Citric acid-cyclodextrin derivative controlled-release composite supramolecular hydrogel and preparation method thereof

Abstract

The invention provides citric acid-cyclodextrin derivative controlled-release composite supramolecular hydrogel and a preparation method thereof.The preparation method comprises the steps that citric acid and cyclodextrin are mixed and fully dissolved through ultrasonic treatment; adjusting the pH value of the solution to 0.5-2.0 to promote a cross-linking reaction, and carrying out the cross-linking reaction for 3-5 hours at 40-60 DEG C based on an optimized temperature condition; cooling the reacted solution to room temperature, and adding a proper amount of cross-linking agent for self-assembly to form gel; and after drying treatment, the gel is molded into a structure with a required form and a stable state. By optimizing the cross-linking reaction conditions of citric acid and cyclodextrin, the hydrogel with a unique net structure and mechanical strength is obtained. The material has excellent water absorption, biocompatibility and mechanical properties, and is especially suitable for the fields of tissue engineering, biomedicine and environmental protection. The preparation process comprises the steps of chemical treatment of raw materials, control of reaction conditions, self-assembly and cross-linking reaction, forming, drying and the like.

Description

Technical Field

[0001] The invention relates to the technical field of polymer chemistry, and in particular to a citric acid-cyclodextrin derivative controllable release composite supramolecular hydrogel and a preparation method thereof. Background Art

[0002] A citric acid-cyclodextrin derivative controlled release composite supramolecular hydrogel and a preparation method thereof relate to a high-strength supramolecular hydrogel formed by composite self-assembly of citric acid and cyclodextrin and a preparation process thereof. By optimizing the cross-linking reaction conditions of citric acid and cyclodextrin, a hydrogel with a unique network structure and mechanical strength can be obtained. The material exhibits excellent water absorption, biocompatibility and mechanical properties, and is particularly suitable for fields such as tissue engineering, biomedicine and environmental protection. However, there may be some problems in the preparation process, such as insufficiently thorough chemical treatment of raw materials and inaccurate control of reaction conditions (such as temperature and pH value), resulting in incomplete self-assembly and cross-linking reactions, thereby affecting the performance and stability of the hydrogel. These problems need to be paid attention to in actual operation and each process step needs to be strictly controlled to ensure the quality and performance of the final product. Summary of the invention

[0003] The purpose of the present invention is to solve the problems existing in the prior art and to propose a citric acid-cyclodextrin derivative controlled release composite supramolecular hydrogel and a preparation method thereof.

[0004] In order to achieve the above object, the present invention adopts the following technical solutions:

[0005] A citric acid-cyclodextrin derivative controlled release composite supramolecular hydrogel and a preparation method thereof, comprising:

[0006] Mix citric acid and cyclodextrin and dissolve them fully by ultrasonic treatment;

[0007] Adjust the pH value of the solution to 0.5-2.0 to promote the cross-linking reaction;

[0008] Based on the optimized temperature conditions, the cross-linking reaction was carried out at 40-60°C for 3-5 hours;

[0009] The reaction solution is cooled to room temperature, and a proper amount of cross-linking agent is added to self-assemble to form a gel;

[0010] After drying, the gel is molded into the desired shape and maintains a stable structure.

[0011] Preferably, the ambient temperature is controlled to be 40-60°C;

[0012] Continue stirring the solution for 3-5 hours;

[0013] Use an infrared thermometer to monitor temperature changes during the reaction;

[0014] When the temperature of the reaction solution reaches the set temperature, stirring is continued to promote the complete cross-linking reaction.

[0015] Preferably, the ambient temperature is controlled to be 40-60°C;

[0016] Continue stirring the solution for 3-5 hours;

[0017] Use an infrared thermometer to monitor the temperature change during the reaction. When the temperature change is less than T1°C, record the reaction start time.

[0018] When the temperature of the reaction solution reaches the set temperature, stirring is continued to promote the complete cross-linking reaction.

[0019] Formula: The temperature change is less than T1°C, where T1 is the temperature change threshold, which is used to determine whether the reaction enters the stable stage.

[0020] Preferably, the ambient temperature is controlled to be 40-60°C;

[0021] Continue stirring the solution for 3-5 hours;

[0022] An infrared thermometer was used to monitor the temperature change during the reaction. When the temperature change was less than T1°C and the reaction time was greater than t1 min, the cross-linking reaction was considered to have achieved the best effect.

[0023] When the temperature of the reaction solution reaches the set temperature, stirring is continued to promote the complete cross-linking reaction.

[0024] Formula: The temperature change is less than T1°C and the reaction time is greater than t1 minutes, where T1 is the temperature change threshold and t1 is the reaction time threshold, which is used to comprehensively judge the optimal time for the cross-linking reaction.

