CN114891239B - Boron-nitrogen internal coordination borate hydrogel and preparation method thereof - Google Patents
Boron-nitrogen internal coordination borate hydrogel and preparation method thereof Download PDFInfo
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- CN114891239B CN114891239B CN202210304805.XA CN202210304805A CN114891239B CN 114891239 B CN114891239 B CN 114891239B CN 202210304805 A CN202210304805 A CN 202210304805A CN 114891239 B CN114891239 B CN 114891239B
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- 239000000017 hydrogel Substances 0.000 title claims abstract description 43
- TZHYBRCGYCPGBQ-UHFFFAOYSA-N [B].[N] Chemical compound [B].[N] TZHYBRCGYCPGBQ-UHFFFAOYSA-N 0.000 title claims abstract description 29
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 239000000243 solution Substances 0.000 claims abstract description 73
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims abstract description 53
- 239000007864 aqueous solution Substances 0.000 claims abstract description 36
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims abstract description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 27
- 238000002156 mixing Methods 0.000 claims abstract description 11
- 239000000499 gel Substances 0.000 claims abstract description 7
- 230000004043 responsiveness Effects 0.000 claims abstract description 7
- 229920000642 polymer Polymers 0.000 claims description 28
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 18
- 108010020346 Polyglutamic Acid Proteins 0.000 claims description 18
- 229920000370 gamma-poly(glutamate) polymer Polymers 0.000 claims description 18
- 239000011734 sodium Substances 0.000 claims description 18
- 229910052708 sodium Inorganic materials 0.000 claims description 18
- 229920002873 Polyethylenimine Polymers 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 238000007112 amidation reaction Methods 0.000 claims description 9
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 7
- 108010010803 Gelatin Proteins 0.000 claims description 7
- 229920000159 gelatin Polymers 0.000 claims description 7
- 239000008273 gelatin Substances 0.000 claims description 7
- 235000019322 gelatine Nutrition 0.000 claims description 7
- 235000011852 gelatine desserts Nutrition 0.000 claims description 7
- 239000000661 sodium alginate Substances 0.000 claims description 7
- 235000010413 sodium alginate Nutrition 0.000 claims description 7
- 229940005550 sodium alginate Drugs 0.000 claims description 7
- 102000008186 Collagen Human genes 0.000 claims description 6
- 108010035532 Collagen Proteins 0.000 claims description 6
- 229920002385 Sodium hyaluronate Polymers 0.000 claims description 6
- 229920001436 collagen Polymers 0.000 claims description 6
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 claims description 6
- 229940010747 sodium hyaluronate Drugs 0.000 claims description 6
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 claims description 6
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 claims description 6
- BYACHAOCSIPLCM-UHFFFAOYSA-N 2-[2-[bis(2-hydroxyethyl)amino]ethyl-(2-hydroxyethyl)amino]ethanol Chemical compound OCCN(CCO)CCN(CCO)CCO BYACHAOCSIPLCM-UHFFFAOYSA-N 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- FKJVYOFPTRGCSP-UHFFFAOYSA-N 2-[3-aminopropyl(2-hydroxyethyl)amino]ethanol Chemical compound NCCCN(CCO)CCO FKJVYOFPTRGCSP-UHFFFAOYSA-N 0.000 claims description 4
- FSVCELGFZIQNCK-UHFFFAOYSA-N N,N-bis(2-hydroxyethyl)glycine Chemical compound OCCN(CCO)CC(O)=O FSVCELGFZIQNCK-UHFFFAOYSA-N 0.000 claims description 4
- CYOIAXUAIXVWMU-UHFFFAOYSA-N 2-[2-aminoethyl(2-hydroxyethyl)amino]ethanol Chemical compound NCCN(CCO)CCO CYOIAXUAIXVWMU-UHFFFAOYSA-N 0.000 claims description 3
- KWNPRVWFJOSGMZ-UHFFFAOYSA-N 2-boronobenzoic acid Chemical compound OB(O)C1=CC=CC=C1C(O)=O KWNPRVWFJOSGMZ-UHFFFAOYSA-N 0.000 claims description 2
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 claims description 2
- 229920001661 Chitosan Polymers 0.000 claims description 2
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- 102000009123 Fibrin Human genes 0.000 claims description 2
- 108010073385 Fibrin Proteins 0.000 claims description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 claims description 2
