CN102304194A - Thermal sensitivity adjustable biocompatible core-shell structured polymer nanogel and preparation method thereof - Google Patents
Thermal sensitivity adjustable biocompatible core-shell structured polymer nanogel and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a thermal sensitivity adjustable biocompatible core-shell structured polymer nanogel and a preparation method thereof. The polymer nanogel is a straight-chain thermosensitive nanogel or a comblike thermosensitive nanogel, wherein in the straight-chain thermosensitive nanogel, a straight-chain polymer chain transfer agent is taken as a shell, thermosensitive polymer prepared through polymerization reaction of methacrylate monomer containing two oxyethyl groups, methacrylate monomer containing 8-9 ethyoxyl side chains and a crosslinking agent of polyethylene glycol dimethacrylate is taken as a core, and a mass ratio of the core to the shell is (2-20):1; and in the comblike thermosensitive nanogel, a comblike polymer chain transfer agent is taken as a shell, thermosensitive polymer prepared through polymerization reaction of methacrylate monomer containing two oxyethyl groups, methacrylate monomer containing 8-9 ethyoxyl side chains and a crosslinking agent of polyethylene glycol dimethacrylate is taken as a core, and a mass ratio of the core to the shell is (2-20):1. The obtained nanogel has uniform size, good colloidal stability and biocompatibility, and can be widely applied to personal care products and nanomedicine aspect.
Description
Technical field
The present invention relates to a kind of high molecular nanometer gel and preparation method thereof, bio-compatibility high molecular nanometer gel that particularly a kind of thermo-sensitivity is adjustable and preparation method thereof.
Background technology
Reversible addition-fracture chain transfer polymerization (RAFT) is a kind of active controllable free radical polymerization process that closely grows up during the last ten years; The accurate molecular weight of controlling polymers; The synthetic polymer has narrow dispersion polymerization, can synthesize the polymer of multiple shape such as the functionalized macromolecular of complex constructions such as block-wise, star, dendroid and comb shape.The heteropolymerization system especially middle mutually RAFT polymerization of water-dispersion is a kind of eco-friendly polymerization process; Can reduce pollution; Practice thrift cost; To bring great potential to the production of the polymeric material of novel better quality, for it provides chance in the application aspect polymer production, coating, personal care product and the nanometer medicine.
The nanogel of nucleocapsid structure has good colloidal stability; It is a kind of intelligent nanometer soft material to temperature response; Can wrap up hydrophobic molecule, improve the water-soluble of molecule, and can reach and vary with temperature and the intelligent effect that discharges institute's carrier band molecule.Studying more biocompatible materials is the block macromolecular of polyoxyethylene class, like PEO-PLA, and PEO-PLGA, main first synthetic macromolecule forms nanoparticle through the emulsion or the nanometer precipitator method then.Along with the development of makeup and nanometer pharmaceutical industries, intelligentized nanogel is favored in the application in some high and new technology fields day by day.For example can change the polymer that produces quick structure phase change to outside atmosphere (like pH, temperature, ionic strength, illumination etc.), the application aspect makeup and bio-science is more and more important.Studying maximum polymers to temperature response is to gather sec.-propyl third rare acid amides PNIPAM, because it has the invert point close with human temperature (~ 32 ℃).Anze victorys etc. utilize (dispersion) polymerization of RAFT deposition successfully to prepare to have nuclear the nanogel of (gathering sec.-propyl third rare acid amides) shell (gathering N, N '-dimethyl propylene acid amides) structure under water-dispersion phase condition under microwave condition.Discoveries such as Lutz are skeleton with C-C, are the PEG analogue of the comb shape structure of side chain with the oligomeric ethylene glycol, in the aqueous solution or Physiological Medium, have adjustable low solution critical temperature (LCST).Therefore comb shape PEG analogue has the double properties of PEG and PNIPAM concurrently.Cai etc. utilize radical polymerization to synthesize comb shape PEG analogue list dispersion microgel, and have obtained having the microgel of Different L CST through the ratio that changes two kinds of polymerization single polymerization monomers.People such as Lutz discover, the polymer with this comb shape PEG analogue monomer polymerization forms not only has narrow adjustable LCST, and the conversion process completely reversibility, is better than PNIPAM.Because the PEG analogue has bio-compatibility, biodegradability, adjustable sharp thermo-sensitivity, for it provides bright prospects in the application aspect personal care and the nanometer medicine.
