A wound repair gel containing five-grain insect oil, its preparation method and application

Abstract

This invention discloses a wound repair gel containing *Pseudolarix amabilis* oil, its preparation method, and its application, belonging to the field of gel technology. The wound repair gel comprises *Pseudolarix amabilis* oil, hyaluronic acid, chitosan, antimicrobial peptides, and a gel matrix, wherein the gel matrix is ​​carbomer and xanthan gum. The preparation method includes first swelling and neutralizing carbomer and xanthan gum to form a gel matrix, then adding *Pseudolarix amabilis* oil, hyaluronic acid, chitosan, and antimicrobial peptides and mixing them at low temperature to form a sol mixture. After homogenization, degassing, and heating, a semi-solid gel is formed, and finally sterilization is performed to obtain the final product. This invention's gel combines *Pseudolarix amabilis* oil with hyaluronic acid, chitosan, and antimicrobial peptides, exerting anti-inflammatory, antibacterial, angiogenesis-promoting, and epithelial cell migration-promoting effects. It can significantly accelerate wound healing, inhibit scar hyperplasia, and exhibits excellent biocompatibility and no cytotoxicity.

Description

Technical Field

[0001] This invention relates to the field of gel technology, specifically to a wound repair gel containing five-grain insect oil, its preparation method, and its application. Background Technology

[0002] Wound repair is a major challenge in clinical surgery, burn care, and dermatology. Traditional wound management methods often use ordinary gauze or petroleum jelly gauze, which only provide basic physical isolation and protection. Their function is limited and they cannot actively promote wound tissue regeneration, effectively control infection, or inhibit scar hyperplasia. For chronic, difficult-to-heal wounds such as deep burns, diabetic foot ulcers, and pressure injuries, conventional dressings often fail to create a suitable wound healing microenvironment, resulting in prolonged healing periods, high risks of secondary infection, and poor healing quality. Post-healing scarring is frequently accompanied by significant scar hyperplasia, severely impacting patients' quality of life and limb function recovery.

[0003] In recent years, hydrogel dressings have become a research hotspot in the field of wound repair materials due to their ability to provide a moist healing environment, good biocompatibility, and drug-carrying capacity. However, most commercially available hydrogel dressings currently use chemically synthesized polymers as a matrix, lacking natural active repair components and having weak active wound repair capabilities. Their antibacterial function often relies on the addition of antibiotics or silver ions, which can easily lead to bacterial resistance with long-term use. Some components also have certain cytotoxicity, making it difficult to balance safety and repair efficacy.

[0004] Therefore, there is an urgent need to develop a natural wound repair gel that combines efficient wound repair, excellent biocompatibility, and inhibition of scar hyperplasia. Summary of the Invention

[0005] In view of this, the present invention provides a wound repair gel containing five-grain insect oil, its preparation method and application, which combines five-grain insect oil with hyaluronic acid, chitosan and antimicrobial peptides in a carbomer / xanthan gum gel matrix to achieve the effects of promoting wound healing and inhibiting scarring.

[0006] The technical solution provided by this invention is as follows: In a first aspect, the present invention provides a wound repair gel containing five-grain insect oil, which is composed of the following components by weight percentage: 5-10% Five Grain Insect Oil, 2-5% Hyaluronic Acid, 1-3% Chitosan, 0.1-0.3% Antimicrobial Peptide, 1-3% Gel Matrix, and the balance is Deionized Water.

[0007] Furthermore, the gel matrix is ​​carbomer and xanthan gum.

[0008] Furthermore, the mass ratio of carbomer to xanthan gum is 1:(0.3~1).

[0009] Furthermore, the antimicrobial peptide is selected from at least one of cephalosporin, mussel adhesive protein, or LL-37.

