Dual temperature response hydroxypropyl methyl cellulose-kappa carrageenan semi-interpenetrating network hydrogel as well as preparation method and application thereof

Abstract

The invention provides a double temperature response hydroxypropyl methyl cellulose-kappa carrageenan semi-interpenetrating network hydrogel as well as a preparation method and an application of the double temperature response hydroxypropyl methyl cellulose-kappa carrageenan semi-interpenetrating network hydrogel. The preparation method comprises a step of respectively preparing a hydroxypropyl methyl cellulose aqueous solution and a kappa carrageenan aqueous solution, and a step of heating and uniformly mixing the hydroxypropyl methyl cellulose aqueous solution and the kappa carrageenan aqueous solution and then cooling, the heating temperature is 50-60 DEG C, and the heating time is more than 30 minutes. The double-temperature-response hydroxypropyl methyl cellulose-kappa carrageenan semi-interpenetrating network hydrogel disclosed by the invention has a good double-temperature-response characteristic, and gel is formed by HPMC (Hydroxy Propyl Methyl Cellulose) at a high temperature and becomes a dispersed phase in a KC continuous phase; kC forms gel at a low temperature and becomes a dispersed phase in an HPMC continuous phase. The semi-interpenetrating network structure of the hydrogel system is changed along with the change of the environment temperature, so that the thermal processing resistance and the low-temperature storage stability can be realized at the same time, and a foundation is provided for the development of novel intelligent foods.

Description

Technical Field

[0001] The invention belongs to the technical field of hydrogels, and in particular relates to a dual temperature-responsive hydroxypropyl methylcellulose-kappa carrageenan semi-interpenetrating network hydrogel and a preparation method and application thereof. Background Art

[0002] As a new type of polymer material, hydrogel has shown broad application prospects in many fields such as medicine, environmental protection, and food due to its unique water absorption and water retention properties and good biocompatibility. In recent years, with the advancement of science and technology and the improvement of people's requirements for material performance, smart hydrogels have gradually become a hot topic of research. Among them, temperature-responsive hydrogels have received widespread attention because they can exhibit different physical and chemical properties according to changes in ambient temperature. For condensation hot melt type thermoreversible gels, gels can be formed at low temperatures to ensure storage stability, but high-temperature sterilization will cause the disintegration of its gel structure; for cold melt hot gel type thermoreversible gels, gels are aggregated at high temperatures to resist thermal processing, but lowering the temperature cannot maintain the stability of the gel structure. Therefore, traditional unidirectional thermoreversible gels (condensation hot melt / cold melt hot gel) cannot simultaneously resist high-temperature sterilization / low-temperature storage conditions during food processing.

[0003] Hydroxypropyl methylcellulose (HPMC) is a nonionic water-soluble polymer. Due to its thickening, gelling and swelling properties, it is widely used in food and drug sustained-release applications. HPMC is a thermosensitive natural polymer that can form hydrogels by its own hydrophobic effect. It has the property of low critical solution temperature (LCST). In terms of gelling properties, it exhibits cold dissolution and hot coagulation, and is usually dissolved in cold water to prepare solutions. κ-Carrageenan (KC) is a natural soluble linear polysaccharide extracted from edible red seaweed. It is composed of galactose monomers and anhydrogalactose connected by (1→3)-galactosidic bonds and (1→4)-galactosidic bonds. The lower dissolution temperature and higher gel strength make KC widely used in the food industry as a gelling agent, thickener and stabilizer. In addition, the high critical solution temperature (UCST) property of KC makes it exhibit condensation hot dissolution in terms of gelling. It is usually dissolved in hot water to prepare solutions. The gelling mechanism mainly relies on its own hydrogen bonding and hydrophobic forces. How to overcome the obstacle that HPMC and KC have opposite dissolution temperatures in aqueous solution and cannot be directly mixed by dry powder to prepare mixed gel is a technical problem to be solved urgently in this field. Summary of the invention

[0004] In view of this, the present invention aims to provide a dual-temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel, its preparation method and application, so as to solve the problem that traditional unidirectional thermoreversible gels cannot simultaneously withstand high-temperature sterilization / low-temperature storage during food processing, and to prepare a hydrogel system with dual-temperature-responsive characteristics, which has the key characteristics of forming gels at low and high temperatures to stabilize the structure, while the gel dissolves at intermediate temperatures (edible temperatures).