Summary of the invention
One of the object of the invention is to provide a kind of macromolecular chain transfer agent.
Two of the object of the invention is to provide the high molecular nanometer gel of the adjustable bio-compatibility nucleocapsid structure of a kind of thermo-sensitivity.
Two of the object of the invention is to provide the preparation method of this nanogel.
For achieving the above object, the reaction mechanism that the present invention adopts is:
According to above-mentioned reaction mechanism, the present invention adopts following technical scheme:
A kind of macromolecular chain transfer agent is characterized in that the structural formula of this chain-transfer agent is:
a. linear polymer chain transfer agent:
, where n =? 22 ~ 220;
b. comb polymer chain transfer agent:
, where n =? 10 ~ 100.
The high molecular nanometer gel of the bio-compatibility nucleocapsid structure that a kind of thermo-sensitivity is adjustable adopts above-mentioned chain-transfer agent, it is characterized in that this high molecular nanometer gel is:
A. straight chain thermo-sensitivity nanogel: this nanogel is to be shell with the straight chain polymer chain-transfer agent; Press (80 ~ 100) by the methacrylate monomer that contains two oxyethyl groups, the methacrylate monomer that contains 8 ~ 9 oxyethyl group side chains and coupling agent polyethylene glycol dimethacrylate: (0 ~ 20): the mol ratio of (3 ~ 6) is nuclear through the thermo-sensitivity polymer that polyreaction forms; And nuclear and shell mass ratio be (2 ~ 20): 1;
B. comb shape thermo-sensitivity nanogel: this nanogel is to be shell with comb shape macromolecular chain transfer agent; Contain two oxyethyl groups, the methacrylate monomer that contains 8 ~ 9 oxyethyl group side chains and coupling agent polyethylene glycol dimethacrylate and press (80 ~ 100): (0 ~ 20): the mol ratio of (3 ~ 6) is nuclear through the thermo-sensitivity polymer that polyreaction forms; And the mass ratio of nuclear and shell is (2 ~ 20): 1.
The particle diameter of above-mentioned high molecular nanometer gel is 40 ~ 100 nanometers, and the particle size dispersion degree is less than 0.15.
A kind of method for preparing the high molecular nanometer gel of the adjustable bio-compatibility nucleocapsid structure of above-mentioned thermo-sensitivity is characterized in that the concrete steps of this method are:
A. prepare the straight chain polymer chain-transfer agent: chain-transfer agent ethyl cyanopentanoic acid trithio carbonic ether, polyoxyethylene glycol and 4-Dimethylamino pyridine are pressed (2 ~ 10): 1: the mol ratio of (0.05 ~ 1) is dissolved in the methylene dichloride; Under inert atmosphere; In the ice-water bath; Divide three times and add N; N '-dicyclohexyl carbodiimide; N, the mol ratio of N '-dicyclohexyl carbodiimide and chain-transfer agent is 1 ~ 2:1; Behind the stirring reaction 1 ~ 6 hour, at room temperature stirring reaction is 12 ~ 36 hours; Behind the suction filtration, filtrating is splashed in the ether, obtain deposition, this throw out is obtained yellow solid straight chain polymer chain-transfer agent through separating to purify;
B. prepare the straight chain nanogel: with step a gained straight chain polymer chain-transfer agent; Monomer and coupling agent polyethylene glycol dimethacrylate are according to 1: (30 ~ 200): the mol ratio of (3 ~ 10) is soluble in water; Wherein the mass percent concentration of monomer in water is 0.5 ~ 5%; After the sealing; In ice-water bath; Under inert atmosphere; Behind constant temperature under 70 ℃ of temperature; The radical initiator 2 that adds deoxygenation; 2'-azo (2-methyl-propyl amidine) dihydrochloride storing solution; The mol ratio of its consumption and macromolecular chain transfer agent is 0.01 ~ 10:1; React after 2.5 hours, be immersed in quencher reaction in the frozen water, obtain appearing nanogel dispersion liquid azury; Described monomer is served as reasons the methacrylate monomer that contains two oxyethyl groups and the methacrylate monomer that contains 8 ~ 9 oxyethyl group side chains by (80 ~ 100): the mol ratio of (0 ~ 20) is formulated;
The number-average molecular weight of above-mentioned polyoxyethylene glycol is 1000-10000.
