Use of glutathione in medical devices / cosmetics, medical devices / cosmetics and method of use

Abstract

The application relates to the field of biological products, in particular to application and application method of glutathione in medical devices or cosmetics, and a medical device / cosmetic containing glutathione, and provides application of glutathione in specific medical devices (such as products for facial superficial dermis injection, products for wound care) and various cosmetics, wherein the amount of glutathione is 0.1-3 wt%, the glutathione is used in combination with sodium hyaluronate at a mass ratio of (0.1-3):(0.6-3), and specific antioxidant components (such as vitamin C, vitamin E, etc.) and chelating agents can be further compounded to form a synergistically stable composite system. The application effectively improves the storage stability of glutathione in the product, and enables the glutathione to be adapted to various application scenes such as injection, wound care and skin care, thereby providing a reliable technical scheme for industrial application of glutathione in the fields of medical devices and cosmetics.

Description

Technical Field

[0001] This invention belongs to the field of biological products, and specifically relates to the application and application methods of glutathione in medical devices / cosmetics, as well as medical devices / cosmetics containing glutathione. Background Technology

[0002] Glutathione (GSH) is an endogenous tripeptide composed of glutamic acid, cysteine, and glycine. It can react with free radicals in skin cells, reducing unstable free radicals and thus reducing cell damage, thereby exerting an antioxidant effect. Simultaneously, it can maintain the activity of intracellular antioxidant enzymes, further enhancing the skin's antioxidant capacity, regulating the redox state of cells, and maintaining normal cellular physiological functions. It has potential application value in areas such as skin barrier protection. From the perspective of glutathione's own characteristics, its molecular structure contains a reactive sulfhydryl group (-SH), which is key to its core functions of antioxidation and detoxification. However, it is also highly susceptible to oxidation by oxygen in the air and metal ions (such as iron and copper ions) in the system. Oxidation forms disulfide bonds, causing glutathione to lose its activity. Furthermore, oxidation products may cause discoloration and odor problems in the system, seriously affecting the product's appearance and user experience.

[0003] In the field of medical devices, most products (such as wound dressings and tissue repair materials) need to be stored for a long time or used in the body fluid environment. The instability of water-soluble medical devices cannot achieve the expected adjuvant therapeutic effects (such as anti-oxidation, anti-inflammation, and promoting wound healing). In the field of cosmetics, water-soluble systems are still the mainstream, whether they are liquids, lotions or creams. The oxidative inactivation of active ingredients will not only reduce the efficacy of the product, but may also increase the risk of skin allergies and irritation due to the presence of oxidation products.

[0004] Currently, glutathione-related products on the market are mainly concentrated in the pharmaceutical and health food sectors. However, their standardized application in medical devices and cosmetics is significantly lacking, especially in the medical device sector where its application is extremely limited, and its application in cosmetics also has many shortcomings. The main reasons for this are: glutathione has poor stability in water-soluble systems and is prone to oxidative inactivation; existing publicly available technologies mostly focus on "whether or not to add glutathione," lacking research on formulation design and application windows tailored to the different uses and scenarios of medical devices and cosmetics.

[0005] Therefore, although glutathione theoretically possesses potential for applications in medical devices and cosmetics, a technical solution that can balance stability and effectiveness is still lacking in actual industrialization. Based on this, there is a need to invent a technical solution that provides a glutathione composite solution / lyophilized fiber, enabling its stable, safe, and effective application in medical devices and / or cosmetics. Summary of the Invention

[0006] To solve the above-mentioned technical problems, this invention explores the concentration of glutathione-based raw materials and conducts numerous efficacy verification experiments, ultimately obtaining a set of application formulas and methods with excellent effects.

[0007] Specifically, the technical solution of the present invention is as follows: Firstly, the application of glutathione in medical devices or cosmetics is provided, wherein the medical devices refer to: products for superficial dermal injection in the face, and products for non-chronic and chronic wound care. The amount of glutathione used is 0.1~3wt%.

[0008] Furthermore, the amount of glutathione used is 0.1~2 wt%.

[0009] Furthermore, the medical device refers to any one of the following: solution, lyophilized fiber, dressing; The cosmetics mentioned are selected from any of the following: moisturizing, skin brightening, soothing and repairing, or firming and anti-wrinkle skincare products.

[0010] As a preferred option, glutathione and sodium hyaluronate are used in combination, with the mass ratio of the two being (0.1~3):(0.6~3).

