KR20190092226A - Composition for forming artificial skin film using hydrophobic nanoparticles, and method of preparing artificial skin film using the same - Google Patents

Abstract

The present invention relates to a composition for forming an artificial skin layer by using hydrophobic nanoparticles, and a method for preparing an artificial skin layer by using the composition for forming an artificial skin layer. The composition for forming an artificial skin layer includes a first agent containing an organopolysiloxane unit, and a second agent comprising nanoparticles coated with a hydrophobic material and a platinum catalyst carried on the nanoparticles.

Description

COMPOSITION FOR FORMING ARTIFICIAL SKIN FILM USING HYDROPHOBIC NANOPARTICLES, AND METHOD OF PREPARING ARTIFICIAL SKIN FILM USING THE SAME}

The present application relates to a composition for forming an artificial skin film using hydrophobic nanoparticles and a method for producing an artificial skin film using the composition for forming an artificial skin film.

Artificial skin is a biomaterial for skin replacement for regenerating skin tissue damaged by severe burns, trauma and skin diseases. Such artificial skin is a material harmless to the human body, and has a function of protecting the wound by forming another layer having elasticity and softness on the skin. Previously, research has been conducted focusing on the development of artificial skin for skin coating to prevent only the influx of harmful substances from outside to protect burns and trauma wounds.

According to a paper published by Nature Materials in 2016 at MIT in the United States, it is possible to form a fast polymer film to develop artificial skin that can improve wrinkles and elasticity in a short time, while improving the skin aesthetically, not medically artificial skin. There is a growing interest in artificial skin technology worldwide.

US 9,114,096 uses a platinum-based Karlstedt's catalyst directly in the name “skin composition and method of use thereof” to induce hydrogensiliconisation. However, since this type of skin film directly utilizes the Calstedt catalyst, there is a limit in the utilization, stability, or safety of the product.

Conventionally, artificial skin membranes prepared by applying a component containing polysiloxane in advance and applying a component having a platinum-based Calstedt catalyst to cause a hydrogen siliconization reaction to crosslink, have a platinum-based catalyst directly stored in cosmetics. In contrast, the activity is poor, and high concentrations of platinum catalysts can cause cytotoxicity. Accordingly, there is a need for a method capable of minimizing cytotoxicity while maintaining the activity of the catalyst.

In addition to improving wrinkles, a method of supporting a functional ingredient or drug on a conventional artificial skin film has not yet been developed to give various skin improvement effects. Thus, carrier-type nanoparticles capable of releasing drugs after skin film formation have been prepared. The need to do so.

Accordingly, the present application is to provide a composition for forming an artificial skin film using hydrophobic nanoparticles and a method for preparing an artificial skin film using the composition for forming an artificial skin film.

However, the problem to be solved by the present application is not limited to the above-mentioned problem, and other problems not mentioned will be clearly understood by those skilled in the art from the following description.

A first aspect of the present disclosure provides an agent comprising an organopolysiloxane unit; And, it provides a composition for forming an artificial skin film comprising a nanoparticle coated with a hydrophobic material and a second agent comprising a platinum catalyst supported on the nanoparticles.

The second aspect of the present application provides a kit for forming an artificial skin film, comprising the composition for forming an artificial skin film according to the first aspect of the present application.

The third aspect of the present application is applied to the skin by applying a first agent comprising an organopolysiloxane unit, and a second agent comprising nanoparticles coated with a hydrophobic material and a platinum catalyst supported on the nanoparticles to the skin To form an artificial skin membrane comprising a polysiloxane polymer; Or artificial skin comprising a polysiloxane polymer by applying a second agent comprising a nanoparticle coated with a hydrophobic material and a platinum catalyst supported on the nanoparticle, and applying a first agent comprising an organopolysiloxane unit to the skin. Provided is a method of making an artificial skin film, the method comprising forming a film.

By forming the artificial skin film by the composition for forming an artificial skin film according to an embodiment of the present application, while the wrinkles of the skin can be improved in a short time (for example, within about 5 minutes), while the elasticity, such as skin, moisture of the skin The protective effect can be maintained.

Composition for forming an artificial skin film according to an embodiment of the present application, while maintaining the stability for a long time storage, it can ensure the safety for the skin.

1, in one embodiment of the present application, is a schematic diagram showing a process of forming a skin film using a composition for forming an artificial skin film comprising a nano-catalyst utilizing hydrophobic nanoparticles.
Figure 2, in one embodiment of the present application, is a manufacturing flowchart of the artificial skin film using the composition for forming a synthetic skin film.
3 is a photograph of non-coated nanoparticles (hydrophilic), and hydrophobic silica nanoparticles coated with PDMS according to an embodiment of the present application in water.
4 is a photograph comparing and measuring contact angles of (a) uncoated silica nanoparticles, and (b) hydrophobic silica nanoparticles coated with PDMS according to an embodiment of the present application.
Figure 5 is a photograph comparing and measuring the contact angle of (a) titanium oxide nanoparticles not coated, and (b) hydrophobic titanium oxide nanoparticles coated with PDMS according to an embodiment of the present application.
FIG. 6 is a photo (a) of uncoated silica nanoparticles (hydrophilic), and hydrophobic silica nanoparticles coated with PDMS according to an embodiment of the present application, respectively, with a platinum catalyst, and centrifugation of (a). It is photograph (b) after separation.
7 is a photograph of artificial skin film formation using only (a) platinum catalyst, and (b) artificial skin film formation using nanoparticles to which platinum catalyst is adsorbed according to an embodiment of the present application.
8A to 8F are graphs showing the difference in surface potential before and after adsorption of a platinum catalyst using zeta-potential in one embodiment of the present application.
9 is a graph showing the adsorption rate according to the ultrasonic reaction time of the platinum catalyst and nanoparticles of the composition for forming an artificial skin film according to one embodiment of the present application.
(A) and (b) of Figure 10, (a) composition for artificial skin film formation using only platinum catalyst, and (b) artificial skin film formation using nanoparticles adsorbed platinum catalyst according to an embodiment of the present application A graph showing the ICP according to the platinum catalyst concentration of the composition for.
FIG. 11 is a schematic diagram showing a lactate dehydrogenase (LDH) analysis method in an example of the present application. FIG.
12 is a graph showing the cytotoxicity of the platinum catalyst alone and the platinum catalyst adsorbed on the nanoparticles according to the example of the present application according to the platinum catalyst concentration.
FIG. 13 is a graph illustrating measurement results (Ra) according to surface roughness parameters when evaluating eye wrinkle coverage of a composition for forming an artificial skin film according to one embodiment of the present application.
FIG. 14 is a graph illustrating measurement results (Rmax) according to surface roughness parameters when evaluating eye wrinkle coverage of a composition for forming an artificial skin film according to one embodiment of the present application.
FIG. 15 is a graph illustrating a standard deviation measurement result before and immediately after application of skin in evaluating makeup sustainability of a composition for forming an artificial skin film according to one embodiment of the present application.
Figure 16, in one embodiment of the present application, a graph showing the measurement results of the standard deviation before and after the application of the skin at the time of makeup makeup evaluation of the composition for forming an artificial skin film after 3 hours.

DETAILED DESCRIPTION Hereinafter, exemplary embodiments of the present disclosure will be described in detail with reference to the accompanying drawings so that those skilled in the art may easily implement the present disclosure. As those skilled in the art would realize, the described embodiments may be modified in various different ways, all without departing from the spirit or scope of the present invention. In the drawings, parts irrelevant to the description are omitted for simplicity of explanation, and like reference numerals designate like parts throughout the specification.

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

Throughout this specification, when a member is located “on” another member, this includes not only when one member is in contact with another member but also when another member exists between the two members.

