Composite gel for skin correction and preparation method thereof

Abstract

The invention discloses a composite gel for skin correction and a preparation method thereof. The composite gel is formed by dissolving sodium hyaluronate, epidermal growth factors and a protein stabilizer in a buffer system; the content of the sodium hyaluronate is 1.0-50.0 g / L, the content of the epidermal growth factor is 1000-30000 IU / mL, and the content of the stabilizer is 5.0-100.0 mg / L; the pH value of the buffer system is 6.5-7.5. The preparation method comprises the following steps: S1, dissolving sodium hyaluronate and a stabilizer in a buffer system under a sterile condition, and stirring to obtain gel A; s2, adding epidermal growth factors into the gel A, and stirring to obtain the composite gel. The composite gel disclosed by the invention can activate epithelial fibroblasts, update and reconstruct ECM and maintain the stability of an ECM microenvironment. The composite gel disclosed by the invention integrates the functions of supplementing lost extracellular matrix, increasing the number of cells and promoting synthesis of collagen by a traditional filling material, can solve the skin problems caused by various factors, and achieves the effect of correcting the skin.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical composite materials and implantable medical devices, and in particular to a composite gel for skin correction and a preparation method thereof. Background Art

[0002] Hyaluronic acid, also known as hyaluronic acid, typically exists in its sodium salt form, sodium hyaluronate, also known as sodium hyaluronate (abbreviated as HA). Hyaluronic acid (HA) is a water-soluble polysaccharide with both high and low molecular weights. The tertiary network structure formed by the interaction between high-molecular-weight HA molecules gives HA a certain viscosity. Hyaluronic acid is a major matrix component of the human epidermis and dermis, and is widely distributed in connective tissues such as intercellular spaces, the lens of the eye, and synovial fluid in joints.

[0003] The skin barrier is composed of the sebum membrane, keratin in the stratum corneum, lipids, and dermal mucopolysaccharides. In healthy skin, the integrity of the keratinocytes and intercellular matrix must be maintained to maintain the integrity of the skin barrier. In daily life, the skin is constantly exposed to a variety of adverse external factors, including physical, chemical, and biological factors. When the skin barrier is damaged, the keratinocytes become disordered and loose, and physiological sebum and water are easily lost. This reduces the water content of the epidermis and increases transepidermal water loss, making it unable to resist external stimuli and even causing skin diseases.

[0004] Changes in skin texture are sequelae of skin aging or skin diseases, usually manifested as dryness, roughness, loss of luster, atrophy and thinning, fine lines, enlarged pores, atrophic scars, etc. Histologically, it is mainly manifested as atrophy of the epidermis and dermis, such as thinning of the epidermis and decreased barrier protection function. The main mechanisms of dermal atrophy include the breakage of collagen fibers in the dermis, the reduction in the number of fibroblasts and the collapse of their morphology, which affect their ability to synthesize the extracellular matrix (ECM), the reduction in the production of extracellular matrix (such as hyaluronic acid, collagen, elastin, etc.), and the increased expression of matrix metalloproteinases, which increases the degradation of the extracellular matrix and leads to the breakage and degradation of collagen. The fundamental mechanism of most methods to improve skin quality is to reverse this atrophy process, such as photoelectric therapy and dermal nutrient injection.

[0005] In skin tissue, fibroblasts are the primary cells responsible for producing all components of the dermal ECM, maintaining the stability of the ECM microenvironment, and participating in ECM renewal and reconstruction. Fibroblasts also regulate the rate of collagen fiber renewal by secreting metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Fibroblast health is inextricably linked to skin health, wound repair, and skin aging. A gradual decrease in dermal fibroblast numbers and a reduced ability to synthesize collagen, coupled with increased protease release, leads to increased collagen degradation. While elastic fiber content remains constant, the elastic fiber network curls, loosens, and loses its elasticity. The elastic fiber network in the papillary dermis decreases or even disappears, leading to epidermal laxity and the formation of fine wrinkles. Furthermore, the thickening of fiber bundles can exacerbate wrinkle depth. The reduction in subcutaneous fat increases the amount of material connecting the subcutaneous tissue to the reticular dermis, reducing elastic fiber elasticity and contributing to the formation of fine wrinkles.

