CN106008863B - One kind is based on poly-（N-isopropyl acrylamide）The antiseptic activity of thermic conformation reversible transition calls switch - Google Patents
One kind is based on poly-（N-isopropyl acrylamide）The antiseptic activity of thermic conformation reversible transition calls switch Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F293/00—Macromolecular compounds obtained by polymerisation on to a macromolecule having groups capable of inducing the formation of new polymer chains bound exclusively at one or both ends of the starting macromolecule
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/52—Amides or imides
- C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/52—Amides or imides
- C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
- C08F220/60—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide containing nitrogen in addition to the carbonamido nitrogen
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/52—Amides or imides
- C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
- C08F220/60—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide containing nitrogen in addition to the carbonamido nitrogen
- C08F220/606—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide containing nitrogen in addition to the carbonamido nitrogen and containing other heteroatoms
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F2438/00—Living radical polymerisation
- C08F2438/03—Use of a di- or tri-thiocarbonylthio compound, e.g. di- or tri-thioester, di- or tri-thiocarbamate, or a xanthate as chain transfer agent, e.g . Reversible Addition Fragmentation chain Transfer [RAFT] or Macromolecular Design via Interchange of Xanthates [MADIX]
Abstract
The invention discloses one kind based on poly-（NN-isopropylacrylamide）The antiseptic activity of thermic conformation reversible transition calls switch.Using reversible addition-fragmentation chain transfer free radical polymerization, a kind of the poly- of one end antibacterial containing fluoquinolone group is prepared for（NN-isopropylacrylamide）Macromolecular.Poly-（NN-isopropylacrylamide）Lower critical solution temperature below, which is dissolved completely in water, in aqueous in extended conformation, fluoquinolone antibacterial end group can free movement, its antibacterial activity can be fully demonstrated；When environment temperature is increased to gather（NN-isopropylacrylamide）Lower critical solution temperature more than when, which will collapse to form bead in aqueous, hinder the free movement of fluoquinolone antibacterial end group so that these antibacterial end groups are difficult to spread, close to its action target, and then shield its antibacterial activity.Using poly-（NN-isopropylacrylamide）Thermic conformation reversible transition evades antiseptic itself toxicity and alleviates drug resistance generation, it can be achieved that controllable calling and the shielding of fluoquinolone antibacterial terminal reactive, and application prospect is extensive.
Description
Technical field
The present invention relates to one kind based on poly-（N- N-isopropylacrylamide）The antiseptic activity of thermic conformation reversible transition is adjusted
With switch, belong to anti-biotic material field.
Background technology
For a long time, it is proved to be a kind of by outer addition small molecule antiseptic to significantly improve the Antimicrobial preservative of product
Effective method.However, many tradition small molecule antiseptics（Such as fluoquinolone）Due to action target prokaryotic with
Selectivity is relatively low between eukaryotic, and while the harmful microorganisms such as bacterium are efficiently killed, human normal tissue cell is also deposited
In toxic action, consumer health's safety is threatened.Secondly, under long-term, the lasting coercion of antiseptic, bacterium DNA replication
Error correcting capability is passivated, bacterioprotein expression, ultrastructural change Showed Very Brisk as caused by aggravating gene mutation, and then can be mediated
Outflow pumps outer row's effect up-regulation, antiseptic intake passage is closed and its irreversible modification of action target, strengthens to antiseptic drug resistance
The selection index system of bacterial strain, drops sharply the original effect of antibacterial components, increases the Antimicrobial preservative difficulty and cost of product.
Certainly, complete abandoning tradition antiseptic and high biological selectivity, low drug resistance are directly had concurrently using antibacterial peptide etc.
Novel antibacterial material can be largely overcoming the above problem.But reality is, natural antibacterial peptide content in vivo
Atomic, direct extraction process is cumbersome, yield is low, costly, artificial synthesized by genetic engineering and face short of donor, host
Cell suicide rate is high, expression product is few, isolates and purifies many bottlenecks such as difficulty, significantly limit the extensive business of this kind of material
With.