Throughout this specification, when a part is said to "include" a certain component, it means that it can further include other components, without excluding the other components unless otherwise stated. As used throughout this specification, the terms “about”, “substantially”, and the like, are used at, or in close proximity to, numerical values when manufacturing and material tolerances inherent in the meanings indicated are provided, and an understanding of the present application may occur. Accurate or absolute figures are used to assist in the prevention of unfair use by unscrupulous infringers. As used throughout this specification, the term “step of” or “step of” does not mean “step for”.

Throughout this specification, the term "combination (s) thereof" included in the expression of a makushi form refers to one or more mixtures or combinations selected from the group consisting of components described in the expression of makushi form, It means to include one or more selected from the group consisting of the above components.

Throughout this specification, the description of “A and / or B” means “A or B, or A and B”.

Hereinafter, with reference to the accompanying drawings will be described embodiments and embodiments of the present application; However, the present disclosure may not be limited to these embodiments, examples, and drawings.

A first aspect of the present disclosure provides an agent comprising an organopolysiloxane unit; And, it provides a composition for forming an artificial skin film comprising a nanoparticle coated with a hydrophobic material and a second agent comprising a platinum catalyst supported on the nanoparticles.

In one embodiment of the present application, the nanoparticles that can be used in the composition for forming an artificial skin film may be porous, or may have a wide surface area by having a bend, irregularities, or holes on the surface, but may not be limited thereto. have. For example, the porous nanoparticles may support a platinum-based catalyst, and may form an artificial skin membrane by hydrogen siliconization with an organopolysiloxane unit by the platinum-based catalyst, but may not be limited thereto. .

In one embodiment of the present application, nanoparticles that can be used in the composition for forming an artificial skin film may be harmless to the human body, but may not be limited thereto.

In one embodiment of the present application, the nanoparticles that can be used in the composition for forming an artificial skin film may be porous and harmless to the human body, but may not be limited thereto. For example, when the nanoparticles are porous, the surface area that can be adsorbed becomes wider, so that the number of adsorption of platinum catalyst per nanoparticle increases, resulting in the formation of an artificial skin membrane using a small concentration of nanoparticles. It may be, but may not be limited thereto.

In one embodiment of the present application, the platinum catalyst may be adsorbed on the surface of the nanoparticles coated with the hydrophobic material, but may not be limited thereto. For example, the nanoparticles coated with the hydrophobic material may adsorb the platinum catalyst by hydrophobic-hydrophobic interaction, but may not be limited thereto.

In one embodiment of the present application, the nanoparticles coated with the hydrophobic material may represent a superhydrophobic surface, but may not be limited thereto. The super water-repellent surface is a surface having a very weak bonding force with water, and may represent a surface at which a contact angle with water becomes 150 ° or more. Representative organisms having a natural superhydrophobic surface include, for example, lotus leaves, taro leaves, wings and legs of insects, and have self-cleaning and waterproofing ability to easily remove external contaminants without special work.

In one embodiment of the present application, the composition for forming an artificial skin film may be viscous, but may not be limited thereto.

In one embodiment of the present application, the hydrophobic material is polydimethylsiloxane, gelatin, polyethylene glycol, hydroxypropylmethyl cellulose, methyl cellulose, polyvinylpyrrolidone, starch, ethyl cellulose, alginate, carboxymethyl cellulose, gum arabic , Trigacanth rubber, and combinations thereof may be included, but may not be limited thereto.

In one embodiment of the present application, by coating the nanoparticles with the hydrophobic material, while maintaining the surface of the nanoparticles superhydrophobic, while increasing the reactivity with the co-organic organopolysiloxane unit, but is not limited thereto. Can be.

In one embodiment of the present application, by coating the nanoparticles with the hydrophobic material, it is possible to reduce the amount of catalyst of the platinum catalyst, or to achieve a faster reactivity to accelerate the hydrogen siliconization crosslinking reaction, but is not limited thereto. You may not.

In one embodiment of the present application, the nanoparticles may be biocompatible nanoparticles or biodegradable nanoparticles, but may not be limited thereto. The biocompatible material may mean a material that is not toxic to the human body, is chemically inert and has no immunogenicity, and the biodegradable material may mean a material that can be decomposed by body fluids or microorganisms in a living body. However, this may not be limited.

In one embodiment of the invention, the biocompatible nanoparticles or biodegradable nanoparticles, for example, polyethylene glycol, polylactic acid, polyglycolic acid, chitosan, gelatin, collagen, manan, dextransulfate, alpha-cyclodextrin , Beta-cyclodextrin, gamma-cyclodextrin, fructooligosaccharide, isomaltoligosaccharide, inulin, hyaluronic acid, alginate, glycogen, amylose, carboxy, carboxymethyldextran, beta glucan, hydroxyethyl cellulose, carboxymethyl cellulose, fucoidan , Chondroitin, sodium hyaluronate, lactose, DW-EGF, polyester, polyhydroxyalkanoate, poly (α-hydroxyacid), poly (β-hydroxyacid), poly (3-hydro formula Butyrate-co-valorate; PHBV), poly (3-hydroxypropionate; PHP), poly (3-hydroxyhexanoate; PHH), poly (4- Hydroxyacid), poly (4-hydroxybutyrate), poly (4-hydroxy valerate), poly (4-hydroxyhexanoate), poly (esteramide), polycaprolactone, polylactide, Polyglycolide, poly (lactide-co-glycolide; PLGA), polydioxanone, polyorthoester, polyetherester, polyanhydride, poly (glycolic acid-co-trimethylene carbonate), polyphospho Ester, polyphosphoester urethane, poly (amino acid), polycyanoacrylate, poly (trimethylene carbonate), poly (iminocarbonate), poly (tyrosine carbonate), polycarbonate, poly (tyrosine arylate), poly Alkylene oxalates, polyphosphazenes, PHA-PEG, ethylene vinyl alcohol copolymers (EVOH), polyurethanes, silicones, polyesters, polyolefins, polyisobutylene and ethylene-alpha Copolymers, styrene-isobutylene-styrene triblock copolymers, acrylic polymers and copolymers, vinyl halide polymers and copolymers, polyvinyl chloride, polyvinyl ether, polyvinyl methyl ether, polyvinylidene halides, polyvinylidene fluoride Ride, polyvinylidene chloride, polyfluoroalkene, polyperfluoroalkene, polyacrylonitrile, polyvinyl ketone, polyvinyl aromatics, polystyrene, polyvinyl ester, polyvinyl acetate, ethylene-methyl methacrylate copolymer , Acrylonitrile-styrene copolymer, ABS resin and ethylene-vinyl acetate copolymer, polyamide, alkyd resin, polyoxymethylene, polyimide, polyether, polyacrylate, polymethacrylate, polyacrylic acid-co-male Acids, chitosan, dextran, cellulose, heparin, alginate, inulin, starch, Glycogen, and combinations thereof may be included, but may not be limited thereto.

In one embodiment of the present application, the nanoparticles may include, but not limited to, those selected from the group consisting of silica, titanium oxide, zinc oxide, and combinations thereof.

In one embodiment of the present application, the titanium oxide may effectively block ultraviolet rays through absorption, scattering, or reflection in a broad wavelength region, for example, a wavelength in the range of about 280 nm to about 400 nm, cosmetic composition In use, but may indicate a more natural feeling, but may not be limited thereto.

In one embodiment of the present application, the titanium oxide is physically very stable, has a high refractive index, and a small particle size, and thus excellent in chemical properties such as whiteness, hiding power, coloring power, and thus, even when applied to the skin, only the skin is applied to the cosmetic composition. It may have a sunscreen effect, but may not be limited thereto.

