CN110423307B - Preparation method and application of photo-thermal dual stimulus response hydrogel containing alpha-cyclodextrin - Google Patents
Preparation method and application of photo-thermal dual stimulus response hydrogel containing alpha-cyclodextrin Download PDFInfo
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Abstract
The invention belongs to the technical field of preparation of environment functional materials, and relates to a preparation method and application of a photo-thermal dual stimulus response hydrogel containing alpha-cyclodextrin; the method comprises the following steps: firstly, preparing alpha-cyclodextrin ester and acrylamide azobenzene, then adding the alpha-cyclodextrin ester and acrylamide azobenzene into a dimethyl sulfoxide solution together with methylene bisacrylamide and isopropyl acrylamide, and performing ultrasonic oscillation to obtain a mixed solution B; then adding azodiisoheptanonitrile into the dimethyl sulfoxide solution to obtain a mixed solution D; finally, adding the mixed solution D into the mixed solution B, mixing and reacting in a water bath kettle to obtain the photo-thermal dual-stimulus response hydrogel; the hydrogel prepared by the invention simultaneously introduces cyclodextrin and light and temperature structural response units, can carry out a large amount of loading on drug molecules, and can timely make a response change for adjusting the release speed of the drug molecules when the external temperature and the illumination wavelength are changed; meanwhile, the method is simple and convenient to operate, and the prepared hydrogel is safe, environment-friendly and good in stability.
Description
Technical Field
The invention belongs to the technical field of preparation of environment functional materials, and particularly relates to a preparation method and application of a photo-thermal dual stimulus response hydrogel containing alpha-cyclodextrin.
Background
With the steady development of modern medical technology and the intensive integration of multiple disciplines, people are implementing further improvement of drug efficacy by using various materials and methods, wherein, implementing more drug enrichment, controllable release speed is two important ways to improve drug efficacy. Hydrogels are one of the ideal materials for such controlled release of drugs. The hydrogel is a polymer with a three-dimensional network structure formed by crosslinking through covalent bonds, hydrogen bonds or van der Waals force and the like, can swell in water and keep a large amount of water without dissolving, has good biocompatibility and permeability, can synthesize hydrogel materials with different performances according to actual needs, and can improve the mechanical strength and stability of the hydrogel material serving as a drug release carrier by increasing the crosslinking ratio of the hydrogel in the synthesis process. The stimulation responsive structural unit is introduced into the hydrogel polymer network, so that the hydrogel can realize the controllable regulation of the release speed and the release mode of the drug molecules through the change of the structure and the performance after being stimulated by the change of the external environment. The intelligent hydrogel capable of spontaneously making intelligent stress response behaviors to external stimuli arouses more and more interests and attention of researchers due to the huge value displayed in theoretical research and practical application. According to the type of external stimulus, the stimulus-responsive macromolecular gel can be divided into thermal response, pH response, photoresponse and the like, and different types of stimulus-responsive systems have the characteristics of the systems and have respective advantages under certain specific environmental conditions. However, in recent years, light stimulus and temperature stimulus responsive polymers have attracted increasing attention from researchers due to their unique advantages in terms of safety, controllability, convenience, and the like. The application of illumination and temperature as external stimuli has the advantages that the application is safe and nontoxic to the environment and human body, non-contact stimulation and control can be realized, the illumination time, the position, the range, the distance and the like can be conveniently adjusted, and the temperature as an important physiological parameter can directly reflect the health state of the human body, so that the hydrogel material capable of performing spontaneous responsive behavior according to the change of the external illumination and the temperature of the human body has important research value in the aspect of drug delivery.
The prior literature research reports that Inomata and the like synthesize hydrogel by using N-isopropyl acrylamide, and the hydrogel has the temperature responsiveness of swelling at low temperature and shrinking at high temperature in aqueous solution. Studies such as Chenli and the like find that the hydrogel containing the azobenzene group has very sensitive responsiveness to ultraviolet light and pH, and the volume of the gel is obviously reduced after the ultraviolet light irradiation; and the rate of gel shrinkage increases with the proportion of azobenzene groups in the copolymeric hydrogel. However, in the current research on hydrogel drug controlled release, a single sensitive control system is mostly adopted, which causes the problems that the hydrogel has insufficient drug molecular load and the loaded drug molecules cannot be effectively released into the environment. However, according to the invention, the azobenzene, the cyclodextrin and the N-isopropyl acrylamide are subjected to graft copolymerization for the first time, and the photosensitive component and the temperature-sensitive component are introduced into the hydrogel polymer network together, so that the loading capacity of the hydrogel on drug molecules is greatly increased, and the controlled release effect of the hydrogel on the drug molecules is further improved.