[0025] Preferably, the ambient temperature is controlled to be 40-60°C;

[0026] Continue stirring the solution for 3-5 hours;

[0027] Use an infrared thermometer to monitor the temperature change during the reaction. When the temperature change is less than T1°C and the reaction time is greater than t1 minutes, adjust the reaction rate R1 to improve the cross-linking efficiency.

[0028] When the temperature of the reaction solution reaches the set temperature, stirring is continued to promote the complete cross-linking reaction.

[0029] Formula: When the temperature change is less than T1°C and the reaction time is greater than t1 minutes, adjust the reaction rate R1=2*R0, where T1 is the temperature change threshold, t1 is the reaction time threshold, and R0 is the initial reaction rate, which is used to dynamically adjust the reaction rate according to temperature and time.

[0030] Preferably, the ambient temperature is controlled to be 40-60°C;

[0031] Continue stirring the solution for 3-5 hours;

[0032] Use an infrared thermometer to monitor the temperature change during the reaction. When the temperature change is less than T1°C and the reaction time is greater than t1 minutes, increase the stirring rate S1 to accelerate the reaction process.

[0033] When the temperature of the reaction solution reaches the set temperature, stirring is continued to promote the complete cross-linking reaction.

[0034] Formula: When the temperature change is less than T1°C and the reaction time is greater than t1 minutes, increase the stirring rate S1 = 5*S0, where T1 is the temperature change threshold, t1 is the reaction time threshold, and S0 is the initial stirring rate, which is used to speed up the reaction speed during the optimal period of the cross-linking reaction.

[0035] Preferably, the ambient temperature is controlled to be 40-60°C;

[0036] Continue stirring the solution for 3-5 hours;

[0037] Use an infrared thermometer to monitor the temperature change during the reaction. When the temperature change is less than T1°C and the reaction time is greater than t1 minutes, adjust the reactant concentration C1 to enhance the reaction effect.

[0038] Compared with the prior art, the present invention has the following advantages:

[0039] The disclosed embodiments provide a citric acid-cyclodextrin derivative controlled release composite supramolecular hydrogel and a preparation method thereof, and by optimizing the cross-linking reaction conditions of citric acid and cyclodextrin, a hydrogel with a unique network structure and mechanical strength is obtained. The material has excellent water absorption, biocompatibility and mechanical properties, and is particularly suitable for tissue engineering, biomedicine and environmental protection fields. The preparation process includes multiple steps such as chemical treatment of raw materials, control of reaction conditions (such as temperature, pH value), self-assembly and cross-linking reaction, molding and drying. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 A flow chart of a citric acid-cyclodextrin derivative controlled release composite supramolecular hydrogel and a preparation method thereof;

[0041] Figure 2A flow chart of a cross-linking reaction based on optimized temperature conditions in a citric acid-cyclodextrin derivative controlled-release composite supramolecular hydrogel and a preparation method thereof;

[0042] Figure 3 A citric acid-cyclodextrin derivative controlled release composite supramolecular hydrogel and a preparation method thereof are further flow charts based on cross-linking reaction under optimized temperature conditions;

[0043] Figure 4 A citric acid-cyclodextrin derivative controlled release composite supramolecular hydrogel and a preparation method thereof are further flow charts based on cross-linking reaction under optimized temperature conditions;

[0044] Figure 5 A citric acid-cyclodextrin derivative controlled release composite supramolecular hydrogel and a preparation method thereof are further flow charts based on cross-linking reaction under optimized temperature conditions;

[0045] Figure 6 A citric acid-cyclodextrin derivative controlled release composite supramolecular hydrogel and a preparation method thereof are further flow charts based on cross-linking reaction under optimized temperature conditions;

[0046] Figure 7 The invention discloses a citric acid-cyclodextrin derivative controlled release composite supramolecular hydrogel and a preparation method thereof, and further comprises a flow chart of a cross-linking reaction based on optimized temperature conditions. DETAILED DESCRIPTION

[0047] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments.

[0048] In the description of the present invention, it is necessary to understand that the terms "upper", "lower", "front", "back", "left", "right", "top", "bottom", "inside", "outside", etc., indicating the orientation or position relationship are based on the orientation or position relationship shown in the drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention.

