KR-20260066490-A - Moisture-resistant hemostatic adhesive

Abstract

The present invention relates to a moisture-resistant hemostatic adhesive, and more specifically, to a freeze-dried sponge patch which is a cross-linked compound of a biocompatible biodegradable polymer, wherein the sponge patch comprises a mushroom-derived chitosan polymer having a mussel-derived protein adhesive function and a catechol-containing functional group or a gallic acid-derived functional group.

Inventors

• 박소영

Assignees

• 주식회사 세븐밸리메디컬

Dates

Publication Date

20260512

Application Date

20241104

Claims (5)

1. It is a cross-linked compound of a biocompatible biodegradable polymer, and as a freeze-dried sponge patch, The above sponge patch is, A hemostatic adhesive comprising a mushroom-derived chitosan polymer having an adhesive function of a mussel-derived protein and combined with a catechol-containing functional group or a gallic acid-derived functional group.
2. In paragraph 1, The above freeze-dried sponge patch is, A hemostatic adhesive that is a freeze-dried body of a chitosan-gallic acid polymer crosslink, which is a biocompatible biodegradable polymer having a functional group represented by the following chemical formula 1 introduced: [Chemical Formula 1] (Here, m = an integer from 16 to 12,000, and x : y = 99 : 1 to 50 : 50.)
3. In paragraph 1, The above hemostatic adhesive is, It comprises a single layer of freeze-dried sponge patch having adhesive and hemostatic functions, and The above freeze-dried sponge patch is a hemostatic adhesive having a porosity of 60% to 80%.
4. In paragraph 1, A step of preparing a bioadhesive polymer solution that is a crosslink of a mushroom-derived chitosan polymer combined with a catechol-containing functional group or a gallic acid-derived functional group; A step of primary freeze-drying the above bioadhesive polymer solution at a temperature of -50 ℃ or lower, a pressure of 50 mtorr to 100 mtorr, and for 1 to 4 days; A step of dissolving the primary freeze-dried product in water to form an aqueous solution; and A step of manufacturing a sponge patch by placing the above aqueous solution in a container and performing secondary freeze-drying at a temperature of -50 ℃ or lower, a pressure of 50 mtorr to 100 mtorr, and for 10 to 30 hours; Hemostatic adhesive obtained by a process including:
5. In paragraph 1, The above sponge patch has a plurality of grooves or micro-protrusions formed on one surface, and the grooves and micro-protrusions are in the shape of a sponge continuous with the sponge patch. The above micro-protrusions are in the shape of octopus suckers or domes, and The height of the above micro-protrusion is 0.1 mm to 0.5 mm, and the width is 100 µm (micrometer) to 500 µm (micrometer), and The depth of the above groove is 10% to 30% of the thickness of the above sponge patch, and The upper diameter of the above groove is 100 μm (micrometer) to 500 μm (micrometer), and A hemostatic adhesive having a slanted surface in the shape of a V (the letter V) for the above groove.

Description

Moisture-resistant hemostatic adhesive The present invention relates to a moisture-resistant hemostatic adhesive. In gastrointestinal surgeries, such as the removal of colorectal or rectal cancer, anastomosis is required after the resection of the gastrointestinal tract. However, it has been reported that anastomotic leakage occurs in 4 to 21% of patients after gastrointestinal surgery; specifically, 5 to 10% after gastroesophageal surgery, 20 to 50% after pancreatic cancer surgery, and 10 to 20% after rectal cancer surgery. Such anastomotic leakage can cause complications such as wound infection, small bowel obstruction, and changes in bowel function, and in severe cases, it has been reported to lead to death. Therefore, hemostatic agents and adhesives that can be used in fluid-rich surgeries and situations requiring hemostasis are essential. However, although various biomimetic technologies, particularly in wound dressings, utilize various biologically derived polymers such as collagen, hyaluronic acid, and chitosan, most of these are hydrophilic and react with water in the body to dissolve. Currently, the most frequently used adhesive is cyanoacrylate, a chlorine-based adhesive with the same components as instant adhesives used on the market, but there is a problem with toxicity occurring when it decomposes. Therefore, to repair the structure and function of damaged tissues and address issues regarding infection rates and tissue compatibility, it is necessary to develop adhesives with excellent biocompatibility and adhesive biomaterials that are free from adhesion and safety issues for the protection of anastomosis sites. Hereinafter, the hemostatic adhesive of the present invention will be described in detail with reference to examples. However, the present invention is not limited to these examples and drawings. According to one embodiment, the hemostatic adhesive of the present invention may be a hemostatic adhesive composite in which a sponge-shaped hemostatic agent is applied, which is a freeze-dried body of a crosslinked bioadhesive polymer comprising an adhesive material of a biocompatible polymer. That is, the hemostatic adhesive may include a sponge patch (layer) made of a freeze-dried biocompatible biodegradable polymer that contacts biological tissue and stops bleeding, comprising mussel-derived catechol or mushroom-derived chitosan combined with gallic acid. According to one embodiment, the bioadhesive polymer is a biocompatible biodegradable polymer (e.g., a catechol-chitosan complex), and by utilizing this, an excellent adhesive can be provided that increases moisture resistance and maintains adhesion even in a bodily fluid environment. This enables the realization of a moisture-resistant medical hemostatic adhesive that maintains strong adhesion in a moisture-rich environment. By utilizing a bioadhesive polymer based on catechol, a mussel-derived protein that enables strong adhesion even in humid environments such as the sea, moisture resistance can be increased, and by utilizing plant-derived chitosan extracted from mushrooms, biocompatibility and adhesive performance can be enhanced. According to one embodiment, the mussel-derived catechol can be applied as a medical adhesive by forming a complex with chitosan as a mussel adhesive protein (catechol). Mussels are organisms that live by adhering in environments with high moisture content, and the main component of mussel adhesion is a protein called 'catechol' or 'gallol'. By utilizing this, a medical adhesive that can be used in surgical or emergency situations can be applied, thereby increasing safety compared to conventional chlorine-based adhesives such as cyanoacrylates, and since it is composed of protein, it can provide biosafety by degrading within the body even if inserted. According to one embodiment, the mussel-derived catechol is a catechol compound extracted from mussels or a derivative thereof, and may include one or more selected from the group consisting of DOPA (3,4-dihydroxyphenylalanine), DOPA o-quinone, TOPA (2,4,5-trihydroxyphenylalanine), TOPA quinone, and derivatives thereof. For example, among the mussel-derived catechols, mussels produce a catecholic amino acid called DOPA (3,4-dihydroxyphenylalanine), which can strongly adhere to various surfaces such as rocks and seabeds. The catechol is 1,2-dihydroxybenzene, in which two hydroxyl groups are located adjacently, and forms chelate complexes with various metal ions, has a strong antioxidant effect, and can strongly adhere to the surface of various materials regardless of whether they are organic or inorganic surfaces. When the above catechol, which has metal ion chelating, antioxidant, and adhesive properties, is combined with various polymers, it can provide film-forming and thickening properties to the polymers. According to one embodiment, the mushroom-derived chitosan is a plant-derived chitosan, which is a biopolymer extracted from mushrooms, and is utilized as