WO2023282525A1

WO2023282525A1 - Hydrogel patch for skin disease, and method for manufacturing same

Info

Publication number: WO2023282525A1
Application number: PCT/KR2022/009282
Authority: WO
Inventors: 김재윤; 최승우; 김예은
Original assignee: 성균관대학교산학협력단
Priority date: 2021-07-07
Filing date: 2022-06-29
Publication date: 2023-01-12
Also published as: KR102584760B1; KR20230008359A

Abstract

The present application relates to a hydrogel patch comprising: a hydrogel including a polymer; and nanoparticles dispersed in the hydrogel, wherein the hydrogel and the nanoparticles have different charges.

Description

Hydrogel patch for skin disease and manufacturing method thereof

The present application relates to a hydrogel patch for skin diseases and a method for manufacturing the same.

Atopic disease is a type of inflammatory disease that occurs in the skin, and is caused by various environmental and genetic factors. Reactive oxygen species are generally rapidly increased in the skin with atopic disease, and thus the abnormally increased oxidative stress acts as a factor that further exacerbates the atopic disease.

In general, it is recommended to use moisturizers such as oil, lotion, and cream to alleviate the symptoms of atopic dermatitis. to alleviate the disease by making In addition, since atopic dermatitis often develops chronically, a combination of treatments such as antihistamines, steroid ointments, and antibiotics is required in addition to moisturizers.

In the skin area where atopy occurs, severe itching is induced due to overexpression of histamine, and patients scratch the skin, which causes secondary skin damage to make atopy more severe and slow recovery of wounds. Although antihistamines are used to suppress histamine, when they are continuously taken, there is a problem that drowsiness is induced due to the central nervous system depressant action and resistance occurs when used for a long time.

In the case of steroid ointment, it alleviates the disease by suppressing the inflammatory response and immune action. However, if the steroid is continuously exposed to a certain level or higher and then the steroid is stopped, the function of the adrenal glands cannot be restored to normal, and glucocorticoids are excessively secreted from the adrenal cortex, resulting in Cushing's syndrome. In the case of Cushing's syndrome, it is considered the biggest side effect of steroids because it leads to emotional changes as well as physical changes such as weight gain and poor wound healing.

In the case of antibiotics, it is used when the skin is constantly scratched and the mucous membrane is exposed, and bacteria infect this place and the inflammation intensifies. When an antigen is introduced, the immune response is further increased and the disease may be aggravated. However, there is a problem that indiscriminate use of antibiotics also causes antibiotic resistance.

All of the aforementioned antihistamines, steroid ointments, and antibiotics are okay for short-term use, but side effects occur when taken continuously. In the case of atopic dermatitis, since the possibility of becoming a chronic disease is high and continuous drug use is common due to the high possibility of recurrence, it is necessary to develop a treatment drug that reduces the incidence of side effects.

Korean Patent Registration No. 10-1848272 is a patent for a hydrogel for treating atopic dermatitis and a method for manufacturing the same. The patent discloses a hydrogel for treating atopic dermatitis that protects the skin from external stimuli such as scratching by forming a film-type film about an hour after application to the skin using a polyvinyl alcohol-alginate hydrogel. No mention is made of a method for removing oxygen species.

The present application is to solve the problems of the prior art described above, and aims to provide a hydrogel patch for skin diseases.

In addition, an object of the present invention is to provide a method for manufacturing a hydrogel patch for skin diseases.

However, the technical problem to be achieved by the embodiments of the present application is not limited to the technical problems described above, and other technical problems may exist.

As a technical means for achieving the above technical problem, the first aspect of the present application is a hydrogel comprising a polymer; and nanoparticles dispersed within the hydrogel; Including, the hydrogel and the nanoparticles provide a hydrogel patch for skin disease that has a different charge.

According to one embodiment of the present application, due to the hydrogel and the nanoparticles having different charges, the bonding strength of the hydrogel and the nanoparticles may be increased, but is not limited thereto.

According to one embodiment of the present application, the hydrogel may further include a crosslinking accelerator, but is not limited thereto.

According to one embodiment of the present application, the mechanical properties of the hydrogel patch for skin diseases may be improved by the crosslinking accelerator, but is not limited thereto.