[0011] Secondly, the company provides medical devices / cosmetics containing glutathione, wherein the glutathione content in the medical device is 0.1 to 3 wt%.

[0012] Furthermore, the medical device also contains 0.6 to 3 wt% sodium hyaluronate.

[0013] Furthermore, the medical device also contains 0.1 to 2 wt% of antioxidant components.

[0014] Furthermore, the antioxidant ingredient is selected from at least one of the following: vitamin C, vitamin E, sodium metabisulfite, trehalose, astaxanthin, and carnosine.

[0015] Furthermore, the medical device also contains 0.01~0.05 wt% of a chelating agent.

[0016] Thirdly, a method for applying glutathione in medical devices / cosmetics is provided, characterized by comprising the following steps: (1) Weigh out water for injection and add it to the mixing reactor, then stir; (2) Add 0.6 to 3 parts of sodium hyaluronate and continue stirring; (3) After dissolving completely, add 0.1-2 parts of antioxidant, 0.1-2 parts of pH adjuster, 0.01-0.05 parts of chelating agent and 0.1-0.5 parts of osmotic pressure adjuster, and continue stirring; the antioxidant is selected from at least one of the following: vitamin C, vitamin E, sodium metabisulfite, trehalose, astaxanthin, carnosine; (4) After the aforementioned materials have been fully dissolved, add 0.1 to 3 parts of glutathione and continue stirring; (5) The prepared solution is sterilized by high-temperature steam / filtration to obtain the medical device product; When the medical device product is freeze-dried fiber, it is subjected to freeze-drying treatment after sterilization. When the medical device product is a dressing, the sterilized solution is filled into an aluminum foil bag containing the dressing.

[0017] Compared with the prior art, the present invention has the following advantages and effects: This invention applies glutathione to medical devices / cosmetics. The results have been verified through a large number of experiments. The results show that glutathione can exist stably in the aqueous system at a concentration of 0.1-3%, effectively inhibiting its oxidative inactivation and significantly improving the storage stability of the product. This solves the problem of poor stability and difficulty in long-term preservation of glutathione in medical device / cosmetic formulations in the prior art. This invention achieves synergistic effects between glutathione and sodium hyaluronate through a scientific ratio (mass ratio 0.1~2:0.6~3). Glutathione can effectively scavenge free radicals and delay the molecular weight degradation of sodium hyaluronate. The moisturizing, adhesive, and wound protection effects of sodium hyaluronate complement the antioxidant effects of glutathione, significantly improving the formulation stability of the product and solving the shortcomings of existing technologies where adding glutathione alone has limited effects and lacks a dedicated formulation design.

[0018] (3) The present invention can flexibly add 1-2% of antioxidant ingredients such as vitamin C, vitamin E, sodium metabisulfite, trehalose, astaxanthin, and carnosine, which form a "chelation-antioxidant" synergistic system with glutathione and disodium edetate, further enhancing the antioxidant efficacy of the formula and delaying the oxidative inactivation of glutathione; at the same time, it can improve the moisturizing and soothing effects of the product, reduce the risk of skin irritation, adapt to different skin types and different applicable scenarios, and expand the scope of application of glutathione products. Compared with the single antioxidant system in the existing technology, it has greater advantages in stability and applicability. (4) The present invention can be prepared into three forms: solution, freeze-dried fiber, and dressing, which are suitable for different medical device usage scenarios: the solution form is convenient for superficial injection into the facial dermis and direct application to the wound, and is easy to use; the freeze-dried fiber form can further extend the shelf life of the product, is convenient for storage and transportation, and has a high activity retention rate after reconstitution; the dressing form has good fit and can be directly applied to the wound to play a protective role, and has both breathability and absorbency, making it suitable for non-chronic wounds and facial minimally invasive postoperative care scenarios; the three forms complement each other, filling the gap of glutathione in different forms of medical device products, and compared with the problem of single product form in the prior art, the market applicability and competitiveness are greatly improved; (5) This invention realizes the standardized and normalized application of glutathione in the fields of medical devices and cosmetics, clarifies its concentration range, formulation ratio and preparation process, breaks the status quo of the lack of application of glutathione in the field of medical devices and the lack of exclusive formulation design in the existing technology, and fills the gap of its concentration application in the field of cosmetics without evidence and insufficient stability. It provides a practical and feasible technical solution for the industrial application of glutathione in the two major fields of medical devices and cosmetics, and has significant innovative value and application prospects. Attached Figure Description

[0019] Figure 1 The images show the appearance of the solutions in Examples 1-6 of this invention after being left at room temperature for 90 days (from left to right: Example 1, Example 2, Example 3, Example 4, Example 5, Example 6).

