CN104892951A - Preparation method of four-arm star-type polymer stable nano-micelle possessing UCST and redox responsiveness - Google Patents
Preparation method of four-arm star-type polymer stable nano-micelle possessing UCST and redox responsiveness Download PDFInfo
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Abstract
The invention relates to a preparation method of four-arm star-type polymer stable nano-micelle possessing UCST and redox responsiveness. Under inert gas, hydroxy in pentaerythritol four arm and epsilon-caprolactone are subjected to a ring-opening polymerisation to obtain a macro-molecule graft copolymer, thiodipropionic acid and a micromolecule bromide with one terminal being hydroxy and one end being bromine are used for performing an esterification reaction on a macro-molecule polymer in order to obtain an atom transfer free radical polymerized macro-molecule initiator, under initiation of cuprous bromide, atom transfer free radical polymerization is carried out on 2-(dimethylamino)ethyl methacrylate monomer, complete quaternization is performed on the polymer, so that a grafting-embedding copolymer possessing UCST temperature responsiveness and redox responsiveness with a four-arm star structure can be obtained, and is dissolved in water to form the stable nano-micelle possessing UCST and redox responsiveness. The stable nano-micelle possessing UCST and redox responsiveness has the advantages of biology compatibility, biological activity and temperature response performance, and has wide application on medicine controlled release carrier, biology intelligent switch and biosensor. The preparation method is easy to operate, raw materials enable industrial production, so that the preparation method has good popularization and application value.
Description
Technical field
The invention belongs to macromolecular material and biomedical engineering field, be specifically related to a kind of preparation method with four arm star polymer stabilizing nano-micelles of UCST and redox responsiveness.
Background technology
Amphipathic star-type polymer is a kind of complicated shape polymkeric substance with ordered structure, due to the singularity of structure, makes it have unique microphase, and some special property and function.The mechanical property of star polymer, optical property, magnetic property, electrical properties and chemical property are obviously different from simple linear polymer, and therefore, phase superior functional is favored widely.Design and synthesize out novel having and determine that the amphipathic star-type polymer of structure is then the prerequisite of carrying out these researchs.The study hotspot of current field of polymer technology especially.Panja(Panja, S; Saha, B; Ghosh, S. K.Synthesis of Novel Four Armed PE-PCL Grafted Superparamagneticand Biocompatible Nanoparticles [J]. Langmuir 2013,29,12530 12540) four arm multipolymer tetramethylolmethane-poly-epsilon-caprolactones by 6-caprolactone and tetramethylolmethane graft reaction are obtained, then be grafted to the new polymers prepared on hydride modified magnetic nano-particle and there is good biocompatibility.Wang(Wang, L; Di, S.B; Wang, W.X.Tunable Temperature Memory Effect of Photo-Cross-Linked StarPCL-PEG Networks [J]. Macromolecules 2014,47,1828 1836) StarPCL-PEG prepares a kind of crosslinked star-type polymer having good biocompatibility and biological degradability by carrying out single photo-crosslinking with Chinese cassia tree, and this polymkeric substance has outstanding temperature memory effect simultaneously.
Also known as intelligent polymer or stimuli responsive type multipolymer, under being namely subject to the small stimulation of external environment, self correspondingly can there is some physics or chemical property variation state and the polymkeric substance of reversible change in environmental response type polymkeric substance.Wherein external stimulus factor comprises the physics and chemistries such as electric field, magnetic field, ionic strength, pH value, temperature stimulates, and self property comprises shape, phase, surface energy, infiltration rate or recognition performance etc.At environmental response type polymkeric substance in protection carrier, the intelligence of the biomacromolecules such as the delivery vehicles of medicament slow release, bioseparation, catalyzer or enzyme or bionical system, biosensor and bio-molecular diagnostics etc. are biomedical and many application of field of nanometer technology, therefore cause the extensive concern of people.Due to the outstanding character of amphipathic nature polyalcohol, and the using value of environmental response type polymkeric substance in a lot of field, so amphipathic environmental response type polymkeric substance becomes study hotspot.Zhao (Housni, A and Zhao, Y.Gold Nanoparticles Functionalized with Block Copolymers Displaying Either LCST or UCST Thermosensitivity in Aqueous Solution [J]. Langmuir.2010,26,12933 – 12939) the polymkeric substance Quaternized-PEO-with UCST has been prepared by the quaternary ammonium reaction of PDMAEMA
b-PDMAEMA, then by itself and gold nano compound, and have studied the temperature-responsive of gained hybrid particle, result shows that golden nanometer particle has stable dispersiveness when LCST and UCST, the functionalization that the technique study metal nanoparticle that this section of document provides a reliable aspect combines with high molecular polymer coat.
