Modulus testing method for thermosensitive gels

Abstract

This application discloses a method for detecting the modulus of a thermosensitive gel. The method employs an oscillation measurement method, wherein the oscillation frequency is fixed, the detection temperature is increased from an initial temperature to an ending temperature, and the strain is simultaneously reduced from a first strain to a second strain as the detection temperature increases. By setting the detection temperature as a variable and adjusting the strain according to the temperature change, this method obtains the modulus of the thermosensitive gel at different temperatures. This ensures sufficient strain and stress at different temperatures to meet the accuracy requirements of the detection, improving the accuracy of the modulus detection results at different temperatures. Furthermore, this method offers fast detection speed and simple operation, further enhancing the accuracy and precision of the modulus detection.

Description

Technical Field

[0001] This invention relates to the field of thermosensitive gel technology, and more particularly to a method for detecting the modulus of thermosensitive gels. Background Technology

[0002] Thermosensitive gels are aqueous gels that undergo reversible sol-gel transformation in response to temperature changes. They have applications in various fields, such as tumor embolization, cell culture, tissue engineering, and drug delivery systems. In tumor embolization, the thermosensitive gel, after injection into the body, transforms from a flowing sol state to a non-flowing gel state in response to body temperature, thereby blocking tumor blood vessels and interrupting the blood supply to tumor cells. The modulus of the thermosensitive gel reflects its gel strength, which is an important performance indicator for evaluating the embolization effect. Therefore, the modulus of the thermosensitive gel needs to be tested before drug design and use. During the reversible sol-gel transformation of the thermosensitive gel with temperature changes, the modulus can change by several orders of magnitude. For example, the modulus of polyisopropylacrylamide gels can change by 3-4 orders of magnitude in the range of 25–45°C. Because the modulus of thermosensitive gels changes with temperature, fixed-temperature modulus testing methods are not effective in detecting the modulus of thermosensitive gels.

[0003] In a currently available method for detecting the modulus of thermosensitive gels, the frequency and strain are kept constant, and the detection temperature is controlled to change at a constant rate to detect the modulus of the thermosensitive gel at different temperatures. However, this method suffers from the technical problem of inaccurate modulus detection results. When the detection temperature is below the phase transition temperature of the thermosensitive gel, the gel is a sol, exhibiting a fluid dynamic state with a low modulus and low yield stress. If the applied stress exceeds the yield stress, it will cause irreversible damage to the material, leading to inaccurate detection results. Conversely, when the detection temperature is above the phase transition temperature, the thermosensitive gel transforms into a gel state, exhibiting a solidified state with an increased modulus and low yield strain. If the strain caused by the applied stress exceeds the yield strain, the detection will also be inaccurate. Summary of the Invention

[0004] The purpose of this invention is to overcome the above-mentioned shortcomings of the prior art and provide a method for detecting the modulus of thermosensitive gels, so as to solve the technical problems such as inaccurate results of existing thermosensitive gel modulus detection.

[0005] To achieve the above-mentioned objective, this application provides a method for detecting the modulus of a thermosensitive gel. The method for detecting the modulus of a thermosensitive gel includes the following steps:

[0006] Provide the temperature-sensitive gel to be tested;

[0007] Place the temperature-sensitive gel to be tested in the modulus testing area;

[0008] The modulus of the thermosensitive gel under test was determined by the oscillation measurement method;

[0009] The detection conditions for the oscillation measurement method include:

[0010] The oscillation frequency is a fixed frequency;

[0011] The temperature is monitored from the initial temperature to the final temperature.

[0012] The strain decreases from the first strain to the second strain as the detection temperature increases, and both the first strain and the second strain are less than the yield strain of the thermosensitive gel to be tested at the corresponding temperature.

[0013] In some embodiments, the initial temperature is lower than the phase transition temperature of the thermosensitive gel to be tested.

[0014] In some embodiments, the termination temperature is higher than the phase transition temperature of the thermosensitive gel to be tested.

