A gel dressing for wound healing and its preparation method

Abstract

This invention relates to the field of gel dressing technology, and discloses a wound healing gel dressing and its preparation method, comprising the following steps: pretreating diatomaceous earth and adding anhydrous ethanol and a silane coupling agent, heating and reacting to obtain silane coupling agent-modified diatomaceous earth; then adding deionized water and phenylalanine dipeptide, heating and reacting to obtain dipeptide-modified diatomaceous earth; then adding deionized water, polyglutamic acid, a condensing agent and a catalyst, reacting at room temperature to obtain modified diatomaceous earth; adding polyvinyl alcohol, chitosan, carboxymethyl cellulose, sumac leaf extract and modified diatomaceous earth to deionized water, mixing and sterilizing to obtain the final product. The wound healing gel dressing of this invention can effectively absorb wound exudate, promote tissue regeneration, accelerate wound healing, and effectively improve scar residue after wound healing.

Description

Technical Field

[0001] This invention relates to the field of gel dressing technology, and more particularly to a gel dressing for wound healing and its preparation method. Background Technology

[0002] As a vital organ of the human epidermal system, the skin plays a crucial role in protecting the body's internal environment and maintaining its stability. It shields the body from external environmental influences, but it is also one of the most vulnerable organs. The ultimate goal of skin injury treatment is to rebuild the skin barrier function. While the skin possesses excellent self-repair and regeneration capabilities, if the trauma is too severe or the wound heals too slowly, various pathogens and chemical pollutants can enter through the wound, leading to fluid loss and infection.

[0003] Due to the complexity of wound healing, wound treatment remains a global clinical challenge. However, traditional wound dressings such as gauze and bandages have limited effectiveness in promoting wound healing and preventing bacterial infection. Granulation tissue often grows into the mesh of the dressing, making it difficult to remove without damaging new tissue. This results in poor hemostasis and barrier function, posing a risk of exogenous infection. Hydrogel dressings, on the other hand, offer advantages such as soft texture, ability to keep the wound moist, and good biocompatibility. They are less likely to adhere to wound tissue, avoiding secondary damage. Furthermore, environmentally responsive hydrogel dressings loaded with active drugs allow for controlled drug release, improving efficacy and thus preventing infection, eliminating inflammation, and promoting wound healing.

[0004] However, existing gel dressings still have technical problems such as poor wound healing ability and easy scarring. Therefore, developing a gel dressing with excellent exudate absorption, accelerated wound healing, and reduced scar residue after wound healing is of great practical significance. Summary of the Invention

[0005] In order to overcome the shortcomings of the prior art, the primary objective of the present invention is to provide a gel dressing for wound healing.

[0006] Another object of the present invention is to provide a method for preparing a gel dressing for wound healing.

[0007] The objective of this invention is achieved through the following technical solution:

[0008] This invention provides a method for preparing a gel dressing for wound healing, comprising the following steps:

[0009] (1) Diatomaceous earth was pretreated and added to anhydrous ethanol, then silane coupling agent was added, and the mixture was heated to react. After filtration, washing and drying, silane coupling agent modified diatomaceous earth was obtained.

[0010] (2) Add the silane coupling agent-modified diatomite from step (1) to deionized water, then add phenylalanine dipeptide, heat the reaction, filter, wash and dry to obtain dipeptide-modified diatomite.

[0011] (3) Add the dipeptide-modified diatomaceous earth from step (2) to deionized water, then add polyglutamic acid, condensing agent and catalyst, react at room temperature, filter, wash and dry to obtain modified diatomaceous earth.

[0012] (4) Add polyvinyl alcohol, chitosan, carboxymethyl cellulose, sumac leaf extract and modified diatomaceous earth to deionized water, stir and mix evenly, and then sterilize to obtain the product.

[0013] Preferably, in step (1), the mass ratio of diatomaceous earth, anhydrous ethanol, and silane coupling agent is 1:(15-18):(0.4-0.6); the heating reaction temperature is 65-75℃ and the time is 12-18h.

[0014] Preferably, in step (1), the specific method for pretreating the diatomaceous earth is as follows: the diatomaceous earth is dispersed in 2-4 mol / L nitric acid, stirred at 70-75℃ for 4-8 hours, then washed until neutral, calcined at 400-500℃ for 1-2 hours under nitrogen protection, and then sieved to obtain the final product.

[0015] Preferably, in step (2), the mass ratio of the silane coupling agent-modified diatomaceous earth, deionized water, and phenylalanine dipeptide is 1:(40-50):(2-3); the heating reaction temperature is 40-50℃ and the time is 5-10h.

