CN107496975B - Polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing with photoresponsive antibacterial function and preparation method thereof - Google Patents
Polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing with photoresponsive antibacterial function and preparation method thereof Download PDFInfo
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- 239000003814 drug Substances 0.000 title claims abstract description 46
- 229940079593 drug Drugs 0.000 title claims abstract description 45
- 239000004372 Polyvinyl alcohol Substances 0.000 title claims abstract description 40
- 229920002451 polyvinyl alcohol Polymers 0.000 title claims abstract description 40
- 239000000017 hydrogel Substances 0.000 title claims abstract description 38
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 235000010413 sodium alginate Nutrition 0.000 title claims abstract description 32
- 239000000661 sodium alginate Substances 0.000 title claims abstract description 32
- 229940005550 sodium alginate Drugs 0.000 title claims abstract description 32
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 239000000243 solution Substances 0.000 claims abstract description 42
- 230000003115 biocidal effect Effects 0.000 claims abstract description 12
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 claims abstract description 8
- 229960003376 levofloxacin Drugs 0.000 claims abstract description 8
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 7
- 239000011259 mixed solution Substances 0.000 claims abstract description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 7
- 238000010257 thawing Methods 0.000 claims abstract description 6
- 238000007710 freezing Methods 0.000 claims abstract description 5
- 230000008014 freezing Effects 0.000 claims abstract description 5
- 125000003277 amino group Chemical group 0.000 claims abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 45
- 238000006243 chemical reaction Methods 0.000 claims description 20
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 10
- 238000000502 dialysis Methods 0.000 claims description 10
- ZJSQZQMVXKZAGW-UHFFFAOYSA-N 2H-benzotriazol-4-ol hydrate Chemical compound O.OC1=CC=CC2=C1N=NN2 ZJSQZQMVXKZAGW-UHFFFAOYSA-N 0.000 claims description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 8
- 239000008367 deionised water Substances 0.000 claims description 8
- 229910021641 deionized water Inorganic materials 0.000 claims description 8
- 238000004108 freeze drying Methods 0.000 claims description 8
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 239000007822 coupling agent Substances 0.000 claims description 7
- 125000006502 nitrobenzyl group Chemical group 0.000 claims description 7
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 238000004090 dissolution Methods 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 239000012535 impurity Substances 0.000 claims description 4
- 230000001376 precipitating effect Effects 0.000 claims description 4
- 238000001132 ultrasonic dispersion Methods 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- DUIJUTBRRZCWRD-UHFFFAOYSA-N 4-[4-(1-hydroxyethyl)-2-methoxy-5-nitrophenoxy]butanoic acid Chemical compound COC1=CC(C(C)O)=C([N+]([O-])=O)C=C1OCCCC(O)=O DUIJUTBRRZCWRD-UHFFFAOYSA-N 0.000 claims description 2
- 230000003213 activating effect Effects 0.000 claims description 2
- -1 benzotriazole-N, N, N ', N' -tetramethyluronium Hexafluorophosphate Chemical compound 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 229920002521 macromolecule Polymers 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 208000027418 Wounds and injury Diseases 0.000 abstract description 18
- 206010052428 Wound Diseases 0.000 abstract description 17
- 239000003242 anti bacterial agent Substances 0.000 abstract description 10
- 229940088710 antibiotic agent Drugs 0.000 abstract description 10
- 239000002994 raw material Substances 0.000 abstract description 2
- 230000004044 response Effects 0.000 abstract 1
- 230000004043 responsiveness Effects 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 230000037314 wound repair Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- PYLFOUFNUBQBGP-UHFFFAOYSA-N 3-hydroxy-4-methoxy-5-nitrobenzaldehyde Chemical compound COC1=C(O)C=C(C=O)C=C1[N+]([O-])=O PYLFOUFNUBQBGP-UHFFFAOYSA-N 0.000 description 2
- 206010048038 Wound infection Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 229940124350 antibacterial drug Drugs 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 235000010407 ammonium alginate Nutrition 0.000 description 1
- 239000000728 ammonium alginate Substances 0.000 description 1
- KPGABFJTMYCRHJ-YZOKENDUSA-N ammonium alginate Chemical compound [NH4+].[NH4+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O KPGABFJTMYCRHJ-YZOKENDUSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
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- A—HUMAN NECESSITIES
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/0066—Medicaments; Biocides
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0042—Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0052—Mixtures of macromolecular compounds
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
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- A61L26/008—Hydrogels or hydrocolloids
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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Abstract
The invention relates to a polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing with photoresponse and antibiosis and a preparation method thereof. The preparation method comprises the following steps: grafting the small-molecular antibiotic levofloxacin onto a polyethylene glycol macromolecular chain with double amino groups through molecules with ultraviolet response characteristics to obtain an ultraviolet-cleavable macromolecular drug; and repeatedly freezing and thawing a mixed solution of the polyvinyl alcohol solution, the sodium alginate solution and the ultraviolet-light breakable macromolecular drug to obtain the polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing with photoresponse and antibiosis. The raw materials of the invention have good biocompatibility, and the obtained hydrogel dressing has certain mechanical property and antibacterial property of ultraviolet responsiveness, namely, the hydrogel dressing can control and release antibiotics under the irradiation of 365nm ultraviolet light, and is suitable for the protection and treatment of wound surfaces.
