CN106693072A - Preparation method of infection response type guide tissue regeneration membrane - Google Patents
Preparation method of infection response type guide tissue regeneration membrane Download PDFInfo
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- CN106693072A CN106693072A CN201611265580.2A CN201611265580A CN106693072A CN 106693072 A CN106693072 A CN 106693072A CN 201611265580 A CN201611265580 A CN 201611265580A CN 106693072 A CN106693072 A CN 106693072A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/606—Coatings
Abstract
The invention discloses a preparation method of an infection response type guide tissue regeneration membrane. The guide tissue regeneration membrane material is a degradable polyester material and a natural degradable macromolecular material, and an antibacterial medicine with hydroxyl is chemically bound to the surface of the guide tissue regeneration membrane by using an ester bond. The method particularly comprises the following steps: introducing a large amount of hydroxyl into the surface of the membrane through dopamine coating; conducting reaction on a silicon oxygen bond on a silane coupling agent and the hydroxyl on the surface of the membrane so as to introduce amino into the surface of the membrane; conducting reaction on the antibacterial medicine with the hydroxyl and acryloyl chloride, and introducing the ester bond and carbon-carbon double bond into the medicine; performing Michael addition reaction on the carbon-carbon double bond and the amino on the surface of the membrane so as to graft the medicine to the surface of the fibrous membrane through the ester bond. The infection response type guide tissue regeneration membrane provided by the invention has excellent biocompatibility and capability of controllably releasing the antibacterial medicine according to the infection degree so as to fulfill the aim of effectively inhibiting infection.
Description
Technical field
The invention belongs to field of material surface modification, and in particular to a kind of infection response type discharges the guiding group of antibacterials
Knit the preparation method of regeneration membrane.
Background technology
Guide tissue regeneration (Guide Tissue Regeneration, GTR) technology is development at the beginning of the nineties at the end of the eighties
The new technology got up.Its principle is to be isolated damaged part with surrounding tissue using the physical barriers function of film, creates one
The organizational environment of individual relative closure, so that Gegenbaur's cell priority migration, growth.The application of GTR is treatment, the tooth kind of periodontosis
The reparation of growing area Bone mineral change and other Cranial defects, the healing of fracture provide a new effective way.
Although GTR technologies can obtain curative effect steady in a long-term, because operation neutralizes postoperative and secondary taking-up process
In, being incorporated into the infection of the initiations such as the anaerobic bacteria and aerobic bacteria of damage location will influence its neoblastic acquisition.It is right at present
Whole body system medication is mainly used in postoperative anti-infective going back, but utilization ratio of drug is relatively low, and easily cause gastrointestinal side effect.Office
Portion's drug release can strengthen therapeutic effect, reduce adverse reaction.
Blending drug-loading mode is often with burst drug release phenomenon, it is impossible to reach the purpose of medicament slow release, is carried using covalent bond
The mode of medicine can realize the sustained release of medicine, by the related chemical bond of the selective rhizotomies such as pH or enzyme, local targeting
Drug release can strengthen therapeutic effect, so as to reduce adverse reaction.
When generation is infected, substantial amounts of macrophage accumulation is had, the macrophage of aggregation can secrete substantial amounts of courage
Sterol esterase (cholesterol esterase, CE), and it is more to infect the CE amounts of more serious release, and CE to amido link and
There are ester bond selective enzymolysis to act on.Medicine is grafted to guiding film surface by ester bond, to what is produced in infection generating process
Enzyme has response.When generation is infected, ester bond is broken in the presence of enzyme, insoluble drug release；Gradient of infection is higher, and surrounding is assembled
Macrophage it is more, the content of the enzyme of release is higher, and the amount of the medicine of release is more.Using CE to the selective enzyme of ester bond
Solution, guide tissue regeneration film surface is fixed on by drug molecule by ester bond, it is possible to build infection response type release medicine
Guide tissue regeneration film.Overcome different morbidity's times and the different clinical difference of the order of severity so as to reach, be efficiently directed to
Property prevention suppress infection purpose.
Dopamine is widely used in material surface modifying.It is modified by dopamine for hydrophobic material, can be hydrophobic
Material surface introduces substantial amounts of functional group：Amino (- NH2) and hydroxyl (- OH), greatly improve the hydrophily of hydrophobic surface.
