阅读说明：本技术 一种可热致原位凝胶化共聚纳米水凝胶及其制备方法 (Copolymerization nano hydrogel capable of thermally induced in-situ gelation and preparation method thereof ) 是由 鲁希华 李晓晓 李雪婷 于 2021-02-09 设计创作，主要内容包括：本发明具体涉及一种制备可热致原位凝胶化共聚纳米水凝胶的方法。该制备方法利用纳米水凝胶对温度的响应性,采用温度触发原位实现溶胶-凝胶化过程,具体步骤为：以N-异丙基丙烯酰胺(NIPAm)为温敏性功能单体,N-叔丁基丙烯酰胺(TBA)为疏水性单体,通过控制调整TBA的引入量,共聚得到具有温度响应性的P(NIPAm-TBA)共聚纳米水凝胶。其凝胶化方法为：将特定TBA引入量的纳米水凝胶在一定温度范围内升温,调节其浓度,其由可流动的溶液状态转为不可流动的宏观水凝胶状态。本发明采用的方法工艺简单,绿色环保,不使用额外的化学交联剂不需添加任何的离子,仅利用温度触发实现原位的溶胶-凝胶化转变,且具有可逆性。(The invention particularly relates to a method for preparing copolymerization nano hydrogel capable of thermally induced in-situ gelation. The preparation method utilizes the responsiveness of the nano hydrogel to temperature and adopts temperature triggering in-situ to realize the sol-gelation process, and comprises the following specific steps: n-isopropyl acrylamide (NIPAm) is used as a temperature-sensitive functional monomer, N-tert-butyl acrylamide (TBA) is used as a hydrophobic monomer, and the P (NIPAm-TBA) copolymerized nano hydrogel with temperature responsiveness is obtained by copolymerization through controlling and adjusting the introduction amount of the TBA. The gelation method comprises the following steps: and (3) heating the nano hydrogel with the specific TBA introduction amount within a certain temperature range, adjusting the concentration of the nano hydrogel, and converting the nano hydrogel from a flowable solution state to a non-flowable macroscopic hydrogel state. The method adopted by the invention has the advantages of simple process, environmental protection, no use of additional chemical cross-linking agent, no need of adding any ion, realization of in-situ sol-gel transformation only by temperature triggering, and reversibility.)

1. A method for preparing copolymerization nano hydrogel capable of being subjected to thermal in-situ gelation is characterized by comprising the following steps:

(1) preparing P (NIPAm-TBA) nano hydrogel: firstly, dissolving monomers of N-isopropylacrylamide, N-tert-butylacrylamide (TBA), N' -methylene bisacrylamide and emulsifier sodium dodecyl sulfate in deionized water, heating to 60-80 ℃ in a nitrogen atmosphere, preserving heat for 20-40 min, then adding initiator ammonium persulfate to react for 4 hours, and dialyzing after reaction to obtain P (NIPAm-TBA) nano hydrogel;

(2) thermal gelation-gelation of nano hydrogel: placing the P (NIPAm-TBA) copolymerized nano hydrogel after dialysis and purification in a 50 ℃ oven, concentrating to obtain a dispersion liquid with a specific concentration, then placing the dispersion liquid in a thermostat with a specific temperature range and a specific heating rate, and keeping the temperature for 5min at intervals of 1 temperature point to enable the dispersion liquid to generate thermal sol-gelation transformation under the condition of no salt ions, thereby obtaining the thermal physical crosslinking macro jelly hydrogel.

2. The thermal in-situ gelation-enabled copolymerization nano-hydrogel as claimed in claim 1, wherein the monomer providing temperature sensitivity to the polymer in step (1) is N-isopropylacrylamide, and the added amount is 50% to 90% of the total molar amount of the three reaction substances of N-isopropylacrylamide, N-tert-butylacrylamide and N, N' -methylenebisacrylamide.

3. The thermally-induced in-situ gelation copolymerizable nanohydrogel according to claim 1, wherein the hydrophobic monomer in the step (1) is N-t-butylacrylamide, and the added amount is 10% to 50% of the total molar amount of the three reactive materials of N-isopropylacrylamide, N-t-butylacrylamide and N, N' -methylenebisacrylamide.

4. The thermally-induced in-situ gelation copolymerized nano-hydrogel in the step (1), wherein the crosslinking agent is N, N '-methylenebisacrylamide, and the addition amount is 1 to 3 percent of the total molar amount of the three reaction substances of N-isopropylacrylamide, N-tert-butylacrylamide and N, N' -methylenebisacrylamide.