According to one embodiment of the present application, the crosslinking accelerator is gluconodeltalactone (GDL), diphenyliodonium nitrate, diphenyliodonium-2-carboxylate and It may include one selected from the group consisting of combinations thereof, but is not limited thereto.

According to one embodiment of the present application, active oxygen species that cause skin diseases may be removed by the nanoparticles, but is not limited thereto.

According to one embodiment of the present application, the nanoparticles are ceria, iron oxide, manganese oxide, vanadium oxide, vanadium oxide sulfate, zinc oxide, gold, platinum, copper, melamine, lignin, polyphenol, carbon nanotube, graphene, carbon It may include one selected from the group consisting of quantum dots and combinations thereof, but is not limited thereto.

According to one embodiment of the present application, the polymer is alginate (Alg), polyethylene glycol (PEG), chitosan (Chitosan), gelatin (Gelatin), polyacrylic acid (PAAc), polyacrylamide (PAM), polynipam (PNIPAM) , Agar, poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS), and combinations thereof, but is not limited thereto.

In addition, the second aspect of the present application is to prepare a first solution containing nanoparticles; preparing a second solution containing a crosslinking agent and a polymer; and preparing a mixed solution by adding the first solution and a crosslinking accelerator to the second solution. It provides a method for producing a hydrogel patch for skin diseases comprising a.

According to one embodiment of the present application, a step of solidifying the mixed solution by pouring it into a mold may be further included, but is not limited thereto.

According to one embodiment of the present application, the metal oxide is iron oxide, manganese oxide, vanadium oxide, vanadium oxide sulfate, zinc oxide, gold, platinum, copper, melamine, lignin, polyphenol, carbon nanotube, graphene, carbon quantum dot And it may include one selected from the group consisting of combinations thereof, but is not limited thereto.

According to one embodiment of the present application, the crosslinking agent may include one selected from the group consisting of calcium carbonate (CaCO ₃ ), calcium chloride (CaCl ₂ ), calcium sulfate (CaSO ₄ ), and combinations thereof, but is limited thereto. it is not going to be

The above-described problem solving means are merely exemplary and should not be construed as intended to limit the present disclosure. In addition to the exemplary embodiments described above, additional embodiments may exist in the drawings and detailed description of the invention.

The hydrogel patch for skin diseases according to the present application contains metal oxide nanoparticles capable of removing active oxygen species, which are the main cause of oxidative stress in the body, and attaches the patch to the skin disease area to reduce active oxygen species. By continuously removing it, it is possible to suppress chronic inflammation and restore the damaged skin barrier and thickened epidermal layer.

In addition, the hydrogel patch for skin disease according to the present application can improve skin disease by providing a wet environment where the skin disease occurs by using the hydrogel.

In addition, since the hydrogel patch for skin diseases according to the present application is strongly bonded to the nanoparticles, the nanoparticles do not remain on the skin when the patch is removed.

In addition, since the hydrogel patch for skin diseases according to the present application is a hydrogel-type patch with soft and flexible properties, it can be easily attached to and detached from joints and protruding areas, and the patient's convenience can be increased when the patch is attached for a long time. there is.

In addition, it is possible to adjust the capacity of nanoparticles that play an antioxidant role, adjust the thickness of the hydrogel, and manufacture a large area, so that various types of patches can be manufactured according to the condition and size of the skin disease area.

In addition, the hydrogel patch for skin diseases according to the present application can be used as a drug delivery system by carrying an additional drug for treatment therein.

However, the effects obtainable herein are not limited to the effects described above, and other effects may exist.

1 is a schematic diagram showing the removal of active oxygen species by attaching a hydrogel patch for skin diseases according to an embodiment of the present application to the skin.

Figure 2 is a flow chart of a method for manufacturing a hydrogel patch for skin diseases according to one embodiment of the present application.

3 is an image of a hydrogel patch according to an embodiment of the present application.

4 (A) is an image of a solution in which ceria nanoparticles according to one embodiment of the present application are dispersed in water, and (B) is a TEM image of ceria nanoparticles according to one embodiment of the present application.

5 is a surface potential measurement result of ceria nanoparticles dispersed in deionized water measured by DLS according to an experimental example of the present application.

