Silk fibroin injection for facial anti-aging filling repair and preparation process thereof

CN122605003APending Publication Date: 2026-08-21刘刚
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Patent Information

Application Number
CN202610853397.1
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2026-06-12
Publication Date
2026-08-21

AI Technical Summary

Technical Problem

[0006]本发明的目的在于克服现有面部填充制剂存在化学交联剂安全风险、注射阻力大、理化性质与人体生理环境不匹配、胶原再生效率低、修护功能单一等缺陷,提供一种用于面部抗衰填充修护的窄分子量丝素蛋白注射液、制备工艺及应用

Benefits of technology

1、生物安全性高,无化学交联风险:本发明摒弃传统填充剂常用的BDDE等化学交联剂,依靠丝素蛋白与低分子透明质酸钠形成物理互穿网络提供力学支撑,从根源杜绝交联剂残留引发的迟发性红肿、肉芽肿、异物排斥等问题。产品降解产物为氨基酸、水、糖醛酸,可被人体完全代谢,无长期体内残留隐患。配方采用磷酸盐-氯化钠生理等渗缓冲体系,成品pH、渗透压与人体组织液高度匹配,搭配甜菜碱调节渗透压,大幅降低注射痛感,术后红斑、水肿发生率极低,缩短恢复期。

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Abstract

This invention provides a silk fibroin injection solution for facial anti-aging filling and repair, and its preparation process, belonging to the fields of biomedical materials, regenerative medicine, and medical aesthetic soft tissue repair technology. Based on 1000mL of injection solution, it consists of the following raw materials in the indicated weight ratios: sodium chloride 8.0–8.5g, sodium dihydrogen phosphate 0.25–0.30g, disodium hydrogen phosphate 0.45–0.50g, narrow molecular weight hydrolyzed silk fibroin 18.0–25.0g, low molecular weight sodium hyaluronate 2.0–2.5g, sodium tocopheryl phosphate 1.2–1.8g, panthenol 1.5–2.0g, betaine 3.0–3.5g, phenoxyethanol 1.7–2.0g, EDTA-2Na 0.10–0.15g, with the remainder being water for injection. The narrow molecular weight hydrolyzed silk fibroin has a molecular weight of 5–10kDa, a polydispersity index (PDI) < 1.2, and a particle size of 2–5nm. This invention does not require the addition of chemical cross-linking agents, but relies on physical interpenetrating networks to achieve mechanical support. It features low injection resistance, high biocompatibility, low irritation, the ability to induce type III collagen regeneration in a targeted manner, and the integration of filling and repair. It is also equipped with a medical preparation process that can be mass-produced.
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Description

Technical Field

[0001] This invention provides a silk fibroin injection solution for facial anti-aging filling and repair, and its preparation process, belonging to the field of biomedical materials technology. Background Technology

[0002] With the rapid development of the regenerative medical aesthetics industry, cross-linked hyaluronic acid, animal-derived collagen, and high-molecular-weight silk fibroin gel have become the mainstream soft tissue filler materials for facial rejuvenation. However, existing products still have many technical defects that are difficult to avoid.

[0003] Traditional hyaluronic acid fillers commonly use chemical cross-linking agents such as BDDE to enhance mechanical support. Residual cross-linking agents can easily cause adverse reactions such as delayed redness and swelling, and granulomas. Furthermore, the chemical cross-linked structure cannot be completely degraded in the human body, posing a risk of foreign body accumulation over time. Currently, most silk fibroin fillers on the market are high-molecular-weight gels with a molecular weight of over 50kDa. Their high molecular aggregation and viscosity result in significant resistance when injected using 30G or 32G microneedles, making them unsuitable for use in delicate areas with thin skin and dense nerves, such as around the eyes and mouth.

