CN110951091B - Preparation method of double-sensitive slow-release beta-cyclodextrin hydrogel - Google Patents
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Abstract
The invention discloses a preparation method of double-sensitive slow-release beta-cyclodextrin hydrogel. The derivative and diethanol amine are subjected to amidation reaction to obtain the functionalized beta-cyclodextrin derivative. Reacting the functionalized beta-cyclodextrin derivative, cholic acid and epichlorohydrin in a sodium hydroxide aqueous solution to obtain a beta-cyclodextrin polymer. The beta-cyclodextrin hydrogel is synthesized by redox free radical polymerization of a beta-cyclodextrin polymer, N-isopropyl acrylamide and an acrylic acid monomer by taking ammonium persulfate as an oxidant, sodium sulfite as a reducing agent, N, N-methylene bisacrylamide as a cross-linking agent and distilled water as a solvent. The invention successfully prepares the double-sensitive slow-release hydrogel which has better temperature and pH sensitivity and slow-release performance.
Description
Technical Field
The invention belongs to the field of high molecular functional materials, and particularly relates to a preparation method of a double-sensitive slow-release beta-cyclodextrin hydrogel.
Background
The hydrogel is a three-dimensional reticular polymer, can not be dissolved in water, and can also be subjected to water absorption swelling in water by utilizing a physical and chemical crosslinking structure of the hydrogel, so that the hydrogel has the advantages of high water content, soft property, high permeability, good biocompatibility and the like. These excellent properties make hydrogels have a wide range of applications in industry, agriculture, biomedicine and even life. In recent years, researchers at home and abroad are dedicated to developing novel hydrogels, and a large number of multifunctional and high-strength novel hydrogels, such as temperature, pH, light and electromagnetic stimulation responsive hydrogels, double-network and interpenetrating network hydrogels, nano-composite hydrogels and self-healing hydrogels, are developed.
Cyclodextrin (CD) is formed by acting Cyclodextrin glucose residual transferase on glucose polymers such as starch, glycogen, maltooligosaccharide and the like, and most commonly comprises three Cyclodextrin alpha, beta and gamma. Among the three cyclodextrins, beta-cyclodextrin (beta-cyclodextrin, abbreviated as beta-CD) is a water-soluble non-reducing white crystal or amorphous powder, and the main body configuration is like a conical cylinder with a hollow in the middle and two unclosed ends. In the hollow structure, the inner cavity is hydrophobic and may contain many guest molecules such as organic molecules, inorganic molecules, complexes, inert gas molecules, etc., so that they may form various inclusion compounds through weak interaction of non-covalent bonds, thereby changing the physicochemical and biological properties of the guest molecules.
Although the hydrogel has a porous structure and can load and release drug molecules, the traditional hydrogel has poor mechanical properties and single function, so that the application of the hydrogel is limited to a certain extent. To modify the hydrogel set of problems, cyclodextrin derivatives with unique structures were incorporated into the hydrogel materials. The cyclodextrin derivative hydrogel has diversified functions, and can change the molecular acting force between drug molecules and polymers, so that the drug slow-release performance of the hydrogel is improved. The cyclodextrin derivatives are diverse, and the structure and the performance of the cyclodextrin derivatives are also diverse, so that the structure and the performance of the hydrogel are different.
Disclosure of Invention
In order to overcome the problems in the prior art, the invention provides a preparation method of a double-sensitive slow-release beta-cyclodextrin hydrogel.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows: a preparation method of a double-sensitive slow-release beta-cyclodextrin hydrogel comprises the following steps:
(1) esterification reaction: fully grinding beta-cyclodextrin and maleic anhydride until the system is uniformly mixed, reacting at esterification temperature, and purifying after the reaction is finished to obtain a maleic anhydride esterified beta-cyclodextrin derivative; the esterification method has the advantages that the product required by the experiment is obtained, the experiment operation is simple, economic and reasonable, and no by-product is generated.
(2) Amide reaction: and (2) reacting the maleic anhydride esterified beta-cyclodextrin derivative prepared in the step (1) with diethanol amine in a tetrahydrofuran solvent, and purifying after the reaction is finished to prepare the amidated beta-cyclodextrin derivative.
(3) Preparation of beta-cyclodextrin polymer: and (3) reacting the amidated beta-cyclodextrin derivative prepared in the step (2), cholic acid and epoxy chloropropane in a sodium hydroxide aqueous solution, and purifying after the reaction is finished to prepare the beta-cyclodextrin polymer.