Disclosure of Invention
In view of the deficiencies of the prior art, the present invention is directed to solving one of the problems; the invention provides a preparation method of intelligent responsive hydrogel for controlled release of drugs; the hydrogel realizes the controllable release of drug molecules through the compounding/dissociation between a host and an object of a photosensitive complex system and the responsive change of the contraction/expansion of temperature-sensitive components when being subjected to the change of external temperature and illumination wavelength, thereby being used as a carrier material in the aspect of intelligent transdermal drug delivery.
In order to achieve the above purpose, the invention adopts the technical scheme that:
the photothermal dual stimulus response hydrogel comprises alpha-cyclodextrin, wherein a macromolecular chain of the hydrogel is provided with a photosensitive unit and a temperature sensitive unit simultaneously. The light-sensitive monomers and the temperature-sensitive monomers are grafted into the polymer network by free-radical polymerization. The preparation steps are as follows:
(1) preparation of alpha-cyclodextrin ester: dissolving alpha-cyclodextrin and Dimethylformamide (DMF) under magnetic stirring, then dropwise adding triethylamine, placing the mixture in an ice water bath, uniformly stirring the mixture under magnetic stirring, slowly dropwise adding acryloyl chloride under the condition of introducing nitrogen for protection, reacting at room temperature after dropwise adding is finished, performing vacuum filtration after reaction is finished, removing precipitated solids, collecting filtrate, precipitating the filtrate with acetone, performing vacuum filtration again, repeatedly washing and filtering the obtained white solids with acetone again, and performing vacuum drying on the final product to constant weight to obtain alpha-cyclodextrin ester;
(2) preparation of acrylamidoazobenzene: dissolving aminoazobenzene and benzene under magnetic stirring, adding triethylamine, slowly dropwise adding acryloyl chloride while magnetically stirring, then carrying out stirring reflux reaction at a certain temperature, cooling to room temperature after the reaction is finished, carrying out vacuum filtration and drying to obtain an orange-red solid, washing with distilled water, carrying out filtration and drying, then carrying out recrystallization with absolute ethyl alcohol, and carrying out vacuum drying on a final product to constant weight to obtain acrylamidoazobenzene;
(3) preparing the photo-thermal dual stimulus response hydrogel: adding methylene Bisacrylamide (BIS), isopropylacrylamide, the alpha-cyclodextrin ester prepared in the step (1) and the acrylamidoazobenzene prepared in the step (2) into the dimethyl sulfoxide solution A, and dissolving by ultrasonic oscillation to obtain a mixed solution B; then adding Azodiisoheptanonitrile (AVBN) into the dimethyl sulfoxide solution C to obtain a mixed solution D; and finally, adding the mixed solution D into the mixed solution B, mixing, placing in a water bath for reaction at a certain temperature, and reacting to obtain the photo-thermal dual-stimulus response hydrogel.
Preferably, the amount ratio of alpha-cyclodextrin to Dimethylformamide (DMF) used in step (1) is 1.94 g: 15-20 mL; the dosage ratio of the triethylamine to the acryloyl chloride to the alpha-cyclodextrin is 2-3 mL: 1-2 mL: 1.94 g.
Preferably, the reaction time in the step (1) at room temperature is 30-60 min; the temperature of the vacuum drying is 60-80 ℃.
Preferably, the dosage ratio of the p-aminoazobenzene to the benzene used in the step (2) is 1.97g: 15-20 mL; the dosage ratio of the triethylamine, the acryloyl chloride and the p-aminoazobenzene is 1.5-2.5 mL: 1-2 mL:1.97 g.
Preferably, the certain temperature condition in the step (2) is 60-80 ℃, and the stirring reflux reaction time is 4-6 h.
Preferably, the temperature of the vacuum drying in the step (2) is 60-80 ℃.