A kind of method for preparing the high molecular nanometer gel of the adjustable bio-compatibility nucleocapsid structure of above-mentioned thermo-sensitivity is characterized in that the concrete steps of this method are:
A. prepare comb shape macromolecular chain transfer agent: with 4-cyanopentanoic acid dithiobenzoic acid ester, methoxypolyethylene glycol methacrylic ester, Diisopropyl azodicarboxylate by 1: (10 ~ 100): the mol ratio of (0.01 ~ 2) is dissolved in the ethanol; After stirring; Deoxygenation is 50 minutes in ice-water bath, and anaerobic was reacted 3.5 hours under 70 ℃ of temperature again; Be then in the ice-water bath, under air atmosphere, in normal hexane, after centrifugation, vacuum-drying, obtain red thick liquid, be required comb shape macromolecular chain transfer agent with methylene dichloride dilution postprecipitation;
B. prepare comb shape polymer thermo-sensitivity nanogel: with step a gained comb shape macromolecular chain transfer agent; Monomer; The coupling agent polyethylene glycol dimethacrylate; According to 1: (30 ~ 200): the mol ratio of (3 ~ 10) is soluble in water; Wherein the mass percent concentration of monomer in water is 0.5 ~ 5%; After the sealing; In ice-water bath; Under inert atmosphere; The adding that under 70 ℃ of temperature, adds deoxygenation is the radical initiator 2 of deoxygenation; 2'-azo (2-methyl-propyl amidine) dihydrochloride storing solution; Radical initiator and consumption are that the mol ratio of macromolecular chain transfer agent is 0.01 ~ 10:1; After the isothermal reaction 6 hours; Quencher reaction in frozen water; Obtain appearing erythroid nanogel colloidal sol, be the comb shape nanogel; Described monomer is served as reasons the methacrylate monomer that contains two oxyethyl groups and the methacrylate monomer that contains 8 ~ 9 oxyethyl group side chains by (80 ~ 100): the mol ratio of (0 ~ 20) is formulated.
The present invention is through in the aqueous solution, and two kinds of monomers that have different oligomeric ethylene glycol side chains of copolymerization through changing both mol ratios, obtain the high molecular nanometer gel with thermo-sensitivity of monodispersity; And control the size of nanogel through changing chain-transfer agent and monomeric ratio.Gained nanogel size is even, has good colloidal stability and bio-compatibility, can be widely used in personal care product and nanometer medicine aspect.
The inventive method is carried out in water-dispersion mutually, avoids the use of organic solvent, belongs to environmentally friendly preparation technology; Present method is simple, and one-step synthesis is realized large-scale industrial production easily.
Description of drawings
Fig. 1 is that the nuclear-magnetism of small molecules chain-transfer agent 4-cyanopentanoic acid dithiobenzoic acid ester (a), polyoxyethylene glycol (b) and straight chain polymer chain-transfer agent (c) characterizes.
Fig. 2 is the granularity phenogram of the embodiment of the invention one gained
nanogel.
Fig. 3The embodiment of the invention two gained
The granularity phenogram of nanogel.
Fig. 4 doesThe embodiment of the invention three gained
The granularity phenogram of nanogel.
Fig. 5 is the pattern phenogram of the embodiment of the invention one gained
nanogel.