[0005] To achieve the above object, the technical solution of the present invention is realized as follows:

[0006] In the first aspect, the present invention provides a dual-temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel. The preparation method of the semi-interpenetrating network hydrogel includes the steps of separately preparing an aqueous solution of hydroxypropyl methylcellulose and an aqueous solution of κ-carrageenan, and heating and mixing the aqueous solution of hydroxypropyl methylcellulose and the aqueous solution of κ-carrageenan and then cooling. The heating temperature is 50-60°C, and the heating time is more than 30 minutes.

[0007] Furthermore, the semi-interpenetrating network hydrogel is a dual-temperature-responsive hydrogel with dynamic structural stability and temperature adaptability formed by hybridizing HPMC as a thermogel and KC as a cryogel. Among them, the hydrogen bond interaction between HPMC and KC provides multiple temperature-responsive characteristics, which can adjust the dynamic network structure and macroscopic tissue state of the system at different temperatures, realizing an integrated temperature phase transition of two types of LCST-UCST, and being able to simultaneously achieve heat processing resistance and low-temperature storage stability, providing a basis for the development of new intelligent foods.

[0008] Furthermore, the mass concentration of hydroxypropyl methylcellulose in the semi-interpenetrating network hydrogel is 5%-10%, for example, it can be 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, and the mass concentration of κ-carrageenan is 0.1%-1%, for example, it can be 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%; preferably, the mass concentration of hydroxypropyl methylcellulose is 6%-8%, and the mass concentration of κ-carrageenan is 0.3%-0.6%; more preferably, the mass concentration of hydroxypropyl methylcellulose is 7.5%, and the mass concentration of κ-carrageenan is 0.3%-0.5%.

[0009] Furthermore, the semi-interpenetrating network hydrogel is in a gel state at low temperature (below 4°C) and high temperature (above 80°C), and can be subjected to high-temperature sterilization / low-temperature storage, and is in a sol state at the edible temperature (37-55°C).

[0010] Furthermore, in the semi - interpenetrating network hydrogel, HPMC forms a gel network at high temperatures and becomes the dispersed phase in the continuous phase of KC; at low temperatures, KC forms a gel and becomes the dispersed phase in the continuous phase of HPMC. With the change of environmental temperature, the semi - interpenetrating network structure of this hydrogel system changes accordingly. Among them, the weak hydrogen bond interaction between HPMC and KC provides dual - temperature response characteristics, which can adjust the dynamic network structure and macroscopic tissue state of the hydrogel system at different temperatures.

[0011] In a second aspect, the present invention provides a preparation method of the dual - temperature - responsive hydroxypropyl methylcellulose - κ - carrageenan semi - interpenetrating network hydrogel as described in the first aspect. The preparation method includes the following steps:

[0012] (1) Prepare an aqueous solution of hydroxypropyl methylcellulose and an aqueous solution of κ - carrageenan respectively;

[0013] (2) Heat and mix the aqueous solution of hydroxypropyl methylcellulose and the aqueous solution of κ - carrageenan evenly, and after cooling, obtain the dual - temperature - responsive hydroxypropyl methylcellulose - κ - carrageenan semi - interpenetrating network hydrogel. The heating temperature is 50 - 60 °C, and the heating time is more than 30 min to ensure thorough mixing.

[0014] Furthermore, the preparation method of the aqueous solution of hydroxypropyl methylcellulose includes the following steps: Stir hydroxypropyl methylcellulose with water until it is completely dissolved, and after sufficient hydration, obtain the aqueous solution of hydroxypropyl methylcellulose; preferably, the stirring speed is 300 - 800 rpm, the stirring time is 4 - 8 h, the hydration temperature is 3 - 8 °C, and the hydration time is 10 - 15 h; more preferably, the concentration of the aqueous solution of hydroxypropyl methylcellulose is 10% - 20%.

[0015] Furthermore, the preparation method of the aqueous solution of κ - carrageenan includes the following steps: Heat and stir κ - carrageenan with water until it is completely dissolved to obtain the aqueous solution of κ - carrageenan; preferably, the heating temperature is 70 - 90 °C, the stirring speed is 300 - 800 rpm, and the stirring time is 20 - 40 min; more preferably, the concentration of the aqueous solution of κ - carrageenan is 1% - 5%.

[0016] Furthermore, in step (2), there is also a step of diluting the aqueous solution of κ - carrageenan to 0.2% - 2% and then heating and mixing it evenly with the aqueous solution of hydroxypropyl methylcellulose; preferably, the dosage ratio of the diluted aqueous solution of κ - carrageenan to the aqueous solution of hydroxypropyl methylcellulose is 1:1.