6 is an XRD result of ceria nanoparticles according to an experimental example of the present application.

7 is an XPS result of ceria nanoparticles according to an experimental example of the present application.

8 is a graph measuring active oxygen species removal ability of ceria nanoparticles according to an experimental example of the present application.

9 is a graph measuring active oxygen species removal ability of ceria nanoparticles according to an experimental example of the present application.

10 is a graph measuring active oxygen species removal ability of ceria nanoparticles according to an experimental example of the present application.

11 is a result of scanning electron microscope images and X-ray spectroscopy of hydrogels according to an example and a comparative example of the present application.

Figure 12 (A) is a graph measuring the transmittance in the visible light region according to the addition amount of nanoparticles of the hydrogel according to an experimental example of the present application, (B) is a hydrogel according to an embodiment and a comparative example of the present application It is the measurement result of the water content of the gel.

13 is a result of measuring mechanical properties of hydrogels according to one embodiment and comparative example of the present application.

14 is a result of measuring the ability to remove reactive oxygen species according to the content of nanoparticles of a hydrogel according to an experimental example of the present application.

15 is a result of measuring the ability to remove reactive oxygen species according to the content of nanoparticles of a hydrogel according to an experimental example of the present application.

Figure 16 (A) is the result of measuring the cytotoxicity of the hydrogel according to one experimental example of the present application, (B) is the result of measuring the cell rescue effect in the cell culture medium containing hydrogen peroxide, (C) is This is the result of measuring the cell rescue effect in the cell culture medium containing DNCB.

17 is a result of observing the treatment effect on the skin of the hydrogel patch according to an experimental example of the present application.

18 (A) is an image obtained by measuring epidermal thickness after recovering the skin tissue of FIG. 18, and (B) is a graph showing the result of epidermal thickness measurement.

Figure 19 (A) is an image of observing the treatment effect on the skin of the hydrogel patch according to an experimental example of the present application, (B) is a graph measuring the size of the wound on the skin over time.

Figure 20 (A) is an image obtained by measuring epidermal thickness by recovering the skin tissue of FIG. 20, and (B) is a graph showing the result of measuring epidermal thickness.

21 is an image observing the atopic treatment effect of the hydrogel patch according to an experimental example of the present application.

22 (A) is an image obtained by measuring epidermal thickness by recovering the skin tissue of FIG. 22, and (B) is an image obtained by observing mast cells by recovering the skin tissue of FIG. 22.

23 is an enzyme-linked immunosorbent assay (ELISA) analysis result according to an experimental example of the present application.

FIG. 24 is a result of analyzing the amount of ceria nanoparticles remaining in the tissue after recovering the skin tissue of FIG. 21 .

Hereinafter, embodiments of the present application will be described in detail so that those skilled in the art can easily practice with reference to the accompanying drawings.

However, the present disclosure may be implemented in many different forms and is not limited to the embodiments described herein. And in order to clearly describe the present application in the drawings, parts irrelevant to the description are omitted, and similar reference numerals are attached to similar parts throughout the specification.

Throughout this specification, when a part is said to be "connected" to another part, this includes not only the case of being "directly connected" but also the case of being "electrically connected" with another element in between. do.

Throughout the present specification, when a member is referred to as being “on,” “above,” “on top of,” “below,” “below,” or “below” another member, this means that a member is located in relation to another member. This includes not only the case of contact but also the case of another member between the two members.

Throughout the present specification, when a certain component is said to "include", it means that it may further include other components without excluding other components unless otherwise stated.

As used herein, the terms "about," "substantially," and the like are used at or approximating that number when manufacturing and material tolerances inherent in the stated meaning are given, and are intended to assist in the understanding of this disclosure. Accurate or absolute figures are used to prevent undue exploitation by unscrupulous infringers of the stated disclosure. In addition, throughout the present specification, “steps of” or “steps of” do not mean “steps for”.

Throughout the present specification, the term "combination thereof" included in the expression of the Markush form means one or more mixtures or combinations selected from the group consisting of the components described in the expression of the Markush form, and the components It means including one or more selected from the group consisting of.

Throughout this specification, reference to "A and/or B" means "A or B, or A and B".

Hereinafter, the hydrogel patch for skin diseases of the present application and its manufacturing method will be described in detail with reference to embodiments and examples and drawings. However, the present application is not limited to these embodiments and examples and drawings.