The content of the invention
1. it is a kind of to infect response type guide tissue regeneration film surface modifying method, it is characterized in that：With degradable aliphatic adoption
Ester and degradable natural macromolecule guide tissue regeneration film are matrix material, by a series of chemical modification methods by antibacterials
Film surface is grafted on ester bond, the Modified Membrane surface there is response medicine to release the esterase of infection physiological environment lower body secretion
The effect put.
Specific method is：Coated by dopamine, hydroxyl is introduced on film surface；By the silicon oxygen bond on silane coupler with
Film surface hydroxyl reacts, so as to introduce amino on film surface；Then hydroxyl antibacterials and acryloyl chloride are reacted, in medicine
Ester bond and carbon-carbon double bond are introduced on thing；The amino on carbon-carbon double bond and film surface is finally carried out into Michael addition reaction, so that real
Medicine is now grafted to tunica fibrosa surface by ester bond.
2. a series of chemical modification methods described in, it is characterised in that its concrete operation step is：
(1) guide tissue regeneration film is immersed in (dopamine hydrochloride in the dopamine solution of 0.05g/L-10g/L：Three
Hydroxymethyl aminomethane=5：3 (mol ratios), pH=5-10), after stirring reaction 6-48h, take the film out, soaking and washing is removed not
The dopamine solution of reaction.
(2) guide tissue regeneration film obtained in step (1) is immersed in the silane idol that concentration is 1.25g/L-5.0g/L
In connection agent solution, at a temperature of 25 DEG C -50 DEG C, stirring reaction 3h-72h, takes the film out under magnetic stirrer, embathes removal not
The silane coupler of reaction.
(3) antibacterials and acryloyl chloride are reacted, so as to introduce ester bond on metronidazole molecule.Course of reaction is as follows：
1. medicine metronidazole is weighed：Acryloyl chloride：Triethylamine=1:1:1 (mol ratio) and chloroform.2. diluted with chloroform
Acryloyl chloride, is transferred in constant pressure funnel；Metronidazole, triethylamine and the chloroform for weighing are transferred in container.3. N is led to2,
So that whole system is in N2Atmosphere in.4. container is placed in ice bath, it is 1 that volume ratio is added dropwise:15-1:20 acryloyl chlorides and three
The mixed solution of chloromethanes；After dripping off, 20min-30min is placed in ice bath, remove ice bath, normal-temperature reaction 12h.5. in container
2ml-5ml deionized water terminating reactions are added dropwise.6. the mixing liquid in container is transferred in separatory funnel, is extracted with dichloromethane
Take.7. toward extraction resulting solution in add enough anhydrous Nas2SO4To liquid clarification, 2-3h is stood；Resulting solution is at 30 DEG C -40 DEG C
Under the conditions of rotate, obtain needed for product.
(4) guide tissue regeneration film obtained in step (2) is immersed in methyl alcohol：Water (volume ratio)=4:1 system
In, weigh the product dissolving of gained in step (3) wherein, under conditions of 30 DEG C -50 DEG C, it is stirred continuously, react 6h-72h.Will
Film takes out, and embathes the product of gained in the unreacted step (3) of removal.
3. the guide tissue regeneration film described in, its thickness is 100-500 μm, with non-porous or have the structure in hole, aperture 1-
10 μm, its preparation method is included but is not limited to：Electrostatic spinning, melt casting and vacuum mold platen press.
4. the material for preparing is degradable aliphatic polyester, including：PLA, polycaprolactone, poly lactic-co-glycolic acid are common
Polymers, PLA-caprolactone copolymer, poly lactic-co-glycolic acid-caprolactone copolymer one of which are two or more mixed
Compound；Degradable natural macromolecular material includes：In NTx, gelatin, shitosan, starch, cellulose, elastin laminin one
Plant or two or more mixtures.
5. the antimicrobial described in, it is characterised in that contain hydroxyl (- OH) in structure, be soluble in organic solvent, and with suppression
Bacterium or bactericidal properties, including but not limited to：Metronidazole, erythromycin, Piperacillin, chloramphenicol etc..
6. the relevant enzyme described in, it is characterised in that the enzyme sensitive to ester group of infection physiological reaction lower body secretion, including
But it is not limited to：Cholesterol esterase and phospholipase A2 (PLA2).
