A composite material of aldehyde benzoic acid grafted capsaicin coupled with collagen and a preparation method and application thereof

Abstract

This invention discloses a composite material of aldehyde-benzoic acid grafted with sorbitan and coupled with collagen, its preparation method, and its application, belonging to the field of biomedical materials technology. The composite material is constructed by a Schiff base reaction between sorbitan modified with p-aldehyde-benzoic acid and collagen; wherein, by introducing an active aldehyde group into the p-aldehyde-benzoic acid, it can undergo a Schiff base reaction with the amino groups in the collagen molecule, thereby achieving efficient binding of sorbitan and the collagen matrix. The preparation method involves: using carbodiimide as a condensing agent to achieve an esterification reaction between sorbitan and p-aldehyde-benzoic acid, followed by coupling with collagen under weakly alkaline conditions, and improving structural stability through reduction treatment. This invention effectively solves the problems of poor stability, easy loss, and weak binding force of sorbitan with collagen, obtaining a functional composite material with excellent antioxidant properties, antibacterial properties, ultraviolet absorption properties, good biocompatibility, and structural stability.

Description

Technical Field

[0001] This invention relates to the field of natural active molecule modification and biomedical materials technology, specifically to a composite material of aldehyde benzoic acid grafted with sorbitol and collagen coupled with the same and its preparation method and application. Background Technology

[0002] Sanshools are a class of unsaturated amide-type natural bioactive molecules derived from the pericarp of plants in the genus *Zanthoxylum* spp., mainly including structural variants such as α-sanshool, β-sanshool, and hydroxy-α-sanshool. Studies have shown that sanshools possess significant free radical scavenging ability, anti-inflammatory properties, and UV protection, indicating broad application prospects in dermatology and cosmetic medicine. However, the presence of reactive unsaturated double bonds and phenolic hydroxyl groups in the sanshool molecule makes it highly susceptible to oxidative degradation in aqueous systems and under light conditions. Furthermore, its high lipid solubility makes it difficult to maintain stable activity in physiological environments, severely limiting its practical application in the biomedical field.

[0003] Collagen is the most abundant structural protein in mammals, accounting for approximately 30% of total protein. Its triple-helix structure provides excellent mechanical support, while its abundant hydroxyproline (Hyp), lysine (Lys), and arginine (Arg) residues provide excellent cell recognition sites, giving it outstanding biocompatibility and tissue repair-promoting capabilities. However, natural collagen has relatively limited functions and lacks active antioxidant capacity, making it difficult to exert a sufficient effect on promoting skin regeneration in the oxidative stress microenvironment.

[0004] In existing technologies, the main ways to introduce fat-soluble active small molecules such as sorbitol into collagen systems include physical blending and microemulsion encapsulation. However, these methods have problems such as weak binding force, easy rapid loss in aqueous environment (72 h release rate >60%), and uneven dispersion of active ingredients, which makes it difficult for the antioxidant properties of composite materials to be sustained.

[0005] Therefore, developing a method to achieve stable covalent binding between sorbitan and collagen, and constructing functional composite materials that combine sustained antioxidant activity with good biocompatibility, is of great scientific significance and application value. Summary of the Invention

[0006] This invention provides a sanshool-collagen composite material, its preparation method, and its application, to solve the technical problems of poor stability, easy loss, and insufficient binding strength of sanshool with collagen in the prior art.

[0007] To achieve the above objectives, in a first aspect, the present invention provides a method for preparing a composite material of aldehyde benzoic acid grafted with sorbitol and collagen, comprising the following steps: S1. Mix sorbitan and aldehyde benzoic acid in an organic solvent and carry out a grafting reaction using carbodiimide as a condensing agent to obtain aldehyde benzoic acid grafted sorbitan. S2. Dissolve the aldehyde-benzoic acid grafted with sorbitol from step S1 in a buffer solution and mix it with a collagen solution. Under weakly alkaline conditions, the mixture reacts to allow the aldehyde group to condense with the collagen amino group to form a Schiff base (–CH=N–) structure. S3. Add sodium cyanoborohydride (NaBH3CN) to the product of step S2 for reduction treatment to convert the Schiff base bond into a stable C–N single bond; S4. The product from step S3 is purified by dialysis and freeze-dried to obtain the target composite material.