The content of the invention
The purpose of the invention is to overcome shortcoming and defect existing in the prior art, and provide a kind of based on poly-（N- different
Propylacrylamide）The antiseptic activity of thermic conformation reversible transition calls switch, it is characterised in that the preparation process of the switch
Step and condition are as follows（The number of wherein described material is parts by weight）：
（1）Fluoquinolone is vinylated：10-20 parts of fluoquinolone, 4-8 parts of catalyst are mixed for 300-500 parts with solvent
Uniformly, stirred in 0-5 DEG C 30-60 minutes, be then added dropwise vinylated reagent 4-8 parts under lasting stirring and nitrogen protection, drop
Be warming up to after adding 20-35 DEG C reaction 1-2.5 it is small when；After completion of the reaction, thing mixed above is poured into precipitating reagent, precipitation warp
Washing, the vinylated fluoquinolone of drying repeatedly；
（2）NThe Invertible ideal of-N-isopropylacrylamide：By Reversible Addition Fragmentation Chain Transfer reagent
1-4 parts,N90-300 parts of-N-isopropylacrylamide, 0.07-0.24 parts of initiator are uniformly mixed for 120-400 parts with solvent, sealing,
Circulating frozen-defrosting deoxygenation, then it is lasting stirring and nitrogen protection under, be warming up to 55-65 DEG C reaction 4-12 it is small when, reaction knot
Beam, thing mixed above is poured into precipitating reagent, and precipitation is vacuum dried up to poly-（N- N-isopropylacrylamide）Macromolecular chain turns
Move agent；
（3）Fluoquinolone antibacterial activity calls the synthesis of switch：Made above is gathered（N- N-isopropylacrylamide）Greatly
120-840 parts of 30-80 parts of molecular chain transfer agent, fluoquinolone 6-160 parts vinylated, 0.04-0.2 parts of initiator and solvent are mixed
Close uniformly, in the case where nitrogen is protected and continuously stirred, when the 60-80 DEG C of 20-30 that flows back is small, after completion of the reaction, by thing mixed above
Pour into precipitating reagent, filter off precipitation, switch is called up to fluoquinolone antibacterial activity after solution drying.
Fluoquinolone described in above method for Ciprofloxacin, lomefloxacin, Norfloxacin, Sarafloxacin, Enoxacin,
One or more in Sparfloxacin, gatifloxacin.
Catalyst described in above method for triethylamine,N,NIn-diisopropylethylamine, pyridine, potassium carbonate, sodium carbonate
It is one or more.
Solvent described in above method for chloroform, dichloromethane, tetrahydrofuran, ethyl acetate,N,N- dimethylformamide,N,NOne or more in-dimethylacetylamide, dimethyl sulfoxide (DMSO), pyridine, 1,4- dioxanes.
Vinylated reagent described in above method is acryloyl chloride, 4- prenyl chlorides, propylene acylbromide, hex- 5- alkene acyl chlorides
In one or more.
Step in above method（1）The precipitating reagent for n-hexane, hexamethylene, pentamethylene, normal heptane, ether, petroleum ether,
One or more in tetrahydrofuran, toluene, ethyl acetate, butyl acetate.
Reversible Addition Fragmentation Chain Transfer reagent described in above method is 4- cyano group -4- (thio benzoyl) valeric acid, 2- benzene
Two sulphur of base -2- propyl group benzo, two sulphur of 2- cyanogen propyl group -2- bases benzo, 4- cyano group -4- (the thio phosphinylidyne of dodecyl sulfanyl) sulphur penta
Acid, 2- cyano group -2- propyl group dodecyls trithiocarbonate, 2- (dodecyl trithiocarbonic acid ester group) -2 Methylpropionic acid, 2-
(1- isobutyl groups）Trithiocarbonic acid ester group -2 Methylpropionic acid, the thio benzoyl acetic acids of 2- sulfydryls-S-, 2- cyanogen propan-2-ol two are thio
One or more in benzoic ether, two sulphur of 2- phenyl -2- propyl group benzo.
Initiator described in above method is azodiisobutyronitrile, azobisisoheptonitrile, two cyclohexanenitrile of azo, peroxidating ring
One or more in hexanone, dibenzoyl peroxide, perbenzoic acid spy butyl ester, tert-butyl hydroperoxide.