[0016] Preferably, in step (3), the mass ratio of the dipeptide-modified diatomaceous earth, deionized water, polyglutamic acid, condensing agent, and catalyst is 1:(50-60):(0.8-1):(0.8-1):(0.7-0.9); and the reaction time at room temperature is 10-15 h.

[0017] Preferably, in step (4), the mass ratio of polyvinyl alcohol, chitosan, carboxymethyl cellulose, sumac leaf extract, modified diatomaceous earth, and deionized water is 1:(0.5-1):(0.1-0.3):(0.05-0.1):(0.7-1.2):(80-100).

[0018] Preferably, in step (4), the preparation method of the sumac leaf extract is as follows: the sumac leaves are crushed and sieved to obtain sumac leaf powder; the sumac leaf powder is mixed with water, hot-extracted, filtered, centrifuged and dried to obtain the extract.

[0019] Preferably, the ratio of sumac leaf powder to water is 1g:15-25mL; the hot extraction temperature is 70-80℃, the hot extraction time is 1-2h, and the hot extraction is performed 1-2 times.

[0020] Preferably, in step (1), the silane coupling agent is KH-560; in step (3), the condensing agent is EDC; and the catalyst is NHS.

[0021] The present invention provides a gel dressing for wound healing, wherein the gel dressing for wound healing is prepared by the preparation method described above.

[0022] The present invention has the following advantages over the prior art:

[0023] This invention provides a gel dressing for wound healing. First, diatomaceous earth is pretreated to increase its porous structure, enabling efficient absorption of wound exudate. Then, it is modified with a silane coupling agent to introduce epoxy groups, and simultaneously, a phenylalanine dipeptide is introduced that can undergo a ring-opening reaction with the epoxy groups. Furthermore, the phenylalanine dipeptide possesses self-assembly capabilities, forming a network structure on the diatomaceous earth surface through self-assembly and π-π stacking. Combined with diatomaceous earth, this effectively absorbs exudate, promotes tissue regeneration, and accelerates wound healing. Moreover, this invention utilizes the condensation reaction between the amino groups of polyglutamic acid and the carboxyl groups on the dipeptide-modified diatomaceous earth. Polyglutamic acid has excellent hydrophilicity and biocompatibility, providing moisturizing and film-forming effects, preventing excessive dryness of the wound, and effectively blocking the invasion of external bacteria to prevent wound infection. Combined with sumac leaf extract, it effectively improves scar residue after wound healing.

[0024] The present invention also provides a method for preparing a gel dressing for wound healing, which is simple in process and suitable for industrial production and widespread application. Attached Figure Description

[0025] Figure 1 This is a scanning electron microscope image of the modified diatomite obtained in Example 1 of the present invention. Detailed Implementation

[0026] The present invention will be further described in detail below with reference to embodiments, but the implementation of the present invention is not limited thereto. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in this technical field. Test methods in the following embodiments that do not specify specific experimental conditions are generally performed according to conventional experimental conditions or experimental conditions recommended by the manufacturer. Unless otherwise specified, the reagents and raw materials used in the present invention are commercially available.

[0027] In the embodiments of the present invention, the molecular weight of polyglutamic acid is 700,000-1,000,000 Da; and the molecular weight of polyvinyl alcohol is 80,000-150,000 Da.

[0028] Example 1

[0029] This embodiment provides a method for preparing a gel dressing for wound healing, including the following steps:

[0030] (1) Pretreatment of diatomaceous earth: Disperse diatomaceous earth in 3 mol / L nitric acid, stir at 75℃ for 6 h, then wash until neutral, calcine at 450℃ for 2 h under nitrogen protection, and pass through a 500-mesh sieve to obtain the diatomaceous earth. Add the pretreated diatomaceous earth to anhydrous ethanol, and then add silane coupling agent (γ-glycidoxypropyltrimethoxysilane, KH-560), wherein the mass ratio of diatomaceous earth, anhydrous ethanol and silane coupling agent is 1:16:0.5; after heating and reacting at 70℃ for 16 h, filter, wash and dry to obtain silane coupling agent modified diatomaceous earth;

[0031] (2) Take the silane coupling agent modified diatomite from step (1) and add it to deionized water, then add phenylalanine dipeptide (i.e. L-phenylalanine-L-phenylalanine), wherein the mass ratio of silane coupling agent modified diatomite, deionized water and phenylalanine dipeptide is 1:45:3; after heating and stirring at 45°C for 8 hours, filter, wash and dry to obtain dipeptide modified diatomite;