[0006] The skin around the eyes is extremely delicate, typically only 0.5mm thick, and dries twice as quickly as other areas of the body. The eyelids are surrounded by 22 muscles and blink 10,000 times daily, making them particularly susceptible to wrinkles and fine lines. The skin around the lips lacks sebaceous glands and is particularly thin, and facial expressions often involve constant lip movement. Consequently, wrinkles are more likely to form. Furthermore, gravity can contribute to eye bags and a double chin. Generally speaking, women begin to develop wrinkles around age 30, first appearing as crow's feet at the corners of the eyes, followed by forehead wrinkles, frown lines, nasolabial folds, upper lip lines, and finally the neck. Wrinkles are generally categorized as linear, patterned, or fine lines.

[0007] Hyaluronic acid injected into the dermis can provide space and nutrition for collagen and elastic fibers, forming a scaffold for the skin. It is an important extracellular matrix that maintains the stability, fusion, and elasticity of skin tissue. As a natural moisturizing factor, hyaluronic acid can significantly improve the permeability barrier function of the epidermis and increase the water content of the stratum corneum, restore the skin barrier, and promote wound healing. It mainly improves skin quality through the following aspects: (1) Directly replenishing hyaluronic acid in the skin to enhance hydration and increase skin volume; (2) Promoting the proliferation of keratinocytes, fibroblasts to produce collagen and polysaccharides, and constructing a new extracellular matrix; (3) By changing the tension in the dermis, it promotes the mechanical traction of collagen fibers on fibroblasts, leading to fibroblast proliferation, thereby promoting the synthesis of collagen and other ECM proteins and inhibiting their decomposition; (4) Upregulating VEGF expression, promoting the proliferation of vascular endothelial cells, facilitating dermal angiogenesis, and increasing blood supply and nutrition to the skin.

[0008] Cytokines are increasingly being researched and applied in cosmetic medicine. Currently, they are most commonly used internationally in plastic surgery, skin repair and regeneration, and cosmetic medicine. The primary growth factors used include EGF, FGF, KGF, and other cytokines (VEGF, hGF, and IGF-1). Epidermal growth factor (EGF) was discovered by American scientists in 1986, earning them the Nobel Prize in Physiology or Medicine. EGF promotes cell division and differentiation, aiding in epidermal wound healing. Experiments have shown that EGF can activate epithelial cells in young people.

[0009] Ultraviolet rays are a major cause of skin aging and damage. Dermal fibroblasts are one of the main cells in the dermis and the primary target of UV-induced skin damage. Studies have shown that concentrated growth factors have good biocompatibility with dermal fibroblasts, promoting their collagen synthesis, proliferation, and migration, and reversing UV-induced damage to dermal fibroblasts. Epidermal growth factor can inhibit the aging and damaging effects of UV on dermal fibroblasts, slowing the aging process of the skin caused by UV rays; it can also increase superoxide dismutase activity in photodamaged cells and significantly reduce the content of reactive oxygen species. Cosmetic surgeons have widely used concentrated growth factors to reduce scars, improve pigmentation, and combat wrinkles. Summary of the Invention

[0010] The present invention provides a composite gel for skin correction and a preparation method thereof. The formula of the composite gel includes sodium hyaluronate, human epidermal growth factor and a protein stabilizer. The composite gel can activate human epithelial cells, promote fibroblast proliferation, solve the problem of skin aging from the root, and repair the skin barrier.

[0011] The present invention is achieved through the following technical solutions:

[0012] The present invention provides a composite gel for skin correction. The composite gel is formed by dissolving high-molecular-weight sodium hyaluronate, human epidermal growth factor, and a protein stabilizer in a buffer system. The composite gel contains 1.0 to 50.0 g / L of sodium hyaluronate, 1,000 to 30,000 IU / mL of human epidermal growth factor, and 5.0 to 100.0 mg / L of protein stabilizer. The pH value of the buffer system is 6.5 to 7.5.

[0013] The composite gel of the present invention belongs to the fields of biomedical composite materials, implantable medical devices, medical cosmetology, etc., and has broad application prospects.

[0014] Specifically, the composite gel sample formed according to the optimized formula of the present invention can activate epithelial fibroblasts, renew and rebuild the ECM, and maintain a stable ECM microenvironment. The resulting composite gel combines the functions of traditional fillers in replenishing lost extracellular matrix with increasing cell numbers and promoting collagen synthesis. It can address skin problems caused by various factors (such as ultraviolet rays and facial expressions), such as sodium hyaluronate and collagen degradation, thereby achieving a corrective effect on the skin.

[0015] Furthermore, a composite gel for skin correction: the molecular weight of the sodium hyaluronate is 300,000 to 3,000,000.