Compared with prior art, the present invention have the positive effect that：
1st, fluoquinolone antiseptic subjective antisepsis spectrum is wide, antibacterial activity is strong.The present invention is using acylation reaction to fluoquinolone
Vinylated modification is carried out, does not interfere with fluoquinolone mother nucleus structure domain and each synergy substituent.Therefore, withN- isopropyl propylene
After acid amides copolymerization, fluoquinolone antiseptic own bioactivity will be retained.
2nd, the present invention prepares one end group of antibacterial containing fluoquinolone using reversible addition-fragmentation chain transfer free radical polymerization
It is poly-（N- N-isopropylacrylamide）, gather（N- N-isopropylacrylamide）Chain length, fluoquinolone antibacterial group content and
Position is controllable.Only when fluoquinolone antibacterial group is positioned at poly-（N- N-isopropylacrylamide）During one end, poly-（N- isopropyl third
Acrylamide）Lower critical solution temperature below, these antibacterial end groups could be spread, into bacterium intracellular, act on its target.When
Fluoquinolone antibacterial group random distribution is in poly-（N- N-isopropylacrylamide）Main chain, or positioned at poly-（N- N-isopropylacrylamide）
During both ends, since steric hindrance acts on, even in poly-（N- N-isopropylacrylamide）Lower critical solution temperature below, these are anti-
Bacterium group will also be difficult to diffuse into bacterium intracellular, act on its target.
3rd, poly-（N- N-isopropylacrylamide）Lower critical solution temperature below, which is dissolved completely in water,
Be in extended conformation in aqueous, fluoquinolone antibacterial end group can free movement, its antibacterial activity retained；Work as environment temperature
It is increased to gather（N- N-isopropylacrylamide）Lower critical solution temperature more than when, which will collapse shape in aqueous
Into bead, the free movement of fluoquinolone antibacterial end group is hindered, these antibacterial end groups will be difficult to spread, close to its action target,
And then shield its antibacterial activity.
4th, the present invention utilizes poly-（N- N-isopropylacrylamide）Thermic conformation reversible transition is, it can be achieved that antibacterial terminal reactive
Controllable calling and shielding, and then evade antiseptic itself toxicity and alleviate drug resistance generation.
5th, molecular switch of the present invention has repeatability, i.e. the antibacterial activity of antiseptic can be with poly-（N- isopropyl
Acrylamide）The transformation of conformation Thermoreversibly is shielded and called repeatedly, this utilizes poly- with forefathers（N- N-isopropylacrylamide）Heat
Quick characteristic realizes that the release on demand of bioactive molecule has essential distinction.
Brief description of the drawings
Fig. 1 is based on poly-（N- N-isopropylacrylamide）The antiseptic activity of thermic conformation reversible transition calls switch
Synthetic route.
Fig. 2 is based on poly-（N- N-isopropylacrylamide）The antiseptic activity of thermic conformation reversible transition calls switch work
Make principle schematic.
Embodiment
The present invention is specifically described below by embodiment, is served only for that the present invention is further described, no
It is understood that for limiting the scope of the present invention, the technician in the field can be according to the content of foregoing invention to the present invention
Make some nonessential modifications and adaptations.
