A temperature-controlled sustained-release amino acid chitosan drug carrier, its preparation method and application
By modifying chitosan with butanetetracarboxylic acid and grafting it with amino acids, the problems of poor mechanical properties and uncontrollable release mechanism of chitosan were solved, realizing the controllable loading and release of temperature-controlled sustained-release amino acid chitosan drug carriers, which are suitable for biomedical materials.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- SHAANXI UNIV OF SCI & TECH
- Filing Date
- 2026-03-24
- Publication Date
- 2026-06-30
AI Technical Summary
Chitosan has poor mechanical properties and an uncontrollable load release mechanism. Traditional chitosan-based composite materials tend to release antibacterial components quickly, making it difficult to meet the requirements for long-term antibacterial effects.
Chitosan was modified with butanetetracarboxylic acid, a long carbon chain structure was introduced, and amino acids were grafted through amide bonds. A temperature-controlled sustained-release mechanism was designed, and the thermal sensitivity of the amide bonds was used to achieve controllable loading and release.
The hydrophobicity and mechanical properties of chitosan were improved, enabling the controlled and sustained release of amino acids, which is suitable for targeted antibacterial drug delivery systems and sustained-release antibacterial materials.
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Figure CN122297710A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biomedical materials technology, specifically relating to a temperature-controlled sustained-release amino acid chitosan drug carrier, its preparation method, and its application. Background Technology
[0002] Natural polymers, due to their high biocompatibility, biodegradability, low toxicity, and immunogenicity in vivo, as well as their wide availability, ease of acquisition, and abundant natural resources, have become an important component of targeted drug delivery systems. Currently, commonly used natural polymer nanocarriers include chitosan, alginate, pectin, and HA. Chitosan is a common natural cationic polysaccharide, and its cationic properties are beneficial for the development of drug delivery systems. Furthermore, the amino groups in chitosan can respond to fluctuations in environmental pH and rapidly cross cell membranes; these advantages make chitosan nanoparticles widely used as potential carriers for therapeutic applications.
[0003] However, the chitosan molecular chain contains a large number of hydroxyl and amino groups, resulting in excessive hydrophilicity. In humid environments, it easily absorbs water and swells, leading to a significant deterioration in mechanical properties (such as tensile strength and elongation at break), severely limiting its development and application as a drug carrier. Furthermore, traditional chitosan-based composites often achieve antibacterial loading through physical blending, which suffers from problems such as rapid release of antibacterial agents, short duration of action, and low utilization rate, making it difficult to meet the demand for long-lasting antibacterial effects. Summary of the Invention
[0004] In order to overcome the shortcomings of the prior art, the present invention aims to provide a temperature-controlled sustained-release amino acid chitosan drug carrier, its preparation method and application, so as to solve the technical problems such as poor mechanical properties of chitosan and uncontrollable loading release mechanism.
[0005] To achieve the above objectives, the present invention employs the following technical solution: This invention provides a method for preparing a temperature-controlled sustained-release amino acid chitosan drug carrier, comprising the following steps: Chitosan is dissolved in a first organic acid solution to prepare a chitosan solution; Add butanetetracarboxylic acid and sodium hypophosphite to the chitosan solution, adjust the solution to the set pH value, and carry out the reaction to obtain the reaction solution; The reaction solution was precipitated with ethanol, then filtered, washed with deionized water until neutral and vacuum dried to obtain modified chitosan CS-BTCA. Modified chitosan CS-BTCA was dispersed in deionized water, amino acids were added, the pH was adjusted to acidic, and then a crosslinking agent was added. The mixture was stirred at room temperature to prepare a crosslinking reaction solution. The crosslinking reaction solution was then subjected to dialysis and freeze-drying to obtain the complex CS-BTCA-A. The composite CS-BTCA-A was mixed with water to prepare an aqueous solution, which was then poured into a polytetrafluoroethylene mold and dried at room temperature to form a nascent film. The nascent membrane was immersed in a second organic acid solution, then rinsed with deionized water overnight, and air-dried at room temperature to obtain a temperature-controlled sustained-release amino acid chitosan drug carrier.