Fig. 6The embodiment of the invention two gained
The pattern phenogram of nanogel.
Fig. 7 doesThe embodiment of the invention three gained
The pattern phenogram of nanogel.
Fig. 8 is that the nuclear-magnetism of comb shape chain-transfer agent of the present invention and comb shape nanogel characterizes, and wherein A is 22 ℃ of comb shape chain-transfer agents; B is 50 ℃ of comb shape chain-transfer agents; C is 23 ℃ of comb shape nanogel balls; D is 40 ℃ of comb shape nanogels.
Fig. 9 down uses laser particle analyzer test result at 25 ℃ for the surface has the high molecular nanogel of comb shape in 90% bovin serum albumin solution.
Figure 10 is the cytotoxicity test of nanogel of the present invention.Wherein 1-surface has the comb shape polymer, contains the nanogel (154 nm) of trithio carbonic ether; 2-surface has the nanogel (54 nm) that straight chain PEG contains the trithio carbonic ether; 3-surface has the nanogel (58 nm) that straight chain PEG contains the trithio carbonic ether; 4-surface has the comb shape polymer, contains the nanogel of dithioesters (61 nm).
Embodiment
After specific embodiment of the present invention being described at present.The preparation of chain-transfer agent ethyl cyanopentanoic acid trithio carbonic ether makes according to literature method.（（1）?Shen,?W.?Q.;?Qiu,?Q.?A.;?Wang,?Y.;?Miao,?M.?A.;?Li,?B.?S.;?Zhang,?T.?S.;?Cao,?A.?N.;?An,?Z.?S.?
Macromol.?Rapid?Commun.? 2010, 31,?1444-1448.?（2）Ishitake,?K.;?Satoh,?K.;?Kamigaito,?M.;?Okamoto,?Y.?
Angew.?Chem.?In.?Ed.? 2009, 48,?1991-1994.）
Embodiment 1: concrete steps are following:
1. prepare the straight chain polymer chain-transfer agent: with ethyl cyanopentanoic acid trithio carbonic ether 5.6909 g of 0.6148 g, polyoxyethylene glycol 5000 (PEG
5000) 0.142 g and 4-Dimethylamino pyridine 0.2 g be dissolved in the methylene dichloride (purification has dewatered) of 60 mL, is added in the flask of 150 mL to stir, and feeds nitrogen and keep oxygen-free environment, after stirring, is placed in the ice-water bath, keeps 0 ℃.Divide three times and add 0.467 g N, N '-dicyclohexyl carbodiimide.After 5 hours, return to room temperature 0 ℃ of reaction gradually, total coreaction is 35 hours under the room temperature.Suction filtration is removed white precipitate, filtrating is splashed in the excessive ether again, and suction filtration is collected solid.Further solid is dissolved in methylene dichloride again, crosses chromatography column.Finally obtain 3.0 g yellow solids, be straight chain polymer chain-transfer agent I.
The nuclear-magnetism characterization result is:
1H?NMR?(CDCl
3,?500?MHz)?
δ:?4.25?(m,?2H,?CO
2CH
2),?3.80-3.47?(m,?CH
2O),?3.37?(s,?3H,?OCH
3),?3.34?(q,?2?H,?CH
3CH
2),?2.66?(m,?2H,?CH
2CO
2),?2.52?(m,?1H,?C(CN)CH
2),?2.38?(m,?1H,?C(CN)CH
2),?1.87?(s,?3H,?CH3C(CN)),?1.35?(t,?3H,?CH
3CH
2)。
Can find out by Fig. 1: the characteristic peak of the medium and small molecular chain transfer agent of the last existing A of C, the characteristic peak of polyoxyethylene glycol is arranged again, and do not have other impurity peaks, illustrate that C is consistent with the structural formula of anticipation, be the product that we want, and have very high purity (>=99%).