[0017] Further, in step (2), the stirring speed for heating and mixing is 300 - 800 rpm, and the cooling temperature is 2 - 5°C. By slowly stirring at a low speed, κ-carrageenan and hydroxypropyl methylcellulose are fully mixed and react sufficiently to form a uniform mixed solution, preventing incomplete reaction from resulting in the inability to form a semi-interpenetrating structure or excessive stirring speed from causing a large number of bubbles in the hydrogel system.

[0018] In a third aspect, the present invention provides the application of the dual-temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel as described in the first aspect or the preparation method as described in the second aspect in food or medicine.

[0019] Further, the food is low-fat or fat-free food.

[0020] Compared with the prior art, the dual-temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel, its preparation method and application of the present invention have the following advantages:

[0021] (1) The dual-temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel of the present invention has good dual-temperature-responsive characteristics. At high temperature, HPMC forms a gel and becomes the dispersed phase in the KC continuous phase; at low temperature, KC forms a gel and becomes the dispersed phase in the HPMC continuous phase. With the change of the ambient temperature, the semi-interpenetrating network structure of the hydrogel system changes accordingly, enabling the simultaneous realization of heat processing resistance and low-temperature storage stability, and having bidirectional thermal reversibility, providing a basis for the development of new intelligent foods.

[0022] (2) The preparation method of the dual-temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel of the present invention is prepared by first dissolving HPMC and KC separately to obtain aqueous solutions, heating and mixing them evenly and then cooling. The raw materials are easily obtained, and the preparation process is easy to operate and implement. Description of the Drawings

[0023] The drawings constituting a part of the present invention are used to provide a further understanding of the present invention. The schematic embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings:

[0024] Figure 1 is a schematic flow chart of the preparation method of the dual-temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel of the present invention;

[0025] Figure 2 is a schematic diagram of the dual-temperature-responsive principle of the dual-temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel of the present invention;

[0026] Figure 3Macrophase diagrams of the hydrogels prepared in Examples 1-3 and Comparative Examples 1-2, where the yellow indicates the solution state and the blue indicates the gel state;

[0027] Figure 4 Temperature response curves of the hydrogels prepared in Examples 1-3 and Comparative Examples 1-2;

[0028] Figure 5 Viscosity change curves of the hydrogels prepared in Examples 1-3 and Comparative Example 2 with temperature and shear rate;

[0029] Figure 6 Viscoelastic curves of the hydrogels prepared in Examples 1-3 and Comparative Example 2 with frequency;

[0030] Figure 7 Magnetic resonance imaging maps of water distribution in the hydrogels prepared in Example 2 and Comparative Examples 1-2;

[0031] Figure 8 Scanning electron microscope images of the hydrogels prepared in Example 2 and Comparative Examples 1-2 at different temperatures. Detailed implementation manners

[0032] It should be noted that, without conflict, the embodiments in the present invention and the features in the embodiments can be combined with each other.

[0033] The present invention will be described in detail below with reference to the drawings and in combination with the embodiments.

[0034] Example 1

[0035] As Figure 1 shown, the preparation method of the dual temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel in this example includes the following steps:

[0036] Step 1, mechanically stir at a speed of 500 rpm for 6 h to completely dissolve hydroxypropyl methylcellulose in an aqueous solution, and after hydrating at 4 °C for 12 h, obtain a hydroxypropyl methylcellulose aqueous solution with a mass concentration of 15%; heat and stir at 80 °C for 30 min to completely dissolve κ-carrageenan in an aqueous solution, and obtain a κ-carrageenan aqueous solution with a mass concentration of 2%.

[0037] Then, use the hydroxypropyl methylcellulose aqueous solution and κ-carrageenan aqueous solution prepared in the above steps to prepare a semi-interpenetrating network hydrogel. The specific method is as follows:

[0038] Step 2: Dilute the 2% κ-carrageenan aqueous solution to 0.6%. After stabilizing at 50 - 60°C, mix it with the aqueous solution of hydroxypropyl methylcellulose stabilized at the same temperature in a mass ratio of 1:1. Stir at 500 rpm for 30 min to ensure thorough mixing. Then refrigerate at 4°C to obtain a dual-temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel.

[0039] As Figure 2 shown, the dual-temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel of the present invention has dual-temperature-responsive properties. At high temperatures, HPMC forms a gel and becomes the dispersed phase in the KC continuous phase; at low temperatures, KC forms a gel and becomes the dispersed phase in the HPMC continuous phase. With the change of the environmental temperature, the semi-interpenetrating network structure of the hydrogel system changes accordingly, enabling simultaneous resistance to thermal processing and low-temperature storage stability, and having bidirectional thermal reversibility.