Preferably, the dosage ratio of the alpha-cyclodextrin ester, the acrylamide-based azobenzene, the methylene-bis-acrylamide, the isopropyl acrylamide and the dimethyl sulfoxide solution A in the step (3) is 0.1g: 0.05-0.1 g: 0.15-0.2 g, 0.6-0.8 g, 4-7 mL.
Preferably, the dosage ratio of the alpha-cyclodextrin ester, the azodiisoheptanonitrile and the dimethyl sulfoxide solution C in the step (3) is 0.1g to 0.05-0.1 g: 1-2 mL.
Preferably, the certain temperature in the step (3) is 50-60 ℃, and the reaction time is 2-4 h.
Wherein the dimethyl sulfoxide solution A and the dimethyl sulfoxide solution C are both dimethyl sulfoxide solutions, and letters are added for distinguishing when in expression.
The invention has the advantages that:
(1) according to the invention, a great amount of loading of hydrogel on drug molecules is realized, a cyclodextrin unit is introduced into a polymer network, the cyclodextrin has a ring structure with a hydrophilic outer wall and a hydrophobic inner cavity, and the drug molecules are combined with a cyclodextrin cavity to form a host-guest compound, so that the water solubility of the guest molecules is greatly changed.
(2) The invention synthesizes alpha-cyclodextrin ester and acrylamide group azobenzene as photosensitive components by esterification reaction of alpha-cyclodextrin and acryloyl chloride, n-isopropyl acrylamide is used as a temperature-sensitive component, methylene bisacrylamide is used as a cross-linking agent, the double-stimulation response hydrogel with temperature sensitivity and light sensitivity is generated by free radical polymerization, the drug loading capacity of the hydrogel is improved by the inclusion and complex action of cyclodextrin cavities in a hydrogel cross-linked network structure on drug molecules, and the hydrogel, the temperature sensitive component and the light sensitive component are combined together, when the external temperature and the illumination wavelength are changed, the controllable release of drug molecules is realized through the compounding/dissociation between the host and the guest of the photosensitive complex system and the response change of the contraction/expansion of the temperature-sensitive component, thereby being used as a carrier material in the aspect of intelligent transdermal drug delivery.
(3) The prepared photo-thermal dual-stimulus response hydrogel simultaneously introduces cyclodextrin and a light-temperature structure response unit, so that the prepared carrier hydrogel can carry out a large amount of load on drug molecules, and can timely make a response change for adjusting the release speed of the drug molecules when the external temperature and the illumination wavelength are changed; meanwhile, the photo-thermal dual stimulus response hydrogel containing the alpha-cyclodextrin is safe and environment-friendly, has better stability, and is simple and convenient to operate in the preparation process.
Drawings
FIG. 1 is an infrared spectrum of an α -cyclodextrin ester having multiple double bonds prepared in example 1.
FIG. 2 is a schematic representation of the preparation of alpha-cyclodextrin esters with multiple double bonds from example 11H nuclear magnetic spectrum.
FIG. 3 is an infrared spectrum of acrylamidoazobenzene prepared in example 1.
FIG. 4 shows acrylamidoazobenzene prepared in example 11H nuclear magnetic spectrum.
Fig. 5 is an infrared spectrum of the photothermal dual stimulus responsive hydrogel prepared in example 1.
Fig. 6 is a schematic structural view of the photothermal dual stimulus responsive hydrogel prepared in example 1.
FIG. 7 is a release profile of salicylic acid loaded photo-thermal dual stimulus responsive hydrogel prepared in example 1, wherein the release rate changes spontaneously with temperature.
Fig. 8 is a release curve showing that the photothermal dual stimulus responsive hydrogel prepared in example 1 is loaded with salicylic acid, and the release rate thereof is changed spontaneously and responsively with the change of the illumination wavelength.
Detailed Description
The present invention is described in further detail below with reference to specific embodiments.
