Light-emitting body activated by ambient light and wound treatment patch comprising same

Abstract

The present invention relates to a light-emitting body activated by ambient light and a wound treatment patch comprising same. The patch, according to the present invention, is capable of promoting wound healing and tissue bonding via photobiomodulation and photochemical tissue bonding, and is capable of exerting therapeutic effects by absorbing light to which a wearer is routinely exposed in indoor and outdoor environments, without requiring a separate external light source.

Description

A luminescent body activated by ambient light and a wound healing patch including the same

[0001] The present invention relates to a light-emitting body activated by ambient light and a wound treatment patch comprising the same.

[0002] Light-based therapy is garnering significant attention in the field of wound care as it can non-invasively regulate biological responses and promote tissue regeneration. Utilizing light of specific wavelengths, phototherapy is a safe and localized treatment that can replace surgical techniques, offering benefits such as enhanced tissue restoration, inflammation suppression, and accelerated wound healing.

[0003] Phototherapy is broadly categorized into photochemical tissue bonding (PTB) and photobiomodulation (PBM). PTB strengthens tissue bonding by inducing collagen cross-linking, while PBM activates tissue regeneration by promoting cell proliferation and collagen synthesis. These methods can replace sutures or adhesives, making them non-invasive and offering the advantages of improved recovery speed and minimized scarring.

[0004] Recently, with the increase in the number of surgeries and growing interest in out-of-hospital recovery, there is a rising demand for minimally invasive wound care techniques that allow patients to manage their own wounds. This demand is particularly pronounced in cosmetically important or externally exposed areas, such as those treated in plastic and reconstructive surgeries, where rapid recovery and scarring are essential.

[0005] However, conventional phototherapy relies on specialized light source systems such as lasers, medical high-power light sources, and fiber optic modules, which results in high costs and poses many limitations on patients receiving continuous treatment in their daily lives.

[0006] Therefore, there is a need to develop phototherapy technology that utilizes ambient light, such as indoor lighting or sunlight, to enable patients to obtain non-dry and continuous therapeutic effects even in their daily lives.

[0007] The objective of the present invention is to provide a novel light-emitting body applicable to phototherapy technology using ambient light and a method for manufacturing the same.

[0008] Another objective of the present invention is to provide a light-emitting layer that is activated by ambient light and emits red light, and a multilayer patch comprising the same.

[0009] Another objective of the present invention is to provide a wound healing patch that allows a patient to obtain a non-invasive and continuous therapeutic effect through ambient light in daily life.

[0010] Another objective of the present invention is to provide a wound healing dressing that can simultaneously achieve photochemical tissue bonding (PTB) and photobiological modulation (PBM) combined with the red light emission of a light source by additionally comprising an active layer containing a photosensitizer.

[0011] The present invention is capable of various modifications and may have various embodiments, and specific embodiments are to be illustrated and described in detail. However, this is not intended to limit the invention to specific embodiments, and it should be understood that the invention includes all modifications, equivalents, and substitutions that fall within the spirit and scope of the invention.

[0012] The terms used in this application are used merely to describe specific embodiments and are not intended to limit the invention. The singular expression includes the plural expression unless the context clearly indicates otherwise. In this application, terms such as "comprising" or "having" are intended to specify the presence of the features, numbers, steps, actions, components, parts, or combinations thereof described in the specification, and should be understood as not precluding the existence or addition of one or more other features, numbers, steps, actions, components, parts, or combinations thereof.

[0013] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as generally understood by those skilled in the art to which the present invention pertains. Terms such as those defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and should not be interpreted in an ideal or overly formal sense unless explicitly defined in this application.

[0014] Furthermore, to prevent clutter with overlapping content, redundant details have been omitted below. In other words, the content of the invention is not limited solely to the following description, and should be interpreted in accordance with the overall context of the invention.

[0015] Hereinafter, the light-emitting body activated by ambient light and the wound treatment patch including the same according to the present invention will be described in detail.

[0016] illuminant

[0017] The present invention provides a light-emitting body represented by the following chemical formula 1.

[0018] [Chemical Formula 1]

[0019] CaSr(S,SO4):Eu,Tm

[0020] Specifically, the light emitter may comprise 20 to 30 at% Ca, 10 to 20 at% Sr, 20 to 40 at% S, 20 to 40 at% O, 0.01 to 2 at% Eu and 0.01 to 5 at% Tm, based on a total of 100 at%.

[0021] Preferably, the light emitter may comprise 23 to 27 at% Ca, 12 to 15 at% Sr, 23 to 30 at% S, 30 to 35 at% O, 0.05 to 1 at% Eu and 1 to 3 at% Tm, based on a total of 100 at%.

[0022] The above-mentioned luminescent body may have a CaSrS matrix and a partially oxidized state in which some of the sulfur (S) within the matrix is ​​substituted with sulfate (SO4).

[0023] The above-mentioned light source may have an emission spectrum peak at a wavelength of 580 to 700 nm, and preferably may absorb light in the wavelength range of 300 to 600 nm and emit red light having an emission spectrum peak at a wavelength of 580 to 700 nm.

[0024] Specifically, the luminescent material is an oxidized particle of CaSrS:Eu,Tm. CaSr(S,SO4):Eu,Tm is a particle that simultaneously possesses high luminescence efficiency and biocompatibility while exhibiting red luminescence in the range of 580 to 700 nm. For photobiomodulation, 5 to 10 mW / cm² 2 A strong luminescence intensity is required, and since the CaSr(S,SO4):Eu,Tm of the present invention has the highest luminescence intensity and photon emission in the wavelength range of 580 to 700 nm, it can provide an optimal effect. That is, the present invention can achieve more powerful and effective phototherapy by using CaSr(S,SO4):Eu,Tm.

[0025] light-emitting layer

[0026] The present invention provides a light-emitting layer comprising: a matrix; and a light-emitting body dispersed in the matrix; wherein the light-emitting body absorbs ambient light and emits red light having a light emission spectrum peak at a wavelength of 580 to 700 nm.

[0027] The above-mentioned light-emitting layer can emit visible light in the red region into the skin, and through this red light, it can treat wounds and promote tissue bonding.

[0028] The above ambient light may be an indoor white light (e.g., white LED, fluorescent lamp, incandescent lamp), a portable white light source (e.g., mobile phone LED flash, portable flashlight, headlamp), or sunlight.

[0029] Preferably, the ambient light may be a light source including a wavelength of 300 to 700 nm.

[0030] Specifically, the indoor white light and portable white light source may include wavelengths of 400 to 700 nm, and the sunlight may include ultraviolet rays (100 to 400 nm), visible light (380 to 780 nm), and infrared rays (700 nm to 1 mm).

[0031] In one embodiment, the luminescent body is a room-light and sun-light activatable luminescent particle (RSLP). The luminescent body included in the luminescent layer can efficiently absorb and convert external light, and can emit red light when absorbing room light or sunlight. The emitted light promotes wound healing and tissue repair, and can enable effective treatment without an additional external light source.

[0032] The above-mentioned light emitter may include one or more selected from the group consisting of nitride phosphors, oxide phosphors, sulfur oxide phosphors, fluoride phosphors, sulfide phosphors, quantum dots, carbon dots, and upconversion light emitters.

[0033] Specifically, the light emitter may be a light emitter doped with europium (Eu) having a emission spectrum peak at a wavelength of 580 to 700 nm.

[0034] In one embodiment, the light emitter is CaSr(S,SO4):Eu,Tm, Y2SiO5:Eu 3+ , Y2Si2O7:Eu 3+ , YAlO3:Eu 3+ , CaAlSiN3:Eu 2+ , CaAl 12 O 19 :Eu 3+ , Sr3Al2O6:Eu 3+ , Ca2SiO4:Eu 3+ , Gd2O3:Eu 3+ , Sr2Si5N8:Eu 2+ , (Sr,Ca)AlSiN3:Eu 2+ , Y2O3:Eu 3+ , CaTiO3:Pr 3+ , Y2O2S:Eu 3+ ,Ti 4+ ,Mg 2+ , SrGa2O4:Cu 2+ , BaMgAl 10 O 17 :Eu 3+ , CaS:Eu 2+ , CaS:Eu 2+ ,Dy 3+ , SrS:Eu 2+ , CaS:Eu 2+ ,Sm 3+It may include one or more selected from the group consisting of , CaS:Eu,Tm, CaSrS:Eu,Sm, CaSrS:Eu,Tm, InP / ZnSeS, CdSe / ZnS, carbon dot, NaYF4:Yb,Er, NaErF4@NaYF4@NaGdF4:x%Yb@NaYF4(x = 0, 10, 49, 80) and NaErF4@NaYF4@NaGdF4:49%Yb / y%Tm@NaYF4(y = 0, 1, 5, 10).

[0035] Preferably, the luminescent body is CaSr(S,SO4):Eu,Tm, Y2SiO5:Eu 3+ , Y2Si2O7:Eu 3+ , YAlO3:Eu 3+ , CaAlSiN3:Eu 2+ , CaAl 12 O 19 :Eu 3+ , Sr3Al2O6:Eu 3+ , Ca2SiO4:Eu 3+ , Gd2O3:Eu 3+ , Sr2Si5N8:Eu 2+ , (Sr,Ca)AlSiN3:Eu 2+ , Y2O3:Eu 3+ , CaTiO3:Pr 3+ , Y2O2S:Eu 3+ ,Ti 4+ ,Mg 2+ , SrGa2O4:Cu 2+ , BaMgAl 10 O 17 :Eu 3+ , CaS:Eu 2+ , CaS:Eu 2+ ,Dy 3+ , SrS:Eu 2+ , CaS:Eu 2+ ,Sm 3+ It may include one or more selected from the group consisting of CaS:Eu,Tm, CaSrS:Eu,Sm, CaSrS:Eu,Tm, InP / ZnSeS, CdSe / ZnS, and carbon dots.

[0036] More preferably, the luminescent material is CaSr(S,SO4):Eu,Tm and Y2SiO5:Eu 3+ It may include one or more types selected from the group consisting of

[0037] The above matrix may include one or more selected from the group consisting of silicone-based elastomers, thermoplastic transparent elastomers, acrylic transparent polymers, and hydrogel-based transparent matrices.

[0038] The above silicone-based elastomer may be Liquid Silicone Rubber (LSR), and preferably may be one or more selected from the group consisting of Ecoflex, Polydimethylsiloxane (PDMS), MED-6015, and Dragon Skin.

[0039] The above thermoplastic transparent elastomer may be thermoplastic polyurethane (TPU) or styrene-ethylene-butylene-styrene.

[0040] The above acrylic transparent polymer may be polyurethane acrylate or polymethyl methacrylate (PMMA).

[0041] The above hydrogel-based transparent matrix may be a polyvinyl alcohol (PVA) hydrogel or a polyethylene glycol diacrylate (PEGDA).

[0042] In one embodiment, the matrix may include a silicon-based elastomer.

[0043] In one embodiment, the matrix may include Ecoflex, specifically Ecoflex 00-10, Ecoflex 00-30, or Ecoflex 00-45. In particular, Ecoflex can be flexibly deformed according to the movement of human skin and has an elongation rate of 100% or more, so it is possible to maintain stable light output without physical damage to the light emitter.

[0044] In one embodiment, the matrix may include polydimethylsiloxane (PDMS).

[0045] In one embodiment, the matrix may include MED-6015.

[0046] That is, the light-emitting layer of the present invention uses a silicon-based elastomer as a matrix, thereby providing high stretchability, flexibility, and biocompatibility required for skin-attached wearable devices.

[0047] The above-mentioned light-emitting layer may include 10 to 100 parts by weight of a light-emitting element based on 100 parts by weight of the matrix, preferably 20 to 95 parts by weight, 30 to 90 parts by weight, 35 to 85 parts by weight, and more preferably 40 to 80 parts by weight. If the amount of the light-emitting element is less than 10 parts by weight, it is difficult to achieve the desired light output density, which is undesirable; if the amount exceeds 100 parts by weight, significant scattering between particles occurs due to the excessive amount of the light-emitting element, which reduces light transmission, and mechanical instability and phase separation into solid and liquid regions occur, which is also undesirable.

[0048] Here, '10 to 100 parts by weight of a emitting agent per 100 parts by weight of a matrix' substantially corresponds to the condition of '100 to 1,000 mg of a emitting agent per 1 mL of matrix' added during the manufacturing step of the emitting layer.

[0049] The thickness of the light-emitting layer may be 0.1 to 1.66 mm, preferably 0.5 to 1.5 mm, and more preferably 0.7 to 1.2 mm. When the thickness of the light-emitting layer is 0.1 to 1.66 mm, sufficient light transmittance can be secured while maintaining structural integrity.

[0050] Multilayer patch

[0051] FIG. 1b shows a multilayer patch according to one embodiment of the present invention. According to FIG. 1b, the present invention provides a multilayer patch comprising: a protective layer; and a light-emitting layer formed on one surface of the protective layer and comprising a matrix and a light-emitting element, wherein the light-emitting element absorbs ambient light and emits red light having a light emission spectrum peak at a wavelength of 580 to 700 nm.

[0052] In the present invention, terms such as "matrix," "luminescent body," and "luminescent layer" are as described above.

[0053] The above protective layer acts as a support layer and can stabilize the physical properties of the light-emitting layer containing a high concentration of light-emitting material and the patch.

[0054] The above protective layer may be the same as or different from the matrix of the light-emitting layer, and preferably may be the same.

[0055] The above protective layer may include one or more selected from the group consisting of silicone-based elastomers, thermoplastic transparent elastomers, acrylic transparent polymers, and hydrogel-based transparent matrices.