This body structure of tetramethylolmethane is utilized to have the symmetry of height, little toxicity, in conjunction with polymerization processs such as ring-opening polymerization, esterification and atom transfer radical polymerization, tetramethylolmethane side base is introduced the polymethyl acrylic acid N with the temperature-responsive of UCST, N-dimethylamino ethyl ester segment and the disulfide linkage segment with redox responsiveness, can prepare the embedding forging multipolymer of grafting with the four arm stars temperature-responsive that is structure and redox responsiveness, this will have widespread use in fields such as biomedicine, nano-medicament carriers.
Summary of the invention
The object of the present invention is to provide a kind of preparation method with four arm star polymer stabilizing nano-micelles of UCST and redox responsiveness.
The embedding forging polymkeric substance that the object of the invention is the temperature-responsive using having UCST is incorporated on tetramethylolmethane as side chain, make obtained graft copolymer have good branched structure, biocompatibility, biological degradability, biological activity, UCST temperature-responsive, redox responsiveness simultaneously, and soluble in water for this graft copolymer obtaining is had the temperature-responsive of UCST and the stable nanometer micelle of hydrogen reduction responsiveness.The commercial tetramethylolmethane of the present invention, 6-caprolactone monomer and methacrylic acid N, N-dimethylamino ethyl ester monomer, thio-2 acid etc., adopt the polymerization processs such as ring-opening polymerization, esterification and atom transfer radical polymerization, prepare temperature-responsive and the redox responsiveness grafting-embedding forging multipolymer of the UCST of four arm stars of different (PC-ss-polymethyl acrylic acid N, the N-dimethylamino ethyl ester) side chain of a series of monomer ratio.
A kind of preparation method with four arm star polymer stabilizing nano-micelles of UCST and redox responsiveness that the present invention proposes, concrete steps are as follows:
(1) tetramethylolmethane is activated in advance, add 6-caprolactone monomer and mix, obtain mixture; Add in mixture by ring-opening polymerization catalyst A again, the amount of substance that ring-opening polymerization catalyst A adds is 1 ~ 1.5 times of the amount of substance of the 6-caprolactone monomer added;
(2) at 60 ~ 120 DEG C by step (1) products therefrom vigorous stirring 24 ~ 48 hours, through concentrated, precipitation, suction filtration, and after vacuum-drying, the macromole graftomer (Star PCL) that to obtain with four arm stars be structure;
(3) bromizating agent B and alcohols C is carried out react preparation one end to be hydroxyl one end is the bromide of bromine;
(4) the macromole graftomer that step (2) obtains is dissolved in solvent D, add the dewatering agent E of thio-2 acid and macromole graftomer (Star PCL) terminal hydroxy groups or amino mole number 1 ~ 10 times amount, obtain the polymkeric substance (Star PCL-ss) with disulfide linkage;
(5) bromide of to be hydroxyl one end be in the one end Star PCL-ss of step (4) gained and step (3) obtained bromine proceeds esterification, obtains the macromole evocating agent (Star PCL-ss-Br) of atom transfer radical polymerization (ATRP);
(6) the ATRP macromole evocating agent of step (5) gained is dissolved in solvent F; add monomer methacrylic acid N; N-dimethylamino ethyl ester; monomer methacrylic acid N; the concrete add-on of N-dimethylamino ethyl ester is determined by designed molecular weight and performance thereof; add catalyzer cuprous bromide, coordination agent and N; N, N', N; ' N''-five methyl diethylentriamine; system is reacted under argon gas or nitrogen protection, and temperature of reaction is 40 ~ 120 DEG C, reacts 2 ~ 24 hours; and through precipitation, vacuum-drying, namely obtain product (Star PCL-
b-PDMAEMA);
(7) be dissolved in solvent F by step (6) products therefrom, add 1, in 3-N-morpholinopropanesulfonic acid, vinegar stirs and spends the night, and carries out completely quaternized, obtains final required product (quaternised Star PCL-
b-PDMAEMA).