5. The thermally in-situ gelation copolymerizable nano-hydrogel according to claim 1, wherein the emulsifier in step (1) is sodium dodecyl sulfate, and the addition amount thereof is 3% to 6% of the total mass of the three reaction substances of N-isopropylacrylamide, N-tert-butylacrylamide and N, N' -methylenebisacrylamide.

6. The thermally-induced in-situ gelation copolymerized nano-hydrogel according to claim 1, wherein the initiator in the step (1) is ammonium persulfate, and the addition amount is 5 to 8 percent of the total mass of three reaction substances of N-isopropylacrylamide, N-tert-butylacrylamide and N, N' -methylenebisacrylamide.

7. The thermal in-situ gelation-enabled copolymerization nano-hydrogel as claimed in claim 1, wherein the specific conditions of dialysis in step (1) are soaking in ultrapure water for 3-7 days, water is changed 3 times per day, and the cut-off molecular weight of a dialysis bag used for dialysis is 8000-14000.

8. The thermally-induced in-situ gelation-copolymerizable nano-hydrogel according to claim 1, wherein the P (NIPAm-TBA) -copolymerized nano-hydrogel purified by dialysis in the step (2) is placed in an oven at 50 ℃ for evaporation concentration, and the concentration is in the range of 3.1 to 8% by mass concentration.

9. The sol-gel method of claim 8, wherein the concentrated nano hydrogel is placed in a thermostat to undergo thermal sol-gel transition, wherein the thermostat temperature is 10-40 ℃ and the heating rate is 1 ℃/min.

Technical Field

The invention belongs to the field of nano hydrogel and preparation thereof, and particularly relates to a copolymerization nano hydrogel capable of thermally induced in-situ gelation and a preparation method thereof.

Background

By in situ-gellable hydrogel is meant a type of hydrogel that rapidly transforms from a fluid solution state to a non-flowable solid/semisolid state under certain conditions, i.e., the hydrogel undergoes an in situ sol-gel transition. Based on crosslinking, hydrogels that can be gelled in situ can be classified into physically crosslinked hydrogels and chemically crosslinked hydrogels. Physically cross-linked gelable hydrogels refer to networks that are linked together by various physical interactions, including ionic, hydrogen bonding, electrostatic interactions, and hydrophobic associations. The composite material not only can overcome partial defects of chemical crosslinking, such as the additional introduction of a toxic crosslinking agent and the like, but also can endow the material with reversibility, self-healing property and stimulus responsiveness. Reversibility is the greatest feature of physically cross-linked hydrogels that can be gelled in situ.

Among them, poly (N-isopropylacrylamide) (PNIPAm) is often combined with other monomers as a main functional component due to its sensitive temperature responsiveness, so as to construct PNIPAm-based thermally-induced in-situ gelation nano-hydrogel. However, PNIPAm itself requires a very high critical gelation concentration to form gelation (15 wt% to 20wt% or more), which makes it difficult to aspirate a mixed solution of the injection gel and the drug with a syringe.

At present, most of poly (N-isopropylacrylamide) (PNIPAm) -based thermally-induced in-situ gelation physically-crosslinked hydrogels are hydrogels based on block, linear and graft structures, and the like, and the preparation methods of the hydrogels have the defects of complex preparation process, high viscosity, high concentration and the like. For example, He et al (Macromolecules 2016, 49, 4236-4244) first prepared a reversible addition-fragmentation chain transfer (RAFT) reagent, and then prepared a triblock hydrogel having PNIPAm as a main functional component by a two-step reaction using the RAFT reagent, and the hydrogel dispersion can undergo a thermally induced in-situ sol-gel transition above the phase transition temperature at a concentration of greater than 10 wt%. In addition, for the PNIPAm-based random copolymerization nano hydrogel, as the PNIPAm-based random copolymerization nano hydrogel generates a rapid dehydration shrinkage behavior above the phase transition temperature, the distance between the hydrogels is increased, and the intermolecular interaction force is weakened, so that the nano hydrogel can complete the temperature-triggered sol-gel transition by adding extra salt ions. For example, Zhang et al (Biomacromolecules, 2009, 10 (6)) prepared a poly (N-isopropylacrylamide-co-2-hydroxymethylacrylate) (P (NIPAm-HEMA) copolymerized nanohydrogel, which was concentrated above the phase transition temperature to achieve a thermally-induced in situ sol-gel transition by the addition of calcium chloride salt.

Therefore, the development of a PNIPAm-based method for thermally-induced in-situ gelation copolymerization nano-hydrogel, which is simple, feasible and easy for large-scale production, has positive significance for promoting further practical application of the PNIPAm-based method.