(4) Preparing hydrogel: and (3) carrying out redox free radical polymerization on the beta-cyclodextrin polymer prepared in the step (3), N-isopropylacrylamide, acrylic acid, ammonium persulfate, sodium sulfite and N, N-methylene bisacrylamide in distilled water to prepare the beta-cyclodextrin hydrogel.
Further, the esterification reaction in the step (1) comprises the following specific preparation steps:
and (3) putting the ground and uniformly mixed beta-cyclodextrin and maleic anhydride powder into a conical flask, reacting for 8 hours at the temperature of 80 ℃, and continuously stirring by using a glass rod at the initial stage of the reaction until the system becomes viscous.
Further, the amidation reaction in the step (2) comprises the following specific preparation steps:
dissolving the maleic anhydride esterified beta-cyclodextrin derivative prepared in the step (1) and diethanol amine by tetrahydrofuran, fully mixing, and reacting for 5 hours at the temperature of 60 ℃ and at the speed of 300 r/min.
Further, the specific preparation steps of the beta-cyclodextrin polymer in the step (3) are as follows:
stirring and mixing the amidated beta-cyclodextrin derivative prepared in the step (2) with cholic acid and sodium hydroxide aqueous solution for 24 hours, adding epoxy chloropropane, stirring for 45 minutes, soaking with acetone for 30 minutes, finally removing the acetone, and standing for 8 hours.
Further, the hydrogel prepared in the step (4) comprises the following specific preparation steps:
and (3) uniformly stirring the beta-cyclodextrin polymer prepared in the step (3) with N-isopropylacrylamide, acrylic acid, ammonium persulfate, sodium sulfite and N, N-methylene bisacrylamide in distilled water, introducing nitrogen for 10min, and reacting for 8h at the temperature of 50 ℃.
Further, the purification operation in the step (1) is: and after the reaction is finished, taking out the solid, grinding the solid into powder, then fully washing, filtering and drying the powder by using acetone and absolute ethyl alcohol in sequence.
Further, the purification operation in the step (2) is: precipitating the product with acetone as precipitant, separating, and drying.
Further, the purification operation in the step (3) is: neutralizing with 6mol/L hydrochloric acid to neutrality, precipitating with anhydrous ethanol as precipitant, separating, and drying.
Further, the step 4 also comprises the steps of soaking the prepared beta-cyclodextrin hydrogel in water for 24 hours and drying.
Further, in the step (1), the molar ratio of the beta-cyclodextrin to the maleic anhydride is 1: 20; the molar ratio of the maleic anhydride esterified beta-cyclodextrin derivative prepared in the step (1) in the step (2) to diethanolamine is 1: 99; the mol ratio of the amidated beta-cyclodextrin derivative prepared in the step (2) in the step (3) to epichlorohydrin is 1: 17; the mass ratio of the beta-cyclodextrin polymer prepared in the step (3) in the step (4) to the N-isopropylacrylamide is 1: 1.
Compared with the prior art, the invention has the beneficial effects that:
(1) the invention prepares the maleic anhydride esterified beta-cyclodextrin derivative by esterification reaction, and the functionalized beta-cyclodextrin derivative is prepared by the method. The hollow cavity structure of the beta-cyclodextrin is not damaged, and simultaneously, a carboxyl functional group is introduced into the beta-cyclodextrin structure, so that more surface modification can be carried out.
(2) According to the invention, the amidated beta-cyclodextrin derivative is obtained through an amide reaction, so that the system becomes more stable under the condition of not damaging the body structure, and a large number of hydroxyl groups can enable the system to be subjected to surface modification through different methods.
(3) The beta-cyclodextrin polymer is synthesized by the method, so that the molecular weight of the system is increased. Not only cholic acid with polyfunctional group is introduced, but also the beta-cyclodextrin derivative and the cholic acid are connected together through epichlorohydrin.
The beta-cyclodextrin hydrogel prepared by redox free radical polymerization has sensitivity to pH and temperature, can swell and include aspirin in water, and is applied to drug sustained release. Therefore, the beta-cyclodextrin hydrogel not only has better double sensitivity, but also has better slow release performance.