In a conventional method for the treatment of atopic dermatitis, which is a type of inflammatory skin disease caused by an excessive amount of active oxygen, a method of alleviating atopic dermatitis by using an antihistamine, a steroid ointment, and an antibiotic in addition to a moisturizer is used. However, the antihistamines, steroid ointments, and antibiotics have side effects such as drowsiness due to central nervous system depressant action, Cushing's syndrome, and resistance to drugs when taken continuously.

Reactive oxygen species are generally rapidly increased in the skin with inflammatory skin disease, and thus abnormally increased oxidative stress acts as a factor that further exacerbates the skin disease. Therefore, removing reactive oxygen species from skin with skin disease is very important in the treatment of skin disease.

In conventional hydrogel patches for skin diseases, the bonding force between the hydrogel and the nanoparticles is weak, so that the nanoparticles remain on the skin when the patch is detached from the skin.

However, in the hydrogel patch for skin diseases according to the present application, the hydrogel and the nanoparticles dispersed in the hydrogel have different charges, and as a result, the bonding force between the hydrogel and the nanoparticles increases to detach the patch from the skin. When doing so, the problem that the nanoparticles remain on the skin may not occur.

The hydrogel patch for skin diseases according to the present application contains a crosslinking accelerator and may have improved mechanical properties compared to conventional hydrogels, and thus may be a material suitable for use as a patch.

In general, for the preparation of alginate hydrogels having uniform properties, calcium salts such as CaSO ₄ or CaCO ₃ that can slowly release Ca ²⁺ ions due to their low solubility in water are used, and the Ca ²⁺ ions are alginate polymers. It serves as an ionic cross-linking agent for the liver. However, in the case of CaCO ₃ , the solubility is very low and the rate of ionization into Ca ²⁺ ions in the solution is too slow. Therefore, in the present application, by additionally using a crosslinking accelerator, the ionization rate is increased to promote crosslinking of the hydrogel, thereby improving the mechanical properties of the hydrogel.

As a cross-linking accelerator, most photoacid generators that generate acids by being decomposed by light in addition to diphenyliodonium nitrate and diphenyliodonium-2-carboxylate ) can be used, but is not limited thereto.

Reactive oxygen species are generally rapidly increased in the skin with inflammatory skin disease, and thus abnormally increased oxidative stress acts as a factor that further exacerbates the skin disease.

The hydrogel patch for skin diseases according to the present application includes metal oxide nanoparticles capable of removing active oxygen species, which are the main cause of oxidative stress in the body, and the metal oxide nanoparticles remove active oxygen species to treat skin diseases. can be improved

Referring to Figure 1, the hydrogel patch for skin diseases of the present application is attached to the epidermis, and the nanoparticles present in the patch remove active oxygen species, thereby suppressing chronic inflammation and helping to recover the damaged skin barrier and the thickened epidermal layer. You can check.

According to one embodiment of the present application, the nanoparticles are iron oxide, manganese oxide, vanadium oxide, vanadium oxide sulfate, zinc oxide, gold, platinum, copper, melamine, lignin, polyphenol, carbon nanotube, graphene, carbon quantum dot And it may include one selected from the group consisting of combinations thereof, but is not limited thereto.

The nanoparticles may have a strong positive charge on the surface so that they can be uniformly dispersed in the negatively charged hydrogel, but are not limited thereto.

Since the hydrogel and the nanoparticles have different charges, bonding strength between the hydrogel and the metal oxide may increase.

Preferably, in order to produce a hydrogel patch having high biocompatibility, the polymer may use a polymer derived from natural materials, but is not limited thereto.

With respect to the method for manufacturing a hydrogel patch according to the second aspect of the present application, detailed descriptions of parts overlapping with the first aspect of the present application have been omitted, but even if the description is omitted, the contents described in the first aspect of the present application The same can be applied to the second aspect.

Hereinafter, a method for manufacturing a hydrogel patch for skin diseases of the present application will be described with reference to FIG. 2 .

First, a first solution containing nanoparticles is prepared (S100).

