Antioxidant and anti-allergic tissue natural collagen complex injectable solution, its preparation method and application

Abstract

This invention discloses an injectable composite solution of antioxidant and anti-allergic tissue-like natural collagen, its preparation, and its application, belonging to the field of biomedical materials technology. It integrates oxidized hyaluronic acid, tissue-like natural collagen, and quercetin, which synergistically enhance the stability, antioxidant, and anti-allergic capabilities of the composite injectable solution, promoting tissue repair. Multiple immersions ensure the purity of the tissue-like natural collagen, preserving its natural aggregated spatial structure and bioactivity. Cross-linking of the tissue-like natural collagen with sodium periodate-oxidized hyaluronic acid enhances bioactivity and stability, prolongs in vivo retention time, and improves moisturizing and lubricating effects, helping to promote the self-repair and regeneration of skin or joint tissues. The introduction of quercetin significantly enhances antioxidant and anti-allergic properties. This composite injectable solution overcomes the problems of short-lasting effects and high allergy risks associated with traditional collagen, and its natural components reduce rejection reactions, providing a new option for medical aesthetic filling, joint treatment, and other fields, demonstrating broad application prospects.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to an antioxidant and anti-allergic tissue natural collagen composite injectable solution, its preparation method, and its application. Background Technology

[0002] With the continuous advancement of modern medical technology, injectable solutions, as a highly efficient and flexible method of drug delivery, have been widely used in aesthetic medicine, joint treatment, ophthalmic surgery, pain management, and the treatment of various diseases. Collagen, as a key component, plays a crucial role in injection therapy due to its natural compatibility and bioactivity with human tissues. However, traditional collagen injection solutions still have some limitations in their application. Significant progress has been made in overcoming these limitations with novel collagen injection solutions and their preparation methods, but some technical challenges remain. Collagen, as a major component of tissues such as skin, bones, and joints, possesses natural compatibility and bioactivity similar to human tissues. In the field of aesthetic medicine, collagen injection solutions can be used to replenish collagen lost due to aging or disease, restoring tissue elasticity and firmness, and improving skin appearance. In joint treatment, it can address issues such as articular cartilage repair, joint pain relief, improved joint function, and relief of joint effusion.

[0003] Traditional collagen injections, containing only collagen components, are often rapidly absorbed and metabolized by the body, making it difficult to maintain therapeutic effects for extended periods. Frequent injections are required to maintain the effect, increasing treatment costs and inconvenience for patients. Furthermore, allergic reactions to collagen in some individuals limit the wider application of collagen injections. Although modern technology has reduced the risk of sensitization through methods such as allergen removal and collagen purification, further improvements are still needed.

[0004] Significant progress has been made in the preparation process of novel collagen injections, overcoming the limitations of traditional methods. More complex steps and processes have improved product quality and stability. By removing allergens and purifying collagen, the sensitization risk of novel collagen injections has been effectively reduced. However, some technical challenges remain. The preparation process of novel collagen injections is often complex, involving multiple steps and processes. Due to the numerous variables involved in the preparation process, quality control is difficult, which not only increases preparation costs but also affects product stability and consistency. The natural triple helix structure and aggregated spatial structure of collagen are still damaged to varying degrees during extraction, purification, and preparation, leading to a decrease in collagen's resistance to enzymatic degradation and its mechanical properties, thus affecting its stability and persistence in vivo. Collagen easily loses its original biological activity during preparation, affecting its therapeutic efficacy. How to effectively protect the biological activity of collagen and prevent its destruction during preparation is a pressing technical problem. Although the risk of sensitization is reduced, some individuals may still experience allergic reactions to collagen, and novel collagen injections may also pose other safety concerns. Therefore, there is an urgent need to develop a composite injection with strong stability, good mechanical properties, and the ability to promote tissue repair and regeneration, achieving longer-lasting therapeutic and self-repair effects while enhancing antioxidant and anti-allergic properties. Summary of the Invention

[0005] To address the shortcomings of existing collagen injection solutions, such as short-lasting effects, susceptibility to sensitization, and insufficient performance due to the lack of natural aggregated structures, there is an urgent need to develop a composite injection solution with high stability, good mechanical properties, and the ability to promote tissue repair and regeneration, achieving longer-lasting therapeutic and self-repair effects while enhancing antioxidant and anti-allergic properties. This invention aims to provide an antioxidant and anti-allergic tissue-derived natural collagen composite injectable solution, its preparation method, and its applications.