[0015] In some embodiments, the starting temperature is increased to the ending temperature at a heating rate of ≤3°C / min.

[0016] In some embodiments, the initial temperature is ≤25°C.

[0017] In some embodiments, the termination temperature is ≥37°C.

[0018] In some embodiments, the heating rate is 0.5-3 °C / min.

[0019] In some embodiments, the strain decreases from the first strain to the second strain according to a logarithmic variation.

[0020] In some embodiments, the first strain is ≤20% strain.

[0021] In some embodiments, the second strain is ≥0.5% strain.

[0022] In some embodiments, the oscillation frequency is 0.1-10Hz.

[0023] In some embodiments, placing the temperature-sensitive gel to be tested in the modulus testing area includes the following steps:

[0024] The temperature-sensitive gel to be tested is placed on a gel carrier platform;

[0025] The rotor is pressed down so that the temperature-sensitive gel to be tested fills the gap between the rotor and the gel carrier platform.

[0026] In a further embodiment, the rotor is a conical plate or a flat plate.

[0027] In some embodiments, the temperature-sensitive gel to be tested comprises a polyisopropylacrylamide gel having a three-dimensional network structure.

[0028] In a further embodiment, the polyisopropylacrylamide gel includes any one of the following: poly(N-isopropylacrylamide-co-butyl methacrylate) crosslinked with a crosslinking agent, poly(N-isopropylacrylamide) crosslinked with a crosslinking agent, poly(N-isopropylacrylamide-co-N-n-propylacrylamide) crosslinked with a crosslinking agent, poly(N-isopropylacrylamide-co-acrylic acid) crosslinked with a crosslinking agent, poly(N-isopropylacrylamide-co-methyl methacrylate) crosslinked with a crosslinking agent, poly(N-isopropylacrylamide-co-hydroxyethyl methacrylate) crosslinked with a crosslinking agent, poly(N-isopropylacrylamide-co-hydroxyethyl acrylate) crosslinked with a crosslinking agent, and poly(N-isopropylacrylamide-co-acrylamide) crosslinked with a crosslinking agent.

[0029] Compared with the prior art, this application has the following technical effects:

[0030] The modulus testing method for thermosensitive gels in this application adjusts the testing temperature during the testing process and simultaneously adjusts the strain according to the temperature change to obtain the modulus of the thermosensitive gel under test at different temperatures. Specifically, the strain decreases as the testing temperature increases, ensuring sufficient strain and stress to meet the accuracy requirements of the test at different temperatures. Simultaneously, the strain does not exceed the yield strain during the testing process, avoiding damage to the structure of the thermosensitive gel and improving the accuracy of the modulus testing results at different temperatures. Furthermore, the modulus testing method for thermosensitive gels in this application is fast and simple to operate, further improving the accuracy and precision of the modulus testing. Attached Figure Description

[0031] To more clearly illustrate the technical solutions in the embodiments of this application, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0032] Figure 1 This is a schematic diagram showing the modulus test results of the poly(N-isopropylacrylamide-co-butyl methacrylate) gel in Example 1;

[0033] Figure 2 This is a schematic diagram of the modulus test results of the poly(N-isopropylacrylamide) gel in Example 2;

[0034] Figure 3 This is a schematic diagram showing the modulus test results of the poly(N-isopropylacrylamide-co-n-propylacrylamide) gel in Example 3;

[0035] Figure 4This is a schematic diagram showing the modulus test results of poly(N-isopropylacrylamide-co-butyl methacrylate) gel in Comparative Example 1. Detailed Implementation

[0036] To make the technical problems, technical solutions, and beneficial effects of this application clearer, the following detailed description is provided in conjunction with embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.

[0037] In this application, the term "and / or" describes the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A existing alone, A and B existing simultaneously, or B existing alone. A and B can be singular or plural. The character " / " generally indicates that the preceding and following related objects have an "or" relationship.

