Anti-allergic polymer and application thereof as skin repairing agent

Abstract

The invention relates to the technical field of antianaphylaxis, in particular to an antianaphylaxis polymer and application of the antianaphylaxis polymer as a skin repairing agent.The antianaphylaxis polymer is composed of chitosan, a tannic acid-ovalbumin compound and amination modified graphene quantum dots; the particle size of the amination modified graphene quantum dots is 5-20 nm, the surface amino density is 3.5-5.0 mmol / g, and the addition amount of the amination modified graphene quantum dots is 0.5-1% of the mass of ovalbumin protein; the mass ratio of the chitosan to the tannic acid-ovalbumin compound is 1: (0.5-0.8); the anti-allergic polymer prepared by the scheme has excellent anti-allergic performance and skin repair effect, all components of the cream prepared by compounding the anti-allergic polymer with specific auxiliary materials are selected from natural materials or materials with good biocompatibility, the preparation process is mild and controllable, no harmful by-product is generated, and the product is mild and non-irritant in use and is suitable for long-term use.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of anti-allergy, in particular to an anti-allergy polymer and its application as a skin repair agent. BACKGROUND

[0002] Allergic skin problems have become a global concern for skin health issues, and the number of patients with allergic skin diseases worldwide continues to grow, with factors such as environmental pollution and lifestyle changes further exacerbating this trend. As the largest barrier organ of the human body, once the skin has an allergic reaction, it will not only cause symptoms such as erythema, itching, and stinging, but also may lead to damaged skin barrier, thereby increasing the risk of infection and seriously affecting people's quality of life. Therefore, developing external products with high-efficiency anti-allergy performance and skin repair function has become a research hotspot in the current skin care and cosmeceutical fields.

[0003] The anti-allergy products on the market at present mainly include preparations containing chemical anti-allergy drugs and care products containing natural ingredients. Although chemical products such as loratadine can quickly relieve allergic symptoms, long-term use may cause skin irritation, drug resistance and other side effects, and lack of repair effect on damaged skin barrier; natural products mostly use hyaluronic acid, ceramide, plant extracts, etc., which are mild and safe, but often have limited anti-allergy effect and single mechanism of action, making it difficult to meet the dual needs of rapid anti-allergy and deep repair of the skin.

[0004] Therefore, it is of great practical significance to develop a polymer with good ingredient synergy, scientific preparation process, and high-efficiency anti-allergy and skin repair function, and its external preparation. SUMMARY

[0005] The purpose of the present application is to overcome the shortcomings of the prior art and provide an anti-allergy polymer.

[0006] The specific technical solution is as follows: an anti-allergy polymer is composed of chitosan, tannic acid-ovalbumin complex and amino-modified graphene quantum dots; the particle size of the amino-modified graphene quantum dots is 5-20 nm, the surface amino group density is 3.5-5.0 mmol / g, and the addition amount is 0.5-1% of the mass of ovalbumin; the mass ratio of chitosan to tannic acid-ovalbumin complex is 1:0.5-0.8.

[0007] As a further technical solution, the degree of deacetylation of the chitosan is ≥85%, and the viscosity average molecular weight is 50000-100000 Da.

[0008] As a further technical solution, the preparation method of the tannic acid-ovalbumin complex is as follows: Dissolve the ovalbumin in a phosphate buffer solution with a pH of 6.5-7.5 and a concentration of 0.01-0.05 mol / L, stir until completely dissolved, add the amino-modified graphene quantum dots, and ultrasonically disperse at a power of 150-200 W for 10-20 min to obtain a mixed solution; dissolve the tannic acid in an ethanol solution with a mass concentration of 5-10% to obtain a tannic acid solution; under the condition of nitrogen protection and a temperature of 25-35℃, add the tannic acid solution to the mixed solution at a rate of 1-2 drops per second through a constant-pressure dropping funnel, stir at a constant temperature for 2-4 h after the dripping is completed, then dialyze in a dialysis bag with a molecular weight cutoff of 8000-14000 Da for 24-48 h, replace the phosphate buffer solution every 8 h, and then freeze-dry under the condition of a vacuum degree of ≤10 Pa and a temperature of -50 to -40℃ for 24-36 h to obtain the tannic acid-ovalbumin complex; wherein the mass ratio of the ovalbumin to the tannic acid is 1:0.8-1.2.