[0016] Preferably, the molecular weight of the sodium hyaluronate is 1,000,000 to 2,000,000.

[0017] Furthermore, a composite gel for skin correction: the human epidermal growth factor is selected from any one or more of deer antler essence, sea plant essence, and ginsenoside.

[0018] Furthermore, a composite gel for skin correction: the protein stabilizer is selected from any one or more of Tween 20, Tween 80, poloxamer, trehalose, mannitol, amino acids, sorbitol, and inositol.

[0019] Furthermore, a composite gel for skin correction: the buffer system is selected from any one or more of phosphate, citrate, histidine, acetate, succinic acid, tromethamine, adipic acid, lactic acid and MES.

[0020] Furthermore, a composite gel for skin correction: the content of the composite gel protein stabilizer is 20.0-100.0 mg / L; the pH value of the buffer system is 6.8-7.2.

[0021] The present invention also provides a method for preparing the composite gel for skin correction, which is used to prepare the composite gel for skin correction, and the method comprises the following steps:

[0022] S1. Under sterile conditions, dissolve sodium hyaluronate and protein stabilizer in a buffer system and stir to obtain gel A;

[0023] S2. Add epidermal growth factor to the above gel A and stir to obtain a composite gel.

[0024] Another method for preparing a composite gel for skin correction is provided. The method comprises: dissolving sodium hyaluronate, a protein stabilizer, and epidermal growth factor in a buffer system under sterile conditions, and stirring to obtain the composite gel.

[0025] The composite gel prepared by the present invention can activate human epithelial cells, promote the proliferation of fibroblasts, solve the problem of skin aging from the root, and repair the skin barrier.

[0026] Beneficial effects of the present invention:

[0027] (1) The sodium hyaluronate in the skin correction composite gel containing high molecular weight sodium hyaluronate and epidermal growth factor provided by the present invention can play a role in replenishing the extracellular matrix (ECM) and maintaining the moisture and elasticity of the skin; at the same time, the human epidermal growth factor in the composite gel can strongly stimulate cell growth, inhibit the expression of aging genes, and prevent skin aging, thereby maintaining the optimal physiological state of the various components of the skin; in addition, the protein stabilizer added in the present invention can effectively maintain the activity of the growth factor in the gel. The composite gel composed of the above ingredients can activate epithelial fibroblasts, renew and rebuild ECM and maintain the stability of the ECM microenvironment, indirectly increase the secretion of collagen, and cooperate with the water absorption and moisturizing effect of sodium hyaluronate to solve skin problems caused by various factors (such as ultraviolet rays and facial expressions) from the source, such as wrinkles of varying depths.

[0028] (2) The composite gel for skin correction provided by the present invention, containing sodium hyaluronate and epidermal growth factor, combines the functions of traditional fillers in replenishing lost extracellular matrix with increasing cell numbers and promoting the synthesis of collagen, thereby fundamentally addressing problems such as skin wrinkles. Furthermore, compared with traditional fillers, the composite gel of the present invention has a higher molecular weight and a longer-lasting effect, making it more suitable for wrinkle filling.

[0029] (3) The composite gel of the present invention uses sodium hyaluronate as a filler for water absorption and moisturizing, which has a higher molecular weight, more pronounced effects, and longer-lasting effects. Simultaneously, the present invention uses epidermal growth factor to activate aging cells, revitalizing the skin. Furthermore, the human body naturally contains epidermal growth factor, which does not cause an immune response, has a short half-life, and does not cause excessive adverse reactions.

[0030] (4) The raw materials used in the composite gel of the present invention are all green and environmentally friendly biomaterials, do not contain any chemical substances harmful to the human body, and do not contain any cross-linking agents. Various concentrations can be prepared according to actual conditions and characteristics, and are safe and environmentally friendly. The composite gel preparation method of the present invention is simple and easy to implement, has high preparation efficiency, does not damage the original structure of the synthetic material, can be industrialized, and has good market application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative work.

[0032] Figure 1 Collagen staining results of the normal group, model group, HA group and experimental group;

[0033] Figure 2 These are the qt-PCR detection results of COL 1α1 mRNA in the normal group, model group, HA group and experimental group. DETAILED DESCRIPTION

[0034] The following will be combined with the accompanying drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is in no way intended to limit the present invention and its application or use. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0035] Example 1

[0036] Provided is a composite gel for skin correction, which is formed by dissolving high molecular weight sodium hyaluronate, human epidermal growth factor (ginsenoside) and protein stabilizer (Tween 80) in a phosphate buffer system;

[0037] Wherein: the content of sodium hyaluronate in the composite gel is 10.0 g / L, the content of human epidermal growth factor is 10,000 IU / mL, and the content of protein stabilizer is 80.0 mg / L; and the pH value of the phosphate buffer system is 7.0.