[0008] As a further preferred embodiment of the present invention, the sanshool is hydroxy-α-sanshool, the carbodiimide is N,N'-dicyclohexylcarbodiimide (DCC) or N,N'-diisopropylcarbodiimide (DIC); and / or, 4-dimethylaminopyridine (DMAP) is used as a catalyst in the grafting reaction for preparing aldehyde benzoic acid grafted sanshool.

[0009] As a further preferred technical solution of the present invention, in step S1: the molar ratio of sanshool to aldehyde benzoic acid is 1:(1.0~1.5); the reaction solvent is dichloromethane (DCM) or N,N-dimethylformamide (DMF); the grafting reaction temperature is 20~30℃, and the reaction time is 12~24 h.

[0010] As a further preferred technical solution of the present invention, in step S2, the mass ratio of aldehyde benzoic acid grafted with sanshool to collagen is 1:(1-5), preferably 1:(2-4).

[0011] As a further preferred technical solution of the present invention, in step S2, the concentration of the collagen solution is 1-5 mg / mL, the solvent is 0.05-0.3 mol / L phosphate buffer (PBS) or 0.2-0.7 mol / L acetic acid solution; and / or, the condensation reaction conditions are: pH 7.0-8.5, temperature 20-37℃, and reaction time 6-12 h.

[0012] As a further preferred technical solution of the present invention, in step S3, each milligram of collagen corresponds to an addition of 0.05 to 0.2 mg of sodium cyanoborohydride; and / or, the reduction treatment time is 2 to 4 h, and the temperature is 25 to 37°C.

[0013] As a further preferred technical solution of the present invention, step S4 specifically involves: using a dialysis bag with a molecular weight cutoff of 3500 Da for dialysis, dialyzing in 0.05~0.3 mol / L PBS buffer for 24~48 h, changing the buffer every 6~8 h; and freeze-drying at a temperature of -45~-65℃, with a vacuum degree of less than 10 Pa, for a drying time of 24~48 h.

[0014] According to a second aspect of the present invention, the present invention also provides a composite material of aldehyde benzoic acid grafted with sanshool and collagen, which is prepared by the preparation method of the first aspect described above.

[0015] According to a third aspect of the present invention, the present invention also provides the application of the above-mentioned composite material of aldehyde benzoic acid grafted with sanshool and collagen in the preparation of skin repair materials, anti-photoaging materials or antioxidant medical dressings.

[0016] According to a fourth aspect of the invention, the invention also provides a functional biomaterial comprising a composite material of aldehyde benzoic acid grafted with sanshool and collagen, as described in the second aspect.

[0017] According to a fifth aspect of the present invention, the present invention also provides a method for preparing a functional biomaterial, comprising further processing the composite material of aldehyde benzoic acid grafted with sanshool and collagen of the second aspect into a hydrogel, film or porous structure material.

[0018] In one alternative embodiment, the hydrogel is obtained by self-assembly at room temperature after dissolving the composite material in PBS buffer; the film is prepared by freeze-drying after casting the composite material; and the porous scaffold is prepared by directional freeze-drying after cross-linking the composite material.

[0019] Compared with the prior art, the present invention can achieve the following beneficial effects: This invention functionalizes sorbitan with aldehyde benzoic acid, introducing an active aldehyde structure. The aldehyde then undergoes a specific condensation reaction with the amino groups in collagen molecules, achieving stable covalent fixation of sorbitan within a collagen matrix. This approach effectively solves the core problem of the difficulty in stably loading active small molecules into collagen systems in existing technologies, resulting in functional biomaterials with high stability, good biocompatibility, and excellent antioxidant properties. Attached Figure Description

[0020] The present invention will now be described in further detail with reference to the accompanying drawings and specific embodiments.

[0021] Figure 1 This is the structural formula of the aldehyde-functionalized sanshool (ABA-San) of the present invention.

[0022] Figure 2 This is the ultraviolet absorption spectrum of sanshool.

[0023] Figure 3 The graph shows the test results of (a) DPPH removal rate and (b) ABTS removal rate of the composite material of the present invention.

[0024] Figure 4 This is a graph showing the cell survival rate test results of the composite material of this invention.

[0025] The objectives, features, and advantages of this invention will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0026] The specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings. It should be understood that the specific embodiments described herein are for illustration and explanation only and are not intended to limit the present invention.

[0027] Unless otherwise defined, the technical terms used in the following embodiments have the same meanings as commonly understood by those skilled in the art to which this invention pertains. Unless otherwise specified, the experimental reagents used in the following embodiments are conventional biochemical reagents; and the experimental methods described are conventional methods.

