the controllable nano silver particles release of the method preparation.
The beneficial effects of the present invention are: the present invention is realized using silane coupling agent to mesoporous silicon dioxide nano microballoon It is modified, while realizing the loading to nano silver particles, by the regulation to nanosphere surface porosity factor realize silver ion can Controlled release is put, then is copolymerized with the gelatin prepolymer of methacrylic acid anhydride modification by ultraviolet light cross-linking, and preparing one kind can be achieved to receive Microballoon/gelatin internet system hydrogel of rice silver particles controlled release, is effectively improved nano silver particles to histocyte Toxic effect, realize long acting antibiotic, bacteria resistance function, so that promotion group casts off reparation and regeneration.
Detailed description of the invention
The anti-bacterial hydrogel of gained nano-silver ionic controllability release when Fig. 1 is modified microballoon and gelatin mass ratio is 1:80 Electron microscope;
Fig. 2 is the anticolibacillary right of anti-bacterial hydrogel and the pure gelatin hydrogel of nano-silver ionic controllability release Compare experimental result.
Fig. 3 is that the continuous 5 days anticolibacillary long acting antibiotics of anti-bacterial hydrogel of nano-silver ionic controllability release are real Test result.
Specific embodiment
More detailed elaboration is carried out to the present invention below in conjunction with the accompanying drawings and the specific embodiments.
The preparation of modified gelatin:
Modified gelatin used in following embodiment is the gelatin being modified using methacrylic anhydride, specific steps Are as follows:
S1. the type A gelatin for weighing 5g from pigskin is dissolved in 50mL PBS, is at the uniform velocity stirred with magnetic stirring apparatus heating It mixes, after dissolution completely, is slowly dropped into the methacrylic acid anhydride solution of 5mL, be added dropwise to complete that continue stirring reaction at 50 DEG C 3 small When, it is eventually adding the dilution of 100mL PBS solution;
S2. the solution diluted is put into the bag filter that molecular cut off is 8000-12000D, is existed with deionized water It dialyses 7 days at 60 DEG C, replaces 5 deionized waters daily, by resulting gelatin solution freeze-drying process after the completion of dialysis, finally Obtain the modified gelatin with UV light sensitivity.
Modified Nano carries the preparation of silver-colored microballoon:
Used modified Nano carries silver-colored microballoon, and as described below prepared by method:
1) preparation of nano silver-carrying microballoon:
S1. the beaker that volume is 200ml is placed on magnetic stirring apparatus, takes 75ml deionized water, 0.75ml ammonium hydroxide, 15ml Ethyl alcohol is placed in a beaker uniformly mixed, and 0.24g cetyl trimethylammonium bromide is then added and stirs to being completely dissolved;
S2. under stirring condition, the mixed solution of 1.5ml ethyl orthosilicate and 30ml ethyl alcohol is equal with 0.1g silver nitrate simultaneously Even to be slowly added in step 1) acquired solution, room temperature sealing reaction 24 hours, revolving speed was 360rmp during sealing reaction, will be reacted Solution is successively filtered afterwards, washes to obtain solid;
S3. solid sample is mixed with secondary water by mass volume ratio (g/ml) 1:500 again, is then standing and soaking 48 Hour, it filters again, washes to obtain solid sample;
S4. sample obtained by S3 is put into 60 DEG C of drying boxes to be dried, thoroughly takes out and is put into Muffle furnace by pre- after drying If temperature is sintered, muffle furnace program setting are as follows: the temperature rising stage is 110 DEG C/h, constant temperature after temperature rises to 550 DEG C 5 hours, setting decrease speed was 150 DEG C/h, takes out sample after muffle furnace drops to room temperature, nano silver-carrying can be obtained Microballoon;
2) modified Nano carries the preparation of silver-colored microballoon:
Take nano silver-carrying microballoon obtained by 0.04g step 1) and 10ml methanol, 3- (trimethoxy silane) propyl third of 1.2ml Diluted acid at the uniform velocity stirs 5 hours at room temperature, and gained sample with methanol eccentric cleaning 3 times, wash rear sample and be placed in ventilation certainly by collection So silver-colored microballoon is carried up to modified Nano after drying.
Embodiment 1
A kind of preparation of the anti-bacterial hydrogel of nano-silver ionic controllability release:
1) by modified Nano carries silver-colored microballoon, mass fraction is 8% UV light sensitivity modified gelatin according to mass ratio 1: 40 are mixed to form pre-polymer solution, and -4 ˊ of photoinitiator 2- hydroxyl-(2- hydroxy ethoxy) -2- methyl is added into pre-polymer solution Propiophenone mixes, and the mass volume ratio (w/v) of photoinitiator and pre-polymer solution is 1%.