[0009] As a further technical solution, the polymer is prepared by a segmented temperature control grafting reaction, and the specific steps are as follows: dissolve the chitosan in a dilute acetic acid solution with a volume concentration of 1-2%, stir until completely dissolved to obtain a chitosan solution; add the tannic acid-ovalbumin complex and the amino-modified graphene quantum dots to the chitosan solution, ultrasonically disperse at a power of 200-250 W for 20-30 min until uniform, add 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide as activators, first react at 30-32℃ for 3-4 h, then warm up to 38-40℃ for 3-4 h; after the reaction is completed, adjust the pH of the system to 6.8-7.2 with a 1 mol / L NaOH solution, and collect the precipitate by centrifugation at a speed of 8000-10000 r / min for 15-20 min; wash the precipitate with deionized water and anhydrous ethanol for 3 times, and then freeze-dry under the condition of a vacuum degree of ≤10 Pa and a temperature of -55 to -45℃ for 36-48 h to obtain the anti-allergic polymer; wherein the molar ratio of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride to N-hydroxysuccinimide is 1:1, and the amount of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride added is 5-8% of the mass of the chitosan.

[0010] As a further technical solution, the preparation method of the amino-modified graphene quantum dots is as follows: disperse the graphene quantum dots in anhydrous ethanol, add 3-aminopropyltriethoxysilane, and reflux at 70-80℃ for 6-8 h; after the reaction is completed, centrifuge and separate the precipitate, wash it with anhydrous ethanol for 3 times, and vacuum dry to obtain the amino-modified graphene quantum dots.

[0011] The anti-allergic polymer is applied as a skin repair agent.

[0012] As a further technical solution, the anti-allergy polymer is compounded with adjuvants to prepare an external preparation with anti-allergy and skin repair functions, which is in the form of a cream.

[0013] As a further technical solution, when preparing the cream, the adjuvants include an oil base, an emulsifier, a humectant, a preservative; the mass percentage of each component is: anti-allergy polymer 4-6%, oil base 15-20%, emulsifier 3-5%, humectant 8-12%, preservative 0.2-0.4%, ginseng extracellular vesicles 0.2-0.3%, red ganoderma extract 0.3-0.4%, and the balance is deionized water; and the preparation method is: heating and melting the oil base to 60-70 DEG C as the oil phase; dissolving the humectant and the preservative in deionized water and heating to 60-70 DEG C as the water phase; slowly adding the water phase to the oil phase, stirring and emulsifying, and cooling to below 40 DEG C to add the anti-allergy polymer, ginseng extracellular vesicles and red ganoderma extract, stirring uniformly until solidification to obtain the cream.

[0014] As a further technical solution, the oil base is a mixture of vaseline and lanolin with a mass ratio of 1:1.

[0015] As a further technical solution, the emulsifier is glyceryl stearate, the humectant is glycerol, and the preservative is nipagin ethyl.

[0016] Compared with the prior art, the present application has the following beneficial effects: Firstly, the chitosan in each component has good water solubility and biocompatibility, can form a breathable and moisturizing protective film on the skin surface, reduce external stimulation, and at the same time provide a mild growth environment for skin cells, thereby repairing damaged skin barrier. The nano-scale structure of the amino-modified graphene quantum dots makes them have excellent permeability, can penetrate into the skin surface and bind to the surface receptors of mast cells, inhibit cell activation and degranulation, reduce histamine release, and thus quickly relieve allergic symptoms, making up for the slow anti-allergy effect of natural ingredients; and the rich amino groups on the surface provide active sites for synergistic action with other components. Tannic acid and egg white protein form a complex through a specific ratio and process, the anti-inflammatory and antioxidant properties of tannic acid are combined with the nutritional supply function of egg white protein, not only reducing the allergenicity of egg white protein, but also synergistically enhancing the anti-inflammatory effect, providing double protection for skin repair.

[0017] Secondly, the scientific preparation process and component ratio further enhanced the synergistic effect and improved the overall performance. During the preparation of the tannic acid-ovalbumin complex, the structural stability and activity of the complex were ensured by controlling the pH value of the phosphate buffer solution, the dropping rate of the tannic acid solution, and conditions such as dialysis and freeze-drying. The segmented temperature-controlled grafting reaction of the polymer first fully activated the functional groups on the surface of chitosan and the complex at 30-32℃, and then promoted the efficient grafting reaction at 38-40℃, allowing the components to be tightly bound by chemical bonds to form a structurally regular polymer, avoiding the component separation problems caused by simple compounding. Meanwhile, the specific mass ratio of chitosan to tannic acid-ovalbumin complex and the amount of aminated graphene quantum dots ensure that the functions of each component are fully utilized: the protective film effect of chitosan provides a platform for the action of other active ingredients, and the anti-allergic effect of aminated graphene quantum dots and the anti-inflammatory and repairing effect of tannic acid-ovalbumin complex work together to form a synergistic mechanism of inhibiting allergies, relieving inflammation, and repairing the skin barrier, thereby achieving the dual effects of rapid anti-allergy and deep skin repair.

