High-oil-loading temperature-sensitive biphase gel as well as preparation method and application thereof

Abstract

The invention discloses high-oil-loading temperature-sensitive biphase gel as well as a preparation method and application thereof, and belongs to the technical field of biomedical materials and cosmetics. The gel is prepared by taking a long-chain alkyl grafted and modified polymer matrix as a basis and reacting with an inorganic cross-linking agent calcium sodium borosilicate. The preparation method comprises the following steps: reacting the component A with the component B in a solvent to obtain a hydrophobically modified polymer matrix; and then mixing with calcium sodium borosilicate in water, and forming gel under the synergistic effect of a physical crosslinking point formed by hydrophobic aggregation of an alkyl chain and ionic crosslinking. The oil carrying capacity of the gel is improved, and the oil carrying capacity can reach 20 wt% or above. Besides, by introducing an alkyl chain, a polymer chain can generate chain curling and intermolecular association in water along with temperature rise, the effect is synergistic with ionic crosslinking, the gel is endowed with a temperature-sensitive characteristic, the gel generates reversible sol-gel conversion near the body temperature, and in-situ fitting with the skin or a wound surface is realized. The application potential is realized in the fields of drug sustained-release dressings and functional cosmetics.

Description

Technical Field

[0001] This invention relates to the fields of biomedicine and cosmetics, and more specifically to a high oil-loading temperature-sensitive biphasic gel, its preparation method, and its application. Background Technology

[0002] As a functional material that is simultaneously rich in aqueous and oil phases, biphasic gels have shown broad application prospects in cosmetics (such as active ingredient delivery carriers) and medical fields (such as skin repair dressings) due to their good biocompatibility, sustained-release properties and carrying potential for hydrophilic and hydrophobic active ingredients.

[0003] However, existing biphasic gels still have significant drawbacks that limit their performance improvement and wider application:

[0004] First, the oil-carrying capacity is insufficient. Most common biphasic gels currently use hydrophilic polymers such as polyvinyl alcohol and sodium hyaluronate as the matrix framework. Their molecular structure has strong hydrophilicity and poor compatibility with oil-soluble components. This results in low loading efficiency of the gel system for the oil phase and oil-soluble active ingredients (such as vitamin E and plant essential oils), leading to typically low oil loading. This limitation in oil loading directly affects the diversity, effective concentration, and final efficacy of active ingredients in the gel, failing to meet the demand for high oil content or highly efficient delivery of oil-soluble components.

[0005] Secondly, their adherence and ease of application are lacking. Most traditional biphasic gels are fully cured during the product preparation stage. During use, this pre-formed solid gel cannot adequately adapt to the complex contours of the skin surface or the shape of irregular wounds, resulting in a lack of tight, close contact with the application site. Gaps or poor adhesion not only affect user comfort but also prevent the efficient and uniform delivery of active ingredients from the aqueous and oil phases to the target area, leading to waste of active ingredients and reduced efficacy.

[0006] Therefore, developing a biphasic gel that has both high oil-carrying capacity to broaden the selection range of active ingredients and good in-situ adhesion during use is of urgent need and great significance for improving its application efficacy in the cosmetic and medical fields. Summary of the Invention

[0007] In view of this, the present invention provides a high oil-loading, temperature-sensitive biphase gel, its preparation method, and its application. This successfully increases its oil loading capacity and endows it with temperature-sensitive properties.

[0008] To solve the above-mentioned technical problems, this application adopts the following technical solution: The primary objective of this application is to provide: a high oil-carrying, temperature-sensitive biphase gel, prepared by coordination and crosslinking of a modified polymer matrix and an inorganic crosslinking agent; The modified polymer matrix is ​​poloxamer or polyvinyl alcohol grafted with long-chain alkyl groups; the inorganic crosslinking agent is sodium calcium borosilicate. The mass ratio of the modified polymer matrix to the inorganic crosslinking agent is 0.1-2 g: 0.01-1 g.