[0020] Figure 2 The images show the appearance of the solutions of Comparative Examples 1-3 after being left at room temperature for 90 days (from left to right: Comparative Example 1, Comparative Example 2, Comparative Example 3).

[0021] Figure 3 The figures represent the DPPH free radical scavenging rates of the present invention in different embodiments and comparative examples.

[0022] Figure 4 The cell survival rates are shown in different embodiments and comparative examples of this invention. Detailed Implementation

[0023] To enable those skilled in the art to better understand the present invention, the present invention will now be further described in conjunction with specific embodiments.

[0024] In this application, glutathione (hereinafter referred to as GSH) refers to injectable glutathione; sodium hyaluronate (hereinafter referred to as HA) is a common commercially available product.

[0025] The amounts of each raw material used in Examples 1-6 are shown in Table 1 below: Table 1. Specific formulation composition (wt%) of Examples 1-6 name Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Sodium hyaluronate 0.6 0.8 1.2 1.5 2.0 3.0 Glutathione 0.1 0.5 0.8 1.0 2.0 3.0 Sodium metabisulfite 0.01 0.02 0.02 0.05 0.05 0.1 Sodium edetate 0.01 0.01 0.02 0.03 0.05 0.05 Vitamin C 0.01 0.02 0.03 0.04 0.04 0.04 Sodium chloride 0.3 0.3 0.3 0.5 0.5 0.5 Anhydrous disodium hydrogen phosphate 0.3 0.4 0.5 0.8 1.0 1.5 Anhydrous sodium dihydrogen phosphate 0.02 0.05 0.01 0.02 0.01 0.01 Water for Injection margin margin margin margin margin margin

[0026] Example 1: Sodium hyaluronate 0.6wt%, glutathione 0.1wt%, sodium metabisulfite 0.01wt%, disodium edetate 0.01wt%, vitamin C 0.01wt%, sodium chloride 0.3wt%, anhydrous disodium hydrogen phosphate 0.3wt%, anhydrous sodium dihydrogen phosphate 0.02wt%, water for injection balance.

[0027] Specific preparation method: S1: Weigh out water for injection and add it to the mixing reactor. Set the stirring speed to about 35 r / min and turn on the stirring. S2: Slowly add accurately weighed sodium hyaluronate and continue stirring for about 1 hour; S3: After there are no obvious white lumps in the liquid, add sodium metabisulfite, disodium edetate, vitamin C, sodium chloride, anhydrous disodium hydrogen phosphate and anhydrous sodium dihydrogen phosphate, and set the stirring speed to about 35 r / min and continue stirring; S4: After the aforementioned materials have fully dissolved, add the accurately weighed glutathione and continue stirring for about 20 minutes; add water for injection to the total volume, stir well, and obtain the composite solution. S5: Once the solution is prepared, prepare the silica gel tubing and the 0.22μm capsule filter, turn on the peristaltic pump, and perform filtration; S6: After filtration, aseptic filling is performed and the contents are filled into vials; S7: Cap the vials with rubber stoppers onto aluminum-plastic caps. Once all vials in the batch have been capped, begin the crimping process. Place the vials on the crimping machine's worktable and pull down the handle to complete the crimping. S8: Labeling, outsourcing.

[0028] Example 2:

[0029] Sodium hyaluronate 0.8wt%, glutathione 0.5wt%, sodium metabisulfite 0.02wt%, disodium edetate 0.01wt%, vitamin C 0.02wt%, sodium chloride 0.3wt%, anhydrous disodium hydrogen phosphate 0.4wt%, anhydrous sodium dihydrogen phosphate 0.05wt%, water for injection balance.

[0030] Specific preparation method: S1: Weigh out water for injection and add it to the mixing reactor. Set the stirring speed to about 40 r / min and turn on the stirring. S2: Slowly add accurately weighed sodium hyaluronate and continue stirring for about 1.5 hours; S3: After there are no obvious white lumps in the liquid, add sodium metabisulfite, disodium edetate, vitamin C, sodium chloride, anhydrous disodium hydrogen phosphate and anhydrous sodium dihydrogen phosphate, and set the stirring speed to about 40 r / min and continue stirring. S4: After the aforementioned materials have been fully dissolved, add the accurately weighed glutathione and continue stirring for about 25 minutes; add water for injection to the total volume, stir evenly, and obtain the composite solution; S5: Once the solution is prepared, prepare the silica gel tubing and the 0.22μm capsule filter, turn on the peristaltic pump, and perform filtration; S6: After filtration, aseptic filling is performed and the contents are filled into vials; S7: Cap the vials with rubber stoppers onto aluminum-plastic caps. Once all vials in the batch have been capped, begin the crimping process. Place the vials on the crimping machine's worktable and pull down the handle to complete the crimping. S8: Labeling, outsourcing.