[0010] Secondly, the present invention provides a method for preparing a wound repair gel containing five-grain insect oil as described in any of the preceding claims, comprising the following steps: S1. Add carbomer and xanthan gum to deionized water, allow them to swell fully, and then add a pH adjuster to neutralize to pH 6.0~7.5 to form a gel matrix; S2. Add five grain insect oil, hyaluronic acid, chitosan and antimicrobial peptides to the gel matrix obtained in step S1, and mix them at 10-20℃ to form a sol mixture. S3. After homogenizing and degassing the sol mixture obtained in step S2, heat it to 25-32℃ to form a semi-solid gel. S4. The semi-solid gel obtained in step S3 is sterilized to obtain a wound repair gel.

[0011] Furthermore, in step S1, the pH adjuster is triethanolamine, aminomethylpropanol, laurylamine, or stearylamine.

[0012] Furthermore, in step S2, the mixing is carried out using high-speed shear dispersion, with a rotation speed of 2000-5000 rpm and a time of 10-30 min.

[0013] Furthermore, the sterilization method in step S4 is cobalt-60 irradiation sterilization.

[0014] Thirdly, the present invention provides the application of a wound repair gel containing five-grain insect oil as described in any of the preceding claims in the preparation of wound repair materials.

[0015] The beneficial effects of this invention are as follows: This invention combines five-grain insect oil with hyaluronic acid, chitosan, and antimicrobial peptides in a carbomer / xanthan gum gel matrix. These four components synergistically exert anti-inflammatory, antibacterial, angiogenesis-promoting, and epithelial cell migration-promoting effects, significantly accelerating wound closure and improving repair efficiency and healing quality. Five-grain insect oil, as the core active ingredient, is rich in unsaturated fatty acids, which can inhibit excessive early inflammatory responses in wounds and promote vascular endothelial cell proliferation, providing nutritional support for wound repair. Hyaluronic acid maintains a moist microenvironment in the wound, aiding in granulation tissue formation. Chitosan imparts broad-spectrum antibacterial properties and excellent bioadhesion to the gel. Antimicrobial peptides enhance the killing effect on drug-resistant bacteria. The synergistic effect of these four components improves wound healing quality from multiple dimensions, including anti-inflammatory, repair, antibacterial, and scar-inhibiting effects, effectively inhibiting scar hyperplasia. This invention employs a low-temperature sol-gel conversion process, which avoids the damage of heat-sensitive active ingredients such as insect oil and antimicrobial peptides caused by high temperatures. At the same time, the composite gel matrix composed of carbomer and xanthan gum can stably encapsulate oil droplets through hydrogen bonding and hydrophobic interactions, forming a uniform three-dimensional network, preventing oil precipitation, and significantly improving product stability. Detailed Implementation

[0016] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Obviously, the described embodiments are only a part of the embodiments of this invention, not all of them. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise stated, percentages and parts are weight percentages and parts by weight.

[0017] Unless otherwise specified, the technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains. It should be noted that the terms used herein are for the purpose of describing particular embodiments only and are not intended to limit the exemplary embodiments of this application.

[0018] Preparation Example A method for preparing five-grain insect oil includes the following steps: After the dried grain insects were crushed and passed through a 40-mesh sieve, the crushed insects were placed in a supercritical extraction vessel. The extraction pressure was set to 25 MPa, the extraction temperature to 43℃, and the CO2 flow rate to 20 L / h. The extraction was carried out for 3 hours, and the extract was collected to obtain crude oil from the grain insects. According to the test results from PONY Testing Group (report number: B1G205033B1F10I3053), the total amount of unsaturated fatty acids in Wugu Worm Oil is 49.1g / 100g, of which the content of EPA is 2.16g / 100g and the content of nervonic acid is 0.0104g / 100g. Example

[0019] A wound healing gel containing five-grain insect oil, comprising the following components by weight percentage: 8% Five Grains Insect Oil, 3% Hyaluronic Acid, 2% Chitosan, 0.2% Antimicrobial Peptide (Castrodin), 1.8% Gel Matrix (Carbomer to Xanthan Gum in a mass ratio of 2:1), Deionized Water to make up to 100%.