Example 1:
(1) preparing alpha-cyclodextrin ester;
weighing 1.94g of alpha-cyclodextrin, dissolving the alpha-cyclodextrin in 20mL of dimethylformamide, completely dissolving the alpha-cyclodextrin by magnetic stirring, then dropwise adding 3mL of triethylamine, placing the triethylamine in an ice water bath at 0 ℃ and magnetically stirring for 5min, slowly dropwise adding 2mL of acryloyl chloride into a flask by using a constant-pressure dropping funnel under the condition of introducing nitrogen gas, reacting at room temperature for 30min after dropwise adding is finished, carrying out vacuum filtration after the reaction is finished, removing precipitated solid, precipitating filtrate by using a large amount of acetone, carrying out suction filtration again, washing and filtering the obtained white solid for multiple times by using acetone, placing the final product in a vacuum oven, and drying the white solid to constant weight at 70 ℃ to obtain alpha-cyclodextrin ester;
(2) preparing acrylamide azobenzene;
weighing 1.97g of p-aminoazobenzene, dissolving the p-aminoazobenzene in 20mL of benzene, after completely dissolving the p-aminoazobenzene by magnetic stirring, adding 1.5mL of triethylamine, slowly dropwise adding 1mL of acryloyl chloride while magnetically stirring at room temperature, then stirring and refluxing for 4 hours at 60 ℃, cooling after the reaction is finished, carrying out vacuum filtration and drying, washing the obtained orange-red solid with a small amount of distilled water, carrying out vacuum filtration twice, drying, then recrystallizing with a small amount of absolute ethyl alcohol, placing the final product in a vacuum oven, and drying at 60 ℃ to constant weight to obtain acrylamidoazobenzene;
(3) preparing the photo-thermal dual stimulus response hydrogel: weighing 0.1g of alpha-cyclodextrin ester, 0.1g of acrylamide azobenzene, 0.15g of methylene bisacrylamide and 0.8g N-isopropyl acrylamide, dissolving in 3mL of dimethyl sulfoxide A, and dissolving by ultrasonic oscillation to obtain a mixed solution B; then 0.05g of azodiisoheptanonitrile is added into 1mL of dimethyl sulfoxide solution C to obtain mixed solution D; and finally, adding the mixed solution D into the mixed solution B, mixing, placing in a water bath, and reacting for 2 hours at 55 ℃ to obtain the photo-thermal dual-stimulation response hydrogel after reaction.
Example 2:
(1) preparing alpha-cyclodextrin ester;
weighing 1.94g of alpha-cyclodextrin, dissolving the alpha-cyclodextrin in 15mL of dimethylformamide, performing magnetic stirring to completely dissolve the alpha-cyclodextrin, then dropwise adding 2.5mL of triethylamine, placing the triethylamine in an ice water bath at 0 ℃ and performing magnetic stirring for 3min, slowly dropwise adding 1.5mL of acryloyl chloride into a flask by using a constant-pressure dropping funnel under the condition of introducing nitrogen protection, reacting at room temperature for 20min after dropwise adding is completed, performing vacuum filtration after the reaction is completed, removing precipitated solid, precipitating the filtrate by using a large amount of acetone, performing suction filtration again, washing and filtering the obtained white solid for multiple times by using acetone, placing the final product in a vacuum oven, and drying at 60 ℃ to constant weight to obtain alpha-cyclodextrin ester;
(2) preparing acrylamide azobenzene;
weighing 1.97g of p-aminoazobenzene, dissolving the p-aminoazobenzene in 15mL of benzene, adding 2.5mL of triethylamine after magnetic stirring is completely dissolved, slowly dropwise adding 2mL of acryloyl chloride while magnetic stirring at room temperature, stirring and refluxing for 3 hours at 60 ℃, cooling after reaction, vacuum-filtering and drying, washing the obtained orange-red solid with a small amount of distilled water, filtering twice and drying, recrystallizing with a small amount of absolute ethyl alcohol, placing the final product in a vacuum oven, and drying at 60 ℃ to constant weight to obtain acrylamido azobenzene;
(3) preparing the photo-thermal dual stimulus response hydrogel: weighing 0.1g of alpha-cyclodextrin ester, 0.05g of acrylamide azobenzene, 0.1g of methylene bisacrylamide and 0.6g N-isopropyl acrylamide, dissolving in 3mL of dimethyl sulfoxide A, and dissolving by ultrasonic oscillation to obtain a mixed solution B; then 0.08g of azodiisoheptanonitrile is added into 1mL of dimethyl sulfoxide solution C to obtain mixed solution D; and finally, adding the mixed solution D into the mixed solution B, mixing, placing in a water bath, and reacting for 4 hours at the temperature of 60 ℃ to obtain the photo-thermal dual-stimulation response hydrogel after reaction.