[0040] Example 2

[0041] The preparation method of the dual-temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel in this example includes the following steps:

[0042] Step 1: Mechanically stir hydroxypropyl methylcellulose in an aqueous solution at a speed of 500 rpm for 6 h to completely dissolve it. After hydrating at 4°C for 12 h, an aqueous solution of hydroxypropyl methylcellulose with a mass concentration of 15% is obtained; heat and stir κ-carrageenan in an aqueous solution at 80°C for 30 min to completely dissolve it to obtain a 2% κ-carrageenan aqueous solution with a mass concentration.

[0043] Then, use the aqueous solution of hydroxypropyl methylcellulose and the aqueous solution of κ-carrageenan prepared in the above steps to prepare a semi-interpenetrating network hydrogel. The specific method is as follows:

[0044] Step 2: Dilute the 2% κ-carrageenan aqueous solution to 0.8%. After stabilizing at 50 - 60°C, mix it with the aqueous solution of hydroxypropyl methylcellulose stabilized at the same temperature in a mass ratio of 1:1. Stir at 500 rpm for 30 min to ensure thorough mixing. Then refrigerate at 4°C to obtain a dual-temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel.

[0045] Example 3

[0046] The preparation method of the dual-temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel in this example includes the following steps:

[0047] Step 1, mechanically stir at a speed of 500 rpm for 6 h to completely dissolve hydroxypropyl methylcellulose in an aqueous solution, and after hydrating at 4 °C for 12 h, obtain an aqueous hydroxypropyl methylcellulose solution with a mass concentration of 15%; heat and stir at 80 °C for 30 min to completely dissolve κ-carrageenan in an aqueous solution, and obtain an aqueous κ-carrageenan solution with a mass concentration of 2%.

[0048] Then, use the aqueous hydroxypropyl methylcellulose solution and aqueous κ-carrageenan solution prepared in the above steps to prepare a semi-interpenetrating network hydrogel. The specific method is as follows:

[0049] Step 2, dilute the 2% aqueous κ-carrageenan solution to 1.0%, mix it with the aqueous hydroxypropyl methylcellulose solution stabilized at the same temperature at a mass ratio of 1:1 after stabilizing at 50 - 60 °C, stir at a speed of 500 rpm for 30 min to ensure thorough mixing, and refrigerate at 4 °C to obtain a double temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel.

[0050] Comparative Example 1

[0051] The preparation method of the thermoreversible κ-carrageenan hydrogel in this comparative example includes the following steps:

[0052] Heat and stir at 80 °C for 30 min to completely dissolve κ-carrageenan in an aqueous solution, obtain an aqueous κ-carrageenan solution with a mass concentration of 0.4%, and refrigerate at 4 °C to obtain a thermoreversible κ-carrageenan hydrogel.

[0053] Comparative Example 2

[0054] The preparation method of the thermoreversible hydroxypropyl methylcellulose hydrogel in this comparative example includes the following steps:

[0055] Mechanically stir at a speed of 500 rpm for 6 h to completely dissolve hydroxypropyl methylcellulose in an aqueous solution, and after hydrating at 4 °C for 12 h, obtain an aqueous hydroxypropyl methylcellulose solution with a mass concentration of 7.5%.

[0056] Comparative Example 3

[0057] The difference between this comparative example and Example 1 is that: in step (2), the mixing temperature of the aqueous κ-carrageenan solution and the aqueous hydroxypropyl methylcellulose solution is 40 °C, and other steps are the same as those in Example 1.

[0058] Comparative Example 4

[0059] The difference between this comparative example and Example 1 is that: in step (2), the aqueous κ-carrageenan solution and the aqueous hydroxypropyl methylcellulose solution are stirred at a speed of 1000 rpm for 30 min, and other steps are the same as those in Example 1.

[0060] Comparative Example 5

[0061] The difference between this comparative example and Example 1 lies in that: in step (2), the κ-carrageenan aqueous solution and the hydroxypropyl methylcellulose aqueous solution are stirred at a speed of 500 rpm for 20 min, and the other steps are the same as those in Example 1.

[0062] The hydroxypropyl methylcellulose used in Examples 1-3 and Comparative Examples 1-5 was purchased from Sigma-Aldrich Co., Ltd. in the United States, and κ-carrageenan was purchased from Shanghai Macklin Biochemical Co., Ltd.