[0038] In this application, "at least one" means one or more, and "more than one" means two or more. "At least one of the following" or similar expressions refer to any combination of these items, including any combination of single or multiple items. For example, "at least one of a, b or c", or "at least one of a, b and c", can both mean: a, b, c, ab (i.e., a and b), ac, bc, or abc, where a, b, and c can be single or multiple.

[0039] The terminology used in the embodiments of this application is for the purpose of describing particular embodiments only and is not intended to be limiting of this application. The singular forms "a" and "the" as used in the embodiments of this application and the appended claims are also intended to include the plural forms, unless the context clearly indicates otherwise.

[0040] The terms "first" and "second" are used for descriptive purposes only, to distinguish objects, such as substances, from one another, and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. For example, without departing from the scope of the embodiments of this application, "first XX" may also be referred to as "second XX," and similarly, "second XX" may also be referred to as "first XX." Thus, features defined with "first" and "second" may explicitly or implicitly include one or more of that feature.

[0041] Thermosensitive gels can undergo reversible sol-gel transformation in response to temperature changes. For example, poly(N-isopropylacrylamide-co-butyl methacrylate) gel is fluid at room temperature (25°C) with a low modulus; when the temperature exceeds the phase transition temperature (32-35°C), it immediately transforms into a solid state, and the modulus increases sharply; the modulus of this material can change by 3-4 orders of magnitude in the range of 25-45°C.

[0042] Due to the reversible sol-gel transition of thermosensitive gels, when performing modulus testing, if the testing temperature is below the phase transition temperature, the thermosensitive gel is in a sol state, exhibiting a fluid dynamic state with a low modulus and low yield stress. If the applied stress exceeds the yield stress, it will cause irreversible damage to the material, leading to inaccurate test results. If the applied stress is too low, the testing accuracy cannot be met. Conversely, if the testing temperature is above the phase transition temperature, the thermosensitive gel transforms into a gel state, exhibiting a solidified state with an increased modulus and low yield strain. If the strain generated by the applied stress exceeds the yield strain, it will also cause inaccurate test results.

[0043] To obtain modulus data of thermosensitive gels at different temperatures, it is necessary to overcome the contradictions arising from the properties of thermosensitive gels. This requires ensuring that the stress applied at low temperatures is less than the yield stress, and that the strain generated at high temperatures is less than the yield strain. Simultaneously, sufficient stress and strain values ​​must be present at each temperature node to meet the accuracy requirements of modulus testing. To address the problem of inaccurate modulus test results for thermosensitive gels at different temperatures, this application proposes the following solution.

[0044] This application provides a method for detecting the modulus of a thermosensitive gel. The method includes the following steps:

[0045] S01: Provide the temperature-sensitive gel to be tested;

[0046] S02: Place the temperature-sensitive gel to be tested in the modulus testing area;

[0047] S03: The modulus of the thermosensitive gel to be tested was determined by the oscillation measurement method.

[0048] In step S01, the temperature-sensitive gel to be tested refers to the gel described above that has a reversible sol-gel transition with temperature changes.

[0049] In some embodiments, the temperature-sensitive gel to be tested may comprise a poly(N-isopropylacrylamide) gel with a three-dimensional network structure. Specifically, it may include any one of the following: poly(N-isopropylacrylamide-co-butyl methacrylate) crosslinked with a crosslinking agent; poly(N-isopropylacrylamide) crosslinked with a crosslinking agent; poly(N-isopropylacrylamide-co-N-n-propylacrylamide) crosslinked with a crosslinking agent; poly(N-isopropylacrylamide-co-acrylic acid) crosslinked with a crosslinking agent; poly(N-isopropylacrylamide-co-methyl methacrylate) crosslinked with a crosslinking agent; poly(N-isopropylacrylamide-co-hydroxyethyl methacrylate) crosslinked with a crosslinking agent; or poly(N-isopropylacrylamide-co-hydroxyethyl acrylate) crosslinked with a crosslinking agent. These gels exhibit excellent reversible sol-gel transition properties with temperature changes and can be applied in fields such as tumor embolization, cell culture, tissue engineering, and drug delivery systems. Modulus testing of these thermosensitive gels provides a reference for improving their applicability.