[0038] The preparation method of the composite gel of Example 1 comprises the following steps:

[0039] S1. Under sterile conditions, sodium hyaluronate and protein stabilizer (Tween 80) were dissolved in a phosphate buffer system according to the ratio and stirred for 24 hours to obtain gel A;

[0040] S2. Add epidermal growth factor to the above gel A according to the ratio, stir for 3 hours to obtain a composite gel, and fill the composite gel into a BD tube to obtain a sterile transparent gel.

[0041] Preferably, Example 1 of the present invention uses Tween 80 as a stabilizer to maintain the activity of human epidermal growth factor, which can achieve the effect of long-term stabilization of the biological activity of epidermal growth factor in the composite gel.

[0042] Example 2

[0043] Provided is a composite gel for skin correction, which is formed by dissolving high molecular weight sodium hyaluronate, human epidermal growth factor (deer antler essence) and a protein stabilizer (trehalose) in a citrate buffer system;

[0044] Wherein: the content of sodium hyaluronate in the composite gel is 5.0 g / L, the content of human epidermal growth factor is 15000 IU / mL, and the content of protein stabilizer is 20.0 mg / L; and the pH value of the citrate buffer system is 6.5.

[0045] The preparation method of the composite gel of Example 2 comprises the following steps:

[0046] S1. Under sterile conditions, dissolve sodium hyaluronate, protein stabilizer, and epidermal growth factor in a citrate buffer system according to the ratio, stir for 20 hours to obtain a composite gel, and fill the composite gel into a BD tube to obtain a sterile transparent gel.

[0047] Example 3

[0048] Provided is a composite gel for skin correction, which is formed by dissolving high molecular weight sodium hyaluronate, human epidermal growth factor (deer antler essence) and a protein stabilizer (sorbitol) in an adipic acid buffer system;

[0049] Wherein: the content of sodium hyaluronate in the composite gel is 27.5 g / L, the content of human epidermal growth factor is 5000 IU / mL, and the content of protein stabilizer is 50.0 mg / L; and the pH value of the adipic acid buffer system is 6.8.

[0050] The preparation method of the composite gel of Example 3 comprises the following steps:

[0051] S1. Under sterile conditions, dissolve sodium hyaluronate and protein stabilizer in adipic acid buffer according to the ratio and stir for 16 hours to obtain gel A;

[0052] S2. Add the above-mentioned epidermal growth factor to the above-mentioned gel A according to the ratio, stir for 4 hours to obtain a composite gel, and fill the composite gel into a BD tube to obtain a sterile transparent gel.

[0053] Example 4

[0054] Provided is a composite gel for skin correction, which is formed by dissolving high molecular weight sodium hyaluronate, human epidermal growth factor (sea plant essence) and protein stabilizer (poloxamer) in an MES buffer system;

[0055] Wherein: the content of sodium hyaluronate in the composite gel is 48.0 g / L, the content of human epidermal growth factor is 10000 IU / mL, and the content of protein stabilizer is 100.0 mg / L; and the pH value of the MES buffer system is 7.2.

[0056] The preparation method of the composite gel of Example 4 comprises the following steps:

[0057] S1. Under sterile conditions, dissolve sodium hyaluronate and protein stabilizer in MES buffer according to the ratio and stir for 20 hours to obtain gel A;

[0058] S2. Add the above-mentioned epidermal growth factor to the above-mentioned gel A according to the ratio, stir for 3 hours to obtain a composite gel, and fill the composite gel into a BD tube to obtain a sterile transparent gel.

[0059] Comparative Example 1

[0060] The difference between Comparative Example 1 and Example 1 is that the content of sodium hyaluronate in the composite gel of Comparative Example 1 is 60.0 g / L (significantly higher than the range of this application), and the other conditions of Comparative Example 1 are the same as those of Example 1.

[0061] The composite gel of Comparative Example 1 easily clogs the syringe during animal experiments and is not suitable for injection filling.

[0062] Comparative Example 2

[0063] The difference between Comparative Example 2 and Example 1 is that the content of human epidermal growth factor in the composite gel of Comparative Example 2 is 800 IU / mL (significantly lower than the range of this application), and the other conditions of Comparative Example 2 are the same as those of Example 1.