[0063] Performance test example

[0064] Measure the macroscopic state and rheological properties of the hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel described in the examples and comparative examples, including the changes of storage modulus and loss modulus with temperature and frequency, the changes of viscosity with time, temperature, and shear rate, as well as the changes of microstructure and water distribution, etc., and compare the hydroxypropyl methylcellulose hydrogel and κ-carrageenan hydrogel at the same time.

[0065] Macroscopic phase diagram of the hydrogel in Performance Test Example 1

[0066] Take out the hydrogels prepared in Examples 1-3 and Comparative Examples 1-5 from the 4°C refrigerator, and then heat them at 37°C for 20 min; then heat them at 80°C for 20 min, cool them to 37°C and maintain for 20 min, and finally cool them to 4°C and maintain for 20 min. After stabilizing at each temperature, invert the sample and take an image, that is, a comparison of the macroscopic state results of the thermoreversible gels of the double-temperature-responsive semi-interpenetrating network hydrogels of Examples 1-3 and Comparative Examples 1-5. The results are as Figure 3As shown, at the initial temperature of 4°C, the blend system of Comparative Example 2 was not sufficient to form a gel network and thus presented as a homogeneous solution system, while the blend systems of Comparative Example 1 and Examples 1-3 all showed a transparent gel state under the domination of KC; when the temperature was raised to 37°C, the phase diagrams of all samples remained unchanged, but water was separated out in the systems with high-concentration KC content, and the gel strength decreased slightly; at 80°C, except for Comparative Example 1, all samples formed white gels under the domination of HPMC. When the temperature was lowered to 37°C, the gel structures of Comparative Example 1 and Examples 1-3 disintegrated, and the system was in a solution state; when the temperature was lowered to 4°C, Comparative Example 2 still presented as a solution, while the blend systems of Comparative Example 1 and Examples 1-3 presented as gels. It shows that the hydrogel products prepared in Examples 1-3 have obvious dual temperature-responsive characteristics, specifically, they are in a gel state at low temperatures (below 4°C) and high temperatures (above 80°C), and in a sol state at edible temperatures (37-55°C). Compared with the hydrogels of Examples 1-3, in Comparative Example 3, KC was not dissolved and still existed in the form of a solid gel, and it was impossible to achieve two-phase mixing with HPMC; in Comparative Example 4, HPMC was emulsified into a large number of foams under high-speed stirring, and a weak gel with a loose structure was formed at 80°C, with large and numerous pores; in Comparative Example 5, the stirring time was short, the mixing was insufficient, and the two phases of KC and HPMC were unevenly distributed. Although the states of low-temperature and high-temperature gels could be achieved, the gel structure was uneven.

[0067] Performance Test Example 2 Temperature-responsive performance test of hydrogels

[0068] Temperature scanning measurement was carried out to clarify the key temperature nodes of phase transition. A parallel plate fixture with a diameter of 40 mm was selected, and the plate spacing was 1 mm. The fixed frequency was 1 Hz, and the strain was 1%. The temperature was raised from 4°C to 80°C at a heating rate of 2°C / min and held at this temperature for 5 min, and then lowered to 4°C at the same rate. The sample loading amount was 2 g, and it was sealed with silicone oil around to avoid water loss during the test, and thus the comparison of the temperature scanning results of the thermoreversible gels of the dual temperature-responsive semi-interpenetrating network hydrogels of Examples 1-3 and Comparative Examples 1-2 was obtained.

[0069] Table 1 Melting (T m ) and gel temperature (T g )

[0070]

[0071] As shown in Figure 43 and Table 1, at low temperatures (5 - 30 °C), the storage modulus of Comparative Example 2 was small and remained stable. As the temperature increased, the storage modulus of HPMC increased rapidly, indicating that the molecular chains of HPMC in the gel system began to aggregate. When the temperature reached 63.1 °C, the storage modulus G' was equal to the loss modulus G", and the loss factor tanδ was 1, indicating the gel transition point of HPMC. As the temperature further increased, the storage modulus was higher than the loss modulus, and the system was completely formed into a gel at this time. During the cooling process, the storage modulus of HPMC decreased rapidly from 60 °C to about 40 °C, which was due to the fact that HPMC redissolved into a sol in this temperature range, and it also illustrated the thermoreversibility of the HPMC gel. Compared with Comparative Example 2, during the temperature change process, the gel transition points of HPMC and KC could be observed respectively in the viscoelasticity change curves of Examples 1 - 3. This phenomenon indicated that both components in the blend system could form their own gel network structures, that is, a phase-separated mixed gel.