2. prepare the straight chain nanogel: with step 1 gained straight chain polymer chain-transfer agent (9.8 mg), monomer 2-methyl-2-vinylformic acid-2-(2-methoxy ethoxy) ethyl ester (MEO
2MA) (52.5 mg), the coupling agent polyethylene glycol dimethacrylate (
M n ~ 750) (4 mg), water (5.0 g) joins the jaw bottle of sealing, in ice-water bath, with nitrogen bubble deoxygenation 40 minutes, the deoxygenation 20 minutes under same condition simultaneously of initiator 2,2'-azo (2-methyl-propyl amidine) dihydrochloride.Again reaction vessel is put into 70 ℃ good oil bath stirring reaction of preheating in advance; After treating temperature-stable; Add 50 μ L deoxygenation 2; 2'-azo (2-methyl-propyl amidine) dihydrochloride storing solution (contains 0.192 mg; 0.7 μ mol); After the isothermal reaction 2.5 hours, reaction vessel is immersed in quencher reaction in the frozen water, obtains appearing blue nanogel; Its particle diameter is that 56.3 nm dispersity are 0.06, referring to Fig. 2.
Embodiment 2:Concrete preparation process is following:
Preparation comb shape macromolecular chain transfer agent: take by weighing 4-cyanopentanoic acid dithiobenzoic acid ester (82.3 mg), the methoxypolyethylene glycol methacrylic ester (7.00 g,
M n =475), Diisopropyl azodicarboxylate (12.1 mg) is dissolved in the 14.74 mL ethanol; Stir back sampling, bubbling deoxygenation 50 minutes in ice-water bath then places 70 ℃ of oil bath anaerobics reactions after 3.5 hours again; Reaction vessel is placed ice-water bath, and be exposed in the air.With reaction mixture with methylene dichloride dilution postprecipitation in normal hexane, centrifugal, repeat 3 times after, vacuum-drying goes out to desolvate, and obtains red thick liquid, is comb shape macromolecular chain transfer agent.
1H NMR (500 MHz, CDCl3): 7.86-7.35 ppm (m, C6H5-), 4.06 ppm (
s, COOCH2_), 3.78-3.50 ppm (m ,-O (CH2) 2O-), 3.37 ppm (s ,-OCH3), 2.0-1.5 ppm (main chain-CH2-), 1.0-0.8 ppm (s ,-CH3).
M n =5300 (GPC, PEO standard specimens),
, M w / M n =(1.10 GPC, PEO standard specimen);
M n =15500 (
1H NMR).
2. prepare the comb shape nanogel: the comb shape macromolecular chain transfer agent (27.4 mg) that step 1 is prepared, monomer 2-methyl-2-vinylformic acid-2-(2-methoxy ethoxy) ethyl ester (MEO
2MA) (50 mg), the coupling agent polyethylene glycol dimethacrylate (
M n ~ 750) (4 mg), water (5.0 g) joins the jaw bottle of sealing, in ice-water bath, with nitrogen bubble deoxygenation 40 minutes, the deoxygenation 20 minutes under same condition simultaneously of initiator 2,2'-azo (2-methyl-propyl amidine) dihydrochloride.Again reaction vessel is put into 70 ℃ good oil bath stirring reaction of preheating in advance; After treating temperature-stable; Add 50 μ L deoxygenation 2; 2'-azo (2-methyl-propyl amidine) dihydrochloride storing solution (contains 0.192 mg; 0.7 μ mol); After the isothermal reaction 2.5 hours, reaction vessel is immersed in quencher reaction in the frozen water, obtains appearing blue nanogel colloidal sol.Particle diameter is that 56.5 nm dispersity are 0.08, referring to Fig. 3.