Example 3:
(1) preparing alpha-cyclodextrin ester;
weighing 1.94g of alpha-cyclodextrin, dissolving the alpha-cyclodextrin in 18mL of dimethylformamide, completely dissolving the alpha-cyclodextrin by magnetic stirring, then dropwise adding 2mL of triethylamine, placing the triethylamine in an ice water bath at 0 ℃ and magnetically stirring for 3min, slowly dropwise adding 1mL of acryloyl chloride into a flask by using a constant-pressure dropping funnel under the condition of introducing nitrogen gas, reacting at room temperature for 40min after dropwise adding is finished, performing vacuum filtration after the reaction is finished, removing precipitated solid, precipitating filtrate by using a large amount of acetone, performing suction filtration again, washing and filtering the obtained white solid for multiple times by using acetone, placing the final product in a vacuum oven, and drying the white solid to constant weight at 80 ℃ to obtain alpha-cyclodextrin ester;
(2) preparing acrylamide azobenzene;
weighing 1.97g of p-aminoazobenzene, dissolving in 10mL of benzene, after completely dissolving by magnetic stirring, adding 1.5mL of triethylamine, slowly dropwise adding 1.5mL of acryloyl chloride while stirring by magnetic stirring at room temperature, then stirring and refluxing for 5h at 60 ℃, cooling after the reaction is finished, carrying out vacuum filtration and drying. Washing the obtained orange-red solid with a small amount of distilled water, performing suction filtration twice, drying, then recrystallizing with a small amount of anhydrous ethanol, placing the final product in a vacuum oven, and drying at 80 ℃ to constant weight to obtain acrylamide azobenzene;
(3) preparing the photo-thermal dual stimulus response hydrogel: weighing 0.1g of alpha-cyclodextrin ester, 0.08g of acrylamide azobenzene, 0.2g of methylene bisacrylamide and 0.8g N-isopropyl acrylamide, dissolving in 5mL of dimethyl sulfoxide A, and dissolving by ultrasonic oscillation to obtain a mixed solution B; then 0.1g of azodiisoheptanonitrile is added into 2mL of dimethyl sulfoxide solution C to obtain mixed solution D; and finally, adding the mixed solution D into the mixed solution B, mixing, placing in a water bath, and reacting for 6 hours at 50 ℃ to obtain the photo-thermal dual-stimulation response hydrogel after reaction.
FIG. 1 is an IR spectrum of a cyclodextrin ester having multiple double bonds prepared in example 1; at 1727cm-1A stretching vibration band of 1657cm appears in the ester group, wherein C is O-1The vicinity is a stretching vibration band of C ═ C. 3363cm-1Has a broad absorption peak and a peak height of 2928cm-1The acicular absorption peaks are respectively the stretching vibration bands of hydroxyl and C-H,these indicate that the double bond has been successfully introduced into the alpha-cyclodextrin.
FIG. 2 is a graph of the preparation of cyclodextrin esters with multiple double bonds from example 11H nuclear magnetic spectrum; position of each hydrogen atom:1H NMR(400MHz,D2O):δ(ppm)＝6.39-6.22(m,1H,AA-H),6.21-6.07(m,1H,AA-H),6.07-5.79(m,1H,AA-H),4.89(d,1H,C(1)H of CD),3.78(s,2H,C(3)H of CD),3.78(d,J＝8.8Hz,8H,C(6)H of CD),3.66(d,J＝9.0Hz,5H,C(5)H of CD),3.54(d,J＝10.0Hz,4H,C(2)H of CD),3.47-3.43(m,4H,C(4)H of CD)。
FIG. 3 is an IR spectrum of acrylamidoazobenzene prepared in example 1; wherein, 3200cm-1And 3135cm-1Stretching vibration of C-H bond on carbon-carbon double bond; 3070cm-1Stretching vibration of C-H bond on benzene ring; 1600cm-1And 1556cm-1The skeleton of the benzene ring vibrates. 985cm-1Flexural vibrations of the C-H bond of the monosubstituted olefin also occur. At 3280cm-1And 1670cm-1And respectively shows the stretching vibration peak of N-H bond of amide and C ═ O.