In the present invention, described ring-opening polymerization catalyst A is a certain in the toluene solution of stannous iso caprylate, the toluene solution of stannous octoate, the diethyl ether solution of hydrogenchloride, native hydroxyl acid or trifluoromethanesulfonic acid.
In the present invention, described bromizating agent B is any one in 2-bromo isobutyl acylbromide, N-bromo-succinimide, 2 bromo propionyl bromide or bromoacetyl bromide.
In the present invention, described alcohols C is ethylene glycol, any one in 1,3-PD or 2,3-butanediol.
In the present invention, described solvent D is one or more in tetrahydrofuran (THF), benzene, ether or tetracol phenixin.
In the present invention, described dewatering agent E is one or both in N, N-dicyclohexylcarbodiimide, DMAP, chlorsulfonic acid or thionyl chloride.
In the present invention, described solvent F to be described solvent F be in tetrahydrofuran (THF), benzene, ether or tetracol phenixin one or more.
Beneficial effect of the present invention is:
Raw material sources of the present invention are extensive, tetramethylolmethane used, 6-caprolactone, methacrylic acid N, N-dimethylamino ethyl ester monomer, thio-2 acid, dewatering agent, solvent, catalyzer, coordination agent, initiator, bromizating agent, 1,3-N-morpholinopropanesulfonic acid lactones etc. all can suitability for industrialized production, and synthetic method is simple.Synthesis the amphipathic embedding forging multipolymer of grafting that is structure with four arm stars has the temperature-responsive of UCST, redox responsiveness, biocompatibility and biodegradability.Multipolymer can be assembled into stable nanometer micelle easily in water.Gained stable nanometer micelle has temperature-responsive, biological degradability and biocompatibility, has a wide range of applications in fields such as drug controlled release carrier, nano-reactor, biological intelligence switch, biosensors.
Accompanying drawing explanation
Fig. 1: the structural representation with the preparation method of four arm star polymer stabilizing nano-micelles of UCST and redox responsiveness prepared by embodiment 1.
Embodiment
Following examples further illustrate of the present invention, instead of limit the scope of the invention.
This four arm star is that the temperature-responsive with UCST of structure and the molecular structure magnetic nuclear resonance analyzer (NMR) of redox responsiveness grafting-embedding forging multipolymer and Fourier transform infrared spectrometer (FTIR) measure.Lower critical solution temperature (LCST) and high Kraft point (UCST) ultraviolet-visible spectrophotometer of band thermal station measure, LCST is defined as temperature corresponding when transmittance is down to 50% of initial value, and UCST is defined as temperature corresponding when transmittance rises to 200% of initial value.Assembling gained nano-micelle transmission electron microscope (TEM) and atomic force microscope (AFM) measure.Nano-micelle particle diameter dynamic laser light scattering instrument (DLS) measures.
