Medical composite dressing for relieving dermatitis and eczema and preparation method thereof

Abstract

This invention belongs to the field of medical materials technology and discloses a medical composite dressing for relieving dermatitis and eczema and its preparation method. First, mussel adhesive protein is dissolved in purified water, and the pH is adjusted to obtain a mussel adhesive protein solution. Trehalose, ectoine, and a portion of glycerin are mixed and dissolved to obtain an active ingredient composite solution. Then, the mussel adhesive protein solution and the active ingredient composite solution are mixed, and the pH is adjusted to obtain phase A. Sodium carboxymethyl cellulose is dissolved in a buffer solution in batches to obtain sodium carboxymethyl cellulose solution A and sodium carboxymethyl cellulose solution B. The two solutions are mixed, and the remaining glycerin and methylparaben are added. After adjusting the pH, phase B is obtained. Finally, phase A is added dropwise to phase B, stirred, and allowed to stand for maturation to obtain the final product. The medical composite dressing provided by this invention has a unique temperature-pH response mechanism, enabling the release of active ingredients such as ectoine and trehalose under weakly acidic conditions, achieving targeted repair and moisturizing of the inflamed area.

Description

Technical Field

[0001] This invention belongs to the field of medical materials technology, specifically relating to a medical composite dressing for relieving dermatitis and eczema and its preparation method. Background Technology

[0002] Medical dressings are medical materials used to cover wounds, protect them, absorb exudate, and create a suitable environment for healing. Their core application is to provide a functional barrier similar to healthy skin, preventing microbial invasion and secondary damage, while managing wound moisture and promoting granulation tissue growth and epithelialization. Modern medical dressings have evolved from traditional passive covering materials (such as gauze and Vaseline gauze) to various functional dressings, such as film dressings, hydrocolloid dressings, hydrogel dressings, foam dressings, and alginate dressings. The composition of these dressings is also becoming increasingly functional and complex. For example, hydrocolloid dressings often use sodium carboxymethyl cellulose (CMC-Na) as a base material, combined with elastomers and semi-permeable membranes; alginate dressings are extracted from natural seaweed; and high-end dressings incorporate active ingredients such as collagen, growth factors, and even silver ions to achieve multiple goals, including moisturizing, debridement, antibacterial properties, and promoting healing.

[0003] Despite advancements in functional dressings, existing technologies still have some limitations. Many dressings rely on a single release mechanism for their active ingredients. The release of drugs or active ingredients (such as ectoine and mussel adhesive proteins) in most dressings depends primarily on simple diffusion mechanisms, making them susceptible to enzyme or pH fluctuations in wound exudate. This can lead to explosive release or premature inactivation, failing to match the dynamic process of wound healing (such as the acidic pH during inflammation), hindering long-term and on-demand treatment. Secondly, traditional single-layer or simple physical stacking designs have limitations, making it difficult to synergistically address multiple requirements such as liquid absorption, moisture barrier, and controlled release of active substances. For example, some single-layer dressings easily become saturated after absorbing exudate, potentially leading to maceration; while double-layer dressings are prone to insufficient interlayer bonding strength, resulting in separation.

[0004] Based on the above-mentioned shortcomings, it is essential to propose a new medical composite dressing for relieving dermatitis and eczema and its preparation method. Summary of the Invention

[0005] In view of the shortcomings of the existing technology, the purpose of this invention is to provide a medical composite dressing for relieving dermatitis and eczema and its preparation method.