[0064] Comparative Example 3

[0065] The difference between Comparative Example 3 and Example 1 is that the content of human epidermal growth factor in the composite gel of Comparative Example 3 is 50,000 IU / mL (significantly higher than the range of this application), and the other conditions of Comparative Example 3 are the same as those of Example 1.

[0066] test:

[0067] (1) The composite gel sample in Example 1 was diluted 10-fold with 1640 medium (Gibco), and then diluted 20-fold with 1640 medium (Gibco) containing 1% fetal bovine serum to culture mouse embryonic fibroblasts (BALB / c 3T3). This group was used as the experimental group.

[0068] BALB / C 3T3 cells were directly cultured in 1640 medium containing 1% fetal bovine serum (Gibco) as a blank control group. After 72 hours of culture, the supernatant was discarded and cell proliferation was assayed using CCK-8. The results are shown in Table 1 below:

[0069] Table 1 shows the relative rates of BALB / C 3T3 cell proliferation in the experimental group and the control group.

[0070] project control group Experimental group P-value Cell proliferation number 100±4％ 173±7％ ＜0.001

[0071] As can be seen from the test data in Table 1, the cell proliferation rate of the experimental group (Example 1) was approximately 173%, which was significantly higher than that of the control group. This fully demonstrates that the composite gel of the present invention can strongly stimulate cell proliferation, thereby inhibiting the expression of aging genes, preventing skin aging, and ultimately maintaining the optimal physiological state of various components of the skin.

[0072] (2) Establishment of a photoaging model in nude mice: After 7 days of adaptation, the nude mice in the model group were irradiated with UVB on their backs 5 times a week for 8 weeks. The irradiation intensity, expressed as the minimum erythema dose (MED), was set at 1 MED (60 mJ / cm 2 ), and increased to 2MED (120mJ / cm 2 ), and increased to 3 MED (180 mJ / cm 2 ), and increased to 4 MED (240 mJ / cm 2 The total UVB volume irradiated is about 115MED (6.9J / cm 2 After modeling, the mice were divided into the following groups: ① the normal group without UVB irradiation; ② the model group with UVB irradiation and injection of normal saline; ③ the HA group with UVB irradiation and injection of sodium hyaluronate solution; and ④ the experimental group with UVB irradiation and injection of the sodium hyaluronate composite gel of Example 1.

[0073] The above groups were injected with drugs at the 6th, 7th and 8th week of modeling, with an injection volume of 50 μL at each site, for a total of four injection sites. One week after the last injection, skin tissues at the injection sites were collected, part of which was paraffin-embedded and then stained for collagen (see the results). Figure 1); the other part used qt-PCR to detect the expression of type I collagen alpha 1 chain (COL 1α1) mRNA (results see Figure 2 ), the results were consistent with those of collagen staining. With the gradual introduction of sodium hyaluronate and human epidermal growth factor, the expression level of COL 1α1 mRNA increased synchronously.

[0074] UVB irradiation causes a significant decrease in collagen in nude mouse skin. Adding sodium hyaluronate partially restores this, suggesting its ability to absorb and retain moisture. The experimental group supplemented with human epidermal growth factor restored collagen secretion to levels similar to those of the normal group, demonstrating that the composite gel of the present invention ultimately exerts its efficacy by promoting collagen secretion.

[0075] (3) Establishment of a Cellular Photoaging Model: BALB / c 3T3 cells were allowed to adhere overnight and then irradiated with a UV light therapy device. A blank control group was formed without UVB irradiation; a negative control group was formed with UV irradiation and the addition of a maintenance medium; and an experimental group was formed with UV irradiation and the addition of the composite gel from Comparative Example 1. After 72 hours of loading, the culture medium was discarded and cell proliferation was assayed using CCK-8. The results are shown in Table 2 below:

[0076] Table 2 shows the relative rates of cell proliferation in each test group.

[0077] project Blank control group Negative control group Experimental group P-value Cell proliferation number 100±4％ 67±8％ 103±7％ ＜0.001

[0078] It can be seen that the cell proliferation rate of the negative control group is only about 67%, while after adding the composite gel of Comparative Example 1, the cell number and activity can be restored to the level of the blank group, but its proliferation effect is obviously not as good as Example 1 of the present invention.

