The invention content is as follows:
in order to overcome the defects mentioned in the background technology, the invention provides a preparation method of ultraviolet light blocking type hydrogel, and the invention uses a reducing agent and Fe3+The solution introduces zero-valent iron particles into hydrogel grids, and generates Fe through oxidation2+When persulfate is added, the system can form a redox system, and can initiate the polymerization of the pre-emulsion containing light barrier under mild conditions, because of Fe2+The ions are supplied by the oxidized nano-iron particles, compared with the direct preparation of Fe2+The reaction speed of the ions is not too fast, and Fe can be controlled by adjusting oxygen supply2+The generated ions and the generated nanoparticles with the light blocking effect contain reactive active functional group carboxyl, and the nanoparticles can react with the active functional group amino of the hydrogel after being activated by EDC/NHS, so that the nanoparticles are fixed.
The invention is realized by the following technical scheme:
a preparation method of ultraviolet light blocking type hydrogel containing immobilized nanoparticles comprises the following steps:
the method comprises the following steps: mixing 20-100ml of the mixture in a volume ratio of 1-4: adding the mixed solvent of water and glycol of 1 into a beaker, adding 10-50g of the monomer mixture 1, performing ultrasonic dispersion at low temperature for 10-30min, adding 0.05-1g of initiator, performing ultrasonic dispersion at low temperature for 15-50min, pouring into a mold after the ultrasonic dispersion is finished, standing for 8-18h at 30-60 ℃, heating to 50-90 ℃, and keeping for 12-36h to obtain an intermediate product;
step two: putting the intermediate product obtained in the step one into a three-neck flask, adding 100-500ml deionized water to soak for 1-3 days, replacing the deionized water every 8h, introducing nitrogen for 20-60min, then transferring the whole system into an oscillating table at an oscillating speed of 20-300rpm/min, firstly adding 10-150ml reducing agent, and then dropwise adding 5-100ml Fe3+Continuously oscillating the solution for 0.5-12h after the dropwise adding is finished to obtain hydrogel 1;
step three: adding 15-30g of monomer mixture 2 (containing vinyl ultraviolet absorbent, carboxyl acrylate and n-butyl acrylate), 1-15g of 1-pentanol and 0.01-1.5g of emulsifier into a three-neck flask filled with 50-300ml of distilled water, and stirring for 20-60min to obtain a pre-emulsion; placing the hydrogel 1 prepared in the step two into a three-neck flask, adding 20-200ml of deionized water, placing on an oscillating shaker, oscillating at the speed of 20-50rpm/min and introducing oxygen, placing 5-40ml of the pre-emulsion into a micro-sample injector, placing 5-50ml of 0.01-1g/ml persulfate aqueous solution for later use, under the oscillation at the speed of 20-100rpm/min, dropwise adding persulfate aqueous solution into the diluted hydrogel and simultaneously injecting the pre-emulsion, maintaining the oscillation at the speed of 20-100rpm/min for 10-24h after the dropwise adding and sample introduction are finished, and stopping oxygen supply to obtain a hydrogel 2;
step four: and (3) putting the hydrogel 2 obtained in the third step into an erlenmeyer flask filled with 50-200ml of PBS aqueous solution with the pH value of 4.5-7, respectively adding (1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride) (EDC) and N-hydroxysuccinimide (NHS), moving the erlenmeyer flask into a shaking table, shaking for 0.5-24h at the speed of 50-300rpm/min, and washing for 1-3 times by using deionized water to obtain the target hydrogel.
Wherein, in the first step, the monomer mixture 1 is prepared by mixing the following components in a mass ratio of 1: 0.01-0.1:0.01-0.2 of hydroxyethyl methacrylate, ethylene glycol dimethacrylate and amino group-containing monomer; wherein the amino-containing monomer is one or a mixture of 1-allyl piperazine, N-ethyl methyl allylamine, N-methyl allylamine and diallyl amine.
Wherein, the initiator in the first step is persulfate or azobisisobutyronitrile;
and in the second step, the reducing agent is sodium borohydride or glucose, and the concentration of the reducing agent solution is 0.2-0.5 g/ml.
Wherein, Fe in the second step3+The solution is ferric trichloride hexahydrate, ferric chloride or ferric nitrate aqueous solution, and the concentration of the solution is 0.1-0.9 g/ml.