- 108010022355 Fibroins Proteins 0.000 claims description 2
- 229920002845 Poly(methacrylic acid) Polymers 0.000 claims description 2
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- 108010039918 Polylysine Proteins 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- ILOJFJBXXANEQW-UHFFFAOYSA-N aminooxy(phenyl)borinic acid Chemical compound NOB(O)C1=CC=CC=C1 ILOJFJBXXANEQW-UHFFFAOYSA-N 0.000 claims description 2
- 229940098773 bovine serum albumin Drugs 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
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- 229940014259 gelatin Drugs 0.000 claims description 2
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- 108010064470 polyaspartate Proteins 0.000 claims description 2
- 229920000656 polylysine Polymers 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 4
- 239000008103 glucose Substances 0.000 abstract description 4
- 239000001301 oxygen Substances 0.000 abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 abstract description 4
- 239000003054 catalyst Substances 0.000 abstract description 2
- 231100000331 toxic Toxicity 0.000 abstract description 2
- 230000002588 toxic effect Effects 0.000 abstract description 2
- 229940083542 sodium Drugs 0.000 description 17
- 239000011259 mixed solution Substances 0.000 description 14
- 238000004108 freeze drying Methods 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 238000010586 diagram Methods 0.000 description 5
- 238000002329 infrared spectrum Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 239000004327 boric acid Substances 0.000 description 3
- -1 boric acid ester Chemical class 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- UTHULKKJYXJZLV-UHFFFAOYSA-N (3-aminophenoxy)boronic acid Chemical compound NC1=CC=CC(OB(O)O)=C1 UTHULKKJYXJZLV-UHFFFAOYSA-N 0.000 description 2
- SLHKDOGTVUCXKX-UHFFFAOYSA-N 4,4'-biphenyldiboronic acid Chemical compound C1=CC(B(O)O)=CC=C1C1=CC=C(B(O)O)C=C1 SLHKDOGTVUCXKX-UHFFFAOYSA-N 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- ZPKSAIWDCQVXSQ-UHFFFAOYSA-N (4-aminophenoxy)boronic acid Chemical compound NC1=CC=C(OB(O)O)C=C1 ZPKSAIWDCQVXSQ-UHFFFAOYSA-N 0.000 description 1
- BODYVHJTUHHINQ-UHFFFAOYSA-N (4-boronophenyl)boronic acid Chemical compound OB(O)C1=CC=C(B(O)O)C=C1 BODYVHJTUHHINQ-UHFFFAOYSA-N 0.000 description 1
- DBVFWZMQJQMJCB-UHFFFAOYSA-N 3-boronobenzoic acid Chemical compound OB(O)C1=CC=CC(C(O)=O)=C1 DBVFWZMQJQMJCB-UHFFFAOYSA-N 0.000 description 1
- SIAVMDKGVRXFAX-UHFFFAOYSA-N 4-carboxyphenylboronic acid Chemical compound OB(O)C1=CC=C(C(O)=O)C=C1 SIAVMDKGVRXFAX-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- ZMUANTVDGHVAHS-UHFFFAOYSA-N OBOB(O)C1=CC=CC=C1 Chemical compound OBOB(O)C1=CC=CC=C1 ZMUANTVDGHVAHS-UHFFFAOYSA-N 0.000 description 1
- PIEUWWVYSBWVRR-UHFFFAOYSA-N OBOBO.C1=CC=CC=C1C1=CC=CC=C1 Chemical compound OBOBO.C1=CC=CC=C1C1=CC=CC=C1 PIEUWWVYSBWVRR-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000037314 wound repair Effects 0.000 description 1
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Abstract
The invention relates to a preparation method of boron-nitrogen internal coordination borate hydrogel, which comprises the steps of blending a phenylboronic acid molecule-containing aqueous solution with an N, N-bis (2-hydroxyethyl) molecule-containing aqueous solution, adjusting the pH value to 2-11, and forming a gel until the solution is gel to obtain the boron-nitrogen internal coordination borate hydrogel. The preparation method is simple, other toxic catalysts are not required to be added, and the obtained hydrogel has multiple pH corresponding intervals, glucose and active oxygen responsiveness, injectability and good biocompatibility.
Description
Technical Field
The invention belongs to the field of hydrogel preparation, and particularly relates to preparation of borate hydrogel with a boron-nitrogen internal coordination structure.
Background
The natural high molecular hydrogel is a water-insoluble crosslinked polymer three-dimensional network, is similar to soft tissues, and has good use effect and application prospect in the fields of wound repair, tissue engineering, drug delivery and the like.