[0049] Reference Figure 1-7, describing a citric acid-cyclodextrin derivative controlled release composite supramolecular hydrogel and a preparation method thereof of the present invention. First, citric acid is mixed with cyclodextrin and fully dissolved by ultrasonic treatment. In this step, the ratio of citric acid and cyclodextrin needs to be precisely controlled to ensure uniform dispersion and mixing of the two. For example, a certain amount of β-cyclodextrin is dissolved in deionized water, citric acid is added in a molar ratio of 1:2, and after mixing, an ultrasonic bath is used for ultrasonic treatment for 30 minutes. Ultrasonic treatment helps to break the hydrogen bond network inside the cyclodextrin, allowing citric acid to better enter the cavity of the cyclodextrin, thereby achieving uniform mixing of the two at the molecular level.

[0050] Then adjust the pH value of the solution to 0.5-2.0 to promote the cross-linking reaction. In this step, the pH value of the mixed solution is accurately adjusted using dilute hydrochloric acid or dilute sodium hydroxide solution. Acidic conditions are conducive to the nucleophilic addition reaction between cyclodextrin and citric acid, and improve the degree of cross-linking and cross-linking density. For example, in one embodiment, a 0.1M dilute sodium hydroxide solution is used to adjust the pH value of the mixed solution to 1.5 to ensure that the pH value is within the optimal range. This adjustment not only promotes the cross-linking reaction, but also ensures that the final product has good mechanical properties and stability.

[0051] Based on the optimized temperature conditions, the cross-linking reaction is carried out at 40-60°C for 3-5 hours. The choice of temperature is a key factor affecting the cross-linking reaction rate and the formation of the final hydrogel network structure. Under suitable temperature conditions, the nucleophilic addition reaction of citric acid and cyclodextrin will proceed more rapidly, while avoiding high temperature causing material decomposition. Specifically, in another embodiment, the pH-adjusted mixed solution is placed in a constant temperature water bath at 50°C and heated for 4 hours. At this temperature, the molecular movement in the mixture is more active, which promotes the formation of cross-linking bonds, and ultimately forms a stable hydrogel with a unique network structure.

[0052] The solution after the reaction is cooled to room temperature, and an appropriate amount of cross-linking agent is added for self-assembly to form a gel. In this step, the added cross-linking agent can further enhance the mechanical properties of the hydrogel. The selection of the cross-linking agent should take into account the biocompatibility and degradability of the material. Common cross-linking agents include glutaraldehyde, epichlorohydrin, etc. For example, after the reaction is completed, the mixed solution is naturally cooled to room temperature, and then a 0.5% mass fraction of glutaraldehyde solution is slowly added dropwise, and stirring is continued for 30 minutes to promote the cross-linking between the cross-linking agent and the existing cross-linking points, thereby obtaining a hydrogel with better mechanical properties.

[0053] After drying, the gel is molded into the desired shape and maintains a stable structure. This process includes two stages: dehydration and fixation. Drying can be achieved by natural drying, vacuum drying, freeze drying, etc. For example, after the initially formed hydrogel is sliced ​​or molded into a predetermined shape, it is placed in a freeze dryer for freeze drying for 24 hours. The dried gel retains the original network structure and reduces excess water, thereby improving its mechanical strength and storage stability. Through the meticulous operation of the above steps, a citric acid-cyclodextrin derivative controlled release composite supramolecular hydrogel with excellent performance was successfully prepared, providing a reliable material basis for subsequent applications.

[0054] Next, the cross-linking reaction based on the optimized temperature conditions of the present invention is described: first, the ambient temperature is controlled to be 40-60°C. This means that before the reaction is carried out, it is necessary to ensure that the temperature of the experimental environment is stable within the range of 40 to 60 degrees Celsius. Too low a temperature may result in insufficient activity of the cross-linking agent, thereby affecting the cross-linking efficiency; while too high a temperature may cause the reaction to be too fast, resulting in the formation of by-products, affecting the purity and performance of the final product. By controlling within this temperature range, the reaction can be carried out under the most suitable conditions to ensure the best effect of the cross-linking reaction. For example, in one embodiment, the reaction system can be placed in a constant temperature water bath at 45°C to keep the ambient temperature stable.

[0055] Secondly, continue to stir the solution for 3-5 hours. Stirring helps to evenly distribute the components in the solution, promotes sufficient contact between molecules, and accelerates the speed of the cross-linking reaction. In this process, the stirring rate should be moderate to avoid excessive stirring to produce bubbles or destroy the cross-linked structure. The time range for continuous stirring is optimized based on the experimental results, and the cross-linking reaction can be effectively completed without introducing other unnecessary variables. Specifically, you can choose to stir at a speed of 200 revolutions per minute for 3-5 hours, which ensures sufficient stirring without introducing impurities for too long.