[0004] Conventional silk fibroin materials have a wide molecular weight distribution and a polydispersity index (PDI) > 1.8. Their degradation products are complex, resulting in weak activation of skin fibroblasts and difficulty in targeted induction of type III collagen synthesis. Consequently, their filling and shaping effects are short-lived and prone to rapid decline. Furthermore, most cosmetic injectable formulations are not matched to the osmotic pressure and pH of human tissue fluid, easily causing significant stinging, erythema, and edema after injection, leading to a longer recovery period and a poor user experience.

[0005] Furthermore, existing filler products have relatively limited functions, relying solely on physical placement to achieve the filling effect without incorporating anti-inflammatory, antioxidant, or skin barrier repair active ingredients. This makes it impossible to simultaneously address post-filler complications such as inflammatory stress, dry skin, and weakened skin barrier. The industry urgently needs to develop a silk fibroin injection formulation that is chemically free of cross-linking, has a narrow molecular weight and low dispersion, isotonic and low-irritation properties, is compatible with microneedle injection, and combines immediate filling, long-lasting collagen regeneration, and post-operative repair. This invention addresses these industry pain points through systematic technological innovation. Summary of the Invention

[0006] The purpose of this invention is to overcome the shortcomings of existing facial filler preparations, such as safety risks associated with chemical cross-linking agents, high injection resistance, mismatch between physicochemical properties and the human physiological environment, low collagen regeneration efficiency, and limited repair functions. This invention provides a narrow molecular weight silk fibroin injection solution, its preparation process, and its application for facial anti-aging filling and repair. This product requires no chemical cross-linking agents, relying on a physical interpenetrating network for mechanical support. It features low injection resistance, high biocompatibility, low irritation, the ability to directionally induce type III collagen regeneration, and integrated filling and repair functions. It also includes a medical-grade preparation process suitable for large-scale production.

[0007] To address the aforementioned problems, the present invention proposes the following technical solution: a silk fibroin injection solution for facial anti-aging filling and repair, comprising, per 1000 mL injection volume, the following raw materials in the indicated weight ratios: sodium chloride 8.0–8.5 g, sodium dihydrogen phosphate 0.25–0.30 g, disodium hydrogen phosphate 0.45–0.50 g, narrow molecular weight hydrolyzed silk fibroin 18.0–25.0 g, low molecular weight sodium hyaluronate 2.0–2.5 g, and sodium tocopheryl phosphate 1 g. The extract contains 0.2–1.8 g of panthenol, 1.5–2.0 g of betaine, 3.0–3.5 g of phenoxyethanol, 1.7–2.0 g of EDTA-2Na, and the balance is water for injection; the narrow molecular weight hydrolyzed silk fibroin has a molecular weight of 5–10 kDa, a polydispersity index (PDI) < 1.2, and a particle size of 2–5 nm; the finished injection solution has a pH of 5.6–6.0 and an osmotic pressure of 290–310 mOsm / kg.

[0008] Furthermore, based on 1000mL of injection solution, the specific proportions of raw materials are as follows: sodium chloride 8.3g, sodium dihydrogen phosphate 0.28g, disodium hydrogen phosphate 0.48g, narrow molecular weight hydrolyzed silk fibroin 22.0g, low molecular weight sodium hyaluronate 2.2g, sodium tocopheryl phosphate 1.5g, panthenol 1.8g, betaine 3.2g, phenoxyethanol 1.9g, EDTA-2Na 0.13g, with the remainder being water for injection; the narrow molecular weight hydrolyzed silk fibroin has a particle size of 3nm, a polydispersity index (PDI) of 1.1, a finished product pH of 5.8, and an osmotic pressure of 302mOsm / kg.

[0009] Furthermore, the molecular weight of the low molecular weight sodium hyaluronate is 200,000 to 400,000 Da.

[0010] Furthermore, the injection solution does not contain any chemical cross-linking agents; instead, it achieves mechanical support by forming a physical interpenetrating network structure from narrow molecular weight hydrolyzed silk fibroin and low molecular weight sodium hyaluronate.