[0006] In one embodiment, the first organic acid solution is one of acetic acid solution, propionic acid solution, and cinnamic acid solution; the mass concentration of the first organic acid solution is 2% to 5%; and the ratio of chitosan to the first organic acid solution is 1 to 3 g: 100 mL.
[0007] In one embodiment, the mass ratio of butanetetracarboxylic acid to sodium hypophosphite is 4-6 g: 0.5-1.0 g; the set pH value is 5-6.5; the reaction temperature is 60-80°C, and the reaction time is 6-8 h.
[0008] In one embodiment, the vacuum drying temperature is 40~70°C and the time is 24~30 h.
[0009] In one embodiment, the ratio of the modified chitosan CS-BTCA, deionized water, amino acids, and crosslinking agent is 1g:50mL:0.1~1g:0.2~0.6g; the crosslinking agent is composed of equal masses of EDC and NHS; and the amino acid is lysine.
[0010] In one embodiment, the stirring reaction takes 12-18 hours; the dialysis is performed using a dialysis bag with a molecular weight cutoff of 3.5 kDa, and the dialysis time is 48-50 hours.
[0011] In one embodiment, the mass concentration of the aqueous solution is 2% to 5%, and the drying time at room temperature is 46 to 50 hours.
[0012] In one embodiment, the second organic acid solution is one of acetic acid solution, propionic acid solution, and cinnamic acid solution, the mass concentration of the second organic acid solution is 2% to 4%, and the soaking time is 30 min to 2 h.
[0013] The present invention also provides a method for preparing a temperature-controlled sustained-release amino acid chitosan drug carrier using the above-mentioned method.
[0014] The present invention also provides an application of the temperature-controlled sustained-release amino acid chitosan drug carrier prepared by the above-mentioned method in biomedical materials.
[0015] Compared with the prior art, the present invention has the following beneficial effects: This invention provides a method for preparing a temperature-controlled sustained-release amino acid chitosan carrier. This preparation method is an improvement based on butanetetracarboxylic acid (BTCA). This invention utilizes the abundant active sites (-NH2 and -OH) of chitosan and chemically modifies it according to application requirements. Through the amidation reaction of BTCA with chitosan, a long carbon chain structure is introduced into the chitosan molecular chain, which significantly improves the hydrophobicity and crosslinking density of the material, thereby improving the mechanical properties of the modified chitosan. At the same time, a large number of carboxyl groups are retained as reaction sites for subsequent grafting. Subsequently, amide bonds are formed between the amino groups of amino acids (such as lysine) and the carboxyl groups of modified chitosan. The hydroxyl groups can react with the retained carboxyl groups to form ester bonds, realizing the efficient grafting of antibacterial components. The temperature-controlled sustained-release mechanism is designed using the thermal sensitivity of amide bonds to achieve controllable loading and release of amino acids by the chitosan carrier.
[0016] The preparation method provided by this invention features a simple synthesis mechanism, controllable reaction, and high yield. First, chitosan is modified with butanetetracarboxylic acid (TTCA) to introduce flexible butane carbon chains, which enhances the hydrophobicity and flexibility of chitosan and strengthens its mechanical properties. By controlling the ratio of chitosan to TTCA and the reaction conditions, the hydrophilic and hydrophobic properties of the modified chitosan can be precisely controlled to meet different application requirements. Second, TTCA modification increases the loading sites for amino acids in chitosan, improving the loading capacity, and the loading capacity can be flexibly adjusted by controlling the reaction conditions. Finally, amino acids and modified chitosan are linked by amide bonds. Utilizing the thermally induced hydrolysis of amide bonds, temperature-controlled sustained release of amino acids from the chitosan drug carrier can be achieved, suitable for various scenarios such as targeted antibacterial drug carriers, sustained-release antibacterial fertilizers, and antibacterial active packaging materials. For example, by leveraging the temperature differences in different sections of the human digestive tract (e.g., the colon temperature is slightly higher than the stomach), temperature-controlled oral microsphere formulations can be designed to achieve targeted release of antibacterial amino acids in the colon for the treatment of diseases related to intestinal flora imbalance. Attached Figure Description
[0017] Figure 1 This is an infrared absorption spectrum of a temperature-controlled sustained-release amino acid chitosan drug carrier according to the present invention. Detailed Implementation
[0018] To enable those skilled in the art to understand the features and effects of the present invention, the terms and expressions mentioned in the specification are explained and defined in general below. Unless otherwise specified, all technical and scientific terms used herein have the ordinary meaning understood by those skilled in the art regarding the present invention, and in case of conflict, the definitions in this specification shall prevail.