FIG. 4 shows acrylamidoazobenzene prepared in example 11H nuclear magnetic spectrum; in the figure, a (5.78 to 5.84) is a peak of hydrogen on a carbon of a double bond at a trans position of a carbonyl group, b (6.26 to 6.37) is a peak of hydrogen on a carbon of a double bond at a cis position of a carbonyl group, c (6.45 to 6.52) is a peak of hydrogen on a carbon of a double bond connected to a carbonyl group, g (7.46 to 7.55) and f (7.94 to 7.96) are peaks of hydrogen on a benzene ring on the right side, and d (7.77 to 7.82) and e (7.89 to 7.94) are peaks of hydrogen on a benzene ring on the left side.
FIG. 5 is an infrared spectrum of a dual stimulus responsive hydrogel prepared in example 1; 3280cm-1And 1670cm-1Stretching vibration peak of N-H bond and C ═ O of amide group at (A) and 3363cm-1The hydroxyl group has a broad absorption peak and a peak of 2928cm-1The C-H acicular absorption peaks appear in the infrared spectrum of the photothermal sensitive hydrogel, which indicates that the photothermal sensitive hydrogel has been successfully synthesized.
FIG. 6 is a schematic structural diagram of a dual stimuli-responsive hydrogel prepared in example 1; wherein Photo-sensitive entity is a photosensitive part; thermo-sensitive mobility is a thermosensitive moiety.
FIG. 7 is a release curve of salicylic acid loaded hydrogel prepared by the method of example 1, wherein the release rate changes spontaneously and responsively with temperature; the release rate of methylene blue at 37 ℃ is fast, the release rate at 20 ℃ is reduced, and the release can be repeated for a plurality of times. This phenomenon is associated with reversible swelling of the hydrogel at different temperatures.
FIG. 8 is a release curve showing that the hydrogel prepared in example 1 and loaded with salicylic acid has a spontaneous response change in release speed with the change of illumination wavelength; the release rate of methylene blue is fast under the condition of 430nm and slow under the condition of 365nm, and the release can be repeatedly tested. When the system is irradiated by light waves of 430nm from the outside, the azobenzene group is isomerized from cis to trans, enters a cyclodextrin cavity and extrudes drug molecules, so that the drug molecules are more easily dispersed in the solution. The phenomenon is related to the structural cis-trans-change of the azobenzene group of the hydrogel under different wavelengths of illumination.
Description of the drawings: the above embodiments are only used to illustrate the present invention and do not limit the technical solutions described in the present invention; thus, although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted; all such modifications and variations that do not depart from the spirit and scope of the invention are intended to be included within the scope of the appended claims.
Claims (10)
1. A preparation method of photo-thermal dual stimulus-responsive hydrogel containing alpha-cyclodextrin is characterized by comprising the following steps of:
(1) dissolving alpha-cyclodextrin and dimethylformamide under magnetic stirring, then dropwise adding triethylamine, placing the mixture in an ice water bath, uniformly stirring by magnetic stirring, slowly dropwise adding acryloyl chloride under the condition of introducing nitrogen for protection, reacting at room temperature after dropwise adding is finished, performing vacuum filtration after reaction is finished, collecting filtrate, precipitating the filtrate by using acetone, performing vacuum filtration again, repeatedly washing and filtering the obtained white solid by using acetone again, and performing vacuum drying on the final product until the weight is constant to obtain alpha-cyclodextrin ester;
(2) dissolving aminoazobenzene and benzene under magnetic stirring, adding triethylamine, slowly dropwise adding acryloyl chloride while magnetically stirring, then carrying out stirring reflux reaction at a certain temperature, cooling to room temperature after the reaction is finished, carrying out vacuum filtration and drying to obtain an orange-red solid, washing with distilled water, carrying out filtration and drying, then carrying out recrystallization with absolute ethyl alcohol, and carrying out vacuum drying on a final product to constant weight to obtain acrylamidoazobenzene;
(3) adding methylene bisacrylamide, isopropyl acrylamide, the alpha-cyclodextrin ester prepared in the step (1) and the acrylamido azobenzene prepared in the step (2) into the dimethyl sulfoxide solution A, and dissolving by ultrasonic oscillation to obtain a mixed solution B; then adding the azodiisoheptanonitrile into the dimethyl sulfoxide solution C to obtain a mixed solution D; and finally, adding the mixed solution D into the mixed solution B, mixing, placing in a water bath for reaction at a certain temperature, and reacting to obtain the photo-thermal dual-stimulus response hydrogel.