Embodiment 1
Take tetramethylolmethane 0.2 gram through overactivation in round-bottomed flask; with 20 grams of 6-caprolactone stirring and dissolving; add 175 μ L stannous iso caprylates again; through vacuumizing-inflated with nitrogen process 3 times; and react 12 hours in 60 DEG C of oil baths under nitrogen protection, products therefrom is precipitated, suction filtration; vacuum-drying, obtains the high polymer (four arm polycaprolactones) of four arm stars.Then taking bromo isobutyryl 7.5 grams dropwise joins in the mixing solutions of 60ml ethylene glycol and 3.5 grams of triethylamines, vigorous stirring 2 hours under the condition of 0 DEG C, at room temperature react 2 hours again, then put into 50 DEG C of oil bath pan reactions 5 hours, obtain the small molecules function bromide that a terminal hydroxy group one end is bromine.Take four arm polycaprolactone A 10 grams to be again dissolved in distillation and to dewater in tetrahydrofuran (THF); add thio-2 acid 3 grams; thionyl chloride 1.04 grams, DMAP (DMAP) 0.49 gram, through vacuumizing-inflated with nitrogen process 3 times; and under nitrogen protection room temperature reaction 48 hours; products therefrom is concentrated, precipitation, suction filtration; vacuum drying, obtains the four arm star polymkeric substance with disulfide linkage.Take 5 grams, the four arm star polymkeric substance with disulfide linkage to be dissolved in distillation and to dewater in tetrahydrofuran (THF), add small molecules function bromide 1.6 grams, thionyl chloride 0.55 gram, DMAP (DMAP) 0.28 gram, through vacuumizing-inflated with nitrogen process 3 times, and under nitrogen protection room temperature reaction 48 hours, products therefrom concentrates, precipitation, suction filtration, vacuum drying, obtain the macromole evocating agent of ATRP, take 1 gram of macromole evocating agent and be dissolved in N, in dinethylformamide, add methacrylic acid N, N-dimethylaminoethyl 0.27 gram, N, N, N', N, ' N''-five methyl diethylentriamine 120 μ l, add catalyzer cuprous bromide 0.082 gram again, through vacuumizing-inflated with nitrogen process 3 times, and react 2 hours in 40 DEG C of oil baths under nitrogen protection.Product deionized water is dialysed, and lyophilize, obtains the temperature-responsive with LCST and the redox responsiveness grafting-embedding forging multipolymer of four arms asteroids, obtain stable nanometer micelle by soluble in water for this multipolymer.Take and have LCST grafting-embedding forging copolymer 1 gram and be dissolved in anhydrous tetrahydro furan, add excessive 1,3-N-morpholinopropanesulfonic acid lactones, overnight at room temperature stirs, and products therefrom carries out suction filtration, washing, vacuum-drying.Obtain temperature-responsive and redox responsiveness grafting-embedding forging multipolymer thing that four arm stars are the UCST of structure, obtain stable nanometer micelle by soluble in water for this multipolymer.
Embodiment 2
Take tetramethylolmethane 0.2 gram through overactivation in round-bottomed flask; with 20 grams of 6-caprolactone stirring and dissolving; add 190 μ L stannous octoates again; through vacuumizing-inflated with nitrogen process 3 times; and react 24 hours in 80 DEG C of oil baths under nitrogen protection, products therefrom is precipitated, suction filtration; vacuum-drying, obtains the high polymer (four arm polycaprolactones) of four arm stars.Then taking bromo isobutyl acylbromide 7.5 grams dropwise joins in the mixing solutions of 60ml ethylene glycol and 3.5 grams of triethylamines, vigorous stirring 2 hours under the condition of 0 DEG C, at room temperature react 2 hours again, then put into 50 DEG C of oil bath pan reactions 5 hours, obtain the small molecules function bromide that a terminal hydroxy group one end is bromine.Taking four arm polycaprolactone 10 grams is again dissolved in anhydrous diethyl ether; add thio-2 acid 3.6 grams; dicyclohexylcarbodiimide (DCC) 1.8 grams, DMAP (DMAP) 0.49 gram, through vacuumizing-inflated with nitrogen process 3 times; and under nitrogen protection room temperature reaction 48 hours; products therefrom is concentrated, precipitation, suction filtration; vacuum drying, obtains the four arm star polymkeric substance with disulfide linkage.Take 5 grams, the four arm star polymkeric substance with disulfide linkage to be dissolved in distillation and to dewater in tetrahydrofuran (THF), add small molecules