[0050] Step S02, placing the temperature-sensitive gel to be tested in the modulus testing area, includes pretreatment steps such as the pretreatment of the temperature-sensitive gel to be tested in step S03. As in the embodiment, placing the temperature-sensitive gel to be tested in the modulus testing area includes the following steps:

[0051] S021: Place the temperature-sensitive gel to be tested on the gel carrier platform;

[0052] S022: Press the rotor down so that the temperature-sensitive gel to be tested fills the space between the rotor and the gel carrier platform.

[0053] In step S021, the gel carrier platform can be the gel carrier platform contained in the modulus testing device. The modulus testing device can be a commonly used instrument for testing gel modulus, such as a rotational rheometer, in which case the gel carrier platform is the gel carrier platform contained in the rotational rheometer.

[0054] The rotor in step S022 is the rotor included in the modulus testing device. For example, when the modulus testing device is a rotational rheometer, the rotor can be a flat plate or a conical plate, such as a conical plate with a diameter of 60 mm and a cone angle of 1°. The distance between the rotor and the gel carrier platform can be set by those skilled in the art according to actual needs, so that the temperature-sensitive gel to be tested can fill the gap between the rotor and the gel carrier platform, for example, it can be 0.5 mm.

[0055] In step S03, to ensure the accuracy and precision of the modulus testing method for the thermosensitive gel in this application embodiment, the testing conditions of the oscillation measurement method in the embodiment include:

[0056] A: The oscillation frequency is a fixed frequency;

[0057] B: The temperature is monitored from the initial temperature to the final temperature;

[0058] C: The strain decreases from the first strain to the second strain as the detection temperature increases, and both the first strain and the second strain are less than the yield strain of the thermosensitive gel to be tested at the corresponding temperature.

[0059] Thus, in the modulus testing method of the thermosensitive gel according to the embodiments of this application, during the process of raising the detection temperature from the initial temperature to the final temperature, the strain is controlled and adjusted to decrease from a first strain to a second strain. For example, when the detection temperature is at the initial temperature, the controlled strain is the first strain; as the detection temperature rises, the corresponding controlled strain decreases until the detection temperature reaches the final temperature, at which point the controlled strain becomes the second strain. Of course, both the first strain and the second strain are less than the yield strain of the thermosensitive gel at the corresponding temperature.

[0060] In this context, strain refers to the deformation of the temperature-sensitive gel under stress. The yield strain of the gel, on the other hand, is the strain produced when the internal stress exceeds its yield point under external force. When the gel reaches yield strain, its strain will continue to increase even without further increase in external force.

[0061] Therefore, the modulus testing method for thermosensitive gels in this application adjusts both the testing temperature and strain simultaneously during the testing process. Specifically, the strain decreases as the testing temperature increases, ensuring sufficient strain and stress to meet the accuracy requirements at different temperatures. Simultaneously, the strain does not exceed the yield strain during testing, preventing damage to the thermosensitive gel structure and improving the accuracy of modulus testing results at different temperatures. Furthermore, the modulus testing method for thermosensitive gels in this application only requires controlling the temperature and adjusting the strain accordingly to accurately determine the modulus of the thermosensitive gel at different temperatures, effectively simplifying the testing procedure and improving testing efficiency.

[0062] Furthermore, when the temperature-sensitive gel under test is at its initial temperature, the detection temperature is relatively low, and a higher strain is set in the detection conditions. This ensures that the applied stress has sufficient detectable accuracy while not exceeding the yield stress of the temperature-sensitive gel, thus improving the accuracy of the modulus test results at lower detection temperatures. When the temperature-sensitive gel under test is at its final temperature, the detection temperature is relatively high, and a lower strain is set in the detection conditions. This ensures that the structure of the temperature-sensitive gel is not damaged by excessive strain, while also ensuring that the strain and stress have sufficient detectable accuracy, thus improving the accuracy of the modulus test results at higher detection temperatures.