[0006] The first aspect of this invention is to provide a method for preparing a medical composite dressing for relieving dermatitis and eczema, comprising the following steps: S1: Dissolve mussel adhesive protein in purified water and adjust the pH value to obtain mussel adhesive protein solution; S2: Mix trehalose, ectoine and glycerin accounting for 25-35% of the total glycerin, add purified water to dissolve and obtain an active ingredient complex solution; S3: Mix the mussel adhesive protein solution and the active ingredient complex solution, and add purified water to bring the volume up to 25-35% of the total volume. After adjusting the pH value, phase A is obtained. S4: Dissolve 35-45% of the total sodium carboxymethyl cellulose in a buffer solution to obtain sodium carboxymethyl cellulose solution A; S5: Dissolve 55-65% of the total sodium carboxymethyl cellulose in a buffer solution to obtain sodium carboxymethyl cellulose solution B; S6: Mix sodium carboxymethyl cellulose solution A and sodium carboxymethyl cellulose solution B, add glycerol and methylparaben (65-75% of the total glycerol), and bring the volume to 65-75% with purified water. After adjusting the pH, phase B is obtained. S7: Add phase A to phase B dropwise. After the addition is complete, stir and let it stand to mature to obtain a medical composite dressing for relieving dermatitis and eczema.

[0007] It should be noted that this invention creatively first performs differentiated pH dissolution treatment on sodium carboxymethyl cellulose (CMC-Na): a portion is dissolved under neutral conditions at pH 7.2-7.6, allowing its molecular chains to fully extend and become negatively charged, forming a stable main gel framework; the other portion is dissolved under weakly acidic conditions at pH 5.5-6, pre-increasing its carboxyl grouping degree. When the ambient pH drops from 7.2-7.6 to 5.5-6, the acidic pre-treated portion exhibits a more significant change in swelling degree. Then, at a low temperature (10±2℃), the pre-treated active ingredients are dispersed in the outer phase of the CMC-Na gel, forming a water-in-water emulsion. The low-temperature environment can inhibit the thermal aggregation of mussel adhesive proteins during processing, maintaining their dissolved state in preparation for subsequent body temperature triggering. Furthermore, the solution at low temperatures has higher viscosity and slower molecular motion, ensuring that the inner phase is stably encapsulated by the gel network in the form of uniform, fine droplets. Finally, heating induces the contraction and strengthening of the gel network, as well as enhances the intermolecular interactions of mussel adhesive proteins. Subsequent long-term low-temperature static incubation (maturation) forms a stable encapsulation structure.

[0008] During application, body temperature triggers the thermal aggregation of mussel adhesive proteins, which rapidly bind to the CMC gel network to form a dense protective film. When it comes into contact with a weakly acidic wound caused by inflammation, the swelling degree of the acidic pretreated portion in the outer phase gel network changes abruptly, and the network structure relaxes, thereby preferentially releasing trehalose and ectoine from the inner phase at that site.

[0009] In some implementations, in S1, the pH value is adjusted to 5.6-6.

[0010] In some implementations, in step S3, the pH value is adjusted to 5.4-5.6.

[0011] In some embodiments, in S4, the dissolution temperature is 55-65°C, and the pH of the buffer solution is 7.2-7.6.

[0012] In some embodiments, in S5, the dissolution temperature is 45-55°C and the pH of the buffer solution is 5.5-6.

[0013] The buffer solution in this invention is purified water that has been pH adjusted.

[0014] In some implementations, in step S6, the pH value is adjusted to 7.1-7.3.

[0015] In some embodiments, in S7, the temperature of phase B is 8-12°C, the stirring temperature is 20-30°C, and the mixture is left to stand for 1-2 hours. Maturation is achieved by transferring the mixture to a 3-5°C environment and leaving it to stand for more than 24 hours.

[0016] The second aspect of the present invention is to provide a method for preparing a medical composite dressing for relieving dermatitis and eczema, and the resulting medical composite dressing for relieving dermatitis and eczema.

[0017] In some embodiments, the ingredients include the following by weight percentage: 2% mussel adhesive protein, 0.1-5% trehalose, 1-10% glycerol, 0.1-1% sodium carboxymethyl cellulose, 0.01-0.5% methylparaben, 0.1-5% ectoine, and the balance being purified water.

[0018] In some embodiments, the ingredients include the following by weight percentage: 2% mussel adhesive protein, 2-3% trehalose, 4-6% glycerol, 0.2-0.7% sodium carboxymethyl cellulose, 0.2-0.4% methylparaben, 1.5-4% ectoine, and the balance being purified water.