Drawings
FIG. 1 is an infrared spectrum of a maleated β -cyclodextrin derivative prepared in step (1) of example 1 of the present invention;
FIG. 2 is an infrared spectrum of an amidated β -cyclodextrin derivative prepared in step (2) of example 1 of the present invention;
FIG. 3 is an infrared spectrum of a β -cyclodextrin polymer prepared in step (3) of example 1 of the present invention;
FIG. 4 is an infrared spectrum of a β -cyclodextrin hydrogel prepared in step (4) of example 1 of the present invention;
FIG. 5 is a swelling curve of a pH sensitivity experiment of a beta-cyclodextrin hydrogel prepared in example 1 of the present invention;
FIG. 6 is a swelling curve of a temperature sensitivity test of a β -cyclodextrin hydrogel prepared in example 1 of the present invention;
FIG. 7 is a swelling curve of a pH sensitivity experiment of a beta-cyclodextrin hydrogel prepared in example 2 of the present invention;
FIG. 8 is a swelling curve of a temperature sensitivity test of a β -cyclodextrin hydrogel prepared in example 2 of the present invention;
fig. 9 is a release profile of a sustained release experiment of the beta-cyclodextrin hydrogel prepared in example 1 of the present invention.
Detailed Description
The invention is described in more detail below with reference to the following examples:
example 1:
a preparation method of a double-sensitive slow-release beta-cyclodextrin hydrogel comprises the following steps:
(1) preparation of maleic anhydride esterified beta-cyclodextrin derivatives by esterification
Weighing 5g of beta-cyclodextrin and 8.8g of maleic anhydride, and fully grinding in a mortar until the system is uniformly mixed. The mixed and ground powder was transferred to a conical flask with a spatula and heated in an oil bath at 80 ℃ for 8 h. Stirring is needed in the early stage of heating to ensure that the powder is fully contacted and reacted, and the stirring is continued when the reaction system begins to become viscous until the system is stirred. The flask was sealed (maleic anhydride sublimes endothermically during the reaction and sealing was required to allow the reaction to proceed adequately). After 8h of reaction, the solid in the flask was taken out and ground into powder. And then, fully washing and filtering with acetone and absolute ethyl alcohol in sequence, washing for 3 times respectively, filtering, and drying to obtain the maleic anhydride esterified beta-cyclodextrin derivative.
FIG. 1 shows that the infrared spectrum of the maleic anhydride esterified beta-cyclodextrin derivative is at 1728cm-1An infrared characteristic vibration absorption peak caused by the symmetric stretching vibration of the unsaturated carboxylic ester appears. And it is in 580cm with beta-cyclodextrin-1Ring vibration of (d) and 940cm-1The skeleton containing alpha-1, 4 glycosidic bonds vibrates basically uniformly. The data show that the maleic anhydride with carboxyl is introduced into the system by adopting esterification reaction, and the maleic anhydride esterified beta-cyclodextrin derivative is successfully prepared;
(2) preparation of amidated beta-cyclodextrin derivatives by amide reaction
And (2) adding 1g of the maleic anhydride esterified beta-cyclodextrin derivative obtained in the step (1), 6.21mL of diethanolamine and 15mL of tetrahydrofuran into a three-neck flask, and putting the three-neck flask into a rotor. Under the action of a magnetic stirrer, the reaction is fully carried out in an oil bath kettle at 60 ℃ and 300r/min, and condensation reflux is needed. Removing the product from the three-neck flask by using a suction pipe after 5h, placing the product into an acetone solution, precipitating by using acetone, and then sequentially separating and drying to obtain the amidated beta-cyclodextrin derivative;
FIG. 2 shows that the infrared spectrum curve of amidated beta-cyclodextrin derivative is 3050-3700 cm-1The stretching vibration peak of-OH appears. since-C ═ O is a tertiary amide, 1630cm-1An absorption peak of-C ═ O, 647cm was observed-1-CN absorption peak. And it is in 580cm with beta-cyclodextrin-1Ring vibration of (d) and 940cm-1The skeleton containing alpha-1, 4 glycosidic bonds vibrates basically uniformly. This data indicates that the introduction of hydroxyl-containing diethanolamine by amide reaction demonstrates the successful preparation of amidated beta-cyclodextrin derivatives;
(3) preparation of beta-cyclodextrin polymers by ring opening reaction
