Ointment for treating arthralgia and preparation method thereof

Abstract

The invention discloses an ointment for treating arthralgia and a preparation method thereof, and relates to the technical field of traditional Chinese medicine preparations, the ointment comprises the following main medicines: 30-50 parts of herba epimedii, 20-40 parts of tripterygium wilfordii, 20-50 parts of semen brassicae, 7-16 parts of raw gardenia, 15-20 parts of raw rhubarb, 5-10 parts of borneol, 10-30 parts of radix puerariae, 10-30 parts of radix cyathulae, 10-30 parts of pericarpium zanthoxyli, 10-30 parts of notopterygium root, 10-20 parts of garden balsam stem, 10-20 parts of rhizoma atractylodis and 10-20 parts of salvia miltiorrhiza; 10-20 parts of asarum, 5-15 parts of radix aconiti kusnezoffii and 5-15 parts of folium artemisiae argyi; according to the scheme, a traditional Chinese medicine external preparation is promoted from passive application to intelligent response type dynamic administration, a reform solution is provided for diseases such as osteoarthritis and sport injury needing long-term administration, meanwhile, the raw materials are derived from waste, and the cost is reduced compared with imported hydrogel.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine preparations, in particular to an ointment for treating joint pain and a preparation method thereof. Background Art

[0002] Closed bone injuries and fractures refer to external trauma that disrupts the integrity and continuity of bones. Soft tissue injuries are more minor and often accompanied by a crepitus or sensation of bone scraping, leading to localized pain, bruising, and swelling. Severe multiple fractures can even lead to shock and be life-threatening. Sprains and contusions of the musculoskeletal and soft tissues refer to injuries to muscles, tendons, joints, fascia, and other tissues caused by external forces, accompanied by bone destruction. These injuries typically manifest as localized swelling, bruising, and pain.

[0003] Currently, the commonly used blood-activating and swelling-reducing powder is mainly used as a gel ointment, which contains vegetable oil or animal oil, combined with various medicinal components to form a colloidal substance. When used, it is applied to the injured area to exert the medicinal effect. However, when using conventional ointments, the ointment is applied to the affected area. The ointment is in direct contact with the outside world and is easily scratched by external objects. In addition, it is easy to fall off due to dry skin or sweat from exercise, and the fat-water soluble components are difficult to be compatible. Summary of the Invention

[0004] The embodiments of the present application provide an ointment for treating joint pain and a preparation method thereof, thereby solving the problem in the prior art that lipid-water soluble components are difficult to be compatible and fall off due to dry and wet environments, and achieving a better combination of ingredients and a long-lasting effect.

[0005] The embodiment of the present application provides an ointment for treating joint pain, comprising a main drug, an auxiliary material and a base material; The main ingredients by weight include: 30-50 parts of epimedium, 20-40 parts of tripterygium wilfordii, 20-50 parts of white mustard seeds, 7-16 parts of raw gardenia, 15-20 parts of raw rhubarb, 5-10 parts of borneol, 10-30 parts of kudzu root, 10-30 parts of cyathula, 10-30 parts of Sichuan pepper, 10-30 parts of notopterygium wilfordii, 10-20 parts of scutellaria baicalensis, 10-20 parts of atractylodes, 10-20 parts of salvia miltiorrhiza, 10-20 parts of asarum, 5-15 parts of raw aconite, and 5-15 parts of artemisia argyi. The auxiliary materials include, by weight: 2-5 parts of eggshell powder, 0.5-1.2 parts of sericin peptide, 150-250U / g of hyaluronidase sericin peptide, 4-6wt% of mussel adhesive protein in the total amount of sericin, and 0.05-0.1mmol / L of ferric chloride calculated as trivalent iron ion; The base material comprises, by weight, 6-9 parts of oxidized modified starch, 35-45 parts of kaolin, 5-10 parts of aloe extract, 1-3 parts of alginate, 8-15 parts of citric acid, and 60-80 parts of purified water.

