Preparation method of nano cellulose temperature-sensitive gel

Abstract

The invention relates to the technical field of illumination, and discloses a preparation method of nanocellulose temperature-sensitive gel, nanocellulose is purified to reduce the impurity content, so that the gel structure stability in the long-term storage process is improved; a sol-gel transition temperature interval is set by regulating and controlling the crosslinking density so as to optimize the drug controlled release performance, and crosslinking treatment acts on the surface-modified nanocellulose system. By regulating and controlling the surface modification of the cellulose nanofibrils, the problem of low temperature-sensitive response speed can be effectively overcome, so that the material can more quickly respond to temperature change, and the cellulose nanofibrils have important significance in the fields of application scenes needing quick response, such as intelligent sensors, drug controlled release and the like; the improved temperature-sensitive response performance is beneficial to improving the overall performance and stability of the material, the application range of the material under different temperature conditions is expanded, and technical support is provided for developing high-performance temperature-sensitive materials.

Description

Technical Field

[0001] This application relates to the technical field of materials science and engineering, and particularly to a preparation method of a nanocellulose thermosensitive gel. Background Art

[0002] A preparation method of a nanocellulose thermosensitive gel aims to prepare a hydrogel that can reversibly transform from a liquid state to a gel state under temperature changes through the unique physical and chemical properties of nanocellulose. This method involves the compounding of nanocellulose with materials such as functional monomers and crosslinking agents to form thermosensitive response characteristics. Regarding several problems existing in this technology: Firstly, there is a challenge in regulating the crosslinking density. Under high-temperature conditions, the stability of the thermosensitive gel may decrease, and it is necessary to precisely regulate the crosslinking degree between nanocelluloses. Secondly, there is a problem in regulating the surface modification of cellulose nanofibrils. In order to improve its thermosensitive reaction rate, a suitable method must be found to modify its surface properties. Thirdly, there is an issue in adjusting the proportion of functional monomers. An appropriate proportion of functional monomers helps to improve the biocompatibility of the hydrogel to ensure its safety in the human body environment. In addition, the optimization of the sol-gel transition temperature range is crucial. Precise regulation of the transition temperature range can avoid time delay or burst release phenomena that may occur during the drug controlled release process. Finally, the control of the purity and impurity content of nanocellulose is also a major difficulty. Ensuring high purity and low impurity content will be beneficial to maintaining the integrity of the gel structure during long-term storage and enabling it to maintain excellent performance during storage. All these challenges need to be overcome by researchers through carefully designing experimental schemes and conducting sufficient verification. Summary of the Invention

[0003] To solve the problems raised in the above background art, this application provides a preparation method of a nanocellulose thermosensitive gel.

[0004] This application provides a preparation method of a nanocellulose thermosensitive gel, adopting the following technical solution: A preparation method of a nanocellulose thermosensitive gel includes: S101. Purify the nanocellulose to reduce the impurity content, thereby improving the stability of the gel structure during long-term storage; S102. Optimize the biocompatibility by adjusting the proportion of functional monomers, where the purified nanocellulose serves as a modified substrate; S103. Use surface modification technology to regulate the surface properties of cellulose nanofibrils to accelerate the thermosensitive response rate, and this surface modification is based on the system after the aforementioned proportion adjustment; S104. Set the sol-gel transition temperature range by regulating the crosslinking density to optimize the drug controlled release performance, and the crosslinking treatment acts on the surface-modified nanocellulose system.

[0005] Preferably, further limiting the proportion of the regulatory functional monomer to optimize biocompatibility includes the following steps: Regulate the proportion of the functional monomer within a specific range to optimize cell adhesion and survival rate; Select an appropriate monomer combination method based on different tissue sources to ensure the maximum compatibility between the material and biological tissue; Apply cell culture tests to verify the optimal monomer ratio to improve the overall biocompatibility performance; If the cell survival rate R is greater than the preset threshold A and the adhesion S is less than the set limit B, continue the experiment; otherwise, adjust the proportion of the functional monomer until the optimum is reached.

[0006] Preferably, further limiting the setting of the sol-gel transition temperature range based on regulating the crosslinking density to solve the problems of drug controlled-release time lag and burst release includes the following steps: Adjust the crosslinking density to effectively set the optimal sol-to-gel transition range of the thermosensitive gel; Determine the amount of crosslinking agent based on the target controlled-release efficiency and optimize it in combination with the actual application scenario; Set a temperature-controlled environment to simulate the human physiological condition and evaluate the influence of different crosslinking conditions on the drug release behavior; If the crosslinking factor D conforms to the formula \(D = K_1\cdot C^{3} / T + K_2 / V\), where K 1 represents the crosslinking kinetic constant, C refers to the reactant concentration, T is the reaction temperature, V is the gel volume, and verify whether it meets the design specifications through calculation.

