CN101962463B - Preparation method of hydrolysis-free biodegradable acrylic polymer nano hydrogel - Google Patents
Preparation method of hydrolysis-free biodegradable acrylic polymer nano hydrogel Download PDFInfo
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Abstract
The invention relates to a preparation method of hydrolysis-free biodegradable acrylic polymer nano hydrogel. Hydroxy propyl cellulose in a water solution is used as a template, some biocompatible monomers containing carboxyl are used for water-phase polymerization to form a polymer, and the high polymer containing the carboxyl and the hydroxy propyl cellulose are interacted through hydrogen bonds between the carboxyl and hydroxyl to cause that the hydroxy propyl cellulose does not dissolve in water to be condensed into nano microspheres, therefore, the high polymer absorbed on the hydroxy propyl cellulose is interlinked to form the nano hydrogel. The invention is simple and easy to synthesize and operate; and the prepared acrylic polymer nano hydrogel has the advantages of smaller and controllable particle size and better dispersibility.
Description
Technical field
The invention belongs to the preparation field of acrylic polymers nano-hydrogel, the preparation method of the biodegradable acrylic polymers nano-hydrogel of particularly a kind of non-hydrolysis.
Background technology
Nano-hydrogel (claiming the hydrogel nanoparticle again) is meant diameter tens to the macromolecule hydrogel microballoons of hundreds of nanometer since the surface-area of its minimum size, super large (the 1g diameter is that the total surface area of the Nano microsphere of 100nm is approximately 60m
2), to compare with general hydrogel, nano-hydrogel shows the external environment inductive pucker & bloat that is exceedingly fast.Application with nano-hydrogel of biocompatibility almost spreads all over each great field; Separation and purifying like protein and DNA; The matrix of the injectable human tissue engineering of non-operation coats and carries the treatment that gene and biopharmaceutical macromolecular drug are used for cancer and AIDS, delivery of drug and release; Coat a large amount of magnetic metal ions and be used for the radiography reagent and the nano biological sensor of novel nucleus magnetic resonance, cause world wide internal medicine scholar's strong interest day by day.The research of nano-hydrogel synthetic system mainly concentrates on PNIPAM, poly N-vinyl hexanolactam, ROHM and polymethyl acrylic acid etc. under the aqueous environment.
The polyacrylic acid nano hydrogel adopts " water-in-oil " reverse microemulsion polymerization method to synthesize (Pelton, R.Adv.ColloidInterface Sci.2000,85,1 usually; Kriwet, B.; Walter, E.; Kissel, T.J.Controlled Release 1998,56,149; Somasundaran, P; Chkraborty; S.US Patent Application 2008/0260851) but this polymerization system contains a large amount of organic solvents and emulsifying agent; Be difficult to from the hydrogel nanoparticle that has made, remove fully; Harmful because of residual organic solvent and emulsifying agent, the polyacrylic acid nano hydrogel that conversed phase micro emulsion copolymerization forms can not use in human body.
Summary of the invention
Technical problem to be solved by this invention provides the preparation method of the biodegradable acrylic polymers nano-hydrogel of a kind of non-hydrolysis; Synthetic operation of the present invention is simple and easy to do; The prepared less and controllable size of polyacrylic acid hydrogel nano-particles size, and have good dispersiveness.
The preparation method of the biodegradable acrylic polymers nano-hydrogel of a kind of non-hydrolysis of the present invention comprises:
(1) under the room temperature hydroxypropylcellulose powder was dissolved in deionized water and magnetic agitation 1～5 day, the homogeneous phase solution that is mixed with 1wt%～10wt% is as subsequent use;
(2) the above-mentioned HPC solution that is mixed with of 10～50g, 0.1～1.2g linking agent are dissolved in 44.6～89.4g deionized water and magnetic agitation 15～60min together;
(3) add 0.05～0.2g initiator, 0.4～4g acrylic monomer and stir 15～60min at the nitrogen protection lower magnetic force;
(4) temperature of reaction rises to 20～40 ℃ and add 0.05g accelerator initiated polymerization;
(5) the polyacrylic acid nano hydrogel that makes is transferred to pH=6～8 with alkali, and dialysed 1～7 day, make non-hydrolysis biodegradable polypropylene acid nano-hydrogel at last.