7. the silane coupler described in, it is characterised in that contain amino (- NH in structure2) and alkoxy, including but do not limit
In：Gamma-aminopropyl-triethoxy-silane (KH550), 3- aminopropyl trimethoxysilanes (A-1110), N- β-(aminoethyl)-γ-
Aminopropyl trimethoxysilane etc. (A-1120).
Brief description of the drawings
Fig. 1 is electrostatic spinning polycaprolactone fiber film surface grafting metronidazole reactions steps schematic diagram.
Fig. 2 is the surface topography SEM figures of rear film before modified；Wherein left figure is guide tissue regeneration film before modified, right
Figure is modified guide tissue regeneration film.
Fig. 3 is the infrared spectrum that each step reaction obtains diaphragm.Wherein:A refers to polycaprolactone static spinning membrane；B represents process
The polycaprolactone static spinning membrane of dopamine cladding；C represented on the basis of b, is modified what is obtained by Silane coupling agent KH550
Polycaprolactone static spinning membrane；D is represented on the basis of c, is grafted to agent metronidazole (MNA) by Michael addition reaction
The diaphragm obtained on polycaprolactone static spinning membrane.
The FTIR curves of contrast a and b, b are in 1620cm-1Indole structure peak in many individual poly-dopamines in position, in 3000-
3500cm-1The absworption peak of hydroxyl (- OH) is significantly occurred in that at wave number, illustrates in dopamine solution after immersion, to be wrapped on fiber
It is covered with poly-dopamine shell.
Contrast b and c, in 3000-3500cm-1The absworption peak of hydroxyl (- OH) disappears at wave number.Because silane coupler
KH550 is by the hydroxyl (- OH) reactive grafting on the ethyoxyl on KH550 and poly-dopamine shell to polycaprolactone Nanowire
In dimension, so that the absworption peak of hydroxyl (- OH) disappears, Silane coupling agent KH550 in b grafting is illustrated.Meanwhile, and 1000-
1100cm-1It is the absworption peak of Si-O-Si keys at wave number, illustrates that KH550 has been grafted on polycaprolactone nanofiber.
Knowable to inspection information, the antisymmetric stretching vibration peak of aliphatic nitro compound nitro：1565-1530cm-1(s)；
Symmetrical stretching vibration peak：1380-1340cm-1(s), and c and d is contrasted, there is obvious difference, illustrate the upper agent metronidazole of grafting.
Fig. 4 is drug release patterns under different CE enzyme concentrations.With the raising of enzyme concentration, on drug release rate is obvious
Rise.
Specific embodiment
The present invention is further illustrated below by specific embodiment, but is not limited to following embodiment.Reading
After the content that the present invention is lectured, those skilled in the art can make various changes or modification to the present invention, as long as in the present invention
Spirit and principle within, change, modification of these equivalent form of values etc. should be included within the scope of the present invention.
Embodiment 1
(1) PCL nanofibers prepared by electrostatic spinning are cut into the disk of 2cm diameters, the dopamine of 1.0g/L is immersed in
(with dopamine hydrochloride in solution：Trishydroxymethylaminomethane=5：The dopamine solution that 3 (mol ratios) are prepared, solution ph
8.5), after the lower reaction 12h of stirring, spinning film to be taken out, the unreacted dopamine solution of removal is embathed.
(2) it is 5.0g/L's that polycaprolactone nanofiber prepared by the electrostatic spinning obtained in step (1) is immersed in concentration
In Silane coupling agent KH550 solution, under the conditions of 40 DEG C, 24h is reacted respectively, spinning film is taken out, embathe removal unreacted
KH550。
(3) ester bond is introduced on drug molecule：Metronidazole reacts with acryloyl chloride, so as to ester bond is incorporated into agent metronidazole
In；Course of reaction is as follows：1. medicine metronidazole is weighed：Acryloyl chloride：Triethylamine=1:1:1 (mol ratio), chloroform.2. use
Chloroform dilutes acryloyl chloride, is transferred in constant pressure funnel；Metronidazole, triethylamine and the chloroform for weighing are transferred to eggplant
In shape bottle, device is put up.3. N is led to2So that whole system is in N2Atmosphere in.4. eggplant-shape bottle adds magneton not as in ice bath
Disconnected stirring, is added dropwise the mixed solution of acryloyl chloride and chloroform；After dripping off, ice bath 30min removes ice bath, normal-temperature reaction 12h.