2) 1) it takes 150 μ l solution to be added dropwise in photo-crosslinking model after acquired solution to be blown and beaten to mixing repeatedly, is placed in ultraviolet light (outer radiant wavelength: 320-480nm, ultraviolet point light source power: 7.0mW/cm2) under be crosslinked 30 seconds after take out, obtain antibacterial water Gel.
Embodiment 2:
1) by modified Nano carries silver-colored microballoon, mass fraction is 8% UV light sensitivity modified gelatin according to mass ratio 1: 80 are mixed to form pre-polymer solution, and -4 ˊ of photoinitiator 2- hydroxyl-(2- hydroxy ethoxy) -2- methyl is added into pre-polymer solution Propiophenone mixes, and the mass volume ratio (g/ml) of photoinitiator and pre-polymer solution is 1%.
2) 1) it takes 150 μ l solution to be added dropwise in photo-crosslinking model after acquired solution to be blown and beaten to mixing repeatedly, is placed in ultraviolet light (outer radiant wavelength: 320-480nm, ultraviolet point light source power: 7.0mW/cm2) under be crosslinked 30 seconds after take out, obtain antibacterial water Gel.
Embodiment 3:
1) by modified Nano carries silver-colored microballoon, mass fraction is 8% UV light sensitivity modified gelatin according to mass ratio 1: 160 are mixed to form pre-polymer solution, and -4 ˊ of photoinitiator 2- hydroxyl-(2- hydroxy ethoxy) -2- methyl is added into pre-polymer solution Propiophenone mixes, and the mass volume ratio (g/ml) of photoinitiator and pre-polymer solution is 1%.
2) 1) it takes 150 μ l solution to be added dropwise in photo-crosslinking model after acquired solution to be blown and beaten to mixing repeatedly, is placed in ultraviolet light (outer radiant wavelength: 320-480nm, ultraviolet point light source power: 7.0mW/cm2) under be crosslinked 30 seconds after take out, obtain antibacterial water Gel.
Embodiment 2 is modified to the antibacterial of gained nano-silver ionic controllability release when microballoon and gelatin mass ratio are 1:80 Hydrogel carries out electron-microscope scanning analysis, obtains electron microscope as shown in Figure 1.It will be seen from figure 1 that prepared anti-bacterial hydrogel In loose and porous structure, in 20-30 microns, modified nano silver-carrying microballoon is uniformly distributed therein in the aperture of gel.
2 gained sample of embodiment is placed on the uniformly culture medium of inoculation colibacillus, culture medium is put in 37 DEG C of insulating boxs Observation is taken out in culture 24 hours.Equally pure gelatin hydrogel is uniformly inoculated on the culture medium of colibacillus, culture medium is put in 37 DEG C insulating box culture 24 hours, take out observation, microscopic comparison as shown in Figure 2 is obtained, figure it is seen that passing through suppression Bacterium experiment, it was confirmed that nano-silver antibacterial hydrogel shows excellent inhibiting effect to Escherichia coli, and is not added with modified Nano The pure gelatin hydrogel for carrying silver-colored microballoon does not show any fungistatic effect then.
In order to further verify the Durability of antimicrobial effect effect for illustrating anti-bacterial hydrogel prepared by the present invention, further to implementation 2 gained samples are made 5 parts, and respectively uniformly on the culture medium of inoculation colibacillus, it is small that culture medium is put in 37 DEG C of insulating box cultures 24 When, 48 hours, 72 hours, 96 hours, 120 hours.Observation is taken out respectively, obtains electron microscope as shown in Figure 3, it can be anti-by Fig. 3 It should go out, after culture 5 days, which still shows the bacteriostasis to Escherichia coli, it was confirmed that the release of controllable nano silver particles Anti-bacterial hydrogel show long-acting antibacterial, antibacterial effect.
Antibacterial bacteriostatic effect verifying is carried out using above-mentioned same method to sample prepared by embodiment 1, embodiment 3, equally Show long-acting antibacterial, bacteriostasis.
Finally, it is stated that preferred embodiment above is only used to illustrate the technical scheme of the present invention and not to limit it, although logical It crosses above preferred embodiment the present invention is described in detail, however, those skilled in the art should understand that, can be Various changes are made to it in form and in details, without departing from claims of the present invention limited range.

Claims (7)

1. a kind of preparation method of the anti-bacterial hydrogel of controllable nano silver particles release, which comprises the steps of:
1) the silver-colored microballoon of modified Nano load, modified gelatin solution are mixed to form pre-polymer solution, light is added into pre-polymer solution Initiator, and be uniformly mixed;
2) it takes step 1) acquired solution in mold, photo-crosslinking plastic is carried out under ultraviolet source, obtains anti-bacterial hydrogel.