[0020] A method for preparing a wound healing gel containing five-grain insect oil includes the following steps: S1. Add carbomer and xanthan gum to deionized water, let stand and swell for 12 hours, then add triethanolamine dropwise with stirring to adjust the pH to 6.8 to form a homogeneous gel matrix. S2. Add five grain insect oil, hyaluronic acid, chitosan and antimicrobial peptides to the gel matrix obtained in step S1, and disperse it at 3000 rpm for 20 minutes at 10°C using a high-speed shear disperser to form a uniform sol mixture. S3. After homogenizing and vacuum degassing the sol mixture obtained in step S2, the temperature is raised to 30°C to form a semi-solid gel. S4. The semi-solid gel obtained in step S3 is sterilized by cobalt-60 irradiation to obtain a wound repair gel. Example

[0021] A wound healing gel containing five-grain insect oil, comprising the following components by weight percentage: 5% Five Grain Insect Oil, 5% Hyaluronic Acid, 1% Chitosan, 0.3% Antimicrobial Peptide (LL-37), 2.3% Gel Matrix (Carbomer to Xanthan Gum in a mass ratio of 2:1), Deionized Water to bring to 100%.

[0022] 5-10% Five Grain Insect Oil, 2-5% Hyaluronic Acid, 1-3% Chitosan, 0.1-0.3% Antimicrobial Peptide, 1-3% Gel Matrix, and the balance is Deionized Water.

[0023] A method for preparing a wound repair gel containing five grain insect oil is consistent with Example 1. Example

[0024] A wound healing gel containing five-grain insect oil, comprising the following components by weight percentage: 10% Five Grain Insect Oil, 2% Hyaluronic Acid, 3% Chitosan, 0.1% Antimicrobial Peptide (Mussel Adhesive Protein), 3% Gel Matrix (Carbomer to Xanthan Gum in a 2:1 mass ratio), Deionized Water to bring to 100%.

[0025] A method for preparing a wound repair gel containing five grain insect oil is consistent with Example 1.

[0026] Comparative Example 1 A wound healing gel containing five-grain insect oil, comprising the following components by weight percentage: 3% hyaluronic acid, 2% chitosan, 0.2% antimicrobial peptide (cephalosporin), 1.8% gel matrix (carbomer to xanthan gum mass ratio of 2:1), deionized water to make up to 100%.

[0027] A method for preparing a wound repair gel containing five grain insect oil is consistent with Example 1.

[0028] Compared to Example 1, this comparative example did not contain any grain insect oil.

[0029] Comparative Example 2 A wound healing gel containing five-grain insect oil, comprising the following components by weight percentage: 8% Five Grains Insect Oil, 3% Hyaluronic Acid, 2% Chitosan, 1.8% Gel Matrix (Carbomer to Xanthan Gum in a mass ratio of 2:1), Deionized Water to make up to 100%.

[0030] A method for preparing a wound repair gel containing five grain insect oil is consistent with Example 1.

[0031] Compared to Example 1, this comparative example did not contain any antimicrobial peptides.

[0032] Comparative Example 3 A wound healing gel containing five-grain insect oil, comprising the following components by weight percentage: 8% Five Grains Insect Oil, 2% Chitosan, 0.2% Antimicrobial Peptide (Castrodin), 1.8% Gel Matrix (Carbomer to Xanthan Gum in a mass ratio of 2:1), Deionized Water to make up to 100%.

[0033] A method for preparing a wound repair gel containing five grain insect oil is consistent with Example 1.

[0034] Compared to Example 1, this comparative example did not contain hyaluronic acid.

[0035] Experimental Example 1: Skin Wound Healing Rate Seventy healthy SPF-grade SD rats, weighing 200±20g, were selected and acclimatized for one week. Before the experiment, each rat was anesthetized by intraperitoneal injection of 1% sodium pentobarbital. The hair on the back was then removed, exposing the skin, which was then covered with a sterile drape. The back skin was disinfected with 75% alcohol. Using a sterile biopsy puncture instrument, a full-thickness skin loss lesion with a diameter of 0.5cm was created on the back of each rat. Care was taken not to damage the muscle layer during the procedure. After achieving adequate hemostasis, the rat skin wound model was obtained.