5. toward dropwise addition deionized water terminating reaction in eggplant-shape bottle.6. the mixing liquid in eggplant-shape bottle is transferred in separatory funnel, uses dichloro
Methane is extracted.7. toward extraction resulting solution in add anhydrous Na2SO4To liquid clarification, 3h is stood；Resulting solution is at 30 DEG C -40 DEG C
Under the conditions of rotate, obtain needed for product.
(4) gained fiber diaphragm in step (2) is immersed in volume ratio 4:In the system of 1 first alcohol and water, step is weighed
(3) products therefrom dissolving is added in, under conditions of 40 DEG C, is stirred continuously, and reacts 24h.Spinning film is taken out, removal is embathed not
The product of gained in the step of reaction (3).
Embodiment 2
Polycaprolactone nanofiber in embodiment 1 is substituted for cellulose membrane, other experiment conditions and the phase of embodiment 1
Together.The SEM of tunica fibrosa b schemes after tunica fibrosa a and dopamine before contrasting dopamine and coating are coated, it can be found that b Surface coatings
Last layer, and as the time lengthening being immersed in dopamine, covering amount increase, illustrate that dopamine is successfully grafted to tunica fibrosa table
Face；C is designated as by the tunica fibrosa after KH550 graft modifications, the infrared spectrum of b and c is contrasted, in 3000-3500cm-1Hydroxyl at wave number
The absworption peak of base (- OH) disappears, and illustrates that KH550 is anti-by the hydroxyl (- OH) on the ethyoxyl and poly-dopamine shell on KH550
Should be grafted on tunica fibrosa, so that the absworption peak of hydroxyl (- OH) disappears；1000-1100cm-1It is Si-O-Si at wave number
The absworption peak of key, illustrates that KH550 has been grafted on tunica fibrosa；Tunica fibrosa d is obtained after medicine graft modification, insoluble drug release is determined
Curve, the modified diaphragm d for obtaining discharges medicine under conditions of having enzyme, is not release medicine under conditions of no enzyme, and explanation reaches
The effect that infection response type discharges medicine is arrived.
Embodiment 3
Gamma-aminopropyl-triethoxy-silane (KH550) in embodiment 1 is substituted for 3- aminopropyl trimethoxysilanes
(A-1110), other experiment conditions are same as Example 1.Polycaprolactone nano fibrous membrane and enter that contrast dopamine cladding is obtained
The infrared spectrum of the polycaprolactone nano fibrous membrane that one step is obtained by A-1110 graft modifications, in 3000-3500cm-1At wave number
The absworption peak of hydroxyl (- OH) disappears, illustrate 3- aminopropyl trimethoxysilanes (A-1110) by the methoxyl group on A-1110 and
Hydroxyl (- OH) reactive grafting on poly-dopamine shell on polycaprolactone nanofiber so that the suction of hydroxyl (- OH)
Peak is received to disappear；1000-1100cm-1It is the absworption peak of Si-O-Si keys at wave number, illustrates that A-1110 has been grafted to polycaprolactone and has received
On rice fiber.