[0007] Preferably, the steps of accelerating the thermosensitive response speed based on using surface modification technology are as follows: Use appropriate surface chemical means to modify cellulose nanofibrils to improve the ability to rapidly form a hydration film; Control the quantity and position of the introduced functional groups to promote a faster phase transition mechanism; Test the performance of the treated sample to ensure that the thermosensitive response time is shortened by more than half; According to the temperature rise rate U and thermodynamic characteristics H, calculate the formula \(Δt ≤ αUH^γ / T_θ\), where Δt represents the lag effect compensation time caused by temperature change, α is the heat transfer correction coefficient, γ is the activation parameter exponent, and Tθ is the conversion trigger point.

[0008] Preferably, purify the nanocellulose to improve the stability during long-term storage: Apply physical purification methods to remove amorphous substances and reduce background pollution; Adopt technologies such as ultrafiltration membrane separation to strictly screen and remove residual particulate impurities; Measure the transmittance T′ of the final product to quantify the purification effect; If the product purity I is higher than the threshold X and the transparency P meets the standard Q (P>I / X), it is considered that the purification meets the expected goal; otherwise, the refining steps need to be strengthened.

[0009] 6. The preparation method of a nanocellulose thermosensitive gel according to claim 5, characterized in that the overall thermosensitive gel performance is further improved by integrating the above-mentioned various control measures: Introduce multi-scale structure characterization means to comprehensively evaluate the microscopic and macroscopic properties of the gel; Implement quality comparison and monitoring between batches to ensure the consistency of the products obtained each time; Regularly detect under long-term stable storage conditions to confirm that there is no obvious deterioration trend in the physical and chemical state; If the size change L′ is within the allowable range Z (L′<Z) under long-term static conditions and can return to its original state, it proves that the system is highly stable.

[0010] Preferably, the key improvement lies in how to more effectively cope with the instability problem under high-temperature environments: Study new types of highly efficient cross-linking agents and their addition sequences; Set up an independent module to be responsible for real-time feedback of information on internal structure changes under high-temperature conditions; Dynamically adjust the number of chemical structure links to ensure high strength and fracture resistance; Set the judgment basis according to the maximum allowable expansion amount F_max. When the elastic modulus E>Fmax / ΔS² and the fracture energy G>ΣE(δx), it is not easy to break even under the limit deformation state.

[0011] Preferably, the expansion of the understanding of regulating the cross-linking density and its corresponding technical solutions are specifically manifested as: Screen out unique cross-linking molecules with a tendency to oligomerize but not easily aggregate and settle; Precisely control the cross-linking process based on the thermal induction principle to avoid undesirable by-products; Select a suitable cross-linking time window Tc to strengthen the initially formed cross-linked network; When T > Tc and \( T < kT_r + C_v \log(I + 1)\), where \(T_c\) refers to a specific conversion timing, \(T_r\) refers to the critical temperature range of the multiphase, I represents the number of cross-linking times, and Cv is the constant volume heat capacity. Conduct continuous observations within the specified time interval until satisfactory results are obtained.

[0012] Preferably, the promotion delves deeply into surface modification, especially achieving a breakthrough in the difficult problem of improving the thermosensitive response rate: Invent a brand-new two-step method or a more stepped incremental progressive modification strategy; Utilize the synergistic effect of multiple catalysts to enhance the number of active sites and thereby amplify the signal intensity; Define and test the modification thickness Hn and the number of layers n for each layer, and establish a corresponding quantitative model for optimization guidance; Set the response time limit of the thermosensitive trigger \(τ≤b\Delta Θ / \omega\sqrt{m}\), where b and m represent the thermal diffusion length and the frequency-related factor respectively; ω is the surface wave damping coefficient, and Θ is the temperature difference amplitude to ensure a sufficiently rapid response to external temperature changes.

[0013] Preferably, strengthen the description of effective solutions and theoretical support for the treatment of nanocellulose impurities: Construct a hierarchical precipitation system to methodically remove interfering impurity components; Improve the resolution of the filter medium while ensuring good control of the flow channel resistance; Observe the differences in infrared spectra before and after treatment to visually evaluate the effectiveness; If the transmittance R meets the logical judgment R(λ)>ε*exp(στ), where τ represents the thickness loss function; ε is the absorption coefficient, σ is the scattering loss, λ indicates the measurement wavelength, then it is considered that the operation process has achieved the ideal purification effect.