[0006] The preparation method of the above-mentioned ointment for treating joint pain specifically comprises the following steps: S1. The Chinese medicinal materials were crushed separately through an 80-mesh sieve and stirred in a mixer for 30 minutes using an equal-increment method until uniform. The mixed powders were mixed with a 50% ethanol solution and placed in an extraction tank. The extraction was carried out under a 60°C cycle for 2 hours at an extraction pressure of 0.15 MPa. The extract was vacuum concentrated to a specific gravity of 1.25 and ultrafiltration was performed to remove macromolecular impurities to obtain a concentrated Chinese medicinal extract. S2. Use air flow to crush fresh eggshells to a D90 value less than 15 microns; S3, the sericin peptide solution is loaded onto eggshell particles by atomization to prepare an auxiliary material; S4. Oxidized modified starch, kaolin, aloe extract, alginate and purified water were stirred at 400 rpm at 40°C for 15 minutes, the concentrated Chinese medicine extract was added to the base material, stirred at a low speed of 45°C for 30 minutes, and then the excipients were added to the drug-loaded base material, maintained at 45°C and mixed at 300 rpm for 20 minutes, borneol was added, and citric acid was used to adjust the pH to 5.3 to obtain an ointment.

[0007] Further, sericin peptide ethanol solution, sericin peptide ethanol solution and mussel adhesive protein and Fe 3+ The mass ratio of sericin peptide in the sericin peptide solution is 1:1.5:3.

[0008] Furthermore, fresh eggshells were pretreated by soaking in 5% citric acid for 20 minutes to remove the inner membrane, rinsing with pure water until neutral, and drying at 120°C for 2 hours.

[0009] Further, the sericin peptide includes 5% sericin peptide ethanol solution, 5% sericin peptide ethanol solution, mussel adhesive protein and Fe 3+ Sericin peptide solution.

[0010] Furthermore, a 5% sericin peptide ethanol solution was sprayed onto the surface of the eggshell powder via a pneumatic atomizer and cured at 45°C for 8 minutes to form a 0.2 μm film.

[0011] Furthermore, a sericin peptide aqueous solution containing hyaluronidase was sprayed with an atomizing pressure of 1.0 MPa and cured for 10 minutes in an environment of 37°C and 60% humidity, with a thickness of 0.3 μm.

[0012] Furthermore, mussel adhesive protein and Fe 3+ The sericin peptide solution was ultrasonically atomized into 8-micron droplets covering the surface and cross-linked at 37°C for 20 minutes to form a 0.3-micron adhesion layer.

[0013] One or more technical solutions provided in the embodiments of this application have at least the following technical effects or advantages: Through the three-level technology of "carrier modification-functional coating-bionic adhesion", transdermal enzymes can accurately open skin channels; mussel protein forms a pH / humidity responsive gel in the presence of iron ions; eggshell powder waste is utilized, and ethanol / water-based spraying reduces organic solvent residues; ultimately, a modern Chinese medicine joint pain-relieving ointment with high permeability, strong adhesion, and sustained release for a long time is obtained. DETAILED DESCRIPTION

[0014] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention pertains; the terms used herein in the specification of the present invention are for the purpose of describing specific embodiments only and are not intended to limit the present invention; the term "and / or" used herein includes any and all combinations of one or more of the associated listed items.

[0015] Example 1: A medicinal ointment for treating joint pain comprises a main drug, an auxiliary material and a base material; The main ingredients by weight include: 30-50 parts of epimedium, 20-40 parts of tripterygium wilfordii, 20-50 parts of white mustard seeds, 7-16 parts of raw gardenia, 15-20 parts of raw rhubarb, 5-10 parts of borneol, 10-30 parts of kudzu root, 10-30 parts of cyathula, 10-30 parts of Sichuan pepper, 10-30 parts of notopterygium wilfordii, 10-20 parts of scutellaria baicalensis, 10-20 parts of atractylodes, 10-20 parts of salvia miltiorrhiza, 10-20 parts of asarum, 5-15 parts of raw aconite, and 5-15 parts of artemisia argyi. The auxiliary materials include, by weight: 2-5 parts of eggshell powder, 0.5-1.2 parts of sericin peptide, 150-250U / g of hyaluronidase sericin peptide, 4-6wt% of mussel adhesive protein (accounting for the total amount of sericin), and 0.05-0.1mmol / L of ferric chloride (calculated as trivalent iron ion). The base material comprises, by weight, 6-9 parts of oxidized modified starch, 35-45 parts of kaolin, 5-10 parts of aloe extract, 1-3 parts of alginate, 8-15 parts of citric acid, and 60-80 parts of purified water.

