Fish skin collagen extract and its use in anti-aging and anti-wrinkle

Abstract

This invention provides a fish skin collagen extract and its application in anti-aging and anti-wrinkle treatments, belonging to the field of biomedical materials. This invention utilizes biomimetic mineralization technology, using collagen fibers as templates to guide the in-situ growth of zeolite molecular sieves, constructing a nano-confined reactor, and then employing a vitamin C / copper ion catalytic system for directional shearing to precisely prepare collagen peptides with molecular weights concentrated in the 1000-1500 Da range. This extract possesses excellent functions in promoting collagen synthesis, anti-oxidation, anti-glycation, and repairing the skin barrier, solving the problems of existing collagen peptide products such as a single anti-aging mechanism, wide molecular weight distribution, uncontrollable activity, and potential sensitization. The preparation process of this invention is simple and mild, and the product has high activity and good safety, making it suitable for preparing high-end anti-aging and anti-wrinkle cosmetics.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials, specifically to a fish skin collagen extract and its application in anti-aging and anti-wrinkle. Background Technology

[0002] Collagen peptides are natural, biodegradable polymers. Fish collagen peptides, especially those extracted from fish skin, possess excellent biocompatibility and absorbability, effectively fulfilling their functions of penetration, moisturizing, and repair. Most fish collagen peptides contain three active peptide segments: collagen tripeptide, Gly-Pro-X sequence active peptide, and antioxidant active peptide. Gly represents glycine, Pro represents proline, and X represents other amino acids. These three active peptide segments can promote the synthesis of type I collagen and elastin fibers, inhibit collagen degradation and damage, scavenge free radicals, and inhibit tyrosinase activity. All of these contribute to enhancing the skin's anti-aging and anti-wrinkle capabilities. Therefore, fish skin collagen extract is an excellent biomaterial for anti-aging and anti-wrinkle treatment.

[0003] Currently, the commonly used fish skin raw materials for preparing anti-wrinkle and anti-aging products mainly come from cod, tilapia, and salmon. Among them, cod skin collagen peptides have excellent collagen synthesis-promoting efficiency, salmon skin collagen peptides have excellent antioxidant activity, and tilapia skin collagen peptides have good thermal stability and a good source of raw materials. CN120694909A discloses an eye cream prepared using cod collagen peptides as raw material. In this method, cod collagen peptides are mixed with eye cream lotion raw materials such as glycerin and synthetic squalane to prepare an anti-wrinkle eye cream with antioxidant and moisturizing capabilities. CN117426996B discloses an anti-wrinkle peptide composition using tilapia skin as raw material. Tilapia skin collagen peptides are extracted by a complex hydrolysis method involving acid, alkali, and enzymes, and then combined with Zn. 2+ and Cu 2+ Chelation was also incorporated, along with a corn protein peptide-hyaluronic acid-pantothenic acid complex, to prepare an anti-wrinkle peptide composition. When this composition is formulated into an anti-wrinkle skincare lotion, it exhibits excellent moisturizing, fine line-reducing, and skin elasticity-improving effects. CN118902109A discloses a full-type collagen anti-aging composition for improving facial and neck wrinkles. Using cod collagen powder, ray collagen powder, salmon nasal cartilage powder, non-denatured type II collagen powder, and salmon hydrolyzed protein peptides as raw materials, an oral anti-wrinkle and anti-aging beverage was formulated. In rat experiments, it was found that rats that consumed this beverage showed a significant increase in type I / II / III collagen. In humans, the consumption also resulted in a significant improvement in facial and neck wrinkles.

[0004] In summary, fish skin collagen extract has shown good efficacy in the preparation of anti-aging and anti-wrinkle products. However, these products offer relatively limited effects and lack effective methods to address collagen glycation and hardening caused by high sugar levels. This reaction is a significant factor in reduced skin elasticity and wrinkle formation. Therefore, developing a novel collagen anti-aging and anti-wrinkle raw material that can work synergistically through multiple mechanisms and has a precisely controllable molecular weight range is a crucial issue that urgently needs to be addressed. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide a fish skin collagen extract and its application in anti-aging and anti-wrinkle effects. This invention uses mackerel skin as raw material to extract acid-soluble collagen. Subsequently, biomimetic mineralization and confined catalytic shearing techniques are employed to achieve precise shearing of collagen peptide chains and precise control of product molecular weight. This results in a fish skin collagen extract with highly concentrated molecular weight, possessing four functions simultaneously: promoting collagen synthesis, anti-oxidation, anti-glycation, and repairing the skin barrier.