[0028] Materials and reagents: Hydroxy-α-sanshool (purity ≥98%, HPLC) was purchased from Chengdu Jicui; 4-formylbenzoic acid (purity ≥99%) was purchased from Shanghai Maclean Biochemical Technology Co., Ltd.; Type I collagen was purchased from Shanghai Maclean Biochemical Technology Co., Ltd. Collagen (from pigskin, purity ≥90%) was purchased from Guangzhou Saijun Biotechnology Co., Ltd.; N,N'-diisopropylcarbodiimide (DIC, purity ≥99%) was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.; 4-dimethylaminopyridine (DMAP, purity ≥99%) was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.; sodium cyanoborohydride (NaBH3CN, purity ≥98%) was purchased from Sigma-Aldrich (China); dichloromethane (DCM, chromatographic grade) and N,N-dimethylformamide (DMF, chromatographic grade) were purchased from Sinopharm Chemical Reagent Co., Ltd.; phosphate buffer (PBS, 0.1 mol / L, pH 7.4) was prepared in-house; DPPH (2,2-diphenyl-1-picrylhydrazyl) was purchased from Sigma-Aldrich; all other reagents were of analytical grade, and the experimental water was ultrapure water (18.2 MΩ·cm).

[0029] Example 1: a. Synthesis of benzoic acid grafted with sorbitol (ABA-San): (1) Weigh 270 mg (1.0 mmol) of salicornin (hydroxy-α-salicornin) and 180 mg (1.2 mmol) of 4-formylbenzoic acid (aldehyde benzoic acid), dissolve them in 20 mL of anhydrous dichloromethane, and stir at room temperature (25°C) under argon protection to ensure complete dissolution.

[0030] (2) DIC (189 mg, 1.5 mmol) and DMAP (12 mg, 0.1 mmol) were added to the above solution as condensing agent and catalyst, respectively. The reaction was carried out under argon protection and magnetically stirred at 25 °C for 24 h. The reaction progress was monitored by TLC (electrolyte: ethyl acetate / petroleum ether = 1:3).

[0031] (3) After the reaction was completed, the insoluble byproduct (diisopropylurea, DIU) was removed by filtration. The filtrate was washed successively with 5% sodium bicarbonate solution (2×20 mL) and saturated saline solution (2×20 mL), dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation under reduced pressure. The crude product was purified by silica gel column chromatography (DCM: methanol = 60-100:1).

[0032] (4) Collect the target fraction, concentrate by rotary evaporation, and vacuum dry (40℃, 24 h) to obtain the following: Figure 1 The aldehyde-functionalized sanshool (ABA-San) with the structure shown is a pale yellow solid powder with a yield of approximately 16.3%. Its UV absorption capacity was also tested, and the absorption spectrum is shown below. Figure 2 As shown.

[0033] b. Preparation of San-Col (San-Collagen Composite Material) (1) Dissolve the above-mentioned aldehyde benzoic acid grafted salicornin (ABA-San) (50 mg) in 1 mL DMF to prepare a homogeneous solution for later use.

[0034] (2) Dissolve type I collagen (150 mg) in 30 mL of 0.1 mol / L PBS buffer (pH 7.4), stir overnight at 4°C to fully dissolve, and prepare a 5 mg / mL collagen solution.

[0035] (3) The DMF solution of ABA-San was slowly added dropwise to the collagen solution under stirring (final DMF concentration <3 vol%). The pH of the system was adjusted to 8.0 ± 0.1 with 0.1 mol / L NaOH solution. The reaction was carried out in a constant temperature water bath at 37℃ with magnetic stirring for 12 h. The aldehyde group and the free amino group (mainly from lysine residue, –NH2) of the collagen molecular chain underwent a condensation reaction to form a Schiff base (–CH=N–) covalent bond.

[0036] (4) Add NaBH3CN (15 mg, 0.24 mmol) to the above reaction system and continue stirring at 37°C for 3 h to reduce the unstable Schiff base to a stable C–N single bond, thereby improving the long-term stability of the composite material.

[0037] (5) The product was transferred into a dialysis bag with a molecular weight cutoff of 3500 Da and placed in 5 L PBS buffer (pH 7.4, 0.1 mol / L) and dialyzed at 4 °C for 48 h. The buffer was changed every 8 h to completely remove free small molecules and DMF solvent. After dialysis, the product was pre-frozen at -80 °C for 4 h and then freeze-dried in a freeze dryer for 48 h (-55 °C, vacuum degree <10 Pa) to obtain a white loose powder of sanshool-collagen composite material (San-Col) and stored at -20 °C for later use.