[0031] Example 3:

[0032] Sodium hyaluronate 1.2wt%, glutathione 0.8wt%, sodium metabisulfite 0.02wt%, disodium edetate 0.02wt%, vitamin C 0.03wt%, sodium chloride 0.3wt%, anhydrous disodium hydrogen phosphate 0.5wt%, anhydrous sodium dihydrogen phosphate 0.01wt%, water for injection balance.

[0033] Specific preparation method: S1: Weigh out water for injection and add it to the mixing reactor. Set the stirring speed to about 40 r / min and turn on the stirring. S2: Slowly add accurately weighed sodium hyaluronate and continue stirring for about 2 hours; S3: After there are no obvious white lumps in the liquid, add sodium metabisulfite, disodium edetate, vitamin C, sodium chloride, anhydrous disodium hydrogen phosphate and anhydrous sodium dihydrogen phosphate, and set the stirring speed to about 40 r / min and continue stirring. S4: After the aforementioned materials have been fully dissolved, add the accurately weighed glutathione and continue stirring for about 25 minutes; add water for injection to the total volume, stir evenly, and obtain the composite solution; S5: Once the solution is prepared, prepare the silica gel tubing and the 0.22μm capsule filter, turn on the peristaltic pump, and perform filtration; S6: After filtration, aseptic filling is performed and the contents are filled into vials; S7: Cap the vials with rubber stoppers onto aluminum-plastic caps. Once all vials in the batch have been capped, begin the crimping process. Place the vials on the crimping machine's worktable and pull down the handle to complete the crimping. S8: Labeling, outsourcing.

[0034] Example 4: Sodium hyaluronate 1.5wt%, glutathione 1.0wt%, sodium metabisulfite 0.05wt%, disodium edetate 0.03wt%, vitamin C 0.04wt%, sodium chloride 0.5wt%, anhydrous disodium hydrogen phosphate 0.8wt%, anhydrous sodium dihydrogen phosphate 0.02wt%, water for injection balance.

[0035] Specific preparation method: S1: Weigh out water for injection and add it to the mixing reactor. Set the stirring speed to about 45 r / min and turn on the stirring. S2: Slowly add accurately weighed sodium hyaluronate and continue stirring for about 2.5 hours; S3: After there are no obvious white lumps in the liquid, add sodium metabisulfite, disodium edetate, vitamin C, sodium chloride, anhydrous disodium hydrogen phosphate and anhydrous sodium dihydrogen phosphate, and set the stirring speed to about 45 r / min and continue stirring. S4: After the aforementioned materials have been fully dissolved, add the accurately weighed glutathione and continue stirring for about 30 minutes; S5: Add water for injection to the total volume, stir well to obtain a composite solution; S6 (Solution Product): The prepared solution is filtered through a 0.22 μm capsule filter for sterilization, aseptically filled into vials, and sealed to obtain a solution-type medical device product for facial injection or wound application.

[0036] S6' (dressing product): After sterilizing the solution obtained in step S5 with high-temperature steam (121°C, 8 min), it is filled into an aluminum foil bag containing a sterile non-woven fabric drape under aseptic conditions and sealed to obtain the wound dressing.

[0037] S6'' (Freeze-dried fiber product): The solution obtained in step S5 is filled into vials, freeze-dried (pre-freezing: -40°C, 4h; sublimation drying: -20°C, 24h; desorption drying: 25°C, 6h), and then sealed to obtain freeze-dried fibers.

[0038] S7: Labeling, outsourcing.

[0039] Example 5: Sodium hyaluronate 2.0wt%, glutathione 2.0wt%, sodium metabisulfite 0.05wt%, disodium edetate 0.05wt%, vitamin C 0.04wt%, sodium chloride 0.5wt%, anhydrous disodium hydrogen phosphate 1.0wt%, anhydrous sodium dihydrogen phosphate 0.01wt%, water for injection balance.