[0019] Mussel adhesive proteins, as bioadhesion and film-forming materials, can aggregate upon contact with skin (body temperature) to form a soft, breathable bioprotein film with excellent adhesion. The purpose is to physically isolate external stimuli and provide a moist and protective microenvironment for wound healing. Trehalose, as a cell protectant and long-lasting moisturizer, can protect damaged skin cells from osmotic stress and dryness damage in dressings, creating a stable extracellular environment for repair. Glycerin, as a moisturizer, penetration enhancer, and plasticizer, can increase the flexibility of dressing gels and help other active ingredients (such as ectoine) to better penetrate the skin surface. Sodium carboxymethyl cellulose (CMC-Na) serves as a gel matrix framework and thickener. In water, CMC-Na rapidly swells to form a transparent three-dimensional gel network, which not only imparts the required viscosity to the dressing, making it easy to apply and leave, but also constitutes the structural framework for encapsulating and protecting other active ingredients. The carboxyl groups on its molecular chain give it pH responsiveness (changes in solubility / swelling in acidic environments). Methylparaben, as a preservative, can inhibit the growth of microorganisms, ensuring the microbial safety of dressings after opening and during use; Ectoin, as a repair and anti-inflammatory active ingredient, can stabilize protein and biomembrane structures, significantly soothe inflammation, reduce redness and itching, and enhance the skin barrier's repair capabilities.

[0020] Compared with the prior art, the present invention has the following technical effects: 1. This invention utilizes a three-dimensional gel network formed by differentially treating sodium carboxymethyl cellulose with pH. The mussel adhesive protein encapsulated in this network aggregates upon contact with the skin through thermal responsiveness, intertwining with the network to form a strong and breathable physical barrier film, achieving immediate film formation and long-lasting adhesion. The complex formed by trehalose and ectoine during pretreatment is jointly loaded within this network. The former provides continuous moisturizing and protection for cells, while the latter focuses on anti-inflammatory and repair functions. The two complement each other and work synergistically.

[0021] 2. This invention is the first to combine CMC-Na pH pretreatment with low-temperature W / W emulsion. The low temperature inhibits the thermal aggregation of mussel adhesive protein, which can form a strong and breathable barrier after contact with the skin. When it comes into contact with the inflammatory weak acid (pH 5.5), the pre-acidified CMC segment swells and mutates, and the network pores increase, thereby preferentially and rapidly releasing trehalose and ectoine at this site, which significantly improves the drug release accuracy and achieves targeted repair and moisturization of the inflamed site. Detailed Implementation

[0022] The present invention will now be described in further detail with reference to specific embodiments.

[0023] Example 1 A medical composite dressing for relieving dermatitis and eczema comprises the following ingredients by weight percentage: 2% mussel adhesive protein, 2.5% trehalose, 5% glycerin, 0.5% sodium carboxymethyl cellulose, 0.25% methylparaben, 2.5% ectoine, and the remainder purified water.

[0024] The above-mentioned medical composite dressing for relieving dermatitis and eczema is prepared by the following steps: S1: Dissolve mussel adhesive protein in purified water and adjust the pH to 5.8 to obtain mussel adhesive protein solution; S2: Mix trehalose, ectoine and glycerin (30% of the total glycerin), add purified water to dissolve and obtain an active ingredient complex solution; S3: Mix the mussel adhesive protein solution and the active ingredient complex solution, add purified water to make up to 30% of the total volume, and adjust the pH to 5.5 to obtain phase A; S4: Dissolve 40% of the total sodium carboxymethyl cellulose in a buffer solution with a pH of 7.4 at 60°C to obtain sodium carboxymethyl cellulose solution A; S5: Dissolve 60% of the total sodium carboxymethyl cellulose in a buffer solution with a pH of 5.8 at 50°C to obtain sodium carboxymethyl cellulose solution B; S6: Mix sodium carboxymethyl cellulose solution A and sodium carboxymethyl cellulose solution B, add glycerol and methylparaben (70% of the total glycerol), and bring the volume up to 70% with purified water. Adjust the pH to 7.2 to obtain phase B. S7: Add phase A dropwise to phase B at a temperature of 10℃. After the addition is complete, stir at 25℃, then let stand for 1.5 hours. Transfer to a 4℃ environment and let stand for more than 24 hours to obtain a medical composite dressing for relieving dermatitis and eczema.