[0056] The above silicone-based elastomer may be Liquid Silicone Rubber (LSR), and preferably may be one or more selected from the group consisting of Ecoflex, Polydimethylsiloxane (PDMS), MED-6015, and Dragon Skin.

[0057] The above thermoplastic transparent elastomer may be thermoplastic polyurethane (TPU) or styrene-ethylene-butylene-styrene.

[0058] The above acrylic transparent polymer may be polyurethane acrylate or polymethyl methacrylate (PMMA).

[0059] The above hydrogel-based transparent matrix may be a polyvinyl alcohol (PVA) hydrogel or a polyethylene glycol diacrylate (PEGDA).

[0060] In one embodiment, the protective layer may include a silicone-based elastomer.

[0061] In one embodiment, the protective layer may include Ecoflex, specifically Ecoflex 00-10, Ecoflex 00-30, or Ecoflex 00-45. Ecoflex is used as a medical silicone and is safe for skin contact and has excellent flexibility. In particular, Ecoflex has high elasticity and durability, providing comfort to the user even when worn for a long time, and has the advantage of excellent skin compatibility.

[0062] In one embodiment, the protective layer may comprise polydimethylsiloxane (PDMS).

[0063] In one embodiment, the protective layer may include MED-6015.

[0064] That is, the present invention uses a silicone-based elastomer as a protective layer to provide high stretchability, flexibility, and biocompatibility required for skin-attached wearable devices.

[0065] In one embodiment, the thickness of the protective layer may be 0.1 to 0.5 mm. Within this thickness range, it is soft and highly flexible, allowing it to adhere closely to the curvature of the user's skin attachment area.

[0066] The above multilayer patch may additionally include an adhesive layer formed on part or all of the other surface of the protective layer, and the adhesive layer may increase adhesion to the skin.

[0067] Specifically, if the adhesive layer is transparent, it may be formed on the entire surface of the protective layer, and if it is opaque, it may be formed on a part of the surface of the protective layer, preferably limited to the edges.

[0068] In one embodiment, the adhesive layer may be formed at the edges of the protective layer. For example, if the protective layer has a rectangular shape, the adhesive layer may be formed at the four edges of the protective layer.

[0069] In one embodiment, the total area ratio of the adhesive layer may be 9 to 18% relative to 100% of the protective layer area. Additionally, when the adhesive layer is formed on multiple edges, each adhesive layer may have the same shape and area.

[0070] The adhesive layer may include one or more selected from the group consisting of silicone-based adhesives, acrylic-based adhesives, wet-adhesive hydrogels, boronic acid ester / diol-based adhesives, NHS-ester / Schiff-based chemical adhesives, and DOPA-containing polymer adhesives.

[0071] The above silicone-based adhesive may be a medical silicone adhesive, and examples include Dow’s BIO-PSA 7-4xxx / 7-46xx series, Factor II, Nusil, etc.

[0072] The above acrylic adhesive may be a medical acrylic adhesive, and for example, 3M’s medical tape or laminate (e.g., 9877, 9875, 1522, 4077 (extended wear), etc.) may be used.

[0073] The above-mentioned wet adhesive hydrogel may be a natural or synthetic hydrogel that does not contain catechol groups, and examples include Gallol (pyrogallol) modified polymers (e.g., HA-Gallol, PEG-Gallol, Gelatin-Gallol), and tannic acid (TA)-polymers / Fe 3+ Network, or alginate-Ca 2+ Ion gels, etc., can be used.

[0074] The above boronic acid ester / diol-based adhesive may, for example, use PVA-borate (PVA-Borax) or PBA (phenylboronic acid)-based polymers.

[0075] The above NHS-ester / Schiff base chemical adhesive may, for example, use a gel with NHS-ester introduced (e.g., PEG-NHS, Gel-NHS) and a primary amine-rich substrate, or a combination of dextran oxide (aldehyde) and gelatin / chitosan (amine).

[0076] The above DOPA-based compounds are, exemplarily, HA-DOPA hydrogels and HA-DOPA / Fe 3+ Hydrogels, etc., may be used.

[0077] The multilayer patch according to the present invention effectively absorbs ambient light (indoor lighting and natural light) to promote photobiomodulation and photochemical tissue bonding, and can be attached to the skin as a wearable patch.

[0078] The multilayer patch of the present invention can be used for treating skin wounds and promoting tissue bonding.

[0079] clothing material

[0080] FIG. 1c shows a coating material according to one embodiment of the present invention.

[0081] According to FIG. 1c, the present invention provides a coating material (10) comprising: a patch (100) comprising a light-emitting layer (110) comprising a matrix and a light-emitting body; and an active layer (200) formed on one surface of the patch and comprising a photosensitive agent, wherein the light-emitting body absorbs indoor light or sunlight and emits red light having a light emission spectrum peak at a wavelength of 580 to 700 nm.

[0082] The above patch (100) may include a protective layer (120) formed on the light-emitting layer (110) and an adhesive layer (130) formed on the protective layer (120), and the active layer (200) may be formed on the adhesive layer (130).

[0083] In the present invention, terms such as "matrix," "luminescent body," "luminescent layer," "protective layer," and "adhesive layer" are as described above.

[0084] Specifically, the above-mentioned covering material (10) may be manufactured by (1) directly forming an active layer (200) containing a photosensitive agent on the adhesive layer (130) of the patch (100), or by (2) forming an active layer (200) by applying a solution containing a photosensitive agent to the skin and then attaching the patch (100).

[0085] The above photosensitizers are Chlorine e6, verteporfin, Methylene Blue (MB), Toluidine Blue O (TBO), Nile Blue A, Thionine, Indocyanine Green (ICG), Zinc Phthalocyanine (ZnPc), Aluminum Phthalocyanine Tetrasulfonate (AlPcS4), Aminolevulinic Acid (ALA), Methyl Aminolevulinate, Temoporfin, Phthalocyanine, Protoporhap IX (PpIX), Allumera™, Cevira™, Hexvix™, Porfimer Sodium, δ-aminolevulinic acid or 5-aminolevulinic acid, Temoporfin, Methyl Aminolevulinate, and Hexaminolevulinate It may be any one selected from the group consisting of hexaminolevulinate hydrochloride, talaporfin, motexafin lutetium, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a, Photosens™, rostaporfin, BF-200 ALA, tetraphenyl chlorin disulfonate, and azadipyrromethene.

[0086] In one embodiment, the photosensitizer may include one or more selected from the group consisting of chlorine e6, verteporfin, and methylene blue (MB).

[0087] Wound healing patches / dressings

[0088] The present invention provides a wound healing patch comprising a matrix and a light-emitting layer, wherein the light-emitting layer absorbs ambient light and emits red light having a light emission spectrum peak at a wavelength of 580 to 700 nm.

[0089] The present invention provides a wound healing dressing comprising: a patch comprising a light-emitting layer comprising a matrix and a light-emitting body; and an active layer formed on one surface of the patch and comprising a photosensitive agent, wherein the light-emitting body absorbs ambient light and emits red light having a light emission spectrum peak at a wavelength of 580 to 700 nm.

[0090] In the present invention, the term "wound" refers to a damaged state of a living organism, encompassing a pathological condition in which tissues forming the internal or external surface of the organism, such as skin, muscle, nerve tissue, bone, soft tissue, internal organ, or vascular tissue, are fragmented or destroyed, and may be used interchangeably with "scar."

[0091] The above wounds are trauma, heat injury, Buerger's disease, vascular and lymphatic injury, postoperative wound, stoma, pressure ulcer, pressure ulcer, diabetic ulcer / scrotum ( It may be any one selected from the group consisting of ), post-herpetic ulcer, drug-induced ulcer, skin ulcer, damage caused by dermatitis, radiation damage, and chemical damage.

[0092] In this invention, the term "treatment" refers to any act in which symptoms of a wound are improved or beneficially altered by the application (attachment) of a patch or covering material according to this invention.

[0093] In the present invention, terms such as "matrix," "luminescent body," "luminescent layer," "protective layer," "adhesive layer," and "active layer" are as described above.

[0094] FIG. 1a schematically illustrates the appearance of a multilayer patch and a covering material according to one embodiment of the present invention being activated by indoor lighting and sunlight.

[0095] Conventional phototherapy devices require light-emitting diodes (LEDs) or external light sources, which limits long-term treatment. On the other hand, according to FIG. 1a, the patch and coating material of the present invention can be activated by indoor light and / or sunlight alone, enabling effective treatment. That is, the patch and coating material are automatically activated when only indoor lighting is turned on, emitting therapeutic light with a wavelength of 580 to 700 nm, specifically about 640 nm, and have the advantage of not requiring separate external equipment or light sources. In addition, effective treatment is possible even when exposed to sunlight outdoors, allowing for convenient treatment to be provided to the user anywhere without being restricted by location.

[0096] The present invention provides a method for treating a wound comprising the step of applying the multilayer patch to a surface to be treated.

[0097] The present invention provides a method for treating a wound comprising the step of applying the above-mentioned covering material to a surface to be treated.

[0098] The present invention provides a use of the multilayer patch in the manufacture of a drug for the treatment of wounds.

[0099] The present invention provides a use of the dressing material in the manufacture of a drug for the treatment of wounds.

[0100] The present invention provides a composition comprising the multilayer patch for use in treating wounds.

[0101] The present invention provides a composition comprising the above-mentioned dressing for use in treating a wound.

[0102] The present invention provides a use of the multilayer patch for the treatment of wounds.

[0103] The present invention provides a use of the above-mentioned dressing for the treatment of a wound.

[0104] The light emitter of the present invention can be applied to phototherapy technology using ambient light.

[0105] In addition, the light-emitting layer of the present invention and the multilayer patch including the same can be activated by ambient light to emit red light, and by utilizing this, a wound treatment patch can be provided that can obtain a non-invasive and continuous therapeutic effect by ambient light.

[0106] The coating material of the present invention comprises an active layer containing a photosensitizer, thereby providing a wound healing coating material capable of simultaneously realizing photochemical tissue bonding (PTB) and photobiological modulation (PBM) combined with the red light emission of a light source.

[0107] In modern medical technology, methods for wound healing and tissue integration often require external light sources or involve invasive procedures, which can impair user convenience. Additionally, existing wearable patches require high-output light sources with specific wavelength bands for effective photobiomodulation and photochemical tissue integration.

[0108] The multilayer patch or coating material according to the present invention overcomes the aforementioned limitations by utilizing ambient light, enabling the wearable patch to operate effectively without a separate external light source. Accordingly, user convenience can be enhanced and the treatment process simplified.

[0109] FIG. 1a schematically illustrates the appearance of a multilayer patch and a covering material according to one embodiment of the present invention being activated by indoor lighting and sunlight.

[0110] FIG. 1b shows a multilayer patch according to one embodiment of the present invention.

[0111] FIG. 1c shows a coating material according to one embodiment of the present invention.

[0112] Figure 2a is an SEM image of CaSrS:Eu,Tm particles before oxidation (scale bar = 10 μm).

[0113] Figure 2b shows the results of the EDS elemental analysis of CaSrS:Eu,Tm particles before oxidation.

[0114] Figure 2c shows the elemental mapping results based on the SEM image of Figure 2a (scale bar = 10 μm).

[0115] Figure 3a is an SEM image of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1 (scale bar = 5 μm).

[0116] Figure 3b shows the results of the EDS elemental analysis of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0117] Figure 3c shows the elemental mapping results based on the SEM image of Figure 3a (scale bar = 5 μm).

[0118] Figure 3d is the result of XPS elemental analysis of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0119] Figure 3e shows the XRD analysis results of CaSrS:Eu,Tm particles before oxidation and CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0120] Figure 3f shows the results of calculating the lattice constant based on the XRD analysis results of Figure 3e.

[0121] Figure 3g shows the emission wavelength range of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0122] Figure 3h shows the afterglow wavelength range of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0123] Figure 3i shows the CIE color purity of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0124] Figure 3j shows the emission (PL) and afterglow (AL) images of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0125] Figure 3k shows the afterglow time analysis results of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0126] Figure 31 shows the results of luminescence and afterglow repeat analysis of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0127] Figure 3m shows the results of the analysis of the luminescence and afterglow mechanisms of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0128] Fig. 4a is an SEM image of Y2SiO5:Eu particles (scale bar = 100 μm).

[0129] Figure 4b shows the results of the EDS elemental analysis of Y2SiO5:Eu particles.

[0130] Figure 4c shows the elemental mapping results based on the SEM image of Figure 4a (scale bar = 100 μm).

[0131] Figure 4d shows the emission wavelength range of Y2SiO5:Eu particles (YSO:Eu).

[0132] Figure 5a is an SEM image of the light-emitting layer of Example 3-1 (RSLP+Ecoflex) (scale bar = 250 μm).

[0133] Figure 5b shows the results of the EDS elemental analysis of the light-emitting layer of Example 3-1 (RSLP+Ecoflex).

[0134] Figure 5c shows the elemental mapping results based on the SEM image of Figure 5a (scale bar = 250 μm).

[0135] Figure 6a is an SEM image of the light-emitting layer of Example 3-2 (RSLP+PDMS) (scale bar = 250 μm).

[0136] Figure 6b shows the results of the EDS elemental analysis of the light-emitting layer of Example 3-2 (RSLP+PDMS).

[0137] Figure 6c shows the elemental mapping results based on the SEM image of Figure 6a (scale bar = 250 μm).

[0138] Figure 7a is an SEM image of the light-emitting layer of Example 3-3 (RSLP+MED-6015) (scale bar = 250 μm).