[0006] To achieve the above objectives, the present invention employs the following technical solution:

[0007] This invention provides an antioxidant and anti-allergic injectable solution of tissue-like natural collagen complex, comprising 4-20 parts of oxidized hyaluronic acid aqueous solution, 20-100 parts of tissue-like natural collagen, and 45-50 parts of quercetin ethanol solution.

[0008] The mass concentration of the oxidized hyaluronic acid aqueous solution is 6%-20%;

[0009] The molar concentration of the quercetin ethanol solution is 10 g / L to 20 g / L;

[0010] The oxidized hyaluronic acid has the following structural formula:

[0011]

[0012] The preparation method of the above-mentioned antioxidant and anti-allergic tissue natural collagen complex injectable solution includes:

[0013] S1, tissue-like natural collagen is prepared through multiple immersion processes;

[0014] S2, using sodium periodate to prepare oxidized hyaluronic acid;

[0015] S3, mix the oxidized hyaluronic acid from step S2 with the tissue-like natural collagen from step S1, adjust the pH value for cross-linking, and obtain mixed solution 1;

[0016] S4. Add the mixed solution 1 obtained in step S3 to the quercetin ethanol solution to react and obtain an antioxidant and anti-allergic tissue natural collagen complex injectable solution.

[0017] The preparation of the tissue-like natural collagen includes: pretreating animal connective tissue, soaking it in Tris-NaCl buffer solution and acetone in sequence and then washing it; then soaking it in a composite solution of NaCl and sodium dodecyl sulfate, pulverizing it and soaking it in acetic acid solution, and homogenizing it to obtain tissue-like natural collagen.

[0018] Furthermore, the impregnation temperature is 37℃, the impregnation time in the Tris-NaCl buffer solution is 3–10 h, and the pH value of the Tris-NaCl buffer solution is 7–8; the acetone impregnation time is 5–10 h; in the impregnation of the composite solution of NaCl solution and sodium dodecyl sulfate, the volume ratio of NaCl solution to sodium dodecyl sulfate is 1:2, wherein the molar concentration of NaCl is 1M–2M, the mass concentration of sodium dodecyl sulfate is 0.2%–1%, and the impregnation time is 3 h–5 h; the pulverization frequency is 20 kHz–25 kHz for 2 h–5 h; and in the acetic acid solution impregnation, the molar concentration of the acetic acid solution is 0.5–1M, and the impregnation time is 5 h–10 h.

[0019] The preparation of oxidized hyaluronic acid using sodium periodate includes: immersing 1-20 parts by weight of hyaluronic acid in 300-800 parts by weight of sodium periodate solution, stirring in the dark; dialyzing; and freeze-drying to obtain oxidized hyaluronic acid.

[0020] Furthermore, the light-protected stirring conditions are: stirring at 50℃~70℃ for 1h~10h; the dialysis uses a dialysis bag with a molecular weight cutoff of 6000-8000, the dialysis time is 3~5 days, and the water is changed 2-4 times a day.

[0021] The volume ratio of the mixed solution 1 to the quercetin ethanol solution is 1:1 to 3:1, and the pH value is adjusted to 5.0-8.5.

[0022] Furthermore, the volume ratio of mixed solution 1 to quercetin ethanol solution is 1:2.

[0023] The reaction conditions are 36℃~38℃ with continuous shaking for 22h~26h.