[0056] Furthermore, an infrared thermometer is used to monitor the temperature changes during the reaction process. The infrared thermometer is a non-contact temperature measurement tool that can monitor the temperature of the reaction solution in real time to ensure accurate temperature control of the entire process. When the temperature deviates, the set temperature range can be restored by adjusting the heating device or cooling system to ensure that the cross-linking reaction is carried out under optimal conditions. In a specific embodiment, the temperature data can be recorded every 5 minutes. If it is found that the temperature deviates from the set value, it can be adjusted by increasing or decreasing the power of the heat source.

[0057] Finally, when the temperature of the reaction solution reaches the set temperature, continue stirring to promote the complete cross-linking reaction. At the set temperature, continuing stirring can not only maintain the temperature stability, but also further promote the dispersion of the cross-linking agent in the reaction solution, so that it can be more fully cross-linked with the citric acid cyclodextrin derivative. For example, when the temperature of the reaction solution reaches 45°C, the stirring speed can be maintained at 200 revolutions per minute, and the reaction progress can be monitored until the cross-linking reaction is complete.

[0058] In summary, the above four steps ensure that the cross-linking reaction is carried out under optimal conditions by optimizing the temperature conditions, and the obtained citric acid cyclodextrin derivative controlled release composite supramolecular hydrogel has good stability and release performance.

[0059] Next, the cross-linking reaction based on the optimized temperature conditions of the present invention is further described. Specifically, the following steps are included: controlling the ambient temperature to 40-60°C; continuously stirring the solution for 3-5 hours; using an infrared thermometer to monitor the temperature change during the reaction, and when the temperature change is less than T1°C, recording the reaction start time; when the temperature of the reaction solution reaches the set temperature, continue stirring to promote the complete cross-linking reaction.

[0060] First, the ambient temperature is controlled at 40-60°C. Within this range, the reactants can obtain the best activation energy, thereby improving the efficiency and yield of the cross-linking reaction. Too low a temperature will inhibit the reaction rate, while too high a temperature may cause the reactants to decompose. Therefore, choosing this temperature range ensures the stability and repeatability of the reaction process.

[0061] Secondly, the solution is stirred for 3-5 hours. This process helps to mix the reactants and make the reaction even. Stirring can reduce local concentration differences, thereby improving the overall efficiency of the reaction. In certain embodiments, a magnetic stirrer can be used for constant stirring to ensure mixing effect.

[0062] Use an infrared thermometer to monitor temperature changes during the reaction. When the temperature change is less than T1°C, record the start time of the reaction. The infrared thermometer can provide accurate temperature measurement to help monitor the reaction status. The temperature change threshold T1 is 0.1-0.5℃, and this range is selected based on the experimental observation of the thermal stability stage of the reaction. For example, when the temperature change is less than 0.1°C, it means that the reaction system has entered a stable reaction stage, and the reaction start time is recorded at this time.

[0063] When the temperature of the reaction solution reaches the set temperature, stirring is continued to promote the complete cross-linking reaction. The set temperature is usually between 40-60°C, and continuous stirring within this temperature range helps to maintain the uniformity and completeness of the reaction. Specifically, in one embodiment, the set temperature is 50°C, the stirring speed is 500 rpm, and the reaction solution is continued to be stirred at the set temperature for 3 hours until the reaction is completed.

[0064] In the formula, the temperature change is less than T1°C, where T1 is the temperature change threshold. The parameter T1 refers to the minimum allowable value of temperature fluctuation during the reaction, which ranges from 0.1-0.5°C, and the optimal value is 0.1°C. The purpose of this formula is to determine when the reaction enters the stable stage. When the temperature change is small to a certain threshold, it indicates that the reaction has begun and is in a stable thermodynamic state, so that the time point of the reaction can be recorded. The selection of this threshold ensures the accuracy and consistency of the reaction and helps standardize the operation of subsequent processes.

[0065] Next, the cross-linking reaction based on the optimized temperature conditions of the present invention is described further.

[0066] Control the ambient temperature to 40-60°C. This step refers to controlling the temperature of the reaction environment between 40 and 60 degrees Celsius. The selection of this temperature range is based on the optimal activity temperature of the reactants, which can ensure that the reactant molecules have enough thermal energy for efficient cross-linking reactions. Too high or too low a temperature will affect the reaction rate and the properties of the final product.

[0067] Continue stirring the solution for 3-5 hours. This step is to ensure that the reactants are evenly mixed during the reaction to prevent incomplete crosslinking caused by local uneven concentrations. Continuous stirring can help the reactant molecules contact and react better, thereby improving the degree of crosslinking and the uniformity of the hydrogel.

[0068] Use an infrared thermometer to monitor the temperature changes during the reaction. When the temperature change is less than T1°C and the reaction time is greater than t1 minutes, the cross-linking reaction is considered to have achieved the best effect. In this step, the temperature changes during the reaction are monitored in real time by an infrared thermometer. When the temperature change is less than the set threshold value T1 and the reaction time is greater than the set time threshold value t1, it can be judged that the cross-linking reaction has achieved the best effect. T1 is usually between 0.5-1.5°C, and t1 is between 30-60 minutes. The specific values ​​need to be optimized according to the actual reaction system.