[0018] Finally, the anti-allergy polymer prepared by this method not only has excellent anti-allergy properties and skin repair effects, but also, when combined with specific excipients to form a cream formulation, all components are made of natural or biocompatible materials. The preparation process is mild and controllable, with no harmful byproducts generated. The product is gentle and non-irritating and suitable for long-term use. Attached Figure Description

[0019] Figure 1 This is a statistical chart showing the histamine release inhibition rate in the experiments of this invention. Detailed Implementation

[0020] 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.

[0021] This invention provides an anti-allergy polymer composed of chitosan, tannic acid-ovalbumin complex, and aminated graphene quantum dots; the aminated graphene quantum dots have a particle size of 5nm-20nm, a surface amino density of 3.5mmol / g-5.0mmol / g, and are added at 0.5%-1% of the egg white protein mass; the mass ratio of chitosan to tannic acid-ovalbumin complex is 1:0.5-0.8.

[0022] In this invention, the degree of deacetylation of the chitosan is preferably not less than 85%, and the viscosity-average molecular weight is preferably 50,000 Da-100,000 Da. Commercially available products well known to those skilled in the art can be used, and there are no special restrictions on their specific sources.

[0023] In this invention, the preferred method for preparing the aminated modified graphene quantum dots is as follows: graphene quantum dots are dispersed in anhydrous ethanol, 3-aminopropyltriethoxysilane is added, and the mixture is refluxed at 70℃-80℃ for 6-8 hours. After the reaction, the mixture is centrifuged, the precipitate is washed three times with anhydrous ethanol, and then vacuum dried to obtain the aminated modified graphene quantum dots. This invention does not impose any special restrictions on the source of the graphene quantum dots or the 3-aminopropyltriethoxysilane; commercially available products well-known to those skilled in the art can be used.

[0024] In this invention, the preferred method for preparing the tannic acid-ovalbumin complex is as follows: Ovalbumin is dissolved in a phosphate buffer solution with a pH of 6.5-7.5 and a concentration of 0.01 mol / L-0.05 mol / L, stirred until completely dissolved, and the aminated modified graphene quantum dots are added. The mixture is then ultrasonically dispersed at 150 W-200 W for 10-20 min to obtain a mixed solution. Tannic acid is dissolved in a 5%-10% (w / w) ethanol solution to obtain a tannic acid solution. The solution is prepared under nitrogen protection at 25℃-35℃. The tannic acid solution was added dropwise to the mixed solution at a rate of 1-2 drops / second using a constant-pressure dropping funnel. After the addition was complete, the mixture was stirred at a constant temperature for 2-4 hours. Subsequently, the mixture was dialyzed through a dialysis bag with a molecular weight cutoff of 8000-14000 Da for 24-48 hours, with the phosphate buffer solution being replaced every 8 hours. The mixture was then freeze-dried at a vacuum degree not exceeding 10 Pa and a temperature of -50℃ to -40℃ for 24-36 hours to obtain the tannic acid-ovalbumin complex. The mass ratio of ovalbumin to tannic acid was 1:0.8-1.2. This invention does not have special restrictions on the source of ovalbumin, tannic acid, phosphate buffer solution, and ethanol; commercially available products well known to those skilled in the art can be used.

[0025] In this invention, the polymer is prepared via a segmented temperature-controlled grafting reaction. The preferred specific steps are: dissolving the chitosan in a 1%-2% (v / v) dilute acetic acid solution and stirring until completely dissolved to obtain a chitosan solution; adding the tannic acid-ovalbumin complex and aminated graphene quantum dots to the chitosan solution and ultrasonically dispersing at 200W-250W for 20-30 minutes until homogeneous; adding 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide as activators; reacting first at 30°C-32°C for 3-4 hours, then increasing the temperature to 38°C-40°C for another 3-4 hours; after the reaction, using... The pH of the system was adjusted to 6.8-7.2 with 1 mol / L NaOH solution, and the precipitate was collected by centrifugation at 8000-10000 rpm for 15-20 min. The precipitate was washed three times with deionized water and anhydrous ethanol, and then freeze-dried at a vacuum of no more than 10 Pa and a temperature of -55℃ to -45℃ for 36-48 h to obtain the anti-allergic polymer. The molar ratio of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride to N-hydroxysuccinimide was 1:1, and the amount of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride added was 5%-8% of the chitosan mass. This invention does not have special restrictions on the sources of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, N-hydroxysuccinimide, dilute acetic acid solution, and NaOH solution; commercially available products well known to those skilled in the art can be used.