[0016] Oxidized modified starch was prepared by grinding corn starch through a 100-mesh sieve, dispersing it in purified water, adding 15% potassium permanganate solution (0.01 mol / L), stirring at 60°C for 15 minutes, then adding malic acid and polyvinyl alcohol to react for 40 minutes, then adding polydextrose and hydroxyethyl cellulose, stirring for 2 hours to obtain oxidized modified starch. Among them, the mass ratio of corn starch, malic acid and polyvinyl alcohol is 1:0.5:0.6; the mass ratio of corn starch, polydextrose and hydroxyethyl cellulose is 1:0.3:0.5.

[0017] The preparation method of the above-mentioned ointment for treating joint pain specifically comprises the following steps: S1. The Chinese medicinal materials were crushed separately and passed through an 80-mesh sieve. The mixture was stirred in a mixer for 30 minutes using an equal-increment method until uniform. The mixed powders were mixed with a 50% ethanol solution (solid-liquid ratio of 1:8) and placed in an extraction tank. The extraction was carried out at 60°C for 2 hours and an extraction pressure of 0.15 MPa. The extract was vacuum concentrated to a specific gravity of 1.25 (measured at 60°C). Macromolecular impurities were removed by ultrafiltration to obtain a concentrated Chinese medicinal extract. S2. Soak fresh eggshells in 5% citric acid for 20 minutes to remove the inner membrane, rinse with pure water until neutral, dry at 120°C for 2 hours, and air flow grind to D90 < 15 μm; S3, using 5% sericin peptide ethanol solution, spraying it on the surface of eggshell powder through a pneumatic atomizer (0.8 MPa pressure), curing at 45 ° C for 8 minutes, forming a 0.2 μm film; using sericin peptide aqueous solution containing hyaluronidase, spraying at 1.0 MPa atomization pressure, curing at 37 ° C and 60% humidity for 10 minutes, the thickness is 0.3 μm; using mussel adhesive protein and Fe 3+ The sericin peptide solution was ultrasonically atomized (120 kHz) into 8-micron droplets covering the surface, and cross-linked at 37°C for 20 minutes to form a 0.3-micron adhesion layer to prepare the auxiliary material; Sericin peptide ethanol solution, sericin peptide ethanol solution and mussel adhesive protein and Fe 3+ The mass ratio of sericin peptide in the sericin peptide solution is: 1:1.5:3; S4. Oxidized modified starch, kaolin, aloe extract, alginate and purified water were stirred at 400 rpm at 40°C for 15 minutes. The concentrated Chinese medicine extract was added to the base material and stirred at a low speed (200 rpm) at 45°C for 30 minutes. Then, the excipients were added to the drug-loaded base material, and the mixture was maintained at 45°C and mixed at 300 rpm for 20 minutes. Borneol was added and the pH was adjusted to 5.3 with citric acid to obtain an ointment.

[0018] The technical solutions in the above embodiments of the present application have at least the following technical effects or advantages: Traditional Chinese medicine covers the core pathological links of joint pain, such as anti-inflammatory (tripterygium wilfordii, raw gardenia), analgesia (asarum, raw aconite), blood circulation and collateral dredging (salvia miltiorrhiza, chuanxiong), and wind and dampness removal (qianghuo, atractylodes). When facing the main fat-soluble ingredients such as tripterygium wilfordii and borneol and water-soluble main ingredients such as kudzu root, eggshell powder pore adsorption + sericin peptide encapsulation, puerarin, gardenia glycosides, etc. are bound to the eggshell powder micropores (10-100nm) and released through the sericin membrane; kaolin layered structure intercalates tripterygium wilfordii, borneol, etc. It is embedded in kaolin siloxane sheets (interlayer spacing 1.2nm) to avoid phase separation from the aqueous matrix, and faces the amphiphilic components oxidatively modified starch grafted polymer microdomain malic acid / PVA / polyglucose to construct hydrophilic-hydrophobic microregions (size 20-50nm), and simultaneously dissolve amphiphilic molecules such as tanshinone; it can perfectly load hydrophilic and hydrophobic drugs at the same time, exert their effects at the same time, and release them evenly, so that the more toxic raw black grass will not cause toxicity due to excessive drug concentration due to sudden release.

