KR-20260065664-A - Hydrogel for chronic wound improvement or treatment containing gallic acid-chitosan methacryloyl copolymer and its manufacturing method

Abstract

The present invention relates to a hydrogel for improving or treating chronic wounds comprising a gallic acid-chitosan methacryloyl copolymer and a method for manufacturing the same. The hydrogel was prepared by photocrosslinking gallic acid-chitosan methacryloyl and flounder-derived gelatin methacryloyl. Rheological properties according to the compositional ratio were confirmed, and intracellular antioxidant, anti-inflammatory, angiogenic, and in vivo wound healing effects were confirmed, which can be usefully utilized in related industries.

Inventors

• 정원교
• 박동주

Assignees

• 국립부경대학교 산학협력단

Dates

Publication Date

20260511

Application Date

20241101

Claims (17)

1. Gallic acid functionalized chitosan methacryloyl; and A hydrogel for improving or treating chronic wounds, comprising fish gelatin methacryloyl.
2. In paragraph 1, The above fish is a hydrogel that is a halibut ( Paralichthys olivaceus ).
3. In paragraph 1, The above hydrogel is a hydrogel that further comprises a photoinitiator.
4. In paragraph 1, The above hydrogel comprises gallic acid-chitosan methacryloyl and fish gelatin methacryloyl in a weight ratio of 0 to 2 : 0 to 5.
5. In paragraph 1, The above hydrogel is a hydrogel that scavenges ABTS, DPPH radicals, or reactive oxygen species (ROS).
6. In paragraph 1, The above hydrogel is a hydrogel that reduces IL-1β, TNF-α, or iNOS protein expression or increases IL-10 protein expression.
7. In paragraph 1, The above hydrogel is a hydrogel that promotes cell migration or angiogenesis in wound tissue or increases collagen fiber density.
8. A pharmaceutical composition for antioxidant or anti-inflammatory purposes comprising the hydrogel of claim 1 as an active ingredient.
9. A wound dressing comprising the hydrogel of claim 1.
10. A step of synthesizing fish-derived gelatin and methacrylate anhydride to form a first copolymer; A step of synthesizing chitosan and methacrylic anhydride to form a second copolymer; A step of synthesizing the second copolymer and gallic acid to form a third copolymer; and A method for preparing a hydrogel for improving or treating chronic wounds, comprising the step of mixing the first copolymer and the third copolymer and irradiating with light.
11. In Paragraph 10, A method in which the first copolymer comprises a compound represented by the following chemical formula 1. [Chemical Formula 1]
12. In Paragraph 10, A method in which the second copolymer comprises a compound represented by the following chemical formula 2. [Chemical Formula 2]
13. In Paragraph 10, A method in which the third copolymer comprises a compound represented by the following chemical formula 3. [Chemical Formula 3]
14. In Paragraph 10, A method in which the above mixture further comprises a photoinitiator.
15. In Paragraph 10, A method wherein the first copolymer and the third copolymer are mixed in a weight ratio of 0 to 2 : 0 to 5.
16. A polymer compound represented by the following chemical formula 3. [Chemical Formula 3]
17. A step of reacting chitosan and methacrylic anhydride; and A method for preparing a polymer compound represented by the following chemical formula 3, comprising the step of reacting the above reactants with gallic acid. [Chemical Formula 3]

Description

Hydrogel for chronic wound improvement or treatment containing gallic acid-chitosan methacryloyl copolymer and its manufacturing method The present invention relates to a hydrogel for improving or treating chronic wounds comprising a gallic acid-chitosan methacryloyl copolymer and a method for manufacturing the same. Unlike general wounds, chronic wounds do not proceed normally and remain in an inflammatory phase, resulting in delayed healing. A prime example is diabetic wounds, where impaired macrophage phenotypic transition from pro-inflammatory M1 to anti-inflammatory M2 and the excessive production of ROS perpetuate the inflammatory environment. This hinders angiogenesis and collagen deposition, thereby slowing wound healing. Due to these complex issues, the treatment of chronic diabetic wounds remains challenging, making the regulation of inflammatory responses and the restoration of vascular networks crucial. Dressing therapy for wound healing primarily involves adding growth factors or drugs to dressings to treat wounds, but there are difficulties in the drug manufacturing process due to high costs and the non-specific diffusion of drugs. Accordingly, it is necessary to develop highly biocompatible medical materials and functional dressings without the addition of wound healing drugs. Recently, naturally derived polymer-based hydrogels have been attracting attention and have advantages favorable for wound healing due to their high porosity and moisture retention capabilities. Meanwhile, gelatin possesses properties that promote cell adhesion and ECM remodeling in addition to biocompatibility and biodegradability; in particular, fish gelatin is highly valuable in the biomedical field because it is economical and free from zoonotic issues and religious restrictions. Additionally, chitosan is a natural polymer primarily extracted from the exoskeletons of crustaceans that has the advantages of high biocompatibility and antibacterial and antioxidant efficacy; however, its application as a biomaterial is significantly limited due to the characteristic that it dissolves only under acidic conditions. To address this, research on the functionalization of natural polymers is being actively conducted, and it is important to develop dressings for chronic wound healing utilizing these polymers. Accordingly, the inventors synthesized gallic acid-functionalized chitosan methacryloyl and flounder-derived gelatin methacryloyl, and photocrosslinked them to produce a new hydrogel, thereby confirming the intracellular antioxidant and anti-inflammatory effects and confirming the in vivo wound healing effect, thereby completing the present invention. All experimental procedures were conducted in accordance with the national regulations of the Republic of Korea, complied with the National Research Council's guidelines for the care and use of experimental animals, and were approved by the Pukyong National University Animal Ethics Committee (PKNUIACUC-2023-21). Figure 1 shows a schematic diagram of the manufacturing process of the hydrogel of the present invention. Figure 2 shows the 1H NMR and FT-IR spectra of the hydrogel of the present invention. Figure 3 shows the SEM image and rheological properties of the hydrogel of the present invention. Figure 4 shows the swelling rate and decomposition rate of the hydrogel of the present invention. Figure 5 shows the evaluation of cytotoxicity of the hydrogel of the present invention through Live/Dead fluorescence staining. Figure 6 shows the cell viability of human dermal fibroblasts (HDF), human keratinocytes (HaCaT), human umbilical vein endothelial cells (HUVEC), and mouse mononuclear macrophages (Raw264.7) of the hydrogel of the present invention. Figure 7 shows the ABTS and DPPH radical scavenging activity of the hydrogel of the present invention. Figure 8 shows the expression of reactive oxygen species (ROS), CD206, and iNOS proteins in the hydrogel of the present invention. Figure 9 shows the expression of nitric oxide, IL-1β, TNF-α, and IL-10 cytokines in the hydrogel of the present invention. Figure 10 shows images of HUVEC angiogenesis and cell migration of the hydrogel of the present invention. Figure 11 shows the diabetic treatment process and wound area of the hydrogel of the present invention. Figure 12 shows H&E and Masson's Trichrome staining images of the hydrogel of the present invention. Figure 13 shows iNOS, Arg1, and CD206 immunofluorescence images of the hydrogel of the present invention. Hereinafter, the present invention will be described in detail with reference to the attached drawings and embodiments thereof. However, the following embodiments are presented as examples of the present invention, and if it is determined that a detailed description of a technology or configuration well known to those skilled in the art may unnecessarily obscure the essence of the present invention, such detailed description may be omitted, and the present invention is not l