Disclosure of Invention

The invention provides a thermotropic in-situ gelation copolymerization nano hydrogel and a preparation method thereof. This thermally induced in situ sol-gelation process is referred to as: the temperature-responsive nano hydrogel is converted from a flowable solution state to a non-flowable macroscopic hydrogel state under certain conditions. This process is reversible, and the nanohydrogel can return to a flowable solution state when the temperature is lowered.

In order to achieve the purpose, the invention is realized by the following technical scheme:

a copolymerization nano-hydrogel capable of thermally gelatinizing in situ and a preparation method thereof comprise the following steps:

(1) preparing P (NIPAm-TBA) nano hydrogel: firstly, dissolving monomers of N-isopropylacrylamide, N-tert-butylacrylamide (TBA), N' -methylene bisacrylamide and emulsifier sodium dodecyl sulfate in deionized water, heating to 60-80 ℃ in a nitrogen atmosphere, preserving heat for 20-40 min, then adding initiator ammonium persulfate to react for 4 hours, and dialyzing after reaction to obtain P (NIPAm-TBA) nano hydrogel;

(2) thermal gelation-gelation of nano hydrogel: placing the P (NIPAm-TBA) copolymerized nano hydrogel after dialysis and purification in a 50 ℃ oven, concentrating to obtain a dispersion liquid with a specific concentration, then placing the dispersion liquid in a thermostat with a specific temperature range and a specific heating rate, and keeping the temperature for 5min at intervals of 1 temperature point to enable the dispersion liquid to generate thermal sol-gelation transformation under the condition of no salt ions, thereby obtaining the thermal physical crosslinking macro jelly hydrogel.

Further, the monomer providing temperature sensitivity for the polymer in the step (1) is N-isopropylacrylamide, and the adding amount is 50-90% of the total mol amount of three reaction substances of N-isopropylacrylamide, N-tert-butylacrylamide and N, N' -methylene bisacrylamide.

Furthermore, the hydrophobic monomer in the step (1) is N-tert-butyl acrylamide, and the adding amount is 10-50% of the total mol amount of the three reaction substances of N-isopropyl acrylamide, N-tert-butyl acrylamide and N, N' -methylene bisacrylamide.

Furthermore, the cross-linking agent in the step (1) is N, N '-methylene bisacrylamide, and the adding amount is 1 to 3 percent of the total mol amount of the three reaction substances of the N-isopropylacrylamide, the N-tert-butylacrylamide and the N, N' -methylene bisacrylamide.

Further, the emulsifier in the step (1) is sodium dodecyl sulfate, and the adding amount of the emulsifier is 3-6% of the total mass of three reaction substances of N-isopropylacrylamide, N-tert-butylacrylamide and N, N' -methylene bisacrylamide.

Further, the initiator in the step (1) is ammonium persulfate, and the adding amount of the initiator is 5-8% of the total mass of three reaction substances of N-isopropylacrylamide, N-tert-butylacrylamide and N, N' -methylene bisacrylamide.

Further, in the step (1), the specific conditions of dialysis are soaking for 3-7 days by adopting ultrapure water, water is changed for 3 times every day, and the cut-off molecular weight of a dialysis bag used for dialysis is 8000-14000.

Further, in the step (2), the P (NIPAm-TBA) copolymerized nano hydrogel after dialysis and purification is placed in an oven at 50 ℃ for evaporation and concentration, and the concentration range is 3.1-8% by mass concentration.

Further, in the step (2), the concentrated nano hydrogel is placed in a thermostat to generate thermal sol-gelation transformation, the temperature range of the thermostat is 10-40 ℃, and the heating rate is 1 ℃/min.

The principle of the invention is as follows:

according to the invention, N-isopropylacrylamide (NIPAm) is used as a functional monomer for providing temperature sensitivity for a polymer, N-tert-butylacrylamide (TBA) is used as a hydrophobic monomer, and P (NIPAm-TBA) copolymerization nano hydrogel with temperature responsiveness is obtained through copolymerization (figure 1). By adjusting the introduction amount of the TBA, the hydrophobic effect in the system is enhanced due to the increase of the content of the TBA, the intermolecular hydrophobic attraction effect is increased, the intermolecular force is increased, the polymer chains are mutually entangled, and physical crosslinking sites are formed, so that the P (NIPAm-TBA) copolymerized nano hydrogel can generate the thermotropic in-situ sol-gel transformation under the condition of salt ion-free under certain condition concentration and temperature.

Compared with the prior art, the invention has the beneficial effects that:

the method adopted by the invention has simple process, is green and environment-friendly, does not use an additional chemical cross-linking agent, does not need to add any ion, realizes in-situ sol-gel transformation only by utilizing temperature triggering, and has reversibility.