[0139] Figure 7b shows the results of the EDS elemental analysis of the light-emitting layer of Example 3-3 (RSLP+MED-6015).

[0140] Figure 7c shows the elemental mapping results based on the SEM image of Figure 7a (scale bar = 250 μm).

[0141] Figure 8a is an SEM image of the light-emitting layer of Example 3-4 (YSO:Eu+Ecoflex) (scale bar = 250 μm).

[0142] Figure 8b shows the results of the EDS elemental analysis of the light-emitting layer of Example 3-4 (YSO:Eu+Ecoflex).

[0143] Figure 8c shows the elemental mapping results based on the SEM image of Figure 8a (scale bar = 250 μm).

[0144] Figure 9a is an SEM image of the light-emitting layer of Example 3-5 (YSO:Eu+PDMS) (scale bar = 250 μm).

[0145] Figure 9b shows the results of the EDS elemental analysis of the light-emitting layer of Example 3-5 (YSO:Eu+PDMS).

[0146] Figure 9c shows the elemental mapping results based on the SEM image of Figure 9a (scale bar = 250 μm).

[0147] Fig. 10a is an SEM image of the light-emitting layer of Example 3-6 (YSO:Eu+MED-6015) (scale bar = 250 μm).

[0148] Figure 10b shows the results of the EDS elemental analysis of the light-emitting layer of Example 3-6 (YSO:Eu+MED-6015).

[0149] Figure 10c shows the elemental mapping results based on the SEM image of Figure 10a (scale bar = 250 μm).

[0150] Figure 11a shows the image of the emitting layer and the emitting / afterglow image according to the RSLP concentration of the emitting layer in Example 3-1 (scale bar = 1 cm).

[0151] Figure 11b shows the luminescence intensity according to the RSLP concentration of the light-emitting layer in Example 3-1.

[0152] FIG. 11c shows an image of the light-emitting layer according to the RSLP concentration of the light-emitting layer in Example 3-1 (scale bar = 1 cm).

[0153] FIG. 11d shows the image of the light-emitting layer and the light emission / afterglow image according to the thickness of the light-emitting layer in Example 3-1 (scale bar = 1 cm).

[0154] Figure 11e shows the luminescence intensity according to the thickness of the light-emitting layer in Example 3-1.

[0155] Figure 12 shows the UV emission image (PL(UV)) and afterglow image (AL(UV)) of the light-emitting layer (YSO:Eu+Ecoflex) of Example 3-4.

[0156] Figure 13a shows the emission wavelength range of the light-emitting layer (RSLP+Ecoflex) of Example 3-1.

[0157] Figure 13b shows the afterglow wavelength range of the light-emitting layer in Example 3-1.

[0158] Figure 13c shows the correlation between the light emission and afterglow of the light-emitting layer in Example 3-1.

[0159] FIG. 13d shows images of the light-emitting layer of Example 3-1, light emission image in UV, afterglow image in UV, afterglow image in indoor light, afterglow image in sunlight, and afterglow retention time image in UV (scale bar = 1 cm).

[0160] Figure 13e shows the PL power density of the light-emitting layer of Example 3-1 under various light sources.

[0161] Figure 14a shows the light emission and afterglow images of the light-emitting layer (RSLP+Ecoflex) of Example 3-1 according to stretching (0~100%) under UV.

[0162] Figure 14b shows the power density according to the stretching of the light-emitting layer (RSLP+Ecoflex) of Example 3-1.

[0163] Figure 14c shows the power density according to the stretching repeatability of the light-emitting layer (RSLP+Ecoflex) of Example 3-1.

[0164] FIG. 14d shows the light emission and afterglow images of the light-emitting layer (RSLP+Ecoflex) of Example 3-1 according to stretching (0~50%) in room light.

[0165] Figure 14e shows the tensile strength analysis results of the light-emitting layer in Example 3-1.

[0166] Fig. 15 shows the HA-DOPA conjugate 1 This shows the results of the H NMR analysis.

[0167] Figure 16a is an image of the attachment and removal of HA-DOPA / Fe hydrogel adhesive to mouse skin.

[0168] Figure 16b is an image of the attachment and removal of the Example 5-2 patch (RSLP+Ecoflex light-emitting layer, Ecoflex protective layer and HA-DOPA / Fe adhesive layer) to mouse skin.

[0169] Figure 16c is an image of the Example 5-1 patch (HA-DOPA Patch), Example 5-2 patch (HA-DOPA / Fe Patch), and the HA-DOPA / Fe hydrogel adhesive (HA-DOPA / Fe Hydrogel).

[0170] Figure 16d shows the results of a tensile strength test on in vitro porcine tissue using the sample of Figure 16c, and the inset of Figure 16d is a schematic diagram showing the tensile strength test setup.

[0171] Figure 17a shows a method for measuring the in vitro cell migration and proliferation effects of a multilayer patch.

[0172] Fig. 17b is a DAPI staining image showing enhanced proliferation of the Example 5-2 patch (RSLP+Ecoflex emissive layer) after room light (RL) treatment (Scale bar = 200 μm).

[0173] Figure 17c shows the quantification of normalized DAPI fluorescence for each group in Figure 17b.

[0174] Fig. 17d is a live cell scratch analysis image showing cell migration at 0, 12, and 24 hours for each group in Fig. 17b (Scale bar = 500 μm).

[0175] Figure 17e shows the quantification of time-dependent cell proliferation after room light (RL) treatment of the Example 5-2 patch (RSLP+Ecoflex light-emitting layer).

[0176] Fig. 18a is a DAPI staining image showing enhanced proliferation after UV treatment of the Example 5-5 patch (YSO:Eu+Ecoflex emissive layer) (Scale bar = 200 μm).

[0177] Figure 18b shows the quantification of normalized DAPI fluorescence for each group in Figure 18a.

[0178] Figure 19a confirms the collagen fiber-forming effect of a multilayer patch using RSLP as a light source.

[0179] Figure 19b confirms the collagen fiber-forming effect of a multilayer patch using YSO:Eu as a light source.

[0180] FIG. 20a illustrates a method for evaluating collagen cross-linking induced by the multilayer patch and coating material of the present invention.

[0181] Figure 20b shows the results of measuring the tensile strength of the control group, the patch of Example 5-2, Ce6, and the coating material of Example 8-1 after treating them with white LED light for 2 hours.

[0182] Figure 21 shows the cell viability of the coating material of Example 8-1 (Ce6+ patch of Example 5-2).

[0183] Figure 22a shows the experimental results confirming the in vivo linear wound healing effect of a multilayer patch / cladding using RSLP as a luminescent material.

[0184] Figure 22b shows the tensile strength values ​​on day 1 of the suture group and the coating material (Ce6+Patch) group of Example 8-1 in the experiment conducted according to Figure 22a.

[0185] FIG. 22c is a gross image showing PTB-based wound closure using the dressing (Ce6+Patch) of Example 8-1.

[0186] Figure 22d shows the tensile strength values ​​of each group on day 7 in the experiment conducted according to Figure 22a.

[0187] Figure 22e shows the tensile strength values ​​of the patch group of Example 5-2 and the coating material group of Example 8-1 (Ce6+Patch) according to the treatment frequency in the experiment conducted according to Figure 22a.

[0188] Figure 23 shows the experimental results confirming the in vivo linear wound healing effect of a multilayer patch / cladding using YSO:Eu as a luminescent material.

[0189] Figure 24a shows the experimental results confirming the in vivo circular wound healing effect of a multilayer patch / cladding using RSLP as a luminescent material.

[0190] Figure 24b shows the quantitative analysis of the wound area in the experiment conducted according to Figure 24a.

[0191] Figure 24c is a macroscopic image showing the nonlinear acceleration of wound healing through the PBM of the covering material (Ce6+Patch) of Example 8-1.

[0192] Figure 24d shows the wound closure effect according to the treatment frequency of the patch group of Example 5-2.

[0193] Figure 24e shows the wound closure effect according to treatment frequency of the dressing material (Ce6+Patch) group of Example 8-1.

[0194] Figure 25a shows the results of H&E staining and Masson's trichrome staining 7 days after healing of an in vivo incision wound (linear wound of Example 12).

[0195] Figure 25b shows the results of immunofluorescence staining 7 days after healing of an in vivo incision wound (linear wound of Example 12).

[0196] Figure 26a shows the results of H&E staining and Masson's trichrome staining 10 days after healing of an in vivo excision wound (the circular wound of Example 12).

[0197] Figure 26b shows the results of immunofluorescence staining 10 days after healing of an in vivo excision wound (the circular wound of Example 12).

[0198] Figure 27a shows the quantified cytokine expression on the second day of healing of an in vivo incision wound (linear wound of Example 12).

[0199] Figure 27b shows the quantified cytokine expression on day 4 of healing of an in vivo incision wound (linear wound of Example 12).

[0200] Figure 28a shows the quantified cytokine expression on the second day of healing of an in vivo resection wound (the original wound of Example 12).

[0201] Figure 28b shows the quantified cytokine expression on the 4th day of healing of an in vivo resection wound (the original wound of Example 12).

[0202] Examples are provided to aid in understanding the present invention. The following examples are provided merely to facilitate a better understanding of the invention, and the scope of the invention is not limited by these examples.

[0203] Example 1: Preparation of CaSr(S,SO4):Eu,Tm luminescent material

[0204] Room light and sunlight-activated luminescent particles (RSLP) denoted by CaSr(S,SO4):Eu,Tm were prepared by a solid-state heat treatment reaction.

[0205] Specifically, CaCO3 (1 mmol), SrCO3 (0.17 mmol), Eu2O3 (0.0004 mmol), thulium(III) acetate hydrate (0.0014 mmol), and H3BO3 (0.01 mmol) were ground in an agate mortar for 30 minutes. Sulfur (4 mmol) was added to the mixed powder, and then heat-treated at 1,100°C for 1 hour in a reducing atmosphere (argon (Ar) gas containing 5% hydrogen) to produce CaSrS:Eu,Tm particles. The produced CaSrS:Eu,Tm particles were stored under vacuum prior to the experiment.

[0206] Subsequently, the above CaSrS:Eu,Tm particles were exposed to air at room temperature for 24 hours to produce partially oxidized CaSr(S,SO4):Eu,Tm (RSLP).

[0207] In the following, CaSrS:Eu,Tm particles before oxidation are referred to as pre-oxidation particles, and oxidized CaSr(S,SO4):Eu,Tm particles are referred to as RSLP.

[0208]

[0209] Example 2: Verification of luminescent properties

[0210] (1) Method

[0211] The morphology, size, and composition of the RSLP were analyzed using a field emission scanning electron microscope (FE-SEM) equipped with dual-energy dispersive spectroscopy (EDS) (JSM-7800F, JEOL Ltd., Akishima, Japan).

[0212] The binding energy spectrum was measured by X-ray photoelectron spectroscopy (XPS) (ESCALAB 250, Thermo Scientific, Waltham, MA).

[0213] X-ray diffraction (XRD) patterns were analyzed using a diffractometer (D / MAX-2500-PC, Rigaku Co., Akishima, Japan) with Cu-Kα radiation (1.5418 Å) at a tube voltage of 100 kV and a tube current of 40 mA.

[0214] Crystallinity was analyzed using Origin software (Microcal Software Inc., Northampton, MA).

[0215] Particle size was calculated from XRD data using the Scherrer equation.

[0216] Lattice constants were calculated from XRD data using Bragg's law.

[0217] The volume was measured by taking into account the lattice structure and lattice constant.

[0218] Photoluminescence (PL) and afterglow luminescence (AL) spectra were obtained using a Horiba FluoroLog Fluorometer spectrophotometer (HORIBA Ltd., Kyoto, Japan). After placing the emitter in a 1 cm quartz cuvette, the PL spectrum was measured within the emission spectrum range of 580 to 700 nm at an excitation wavelength of 365 nm. Additionally, the PL spectrum was measured within the excitation spectrum range of 300 to 600 nm at an emission wavelength of 640 nm. Before AL measurement, the excitation light source was turned off, and the emitter was charged with white LED light for 5 seconds. The AL spectrum was measured within the emission spectrum range of 580 to 700 nm.

[0219] Afterglow decay curves were investigated using a microplate fluorescence meter (Fluoroskan Ascent FL, Thermo Scientific, Waltham, MA). Specifically, after placing the emitter into a 96-well microplate, the AL intensity was measured for 30 minutes after turning off the charging light. To analyze the repetitive recharge stability, the emitter was recharged with 365 nm UV illumination for 5 seconds, followed by a subsequent AL measurement and the AL intensity being measured for 5 minutes.

[0220] PL images were captured using a charge-coupled device (CCD) camera (Canon EOS 100D; Canon, Tokyo, Japan) by irradiating with a UV flash light (365 nm, 6 W, distance: 3 cm). Afterglow images were captured using a CCD camera every 30 seconds after irradiating with the UV flash light for 5 seconds.

[0221] (2) Result

[0222] Figure 2a is an SEM image of CaSrS:Eu,Tm particles before oxidation (scale bar = 10 μm), Figure 2b shows the results of EDS elemental analysis of CaSrS:Eu,Tm particles before oxidation, and Figure 2c shows the results of elemental mapping based on the SEM image of Figure 2a (scale bar = 10 μm).

[0223] Figure 3a is an SEM image of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1 (scale bar = 5 μm), Figure 3b shows the EDS elemental analysis results of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1, and Figure 3c shows the elemental mapping results based on the SEM image of Figure 3a (scale bar = 5 μm).

[0224] According to Figures 2a and 3a, the particles before oxidation exhibit a uniform shape and smooth surface characteristics, whereas the RSLPs show a rough particle surface and some changes in the surface.