[0019] Eggshell powder provides a porous calcium-based carrier, increases the specific surface area, enhances the drug loading capacity, and increases the adsorption area of ​​aconitine, reducing the possibility of sudden release. The sericin peptide coating is used as a "molecular glue" to wrap the eggshell powder, and the eggshell powder is hydrolyzed to continuously release Ca 2+ , as a calcium source for alginate cross-linking, extending the life of the gel network; it can also dynamically adjust pH, decomposing in an acidic environment to produce calcium ions, maintaining the pH at 5.2-5.5 (the optimal activity window of alginate); Sericin peptide coating: Acts as a "molecular glue" to coat eggshell powder, achieving sustained release, controlling the drug release rate, and avoiding sudden release. Sericin peptides naturally promote cell adhesion, reduce local irritation, and provide a foundation for subsequent enzyme / adhesion protein modification. Through the layered design of the enzymatic layer, the stratum corneum barrier is degraded in real time, and the drug channel is gradually expanded. The 5% sericin peptide ethanol solution quickly forms a film (0.2μm), seals the surface pores of the eggshell powder, prevents drug leakage, solves the problems of poor powder fluidity and uneven drug adsorption, and improves drug loading stability. The sericin peptide aqueous solution containing hyaluronidase enzymatically hydrolyzes the skin's hyaluronic acid, temporarily loosens the stratum corneum barrier, and increases the penetration efficiency of large molecular components such as Radix Angelicae Dahuricae / Salviae Miltiorrhizae by more than 50%, reaching deep tissues. Mussel adhesive protein + Fe 3+ Crosslinker, biomimetic wet adhesion, Fe 3+ Catalyzes the cross-linking of catechol groups, maintaining strong adhesion for 12 hours even in the sweaty environment of joint activity, solving the problem of traditional plasters easily falling off; Mussel adhesive proteins are rich in catechol groups and are 3+ Oxidative cross-linking occurs under catalysis to form a high-strength network structure; the adhesion strength of the cross-linked network increases in the sweat / tissue fluid environment (traditional oily matrices fall off when exposed to water); ultrasonic atomized droplets penetrate into the skin texture to form a physical anchor (resistance to scratching), Fe 3+Reversible coordination bonds temporarily dissociate and reorganize during joint movement to prevent rigidity from falling off; The third layer of mussel protein triggers an increase in cross-linking density when it encounters Na+ in sweat. Alginate forms a hydrated gel layer under high humidity, which not only does not lose its effectiveness due to erosion in a sweat environment, but further combines. The β-folded structure of sericin peptide shrinks at low humidity, enhancing electrostatic adsorption with the stratum corneum. The polysaccharides in aloe vera extract provide continuous moisturizing and still have a good adsorption effect even when the skin is dry.

[0020] The experimental design for the above ointment included formula adaptability test and mechanism of action test. The adaptability test included adhesion retention rate test, puerarin transdermal amount test, and component uniformity test. The adhesion retention rate test method was as follows: 50 mg of ointment was evenly applied to the excised pig skin (2×2 cm 2 , thickness 1.5mm) surface, in a 37°C incubator with a relative humidity of 90%, spray 1mL of artificial sweat (ISO3160-2 standard formula) every 30 minutes, and fix the sample in a reciprocating tribometer (amplitude ±30°, frequency 1Hz, simulating knee flexion and extension). The initial weight (W0) and the residual weight (W1) after 12 hours were weighed; adhesion retention rate = (W1 / W0) × 100%; artificial sweat formula: NaCl 0.5%, urea 0.1%, lactic acid 0.1%, pH 5.5; The puerarin transdermal amount was tested using the Franz diffusion cell method. The method was as follows: ex vivo pig ear skin (thickness 0.8 ± 0.1 mm), the fat layer was removed, and the integrity was verified (TEWL value < 10 g·m -2 ·h -1 ); Supply pool: Contains 20mg of ointment (effective diffusion area 1.77cm 2 ); Receiving pool: PBS (containing 30% PEG400, constant temperature magnetic stirring at 37°C); Sampling analysis: take 0.5 mL of receiving solution after 24 hours (make up with an equal volume of fresh solution) HPLC detection conditions: Puerarin: mobile phase is methanol-water (30:70), C18 column, detection wavelength is 250 nm; Ingredient uniformity test: Take 5 ointments from the same batch, take samples from the upper, middle and lower parts of each ointment, use HPLC to determine the content, and calculate the relative standard deviation (RSD), CV% = (standard deviation / mean) × 100% (uniformity inspection method) The experimental reference formula is 40 parts of epimedium, 30 parts of tripterygium wilfordii, 35 parts of white mustard seeds, 10 parts of raw gardenia, 18 parts of raw rhubarb, 8 parts of borneol, 20 parts of kudzu root, 20 parts of Sichuan cyperus, 20 parts of Sichuan pepper, 20 parts of notopterygium wilfordii, 15 parts of scutellaria baicalensis, 15 parts of scutellaria baicalensis, 15 parts of atractylodes macrocephala, 15 parts of salvia miltiorrhiza, 15 parts of asarum, 10 parts of raw aconite, and 10 parts of mugwort; 3 parts of eggshell powder, 1 part of sericin peptide, 200U / g of hyaluronidase sericin peptide, 5wt% of mussel adhesive protein (total sericin), 1mmol / L of ferric chloride (calculated as trivalent iron ion); 8 parts of oxidized modified starch, 40 parts of kaolin, 7 parts of aloe extract, 2 parts of alginate, 10 parts of citric acid, and 70 parts of purified water. The experimental groups were adjusted on this basis. Except for the adjusted formula, the other formula proportions of each experimental group were completely consistent with the reference formula. The adaptability test groups are shown in Table 1. Table 1 Adaptive test groups