In one embodiment of the present application, since the titanium oxide has a strong cohesive force between particles, the dispersion force may be reduced, but may not be limited thereto. Thus, by coating a hydrophobic material on the titanium oxide can reduce the cohesive force to increase the dispersibility, but may not be limited thereto.

In one embodiment of the present application, when the nanoparticles exhibit hydrophilicity, adsorption does not occur well after the reaction with the platinum catalyst exhibiting hydrophobicity, separation may appear, but may not be limited thereto.

In one embodiment of the present application, the titanium oxide coated with the hydrophobic material may exhibit a hydrophobic property, and thus may support a platinum catalyst having hydrophobic properties, but may not be limited thereto.

In one embodiment of the present application, the hydrophobic coating method may be performed through deposition, but may not be limited thereto. For example, a liquid or gel-like organic polymer is placed in a reaction vessel, the nanoparticles are placed in a layered structure with a separator in a net form therebetween, and then the organic polymer is deposited on the nanoparticles by vapor phase by heating. To form a hydrophobic film, but may not be limited thereto.

In one embodiment of the present application, the hydrophobic nanoparticles loaded with the platinum catalyst may maintain the activity of the catalyst, may be stored for a long time, but may not be limited thereto.

In one embodiment of the present application, the hydrophobic nanoparticles loaded with the platinum catalyst may alleviate the toxicity of skin or cells, but may not be limited thereto.

In one embodiment of the present application, mixing the first agent comprising the organopolysiloxane unit and the second agent comprising the hydrophobic nanoparticles loaded with the catalyst to form a thin artificial skin film in minutes. Accordingly, the activity of the platinum catalyst can be maintained, and since the platinum catalyst comes out of the mixed solution after the first agent and the second agent are mixed, the catalyst is not directly exposed to the skin, thereby minimizing skin or cytotoxicity. However, this may not be limited.

In one embodiment of the present invention, the platinum catalyst is a platinum carbonyl cyclovinylmethylsiloxane complex, platinum divinyltetramethyldisiloxane complex, platinum cyclovinylmethylsiloxane complex, platinum octanealdehyde / octanol complex, and combinations thereof It may be to include one selected from the group consisting of, but may not be limited thereto. For example, the platinum catalyst may be Karlstedt's catalyst, but may not be limited thereto.

In one embodiment of the present application, the content (% by weight) of the platinum may range from about 0.05% to about 10% based on the total weight of the second agent, but may not be limited thereto. For example, the content (% by weight) of platinum may be about 0.05% to about 10%, about 0.05% to about 8%, about 0.05% to about 6%, and about 0.05% to the total weight of the second agent. About 4%, about 0.05% to about 1%, about 1% to about 10%, about 1% to about 8%, about 1% to about 6%, about 1% to about 4%, about 1% to about 2 %, About 2% to about 10%, about 2% to about 8%, about 2% to about 6%, about 2% to about 4%, about 4% to about 10%, about 4% to about 8%, From about 4% to about 6%, about 6% to about 10%, about 6% to about 8%, about 8% to about 10%, about 0.05% to about 0.1%, or about 0.1% to about 1% It may be, but may not be limited thereto.

In one embodiment of the present application, an appropriate solvent may be used to adsorb the platinum catalyst to the nanoparticles coated with the hydrophobic material.

In one embodiment of the present application, the second agent may be prepared by mixing the solution containing the nanoparticles coated with a hydrophobic material and the solution containing the platinum catalyst and then ultrasonic reaction, but is not limited thereto. have. For example, the ultrasonic response is about 1 minute to about 10 hours, about 1 minute to about 5 hours, about 1 minute to about 4 hours, about 1 minute to about 1 hour, about 1 minute to about 40 minutes, about 1 Minutes to about 30 minutes, about 30 minutes to about 10 hours, about 30 minutes to about 5 hours, about 30 minutes to about 4 hours, about 30 minutes to about 1 hour, or about 5 minutes to about 30 minutes It may be, but may not be limited thereto.

In one embodiment of the present application, the preparation process of the second agent may further include, for about 1 minute to about 1 hour at room temperature for adsorption of the platinum catalyst to the nanoparticles after the ultrasonic reaction. However, this may not be limited.

In one embodiment of the present application, the solvent of the solution containing the platinum catalyst may include water, alcohol, or an organic solvent, but may not be limited thereto. For example, the organic solvent may be one selected from the group consisting of methanol, ethanol, isopropanol, n-hexane, chloroform, cyclohexane, ether, dichloromethane, benzene, ethyl acetate, and combinations thereof. However, this may not be limited.

In one embodiment of the present application, when the solvent of the solution containing the platinum catalyst is an organic solvent exhibiting a non-polar, the hydrophobic-hydrophobic interaction between the platinum catalyst and the nanoparticles mixed in the solvent may not be well However, this may not be limited.

In one embodiment of the present application, the solvent content of the solution containing the platinum catalyst may range from about 50% to 90%, but may not be limited thereto. For example, when the solvent is ethanol, nanoparticles coated with the hydrophobic material may not be mixed well with hydrophilic solvent in less than about 50% ethanol, and the platinum catalyst is completely dissolved in more than about 90% ethanol. May not be adsorbed by the nanoparticles, but may not be limited thereto.

In one embodiment of the present application, nanoparticles coated with a hydrophobic material may further include a functional protein or drug, but may not be limited thereto. For example, in the process of preparing the nanoparticles coated with the hydrophobic material, the functional protein or drug may be additionally included to be adsorbed or synthesized, but may not be limited thereto.

In one embodiment of the present application, the drug is a chemical drug, protein medicine, peptide medicine, gene therapy nucleic acid molecule, anti-inflammatory, analgesic, anti-arthritis, antispasmodic, antidepressant, antipsychotic, neurostable, anti-anxiety, drug Antagonists, antiparkin disease drugs, cholinergic agonists, anticancer agents, antiangiogenic agents, immunosuppressants, antiviral agents, antibiotics, appetite suppressants, analgesics, anticholinergic agents, antihistamines, antimigraine, hormones, coronary vessels, cerebrovascular or Peripheral vasodilators, contraceptives, antithrombotics, diuretics, antihypertensives, cardiovascular diseases, cosmetic ingredients (e.g., wrinkle improvement agents, skin aging inhibitors and skin whitening agents), and combinations thereof. It may be, but may not be limited thereto.

In one embodiment of the present application, the drug may be a protein medicine, a peptide medicine, or a vitamin containing, but may not be limited thereto. For example, hormones, hormone analogs, enzymes, inhibitors, signaling proteins or portions thereof, antibodies or portions thereof, short chain antibodies, binding proteins or binding domains thereof, antigens, adhesion proteins, structural proteins, regulatory proteins, toxin proteins, Cytokines, transcriptional regulators, blood clotting factors and vaccines, and the like. More specifically, the protein / peptide medicament includes insulin, insulin-like growth factor 1 (IGF-1), growth hormone, erythropoietin, granulocyte-colony stimulating factors (G-CSFs), and GM-CSFs (granulocytes). / macrophage-colony stimulating factors, interferon alpha, interferon beta, interferon gamma, interleukin-1 alpha and beta, interleukin-3, interleukin-4, interleukin-6, interleukin-2, epidermal growth factors (EGGFs), calcitonin ), Adrenocorticotropic hormone (ACTH), tumor necrosis factor (TNF), atobisban, buserelin, cetrorelix, deslorelin, desmopressin ), Dynorphin A (1-13), elcatonin, eleidosin, eptifibatide, growth hormone releasing hormone-II (GHRH-II), gonadore Gonadorelin, goserelin, hystrelin, leuprorelin, lifelessin ( lypressin, octreotide, oxytocin, phytocin, pitressin, secretin, sincalide, terlipressin, thymopentin, thymosine ) α1, triptorelin, bivalirudin, carbetocin, cyclosporin, exedine, lanreotide, LHRH (luteinizing hormone-releasing hormone), na At least one selected from the group consisting of parelin, parathyroid hormone, pramlintide, T-20 (enfuvirtide), thymalfasin, ziconoid, and combinations thereof It may be, but may not be limited thereto.