Description
Technical Field
The invention relates to a hydrogel dressing and a preparation method thereof, in particular to a polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing with photoresponse and antibiosis and a preparation method thereof.
Background
The skin, the largest organ of the human body, is susceptible to various injuries due to long-term exposure to a large area. Wound repair is a complex and dynamic process involving the combined action of various cells, factors, etc. The development of the wound dressing improves the process of wound repair, and the ideal wound dressing not only can be used as a physical barrier of the wound to avoid the wound from further damage and pollution, but also can provide a moist environment for the wound to accelerate the wound healing. The commonly used dressings are mainly of hydrogel type, foam type, film type and hydrogel type, wherein the hydrogel type dressings have been rapidly developed in recent years because of their unique excellent properties. However, wound repair is very susceptible to various factors, especially infection, and at present, wound infection becomes the most common complication in the wound repair process, and even death can be caused seriously. For the treatment of wound infections, antibacterial wound dressings have been developed, with antibiotic-loaded wound dressings being the most common. In the traditional antibacterial wound dressing, antibiotics mainly act on a wound surface in a free diffusion mode, so that the using amount of the antibiotics is difficult to control, and meanwhile, in order to achieve effective antibacterial concentration, the using amount of the antibiotics is often required to be increased. Therefore, how to design the antibacterial wound dressing enables the antibacterial wound dressing to release antibiotics when the wound surface is infected, and not release antibiotics when the wound surface is not infected, so that the controlled release of the antibiotics according to needs is realized, side effects caused by the large-scale use of the antibiotics are avoided, and the antibacterial wound dressing becomes a development target of the antibacterial wound dressing.
Disclosure of Invention
The invention aims to provide a polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing with photoresponse and antibacterial properties and a preparation method thereof.
The invention relates to a polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing with photoresponse and antibiosis, wherein macromolecular drugs which can be broken by ultraviolet light are distributed inside the hydrogel dressing; the hydrogel dressing is prepared by repeatedly freezing and thawing a mixed solution of a polyvinyl alcohol solution, a sodium alginate solution and an ultraviolet-light-breakable macromolecular drug, and specifically, the mixed solution is frozen at-20 ℃ for 20h, thawed at 25 ℃ for 4h, and repeated for three times.
The molecular weight of the polyvinyl alcohol solution is 72000g/mol, the concentration is 10% (W/V), the concentration of sodium alginate is 1.5% (W/V), and the mixing ratio of the polyvinyl alcohol and the sodium alginate is 3:1 (V/V);
the ultraviolet light-cleavable macromolecular drug is distributed in the hydrogel, and the concentration of the ultraviolet light-cleavable macromolecular drug is 5 mg/ml.