[0024] The above-mentioned antioxidant and anti-allergic tissue natural collagen complex injection can be used in the preparation of medical aesthetic and joint treatment drugs.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] This invention provides an antioxidant and anti-allergic tissue-like natural collagen composite injectable solution, comprising an aqueous solution of oxidized hyaluronic acid, tissue-like natural collagen, and a quercetin ethanol solution. Through the synergistic effect of these components, the stability, antioxidant properties, and anti-allergic effects of the tissue-like natural collagen composite injectable solution are improved, while simultaneously promoting tissue repair and regeneration. Oxidized hyaluronic acid enhances the bioactivity and stability of hyaluronic acid, helping to prolong the retention time of the injectable solution in the body. Tissue-like natural collagen retains the aggregated spatial structure of natural collagen, improving its stability and mechanical properties in vivo. Quercetin, as an antioxidant and anti-allergic component, further enhances the biocompatibility and safety of the injectable solution, improving its hydrophilicity and biocompatibility, making it easier for tissues to absorb and utilize, thus further improving the therapeutic effect. The three components combined in this tissue-like natural collagen composite injectable solution exhibits a more stable structure and properties, as well as better filling performance and anti-degradation capabilities.

[0027] The method for preparing the antioxidant and anti-allergic tissue-like natural collagen composite injectable solution provided by this invention is simple, quick, and highly reproducible. Through pretreatment and multiple soaking, impurities in animal connective tissue are effectively removed, ensuring the purity of the tissue-like natural collagen. This also helps maintain the natural structure and bioactivity of collagen, particularly preserving its aggregated spatial structure, which is crucial for improving the stability and mechanical properties of collagen in vivo. The oxidation of hyaluronic acid with sodium periodate enhances its bioactivity and stability. Combined with tissue-like natural collagen, this not only forms a stronger cross-linked structure but also produces a positive synergistic effect, resulting in a longer retention time and more lasting filling effect in the body. It also further improves moisturizing and lubrication effects, helping to promote the self-repair and regeneration of skin or joint tissues. The introduction of quercetin significantly enhances the antioxidant and anti-allergic properties of the tissue-like natural collagen composite injectable solution, reducing post-injection inflammatory and allergic reactions, improving patient comfort and safety, maintaining therapeutic effects for a longer period, reducing the need for frequent injections, and thus lowering treatment costs and time for patients.

[0028] Furthermore, impurities in animal connective tissue were effectively removed by immersion in Tris-NaCl buffer solution and acetone, ensuring the purity of collagen. At the same time, the immersion process was carried out at 37°C, which helped maintain the natural structure and bioactivity of collagen. Soaking in a composite solution of NaCl and sodium dodecyl sulfate further removed residual impurities. Pulverization and immersion in acetic acid solution made the collagen molecules more uniformly dispersed, improving the efficiency and effect of subsequent cross-linking reactions.

[0029] Furthermore, oxidation of hyaluronic acid with sodium periodate enhanced its bioactivity and stability. Light-protected stirring ensured the smooth progress of the oxidation reaction while preventing the degradation of photosensitive substances. Dialysis removed unreacted sodium periodate and other small-molecule impurities, improving the purity of the oxidized hyaluronic acid. Freeze-drying preserved its original structure and activity, facilitating subsequent complexation with collagen.

[0030] The present invention provides an injectable compound of natural collagen in tissues with antioxidant and anti-allergic properties. This injectable compound exhibits excellent technical effects in terms of stability, mechanical strength, tissue repair and regeneration, antioxidant and anti-allergic properties, hydrophilicity and biocompatibility, making it better adaptable to various tissue environments. It has broad application prospects and important clinical significance in the fields of medical aesthetics and joint treatment. Attached Figure Description

[0031] Figure 1 The present invention relates to a scanning electron microscope for natural collagen in tissues.

[0032] Figure 2 The growth of fibroblasts on different injectable solutions (1, 3 and 5 days) is shown, where a is a composite injectable solution prepared based on gelatin, b is a composite injectable solution prepared based on conventional collagen molecular materials, and c is the tissue natural collagen composite injectable solution of Example 3 of the present invention.

[0033] Figure 3 The degradation of different composite injectable solutions in bacterial collagen hydrolysate is shown in Figure 3. a is a composite injectable solution prepared based on gelatin, b is a composite injectable solution prepared based on conventional collagen molecular materials, and c is the composite injectable solution of tissue natural collagen in Example 3 of this invention.