Responsive drug-releasing hydrogels are increasingly used due to the specific tissue microenvironment and lesion area requirements. The dynamic chemical bond hydrogel has the advantages of no need of external field driving and self-suitability for drug release, wherein the boric acid ester bond hydrogel has multifactor responsiveness (acidity, glucose and active oxygen) and is suitable for responsive drug release in microenvironments such as inflammation, tumor, diabetes and the like. However, the pH response interval is single, the regulation and control are difficult, the degradation rate is high, and the application of the pH response interval is limited.
Disclosure of Invention
The invention aims to provide a borate hydrogel with a boron-nitrogen internal coordination structure and a preparation method thereof, wherein the preparation method is simple, no other toxic catalyst is needed to be added, and the obtained hydrogel has multiple pH corresponding intervals, glucose and active oxygen responsiveness, injectability and good biocompatibility.
The invention solves the technical problems by adopting the following scheme:
the preparation method of the boron-nitrogen internal coordination borate hydrogel comprises the following steps:
1) Dissolving phenylboronic acid-containing molecules in an aqueous solution to obtain a solution A;
2) Dissolving N, N-bis (2-hydroxyethyl) containing molecules in an aqueous solution to obtain a solution B;
3) And (3) blending the solution A and the solution B, and adjusting the pH value to 2-11 until the solution forms gel to obtain the boron-nitrogen internal coordination borate hydrogel.
Preferably, the phenylboronic acid-containing molecule is selected from one or more of phenyldiboronic acid, biphenyl diboronic acid, carboxyl-containing polymer grafted phenylboronic acid and amino-containing polymer grafted phenylboronic acid; the N, N-bis (2-hydroxyethyl) containing molecule is selected from one or more of N, N, N ', N' -tetra (2-hydroxyethyl) ethylenediamine, ethoxylated polyethyleneimine, carboxyl containing polymer grafted N, N-bis (2-hydroxyethyl), amino containing polymer grafted N, N-bis (2-hydroxyethyl).
Preferably, the carboxyl-containing polymer grafted phenylboronic acid is obtained by grafting a carboxyl-containing polymer and aminophenylboronic acid through amidation reaction; the amino-containing polymer grafted phenylboronic acid is obtained by grafting an amino-containing polymer and carboxyphenylboronic acid through amidation reaction.
Preferably, the carboxyl-containing polymer is grafted by N, N-bis (2-hydroxyethyl) and N, N-bis (2-hydroxyethyl) ethylenediamine or N, N-bis (2-hydroxyethyl) -1, 3-diaminopropane through amidation reaction; the amino-containing polymer grafted N, N-bis (2-hydroxyethyl) is obtained by grafting an amino-containing polymer and N, N-bis (2-hydroxyethyl) glycine through amidation reaction.
Preferably, the carboxyl-containing polymer is any one of sodium polyglutamate, polyaspartic acid, sodium polyacrylate, polymethacrylic acid, sodium alginate, sodium hyaluronate, chondroitin sulfate and sodium carboxymethyl cellulose; the amino-containing polymer is any one of polyethylenimine, polylysine, polyallylamine, chitosan, gelatin, collagen, fibrin, bovine serum albumin and fibroin.
Preferably, the mass fraction of the solute in the solution A is 0.5-60% wt, and the mass fraction of the solute in the solution B is 0.5-60% wt.
Preferably, the volume ratio of the solution A to the solution B is 1:1.
The invention also provides boron-nitrogen internal coordination borate hydrogel which is prepared by the method.
The invention also relates to a boron-nitrogen internal coordination borate hydrogel, which comprises a crosslinking point formed by boron-nitrogen internal coordination borate bonds, wherein the structural formula of the boron-nitrogen internal coordination borate bonds is as follows:
The hydrogel has pH responsiveness, forms gel within the lower limit (2-8) and the upper limit (9-11) of the pH value, and is an injectable liquid with good fluidity outside the pH value range.
Compared with the prior art, the invention has the beneficial effects that:
1) According to the invention, the boric acid ester hydrogel with a special boron-nitrogen internal coordination crosslinking structure can be obtained through the blending reaction of the phenylboronic acid molecule-containing solution and the N, N-bis (2-hydroxyethyl) molecule-containing solution, and the hydrogel has an adjustable multiple pH response interval and a slower degradation rate relative to the boric acid ester linkage hydrogel due to the existence of boron-nitrogen coordination bonds.
2) The phenylboronic acid molecule-containing solution and the N, N-bis (2-hydroxyethyl) molecule can be grafted on the carboxyl-containing polymer or the amino-containing polymer through amidation reaction besides the commercial reagent, and the preparation method is simple, economical and applicable.