[0225] In addition, according to Figures 2b and 2c, almost no oxygen (O) was detected in the particles before oxidation, confirming that no oxidation occurred. This non-oxidation characteristic of the initial state was used for comparison with other samples.

[0226] According to Figures 3b and 3c, it can be confirmed that the concentration of oxygen (O) atoms in RSLP increased significantly, and that partial oxidation occurred on the particle surface. Compared to the particle before oxidation, the increase in oxygen content supports the fact that an oxidation reaction actually occurred.

[0227] Figure 3d is the result of XPS elemental analysis of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0228] Through Figure 3d, oxygen (O) can be seen on the particle surface of RSLP, which supports the fact that oxidation occurred on the particle surface.

[0229] Figure 3e shows the XRD analysis results of CaSrS:Eu,Tm particles before oxidation and CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1, and Figure 3f shows the lattice constant calculation results based on the XRD analysis results of Figure 3e.

[0230] Changes in the crystal structure of the particles can be confirmed through Figures 3e and 3f. Specifically, in the RSLP where oxidation occurred, a new diffraction peak of the SrSO4 crystal phase appeared, suggesting that sulfation occurred due to oxidation. In addition, the decrease in the linewidth of the XRD peak indicates grain growth, which signifies a structural change due to thermal or chemical stimulation. On the other hand, such oxidation-related diffraction peaks were not observed in the particles prior to oxidation.

[0231] Figure 3g shows the emission wavelength range of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1, and Figure 3h shows the afterglow wavelength range of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0232] According to Figures 3g and 3h, it was confirmed that CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1 can be automatically activated in indoor light and sunlight to emit therapeutic light with a wavelength of about 640 nm.

[0233] Figure 3i shows the CIE color purity of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0234] According to Fig. 3i, the PL and AL emission of the RSLP is located near the red boundary of the International Commission on Illumination (CIE) chromaticity diagram, and it can be confirmed that it exhibits red emission of very high purity.

[0235] Figure 3j shows the emission (PL) and afterglow (AL) images of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0236] According to Fig. 3j, it can be seen that RSLP exhibits a luminescence intensity strong enough to be clearly visible to the naked eye for more than 300 seconds even without an external light source.

[0237] Figure 3k shows the afterglow time analysis results of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0238] According to Fig. 3k, it can be seen that the afterglow phenomenon lasted for more than 1,800 seconds. The half-life was measured to be 15.39 seconds.

[0239] Figure 31 shows the results of luminescence and afterglow repeat analysis of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0240] According to Fig. 3l, it can be confirmed that RSLP exhibits excellent recharge characteristics and optical stability even under repeated light irradiation cycles.

[0241] Figure 3m shows the results of the analysis of the luminescence and afterglow mechanisms of CaSr(S,SO4):Eu,Tm (RSLP) prepared according to Example 1-1.

[0242] The expansion of the absorption region and the enhancement of luminescence characteristics are analyzed to be attributed to defect engineering and heterojunction structures. Specifically, according to Fig. 3m, RSLP has positively charged substitution defects ([Tm Ca ] + and [Tm Sr ] + ) and Hwang Gonggong([V s] 2+ It includes ) which acts as an electron trap, delaying the recombination of electrons and holes. These defects absorb a wider range of excitation energies, and the band offset at the heterojunction interface expands the energy window of the conduction band. Consequently, the energy generated from the recombination of electrons and holes is transferred non-radiatively to Tm 3+ and Eu 2+ It is delivered to the light-emitting center and can continuously emit red light in the range of 580 to 700 nm with high light intensity for a long time.

[0243]

[0244] Example 3: Preparation of emissive layer

[0245] The light-emitting layer of the present invention comprises a matrix and a light-emitting element dispersed in the matrix. Specifically, the matrix was selected from the group consisting of Ecoflex, polydimethylsiloxane (PDMS), and MED-6015, and the light-emitting element was the light-emitting element of Example 1-1 (CaSr(S,SO4):Eu,Tm, RSLP) or purchased and used Y2SiO5:Eu (YSO:Eu).

[0246] Purchased Y2SiO5:Eu particles were analyzed using SEM. Specifically, Fig. 4a is an SEM image of Y2SiO5:Eu particles (scale bar = 100 μm), Fig. 4b shows the results of EDS elemental analysis of Y2SiO5:Eu particles, and Fig. 4c shows the results of elemental mapping based on the SEM image of Fig. 4a (scale bar = 100 μm).

[0247] According to Figures 4a to 4c, it was confirmed that the surface structure of the Y2SiO5:Eu particles is uniform, and the elemental composition of the particles was also confirmed.

[0248] Figure 4d shows the emission wavelength range of Y2SiO5:Eu particles (YSO:Eu). Specifically, the photoluminescence (PL) spectrum of YSO:Eu was obtained using a Horiba FluoroLog Fluorometer spectrophotometer (HORIBA Ltd., Kyoto, Japan). After placing YSO:Eu in a 1 cm quartz cuvette, the PL spectrum was measured within the emission spectrum range of 580 to 700 nm at an excitation wavelength of 365 nm. Additionally, the PL spectrum was measured within the excitation spectrum range of 250 to 550 nm at an emission wavelength of 635 nm.

[0249] According to Figure 4d, it was confirmed that YSO:Eu can be activated in the presence of UV and emit therapeutic light with a wavelength of approximately 635 nm.

[0250] The specific manufacturing method of six types of light-emitting layers, each prepared by mixing two types of light-emitting materials and three types of matrices, is as follows.

[0251] Example 3-1. Preparation of RSLP+Ecoflex Emitting Layer

[0252] An RSLP+Ecoflex emitting layer was prepared by mixing the Ecoflex 00-45 solution with the emitting agent of Example 1-1 (CaSr(S,SO4):Eu,Tm, RSLP).

[0253] Specifically, components A and B of Ecoflex 00-45 were thoroughly mixed according to the manufacturer's instructions. Subsequently, the luminescent material (RSLP) of Example 1-1 was synthesized in 1 mL of the Ecoflex mixture at various concentrations (0 to 1400 mg / mL). A total volume of 1.0 to 2.0 mL of the synthesized material was poured into a pre-prepared dish and cured at room temperature for 4 hours to produce a luminescent layer.

[0254] Example 3-2. Preparation of RSLP+PDMS emissive layer

[0255] An RSLP+PDMS emitting layer was prepared by mixing a PDMS mixture with the emitting agent of Example 1-1 (CaSr(S,SO4):Eu,Tm, RSLP).

[0256] Specifically, a PDMS mixture was prepared by mixing a polydimethylsiloxane precursor and a curing agent in a weight ratio of approximately 10:1 and then stirring to form a homogeneous mixture. Subsequently, the luminescent material (RSLP) of Example 1-1 was synthesized in 1 mL of the PDMS mixture at various concentrations (0 to 1400 mg / mL). A total volume of 1.0 to 2.0 mL of the synthesized material was poured into a pre-prepared dish and cured at room temperature for 4 hours to produce a luminescent layer.

[0257] Example 3-3. Preparation of RSLP+MED-6015 Emitting Layer

[0258] An RSLP+MED-6015 emitting layer was prepared by mixing the MED-6015 mixture with the emitting agent of Example 1-1 (CaSr(S,SO4):Eu,Tm, RSLP).

[0259] Specifically, a MED-6015 mixture was prepared by mixing a MED-6015 precursor and a curing agent in a predetermined weight ratio to form a uniform mixture. Subsequently, the luminescent material (RSLP) of Example 1-1 was synthesized in 1 mL of the MED-6015 mixture at various concentrations (0 to 1400 mg / mL). A total volume of 1.0 to 2.0 mL of the synthesized material was poured into a pre-prepared dish and cured at room temperature for 4 hours to produce a luminescent layer.

[0260] Examples 3-4. Preparation of YSO:Eu+Ecoflex Emitting Layer

[0261] A YSO:Eu+Ecoflex emitting layer was prepared in the same manner as in Example 3-1, except that Y2SiO5:Eu particles (YSO:Eu) were used instead of the emitting material (CaSr(S,SO4):Eu,Tm, RSLP) of Example 1-1.

[0262] Examples 3-5. Preparation of YSO:Eu+PDMS emissive layer

[0263] A YSO:Eu+PDMS emitting layer was prepared in the same manner as in Example 3-2, except that Y2SiO5:Eu particles (YSO:Eu) were used instead of the emitting material (CaSr(S,SO4):Eu,Tm, RSLP) of Example 1-1.

[0264] Examples 3-6. Preparation of YSO:Eu+MED-6015 emissive layer

[0265] A YSO:Eu+ MED-6015 emitting layer was prepared in the same manner as in Example 3-3, except that Y2SiO5:Eu particles (YSO:Eu) were used instead of the emitting material (CaSr(S,SO4):Eu,Tm, RSLP) of Example 1-1.

[0266]

[0267] Example 4: Verification of light-emitting layer characteristics

[0268] (1) Method

[0269] The thickness and elemental distribution of the emissive layer were investigated using a cross-sectional FE-SEM equipped with EDS. Photographic images of the emissive layer were obtained using a CCD camera.

[0270] The EDS elemental analysis of the light-emitting layer was measured using the same method as described in Example 2.

[0271] PL and AL spectra were obtained using a Horiba FluoroLog Fluorometer spectrophotometer. The PL spectrum was measured in an emission spectrum range of 550 to 700 nm and an excitation spectrum range of 300 to 600 nm. Before AL measurement, the excitation light source was turned off, and white LED light was applied to the emissive layer for 5 seconds. The AL spectrum was measured within an emission spectrum range of 580 to 700 nm.

[0272] The front side of the emissive layer was charged with a UV flashlight (365 nm, 6 W, distance: 3 cm) or white LED light (distance: 15 cm, power density equivalent to indoor lighting). PL images of the back side were obtained using a CCD camera. For afterglow images, the front side of the emissive layer was charged with a UV flashlight or white LED light for 5 seconds, and afterglow images of both the front and back sides were obtained using a CCD camera. Time-dissolved afterglow images were obtained using a CCD camera every minute after irradiating with the UV flashlight or white LED light for 5 seconds. The relative afterglow intensity of the emissive layer was measured using ImageJ software (n = 4).

[0273] The power densities of PL and AL were evaluated using a power meter (PM100D, Thorlabs, Newton, New Jersey) equipped with a power sensor (S120VC, Thorlabs, Newton, New Jersey). A green laser (532 nm, 11.35 mW / cm²) 2 The power densities of PL and AL were measured using ) as a reference. The power density of the external light source was varied by charging the front side of the emissive layer at different distances with a UV flashlight (365 nm, 6 W), while PL power measurements on the back side were performed at a wavelength of 640 nm. The intensity of UV light was measured at 640 nm and subtracted from the PL power measurement to eliminate the influence of UV light on power density. After irradiating with UV light for 5 seconds, the power of the afterglow was measured at 640 nm. The normalized power densities of PL and AL under different power densities of the external light source were expressed by Equations 1 and 2 below:

[0274] [Equation 1]

[0275] yPL = 0.0358 + 0.0024x

[0276] [Equation 2]

[0277] yAL = 0.0008 + 2.4147e-5x

[0278] yPL and yAL represent the power densities of PL and AL of the emissive layer, respectively, and x represents the power density of the external light source. By substituting x in Equation 1 with x in Equation 2, the relationship between the PL and AL power densities is expressed by Equation 3:

[0279] [Equation 3]

[0280] yPL = 0.0358 + 99.3912(yAL - 0.0008)

[0281] Under sunlight, the PL power density of the emissive layer was measured using a custom light-proof camera box equipped with a CCD camera. The front side of the emissive layer was exposed to direct sunlight for 5 seconds to ensure proper charging. Immediately after solar irradiation, the emissive layer was moved to the light-proof box, and afterglow images were captured using the CCD camera. Under sunlight, the power densities of PL and AL were calculated by correlating the afterglow intensity with predetermined calibration data (Equation 3).

[0282] The tensile strength of the light-emitting layer was evaluated using an Instron tester equipped with a 10 N load cell at a constant speed of 5 mm / min. The light-emitting layer was firmly secured at both ends using clamps, and tensile force was applied simultaneously in both directions. The maximum tensile strength and failure point were recorded by analyzing the stress-strain curve.

[0283] The strain of the emissive layer was controlled using a custom stretcher. The emissive layer was stretched from 0% to 100%, and photographic images of the emissive layer were obtained with a CCD camera for every 10% increase in stretch. The front side of the emissive layer was charged with a UV flashlight or white LED light (distance: 15 cm, power density equivalent to indoor lighting) for every 10% increase in stretch. PL images of the back side were obtained with a CCD camera by irradiating with a UV flashlight or white LED light. For afterglow images, the front side of the emissive layer was charged with a UV flashlight or white LED light for 5 seconds, and afterglow images of the back side were obtained with a CCD camera after stopping irradiation with the UV flashlight or white LED light.

[0284] To evaluate the stability and repeatability of PL power density, the emissive layer was repeatedly increased five times in succession from 0% to 100%. The front side of the emissive layer was charged with a UV flashlight for 5 seconds, and afterglow images on the back side were obtained with a CCD camera after the UV flashlight irradiation was stopped. Before each pressure application, all emissive layers were recharged with UV light (365 nm) for 5 seconds. The relative afterglow intensity of the emissive layer was quantified using a power meter, and the power densities of PL and AL were calculated by correlating the afterglow intensity with a predetermined calibration equation 3 (n = 4).