The nanoparticles have a strong positive charge of +20 mV on the surface, and thus can be uniformly dispersed in the negatively charged hydrogel, and the hydrogel and the nanoparticles have different charges, so the bonding strength can be increased there is.

Subsequently, a second solution containing a crosslinking agent and a polymer is prepared (S200).

The hydrogel patch for skin diseases according to the present application may be prepared by adding a crosslinking material to improve the physical properties of the hydrogel.

Subsequently, a mixed solution is prepared by adding the first solution and the crosslinking accelerator to the second solution (S300).

The hydrogel patch for skin diseases according to the present application may be prepared by adding a crosslinking accelerator to improve the physical properties of the hydrogel.

After adding the first solution to the second solution, the crosslinking accelerator may be added in the order of adding.

Due to the addition of the crosslinking agent and the crosslinking accelerator, it may have mechanical properties suitable for use as a patch.

In general, a calcium salt such as CaCO ₃ capable of releasing Ca ²⁺ ions is used to prepare a hydrogel, and the Ca ²⁺ ions serve as a cross-linking agent in a solution. However, in the case of CaCO ₃ , the solubility is very low and the rate of ionization into Ca ²⁺ ions in the solution is slow. Therefore, in the present application, by additionally using a crosslinking accelerator, the ionization rate is increased to promote crosslinking of the hydrogel, thereby improving the mechanical properties of the hydrogel.

The present invention will be described in more detail through the following examples, but the following examples are for illustrative purposes only and are not intended to limit the scope of the present application.

[Example] Manufacturing hydrogel patch supported with ceria nanoparticles

First, Cerium (III) acetate hydrate and imidazole were dissolved in distilled water, respectively, and the respective solutions were mixed and stirred to react at room temperature for 3 hours. As the reaction proceeds, the reaction solution turns cloudy within about 3 minutes, and turns into a brown solution while becoming transparent again after about 1 hour and 45 minutes. Thereafter, after washing with acetone three times, particles are obtained and dispersed in distilled water to prepare a first solution containing nanoparticles.

Subsequently, alginic acid sodium salt from brown algae and calcium carbonate are dissolved in distilled water, respectively, and each solution is mixed in a certain ratio and then mixed uniformly by vortexing. Thereafter, the mixed solution is degassed to prepare a second solution containing a crosslinking agent and a polymer.

Subsequently, the first solution and GDL (D-(+)-Gluconic acid δ-lactone) are sequentially added to the second solution, and then stirred with vortexin to prepare a mixed solution.

Finally, the mixed solution is poured into a mold and hardened for one day to obtain a hydrogel carrying ceria nanoparticles.

Referring to Figure 3, it can be confirmed that a colorless transparent hydrogel was prepared.

[Comparative Example] Preparation of hydrogel not carrying ceria nanoparticles

Alginic acid sodium salt from brown algae and calcium carbonate are dissolved in distilled water, respectively, and each solution is mixed in a certain ratio, and then mixed uniformly by vortexing. Thereafter, the mixed solution is degassed to prepare a second solution containing a crosslinking agent and a polymer.

Subsequently, a predetermined amount of distilled water and D-(+)-Gluconic acid δ-lactone are sequentially added to the second solution, followed by stirring with vortexin to prepare a mixed solution.

Finally, the mixed solution is poured into a mold and hardened for one day to obtain a hydrogel.

[Experimental Example 1] Analysis of characteristics of ceria nanoparticles

Referring to (A) of FIG. 4 , it can be confirmed that the ceria nanoparticles can be stably dispersed in water.

Referring to (B) of FIG. 4 , ceria nanoparticles having a uniform size distribution and having a diameter of about 5 nm can be confirmed.

Referring to FIG. 5, since the zeta potential of the surface of the nanoparticles is 25.37 ± 1.63 mV, long-term storage in a highly dispersed state in an aqueous solution is possible, and uniform dispersion without being strongly bound and released even on a negatively charged alginate hydrogel matrix this is possible

Referring to FIG. 6 , it can be confirmed that the measured peak has a structure of CeO ₂ .

Referring to FIG. 7 , a mixed state of Ce ³⁺ and Ce ⁴⁺ could be confirmed.