[0034] Figure 4 The ability of different injectable solutions to scavenge DPPH free radicals was compared. Among them, a is a composite injectable solution prepared based on gelatin, and b is the tissue-natural collagen composite injectable solution of Example 3 of the present invention. Detailed Implementation

[0035] To enable those skilled in the art to better understand the present invention, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. 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 should fall within the scope of protection of the present invention.

[0036] The present invention will now be described in further detail with reference to the accompanying drawings:

[0037] Example 1

[0038] The preparation method of tissue-like natural collagen includes the following steps: Take 10g of animal connective tissue, carefully remove fat, residual muscle, fascia and other non-collagenous waste by hand, then cut it into small pieces of 5.0mm×5.0mm, and soak in Tris-NaCl buffer solution with pH 7.5 at 37℃ for 5h; then add acetone to submerge the tissue pieces, soak at 37℃ for 7h, recover the acetone, and wash the tissue pieces repeatedly with purified water 4 times; then place the tissue pieces in a composite solution of 1M NaCl solution (volume ratio 1:2 and mass concentration 1% sodium dodecyl sulfate) and soak for 4h, then place in a cell disruptor and process at a frequency of 25KHz for 3h; finally, place the above tissue pieces in a 1M acetic acid solution and soak for 8h, then homogenize with a disruptor for 8min until no tissue pieces are visible to the naked eye, and tissue-like natural collagen is obtained, which can be stored at 4℃ for later use.

[0039] The tissue-like collagen obtained in this embodiment was subjected to scanning electron microscopy testing, as detailed in the appendix. Figure 1 As shown.

[0040] From the appendix Figure 1 Data shows that the tissue-like collagen obtained by this invention exhibits a fibrous network weave structure, and the characteristic light and dark horizontal stripe D-periodic structure of the natural aggregated structure can be clearly identified. This indicates that the tissue-like collagen of this invention exhibits a highly organized fibrous network weave structure and retains the aggregated structure and D-periodic characteristics of natural collagen. It has high fidelity in both structure and performance and is expected to be widely used in biomedicine, tissue engineering and other fields.

[0041] Example 2

[0042] Weigh 1g of hyaluronic acid and immerse it in 300mL of 0.5% sodium periodate solution. Stir the solution at 50℃ for 1 hour under light-protected conditions. Dialyze the mixture for 3 days using a dialysis bag with a molecular weight cutoff of 6000, changing the water twice a day. After dialysis, freeze-dry the mixture to obtain oxidized hyaluronic acid.

[0043] Oxidized hyaluronic acid was prepared into an aqueous solution with a mass concentration of 6%. 4g of the aqueous solution of oxidized hyaluronic acid was weighed and mixed with 20g of the tissue-like natural collagen obtained in Example 1. 1mL of 1.0M sodium hydroxide solution was added dropwise and the solution was rapidly stirred at room temperature to adjust the pH to 5.0. Crosslinking was then carried out to obtain mixed solution 1.

[0044] Weigh 400 mg of quercetin and dissolve it in 40 mL of anhydrous ethanol. Sonicate the solution for 15 min to obtain a homogeneous quercetin ethanol solution. Add 1 mL of mixed solution 1 to 1 mL of quercetin ethanol solution and react at 36 °C with continuous shaking for 22 hours to obtain an antioxidant and anti-allergic tissue natural collagen complex injectable solution.

[0045] Example 3

[0046] Weigh 10g of hyaluronic acid and immerse it in 500mL of 1.5% sodium periodate solution. Stir the solution at 60℃ for 5 hours under light-protected conditions. Dialyze the mixture for 3 days using a dialysis bag with a molecular weight cutoff of 7000, changing the water 3 times a day. After dialysis, freeze-dry the mixture to obtain oxidized hyaluronic acid.

[0047] Oxidized hyaluronic acid was prepared into an aqueous solution with a mass concentration of 12%; 10g of the aqueous solution of oxidized hyaluronic acid was weighed and mixed with 60g of the tissue-like natural collagen obtained in Example 1, and 3mL of 1.0M sodium hydroxide solution was added dropwise. The solution was stirred rapidly at room temperature to adjust the pH to 7.0, and crosslinking was performed to obtain mixed solution 1.