[0011] Furthermore, the preparation process of the silk fibroin injection solution for facial anti-aging filling and repair includes the following steps: S1. Preparation of basic buffer solution: Heat water for injection to 55-60℃, add sodium chloride, sodium dihydrogen phosphate, disodium hydrogen phosphate and betaine in sequence, stir until completely dissolved, adjust the pH and osmotic pressure of the system, and then cool to 4-10℃ to obtain basic buffer solution for later use. S2. Combination of active ingredients: Under light-protected conditions, stir at a low speed of ≤60r / min and add narrow molecular weight hydrolyzed silk fibroin, low molecular weight sodium hyaluronate, sodium tocopheryl phosphate, and panthenol to the basic buffer solution in sequence, and stir until the system is completely clear. S3. Stabilization: Add phenoxyethanol and EDTA-2Na to the system, and recalibrate the pH and osmotic pressure to the specified acceptable range. S4. Sterilization and pyrogen removal: The prepared liquid is treated with a 0.22μm PES double-layer filter membrane to remove bacteria and pyrogens. S5. Aseptic filling: In the Class A clean laminar flow area, the sterilized liquid is filled into the pre-filled syringe and vacuum sealed. S6. Sterilization and analysis: Ethylene oxide is used for low-temperature sterilization. After sterilization, analysis is performed for more than 7 days. After passing all tests, the product is released.

[0012] Furthermore, steps S1 and S2 are performed entirely in a low-temperature environment to avoid high temperatures damaging the bioactivity of silk fibroin.

[0013] Furthermore, the narrow molecular weight hydrolyzed silk fibroin is prepared by enzymatic hydrolysis combined with gradient ultrafiltration, which precisely retains silk fibroin raw materials with a molecular weight of 5-10 kDa and a PDI < 1.2.

[0014] Furthermore, in step S2, during the compounding process, a stable physical interpenetrating network structure is formed between narrow molecular weight hydrolyzed silk fibroin and low molecular weight sodium hyaluronate under a pressure of 800–1200 bar by using low-temperature physical homogenization and high-pressure microfluidic technology.

[0015] Furthermore, the silk fibroin injection solution used for facial anti-aging filling and repair is applied in the preparation of facial medical aesthetic products, which are used for filling fine lines in the dermis, repairing facial soft tissue depressions, and inducing the regeneration of human type III collagen; the injection solution is also used for skin barrier repair after medical aesthetic procedures and to relieve post-injection skin stinging, erythema and edema symptoms.

[0016] Due to the adoption of the above technical solution, the beneficial effects of the silk fibroin injection for facial anti-aging filling and repair and its preparation process of the present invention are as follows: 1. High biocompatibility and no risk of chemical cross-linking: This invention abandons the chemical cross-linking agents such as BDDE commonly used in traditional fillers. It relies on the physical interpenetrating network formed by silk fibroin and low molecular weight sodium hyaluronate to provide mechanical support, thus eliminating problems such as delayed redness, granulomas, and foreign body rejection caused by cross-linking agent residues. The product degradation products are amino acids, water, and uronic acid, which can be completely metabolized by the human body, with no long-term residual risks in the body. The formula uses a phosphate-sodium chloride physiological isotonic buffer system, and the pH and osmotic pressure of the finished product are highly matched with human tissue fluid. The addition of betaine to adjust the osmotic pressure significantly reduces injection pain, resulting in a very low incidence of postoperative erythema and edema, and shortening the recovery period.

[0017] 2. Excellent injection performance, suitable for delicate medical aesthetic procedures: This invention limits the molecular weight of silk fibroin to 5-10kDa, PDI<1.2, and particle size to 2-5nm. The molecules are uniformly dispersed and the system viscosity is low. It can pass smoothly through 30G and 32G fine microneedles, with low injection resistance and good operation feel. It can meet the delicate filling needs of thin skin areas such as around the eyes and mouth, and has a wider range of applicable scenarios.