3mL of the amidated β -cyclodextrin derivative obtained in step (2), 0.1g of cholic acid, 10g of sodium hydroxide, and 10mL of water were measured in a three-necked flask. Reacting in a water bath kettle at 25 ℃ for 24 hours under the action of an electronic stirrer to fully activate and amidate beta-cyclodextrin derivatives and hydroxyl of cholic acid, and then dripping 2.5ml of epoxy chloropropane for crosslinking reaction, wherein the crosslinking reaction condition is stirring at 30 ℃ for 45 min. Then 15mL of acetone was added, and the mixture was soaked for 30min to stop the crosslinking reaction, and then acetone was removed (a specific acetone removal method: pouring acetone directly into a beaker, during which the product could not be poured out (delamination occurred during acetone soaking and direct separation was possible)), and the mixture was allowed to stand at 50 ℃ for 8 h. Neutralizing the product to be neutral by using 6mol/L hydrochloric acid, precipitating by using absolute ethyl alcohol, separating and drying to obtain a beta-cyclodextrin polymer;
as can be seen from the infrared spectrum curve of the beta-cyclodextrin polymer in figure 3, the absorption peak of-C ═ O shifts to 1640cm-1，1040cm-1The characteristic absorption peak of epichlorohydrin is shown, 737cm-1The C-Cl disappears in the region of 580cm with beta-cyclodextrin-1Ring vibration of (d) and 940cm-1The skeleton containing alpha-1, 4 glycosidic bonds vibrates basically consistently, which indicates that the ring-opening reaction successfully prepares the beta-cyclodextrin polymer;
(4) preparation of beta-cyclodextrin hydrogels by redox radical polymerization
Weighing 1.5g of the beta-cyclodextrin polymer obtained in the step (3), 1.5g of N-isopropylacrylamide, 0.05g of ammonium persulfate, 0.023g of sodium sulfite, 0.008g of N, N-methylenebisacrylamide, 0.45mL of acrylic acid and 10mL of distilled water in a three-necked flask. After stirring uniformly, nitrogen is introduced for 10 min. And reacting for 8 hours in a water bath environment at 50 ℃. Soaking the product in distilled water for 24h to remove unreacted raw materials and product with insufficient crosslinking degree, and drying (specifically, hydrogel shrinks at 50 deg.C, then the hydrogel is taken out with tweezers and placed in a beaker, and dried at 80 deg.C under vacuum). To obtain the beta-cyclodextrin hydrogel.
FIG. 4 shows that from the infrared spectrum curve of beta-cyclodextrin hydrogel, 3130-3760 cm-1at-NH and-OH absorption peaks at 1730cm-1Is the absorption peak of-C ═ O in carboxylic ester, 1640cm-1Absorption peak of-C ═ O in the amide group, 1540cm-1A band II of-NH, which is at 580cm with beta-cyclodextrin-1Ring vibration of (d) and 940cm-1The skeleton containing alpha-1, 4 glycosidic bonds vibrates basically in a consistent way, and the result shows that the beta-cyclodextrin hydrogel is prepared by free radical synthesis work.
Example 2
(1) The method for preparing the maleic anhydride esterified beta-cyclodextrin derivative by esterification reaction is the same as that of example 1;
(2) the process for the preparation of amidated beta-cyclodextrin derivatives by amide reaction is the same as in example 1;
(3) the method for preparing the beta-cyclodextrin polymer by ring opening and ring closing is the same as the example 1;
(4) preparing beta-cyclodextrin hydrogel by redox free radical polymerization;
weighing 1.5g of the beta-cyclodextrin polymer obtained in the step (3), 1.5g of N-isopropylacrylamide, 0.05g of ammonium persulfate, 0.023g of sodium sulfite, 0.008g of N, N-methylenebisacrylamide, 0.15mL of acrylic acid and 10mL of distilled water in a three-necked flask. After stirring uniformly, nitrogen is introduced for 10 min. And reacting for 8 hours in a water bath environment at 50 ℃. And soaking the product in distilled water for 24 hours, and drying to obtain the beta-cyclodextrin hydrogel.
Effects of the embodiment
1. The pH sensitivity of the beta-cyclodextrin hydrogel is tested as follows;
the beta-cyclodextrin hydrogel is respectively placed in buffer solutions with pH values of 2.2, 5.0, 7.4, 8.0 and 8.6 to swell at 25 ℃. The time is set to be 0h, 0.5h, 1.0h, 1.5h, 2.0h, 2.5h, 3h, 5h, 7h, 9h, 13h, 17h, 21h, 25h, 33h and 41h, the gel is taken out at each time point, the buffer solution on the surface of the gel is sucked by filter paper, the mass of the buffer solution is weighed, and the swelling ratio is calculated.