[Experimental Example 2] Test of reactive oxygen species removal ability of ceria nanoparticles

Referring to FIG. 8, the catalase-mimetic activity of the material was measured using the Amplex™ Red Hydrogen Peroxide/Peroxidase Assay, and it was confirmed that the amount of remaining hydrogen peroxide decreased as the amount of cerium increased.

Referring to FIG. 9 , the superoxide dismutase-mimetic activity of the material was measured using the SOD Assay, and it was confirmed that the SOD activity increased as the amount of cerium increased.

Referring to FIG. 10, the degree of hydroxyl radical removal of the material was measured using the Hydroxyl Radical Antioxidant Capacity Assay, and it was confirmed that the amount of hydroxyl radicals generated decreased as the amount of cerium increased.

Through Experimental Example 2, it was confirmed that ceria nanoparticles, which are nanoparticles used in the hydrogel patch for skin diseases of the present application, effectively remove representative active oxygen species such as H ₂ O ₂ , oxygen radicals, and hydroxyl radicals.

[Experimental Example 3] Measurement of properties of hydrogel

Referring to FIG. 11 , it can be seen that both the hydrogels of Example and Comparative Example have a pore structure, and in the case of Example, ceria nanoparticles are uniformly distributed inside the hydrogel.

Referring to (A) of FIG. 12, as the amount of ceria nanoparticles added increases, the permeability decreases, but even in the case of a hydrogel loaded with 8 mM ceria nanoparticles, the extent to which a wound can be observed with a patch applied It was confirmed that the permeability of

Referring to (B) of FIG. 12, it was confirmed that the water content of the hydrogel was close to 100% regardless of whether or not the ceria nanoparticles were supported.

[Experimental Example 4] Mechanical property test

Experiments were conducted to compare mechanical properties depending on whether or not nanoparticles were supported in the hydrogel.

Referring to FIG. 13, when the modulus of elasticity is measured through a compression test to measure the pressing force and a tensile test to measure the pulling force, whether the ceria nanoparticles are supported has a significant effect on the mechanical properties. has been shown not to give

Through Experimental Example 4, it was confirmed that the hydrogel according to the example had mechanical properties suitable for use as a patch through the addition of D-(+)-Gluconic acid δ-lactone.

[Experimental Example 5] Hydrogel's ability to remove reactive oxygen species

Referring to FIG. 14, the catalase-mimetic activity of the material was measured using Amplex™ Red Hydrogen Peroxide/Peroxidase Assay. It was confirmed that the amount of remaining hydrogen peroxide decreased as the amount of ceria nanoparticles increased.

Referring to FIG. 15, the degree of hydroxyl radical removal of the material was measured using a Hydroxyl Radical Antioxidant Capacity Assay. It was confirmed that as the amount of ceria nanoparticles increased, the number of hydroxyl radicals generated decreased.

Through Experimental Example 5, it was confirmed that the hydrogel patch according to an embodiment of the present application has an effective reactive oxygen species removal ability.

[Experimental Example 6]

Referring to (A) of FIG. 16, it was found that the hydrogel had almost no cytotoxicity regardless of whether or not ceria nanoparticles were supported, and referring to (B) of FIG. 17, as the content of ceria nanoparticles increased, the cell It can be confirmed that the survival rate is high, and the survival rate of cells in the presence of hydrogen peroxide in the hydrogel having ceria nanoparticles of 8 mM is about 20% higher than that of the hydrogel without ceria nanoparticles. Referring to (C) of FIG. 17 , it can be seen that the amount of intracellular active oxygen is reduced by about 50% in the hydrogel containing ceria nanoparticles.

[Experimental Example 7]

An experiment was conducted to confirm the therapeutic effect of the hydrogel patch for skin diseases of the present application. Gauze soaked in a 3% hydrogen peroxide solution was attached to the back skin of the rat, and the hydrogel of one embodiment of the present application was attached thereon to observe the toxic effect of hydrogen peroxide on the skin.

17, the normal group is healthy skin to which hydrogen peroxide gauze is not applied, the control group is skin to which hydrogen peroxide gauze is applied to the skin to give strong oxidative stimulation and is not treated, and the comparative example treatment group is the skin to which hydrogen peroxide gauze is applied to the skin After application, the hydrogel on which the ceria nanoparticles are not supported according to the comparative example is attached to the skin, and the treatment group in the example is a hydrogen peroxide gauze applied to the skin, and then the hydrogel on which the ceria nanoparticles are supported according to the example is applied. It means attached skin.