Drawings

FIG. 1 is a schematic diagram of the synthesis of P (NIPAm-TBA) copolymerized nano-hydrogel;

FIG. 2 is a graph of the viscosity of P (NIPAm-TBA) copolymerized nano hydrogel (mass concentration 5 wt%) of examples 1 to 3 with temperature, and an inset is a graph of the viscosity with temperature of comparative example 1;

FIGS. 3 (a) - (c) are the modulus-temperature curves of the P (NIPAm-TBA) copolymerized nanohydrogel of examples 1-3, which are characteristic of the formation of the thermophysically crosslinked hydrogel. (d) The (f) is the modulus-time curve of the example 1-3, namely the characteristic that the thermotropic sol-gelation transformation process has reversibility;

FIG. 4 is an optical photograph of the P (NIPAm-TBA) copolymerized nanohydrogel of example 1 during the sol-gel transition (from left to right, the gel gradually immobilized and inverted without flowing as 4 ℃ shifts to 29 ℃);

FIG. 5 is a graph showing the effect of P (NIPAm-TBA) copolymerized nanohydrogel of example 1 and comparative example 2 on the time to achieve gelation and the temperature to achieve gelation (when the hydrogel dispersion concentration is less than 3wt%, thermal sol-gel transition cannot occur) at various concentrations.

Detailed Description

The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Further, it should be understood that various changes or modifications of the present invention may be made by those skilled in the art after reading the teaching of the present invention, and such equivalents may fall within the scope of the present invention as defined in the appended claims.

Examples 1-9 are examples of the preparation of P (NIPAm-TBA) copolymerized nanohydrogels with reversibility for the formation of the present thermophysically crosslinked macrocogel-like hydrogels.

Comparative example 1 is a preparation example of P (NIPAm-TBA) copolymerized nano-hydrogel incorporating very low content of hydrophobic N-t-butylacrylamide, and in case that the N-t-butylacrylamide incorporation amount is insufficient, the nano-hydrogel of comparative example 1 does not undergo sol-gel transition even though the concentration and temperature of the nano-hydrogel are adjusted. Comparative example 2 is that when the hydrogel concentration thereof was too low, thermal sol-gel transition could not occur even though the N-t-butylacrylamide was introduced in a sufficient amount.

Comparative example 1:

about 1.0283g of monomeric N-isopropylacrylamide (NIPAm), 0.0889g of monomeric N-tert-butylacrylamide, 0.035g of crosslinker N, N' -methylenebisacrylamide and 0.0415g of emulsifier sodium dodecyl sulfate were dissolved in 95 ml of deionized water, and N was bubbled at room temperature₂Deoxidizing and magnetically stirring for 30 minutes;

the reaction temperature was raised to 70 ℃ and maintained at N₂Preserving the heat for 30 minutes under protection;

about 0.0622 g of initiator ammonium persulfate was then dissolved in 5 ml of deionized water and added to the above solution, maintaining N₂Continuing the reaction for 4 hours under the atmosphere;

then soaking the obtained reactant in deionized water for dialysis for 7 days, changing water three times a day, and removing residual reaction raw materials and electrolyte in the reaction system. The cut-off molecular weight of the dialysis bag is 8000-14000. Thus obtaining the P (NIPAm-TBA) copolymerized nano hydrogel.

And (3) placing the dialyzed and purified P (NIPAm-TBA) copolymerized nano hydrogel in a 50 ℃ oven, and concentrating until the mass concentration is 5 wt%. Then placing the mixture in a constant temperature box, wherein the temperature rise range is 15-40 ℃, the temperature rise rate is 1 ℃/min, and the temperature is kept for 5min at every other temperature point. Because the TBA is introduced in too small amount, the viscosity of the hydrogel does not increase significantly with the continuous increase of the temperature at 15-40 ℃ (see the inset in figure 2), i.e. the thermotropic sol-gel transition cannot occur, so that the thermotropic physical crosslinking macroscopic jelly-like hydrogel cannot be obtained.

Comparative example 2:

approximately 0.9718g of monomeric N-isopropylacrylamide (NIPAm), 0.1526g of monomeric N-tert-butylacrylamide, 0.035g of crosslinker N, N '-methylenebisacrylamide and 0.0412g of emulsifier sodium dodecyl sulfate were dissolved in 95 ml of deionized water and N.N' -methyl-bisacrylamide was bubbled through at room temperature₂Deoxidizing and magnetically stirring for 30 minutes;

the reaction temperature was raised to 70 ℃ and maintained at N₂Preserving the heat for 30 minutes under protection;

about 0.0639 g of initiator ammonium persulfate was then dissolved in 5 ml of deionized water and added to the above solution, maintaining N₂Continuing the reaction for 4 hours under the atmosphere;

then soaking the obtained reactant in deionized water for dialysis for 7 days, changing water three times a day, and removing residual reaction raw materials and electrolyte in the reaction system. The cut-off molecular weight of the dialysis bag is 8000-14000. Thus obtaining the P (NIPAm-TBA) copolymerized nano hydrogel.