[0019] The theories or mechanisms described and disclosed herein, whether right or wrong, should not in any way limit the scope of the invention, that is, the contents of the invention can be implemented without being limited by any particular theory or mechanism.
[0020] In this document, all features defined by numerical ranges or percentage ranges, such as numerical values, quantities, contents, and concentrations, are for the sake of brevity and convenience only. Accordingly, descriptions of numerical ranges or percentage ranges should be considered as covering and specifically disclosing all possible sub-ranges and individual numerical values (including integers and fractions) within those ranges.
[0021] In this article, unless otherwise specified, “contains,” “includes,” “containing,” “has,” or similar terms cover the meanings of “composed of” and “mainly composed of,” for example, “A contains a” covers the meanings of “A contains a and others” and “A contains only a.”
[0022] For the sake of brevity, not all possible combinations of the technical features in each implementation scheme or embodiment are described herein. Therefore, as long as there is no contradiction in the combination of these technical features, the technical features in each implementation scheme or embodiment can be combined arbitrarily, and all possible combinations should be considered within the scope of this specification.
[0023] To address the shortcomings of chitosan, such as poor mechanical properties and uncontrollable loading release mechanism, this invention prepares a chitosan modified with butanetetracarboxylic acid, which improves the hydrophobicity, flexibility and mechanical properties of traditional chitosan. Then, amino acids are grafted onto the modified chitosan through amide bonds to form a modified chitosan-amino acid composite material. By utilizing the thermal hydrolysis properties of amide bonds, temperature-controlled sustained release of amino acids on chitosan-loaded drugs is achieved.
[0024] The present invention uses butanetetracarboxylic acid as a modifier to prepare a temperature-controlled sustained-release amino acid-chitosan drug carrier (modified chitosan-amino acid composite material) grafted with amino acids onto modified chitosan. The preparation principle is as follows: Chitosan, rich in active sites (-NH2 and -OH), can be chemically modified to introduce long carbon chains into its molecular chain through the reaction of BTCA with chitosan, while retaining certain carboxyl groups as reaction sites for subsequent grafting. Subsequently, amide bonds are formed between the amino groups of amino acids (such as lysine) and the carboxyl groups of modified chitosan, achieving efficient grafting of antibacterial components. Furthermore, the hydroxyl groups on amino acids (such as lysine) can react with the retained carboxyl groups to form ester bonds. A temperature-controlled sustained-release mechanism is designed using the thermal sensitivity of amide and ester bonds, allowing for the gradual release of the load through autonomous temperature regulation.
[0025] The preparation of modified chitosan includes: Reaction characteristics: The abundant carboxyl groups of butanetetracarboxylic acid react with the amino groups of chitosan ( NH2), hydroxyl group ( The butanetetracarboxylic acid skeleton is introduced into chitosan through a condensation reaction of OH and ester bonds.
[0026] The flexible carbon chain backbone of butanetetracarboxylic acid can improve the hydrophobicity and flexibility of chitosan, thereby enhancing its mechanical properties.
[0027] Among them, the preparation of butanetetracarboxylic acid modified chitosan-amino acid composite material: Reaction formula: Modified chitosan (containing COOH / NH2) + H2N-CH(R)-COOH (amino acids) → Modified chitosan-amino acid composite material.