The molecular-weight average of the hydroxypropylcellulose in the said step (1) is M
w=1.0 * 10
3～1.0 * 10
6
Linking agent in the said step (2) is N, N '-methylene-bisacrylamide Bis, polyoxyethylene glycol PEG, oxyacetic acid β-ester or (polyethylene glycol-lactic acid-polyoxyethylene glycol) diacrylate.
Initiator in the said step (3) is ammonium persulphate APS or Potassium Persulphate KPS, and acrylic monomer is acrylic or methacrylic acid.
Accelerator in the said step (4) is Tetramethyl Ethylene Diamine TEMED or S-WAT.
Alkali in the said step (5) is sodium hydroxide or Pottasium Hydroxide.
The present invention proposes and has realized utilizing the polymer hydrogen bond can reduce thermo-sensitivity hydroxypropylcellulose phase transition temperature; In hydroxypropyl cellulose aqueous solution, can there be the saponification letex polymerization; " water-in-oil " reverse microemulsion polymerization method of having avoided common employing is because of containing a large amount of organic solvents and emulsifying agent; The problem that hydrogel product can not use in human body has realized that really the green of nano-hydrogel is synthetic.The compound method of the polymer nanocomposite hydrogel of statement; Be as template with hydroxypropylcellulose in the aqueous solution; Contain the biocompatibility monomer water synthetic polymer of carboxyl with some; Form the intensive hydrogen bond action between carboxyl on the high molecular polymer and the hydroxyl on the hydroxypropylcellulose; " plunder " interaction between hydroxypropylcellulose and the water molecules, make that hydroxypropylcellulose is water insoluble and be shrunk to Nano microsphere, thereby make the high molecular polymer (equally also being shrunk to Nano microsphere) that is attached on the hydroxypropylcellulose and be cross-linked into nano-hydrogel.Hydroxypropylcellulose is a kind of natural polymer of thermo-sensitivity; The promptly at room temperature water-soluble polymer aqueous solution that is homogeneous phase transparent; When temperature rises to 41 ℃; Hydroxypropylcellulose becomes water-fast polymer, and the natural polymer of this type of thermo-sensitivity also comprises methylhydroxypropylcellulose and methylcellulose gum.The median size that dynamic light scattering (DLS) test has characterized the hydrogel nanoparticle is 79.4nm, and its size and distribution of sizes are seen Fig. 2.Fig. 3 and Fig. 4 represent hydroxypropylcellulose and polyacrylic infrared spectrogram respectively, and the ir spectra that contains the polyacrylic acid nano hydrogel of hydroxypropylcellulose is seen Fig. 5.
Beneficial effect
(1) simple, the environmental protection of this method technology, required equipment be simple and easy to, and can realize producing in batches, avoided using a large amount of organic solvents and emulsifying agent in the preparation process, realized that really the green of nano-hydrogel is synthetic;
(2) the prepared less and controllable size of polyacrylic acid hydrogel nano-particles size, and have good dispersiveness.
Description of drawings
Fig. 1 is for the hydroxypropylcellulose being the synoptic diagram that template does not have the synthetic polyacrylic acid nano hydrogel of saponification;
Fig. 2 is the polyacrylic acid nano hydrogel size and the size distribution plot of dynamic light scattering (DLS) test
Fig. 3 is the infrared spectrogram of hydroxypropylcellulose;
Fig. 4 is polyacrylic infrared spectrogram;
Fig. 5 is the infrared spectrogram that contains the polyacrylic acid nano hydrogel of hydroxypropylcellulose;
Fig. 6 is the polyacrylic acid nano hydrogel size and the size distribution plot of dynamic light scattering (DLS) test of embodiment 1;
Fig. 7 is the polyacrylic acid nano hydrogel size and the size distribution plot of dynamic light scattering (DLS) test of embodiment 7.