And (3) placing the dialyzed and purified P (NIPAm-TBA) copolymerized nano hydrogel in a 50 ℃ oven, and concentrating to the mass concentration of 1wt% and 3 wt%. Then placing the mixture in a constant temperature box, wherein the temperature rise range is 15-40 ℃, the temperature rise rate is 1 ℃/min, and the temperature is kept for 5min at every other temperature point. Since the concentration is too low, the thermally induced sol-gel transition cannot occur, and thus the thermally induced physically crosslinked hydrogel cannot be obtained (see fig. 5).

Example 1:

approximately 0.9718g of monomeric N-isopropylacrylamide (NIPAm), 0.1526g of monomeric N-tert-butylacrylamide, 0.035g of crosslinker N, N '-methylenebisacrylamide and 0.0412g of emulsifier sodium dodecyl sulfate were dissolved in 95 ml of deionized water and N.N' -methyl-bisacrylamide was bubbled through at room temperature₂Deoxidizing and magnetically stirring for 30 minutes;

the reaction temperature was raised to 70 ℃ and maintained at N₂Preserving the heat for 30 minutes under protection;

about 0.0639 g of initiator ammonium persulfate was then dissolved in 5 ml of deionized water and added to the above solution, maintaining N₂Continuing the reaction for 4 hours under the atmosphere;

then soaking the obtained reactant in deionized water for dialysis for 7 days, changing water three times a day, and removing residual reaction raw materials and electrolyte in the reaction system. The cut-off molecular weight of the dialysis bag is 8000-14000. Thus obtaining the P (NIPAm-TBA) copolymerized nano hydrogel.

And (3) placing the dialyzed and purified P (NIPAm-TBA) copolymerized nano hydrogel in a 50 ℃ oven, and concentrating until the mass concentration is 5 wt%. Then placing the mixture in a constant temperature box, wherein the temperature rise range is 15-40 ℃, the temperature rise rate is 1 ℃/min, and the temperature is kept for 5min at every other temperature point.

As can be seen from the temperature-dependent viscosity curve of the sample of fig. 2, the viscosity of the sample of example 1 significantly increases with a continuous increase in temperature at about 25 ℃ temperature point, which represents the occurrence of the sol-gel transition process.

Fig. 3 (a) the modulus-temperature curve shows that the change curves of the moduli G' and G ″ with temperature can characterize the sol-gel transition of the nanohydrogel. Wherein, G ' < G ' ' indicates that the nano hydrogel is in a flowable dispersion state; the temperature corresponding to G' = G "may be expressed as a gelation temperature; g' > G ", indicating the transition of the sol-gelation process, i.e. the formation of a thermophysically crosslinked macrocogel-like hydrogel. Formation of the thermotropic physically crosslinked hydrogel of example 1. Fig. 3 (d) modulus-time curve shows that the time of thermal sol-gel transition of the sample of example 1 is 108 s, and G' and G ″ of the sample are maintained in a relatively stable value range through multiple temperature rise-fall tests, i.e. the thermal sol-gel transition process is reversible.

The optical photograph of the sol-gel transition process in FIG. 4 shows the phase transition process of the sol-gel transition process with time when the sample of example 1 is transferred from 4 ℃ to 29 ℃.

FIG. 5 is a graph showing the effect of sample concentration on gelation time and gelation temperature. I.e., the higher the sample concentration, the faster the time to achieve the sol-gel transition, and the lower the temperature required. When the hydrogel dispersion concentration is less than 3% by weight, the thermally induced sol-gel transition cannot occur.

Example 2:

about 0.9266g of monomeric N-isopropylacrylamide (NIPAm), 0.2032g of monomeric N-tert-butylacrylamide, 0.035g of crosslinker N, N' -methylenebisacrylamide and 0.0422g of emulsifier sodium dodecyl sulfate were dissolved in 95 ml of deionized water, and N was bubbled at room temperature₂Deoxidizing and magnetically stirring for 30 minutes;

the reaction temperature was raised to 70 ℃ and maintained at N₂Preserving the heat for 30 minutes under protection;

about 0.0605g of initiator ammonium persulfate was then dissolved in 5 ml of deionized water and added to the above solution, maintaining N₂Continuing the reaction for 4 hours under the atmosphere;

then soaking the obtained reactant in deionized water for dialysis for 7 days, changing water three times a day, and removing residual reaction raw materials and electrolyte in the reaction system. The cut-off molecular weight of the dialysis bag is 8000-14000. Thus obtaining the P (NIPAm-TBA) copolymerized nano hydrogel.