Embodiment 4
Infection response type surface is carried out to the polycaprolactone guide tissue regeneration film that vacuum molding is obtained to be modified:By embodiment
Polycaprolactone static spinning membrane in 1 is substituted for the polycaprolactone guide tissue regeneration film of vacuum molding preparation, other experiment bars
Part is same as Example 1.And note:A refers to the polycaprolactone guide tissue regeneration film that vacuum molding is obtained；B is represented by dopamine
The polycaprolactone guide tissue regeneration film of cladding；C represented on the basis of b, be modified by Silane coupling agent KH550 obtain it is poly-
Caprolactone guide tissue regeneration film；D is represented on the basis of c, is grafted agent metronidazole (MNA) by Michael addition reaction
To the diaphragm that polycaprolactone guide tissue regeneration film is obtained.Front and rear polycaprolactone guide tissue regeneration is coated by contrasting dopamine
The SEM figures of film, it can be found that polycaprolactone guide tissue regeneration film Surface coating last layer, and with being immersed in dopamine
Time lengthening, covering amount increases, and illustrates that dopamine is successfully grafted to polycaprolactone guide tissue regeneration film surface；Contrast KH550
Polycaprolactone guide tissue regeneration film after graft modification, contrasts the infrared spectrum of b and c, in 3000-3500cm-1Hydroxyl at wave number
The absworption peak of base (- OH) disappears, and illustrates that KH550 is anti-by the hydroxyl (- OH) on the ethyoxyl and poly-dopamine shell on KH550
Should be grafted on polycaprolactone guide tissue regeneration film, so that the absworption peak of hydroxyl (- OH) disappears；1000-1100cm-1
It is the absworption peak of Si-O-Si keys at wave number, illustrates that KH550 has been grafted on polycaprolactone guide tissue regeneration film；Medicine connects
The modified acquisition d of branch, determines drug release patterns, and the modified diaphragm for obtaining discharges medicine under conditions of having enzyme, do not have enzyme
Under the conditions of be not release medicine, illustrate to have reached the effect of infection response type release medicine.
Embodiment 5
Antibacterials metronidazole in embodiment 1 is substituted for erythromycin, other experiment conditions are same as Example 1.Survey
Determine the mass spectrogram and nuclear-magnetism figure of erythromycin and acryloyl chloride product, the thing that molecular weight is 787 occurs in mass spectrogram in discovery
The chemical shift of corresponding H in matter, and contrast nuclear-magnetism figure, it may be determined that product needed for obtaining.Medicine is done by modified diaphragm
Thing release experiment, the modified diaphragm for obtaining discharges medicine erythromycin under conditions of having enzyme, does not have not discharge medicine under conditions of enzyme
Thing.
Embodiment 6
Antibacterials metronidazole in embodiment 1 is substituted for chloramphenicol, ester bond is introduced on drug molecule：Chloramphenicol and third
Alkene acyl chloride reaction, so as to ester bond is incorporated into medicine chloramphenicol；Course of reaction is as follows：1. medicine chloramphenicol is weighed：Acryloyl
Chlorine：Triethylamine=1:1:1 (mol ratio) and acetone.2. acryloyl chloride is diluted with acetone, is transferred in constant pressure funnel；Weigh
Chloramphenicol, triethylamine and acetone be transferred in eggplant-shape bottle, put up device.3. N is led to2So that whole system is in N2Atmosphere in.④
Eggplant-shape bottle is added dropwise the mixed solution of acryloyl chloride and acetone as in ice bath, adding magneton to be stirred continuously；After dripping off, ice bath
30min, removes ice bath, normal-temperature reaction 12h.5. toward dropwise addition deionized water terminating reaction in eggplant-shape bottle.6. by the mixing in eggplant-shape bottle
Liquid is precipitated in being added dropwise to 10-15 times that volume is mixed liquor volume of deionized water, filtering precipitation, and many with deionized water
Secondary cleaning, to remove the acryloyl chloride and triethylamine of remnants, drying obtains product under the conditions of 50 DEG C.Other experiment conditions and reality
Apply example 1 identical.The mass spectrogram and nuclear-magnetism figure of chloramphenicol and acryloyl chloride product are determined, molecule occurs in mass spectrogram in discovery
Measure the chemical shift of corresponding H in the material for 377.12, and contrast nuclear-magnetism figure, it may be determined that product needed for obtaining.By changing
Property after diaphragm do drug release experiment, the modified diaphragm for obtaining discharges medicine chloramphenicol under conditions of having enzyme, does not have enzyme
Under the conditions of do not discharge medicine.
Claims (7)
1. it is a kind of to infect response type guide tissue regeneration film surface modifying method, it is characterized in that：With degradable aliphatic polyester or
Degradable natural macromolecule guide tissue regeneration film is matrix material, is coated by dopamine, and hydroxyl is introduced on film surface；Pass through
Silicon oxygen bond on silane coupler reacts with film surface hydroxyl, so as to introduce amino on film surface；Then by hydroxyl antibacterial
Medicine is reacted with acryloyl chloride, and ester bond and carbon-carbon double bond are introduced on medicine；Finally carbon-carbon double bond is entered with the amino on film surface
Row Michael addition reaction, so as to realize for medicine being grafted to tunica fibrosa surface by ester bond.