[0285] (2) SEM analysis results

[0286] FIG. 5a is an SEM image of the light-emitting layer of Example 3-1 (RSLP+Ecoflex) (scale bar = 250 μm), FIG. 5b shows the results of the EDS elemental analysis of the light-emitting layer of Example 3-1 (RSLP+Ecoflex), and FIG. 5c shows the results of elemental mapping based on the SEM image of FIG. 5a (scale bar = 250 μm).

[0287] Fig. 6a is an SEM image of the emitting layer of Example 3-2 (RSLP+PDMS) (scale bar = 250 μm), Fig. 6b shows the EDS elemental analysis results of the emitting layer of Example 3-2 (RSLP+PDMS), and Fig. 6c shows the elemental mapping results based on the SEM image of Fig. 6a (scale bar = 250 μm).

[0288] Fig. 7a is an SEM image of the light-emitting layer of Example 3-3 (RSLP+MED-6015) (scale bar = 250 μm), Fig. 7b shows the results of the EDS elemental analysis of the light-emitting layer of Example 3-3 (RSLP+MED-6015), and Fig. 7c shows the results of the elemental mapping based on the SEM image of Fig. 7a (scale bar = 250 μm).

[0289] FIG. 8a is an SEM image of the emitting layer of Example 3-4 (YSO:Eu+Ecoflex) (scale bar = 250 μm), FIG. 8b shows the results of the EDS elemental analysis of the emitting layer of Example 3-4 (YSO:Eu+Ecoflex), and FIG. 8c shows the results of elemental mapping based on the SEM image of FIG. 8a (scale bar = 250 μm).

[0290] Fig. 9a is an SEM image of the emitting layer of Example 3-5 (YSO:Eu+PDMS) (scale bar = 250 μm), Fig. 9b shows the results of the EDS elemental analysis of the emitting layer of Example 3-5 (YSO:Eu+PDMS), and Fig. 9c shows the results of the elemental mapping based on the SEM image of Fig. 9a (scale bar = 250 μm).

[0291] FIG. 10a is an SEM image of the emitting layer of Example 3-6 (YSO:Eu+MED-6015) (scale bar = 250 μm), FIG. 10b shows the results of EDS elemental analysis of the emitting layer of Example 3-6 (YSO:Eu+MED-6015), and FIG. 10c shows the results of elemental mapping based on the SEM image of FIG. 10a (scale bar = 250 μm).

[0292] According to FIGS. 5 to 10, it can be confirmed that the light-emitting layers prepared according to Examples 3-1 to 3-6 each have a uniformly distributed light-emitting element (RSLP or YSO:Eu).

[0293] (3) Confirmation of optimized emitting concentration and emitting layer thickness

[0294] FIG. 11a shows the image of the emitting layer and the emitting / afterglow image according to the RSLP concentration of the emitting layer in Example 3-1 (scale bar = 1 cm), FIG. 11b shows the emitting intensity according to the RSLP concentration of the emitting layer in Example 3-1, and FIG. 11c shows the image of the emitting layer according to the RSLP concentration of the emitting layer in Example 3-1 (scale bar = 1 cm).

[0295] According to FIGS. 11a to 11c, it can be seen that power density increases as the concentration of the emitting agent (RSLP) increases, but the power density of the patch decreases when it exceeds 800 mg / ml. In addition, it can be seen that the physical properties of the patch deteriorate when the concentration of the emitting agent exceeds 600 mg / ml. That is, it can be seen that the emitting layer has an excellent effect when it contains a emitting agent at a concentration of 400 to 600 mg / ml.

[0296] FIG. 11d shows an image of the light-emitting layer and a light emission / afterglow image according to the thickness of the light-emitting layer in Example 3-1 (scale bar = 1 cm), and FIG. 11e shows the light emission intensity according to the thickness of the light-emitting layer in Example 3-1.

[0297] According to Figures 11d and 11e, it was confirmed that sufficient light transmission can be ensured while maintaining structural integrity when the thickness of the light-emitting layer is 1.1 mm.

[0298] Additionally, according to FIGS. 11a to 11e, under UV excitation, the optimized Example 3-1 light-emitting layer (Ecoflex / RSLP) yields approximately 25 mW / cm² 2 The transmitted PL power density was shown to be approximately 10 mW / cm² under indoor light (RL) excitation. 2 It showed a power density of , and it can be confirmed that it showed a similar trend to UV-induced activation.

[0299] (4) Analysis of PL and AL characteristics of the light-emitting layer

[0300] Figure 12 shows the UV emission image (PL(UV)) and afterglow image (AL(UV)) of the light-emitting layer (YSO:Eu+Ecoflex) of Example 3-4.

[0301] According to FIG. 12, it can be seen that the light-emitting layer of Examples 3-4 exhibits strong light emission and afterglow intensity that can be clearly observed with the naked eye.

[0302] FIG. 13a shows the emission wavelength range of the emission layer (RSLP+Ecoflex) of Example 3-1, FIG. 13b shows the afterglow wavelength range of the emission layer of Example 3-1, and FIG. 13c shows the correlation between the emission and afterglow of the emission layer of Example 3-1.

[0303] According to FIGS. 13a to 13c, it was confirmed that the light-emitting layer of Example 3-1 exhibits strong red emission at 640 nm in both PL and AL spectra over a wide excitation range of 300 to 600 nm. That is, it can be confirmed that the light-emitting layer of Example 3-1 is automatically activated under indoor lighting and can emit therapeutic light with a wavelength of approximately 640 nm.

[0304] FIG. 13d shows images of the light-emitting layer of Example 3-1, light emission image in UV (PL(UV)), afterglow image in UV (AL(UV)), afterglow image in indoor light (AL(RL)), afterglow image in sunlight (AL(SL)), and afterglow retention time image in UV (scale bar = 1 cm).

[0305] According to FIG. 13d, the light-emitting layer of Example 3-1 has strong light emission and afterglow, and it can be visually confirmed that it emits afterglow, especially under various light sources (UV, indoor lighting, and sunlight). In addition, it was confirmed that the afterglow is maintained for more than 5 minutes even without an external light source.

[0306] Figure 13e shows the PL power density of the light-emitting layer of Example 3-1 under various light sources.

[0307] According to FIG. 13e, the average value of the PL power density calculated from the transmitted surface of the light-emitting layer in Example 3-1 is 25.40 mW / cm² during UV exposure. 2 , 10.75 mW / cm² for indoor lighting 2 , and 13.06 mW / cm² under sunlight 2 You can confirm that it is.

[0308] Considering the red light intensity threshold required for effective PTB and PBM, these results demonstrate that the light-emitting layer of the present invention can reliably support both treatments under everyday ambient lighting conditions and can be seamlessly integrated into daily wound care routines without the need for an external power source.

[0309] (5) Confirmation of mechanical properties of the light-emitting layer

[0310] The mechanical elasticity of the light-emitting layer of the present invention was evaluated at various strain rates to assess its suitability as a wearable phototherapy tool applicable to various body parts, including areas subjected to extreme bending or daily movements.

[0311] FIG. 14a shows the light emission and afterglow images of the light-emitting layer (RSLP+Ecoflex) of Example 3-1 according to stretching (0~100%) under UV, FIG. 14b shows the power density according to stretching, FIG. 14c shows the power density according to stretching repeatability, FIG. 14d shows the light emission and afterglow images of the light-emitting layer (RSLP+Ecoflex) of Example 3-1 according to stretching (0~50%) under room light, and FIG. 14e shows the tensile strength analysis results of the light-emitting layer of Example 3-1.

[0312] According to FIG. 14a, it can be seen that the light-emitting layer of Example 3-1 exhibited high PL and AL brightness at 0% strain and maintained light emission even at 100% strain.

[0313] According to Fig. 14b, as the area increases at a fixed RSLP concentration, the output density decreases slightly, but it can be seen that the decrease in output density of the light-emitting layer with an optimized RSLP concentration (400 mg / mL) is minimal compared to the light-emitting layer with a low RSLP concentration (100 mg / mL).

[0314] According to FIG. 14c, it can be confirmed that the PL output density of the light-emitting layer of Example 3-1 is maintained stably even after repeated stretching cycles.

[0315] According to FIG. 14d, it can be seen that AL induced under indoor light in the light-emitting layer of Example 3-1 also exhibits consistent light-emitting characteristics during gradual stretching up to 100%.

[0316] According to FIG. 14e, the light-emitting layer of Example 3-1 showed maximum strength at approximately 550% tensile strength and mechanical failure at approximately 600% elongation, demonstrating excellent flexibility suitable for skin-attached applications.

[0317]

[0318] Example 5: Manufacture of a multilayer patch including an adhesive layer and a protective layer

[0319] A multilayer patch was manufactured comprising a protective layer, a light-emitting layer formed on one side of the protective layer and including a matrix and a light-emitting element, and an adhesive layer formed on a part of the other side of the protective layer.

[0320] Specifically, the protective layer used the same material as the matrix, and the adhesive layer used HA-DOPA / Fe hydrogel.

[0321] The above HA-DOPA / Fe hydrogel was prepared by the following method.

[0322] First, HA (100 kDa, 0.25 mmol, 100 mg) was completely dissolved in DI water at a concentration of 5 mg / mL. Then, the solution was mixed with EDC (1 mmol, 191 mg) and NHS (1 mmol, 120 mg) at pH 5.5. Next, dopamine chloride (1 mmol, 191.4 mg) was added to the solution, and the pH of the solution was maintained at 5.5.

[0323] After stirring the solution at 40°C for 24 hours, the HA-DOPA conjugate was dialyzed using a dialysis tube (molecular weight cutoff, MWCO = 7000 Da) with acidified DI water (pH 5.5) for 2 days to inhibit the oxidation of catechol groups, and the pH was adjusted to neutral water for 1 day. The HA-DOPA conjugate was freeze-dried for 3 days. The chemical structure and catechol modification ratio of the HA-DOPA conjugate 1 The HA-DOPA conjugate was analyzed by ¹H NMR (DRX500, Bruker). 1 The results of the 1H NMR analysis are shown in Figure 15. The catechol conjugation ratio in the HA backbone was calculated by comparing the 6.8-7.2 and 1.8-2.2 ppm peaks.

[0324] The HA-DOPA conjugate was completely dissolved in DI water at 5 wt% (w / v) (preparation of HA-DOPA solution), and 100 μL was uniformly dispensed into a Petri dish. Then, iron(III) chloride hexahydrate was added to a 5% aqueous acetic acid solution to Fe 3+ A solution (120 mM) (v / v) was prepared. The HA-DOPA / Fe hydrogel is Fe 3+ It was obtained after mixing 20 μL of the solution with the HA-DOPA solution for 30 seconds (Fe 3+ :DOPA molar ratio = 1:3).

[0325] The specific manufacturing method of a multilayer patch prepared using the above-mentioned HA-DOPA hydrogel, HA-DOPA / Fe hydrogel, luminescent material (RSLP), and matrix (Ecoflex) is as follows.

[0326] Example 5-1. Preparation of a patch including an HA-DOPA adhesive layer

[0327] Ecoflex 00-45 components A and B were thoroughly mixed according to the manufacturer's instructions.

[0328] 0.4 mL of the Ecoflex mixture was poured into a Petri dish (diameter: 3.5 cm) to create a protective layer. The protective layer was cured at room temperature for 4 hours to complete the crosslinking process.

[0329] For the light-emitting layer, the light emitter (RSLP) of Example 1-1 was synthesized in 1 mL of an Ecoflex mixture at various concentrations (0 to 1,400 mg / mL) and prepared using a composite. Specifically, a total volume of 1.0 to 2.0 mL of the composite was poured onto the protective layer and then cured at room temperature for 4 hours.

[0330] A patch composed of a light-emitting layer (RSLP+Ecoflex), a protective layer (Ecoflex), and an adhesive layer (HA-DOPA) was prepared by attaching an HA-DOPA hydrogel adhesive to the edge of the other side of a protective layer on which a light-emitting layer was formed on one side.

[0331] Example 5-2. Preparation of a patch composed of a light-emitting layer (RSLP+Ecoflex), a protective layer (Ecoflex), and an adhesive layer (HA-DOPA / Fe).

[0332] A patch composed of a light-emitting layer (RSLP+Ecoflex), a protective layer (Ecoflex), and an adhesive layer (HA-DOPA / Fe) was prepared in the same manner as in Example 5-1, except that an HA-DOPA / Fe hydrogel adhesive was used instead of an HA-DOPA hydrogel adhesive.

[0333] Example 5-3. Preparation of a patch composed of an emissive layer (RSLP+PDMS), a protective layer (PDMS), and an adhesive layer (HA-DOPA / Fe).

[0334] A PDMS mixture was prepared by mixing a polydimethylsiloxane precursor and a curing agent in a weight ratio of about 10:1 and then stirring to form a uniform mixture.

[0335] A patch composed of a light-emitting layer (RSLP+PDMS), a protective layer (PDMS), and an adhesive layer (HA-DOPA / Fe) was prepared in the same manner as in Example 5-2, except that instead of preparing the matrix of the protective layer and the light-emitting layer using an Ecoflex mixture, the matrix of the protective layer and the light-emitting layer was prepared using a PDMS mixture.

[0336] Example 5-4. Preparation of a patch composed of a light-emitting layer (RSLP+MED-6015), a protective layer (MED-6015), and an adhesive layer (HA-DOPA / Fe).

[0337] A MED-6015 mixture was prepared by mixing a MED-6015 precursor and a curing agent in a predetermined weight ratio to form a uniform mixture.

[0338] A patch composed of a light-emitting layer (RSLP+ MED-6015), a protective layer (MED-6015), and an adhesive layer (HA-DOPA / Fe) was prepared in the same manner as in Example 5-2, except that instead of preparing the matrix of the protective layer and the light-emitting layer using an Ecoflex mixture, the matrix of the protective layer and the light-emitting layer was prepared using a MED-6015 mixture.