The preparation method of the ultraviolet light cleavable macromolecular drug comprises the following steps:
the first step is as follows: taking a certain amount of photolabile nitrobenzyl coupling agent into a flask, adding a certain volume of methyl pyrrolidone for ultrasonic dispersion and dissolution, introducing nitrogen for purification for 10min, adding a certain amount of condensing agent benzotriazole-N, N, N ', N' -tetramethyluronium Hexafluorophosphate (HBTU), hydroxybenzotriazole monohydrate (HOBT) and N, N-Diisopropylethylamine (DIEA) for ultrasonic dispersion and dissolution, dissolving a certain amount of amino-terminated polyethylene glycol into the methyl pyrrolidone, dropwise adding the solution, reacting at room temperature in a dark place for overnight;
the second step is that: after the reaction is finished, precipitating the reaction solution by using ethyl acetate, centrifuging, washing a precipitated product by using ethyl acetate again, centrifuging twice, drying the obtained centrifugal product in vacuum, dissolving the centrifugal product in deionized water again, centrifuging to remove undissolved impurities, dialyzing for three days by using a dialysis bag with the molecular weight cutoff of 1000, and freeze-drying to obtain a product;
dissolving a certain amount of antibiotic levofloxacin into anhydrous DMSO, adding a certain amount of condensing agent N, N' -Dicyclohexylcarbodiimide (DCC) and catalyst Dimethylaminopyridine (DMAP) into the anhydrous DMSO, activating the mixture at room temperature for 2 hours, dissolving a certain amount of product obtained in the second step into the anhydrous DMSO, dropwise adding the product into the activated solution, and reacting the solution in a dark place;
the fourth step: after the reaction is finished, the reaction solution is dialyzed for one day by a dialysis bag DMSO with the molecular weight cutoff of 1000, then deionized water is changed for dialysis for 2 days, and the macromolecular drug which can be broken by ultraviolet light is obtained by freeze-drying.
The nitrobenzyl coupling agent in the first step is 4- [4- (1-hydroxyethyl) -2-methoxy-5-nitrophenoxy ] butanoic acid.
The molecular weight of the polyethylene glycol with double amino groups in the first step is 5000.
In the first step, a nitrobenzyl coupling agent: HBTU: HOBT: DIEA: amino-terminated polyethylene glycol ═ 1: 1.08: 1.08: 1.97: 0.1 (molar ratio).
DCC in the third step: DMAP: antibiotic levofloxacin: the second product 25: 25: 5: 1 (molar ratio).
The reaction time in the third step was 48 h.
According to the ultraviolet-light-responsive antibacterial drug-loaded polyvinyl alcohol/sodium alginate hydrogel dressing, polyvinyl alcohol/sodium alginate is repeatedly frozen and thawed and is crosslinked into gel through hydrogen bonds, and antibiotic levofloxacin is grafted onto a macromolecular chain of polyvinyl alcohol through a photolabile nitrobenzyl coupling agent to obtain an ultraviolet-light-breakable macromolecular drug which is distributed inside polyvinyl alcohol/ammonium alginate hydrogel. Under the irradiation of ultraviolet light, the antibiotic is broken from the macromolecular medicine and is diffused out from the hydrogel to act on bacteria, thereby playing an antibacterial role.
The raw materials used in the ultraviolet-responsive antibacterial drug-loaded polyvinyl alcohol/sodium alginate hydrogel dressing have good biocompatibility, the obtained hydrogel dressing has certain mechanical property and ultraviolet-responsive antibacterial property, and can control the release of antibiotics, so that the side effect caused by the large-scale use of the antibiotics is avoided, and the dressing is suitable for the protection and treatment of wound surfaces.
Drawings
FIG. 1 is a schematic diagram of an antibacterial mechanism of a photo-responsive antibacterial polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing;
FIG. 2 is a scheme for the synthesis of UV-cleavable macromolecular drugs;
FIG. 3 is a macro (a) and micro (b) structural view of the photo-responsive antibacterial polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing in example 2;
FIG. 4 is a graph showing the biocompatibility analysis of the photo-responsive antibacterial polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing in example 2;
fig. 5 is a graph (a) and data (b) of the in vitro uv-responsive antibacterial effect of the photo-responsive antibacterial polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing in example 1.
Detailed Description
The present invention will be described in detail with reference to examples.
Example 1
a) Ultraviolet light cleavable macromolecular drug synthesis
Dissolving 0.3g (1mmol) of HMNB in 4ml of methyl pyrrolidone, ultrasonic heating to dissolve completely, introducing N2Purifying for 10min, adding 0.41g (1.08mmol) HBTU, 0.146g (1.08mmol) HOBT, 0.25g (1.97mmol) DIEA, ultrasonic dispersing, dissolving and stirring for 5min, and collecting 0.5g (0.1mmol) NH2-PEG5000-NH2Dissolved in 4ml of methyl pyrrolidone and added dropwise to the above solution, and the mixed solution was immediately vortexed and heated until all the reagents were dissolved. The reaction was left to stand at room temperature overnight in the dark. After the reaction is finished, precipitating the reaction solution by using ethyl glacial ether (slowly adding the reaction solution into 10 times of the volume of the ethyl glacial ether), centrifuging, washing a precipitated product by using ethyl glacial ether again, centrifuging twice, drying the obtained centrifugal product in vacuum, dissolving the dried centrifugal product in deionized water again, centrifuging to remove undissolved impurities, dialyzing for three days by using a dialysis bag with the molecular weight cutoff of 1000, and freeze-drying to obtain the product.