[0026] The present invention also provides the application of the above-mentioned anti-allergy polymer as a skin repair agent, specifically by compounding the anti-allergy polymer with excipients to prepare a topical preparation with anti-allergy and skin repair functions, wherein the topical preparation is used in the form of a cream.

[0027] In this invention, when preparing the cream, the excipients include an oily matrix, emulsifier, humectant, and preservative; the mass percentages of each component are as follows: anti-allergy polymer 4%-6%, oily matrix 15%-20%, emulsifier 3%-5%, humectant 8%-12%, preservative 0.2%-0.4%, ginseng extracellular vesicles 0.2-0.3%, Ganoderma lucidum extract 0.3-0.4%, and the balance being deionized water. The preparation method is as follows: the oily matrix is ​​heated and melted to 60℃-70℃ to form the oil phase; the humectant and preservative are dissolved in deionized water and heated to 60℃-70℃ to form the aqueous phase; the aqueous phase is slowly added to the oil phase, stirred and emulsified, and when the temperature drops below 40℃, the anti-allergy polymer, ginseng extracellular vesicles, and Ganoderma lucidum extract are added, and stirred until solidified to obtain the cream.

[0028] In this invention, the oily matrix is ​​preferably a mixture of petrolatum and lanolin in a mass ratio of 1:1; the emulsifier is preferably glyceryl stearate, the humectant is preferably glycerin, and the preservative is preferably ethylparaben; commercially available products well known to those skilled in the art can be used, and there are no special restrictions on their specific sources.

[0029] The method for preparing ginseng extracellular vesicles is as follows: Ginseng and pure water are mixed in a mass ratio of 3:1, juiced, filtered, and the filter residue is removed to obtain ginseng juice. The ginseng juice is centrifuged at 1200g for 20 minutes, and the supernatant is collected. The supernatant is then centrifuged at 3500g for 20 minutes, and the supernatant is collected again. Finally, the supernatant is centrifuged at 13000g for 60 minutes, and the supernatant is collected again. The supernatant is then centrifuged at 200000g for 120 minutes, and the precipitate is collected to obtain the ginseng juice.

[0030] The preparation method of Ganoderma lucidum extract is as follows: Ganoderma lucidum is pulverized, mixed with 75% ethanol solution at a material-to-liquid ratio of 1:12, stirred at 500 r / min for 5 hours, filtered to remove filter residue, and evaporated to dry to obtain the extract.

[0031] The anti-allergy polymer provided by this invention, through the selection and proportioning of specific components and a proprietary preparation process, achieves a synergistic effect among the components, significantly enhancing the polymer's anti-allergy properties and skin repair efficacy. Furthermore, the polymer's preparation process is simple and controllable, resulting in a cream formulation with good stability and ease of use. It effectively alleviates skin allergy symptoms and promotes the repair of damaged skin, demonstrating broad application prospects.

[0032] To further illustrate the present invention, the following detailed description is provided through the examples and comparative examples.

[0033] In the following examples and comparative examples of this invention: the degree of deacetylation of the chitosan used was 88%, and the viscosity-average molecular weight was 70,000 Da; the graphene quantum dots used were commercially available conventional products; and the 3-aminopropyltriethoxysilane, ovalbumin, tannic acid, phosphate buffer solution, ethanol, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, N-hydroxysuccinimide, dilute acetic acid solution, NaOH solution, petrolatum, lanolin, glyceryl stearate, glycerol, and ethylparaben were all commercially available analytical grade reagents.

[0034] Example 1: Preparation of aminated graphene quantum dots: Graphene quantum dots were dispersed in anhydrous ethanol, and 3-aminopropyltriethoxysilane was added. The mixture was refluxed at 70 °C for 6 h. After the reaction, the mixture was centrifuged, and the precipitate was washed three times with anhydrous ethanol and dried under vacuum to obtain aminated graphene quantum dots. The particle size of the aminated graphene quantum dots was 5 nm, and the surface amino density was 3.5 mmol / g.

[0035] Preparation of tannic acid-ovalbumin complex: Ovalbumin was dissolved in a phosphate buffer solution with a pH of 6.5 and a concentration of 0.01 mol / L, and stirred until completely dissolved. Aminated modified graphene quantum dots prepared in step 1 (0.5% of the ovalbumin mass) were added, and the mixture was ultrasonically dispersed at 150 W for 10 min to obtain a mixed solution. Tannic acid was dissolved in a 5% (w / w) ethanol solution to obtain a tannic acid solution. Under nitrogen protection and at 25 °C, the tannic acid solution was added dropwise to the mixed solution at a rate of 1 drop / second through a constant pressure dropping funnel. After the addition was complete, the mixture was stirred at a constant temperature for 2 h. Then, the mixture was dialyzed for 24 h through a dialysis bag with a molecular weight cutoff of 8000 Da, and the phosphate buffer solution was replaced every 8 h. Finally, the mixture was freeze-dried for 24 h under a vacuum of 10 Pa and a temperature of -50 °C to obtain the tannic acid-ovalbumin complex. The mass ratio of ovalbumin to tannic acid was 1:0.8.