2. The temperature sensitivity test method of the beta-cyclodextrin hydrogel comprises the following steps:
the beta-cyclodextrin hydrogel is placed in buffer solution with pH of 2.2, 5.0, 7.4, 8.0, 8.6, and is respectively placed in environment with temperature of 25 deg.C, 30 deg.C, 35 deg.C, 40 deg.C, 45 deg.C, 50 deg.C, 55 deg.C, and 60 deg.C for swelling for 41 h. The swollen gel was taken out, the buffer solution on the surface was aspirated by a filter paper, the mass was measured, and the swelling ratio was calculated.
3. The method for testing the slow release performance of the beta-cyclodextrin hydrogel comprises the following steps: 7.54g of aspirin was weighed and dissolved in 100mL of distilled water. Soaking 0.5g of beta-cyclodextrin hydrogel in 10mL of aspirin aqueous solution, clathrating at 50 ℃ for 24h, and drying. 0.1g of the included hydrogel was placed in 50mL of distilled water, and a sustained-release test was performed at 37 ℃. The time is set to 15min, 30min, 45min, 60min, 90min, 120min, 150min, 180min, 210min, 270min, 330min, 390min, 450min, 510min, 570min, 630 min. Every time 3mL of the clear solution is taken, 3mL of the subsequent filtrate at the same temperature is supplemented, 0.1mol/mL of sodium hydroxide is used for titration until the pH value is 9-10, 0.1mol/mL of hydrochloric acid is used for titration until the pH value is 3-4, a little excessive ferric chloride hexahydrate is added, and the absorbance A of the sample is measured under the condition of the visible light wavelength of 526.5 nm.
Referring to fig. 5, for the pH sensitivity curve of the β -cyclodextrin hydrogel prepared in example 1, it can be seen that the degree of swelling increases with time and eventually reaches equilibrium. Meanwhile, the pH value of the system is continuously increased, and the swelling degree of the hydrogel is continuously improved. After the pH value reaches 8.0, the swelling degree of the hydrogel gradually becomes stable, and the maximum swelling multiple can reach 29.03.
Referring to fig. 6, temperature sensitivity curves of the β -cyclodextrin hydrogels prepared in example 1, it can be seen that the hydrogels swell differently at different temperatures. When the temperature was increased from 25 ℃ to 60 ℃, the equilibrium swelling decreased regardless of the PH. The equilibrium swelling times are reduced with the temperature increase, and are most obvious at 35-40 ℃. And after the temperature reaches 45 ℃, the equilibrium swelling of the system gradually tends to be stable, so that the hydrogel is known to have temperature sensitivity.
Referring to fig. 7, which is a pH sensitive curve of the β -cyclodextrin hydrogel prepared in example 2, it can be seen that the swelling degree of the hydrogel is continuously increased and gradually reaches a stable state with the increase of time. In the process of adjusting the pH from 2.2 to 8.6, the swelling degree of the hydrogel is greatly changed, and gradually becomes stable after the pH reaches 8.0, and the highest swelling degree can reach 21.99.
Referring to fig. 8, which is a temperature sensitive curve of the β -cyclodextrin hydrogel prepared in example 2, it was found that the hydrogel had different equilibrium swelling degrees at different temperatures, and the equilibrium swelling was continuously decreased as the temperature was increased. The initial decrease was rapid and the hydrogel gradually stabilized after 40 ℃ indicating temperature sensitivity.
Referring to fig. 9, a sustained release curve of the β -cyclodextrin hydrogel prepared in example 1, it can be found that the hydrogel has a sustained release effect on ASA. With the prolonging of time, the hydrogel has a fast slow release rate at the beginning, the slow release rate is reduced after 210min, and then gradually approaches to an equilibrium state, which shows that the slow release amount reaches the highest.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and their concepts should be equivalent or changed within the technical scope of the present invention.
Claims (10)
1. A preparation method of a double-sensitive slow-release beta-cyclodextrin hydrogel is characterized by comprising the following steps: the preparation method comprises the following steps:
(1) esterification reaction: fully grinding beta-cyclodextrin and maleic anhydride until the system is uniformly mixed, reacting at esterification temperature, and purifying after the reaction is finished to obtain a maleic anhydride esterified beta-cyclodextrin derivative;
(2) amide reaction: reacting the maleic anhydride esterified beta-cyclodextrin derivative prepared in the step (1) with diethanol amine in a tetrahydrofuran solvent, and purifying after the reaction is finished to prepare an amidated beta-cyclodextrin derivative;
(3) preparation of beta-cyclodextrin polymer: reacting the amidated beta-cyclodextrin derivative prepared in the step (2), cholic acid and epoxy chloropropane in a sodium hydroxide aqueous solution, and purifying after the reaction is finished to prepare a beta-cyclodextrin polymer;
(4) preparing hydrogel: and (3) carrying out redox free radical polymerization on the beta-cyclodextrin polymer prepared in the step (3), N-isopropylacrylamide, acrylic acid, ammonium persulfate, sodium sulfite and N, N-methylene bisacrylamide in distilled water to prepare the beta-cyclodextrin hydrogel.