[0040] Specific preparation method: S1: Weigh out water for injection and add it to the mixing reactor. Set the stirring speed to about 40 r / min and turn on the stirring. S2: Slowly add accurately weighed sodium hyaluronate and continue stirring for about 2 hours; S3: After there are no obvious white lumps in the liquid, add sodium metabisulfite, disodium edetate, vitamin C, sodium chloride, anhydrous disodium hydrogen phosphate and anhydrous sodium dihydrogen phosphate, and set the stirring speed to about 40 r / min and continue stirring. S4: After the aforementioned materials have been fully dissolved, add the accurately weighed glutathione and continue stirring for about 25 minutes; add water for injection to the total volume, stir evenly, and obtain the composite solution; S5: Once the solution is prepared, prepare the silica gel tubing and the 0.22μm capsule filter, turn on the peristaltic pump, and perform filtration; S6: After filtration, aseptic filling is performed and the contents are filled into vials; S7: Cap the vials with rubber stoppers onto aluminum-plastic caps. Once all vials in the batch have been capped, begin the crimping process. Place the vials on the crimping machine's worktable and pull down the handle to complete the crimping. S8: Labeling, outsourcing.

[0041] Example 6: Sodium hyaluronate 3.0wt%, glutathione 3.0wt%, sodium metabisulfite 0.1wt%, disodium edetate 0.05wt%, vitamin C 0.04wt%, sodium chloride 0.5wt%, anhydrous disodium hydrogen phosphate 1.5wt%, anhydrous sodium dihydrogen phosphate 0.01wt%, water for injection balance.

[0042] Specific preparation method: S1: Weigh out water for injection and add it to the mixing reactor. Set the stirring speed to about 40 r / min and turn on the stirring. S2: Slowly add accurately weighed sodium hyaluronate and continue stirring for about 2 hours; S3: After there are no obvious white lumps in the liquid, add sodium metabisulfite, disodium edetate, vitamin C, sodium chloride, anhydrous disodium hydrogen phosphate and anhydrous sodium dihydrogen phosphate, and set the stirring speed to about 40 r / min and continue stirring. S4: After the aforementioned materials have been fully dissolved, add the accurately weighed glutathione and continue stirring for about 25 minutes; add water for injection to the total volume, stir evenly, and obtain the composite solution; S5: Once the solution is prepared, prepare the silica gel tubing and the 0.22μm capsule filter, turn on the peristaltic pump, and perform filtration; S6: After filtration, aseptic filling is performed and the contents are filled into vials; S7: Cap the vials with rubber stoppers onto aluminum-plastic caps. Once all vials in the batch have been capped, begin the crimping process. Place the vials on the crimping machine's worktable and pull down the handle to complete the crimping. S8: Labeling, outsourcing.

[0043] Comparative Example 1: Sodium hyaluronate 1.5 wt%, glutathione 0.8 wt%, vitamin C 0.04 wt%, anhydrous disodium hydrogen phosphate 1.0 wt%, water for injection balance. (Key stabilizers such as sodium metabisulfite and disodium edetate are missing.) Specific preparation method: S1: Weigh out water for injection and add it to the mixing reactor. Set the stirring speed to about 40 r / min and turn on the stirring. S2: Slowly add accurately weighed sodium hyaluronate and continue stirring for about 2 hours; S3: After there are no obvious white lumps in the liquid, add vitamin C and anhydrous disodium hydrogen phosphate, and continue stirring at a stirring speed of about 40 r / min. S4: After the aforementioned materials have been fully dissolved, add the accurately weighed glutathione and continue stirring for about 25 minutes; S5: Once the solution is prepared, prepare the silica gel tubing and the 0.22μm capsule filter, turn on the peristaltic pump, and perform filtration; S6: After filtration, aseptic filling is performed and the contents are filled into vials; S7: Cap the vials with rubber stoppers onto aluminum-plastic caps. Once all vials in the batch have been capped, begin the crimping process. Place the vials on the crimping machine's worktable and pull down the handle to complete the crimping. S8: Labeling, outsourcing.

[0044] After sterilization, the liquid solution was observed to be quite thin. The sterilized product was stored away from light and left at room temperature for 30 days, during which time the liquid solution turned a light yellow color. After 90 days at room temperature, the product showed a distinctly yellow color. This indicates that the stability of the above formula needs improvement.

[0045] Comparative Example 2: Sodium hyaluronate 1.5wt%, glutathione 0.8wt%, sodium metabisulfite 0.1wt%, anhydrous disodium hydrogen phosphate 0.8wt%, water for injection balance.