[0036] Preparation of anti-allergy polymer: Chitosan was dissolved in a 1% (v / v) dilute acetic acid solution and stirred until completely dissolved to obtain a chitosan solution; the tannic acid-ovalbumin complex prepared in step 2 and the aminated graphene quantum dots prepared in step 1 were added to the chitosan solution (the mass ratio of chitosan to tannic acid-ovalbumin complex was 1:0.5), and ultrasonically dispersed at 200W power for 20 min until uniform; 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide were added as activators ( The molar ratio of the two was 1:1, and the amount of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride added was 5% of the mass of chitosan. The reaction was first carried out at 30℃ for 3 hours, and then the temperature was raised to 38℃ for 3 hours. After the reaction was completed, the pH of the system was adjusted to 6.8 with 1 mol / L NaOH solution, and the precipitate was collected by centrifugation at 8000 r / min for 15 min. The precipitate was washed three times with deionized water and anhydrous ethanol, and then freeze-dried at a vacuum of 10 Pa and a temperature of -55℃ for 36 hours to obtain the anti-allergic polymer.

[0037] Preparation of an anti-allergy and skin-repairing cream: The following components were weighed by weight percentage: anti-allergy polymer 4%, oily matrix (petrolatum and lanolin in a 1:1 mass ratio) 15%, emulsifier glyceryl stearate 3%, moisturizer glycerin 8%, preservative ethylparaben 0.2%, ginseng extracellular vesicles 0.2%, Ganoderma lucidum extract 0.4%, and the balance being deionized water. The oily matrix was heated and melted to 60°C to obtain the oil phase. The moisturizer and preservative were dissolved in deionized water and heated to 60°C to obtain the aqueous phase. The aqueous phase was slowly added to the oil phase, stirred and emulsified. When the temperature was lowered to 35°C, the anti-allergy polymer, ginseng extracellular vesicles, and Ganoderma lucidum extract were added, and the mixture was stirred until it solidified to obtain the cream.

[0038] Example 2: Preparation of aminated graphene quantum dots: Graphene quantum dots were dispersed in anhydrous ethanol, and 3-aminopropyltriethoxysilane was added. The mixture was refluxed at 75°C for 7 h. After the reaction, the mixture was centrifuged, and the precipitate was washed three times with anhydrous ethanol and dried under vacuum to obtain aminated graphene quantum dots. The particle size of the aminated graphene quantum dots was 12 nm, and the surface amino density was 4.2 mmol / g.

[0039] Preparation of tannic acid-ovalbumin complex: Ovalbumin was dissolved in a phosphate buffer solution with a pH of 7.0 and a concentration of 0.03 mol / L, and stirred until completely dissolved. Aminated modified graphene quantum dots prepared in step 1 (0.8% of the ovalbumin mass) were added, and the mixture was ultrasonically dispersed at 180 W for 15 min to obtain a mixed solution. Tannic acid was dissolved in an 8% (w / w) ethanol solution to obtain a tannic acid solution. Under nitrogen protection and at 30 °C, the tannic acid solution was added dropwise to the mixed solution at a rate of 1.5 drops / second through a constant pressure dropping funnel. After the addition was complete, the mixture was stirred at a constant temperature for 3 h. Then, the mixture was dialyzed for 36 h through a dialysis bag with a molecular weight cutoff of 11000 Da, with the phosphate buffer solution being replaced every 8 h. Finally, the mixture was freeze-dried at a vacuum of 8 Pa and a temperature of -45 °C for 30 h to obtain the tannic acid-ovalbumin complex. The mass ratio of ovalbumin to tannic acid was 1:1.0.

[0040] Preparation of anti-allergy polymer: Chitosan was dissolved in a 1.5% (v / v) dilute acetic acid solution and stirred until completely dissolved to obtain a chitosan solution; the tannic acid-ovalbumin complex prepared in step 2 and the aminated graphene quantum dots prepared in step 1 were added to the chitosan solution (the mass ratio of chitosan to tannic acid-ovalbumin complex was 1:0.65), and ultrasonically dispersed at 220W power for 25 min until uniform; 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide were added as activators (di... The molar ratio of chitosan to ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride was 1:1, and the amount of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride added was 6.5% of the mass of chitosan. The reaction was first carried out at 31℃ for 3.5h, and then the temperature was raised to 39℃ for 3.5h. After the reaction was completed, the pH of the system was adjusted to 7.0 with 1mol / L NaOH solution, and the precipitate was collected by centrifugation at 9000r / min for 18min. The precipitate was washed three times with deionized water and anhydrous ethanol, and then freeze-dried at a vacuum of 8Pa and a temperature of -50℃ for 42h to obtain the anti-allergic polymer.