2. The method for preparing photothermal dual stimulus responsive hydrogel comprising α -cyclodextrin according to claim 1, wherein the amount ratio of α -cyclodextrin to dimethylformamide used in step (1) is 1.94 g: 15-20 mL; the dosage ratio of the triethylamine to the acryloyl chloride to the alpha-cyclodextrin is 2-3 mL: 1-2 mL: 1.94 g.
3. The method for preparing the photothermal dual stimulus responsive hydrogel comprising α -cyclodextrin of claim 1, wherein the reaction time in step (1) is 30 to 60min at room temperature; the temperature of the vacuum drying is 60-80 ℃.
4. The method for preparing the photothermal dual stimulus responsive hydrogel containing the alpha-cyclodextrin as claimed in claim 1, wherein the dosage ratio of the p-aminoazobenzene and the benzene used in the step (2) is 1.97g: 15-20 mL; the dosage ratio of the triethylamine, the acryloyl chloride and the p-aminoazobenzene is 1.5-2.5 mL: 1-2 mL:1.97 g.
5. The method for preparing the photothermal dual stimulus response hydrogel containing the α -cyclodextrin as claimed in claim 1, wherein the certain temperature in the step (2) is 60 ℃ to 80 ℃, and the stirring reflux reaction time is 4 to 6 hours.
6. The method for preparing photothermal dual stimulus responsive hydrogel comprising α -cyclodextrin of claim 1, wherein the temperature of said vacuum drying in step (2) is 60 ℃ to 80 ℃.
7. The method for preparing photothermal dual stimulus responsive hydrogel comprising α -cyclodextrin as claimed in claim 1, wherein the amount ratio of α -cyclodextrin ester, acrylamidoazobenzene, methylenebisacrylamide, isopropylacrylamide and dimethylsulfoxide solution a in step (3) is 0.1g: 0.05-0.1 g: 0.15-0.2 g, 0.6-0.8 g, 4-7 mL.
8. The method for preparing the photothermal dual stimulus responsive hydrogel comprising alpha-cyclodextrin of claim 1, wherein the amount ratio of the alpha-cyclodextrin ester, the azobisisoheptonitrile and the dimethylsulfoxide solution C in step (3) is 0.1g: 0.05-0.1 g: 1-2 mL.
9. The method for preparing the photothermal dual stimulus responsive hydrogel comprising α -cyclodextrin of claim 1, wherein the certain temperature in step (3) is 50 to 60 ℃ and the reaction time is 2 to 4 hours.
10. The hydrogel prepared by the method according to any one of claims 1 to 9 is applied to the loading of drug molecules and the adjustment of the release rate of the drug molecules in the drug delivery process.
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| CN111548512B (en) * | 2020-03-31 | 2022-10-25 | 渤海大学 | Method for preparing dendritic hydrogel based on cyclodextrin-based metal-organic framework |
| CN112138636B (en) * | 2020-08-19 | 2023-04-07 | 江苏大学 | Environment-friendly intelligent adsorption material and preparation method and application thereof |
| CN112708149B (en) * | 2020-12-24 | 2022-08-23 | 山东师范大学 | Reversible photosensitive hydrogel and preparation method and application thereof |
| CN115160488A (en) * | 2022-07-13 | 2022-10-11 | 常州工学院 | Preparation method of azopyridine-containing multiple-response intelligent hydrogel |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102321250A (en) * | 2011-07-26 | 2012-01-18 | 浙江大学 | Temperature-sensitive amphiphilic cyclodextrin polymer as well as preparation method and application |
| CN103554369A (en) * | 2013-11-11 | 2014-02-05 | 江苏大学 | Double-stimulus response hydrogel with cyclodextrin and preparation method thereof |