3) Because of the unique gel mechanism of the boron-nitrogen internal coordination borate ester bond, the adjustability of the pH response interval can be realized through the coordination effect between different raw materials, and the boron-nitrogen internal coordination borate ester hydrogel obtained by the invention has the gelling interval which can be adjusted and controlled within the lower limit (2-8) and the upper limit (9-11) of the pH value.
Drawings
FIG. 1 is an infrared spectrum of a1, 4-phenyldiboronic acid/ethoxylated polyethyleneimine hydrogel obtained in example 1 of the present invention;
FIG. 2 is a schematic diagram of the sodium polyglutamate grafted phenylboronic acid/N, N, N ', N' -tetrakis (2-hydroxyethyl) ethylenediamine hydrogel obtained in example 2 of the present invention, wherein the left diagram is the state of the hydrogel in a centrifuge tube, and the right diagram is the state of the hydrogel on a plane;
FIG. 3 is a schematic diagram showing the effect of the responsiveness test of the sodium polyglutamate grafted phenylboronic acid/N, N, N ', N' -tetra (2-hydroxyethyl) ethylenediamine hydrogel obtained in example 2 of the present invention, wherein the hydrogel has pH, active oxygen, glucose and temperature responsiveness;
FIG. 4 is an infrared spectrum of polyethyleneimine grafted phenylboronic acid obtained in example 3 of the present invention;
FIG. 5 is an infrared spectrum of the sodium polyglutamate grafted N, N-bis (2-hydroxyethyl) obtained in example 3 of the present invention;
FIG. 6 is a schematic diagram of a 4,4' -biphenyldiboronic acid/sodium polyglutamate grafted N, N-bis (2-hydroxyethyl) hydrogel obtained in example 4 of the present invention;
FIG. 7 is an infrared spectrum of polyethyleneimine grafted N, N-bis (2-hydroxyethyl) obtained in example 5 of the present invention.
Detailed Description
For a better understanding of the present invention, the following examples are further illustrative of the present invention, but the contents of the present invention are not limited to the following examples only.
Example 1
Dissolving 1, 4-phenyldiboronic acid in an aqueous solution to give a solution A of 15% wt; taking 37% wt of 80% ethoxylated polyethyleneimine solution as solution B; and (3) mixing the solution A and the solution B in equal volume to obtain a mixed solution with good fluidity, and adjusting the pH value of the mixed solution to 7-10, so that the borate hydrogel with the boron-nitrogen internal coordination structure can be formed quickly.
Example 2
Dissolving a certain amount of sodium polyglutamate in an aqueous solution to obtain a 2%wt sodium polyglutamate solution, adding a certain amount of 3-aminophenylboric acid into the aqueous solution, adjusting the pH to 5.5, uniformly stirring, adding EDC/NHS, reacting for 24 hours, dialyzing the solution, and performing freeze-drying treatment to obtain the sodium polyglutamate grafted phenylboric acid. Dissolving sodium polyglutamate grafted phenylboronic acid in an aqueous solution to obtain a 50%wt solution A; dissolving N, N, N ', N' -tetra (2-hydroxyethyl) ethylenediamine in an aqueous solution to obtain a solution B of 6% wt; and (3) mixing the solution A and the solution B in equal volume to obtain a mixed solution with good fluidity, and adjusting the pH value of the mixed solution to 6 to 10, so that the borate hydrogel with the boron-nitrogen internal coordination structure can be formed quickly.
Example 3
Diluting a certain amount of polyethyleneimine solution in water to obtain 10%wt of polyethyleneimine solution, adding a certain amount of 4-carboxyphenylboronic acid into the polyethyleneimine solution, adjusting the pH to 5.5, uniformly stirring, adding EDC/NHS, reacting for 24 hours, dialyzing the mixture, and performing freeze-drying treatment to obtain the polyethyleneimine grafted phenylboronic acid. Dissolving a certain amount of sodium polyglutamate in an aqueous solution to obtain a 2%wt sodium polyglutamate solution, adding a certain amount of N, N-bis (2-hydroxyethyl) -1, 3-diaminopropane into the aqueous solution, adjusting the pH to 5.5, adding EDC/NHS into the aqueous solution after uniformly stirring the aqueous solution, reacting the aqueous solution for 24 hours, dialyzing the aqueous solution, and performing freeze-drying treatment to obtain sodium polyglutamate grafted N, N-bis (2-hydroxyethyl). Dissolving polyethyleneimine grafted phenylboronic acid in an aqueous solution to obtain a solution A with 15%wt; sodium polyglutamate grafted N, N-bis (2-hydroxyethyl) is dissolved in an aqueous solution to obtain a solution B of 16%wt; and (3) mixing the solution A and the solution B in equal volume to obtain a mixed solution with good fluidity, and adjusting the pH value of the mixed solution to 2 to 11, so that the borate hydrogel with the boron-nitrogen internal coordination structure can be formed quickly.