[0038] Example 2: Preparation of a series of sorbitan-collagen composite materials with different ratios of sorbitan to collagen. The preparation method was basically the same as in Example 1, except that the amount of collagen was fixed (150 mg), and the mass ratio of sanshool (calculated as ABA-San) to collagen was set to 1:1, 1:2, 1:3, 1:4, and 1:5, respectively, to prepare 5 groups of sanshool-collagen composite material samples, which were numbered San-Col-1 to San-Col-5.

[0039] The free amino content (reflecting grafting efficiency) of each group of composite materials was determined by the ninhydrin method. The free amino reduction rate (%) was calculated as follows: (free amino content of blank collagen – free amino content of composite material) / free amino content of blank collagen × 100%. Simultaneously, the DPPH free radical scavenging rate of each group of composite materials was determined (1 mg / mL solution, method same as in Test Example 1). The results are shown in Table 1 below.

[0040] Table 1

[0041] Results analysis: ① Grafting efficiency: As the proportion of collagen increases, the decrease in free amino groups initially rises and then falls, reaching a peak at 1:3 (53.2±1.6%), indicating that the functional groups of sanshool and collagen are optimally matched at this ratio. When the ratio continues to increase, the amount of sanshool is insufficient to effectively occupy all available amino sites, leading to a decrease in grafting rate. ② Antioxidant activity: The DPPH scavenging rate tends to plateau between 1:3 and 1:5 (85.6%–86.1%), which is close to the level of pure sanshool (88.2%), indicating that the antioxidant activity of sanshool is basically preserved after covalent grafting. ③ Controlled Verification: The DPPH scavenging rate of San-Col-3 (85.6±1.5%) was significantly higher than that of pure collagen (9.3±1.2%), and also higher than the theoretical superposition value calculated by weighted ratio (at a 1:3 ratio, sanshool contributes approximately 25%×88.2% + collagen contributes approximately 75%×9.3%≈29.0%), far exceeding the theoretical superposition, demonstrating the synergistic effect brought about by covalent bonding (see detailed controlled analysis in Example 4). ④ Optimal Ratio: Considering both grafting efficiency (determining stability) and antioxidant activity, the optimal ratio of sanshool to collagen protein is 1:(2~4), with 1:3 being the best.

[0042] The following are further performance tests of the sanshool-collagen composite material sample prepared based on the above-mentioned sanshool (calculated as ABA-San) and collagen at a mass ratio of 1:3, as detailed below.

[0043] Test Example 1: Evaluation of Antioxidant Performance The San-Col composite material prepared in Example 1 and control samples (pure collagen Col and physical blend San / Col-mix) were used to prepare PBS dispersions at concentrations of 0.1, 0.25, 0.5, 0.75, and 1.0 mg / mL, respectively. The DPPH and ABTS free radical scavenging rates were then determined using the following methods. The physical blend San / Col-mix was a direct blend of sanshool and collagen at a 1:3 mass ratio without chemical coupling.

[0044] DPPH free radical scavenging rate determination: Each concentration of sample solution (0.1 mL) was mixed with an equal volume of 0.1 mmol / L DPPH ethanol solution, reacted at 37°C for 30 min in the dark, and the absorbance was measured at 517 nm (Asample). An equal volume of anhydrous ethanol was used as a blank (Ablank), and pure ethanol was used as a control (Acontrol). Scavenging rate (%) = (Acontrol – Asample) / (Acontrol – Ablank) × 100%.

[0045] ABTS free radical scavenging rate determination: An ABTS•+ stock solution was prepared by mixing equal volumes of ABTS (7 mmol / L) and potassium persulfate (2.45 mmol / L) and reacting at room temperature in the dark for 12 h. Before measurement, the solution was diluted with PBS to an absorbance (734 nm) of 0.70 ± 0.02. Each sample solution (0.05 mL) was mixed with the ABTS•+ solution (1 mL), and reacted at room temperature in the dark for 6 min. The absorbance was measured at 734 nm. The results are shown in Table 2 below. Figure 3 As shown.