function bromide 1.6 grams, dicyclohexylcarbodiimide (DCC) 0.95 gram, DMAP (DMAP) 0.28 gram, through vacuumizing-inflated with nitrogen process 3 times, and under nitrogen protection room temperature reaction 48 hours, products therefrom concentrates, precipitation, suction filtration, vacuum drying, obtain the macromole evocating agent of ATRP, take 1 gram of macromole evocating agent and be dissolved in N, in dinethylformamide, add methacrylic acid N, N-dimethylaminoethyl 0.54 gram, N, N, N', N, ' N''-five methyl diethylentriamine 120 μ l, add catalyzer cuprous bromide 0.082 gram again, through vacuumizing-inflated with nitrogen process 3 times, and react 10 hours in 50 DEG C of oil baths under nitrogen protection.Product deionized water is dialysed, and lyophilize, obtains the temperature-responsive with LCST and the redox responsiveness grafting-embedding forging multipolymer of four arms asteroids, obtain stable nanometer micelle by soluble in water for this multipolymer.Take and have LCST grafting-embedding forging copolymer 1 gram and be dissolved in anhydrous diethyl ether, add excessive 1,3-N-morpholinopropanesulfonic acid lactones, overnight at room temperature stirs, and products therefrom carries out suction filtration, washing, vacuum-drying.Obtain temperature-responsive and redox responsiveness grafting-embedding forging multipolymer thing that four arm stars are the UCST of structure, obtain stable nanometer micelle by soluble in water for this multipolymer.
Embodiment 3
Take tetramethylolmethane 0.2 gram through overactivation in round-bottomed flask; with 20 grams of 6-caprolactone stirring and dissolving; add 210 μ L stannous octoates again; through vacuumizing-inflated with nitrogen process 3 times; and react 32 hours in 100 DEG C of oil baths under nitrogen protection, products therefrom is precipitated, suction filtration; vacuum-drying, obtains the high polymer (four arm polycaprolactones) of four arm stars.Then taking bromoacetyl bromide 6.6 grams dropwise joins in the mixing solutions of 50ml butyleneglycol and 3.5 grams of triethylamines, vigorous stirring 2 hours under the condition of 0 DEG C, at room temperature react 2 hours again, then put into 50 DEG C of oil bath pan reactions 5 hours, obtain the small molecules function bromide that a terminal hydroxy group one end is bromine.Taking four arm polycaprolactone 10 grams is again dissolved in anhydrous dimethyl benzene; add thio-2 acid 4.3 grams; dicyclohexylcarbodiimide (DCC) 1.8 grams, DMAP (DMAP) 0.49 gram, through vacuumizing-inflated with nitrogen process 3 times; and under nitrogen protection room temperature reaction 48 hours; products therefrom is concentrated, precipitation, suction filtration; vacuum drying, obtains the four arm star polymkeric substance with disulfide linkage.Take 5 grams, the four arm star polymkeric substance with disulfide linkage to be dissolved in distillation and to dewater in tetrahydrofuran (THF), add small molecules function bromide 1.17 grams, dicyclohexylcarbodiimide (DCC) 0.95 gram, DMAP (DMAP) 0.28 gram, through vacuumizing-inflated with nitrogen process 3 times, and under nitrogen protection room temperature reaction 48 hours, products therefrom concentrates, precipitation, suction filtration, vacuum drying, obtain the macromole evocating agent of ATRP, take 1 gram of macromole evocating agent and be dissolved in N, in dinethylformamide, add methacrylic acid N, N-dimethylaminoethyl 0.9 gram, N, N, N', N, ' N''-five methyl diethylentriamine 120 μ l, add catalyzer cuprous bromide 0.082 gram again, through vacuumizing-inflated with nitrogen process 3 times, and react 15 hours in 70 DEG C of oil baths under nitrogen protection.Product deionized water is dialysed, and lyophilize, obtains the temperature-responsive with LCST and the redox responsiveness grafting-embedding forging multipolymer of four arms asteroids, obtain stable nanometer micelle by soluble in water for this multipolymer.Take and have LCST grafting-embedding forging copolymer 1 gram and be dissolved in anhydrous dimethyl benzene, add excessive 1,3-N-morpholinopropanesulfonic acid lactones, overnight at room temperature stirs, and products therefrom carries out suction filtration, washing, vacuum-drying.Obtain temperature-responsive and redox responsiveness grafting-embedding forging multipolymer thing that four arm stars are the UCST of structure, obtain stable nanometer micelle by soluble in water for this multipolymer.