[0006] This invention discloses a fish skin collagen extract, the specific technical solution of which is as follows: Step 1: Clean the mackerel skin and cut it into small pieces. Put it into an acetic acid solution of a specific concentration and stir continuously at low temperature. Then, centrifuge to collect the supernatant and adjust the pH to neutral with alkali solution. Concentrate the solution at low temperature using a rotary evaporator to finally obtain concentrated collagen solution.

[0007] Step 2: Tetraethyl orthosilicate, aluminum isopropoxide, and tetrapropylammonium hydroxide are dissolved in a solvent and stirred to form a homogeneous precursor sol, which is then mixed with the collagen solution and transferred to a high-pressure reactor for hydrothermal reaction. The reaction product is collected by centrifugation, washed with solvent, and dried to obtain a collagen-zeolite molecular sieve composite material.

[0008] Step 3: The composite material is uniformly dispersed in a buffer solution to form a suspension system. Then, a metal salt solution and an organic acid solution are added to the system in sequence. The mixture is then transferred to a constant temperature environment and continuously stirred to carry out a confined catalytic shear reaction.

[0009] Step 4: Centrifuge the mixture after the shear reaction to obtain a supernatant containing peptides. Pass the supernatant through an ultrafiltration membrane device with a specific molecular weight cutoff and collect the retentate. Concentrate the retentate under low temperature and reduced pressure, then transfer it to a freeze dryer for freeze drying to obtain a dry powdered final product.

[0010] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. This invention achieves precise cleavage of collagen peptide chains through the synergistic effect of a nano-confined reaction space constructed using biomimetic mineralization technology and a vitamin C / copper ion catalytic system. This ensures that the molecular weight of most products is strictly controlled within the ideal range of 1000-1500 Da, solving the technical problem of wide molecular weight distribution and unclear active ingredients in collagen peptides produced by traditional acid, alkaline, or enzymatic methods.

[0011] 2. Collagen peptides with a molecular weight in the range of 1000-1500 Da can significantly promote the synthesis of collagen I in human fibroblasts, exhibit excellent intracellular antioxidant activity, effectively inhibit the formation of advanced glycation end products (AGEs), and significantly upregulate the expression of skin barrier-related genes. This quadruple synergistic mechanism of "promoting synthesis + antioxidation + anti-glycation + barrier repair" achieves comprehensive intervention on multiple pathways of skin aging.

[0012] 3. This invention employs a one-step method to complete the pore-forming, catalytic, and shearing processes, integrating the multi-step processes required in traditional methods into a single reaction system. Compared to traditional processes that require complex template preparation and removal steps, this method has a clear process route, mild reaction conditions (room temperature and pressure), simple operation, and significantly reduced energy consumption. The entire process does not require expensive equipment or special reaction conditions, exhibits good process stability and reproducibility, and provides a reliable guarantee for industrial-scale production.

[0013] 4. Because the use of strong acids and alkalis is avoided in the preparation process, and the molecular weight range of 1000~1500Da is the optimal balance point between transdermal absorption and bioactivity, it ensures that the functional ingredients can reach the skin's target sites efficiently, making this extract particularly suitable for all skin types, including sensitive skin. Attached Figure Description

[0014] Appendix Figure 1 This is a flowchart illustrating the preparation process of fish skin collagen extract. Appendix Figure 2 This is a molecular weight distribution diagram of the sample from Example 1; Appendix Figure 3 This is a graph showing the effect of fish skin collagen extract on enhancing the anti-aging and anti-wrinkle capabilities of cells. Detailed Implementation

[0015] The following embodiments further explain and illustrate the technical solutions of the present invention. It should be specifically noted that each specific embodiment is a concretization and explanation of the technical solution and should not be considered as a limitation on the scope of protection of the present invention. Those skilled in the art still have the right to modify the technical solutions of these embodiments and make equivalent substitutions for some or all of the technical features, and these modifications or substitutions do not change the essence of the corresponding technical solutions, nor do they cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions described in the present invention.