In one embodiment of the present application, the functional protein, the functional protein is etanercept (etanercept), epoetin alpha (epoetin alpha), infliximab, interferon beta (interferon alpha), insulin lispro (insulin) lispro, filgrastim, imiglucerase, glatiramer acetate, rituximab, pegfilgrastim, insulin grastim, Adalimumab, trastuzumab, bevacizumab, ranibizumab, insulin, growth hormone, tumor necrosis factor-alpha , Interleukin-7, insulin-like growth factor 2, interferon gamma, interferon alpha, interleukin-2, bone formation protein ( osteogenic protein), recombinant plasminogen activator (Recombinant plasminogen-activator), Bone morphogenetic protein 2, antifungal peptide, tissue plasminogen activator, immunoglobulin G, erythropoietin, Granulocyte-macrophage stimulating factor, granulocyte-colony stimulating factor, muromomab, aciximab, dacizumab, daclizumab, basilic Simabimab, palivizumab, ibritumomab, ibritumomab, omalizumab, epalizumab, tositumomab, cetuximab, cetuximab, natalizumab (natalizumab), alkaline phosphatase (PhoA), levan fructotransferase (LFT), cellulose binding domain, cholera toxin B, organic phosphate One selected from the group consisting of enzymes (Organophosphohydrolase), calcitonin, blood coagulation factors, hirudin, monoclonal antibody 5T4, and combinations thereof It may be, but may not be limited thereto.

The second aspect of the present application provides a kit for forming an artificial skin film, comprising the composition for forming an artificial skin film according to the first aspect of the present application.

With respect to the kit for forming the artificial skin film according to the second aspect of the present application, detailed descriptions of portions overlapping with the first aspect of the present application have been omitted, but the contents described in the first aspect of the present application may be The same can be applied to the second aspect.

The third aspect of the present application is applied to the skin by applying a first agent comprising an organopolysiloxane unit, and a second agent comprising nanoparticles coated with a hydrophobic material and a platinum catalyst supported on the nanoparticles to the skin To form an artificial skin membrane comprising a polysiloxane polymer; Alternatively, a synthetic agent comprising a polysiloxane polymer is prepared by applying a second agent comprising a nanoparticle coated with a hydrophobic material and a platinum catalyst supported on the nanoparticle, and applying a first agent including an organopolysiloxane unit to the skin. Provided is a method for manufacturing an artificial skin film, comprising forming a skin film.

With respect to the method for manufacturing the artificial skin film according to the third aspect of the present application, detailed descriptions of portions overlapping with the first side and the second side of the present application are omitted, although the description is omitted the first and second aspects of the present application. The content described in the aspects may equally apply to the third aspect of the present application.

In one embodiment of the present application, the second agent may be prepared by mixing the solution containing the nanoparticles coated with the hydrophobic material and the solution containing the platinum catalyst and then ultrasonic reaction, but is not limited thereto. Can be.

For example, the ultrasonic response is about 1 minute to about 10 hours, about 1 minute to about 5 hours, about 1 minute to about 4 hours, about 1 minute to about 1 hour, about 1 minute to about 40 minutes, about 1 Minutes to about 30 minutes, about 30 minutes to about 10 hours, about 30 minutes to about 5 hours, about 30 minutes to about 4 hours, about 30 minutes to about 1 hour, or about 5 minutes to about 30 minutes It may be, but may not be limited thereto.

In one embodiment of the present application, the preparation process of the second agent may further include, for about 1 minute to about 1 hour at room temperature for adsorption of the platinum catalyst to the nanoparticles after the ultrasonic reaction. However, this may not be limited.

In one embodiment of the present application, the nanoparticles may be porous, or have a curved surface, irregularities, or holes on the surface to have a wide surface area, but may not be limited thereto. For example, the porous nanoparticles may support a platinum-based catalyst, and may form an artificial skin membrane by hydrogen siliconization with an organopolysiloxane unit by the platinum-based catalyst, but may not be limited thereto. .

In one embodiment of the present application, the nanoparticles may be harmless to the human body, but may not be limited thereto.

In one embodiment of the present application, the nanoparticles are porous, may be harmless to the human body, but may not be limited thereto. For example, when the nanoparticles are porous, the surface area that can be adsorbed becomes wider, so that the number of adsorption of platinum catalyst per nanoparticle increases, resulting in the formation of an artificial skin membrane using a small concentration of nanoparticles. It may be, but may not be limited thereto.

In one embodiment of the present application, the platinum catalyst may be adsorbed on the surface of the nanoparticles coated with the hydrophobic material, but may not be limited thereto. For example, the nanoparticles coated with the hydrophobic material may adsorb the platinum catalyst by hydrophobic-hydrophobic interaction, but may not be limited thereto.

In one embodiment of the present application, the nanoparticles coated with the hydrophobic material may represent a superhydrophobic surface, but may not be limited thereto. The super water-repellent surface is a surface having a very weak bonding force with water, and may represent a surface at which a contact angle with water becomes 150 ° or more. Representative organisms having a natural superhydrophobic surface include, for example, lotus leaves, taro leaves, wings and legs of insects, and have self-cleaning and waterproofing ability to easily remove external contaminants without special work.

In one embodiment of the present application, the hydrophobic material is polydimethylsiloxane, gelatin, polyethylene glycol, hydroxypropylmethyl cellulose, methyl cellulose, polyvinylpyrrolidone, starch, ethyl cellulose, alginate, carboxymethyl cellulose, gum arabic , Trigacanth rubber, and combinations thereof may be included, but may not be limited thereto.

In one embodiment of the present application, by coating the nanoparticles with the hydrophobic material, while maintaining the surface of the nanoparticles superhydrophobic, while increasing the reactivity with the co-organic organopolysiloxane unit, but is not limited thereto. Can be.

In one embodiment of the present application, by coating the nanoparticles with the hydrophobic material, it is possible to reduce the amount of catalyst of the platinum catalyst, or to achieve a faster reactivity to accelerate the hydrogen siliconization crosslinking reaction, but is not limited thereto. You may not.

In one embodiment of the present application, the nanoparticles may be biocompatible nanoparticles or biodegradable nanoparticles, but may not be limited thereto. The biocompatible material may mean a material that is not toxic to the human body, is chemically inert and has no immunogenicity, and the biodegradable material may mean a material that can be decomposed by body fluids or microorganisms in a living body. However, this may not be limited.