[0032] (3) The dipeptide-modified diatomaceous earth from step (2) was added to deionized water, followed by polyglutamic acid, a condensing agent (1-ethyl-(3-dimethylaminopropyl)carbodiimide, EDC), and a catalyst (N-hydroxysuccinimide, NHS). The mass ratio of the dipeptide-modified diatomaceous earth, deionized water, polyglutamic acid, condensing agent, and catalyst was 1:55:0.9:0.9:0.8. After reacting at room temperature for 12 hours, the mixture was filtered, washed, and dried to obtain modified diatomaceous earth. The scanning electron microscope image of the obtained modified diatomaceous earth is shown below. Figure 1 As shown.

[0033] (4) After pulverizing the leaves of *Rhus chinensis*, pass them through an 80-mesh sieve to obtain *Rhus chinensis* leaf powder. Mix the *Rhus chinensis* leaf powder with water at a ratio of 1g:20mL, and extract by hot extraction at 75℃ for 1.5h. Repeat the hot extraction twice. After filtration, centrifugation, and drying, obtain *Rhus chinensis* leaf extract. Add polyvinyl alcohol, chitosan, carboxymethyl cellulose, *Rhus chinensis* leaf extract, and modified diatomaceous earth to deionized water. The mass ratio of polyvinyl alcohol, chitosan, carboxymethyl cellulose, *Rhus chinensis* leaf extract, modified diatomaceous earth, and deionized water is 1:0.8:0.2:0.08:1:90. Stir and mix evenly, then sterilize to obtain the final product.

[0034] Example 2

[0035] This embodiment provides a method for preparing a gel dressing for wound healing, including the following steps:

[0036] (1) Pretreatment of diatomaceous earth: Disperse diatomaceous earth in 4 mol / L nitric acid, stir at 75℃ for 4 h, then wash until neutral, calcine at 500℃ for 1 h under nitrogen protection, and pass through a 500 mesh sieve to obtain the diatomaceous earth; add the pretreated diatomaceous earth to anhydrous ethanol, and then add silane coupling agent (KH-560), wherein the mass ratio of diatomaceous earth, anhydrous ethanol and silane coupling agent is 1:18:0.6; after heating and reacting at 75℃ for 12 h, filter, wash and dry to obtain silane coupling agent modified diatomaceous earth;

[0037] (2) Take the silane coupling agent modified diatomite from step (1) and add it to deionized water, then add phenylalanine dipeptide, wherein the mass ratio of silane coupling agent modified diatomite, deionized water and phenylalanine dipeptide is 1:50:3; after heating and stirring at 50°C for 5 hours, filter, wash and dry to obtain dipeptide modified diatomite.

[0038] (3) Add the dipeptide-modified diatomaceous earth from step (2) to deionized water, then add polyglutamic acid, condensing agent (EDC) and catalyst (NHS), wherein the mass ratio of dipeptide-modified diatomaceous earth, deionized water, polyglutamic acid, condensing agent and catalyst is 1:60:1:1:0.9; after reacting at room temperature for 15 h, filter, wash and dry to obtain modified diatomaceous earth;

[0039] (4) After pulverizing the leaves of *Rhus chinensis*, pass them through an 80-mesh sieve to obtain *Rhus chinensis* leaf powder. Mix the *Rhus chinensis* leaf powder with water at a ratio of 1g:25mL, and extract by hot soaking at 80℃ for 1h. Repeat the hot extraction twice. After filtration, centrifugation, and drying, obtain *Rhus chinensis* leaf extract. Add polyvinyl alcohol, chitosan, carboxymethyl cellulose, *Rhus chinensis* leaf extract, and modified diatomaceous earth to deionized water, wherein the mass ratio of polyvinyl alcohol, chitosan, carboxymethyl cellulose, *Rhus chinensis* leaf extract, modified diatomaceous earth, and deionized water is 1:1:0.3:0.1:1.2:100. Stir and mix evenly, then sterilize to obtain the final product.