[0048] Weigh 600 mg of quercetin and dissolve it in 40 mL of anhydrous ethanol. Sonicate the solution for 20 min to obtain a homogeneous solution, which is then used to obtain a quercetin ethanol solution. Add 1 mL of mixed solution 1 to 2 mL of quercetin ethanol solution and react at 37 °C with continuous shaking for 24 hours to obtain an antioxidant and anti-allergic tissue natural collagen complex injectable solution.

[0049] Example 4

[0050] Weigh 20g of hyaluronic acid and immerse it in 800mL of 2.67% sodium periodate solution. Stir the solution at 70℃ for 10 hours under light-protected conditions. Dialyze the mixture for 3 days using a dialysis bag with a molecular cutoff of 8000, changing the water 4 times a day. After dialysis, freeze-dry the mixture to obtain oxidized hyaluronic acid.

[0051] Oxidized hyaluronic acid was prepared into an aqueous solution with a mass concentration of 20%. 20g of the aqueous solution of oxidized hyaluronic acid was weighed and mixed with 100g of the tissue-like natural collagen obtained in Example 1. 5mL of 1.0M sodium hydroxide solution was added dropwise, and the solution pH was adjusted to 8.5 by rapid stirring at room temperature. Crosslinking was then carried out to obtain mixed solution 1.

[0052] Weigh 800 mg of quercetin and dissolve it in 40 mL of anhydrous ethanol. Sonicate the solution for 25 min to obtain a homogeneous solution, and obtain a quercetin ethanol solution. Add 1 mL of mixed solution 1 to 3 mL of quercetin ethanol solution and react at 38 °C with continuous shaking for 26 hours to obtain an antioxidant and anti-allergic tissue natural collagen complex injectable solution.

[0053] Example 5

[0054] (1) Effects of different injection solutions on cell proliferation and growth

[0055] Following the method described in national standard GB / T16175, fibroblasts (L929) were used as the model cells, and the MTT assay was employed to detect the samples. Specific results are detailed in the appendix. Figure 2 As shown.

[0056] From the appendix Figure 2 The data shows that, attached Figure 2 In the diagram, 'a' represents a composite injectable solution prepared using gelatin as a raw material, 'b' represents a composite injectable solution prepared using conventional collagen molecular materials as raw materials, and 'c' represents the tissue-like natural collagen composite injectable solution of Example 3 of this invention. At the same time points (1 day, 3 days, and 5 days), the cell density on the tissue-like natural collagen composite injectable solution was significantly higher than that on other composite injectable solutions. This indicates that the tissue-like natural collagen composite injectable solution provides superior growth conditions for cells, promoting rapid cell proliferation. The increased cell density not only reflects the cell growth rate but also demonstrates the supporting and promoting effect of the material on cell growth. The tissue-like natural collagen composite injectable solution of this invention highly mimics the structure and bioactivity of natural collagen. Natural collagen is a major component of the extracellular matrix and has a significant impact on cell growth, differentiation, and migration. The tissue-like natural collagen can better interact with cells, providing a growth microenvironment similar to natural tissue. Furthermore, the tissue-like natural collagen composite injectable solution of this invention also contains other bioactive factors or components, further promoting cell proliferation and growth.

[0057] Therefore, given the significant advantages of tissue-like natural collagen composite injectable solutions in promoting cell proliferation and growth, they have broad application prospects in biomedicine, tissue engineering, and other fields. For example, in tissue repair and regenerative medicine, this material can serve as a cell scaffold or carrier to promote the repair and regeneration of damaged tissues. Furthermore, tissue-like natural collagen composite injectable solutions can also be used in drug controlled-release systems, achieving precise drug release and long-term therapeutic effects by regulating the material's degradation rate and cell proliferation rate.

[0058] (2) Degradation of different injection solutions in bacterial collagen hydrolysate

[0059] Bacterial type I collagenase was dissolved in PBS buffer to prepare a type I collagenase degradation solution with a concentration of 2 mL / mg (1 U / mL). The samples were lyophilized and then immersed in the degradation solution. The degradation experiment was carried out in a 37°C constant temperature biochemical incubator.