[0046] Table 2

[0047] Note: The theoretical superposition value was calculated at a 1:3 mass ratio: San contribution 25% × 88.2% + Col contribution 75% × 9.3% ≈ 29.0% (based on equal mass); here, the overall measured value of San-Col at a concentration of 1 mg / mL was compared with the control. ★The measured DPPH scavenging rate of San-Col (85.6%) was slightly lower than that of the equivalent pure sanshool (88.2%) (difference <3%), indicating that covalent grafting has minimal impact on the antioxidant activity of sanshool; compared with physical mixing (76.4%), San-Col was about 9 percentage points higher, and the difference was statistically significant (p < 0.05). More importantly, the advantage of San-Col is reflected in its long-term stability (see Test Example 3 and Test Example 4).

[0048] Test Example 2: Cell Compatibility Assessment (MTT Method) L929 mouse fibroblasts (ATCC CCL-1) were seeded at 5×10³ cells / well in 96-well plates and cultured in DMEM complete medium (10% FBS, 1% antibiotics) at 37°C in a 5% CO2 incubator for 24 h. After the cells adhered, the medium was changed.

[0049] The San-Col, San / Col-mix, and Col from Example 1 were prepared into culture medium solutions with concentrations of 0.05, 0.1, 0.25, 0.5, and 1.0 mg / mL, respectively. These solutions were then added to 96-well plates (100 μL per well) and cultured for 24 h and 48 h, respectively.

[0050] Add 10 μL of MTT solution (5 mg / mL) to each well and incubate for 4 h. Afterward, remove the culture medium, add 150 μL of DMSO to each well to dissolve the formazan crystals, shake to mix for 10 min, and measure the absorbance at 570 nm. Cell viability (%) = OD value of experimental group / OD value of control group × 100%. Results are as follows: Figure 4As shown, the cell compatibility of the three materials was all above 85%, indicating that the materials did not cause significant damage to the cells.

[0051] Test Example 3: Stability (Release) Control Experiment The cumulative release rate of sanshool under three material forms was quantitatively compared to demonstrate the stability advantage of covalent reduction (stabilizing C–N bonds) treatment.

[0052] ①San / Col-mix: Physical blend material (sanshool and collagen are directly blended at a mass ratio of 1:3, without chemical coupling); ②San-Col-NR: Unreduced covalent composite material (completed Schiff base coupling but not reduced by NaBH3CN, retaining reversible –CH=N– bonds); ③San-Col: The composite material obtained by the complete preparation process (Example 1) (Schiff base coupling followed by reduction to stable C–N bonds by NaBH3CN).

[0053] Experimental Methods: Samples from each group were accurately weighed (approximately 10 mg of salicornin equivalent) and placed in dialysis bags with a molecular weight cutoff of 3500 Da. The bags were immersed in 50 mL of PBS buffer (pH 7.4, 37℃, simulating a physiological environment) and shaken on a constant-temperature shaker (100 rpm). Samples were taken at 0, 6, 12, 24, 48, and 72 h (2 mL of the release solution was taken each time, and an equal volume of fresh PBS was added). The concentration of salicornin in the release solution was measured at 310 nm using a UV-Vis spectrophotometer (quantified using a standard curve), and the cumulative release rate was calculated. The results are shown in Table 3 below.

[0054] Table 3

[0055] Test Example 4: Effect of Reduction Treatment on Stability and Antioxidant Properties Experimental design: Three groups of samples—San-Col-NR (complete Schiff base coupling, unreduced), San-Col (stable C–N bond, reduced), and pure sanshool (San control)—were immersed in a simulated physiological environment (PBS, pH 7.4, 37℃) for 0, 24, 48, and 72 h, respectively. After immersion and drying, the DPPH free radical scavenging rate (1 mg / mL) of the samples was measured at each time point to investigate their long-term antioxidant activity maintenance. The results are shown in Table 4 below.

[0056] Table 4

[0057] Results Analysis. ① The DPPH scavenging rate of pure sanshool (San) in PBS decreased sharply from 88.2% to 41.3% after 72 h, a decrease of 53.1%, confirming that free sanshool is extremely unstable in an aqueous environment and is easily oxidized and degraded under aqueous systems and light conditions, making it difficult to maintain stable activity in a physiological environment. ② The DPPH scavenging rate of the unreduced covalent material (San-Col-NR) decreased from 84.1% to 43.2% after 72 h, a decrease of approximately 48.6%, similar to that of pure sanshool, indicating that the unreduced Schiff base bond is insufficient to prevent the degradation of sanshool after release. ③ The DPPH scavenging rate of the reduced covalent material (San-Col) decreased only 3.4% from 85.6% to 82.7% after 72 h, and still maintained 96.6% of the initial activity after 72 h, indicating that the introduction of stable C–N bonds enabled the long-term maintenance of the antioxidant activity of sanshool. Therefore, the reduction treatment step in this invention is a key innovative step. Its importance lies in converting the reversible Schiff base coupling into irreversible covalent fixation, which fundamentally solves the stability problem of sanshool in composite materials and extends the duration of the antioxidant activity of composite materials by more than 4 times (based on the time it takes for the activity to drop to 50% of the initial value, San-Col exceeds 72 h, San is about 48 h, and San-Col-NR is about 48 h).