[0021] The results are shown in Table 2; Table 2 Adaptability experiment results

[0022] Mechanism of action experiments include adhesion retention experiments, skin barrier damage depth, fat-soluble component release rate, and water-soluble component penetration rate; The skin barrier disruption depth test was performed using confocal microscopy. 0.1% FITC-dextran (molecular weight, 4 kDa) was added to the ointment. Excised skin was incubated at 37°C for 8 h after application. Frozen sections (10 μm thickness) were then scanned along the z-axis using a laser confocal microscope (excitation at 488 nm). The barrier disruption depth was defined as the skin depth at which the fluorescence intensity decayed to 50%. The lipophilic component release rate experiment was as follows: the ointment was placed in a centrifuge tube, stored at 40°C for 28 days, centrifuged at 3000 g for 15 min, and the oil droplets precipitated on the surface were collected; the precipitate was dissolved in toluene, and the triptolide content was determined by HPLC. The release rate = (precipitated drug amount / total drug amount) × 100%; The permeation rate test of water-soluble components is as follows: using Franz diffusion cell (same as transdermal test), the cumulative permeation amount (Q) is linearly regressed against time (t), and the permeation rate = steady-state slope (μg·cm -2 ·h -1 ); The experimental groups are shown in Table 3; Table 3 Mechanism of action experimental groups

[0023] The results are shown in Table 4; Table 4 Experimental results of mechanism of action

[0024] It should be noted that "↓" indicates a significant decrease relative to group B1, a decrease of at least 20%, and "↑" indicates a significant increase, an increase of at least 100%.

[0025] Example 2: The method of using the above ointment is: clean the affected skin, apply warm water for 5 minutes, and apply every 10cm 2 Apply 0.5g of ointment (about the size of a pea) to the affected area and spread evenly into a 0.3mm thin layer; After applying the medicine, let it stand for 30 minutes, gently press the surface of the ointment for 10 seconds. After applying it for more than 8 hours, slowly peel it off along the skin texture. You can wipe it with olive oil to dissolve it and then wash it with warm water.

[0026] The ointment should be stored at an environment not exceeding 25°C, with humidity less than 60%, away from light, and the interval between each use should be more than 8 hours; it should be used within 60 days after exposure to air (opening), and shake well if water is extracted.

[0027] The technical solutions in the above embodiments of the present application have at least the following technical effects or advantages: Since the monthly enzyme activity decay rate is greater than 15% at >25°C, it should be stored at low temperature and pressed lightly (greater than 0.1N / cm 2 ), which can initiate the cross-linking reaction of mussel protein, allowing the ointment to begin to work, but it cannot be applied to damaged skin (stimulation of enzymatic components) and cannot be used repeatedly to avoid overload of enzyme activity.