[0028] The unreacted carboxyl groups on butanetetracarboxylic acid-modified chitosan undergo an amidation reaction with the amino groups of amino acids to form amide bonds. CONH ), grafting amino acids onto the chitosan backbone.
[0029] By utilizing the property that amide bonds can undergo different degrees of hydrolysis or pyrolysis under different temperatures or pH conditions, composite materials can achieve controlled loading and sustained release through temperature.
[0030] Based on the above principles, this invention provides a method for preparing a temperature-controlled sustained-release amino acid chitosan drug carrier, comprising the following steps: Step 1: Dissolve chitosan in an organic acid solution with a mass concentration of 2%~5%, stirring until completely dissolved to obtain a chitosan solution; the organic acid solution is one of acetic acid solution, propionic acid solution, or cinnamic acid solution. The ratio of chitosan to organic acid solution is 1~3g:100mL.
[0031] Step 2: Add butanetetracarboxylic acid and sodium hypophosphite to the chitosan solution, adjust the pH of the solution to 5-6.5, and react at 60-80℃ for 6-8 h to obtain a reaction solution; the amount of butanetetracarboxylic acid added is 4-6 g, and the amount of sodium hypophosphite added is 0.5-1.0 g.
[0032] Step 3: Precipitate the reaction solution obtained in Step 2 with ethanol, filter it, wash it with deionized water until neutral, and then vacuum dry it at 40~70℃ for 24~30 h to obtain modified chitosan CS-BTCA.
[0033] Step 4: Disperse 1 g of the modified chitosan CS-BTCA in 50 mL of deionized water, add amino acids (such as lysine), adjust the pH to acidic, and then add equal masses of crosslinking agents EDC and NHS. Stir the mixture at room temperature for 12-18 h to obtain a crosslinking reaction solution. The mass range of the amino acids is 0.1 g to 1 g, and the mass range of the crosslinking agents is 0.2 g to 0.6 g.
[0034] Step 5: Place the cross-linking reaction solution in a dialysis bag with a molecular weight cutoff of 3.5 kDa and dialyze for 48-50 h, then freeze-dry to obtain the complex CS-BTCA-A.
[0035] Step 6: Prepare the composite CS-BTCA-A into an aqueous solution with a mass concentration of 2%~5%, pour it into a polytetrafluoroethylene mold, and dry it at room temperature for 46~50 h to form a nascent film.
[0036] Step 7: Immerse the nascent film in an organic acid solution with a mass concentration of 2%~4% for 30 min~2 h, then rinse with deionized water overnight and air dry at room temperature to obtain the modified chitosan-amino acid composite material. The organic acid solution is one of acetic acid solution, propionic acid solution, or cinnamic acid solution.
[0037] This invention also provides a temperature-controlled sustained-release amino acid chitosan drug carrier, which is prepared using the above-described method.
[0038] This invention also provides an application of a temperature-controlled sustained-release amino acid chitosan drug carrier in biomedical materials.
[0039] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined in this application.
[0040] The following examples use instruments and equipment conventional in the art. Experimental methods in the following examples, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. All raw materials used in the following examples are conventional commercially available products with specifications conventional in the art. In this specification and the following examples, unless otherwise specified, "%" refers to weight percentage, "parts" refers to parts by weight, and "ratio" refers to weight proportion.
[0041] Example 1 Weigh 1 g of chitosan and dissolve it in 100 mL of 2% acetic acid solution, stirring until completely dissolved. Add 4 g of butanetetracarboxylic acid (BTCA) and 0.5 g of sodium hypophosphite (catalyst), adjust the pH to 5, and react in a constant temperature water bath at 60 °C for 6 h. After the reaction is complete, precipitate the product with ethanol, filter, wash with deionized water until neutral, and dry under vacuum at 40 °C for 24 h to obtain modified chitosan (CS-BTCA).
[0042] 1 g of CS-BTCA was dispersed in 50 mL of deionized water, 0.1 g of an amino acid (such as lysine) was added, the pH was adjusted to acidic, and 0.2 g of EDC / NHS (crosslinking agent) was added. The mixture was stirred at room temperature for 12 h. The reaction solution was dialyzed through a dialysis bag (molecular weight cutoff 3.5 kDa) for 48 h, and then lyophilized to obtain the complex (CS-BTCA-A).