[0063] The initial temperature is the initial temperature of the thermosensitive gel under test during detection, and can be lower than the phase transition temperature of the thermosensitive gel. In some embodiments, the initial temperature can be controlled to be ≤25°C, for example, the initial temperature can be set to 23°C. The termination temperature can be higher than the phase transition temperature of the thermosensitive gel under test. In some embodiments, the termination temperature can be controlled to be ≥37°C, for example, the termination temperature can be set to 45°C. Therefore, in one embodiment, during the process of detecting the modulus of the thermosensitive gel under test using the oscillation measurement method in step S03, the detection temperature is increased from the initial temperature of 23°C to the termination temperature of 45°C.

[0064] The heating process from the initial temperature to the final temperature in step S03 can be carried out at a certain heating rate. For example, in one embodiment, the heating rate can be ≤3℃ / min, and more specifically, it can be 0.5-3℃ / min. In specific embodiments, it can be a specific but not limiting heating rate such as 0.5℃ / min, 1℃ / min, 1.5℃ / min, 2℃ / min, 2.5℃ / min, 3℃ / min, etc. During modulus testing, the temperature of the temperature-sensitive gel under test changes with the detection temperature. However, in actual processes, temperature conduction requires a certain amount of time, and there is a certain lag in the temperature rise of the temperature-sensitive gel under test. Therefore, when the detection temperature rises too quickly, there is a time difference in the transmission of the detection temperature change to the temperature-sensitive gel under test, resulting in a temperature difference between the detection temperature and the temperature-sensitive gel. This temperature difference will increase the error of the modulus testing result, reduce the accuracy, and also reduce the accuracy of the phase transition temperature value of the temperature-sensitive gel determined based on the temperature value with the largest modulus change rate. Conversely, when the detection temperature rises too slowly, the detection process takes too long. Therefore, an appropriate heating rate ensures that the temperature change is fully transmitted to the thermosensitive gel, improving the accuracy of modulus detection. On the other hand, controlling the heating rate improves detection efficiency and avoids excessively long detection times, which could lead to solvent evaporation affecting the accuracy of the detection results.

[0065] While the above-mentioned temperature regulation and control are being carried out, in some embodiments, the strain is controlled to decrease from the first strain to the second strain according to the logarithmic change law. The change law is a logarithmic change law, which can be set in a stepwise manner from large to small. For details, refer to page 12 of the "Anton Paar Rheometer Introductory Manual", 3.2.2 Parameter settings in CSR mode (2) Strain scanning test.

[0066] In some embodiments, the first strain is controlled to be ≤20% and the second strain to be ≥0.5%. Therefore, as the detection temperature rises, the first strain can decrease from 20% to 0.5% of the second strain according to a logarithmic change law. Further, the first strain is controlled to be 9% and the second strain to be 1%, meaning the strain is controlled to decrease from 9% to 1% according to a logarithmic change law. For example, in an exemplary embodiment, when the detection temperature is the initial temperature, specifically 23°C, the first strain can be set to 9%. When the detection temperature rises from the initial temperature to the final temperature, such as at a heating rate of 1°C / min, the strain is set to the second strain. Specifically, when the final temperature is 45°C, the second strain can be set to 1%. Therefore, in a specific embodiment, the initial temperature is 23°C, and the temperature is increased at a heating rate of 0.5°C / min to the final temperature of 45°C. At this time, the strain set at the initial temperature of 23°C is 9%, and the strain set at the final temperature of 45°C is 1%.