[0339] Example 5-5. Preparation of a patch composed of a light-emitting layer (YSO:Eu+Ecoflex), a protective layer (Ecoflex), and an adhesive layer (HA-DOPA / Fe).

[0340] A patch composed of a light-emitting layer (YSO:Eu+Ecoflex), a protective layer (Ecoflex), and an adhesive layer (HA-DOPA / Fe) was prepared in the same manner as in Example 5-2, except that Y2SiO5:Eu particles (YSO:Eu) were used instead of the light-emitting material (CaSr(S,SO4):Eu,Tm, RSLP) of Example 1-1.

[0341] Examples 5-6. Preparation of a patch composed of a light-emitting layer (YSO:Eu+PDMS), a protective layer (PDMS), and an adhesive layer (HA-DOPA / Fe).

[0342] A patch composed of a light-emitting layer (YSO:Eu+PDMS), a protective layer (PDMS), and an adhesive layer (HA-DOPA / Fe) was prepared in the same manner as in Example 5-3, except that Y2SiO5:Eu particles (YSO:Eu) were used instead of the light-emitting material (CaSr(S,SO4):Eu,Tm, RSLP) of Example 1-1.

[0343] Examples 5-7. Preparation of a patch composed of a light-emitting layer (YSO:Eu+MED-6015), a protective layer (MED-6015), and an adhesive layer (HA-DOPA / Fe).

[0344] A patch composed of a light-emitting layer (YSO:Eu+ MED-6015), a protective layer (MED-6015), and an adhesive layer (HA-DOPA / Fe) was prepared in the same manner as in Example 5-4, except that Y2SiO5:Eu particles (YSO:Eu) were used instead of the light-emitting material (CaSr(S,SO4):Eu,Tm, RSLP) of Example 1-1.

[0345]

[0346] Example 6: Confirmation of adhesive properties of a multilayer patch

[0347] (1) Method

[0348] The multilayer patch prepared according to Example 5 and the HA-DOPA / Fe hydrogel were attached to in vitro porcine tissue and in vitro mouse skin for 30 minutes to analyze the adhesion properties of the multilayer patch and the HA-DOPA / Fe hydrogel. Then, the multilayer patch and the HA-DOPA / Fe hydrogel were separated from the tissue to evaluate the presence of residues of the multilayer patch and the HA-DOPA / Fe hydrogel.

[0349] (2) Result

[0350] Figure 16a is an image of the attachment and removal of the HA-DOPA / Fe hydrogel adhesive to mouse skin, and Figure 16b is an image of the attachment and removal of the Example 5-2 patch (RSLP+Ecoflex light-emitting layer, Ecoflex protective layer and HA-DOPA / Fe adhesive layer) to mouse skin.

[0351] According to Figures 16a and 16b, it can be seen that the HA-DOPA / Fe hydrogel adheres strongly to tissue and separates cleanly, both when used alone and when used as an adhesive layer in a patch.

[0352] Figure 16c is an image of the Example 5-1 patch (RSLP+Ecoflex light-emitting layer, Ecoflex protective layer and HA-DOPA adhesive layer; HA-DOPA Patch), the Example 5-2 patch (RSLP+Ecoflex light-emitting layer, Ecoflex protective layer and HA-DOPA / Fe adhesive layer; HA-DOPA / Fe Patch), and the HA-DOPA / Fe hydrogel adhesive (HA-DOPA / Fe Hydrogel), and Figure 16d shows the results of a tensile strength test on in vitro porcine tissue using the sample of Figure 16c (n = 4; **p<0.01, ***p<0.001, ****p < 0.0001 vs. control group). The inset of Figure 16d is a schematic diagram showing the tensile strength test setup.

[0353] According to Fig. 16d, the HA-DOPA / Fe hydrogel exhibited the highest tensile strength among all groups, mainly because the high density of catechol functionalization further improved the cohesive network integrity and interfacial adhesion.

[0354] When considering these results comprehensively, it can be seen that the multilayer patch according to the present invention is a soft, elastic, and light-responsive platform with excellent skin adhesion, making it a product suitable for phototherapy that can be worn in daily life.

[0355]

[0356] Example 7: Confirmation of in vitro cell migration and proliferation effects of the multilayer patch

[0357] (1) Method

[0358] To confirm the effect of the multilayer patch on cell migration, a cell scratch healing test was performed, based on Figure 17a.

[0359] 1.0 x 10 NIH3T3 cells per well in a 24-well plate 5The cells were dispensed and cultured in a humidified 5% CO2 incubator at 37°C until they became confluent. Before dispensing the cells, polydimethylsiloxane (PDMS) was uniformly sliced ​​(10 mm x 1 mm) and placed on a plate to provide a uniform cell scratch. The PDMS was removed to create the scratch. Then, the multilayer patch of Example 5 was attached to the bottom of the plate, and the sample was irradiated with white LED light (distance: 15 cm, power density equivalent to room light) in an incubator for 12 hours. At 0, 12, and 24 hours after the scratch, images were taken using an optical microscope to evaluate the extent of cell migration into the scratch area.

[0360] To quantitatively analyze cell proliferation, NIH3T3 cells were placed in confocal plates at a rate of 10 per well. 4 Cells were seeded at a cell density of 10 and cultured in a humidified 5% CO2 incubator at 37°C. The multilayer patch of Example 5 was attached to the bottom of the plate, and the samples were irradiated with white LED light (distance: 15 cm, power density equivalent to indoor light) in the incubator for 12 hours (n = 4) or with UV light for 10 minutes (n = 4). After an additional 12 hours of culture, the cells were washed with PBS, fixed with a 4% paraformaldehyde solution, and stained with DAPI. Fluorescence was observed using a confocal microscope (TCS SP5, Leica). Quantitative analysis of fluorescence was performed using ImageJ software.

[0361] Additionally, cell proliferation was evaluated using the CCK-8 assay. NIH3T3 cells were placed in 96-well plates at a rate of 10 per well. 4Cells were seeded at cell densities and incubated in a humidified 5% CO2 incubator at 37°C for predetermined time points (0, 24, 72, 120 hours). The multilayer patch of Example 5 was attached to the bottom of the plate, and the samples were irradiated with white LED light (distance: 15 cm, power density equivalent to room light) for 12 hours on days 0 and 1 in the incubator (n = 4). At each time point, the medium in each well was replaced with 10 vol% CCK-8 solution, and the samples were incubated for an additional 2 hours. Relative cell viability was obtained by measuring optical density at 450 nm using a microplate reader.

[0362] (2) Result

[0363] Figure 17b is a DAPI staining image showing enhanced proliferation of the Example 5-2 patch (RSLP+Ecoflex emissive layer, Ecoflex protective layer and HA-DOPA / Fe adhesive layer; HA-DOPA / Fe Patch) after room light (RL) treatment (Scale bar = 200 μm), and Figure 17c shows the quantification of normalized DAPI fluorescence for each group in Figure 17b (n = 4; ***p<0.001, ****p < 0.0001 vs Control after treatment; NS, not significant).

[0364] According to Fig. 17b, DAPI staining results show that under room light (RL), the patch-treated group (Patch+RL) of Example 5-2 has a significantly increased number of cells compared to the control group (Control) with no treatment and the room light-only treated group (Control+RL).

[0365] According to Figure 17c, which shows the normalization of DAPI fluorescence to quantitatively analyze the proliferation effect for each group, it was confirmed that proliferation was significantly increased in the group treated with the patch of Example 5-2 (Patch+RL) under room light (RL), whereas there was no difference in proliferation between the control group that was not treated (Control) and the group treated with room light alone (Control+RL).

[0366] Fig. 17d is a live cell scratch analysis image showing cell migration at 0, 12, and 24 hours for each group in Fig. 17b (Scale bar = 500 μm), and Fig. 17e shows the quantification of time-dependent cell proliferation after room light (RL) treatment of the Example 5-2 patch (RSLP+Ecoflex emissive layer, Ecoflex protective layer and HA-DOPA / Fe adhesive layer; HA-DOPA / Fe Patch) (n = 4; ****p < 0.0001 vs. control group).

[0367] According to Fig. 17d, it was confirmed that wound closure was improved in the patch treatment group (Patch+RL) of Example 5-2, particularly after 24 hours, under room light (RL). This means that the red light emitted from the patch effectively stimulated cell migration.

[0368] According to Fig. 17e, it can be seen that cell proliferation significantly increased in the patch treatment group (Patch+RL) of Example 5-2 under room light (RL). In particular, the proliferation rate between day 1 and day 3 increased by approximately 1.94 times, which is faster than the 1.50-fold increase between day 3 and day 5. This indicates that the red light emission of the multilayer patch of the present invention promoted cell proliferation.

[0369] Figure 18a is a DAPI staining image showing enhanced proliferation after UV treatment of the Example 5-5 patch (YSO:Eu+Ecoflex emissive layer, Ecoflex protective layer and HA-DOPA / Fe adhesive layer; HA-DOPA / Fe Patch) (Scale bar = 200 μm), and Figure 18b shows the quantification of normalized DAPI fluorescence for each group in Figure 18a (n = 4).

[0370] According to Figures 18a and 18b, after exposure to UV light for 15 minutes, a significantly higher number of cells was observed in the group treated with the Example 5-5 patch compared to the untreated control group. This result was obtained by quantitatively analyzing the number of cell nuclei through DAPI staining, suggesting that the red light emitted from the patch induced cell proliferation.

[0371]

[0372] Example 8: Preparation of a coating material containing an active layer (photosensitive agent)

[0373] A coating material was prepared by forming an active layer containing a photosensitive agent on one side of a multilayer patch prepared according to Example 5.

[0374] The above photosensitizer used was one of chlorin e6 (Ce6), verteporfin (BPD), and methylene blue (MB).

[0375] Specifically, the above coating material may be manufactured by (1) directly forming an active layer containing a photosensitive agent on the adhesive layer portion of a multilayer patch, or (2) by applying a solution containing a photosensitive agent to the skin to form an active layer and then attaching the multilayer patch.

[0376] The materials used for the light-emitting layer, protective layer, adhesive layer, and active layer forming the coating material of Examples 8-1 to 8-6, respectively, are shown in Table 1 below.

[0377] Separation Emitting Layer Protective Layer Adhesive Layer Active Layer Example 8-1 RSLP + Ecoflex EcoflexHA-DOPA / FeCe6 Example 8-2 RSLP + PDMS PDMSHA-DOPA / FeMB Example 8-3 RSLP + MED-6015 MED-6015HA-DOPA / FeBPD Example 8-4 YSO:Eu + Ecoflex EcoflexHA-DOPA / FeCe6 Example 8-5 YSO:Eu + PDMS PDMSHA-DOPA / FeMB Example 8-6 YSO:Eu + MED-6015 MED-6015HA-DOPA / FeBPD

[0378]

[0379] Example 9: Collagen fiber-forming effect of multilayer patch / coating material

[0380] (1) Method

[0381] Collagen fibrillation was monitored at 37°C using a temperature-controlled microplate spectrometer (EMax End point ELISA microplate reader, Molecular Devices, Sunnyvale, CA). Type 1 collagen extracted from rat tails was dispersed in acetic acid (20 mM) at a concentration of 3.0 mg / mL and diluted in 0.2 M HEPES and 10x PBS (pH 7.4) at a volume ratio of 8:1:1. The collagen solution was neutralized on ice, and 200 μL of the collagen solution was mixed with 200 μL of PBS, Ce6, verteporfin (BPD, Visudyne®), or methylene blue (MB) solution (100 μM).

[0382] To confirm the collagen fibrillation effect of a multilayer patch using RSLP as a luminescent agent, the mixed solution was transferred to a 96-well plate and the plate was divided into four groups:

[0383] i) PBS with indoor light (control group)

[0384] ii) Patch of Example 5-2 (RSLP+Ecoflex)

[0385] iii) Ce6 with indoor light

[0386] iv) Covering material of Example 8-1 with indoor light (Ce6 + Example 5-2 patch) (n = 4).

[0387] To confirm the collagen fibrillation effect of a multilayer patch using YSO:Eu as a luminescent agent, the mixed solution was transferred to a 96-well plate and the plate was divided into four groups:

[0388] i) PBS with UV light (control group)

[0389] ii) Coating material of Example 8-4 with UV light (Ce6 + Example 5-5 patch (YSO:Eu + Ecoflex))

[0390] iii) Coating material of Example 8-5 with UV light (Methylene blue + Example 5-6 patch (YSO:Eu+PDMS))

[0391] iv) Coating material of Example 8-6 with UV light (Vertaporfin + Patch of Example 5-7 (YSO:Eu + MED-6015)) (n = 4).

[0392] A patch was attached to the bottom of a plate, and the sample was irradiated from the bottom with white LED light (distance: 15 cm, power density equivalent to indoor lighting) for 10 minutes or with UV light for 8 minutes. Collagen fiber production was measured by acquiring optical density at 405 nm every minute.

[0393] (2) Result

[0394] Figure 19a confirms the collagen fiber-forming effect of a multilayer patch using RSLP as a light source.

[0395] According to Fig. 19a, the optical density was significantly increased in the group of coating materials of Example 8-4 (Ce6 + Example 5-5 patch) with indoor light, and it can be confirmed that light-induced collagen crosslinking reaction occurred.

[0396] Figure 19b confirms the collagen fiber-forming effect of a multilayer patch using YSO:Eu as a light source.