[0018] 3. Effectively induces collagen regeneration for long-lasting anti-aging: The degradation products of specific narrow molecular weight silk fibroin can specifically activate skin fibroblasts, block inflammation-related signaling pathways, reverse the aging phenotype of fibroblasts, and induce the synthesis of human type III collagen in a targeted manner, while inhibiting collagen degradation. This breaks through the limitations of traditional fillers that only physically occupy space, achieving an integrated effect of filling, regeneration, and anti-aging, and maintaining the shaping and anti-aging effect for a longer period of time.

[0019] 4. Synergistic effect of ingredients, simultaneous filling and barrier repair: The formula combines active ingredients such as sodium tocopheryl phosphate, panthenol, and betaine, which have antioxidant, anti-inflammatory, moisturizing, and repairing effects. While achieving physical filling, it neutralizes free radicals and reduces postoperative inflammatory stress. Combined with the excellent biocompatibility and film-forming properties of silk fibroin, it quickly repairs the damaged skin barrier, solving problems such as dry skin and fragile barrier after cosmetic filling, achieving a comprehensive effect of "treatment as repair".

[0020] 5. Stable preparation process and good product storage: The entire process adopts mild preparation conditions of low temperature, light protection, and low-speed stirring to maximize the preservation of the bioactivity of silk fibroin and active ingredients; combined with 0.22μm PES double-layer filter membrane sterilization, Class A aseptic filling, and ethylene oxide low-temperature sterilization and analysis process, the product's sterility and pyrogen index meet the standards, the system is clear and stable for a long time, and can be stored at room temperature for 24 months, meeting the requirements for large-scale production and clinical use of medical injection solutions. Attached Figure Description

[0021] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used in conjunction with embodiments of the invention to explain the invention and do not constitute a limitation thereof. In the drawings: Figure 1 This is a product composition diagram of the silk fibroin injection solution for facial anti-aging filling and repair, and its preparation process, as described in this invention.

[0022] Figure 2 This is a process diagram of the silk fibroin injection solution for facial anti-aging filling and repair according to the present invention.

[0023] Figure 3 This is a product application diagram of the silk fibroin injection solution for facial anti-aging filling and repair, and its preparation process, according to the present invention. Detailed Implementation

[0024] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0025] Example 1 (Optimal Example) 1. Formula (total volume 1000mL) Sodium chloride 8.3g, sodium dihydrogen phosphate 0.28g, disodium hydrogen phosphate 0.48g, narrow molecular weight hydrolyzed silk fibroin 22.0g, low molecular weight sodium hyaluronate 2.2g, sodium tocopheryl phosphate 1.5g, panthenol 1.8g, betaine 3.2g, phenoxyethanol 1.9g, EDTA-2Na 0.13g, the balance being water for injection; Among them: narrow molecular weight hydrolyzed silk fibroin has a molecular weight of 7kDa, PDI=1.1, and particle size of 3nm; finished product test results show pH=5.8 and osmotic pressure=302mOsm / kg.

[0026] 2. Preparation process S1. Prepare the basic buffer solution: Heat water for injection to 58°C, add sodium chloride, sodium dihydrogen phosphate, disodium hydrogen phosphate and betaine in the above ratio in sequence, stir until completely dissolved, adjust the pH and osmotic pressure of the system, and then cool to 6°C for later use. S2. Active ingredient compounding: Under light-protected conditions, set the stirring speed to 50 r / min, and add narrow molecular weight hydrolyzed silk fibroin, low molecular weight sodium hyaluronate, sodium tocopheryl phosphate, and panthenol to the basic buffer solution in sequence, and stir until the system is completely clear; then perform high-pressure microfluidic treatment, with the pressure controlled at 1000 bar, to form a physical interpenetrating network structure. S3. Stabilization: Add phenoxyethanol and EDTA-2Na, and recalibrate the pH and osmotic pressure to the acceptable range. S4. Sterilization and pyrogen removal: The feed liquid is filtered using a 0.22μm PES double-layer filter membrane to achieve sterilization and pyrogen removal; S5. Aseptic filling: In the Class A clean laminar flow area, the liquid is filled into the pre-filled syringe and vacuum sealed. S6. Sterilization and analysis: The product is sterilized at low temperature with ethylene oxide, analyzed for 8 days, and obtained as a finished injection solution after passing all tests.