Embodiment 4
Take tetramethylolmethane 0.2 gram through overactivation in round-bottomed flask; with 20 grams of 6-caprolactone stirring and dissolving; add 220 μ L stannous octoates again; through vacuumizing-inflated with nitrogen process 3 times; and react 32 hours in 100 DEG C of oil baths under nitrogen protection, products therefrom is precipitated, suction filtration; vacuum-drying, obtains the high polymer (four arm polycaprolactones) of four arm stars.Then taking bromoacetyl bromide 6.6 grams dropwise joins in the mixing solutions of 43ml3-propylene glycol and 3.5 grams of triethylamines, vigorous stirring 2 hours under the condition of 0 DEG C, at room temperature react 2 hours again, then put into 50 DEG C of oil bath pan reactions 7 hours, obtain the small molecules function bromide that a terminal hydroxy group one end is bromine.Taking four arm polycaprolactone 10 grams is again dissolved in anhydrous tetracol phenixin; add thio-2 acid 4.9 grams; chlorsulfonic acid 1.02 grams, DMAP (DMAP) 0.49 gram, through vacuumizing-inflated with nitrogen process 3 times; and under nitrogen protection room temperature reaction 48 hours; products therefrom is concentrated, precipitation, suction filtration; vacuum drying, obtains the four arm star polymkeric substance with disulfide linkage.Take 5 grams, the four arm star polymkeric substance with disulfide linkage to be dissolved in distillation and to dewater in tetrahydrofuran (THF), add bromide B1.45 gram, dicyclohexylcarbodiimide (DCC) 0.95 gram, DMAP (DMAP) 0.28 gram, through vacuumizing-inflated with nitrogen process 3 times, and under nitrogen protection room temperature reaction 48 hours, products therefrom concentrates, precipitation, suction filtration, vacuum drying, obtain the macromole evocating agent of ATRP, take 1 gram of macromole evocating agent and be dissolved in N, in dinethylformamide, add methacrylic acid N, N-dimethylaminoethyl 1.8 grams, N, N, N', N, ' N''-five methyl diethylentriamine 120 μ l, add catalyzer cuprous bromide 0.082 gram again, through vacuumizing-inflated with nitrogen process 3 times, and react 20 hours in 100 DEG C of oil baths under nitrogen protection.Product deionized water is dialysed, and lyophilize, obtains the temperature-responsive with LCST and the redox responsiveness grafting-embedding forging multipolymer of four arms asteroids, obtain stable nanometer micelle by soluble in water for this multipolymer.Take and have LCST grafting-embedding forging copolymer 1 gram and be dissolved in anhydrous tetracol phenixin, add excessive 1,3-N-morpholinopropanesulfonic acid lactones, overnight at room temperature stirs, and products therefrom carries out suction filtration, washing, vacuum-drying.Obtain temperature-responsive and redox responsiveness grafting-embedding forging multipolymer thing that four arm stars are the UCST of structure, obtain stable nanometer micelle by soluble in water for this multipolymer.
