US-12616778-B2 - Composite ultrathin coating film with inhibitory activity against hyperinflammatory response and bacteria, implant including same, and preparation method therefor

US12616778B2US 12616778 B2US12616778 B2US 12616778B2US-12616778-B2

Abstract

A composite ultra-thin coating film with hypersensitivity inflammatory reaction inhibition and antibacterial activity, an implant comprising the same, and a method for preparing the same are described. The composite ultra-thin coating film can be applied to medical silicone-based polymers and exhibits excellent antibacterial activity and inhibits deformed cell proliferation so that hypertrophic tissue is not formed and there is no cytotoxicity.

Inventors

Sung Yun Yang
Su Jin Lee
Dong Woon Kim
Sang-Ha OH

Assignees

THE INDUSTRY & ACADEMIC COOPERATION IN CHUNGNAM NATIONAL UNIVERSITY (IAC)

Dates

Publication Date: 20260505
Application Date: 20220214
Priority Date: 20210226

Claims (15)

1 . A composite ultra-thin coating film comprising: an inner layer in which materials selected from the group consisting of a hyaluronic acid polymer (HA), a polymer represented by the following Formula 1, and poly(allylamine hydrochloride) (PAH) are alternately laminated; and an outermost layer in contact with cells, wherein the outermost layer is laminated with a hyaluronic acid polymer (HA) or a polymer represented by the following Formula 1: where, *refers to a part that is combined, n, m, and o are the same as or different from each other and are each independently an integer of 1 to 100, L 1 to L 8 are the same as or different from each other, and are each independently a single bond or a substituted or unsubstituted alkylene group having 1 to 10 carbon atoms, and X 1 to X 3 are the same as or different from each other, and are each independently selected from the group consisting of cyclodextrin, a compound represented by Formula 2 above, and a compound represented by Formula 3 above.
2 . The composite ultra-thin coating film of claim 1 , wherein the compound represented by Formula 1 above is a cationic polymer (Cat-CyD) including the compound represented by Formula 2 above, and is alternately laminated with hyaluronic acid (HA) or poly(allylamine hydrochloride) (PAH).
3 . The composite ultra-thin coating film of claim 2 , wherein the compound represented by Formula 1 above is an anionic polymer (Ani-CyD) including the compound represented by Formula 3 above, and is alternately laminated with the cationic polymer (Cat-CyD).
4 . The composite ultra-thin coating film of claim 3 , wherein the inner layer is [PAH/HA], [PAH/Cat-CyD], [Cat-CyD/HA], or [Cat-CyD/Ani-CyD] laminated in a plurality.
5 . The composite ultra-thin coating film of claim 4 , wherein the inner layer is formed by laminating [PAH/HA], [PAH/Cat-CyD], [Cat-CyD/HA] or [Cat-CyD/Ani-CyD] in a plurality, and then additionally laminating [Cat-CyD].
6 . The composite ultra-thin coating film of claim 1 , wherein the inner layer has a pH of 3 to 5.
7 . The composite ultra-thin coating film of claim 1 , wherein the composite ultra-thin coating film inhibits the formation of a biofilm produced by Staphylococcus epidermidis.
8 . The composite ultra-thin coating film of claim 1 , wherein the composite ultra-thin coating film inhibits malformed cell proliferation.
9 . The composite ultra-thin coating film of claim 1 , wherein the composite ultra-thin coating film has a thickness of 20 nm or less.
10 . A method for preparing a composite ultra-thin coating film comprising steps of: forming an inner layer by alternately laminating materials selected from the group consisting of a hyaluronic acid polymer (HA), a polymer represented by the following Formula 1, and poly(allylamine hydrochloride) (PAH); and forming an outermost layer in contact with cells by laminating the hyaluronic acid polymer (HA) or the polymer represented by the following Formula 1: where, *refers to a part that is combined, n, m, and o are the same as or different from each other and are each independently an integer of 1 to 100, L 1 to L 8 are the same as or different from each other, and are each independently a single bond or a substituted or unsubstituted alkylene group having 1 to 10 carbon atoms, and X 1 to X 3 are the same as or different from each other, and are each independently selected from the group consisting of cyclodextrin, a compound represented by Formula 2 above, and a compound represented by Formula 3 above.
11 . The method of claim 10 , wherein the inner layer is formed under conditions of pH 3 to 5.
12 . An implant comprising: a substrate; and the composite ultra-thin coating film according to claim 1 formed on a surface of the substrate.
13 . The implant of claim 12 , wherein the substrate is a silicone-based polymer or metal.
14 . A method for manufacturing an implant on which a composite ultra-thin coating film is formed comprising steps of: forming an inner layer by alternately laminating materials selected from the group consisting of a hyaluronic acid polymer (HA), a polymer represented by the following Formula 1, and poly(allylamine hydrochloride) (PAH) on a substrate; and forming an outermost layer in contact with cells by laminating the hyaluronic acid polymer (HA) or the polymer represented by the following Formula 1: where, * refers to a part that is combined, n, m, and o are the same as or different from each other and are each independently an integer of 1 to 100, L 1 to L 8 are the same as or different from each other, and are each independently a single bond or a substituted or unsubstituted alkylene group having 1 to 10 carbon atoms, and X 1 to X 3 are the same as or different from each other, and are each independently selected from the group consisting of cyclodextrin, a compound represented by Formula 2 above, and a compound represented by Formula 3 above.
15 . A contact lens for ophthalmic surgery comprising: a silicone-based polymer substrate; and the composite ultra-thin coating film according to claim 1 formed on a surface of the substrate.