[0025] Example 2 A medical composite dressing for relieving dermatitis and eczema comprises the following ingredients by weight percentage: 2% mussel adhesive protein, 5% trehalose, 10% glycerin, 1% sodium carboxymethyl cellulose, 0.5% methylparaben, 5% ectoine, and the remainder purified water.

[0026] The above-mentioned medical composite dressing for relieving dermatitis and eczema is prepared by the following steps: S1: Dissolve mussel adhesive protein in purified water and adjust the pH to 6 to obtain a mussel adhesive protein solution; S2: Mix trehalose, ectoine and glycerin (35% of the total glycerin), add purified water to dissolve and obtain an active ingredient complex solution; S3: Mix the mussel adhesive protein solution and the active ingredient complex solution, add purified water to make up to 35% of the total volume, and adjust the pH to 5.6 to obtain phase A; S4: Dissolve 45% of the total sodium carboxymethyl cellulose in a buffer solution with a pH of 7.6 at 65°C to obtain sodium carboxymethyl cellulose solution A; S5: Dissolve 55% of the total sodium carboxymethyl cellulose in a buffer solution with a pH of 6 at 55°C to obtain sodium carboxymethyl cellulose solution B. S6: Mix sodium carboxymethyl cellulose solution A and sodium carboxymethyl cellulose solution B, add glycerol and methylparaben (65% of the total glycerol), and bring the volume to 65% with purified water. Adjust the pH to 7.1-7.3 to obtain phase B. S7: Add phase A dropwise to phase B at a temperature of 12℃. After the addition is complete, stir at 30℃, then let stand for 2 hours. Transfer to a 5℃ environment and let stand for more than 24 hours to obtain a medical composite dressing for relieving dermatitis and eczema.

[0027] Example 3 A medical composite dressing for relieving dermatitis and eczema comprises the following ingredients by weight percentage: 2% mussel adhesive protein, 0.1% trehalose, 1% glycerin, 0.1% sodium carboxymethyl cellulose, 0.01% methylparaben, 0.1% ectoine, and the remainder purified water.

[0028] The above-mentioned medical composite dressing for relieving dermatitis and eczema is prepared by the following steps: S1: Dissolve mussel adhesive protein in purified water and adjust the pH to 5.6 to obtain a mussel adhesive protein solution; S2: Mix trehalose, ectoine and glycerin accounting for 25% of the total glycerin, add purified water to dissolve and obtain an active ingredient complex solution; S3: Mix the mussel adhesive protein solution and the active ingredient complex solution, add purified water to make up to 25% of the total volume, and adjust the pH to 5.4 to obtain phase A; S4: Dissolve 35% of the total sodium carboxymethyl cellulose in a buffer solution with a pH of 7.2 at 55°C to obtain sodium carboxymethyl cellulose solution A; S5: Dissolve 65% of the total sodium carboxymethyl cellulose in a buffer solution with a pH of 5.5 at 45°C to obtain sodium carboxymethyl cellulose solution B; S6: Mix sodium carboxymethyl cellulose solution A and sodium carboxymethyl cellulose solution B, add glycerol and methylparaben (75% of the total glycerol), and bring the volume up to 75% with purified water. Adjust the pH to 7.1 to obtain phase B. S7: Add phase A dropwise to phase B at a temperature of 8℃. After the addition is complete, stir at 20℃, then let stand for 1 hour. Transfer to a 3℃ environment and let stand for more than 24 hours to obtain a medical composite dressing for relieving dermatitis and eczema.

[0029] Example 4 It is basically the same as Example 1, except that: by mass percentage, trehalose is 3%, glycerol is 6%, sodium carboxymethyl cellulose is 0.7%, methylparaben is 0.4%, and ectoine is 4%.