[0041] Preparation of an anti-allergy and skin-repairing cream: The components were weighed according to the following percentages by mass: 5% anti-allergy polymer, 18% oily matrix (petrolatum and lanolin in a 1:1 mass ratio), 4% glyceryl stearate emulsifier, 10% glycerin moisturizer, 0.3% ethylparaben preservative, 0.26% ginseng extracellular vesicles, 0.32% Ganoderma lucidum extract, and the balance being deionized water. The oily matrix was heated and melted to 65°C to form the oil phase. The moisturizer and preservative were dissolved in deionized water and heated to 65°C to form the aqueous phase. The aqueous phase was slowly added to the oil phase, and the mixture was stirred to emulsify. When the temperature was lowered to 38°C, the anti-allergy polymer, ginseng extracellular vesicles, and Ganoderma lucidum extract were added, and the mixture was stirred until it solidified to obtain the cream.

[0042] Example 3: Preparation of aminated graphene quantum dots: Graphene quantum dots were dispersed in anhydrous ethanol, and 3-aminopropyltriethoxysilane was added. The mixture was refluxed at 80 °C for 8 h. After the reaction, the mixture was centrifuged, and the precipitate was washed three times with anhydrous ethanol and dried under vacuum to obtain aminated graphene quantum dots. The particle size of the aminated graphene quantum dots was 20 nm, and the surface amino density was 5.0 mmol / g.

[0043] Preparation of tannic acid-ovalbumin complex: Ovalbumin was dissolved in a phosphate buffer solution with a pH of 7.5 and a concentration of 0.05 mol / L, and stirred until completely dissolved. Aminated modified graphene quantum dots prepared in step 1 (1% of the ovalbumin mass) were added, and the mixture was ultrasonically dispersed at 200 W for 20 min to obtain a mixed solution. Tannic acid was dissolved in a 10% ethanol solution to obtain a tannic acid solution. Under nitrogen protection and at 35 °C, the tannic acid solution was added dropwise to the mixed solution at a rate of 2 drops / second through a constant pressure dropping funnel. After the addition was complete, the mixture was stirred at a constant temperature for 4 h. Then, the mixture was dialyzed through a dialysis bag with a molecular weight cutoff of 14000 Da for 48 h, with the phosphate buffer solution being replaced every 8 h. Finally, the mixture was freeze-dried at a vacuum of 5 Pa and a temperature of -40 °C for 36 h to obtain the tannic acid-ovalbumin complex. The mass ratio of ovalbumin to tannic acid was 1:1.2.

[0044] Preparation of anti-allergy polymer: Chitosan was dissolved in a 2% (v / v) dilute acetic acid solution and stirred until completely dissolved to obtain a chitosan solution; the tannic acid-ovalbumin complex prepared in step 2 and the aminated graphene quantum dots prepared in step 1 were added to the chitosan solution (the mass ratio of chitosan to tannic acid-ovalbumin complex was 1:0.8), and ultrasonically dispersed at 250W power for 30 min until uniform; 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide were added as activators ( The molar ratio of the two was 1:1, and the amount of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride added was 8% of the mass of chitosan. The reaction was first carried out at 32℃ for 4 hours, and then the temperature was raised to 40℃ for 4 hours. After the reaction was completed, the pH of the system was adjusted to 7.2 with 1 mol / L NaOH solution, and the precipitate was collected by centrifugation at 10000 r / min for 20 min. The precipitate was washed three times with deionized water and anhydrous ethanol, and then freeze-dried at a vacuum of 5 Pa and a temperature of -45℃ for 48 hours to obtain the anti-allergic polymer.

[0045] Preparation of an anti-allergy and skin-repairing cream: The following components were weighed by weight percentage: 6% anti-allergy polymer, 20% oily matrix (petrolatum and lanolin in a 1:1 mass ratio), 5% glyceryl stearate emulsifier, 12% glycerin moisturizer, 0.4% ethylparaben preservative, 0.3% ginseng extracellular vesicles, 0.4% Ganoderma lucidum extract, and the balance being deionized water. The oily matrix was heated and melted to 70°C to obtain the oil phase. The moisturizer and preservative were dissolved in deionized water and heated to 70°C to obtain the aqueous phase. The aqueous phase was slowly added to the oil phase, stirred and emulsified. When the temperature was lowered to 39°C, the anti-allergy polymer, ginseng extracellular vesicles, and Ganoderma lucidum extract were added, and the mixture was stirred until it solidified to obtain the cream.