Embodiment 1
（1）Ciprofloxacin is vinylated：10 parts of Ciprofloxacin, 4 parts of triethylamine are uniformly mixed for 300 parts with dichloromethane,
Stirred in 0 DEG C 30 minutes, 4 parts of acryloyl chloride then is added dropwise under lasting stirring and nitrogen protection, 20 are warming up to after being added dropwise
DEG C reaction 1 it is small when；After completion of the reaction, thing mixed above is poured into n-hexane, precipitated through washing repeatedly, drying vinyl
Change Ciprofloxacin；
（2）NThe Invertible ideal of-N-isopropylacrylamide：By two sulphur 1 of 2- phenyl -2- propyl group benzo
Part,N90 parts of-N-isopropylacrylamide, 0.07 part of azodiisobutyronitrile are uniformly mixed for 120 parts with tetrahydrofuran, seal, circulate it is cold
Jelly-defrosting deoxygenation, then under lasting stirring and nitrogen protection, be warming up to 55 DEG C of reactions 4 it is small when, reaction terminates, will more than it is mixed
Compound is poured into ether, and precipitation is vacuum dried up to poly-（N- N-isopropylacrylamide）Macromolecular chain transfer agent；
（3）Ciprofloxacin antibacterial activity calls the synthesis of switch：Made above is gathered（N- N-isopropylacrylamide）Greatly
30 parts of molecular chain transfer agent, 6 parts of vinylated Ciprofloxacin, 0.04 part of azodiisobutyronitrile andN,N- dimethylformamide 120
Part is uniformly mixed, and in the case where nitrogen is protected and continuously stirred, when 60 DEG C of reflux 20 are small, after completion of the reaction, thing mixed above is fallen
Enter in toluene, filter off precipitation, switch is called up to Ciprofloxacin antibacterial activity after solution drying.
Prepare 0.1mg mL-1Ciprofloxacin antibacterial activity call switch solution, be preheated to 37 DEG C, then draw 0.1mL
Ciprofloxacin antibacterial activity calls switch solution and is rapidly added 0.9mL, the bacteria suspension that temperature is 37 DEG C（Concentration is 106 CFU）
In, 2h is vibrated in 37 DEG C of constant temperature oscillation case, 100 μ L mixed liquor spread plates is taken, is cultivated in 37 DEG C of constant incubators
12h, is 7.8% with blank group comparing calculation bacteriostasis rate；
Prepare 0.1mg mL-1Ciprofloxacin antibacterial activity call switch solution, be preheated to 27 DEG C, then draw 0.1mL
Ciprofloxacin antibacterial activity calls switch solution and is rapidly added 0.9mL, the bacteria suspension that temperature is 27 DEG C（Concentration is 106 CFU）
In, 2h is vibrated in 27 DEG C of constant temperature oscillation case, 100 μ L mixed liquor spread plates is taken, is cultivated in 27 DEG C of constant incubators
12h, is 99.2% with blank group comparing calculation bacteriostasis rate；
Prepared Ciprofloxacin antibacterial activity calls switch strong in the following antibacterial activity of its lower critical solution temperature, and
More than its lower critical solution temperature, its bioactivity is suppressed.
Embodiment 2
（1）Gatifloxacin is vinylated：15 parts of gatifloxacin, 6 parts of pyridine are uniformly mixed for 400 parts with tetrahydrofuran, in 2
DEG C stirring 45 minutes, is then added dropwise 6 parts of 4- prenyl chlorides under lasting stirring and nitrogen protection, 30 DEG C is warming up to after being added dropwise
React 1.5 it is small when；After completion of the reaction, thing mixed above is poured into hexamethylene, precipitated through washing repeatedly, drying vinyl
Change gatifloxacin；
（2）NThe Invertible ideal of-N-isopropylacrylamide：By two sulphur 2 of 2- cyanogen propyl group -2- bases benzo
Part,N140 parts of-N-isopropylacrylamide, 0.14 part of azobisisoheptonitrile are uniformly mixed for 180 parts with Isosorbide-5-Nitrae-dioxanes, are sealed, are followed
Ring freeze-thaw deoxygenation, then under lasting stirring and nitrogen protection, be warming up to 60 DEG C of reactions 6 it is small when, reaction terminates, will be with
Upper mixture is poured into n-hexane, and precipitation is vacuum dried up to poly-（N- N-isopropylacrylamide）Macromolecular chain transfer agent；
（3）Gatifloxacin antibacterial activity calls the synthesis of switch：Made above is gathered（N- N-isopropylacrylamide）Greatly
40 parts of molecular chain transfer agent, 10 parts of vinylated gatifloxacin, 0.06 part of azobisisoheptonitrile andN,N- dimethylacetylamide 180
Part is uniformly mixed, and in the case where nitrogen is protected and continuously stirred, when 70 DEG C of reflux 25 are small, after completion of the reaction, thing mixed above is fallen
Enter in ethyl acetate, filter off precipitation, switch is called up to gatifloxacin antibacterial activity after solution drying.