100mg of levofloxacin is dissolved in 10ml of anhydrous DMSO, then 0.28g of DCC and 0.16g of DMAP are added for activation for 2h at 25 ℃, then 150mg of the product obtained in the previous step is dissolved in 5ml of anhydrous DMSO, and the activated solution is added dropwise and reacted for 48h in a dark place. After the reaction is finished. And dialyzing the reaction solution for one day by using a dialysis bag DMSO with the molecular weight cutoff of 1000, then dialyzing for 2 days by changing deionized water, and freeze-drying to obtain the ultraviolet-cleavable macromolecular drug.
b) Preparation of photo-responsive antibacterial polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing
10% (w/v) PVA (Mn 72000g/mol) solution, 1.5% (w/v) SA (national drug group) solution, PVA and SA were mixed at a volume ratio of 3:1, and the mixture was sonicated and stirred to form a uniform solution. Mixing ultraviolet-cleavable macromolecular drug with PVA/SA at a concentration of 5mg/ml to obtain a uniform solution, injecting the solution into a 96-well plate, injecting 100ul of the solution into each well, freezing at-20 ℃ for 20h, thawing at room temperature of 25 ℃ for 4h, and repeating the steps for three times to prepare the gel with certain mechanical properties.
Example 2
a) Synthesis of ultraviolet-cleavable macromolecular drug 0.3g (1mmol) of HMNB was dissolved in 4ml of methylpyrrolidone and sufficiently dissolved by ultrasonic heating, and N was introduced2Purifying for 10min, adding 0.41g (1.08mmol) HBTU, 0.146g (1.08mmol) HOBT, 0.25g (1.97mmol) DIEA, ultrasonic dispersing, dissolving and stirring for 5min, and collecting 0.5g (0.1mmol) NH2-PEG5000-NH2Dissolved in 4ml of methyl pyrrolidone and added dropwise to the above solution, and the mixed solution was immediately vortexed and heated until all the reagents were dissolved. The reaction was left to stand at room temperature overnight in the dark. After the reaction is finished, precipitating the reaction solution by using ethyl glacial ether (slowly adding the reaction solution into 10 times of the volume of the ethyl glacial ether), centrifuging, washing a precipitated product by using ethyl glacial ether again, centrifuging twice, drying the obtained centrifugal product in vacuum, dissolving the dried centrifugal product in deionized water again, centrifuging to remove undissolved impurities, dialyzing for three days by using a dialysis bag with the molecular weight cutoff of 1000, and freeze-drying to obtain the product.
100mg of levofloxacin is dissolved in 10ml of anhydrous DMSO, then 0.28g of DCC and 0.16g of DMAP are added for activation for 2h at 25 ℃, then 150mg of the product obtained in the previous step is dissolved in 5ml of anhydrous DMSO, and the activated solution is added dropwise and reacted for 48h in a dark place. After the reaction is finished. And dialyzing the reaction solution for one day by using a dialysis bag DMSO with the molecular weight cutoff of 1000, then dialyzing for 2 days by changing deionized water, and freeze-drying to obtain the ultraviolet-cleavable macromolecular drug.
b) Preparation of photo-responsive antibacterial polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing
10% (w/v) PVA (Mn 72000g/mol) solution, 1.5% (w/v) SA (national drug group) solution, PVA and SA were mixed at a volume ratio of 3:1, and the mixture was sonicated and stirred to form a uniform solution. Mixing ultraviolet-cleavable macromolecular drug with PVA/SA at a concentration of 5mg/ml to obtain a uniform solution, injecting the solution into a 6-hole plate, injecting 500ul of the solution into each hole, freezing at-20 ℃ for 20h, thawing at room temperature of 25 ℃ for 4h, and repeating the steps for three times to prepare the gel with certain mechanical properties.