[0067] This allows the temperature-sensitive gel to exhibit larger strain at lower detection temperatures, generating sufficient stress to meet the accuracy requirements of the measurement and improving the accuracy of the modulus test results at lower detection temperatures. Simultaneously, at higher detection temperatures, the temperature-sensitive gel exhibits smaller strain, preventing structural damage due to strain exceeding the yield strain of the temperature-sensitive gel, which could lead to inaccurate test results and improve the accuracy of the modulus test results at higher detection temperatures. Overall, the detection method for the temperature-sensitive gel in this application improves the accuracy of modulus test results at different detection temperatures by adjusting the strain accordingly as the detection temperature increases. It should be noted that the modulus in this application includes storage modulus, loss modulus, and complex modulus.

[0068] In some embodiments, a plurality of modulus detection points are set within the time range from the initial temperature to the final temperature. In a further embodiment, the interval time between adjacent detection points can be the same. For example, in the embodiment, during the heating process from the initial temperature to the final temperature, such as the heating process from 23°C to 45°C, multiple tests are performed with an interval time of 0.25 min between adjacent detection points, specifically 100 modulus detection points.

[0069] To ensure the accuracy of the modulus test results of the thermosensitive gel, the oscillation frequency is set to a fixed frequency in the above embodiments. For example, in the embodiments, the fixed frequency can be 0.1-10Hz, and specifically, it can be, but is not limited to, a fixed frequency of 1Hz.

[0070] In a specific embodiment, a fixed frequency of 1Hz is set based on the following detection conditions:

[0071] The starting temperature was 23℃, and the temperature was increased at a rate of 1℃ / min to a final temperature of 45℃. The strain was set to 9% at the starting temperature of 23℃ and 1% at the final temperature of 45℃.

[0072] Thermosensitive gels exhibit good dispersibility and are not prone to sedimentation. Using the aforementioned relatively low frequency allows the thermosensitive gel to be subjected to strain over a longer timescale (i.e., a short oscillation period of the sine wave) during modulus testing. At lower frequencies, the shear rate is lower, and the structure of the thermosensitive gel tends to be more static. Therefore, the modulus test results are closer to the modulus of the thermosensitive gel's intrinsic structure.

[0073] To better explain the technical solutions of the embodiments of this application, the modulus testing method of the above-mentioned thermosensitive gel is illustrated below through multiple embodiments.

[0074] Example 1

[0075] This embodiment 1 provides a method for detecting the modulus of a thermosensitive gel. Specifically, this embodiment uses poly(N-isopropylacrylamide-co-butyl methacrylate) gel as the thermosensitive gel to be tested, and a rheometer is used for modulus detection. The detection method of this embodiment 1 specifically includes the following steps:

[0076] S1: Preparation of the temperature-sensitive gel to be tested: N-isopropylacrylamide (20 mmol), butyl methacrylate (1 mmol), N,N'-methylenebisacrylamide (1 mmol) and sodium dodecyl sulfate were dissolved in water and reacted at 70°C for 4.5 hours.

[0077] S2: Slowly push the poly(N-isopropylacrylamide-co-butyl methacrylate) gel to the center of the base plate, ensuring that there are no air bubbles in the sample on the base plate during the pushing process; after the rotor falls and presses the sample, the gel sample fills the entire base plate, scrape off the excess gel sample outside the base plate, and cover with a protective cover; the rotor is a flat plate, and the distance between the rotor and the base plate is 0.5 mm.

[0078] S3: Set the test parameters shown in Table 1 on the Anton Paar rotary rheometer and start the test. After the test is completed, restore the rheometer temperature to room temperature of 25°C.

[0079] Table 1

[0080]

[0081] Test results as follows Figure 1 , Figure 1 This is a schematic diagram of the modulus test results of poly(N-isopropylacrylamide-co-butyl methacrylate) gel in Example 1.

[0082] In oscillation measurements, changes in storage modulus are quite sensitive; the storage modulus changes first when the gel sample is outside the linear viscoelastic range. Figure 1 It can be seen that when the detection temperature in step S3 is raised from 23℃ to 45℃, the strain changes from 9% strain at the beginning of the detection according to the logarithmic law and drops to 1% strain at the end of the detection. The storage modulus detection result curve is relatively smooth and the modulus detection result value is stable, indicating that the gel sample is in the linear viscoelastic range during the detection. The method of Example 1 can effectively detect the modulus of temperature-sensitive gel samples in the range of 23-45℃.