[0058] While specific embodiments of the present invention have been described above, those skilled in the art should understand that these are merely illustrative examples, and various changes or modifications can be made to these embodiments without departing from the principles and essence of the present invention. The scope of protection of the present invention is defined only by the appended claims.

Claims

1. A method for preparing a composite material of aldehyde benzoyl acid grafted shogaol coupled with collagen, characterized by, Includes the following steps: S1. Mix sorbitan and aldehyde benzoic acid in an organic solvent and carry out a grafting reaction using carbodiimide as a condensing agent to obtain aldehyde benzoic acid grafted sorbitan. S2. Dissolve the aldehyde-benzoic acid grafted with sorbitol from step S1 in a buffer solution and mix it with a collagen solution. Under weakly alkaline conditions, the mixture reacts to allow the aldehyde group to condense with the collagen amino group to form a Schiff base structure. S3. Add sodium cyanoborohydride to the product of step S2 for reduction treatment to convert the Schiff base bond into a stable C–N single bond. S4. The product from step S3 is purified by dialysis and freeze-dried to obtain the target composite material.

2. The method for preparing the composite material of aldehyde benzoic acid grafted with sorbitol and collagen according to claim 1, characterized in that, The sanshool is hydroxy-α-sanshool, and the carbodiimide is N,N'-dicyclohexylcarbodiimide or N,N'-diisopropylcarbodiimide; And / or, 4-dimethylaminopyridine is used as a catalyst in the grafting reaction.

3. The method for preparing the composite material of aldehyde benzoic acid grafted with sorbitol and collagen according to claim 1, characterized in that, In step S1: the molar ratio of sanshool to aldehyde benzoic acid is 1:(1.0-1.5); the reaction solvent is at least one of dichloromethane and N,N-dimethylformamide; the grafting reaction temperature is 20-30℃ and the reaction time is 12-24h.

4. The method for preparing the composite material of aldehyde benzoic acid grafted with sorbitol and collagen according to claim 1, characterized in that, In step S2, the mass ratio of aldehyde benzoic acid grafted with sanshool to collagen is 1:(1-5).

5. The method for preparing the composite material of aldehyde benzoic acid grafted with sorbitol and collagen according to claim 1, characterized in that, In step S2, the concentration of the collagen solution is 1–5 mg / mL, and the solvent is 0.05–0.3 mol / L phosphate buffer or 0.2–0.7 mol / L acetic acid solution; And / or, the condensation reaction conditions are: pH 7.0–8.5, temperature 20–37℃, and reaction time 6–12 h.

6. The method for preparing the composite material of aldehyde benzoic acid grafted with sorbitol and collagen according to claim 1, characterized in that, In step S3, each milligram of collagen corresponds to an addition of 0.05–0.2 mg of sodium cyanoborohydride; And / or, the reduction treatment time is 2 to 4 hours, and the temperature is 25 to 37°C.

7. The method for preparing the composite material of aldehyde benzoic acid grafted with sorbitol and collagen according to claim 1, characterized in that, Step S4 is as follows: Dialysis is performed using a dialysis bag with a molecular weight cutoff of 3500 Da, in 0.05~0.3mol / L PBS buffer for 24~48 h, with the buffer changed every 6~8 h; freeze-drying temperature is -45~-65℃, vacuum degree is less than 10 Pa, and drying time is 24~48 h.

8. A composite material of aldehyde benzoic acid grafted with sorbitan and collagen, characterized in that, It is prepared by the preparation method according to any one of claims 1-7.

9. The application of the composite material of aldehyde benzoic acid grafted with sorbitol and collagen as described in claim 8 in the preparation of skin repair materials, anti-photoaging materials or antioxidant medical dressings.

10. A functional biomaterial, characterized in that, The functional biomaterial comprises a composite material of aldehyde benzoic acid grafted with sorbitol and collagen.

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