[0016] This invention proposes a fish skin collagen extract, the specific technical solution of which is as follows: 1. Extraction of acid-soluble collagen Using mackerel skin as raw material, a low-concentration acetic acid solution was used for long-term extraction at low temperature. After centrifugation, the supernatant was collected, and the pH was adjusted to neutral before being concentrated by rotary evaporation at low temperature to obtain an acid-soluble collagen solution. Since acetic acid is a weak acid, using a low-concentration acetic acid solution for long-term extraction at low temperature effectively dissolves collagen fibers while minimizing damage to the natural triple helix structure of collagen, preserving its complete biological activity. This facilitates the acquisition of intact long-chain collagen molecules, providing a suitable substrate for subsequent precise tailoring within a confined space, and achieving precise control over the molecular weight of the final product. Adjusting the pH to neutral and concentrating after extraction also creates a suitable environment and provides sufficient collagen concentration for subsequent biomimetic mineralization reactions.

[0017] 2. Preparation of zeolite molecular sieve precursors and biomimetic mineralization reaction A zeolite molecular sieve precursor sol was prepared using tetraethyl orthosilicate as the silicon source, aluminum isopropoxide as the aluminum source, and tetrapropylammonium hydroxide as the structure directing agent and alkali source. This sol was then mixed with a concentrated collagen solution and subjected to a hydrothermal reaction in a high-pressure reactor. After washing and drying, the reaction product yielded a collagen-zeolite composite material. Using collagen fibers as an organic template, zeolite molecular sieves were guided to crystallize in situ on their surface and within, forming an organic-inorganic hybrid composite material. The zeolite phase provided uniform nanoscale channels with a diameter of approximately 1.5 nm, confining the long collagen chains within. This physical confinement effect fundamentally predetermined the upper limit of the final shear product size, allowing for precise control of the final product's molecular weight. After washing with deionized water and organic solvents, unwanted free polypeptide chains were removed, leaving only the zeolite framework and the collagen peptides fixed within it.

[0018] 3. Confined catalytic shear reaction Collagen-zeolite composite material was dispersed in a neutral buffer solution, and a catalytic system composed of vitamin C and copper ions was added. The mixture was then transferred to a constant-temperature environment and continuously stirred to achieve confined shearing of collagen. Vitamin C and copper ions in the system can form a Fenton-like system, which catalyzes the oxidative shearing of collagen molecular chains within a limited spatial region. The reactive oxygen species generated by this system under mild conditions are confined within the nanopores of the zeolite, and can only randomly cleave local collagen peptide bonds. However, this cleavage effect is spatially constrained, thus avoiding excessive hydrolysis that occurs in free solution. It is like cutting within a mold, ultimately generating peptides (1000~1500 Da) with highly uniform molecular weight that match the pore size. This overcomes the shortcomings of traditional enzymatic hydrolysis methods, which have fixed cleavage sites and may still have a wide molecular weight distribution of the product.

[0019] 4. Separation, purification and post-processing of the product The reaction solution after catalytic shearing was centrifuged, and the supernatant rich in target peptides was collected. This supernatant was then separated using an ultrafiltration membrane with a molecular weight cutoff of 1000 Da. The retentate was collected, concentrated, and freeze-dried to obtain fish skin collagen extract with precisely controlled molecular weight. The generated peptide solution was separated from insoluble zeolite framework fragments by centrifugation. Subsequently, a 1000 Da ultrafiltration membrane was used to precisely enrich the 1000-1500 Da target peptides, while removing fragments with excessively small molecular weights and free amino acids, ensuring an extremely concentrated molecular weight range and high purity in the final product. The 1000-1500 Da collagen peptides are long enough to fold into specific spatial conformations, enabling them not only to act as efficient signal peptides binding to specific receptors (such as integrins) on fibroblast membranes to stimulate collagen regeneration, but also to possess specific amino acid residues (such as histidine and tyrosine) that endow them with the dual ability to scavenge free radicals and inhibit AGEs formation, making them key collagen peptides beneficial for anti-aging and wrinkle reduction.

[0020] The following are some specific embodiments of the present invention, and Table 1 shows the raw material information used in the embodiments.

[0021] Table 1 Raw Material Information Table Example 1 S1: Fresh mackerel skin was repeatedly rinsed with running deionized water to remove attached fish meat. The skin was then immersed in a 0.1 mol / L NaOH solution and stirred at 5°C for 4 hours. Afterward, it was rinsed with deionized water until neutral and then immersed in anhydrous ethanol at room temperature with shaking for 1 hour to remove subcutaneous fat tissue. The treated skin was then cut into 1 cm × 1 cm pieces and added to a 0.5 mol / L acetic acid solution at a material-to-liquid ratio of 1:10. The solution was slowly stirred at 100 rpm at 5°C for 48 hours. After the reaction was completed, the reaction solution was centrifuged and the supernatant was collected. The pH of the supernatant was adjusted to 7.0 with a 1 mol / L NaOH solution. The supernatant was then rotary evaporated in a 40°C water bath to concentrate the liquid volume to 1 / 4 of the original volume, resulting in a concentrated collagen solution.