And (3) placing the dialyzed and purified P (NIPAm-TBA) copolymerized nano hydrogel in a 50 ℃ oven, and concentrating until the mass concentration is 5 wt%. Then placing the mixture in a constant temperature box, wherein the temperature rise range is 15-40 ℃, the temperature rise rate is 1 ℃/min, and the temperature is kept for 5min at every other temperature point.

As can be seen from the temperature-dependent viscosity curve of the sample of fig. 2, the viscosity of the sample of example 2 significantly increases with the continuous increase of temperature at about 23 ℃ temperature point, which represents the occurrence of the sol-gel transition process.

Fig. 3 (b) modulus-temperature curve it can be seen that the change curves of the moduli G' and G ″ with temperature can characterize the sol-gel transition of the nanohydrogel. Wherein, G ' < G ' ' indicates that the nano hydrogel is in a flowable dispersion state; the temperature corresponding to G' = G "may be expressed as a gelation temperature; g' > G ", indicating the transition of the sol-gelation process, i.e. the formation of a thermophysically crosslinked macrocogel-like hydrogel. Formation of the thermotropic physically crosslinked hydrogel of example 2. Fig. 3 (e) modulus-time curve shows that the time of the thermal sol-gel transition of the sample of example 2 is 90s, and G' and G ″ of the sample are maintained in a relatively stable value range through multiple temperature rise-fall tests, i.e. the thermal sol-gel transition process is reversible.

Example 3:

0.8588g of monomeric N-isopropylacrylamide (NIPAm), 0.2798g of monomeric N-tert-butylacrylamide, 0.035g of crosslinker N, N' -methylenebisacrylamide and 0.0411g of emulsifier sodium dodecyl sulfate were dissolved in 95 ml of deionized water, and N was bubbled at room temperature₂Deoxidizing and magnetically stirring for 30 minutes;

the reaction temperature was raised to 70 ℃ and maintained at N₂Preserving the heat for 30 minutes under protection;

about 0.0603g of initiator ammonium persulfate was then dissolved in 5 ml of deionized water and added to the above solution, maintaining N₂Continuing the reaction for 4 hours under the atmosphere;

then soaking the obtained reactant in deionized water for dialysis for 7 days, changing water three times a day, and removing residual reaction raw materials and electrolyte in the reaction system. The cut-off molecular weight of the dialysis bag is 8000-14000. Thus obtaining the P (NIPAm-TBA) copolymerized nano hydrogel.

And (3) placing the dialyzed and purified P (NIPAm-TBA) copolymerized nano hydrogel in a 50 ℃ oven, and concentrating until the mass concentration is 5 wt%. Then placing the mixture in a constant temperature box, wherein the temperature rise range is 15-40 ℃, the temperature rise rate is 1 ℃/min, and the temperature is kept for 5min at every other temperature point.

As can be seen from the temperature-dependent viscosity curve of the sample of fig. 2, the viscosity of the sample of example 3 significantly increases with a continuous increase in temperature around the temperature point of 21 ℃, which represents the occurrence of the sol-gel transition process.

As can be seen from the modulus-temperature curve of fig. 3 (c), the change curves of the moduli G' and G ″ with temperature can characterize the sol-gel transition of the nanohydrogel. Wherein, G ' < G ' ' indicates that the nano hydrogel is in a flowable dispersion state; the temperature corresponding to G' = G "may be expressed as a gelation temperature; g' > G ", indicating the transition of the sol-gelation process, i.e. the formation of a thermophysically crosslinked macrocogel-like hydrogel. Formation of the thermotropic physically crosslinked hydrogel of example 3. Fig. 3 (f) modulus-time curve shows that the time of the thermal sol-gel transition of the sample of example 3 is 45s, and G' and G ″ of the sample are maintained in a relatively stable value range through multiple temperature rise-fall tests, i.e. the thermal sol-gel transition process is reversible.