2. The preparation method of the double-sensitive slow-release beta-cyclodextrin hydrogel according to claim 1, wherein the preparation method comprises the following steps: the esterification reaction in the step (1) comprises the following specific preparation steps:
and (3) putting the ground and uniformly mixed beta-cyclodextrin and maleic anhydride powder into a conical flask, reacting for 8 hours at the temperature of 80 ℃, and continuously stirring by using a glass rod at the initial stage of the reaction until the system becomes viscous.
3. The preparation method of the double-sensitive slow-release beta-cyclodextrin hydrogel according to claim 1, wherein the preparation method comprises the following steps: the specific preparation steps of the step (2) are as follows:
dissolving the maleic anhydride esterified beta-cyclodextrin derivative prepared in the step (1) and diethanol amine by tetrahydrofuran, fully mixing, and reacting for 5 hours at the temperature of 60 ℃ and at the speed of 300 r/min.
4. The preparation method of the double-sensitive slow-release beta-cyclodextrin hydrogel according to claim 1, wherein the preparation method comprises the following steps: the specific preparation steps of the beta-cyclodextrin polymer in the step (3) are as follows:
stirring and mixing the amidated beta-cyclodextrin derivative prepared in the step (2) with cholic acid and sodium hydroxide aqueous solution for 24 hours, adding epoxy chloropropane, stirring for 45 minutes, soaking with acetone for 30 minutes, finally removing the acetone, and standing for 8 hours.
5. The preparation method of the double-sensitive slow-release beta-cyclodextrin hydrogel according to claim 1, wherein the preparation method comprises the following steps: the hydrogel prepared in the step (4) comprises the following specific preparation steps:
and (3) uniformly stirring the beta-cyclodextrin polymer prepared in the step (3) with N-isopropylacrylamide, acrylic acid, ammonium persulfate, sodium sulfite and N, N-methylene bisacrylamide in distilled water, introducing nitrogen for 10min, and reacting for 8h at the temperature of 50 ℃.
6. The preparation method of the double-sensitive slow-release beta-cyclodextrin hydrogel according to claim 2, wherein the preparation method comprises the following steps: the purification operation in the step (1) is as follows: and after the reaction is finished, taking out the solid, grinding the solid into powder, then fully washing, filtering and drying the powder by using acetone and absolute ethyl alcohol in sequence.
7. The method for preparing the dual-sensitive slow-release beta-cyclodextrin hydrogel as claimed in claim 3, wherein the method comprises the following steps: the purification operation in the step (2) is as follows: precipitating the product with acetone as precipitant, separating, and drying.
8. The preparation method of the double-sensitive slow-release beta-cyclodextrin hydrogel according to claim 4, wherein the preparation method comprises the following steps: the purification operation in the step (3) is as follows: neutralizing with 6mol/L hydrochloric acid to neutrality, precipitating with anhydrous ethanol as precipitant, separating, and drying.
9. The method for preparing the dual-sensitive slow-release beta-cyclodextrin hydrogel as claimed in claim 3, wherein the method comprises the following steps: and step 4, soaking the prepared beta-cyclodextrin hydrogel in water for 24 hours, and drying.
10. The method for preparing the dual-sensitive slow-release beta-cyclodextrin hydrogel as claimed in claim 1, wherein the method comprises the following steps: in the step (1), the mol ratio of the beta-cyclodextrin to the maleic anhydride is 1: 20; the molar ratio of the maleic anhydride esterified beta-cyclodextrin derivative prepared in the step (1) in the step (2) to diethanolamine is 1: 99; the mol ratio of the amidated beta-cyclodextrin derivative prepared in the step (2) in the step (3) to epichlorohydrin is 1: 17; the mass ratio of the beta-cyclodextrin polymer prepared in the step (3) in the step (4) to the N-isopropylacrylamide is 1: 1.
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