[0069] When the temperature of the reaction solution reaches the set temperature, continue stirring to promote the complete cross-linking reaction. This means that after reaching the set reaction temperature, it is necessary to continue stirring to ensure that the reaction is complete. The purpose of this step is to further increase the degree of cross-linking so that the final hydrogel has more ideal mechanical properties and release characteristics.

[0070] Formula: Temperature change is less than T1℃ and reaction time is greater than t1 minutes. In this formula, T1 is the temperature change threshold, usually between 0.5-1.5℃; t1 is the reaction time threshold, usually between 30-60 minutes. The setting of these parameters is intended to ensure that the reaction is carried out under optimal conditions. Specifically, a temperature change of less than T1℃ means that the reaction system has reached a stable state, and a reaction time greater than t1 minutes ensures that the reaction has enough time to proceed. This combination of settings can effectively avoid premature or late termination of the reaction, thereby ensuring the consistency and quality of the final product.

[0071] For example, in one embodiment, in order to prepare a citric acid-cyclodextrin derivative controlled release composite supramolecular hydrogel, the experimenter first sets the temperature of the reaction vessel to 50°C, and ensures that the temperature fluctuates within this range by means of a heating device and a temperature control device. Subsequently, a solution of citric acid and a cyclodextrin derivative is added to the reaction vessel, and the agitator is turned on and stirred continuously for 4 hours. During the entire reaction process, an infrared thermometer is used to monitor the temperature change. Once it is found that the temperature change is stable within 0.8°C and the reaction time exceeds 45 minutes, the experimenter determines that the cross-linking reaction has achieved the best effect. At this point, stirring is continued for 1 hour to ensure that the cross-linking reaction is completely carried out, and finally a supramolecular hydrogel with ideal mechanical properties and controlled release characteristics is obtained.

[0072] In conclusion, through the above detailed step description and specific examples, the method based on optimized temperature conditions for cross-linking reaction can be better understood and applied to prepare high-quality citric acid-cyclodextrin derivative controlled release composite supramolecular hydrogels.

[0073] Next, the cross-linking reaction based on the optimized temperature conditions of the present invention is further described. First, the ambient temperature is controlled to be 40 to 60 degrees Celsius to ensure that the temperature reacts within a suitable range. Then, the solution is stirred for 3 to 5 hours to ensure that the components in the solution are evenly mixed, thereby promoting the reaction. An infrared thermometer is used to monitor the change of temperature during the reaction in real time. When the temperature change is less than the set threshold value T1 degrees Celsius and the reaction time exceeds the threshold value t1 minute, the reaction rate R1 needs to be adjusted, specifically by setting it to twice the initial reaction rate R0. Finally, when the temperature of the reaction solution reaches and stabilizes at the set temperature, continue stirring to promote the complete progress of the cross-linking reaction.

[0074] The specific operations of these steps are as follows: First, the reaction system is placed in a temperature-controllable environment, such as a constant temperature water bath, and the temperature is adjusted to be maintained between 40 and 60 degrees Celsius. The purpose of this step is to provide a stable reaction environment so that the crosslinking agent can better act on the citric acid cyclodextrin derivative to form a stable supramolecular hydrogel. For example, if the set temperature is 50 degrees Celsius, the ambient temperature should be maintained at this value by a temperature control device in order to provide an optimal reaction condition.

[0075] While maintaining the ambient temperature, the solution is continuously stirred for 3 to 5 hours using a mechanical stirrer or a magnetic stirrer. By stirring, the citric acid cyclodextrin derivative in the solution can be fully contacted with other reactants, thereby improving the uniformity and efficiency of the cross-linking reaction. In one embodiment, stirring can be performed at a speed of 50 rpm for 4 hours to ensure that the substances in the solution are evenly distributed, thereby promoting the smooth progress of the cross-linking reaction.

[0076] In order to ensure accurate control of the reaction, an infrared thermometer is used to continuously monitor the temperature change of the reaction solution. Specifically, when the temperature change is less than a preset threshold value T1 degrees Celsius (such as 0.5 degrees Celsius), and the reaction time exceeds a preset time threshold value t1 minutes (such as 30 minutes), the reaction rate R1 is adjusted to optimize the progress of the cross-linking reaction. Specifically, the reaction rate should be adjusted to R1=2*R0 at this time, that is, the reaction rate is doubled, thereby accelerating the reaction and improving the cross-linking efficiency. Here, the range of T1 is generally 0.1 to 1 degrees Celsius, and the preferred value is 0.5 degrees Celsius; the range of t1 is generally 20 to 60 minutes, and the preferred value is 30 minutes; R0 is the reaction rate initially set, and R1 is the adjusted reaction rate.