[0072] In the first plateau of the HPMC / KC blend, G' was one order of magnitude higher than G", which meant that a three-dimensional helical network was established between KC molecules, forming a strong gel. As the temperature increased to 40 °C, G' decreased and was less than G", indicating that the KC network changed from a gel to a sol; at the same time, the loss factor tanδ increased, that is, the elasticity of the gel decreased. During the process of KC forming a gel at low temperatures, HPMC, as a sol, penetrated through the KC gel network in a linear molecular structure. Therefore, when the temperature gradually increased to about 50 °C, due to the thermogelation of HPMC, the storage modulus G' was again higher than the loss modulus G". During the cooling stage, the gel-sol transition point shifted to a lower temperature, indicating the occurrence of hysteresis.

[0073] The gelling temperature and melting temperature of HPMC are 50.8 °C and 43.6 °C respectively. As can be seen from Table 1, the phase transition temperature of the blend depends on the HPMC / KC ratio. During the heating stage, as the KC ratio in the blend increases from 0.2 wt% to 0.4 wt%, the gel melting temperature of the blend increases from 40.2 °C to 51.9 °C. On the one hand, due to the thermal incompatibility between KC and HPMC, the increase in the KC ratio causes sufficient KC polymerization to form a dense cross-linked network, which requires more energy to break the bonds during the heating process, resulting in an increase in the gel melting temperature. When the KC ratio further increases (≥0.5 wt%), the thermal energy at 50 °C is not sufficient to force the gel network of KC to disintegrate, so the HPMC / KC blend remains in a gel state during the heating process. On the other hand, as the KC content increases, the entanglement ratio of HPMC molecular chains and KC molecular chains increases, further strengthening the gel network. At the same time, the increase in the total polymer concentration in the blend system can also lead to an increase in gel strength. During the cooling stage, as the KC ratio in the blend increases from 0.2% to 0.7%, the gelling temperature of the blend increases from 11.9 °C to 38.7 °C. This is because when the system temperature drops between the gelling temperature of HPMC and the gelling temperature of KC, both KC and HPMC are in a sol state. At this time, due to the higher concentration of KC, self-aggregation is more likely to occur, resulting in an increase in the gelling temperature of KC. When the KC concentration increases to 0.8%, the blend system shows a gel state throughout the temperature change process.

[0074] For the reasons for the above results, the rheological properties of the gel can be analyzed.

[0075] Performance Test Example 3 Viscosity change of the hydrogel with temperature and shear rate

[0076] The viscosity results of Examples 1-3 and Comparative Example 2 were compared using shear scanning and temperature-viscosity scanning. For the shear scanning test, a 2° cone-plate fixture with a diameter of 40 mm and a plate spacing of 57 μm was used. The viscosity change with shear rate was measured at different temperatures, and the shear rate increased from 0 to 10001 / s within 1 min. For the temperature-viscosity scanning test, a parallel plate fixture with a diameter of 40 mm and a plate spacing of 1000 μm was used. The temperature was increased from 4 °C to 80 °C at a heating rate of 2 °C / min, and then decreased from 80 °C to 4 °C at a cooling rate of 2 °C / min. The change in viscosity with temperature and shear rate as shown Figure 5 was obtained.

[0077] From Figure 5It can be seen that Examples 1-3 exhibit obvious shear-thinning behavior with the increase of shear rate, indicating that the blend system is a pseudoplastic fluid. In addition, at all temperatures, the apparent viscosity of Comparative Example 2 is lower than that of Examples 1-3, and when the KC concentration reaches 0.4%, the viscosity increase of the blend is not obvious. At the same shear rate, the viscosity of the blend is higher than that of pure HPMC, mainly because KC is in a gel state with a large viscosity at low temperatures, while the addition of KC promotes the aggregation of HPMC molecules at high temperatures.

[0078] When the temperature is relatively low (<50 °C), Comparative Example 2 has the lowest viscosity throughout the temperature change process. During the heating process, the viscosity of HPMC decreases with the increase of temperature, then shows a small increase, and appears a peak value near 60 °C and then the viscosity continues to decrease. The appearance of the peak value is due to the increase in viscosity caused by the transformation of HPMC into a gel at high temperatures. However, the continuous shear force forces the destruction of the gel structure, resulting in a decrease in viscosity. With the increase of the KC concentration, the viscosity peak values of Examples 1-3 shift towards lower temperatures. Compared with Comparative Example 2, the viscosity of the HPMC / KC blend system shows a rapid downward change trend in the temperature range of 40-60 °C. This is due to the dissolution of the KC-dominated gel network at high temperatures. During the cooling process, the viscosity of Comparative Example 2 increases with the decrease of temperature, then rapidly decreases, and appears a trough value near 40 °C and then the viscosity continues to increase. The appearance of the trough value is due to the decrease in viscosity caused by the melting of the HPMC gel at low temperatures, while the gelling effect of KC is obvious at this time, which leads to the continuous increase in the viscosity of Examples 1-3. With the increase of the KC concentration, the viscosity peak values of the blend system shift towards higher temperatures.