Example 4:

approximately 0.9718g of monomeric N-isopropylacrylamide (NIPAm), 0.1526g of monomeric N-tert-butylacrylamide, 0.035g of crosslinker N, N '-methylenebisacrylamide and 0.0412g of emulsifier sodium dodecyl sulfate were dissolved in 95 ml of deionized water and N.N' -methyl-bisacrylamide was bubbled through at room temperature₂Deoxidizing and magnetically stirring for 30 minutes;

the reaction temperature was raised to 70 ℃ and maintained at N₂Preserving the heat for 30 minutes under protection;

about 0.0659 g of initiator ammonium persulfate was then dissolved in 5 ml of deionized water and added to the above solution, maintaining N₂Continuing the reaction for 4 hours under the atmosphere;

then soaking the obtained reactant in deionized water for dialysis for 7 days, changing water three times a day, and removing residual reaction raw materials and electrolyte in the reaction system. The cut-off molecular weight of the dialysis bag is 8000-14000. Thus obtaining the P (NIPAm-TBA) copolymerized nano hydrogel.

And (3) placing the dialyzed and purified P (NIPAm-TBA) copolymerized nano hydrogel in a 50 ℃ oven, and concentrating until the mass concentration is 4 wt%. Then placing the mixture in a constant temperature box, wherein the temperature rise range is 15-40 ℃, the temperature rise rate is 1 ℃/min, and the temperature is kept for 5min at every other temperature point. Finally, the formation of the thermotropic physical crosslinking macroscopic jelly-shaped hydrogel can be realized, and the reversibility is realized.

Example 5:

approximately 0.9718g of monomeric N-isopropylacrylamide (NIPAm), 0.1526g of monomeric N-tert-butylacrylamide, 0.035g of crosslinker N, N '-methylenebisacrylamide and 0.0412g of emulsifier sodium dodecyl sulfate were dissolved in 95 ml of deionized water and N.N' -methyl-bisacrylamide was bubbled through at room temperature₂Deoxidizing and magnetically stirring for 30 minutes;

the reaction temperature was raised to 70 ℃ and maintained at N₂Preserving the heat for 30 minutes under protection;

about 0.0629 g of initiator ammonium persulfate was then dissolved in 5 ml of deionized water and added to the above solution, maintaining N₂Continuing the reaction for 4 hours under the atmosphere;

then soaking the obtained reactant in deionized water for dialysis for 7 days, changing water three times a day, and removing residual reaction raw materials and electrolyte in the reaction system. The cut-off molecular weight of the dialysis bag is 8000-14000. Thus obtaining the P (NIPAm-TBA) copolymerized nano hydrogel.

And (3) placing the dialyzed and purified P (NIPAm-TBA) copolymerized nano hydrogel in a 50 ℃ oven, and concentrating until the mass concentration is 7 wt%. Then placing the mixture in a constant temperature box, wherein the temperature rise range is 15-40 ℃, the temperature rise rate is 1 ℃/min, and the temperature is kept for 5min at every other temperature point. Finally, the formation of the thermotropic physical crosslinking macroscopic jelly-shaped hydrogel can be realized, and the reversibility is realized.

Example 6:

approximately 0.7910g of monomeric N-isopropylacrylamide (NIPAm), 0.3556g of monomeric N-tert-butylacrylamide, 0.035g of crosslinker N, N '-methylenebisacrylamide and 0.0412g of emulsifier sodium dodecyl sulfate were dissolved in 95 ml of deionized water and N.N' -methyl-bisacrylamide was bubbled through at room temperature₂Deoxidizing and magnetically stirring for 30 minutes;

the reaction temperature was raised to 70 ℃ and maintained at N₂Preserving the heat for 30 minutes under protection;

about 0.0614 g of initiator ammonium persulfate was then dissolved in 5 ml of deionized water and added to the above solution, maintaining N₂Continuing the reaction for 4 hours under the atmosphere;

then soaking the obtained reactant in deionized water for dialysis for 7 days, changing water three times a day, and removing residual reaction raw materials and electrolyte in the reaction system. The cut-off molecular weight of the dialysis bag is 8000-14000. Thus obtaining the P (NIPAm-TBA) copolymerized nano hydrogel.

And (3) placing the dialyzed and purified P (NIPAm-TBA) copolymerized nano hydrogel in a 50 ℃ oven, and concentrating until the mass concentration is 5 wt%. Then placing the mixture in a constant temperature box, wherein the temperature rise range is 15-40 ℃, the temperature rise rate is 1 ℃/min, and the temperature is kept for 5min at every other temperature point. Finally, the formation of the thermotropic physical crosslinking macroscopic jelly-shaped hydrogel can be realized, and the reversibility is realized.