[0043] Pour a 2% CS-BTCA-A solution into a polytetrafluoroethylene mold and dry at room temperature for 48 h to form a uniform nascent film. Immerse the nascent film in a 2% acetic acid solution for 30 min to remove unreacted substances; then rinse with deionized water overnight, air dry at room temperature, and store.
[0044] The infrared absorption spectrum of the temperature-controlled sustained-release amino acid chitosan drug carrier prepared in this embodiment is shown in the figure below. Figure 1 As shown.
[0045] Example 2 Weigh 2 g of chitosan and dissolve it in 100 mL of 3% propionic acid solution, stirring until completely dissolved. Add 5 g of butanetetracarboxylic acid (BTCA) and 0.6 g of sodium hypophosphite (catalyst), adjust the pH to 5.5, and react in a constant temperature water bath at 70 °C for 7 h. After the reaction is complete, precipitate the product with ethanol, filter, wash with deionized water until neutral, and dry under vacuum at 50 °C for 26 h to obtain modified chitosan (CS-BTCA).
[0046] 1 g of CS-BTCA was dispersed in 50 mL of deionized water, 0.4 g of an amino acid (such as lysine) was added, the pH was adjusted to acidic, and 0.3 g of EDC / NHS (crosslinking agent) was added. The mixture was stirred at room temperature for 14 h. The reaction solution was dialyzed through a dialysis bag (molecular weight cutoff 3.5 kDa) for 48 h, and then lyophilized to obtain the complex (CS-BTCA-A).
[0047] A 2% CS-BTCA-A solution was poured into a polytetrafluoroethylene mold and dried at room temperature for 49 h to form a uniform nascent film. The nascent film was then immersed in a 3% propionic acid solution for 1 h to remove unreacted substances; subsequently, it was rinsed with deionized water overnight, air-dried at room temperature, and stored.
[0048] Example 3 Weigh 3 g of chitosan and dissolve it in 100 mL of 4% cinnamic acid solution, stirring until completely dissolved. Add 6 g of butanetetracarboxylic acid (BTCA) and 0.8 g of sodium hypophosphite (catalyst), adjust the pH to 6, and react in a constant temperature water bath at 80 °C for 8 h. After the reaction is complete, precipitate the product with ethanol, filter, wash with deionized water until neutral, and dry under vacuum at 60 °C for 28 h to obtain modified chitosan (CS-BTCA).
[0049] 1 g of CS-BTCA was dispersed in 50 mL of deionized water, 0.8 g of an amino acid (such as lysine) was added, the pH was adjusted to acidic, and 0.4 g of EDC / NHS (crosslinking agent) was added. The mixture was stirred at room temperature for 16 h. The reaction solution was dialyzed through a dialysis bag (molecular weight cutoff 3.5 kDa) for 49 h, and then lyophilized to obtain the complex (CS-BTCA-A).
[0050] A 2% CS-BTCA-A solution was poured into a polytetrafluoroethylene mold and dried at room temperature for 50 h to form a uniform nascent film. The nascent film was then immersed in a 4% cinnamic acid solution for 2 h to remove unreacted substances; subsequently, it was rinsed with deionized water overnight, air-dried at room temperature, and stored.
[0051] Example 4 Weigh 3 g of chitosan and dissolve it in 100 mL of 5% acetic acid solution, stirring until completely dissolved. Add 4 g of butanetetracarboxylic acid (BTCA) and 1.0 g of sodium hypophosphite (catalyst), adjust the pH to 6.5, and react in a constant temperature water bath at 80 °C for 8 h. After the reaction is complete, precipitate the product with ethanol, filter, wash with deionized water until neutral, and dry under vacuum at 70 °C for 30 h to obtain modified chitosan (CS-BTCA).