[0077] When the temperature of the reaction solution reaches and stabilizes at the preset temperature, continue stirring for a certain period of time to ensure that the cross-linking reaction is fully carried out. The purpose of this step is to further promote the thorough completion of the cross-linking reaction through mechanical action to ensure that the final supramolecular hydrogel structure is uniform and stable. For example, when the reaction temperature is stabilized at 50 degrees Celsius, continuing to stir for 1 hour can significantly improve the effect of the cross-linking reaction, thereby obtaining a supramolecular hydrogel with good performance.

[0078] Through the above steps, the cross-linking reaction of the citric acid cyclodextrin derivative can be effectively controlled according to the optimized temperature conditions, thereby preparing a composite supramolecular hydrogel with controlled release and superior performance. Specifically, strict control of temperature changes and timely adjustment of reaction rate can ensure the efficiency and stability of the reaction process, thereby meeting the needs of practical applications.

[0079] Next, the cross-linking reaction based on the optimized temperature conditions of the present invention is described further.

[0080] First, the ambient temperature is controlled to be 40 to 60 degrees Celsius. This is to ensure that the cross-linking reaction is carried out within a suitable temperature range so that the reactants can effectively form a cross-linked network, thereby preparing a hydrogel with stable properties. Too high or too low a temperature may affect the reaction rate and the quality of the product. Specifically, in one embodiment, the reaction environment temperature is set to 50 degrees Celsius, and the temperature is accurately controlled by a constant temperature water bath or a heating plate.

[0081] Secondly, the solution is stirred continuously for 3 to 5 hours. This operation is to ensure that the reactants are evenly distributed, promote effective collisions between molecules, and improve the efficiency of the reaction. Continuous stirring helps to avoid local concentration differences and ensure that the reaction proceeds evenly throughout the solution. For example, in actual operation, a magnetic stirrer or mechanical stirrer is used for continuous stirring to ensure that the solution is fully mixed.

[0082] Third, use an infrared thermometer to monitor the temperature change during the reaction. When the temperature change is less than T1 degrees Celsius and the reaction time is greater than t1 minutes, increase the stirring rate S1 to accelerate the reaction process. T1 and t1 are the temperature change threshold and reaction time threshold, respectively. The selection of these parameters needs to be determined based on experimental data. In certain cases, if the temperature change during the reaction is very small (such as less than 0.5 degrees Celsius) and the reaction time exceeds 30 minutes, it means that the reaction has entered a relatively stable stage. At this time, appropriately increasing the stirring rate can improve the rate and effect of the reaction. For example, T1 is set to 0.5 degrees Celsius and t1 is set to 30 minutes.

[0083] Finally, when the temperature of the reaction solution reaches the set temperature, stirring is continued to promote the complete cross-linking reaction. This is because at a higher temperature, the reaction rate will be significantly increased, and continued stirring can ensure that the cross-linking reaction is fully carried out to generate a hydrogel with desired properties. In one embodiment, the set reaction temperature is 50 degrees Celsius. After the reaction reaches this temperature, stirring is continued at a higher rate (such as 100 rpm) for 2 hours to ensure that the cross-linking reaction is completely completed.

[0084] In the formula, T1 is the temperature change threshold, which is usually set between 0.1 and 1.0 degrees Celsius, and the optimal value is 0.5 degrees Celsius; t1 is the reaction time threshold, which is usually set between 20 and 40 minutes, and the optimal value is 30 minutes; S0 is the initial stirring rate, which ranges from 50 to 100 rpm, and the specific value is adjusted according to the actual situation. When the temperature change is less than T1 degrees Celsius and the reaction time is greater than t1 minutes, the stirring rate is increased by S1=5*S0. This setting is to increase the reaction rate by enhancing mixing in the stable stage of the reaction, accelerate the formation of the cross-linked network, so that the hydrogel has better structural stability and mechanical properties. For example, in a specific embodiment, the initial stirring rate is 80rpm. When the temperature change is less than 0.5 degrees Celsius and the reaction time exceeds 30 minutes, the stirring rate is increased to 400rpm, thereby significantly accelerating the process of the cross-linking reaction.

[0085] Next, the cross-linking reaction based on the optimized temperature conditions of the present invention is described further.