In one embodiment of the invention, the biocompatible nanoparticles or biodegradable nanoparticles, for example, polyethylene glycol, polylactic acid, polyglycolic acid, chitosan, gelatin, collagen, manan, dextransulfate, alpha-cyclodextrin , Beta-cyclodextrin, gamma-cyclodextrin, fructooligosaccharide, isomaltoligosaccharide, inulin, hyaluronic acid, alginate, glycogen, amylose, carboxy, carboxymethyldextran, beta glucan, hydroxyethyl cellulose, carboxymethyl cellulose, fucoidan , Chondroitin, sodium hyaluronate, lactose, DW-EGF, polyester, polyhydroxyalkanoate, poly (α-hydroxyacid), poly (β-hydroxyacid), poly (3-hydro formula Butyrate-co-valorate; PHBV), poly (3-hydroxypropionate; PHP), poly (3-hydroxyhexanoate; PHH), poly (4- Hydroxyacid), poly (4-hydroxybutyrate), poly (4-hydroxy valerate), poly (4-hydroxyhexanoate), poly (esteramide), polycaprolactone, polylactide, Polyglycolide, poly (lactide-co-glycolide; PLGA), polydioxanone, polyorthoester, polyetherester, polyanhydride, poly (glycolic acid-co-trimethylene carbonate), polyphospho Ester, polyphosphoester urethane, poly (amino acid), polycyanoacrylate, poly (trimethylene carbonate), poly (iminocarbonate), poly (tyrosine carbonate), polycarbonate, poly (tyrosine arylate), poly Alkylene oxalates, polyphosphazenes, PHA-PEG, ethylene vinyl alcohol copolymers (EVOH), polyurethanes, silicones, polyesters, polyolefins, polyisobutylene and ethylene-alpha Copolymers, styrene-isobutylene-styrene triblock copolymers, acrylic polymers and copolymers, vinyl halide polymers and copolymers, polyvinyl chloride, polyvinyl ether, polyvinyl methyl ether, polyvinylidene halides, polyvinylidene fluoride Ride, polyvinylidene chloride, polyfluoroalkene, polyperfluoroalkene, polyacrylonitrile, polyvinyl ketone, polyvinyl aromatics, polystyrene, polyvinyl ester, polyvinyl acetate, ethylene-methyl methacrylate copolymer , Acrylonitrile-styrene copolymer, ABS resin and ethylene-vinyl acetate copolymer, polyamide, alkyd resin, polyoxymethylene, polyimide, polyether, polyacrylate, polymethacrylate, polyacrylic acid-co-male Acids, chitosan, dextran, cellulose, heparin, alginate, inulin, starch, Glycogen, and combinations thereof may be included, but may not be limited thereto.

In one embodiment of the present application, the nanoparticles may include, but not limited to, those selected from the group consisting of silica, titanium oxide, zinc oxide, and combinations thereof.

In one embodiment of the present application, the titanium oxide may effectively block ultraviolet rays through absorption, scattering, or reflection in a broad wavelength region, for example, a wavelength in the range of about 280 nm to about 400 nm, cosmetic composition In use, but may indicate a more natural feeling, but may not be limited thereto.

In one embodiment of the present application, the titanium oxide is physically very stable, has a high refractive index, and a small particle size, and thus excellent in chemical properties such as whiteness, hiding power, coloring power, and thus, even when applied to the skin, only the skin is applied to the cosmetic composition. It may have a sunscreen effect, but may not be limited thereto.

In one embodiment of the present application, since the titanium oxide has a strong cohesive force between particles, the dispersion force may be reduced, but may not be limited thereto. Thus, by coating a hydrophobic material on the titanium oxide can reduce the cohesive force to increase the dispersibility, but may not be limited thereto.

In one embodiment of the present application, when the nanoparticles exhibit hydrophilicity, adsorption does not occur well after the reaction with the platinum catalyst exhibiting hydrophobicity, separation may appear, but may not be limited thereto.

In one embodiment of the present application, the titanium oxide coated with the hydrophobic material may exhibit a hydrophobic property, and thus may support a platinum catalyst having hydrophobic properties, but may not be limited thereto.

In one embodiment of the present application, the hydrophobic coating method may be performed through deposition, but may not be limited thereto. For example, a liquid or gel-like organic polymer is placed in a reaction vessel, the nanoparticles are placed in a layered structure with a separator in a net form therebetween, and then the organic polymer is deposited on the nanoparticles by vapor phase by heating. It may be to form a film, but may not be limited thereto.

In one embodiment of the present application, the hydrophobic nanoparticles loaded with the platinum catalyst may maintain the activity of the catalyst, may be stored for a long time, but may not be limited thereto.

In one embodiment of the present application, the hydrophobic nanoparticles loaded with the platinum catalyst may alleviate the toxicity of skin or cells, but may not be limited thereto.

In one embodiment of the present application, mixing the first agent comprising the organopolysiloxane unit and the second agent comprising the hydrophobic nanoparticles loaded with the catalyst to form a thin artificial skin film in minutes. Accordingly, the activity of the platinum catalyst can be maintained, and since the platinum catalyst comes out of the mixed solution after the first agent and the second agent are mixed, the catalyst is not directly exposed to the skin, thereby minimizing skin or cytotoxicity. However, this may not be limited.

In one embodiment of the present invention, the platinum catalyst is a platinum carbonyl cyclovinylmethylsiloxane complex, platinum divinyltetramethyldisiloxane complex, platinum cyclovinylmethylsiloxane complex, platinum octanealdehyde / octanol complex, and combinations thereof It may be to include one selected from the group consisting of, but may not be limited thereto. For example, the platinum catalyst may be Karlstedt's catalyst, but may not be limited thereto.

In one embodiment of the present application, the content (% by weight) of the platinum may range from about 0.05% to about 10% based on the total weight of the second agent, but may not be limited thereto. For example, the content (% by weight) of platinum may be about 0.05% to about 10%, about 0.05% to about 8%, about 0.05% to about 6%, and about 0.05% to the total weight of the second agent. About 4%, about 0.05% to about 1%, about 1% to about 10%, about 1% to about 8%, about 1% to about 6%, about 1% to about 4%, about 1% to about 2 %, About 2% to about 10%, about 2% to about 8%, about 2% to about 6%, about 2% to about 4%, about 4% to about 10%, about 4% to about 8%, From about 4% to about 6%, about 6% to about 10%, about 6% to about 8%, about 8% to about 10%, about 0.05% to about 0.1%, or about 0.1% to about 1% It may be, but may not be limited thereto.

In one embodiment of the present application, an appropriate solvent may be used to adsorb the platinum catalyst to the nanoparticles coated with the hydrophobic material.

In one embodiment of the present application, the second agent may be prepared by mixing the solution containing the nanoparticles coated with a hydrophobic material and the solution containing the platinum catalyst and then ultrasonic reaction, but is not limited thereto. have.

In one embodiment of the present application, the solvent of the solution containing the platinum catalyst may include water, alcohol, or an organic solvent, but may not be limited thereto. For example, the organic solvent may be one selected from the group consisting of methanol, ethanol, isopropanol, n-hexane, chloroform, cyclohexane, ether, dichloromethane, benzene, ethyl acetate, and combinations thereof. However, this may not be limited.

In one embodiment of the present application, when the solvent of the solution containing the platinum catalyst is an organic solvent exhibiting a non-polar, the hydrophobic-hydrophobic interaction between the platinum catalyst and the nanoparticles mixed in the solvent may not be well However, this may not be limited.

In one embodiment of the present application, the solvent content of the solution containing the platinum catalyst may range from about 50% to 90%, but may not be limited thereto. For example, when the solvent is ethanol, nanoparticles coated with the hydrophobic material may not be mixed well with hydrophilic solvent in less than about 50% ethanol, and the platinum catalyst is completely dissolved in more than about 90% ethanol. May not be adsorbed by the nanoparticles, but may not be limited thereto.

In one embodiment of the present application, the viscosity of the solution containing the platinum catalyst may range from about 200 to about 1,000 Cs, but may not be limited thereto. For example, about 200 to about 1,000 Cs, about 200 to about 800 Cs, about 200 to about 600 Cs, about 200 to about 400 Cs, about 400 to about 1,000 Cs, about 400 to about 800 Cs, about 400 to about 600 Cs, about 600 to about 1,000 Cs, about 600 to about 800 Cs, or about 800 to about 1,000 Cs, but may not be limited thereto.