| CN104086705A (en) * | 2014-06-25 | 2014-10-08 | 中科院广州化学有限公司南雄材料生产基地 | Intelligent aquagel based on cyclodextrin functional groups, and preparation method and application thereof |
| CN104829779A (en) * | 2015-05-07 | 2015-08-12 | 宁波大学 | Light-response polymer microgel particle and preparation method thereof |
| CN106432591A (en) * | 2016-09-28 | 2017-02-22 | 江南大学 | Preparation method of photo-responding molecularly imprinted material for selectively separating and purifying cyclodextrin and derivatives of cyclodextrin |
| CN106589410A (en) * | 2016-11-28 | 2017-04-26 | 武汉大学 | Photo-thermal dual-responsive high-strength hydrogel and its preparation method and application |
| CN108484435A (en) * | 2018-04-10 | 2018-09-04 | 杨仲辉 | Modified azobenzene derivative for dyeing and finishing fabric and preparation method thereof |
| CN109867747A (en) * | 2019-03-21 | 2019-06-11 | 济南大学 | A kind of preparation method of the hydrogel with double stimuli responsive and self-healing performance |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10858555B2 (en) * | 2017-06-14 | 2020-12-08 | City University Of Hong Kong | Adhesive system, method of manufacture thereof and biological kit comprising same |
-
2019
- 2019-07-26 CN CN201910680036.1A patent/CN110423307B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102321250A (en) * | 2011-07-26 | 2012-01-18 | 浙江大学 | Temperature-sensitive amphiphilic cyclodextrin polymer as well as preparation method and application |
| CN103554369A (en) * | 2013-11-11 | 2014-02-05 | 江苏大学 | Double-stimulus response hydrogel with cyclodextrin and preparation method thereof |
| CN104086705A (en) * | 2014-06-25 | 2014-10-08 | 中科院广州化学有限公司南雄材料生产基地 | Intelligent aquagel based on cyclodextrin functional groups, and preparation method and application thereof |
| CN104829779A (en) * | 2015-05-07 | 2015-08-12 | 宁波大学 | Light-response polymer microgel particle and preparation method thereof |
| CN106432591A (en) * | 2016-09-28 | 2017-02-22 | 江南大学 | Preparation method of photo-responding molecularly imprinted material for selectively separating and purifying cyclodextrin and derivatives of cyclodextrin |
| CN106589410A (en) * | 2016-11-28 | 2017-04-26 | 武汉大学 | Photo-thermal dual-responsive high-strength hydrogel and its preparation method and application |
| CN108484435A (en) * | 2018-04-10 | 2018-09-04 | 杨仲辉 | Modified azobenzene derivative for dyeing and finishing fabric and preparation method thereof |
| CN109867747A (en) * | 2019-03-21 | 2019-06-11 | 济南大学 | A kind of preparation method of the hydrogel with double stimuli responsive and self-healing performance |
Non-Patent Citations (10)
| Title |
|---|
| Cyclodextrin-Based Polymeric Materials: Synthesis, Properties, and Pharmaceutical/Biomedical Applications;Frank van de Manakker;《Biomacromolecules》;20091118;3157–3175 * |
| Dual Stimuli-Responsive Supramolecular Hydrogel Based on Hybrid Inclusion Complex (HIC);Jianghua Liu;《 Macromolecules》;20100930;8086–8093 * |
| β-环糊精大分子单体/N-异丙基丙烯酰胺共聚水凝胶;刘郁杨等;《高分子材料科学与工程》;20040328(第02期);全文 * |
| 丙烯酰胺基偶氮苯的RAFT聚合反应动力学;李光华等;《化学研究与应用》;20120715(第07期);全文 * |
| 偶氮苯衍生物--β-环糊精包合物的自组装行为;王臻等;《物理化学学报》;20181231(第07期);全文 * |
| 光响应性聚丙烯酰胺基偶氮苯的合成与表征;李光华等;《广西大学学报(自然科学版)》;20100620(第03期);全文 * |
| 温度及pH敏感N-异丙基丙烯酰胺/β-环糊精水凝胶的辐射制备及其性能研究;单廷等;《辐射研究与辐射工艺学报》;20080420(第02期);全文 * |
| 温度和光双重敏感的含偶氮苯端基的聚N-异丙基丙烯酰胺研究;罗春华等;《高分子学报》;20131020(第10期);全文 * |
| 温敏性聚(N-异丙基丙烯酰胺)/聚氨酯-β-环糊精互穿网络水凝胶的溶胀特性;贾剑飞等;《功能高分子学报》;20020930(第03期);全文 * |
| 端基含丙氧基偶氮苯PNIPAM自组装及其响应性能;薛小强等;《高分子材料科学与工程》;20181231(第11期);全文 * |
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