[0083] Example 2

[0084] This embodiment provides a method for detecting thermosensitive gels, using the poly(N-isopropylacrylamide) gel from Example 1 as the thermosensitive gel to be tested, and employing a rheometer to detect its modulus. The specific steps of the detection method in this embodiment include the following:

[0085] S1: Preparation of poly(N-isopropylacrylamide) gel, which differs from Example 1 in that butyl methacrylate was not added for the reaction;

[0086] S2: Refer to step S2 in Example 1;

[0087] S3: Set the test parameters shown in Table 2 on the Anton Paar rotary rheometer and start the measurement. After the test is completed, restore the rheometer temperature to room temperature of 25°C.

[0088] Table 2

[0089]

[0090] Test results as follows Figure 2 , Figure 2 This is a schematic diagram showing the modulus test results of the poly(N-isopropylacrylamide) gel in Example 2. Figure 2 It can be seen that when the detection temperature is increased from 25℃ to 41℃, the strain changes from 15% strain at the beginning of the detection according to the logarithmic law and drops to 0.5% strain at the end of the detection. The storage modulus detection result curve is relatively smooth and the modulus detection result value is stable, indicating that the gel sample is in the linear viscoelastic range during the detection. The method of Example 2 can effectively detect the modulus of temperature-sensitive gel samples in the range of 25-41℃.

[0091] Example 3

[0092] This embodiment provides a method for detecting thermosensitive gels. The poly(N-isopropylacrylamide-co-N-n-propylacrylamide) gel from Example 1 is used as the thermosensitive gel to be tested, and its modulus is measured using a rheometer. The specific steps of this detection method include the following:

[0093] S1: Preparation of poly(N-isopropylacrylamide-co-N-n-propylacrylamide) gel, which differs from Example 1 in that butyl methacrylate is replaced with n-propylacrylamide;

[0094] S2: Refer to step S2 in Example 1;

[0095] S3: Set the test parameters shown in Table 3 on the Anton Paar rotary rheometer and start the measurement. After the test is completed, restore the rheometer temperature to room temperature of 25°C.

[0096] Table 3

[0097]

[0098] Test results as follows Figure 3 , Figure 3 This is a schematic diagram showing the modulus test results of the poly(N-isopropylacrylamide-co-n-propylacrylamide) gel in Example 3. Figure 3 It can be seen that when the detection temperature is increased from 25℃ to 40℃, the strain changes from 20% strain at the beginning of the detection according to the logarithmic law and drops to 0.9% strain at the end of the detection. The storage modulus detection result curve is relatively smooth and the modulus detection result value is stable, indicating that the gel sample is in the linear viscoelastic range during the detection. The method of Example 3 can effectively detect the modulus of temperature-sensitive gel samples in the range of 25-40℃.

[0099] Comparative Example 1

[0100] Comparative Example 1 provides a method for determining the modulus of a thermosensitive gel. In this comparative example, the poly(N-isopropylacrylamide-co-butyl methacrylate) gel from Example 1 is used as the thermosensitive gel to be tested, and its modulus is determined using a rheometer. The specific steps of the method in Comparative Example 1 include the following:

[0101] S1: Provide a thermosensitive gel, which is the poly(N-isopropylacrylamide-co-butyl methacrylate) gel in Example 1;

[0102] S2: Refer to step S2 in Example 1;

[0103] S3: Set the test parameters shown in Table 4 on the Anton Paar rotary rheometer and start the measurement. After the test is completed, restore the rheometer temperature to room temperature of 25°C.

[0104] Table 4

[0105] Starting temperature 23℃ Termination temperature 45℃ heating rate 1℃ / min Equilibrium time 5min Fixed oscillation frequency 1Hz strain Fixed 3% strain

[0106] Test results as follows Figure 4 As shown, Figure 4This is a schematic diagram showing the gel modulus test results of poly(N-isopropylacrylamide-co-butyl methacrylate) in Comparative Example 1.