In one embodiment of the present application, the nanoparticles coated with the hydrophobic material may further include a functional protein or drug, but may not be limited thereto. For example, in the process of preparing the nanoparticles coated with the hydrophobic material, the functional protein or drug may be additionally included to be adsorbed or synthesized, but may not be limited thereto.

In one embodiment of the present application, the drug is a chemical drug, protein medicine, peptide medicine, gene therapy nucleic acid molecule, anti-inflammatory, analgesic, anti-arthritis, antispasmodic, antidepressant, antipsychotic, neurostable, anti-anxiety, drug Antagonists, antiparkin disease drugs, cholinergic agonists, anticancer agents, antiangiogenic agents, immunosuppressants, antiviral agents, antibiotics, appetite suppressants, analgesics, anticholinergic agents, antihistamines, antimigraine, hormones, coronary vessels, cerebrovascular or Peripheral vasodilators, contraceptives, antithrombotics, diuretics, antihypertensives, cardiovascular diseases, cosmetic ingredients (e.g., wrinkle improvement agents, skin aging inhibitors and skin whitening agents), and combinations thereof. It may be, but may not be limited thereto.

In one embodiment of the present application, the drug may be a protein medicine, a peptide medicine, or a vitamin containing, but may not be limited thereto. For example, hormones, hormone analogs, enzymes, inhibitors, signaling proteins or portions thereof, antibodies or portions thereof, short chain antibodies, binding proteins or binding domains thereof, antigens, adhesion proteins, structural proteins, regulatory proteins, toxin proteins, Cytokines, transcriptional regulators, blood clotting factors and vaccines, and the like. More specifically, the protein / peptide medicament includes insulin, insulin-like growth factor 1 (IGF-1), growth hormone, erythropoietin, granulocyte-colony stimulating factors (G-CSFs), and GM-CSFs (granulocytes). / macrophage-colony stimulating factors, interferon alpha, interferon beta, interferon gamma, interleukin-1 alpha and beta, interleukin-3, interleukin-4, interleukin-6, interleukin-2, epidermal growth factors (EGGFs), calcitonin ), Adrenocorticotropic hormone (ACTH), tumor necrosis factor (TNF), atobisban, buserelin, cetrorelix, deslorelin, desmopressin ), Dynorphin A (1-13), elcatonin, eleidosin, eptifibatide, growth hormone releasing hormone-II (GHRH-II), gonadore Gonadorelin, goserelin, hystrelin, leuprorelin, leiprenin ( lypressin, octreotide, oxytocin, phytocin, pitressin, secretin, sincalide, terlipressin, thymopentin, thymosine ) α1, triptorelin, bivalirudin, carbetocin, cyclosporin, exedine, lanreotide, LHRH (luteinizing hormone-releasing hormone), na At least one selected from the group consisting of parelin, parathyroid hormone, pramlintide, T-20 (enfuvirtide), thymalfasin, ziconoid, and combinations thereof It may be, but may not be limited thereto.

In one embodiment of the present application, the functional protein, the functional protein is etanercept (etanercept), epoetin alpha (epoetin alpha), infliximab, interferon beta (interferon alpha), insulin lispro (insulin) lispro, filgrastim, imiglucerase, glatiramer acetate, rituximab, pegfilgrastim, insulin grastim, Adalimumab, trastuzumab, bevacizumab, ranibizumab, insulin, growth hormone, tumor necrosis factor-alpha , Interleukin-7, insulin-like growth factor 2, interferon gamma, interferon alpha, interleukin-2, bone formation protein ( osteogenic protein), recombinant plasminogen activator (Recombinant plasminogen-activator), Bone morphogenetic protein 2, antifungal peptide, tissue plasminogen activator, immunoglobulin G, erythropoietin, Granulocyte-macrophage stimulating factor, granulocyte-colony stimulating factor, muromomab, aciximab, dacizumab, daclizumab, basilic Simabimab, palivizumab, ibritumomab, ibritumomab, omalizumab, epalizumab, tositumomab, cetuximab, cetuximab, natalizumab (natalizumab), alkaline phosphatase (PhoA), levan fructotransferase (LFT), cellulose binding domain, cholera toxin B, organic phosphate One selected from the group consisting of enzymes (Organophosphohydrolase), calcitonin, blood coagulation factors, hirudin, monoclonal antibody 5T4, and combinations thereof It may be, but may not be limited thereto.

In one embodiment of the present application, the content of the platinum catalyst with respect to the total weight of the second agent may range from about 0.05% to about 20%, but may not be limited thereto. For example, the content of the platinum catalyst is about 0.05% to about 20%, about 0.05% to about 18%, about 0.05% to about 16%, about 0.05% to about 14%, about 0.05% to about 12%, About 0.05% to about 10%, about 0.05% to about 5%, about 0.05% to about 2%, about 0.05% to about 1%, about 0.05% to about 0.1%, about 0.1% to about 20%, about 0.1 % To about 18%, about 0.1% to about 16%, about 0.1% to about 14%, about 0.1% to about 12%, about 0.1% to about 10%, about 0.1% to about 5%, about 0.1% to About 2%, about 0.1% to about 1%, about 1% to about 20%, about 1% to about 16%, about 1% to about 12%, about 1% to about 10%, about 1% to about 5 %, About 5% to about 20%, about 5% to about 15%, about 5% to about 10%, about 10% to about 20%, about 10% to about 15%, or about 15% to about 20% Range, but may not be limited to this.

1 and 2, one embodiment of the artificial skin film manufacturing method can be described in detail. First, a nanoparticle coated with a hydrophobic surface and a platinum-based catalyst are prepared and weighed. In this case, the platinum catalyst may include a Karlstedt catalyst, the content of which may be 2% based on the total weight of the second agent, and the viscosity of the Karlstedt catalyst in solution may be about 200 cS. This may not be limited. The viscosity of the solution of the Karlstedt catalyst in the form of a solution that can be used as the platinum catalyst may have a variety of values of the commercially available Karlstedt catalyst, various commercially available Karlstedt catalysts can be selected and used appropriately. Then, the nanoparticles coated with the hydrophobic material are dispersed in a solvent and then washed. The dispersion may be performed by ultrasonic waves, but may not be limited thereto.

Thereafter, the platinum catalyst is mixed and dispersed in a solvent. In this case, the dispersion may be performed through the ultrasonic waves as described above, but may not be limited thereto. The dispersed platinum catalyst and the nanoparticles coated with the hydrophobic material are mixed and mixed by an ultrasonic reaction to support the platinum catalyst on the nanoparticles coated with the hydrophobic material. In this case, the nanoparticles coated with the hydrophobic material may carry a functional protein or drug together, but may not be limited thereto.

Finally, the nanoparticles loaded with the platinum catalyst are centrifuged to remove and wash the supernatant to obtain two agents, and the two agents are mixed with one agent containing organopolysiloxane units to form an artificial skin membrane.

Hereinafter, the present invention will be described in more detail with reference to examples of the present application, but the following examples are merely illustrated to aid the understanding of the present application, and the content of the present application is not limited to the following examples.

EXAMPLE

1. Preparation of artificial skin film forming composition

1-1. Compositions for forming artificial skin membranes (1)

Part 1: Ingredient Composition and Preparation

1st is An agent comprising organopolysiloxane units, which is composed of a silicone phase and an aqueous phase. First, in order to prepare an aqueous phase of the above, put the samples shown in Table 1 in a 300 mL bottle, then mixed for 15 minutes at 350 rpm using a homogenizer, and then increase the step by step 450 rpm, 550 Mix for 15 minutes at rpm. Thereafter, the samples shown in Table 1 below were prepared in another 300 mL bottle for preparation of the first silicone phase, followed by mixing at 650 rpm for 15 minutes using a homogenizer. Then, the aqueous solution phase was poured slowly onto the silicon being mixed. After mixing the mixed solution using a homogenizer for 10 minutes at 650 rpm, 27% of fumed silica was added and then mixed again for 5 minutes. Thereafter, 10 N sodium hydroxide was added, followed by mixing at 650 rpm for 5 minutes using a homogenizer to obtain a first agent.