[0022] S2: Take beaker A and beaker B. In beaker A, add 104.2 g (0.5 mol) tetraethyl orthosilicate, 4.08 g (0.02 mol) aluminum isopropoxide, and 400 mL anhydrous ethanol sequentially, and stir for 30 min to form a clear and transparent mixture. In beaker B, add 90 g tetrapropylammonium hydroxide solution and 270 g deionized water, and stir until homogeneous. While continuing to stir, slowly add the solution in beaker B dropwise to solution A. After the addition is complete, continue stirring for 2 h to obtain a homogeneous sol. Subsequently, 500 mL of the concentrated collagen solution prepared in S1 was mixed with the sol and stirred for 1 h. The mixture was then transferred to a reaction vessel and heated to 50 °C at a heating rate of 1 °C / min. The reaction was carried out at a constant temperature for 120 h. After the reaction was completed, the reaction vessel was naturally cooled to room temperature. The reactants were removed and centrifuged. The white precipitate was collected and washed three times with deionized water and anhydrous ethanol. The precipitate was then dried in a vacuum drying oven at 60 °C for 12 h to obtain the collagen-zeolite composite material.

[0023] S3: Weigh 20g of the composite material obtained in S2 and disperse it in 0.1mol / L phosphate buffer. Place the system in a 25℃ constant temperature water bath and stir at 200rpm for 2h. Then, add 20mL of 100mmol / L copper sulfate aqueous solution and 200mL of 1mol / L vitamin C aqueous solution to the system to make the Cu concentration in the system... 2+ The concentration ratio of vitamin C to vitamin C was 1:100. The system was allowed to react continuously for 8 hours while maintaining the temperature and rotation speed, yielding a vitamin C / Cu mixture. 2+ The system generates collagen peptide chains that are specifically cleaved by reactive oxygen species.

[0024] S4: Centrifuge the reaction solution and collect the supernatant. Pass the supernatant through an ultrafiltration membrane with a molecular weight cutoff of 1000 Da at a pressure of 0.25 MPa. Collect the retentate remaining on the ultrafiltration membrane and rotary evaporate it at 40 °C until the volume is concentrated to 1 / 10 of the original volume. Then, freeze it in an ultra-low temperature freezer at -80 °C for 5 hours, and then transfer it to a refrigerated dryer and freeze-dry it at -40 °C for 48 hours to obtain a powdered mackerel skin collagen extract. Then, take 1 mg of the sample, dissolve it in 0.1 mol / L phosphate buffer, and send it to gel permeation chromatography to determine its molecular weight distribution. The results are as follows. Figure 2 As shown.

[0025] Example 2 The preparation method is the same as in Example 1, except that: S2: The molar ratio of tetraethyl orthosilicate and aluminum isopropoxide is 15:1. The reaction vessel is heated to 35°C and the reaction time is 72h. S3: The concentration of the added vitamin C solution is 0.5 mol / L, and the rest of the steps are the same.

[0026] Example 3 The preparation method is the same as in Example 1, except that: S2: The molar ratio of tetraethyl orthosilicate and aluminum isopropoxide is 30:1. The reactor is heated to 70°C and the reaction time is 168h. S3: The concentration of the added vitamin C solution is 2 mol / L, and the rest of the steps are the same.

[0027] Example 4 The preparation method is the same as in Example 1, except that: S2: The molar ratio of tetraethyl orthosilicate to aluminum isopropoxide is 20:1. The reactor is heated to 60°C and the reaction time is 144h. S3: The concentration of the added vitamin C solution is 1.5 mol / L, and the rest of the steps are the same.

[0028] Comparative Example 1 The preparation method is the same as in Example 1, except that: S2: Add 1.0g of complex protease to 100mL of concentrated collagen solution prepared in S1. The complex protease consists of alkaline protease and flavor protease in a mass ratio of 1:1. Enzymatically hydrolyze for 4h at 50℃ and pH=7.0, then heat to 95℃ to inactivate the enzyme, centrifuge and collect the supernatant. Prepare powdered enzymatically hydrolyzed collagen extract from the supernatant according to step S4.