Embodiment 3:Concrete preparation process is following:
1. prepare comb shape macromolecular chain transfer agent: step is with embodiment one;
2. prepare the comb shape nanogel: with comb shape macromolecular chain transfer agent (34 mg), monomer 2-methyl-2-vinylformic acid-2-(2-methoxy ethoxy) ethyl ester (MEO
2MA) (74 mg), methoxypolyethylene glycol methacrylic ester (OEGMA
M n ~ 475,31 mg) the coupling agent polyethylene glycol dimethacrylate (
M n ~ 750,4.9 mg), acetate buffer (5 mL) joins the jaw bottle of sealing, in ice-water bath, and with nitrogen bubble deoxygenation 40 minutes, the deoxygenation 20 minutes under same condition simultaneously of initiator 2,2'-azo (2-methyl-propyl amidine) dihydrochloride.Again reaction vessel is put into 70 ℃ good oil bath stirring reaction of preheating in advance; After treating temperature-stable; Add 50 μ L deoxygenation 2; 2'-azo (2-methyl-propyl amidine) dihydrochloride storing solution (containing 0.24 mg); After the isothermal reaction 6 hours; Reaction vessel is immersed in quencher reaction in the frozen water, obtains appearing erythroid nanogel colloidal sol.Particle diameter is 54.1 nm, and dispersity is 0.06, referring to Fig. 4.
Embodiment 4: with step 1 gained straight chain polymer chain-transfer agent (18.6 mg), monomer 2-methyl-2-vinylformic acid-2-(2-methoxy ethoxy) ethyl ester (MEO
2MA) (105.0 mg), methoxypolyethylene glycol methacrylic ester (OEGMA
M n ~ 475,25.2 mg), the coupling agent polyethylene glycol dimethacrylate (
M n ~ 750) (8.0 mg), water (10.0 g) joins the jaw bottle of sealing, in ice-water bath, with nitrogen bubble deoxygenation 40 minutes, the deoxygenation 20 minutes under same condition simultaneously of initiator 2,2'-azo (2-methyl-propyl amidine) dihydrochloride.Again reaction vessel is put into 70 ℃ good oil bath stirring reaction of preheating in advance; After treating temperature-stable; Add 50 μ L deoxygenation 2; 2'-azo (2-methyl-propyl amidine) dihydrochloride storing solution (0.24 mg); After the isothermal reaction 2.5 hours; Reaction vessel is immersed in quencher reaction in the frozen water, obtains appearing blue nanogel.Particle diameter is 82.5 nm, and dispersity is 0.14.
Prepared sample in the foregoing description carries out each item characteristic test with instrument, and its test case and result thereof are following:
The granularity of nanogel characterizes:Detect ydrodynamics diameter and the dispersity of synthetic nanogel 25 ℃ under with laser particle size analyzer, can find out that by the particle size distribution figure of figure two the nanoparticle dispersity that utilizes this kind method to obtain is very little, very even referring to Fig. 2, Fig. 3 and Fig. 4.Therefore this chain-transfer agent is described, very good to this monomer control in water.
The pattern of nanogel characterizes:All very even by the granularity that can find out every kind of nanogel among Fig. 5, Fig. 6, Fig. 7, dispersiveness is also fine.
The thermo-sensitivity of nanogel characterizes:By finding out among Fig. 8 that any variation does not take place the nuclear magnetic spectrogram of comb shape chain-transfer agent 22 ℃ and 50 ℃, therefore illustrates that chain-transfer agent does not have thermo-sensitivity.After this chain-transfer agent polymerization single polymerization monomer 2-methyl-2-vinylformic acid-2-(2-methoxy ethoxy) ethyl ester formed the comb shape nanogel, obvious change (arrow marks) took place at the nuclear-magnetism figure of 23 ℃ and 40 ℃ in nanogel.This is that therefore constantly curling makes it in 3.39 ppm place signal weaker because after the temperature rising, the hydrophobic part of post polymerization is along with the rising of temperature becomes more hydrophobic.Therefore prove that this nanogel has thermo-sensitivity.
The colloidal stability of nanogel:This nanogel has excellent colloidal stability in high salt concentration solution (1.5 M), 10% bovine serum albumen solution.Wherein in 1.5 M NaCl solution, keep colloidal stability to reach the several months; And but stable existence reaches 4 days in 90% bovine serum albumen solution.