Wherein, the vinyl-containing ultraviolet absorbent in the third step is one or more of 2- (2 '-hydroxy-5' -2- (methacryloyloxy) ethyl) phenyl) -2H-benzotriazole, 2- [3- (2H-benzotriazole-2-yl) -4-hydroxyphenyl ] ethyl 2-methacrylate, and 2- (4-benzoyl-3-hydroxyphenoxy) ethyl 2-acrylate.
Wherein the mass ratio of the vinyl-containing ultraviolet absorbent, the carboxyl-containing acrylate and the n-butyl acrylate in the third step is 1:50-150: 100-300.
Wherein the emulsifier in the third step is one or a mixture of more of an op-10 emulsifier, sodium dodecyl sulfate, sodium dodecyl benzene sulfonate and octadecyl trimethyl ammonium chloride.
Wherein, the persulfate in the third step is one or a mixture of more of ammonium persulfate, potassium persulfate and sodium persulfate.
Wherein the concentration range of (1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride) in the fourth step is 0.5-20mg/ml, and the dosage of the concentration is 0.05-0.2 percent of the total amount of the amino monomer and the carboxyl monomer; the concentration range of the N-hydroxysuccinimide is 0.1-15mg/ml, and the dosage of the N-hydroxysuccinimide accounts for 0.05% -0.2% of the total amount of the amino monomer and the carboxyl monomer.
The ultraviolet light blocking hydrogel loaded with the nano particles is prepared by the preparation method.
Compared with the prior art, the invention has the beneficial effects that:
1. the invention uses reducing agent and Fe3+The solution introduces zero-valent iron particles into hydrogel grids, and generates Fe through oxidation2+The oxide of (2) forms a redox system after adding persulfate, and can initiate the polymerization of the pre-emulsion containing light barrier under mild conditions, because of Fe2+The ions are supplied by the oxidized nano-iron particles, compared with the direct preparation of Fe2+The reaction speed of ions is not too fast, the reaction is mild, the hydrogel structure is not easy to be damaged, and Fe can be controlled by supplying oxygen2+Ions are generated, thereby controlling the extent of the reaction. Solves the technical problem that the preparation process and reaction conditions of the hydrogel heavy-load nano particles need to be very mild. In addition, the mild and controllable reaction enables the nano ions to form slowly without agglomeration, so that the prepared hydrogel keeps good light transmittance.
2. According to the invention, the amino groups of the EDC/NHS activated hydrogel react with the carboxyl groups of the nanoparticles to fix the nanoparticles with ultraviolet light blocking performance in the hydrogel system, the reaction conditions are mild, and the problems of nanoparticle overflow and agglomeration after long-term use are solved.
The specific implementation mode is as follows:
the present invention is described in detail below with reference to examples, which are provided for further illustration of the present invention and are not to be construed as limiting the scope of the present invention. It should be understood that various changes and modifications can be made by those skilled in the art after reading the disclosure of the present invention, and equivalents fall within the scope of the appended claims.
Example 1
The method comprises the following steps: 50ml of the mixture is mixed into a mixture with the volume ratio of 3: 1, adding a mixed solvent of water and ethylene glycol into a beaker, and adding 30g of a mixed solvent with the mass ratio of 1: 0.05:0.015 of a mixture of hydroxyethyl methacrylate, ethylene glycol dimethacrylate and 1-allylpiperazine, ultrasonically dispersing for 15min at low temperature, adding 0.1g of azobisisobutyronitrile, ultrasonically separating for 45min at low temperature, pouring into a mold after the ultrasonic dispersion is finished, standing for 9h at 40 ℃, heating to 60 ℃, and keeping for 12h to obtain an intermediate product;
step two: putting the intermediate product obtained in the first step into a three-neck flask, adding 200ml of deionized water, soaking for 2 days, replacing the deionized water every 8 hours, then introducing nitrogen for 30min, then transferring the whole system into an oscillating table, adjusting the oscillation speed to 200rpm/min, firstly adding 60mlm of 0.3g/ml sodium borohydride solution, then dropwise adding 55ml of 0.5g/ml ferric chloride solution, and continuing to oscillate for 5 hours after dropwise adding is finished to obtain hydrogel 1;
step three: adding 20g of 2- (2 '-hydroxy-5' -2- (methacryloyloxy) ethyl) phenyl) -2H-benzotriazole, a mixture of carboxyl-containing acrylate and n-butyl acrylate, 7g of 1-Pentanol (1-Pentanol) and 0.3g of op-10 emulsifier in a mass ratio of 1:100:210 into a three-neck flask filled with 120ml of distilled water, stirring for 35min to obtain a pre-emulsion, putting hydrogel 1 into the three-neck flask, adding 60ml of deionized water, placing on a shaking table, shaking at a speed of 40rpm/min and introducing oxygen, taking 20ml of the pre-emulsion into a microsyringe, taking 30ml of 0.05g/ml ammonium persulfate aqueous solution for standby, dropping the ammonium persulfate aqueous solution into the hydrogel and injecting the pre-emulsion simultaneously under shaking at a speed of 70rpm/min, after the dripping and the sample introduction are finished, maintaining the speed of 60rpm/min for oscillation for 16h, and stopping supplying oxygen to obtain hydrogel 2;
step four: placing the hydrogel 2 obtained in the third step into an erlenmeyer flask containing 120ml of PBS aqueous solution with the pH value of 7, adding 8ml of (1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride) (EDC) with the concentration of 1mg/ml and 4ml of N-hydroxysuccinimide (NHS) with the concentration of 2mg/ml respectively, moving the erlenmeyer flask into a shaking table, shaking for 1h at the speed of 100rpm/min, and washing for 3 times by using deionized water to obtain the target hydrogel.