[0029] This comparative preparation uses fish skin collagen extract obtained by traditional enzymatic hydrolysis.

[0030] Comparative Example 2 The preparation method is the same as in Example 1, except that: Eliminate step S2 and directly mix the concentrated collagen solution obtained in S1 with Cu. 2+ Mix with vitamin C to induce a catalytic shearing reaction; the remaining steps are the same.

[0031] This comparative example prepares fish skin collagen extract without zeolite confinement.

[0032] Comparative Example 3 The preparation method is the same as in Example 1, except that: S3: Physically mix the concentrated collagen solution prepared in S1 with commercially available zeolite molecular sieves, then add copper sulfate solution and vitamin C solution to it, and the remaining steps are the same.

[0033] This comparative preparation uses physical mixing instead of biomimetic mineralization to obtain fish skin collagen extract.

[0034] Experimental Example 1 The fish skin collagen extracts prepared in Examples 1-4 and Comparative Examples 1-3 were dissolved in sterile, preheated to 37°C complete cell culture medium (DMEM high glucose, containing 10% fetal bovine serum FBS) to a concentration of 100 μg / mL.

[0035] The test was performed using human dermal fibroblasts HFF-1, with HFF-1 cells at a density of 1 × 10⁶ cells per well. 5 Cells were seeded at a density of [number] cells per well in 24-well plates. After 24 hours of culture and adherence, the original culture medium was discarded. Half of the culture medium was added to a medium containing fish skin collagen extract, and the other half was added to normal culture medium. Cells were cultured for another 48 hours. The supernatant from each well was collected and centrifuged at 3000 rpm for 10 minutes at 4°C. The concentration of total type I collagen N-terminal extended peptide (PINP) in the supernatant was measured. The PINP concentration in the medium containing the extract was designated C1, and the PINP concentration in the normal culture medium was designated C0. The type I collagen growth rate was calculated as follows: Type I collagen growth rate = Experiment Example 2 HFF-1 cells were added at a rate of 1 × 10⁶ cells per well. 5 The cells were seeded at a density of [number] cells / well in 24-well plates, and after 24 hours of incubation and adhesion, they were treated with ultraviolet light (UVA, 10 J / cm²). 2Cells were irradiated to establish a photoaging model, inducing high expression of matrix metalloproteinase-1 (MMP-1). Immediately after irradiation, the culture medium was replaced with one containing fish skin collagen extract. A control group was established, irradiated only with ultraviolet light but without the extract. After 24 hours of culture, cell supernatants were collected, and the MMP-1 content was measured. The MMP-1 content in the extract-containing medium was designated as D1, and the MMP-1 content in the control group was designated as D0. The inhibition rate of MMP-1 was calculated as follows: MMP-1 inhibition rate = ( ) Experimental Example 3 HFF-1 cells were seeded in black 96-well plates and cultured for 24 h. The culture medium was discarded, and the DCFH-DA probe was diluted with serum-free medium to a final concentration of 10 μM. 100 μL was added to each well, and the cells were incubated at 37°C for 45 min. The probe solution was discarded, and the cells were washed three times with serum-free medium. Experimental group A was serum-free medium with the extract added, control group B was medium with ordinary medium added, and control group C was ordinary medium without H2O2. Except for control group C, 200 μmol / L H2O2 was added to all other groups to induce oxidative stress. Immediately afterwards, the cell plates were placed in a microplate reader, and the fluorescence intensity F was measured every 5 min under excitation light of 485 nm and emission light of 535 nm for 1 h. The final ROS removal rate in the cells was calculated as follows: ROS removal rate = The test results are shown in Table 2.