[0009] As a preferred technical solution, the modified polymer matrix is ​​prepared by the following method: Components A and B were added to N-methylpyrrolidone solvent, stirred and reacted, and then freeze-dried to prepare poloxamer or polyvinyl alcohol grafted with long-chain alkyl groups. Component A is one or a combination of poloxamer and polyvinyl alcohol; component B is one or a combination of hexadecyl isocyanate and dodecyl isocyanate. As a preferred technical solution, the mass-to-volume ratio of component A to N-methylpyrrolidone solvent is 0.1-2 g: 10 mL; the mass-to-volume ratio of component B to N-methylpyrrolidone solvent is 0.1-5 g: 10 mL.

[0010] As a preferred technical solution, the reaction temperature of the stirring reaction is 25-200℃.

[0011] Another objective of this application is to provide a method for preparing the aforementioned high oil-loaded temperature-sensitive biphasic gel, comprising the following steps: S1. Preparation of modified polymer matrix: Component A and component B are added to N-methylpyrrolidone and stirred at a temperature of 25-200℃ to react the hydroxyl groups of component A with the isocyanate groups of component B to obtain a mixture; the mixture is freeze-dried to remove the solvent and obtain the modified polymer matrix. S2. Gelation: The modified polymer matrix and inorganic crosslinking agent obtained in step S1 are added to water and stirred to allow the calcium ions and borate ions released by the inorganic crosslinking agent to coordinate and crosslink with the hydroxyl groups on the molecular chain of the modified polymer matrix, forming a high oil-carrying temperature-sensitive biphase gel.

[0012] As a preferred technical solution, in step S1, component A is one or a combination of two of poloxamer and polyvinyl alcohol; component B is one or a combination of two of hexadecyl isocyanate and dodecyl isocyanate. The mass-to-volume ratio of component A to N-methylpyrrolidone solvent is 0.1-2 g: 10 mL; the mass-to-volume ratio of component B to N-methylpyrrolidone solvent is 0.1-5 g: 10 mL.

[0013] As a preferred technical solution, in step S2, the mass-to-volume ratio of the modified polymer matrix to water is 0.1-2 g:10 mL; the mass-to-volume ratio of the inorganic crosslinking agent to water is 0.01-1 g:10 mL; and the inorganic crosslinking agent is sodium calcium borosilicate.

[0014] Another object of this application is to provide: the oil loading of the high oil loading temperature-sensitive biphase gel or the high oil loading temperature-sensitive biphase gel prepared by the method is ≥20wt%.

[0015] Another object of this application is to provide the application of the high oil-loading temperature-sensitive biphase gel or the high oil-loading temperature-sensitive biphase gel prepared by the method in the preparation of medical products or cosmetics.

[0016] As can be seen from the above technical solution, compared with the prior art, the present invention has the following beneficial effects: (1) Significantly improves oil carrying capacity and compatibility By chemically grafting hydrophobic segments containing long-chain alkyl groups (derived from component B) onto a hydrophilic polymer backbone (component A), the hydrophilic-hydrophobic balance of the gel matrix is ​​fundamentally improved. The resulting modified polymer possesses both a hydrophilic backbone and hydrophobic side chains, significantly enhancing its affinity for oily components. This increases the oil loading capacity of the gel system to a high level of 20 wt%, overcoming the bottleneck of low oil loading efficiency in traditional hydrophilic gels and broadening the loading range for oil-soluble active ingredients.

[0017] (2) Achieving temperature-sensitive in-situ gelation and excellent adhesion Using sodium calcium borosilicate as a crosslinking agent, the released ions dynamically coordinate and crosslink with the hydroxyl groups on the modified polymer matrix molecular chains. Simultaneously, they synergistically interact with physical crosslinking points formed by the hydrophobic aggregation of alkyl chains, creating a three-dimensional network sensitive to external temperature. The gel exists as a flowable sol at room temperature, facilitating injection or application; upon contact with body temperature, it rapidly transforms into a stable gel. This temperature-triggered sol-gel transition allows the gel to perfectly conform to irregular skin surfaces or wound shapes, achieving tight, gapless coverage and significantly improving the delivery efficiency and local efficacy of the active ingredients.