Embodiment
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in the restriction scope of the present invention.Should be understood that in addition those skilled in the art can do various changes or modification to the present invention after the content of having read the present invention's instruction, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
This embodiment step is following: (1) is with 2g hydroxypropylcellulose (HPC) powder (average M
w=1.0 * 10
5) being dissolved in the 98g deionized water, magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 10g2% (wt%) HPC solution and 0.1gBis are dissolved in the 88g deionized water, stir 15min; (3) add 2g vinylformic acid and 0.05gAPS, at N
245min is stirred in protection down; (4) be warming up to 28 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes was neutralized to behind the pH=7 dialysis 2 days with sodium hydroxide, the polyacrylic acid nano hydrogel size and the distribution of sizes of gained are seen Fig. 6.
Embodiment 2
This embodiment step is following: (1) is with 2g hydroxypropylcellulose (HPC) powder (average M
w=1.0 * 10
5) being dissolved in the 98g deionized water, magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 20g2% (wt%) HPC solution and 0.2gBis are dissolved in the 78g deionized water, stir 15min; (3) add 2g vinylformic acid and 0.05g APS, at N
245min is stirred in protection down; (4) be warming up to 28 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes is neutralized to behind the pH=7 dialysis 2 days with sodium hydroxide, makes the polyacrylic acid nano hydrogel.
Embodiment 3
This embodiment step is following: (1) is with 2g hydroxypropylcellulose (HPC) powder (average M
w=1.0 * 10
5) being dissolved in the 98g deionized water, magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 20g2% (wt%) HPC solution and 0.2gBis are dissolved in the 78g deionized water, stir 15min; (3) add 2g vinylformic acid and 0.05g APS, at N
245min is stirred in protection down; (4) be warming up to 38 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes is neutralized to behind the pH=7 dialysis 2 days with sodium hydroxide, makes the polyacrylic acid nano hydrogel.
Embodiment 4
This embodiment step is following: (1) is with 2g hydroxypropylcellulose (HPC) powder (average M
w=1.0 * 10
5) being dissolved in the 98g deionized water, magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 10g2% (wt%) HPC solution and 0.1gBis are dissolved in the 86g deionized water, stir 15min; (3) add 4g vinylformic acid and 0.2gAPS, at N
245min is stirred in protection down; (4) be warming up to 28 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes is neutralized to behind the pH=7 dialysis 2 days with sodium hydroxide, makes the polyacrylic acid nano hydrogel.
Embodiment 5
This embodiment step is following: (1) is with 2g hydroxypropylcellulose (HPC) powder (average M
w=1.0 * 10
5) being dissolved in the 98g deionized water, magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 20g2% (wt%) HPC solution and 0.2gBis are dissolved in the 78g deionized water, stir 15min; (3) add 2g vinylformic acid and 0.05g APS, at N
245min is stirred in protection down; (4) be warming up to 26 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes is neutralized to behind the pH=7 dialysis 2 days with sodium hydroxide, makes the polyacrylic acid nano hydrogel.
This embodiment step is following: (1) is with 2g hydroxypropylcellulose (HPC) powder (average M
w=1.0 * 10
5) being dissolved in the 98g deionized water, magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 50g2% (wt%) HPC solution and 0.3gBis are dissolved in the 48g deionized water, stir 15min; (3) add 2g vinylformic acid and 0.05g APS, at N
245min is stirred in protection down; (4) be warming up to 28 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes is neutralized to behind the pH=7 dialysis 2 days with sodium hydroxide, makes the polyacrylic acid nano hydrogel.
Embodiment 7
This embodiment step is following: (1) is dissolved in the 98g deionized water with 2g hydroxypropylcellulose (HPC) powder (average Mw=1.0 * 105), and magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 20g2% (wt%) HPC solution and 0.4gPEG are dissolved in the 79.2g deionized water, stir 15min; (3) add 0.4g vinylformic acid and 0.05gAPS, under the N2 protection, stir 45min; (4) be warming up to 26 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes was neutralized to behind the pH=7 dialysis 2 days with sodium hydroxide, the polyacrylic acid nano hydrogel size and the distribution of sizes of gained are seen Fig. 7.