Can find out by Fig. 9; Nanogel was diluted to 100% bovine serum after 4 days; The peak of proteic peak and nanometer ball Individual existence still in the serum; Size does not become; And do not detect big particle; Illustrate between nanogel and the serum and do not adsorb, so proof list is worn the high molecular nanogel of brush and sac like and had extremely strong anti-adsorptivity and stability.
The cytotoxicity test:Through lung cancer cell line being carried out cytotoxicity test with the MTT method, find that various nanogels can the pair cell toxigenicity under very high concentration, illustrate that these nanogels are Biosafeties.
Claims (5)
1. macromolecular chain transfer agent is characterized in that the structural formula of this chain-transfer agent is:
a. linear polymer chain transfer agent:
, where n =? 22 ~ 220?;
b. comb polymer chain transfer agent:
, where n =? 10 ~ 100.
2. the high molecular nanometer gel of the adjustable bio-compatibility nucleocapsid structure of a thermo-sensitivity adopts chain-transfer agent according to claim 1, it is characterized in that this high molecular nanometer gel is:
A. straight chain thermo-sensitivity nanogel: this nanogel is to be shell with the straight chain polymer chain-transfer agent; Press (80 ~ 100) by the methacrylate monomer that contains two oxyethyl groups, the methacrylate monomer that contains 8 ~ 9 oxyethyl group side chains and coupling agent polyethylene glycol dimethacrylate: (0 ~ 20): the mol ratio of (3 ~ 6) is nuclear through the thermo-sensitivity polymer that polyreaction forms; And nuclear and shell mass ratio be (2 ~ 20): 1;
B. comb shape thermo-sensitivity nanogel: this nanogel is to be shell with comb shape macromolecular chain transfer agent; Contain two oxyethyl groups, the methacrylate monomer that contains 8 ~ 9 oxyethyl group side chains and coupling agent polyethylene glycol dimethacrylate and press (80 ~ 100): (0 ~ 20): the mol ratio of (3 ~ 6) is nuclear through the thermo-sensitivity polymer that polyreaction forms; And the mass ratio of nuclear and shell is (2 ~ 20): 1.
3. the high molecular nanometer gel of the bio-compatibility nucleocapsid structure that thermo-sensitivity according to claim 2 is adjustable, the particle diameter that it is characterized in that described high molecular nanometer gel is 40 ~ 100 nanometers, the particle size dispersion degree is less than 0.15.
4. method for preparing according to the high molecular nanometer gel of the adjustable bio-compatibility nucleocapsid structure of claim 2 or 3 described thermo-sensitivitys is characterized in that the concrete steps of this method are:
A. prepare the straight chain polymer chain-transfer agent: chain-transfer agent ethyl cyanopentanoic acid trithio carbonic ether, polyoxyethylene glycol and 4-Dimethylamino pyridine are pressed (2 ~ 10): 1: the mol ratio of (0.05 ~ 1) is dissolved in the methylene dichloride; Under inert atmosphere; In the ice-water bath; Divide three times and add N; N '-dicyclohexyl carbodiimide; N, the mol ratio of N '-dicyclohexyl carbodiimide and chain-transfer agent is 1 ~ 2:1; Behind the stirring reaction 1 ~ 6 hour, at room temperature stirring reaction is 12 ~ 36 hours; Behind the suction filtration, filtrating is splashed in the ether, obtain deposition, this throw out is obtained yellow solid straight chain polymer chain-transfer agent through separating to purify;
B. prepare the straight chain nanogel: with step a gained straight chain polymer chain-transfer agent; Monomer and coupling agent polyethylene glycol dimethacrylate are according to 1: (30 ~ 200): the mol ratio of (3 ~ 10) is soluble in water; Wherein the mass percent concentration of monomer in water is 0.5 ~ 5%; After the sealing; In ice-water bath; Under inert atmosphere; Behind constant temperature under 70 ℃ of temperature; The radical initiator 2 that adds deoxygenation; 2'-azo (2-methyl-propyl amidine) dihydrochloride storing solution; The mol ratio of its consumption and macromolecular chain transfer agent is 0.01 ~ 10:1; React after 2.5 hours, be immersed in quencher reaction in the frozen water, obtain appearing nanogel dispersion liquid azury; Described monomer is served as reasons the methacrylate monomer that contains two oxyethyl groups and the methacrylate monomer that contains 8 ~ 9 oxyethyl group side chains by (80 ~ 100): the mol ratio of (0 ~ 20) is formulated;
5. preparation method according to claim 4, the number-average molecular weight that it is characterized in that described polyoxyethylene glycol is 1000-10000.