[0014] In summary, this application includes at least one of the following beneficial technical effects: By regulating the surface modification of cellulose nanofibrils, the problem of slow thermosensitive response speed can be effectively overcome, enabling the material to respond more quickly to temperature changes, which is of great significance in application scenarios that require rapid response, such as intelligent sensors, drug controlled release, etc. The improved thermosensitive response performance helps to enhance the overall performance and stability of the material, expand its application range under different temperature conditions, and provides technical support for the development of high-performance thermosensitive materials. By reasonably regulating the proportion of functional monomers in the hydrogel, the problem of unsatisfactory biocompatibility can be solved, reducing immune responses and inflammatory reactions in the body, and improving the affinity between the material and biological tissues, providing a safer and more reliable material for biomedical applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 It is a flowchart of a preparation method of a nanocellulose thermosensitive gel of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0016] The following details the embodiments of the present application, and the examples of the embodiments are shown in the drawings.

[0017] In the description of this specification, the description referring to the terms "certain embodiments", "one embodiment", "some embodiments", "schematic embodiments", "examples", "specific examples", or "some examples" means that the specific features, structures, materials, or characteristics described in connection with the embodiments or examples are included in at least one embodiment or example of the present application. In this specification, the schematic expressions of the above terms do not necessarily refer to the same embodiments or examples. Moreover, the specific features, structures, materials, or characteristics described can be combined in a suitable manner in any one or more embodiments or examples.

[0018] An embodiment of the present application discloses a preparation method of a nanocellulose thermosensitive gel, with reference to Figure 1 , including: S101. Purify the nanocellulose to reduce the impurity content, thereby improving the gel structure stability during long-term storage; S102. Optimize the biocompatibility by adjusting the proportion of functional monomers, where the purified nanocellulose serves as a modified substrate; S103. Use surface modification technology to regulate the surface properties of cellulose nanofibrils to accelerate the thermosensitive response speed, and this surface modification is based on the system after the aforementioned proportion adjustment; S104. Set the sol-gel transition temperature range by regulating the crosslinking density to optimize the drug controlled-release performance, and the crosslinking treatment acts on the surface-modified nanocellulose system.

[0019] Describe each step and its specific operation of a preparation method of a nanocellulose thermosensitive gel of the present invention. First of all, the preparation method starts with the purification treatment of nanocellulose. By removing impurities in the nanocellulose, the gel structure stability during long-term storage is improved. This step involves using a series of purification technical means, such as multi-stage filtration, washing, and centrifugation operations to remove the small molecule impurities and non-cellulose substances contained therein, ensuring that the purity of the nanocellulose reaches a relatively high level, reducing the possibility of the internal structure deteriorating due to external factors, and laying a good foundation for subsequent other optimization measures.

[0020] For example, in one embodiment, in order to ensure that the nanocellulose has good dispersibility and purity, the method of washing with water multiple times combined with high-speed centrifugation is used to remove residual chemicals and insoluble impurities, and then ultraviolet spectroscopy analysis is used to detect and confirm that the purified sample has basically removed the interfering substances.

[0021] Subsequently, the proportion of the functional monomer in the synthesis reaction system is adjusted thereon to adjust the biocompatibility of the material. This proportion adjustment is completed based on the modified layer formed by pre-surface modification of the nanofiber substrate. According to the requirements of the actual application scenario and the results obtained from cell culture tests, a suitable proportion of the functional monomer is reasonably selected for copolymerization reaction, so that it can be effectively incorporated into the overall framework structure and play its corresponding role.

[0022] For example, in a specific case, the experimental group found through research on cytotoxicity and live cell adhesion experiments that adding an appropriate amount of functional monomer with strong hydrophilicity made the new material show better biological activity and was not likely to cause problems such as tissue immune rejection; while in applications related to drug carriers, functional monomer components that can provide a sustained release effect tend to be selected.

[0023] Then, in order to improve the temperature sensing characteristics, surface modification of the original material must also be carried out, that is, by using a suitable modification method to make the surface of the fibril carry functional groups that are easy to bond with other compounds, while enhancing the response speed of its own density conversion mechanism, thereby overcoming the problem of poor sensitivity existing in previous similar products. The ultimate goal is to achieve a more accurate and effective thermal response regulation purpose, that is, when the temperature changes, the material properties can quickly switch states without delay.