[0040] Example 3

[0041] This embodiment provides a method for preparing a gel dressing for wound healing, including the following steps:

[0042] (1) Pretreatment of diatomaceous earth: Disperse diatomaceous earth in 2 mol / L nitric acid, stir at 70℃ for 8 h, then wash until neutral, calcine at 400℃ for 2 h under nitrogen protection, and pass through a 500 mesh sieve to obtain the diatomaceous earth; add the pretreated diatomaceous earth to anhydrous ethanol, and then add silane coupling agent (KH-560), wherein the mass ratio of diatomaceous earth, anhydrous ethanol and silane coupling agent is 1:15:0.4; after heating and reacting at 65℃ for 18 h, filter, wash and dry to obtain silane coupling agent modified diatomaceous earth;

[0043] (2) Take the silane coupling agent modified diatomite from step (1) and add it to deionized water, then add phenylalanine dipeptide, wherein the mass ratio of silane coupling agent modified diatomite, deionized water and phenylalanine dipeptide is 1:40:2; after heating and stirring at 40℃ for 10h, filter, wash and dry to obtain dipeptide modified diatomite;

[0044] (3) Add the dipeptide-modified diatomaceous earth from step (2) to deionized water, then add polyglutamic acid, condensing agent (EDC) and catalyst (NHS), wherein the mass ratio of dipeptide-modified diatomaceous earth, deionized water, polyglutamic acid, condensing agent and catalyst is 1:50:0.8:0.8:0.7; after reacting at room temperature for 10 h, filter, wash and dry to obtain modified diatomaceous earth;

[0045] (4) After pulverizing the leaves of *Rhus chinensis*, pass them through an 80-mesh sieve to obtain *Rhus chinensis* leaf powder. Mix the *Rhus chinensis* leaf powder with water at a ratio of 1g:15mL, and extract at 70℃ for 2 hours. Repeat the hot extraction once. After filtration, centrifugation, and drying, obtain *Rhus chinensis* leaf extract. Add polyvinyl alcohol, chitosan, carboxymethyl cellulose, *Rhus chinensis* leaf extract, and modified diatomaceous earth to deionized water. The mass ratio of polyvinyl alcohol, chitosan, carboxymethyl cellulose, *Rhus chinensis* leaf extract, modified diatomaceous earth, and deionized water is 1:0.5:0.1:0.05:0.7:80. Stir and mix evenly, then sterilize to obtain the final product.

[0046] Comparative Example 1

[0047] The difference between this comparative example and Example 1 is that step (2) is omitted, and the dipeptide-modified diatomaceous earth in step (3) is replaced with silane coupling agent-modified diatomaceous earth to obtain polyglutamic acid-modified diatomaceous earth; the modified diatomaceous earth in step (4) is replaced with polyglutamic acid-modified diatomaceous earth, and the rest is the same as in Example 1.

[0048] Comparative Example 2

[0049] The difference between this comparative example and Example 1 is that steps (1)-(3) are omitted, and the modified diatomaceous earth in step (4) is replaced by a direct mixture of diatomaceous earth and phenylalanine dipeptide. Otherwise, it is the same as Example 1.

[0050] Comparative Example 3

[0051] The difference between this comparative example and Example 1 is that the sumac leaf extract in step (4) is omitted, while the rest is the same as in Example 1.

[0052] Test case

[0053] 1. Fifteen healthy New Zealand rabbits weighing approximately 2 kg were selected as test subjects and randomly divided into three groups of five rabbits each. The skin on both sides of the spine on the back was prepared, and 0.5 g of the gel dressing obtained in Examples 1-3 of this invention was applied to the prepared skin. After covering and fixing for 12 hours, reactions such as erythema, purplish-red erythema with eschar, edema, and raised edema were observed. The results showed that the gel dressing obtained in this invention did not cause skin irritation or sensitization.

[0054] 2. Take the gel dressings obtained in Examples 1-3 and Comparative Examples 1-3, dry them, and weigh them. Record the mass as W0. Place the dried gel dressing in PBS with pH 7.4 at 37°C. After 24 hours, remove it, wipe off the surface moisture, and weigh it. Repeat this process every 1 hour until the weight of the gel dressing reaches a constant weight. Record the mass at this point as Wt. Calculate the swelling ratio: Swelling ratio = (Wt - W0) / W0 × 100%. The results are shown in Table 1.

[0055] 3. Sixty male SD mice, weighing 36-40g, were randomly divided into 6 groups of 10 mice each. Mice were anesthetized with 1wt% sodium pentobarbital. After anesthesia, the back hair of the mice was shaved, and a full-thickness circular wound (8mm diameter) was created on the back of each mouse using an 8mm skin biopsy punch. The gel dressings (8mm diameter, 2mm thickness) obtained in Examples 1-3 and Comparative Examples 1-3 were used to treat the mouse wounds. The gel dressings were changed daily, and the wound condition was observed. Wound healing was recorded on days 6 and 12. The wound healing rate was calculated as: Wound healing rate = (Wound healing area on day n / Initial wound area) × 100%. After wound healing, the residual scar width was recorded for each group of mice. The results are shown in Table 1.