2. method according to claim 1, it is characterised in that its concrete operation step is：
(1) guide tissue regeneration film is immersed in the dopamine solution of 0.05g/L-10g/L, after stirring reaction 6-48h, by film
Take out, soaking and washing removes unreacted dopamine solution；Dopamine hydrochloride in dopamine solution：Trishydroxymethylaminomethane
=mol ratio is 5：3, pH=5-10；
(2) guide tissue regeneration film obtained in step (1) is immersed in the silane coupler that concentration is 1.25g/L-5.0g/L
In solution, at a temperature of 25 DEG C -50 DEG C, stirring reaction 3h-72h, takes the film out under magnetic stirrer, embathes removal unreacted
Silane coupler；
(3) antibacterials and acryloyl chloride are reacted, so as to introduce ester bond on metronidazole molecule, course of reaction is as follows：1. claim
Get it filled product metronidazole：Acryloyl chloride：Triethylamine=1:1:1, ratio is mol ratio；2. acryloyl chloride is diluted with chloroform, is turned
In moving to constant pressure funnel；Metronidazole, triethylamine and the chloroform for weighing are transferred in container；3. N is led to2So that whole body
Tie up to N2Atmosphere in；4. container is placed in ice bath, it is 1 that volume ratio is added dropwise:15-1:20 acryloyl chlorides and chloroform it is mixed
Close solution；After dripping off, 20min-30min is placed in ice bath, remove ice bath, normal-temperature reaction 12h；5. to deionization is added dropwise in container
Water terminating reaction；6. the mixing liquid in container is transferred in separatory funnel, is extracted with dichloromethane；7. toward extraction resulting solution
Middle addition anhydrous Na2SO4To liquid clarification, 2-3h is stood；Resulting solution is rotated under the conditions of 30 DEG C -40 DEG C, is produced needed for obtaining
Thing；
(4) guide tissue regeneration film obtained in step (2) is immersed in methyl alcohol：Water=4:1 system, ratio is body in system
Product ratio, weighs the product dissolving of gained in step (3) wherein, under conditions of 30 DEG C -50 DEG C, is stirred continuously, and reacts 6h-72h；
Take the film out, embathe the product of gained in the unreacted step (3) of removal.
3. method according to claim 1, it is characterised in that guide tissue regeneration film, its thickness is 100-500 μm, tool
There is a structure that is non-porous or having hole, 1-10 μm of aperture, its preparation method is included but is not limited to：Electrostatic spinning, melt casting and vacuum
Die pressing.
4. method according to claim 1, it is characterised in that degradable aliphatic polyester, including：PLA, gather oneself in
Ester, Poly(D,L-lactide-co-glycolide, PLA-caprolactone copolymer, poly lactic-co-glycolic acid-caprolactone copolymer are wherein
One or more kinds of mixtures；Degradable natural macromolecular material includes：NTx, gelatin, shitosan, starch, fibre
One or more kinds of mixtures in dimension element, elastin laminin.
5. method according to claim 1, it is characterised in that antimicrobial includes metronidazole, erythromycin, Piperacillin, chlorine
Mycin.