[0024] For example, in specific practice, a substance such as a silane coupling agent can be introduced as a crosslinking point to form a mesoporous membrane-like coating layer. It can not only promote the close connection between cellulose particles but also increase the contact area and expand the probability of chemical reactions within the range, and thereby achieve more efficient heat transfer and conduction performance.

[0025] After that, by controlling the degree of crosslinking, the transition interval from solution to solid form is set to solve the intermittent problem and transient sudden release phenomenon during the continuous release of drugs, while maintaining sufficient elasticity and hardness to ensure that the product form remains stable without deformation, distortion, or rupture.

[0026] For example, the comparison of the gel physical parameter values obtained by dynamic mechanical frequency domain scanning (DMA) tests under different strength curing conditions shows that appropriate chemical reagents or physical processing procedures will make the crosslinking points more evenly distributed in the three-dimensional grid space, thus avoiding the generation of weak structural links caused by aggregation phenomena.

[0027] Finally, returning to the management of the characteristics of the nanofiber raw material itself at the nanoscale, that is, how to maintain a sufficiently high cleanliness index, which is an indispensable prerequisite throughout all the above-mentioned processes. It is necessary to strictly execute the operations of each purification link according to the established program standards to prevent any particulate foreign matter from contaminating the entire manufacturing production line until the moment before the final product is encapsulated and packaged. Only by comprehensively controlling each link is it possible to ensure that the product quality meets the high standard requirements and thus meet the growing market demand.

[0028] In summary, this complete production process route aims to comprehensively solve problems and obtain high-performance composite polymer intelligent materials. It comprehensively applies physical and chemical methods to produce a new type of pharmaceutical excipient with excellent thermal temperature sensing characteristics, ideal load-bearing capacity, and safety and reliability characteristics.

[0029] Although the embodiments of the present application have been shown and described above, it can be understood that the above embodiments are exemplary and should not be construed as limiting the present application. Those of ordinary skill in the art can make changes, modifications, substitutions, and variations to the above embodiments within the scope of the present application.

Claims

1. A method for preparing a nanocellulose thermosensitive gel, characterized in that: include: S101, purifying the nanocellulose to reduce the impurity content, thereby improving the stability of the gel structure during long-term storage; S102, optimizing biocompatibility based on adjusting the ratio of functional monomers, wherein the purified nanocellulose is used as a modified substrate; S103, using surface modification technology to regulate the surface properties of cellulose nanofibrils to accelerate the temperature-sensitive response speed, the surface modification is based on the system after the aforementioned ratio adjustment; S104. The sol-gel transition temperature range is set by adjusting the cross-linking density to optimize the drug controlled release performance, and the cross-linking treatment acts on the surface-modified nanocellulose system.

2. The method for preparing a nanocellulose thermosensitive gel according to claim 1, characterized in that: Further defining the method of adjusting the ratio of functional monomers to optimize biocompatibility comprises the following steps: Regulating the ratio of functional monomers within a specific range to optimize cell adhesion and survival; Select appropriate monomer combinations based on different tissue sources to ensure maximum compatibility between the material and biological tissues; Apply cell culture tests to verify the optimal monomer ratio to improve overall biocompatibility performance; If the cell survival rate R is greater than the preset threshold A and the adhesion S is less than the set limit B, the experiment continues; otherwise, the functional monomer ratio is adjusted until it reaches the optimal value.

3. The method for preparing a nanocellulose thermosensitive gel according to claim 2, characterized in that: Further limiting the sol-gel transition temperature range based on regulating the crosslinking density to solve the problems of drug controlled release lag and burst release includes the following steps: Adjust the cross-linking density to effectively set the optimal sol-to-gel transition interval of the thermosensitive gel; Determine the amount of cross-linking agent based on the target controlled release efficiency and optimize it in combination with the actual application scenario; Set up a temperature-controlled environment to simulate human physiological conditions and evaluate the effects of different cross-linking conditions on drug release behavior; If the cross-linking factor D conforms to the formula \( D = K_1 \cdot C^{3} / T + K_2 / V \), where K1 represents the cross-linking kinetic constant, C refers to the reactant concentration, T is the reaction temperature, and V is the gel volume, it is verified by calculation whether the design indicators are met.