Description

TECHNICAL FIELD The present invention relates to a composite ultra-thin coating film with hypersensitivity inflammatory reaction inhibition and antibacterial activity, an implant comprising the same, and a method for preparing the same. BACKGROUND ART Due to the rapid aging of Korea in recent years, the population aged 65 or older is expected to account for 20.3% in 2025, and the use of implants is expected to increase for replacement of organs that have lost function due to aging and accidents, as well as for health promotion and beauty. In modern medicine, many defects in the human or animal body can be compensated for or minimized by their effectiveness by the use of implants. For example, it is well known that space holders for vertebrae or intervertebral discs serve to put the vertebral bodies or intervertebral discs in place. In a further example, a fixation or stabilization system may be mentioned for the spinal columns in which pedicle screws are fixed to the vertebrae and connected to each other via connecting rods, and therefore, the spacing and arrangement of the vertebrae may be arranged or fixed with respect to each other. For all implants, it is important that materials that are compatible with human or animal organs, that is, materials that do not cause rejection reaction due to decomposition phenomenon or do not produce harmful substances in the organ are used. Therefore, the choice of materials for implants is practically limited. A silicone material is the most representative soft material in addition to hard metallic materials among the materials used in implants. Silicone has been known to be the most common and stable material to date, but after insertion into the human body after surgery/procedures, it still causes deformation of the tissue at the insertion site due to frequent inflammatory reactions so that there is controversy over safety issues due to reoperation and removal surgery. Meanwhile, Korean Patent No. 1081336 has disclosed the synthesis of metal or sol-gel nanoparticles using a polymer electrolyte membrane with nanopores as a template and its application to biosensors, and Korean Patent Publication No. 2012-0124769 has disclosed a silicone implant material coated with a biodegradable polymer and a preparation method thereof, but a composite ultra-thin coating film with hypersensitivity inflammatory reaction inhibition and antibacterial activity according to the present invention, an implant comprising the same, and a method for preparing the same have not yet been disclosed. DISCLOSURE Technical Problem An object of the present invention is to provide, as a composite ultra-thin coating film that can be applied to medical silicone-based polymers, a composite ultra-thin coating film with hypersensitivity inflammatory reaction inhibition and antibacterial activity, which exhibits excellent antibacterial activity, and inhibits deformed cell proliferation so that hypertrophic tissue is not formed, and there is no cytotoxicity. Another object of the present invention is to provide a composite ultra-thin coating film with hypersensitivity inflammatory reaction inhibition and antibacterial activity, which can inhibit biofilm formation caused by the proliferation of S. epidermidis, which is best known as a risk factor for film construction after silicone-based polymer insertion, and can reduce film construction due to increased thickness of the film, an implant including the same, and a method for preparing the same. Technical Solution In order to achieve the above object, the present invention is a composite ultra-thin coating film including: an inner layer in which materials selected from the group consisting of a hyaluronic acid polymer (HA), a polymer represented by the following Formula 1, and poly(allylamine hydrochloride) (PAH) are alternately laminated; and an outermost layer in contact with cells, wherein the outermost layer may be laminated with a hyaluronic acid polymer (HA) or a polymer represented by the following Formula 1: where,* refers to a part that is combined,n, m, and o are the same as or different from each other and are each independently an integer of 1 to 100,L1 to L8 are the same as or different from each other, and are each independently a single bond or a substituted or unsubstituted alkylene group having 1 to 10 carbon atoms, andX1 to X3 are the same as or different from each other, and are each independently selected from the group consisting of cyclodextrin, a compound represented by Formula 2 above, and a compound represented by Formula 3 above. The compound represented by Formula 1 above is a cationic polymer (Cat-CyD) including the compound represented by Formula 2 above, and may be alternately laminated with hyaluronic acid (HA) or poly(allylamine hydrochloride) (PAH). The compound represented by Formula 1 above is an anionic polymer (Ani-CyD) including the compound represented by Formula 3 above, and may be alternately laminated with the cationi