[0018] (3) Constructing a stable two-phase structure The aqueous and oil phases exhibit good stability within the gel. Verified by constant temperature and humidity aging tests at 40℃ and 70% humidity, the product can be stably retained for one month under these stringent conditions, effectively ensuring the consistency of product performance throughout its shelf life.

[0019] (4) The preparation method is simple and controllable. The preparation process is clear and the conditions are mild. It can be prepared efficiently in two steps (first chemical grafting modification, then ionic crosslinking), and has good process controllability and reproducibility.

[0020] (5) It has both biocompatibility and functional expandability The selected base materials (such as poloxamer and polyvinyl alcohol) have good biocompatibility, and no toxic reagents are introduced during the modification process. Furthermore, the platform boasts strong technological compatibility, facilitating the flexible integration of different functional active ingredients in aqueous or oil phases to meet the needs of various scenarios, including moisturizing and repairing in cosmetics and sustained-release drugs in the medical field.

[0021] In summary, this application has successfully prepared a biphasic gel with high oil loading capacity, temperature-sensitive injectability, and good in-situ adhesion through an innovative synergistic strategy of "hydrophobic grafting modification" and "ion thermosensitive crosslinking". It effectively solves the two core problems of poor oil loading capacity and poor adhesion of traditional biphasic gels, and has outstanding application advantages in the fields of cosmetics and medical dressings. Attached Figure Description

[0022] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0023] Figure 1 Here is a microscope image of the biphasic gel prepared in Example 1 of this invention.

[0024] Figure 2 Here is a microscope image of the biphasic gel prepared in Example 2 of this invention.

[0025] Figure 3 Here is a microscope image of the biphasic gel prepared in Example 3 of this invention.

[0026] Figure 4 Here is a microscope image of the biphasic gel prepared in Comparative Example 1 of this invention.

[0027] Figure 5 Here is a microscope image of the biphasic gel prepared in Comparative Example 2 of this invention.

[0028] Figure 6 Here is an optical photograph of the biphasic gel prepared in Example 1 of this invention.

[0029] Figure 7 Here is an optical photograph of the biphasic gel prepared in Example 2 of this invention.

[0030] Figure 8Example 3 of the present invention: Optical photograph of the biphase gel prepared.

[0031] Figure 9 Here is an optical photograph of the biphase gel prepared in Comparative Example 1 of this invention.

[0032] Figure 10 Here is an optical photograph of the biphase gel prepared in Comparative Example 2 of this invention.

[0033] Figure 11 The figure shows the viscosity-shear rate curve of the biphase gel in Example 1 of this invention.

[0034] Figure 12 The figure shows the viscosity-shear rate curve of the biphase gel in Example 2 of this invention.

[0035] Figure 13 The figure shows the viscosity-shear rate curve of the biphase gel in Example 3 of this invention.

[0036] Figure 14 Here is the viscosity-shear rate curve of the biphase gel in Comparative Example 1 of this invention.

[0037] Figure 15 Here is the viscosity-shear rate curve of the biphase gel in Comparative Example 2 of this invention.

[0038] Figure 16 Here is the viscosity-shear rate curve of the biphase gel in Comparative Example 4 of this invention.

[0039] Figure 17 Here is a schematic diagram of the thermosensitive effect of the biphase gel in Example 1 of the present invention.

[0040] Figure 18 Here is a schematic diagram of the thermosensitive effect of the biphasic gel in Example 2 of the present invention.

[0041] Figure 19 Here is a schematic diagram of the thermosensitive effect of the biphasic gel in Example 3 of the present invention.