[0052] 1 g of CS-BTCA was dispersed in 50 mL of deionized water, 1 g of an amino acid (such as lysine) was added, the pH was adjusted to acidic, and 0.6 g of EDC / NHS (crosslinking agent) was added. The mixture was stirred at room temperature for 18 h. The reaction solution was dialyzed through a dialysis bag (molecular weight cutoff 3.5 kDa) for 49 h, and then lyophilized to obtain the complex (CS-BTCA-A).
[0053] Pour a 2% CS-BTCA-A solution into a polytetrafluoroethylene mold and dry at room temperature for 48 h to form a uniform nascent film. Immerse the nascent film in a 5% acetic acid solution for 2 h to remove unreacted substances; then rinse with deionized water overnight, air dry at room temperature, and store.
[0054] Performance testing (1) Water absorption rate test Unmodified chitosan-amino acid membranes and modified chitosan-amino acid composite membranes were prepared separately and vacuum-dried to constant weight for later use. Both membranes were cut into 3 cm × 3 cm sheets, and their dry weight (M1) was recorded. The sheets were placed in beakers containing 50 mL of deionized water, and samples were removed at different time points. Surface moisture was wiped off with filter paper, and the samples were weighed (M2). Three parallel samples were prepared for each group, and the average value was taken.
[0055] Water absorption rate calculation formula: Wu(%)=[(M2-M l ) / M l ]×100 Experimental results: The water absorption rate of the modified chitosan-amino acid composite membrane was significantly lower than that of the unmodified chitosan membrane, indicating that the hydrophobicity of the modified material was improved, which can effectively reduce swelling and deformation in the water environment and provide a basis for stable mechanical properties.
[0056] (2) Tensile property test The two types of films were cut into standard samples of 8 cm × 1 cm, and the thickness of the samples was measured with a digital micrometer. Tensile tests were performed using a tensile testing machine with a tensile rate of 10 mm / min, and the tensile strength and elongation at break data were recorded.
[0057] Experimental results: The tensile strength and elongation at break of the modified chitosan-amino acid composite film were significantly improved compared with the unmodified chitosan film, indicating that the intermolecular forces of the modified material were enhanced, the toughness and tensile strength were improved, and the flexibility index was optimized simultaneously.
[0058] (3) Amino acid release experiment Modified chitosan-amino acid composite membranes were placed in isothermal release media at 30℃ and 90℃, respectively. Samples were taken at different time points, and the amino acid concentration in the release media was determined by high-performance liquid chromatography (HPLC). Three parallel samples were set up for each group, and amino acid release curves were plotted.
[0059] The experimental data results are shown in Table 1 below: Table 1
[0060] The results show that, compared with the unmodified system, the modified chitosan-amino acid composite system significantly reduced water absorption from 185% to 38%, increased tensile strength from 26 MPa to 59 MPa, and increased elongation at break from 29% to 50%, demonstrating a significant improvement in water resistance and mechanical strength. The modified chitosan-amino acid composite system exhibited a large difference in release rate between 37℃ and 90℃; at 90℃, the release rate of amino acids was significantly increased, indicating that the system can achieve controlled release at different temperatures, showcasing the application potential of this invention in the field of temperature-responsive controlled release.
[0061] This invention discloses a temperature-controlled sustained-release chitosan drug carrier, its preparation method, and its applications, belonging to the field of biomedical materials technology. The method uses butanetetracarboxylic acid (BTCA) as a modifier to chemically modify chitosan through an amidation reaction, introducing a long carbon chain structure to improve the material's hydrophobicity, mechanical properties, and crosslinking density. Then, using an EDC / NHS crosslinking agent, amino acids are grafted onto the modified chitosan via amide bonds to form a CS-BTCA-A composite material. This material exhibits temperature-responsive release characteristics; the amide bonds break under elevated temperatures, achieving controlled sustained release of the antibacterial components. The preparation process of this invention is simple and highly efficient, and the resulting material possesses excellent mechanical properties, thermal stability, and antibacterial effects, making it suitable for applications such as controlled drug release and antibacterial dressings.