[0079] (4) The composite gel sample of Comparative Example 2 was diluted 10-fold with 1640 medium (Gibco), and then diluted 20-fold with 1640 medium (Gibco) containing 1% fetal bovine serum to culture mouse embryonic fibroblasts (BALB / c 3T3). This group served as the experimental group.

[0080] BALB / C 3T3 cells were directly cultured in 1640 medium containing 1% fetal bovine serum (Gibco) as a blank control group. After 72 hours of culture, the supernatant was discarded and cell proliferation was assayed using CCK-8. The results are shown in Table 3 below:

[0081] Table 3 shows the relative rates of BALB / C 3T3 cell proliferation in the experimental group and the control group.

[0082] project control group Experimental group P-value Cell proliferation number 100±4％ 113±7％ ＜0.05

[0083] The test results in Table 3 show that after significantly reducing the unit activity of human epidermal growth factor in the composite gel, the cell proliferation rate in the experimental group also decreased, but the effect was not obvious compared with the control group. This shows that the precisely regulated unit activity of epidermal growth factor in the present invention can strongly stimulate cell proliferation, facilitate skin correction, and revitalize the skin.

[0084] (5) The composite gel sample of Comparative Example 3 was diluted 10-fold with 1640 medium (Gibco), and then diluted 20-fold with 1640 medium (Gibco) containing 1% fetal bovine serum to culture mouse embryonic fibroblasts (BALB / c 3T3). This group was used as the experimental group.

[0085] BALB / C 3T3 cells were directly cultured in 1640 medium containing 1% fetal bovine serum (Gibco) as a blank control group. After 72 hours of culture, the supernatant was discarded and cell proliferation was assayed using CCK-8. The results are shown in Table 4 below:

[0086] Table 4 shows the relative rates of BALB / C 3T3 cell proliferation in the experimental group and the control group.

[0087] project control group Experimental group P-value Cell proliferation number 100±4％ 169±9％ ＜0.001

[0088] The test results in Table 4 show that after significantly increasing the unit activity of human epidermal growth factor in the composite gel, the cell proliferation rate of the experimental group did not increase synchronously, and its cell proliferation rate was close to that of Example 1. This shows that excessively high epidermal growth factor activity does not bring further effects to the composite gel, but instead increases the cost of raw materials.

[0089] The above preferred embodiments of the present invention are only used to explain the present invention and are not used to limit the present invention. Any obvious changes or modifications derived from the technical solution of the present invention are still within the scope of protection of the present invention.

Claims

1. A composite gel for skin correction, characterized in that: The composite gel is formed by dissolving high molecular weight sodium hyaluronate, human epidermal growth factor and protein stabilizer in a buffer system; Wherein: the content of sodium hyaluronate in the composite gel is 1.0-50.0 g / L, the content of human epidermal growth factor is 1000-30000 IU / mL, and the content of protein stabilizer is 5.0-100.0 mg / L; and the pH value of the buffer system is 6.5-7.

5.

2. The composite gel for skin correction according to claim 1, characterized in that: The molecular weight of the sodium hyaluronate is 300,000 to 3,000,000.

3. The composite gel for skin correction according to claim 1, characterized in that: The human epidermal growth factor is selected from any one or more of deer antler essence, sea plant essence, and ginsenoside.

4. The composite gel for skin correction according to claim 1, characterized in that: The protein stabilizer is selected from any one or more of Tween 20, Tween 80, poloxamer, trehalose, mannitol, amino acids, sorbitol, and inositol.

5. The composite gel for skin correction according to claim 1, characterized in that: The buffer system is selected from any one or more of phosphate, citrate, histidine, acetate, succinic acid, tromethamine, adipic acid, lactic acid and MES.

6. The composite gel for skin correction according to claim 1, characterized in that: The content of the composite gel protein stabilizer is 20.0-100.0 mg / L; and the pH value of the buffer system is 6.8-7.

2.

7. A method for preparing a composite gel for skin correction, characterized in that: The method is used to prepare the composite gel for skin correction according to any one of claims 1 to 6, and the method comprises the following steps: S1. Under sterile conditions, dissolve sodium hyaluronate and protein stabilizer in a buffer system and stir to obtain gel A; S2. Add epidermal growth factor to the above gel A and stir to obtain a composite gel.

8. A method for preparing a composite gel for skin correction, characterized in that: The method is used to prepare the composite gel for skin correction according to any one of claims 1 to 6, and the method comprises: dissolving sodium hyaluronate, a protein stabilizer and epidermal growth factor in a buffer system under sterile conditions, and stirring to obtain the composite gel.

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