[0036] After modeling, the rats were randomly divided into 7 groups of 10 rats each: blank control group, Example 1 group, Example 2 group, Example 3 group, Comparative Example 1 group, Comparative Example 2 group, and Comparative Example 3 group. The prepared wound repair gel was applied evenly to the wound surface of each experimental group, ensuring complete coverage. The blank control group had its wound covered with sterile gauze and secured with medical tape. All groups received the medication once daily, with the gel or gauze changed every 24 hours.

[0037] The wounds of rats in each group were photographed on days 0, 3, 7, and 14 after drug administration. The wound area at each time point was measured using ImageJ image analysis software, and the wound healing rate was calculated.

[0038] Wound healing rate (%) = (Original wound area - Unhealed wound area) / Original wound area × 100%.

[0039] Table 1. Effects of each group of wound repair gels on wound healing rate.

[0040] As shown in Table 1, compared with the blank control group, the wound healing rate of each embodiment group of the present invention was significantly improved at different time points, and the wound repair effect was excellent, indicating that the wound repair gel prepared by the present invention has a good effect on promoting wound healing. Compared with each embodiment group, the wound healing rate of each comparative group at the same time point was significantly decreased, indicating that the components of five-grain insect oil, hyaluronic acid, chitosan and antimicrobial peptides can work synergistically to improve the wound healing effect. Among them, the wound healing rate of the comparative group lacking five-grain insect oil was the most significantly reduced, suggesting that five-grain insect oil plays a core role in promoting wound healing in the gel of the present invention.

[0041] Experimental Example 2: Biocompatibility 1 g of each wound repair gel sample was weighed and immersed in 10 mL of DMEM complete medium containing 10% fetal bovine serum under aseptic conditions. The mixture was then incubated at 37°C with shaking at 60 rpm for 24 hours. After filtration through a 0.22 μm microporous membrane for sterilization, the sterile supernatant was collected to obtain the gel extract. Complete medium without gel was used as a control group. All extracts were stored at 4°C for later use. HaCaT cells in logarithmic growth phase were digested with 0.25% trypsin, resuspended in complete medium, and the cell concentration was adjusted to 5 × 10⁶ cells / mL. 4 Cells were seeded at a density of 100 μL / mL into 96-well culture plates and incubated at 37°C with 5% CO2 for 24 hours until complete cell adhesion. After aspirating the original culture medium, 100 μL of the extracts from each of the experimental and comparative groups were added to each well, while the control group received an equal volume of complete culture medium. Each group was divided into six replicates. The culture plates were then incubated at 37°C with 5% CO2 for 24 and 48 hours, respectively. After incubation, the liquid in the wells was aspirated, and 100 μL of fresh complete culture medium and 10 μL of CCK-8 reagent were added to each well. Cell-free blank wells were also included. The culture plates were incubated at 37°C in the dark for 2 hours. The absorbance (OD value) of each well at 450 nm was measured using a microplate reader, and cell viability was calculated.

[0042] Table 2. Effects of each group of wound repair gels on cell viability

[0043] As shown in Table 2, compared with the control group, the cell viability of each example group was higher than 100%, indicating that the wound repair gel prepared by this invention is non-cytotoxic and can significantly promote HaCaT cell proliferation, exhibiting good biocompatibility and cell proliferation-promoting activity. The cell viability of each comparative example group was lower than that of the example group, with comparative example 1 showing the lowest cell viability, indicating that the insect oil plays a key role in promoting cell proliferation. The cell viability of comparative examples 2 and 3 was also significantly lower than that of the example group, indicating that antimicrobial peptides and hyaluronic acid also help maintain cell viability and promote cell growth. These results demonstrate that the insect oil, hyaluronic acid, chitosan, and antimicrobial peptides in the gel of this invention can work synergistically, ensuring excellent biocompatibility while providing a suitable cell growth microenvironment for wound repair, effectively promoting the proliferation of keratinocytes during wound healing, and accelerating the wound repair process.