[0036] Table 2 Results of in vitro anti-aging and anti-wrinkle tests From Table 2 and Figure 3 As can be seen, the sample from the examples showed superior ability to promote collagen synthesis, resist oxidation, and inhibit collagen degradation compared to the comparative sample. The products in the comparative samples had disordered molecular weights, with only a small number of peptides being useful for anti-aging and wrinkle reduction. Most peptides were ineffective and may even contain interfering fragments. Therefore, the anti-aging and wrinkle reduction capabilities of the comparative samples were not improved and may even have decreased. Comparative Example 1 used a traditional enzymatic hydrolysis method to prepare the extract. Due to the randomness of the enzyme cleavage sites and the uncontrollability of molecular weight distribution, the final product was a complex mixture of peptides with different molecular weights, resulting in limited and unstable effects in anti-oxidation and anti-glycation functions. Comparative Example 2 was a product obtained by direct catalytic shearing without zeolite confinement. Without the physical restriction of zeolite channels, the collagen peptide chains, regardless of length, remained in the solution after shearing and continued to react, easily being over-sheared into smaller fragments. Furthermore, Cu... 2+The free radicals generated by vitamin C diffuse throughout the solution, and their collisions and cleavage with collagen chains are completely random. Therefore, the final product is a mixture with a wide molecular weight distribution, resulting in the worst effect. Comparative Example 3 is an extract prepared solely by the physical mixing of collagen and zeolite molecular sieves. Collagen molecules can only be adsorbed on the outer surface of zeolite particles, resulting in very low efficiency and control of catalytic shearing. The molecular weight distribution of the product is very wide, and it contains almost no enriched target active peptides. However, some peptides can still enter the zeolite pores through the flow in the liquid phase, so it will contain some peptides that have been precisely catalytically sheared, which has a certain positive effect on anti-aging and anti-wrinkle effects.

Claims

1. A fish skin collagen extract, characterized in that: The extract is prepared by converting raw materials into weakly acid-soluble collagen, then using a biomimetic mineralization reaction to form an organic-inorganic hybrid composite material, confining the collagen in nanoscale channels, and finally catalytically shearing collagen peptides in a confined environment to form peptides within a narrow molecular weight range. After separation and purification, the target extract is obtained.

2. The fish skin collagen extract according to claim 1, characterized in that, It is prepared through the following steps: S1: Clean the fish skin and cut it into small pieces. Put it into an organic acid solution and stir continuously at low temperature. Then, centrifuge to collect the supernatant and adjust the pH to neutral with alkali solution. Concentrate the solution at low temperature using a rotary evaporator to obtain concentrated collagen solution. S2: The silicon source and aluminum source, which are used as zeolite molecular sieve precursors, and the structure directing agent are dissolved together in a solvent, stirred to form a uniform precursor sol, and mixed with the concentrated collagen liquid obtained in S1. The mixture is then transferred to a high-pressure reactor for hydrothermal reaction. The reaction product is collected by centrifugation, washed with solvent and dried to obtain collagen-zeolite molecular sieve composite material. S3: The composite material obtained in S2 is uniformly dispersed in a buffer solution to form a suspension system. Then, a catalytic shear reaction system is added to the suspension system. The mixture is then transferred to a constant temperature environment and continuously stirred to carry out a confined catalytic shear reaction. S4: Centrifuge the mixture after the shear reaction to separate the supernatant containing peptides. Collect the retentate through an ultrafiltration membrane device with a specific molecular weight cutoff. Concentrate the retentate under low temperature and reduced pressure, and then transfer it to a freeze dryer for freeze drying to obtain a dry powdered final product.

3. The fish skin collagen extract according to claim 2, characterized in that: The organic acid solution mentioned in S1 is an acetic acid solution.

4. The fish skin collagen extract according to claim 2, characterized in that: The silicon source of the zeolite molecular sieve precursor described in S2 is tetraethyl orthosilicate, the aluminum source is aluminum isopropoxide, and the structure directing agent is tetrapropylammonium hydroxide.

5. The fish skin collagen extract according to claim 2, characterized in that: In the zeolite molecular sieve precursor described in S2, the molar ratio of tetraethyl orthosilicate to aluminum isopropoxide is 15:1 to 30:1, the hydrothermal reaction temperature is 35 to 70°C, and the reaction time is 72 to 168 h.

6. The fish skin collagen extract according to claim 2, characterized in that: The catalytic shearing reaction system described in S3 consists of vitamin C and Cu 2+ constitute.

7. The fish skin collagen extract according to claim 2, characterized in that: In the catalytic shear reaction system described in S3, Cu 2+ The concentration ratio with vitamin C is 1:50 to 1:

200.

8. The fish skin collagen extract according to claim 2, characterized in that: The ultrafiltration membrane described in S4 is a 1000 Da ultrafiltration membrane.

9. The fish skin collagen extract according to claim 2, characterized in that: The retentate in S4 is collagen peptides with a molecular weight in the range of 1000~1500 Da.

10. The application of a fish skin collagen extract according to any one of claims 1 to 9 in anti-aging and anti-wrinkle effects, characterized in that: The fish skin collagen extract can be added to anti-aging and anti-wrinkle drugs as a main ingredient or excipient.

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