[0107] Depend on Figure 4 It can be seen that from the start to the end of the test, the test temperature was raised from 23℃ to 25℃, and the strain was fixed at 3%. Within the temperature range of 27.5℃-32.5℃, the curve of the storage modulus measurement result was sawtooth-shaped, and the measured modulus value was unstable. The fixed strain method in Comparative Example 1 could not effectively detect the modulus of the gel sample in the temperature range of 23-45℃.

[0108] The test results show that during the modulus testing process, from the start to the end of the test, reducing strain in a logarithmic manner while raising the testing temperature can effectively and accurately detect the modulus of the thermosensitive gel within different temperature ranges. Specifically, reducing strain during the temperature rise results in higher strain at lower temperatures to generate sufficient stress to meet the testing accuracy requirements; simultaneously, it ensures lower strain at higher temperatures to avoid strain exceeding the yield strain of the thermosensitive gel, which could lead to sample damage, thus improving the modulus testing accuracy of the thermosensitive gel.

Claims

1. A method for detecting the modulus of a thermosensitive gel, characterized in that, Includes the following steps: Provide the temperature-sensitive gel to be tested; Place the temperature-sensitive gel to be tested in the modulus testing area; The modulus of the temperature-sensitive gel under test was determined using an oscillation measurement method. The temperature-sensitive gel to be tested includes a polyisopropylacrylamide gel with a three-dimensional network structure. The detection conditions for the oscillation measurement method include: The oscillation frequency is a fixed frequency; The temperature is monitored from the initial temperature to the final temperature. The initial temperature is lower than the phase transition temperature of the temperature-sensitive gel to be tested; the final temperature is higher than the phase transition temperature of the temperature-sensitive gel to be tested; the initial temperature is increased to the final temperature at a heating rate of ≤3℃ / min. The strain decreases from the first strain to the second strain as the detection temperature increases, and both the first strain and the second strain are less than the yield strain of the temperature-sensitive gel to be tested at the corresponding temperature. The strain decreases from the first strain to the second strain according to a logarithmic variation law; the first strain is ≤20% of the strain; the second strain is ≥0.5% of the strain.

2. The modulus testing method as described in claim 1, characterized in that: The starting temperature is ≤25℃, and the ending temperature is ≥37℃; and / or The heating rate is 0.5-3℃ / min.

3. The modulus testing method as described in claim 1 or 2, characterized in that, The oscillation frequency is 0.1-10Hz.

4. The modulus testing method as described in claim 1 or 2, characterized in that: The step of placing the temperature-sensitive gel to be tested in the modulus testing area includes the following steps: The temperature-sensitive gel to be tested is placed on a gel carrier platform; The rotor is pressed down so that the temperature-sensitive gel to be tested fills the gap between the rotor and the gel carrier platform.

5. The modulus testing method as described in claim 4, characterized in that: The rotor is a conical plate or a flat plate.

6. The modulus testing method as described in claim 1, characterized in that: The polyisopropylacrylamide gel includes any one of the following: poly(N-isopropylacrylamide-co-butyl methacrylate) crosslinked with a crosslinking agent, poly(N-isopropylacrylamide) crosslinked with a crosslinking agent, poly(N-isopropylacrylamide-co-N-n-propylacrylamide) crosslinked with a crosslinking agent, poly(N-isopropylacrylamide-co-acrylic acid) crosslinked with a crosslinking agent, poly(N-isopropylacrylamide-co-methyl methacrylate) crosslinked with a crosslinking agent, poly(N-isopropylacrylamide-co-hydroxyethyl methacrylate) crosslinked with a crosslinking agent, poly(N-isopropylacrylamide-co-hydroxyethyl acrylate) crosslinked with a crosslinking agent, and poly(N-isopropylacrylamide-co-acrylamide) crosslinked with a crosslinking agent.

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