[0030] Example 5 It is basically the same as Example 1, except that: by mass percentage, trehalose is 2%, glycerol is 4%, sodium carboxymethyl cellulose is 0.2%, methylparaben is 0.2%, and ectoine is 1.5%.

[0031] Comparative Example 1 The process is essentially the same as in Example 1, except that a physical mixing process is used. Specifically, purified water, sodium carboxymethyl cellulose, glycerol, and methylparaben are added sequentially in equal proportions to an emulsifier / mixing tank. The emulsifier / mixing tank is then turned on, the stirring speed is 25 rpm, and the temperature is raised to 85℃±5℃ and maintained for 20 minutes. The temperature is then lowered to 40±5℃, and mussel adhesive protein, trehalose, and ectoine are added. The mixture is stirred for 10 minutes at a stirring speed of 25 rpm.

[0032] Comparative Example 2 The process is basically the same as in Example 1, except that all sodium carboxymethyl cellulose is dissolved under a single pH condition. That is, steps S4 and S5 are changed to dissolving sodium carboxymethyl cellulose in a buffer aqueous solution with a pH of 7.0 at 55°C to obtain sodium carboxymethyl cellulose solution.

[0033] Comparative Example 3 The process is basically the same as in Example 1, except that low-temperature emulsification is not performed. Instead, in step S7, the pretreated A phase and B phase are directly combined at room temperature and stirred and mixed evenly at 500 rpm for about 20-30 minutes. After mixing evenly, the mixture is allowed to stand to defoam.

[0034] The medical composite dressings prepared in Examples 1-5 and Comparative Examples 1-3 were tested, and the test results are shown in Table 1.

[0035] Film-forming performance test: 0.5g of sample was evenly coated onto simulated skin (Teflon plate, surface moistened to simulate a wound with exudate), with an area of ​​5×5 cm. 2 Record the time required from application to the formation of a complete, non-sticky, and touchable continuous film; Adhesion strength test: The sample is coated on a high-density polyethylene board and left to stand at 25°C and 50% RH for 30 minutes to allow it to fully form a film. After film formation, it is bonded to a standard test tape and the 180° peel force is tested using a tensile tester. Moisture retention test: Spread 5g of sample into a permeation cup, place it in a desiccator (control humidity), weigh it periodically, and calculate the moisture retention rate; pH-responsive release test: A sample containing 5.0 mg of ectoine was evenly coated onto a semi-permeable membrane and placed in the supply cell. The receiving cells were a phosphate buffer solution with pH 7.4 (simulating normal skin) and a buffer solution with pH 5.5 (simulating inflamed skin). The test was conducted at 32°C and 200 rpm. After 6 hours, samples were taken and the cumulative release rate of ectoine and trehalose was determined by HPLC.

[0036] Table 1

[0037] As can be seen from Table 1, the medical composite dressings for relieving dermatitis and eczema prepared in Examples 1-5 of this invention have excellent film-forming properties. Mussel adhesive protein can rapidly accumulate thermally, resulting in a fast film-forming speed. The pH-responsive release performance is also excellent, with a significantly increased release rate in acidic environments and a release difference ratio much greater than that of the comparative example. In addition, the synergistic enhancement of mussel adhesive protein and CMC network results in excellent adhesion strength, and it can also effectively lock in moisture and trehalose, exhibiting optimal moisturizing performance.

[0038] As can be seen from the comparative examples, Comparative Example 1, using a physical mixing process, lacked synergistic assembly between mussel adhesive protein, CMC-Na, and trehalose, failing to form a dense network. This resulted in slow film formation and poor adhesion. The active ingredients were directly exposed to both pH levels, leading to rapid diffusion. Liquid water and moisturizing components (glycerin and trehalose) were not effectively locked in the gel network, resulting in easy water evaporation and poor moisturizing properties. In Comparative Example 2, CMC-Na did not undergo pH differentiation treatment, and the swelling degree of the gel network did not change significantly in both environments, resulting in a substantial decrease in pH response performance. Comparative Example 3 lacked a low-temperature emulsification step. Phase A (active ingredients) and Phase B (gel matrix) were simply mixed at room temperature without forming an encapsulation structure, leading to a decrease in film formation and adhesion performance. The active ingredients were not physically encapsulated, resulting in non-targeted release. The gel network structure was uneven and incomplete, with weak water retention capacity.