[0060] From the appendix Figure 3 The data shows that, attached Figure 3 In the diagram, a represents a composite injectable solution prepared based on gelatin, b represents a composite injectable solution prepared based on conventional collagen molecular materials, and c represents the tissue-like natural collagen composite injectable solution of Example 3 of this invention. It is evident that the degradation rate of the tissue-like natural collagen composite injectable solution at the same time point is significantly lower than the other two composite injectable solutions, indicating that the tissue-like natural collagen composite injectable solution has stronger resistance to enzyme degradation. Strong resistance to enzyme degradation means that the material can maintain its structure and function in the in vivo environment for a longer period, which is particularly important for medical applications requiring long-term support or sustained-release of drugs. This characteristic of the tissue-like natural collagen composite injectable solution may stem from its molecular conformation, which is closer to the structure of natural tissues, and its more complex cross-linking mechanism, making it difficult for enzymes to easily destroy it.

[0061] Based on the degradation rate data mentioned above, it can be inferred that the tissue-like natural collagen composite injectable solution may have a longer support time in vivo. This is of great significance for applications such as tissue repair, regenerative medicine, and drug controlled-release systems that require long-term maintenance of structural integrity.

[0062] (3) Comparison of the ability of different injection solutions to scavenge DPPH free radicals during storage

[0063] The injectable compound of natural collagen from this invention and a compound injectable compound prepared from gelatin under the same conditions were stored in a humidity-controlled chamber at 20°C. After 2 and 30 days of storage, the injectable solutions were taken out for analysis. 0.1 g of the injectable solution was dissolved in 2 ml of distilled water at 45°C, and 4 ml of ethanol was added. The solution was then centrifuged at 4000×g for 10 min at 20°C in an Amicon Ultra-15 ultrafiltration centrifuge tube. The 1,1-diphenyl-2-pyridinium hydrazine (DPPH) free radical scavenging activity of the resulting filtrate was analyzed.

[0064] DPPH free radical scavenging activity was determined using a slightly modified Yen and Hsieh 28 method. 500 μL of the above ethanol extract was mixed with 5.5 mL of 0.036 mmol L⁻¹ DPPH ethanol, incubated at room temperature for 30 min, and the absorbance was measured at 517 nm using a spectrophotometer. The control was measured using the same method, but with ethanol instead of the sample. DPPH free radical scavenging activity was calculated using the following formula:

[0065] Free radical scavenging activity (%) = [1-(A s -A0) / Ac ]×100,

[0066] Where As is the absorbance of the sample, Ac is the absorbance of the control, and A0 is the absorbance of the mixture of 5.5 mL of ethanol and 500 μL of sample.

[0067] From the appendix Figure 4 The data shows that, attached Figure 4 In the diagram, 'a' represents a composite injectable solution prepared using gelatin as a raw material, and 'b' represents the tissue-based natural collagen composite injectable solution of Example 3 of this invention. The composite injectable solution prepared using gelatin as a raw material exhibits certain free radical scavenging activity, which is attributed to the fact that the peptide portion of gelatin contains specific amino acids, such as glycine and proline. However, the free radical scavenging activity of the tissue-based natural collagen composite injectable solution of this invention is significantly higher than that of the gelatin-based composite injectable solution. Quercetin, as a potent antioxidant, significantly enhances the overall antioxidant performance of the injectable solution.

[0068] After 30 days of storage, the free radical scavenging activity of both the tissue-like natural collagen composite injectable solution and the composite injectable solution prepared based on gelatin increased. However, the free radical scavenging activity of the tissue-like natural collagen composite injectable solution increased more significantly. This is because during storage, quercetin in the tissue-like natural collagen composite injectable solution is gradually released into the solution, thereby further enhancing its antioxidant capacity. This is of great significance for extending the shelf life of medical materials and enhancing their effectiveness.

[0069] In summary, the tissue-like natural collagen complex injectable solution exhibits superior free radical scavenging activity compared to gelatin-based injectable solutions, and its activity significantly improves during storage. This finding is of great significance for the development of medical materials, cosmetics, food, and health products with enhanced antioxidant capabilities.