[0397] According to Figure 19b, optical density increased in the UV light patch group in the order of methylene blue (MB), verteporfin, and Ce6, and it can be confirmed that photo-induced collagen cross-linking reaction occurred.

[0398]

[0399] Example 10: Collagen cross-linking effect of multilayer patch / coating material

[0400] (1) Method

[0401] An in vitro experimental device was designed to evaluate collagen crosslinking induced by a multilayer patch or coating material, and this is shown in Fig. 20a.

[0402] According to Fig. 20a, the in vitro tensile strength of the bound mouse skin was evaluated at a constant speed of 5 mm / min using an Instron tester (Instron 3340, Instron Co., Norwood, MA) equipped with a 10 N load cell. The mouse skin was 1 x 2 cm 2 Cut to size and make the joining area 1 x 1 cm 2 The samples were prepared as follows. 10 μL of control (PBS) or Ce6 solution (1 mM) was applied to each bonding site, and a second skin piece was placed on top to form a double-layer structure. Then, the multilayer patch of Example 5 was attached, and white LED lighting (distance: 15 cm, matching the output density of ambient indoor lighting) was irradiated for 2 hours. After irradiation, the samples were incubated in humid conditions at room temperature for 30 minutes to facilitate bonding. Tensile tests were performed by securing both ends of each specimen with forceps and applying bidirectional tension, and the maximum tensile strength and fracture point were determined via stress-strain curves (n=4).

[0403] (2) Result

[0404] Figure 20b shows the results of measuring the tensile strength of the control group, the patch of Example 5-2, Ce6, and the coating material of Example 8-1 after treating them with white LED light for 2 hours.

[0405] According to Fig. 20b, under indoor light, the cross-linking of porcine tissue was highest in the group of the coating material of Example 8-1 (Ce6 + patch of Example 5-2) compared to other groups treated with only Ce6 or patch.

[0406]

[0407] Example 11: Biocompatibility of Multilayer Patch / Coating Material

[0408] (1) Method

[0409] NIH3T3 fibroblasts were cultured in DMEM medium supplemented with 10 vol% FBS and 1 vol% penicillin-streptomycin. Cells were placed in 96-well plates at a ratio of 1.0 × 10 per well. 5 Cells were seeded at appropriate cell densities and maintained at 37°C in a humid incubator containing 5% CO2. To evaluate the cytotoxicity of degradation products, photon patches (3.5 cm in diameter) were pre-cultured in 10 mL of DMEM medium for 24 hours. Subsequently, 200 μL of the extract was added to each well (n=8). Simultaneously, chlorine e6 (Ce6) solutions at various concentrations (0–50 μg / mL, 200 μL) were added to each well and incubated under the same conditions for 24 hours (n=8). Afterward, the medium in all wells was replaced with fresh medium containing 10 vol% CCK-8 reagent, and incubated for an additional 2 hours. Cell viability was quantified by measuring absorbance at 450 nm using a microplate reader.

[0410] (2) Result

[0411] Figure 21 shows the cell viability of the coating material of Example 8-1 (Ce6+ patch of Example 5-2).

[0412] According to Fig. 21, it can be seen that the coating material of Example 8-1 (Ce6+ patch of Example 5-2) maintained a cell viability of over 90% throughout a culture period of 192 hours (8 days). This indicates that the patch (or coating material) has high cytocompatibility. In addition, it can be confirmed that there is no cytotoxicity and that it is safe for long-term use.

[0413]

[0414] Example 12: In vivo wound healing effect of multilayer patch / dressing

[0415] (1) Method

[0416] In vivo experiments followed the experimental animal protocol approved by the Pohang University of Science and Technology Animal Ethics Committee in accordance with the National Institutes of Health (NIH) Guidelines for the Management of Laboratory Animals (Approval No.: POSTECH-2023-0065).

[0417] An in vivo incision wound model was used to evaluate the effects of the patch or coating material of the present invention on PTB and PBM. Female BALB / c nude mice (6 weeks old) were anesthetized, and an incision 1 cm in length was made on the back using a blade (hereinafter referred to as a linear wound).

[0418] To confirm the in vivo linear wound healing effect of multilayer patches / claddings using RSLP as a luminescent agent, the treatment groups were divided as follows.

[0419] (i) PBS (20 μL, control group)

[0420] (ii) Ce6 (500 μM, 20 μL)

[0421] (iii) Ecoflex

[0422] (iv) Suture

[0423] (v) Patch of Example 5-2 (RSLP+Ecoflex light-emitting layer)

[0424] (vi) Coating material of Example 8-1 (Ce6 + Example 5-2 patch).

[0425] Specifically, (vi) above involved topically applying a Ce6 solution to the wound and then covering it with a photon patch. To prevent the mice from removing the patch themselves, a clear adhesive film (Tegaderm 1626W, 3M, St. Paul, MN) was applied to the edges of the patch. All groups were exposed to white LED light (distance: 15 cm, power density equivalent to indoor light) for 12 hours. After treatment on Day 0, the treated skin was monitored for 7 days, and optical images of the wound site were obtained at predetermined time intervals using a CCD camera.

[0426] Meanwhile, after treatment on Day 0, mice treated with sutures and an RSLP coating containing an adhesive layer with Ce6 were euthanized using CO2, and on Day 1, 1 x 2 cm 2 Tissue specimens were collected (n = 4). After storing in a humid atmosphere for 30 minutes, the tensile strength of the bonded specimens was measured using a 10 N load cell at a constant speed of 5 mm / min in an Instron. Both ends of the specimens were secured with forceps and pulled simultaneously in both directions. The maximum tensile strength was recorded by measuring the tensile strength until the bonded tissues were completely separated.

[0427] To confirm the in vivo linear wound healing effect of a multilayer patch / cladding using YSO:Eu as a luminescent agent, the treatment groups were divided as follows.

[0428] (i) PBS (20 μL, control group)

[0429] (ii) Coating material of Example 8-2 (MB + Example 5-3 patch (RSLP + PDMS))

[0430] (iii) Coating material of Example 8-3 (BPD + Patch of Example 5-4 (RSLP + MED-6015))

[0431] (iv) Coating material of Example 8-4 (Ce6 + Patch of Example 5-5 (YSO:Eu + Ecoflex)

[0432] (v) Coating material of Example 8-5 (MB + Example 5-6 patch (YSO:Eu+PDMS))

[0433] (vi) Coating material of Examples 8-6 (BPD + Patch of Examples 5-7 (YSO:Eu + MED-6015))

[0434] Specifically, for the coatings of (ii) to (vi) above, MB, BPD, and Ce6 solutions were applied to the wound site, and the wound was covered with an RSLP patch or a YSO:Eu patch. To prevent the mice from removing the patch themselves, a clear adhesive film (Tegaderm 1626W, 3M, St. Paul, MN) was applied to the edges of the patch. All groups were exposed to UV light for 15 minutes. After treatment on Day 0, the treated skin was monitored for 5 days, and optical images of the wound site were obtained at predetermined time intervals using a CCD camera.

[0435] Female BALB / c nude mice (6 weeks old) were anesthetized, and a biopsy punch (Kasco, Sialkot, Pakistan) was used to create an 8 mm diameter wound on the dorsal flank of the mouse (hereinafter referred to as the circular wound).

[0436] To confirm the in vivo circular wound healing effect of a multilayer patch / cladding using RSLP as a luminescent agent, the treatment groups were divided as follows.

[0437] (i) PBS (20 μL, control group)

[0438] (ii) Ce6 (500 μM, 20 μL)

[0439] (iii) Ecoflex

[0440] (iv) Suture

[0441] (v) Patch of Example 5-2 (RSLP+Ecoflex light-emitting layer)

[0442] (vi) Coating material of Example 8-1 (Ce6 + Example 5-2 patch).

[0443] Specifically, (vi) above involved topically applying a Ce6 solution to the wound and then covering it with a photon patch. To prevent the mouse from removing the patch itself, a clear adhesive film (Tegaderm 1626W, 3M, St. Paul, MN) was applied to the edges of the patch. All groups were exposed to white LED light (distance: 15 cm, power density equivalent to indoor light) for 12 hours. After treatment on days 0 and 2, the treated skin was monitored for 10 days. Photographic images of the wound site were taken with a CCD camera at predetermined time intervals, and the wound area was calculated using ImageJ software.

[0444] (2) Confirmation of in vivo linear wound healing effect of multilayer patch / cladding using RSLP as a luminescent material

[0445] Linear wounds were designed to simultaneously induce photochemical tissue bonding (PTB) and photobiological regulation (PBM).

[0446] Figure 22a shows the experimental results confirming the in vivo linear wound healing effect of a multilayer patch / cladding using RSLP as a luminescent material.

[0447] According to Fig. 22a, when the wound site was observed for 7 days after 12 hours of exposure to indoor light (RL), it was confirmed that the wound healing effect was superior in the group of multilayer patches using RSLP as a light source and the group of coatings using both the patch and a photosensitizer (Ce6+Patch). In particular, the wound site is bonded on day 1 by photochemical skin bonding.

[0448] Figure 22b shows the tensile strength values ​​on day 1 of the suture group and the dressing material (Ce6+Patch) group of Example 8-1 in the experiment conducted according to Figure 22a (n = 4; ****p<0.0001 vs control group).

[0449] According to Fig. 22b, on day 1, the covering material (Ce6+Patch) group of Example 8-1 showed significantly higher tensile strength compared to the suture group, suggesting that PTB played a major role in rapid tissue closure.

[0450] FIG. 22c is a gross image showing PTB-based wound closure using the dressing (Ce6+Patch) of Example 8-1.

[0451] The improvement in wound closure was found to be due to cell proliferation induced by PBM. This synergistic effect is further confirmed by the fact that the wound margins are well aligned and adhered on both the front and back sides of the excised mouse skin in Fig. 22c.

[0452] Figure 22d shows the tensile strength values ​​of each group on day 7 in the experiment conducted according to Figure 22a (n = 4; *p < 0.05, ***p < 0.001, ****p < 0.0001, compared to control group; NS, not significant).

[0453] According to Fig. 22d, the tensile strength measurement results on day 7 showed that the coating material (Ce6+Patch) group of Example 8-1 had significantly higher values ​​than the patch (Patch) alone group and the Suture group of Example 5-2. These results confirm that the coating material of Example 8-1 promotes wound healing and exhibits excellent therapeutic efficacy by including a photosensitizer.

[0454] Figure 22e shows the tensile strength values ​​of the patch group of Example 5-2 and the coating material group of Example 8-1 (Ce6+Patch) according to treatment frequency in the experiment conducted according to Figure 22a (n = 4; **p < 0.01, ****p < 0.0001, compared to control group; NS, not significant).

[0455] According to Fig. 22e, the group of the dressing (Ce6+Patch) of Example 8-1 showed only minimal improvement with additional treatment, because tissue closure by the initial PTB was already completed after the first treatment. Since repeated treatments can reduce patient convenience and compliance, a single treatment with the dressing (Ce6+Patch) of Example 8-1 at 12 hours can be considered the optimal condition for linear wound healing. Overall, the excellent treatment results of the treatment using the dressing (Ce6+Patch) of Example 8-1 were observed in both photochemical tissue closure (PTB) and photobiological control (PBM), enabling immediate tissue access and rapid wound closure.

[0456] (3) Confirmation of in vivo linear wound healing effect of multilayer patch / cladding using YSO:Eu as a luminescent agent

[0457] Figure 23 shows the experimental results confirming the in vivo linear wound healing effect of a multilayer patch / cladding using YSO:Eu as a luminescent material.

[0458] Linear wounds were observed for 5 days after exposure to UV light for 15 minutes, and it can be seen in Figure 23 that the group of coating materials containing both a patch and a photosensitizer showed significantly superior skin adhesion effects compared to the control group.

[0459] In addition, it can be seen that there are differences in the wound healing effect depending on the type of photosensitizer. However, since photochemical tissue bonding (PTB) did not proceed completely with 15 minutes and 1 treatment, it was observed that the wound site opened on day 1.

[0460] (4) Confirmation of the in vivo circular wound healing effect of a multilayer patch / cladding using RSLP as a luminescent material

[0461] Prototype wounds rely primarily on photobiological regulation (PBM) rather than photochemical tissue bonding (PTB), and sustained anti-inflammatory activity and enhanced cell proliferation are required for meaningful wound healing.

[0462] Figure 24a shows the experimental results confirming the in vivo circular wound healing effect of a multilayer patch / cladding using RSLP as a luminescent material.

[0463] According to Fig. 24a, both the patch group of Example 5-2 and the dressing group of Example 8-1 (Ce6+Patch) showed gradual wound closure during the treatment period, and a significantly accelerated non-linear healing phase was observed, particularly between day 2 and day 4.

[0464] Figure 24b is a quantitative wound area analysis from the experiment conducted according to Figure 24a (n = 4; ****p < 0.0001 vs control group; NS, not significant), and Figure 24c is a macroscopic image showing the non-linear acceleration of wound healing through the PBM of the dressing (Ce6+Patch) of Example 8-1.

[0465] According to Figures 24b and 24c, quantitative analysis results showed that the wound area was significantly reduced by day 4, which is consistent with the non-linear healing trajectory and suggests that PBM effectively accelerated the proliferative phase of wound healing.

[0466] Figure 24d shows the wound closure effect according to treatment frequency of the patch group of Example 5-2, and Figure 24e shows the wound closure effect according to treatment frequency of the dressing (Ce6+Patch) group of Example 8-1.

[0467] According to Figures 24d and 24e, the group administered with the patch alone of Example 5-2 and the group administered with the coating material (Ce6+Patch) of Example 8-1 showed only minimal improvement upon additional treatment. In particular, it was observed that wound healing tended to be delayed when treatment was performed daily. This phenomenon is believed to be due to insufficient time for apoptosis to be naturally removed in the circular wound environment.