5. method for preparing the high molecular nanometer gel of the adjustable bio-compatibility nucleocapsid structure of thermo-sensitivity according to claim 2 is characterized in that the concrete steps of this method are:
A. prepare comb shape macromolecular chain transfer agent: with 4-cyanopentanoic acid dithiobenzoic acid ester, methoxypolyethylene glycol methacrylic ester, Diisopropyl azodicarboxylate by 1: (10 ~ 100): the mol ratio of (0.01 ~ 2) is dissolved in the ethanol; After stirring; Deoxygenation is 50 minutes in ice-water bath, and anaerobic was reacted 3.5 hours under 70 ℃ of temperature again; Be then in the ice-water bath, under air atmosphere, in normal hexane, after centrifugation, vacuum-drying, obtain red thick liquid, be required comb shape macromolecular chain transfer agent with methylene dichloride dilution postprecipitation;
B. prepare comb shape polymer thermo-sensitivity nanogel: with step a gained comb shape macromolecular chain transfer agent; Monomer; The coupling agent polyethylene glycol dimethacrylate; According to 1: (30 ~ 200): the mol ratio of (3 ~ 10) is soluble in water; Wherein the mass percent concentration of monomer in water is 0.5 ~ 5%; After the sealing; In ice-water bath; Under inert atmosphere; The adding that under 70 ℃ of temperature, adds deoxygenation is the radical initiator 2 of deoxygenation; 2'-azo (2-methyl-propyl amidine) dihydrochloride storing solution; Radical initiator and consumption are that the mol ratio of macromolecular chain transfer agent is 0.01 ~ 10:1; After the isothermal reaction 6 hours; Quencher reaction in frozen water; Obtain appearing erythroid nanogel colloidal sol, be the comb shape nanogel; Described monomer is served as reasons the methacrylate monomer that contains two oxyethyl groups and the methacrylate monomer that contains 8 ~ 9 oxyethyl group side chains by (80 ~ 100): the mol ratio of (0 ~ 20) is formulated.
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| CN114230739A (en) * | 2021-12-14 | 2022-03-25 | 西安交通大学 | Linear-nonlinear block polymer and preparation method thereof |
| CN115558133A (en) * | 2022-10-20 | 2023-01-03 | 南京工业大学 | Temperature response type particle gel and preparation method thereof |
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| CN103992441A (en) * | 2014-02-25 | 2014-08-20 | 上海大学 | High-molecular monomer method for preparing star polymer |
| CN108265528A (en) * | 2018-01-28 | 2018-07-10 | 于美花 | A kind of protective gloves and preparation method thereof |
| CN108265528B (en) * | 2018-01-28 | 2021-02-19 | 东营百华石油技术开发有限公司 | Protective gloves and manufacturing method thereof |
| CN113289054A (en) * | 2021-06-16 | 2021-08-24 | 四川大学 | Wound dressing capable of absorbing heat rapidly and preparation method and application thereof |
| CN114230739A (en) * | 2021-12-14 | 2022-03-25 | 西安交通大学 | Linear-nonlinear block polymer and preparation method thereof |
| CN114230739B (en) * | 2021-12-14 | 2023-08-11 | 西安交通大学 | Linear-nonlinear block polymer and preparation method thereof |
| CN115558133A (en) * | 2022-10-20 | 2023-01-03 | 南京工业大学 | Temperature response type particle gel and preparation method thereof |
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