Referring to FIG. 17, when visually checking the wound, it was confirmed that the size of the wound was the smallest in the case of the example treatment group to which the hydrogel according to the example was attached.

(A) of FIG. 18 is an image obtained by measuring epidermal thickness after recovering the skin tissue of FIG. 17, and (B) is a graph showing the result of epidermal thickness measurement.

Referring to (A) of FIG. 18, the skin tissues of the normal group, the comparative group, the comparative example treatment group, and the example treatment group were recovered and stained with hematoxylin & eosin (H&E) to show changes in epidermis thickness (arrow) When comparing, it was confirmed that the thickness of the epidermis of the Example treatment example increased the least compared to the Comparative group and the Comparative Example treatment group. Through this, it was found that the ceria nanoparticles in the hydrogel patch according to an embodiment of the present application can minimize the effect on the skin when directly exposed to reactive oxygen species by immediately removing hydrogen peroxide present in the gauze. .

[Experimental Example 8]

An experiment was conducted to confirm the therapeutic effect of the hydrogel patch for skin diseases of the present application. This is the result of applying a gauze soaked with an 8% hydrogen peroxide solution to the back skin of a rat for one day to induce wounds, and then attaching a hydrogel patch prepared according to an embodiment of the present application to the wound and treating it for 6 days.

In FIG. 19, the normal group is skin that is not stimulated with hydrogen peroxide gauze, and the control group is skin that is not treated after giving strong oxidative stimulation by attaching hydrogen peroxide gauze and removing it, and the comparative example treatment group is skin that is not treated with hydrogen peroxide gauze After giving a strong oxidative stimulus and removing it, the treated skin was treated by attaching a hydrogel not loaded with ceria nanoparticles according to the comparative example. It means the skin treated by attaching the hydrogel carrying the ceria nanoparticles according to the embodiment.

Referring to (A) of FIG. 19, it can be seen that the size of the wound decreased the most in the case of the Example treatment group when visually confirmed, and referring to (B), in the case of the Example treatment group, the comparative group and the comparative example treatment group Compared to , the increase in the size of the wound was the lowest on the 3rd day, and it was confirmed that the size of the wound decreased the most on the 7th day.

(A) of FIG. 20 is an image obtained by measuring epidermal thickness after recovering the skin tissue of FIG. 19, and (B) is a graph showing the result of epidermal thickness measurement.

Referring to Figure 20, when comparing the change in epidermal thickness (arrow) by recovering the skin tissues of the normal group, the comparative group, the comparative example treatment group, and the example treatment group and staining with hematoxylin & eosin, the comparison group and the comparative example It can be seen that the thickness of the epidermis of the Example treatment group was thinner than that of the treatment group. Through this, it can be seen that the hydrogel patch for skin diseases according to an embodiment of the present application has a positive effect on healing skin tissue damaged by exposure to hydrogen peroxide.

[Experimental Example 9]

An experiment was conducted to confirm the atopic dermatitis treatment effect of the hydrogel patch for skin diseases of the present application. An animal model that induced atopic disease on the back of a rat was produced using a chemical substance, and the hydrogel patch synthesized according to an embodiment of the present application was attached to observe the atopic treatment effect.

21, the normal group is the skin of healthy mice without any treatment, the control group is the skin that has not been treated after inducing atopic dermatitis with DNCB, and the comparative example treatment group is the comparison after inducing atopic dermatitis with DNCB Skin treated by attaching the hydrogel without carrying ceria nanoparticles according to the example, and in the treatment group of the example, after inducing atopic dermatitis with DNCB, the skin treated by attaching the hydrogel carrying ceria nanoparticles according to the example means

Referring to FIG. 21 , in the case of the Example treatment group, unlike the other groups, it can be visually confirmed that the scars present on the skin have almost disappeared.

22 (A) is an image obtained by measuring epidermal thickness by recovering the skin tissue of FIG. 21, and (B) is an image obtained by observing mast cells by recovering the skin tissue of FIG. 21.