[0079] Performance Test Example 4 Viscoelasticity of the hydrogel varying with frequency

[0080] For the frequency sweep test, a parallel plate fixture with a diameter of 40 mm is selected, the plate spacing is set to 1 mm, and the strain is 1%. The angular frequency (ω) varies in the range of 0.1 to 100 1 / s. The sample loading amount is 2 g, and it is sealed with silicone oil around. Record the curves of the dynamic moduli of Examples 1-3 and Comparative Example 2 varying with the angular frequency. The results are as Figure 6 shown.

[0081] From Figure 6It can be seen that Comparative Example 2 has strong frequency dependence both at the initial temperature of 4°C and when cooled to 4°C. By increasing the KC content, the frequency dependence of the HPMC / KC system rapidly weakens, and the modulus increases with the increase in KC content. When the temperature is raised to 80°C, during the entire frequency sweep, both the examples and the comparative examples exhibit a strong elastic network, and the dependence of G′ and G″ on frequency is weak. This is mainly attributed to the fact that hydrophobic interactions dominate the association of HPMC at high temperatures, further connecting to form a stable gel structure, further confirming the solid-like behavior of the system. In addition, the gel strength of Comparative Example 2 is less than that of Examples 1-3, indicating that the HPMC / KC blend system is closer to a solid than pure HPMC. This shows that the presence of KC optimizes the continuity of the pure HPMC network, and KC is dispersed in the HPMC gel network in the form of a sol, increasing the viscosity of the system. When cooled to 37°C, Examples 1-3 exhibit strong frequency dependence, which reflects a relatively high degree of relaxation of the polymer molecular chains, that is, the structure is active and the fluidity is good.

[0082] Magnetic resonance imaging of the water distribution in the hydrogel for Performance Test Example 5

[0083] The sample was subjected to magnetic resonance imaging. The sample was placed in the sample tube bracket and stabilized for 20 min at each temperature, and then the MRI-SE function was run. The experimental parameters were set as follows: echo time was 24000 us; Echo shift was 400 us; Rep.time was 1 s; Scans was 4 times; G_phase_start was -6000, G_phase_end was 6000, G_phase_step was 256. After the MRI-2D inversion of the measured data, the water distribution of Example 2 and Comparative Examples 1-2 at different temperatures was obtained as Figure 7 shown. Regions with high signal intensity and brightness represent more bound water molecules, while low-intensity regions represent free water. In the comparative examples, the water distribution is uneven. At low temperatures, the water level in the center of the KC gel is lower than that at the surface layer, while at high temperatures, the water level at the surface layer of the HPMC gel is lower than that in the middle part. An increase in water content can be clearly observed in Example 2. In addition, the HPMC / KC gel exhibits a uniform water distribution and a higher water content throughout the temperature change, as evidenced by the high proton density. Due to the confinement effect of the multi-level network, the establishment of a dynamic semi-interpenetrating network leads to an increase in the proportion of bound water and a more uniform distribution.

[0084] Gel network conditions of the hydrogel at different temperatures for Performance Test Example 6

[0085] The gel network structure was directly observed by scanning electron microscopy. After the prepared hydrogel was heated to a specified temperature and stabilized for 20 min, its structure was immediately fixed by rapid freezing in liquid nitrogen, and then vacuum freeze-dried for 48 h. The freeze-dried gel was cut into thin slices, sputter-coated with gold using an ion sputtering device, and then observed under the electron microscope. The microstructures of Example 2 and Comparative Examples 1-2 at different temperatures are as Figure 8 shown. Among them, the two comparative examples showed completely opposite network aggregations. Comparative Example 1 had a uniform polysaccharide chain aggregation network at an initial temperature of 4 °C. As the temperature increased, the aggregates gradually dispersed into double helices. When the temperature rose to 80 °C, it presented a disordered linear structure. As the temperature decreased, the random coils transformed into single helix structures. When the temperature dropped to 4 °C, the helical structures further aggregated and gelation occurred. Comparative Example 2 showed a rigid cage-like structure at low temperatures, and the voids between the layers were left by the sublimation of water molecules. As the temperature increased, the hydrogen bond interaction between HPMC and water molecules weakened, and the structure showed a collapsed corrugated shape. When the temperature rose to 80 °C, more hydrophobic groups of HPMC were exposed, and hydrophobic aggregation occurred between molecules to form a compact network. During the cooling process, the aggregated molecular chains dispersed, and the hydrogen bond interaction with water molecules increased as the temperature decreased, reforming the cage-like structure. The semi-interpenetrating network of Example 2 was a three-dimensional structure in which the linear chains of KC and HPMC semi-interpenetrated. The results showed that they were all homogeneous porous networks, presenting uniform and fine small mesh pores at 4 °C and 80 °C, with good water retention capacity and gel structure, while showing large and non-uniform mesh pores at 37 °C during the heating and cooling processes, corresponding to the above-mentioned weaker rheological properties.