[0046] Specific preparation method: S1: Weigh out water for injection and add it to the mixing reactor. Set the stirring speed to about 40 r / min and turn on the stirring. S2: Slowly add accurately weighed sodium hyaluronate and continue stirring for about 2 hours; S3: After there are no obvious white lumps in the liquid, add sodium metabisulfite and anhydrous disodium hydrogen phosphate, and continue stirring at a stirring speed of about 40 r / min. S4: After the aforementioned materials have been fully dissolved, add the accurately weighed glutathione and continue stirring for about 25 minutes; S5: Once the solution is prepared, prepare the silica gel tubing and the 0.22μm capsule filter, turn on the peristaltic pump, and perform filtration; S6: After filtration, aseptic filling is performed and the contents are filled into vials; S7: Cap the vials with rubber stoppers onto aluminum-plastic caps. Once all vials in the batch have been capped, begin the crimping process. Place the vials on the crimping machine's worktable and pull down the handle to complete the crimping. S8: Labeling, outsourcing.

[0047] The sterilized product was stored away from light and left at room temperature for 30 days, during which time the liquid turned a light yellow color. After being left at room temperature for 90 days, the product turned a distinctly yellow color upon observation.

[0048] Comparative Example 3: Sodium hyaluronate 3.5wt%, glutathione 3.5wt%, sodium metabisulfite 0.3wt%, anhydrous disodium hydrogen phosphate 2.0wt%, water for injection balance.

[0049] Specific preparation method: S1: Weigh out water for injection and add it to the mixing reactor. Set the stirring speed to about 40 r / min and turn on the stirring. S2: Slowly add accurately weighed sodium hyaluronate and continue stirring for about 2 hours; S3: After there are no obvious white lumps in the liquid, add sodium metabisulfite and anhydrous disodium hydrogen phosphate, and continue stirring at a stirring speed of about 40 r / min. S4: After the aforementioned materials have been fully dissolved, add the accurately weighed glutathione and continue stirring for about 25 minutes; S5: Once the solution is prepared, prepare the silica gel tubing and the 0.22μm capsule filter, turn on the peristaltic pump, and perform filtration; S6: The solution is viscous, making filtration extremely difficult and unable to complete the sterilization filtration process within a reasonable time. After filtration, the integrity of the capsule filter membrane is damaged. S7: The filtered solution is filled into vials. The vials with rubber stoppers are then capped with aluminum-plastic caps. Once all vials in the batch are capped, the capping process begins. The vials are placed on the capping machine's worktable, and the handle is pulled down to complete the capping. S8: Labeling, outsourcing.

[0050] The feed solution was too viscous, making filtration and sterilization difficult and damaging the integrity of the filter membrane. After sterilization, the product was stored away from light at room temperature for 30 days, during which time the feed solution turned a light yellow. After 90 days at room temperature, the product showed a distinctly yellow color.

[0051] Comparative Example 4: The preparation method is the same as that of Comparative Example 3, except that the formulation of this comparative example is: containing 1.2% sodium hyaluronate (HA), 0.5% sodium chloride, 0.5% anhydrous disodium hydrogen phosphate, and the balance being water for injection.

[0052] Performance Testing and Results Analysis I. Stability Testing (Chemical Stability and Physical Stability): Glutathione (GSH) content determination: Samples from Examples 1-6 and Comparative Examples 1-3 were placed under accelerated conditions at 40°C and samples were taken at 0, 1, 2, and 3 months. The GSH content was determined by high-performance liquid chromatography (HPLC). The results are shown in Table 2. The GSH retention rate of the Example samples was >90% after 3 months, while the content of Comparative Examples 1 and 2 decreased significantly due to incomplete stability systems. The content of Comparative Example 3 (GSH 3.5%) rapidly decreased to below 85% after 1 month, demonstrating that stability deteriorates beyond the concentration range of this invention.

[0053] Protective effect of sodium hyaluronate on molecular weight: To verify the synergistic protective effect of glutathione on sodium hyaluronate, Comparative Example 4 (containing HA, without GSH) and Example 3 (containing HA and GSH) were set up as controls. After being placed at 40°C for 3 months, the change in HA molecular weight was determined by gel permeation chromatography. The results showed that the HA molecular weight of Comparative Example 4 (without GSH protection) decreased by approximately 25%, while the HA molecular weight in Example 3 decreased by only approximately 8%, demonstrating that GSH has a significant protective effect against HA degradation, and that the two have a synergistic effect.