[0468]

[0469] Example 13: Histological and Immunohistochemical Analysis

[0470] (1) Method

[0471] Seven days after healing of the in vivo incision wound (linear wound of Example 12) and ten days after healing of the in vivo excision wound (circular wound of Example 12), mice were sacrificed by CO2 euthanasia to obtain processed tissue specimens (1 x 1 cm) for histological analysis. 2 ) was collected. After fixing the specimens in 4% formaldehyde for 1 day, they were dehydrated, fixed in paraffin, and sectioned. Subsequently, the wound closure area was measured using H&E staining, and collagen accumulation was quantified using Masson's trichrome staining (MTTS). The stained sections were observed under a light microscope.

[0472] For immunofluorescence staining, paraffin was removed from the sections with xylene and rehydrated with ethanol of varying concentrations. After unmasking, permeation, and blocking steps, the sections were incubated overnight with the primary antibody at room temperature. After rinsing the slides, they were incubated with the secondary antibody at room temperature for 4 hours. Immunofluorescence staining for CD31 (1:200), α-SMA (1:200), TNF-α (1:200), and K-14 (1:400) was performed with the primary antibody, and immunofluorescence staining for Alexa Fluor 488 goat anti-rabbit IgG H&L (1:400) and Alexa Fluor 546 goat anti-rat IgG H&L (1:400) was performed with the secondary antibody. After rinsing the sections, they were covered with VECTASHIELD anti-fade mounting medium containing DAPI at room temperature before imaging. To observe immune differentiation at the wound site, fluorescence was observed using a confocal microscope (TCS SP5, Leica).

[0473] (2) Result

[0474] Figure 25a shows the results of H&E staining and Masson's trichrome staining 7 days after healing of an in vivo incision wound (linear wound of Example 12), and Figure 25b shows the results of immunofluorescence staining 7 days after healing of an in vivo incision wound (linear wound of Example 12).

[0475] According to Fig. 25a, it was confirmed that the coating material group of Example 8-1 (Ce6+Patch) achieved the most complete re-epithelialization, with a well-organized epidermal layer and densely arranged collagen fibers similar to the normal control group.

[0476] According to Fig. 25b, the suture, the patch of Example 5-2 alone, and the dressing of Example 8-1 (Ce6+Patch) groups showed normalized marker expression similar to that of adjacent, unwound tissue, suggesting the completion of the regeneration process. In addition, while α-SMA and TNF-α expression levels increased in wounds with incomplete healing, they were significantly reduced in the aforementioned groups, confirming complete tissue regeneration, effective resolution of inflammation, and inhibition of fibrotic remodeling.

[0477] Figure 26a shows the results of H&E staining and Masson's trichrome staining 10 days after healing of an in vivo excision wound (circular wound of Example 12), and Figure 26b shows the results of immunofluorescence staining 10 days after healing of an in vivo excision wound (circular wound of Example 12).

[0478] According to Fig. 26a, both the patch of Example 5-2 alone and the coating material of Example 8-1 (Ce6+Patch) showed a high degree of re-epithelialization characterized by remodeling of the epithelial layer and density and uniform distribution of collagen fibers.

[0479] According to Fig. 26b, marker expression in the patch (Patch) alone of Example 5-2 and the coating material (Ce6+Patch) group of Example 8-1 was restored to a level similar to that of adjacent healthy tissue, suggesting more complete tissue regeneration. This decrease in marker expression and the increase in the expression of anti-inflammatory cytokines supported the conclusion that continuous PBM promotes M2 macrophage polarization, thereby facilitating inflammation resolution and tissue remodeling during the circular wound healing process.

[0480]

[0481] Example 14: Quantification of cytokine expression

[0482] (1) Method

[0483] After 2 and 4 days of healing of incision wounds (linear wound of Example 12) or excision wounds (circular wound of Example 12) in vivo, mice were sacrificed by CO2 euthanasia, and treated tissue specimens were collected to quantify cytokine expression. Skin tissue was immersed in cell lysis buffer, cut into small pieces, and mechanically lysed. Cytokines were separated from the tissue debris by centrifugation at 12,000 rpm for 20 minutes. Mediator concentrations were determined in the wound lysates using ELISA kits for TGF-β and IL-1β according to the manufacturer's instructions.

[0484] (2) Result

[0485] Figure 27a shows the quantified cytokine expression on day 2 of healing of the in vivo incision wound (linear wound of Example 12) (n = 4; *p<0.05, **p<0.01, ***p<0.001, ****p < 0.0001 vs. negative control for each cytokine; NS, not significant), and Figure 27b shows the quantified cytokine expression on day 4 of healing of the in vivo incision wound (linear wound of Example 12) (n = 4; *p<0.05, **p<0.01, ***p<0.001, ****p < 0.0001 vs. negative control for each cytokine; NS, not significant).

[0486] According to Figures 27a and 27b, the patch alone of Example 5-2 and the coating material group of Example 8-1 (Ce6+Patch) showed a tendency for the expression of inflammatory cytokines (IL-1β) to be suppressed and the expression of anti-inflammatory cytokines (TGF-β) to increase. In particular, on day 2, the expression levels of inflammatory cytokines were lower and the expression levels of regenerative cytokines were higher in the coating material (Ce6+Patch) group compared to the control group, suggesting that a microenvironment favorable for tissue regeneration was formed through effective tissue adhesion induced by PTB. Furthermore, on day 4, cytokine expression returned to baseline levels in all groups except the untreated control group, indicating that the proliferative phase of the wound healing process was completed.

[0487] Figure 28a shows the quantified cytokine expression on day 2 of healing of the in vivo resection wound (circular wound of Example 12) (n = 4; *p<0.05, **p<0.01, ***p<0.001, ****p < 0.0001 vs. negative control for each cytokine; NS, not significant), and Figure 28b shows the quantified cytokine expression on day 4 of healing of the in vivo resection wound (circular wound of Example 12) (n = 4; *p<0.05, **p<0.01, ***p<0.001, ****p < 0.0001 vs. negative control for each cytokine; NS, not significant).

[0488] Continuous immune modulation is particularly important for circular wounds because they have a larger surface area and a slower healing rate. According to Figures 28a and 28b, it can be seen that the expression level of the inflammatory cytokine (IL-1β) in the control group remained consistently high on both day 2 and day 4. On the other hand, in the patch group of Example 5-2 alone and the coating group of Example 8-1 (Ce6+Patch), the expression of TGF-β, an indicator of M2 macrophage polarization, was significantly increased at both time points, and it was confirmed that the expression level was further elevated, especially on day 4.

[0489]

[0490] The specification omits detailed descriptions of matters that can be sufficiently recognized and inferred by those skilled in the art of the present invention, and various modifications are possible within the scope of not altering the technical concept or essential configurations of the present invention, in addition to the specific examples described in this specification. Accordingly, the present invention may be implemented in a manner different from that specifically described and exemplified in this specification, and this is a matter that can be understood by those skilled in the art.

Claims

A luminescent material represented by the following chemical formula 1: [Chemical Formula 1] CaSr(S,SO4):Eu,Tm In paragraph 1, A luminescent body comprising, based on a total of 100 at%, 20 to 30 at% Ca, 10 to 20 at% Sr, 20 to 40 at% S, 20 to 40 at% O, 0.01 to 2 at% Eu and 0.01 to 5 at% Tm. In paragraph 1, A light source having a partial oxidation state in which a portion of sulfur (S) within the matrix is ​​substituted with sulfate (SO4), wherein the light source is based on CaSrS. In paragraph 1, The above-mentioned light source is a light source having a emission spectrum peak at a wavelength of 580 to 700 nm. In paragraph 4, The above-mentioned light-emitting body absorbs light in the wavelength range of 300 to 600 nm and emits red light having a emission spectrum peak at a wavelength of 580 to 700 nm. Matrix; and Includes a light source dispersed in the above matrix; The light-emitting layer is one in which the light-emitting body absorbs ambient light and emits red light having a emission spectrum peak at a wavelength of 580 to 700 nm. In paragraph 6, A light-emitting layer in which the above ambient light is an indoor white light, a portable white light source, or sunlight. In paragraph 6, A light-emitting layer in which the above ambient light is a light source including a wavelength of 300 to 700 nm. In paragraph 6, A light-emitting layer comprising one or more types selected from the group consisting of nitride phosphors, oxide phosphors, sulfur oxide phosphors, fluoride phosphors, sulfide phosphors, quantum dots, carbon dots, and upconversion phosphors. In paragraph 6, The above luminescent material is CaSr(S,SO4):Eu,Tm, Y2SiO5:Eu 3+ , Y2Si2O7:Eu 3+ , YAlO3:Eu 3+ , CaAlSiN3:Eu 2+ , CaAl 12 O 19 :Eu 3+ , Sr3Al2O6:Eu 3+ , Ca2SiO4:Eu 3+ , Gd2O3:Eu 3+ , Sr2Si5N8:Eu 2+ , (Sr,Ca)AlSiN3:Eu 2+ , Y2O3:Eu 3+ , CaTiO3:Pr 3+ , Y2O2S:Eu 3+ ,Ti 4+ ,Mg 2+ , SrGa2O4:Cu 2+ , BaMgAl 10 O 17 :Eu 3+ , CaS:Eu 2+ , CaS:Eu 2+ ,Dy 3+ , SrS:Eu 2+ , CaS:Eu 2+ ,Sm 3+ A light-emitting layer comprising one or more selected from the group consisting of , CaS:Eu,Tm, CaSrS:Eu,Sm, CaSrS:Eu,Tm, InP / ZnSeS, CdSe / ZnS, carbon dot, NaYF4:Yb,Er, NaErF4@NaYF4@NaGdF4:x%Yb@NaYF4(x = 0, 10, 49, 80), and NaErF4@NaYF4@NaGdF4:49%Yb / y%Tm@NaYF4(y = 0, 1, 5, 10). In paragraph 6, A light-emitting layer comprising one or more selected from the group consisting of a silicone-based elastomer, a thermoplastic transparent elastomer, an acrylic transparent polymer, and a hydrogel-based transparent matrix. In paragraph 6, The light-emitting layer comprises 10 to 100 parts by weight of a light-emitting body based on 100 parts by weight of the matrix. In paragraph 6, A light-emitting layer having a thickness of 0.1 to 1.66 mm. protective layer; and A light-emitting layer formed on one surface of the above protective layer and comprising a matrix and a light-emitting body; A multilayer patch in which the light emitter absorbs ambient light and emits red light having a emission spectrum peak at a wavelength of 580 to 700 nm. In Paragraph 14, A multilayer patch comprising one or more types selected from the group consisting of a silicone-based elastomer, a thermoplastic transparent elastomer, an acrylic transparent polymer, and a hydrogel-based transparent matrix. In Paragraph 14, A multilayer patch having a protective layer thickness of 0.1 to 0.5 mm. In Paragraph 14, A multilayer patch comprising an adhesive layer formed on part or all of the protective layer surface of the multilayer patch. In Paragraph 14, A multilayer patch comprising one or more adhesive layers selected from the group consisting of silicone-based adhesives, acrylic-based adhesives, wet-adhesive hydrogels, boronic acid ester / diol-based adhesives, NHS-ester / Schiff-based chemical adhesives, and DOPA-containing polymer adhesives. It includes a light-emitting layer comprising a matrix and a light-emitting body, and A wound healing patch, wherein the above-mentioned light-emitting body absorbs ambient light and emits red light having a emission spectrum peak at a wavelength of 580 to 700 nm. In Paragraph 19, A wound healing patch comprising a protective layer formed on the light-emitting layer. In paragraph 20, A wound healing patch comprising an adhesive layer formed on the protective layer. In Paragraph 19, The above wounds are trauma, heat injury, Buerger's disease, vascular and lymphatic injury, postoperative wound, stoma, pressure ulcer, pressure ulcer, diabetic ulcer / scrotum ( A wound healing patch selected from the group consisting of ), post-herpetic ulcer, drug-induced ulcer, skin ulcer, damage caused by dermatitis, radiation damage, and chemical damage. A patch comprising a light-emitting layer including a matrix and a light emitter; and An active layer formed on one surface of the above patch and comprising a photosensitive agent; comprising, A wound healing dressing, wherein the above-mentioned light-emitting body absorbs ambient light and emits red light having a emission spectrum peak at a wavelength of 580 to 700 nm. In Paragraph 23, The above patch includes a protective layer formed on the light-emitting layer and an adhesive layer formed on the protective layer, and A wound healing dressing in which the above active layer is formed on the above adhesive layer. In Paragraph 23, The above photosensitizers are Chlorine e6, verteporfin, Methylene Blue (MB), Toluidine Blue O (TBO), Nile Blue A, Thionine, Indocyanine Green (ICG), Zinc Phthalocyanine (ZnPc), Aluminum Phthalocyanine Tetrasulfonate (AlPcS4), Aminolevulinic Acid (ALA), Methyl Aminolevulinate, Temoporfin, Phthalocyanine, Protoporhap IX (PpIX), Allumera™, Cevira™, Hexvix™, Porfimer Sodium, δ-aminolevulinic acid or 5-aminolevulinic acid, Temoporfin, Methyl Aminolevulinate, and Hexaminolevulinate A wound healing dressing selected from the group consisting of hexaminolevulinate hydrochloride, talaporfin, motexafin lutetium, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a, Photosens™, rostaporfin, BF-200 ALA, tetraphenyl chlorin disulfonate, and azadipyrromethene.

Images