[0046] Comparative Example 1: The difference between this comparative example and Example 2 is that no aminated graphene quantum dots were added; the rest of the preparation steps and parameters are completely consistent with Example 2.

[0047] Preparation of cream: The polymer and excipients were compounded according to the cream preparation method and parameters in Example 2 to obtain the cream.

[0048] Comparative Example 2: The difference between this comparative example and Example 2 is that the tannic acid-ovalbumin complex was not used; only ovalbumin was used. The remaining preparation steps and parameters were completely consistent with those of Example 2.

[0049] Preparation of cream: The above polymer and excipients were compounded according to the cream preparation method and parameters in Example 2 to obtain cream.

[0050] Experimental verification: Anti-allergic performance test (histamine release inhibition rate test); Rat peritoneal mast cells were collected, washed three times with phosphate buffer solution at pH 7.4, and the cell concentration was adjusted to 1×10⁻⁶. 6 Quantity / mL, for later use.

[0051] The creams prepared in Examples 1-3 and Comparative Examples 1-2 were diluted with phosphate buffer solution to a sample solution containing a polymer concentration of 1 mg / mL. A blank control group (phosphate buffer solution only) and a positive control group (phosphate buffer solution containing loratadine concentration of 0.1 mg / mL) were also set up.

[0052] Take a 96-well cell culture plate, add 100 μL of cell suspension to each well, and then add 100 μL of each sample solution, blank control solution and positive control solution respectively. Incubate at 37℃ for 30 min.

[0053] Add 50 μL of Compound48 / 80 (mast cell degranulation inducer) at a concentration of 1 μg / mL to each well and continue incubation at 37°C for 30 min.

[0054] Centrifuge the culture plates, collect the supernatant, and use a histamine ELISA kit to determine the histamine content in the supernatant of each well. Calculate the histamine release inhibition rate using the following formula: Histamine release inhibition rate (%) = (Histamine content in blank control group - Histamine content in sample group) / (Histamine content in blank control group - Histamine content in negative control group) × 100% (Note: The negative control group is the histamine content in the supernatant of cell suspension without inducing agent). The results are as follows: Table 1

[0055] The experimental results show that the anti-allergy polymer creams prepared in Examples 1-3 all exhibit excellent histamine release inhibition effects, indicating that the technical solution of the present invention can effectively inhibit the release of histamine from mast cell degranulation and has significant anti-allergy properties.

[0056] Skin repair performance test (wound healing rate test); Forty-eight healthy SD rats were randomly divided into six groups of six rats each, corresponding to Examples 1-3, Comparative Examples 1-2, and the blank control group, respectively.

[0057] Hair was removed from the back of the rat, and after disinfection with 75% ethanol, a full-thickness skin defect was prepared using a skin punch with a diameter of 8 mm. After hemostasis, routine disinfection was performed.

[0058] The blank control group had their wounds covered only with sterile gauze; the other groups had their corresponding creams evenly applied to their wounds (at a rate of 0.1 g / cm³). 2 Then cover with sterile gauze, change the cream and gauze once a day, and observe for 14 consecutive days.

[0059] Wound area was measured on postoperative days 3, 7, and 14, and wound healing rate was calculated using the following formula: Wound healing rate (%) = (Initial wound area - Wound area at different time points) / Initial wound area × 100%. The results are as follows: Table 2

[0060] The experimental results showed that the creams prepared in Examples 1-3 could significantly promote the healing of skin wounds in rats. Fourteen days post-surgery, the wound healing rate in Example 2 reached 98.6%, while Examples 1 and 3 reached 95.3% and 97.2% respectively, far exceeding the 75.1% of the blank control group, indicating that the anti-allergic polymer of the present invention has excellent skin repair properties.

[0061] The preferred embodiments of the present invention disclosed above are merely illustrative of the invention. These preferred embodiments do not describe all details exhaustively, nor do they limit the invention to the specific implementations described. Clearly, many modifications and variations can be made based on the content of this specification.

Claims

1. An anti-allergy polymer, characterized in that, It is composed of chitosan, tannic acid-ovalbumin complex and aminated graphene quantum dots; the particle size of the aminated graphene quantum dots is 5-20 nm, the surface amino density is 3.5-5.0 mmol / g, and the amount added is 0.5-1% of the egg white protein mass; the mass ratio of chitosan to tannic acid-ovalbumin complex is 1:0.5-0.

8.