[0086] In this process, controlling the ambient temperature is the first key step. The ambient temperature is strictly set between 40 and 60 degrees Celsius. The selection of this temperature range is based on experimental results, which show that within this range, the kinetics of the cross-linking reaction is optimal and can effectively promote the reaction. Too high or too low temperature may affect the reaction rate and the quality of the product. For example, in one embodiment, the ambient temperature is selected to be 50 degrees Celsius, which makes the reaction of the citric acid cyclodextrin derivative more uniform and stable.

[0087] The second step is to continue stirring the solution for 3 to 5 hours. By continuing to stir, uniform mixing within the reaction system is ensured, avoiding problems such as uneven local reactions and uneven product distribution. In addition, stirring also helps to remove the generated gas and reduce the occurrence of side reactions. Specifically, a magnetic stirrer or a mechanical stirring device can be used to achieve this. Under the condition of continuous stirring for 3 hours, the mixing of the citric acid cyclodextrin derivative is more uniform and the reaction rate is faster.

[0088] The third step is to use an infrared thermometer to monitor the temperature changes during the reaction. The change in temperature directly reflects the progress and stability of the reaction. When the temperature change is less than T1 degrees Celsius and the reaction time is greater than t1 minutes, it means that the reaction has entered the steady-state stage, and the reaction effect can be further enhanced by adjusting the concentration of the reactants. Specifically, T1 is usually set to 0.1 to 0.5 degrees Celsius, because within such a temperature fluctuation range, it is possible to accurately judge whether the reaction is stable; t1 is generally set to 30 to 60 minutes, which ensures sufficient time to judge whether the reaction has entered a stable state. The formulas (T1 = 0.3 ° C) and (t1 = 45 min) are considered to be optimal values ​​because these two values ​​can strike a balance between accuracy and ease of operation, making the reaction more controllable and efficient.

[0089] The last step is to adjust the reactant concentration C1. When the above conditions are met, appropriately increasing the concentration of the reactants can speed up the reaction rate and improve the quality of the product. The specific adjustment method is to gradually increase the amount of reactants added while monitoring the temperature and pH value of the reaction system. For example, in one embodiment, the concentration of the citric acid cyclodextrin derivative was increased from 1wt% to 1.5wt%, and the reaction rate was observed to be significantly improved, and the composite supramolecular hydrogel finally obtained had a higher degree of cross-linking and better mechanical properties.

[0090] The present invention discloses a citric acid-cyclodextrin derivative controlled release composite supramolecular hydrogel and a preparation method thereof, comprising: firstly, mixing citric acid and cyclodextrin, and dissolving them fully by ultrasonic treatment, thereby ensuring that the two main components can be evenly dispersed. This step solves the technical problem that the structural defects and unstable performance of the final hydrogel may occur due to the problem of incomplete dissolution or uneven mixing between the two components. Next, the pH value of the solution is adjusted to 0.5-2.0. This step is to promote the effective cross-linking reaction, so that cyclodextrin and citric acid form a stable spatial network structure under a specific pH environment, enhance the mechanical properties and stability of the hydrogel, and overcome the disadvantages of degradation or insufficient cross-linking that may occur under extreme pH conditions.

[0091] After pH adjustment, the cross-linking reaction is carried out at 40-60°C for 3-5 hours based on the optimized temperature conditions. In this process, the appropriate temperature promotes the chemical reaction between the cross-linking agent and the matrix material, making the cross-linking reaction more thorough and forming a denser and more stable network structure. This step not only improves the physical properties of the hydrogel, but also solves the problem of slow reaction speed due to too low temperature, low degree of cross-linking or side reactions caused by too high temperature.

[0092] After the reaction is completed, the solution is cooled to room temperature, and then an appropriate amount of cross-linking agent is added for self-assembly to form a gel. Through this step, the three-dimensional network structure of the hydrogel is further strengthened, and its physical and mechanical properties and chemical stability are enhanced, so that it can maintain its shape and function for a long time, meeting the requirements of high stability and long life of materials in the fields of tissue engineering and biomedicine. In addition, by adjusting the amount of cross-linking agent, the structure and properties of the hydrogel can be fine-tuned to improve the adaptability of applications.

[0093] Finally, after drying, the gel is molded into the desired shape and maintains a stable structure. This not only makes the hydrogel easier to operate and transport in practical applications, but also can be made into different shapes according to specific needs to improve its functionality. Through the above steps, the present invention effectively solves various technical problems that may arise in the preparation process of traditional hydrogels, including uneven mixing, incomplete cross-linking, insufficient physical and mechanical properties, and difficulty in molding and preservation, thereby providing a new and efficient material selection for applications in tissue engineering, biomedicine and environmental protection.