Example 4
Dissolving a certain amount of sodium polyglutamate in an aqueous solution to obtain a 2%wt sodium polyglutamate solution, adding a certain amount of N, N-bis (2-hydroxyethyl) ethylenediamine into the aqueous solution, adjusting the pH to 5.5, adding EDC/NHS into the aqueous solution after uniformly stirring the aqueous solution, reacting the aqueous solution for 24 hours, dialyzing the aqueous solution, and performing freeze-drying treatment to obtain sodium polyglutamate grafted N, N-bis (2-hydroxyethyl). Dissolving 4,4' -biphenyldiboronic acid in an aqueous solution to give a solution A of 3% wt; sodium polyglutamate grafted N, N-bis (2-hydroxyethyl) is dissolved in an aqueous solution to obtain a solution B of 12%wt; and (3) mixing the solution A and the solution B in equal volume to obtain a mixed solution with good fluidity, and adjusting the pH value of the mixed solution to 8-11, so that the borate hydrogel with the boron-nitrogen internal coordination structure can be formed quickly.
Example 5
Dissolving a certain amount of gelatin in 37 ℃ water to obtain a 4%wt gelatin solution, adding a certain amount of 3-carboxyphenylboronic acid into the gelatin solution, adjusting the pH to 5.5, uniformly stirring, adding EDC/NHS, reacting for 24 hours, dialyzing the mixture, and performing freeze-drying treatment to obtain gelatin grafted phenylboronic acid. Diluting a certain amount of polyethyleneimine solution in water to obtain 10%wt of polyethyleneimine solution, adding a certain amount of N, N-bis (2-hydroxyethyl) glycine into the polyethyleneimine solution, adjusting the pH to 5.5, adding EDC/NHS after uniformly stirring, reacting for 24 hours, dialyzing the obtained product, and performing freeze drying treatment to obtain polyethyleneimine grafted N, N-bis (2-hydroxyethyl). Dissolving gelatin grafted phenylboronic acid in an aqueous solution to obtain a 40%wt solution A; dissolving polyethyleneimine grafted N, N-bis (2-hydroxyethyl) in an aqueous solution to obtain 35%wt of solution B; and (3) mixing the solution A and the solution B in equal volume to obtain a mixed solution with good fluidity, and adjusting the pH value of the mixed solution to 4 to 9, so that the borate hydrogel with the boron-nitrogen internal coordination structure can be formed quickly.
Example 6
Dissolving a certain amount of sodium hyaluronate in an aqueous solution to obtain a sodium hyaluronate solution with the weight of 2%, adding a certain amount of 4-aminophenylboric acid into the aqueous solution, adjusting the pH to 5.5, uniformly stirring, adding EDC/NHS, reacting for 24 hours, dialyzing the solution, and performing freeze-drying treatment to obtain the sodium hyaluronate grafted phenylboric acid. Dissolving a certain amount of collagen in dilute hydrochloric acid to obtain a 1%wt collagen solution, adding a certain amount of N, N-bis (2-hydroxyethyl) glycine into the solution, adjusting the pH to 5.5, stirring uniformly, adding EDC/NHS, reacting for 24 hours, dialyzing the solution, and performing freeze drying treatment to obtain collagen grafted N, N-bis (2-hydroxyethyl). Dissolving sodium hyaluronate grafted phenylboronic acid in an aqueous solution to obtain a solution A with the weight of 4%; dissolving collagen grafted N, N-bis (2-hydroxyethyl) in an aqueous solution to obtain a 2%wt solution B; and (3) mixing the solution A and the solution B in equal volume to obtain a mixed solution with good fluidity, and adjusting the pH value of the mixed solution to 7-11, so that the borate hydrogel with the boron-nitrogen internal coordination structure can be formed quickly.