Part 2: Ingredient Composition and Preparation

The second agent is a preparation on which a platinum catalyst is supported and is composed of a silicon phase and an aqueous solution phase. Among them, in order to prepare an aqueous phase, first, the samples shown in Table 2 were put in a 300 mL bottle, and then mixed at a 280 rpm for 10 minutes using a homogenizer. Next, in order to prepare a second silicone phase, the silicon phase samples shown in Table 2 below were placed in another 300 mL bottle, and mixed for 10 minutes at 650 rpm using a homogenizer. Then, the aqueous phase was poured slowly on the said silicon being mixed. Next, the mixed solution was mixed for 5 minutes at 680 rpm using a homogenizer. After mixing, 2% Pt was added according to the ratio shown in Table 2 below, followed by mixing at 700 rpm for 5 minutes using a homogenizer to obtain a second agent.

1-2. synthetic Skin  Forming composition (2)

Part 1: Ingredient Composition and Preparation

To prepare a first aqueous phase consisting of a silicone phase and an aqueous phase, put the samples shown in Table 3 in a 300 mL bottle, mix for 15 minutes at 350 rpm using a homogenizer, and then step rpm The mixture was raised to 450 rpm and 550 rpm for 15 minutes each. Thereafter, the samples shown in Table 3 below were put in another 300 mL bottle for preparation of the first silicone phase, and mixed for 15 minutes at 650 rpm using a homogenizer. Then, the aqueous phase was poured slowly onto the silicon being mixed. After mixing the mixed solution at 650 rpm for 10 minutes using a homogenizer, 27% of fumed silica was added and then mixed again for 5 minutes. 10 N sodium hydroxide was added to the mixed solution, followed by mixing for 5 minutes at 650 rpm using a homogenizer to obtain a first agent.

Part 2: Ingredient Composition and Preparation

The second agent is a preparation on which a platinum catalyst is supported and is formed of a silicon phase and an aqueous solution phase. Among them, in order to prepare an aqueous phase, the samples shown in Table 4 were placed in a 300 mL bottle, followed by mixing at 280 rpm for 10 minutes using a homogenizer. Then, the silicon phase samples shown in Table 4 below were prepared in a second 300 mL bottle for the preparation of the second silicone phase, and then mixed at 650 rpm for 10 minutes using a homogenizer. After slowly pouring the aqueous solution onto the silicone, the mixture was mixed at 680 rpm for 5 minutes using a homogenizer. 2% platinum catalyst was added to the mixed solution according to the ratio shown in Table 4, followed by mixing at 700 rpm for 5 minutes using a homogenizer to obtain a second agent.

2. artificial Skin  Preparation of the composition for forming and artificial Skin  formation

2-1. synthetic Skin  Formation-(1)

In a 15 mL container was weighed 60 mg of silica nanoparticles, nanoparticles coated with a hydrophobic material, and 6 mL of a 70% ethanol solution was added dropwise. After stirring to mix the silica nanoparticles coated with the hydrophobic material and ethanol using a stirrer, the particles were dispersed for 30 minutes using an ultrasonic reactor. The dispersed nanoparticles were centrifuged at 10000 rpm for 10 minutes and the supernatant was removed. This process was repeated twice to disperse and wash the silica particles. Next, 30 mg of the platinum catalyst was weighed into a new container, mixed with 1 mL of 70% ethanol, and then dispersed well in an ultrasonic reactor. The washed silica nanoparticles were transferred to a vessel containing the platinum catalyst to have a total volume of 6 mL. The silica nanoparticles and the platinum catalyst were stirred and mixed, and then reacted for 20 minutes using an ultrasonic reactor, and then left at room temperature for 1 hour. Thereafter, the reaction sample was centrifuged at 10000 rpm for 10 minutes and the supernatant was removed and washed twice. After washing, the sample was dried and then prepared by mixing a second emulsion with a composition excluding the catalyst. After the first agent prepared above was applied to the skin, a second agent emulsion was applied thereon to form an artificial skin membrane.

2-2. synthetic Skin  Formation-(2)

In a 15 mL container was weighed 60 mg of titanium oxide particles, nanoparticles coated with hydrophobic material, and 6 mL of 70% ethanol solution was added dropwise. After stirring to mix using a stirrer, the particles were dispersed for 30 minutes using an ultrasonic reactor. The dispersed nanoparticles were centrifuged at 10000 rpm for 10 minutes and the supernatant was removed. This process was repeated twice to disperse and wash the titanium oxide particles. Next, 30 mg of the platinum catalyst was quantified in a new container, mixed with 1 mL of 70% ethanol, and dispersed well in an ultrasonic reactor. The titanium oxide nanoparticles washed were transferred to a vessel containing the platinum catalyst to have a total volume of 6 mL. The titanium oxide nanoparticles and the platinum catalyst were stirred and mixed, and then reacted for 20 minutes using an ultrasonic reactor, and then left at room temperature for 1 hour. After the reaction, the sample was centrifuged at 10000 rpm for 10 minutes, and the supernatant was removed and washed twice. After washing, the sample was dried and mixed in a second emulsion. After the first agent prepared above was applied to the skin, a second agent emulsion containing hydrophobic coated nanoparticles onto which a platinum catalyst was adsorbed was applied thereon to form an artificial skin film.

FIG. 4 is a photograph comparing measured and contact angles of hydrophilic silica nanoparticles (left) and hydrophobic silica nanoparticles (right), which are coated with PDMS and have been treated with PDMS without surface treatment, and FIG. It is a photograph comparing and measuring the contact angle of the hydrophilic titanium oxide nanoparticles (left) and the titanium oxide nanoparticles (right) showing hydrophobicity by coating with PDMS. As shown in FIGS. 4 and 5, in the case of hydrophilic nanoparticles, the contact angle cannot be measured because most of the water is absorbed, whereas in the case of nanoparticles coated with a hydrophobic material, the contact angle is 150 ° or more, which has superhydrophobic properties. You can see that.

6 is a photograph of (a) uncoated silica nanoparticles (hydrophilic) and hydrophobic silica nanoparticles coated with PDMS, respectively, mixed with a platinum catalyst and (b) a photograph after centrifugation of (a). As shown in FIG. 6, the hydrophilic silica nanoparticles are not adsorbed after the reaction with the hydrophobic platinum catalyst, and thus the platinum catalyst is not adsorbed onto the particles and is separated from the silica particles. However, silica nanoparticles coated with a hydrophobic material and having superhydrophobic properties can be confirmed that the platinum catalyst is adsorbed by hydrophobic-hydrophobic interaction.

7 is a photograph of artificial skin film formation using only (a) platinum catalyst and (b) artificial skin film formation using nanoparticles to which platinum catalyst is adsorbed.

8A to 8D are graphs showing the difference in surface potential before and after adsorption of a platinum catalyst using zeta-potential. As compared with the conventional Bare SiO ₂ , it can be seen that the zeta potential is changed as the platinum catalyst is adsorbed in this embodiment. However, as the reaction time passes over 4 hours, the zeta potential is very low, and it can be confirmed that the stability is lowered. Therefore, the reaction time of 1 hour was confirmed as the maximum reaction time and the experiment was conducted using the reaction time within 1 hour.