[0042] Figure 20 Here is a schematic diagram of the thermosensitive effect of the biphase gel in Comparative Example 1 of the present invention.

[0043] Figure 21 Here is a schematic diagram of the thermosensitive effect of the biphase gel in Comparative Example 2 of the present invention.

[0044] Figure 22 Here is a schematic diagram of the thermosensitive effect of the biphasic gel in Comparative Example 3 of the present invention. Detailed Implementation

[0045] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0046] Example 1 A high oil-loading, temperature-sensitive biphase gel was prepared by coordination and crosslinking of polyvinyl alcohol grafted with long-chain alkyl groups and sodium borosilicate calcium. The specific preparation process is as follows: S1. Preparation of modified polymer matrix: 0.5 g polyvinyl alcohol and 1 g hexadecyl isocyanate were added to 10 mL N-methylpyrrolidone and stirred at 60 °C for 24 h to allow the hydroxyl groups of polyvinyl alcohol to react with the isocyanate groups of hexadecyl isocyanate to obtain a mixture; freeze-drying was performed to remove the solvent and obtain the modified polymer matrix. S2. Gelation: Take 0.5 g of the modified polymer matrix obtained in step S1 and 0.04 g of sodium calcium borosilicate. To verify its oil carrying capacity, also take 2.635 g of MCT oil. Add all three to 10 mL of water and stir at 30°C for 1 h. This allows the calcium ions and borate ions released by the sodium calcium borosilicate to coordinate and crosslink with the hydroxyl groups on the molecular chain of the modified polymer matrix, forming a high oil carrying capacity temperature-sensitive biphase gel.

[0047] Example 2 A high oil-loading, temperature-sensitive biphase gel was prepared by coordination and crosslinking of polyvinyl alcohol grafted with long-chain alkyl groups and sodium borosilicate calcium. The specific preparation process is as follows: S1. Preparation of modified polymer matrix: 0.1 g polyvinyl alcohol and 0.1 g dodecyl isocyanate were added to 10 mL N-methylpyrrolidone and stirred at 25 °C for 24 h to allow the hydroxyl groups of polyvinyl alcohol to react with the isocyanate groups of dodecyl isocyanate to obtain a mixture; freeze-drying was performed to remove the solvent and obtain the modified polymer matrix. S2. Gelation: Take 0.1 g of the modified polymer matrix obtained in step S1 and 0.01 g of sodium calcium borosilicate. To verify its oil carrying capacity, also take 2.5275 g of vitamin E. Add all three to 10 mL of water and stir at 30°C for 1 h. This allows the calcium ions and borate ions released by the sodium calcium borosilicate to coordinate and crosslink with the hydroxyl groups on the molecular chain of the modified polymer matrix, forming a high oil carrying capacity temperature-sensitive biphase gel.

[0048] Example 3 A high oil-loading, temperature-sensitive biphase gel was prepared by coordination and crosslinking of polyvinyl alcohol grafted with long-chain alkyl groups and sodium borosilicate calcium. The specific preparation process is as follows: S1. Preparation of modified polymer matrix: 2 g poloxamer and 5 g dodecyl isocyanate were added to 10 mL N-methylpyrrolidone and stirred at 200 °C for 24 h to allow the hydroxyl groups of polyvinyl alcohol to react with the isocyanate groups of dodecyl isocyanate to obtain a mixture; freeze-drying was performed to remove the solvent and obtain the modified polymer matrix. S2. Gelation: Take 2 g of the modified polymer matrix obtained in step S1 and 1 g of sodium calcium borosilicate. To verify its oil carrying capacity, also take 3.25 g of orange blossom essential oil. Add all three to 10 mL of water and stir at 30°C for 1 h. This allows the calcium ions and borate ions released by the sodium calcium borosilicate to coordinate and crosslink with the hydroxyl groups on the molecular chain of the modified polymer matrix, forming a high oil carrying capacity temperature-sensitive biphase gel.