[0070] The above content is only for illustrating the technical concept of the present invention and should not be construed as limiting the scope of protection of the present invention. Any modifications made to the technical solution based on the technical concept proposed in this invention shall fall within the scope of protection of the claims of this invention.

Claims

1. A method for preparing an anti-oxidative and anti-allergic tissue natural collagen complex injectable solution, characterized in that, The tissue-like natural collagen composite injectable solution comprises 4-20 parts of an aqueous solution of oxidized hyaluronic acid, 20-100 parts of tissue-like natural collagen, and 45-50 parts of an ethanol solution of quercetin. ​ The preparation method of the anti-oxidation and anti-allergy tissue-like natural collagen composite injectable solution comprises the following steps: S1, preparing tissue-like natural collagen by multiple immersions; S2, preparing oxidized hyaluronic acid by using sodium periodate; S3, mixing the oxidized hyaluronic acid prepared in step S2 with the tissue-like natural collagen prepared in step S1, adjusting pH value for cross-linking to obtain a mixed solution 1; S4, adding the mixed solution 1 obtained in step S3 to an ethanol solution of quercetin to obtain the anti-oxidation and anti-allergy tissue-like natural collagen composite injectable solution. The preparation of the tissue-like natural collagen comprises the following steps: pretreating animal connective tissue, sequentially immersing and washing the animal connective tissue in a Tris-NaCl buffer solution and acetone, immersing the animal connective tissue in a composite solution of NaCl and sodium dodecyl sulfate, crushing the animal connective tissue, immersing the crushed animal connective tissue in an acetic acid solution, and homogenizing to obtain the tissue-like natural collagen. The preparation of the oxidized hyaluronic acid by using sodium periodate comprises the following steps: immersing 1-20 parts of hyaluronic acid in 300-800 parts of a sodium periodate solution, stirring in the dark, dialysis, and freeze-drying to obtain the oxidized hyaluronic acid.

2. The method for preparing the antioxidant and anti-allergic injectable tissue natural collagen complex according to claim 1, characterized in that, The mass concentration of the aqueous solution of oxidized hyaluronic acid is 6%-20%, and the molar concentration of the ethanol solution of quercetin is 10 g / L-20 g / L.

3. The method for preparing the antioxidant and anti-allergic injectable tissue natural collagen complex according to claim 1, characterized in that, The immersion temperature is 37℃, the Tris-NaCl buffer solution immersion time is 3-10 h, the pH value of the Tris-NaCl buffer solution is 7-8, the acetone immersion time is 5-10 h, in the immersion of the composite solution of NaCl and sodium dodecyl sulfate, the volume ratio of the NaCl solution to the sodium dodecyl sulfate is 1:2, the molar concentration of the NaCl is 1M-2M, the mass concentration of the sodium dodecyl sulfate is 0.2%-1%, the immersion time is 3h-5h, the crushing frequency is 20KHz-25KHz, and the crushing time is 2h-5h, the immersion of the acetic acid solution, the molar concentration of the acetic acid solution is 0.5-1M, and the immersion time is 5h-10h.

4. The preparation method of the anti-oxidative and anti-allergic tissue natural collagen complex injectable solution according to claim 1, characterized in that, The stirring condition in the dark is: stirring at 50℃-70℃ for 1h-10h, the dialysis is performed by using a dialysis bag with a molecular weight cut-off of 6000-8000, the dialysis time is 3-5 days, and the water is changed 2-4 times per day.

5. The method for preparing the antioxidant and anti-allergic injectable tissue natural collagen complex according to claim 1, characterized in that, The volume ratio of the mixed solution 1 to the ethanol solution of quercetin is: 1:1-3:1, and the pH value for cross-linking is adjusted to 5.0-8.

5.

6. The preparation method of the anti-oxidative and anti-allergic tissue-like natural collagen complex injectable solution according to claim 1, characterized in that, The reaction condition is: 36℃-38℃ for 22h-26h of continuous shaking reaction.

7. The injectable solution prepared by the preparation method of the anti-oxidation and anti-allergy tissue-like natural collagen composite injectable solution according to any one of claims 1-6 is used for preparing medical and cosmetic drugs and joint treatment drugs.

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