[0027] Example 2 (Low-content silk fibroin formula) 1. Formula (total volume 1000mL) Sodium chloride 8.0g, sodium dihydrogen phosphate 0.25g, disodium hydrogen phosphate 0.45g, narrow molecular weight hydrolyzed silk fibroin 18.0g, low molecular weight sodium hyaluronate 2.0g, sodium tocopheryl phosphate 1.2g, panthenol 1.5g, betaine 3.0g, phenoxyethanol 1.7g, EDTA-2Na 0.10g, the balance being water for injection; Among them: narrow molecular weight hydrolyzed silk fibroin has a molecular weight of 5kDa, PDI=1.15, and particle size of 2nm; finished product test results show pH=5.6 and osmotic pressure=290mOsm / kg.

[0028] 2. Preparation process The preparation steps, process parameters, and operating environment were kept the same as in Example 1.

[0029] Example 3 (High-content silk fibroin formula) 1. Formula (total volume 1000mL) Sodium chloride 8.5g, sodium dihydrogen phosphate 0.30g, disodium hydrogen phosphate 0.50g, narrow molecular weight hydrolyzed silk fibroin 25.0g, low molecular weight sodium hyaluronate 2.5g, sodium tocopheryl phosphate 1.8g, panthenol 2.0g, betaine 3.5g, phenoxyethanol 2.0g, EDTA-2Na 0.15g, the balance being water for injection; Among them: narrow molecular weight hydrolyzed silk fibroin has a molecular weight of 10kDa, PDI=1.18, and particle size of 5nm; the finished product test results show pH=6.0 and osmotic pressure=310mOsm / kg.

[0030] 2. Preparation process The preparation steps, process parameters, and operating environment were kept the same as in Example 1.

[0031] Example 4 (Intermediate formulation) 1. Formula (total volume 1000mL) Sodium chloride 8.2g, sodium dihydrogen phosphate 0.27g, disodium hydrogen phosphate 0.47g, narrow molecular weight hydrolyzed silk fibroin 20.0g, low molecular weight sodium hyaluronate 2.3g, sodium tocopheryl phosphate 1.6g, panthenol 1.7g, betaine 3.3g, phenoxyethanol 1.8g, EDTA-2Na 0.12g, the balance being water for injection; Among them: narrow molecular weight hydrolyzed silk fibroin has a molecular weight of 8kDa, PDI=1.12, and particle size of 4nm; the finished product test results show pH=5.7 and osmotic pressure=298mOsm / kg.

[0032] 2. Preparation process The preparation steps, process parameters, and operating environment were kept the same as in Example 1.

[0033] Product performance testing and effect verification 3. Injection performance test Rheological and injection resistance tests were conducted on the finished products of Examples 1-4, commercially available high molecular weight silk fibroin gel (Comparative Example 1), and cross-linked hyaluronic acid filler (Comparative Example 2), using 32G microneedles for unified testing. The results showed that the viscosity of the product systems of the four examples of this invention was significantly lower than that of Comparative Example 1, and the injection thrust was only about 1 / 3 of that of Comparative Example 1. The injection was smooth and there was no needle blockage, making it easy to apply for precise injection around the eyes and mouth. Although conventional cross-linked hyaluronic acid (Comparative Example 2) had moderate injection resistance, there was a risk of residual chemical cross-linking agent.