Claims (9)
1. A polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing with photoresponse and antibacterial properties is characterized in that the hydrogel dressing is prepared from a mixed solution of a polyvinyl alcohol solution, a sodium alginate solution and an ultraviolet-light-breakable macromolecular drug by a repeated freeze thawing method; the ultraviolet-cleavable macromolecular drug is distributed inside the hydrogel dressing; the ultraviolet-cleavable macromolecular drug is prepared by the following method, and the preparation method comprises the following steps:
the first step is as follows: adding a photolabile nitrobenzyl coupling agent into a small flask, adding methyl pyrrolidone for ultrasonic dispersion and dissolution, introducing nitrogen for purification for 10min, adding condensing agents benzotriazole-N, N, N ', N' -tetramethyluronium Hexafluorophosphate (HBTU), hydroxybenzotriazole monohydrate (HOBT) and N, N-Diisopropylethylamine (DIEA) for ultrasonic dispersion and dissolution, dissolving polyethylene glycol with double amino groups into the methyl pyrrolidone, dropwise adding the solution, and reacting at room temperature in a dark place overnight;
the second step is that: after the reaction is finished, precipitating the reaction solution by using ethyl acetate, centrifuging, washing a precipitated product by using ethyl acetate again, centrifuging twice, drying the obtained centrifugal product in vacuum, dissolving the centrifugal product in deionized water again, centrifuging to remove undissolved impurities, dialyzing for three days by using a dialysis bag with the molecular weight cutoff of 1000, and freeze-drying to obtain a product;
dissolving antibiotic levofloxacin into anhydrous DMSO, adding a condensing agent N, N' -Dicyclohexylcarbodiimide (DCC) and a catalyst Dimethylaminopyridine (DMAP) into the anhydrous DMSO, activating the mixture at room temperature for 2 hours, dissolving the product obtained in the second step into the anhydrous DMSO, dropwise adding the activated solution into the anhydrous DMSO, and reacting the mixture in a dark place;
the fourth step: after the reaction is finished, the reaction solution is dialyzed for one day by a dialysis bag DMSO with the molecular weight cutoff of 1000, then deionized water is changed for dialysis for 2 days, and the macromolecular drug which can be broken by ultraviolet light is obtained by freeze-drying.
2. The polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing with photoresponsive and antibacterial effects as claimed in claim 1, wherein the polyvinyl alcohol solution used has a molecular weight of 72000g/mol and a concentration of 10% (W/V), the sodium alginate solution used has a concentration of 1.5% (W/V), and the polyvinyl alcohol solution and the sodium alginate solution are mixed in a ratio of 3:1 (V/V).
3. The polyvinyl alcohol sodium alginate drug-loaded hydrogel dressing with the photoresponsive and antibacterial effects as claimed in claim 1, wherein the repeated freeze-thaw method comprises the following steps: freezing at-20 deg.C for 20 hr, thawing at 25 deg.C for 4 hr, and repeating three times.
4. The polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing with the photo-responsive antibacterial function as claimed in claim 1, wherein the concentration of the ultraviolet light-cleavable macromolecule drug in the mixed solution is 5 mg/ml.
5. The polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing having a photoresponsive property and an antibacterial property as claimed in claim 1, wherein the nitrobenzyl coupling agent used in the first step is |4- [4- (1-hydroxyethyl) -2-methoxy-5-nitrophenoxy ] butyric acid.
6. The polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing having the photoresponsive antibacterial property as claimed in claim 1, wherein the amino group-terminated polyethylene glycol used in the first step has a molecular weight of 5000.
7. The polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing with photoresponsive and antibacterial effects as claimed in claim 1, wherein the nitrobenzyl coupling agent used in the first step: HBTU: HOBT: DIEA: amino-terminated polyethylene glycol ═ 1: 1.08: 1.08: 1.97: 0.1 (molar ratio).
8. The polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing having a photoresponsive antibacterial property according to claim 1, wherein the DCC: DMAP: antibiotic levofloxacin: the second product 25: 25: 5: 1 (molar ratio).
9. The polyvinyl alcohol/sodium alginate drug-loaded hydrogel dressing with photoresponsive and antibacterial effects as claimed in claim 1, wherein the light-shielding reaction time in the third step is 48 hours.
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| CN111748108A (en) * | 2020-07-06 | 2020-10-09 | 内蒙古大学 | Preparation method of recyclable N-halamine hydrogel capable of selectively sterilizing |
| CN112321850B (en) * | 2020-10-12 | 2022-06-14 | 浙江工业大学 | Hydrogel bait and preparation method thereof |
| CN113018505B (en) * | 2021-03-17 | 2022-06-10 | 广西医科大学 | Preparation method of sodium alginate nano-silver antibacterial hydrogel dressing |
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