Embodiment 5
Take tetramethylolmethane 0.2 gram through overactivation in round-bottomed flask; with 20 grams of 6-caprolactone stirring and dissolving; add 260 μ L stannous octoates again; through vacuumizing-inflated with nitrogen process 3 times; and react 48 hours in 120 DEG C of oil baths under nitrogen protection, products therefrom is precipitated, suction filtration; vacuum-drying, obtains the high polymer (four arm polycaprolactones) of four arm stars.Then taking 2 bromo propionyl bromide 7.06 grams dropwise joins in the mixing solutions of 60ml ethylene glycol and 3.5 grams of triethylamines, vigorous stirring 2 hours under the condition of 0 DEG C, at room temperature react 2 hours again, then put into 120 DEG C of oil bath pan reactions 48 hours, obtain the small molecules function bromide that a terminal hydroxy group one end is bromine.Taking four arm polycaprolactone 10 grams is again dissolved in anhydrous tetrahydro furan; add thio-2 acid 5.52 grams; dicyclohexylcarbodiimide (DCC) 1.8 grams, DMAP (DMAP) 0.49 gram, through vacuumizing-inflated with nitrogen process 3 times; and under nitrogen protection room temperature reaction 48 hours; products therefrom is concentrated, precipitation, suction filtration; vacuum drying, obtains the four arm star polymkeric substance with disulfide linkage.Take 5 grams, the four arm star polymkeric substance with disulfide linkage to be dissolved in distillation and to dewater in tetrahydrofuran (THF), add small molecules function bromide 1.5 grams, dicyclohexylcarbodiimide (DCC) 0.95 gram, DMAP (DMAP) 0.28 gram, through vacuumizing-inflated with nitrogen process 3 times, and under nitrogen protection room temperature reaction 48 hours, products therefrom concentrates, precipitation, suction filtration, vacuum drying, obtain the macromole evocating agent of ATRP, take 1 gram of macromole evocating agent and be dissolved in N, in dinethylformamide, add methacrylic acid N, N-dimethylaminoethyl 1.35 grams, N, N, N', N, ' N''-five methyl diethylentriamine 120 μ l, add catalyzer cuprous bromide 0.082 gram again, through vacuumizing-inflated with nitrogen process 3 times, and react 24 hours in 120 DEG C of oil baths under nitrogen protection.Product deionized water is dialysed, and lyophilize, obtains the temperature-responsive with LCST and the redox responsiveness grafting-embedding forging multipolymer of four arms asteroids, obtain stable nanometer micelle E by soluble in water for this multipolymer.Take and have LCST grafting-embedding forging copolymer 1 gram and be dissolved in anhydrous tetrahydro furan, add excessive 1,3-N-morpholinopropanesulfonic acid lactones, overnight at room temperature stirs, and products therefrom carries out suction filtration, washing, vacuum-drying.Obtain temperature-responsive and redox responsiveness grafting-embedding forging multipolymer thing that four arm stars are the UCST of structure, obtain stable nanometer micelle by soluble in water for this multipolymer.
Claims (7)
1. there is a preparation method for four arm star polymer stabilizing nano-micelles of UCST and redox responsiveness, it is characterized in that concrete steps are as follows:
(1) tetramethylolmethane is activated in advance, add 6-caprolactone monomer and mix, obtain mixture; Add in mixture by ring-opening polymerization catalyst A again, the amount of substance that ring-opening polymerization catalyst A adds is 1 ~ 1.5 times of the amount of substance of the 6-caprolactone monomer added;
(2) at 60 ~ 120 DEG C by step (1) products therefrom vigorous stirring 24 ~ 48 hours, through concentrated, precipitation, suction filtration, and after vacuum-drying, the macromole graftomer (Star PCL) that to obtain with four arm stars be structure;
(3) bromizating agent B and alcohols C is carried out react preparation one end to be hydroxyl one end is the bromide of bromine;
(4) the macromole graftomer that step (2) obtains is dissolved in solvent D, add the dewatering agent E of thio-2 acid and macromole graftomer (Star PCL) terminal hydroxy groups or amino mole number 1 ~ 10 times amount, obtain the polymkeric substance (Star PCL-ss) with disulfide linkage;
(5) bromide of to be hydroxyl one end be in the one end Star PCL-ss of step (4) gained and step (3) obtained bromine proceeds esterification, obtains the macromole evocating agent (Star PCL-ss-Br) of atom transfer radical polymerization (ATRP);
(6) the ATRP macromole evocating agent of step (5) gained is dissolved in solvent F; add monomer methacrylic acid N; N-dimethylamino ethyl ester; monomer methacrylic acid N; the concrete add-on of N-dimethylamino ethyl ester is determined by designed molecular weight and performance thereof; add catalyzer cuprous bromide, coordination agent and N; N, N', N; ' N''-five methyl diethylentriamine; system is reacted under argon gas or nitrogen protection, and temperature of reaction is 40 ~ 120 DEG C, reacts 2 ~ 24 hours; and through precipitation, vacuum-drying, namely obtain product (Star PCL-
b-PDMAEMA);
(7) be dissolved in solvent F by step (6) products therefrom, add 1, in 3-N-morpholinopropanesulfonic acid, vinegar stirs and spends the night, and carries out completely quaternized, obtains final required product (quaternised Star PCL-
b-PDMAEMA).