Example 2
The method comprises the following steps: mixing 60ml of the mixture in a volume ratio of 3: 1, adding a mixed solvent of water and ethylene glycol into a beaker, and adding 30g of a mixed solvent with the mass ratio of 1: 0.05:0.05 of mixture of hydroxyethyl methacrylate, ethylene glycol dimethacrylate and N-ethyl methyl acrylamide, ultrasonically dispersing for 25min at low temperature, then adding 0.07g of azodiisobutyronitrile, ultrasonically dispersing for 40min at low temperature, pouring into a mold after the ultrasonic dispersion is finished, standing for 10h at 50 ℃, heating to 60 ℃, and keeping for 24h to obtain an intermediate product;
step two: putting the intermediate product obtained in the first step into a three-neck flask, adding 200ml of deionized water, soaking for 3 days, replacing the deionized water every 8 hours, then introducing nitrogen for 50min, then transferring the whole system into an oscillating table, adjusting the oscillating speed to 200rpm/min, firstly adding 100ml of 0.3g/ml sodium borohydride solution, then dropwise adding 90ml of 0.6g/ml ferric chloride solution, and continuing to oscillate for 6 hours after dropwise adding is finished to obtain hydrogel 1;
step three: adding 25g of 2- (2 '-hydroxy-5' -2- (methacryloyloxy) ethyl) phenyl) -2H-benzotriazole, a mixture of carboxyl-containing acrylate and n-butyl acrylate, 10g of 1-Pentanol (1-Pentanol) and 1g of sodium dodecyl sulfate in a mass ratio of 1:120:200 into a three-neck flask filled with 100ml of distilled water, stirring for 60min to obtain a pre-emulsion, putting the hydrogel 1 into the three-neck flask, adding 100ml of deionized water, placing on a shaking table, shaking at a speed of 50rpm/min and introducing oxygen, taking 30ml of the pre-emulsion into a microsyringe, taking 40ml of 0.5g/ml ammonium persulfate aqueous solution for standby, dropping the ammonium persulfate aqueous solution into the hydrogel and simultaneously injecting the pre-emulsion under shaking at a speed of 80rpm/min, after the dripping and the sample introduction are finished, the speed of 70rpm/min is maintained for oscillation for 20h, and oxygen supply is stopped to obtain hydrogel 2;
step four: placing the hydrogel 2 obtained in the third step into an erlenmeyer flask containing 100ml of PBS aqueous solution with the pH value of 4.5, adding 10ml of (1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride) (EDC) with the concentration of 1mg/ml and 10ml of N-hydroxysuccinimide (NHS) with the concentration of 1.5mg/ml respectively, moving the erlenmeyer flask into a shaking table, shaking for 0.5h at the speed of 250rpm/min, and washing for 2 times with deionized water to obtain the target hydrogel.