Prepare 0.1mg mL-1Gatifloxacin antibacterial activity call switch solution, be preheated to 37 DEG C, then draw 0.1mL
Gatifloxacin antibacterial activity calls switch solution and is rapidly added 0.9mL, the bacteria suspension that temperature is 37 DEG C（Concentration is 106 CFU）
In, 2h is vibrated in 37 DEG C of constant temperature oscillation case, 100 μ L mixed liquor spread plates is taken, is cultivated in 37 DEG C of constant incubators
12h, is 8.4% with blank group comparing calculation bacteriostasis rate；
Prepare 0.1mg mL-1Gatifloxacin antibacterial activity call switch solution, be preheated to 27 DEG C, then draw 0.1mL
Gatifloxacin antibacterial activity calls switch solution and is rapidly added 0.9mL, the bacteria suspension that temperature is 27 DEG C（Concentration is 106 CFU）
In, 2h is vibrated in 27 DEG C of constant temperature oscillation case, 100 μ L mixed liquor spread plates is taken, is cultivated in 27 DEG C of constant incubators
12h, is 99.5% with blank group comparing calculation bacteriostasis rate；
Prepared gatifloxacin antibacterial activity calls switch strong in the following antibacterial activity of its lower critical solution temperature, and
More than its lower critical solution temperature, its bioactivity is suppressed.
Embodiment 3
（1）Norfloxacin is vinylated：By 20 parts of Norfloxacin,N,N500 parts with chloroform of 8 parts of-diisopropylethylamine mixes
Uniformly, stirred in 5 DEG C 60 minutes, 8 parts of hex- 5- alkene acyl chlorides then is added dropwise under lasting stirring and nitrogen protection, after being added dropwise
Be warming up to 35 DEG C reaction 2.5 it is small when；After completion of the reaction, thing mixed above is poured into normal heptane, precipitated through washing, drying repeatedly
Up to vinylated Norfloxacin；
（2）NThe Invertible ideal of-N-isopropylacrylamide：By 2- cyano group -2- propyl group dodecyl three
4 parts of sulfocarbonate,N300 parts of-N-isopropylacrylamide, 0.24 part of two cyclohexanenitrile of azo are uniformly mixed for 400 parts with pyridine, close
Envelope, circulating frozen-defrosting deoxygenation, then it is lasting stirring and nitrogen protection under, be warming up to 65 DEG C reaction 12 it is small when, reaction knot
Beam, thing mixed above is poured into petroleum ether, and precipitation is vacuum dried up to poly-（N- N-isopropylacrylamide）Macromolecular chain turns
Move agent；
（3）Norfloxacin antibacterial activity calls the synthesis of switch：Made above is gathered（N- N-isopropylacrylamide）Greatly
840 parts of 80 parts of molecular chain transfer agent, 160 parts of vinylated Norfloxacin, 0.2 part of two cyclohexanenitrile of azo and pyridine are uniformly mixed,
In the case where nitrogen is protected and continuously stirred, when 80 DEG C of reflux 30 are small, after completion of the reaction, thing mixed above is poured into tetrahydrofuran
In, precipitation is filtered off, switch is called up to Norfloxacin antibacterial activity after solution drying.
Prepare 0.1mg mL-1Norfloxacin antibacterial activity call switch solution, be preheated to 37 DEG C, then draw 0.1mL
Norfloxacin antibacterial activity calls switch solution and is rapidly added 0.9mL, the bacteria suspension that temperature is 37 DEG C（Concentration is 106 CFU）
In, 2h is vibrated in 37 DEG C of constant temperature oscillation case, 100 μ L mixed liquor spread plates is taken, is cultivated in 37 DEG C of constant incubators
12h, is 4.4% with blank group comparing calculation bacteriostasis rate；
Prepare 0.1mg mL-1Norfloxacin antibacterial activity call switch solution, be preheated to 27 DEG C, then draw 0.1mL
Norfloxacin antibacterial activity calls switch solution and is rapidly added 0.9mL, the bacteria suspension that temperature is 27 DEG C（Concentration is 106 CFU）
In, 2h is vibrated in 27 DEG C of constant temperature oscillation case, 100 μ L mixed liquor spread plates is taken, is cultivated in 27 DEG C of constant incubators
12h, is 99.9% with blank group comparing calculation bacteriostasis rate；
Prepared Norfloxacin antibacterial activity calls switch strong in the following antibacterial activity of its lower critical solution temperature, and
More than its lower critical solution temperature, its bioactivity is suppressed.