Example 7:

about 0.7119g of monomeric N-isopropylacrylamide (NIPAm), 0.3810g of monomeric N-tert-butylacrylamide, 0.035g of crosslinker N, N' -methylenebisacrylamide and 0.0428g of emulsifier sodium dodecyl sulfate were dissolved in 95 ml of deionized water, and N was bubbled at room temperature₂Deoxidizing and magnetically stirring for 30 minutes;

the reaction temperature was raised to 70 ℃ and maintained at N₂Preserving the heat for 30 minutes under protection;

about 0.0618 g of initiator ammonium persulfate was then dissolved in 5 ml of deionized water and added to the above solution, maintaining the N₂Continuing the reaction for 4 hours under the atmosphere;

then soaking the obtained reactant in deionized water for dialysis for 7 days, changing water three times a day, and removing residual reaction raw materials and electrolyte in the reaction system. The cut-off molecular weight of the dialysis bag is 8000-14000. Thus obtaining the P (NIPAm-TBA) copolymerized nano hydrogel.

And (3) placing the dialyzed and purified P (NIPAm-TBA) copolymerized nano hydrogel in a 50 ℃ oven, and concentrating until the mass concentration is 5 wt%. Then placing the mixture in a constant temperature box, wherein the temperature rise range is 15-40 ℃, the temperature rise rate is 1 ℃/min, and the temperature is kept for 5min at every other temperature point. Finally, the formation of the thermotropic physical crosslinking macroscopic jelly-shaped hydrogel can be realized, and the reversibility is realized.

Example 8:

about 0.6554g of monomeric N-isopropylacrylamide (NIPAm) and 0.5080g of monomeric N-tert-butyl acrylamide (NIPAm) were takenButyl acrylamide, 0.035g of crosslinker N, N' -methylenebisacrylamide, 0.0433g of emulsifier sodium dodecyl sulfate were dissolved in 95 ml of deionized water, and N was bubbled in at room temperature₂Deoxidizing and magnetically stirring for 30 minutes;

the reaction temperature was raised to 70 ℃ and maintained at N₂Preserving the heat for 30 minutes under protection;

about 0.0612 g of initiator ammonium persulfate was then dissolved in 5 ml of deionized water and added to the above solution, maintaining the N₂Continuing the reaction for 4 hours under the atmosphere;

then soaking the obtained reactant in deionized water for dialysis for 7 days, changing water three times a day, and removing residual reaction raw materials and electrolyte in the reaction system. The cut-off molecular weight of the dialysis bag is 8000-14000. Thus obtaining the P (NIPAm-TBA) copolymerized nano hydrogel.

And (3) placing the dialyzed and purified P (NIPAm-TBA) copolymerized nano hydrogel in a 50 ℃ oven, and concentrating until the mass concentration is 5 wt%. Then placing the mixture in a constant temperature box, wherein the temperature rise range is 15-40 ℃, the temperature rise rate is 1 ℃/min, and the temperature is kept for 5min at every other temperature point. Finally, the formation of the thermotropic physical crosslinking macroscopic jelly-shaped hydrogel can be realized, and the reversibility is realized.

Example 9:

about 0.6102g of monomeric N-isopropylacrylamide (NIPAm), 0.5588g of monomeric N-tert-butylacrylamide, 0.035g of crosslinker N, N' -methylenebisacrylamide and 0.0411g of emulsifier sodium dodecyl sulfate were dissolved in 95 ml of deionized water, and N was bubbled at room temperature₂Deoxidizing and magnetically stirring for 30 minutes;

the reaction temperature was raised to 70 ℃ and maintained at N₂Preserving the heat for 30 minutes under protection;

about 0.0633 g of initiator ammonium persulfate was then dissolved in 5 ml of deionized water and added to the above solution, maintaining N₂Continuing the reaction for 4 hours under the atmosphere;

then soaking the obtained reactant in deionized water for dialysis for 7 days, changing water three times a day, and removing residual reaction raw materials and electrolyte in the reaction system. The cut-off molecular weight of the dialysis bag is 8000-14000. Thus obtaining the P (NIPAm-TBA) copolymerized nano hydrogel.

And (3) placing the dialyzed and purified P (NIPAm-TBA) copolymerized nano hydrogel in a 50 ℃ oven, and concentrating until the mass concentration is 5 wt%. Then placing the mixture in a constant temperature box, raising the temperature within the range of 5-40 ℃, raising the temperature at the rate of 1 ℃/min, and keeping the temperature for 5min at every other temperature point. Finally, the formation of the thermotropic physical crosslinking macroscopic jelly-shaped hydrogel can be realized, and the reversibility is realized.

The foregoing is a more detailed description of the invention in connection with specific preferred embodiments and it is not intended that the invention be limited to these specific details. For those skilled in the art to which the invention pertains, several simple deductions or substitutions can be made without departing from the spirit of the invention, and all shall be considered as belonging to the protection scope of the invention.