[0049] Comparative Example 1 The difference from Example 1 is that the mass of component B is 0 g. Without the addition of component B, it is impossible to graft alkyl chains onto component A; therefore, this serves as a control experiment.

[0050] Comparative Example 2 The difference from Example 1 is that component B is replaced with another isocyanate having a long-chain alkyl group, namely octadecyl isocyanate. This change in component B alters the alkyl grafting configuration, making it impossible to construct effective hydrophobic microdomains and thus hindering efficient oil loading. This demonstrates that the gel can only be obtained with the aforementioned component B.

[0051] Comparative Example 3 The difference from Example 1 is that component A is replaced with another polymeric material with a large number of hydroxyl groups, namely polyethylene glycol. This change in component A alters the polymeric framework, preventing the formation of a gel network. This demonstrates that the gel can only be obtained with the aforementioned component A.

[0052] Comparative Example 4 The difference from Example 1 is that the MCT mass is 3 g, which means the oil phase accounts for approximately 22%. This is to determine the upper limit of oil loading in the gel of the present invention.

[0053] To verify the performance of the gels prepared in Examples 1-3 and Comparative Examples 1-4 of this application, the following experiments were conducted: The samples from Examples 1-3 and Comparative Examples 1-2 were stored in a constant temperature and humidity chamber at 40°C and 70% humidity for one month. Subsequently, their microstructure and rheological behavior (viscosity-shear rate) were tested, and the experimental results are as follows: Figures 1-15 As shown.

[0054] Microscopic morphology results ( Figure 1-3The results showed that the oil droplets were uniformly dispersed in all samples in the initial state. After one month of damp heat aging, the oil droplet distribution in each example remained uniform, and no significant changes in morphology were observed, confirming that it still had good stability at a high oil loading of 20 wt%. This is because the grafting of long-chain alkyl groups provided hydrophobic microregions that could accommodate the oil phase, significantly improving the oil loading of the gel.

[0055] Figure 4-5 The results show that the oil droplets in Comparative Examples 1-2 exhibit significant aggregation, with the oil phase rising and precipitating. It is impossible to observe that the oil droplets are uniformly distributed in the gel, indicating that it cannot stably maintain a high oil loading state without grafting or grafting other long-chain alkyl groups.

[0056] Optical photographs show that all samples were initially pale yellow, homogeneous, creamy solids. Figures 6-10 ). Figures 6-8 The results show that after one month of damp heat aging, the samples of each embodiment still maintained a pale yellow, homogeneous cream state, which also proves that they still have good stability under a high oil loading of 20wt%. Figures 9-10 This indicates that the samples of Comparative Examples 1-2 showed obvious phase separation, significant aggregation of oil droplets, and precipitation of the oil phase, which also shows that they could not stably maintain a high oil loading state.

[0057] Rheological test results ( Figures 11-15 This further supports the above conclusions. In the initial state, the viscosity-shear rate curves of all samples exhibited continuous and regular shear-thinning behavior, indicating a homogeneous structure. After aging, the rheological curves of each embodiment basically coincided with the initial state, proving their long-term structural stability. However, the curves of Comparative Examples 1-2 showed abnormal fluctuations, indicating that the internal homogeneity had been disrupted and the oil phase had precipitated. This comparative experiment fully demonstrates that the biphase gel constructed in this invention can effectively solve the stability problem under high oil loading conditions.

[0058] Figure 16 This indicates that when the oil loading of the gel exceeds 20%, abnormal rheological fluctuations occur, indicating internal heterogeneity. Therefore, the upper limit of oil loading for this gel is 20%.

[0059] Figure 17-22 This indicates that the sample of the example has thermosensitive response characteristics. As the temperature rises, the sample of the example changes from liquid to solid. This is because the alkyl chain of a specific length introduced in this invention enhances the hydrophobic interaction between polymer chains, enabling them to coil and associate in molecules in water as the temperature rises. In contrast, the control group remains in a liquid state after heating and does not have thermosensitive response characteristics.