[0044] Experimental Example 3: Thirty volunteers with different types of scars (including surgical scars, burn scars, acne scars, and traumatic scars) were randomly divided into an experimental group and a control group, with 15 patients in each group. Patients in the experimental group applied the wound repair gel prepared in Example 1 of this invention to the scar area twice daily for 8 weeks. Patients in the control group applied the gel prepared in Comparative Example 1, with the same application method and treatment course as the experimental group. At week 8 after the end of treatment, the Vancouver Scar Scale (VSS) was used to score the scar thickness, vascular distribution, color, and softness in both groups; higher scores indicated more severe scars.

[0045] Table 3 VSS Scoring Results

[0046] Table 3 shows that there was no significant difference in VSS scores between the experimental group and the control group before treatment, indicating comparability. After 8 weeks of treatment, the VSS score of the experimental group was significantly lower than that of the control group, demonstrating that the wound repair gel prepared in Example 1 of this invention can effectively improve scar thickness, vascular distribution, pigmentation, and softness, and inhibit scar hyperplasia. The control group used the gel prepared in Comparative Example 1, which showed a significantly weaker scar improvement effect, further confirming that the five-grain insect oil plays a key role in inhibiting scar hyperplasia and improving wound healing quality. The above results indicate that the wound repair gel of this invention can significantly improve scar appearance, reduce scar hyperplasia, and effectively improve wound healing quality.

[0047] The above descriptions are merely embodiments of the present invention, and common knowledge such as specific technical solutions and / or characteristics are not described in detail here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the technical solutions of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the implementation of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A wound healing gel containing five-grain insect oil, characterized in that, It consists of the following components by weight percentage: 5-10% Five Grain Insect Oil, 2-5% Hyaluronic Acid, 1-3% Chitosan, 0.1-0.3% Antimicrobial Peptide, 1-3% Gel Matrix, and the balance is Deionized Water.

2. The wound healing gel containing five-grain insect oil according to claim 1, characterized in that, The gel matrix is ​​composed of carbomer and xanthan gum.

3. The wound healing gel containing five-grain insect oil according to claim 2, characterized in that, The mass ratio of carbomer to xanthan gum is 1:(0.3~1).

4. The wound healing gel containing five-grain insect oil according to claim 1, characterized in that, The antimicrobial peptide is selected from at least one of cephalosporin, mussel adhesive protein, or LL-37.

5. A method for preparing a wound repair gel containing five-grain insect oil as described in any one of claims 1-4, characterized in that, Includes the following steps: S1. Add carbomer and xanthan gum to deionized water, allow them to swell fully, and then add a pH adjuster to neutralize to pH 6.0~7.5 to form a gel matrix; S2. Add five grain insect oil, hyaluronic acid, chitosan and antimicrobial peptides to the gel matrix obtained in step S1, and mix them at 10-20℃ to form a sol mixture. S3. After homogenizing and degassing the sol mixture obtained in step S2, heat it to 25-32℃ to form a semi-solid gel. S4. The semi-solid gel obtained in step S3 is sterilized to obtain a wound repair gel.

6. The method for preparing a wound repair gel containing five-grain insect oil according to claim 5, characterized in that, In step S1, the pH adjuster is triethanolamine, aminomethylpropanol, laurylamine, or stearylamine.

7. The method for preparing a wound repair gel containing five-grain insect oil according to claim 5, characterized in that, In step S2, the mixing is carried out by high-speed shear dispersion, with a rotation speed of 2000-5000 rpm and a time of 10-30 min.

8. The method for preparing a wound repair gel containing five-grain insect oil according to claim 5, characterized in that, The sterilization method in step S4 is cobalt-60 irradiation sterilization.

9. The use of a wound repair gel containing five-grain insect oil as described in any one of claims 1-4 in the preparation of wound repair materials.

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