Example 7
Dissolving a certain amount of sodium polyacrylate in an aqueous solution to obtain a sodium polyacrylate solution with the weight of 4%, adding a certain amount of 3-aminophenylboric acid into the solution, adjusting the pH to 5.5, uniformly stirring, adding EDC/NHS, reacting for 24 hours, dialyzing the solution, and performing freeze-drying treatment to obtain the sodium polyacrylate grafted phenylboric acid. Dissolving a certain amount of sodium alginate in water to obtain a sodium alginate solution with the weight of 2 percent, adding a certain amount of N, N-bis (2-hydroxyethyl) -1, 3-diaminopropane into the sodium alginate solution, uniformly stirring, adding EDC/NHS into the mixture, reacting for 24 hours, dialyzing the mixture, and performing freeze-drying treatment to obtain sodium alginate grafted N, N-bis (2-hydroxyethyl). Dissolving sodium polyacrylate grafted phenylboronic acid in an aqueous solution to obtain a solution A with the weight of 10%; sodium alginate grafted N, N-bis (2-hydroxyethyl) is dissolved in an aqueous solution to obtain a solution B with the weight of 1.5%; and (3) mixing the solution A and the solution B in equal volume to obtain a mixed solution with good fluidity, and adjusting the pH value of the mixed solution to 6 to 11, so that the borate hydrogel with the boron-nitrogen internal coordination structure can be formed quickly.
While the invention has been described with respect to the preferred embodiments, it will be understood that the invention is not limited thereto, but is capable of modification and variation without departing from the spirit of the invention, as will be apparent to those skilled in the art.
Claims (10)
1. The preparation method of the boron-nitrogen internal coordination borate hydrogel is characterized by comprising the following steps of:
1) Dissolving phenylboronic acid-containing molecules in an aqueous solution to obtain a solution A; the phenylboronic acid-containing molecule is selected from one or a combination of a plurality of carboxyl-containing polymer grafted phenylboronic acid and amino-containing polymer grafted phenylboronic acid;
2) Dissolving N, N-bis (2-hydroxyethyl) containing molecules in an aqueous solution to obtain a solution B;
3) And (3) blending the solution A and the solution B, and adjusting the pH to 2-11 until the solution forms gel to obtain the boron-nitrogen internal coordination borate hydrogel.
2. The method of claim 1, wherein the N, N-bis (2-hydroxyethyl) -containing molecule is selected from one or more of N, N' -tetra (2-hydroxyethyl) ethylenediamine, carboxyl-containing polymer grafts N, N-bis (2-hydroxyethyl), amino-containing polymer grafts N, N-bis (2-hydroxyethyl).
3. The preparation method according to claim 1, wherein the carboxyl-containing polymer grafted phenylboronic acid is obtained by grafting a carboxyl-containing polymer and aminophenylboronic acid through an amidation reaction; the amino-containing polymer grafted phenylboronic acid is obtained by grafting an amino-containing polymer and carboxyphenylboronic acid through amidation reaction.
4. The method according to claim 2, wherein the carboxyl group-containing polymer is grafted with N, N-bis (2-hydroxyethyl) ethylenediamine or N, N-bis (2-hydroxyethyl) -1, 3-diaminopropane by amidation reaction; the amino-containing polymer grafted N, N-bis (2-hydroxyethyl) is obtained by grafting an amino-containing polymer and N, N-bis (2-hydroxyethyl) glycine through amidation reaction.
5. The preparation method according to claim 2, wherein the carboxyl group-containing polymer is any one of sodium polyglutamate, polyaspartic acid, sodium polyacrylate, polymethacrylic acid, sodium alginate, sodium hyaluronate, chondroitin sulfate, and sodium carboxymethyl cellulose; the amino-containing polymer is any one of polyethylenimine, polylysine, poly (allylamine), chitosan, gelatin, collagen, fibrin, bovine serum albumin and fibroin.
6. The method according to claim 1, wherein the mass fraction of the solute in the solution a is 0.5% -60% by weight, and the mass fraction of the solute in the solution B is 0.5% -60% by weight.
7. The preparation method according to claim 1, wherein the volume ratio of the solution a to the solution B is 1:1.
8. The boron-nitrogen internal coordination borate hydrogel is characterized by being prepared by the method of any one of claims 1-7.
9. The boron-nitrogen internally coordinated borate hydrogel according to claim 8, wherein the hydrogel comprises cross-links of boron-nitrogen internally coordinated borate linkages having the formula:
。
10. The boron-nitrogen internally coordinated borate hydrogel of claim 8 or 9, wherein the hydrogel has pH responsiveness and gels at a pH in the range of a lower limit of 2 to 8 and an upper limit of 9 to 11.
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