[0094] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A citric acid-cyclodextrin derivative controlled release composite supramolecular hydrogel and a preparation method thereof, characterized in that: include: Mix citric acid and cyclodextrin and dissolve them fully by ultrasonic treatment; Adjust the pH value of the solution to 0.5-2.0 to promote the cross-linking reaction; Based on the optimized temperature conditions, the cross-linking reaction was carried out at 40-60°C for 3-5 hours; The reaction solution is cooled to room temperature, and a proper amount of cross-linking agent is added to self-assemble to form a gel; After drying, the gel is molded into the desired shape and maintains a stable structure.

2. A citric acid cyclodextrin derivative controlled release composite supramolecular hydrogel and a preparation method thereof according to claim 1, characterized in that: The cross-linking reaction is carried out based on the optimized temperature conditions, comprising: Control the ambient temperature to 40-60℃; Continue stirring the solution for 3-5 hours; Use an infrared thermometer to monitor temperature changes during the reaction; When the temperature of the reaction solution reaches the set temperature, stirring is continued to promote the complete cross-linking reaction.

3. A citric acid cyclodextrin derivative controlled release composite supramolecular hydrogel and a preparation method thereof according to claim 2, characterized in that: The cross-linking reaction based on the optimized temperature conditions further comprises: Control the ambient temperature to 40-60℃; Continue stirring the solution for 3-5 hours; Use an infrared thermometer to monitor the temperature change during the reaction. When the temperature change is less than T1°C, record the reaction start time. When the temperature of the reaction solution reaches the set temperature, stirring is continued to promote the complete cross-linking reaction. Formula: The temperature change is less than T1°C, where T1 is the temperature change threshold, which is used to determine whether the reaction enters the stable stage.

4. The controlled release composite supramolecular hydrogel of citric acid cyclodextrin derivative and the preparation method thereof according to claim 3, characterized in that: The cross-linking reaction based on the optimized temperature conditions further comprises: Control the ambient temperature to 40-60℃; Continue stirring the solution for 3-5 hours; An infrared thermometer was used to monitor the temperature change during the reaction. When the temperature change was less than T1°C and the reaction time was greater than t1 min, the cross-linking reaction was considered to have achieved the best effect. When the temperature of the reaction solution reaches the set temperature, stirring is continued to promote the complete cross-linking reaction. Formula: The temperature change is less than T1°C and the reaction time is greater than t1 minutes, where T1 is the temperature change threshold and t1 is the reaction time threshold, which is used to comprehensively judge the optimal time for the cross-linking reaction.

5. The controlled release composite supramolecular hydrogel of citric acid cyclodextrin derivative and the preparation method thereof according to claim 4, characterized in that: The cross-linking reaction based on the optimized temperature conditions further comprises: Control the ambient temperature to 40-60℃; Continue stirring the solution for 3-5 hours; Use an infrared thermometer to monitor the temperature change during the reaction. When the temperature change is less than T1°C and the reaction time is greater than t1 minutes, adjust the reaction rate R1 to improve the cross-linking efficiency. When the temperature of the reaction solution reaches the set temperature, stirring is continued to promote the complete cross-linking reaction. Formula: When the temperature change is less than T1°C and the reaction time is greater than t1 minutes, adjust the reaction rate R1=2*R0, where T1 is the temperature change threshold, t1 is the reaction time threshold, and R0 is the initial reaction rate, which is used to dynamically adjust the reaction rate according to temperature and time.

6. The controlled release composite supramolecular hydrogel of citric acid cyclodextrin derivative and the preparation method thereof according to claim 5, characterized in that: The cross-linking reaction based on the optimized temperature conditions further comprises: Control the ambient temperature to 40-60℃; Continue stirring the solution for 3-5 hours; Use an infrared thermometer to monitor the temperature change during the reaction. When the temperature change is less than T1°C and the reaction time is greater than t1 minutes, increase the stirring rate S1 to accelerate the reaction process. When the temperature of the reaction solution reaches the set temperature, stirring is continued to promote the complete cross-linking reaction. Formula: When the temperature change is less than T1°C and the reaction time is greater than t1 minutes, increase the stirring rate S1=5*S0, where T1 is the temperature change threshold, t1 is the reaction time threshold, and S0 is the initial stirring rate, which is used to speed up the reaction during the optimal period of the cross-linking reaction.

7. The controlled release composite supramolecular hydrogel of citric acid cyclodextrin derivative and the preparation method thereof according to claim 6, characterized in that: The cross-linking reaction based on the optimized temperature conditions further comprises: Control the ambient temperature to 40-60℃; Continue stirring the solution for 3-5 hours; Use an infrared thermometer to monitor the temperature change during the reaction. When the temperature change is less than T1°C and the reaction time is greater than t1 minutes, adjust the reactant concentration C1 to enhance the reaction effect.

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