[0034] 4. Cell viability and collagen induction experiments Human skin fibroblasts (HDFs) were co-cultured for 7 days with extracts from the products of Examples 1-4 and ordinary broad-distribution silk fibroin extract, respectively, and the expression level of type III collagen mRNA was detected. The results showed that all four products of this invention could significantly enhance type III collagen expression, with expression levels 2.3-2.5 times that of the ordinary silk fibroin group, demonstrating that the narrow molecular weight silk fibroin of this invention has excellent collagen regeneration induction ability.

[0035] 5. In vivo irritation and safety tests Intradermal irritation tests were conducted on rabbits. The products of Examples 1-4 and the hyaluronic acid product containing BDDE cross-linking agent were injected, and skin conditions were observed continuously for 24h, 48h, and 72h. Results showed that the primary irritation index of all products in this invention was 0, and no erythema, edema, or induration occurred at the injection site. The cross-linked hyaluronic acid in the control group still showed slight erythema after 72h, further verifying that the isotonic, non-cross-linked formulation of this invention has higher biocompatibility.

[0036] 6. Stability test The finished products from Examples 1-4 were stored at room temperature and away from light for 24 months, with periodic testing of appearance, pH, osmotic pressure, and clarity. Results showed that all four products remained clear throughout the storage period, with no significant changes in physicochemical indicators, no significant attenuation of active ingredients, and their stability met the storage requirements for medical injection solutions.

[0037] In summary, all raw materials used in this invention are pharmacopoeia-grade / medical injection-grade raw materials. Narrow molecular weight hydrolyzed silk fibroin is prepared by enzymatic hydrolysis + gradient ultrafiltration process, and the molecular weight of low molecular weight sodium hyaluronate is controlled at 200,000 to 400,000 Da.

[0038] 7. Detailed Application Instructions The narrow molecular weight silk fibroin injection prepared by this invention can be directly used in facial aesthetic medicine: firstly, it fills dry lines and fine lines in the dermis of the face, and repairs soft tissue depressions in areas such as the forehead, cheekbones, and face; secondly, it can target and activate fibroblasts, induce the synthesis of the body's own type III collagen, and achieve long-lasting anti-aging effects; and thirdly, it can be used for post-operative repair of various aesthetic injections and microneedling procedures, relieving stinging, redness, and swelling caused by injections, and repairing damaged skin barriers. It has a wide range of applicable populations and high safety in clinical use.

[0039] The present invention and its embodiments have been described above. This description is not restrictive. In short, if a person skilled in the art is inspired by this description and designs a similar structure and embodiment without departing from the spirit of the present invention, such design should fall within the protection scope of the present invention.

Claims

1. A silk fibroin injection solution for facial anti-aging and filling repair, characterized in that: The injection solution, in 1000 mL, is composed of the following raw materials in the indicated weight ratios: sodium chloride 8.0–8.5 g, sodium dihydrogen phosphate 0.25–0.30 g, disodium hydrogen phosphate 0.45–0.50 g, narrow molecular weight hydrolyzed silk fibroin 18.0–25.0 g, low molecular weight sodium hyaluronate 2.0–2.5 g, sodium tocopheryl phosphate 1.2–1.8 g, panthenol 1.5–2.0 g, betaine 3.0–3.5 g, phenoxyethanol 1.7–2.0 g, EDTA-2Na 0.10–0.15 g, with the remainder being water for injection. The narrow molecular weight hydrolyzed silk fibroin has a molecular weight of 5–10 kDa, a polydispersity index (PDI) < 1.2, and a particle size of 2–5 nm. The finished injection solution has a pH of 5.6–6.0 and an osmotic pressure of 290–310 mOsm / kg.