2. the preparation method with four arm star polymer stabilizing nano-micelles of UCST and redox responsiveness according to claim 1, is characterized in that described ring-opening polymerization catalyst A is any one in the toluene solution of stannous iso caprylate, the toluene solution of stannous octoate, the diethyl ether solution of hydrogenchloride, native hydroxyl acid or trifluoromethanesulfonic acid.
3. the preparation method with four arm star polymer stabilizing nano-micelles of UCST and redox responsiveness according to claim 1, is characterized in that described bromizating agent B is any one in 2-bromo isobutyl acylbromide, N-bromo-succinimide, 2 bromo propionyl bromide or bromoacetyl bromide.
4. the preparation method with four arm star polymer stabilizing nano-micelles of UCST and redox responsiveness according to claim 1, is characterized in that described alcohols C is ethylene glycol, any one in 1,3-PD or 2,3-butanediol.
5. the preparation method with four arm star polymer stabilizing nano-micelles of UCST and redox responsiveness according to claim 1, is characterized in that described solvent D is one or more in tetrahydrofuran (THF), benzene, ether or tetracol phenixin.
6. the preparation method with four arm star polymer stabilizing nano-micelles of UCST and redox responsiveness according to claim 1, it is characterized in that described dewatering agent E is one or both in N, N-dicyclohexylcarbodiimide, DMAP, chlorsulfonic acid or thionyl chloride.
7. the preparation method with four arm star polymer stabilizing nano-micelles of UCST and redox responsiveness according to claim 1, it is characterized in that described solvent F to be described solvent F be in tetrahydrofuran (THF), benzene, ether or tetracol phenixin one or more.
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| CN106893055A (en) * | 2017-03-15 | 2017-06-27 | 北京科技大学 | A kind of preparation and its application with quadruple response block copolymer |
| CN108641096A (en) * | 2018-04-27 | 2018-10-12 | 同济大学 | With weary oxygen, pH dual responsiveness mixed micelles and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105802106A (en) * | 2016-04-22 | 2016-07-27 | 同济大学 | Preparation method of supermolecular nanometer aggregate with triple responses of temperature, UV (ultraviolet) and reducing agent |
| CN105802106B (en) * | 2016-04-22 | 2018-02-09 | 同济大学 | A kind of preparation method of the supermolecule nano aggregation of temperature, UV and the triple responses of reducing agent |
| CN106866902A (en) * | 2017-01-11 | 2017-06-20 | 华南理工大学 | The preparation method of a kind of degradable double-bang firecracker emergencing copolymer and its carrying medicament and golden nanometer particle micella and application |
| CN106893055A (en) * | 2017-03-15 | 2017-06-27 | 北京科技大学 | A kind of preparation and its application with quadruple response block copolymer |
| CN106893055B (en) * | 2017-03-15 | 2019-02-01 | 北京科技大学 | A kind of preparation and its application with quadruple responsiveness block copolymer |
| CN108641096A (en) * | 2018-04-27 | 2018-10-12 | 同济大学 | With weary oxygen, pH dual responsiveness mixed micelles and preparation method thereof |
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