Claims (8)
1. a kind of antiseptic activity based on poly(N-isopropylacrylamide) thermic conformation reversible transition calls switch, its feature
It is that step of preparation process and the condition of the switch are as follows, the number of the material is parts by weight：
(1) fluoquinolone is vinylated：10-20 parts of fluoquinolone, 4-8 parts of catalyst are uniformly mixed for 300-500 parts with solvent,
Stirred in 0-5 DEG C 30-60 minutes, be then added dropwise vinylated reagent 4-8 parts under lasting stirring and nitrogen protection, be added dropwise
After be warming up to 20-35 DEG C reaction 1-2.5 it is small when；After completion of the reaction, thing mixed above is poured into precipitating reagent, precipitated through water repeatedly
Wash, the vinylated fluoquinolone of drying；
(2) Invertible ideal of n-isopropyl acrylamide：By Reversible Addition Fragmentation Chain Transfer reagent 1-4
Part, 90-300 parts of n-isopropyl acrylamide, 0.07-0.24 parts of initiator are uniformly mixed for 120-400 parts with solvent, are sealed, are followed
Ring freeze-thaw deoxygenation, then it is lasting stirring and nitrogen protection under, be warming up to 55-65 DEG C reaction 4-12 it is small when, reaction knot
Beam, thing mixed above is poured into precipitating reagent, and precipitation is vacuum dried to be turned up to poly(N-isopropylacrylamide) macromolecular chain
Move agent；
(3) fluoquinolone antibacterial activity calls the synthesis of switch：By poly(N-isopropylacrylamide) macromolecular made above
30-80 parts of chain-transferring agent, fluoquinolone 6-160 parts vinylated, 0.04-0.2 parts of initiator and 120-840 parts of mixing of solvent are equal
It is even, in the case where nitrogen is protected and continuously stirred, when the 60-80 DEG C of 20-30 that flows back is small, after completion of the reaction, thing mixed above is poured into
In precipitating reagent, precipitation is filtered off, switch is called up to fluoquinolone antibacterial activity after solution drying.
A kind of 2. antiseptic based on poly(N-isopropylacrylamide) thermic conformation reversible transition according to claim 1
Activity calls switch, it is characterised in that fluoquinolone described in the switch preparation method is Ciprofloxacin, lomefloxacin, promise fluorine are husky
One or more in star, Sarafloxacin, Enoxacin, Sparfloxacin, gatifloxacin.
A kind of 3. antiseptic based on poly(N-isopropylacrylamide) thermic conformation reversible transition according to claim 1
Activity calls switch, it is characterised in that catalyst described in the switch preparation method is triethylamine, n,N-diisopropylethylamine, pyrrole
One or more in pyridine, potassium carbonate, sodium carbonate.
A kind of 4. antiseptic based on poly(N-isopropylacrylamide) thermic conformation reversible transition according to claim 1
Activity calls switch, it is characterised in that solvent described in the switch preparation method is chloroform, dichloromethane, tetrahydrofuran, acetic acid
Ethyl ester, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, dimethyl sulfoxide (DMSO), pyridine, one kind in 1,4- dioxanes or more
Kind.
A kind of 5. antiseptic based on poly(N-isopropylacrylamide) thermic conformation reversible transition according to claim 1
Activity call switch, it is characterised in that vinylated reagent described in the switch preparation method for acryloyl chloride, 4- prenyl chlorides,
One or more in propylene acylbromide, hex- 5- alkene acyl chlorides.
A kind of 6. antiseptic based on poly(N-isopropylacrylamide) thermic conformation reversible transition according to claim 1
Activity calls switch, it is characterised in that step (1) described precipitating reagent is n-hexane, hexamethylene, ring penta in the switch preparation method
One or more in alkane, normal heptane, ether, petroleum ether, tetrahydrofuran, toluene, ethyl acetate, butyl acetate.