[0086] In summary, the semi-interpenetrating network hydrogel sample prepared by the method of the present invention has dual temperature-responsive properties. It can maintain the gel structure during low-temperature storage (4 °C) and high-temperature processing (80 °C), and transforms into a sol state near the edible temperature (37 - 55 °C), and is a potential new type of intelligent food.

[0087] The above-described embodiments are only a part of the embodiments of the present invention, rather than all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative efforts fall within the scope of protection of the present invention.

Claims

1. A dual-temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel, characterized in that: The preparation method of the semi-interpenetrating network hydrogel includes the steps of separately preparing an aqueous solution of hydroxypropyl methylcellulose and an aqueous solution of κ-carrageenan, and heating and mixing the aqueous solution of hydroxypropyl methylcellulose and the aqueous solution of κ-carrageenan and then cooling. The heating temperature is 50-60 °C, and the heating time is more than 30 min.

2. The double temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel according to claim 1, characterized in that: In the semi-interpenetrating network hydrogel, the mass concentration of hydroxypropyl methylcellulose is 5%-10%, and the mass concentration of κ-carrageenan is 0.1%-1%.

3. The double temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel according to claim 1, characterized in that: The semi-interpenetrating network hydrogel is in a gel state below 4 °C and above 80 °C, and in a sol state at 37-55 °C.

4. A method for preparing a dual temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel according to any one of claims 1-3, characterized in that, The preparation method includes the following steps: (1) Separately prepare an aqueous solution of hydroxypropyl methylcellulose and an aqueous solution of κ-carrageenan; (2) Heat and mix the aqueous solution of hydroxypropyl methylcellulose and the aqueous solution of κ-carrageenan, and cool to obtain the double temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel. The heating temperature is 50-60 °C, and the heating time is more than 30 min.

5. The preparation method according to claim 4, characterized in that, The preparation method of the aqueous solution of hydroxypropyl methylcellulose includes the following steps: Stir hydroxypropyl methylcellulose and water until completely dissolved, and fully hydrate to obtain an aqueous solution of hydroxypropyl methylcellulose; preferably, the stirring speed is 300-800 rpm, the stirring time is 4-8 h, the hydration temperature is 3-8 °C, and the hydration time is 10-15 h; further preferably, the concentration of the aqueous solution of hydroxypropyl methylcellulose is 10%-20%.

6. The preparation method according to claim 4, characterized in that, The preparation method of the aqueous solution of κ-carrageenan includes the following steps: Heat and stir κ-carrageenan and water until completely dissolved to obtain an aqueous solution of κ-carrageenan; preferably, the heating temperature is 70-90 °C, the stirring speed is 300-800 rpm, and the stirring time is 20-40 min; further preferably, the concentration of the aqueous solution of κ-carrageenan is 1%-5%.

7. The preparation method according to claim 4, characterized in that: Step (2) also includes the step of diluting the aqueous solution of κ-carrageenan to 0.2%-2% and then heating and mixing it with the aqueous solution of hydroxypropyl methylcellulose; preferably, the dosage ratio of the diluted aqueous solution of κ-carrageenan to the aqueous solution of hydroxypropyl methylcellulose is 1:

1.

8. The preparation method according to claim 4, characterized in that: In step (2), the stirring speed for heating and mixing is 300-800 rpm, and the cooling temperature is 2-5 °C.

9. Application of the double temperature-responsive hydroxypropyl methylcellulose-κ-carrageenan semi-interpenetrating network hydrogel according to any one of claims 1-3 or the preparation method according to any one of claims 4-8 in the preparation of food or medicine.

10. The application according to claim 9, wherein The food is low-fat or fat-free food.

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