2. The silk fibroin injection solution for facial anti-aging filling and repair according to claim 1, characterized in that: Based on 1000mL of injection solution, the specific raw material ratio is as follows: sodium chloride 8.3g, sodium dihydrogen phosphate 0.28g, disodium hydrogen phosphate 0.48g, narrow molecular weight hydrolyzed silk fibroin 22.0g, low molecular weight sodium hyaluronate 2.2g, sodium tocopheryl phosphate 1.5g, panthenol 1.8g, betaine 3.2g, phenoxyethanol 1.9g, EDTA-2Na 0.13g, with the remainder being water for injection; the narrow molecular weight hydrolyzed silk fibroin has a particle size of 3nm, a polydispersity index (PDI) of 1.1, a finished product pH of 5.8, and an osmotic pressure of 302mOsm / kg.

3. The silk fibroin injection solution for facial anti-aging filling and repair according to claim 1, characterized in that: The molecular weight of the low molecular weight sodium hyaluronate is 200,000 to 400,000 Da.

4. The silk fibroin injection solution for facial anti-aging filling and repair according to claim 1, characterized in that: The injection solution does not contain any chemical cross-linking agents. Mechanical support is achieved by a physical interpenetrating network structure formed by narrow molecular weight hydrolyzed silk fibroin and low molecular weight sodium hyaluronate.

5. The preparation process of the silk fibroin injection solution for facial anti-aging filling and repair according to claim 1, characterized in that: Includes the following steps: S1. Preparation of basic buffer solution: Heat water for injection to 55-60℃, add sodium chloride, sodium dihydrogen phosphate, disodium hydrogen phosphate and betaine in sequence, stir until completely dissolved, adjust the pH and osmotic pressure of the system, and then cool to 4-10℃ to obtain basic buffer solution for later use. S2. Combination of active ingredients: Under light-protected conditions, stir at a low speed of ≤60r / min and add narrow molecular weight hydrolyzed silk fibroin, low molecular weight sodium hyaluronate, sodium tocopheryl phosphate, and panthenol to the basic buffer solution in sequence, and stir until the system is completely clear. S3. Stabilization: Add phenoxyethanol and EDTA-2Na to the system, and recalibrate the pH and osmotic pressure to the specified acceptable range. S4. Sterilization and pyrogen removal: The prepared liquid is treated with a 0.22μm PES double-layer filter membrane to remove bacteria and pyrogens. S5. Aseptic filling: In the Class A clean laminar flow area, the sterilized liquid is filled into the pre-filled syringe and vacuum sealed. S6. Sterilization and analysis: Ethylene oxide is used for low-temperature sterilization. After sterilization, analysis is performed for more than 7 days. After passing all tests, the product is released.

6. The preparation process of the silk fibroin injection solution for facial anti-aging filling and repair according to claim 5, characterized in that: Steps S1 and S2 are performed entirely in a low-temperature environment to avoid high temperatures damaging the bioactivity of silk fibroin.

7. The preparation process of the silk fibroin injection solution for facial anti-aging filling and repair according to claim 5, characterized in that: The narrow molecular weight hydrolyzed silk fibroin is prepared by enzymatic hydrolysis combined with gradient ultrafiltration, which precisely retains silk fibroin raw materials with a molecular weight of 5-10 kDa and PDI < 1.

2.

8. The preparation process of the silk fibroin injection solution for facial anti-aging filling and repair according to claim 5, characterized in that: In step S2, during the compounding process, a stable physical interpenetrating network structure is formed between narrow molecular weight hydrolyzed silk fibroin and low molecular weight sodium hyaluronate under a pressure of 800–1200 bar by using low-temperature physical homogenization and high-pressure microfluidic technology.

9. The application of the silk fibroin injection solution for facial anti-aging filling and repair according to claim 1 in the preparation of facial medical aesthetic products, characterized in that: The facial cosmetic product is used for filling fine lines in the dermis, repairing facial soft tissue depressions, and inducing the regeneration of type III collagen in the human body. The injection solution is also used for skin barrier repair after cosmetic procedures and to relieve post-injection skin stinging, erythema, and edema.