A kind of 7. antiseptic based on poly(N-isopropylacrylamide) thermic conformation reversible transition according to claim 1
Activity calls switch, it is characterised in that Reversible Addition Fragmentation Chain Transfer reagent described in the switch preparation method is 4- cyano group -4-
(thio benzoyl) valeric acid, two sulphur of 2- phenyl -2- propyl group benzo, two sulphur of 2- cyanogen propyl group -2- bases benzo, 4- cyano group -4- (dodecyls
The thio phosphinylidyne of sulfanyl) sulphur valeric acid, 2- cyano group -2- propyl group dodecyls trithiocarbonate, 2- (dodecyl trithiocarbonic acids
Ester group) -2 Methylpropionic acid, 2- (1- isobutyl groups) trithiocarbonic acids ester group -2 Methylpropionic acid, the thio benzoyl second of 2- sulfydryls-S-
One or more in acid, 2- cyanogen propan-2-ol dithiobenzoic acids ester, two sulphur of 2- phenyl -2- propyl group benzo.
A kind of 8. antiseptic based on poly(N-isopropylacrylamide) thermic conformation reversible transition according to claim 1
Activity call switch, it is characterised in that initiator described in the switch preparation method for azodiisobutyronitrile, azobisisoheptonitrile,
In two cyclohexanenitrile of azo, cyclohexanone peroxide, dibenzoyl peroxide, perbenzoic acid spy butyl ester, tert-butyl hydroperoxide
One or more.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610378557.8A CN106008863B (en) | 2016-05-30 | 2016-05-30 | One kind is based on poly-（N-isopropyl acrylamide）The antiseptic activity of thermic conformation reversible transition calls switch |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610378557.8A CN106008863B (en) | 2016-05-30 | 2016-05-30 | One kind is based on poly-（N-isopropyl acrylamide）The antiseptic activity of thermic conformation reversible transition calls switch |
Publications (2)
| Publication Number | Publication Date |
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| CN106008863A CN106008863A (en) | 2016-10-12 |
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| CN109513036B (en) * | 2019-01-11 | 2021-04-20 | 四川大学 | Collagen material capable of automatically closing antibacterial function under receptor temperature induction |
| CN113207907A (en) * | 2021-04-29 | 2021-08-06 | 安徽江淮汽车集团股份有限公司 | Preparation method of antibacterial agent, thermoplastic resin composite material and preparation method thereof |
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| WO2005020933A3 (en) * | 2003-09-02 | 2005-06-09 | Univ South Florida | Nanoparticles for drug-delivery |
| CN105111356A (en) * | 2015-09-14 | 2015-12-02 | 四川大学 | Macromolecule antibacterial agent used for water-based ecological synthetic leather and preparation method thereof |
| CN105218662A (en) * | 2015-09-18 | 2016-01-06 | 四川大学 | A kind of purification of the collagen based on the recyclable nano antibacterial agent of magnetic and anti-corrosion method |
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| WO2005020933A3 (en) * | 2003-09-02 | 2005-06-09 | Univ South Florida | Nanoparticles for drug-delivery |
| CN105111356A (en) * | 2015-09-14 | 2015-12-02 | 四川大学 | Macromolecule antibacterial agent used for water-based ecological synthetic leather and preparation method thereof |
| CN105218662A (en) * | 2015-09-18 | 2016-01-06 | 四川大学 | A kind of purification of the collagen based on the recyclable nano antibacterial agent of magnetic and anti-corrosion method |
Non-Patent Citations (2)
| Title |
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| New insights into the effects of molecular weight and end group on the temperature-induced phase transition of poly(N-isopropylacrylamide) in water;Qiu XingPing;《Science China Chemistry》;20130131;第56卷(第1期);56-64 * |
| 键合喹诺酮类药物基团的抗菌聚丙烯酰胺的制备及其抗菌性能;薛艳;《功能高分子学报》;20141231;第27卷(第4期);353-359 * |
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