[0054] Table 2. Glutathione content retention rate after accelerated stability test Group 0% content Content retention rate after 3 months (%) Appearance changes Example 3 100 95.2 Colorless and clear Example 4 100 96.8 Colorless and clear Comparative Example 1 100 68.5 Dark yellow Comparative Example 2 100 75.3 brownish-yellow Comparative Example 3 100 72.1 Yellowish-brown, with increased viscosity II. Antioxidant Capacity Test: Accurately weigh 4 mg of DPPH powder, dissolve it completely in 70% ethanol, and dilute to 100 mL to prepare a 0.1 mM DPPH solution. Store the solution in a brown bottle protected from light at 4°C. Prepare composite solutions of different concentrations, mix them according to the specified ratio, and allow them to react in the dark at room temperature for 1 h. Use purified water as a blank control group, and measure the absorbance at 517 nm using a UV spectrophotometer. The DPPH free radical scavenging rate is expressed by the following formula: ; Where A1 is the absorbance of the solution with DPPH and sample as the experimental group, A2 is the absorbance of the solution with DPPH and anhydrous ethanol as the background group, and A3 is the absorbance of the anhydrous ethanol solution as the blank group. The test results are shown in Table 3 below: Table 3. DPPH free radical scavenging rate of glutathione at different concentrations Group Absorbance value (A) DPPH free radical scavenging rate (%) Blank control group 1.243±0.035 0.0±2.1 Example 1 0.942±0.028 23.6±1.8 Example 2 0.326±0.019 73.7±1.5 Example 3 0.184±0.015 85.3±1.2 Example 4 0.158±0.012 87.3±0.9 Example 5 0.126±0.011 89.7±0.8 Example 6 0.126±0.010 89.7±0.7 Comparative Example 1 1.093±0.021 12.07±1.6 Comparative Example 2 1.097±0.017 11.74±0.8 Comparative Example 3 1.012±0.013 18.58±1.1 As shown in Table 3, the DPPH scavenging rate of the example samples increased with increasing GSH concentration, and was significantly higher than that of the comparative samples, exhibiting DPPH free radical scavenging activity in a dose-dependent manner, proving that the formulation of the present invention can effectively maintain the antioxidant activity of GSH. In contrast, the comparative samples were inactivated due to the instability of GSH, resulting in a low DPPH free radical scavenging rate.

[0055] III. In vitro cytotoxicity experiments: 1. Digest the cultured L929 cells with 0.25% trypsin solution to prepare a cell suspension, and adjust the cell concentration to 1×10⁻⁶. 5 per mL.

[0056] 2. The prepared cell suspension was seeded into 96-well plates, with blank control (MEM medium containing 10% fetal bovine serum), negative control (high-density polyethylene resin), positive control (DMSO), and Examples 1, 2, 3, 4, 5 and 6. Each group was divided into 6 replicates, and 100 μL of cell suspension was seeded into each well.

[0057] 3. Place the 96-well plate in a CO2 incubator at 37°C and 5% CO2 for 24 hours. After 24 hours, discard the culture medium, add the corresponding samples, and place the plate in a CO2 incubator at 37°C and 5% CO2 for 24 hours.

[0058] 4. Discard the sample and control solutions, add 50µL of MTT (1mg / mL) solution to each well, and continue to incubate in a carbon dioxide incubator at 37℃ with 5% CO2 for 2h. Discard the MTT solution, add 100µL of isopropanol to each well, and incubate in a shaker at 37℃ with 60rpm for 30min.

[0059] 5. Measure the absorbance at a wavelength of 570 nm using an ELISA reader.

[0060]

[0061] Where: OD 570e —The average optical density (OD) of 100% extract of the test sample. 570b — Average blank optical density.

[0062] The experimental results are shown in Table 4 below. Table 4. Cell viability of different samples Group Cell viability (%) SD(%) negative control 100.00 5.78 Example 1 83.60 3.83 Example 2 84.23 4.13 Example 3 82.65 3.30 Example 4 84.42 4.14 Example 5 83.67 2.04 Example 6 82.25 4.63 Comparative Example 1 76.85 4.28 Comparative Example 2 57.23 3.27 Comparative Example 3 77.42 3.14 like Figure 4 As shown, the lower the L929 cell survival rate, the higher the cytotoxicity of the sample. Table 4 shows that the cell survival rates in Examples 1-6 were all above 70%, indicating no potential cytotoxicity.

[0063] Example 7: The formula is as follows: 1.2 wt% HA, 1.0 wt% GSH, 0.5 wt% Vitamin E (dissolved in a small amount of ethanol before addition), 0.02 wt% disodium edetate, 0.5 wt% anhydrous disodium hydrogen phosphate, with the balance being water for injection. The preparation method is the same as in Example 4, followed by filtration for sterilization. This formula has a moisturizing feel and is suitable for dry skin care.