[0062] The above content is only for illustrating the technical concept of the present invention and should not be construed as limiting the scope of protection of the present invention. Any modifications made to the technical solution based on the technical concept proposed in this invention shall fall within the scope of protection of this invention.
Claims
1. A method for preparing a temperature-controlled sustained-release amino acid chitosan drug carrier, characterized in that, Includes the following steps: Chitosan is dissolved in a first organic acid solution to prepare a chitosan solution; Add butanetetracarboxylic acid and sodium hypophosphite to the chitosan solution, adjust the solution to the set pH value, and carry out the reaction to obtain the reaction solution; The reaction solution was precipitated with ethanol, then filtered, washed with deionized water until neutral and vacuum dried to obtain modified chitosan CS-BTCA. Modified chitosan CS-BTCA was dispersed in deionized water, amino acids were added, the pH was adjusted to acidic, and then a crosslinking agent was added. The mixture was stirred at room temperature to prepare a crosslinking reaction solution. The cross-linking reaction solution was sequentially dialyzed and freeze-dried to obtain the complex CS-BTCA-A; The composite CS-BTCA-A was mixed with water to prepare an aqueous solution, which was then poured into a polytetrafluoroethylene mold and dried at room temperature to form a nascent film. The nascent membrane was immersed in a second organic acid solution, then rinsed with deionized water overnight, and air-dried at room temperature to obtain a temperature-controlled sustained-release amino acid chitosan drug carrier.
2. The method for preparing a temperature-controlled sustained-release amino acid chitosan drug carrier according to claim 1, characterized in that, The first organic acid solution is one of acetic acid solution, propionic acid solution, and cinnamic acid solution; the mass concentration of the first organic acid solution is 2%~5%; the ratio of chitosan to the first organic acid solution is 1~3g:100mL.
3. The method for preparing a temperature-controlled sustained-release amino acid chitosan drug carrier according to claim 1, characterized in that, The mass ratio of butanetetracarboxylic acid to sodium hypophosphite is 4-6 g: 0.5-1.0 g; the set pH value is 5-6.5; the reaction temperature is 60-80℃ and the reaction time is 6-8 h.
4. The method for preparing a temperature-controlled sustained-release amino acid chitosan drug carrier according to claim 1, characterized in that, The vacuum drying temperature is 40~70℃, and the time is 24~30 h.
5. The method for preparing a temperature-controlled sustained-release amino acid chitosan drug carrier according to claim 1, characterized in that, The ratio of modified chitosan CS-BTCA, deionized water, amino acids, and crosslinking agent is 1g:50mL:0.1~1g:0.2~0.6g; the crosslinking agent is composed of equal masses of EDC and NHS; the amino acid is lysine.
6. The method for preparing a temperature-controlled sustained-release amino acid chitosan drug carrier according to claim 1, characterized in that, The stirring reaction time is 12-18 h; the dialysis uses a dialysis bag with a molecular weight cutoff of 3.5 kDa, and the dialysis time is 48-50 h.
7. The method for preparing a temperature-controlled sustained-release amino acid chitosan drug carrier according to claim 1, characterized in that, The aqueous solution has a mass concentration of 2% to 5%, and the drying time at room temperature is 46 to 50 hours.
8. The method for preparing a temperature-controlled sustained-release amino acid chitosan drug carrier according to claim 1, characterized in that, The second organic acid solution is one of acetic acid solution, propionic acid solution, and cinnamic acid solution, and the mass concentration of the second organic acid solution is 2% to 5%, and the soaking time is 30 min to 2 h.
9. A temperature-controlled sustained-release amino acid chitosan drug carrier, characterized in that, The drug was prepared using the method described in any one of claims 1 to 8 for the preparation of a temperature-controlled sustained-release amino acid chitosan carrier.
10. The application of a temperature-controlled sustained-release amino acid chitosan drug carrier in biomedical materials, characterized in that, The drug was prepared using the method described in any one of claims 1 to 8 for the preparation of a temperature-controlled sustained-release amino acid chitosan carrier.