[0039] The above descriptions are merely some embodiments of the present invention. Those skilled in the art can make various modifications and improvements without departing from the inventive concept of the present invention, and these all fall within the scope of protection of the present invention.

Claims

1. A method for preparing a medical composite dressing for alleviating dermatitis eczema, characterized by, Includes the following steps: S1: Dissolve mussel adhesive protein in purified water and adjust the pH value to obtain mussel adhesive protein solution; S2: Mix trehalose, ectoine and glycerin accounting for 25-35% of the total glycerin, add purified water to dissolve and obtain an active ingredient complex solution; S3: Mix the mussel adhesive protein solution and the active ingredient complex solution, and dilute with purified water to 25-35% of the total volume. After adjusting the pH value, phase A is obtained. S4: Dissolve 35-45% of the total sodium carboxymethyl cellulose in a buffer solution to obtain sodium carboxymethyl cellulose solution A; S5: Dissolve 55-65% of the total sodium carboxymethyl cellulose in a buffer solution to obtain sodium carboxymethyl cellulose solution B; S6: Mix the sodium carboxymethyl cellulose solution A and the sodium carboxymethyl cellulose solution B, add glycerol and methylparaben accounting for 65-75% of the total glycerol, and adjust the volume with purified water to 65-75% of the total volume. After adjusting the pH value, phase B is obtained. S7: Add phase A dropwise to phase B, stir after addition, and let stand to mature to obtain the medical composite dressing for relieving dermatitis and eczema.

2. The method for preparing the medical composite dressing for relieving dermatitis and eczema according to claim 1, characterized in that, In S1, the pH value is adjusted to 5.6-6.

3. The method for preparing the medical composite dressing for relieving dermatitis and eczema according to claim 1, characterized in that, In step S3, the pH value is adjusted to 5.4-5.

6.

4. The method for preparing the medical composite dressing for relieving dermatitis and eczema according to claim 1, characterized in that, In S4, the dissolution temperature is 55-65℃, and the pH value of the buffer aqueous solution is 7.2-7.

6.

5. The method for preparing the medical composite dressing for relieving dermatitis and eczema according to claim 1, characterized in that, In S5, the dissolution temperature is 45-55℃, and the pH value of the buffer aqueous solution is 5.5-6.

6. The method for preparing the medical composite dressing for relieving dermatitis and eczema according to claim 1, characterized in that, In step S6, the pH value is adjusted to 7.1-7.

3.

7. The method for preparing the medical composite dressing for relieving dermatitis and eczema according to claim 1, characterized in that, In S7, the temperature of phase B is 8-12℃, the stirring temperature is 20-30℃, and the mixture is left to stand for 1-2 hours. For maturation, the mixture is transferred to a 3-5℃ environment and left to stand for more than 24 hours.

8. A medical composite dressing for relieving dermatitis and eczema prepared by the method of any one of claims 1-7.

9. The medical composite dressing for relieving dermatitis and eczema according to claim 8, characterized in that, The ingredients, by weight percentage, include: 2% mussel adhesive protein, 0.1-5% trehalose, 1-10% glycerol, 0.1-1% sodium carboxymethyl cellulose, 0.01-0.5% methylparaben, 0.1-5% ectoine, and the remainder purified water.

10. The medical composite dressing for relieving dermatitis and eczema according to claim 9, characterized in that, The ingredients, by weight percentage, include: 2% mussel adhesive protein, 2-3% trehalose, 4-6% glycerol, 0.2-0.7% sodium carboxymethyl cellulose, 0.2-0.4% methylparaben, 1.5-4% ectoine, and the remainder purified water.

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