2. The anti-allergy polymer according to claim 1, characterized in that, The degree of deacetylation of the chitosan is ≥85%, and the viscosity-average molecular weight is 50,000-100,000 Da.

3. The anti-allergy polymer according to claim 1, characterized in that, The preparation method of the tannic acid-ovalbumin complex is as follows: Egg white protein was dissolved in a phosphate buffer solution with a pH of 6.5-7.5 and a concentration of 0.01-0.05 mol / L, and stirred until completely dissolved. The aminated modified graphene quantum dots were then added, and the solution was ultrasonically dispersed at 150-200 W for 10-20 min to obtain a mixed solution. Tannic acid was dissolved in a 5-10% (w / w) ethanol solution to obtain a tannic acid solution. Under nitrogen protection and at 25-35℃, the tannic acid solution was dissolved in a constant pressure dropping funnel. The solution was added dropwise to the mixed solution at a rate of 1-2 drops / second. After the addition was complete, the mixture was stirred at a constant temperature for 2-4 hours. Then, the mixture was dialyzed through a dialysis bag with a molecular weight cutoff of 8000-14000 Da for 24-48 hours, with the phosphate buffer solution being replaced every 8 hours. Finally, the mixture was freeze-dried at a vacuum degree ≤10 Pa and a temperature of -50 to -40 °C for 24-36 hours to obtain the tannic acid-ovalbumin complex. The mass ratio of ovalbumin to tannic acid was 1:0.8-1.

2.

4. The anti-allergy polymer according to claim 1, characterized in that, The polymer is prepared via a segmented temperature-controlled grafting reaction. The specific steps are as follows: Chitosan is dissolved in a 1-2% (v / v) dilute acetic acid solution and stirred until completely dissolved to obtain a chitosan solution; tannic acid-ovalbumin complex and aminated graphene quantum dots are added to the chitosan solution and ultrasonically dispersed at 200-250W for 20-30 minutes until homogeneous; 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide are added as activators, and the reaction is first carried out at 30-32℃ for 3-4 hours, then the temperature is increased to 38-40℃ for another 3-4 hours; after the reaction, 1m... The pH of the system was adjusted to 6.8-7.2 with 1 ol / L NaOH solution, and the precipitate was collected by centrifugation at 8000-10000 r / min for 15-20 min. The precipitate was washed three times with deionized water and anhydrous ethanol, and then freeze-dried at a vacuum of ≤10 Pa and a temperature of -55 to -45℃ for 36-48 h to obtain the anti-allergic polymer. The molar ratio of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride to N-hydroxysuccinimide was 1:1, and the amount of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride added was 5-8% of the mass of chitosan.

5. The anti-allergy polymer according to claim 1, characterized in that, The preparation method of the aminated modified graphene quantum dots is as follows: graphene quantum dots are dispersed in anhydrous ethanol, 3-aminopropyltriethoxysilane is added, and the mixture is refluxed at 70-80℃ for 6-8 hours. After the reaction is completed, the mixture is centrifuged, the precipitate is washed three times with anhydrous ethanol, and then dried under vacuum to obtain the aminated modified graphene quantum dots.

6. The use of the anti-allergy polymer according to any one of claims 1-5 as a skin repair agent.

7. The application according to claim 6, characterized in that, The anti-allergy polymer is compounded with excipients to prepare a topical preparation with anti-allergy and skin repair functions. The topical preparation is used in the form of a cream.

8. The application according to claim 7, characterized in that, When preparing the cream, the excipients include an oily matrix, emulsifier, moisturizer, preservative, ginseng extracellular vesicles, and Ganoderma lucidum extract; the mass percentages of each component are as follows: anti-allergy polymer 4-6%, oily matrix 15-20%, emulsifier 3-5%, moisturizer 8-12%, preservative 0.2-0.4%, ginseng extracellular vesicles 0.2-0.3%, Ganoderma lucidum extract 0.3-0.4%, and the balance being deionized water. The preparation method is as follows: the oily matrix is ​​heated and melted to 60-70℃ as the oil phase; the moisturizer and preservative are dissolved in deionized water and heated to 60-70℃ as the aqueous phase; the aqueous phase is slowly added to the oil phase, stirred and emulsified, and when the temperature is lowered to below 40℃, the anti-allergy polymer, ginseng extracellular vesicles, and Ganoderma lucidum extract are added, and stirred until solidified to obtain the cream.

9. The application according to claim 8, characterized in that, The oily matrix is ​​a mixture of petrolatum and lanolin in a mass ratio of 1:

1.

10. The application according to claim 8, characterized in that, The emulsifier is glyceryl stearate, the humectant is glycerin, and the preservative is ethylparaben.

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