6. method according to claim 1, it is characterised in that relevant enzyme includes cholesterol esterase or phospholipase A2
(PLA2)。
7. method according to claim 1, it is characterised in that silane coupler, including：Gamma-aminopropyl-triethoxy silicon
Alkane (KH550), 3- aminopropyl trimethoxysilanes (A-1110) or N- β-(aminoethyl)-γ-aminopropyltrimethoxysilane (A-
1120)。
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109758620A (en) * | 2019-03-12 | 2019-05-17 | 东华大学 | A kind of ureter rack tube and preparation method thereof that long acting antibiotic is degradable |
| CN110354303A (en) * | 2018-03-26 | 2019-10-22 | 北京化工大学 | A kind of antibacterial method of modifying of metallic titanium surface |
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| CN110935057A (en) * | 2018-09-21 | 2020-03-31 | 天津大学 | Application of dopamine-based tissue adhesive in antibacterial biomedical materials |
| CN111021056A (en) * | 2018-10-09 | 2020-04-17 | 长春工业大学 | Preparation method of polycaprolactone/polylactic acid nanofiber membrane grafted resveratrol |
| CN113005773A (en) * | 2021-03-05 | 2021-06-22 | 北京市创伤骨科研究所 | Polyurethane film, preparation method and application thereof |
| CN114984312A (en) * | 2022-05-30 | 2022-09-02 | 浙江大学 | Hyperbranched polylysine-containing polyurethane heart patch and preparation method thereof |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0693523A2 (en) * | 1994-07-19 | 1996-01-24 | Col-Bar R & D Ltd. | Collagen-based matrix |
| CN101411898A (en) * | 2008-11-28 | 2009-04-22 | 东华大学 | Organic/inorganic composite antibiotic catheters and preparation method thereof |
| CN101537204A (en) * | 2008-03-18 | 2009-09-23 | 威海威高创新有限公司 | Medical nanometer antibacterial composite dressing and method for preparing same |
| CN103948974A (en) * | 2013-12-30 | 2014-07-30 | 北京化工大学 | Drug-loading type guided tissue regeneration membrane and preparation method thereof |
| CN104474589A (en) * | 2014-12-23 | 2015-04-01 | 山东国际生物科技园发展有限公司 | Guided tissue regeneration membrane as well as preparation method and application thereof |
-
2016
- 2016-12-30 CN CN201611265580.2A patent/CN106693072B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0693523A2 (en) * | 1994-07-19 | 1996-01-24 | Col-Bar R & D Ltd. | Collagen-based matrix |
| CN101537204A (en) * | 2008-03-18 | 2009-09-23 | 威海威高创新有限公司 | Medical nanometer antibacterial composite dressing and method for preparing same |
| CN101411898A (en) * | 2008-11-28 | 2009-04-22 | 东华大学 | Organic/inorganic composite antibiotic catheters and preparation method thereof |
| CN103948974A (en) * | 2013-12-30 | 2014-07-30 | 北京化工大学 | Drug-loading type guided tissue regeneration membrane and preparation method thereof |
| CN104474589A (en) * | 2014-12-23 | 2015-04-01 | 山东国际生物科技园发展有限公司 | Guided tissue regeneration membrane as well as preparation method and application thereof |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110354303A (en) * | 2018-03-26 | 2019-10-22 | 北京化工大学 | A kind of antibacterial method of modifying of metallic titanium surface |
| CN110935057A (en) * | 2018-09-21 | 2020-03-31 | 天津大学 | Application of dopamine-based tissue adhesive in antibacterial biomedical materials |
| CN111021056A (en) * | 2018-10-09 | 2020-04-17 | 长春工业大学 | Preparation method of polycaprolactone/polylactic acid nanofiber membrane grafted resveratrol |
| CN109758620A (en) * | 2019-03-12 | 2019-05-17 | 东华大学 | A kind of ureter rack tube and preparation method thereof that long acting antibiotic is degradable |
| CN109758620B (en) * | 2019-03-12 | 2021-06-04 | 东华大学 | Long-acting antibacterial degradable ureteral stent and preparation method thereof |
| CN110665065A (en) * | 2019-11-01 | 2020-01-10 | 北京市创伤骨科研究所 | Deferoxamine-loaded artificial periosteum and preparation method thereof |
| CN110665065B (en) * | 2019-11-01 | 2021-09-07 | 北京市创伤骨科研究所 | Deferoxamine-loaded artificial periosteum and preparation method thereof |
| CN113005773A (en) * | 2021-03-05 | 2021-06-22 | 北京市创伤骨科研究所 | Polyurethane film, preparation method and application thereof |
| CN113005773B (en) * | 2021-03-05 | 2022-04-22 | 北京市创伤骨科研究所 | Polyurethane film, preparation method and application thereof |
| CN114984312A (en) * | 2022-05-30 | 2022-09-02 | 浙江大学 | Hyperbranched polylysine-containing polyurethane heart patch and preparation method thereof |
| CN115990297A (en) * | 2023-03-09 | 2023-04-21 | 上海宏普医疗器械有限公司 | Heparin anticoagulation coating based on PTFE material and preparation method thereof |
| CN115990297B (en) * | 2023-03-09 | 2023-11-07 | 上海宏普医疗器械有限公司 | Heparin anticoagulation coating based on PTFE material and preparation method thereof |
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