Example 3
The method comprises the following steps: mixing 65ml of the mixture in a volume ratio of 4: 1, adding a mixed solvent of water and ethylene glycol into a beaker, and adding 45g of a mixed solvent with the mass ratio of 1: 0.05:0.015 of a mixture of hydroxyethyl methacrylate, ethylene glycol dimethacrylate and 1-allylpiperazine, ultrasonically dispersing for 30min at low temperature, adding 0.8g of azobisisobutyronitrile, ultrasonically dispersing for 50min at low temperature, pouring into a mold after the ultrasonic dispersion is finished, standing for 18h at 55 ℃, heating to 80 ℃, and keeping for 30h to obtain an intermediate product;
step two: putting the intermediate product obtained in the step one into a three-neck flask, adding 300ml of deionized water, soaking for 2 days, replacing the deionized water every 8 hours, then introducing nitrogen for 50 minutes, then transferring the whole system into an oscillating table, adjusting the oscillation speed to 250rpm/min, firstly adding 125ml of 0.3g/ml sodium borohydride solution, then dropwise adding 95ml of 0.6g/ml ferric chloride solution, and continuing to oscillate for 11 hours after dropwise adding is finished to obtain hydrogel 1;
step three: adding 30g of 2- (4-benzoyl-3-hydroxyphenoxy) ethyl 2-acrylate, a mixture of carboxyl-containing acrylate and n-butyl acrylate, 15g of 1-Pentanol (1-Pentanol) and 1.3 gp-10 emulsifier in a mass ratio of 1:100:200 into a three-neck flask filled with 300ml of distilled water, stirring for 60min to obtain a pre-emulsion, putting the hydrogel 1 into the three-neck flask, adding 180ml of deionized water, placing on a shaking table, shaking at a speed of 50rpm/min and introducing oxygen, taking 30ml of the pre-emulsion into a microsyringe, taking 50ml of 0.5g/ml sodium persulfate aqueous solution for standby, dropping the sodium persulfate aqueous solution into the hydrogel and simultaneously injecting the pre-emulsion under the shaking at a speed of 100rpm/min, maintaining the shaking speed of 100rpm/min for 24h after dropping and sample introduction, stopping supplying oxygen to obtain hydrogel 2;
step four: placing the hydrogel 2 obtained in the third step into an erlenmeyer flask containing 130ml of PBS aqueous solution with the pH value of 5, respectively adding 20ml of (1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride) (EDC) with the concentration of 1mg/ml and 10ml of N-hydroxysuccinimide (NHS) with the concentration of 2mg/ml, moving the erlenmeyer flask into a shaking table, shaking for 3 hours at the speed of 250rpm/min, and then washing for 3 times by using deionized water to obtain the target hydrogel.
Example 4
The method comprises the following steps: mixing 40ml of the mixture in a volume ratio of 2: 1, adding 20g of a mixed solvent of water and glycol into a beaker, wherein the mixed solvent is prepared by mixing the following components in a mass ratio of 1: 0.06:0.1 of a mixture of hydroxyethyl methacrylate, ethylene glycol dimethacrylate and 1-allylpiperazine, ultrasonically dispersing for 15min at low temperature, adding 0.3g of azobisisobutyronitrile, ultrasonically dispersing for 20min at low temperature, pouring into a mold after the ultrasonic dispersion is finished, standing for 9h at 40 ℃, heating to 50 ℃, and keeping for 15h to obtain an intermediate product;
step two: putting the intermediate product obtained in the first step into a three-neck flask, adding 150ml of deionized water, soaking for 2 days, replacing the deionized water every 8 hours, then introducing nitrogen for 20min, then transferring the whole system into an oscillating table, adjusting the oscillating speed to 100rpm/min, firstly adding 80ml of 0.3g/ml sodium borohydride solution, then dropwise adding 60ml of 0.7g/ml ferric chloride hexahydrate solution, and continuing to oscillate for 5 hours after dropwise adding is finished to obtain hydrogel 1;
step three: adding 15g of 2- (4-benzoyl-3-hydroxyphenoxy) ethyl 2-acrylate, a mixture of acrylic ester containing carboxyl and n-butyl acrylate, 6g of 1-Pentanol (1-Pentanol) and 1.3g of sodium dodecyl benzene sulfonate in a mass ratio of 1:150:200 into a three-neck flask filled with 200ml of distilled water, stirring for 50min to obtain a pre-emulsion, putting the hydrogel 1 into the three-neck flask, adding 150ml of deionized water into the three-neck flask, placing the hydrogel on a shaking table, shaking at a speed of 40rpm/min and introducing oxygen, putting 30ml of the pre-emulsion into a microsyringe, taking 20ml of 0.2g/ml of sodium persulfate aqueous solution for standby, dripping the sodium persulfate aqueous solution into the hydrogel under shaking at a speed of 100rpm/min and simultaneously injecting the pre-emulsion, maintaining the shaking speed of 100rpm/min after dripping and sample injection for 14h, stopping supplying oxygen to obtain hydrogel 2;
step four: and (2) putting the hydrogel 2 obtained in the third step into an erlenmeyer flask containing 60ml of PBS (phosphate buffer solution) with the pH value of 6, respectively adding 10ml of (1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride) (EDC) with the concentration of 1mg/ml and 7ml of N-hydroxysuccinimide (NHS) with the concentration of 1mg/ml, moving the erlenmeyer flask into a shaking table, shaking for 2 hours at the speed of 200rpm/min, and washing for 2 times by using deionized water to obtain the target hydrogel.