[0064] Example 8: The formulation is as follows: 1.0 wt% HA, 0.5 wt% GSH, 0.8 wt% carnosine, 0.05 wt% sodium metabisulfite, 0.03 wt% disodium edetate, 0.3 wt% sodium chloride, with the balance being water for injection. The preparation method is the same as in Example 4. This formulation exhibits both antioxidant and anti-glycation effects.

[0065] The accelerated stability tests described above were performed on Examples 7 and 8, following the test method of Example 3. After 3 months, the GSH retention rates were 94.5% and 93.1%, respectively, the DPPH scavenging rates were 82.1% and 78.6%, respectively, and the cell survival rates were all above 80%, demonstrating that different types and concentrations of antioxidant components can achieve good stability and effects under the system of the present invention.

[0066] Product form verification Reconstitution activity of lyophilized fibers: The lyophilized fibers prepared in Example 4 were reconstituted with sterile water for injection, and their DPPH free radical scavenging rate was measured. The results showed that the scavenging rate of the reconstituted solution was 98.5% of that of the initial solution, proving that the lyophilization process can greatly preserve the product activity.

[0067] Dressing performance: The dressing prepared in Example 3 has a moderate liquid carrying capacity for the solution and exhibits good fit and breathability when applied to an artificial skin model, making it suitable for wound care.

[0068] Of course, the above description is not limited to the examples above. Technical features not described in this invention can be implemented by or using existing technology, and will not be repeated here. The above embodiments and drawings are only used to illustrate the technical solutions of this invention and are not intended to limit this invention. This invention has been described in detail with reference to preferred embodiments. Those skilled in the art should understand that any changes, modifications, additions or substitutions made by those skilled in the art within the scope of this invention do not depart from the spirit of this invention and should also fall within the scope of protection of the claims of this invention.

Claims

1. The application of glutathione in medical devices or cosmetics, characterized in that, The medical devices mentioned refer to: products for superficial dermal injections in the face, and products for non-chronic and chronic wound care. The amount of glutathione used is 0.1~3wt%.

2. The application as described in claim 1, characterized in that, The amount of glutathione used is 0.1~2 wt%.

3. The application as described in claim 1, wherein the medical device refers to any one of the following: solution, lyophilized fiber, dressing; The cosmetics mentioned are selected from any of the following: moisturizing, skin brightening, soothing and repairing, or firming and anti-wrinkle skin care products.

4. The application as described in claim 1, characterized in that, When glutathione and sodium hyaluronate are used together, the mass ratio of the two is (0.1~3): (0.6~3).

5. A medical device / cosmetic containing glutathione, characterized in that, The medical device contains 0.1-3 wt% glutathione.

6. The medical device / cosmetic as described in claim 5, characterized in that, The medical device also contains 0.6-3 wt% sodium hyaluronate.

7. The medical device / cosmetic as described in claim 6, characterized in that, The medical device also contains 0.1 to 2 wt% antioxidant components.

8. The medical device / cosmetic as described in claim 7, characterized in that, The antioxidant component is selected from at least one of the following: vitamin C, vitamin E, sodium metabisulfite, trehalose, astaxanthin, and carnosine.

9. The medical device / cosmetic as described in claim 8, characterized in that, The medical device also contains 0.01 to 0.05 wt% of a chelating agent.

10. A method for applying glutathione in medical devices / cosmetics, characterized in that, The steps include the following: (1) Weigh out water for injection and add it to the mixing reactor, then stir; (2) Add 0.6 to 3 parts of sodium hyaluronate and continue stirring; (3) After dissolving completely, add 0.1-2 parts of antioxidant, 0.1-2 parts of pH adjuster, 0.01-0.05 parts of chelating agent and 0.1-0.5 parts of osmotic pressure adjuster, and continue stirring; the antioxidant is selected from at least one of the following: vitamin C, vitamin E, sodium metabisulfite, trehalose, astaxanthin, carnosine; (4) After the aforementioned materials have been fully dissolved, add 0.1 to 3 parts of glutathione and continue stirring; (5) The prepared solution is sterilized by high-temperature steam / filtered to obtain the medical device product; When the medical device product is freeze-dried fiber, it is freeze-dried after sterilization. When the medical device product is a dressing, the sterilized solution is filled into an aluminum foil bag containing the dressing.

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