2. a kind of preparation method of the anti-bacterial hydrogel of controllable nano silver particles release, feature exist according to claim 1 In the modified Nano carries silver-colored microballoon, and as described below prepared by method:
1) preparation of nano silver-carrying microballoon:
S1. the beaker that volume is 200ml is placed on magnetic stirring apparatus, takes 75ml deionized water, 0.75ml ammonium hydroxide, 15ml ethyl alcohol It is placed in a beaker uniformly mixed, 0.24g cetyl trimethylammonium bromide is then added and stirs to being completely dissolved;
S2. under stirring condition, the mixed solution of 1.5ml ethyl orthosilicate and 30ml ethyl alcohol is uniformly delayed with 0.1g silver nitrate simultaneously Slow to be added in step 1) acquired solution, room temperature sealing reaction 24 hours, revolving speed was 360rmp during sealing reaction, will be molten after reaction Liquid is successively filtered, and solid is washed to obtain;
S3. solid sample is mixed with secondary water by mass volume ratio (g/ml) 1:500 again, and it is small to be then standing and soaking 48 When, it filters again, washes to obtain solid sample;
S4. sample obtained by S3 is put into 60 DEG C of drying boxes to be dried, thoroughly takes out and is put into Muffle furnace by default temperature after drying Degree is sintered, muffle furnace program setting are as follows: the temperature rising stage is 110 DEG C/h, and constant temperature 5 is small after temperature rises to 550 DEG C When, setting decrease speed is 150 DEG C/h, takes out sample after muffle furnace drops to room temperature, it is micro- that nano silver-carrying can be obtained Ball;
2) modified Nano carries the preparation of silver-colored microballoon:
Take nano silver-carrying microballoon obtained by 0.04g step 1) and 10ml methanol, 3- (trimethoxy silane) propyl acrylic acid of 1.2ml It at the uniform velocity stirs 5 hours at room temperature, with methanol eccentric cleaning 3 times, collection is washed rear sample and is placed in ventilation to be done gained sample naturally Silver-colored microballoon is carried after dry up to modified Nano.
3. a kind of preparation method of the anti-bacterial hydrogel of controllable nano silver particles release, feature exist according to claim 1 In the step 1) modified Nano carries silver-colored microballoon, the mass ratio of modified gelatin solution is 1:20-240, the modified gelatin solution Quality volume fraction be 5%-10%.
4. a kind of preparation method of the anti-bacterial hydrogel of controllable nano silver particles release, feature exist according to claim 1 In the step 1) photoinitiator is -4 ˊ of 2- hydroxyl-(2- hydroxy ethoxy) -2- methyl phenyl ketone, added photoinitiator and pre-polymerization The mass volume ratio (g/ml) of object solution is 0.5%-1.5%.
5. a kind of preparation method of the anti-bacterial hydrogel of controllable nano silver particles release, feature exist according to claim 1 In the step 2) mold is diameter 0.8cm, the cylinder type of height 0.3cm.
6. a kind of preparation method of the anti-bacterial hydrogel of controllable nano silver particles release, feature according to right right 1 exist In step 2) the ultraviolet source wavelength: 320-480nm, ultraviolet point light source power: 7.0mW/cm2, the photo-crosslinking time is 30 Second.
7. the anti-bacterial hydrogel of the controllable nano silver particles release of any one the method preparation according to claim 1~6.
CN201811531940.8A 2018-12-14 2018-12-14 A kind of antibacterial hydrogel with controllable release of nano silver ions and preparation method thereof Pending CN109758618A (en)

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CN110256856A (en) * 2019-07-01 2019-09-20 重庆科技学院 Sodium alginate is porous congeals glue and preparation method thereof for a kind of injectable gelatin-with shape memory
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CN114316307A (en) * 2021-12-31 2022-04-12 广东粤港澳大湾区国家纳米科技创新研究院 Modified hydrogel and preparation method and application thereof
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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110256856A (en) * 2019-07-01 2019-09-20 重庆科技学院 Sodium alginate is porous congeals glue and preparation method thereof for a kind of injectable gelatin-with shape memory
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CN114405486A (en) * 2021-11-17 2022-04-29 重庆科技学院 Preparation method of porous cryogel with antifouling, antibacterial and anti-dye adsorption functions
CN114316307A (en) * 2021-12-31 2022-04-12 广东粤港澳大湾区国家纳米科技创新研究院 Modified hydrogel and preparation method and application thereof
CN114316307B (en) * 2021-12-31 2023-10-27 广东粤港澳大湾区国家纳米科技创新研究院 Modified hydrogel and preparation method and application thereof

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Application publication date: 20190517