[0060] The above experiments demonstrate that components A and B are necessary conditions for obtaining the gel. Changing component A alters the polymer framework, preventing the formation of a gel network. Changing component B alters the alkyl grafting, preventing the construction of effective hydrophobic microdomains and hindering efficient oil loading.

[0061] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.

[0062] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A high oil-loading, temperature-sensitive biphase gel, characterized in that, It was prepared by coordination and crosslinking of a modified polymer matrix and an inorganic crosslinking agent; The modified polymer matrix is ​​poloxamer or polyvinyl alcohol grafted with long-chain alkyl groups; the inorganic crosslinking agent is sodium calcium borosilicate. The mass ratio of the modified polymer matrix to the inorganic crosslinking agent is 0.1-2 g: 0.01-1 g.

2. The high oil-loading temperature-sensitive biphase gel according to claim 1, characterized in that, The modified polymer matrix was prepared using the following method: Components A and B were added to N-methylpyrrolidone solvent, stirred and reacted, and then freeze-dried to prepare poloxamer or polyvinyl alcohol grafted with long-chain alkyl groups. Component A is one or a combination of poloxamer and polyvinyl alcohol; component B is one or a combination of hexadecyl isocyanate and dodecyl isocyanate.

3. The high oil-loading temperature-sensitive biphase gel according to claim 2, characterized in that, The mass-to-volume ratio of component A to N-methylpyrrolidone solvent is 0.1-2 g: 10 mL; the mass-to-volume ratio of component B to N-methylpyrrolidone solvent is 0.1-5 g: 10 mL.

4. The high oil-loading temperature-sensitive biphase gel according to claim 2, characterized in that, The reaction temperature of the stirring reaction is 25-200℃.

5. A method for preparing a high oil-loading temperature-sensitive biphase gel as described in any one of claims 1-4, characterized in that, Includes the following steps: S1. Preparation of modified polymer matrix: Component A and component B are added to N-methylpyrrolidone and stirred at a temperature of 25-200℃ to react the hydroxyl groups of component A with the isocyanate groups of component B to obtain a mixture; the mixture is freeze-dried to remove the solvent and obtain the modified polymer matrix. S2. Gelation: The modified polymer matrix and inorganic crosslinking agent obtained in step S1 are added to water and stirred to allow the calcium ions and borate ions released by the inorganic crosslinking agent to coordinate and crosslink with the hydroxyl groups on the molecular chain of the modified polymer matrix, forming a high oil-carrying temperature-sensitive biphase gel.

6. The preparation method according to claim 5, characterized in that, In step S1, component A is one or a combination of two of poloxamer and polyvinyl alcohol; component B is one or a combination of two of hexadecyl isocyanate and dodecyl isocyanate. The mass-to-volume ratio of component A to N-methylpyrrolidone solvent is 0.1-2 g: 10 mL; the mass-to-volume ratio of component B to N-methylpyrrolidone solvent is 0.1-5 g: 10 mL.

7. The preparation method according to claim 5, characterized in that, In step S2, the mass-to-volume ratio of the modified polymer matrix to water is 0.1-2 g:10 mL; the mass-to-volume ratio of the inorganic crosslinking agent to water is 0.01-1 g:10 mL; and the inorganic crosslinking agent is sodium calcium borosilicate.

8. The high oil-loading temperature-sensitive biphase gel according to any one of claims 1-4 or the high oil-loading temperature-sensitive biphase gel prepared by the method according to any one of claims 5-7, characterized in that, The oil loading capacity of the high oil-loaded temperature-sensitive biphase gel is ≥20wt%.

9. The use of the high oil-loading temperature-sensitive biphasic gel according to any one of claims 1-4 or the high oil-loading temperature-sensitive biphasic gel prepared by the method according to any one of claims 5-7 in the preparation of medical products or cosmetics.

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