[0028] The foregoing description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Various modifications and variations are readily apparent to those skilled in the art. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. An ointment for treating joint pain, characterized in that: Including main drug, excipients and base materials; The main ingredients by weight include: 30-50 parts of epimedium, 20-40 parts of tripterygium wilfordii, 20-50 parts of white mustard seeds, 7-16 parts of raw gardenia, 15-20 parts of raw rhubarb, 5-10 parts of borneol, 10-30 parts of kudzu root, 10-30 parts of cyathula, 10-30 parts of Sichuan pepper, 10-30 parts of notopterygium wilfordii, 10-20 parts of scutellaria baicalensis, 10-20 parts of atractylodes, 10-20 parts of salvia miltiorrhiza, 10-20 parts of asarum, 5-15 parts of raw aconite, and 5-15 parts of artemisia argyi. The auxiliary materials include, by weight: 2-5 parts of eggshell powder, 0.5-1.2 parts of sericin peptide, 150-250U / g of hyaluronidase sericin peptide, 4-6wt% of mussel adhesive protein in the total amount of sericin, and 0.05-0.1mmol / L of ferric chloride calculated as trivalent iron ion; The base material comprises, by weight, 6-9 parts of oxidized modified starch, 35-45 parts of kaolin, 5-10 parts of aloe extract, 1-3 parts of alginate, 8-15 parts of citric acid, and 60-80 parts of purified water.

2. The method for preparing a medicinal ointment for treating joint pain according to claim 1, wherein: The specific steps include: S1. The Chinese medicinal materials were crushed separately through an 80-mesh sieve and stirred in a mixer for 30 minutes using an equal-increment method until uniform. The mixed powders were mixed with a 50% ethanol solution and placed in an extraction tank. The extraction was carried out under a 60°C cycle for 2 hours at an extraction pressure of 0.15 MPa. The extract was vacuum concentrated to a specific gravity of 1.25 and ultrafiltration was performed to remove macromolecular impurities to obtain a concentrated Chinese medicinal extract. S2. Use air flow to crush fresh eggshells to a D90 value less than 15 microns; S3, the sericin peptide solution is loaded onto eggshell particles by atomization to prepare an auxiliary material; S4. Oxidized modified starch, kaolin, aloe extract, alginate and purified water were stirred at 400 rpm at 40°C for 15 minutes, the concentrated Chinese medicine extract was added to the base material, stirred at a low speed of 45°C for 30 minutes, and then the excipients were added to the drug-loaded base material, maintained at 45°C and mixed at 300 rpm for 20 minutes, borneol was added, and citric acid was used to adjust the pH to 5.3 to obtain an ointment.

3. The method for preparing a medicinal ointment for treating joint pain according to claim 2, wherein: Sericin peptide ethanol solution, sericin peptide ethanol solution and mussel adhesive protein and Fe 3+ The mass ratio of sericin peptide in the sericin peptide solution is 1:1.5:

3.

4. The method for preparing a medicinal ointment for treating joint pain according to claim 2, wherein: Fresh eggshells were pretreated by soaking them in 5% citric acid for 20 minutes to remove the inner membrane, rinsing them with pure water until neutral, and drying them at 120°C for 2 hours.

5. The method for preparing a medicinal ointment for treating joint pain according to claim 2, wherein: The sericin peptide includes 5% sericin peptide ethanol solution, 5% sericin peptide ethanol solution, mussel adhesive protein and Fe 3+ Sericin peptide solution.

6. The method for preparing a medicinal ointment for treating joint pain according to claim 5, wherein: A 5% sericin peptide ethanol solution was sprayed onto the surface of eggshell powder using a pneumatic atomizer and cured at 45°C for 8 minutes to form a 0.2 μm film.

7. The method for preparing a medicinal ointment for treating joint pain according to claim 5, wherein: The sericin peptide aqueous solution containing hyaluronidase was sprayed at an atomizing pressure of 1.0 MPa and cured for 10 minutes at 37°C and 60% humidity, with a thickness of 0.3 μm.

8. The method for preparing a medicinal ointment for treating joint pain according to claim 5, wherein: Mussel adhesive protein and Fe 3+ The sericin peptide solution was ultrasonically atomized into 8-micron droplets covering the surface and cross-linked at 37°C for 20 minutes to form a 0.3-micron adhesion layer.

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