[0056] Table 1

[0057]

[0058] As shown in Table 1, the gel dressings obtained in Examples 1-3 of this invention have a higher swelling ratio, a higher wound healing rate, and less residual scarring after wound healing compared to Comparative Examples 1-3. The reason for this is that the pretreatment of diatomaceous earth in this invention increases its porous structure, enabling efficient absorption of wound exudate. After modification with a silane coupling agent and the introduction of phenylalanine dipeptide, the combination of phenylalanine dipeptide and diatomaceous earth effectively absorbs exudate, promotes tissue regeneration, and accelerates wound healing. Furthermore, this invention utilizes the excellent hydrophilicity and biocompatibility of polyglutamic acid, which can exert moisturizing and film-forming effects. Combined with sumac leaf extract, it can effectively improve the residual scarring after wound healing.

[0059] The above embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-substantial changes and substitutions made by those skilled in the art based on the present invention shall fall within the scope of protection claimed by the present invention.

Claims

1. A method of preparing a wound healing gel dressing, characterized in that, The preparation method comprises the following steps: (1) adding diatomite into anhydrous ethanol after pretreatment, then adding silane coupling agent, and then performing heating reaction, and then performing filtration, washing and drying to obtain silane coupling agent modified diatomite; (2) adding the silane coupling agent modified diatomite in step (1) into deionized water, then adding phenylalanine dipeptide, and then performing heating reaction, and then performing filtration, washing and drying to obtain dipeptide modified diatomite; (3) adding the dipeptide modified diatomite in step (2) into deionized water, then adding polyglutamic acid, condensing agent and catalyst, and then performing room temperature reaction, and then performing filtration, washing and drying to obtain modified diatomite; (4) adding polyvinyl alcohol, chitosan, carboxymethyl cellulose, leaf extract of Rhus succedanea and modified diatomite into deionized water, stirring and mixing uniformly, and then sterilizing to obtain the gel dressing for wound healing. In step (1), the mass ratio of the diatomite, the anhydrous ethanol and the silane coupling agent is 1:(15-18):(0.4-0.6); the heating reaction is performed at a temperature of 65-75 DEG C for 12-18 h.

2. A process for the preparation of a gel dressing for wound healing as claimed in claim 1, wherein, In step (1), the specific method for pretreating the diatomite is as follows: dispersing diatomite in 2-4 mol / L nitric acid, stirring at 70-75 DEG C for 4-8 h, then washing to neutral, calcining at 400-500 DEG C under nitrogen protection for 1-2 h, and then sieving to obtain the pretreated diatomite.

3. A process for the preparation of a gel dressing for wound healing as claimed in claim 1, wherein, In step (2), the mass ratio of the silane coupling agent modified diatomite, the deionized water and the phenylalanine dipeptide is 1:(40-50):(2-3); the heating reaction is performed at a temperature of 40-50 DEG C for 5-10 h.

4. A process for the preparation of a gel dressing for wound healing as claimed in claim 1, wherein, In step (3), the mass ratio of the dipeptide modified diatomite, the deionized water, the polyglutamic acid, the condensing agent and the catalyst is 1:(50-60):(0.8-1):(0.8-1):(0.7-0.9); the room temperature reaction is performed for 10-15 h.

5. A process for the preparation of a gel dressing for wound healing as claimed in claim 1 wherein, In step (4), the mass ratio of the polyvinyl alcohol, the chitosan, the carboxymethyl cellulose, the leaf extract of Rhus succedanea, the modified diatomite and the deionized water is 1:(0.5-1):(0.1-0.3):(0.05-0.1):(0.7-1.2):(80-100).

6. A process for the preparation of a gel dressing for wound healing as claimed in claim 1, wherein, In the preparation method of the leaf extract of Rhus succedanea, the dosage ratio of the leaf powder of Rhus succedanea to water is 1g:15-25 mL; the heating extraction is performed at a temperature of 70-80 DEG C for 1-2 h, and the heating extraction is performed for 1-2 times.

7. A process for the preparation of a gel dressing for wound healing as claimed in claim 1, wherein, In step (1), the silane coupling agent is KH-560; in step (3), the condensing agent is EDC, and the catalyst is NHS.

8. A process for the preparation of a gel dressing for wound healing as claimed in claim 1, wherein, The gel dressing for wound healing is prepared by the preparation method in any one of claims 1-8.

9. A gel dressing for wound healing, characterized in that, ​

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