Embodiment 8
This embodiment step is following: (1) is dissolved in the 98g deionized water with 2g hydroxypropylcellulose (HPC) powder (average Mw=1.0 * 105), and magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 20g2% (wt%) HPC solution and 1gPEG are dissolved in the 79g deionized water, stir 15min; (3) add 0.4g vinylformic acid and 0.05gAPS, under the N2 protection, stir 45min; (4) be warming up to 26 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes is neutralized to behind the pH=7 dialysis 2 days with sodium hydroxide, makes the polyacrylic acid nano hydrogel.
Embodiment 9
This embodiment step is following: (1) is dissolved in the 98g deionized water with 2g hydroxypropylcellulose (HPC) powder (average Mw=1.0 * 105), and magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 20g2% (wt%) HPC solution and 1.2gPEG are dissolved in 78.8 deionized waters, stir 15min; (3) add 0.4g vinylformic acid and 0.05gAPS, under the N2 protection, stir 45min; (4) be warming up to 26 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes is neutralized to behind the pH=7 dialysis 2 days with sodium hydroxide, makes the polyacrylic acid nano hydrogel.
Claims (6)
1. the preparation method of the biodegradable acrylic polymers nano-hydrogel of non-hydrolysis comprises:
(1) under the room temperature hydroxypropylcellulose powder was dissolved in deionized water and magnetic agitation 1～5 day, the homogeneous phase solution that is mixed with 1wt%～10wt% is as subsequent use;
(2) the above-mentioned HPC solution that is mixed with of 10～50g, 0.1～1.2g linking agent are dissolved in 44.6～89.4g deionized water and magnetic agitation 15～60min together;
(3) add 0.05～0.2g initiator, 0.4～4g acrylic monomer and stir 15～60min at the nitrogen protection lower magnetic force;
(4) temperature of reaction rises to 20～40 ℃ and add the accelerator initiated polymerization of 0.05g;
(5) the polyacrylic acid nano hydrogel that makes is transferred to pH=6～8 with alkali, and dialysed 1～7 day, make non-hydrolysis biodegradable polypropylene acid nano-hydrogel at last.
2. the preparation method of the biodegradable acrylic polymers nano-hydrogel of a kind of non-hydrolysis according to claim 1, it is characterized in that: the molecular-weight average of the hydroxypropylcellulose in the said step (1) is M
w=1.0 * 10
3～1.0 * 10
6
3. the preparation method of the biodegradable acrylic polymers nano-hydrogel of a kind of non-hydrolysis according to claim 1; It is characterized in that: the linking agent in the said step (2) is N, N '-methylene-bisacrylamide Bis, polyoxyethylene glycol PEG, oxyacetic acid β-ester or (polyethylene glycol-lactic acid-polyoxyethylene glycol) diacrylate.
4. the preparation method of the biodegradable acrylic polymers nano-hydrogel of a kind of non-hydrolysis according to claim 1; It is characterized in that: the initiator in the said step (3) is ammonium persulphate APS or Potassium Persulphate KPS, and acrylic monomer is acrylic or methacrylic acid.
5. the preparation method of the biodegradable acrylic polymers nano-hydrogel of a kind of non-hydrolysis according to claim 1, it is characterized in that: the accelerator in the said step (4) is Tetramethyl Ethylene Diamine TEMED or S-WAT.
6. the preparation method of the biodegradable acrylic polymers nano-hydrogel of a kind of non-hydrolysis according to claim 1, it is characterized in that: the alkali in the said step (5) is sodium hydroxide or Pottasium Hydroxide.
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| CN102358796B (en) * | 2011-08-03 | 2013-06-05 | 东华大学 | Method for preparing core-shell structured intelligent nano hydrogel |
| CN103724633A (en) * | 2012-10-15 | 2014-04-16 | 中国科学院兰州化学物理研究所 | Granular hydrogel |
| CN108164636B (en) * | 2017-12-08 | 2019-07-26 | 东华大学 | A kind of preparation method of pH response type copolymer nano hydrogel |
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| CN100424130C (en) * | 2005-05-27 | 2008-10-08 | 中国林业科学研究院林产化学工业研究所 | Process for preparing cellulose acrylate composited high molecular degradable material |
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