Example 5
The method comprises the following steps: mixing 35ml of the mixture in a volume ratio of 3: 1, adding a mixed solvent of water and ethylene glycol into a beaker, and adding 1g of a mixed solvent of water and ethylene glycol in a mass ratio of 1: 0.06:0.05 of a mixture of hydroxyethyl methacrylate, ethylene glycol dimethacrylate and N-ethyl methyl acrylamide, ultrasonically dispersing for 15min at low temperature, then adding 0.25g of azobisisobutyronitrile, ultrasonically dispersing for 20min at low temperature, pouring into a mold after the ultrasonic dispersion is finished, standing for 12h at 35 ℃, heating to 65 ℃ and keeping for 20h to obtain an intermediate product;
step two: putting the intermediate product obtained in the first step into a three-neck flask, adding 150ml of deionized water, soaking for 2 days, replacing the deionized water every 8 hours, then introducing nitrogen for 30min, then transferring the whole system into an oscillating table, adjusting the oscillation speed to 150rpm/min, firstly adding 55ml of sodium borohydride solution with the concentration of 0.3g/ml, then dropwise adding 40ml of ferric chloride solution with the concentration of 0.7g/ml, and continuing to oscillate for 8 hours after dropwise adding is finished to obtain hydrogel 1;
step three: adding 15g of 2- (4-benzoyl-3-hydroxyphenoxy) ethyl 2-acrylate, a mixture of acrylic ester containing carboxyl and n-butyl acrylate, 6g of 1-Pentanol (1-Pentanol) and 1g of sodium dodecyl benzene sulfonate in a mass ratio of 1:150:200 into a three-neck flask filled with 100ml of distilled water, stirring for 35min to obtain a pre-emulsion, putting the hydrogel 1 into the three-neck flask, adding 120ml of deionized water, placing on a shaking table, shaking at a speed of 30rpm/min and introducing oxygen, taking 25ml of the pre-emulsion into a microsyringe, taking 35ml of 0.6g/ml ammonium persulfate aqueous solution for standby, adding the ammonium persulfate aqueous solution into the hydrogel dropwise and injecting the pre-emulsion simultaneously under the speed of 80rpm/min, keeping the dropping and sample injection speeds of 800rpm/min for 16h, stopping supplying oxygen to obtain hydrogel 2;
step four: putting the hydrogel 2 obtained in the third step into an erlenmeyer flask containing 90ml of PBS aqueous solution with the pH value of 7, respectively adding 8ml of (1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride) (EDC) with the concentration of 1mg/ml and 5ml of N-hydroxysuccinimide (NHS) with the concentration of 2mg/ml, moving the erlenmeyer flask into a shaking table, shaking for 0.5h at the speed of 200rpm/min, and washing for 2 times by using deionized water to obtain the target hydrogel.
The attached figure 1 in the description shows the ultraviolet transmittance of the hydrogel prepared in the embodiment 1-5, and the ultraviolet transmittance of the ultraviolet light barrier hydrogel prepared in the embodiment 1-5 is 63% -70%.
Fig. 2 in the specification is a condition of nanoparticle cumulative release after 10 days of the hydrogel prepared in the embodiments 1 to 5, and the cumulative release rates of the nanoparticles after 10 days of the ultraviolet light blocking hydrogel prepared in the embodiments 1 to 5 are respectively 11%, 9%, 9%, 10% and 8%, which shows that in the ultraviolet light blocking hydrogel prepared in the embodiments of the present invention, the nanoparticles with ultraviolet light blocking performance are fixed in the hydrogel system and are not easy to overflow.