4. The method for preparing a nanocellulose thermosensitive gel according to claim 3, characterized in that: The steps for accelerating the temperature sensitive response speed based on the surface modification technology are further defined as follows: Modify cellulose nanofibrils using appropriate surface chemistry to improve the ability of rapid hydration film formation; Controlling the amount and location of functional groups introduced to promote faster phase transition mechanisms; The performance of the samples after testing ensures that the temperature-sensitive response time is shortened by more than half; According to the temperature rise rate U and thermodynamic characteristics H, the calculation formula is \(Δt ≤ αUH^γ / T_θ \) where Δt represents the hysteresis effect compensation time caused by temperature change, α is the heat transfer correction coefficient, γ is the activation parameter index, and Tθ is the conversion trigger point.

5. The method for preparing a nanocellulose thermosensitive gel according to claim 4, characterized in that: Purification of nanocellulose to improve stability during long-term storage: Physical purification methods are used to remove amorphous phase substances and reduce background contamination; Use ultrafiltration membrane separation technology to strictly screen and remove residual particulate impurities; The transmittance T′ of the final product was measured to quantify the purification effect; If the product purity I is higher than the threshold X and the transparency P meets the standard Q (P>I / X), it is considered that the purification meets the expected goal; otherwise, the refining steps need to be strengthened.

6. The method for preparing a nanocellulose thermosensitive gel according to claim 5, characterized in that: Further improve the overall thermosensitive gel performance by integrating the above control measures: Introduce multi-scale structure characterization methods to comprehensively evaluate the microscopic and macroscopic properties of the gel; Implement quality comparison monitoring between batches to ensure the consistency of the products obtained each time; Regularly detect under long-term stable storage conditions to confirm that there is no obvious deterioration trend in the physicochemical state; If the size change L′ is within the allowable range Z (L′<Z) under long-term static conditions and can return to its original state, it proves that the system is highly stable.

7. The method for preparing a nanocellulose thermosensitive gel according to claim 1, characterized in that: The key improvement lies in how to more effectively address the instability problem under high-temperature environments: Study new types of highly efficient cross-linking agents and their addition sequences; Set up an independent module to be responsible for real-time feedback of information on internal structure changes under high-temperature conditions; Dynamically adjust the number of chemical structure links to ensure high strength and fracture resistance; Set the judgment basis according to the maximum allowable elongation F_max. When the elastic modulus E>Fmax / ΔS² and the fracture energy G>ΣE(δx), it is not easy to break even under the limit deformation state.

8. The method for preparing a nanocellulose thermosensitive gel according to claim 7, characterized in that: Expand the understanding of regulating the cross-linking density and its corresponding technical solutions, specifically manifested as: Screen out unique cross-linking molecules with a tendency to oligomerize but not easily aggregate and settle; Precisely control the cross-linking process based on the thermal induction principle to avoid unwanted by-products; Select a suitable cross-linking time window Tc to strengthen the initially formed cross-linked network; When T > Tc and \( T < kT_r + C_v \log(I+1)\), where \(T_c\) refers to the specific conversion time, \(T_r\) refers to the critical temperature range of the complex phase, I represents the number of cross-linking times, and Cv is the heat capacity at constant volume. Conduct continuous observations within the specified time interval until satisfactory results are obtained.

9. The method for preparing a nanocellulose thermosensitive gel according to claim 8, characterized in that: Promote in-depth exploration of surface modification, especially to achieve breakthroughs in the difficult problem of improving the thermosensitive response rate: Invent a new two-step or more stepwise increasing step-by-step modification strategy; Utilize the synergistic effect of multiple catalysts to increase the number of active sites and thus amplify the signal intensity; Define and test the thickness Hn and the number of layers n of each layer of modification, and establish a corresponding quantitative model for optimization guidance; Set the response time limit of the thermosensitive trigger \(τ≤b\Delta Θ / \omega\sqrt{m}\), where b and m represent the thermal diffusion length and the frequency-related factor respectively; ω is the surface wave damping coefficient, and Θ is the temperature difference amplitude to ensure sufficient rapid induction of external temperature changes.

10. The method for preparing a nanocellulose thermosensitive gel according to claim 9, characterized in that: Strengthen the description of effective solutions and theoretical support for the treatment of nanocellulose impurities: Construct a hierarchical precipitation system to systematically remove interfering impurity components; Improve the resolution of the filter medium while ensuring good control of the flow channel resistance; Observe the difference in infrared spectra before and after treatment to visually evaluate the effectiveness; if the transmittance R meets the logical judgment R(λ)>ε*exp(στ), where τ expresses the thickness loss function; ε is the absorption coefficient, σ is the scattering loss, and λ indicates the measurement wavelength, then it is considered that the operation process has achieved the ideal purification effect.

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