Referring to (A) of FIG. 22 , it can be seen that the greatest decrease in epidermal thickness (arrow) appeared in the Example treatment group when hematoxylin & eosin staining of skin tissue was performed.

Referring to (B) of FIG. 22, as a result of observing mast cells associated with an increase in atopic inflammation in skin tissue by staining with toluidine blue, it can be seen that the number is the lowest in the Example treatment group.

Referring to FIG. 23 , it can be seen that the concentrations of IgE antibody, which is a biomarker of atopic disease, IL-1β, which is an inflammatory cytokine, and IL-4, which is a Th2 cytokine, all show a great decrease in the Example treatment group.

Referring to FIG. 24, it was found that there was no penetration of ceria nanoparticles into the skin tissue, and it could be seen that there would be no toxicity problem that may occur when the nanoparticles enter the body.

Through this, it can be confirmed that the hydrogel patch for skin diseases of the present application can not only greatly recover the damage of skin tissue caused by atopy, but also have a positive effect on the improvement and treatment of atopic disease by exhibiting an immunosuppressive action. there was.

The above description of the present application is for illustrative purposes, and those skilled in the art will understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present application. Therefore, the embodiments described above should be understood as illustrative in all respects and not limiting. For example, each component described as a single type may be implemented in a distributed manner, and similarly, components described as distributed may be implemented in a combined form.

The scope of the present application is indicated by the following claims rather than the detailed description above, and all changes or modifications derived from the meaning and scope of the claims and equivalent concepts thereof should be construed as being included in the scope of the present application.

Claims

Hydrogel containing a polymer; and

nanoparticles dispersed in the hydrogel;

including,

The hydrogel and the nanoparticles having different charges,

Hydrogel patch for skin diseases.
According to claim 1,

Due to the hydrogel and the nanoparticles having different charges, the bonding strength of the hydrogel and the nanoparticles increases,

Hydrogel patch for skin diseases.
According to claim 1,

The hydrogel further comprises a crosslinking accelerator,

Hydrogel patch for skin diseases.
According to claim 3,

The cross-linking accelerator improves the mechanical properties of the hydrogel patch for skin diseases,

Hydrogel patch for skin diseases.
According to claim 3,

The crosslinking accelerator is from the group consisting of gluconodeltalactone (GDL), diphenyliodonium nitrate, diphenyliodonium-2-carboxylate and combinations thereof which includes selected ones,

Hydrogel patch for skin diseases.
According to claim 1,

Reactive oxygen species that cause skin diseases are removed by the nanoparticles,

Hydrogel patch for skin diseases.
According to claim 6,

The nanoparticles are selected from the group consisting of iron oxide, manganese oxide, vanadium oxide, vanadium oxide sulfate, zinc oxide, gold, platinum, copper, melamine, lignin, polyphenol, carbon nanotube, graphene, carbon quantum dot, and combinations thereof. Which includes being selected from,

Hydrogel patch for skin diseases.
According to claim 1,

The polymer is alginate (Alg), polyethylene glycol (PEG), chitosan, gelatin, polyacrylic acid (PAAc), polyacrylamide (PAM), polynipam (PNIPAM), agar (Agar), poly( 2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) and combinations thereof,

Hydrogel patch for skin diseases.
preparing a first solution comprising nanoparticles;

preparing a second solution containing a crosslinking agent and a polymer; and

preparing a mixed solution by adding the first solution and a crosslinking accelerator to the second solution;

including,

Method for manufacturing a hydrogel patch for skin diseases.
According to claim 9,

Further comprising the step of solidifying the mixed solution by pouring it into a mold,

Method for manufacturing a hydrogel patch for skin diseases.
According to claim 9,

The nanoparticles are selected from the group consisting of iron oxide, manganese oxide, vanadium oxide, vanadium oxide sulfate, zinc oxide, gold, platinum, copper, melamine, lignin, polyphenol, carbon nanotube, graphene, carbon quantum dot, and combinations thereof. Which includes being selected from,

Method for manufacturing a hydrogel patch for skin diseases.
According to claim 9,

The crosslinking agent is selected from the group consisting of calcium carbonate (CaCO 3 ), calcium chloride (CaCl 2 ), calcium sulfate (CaSO 4 ) and combinations thereof,

Method for manufacturing a hydrogel patch for skin diseases.