3. artificial Skin  Optimization and Characterization of Forming Compositions

3-1. Optimization of Adsorption Conditions for Platinum Catalysts and Nanoparticles

In order to confirm the optimum adsorption conditions of the composition for forming an artificial skin film, the adsorption rate according to the ultrasonic reaction time when the platinum catalyst and the nanoparticles were mixed was measured.

9 shows results of optimization experiments on adsorption conditions of hydrophobic silica nanoparticles and a platinum catalyst. A platinum catalyst at a concentration of 1% was used for adsorption experiments on 2% mass of silica by volume of solvent. The control sample without sonication showed a 50% adsorption rate compared to the control, and immediately after sonication for 20 minutes (0 minutes), adsorption after 20 minutes, 40 minutes, 1 hour, and 4 hours. The rates were compared respectively. The concentration analysis of the platinum catalyst was analyzed using ICP-OES. As a result of the experiment, it was confirmed that the adsorption rate was the highest when the ultrasonic reaction was performed for 20 minutes and then left at room temperature for 20 minutes.

3-2. ICP measurement by catalyst concentration

Next, the platinum catalyst alone and the silica nanoparticles which adsorbed the platinum catalyst were respectively After dispersion in the solvent at concentrations of 0.1%, 0.2%, 0.5%, 1%, 2%, 3%, 4%, and 5%, the platinum concentration at each concentration was analyzed by ICP-OES.

Adsorption of the platinum catalyst to the nanoparticles was measured at a higher concentration at most concentrations than at the control using only the platinum catalyst without the nanoparticles, and the concentration of the catalyst was 2% or more (nanoparticle concentration: 2%). In one case, the catalyst was no longer adsorbed to the nanoparticles, and the concentration tended to decrease (FIG. 10). The above results indicate that as the concentration of the platinum catalyst increases, the catalysts aggregate together, so that the dispersion is not well performed in the ethanol solvent. However, when the platinum catalyst is adsorbed on the nanoparticles, it is more dispersed in the solvent. Inferred.

3-3. Cytotoxicity Test- LDH (Lactate dehydrogenase ) analysis

Lactate dehydrogenase (LDH) analysis was performed to compare the toxicity of platinum catalyst alone and silica nanoparticles adsorbed platinum catalyst (FIG. 11).

First, a 96-well assay plate containing cells in cell culture was prepared. Thereafter, test compounds and vehicle controls were placed in appropriate wells and the cells were incubated at a temperature of 37 ° C. with a final volume of 100 μl to 150 μl.

Afterwards, a maximum LDH release control was made using a Lysis solution. 10 × lysis solution (per 100 μl original volume) was added to positive control wells 45 minutes prior to adding assay reagent. Samples of all wells were taken 50 μl and transferred to a new 96-well flat clear bottom plate. 50 μl of the reaction reagent was added to each well, and wrapped in a foil or an opaque box and incubated at room temperature for 30 minutes while protected from light. After incubation, the stop solution was added to each well to terminate the reaction. Bubbles formed in the wells were removed using a syringe needle, and the absorbance was measured at 490 nm or 492 nm within 1 hour after the stop solution treatment.

After absorbance measurement, the result value was obtained by subtracting the average value of the cell culture background from the experimental value of each well, and then using the following formula for calculating the cytotoxicity (percent cytotoxicity).

As a result of cytotoxicity experiments, increasing the concentration of the platinum catalyst to 2% or more increased the toxicity of the catalyst to the cells. In the case of adsorbing the platinum catalyst to the nanoparticles, it was confirmed that the cytotoxicity was reduced by about 20% or more than when the platinum catalyst was used without the nanoparticles (FIG. 12).

4. artificial Skin  Experimental application of the composition-skin irritation

The primary skin irritation test (primary patch test) of the composition for forming an artificial skin film prepared in the above embodiments was performed. The concentration of the artificial skin film forming composition used was the same as in Examples 2-1, 2-2, and the sample names are shown in Table 5 below.

The subjects were based on 33 healthy men and women between 20 and 55 years of age, and a total of 4 times (24 days after patch removal, 24 hours after patch removal, 48 hours after patch removal) were evaluated for skin irritation.

First, a sample was applied between the shoulder blade and the waistline using the van der Bend chamber (Van der Bend, Brielle, the Netherlands) on the back of the subjects. Immediately before the experiment, the composition 1 agent for artificial skin film formation (sample # 1) and the composition 2 agent for artificial skin film formation (sample # 2) were mixed at a 1: 1 ratio. After wiping the test site with distilled water and drying, 35 mg of each of composition 1 for artificial skin film formation and composition 2 for artificial skin film formation were added dropwise, and sample # 3 was 35 mg of van der Bend chamber (Van der Bend). , Brielle, the Netherlands) and fixed on the test site. The patch was applied to the skin for 24 hours, and after removal, the area was marked with a marking pen and observed after 30 minutes, 24 hours, and 48 hours, respectively.

4-1. Skin irritation determination method

Skin irritation is described in Draize Dermal Irritation Scoring System [Draize, JH, Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, The Association of Food and Drug Officials of the United States, Austin, TX, 1959, p. . 49].

After calculating the stimulus value according to the Mean Irritation Index (MII) formula, the skin primary stimulation test result determination table reflecting the stimulation classification criteria of the Environmental Protection Agency (EPA) Standard Evaluation Procedure Dermal Classification System ( The stimulus group was determined according to Table 7).

Mean Skin Irritation Calculation Formula (M.I.I.)

4- 2. Skin  Stimulus evaluation results

Table 8 shows the experimental results of the subjects who completed the skin irritation evaluation experiment. First, the average skin irritation degree of the composition 1 for artificial skin film formation was 0.11 and was determined to be non-irritating according to the above criteria. The average skin irritation degree of the composition 2 for artificial skin film formation was 0.04 and also non-irritating. It became. Even when the composition 1 and agent 2 for artificial skin film formation were mixed, the average skin irritation was 0.14, which was determined to be non-irritating.

In addition, the subjects who completed the experiment did not show any special skin abnormalities other than skin reactions that could be expected or involved in patch tests during the experiment.

5. Artificial Skin  Experimental application of the composition-eye wrinkles Coverage

The human efficacy of the eyelid wrinkle coverage of the composition for artificial skin film preparation prepared in the above examples was confirmed. Sample names and the like of the artificial skin film forming composition used are shown in Table 9 below.

The test subjects were based on those with 20 eyes of 30-55 years old healthy females with wrinkles around the eyes corresponding to a photodamage score of 2-6. One week before the start of the experiment, the use of treatments, cosmetics, quasi-drugs, and medical treatments and massages for the purpose of skin improvement that could affect the evaluation results were prohibited. The experiment was carried out a total of three times (before sample application, immediately after sample application, and after 3 hours of sample application).

First, apply the first cream of the composition for artificial skin film formation to the size of the bean lip and evenly spread it on the area of the eye wrinkles, which is the designated sample application site, and then apply the second cream in the same amount as the first agent, The sample was allowed to dry sufficiently for 5 minutes.

5-1. Eye wrinkles Coverage  Assessment Methods

(1) Eye wrinkle measurement using PRIMOS high resolution equipment

Eye wrinkles were measured using PRIMOS High Resolution (Phaseshift Rapid In vivo Measurement Of Skin, GFMesstechnik GmbH, Germany). In order to prevent contraction relaxation and movement of the measurement site, the faces of the test subjects were fixed on a specially designed PRIMOS measuring equipment set. The instrument was fixed and measured to match the test site to determine the same site at each measurement.

(2) Eye wrinkle analysis through image analysis

Eye wrinkles were analyzed using PRIMOS software (PRIMOS version 5.8E). The three-dimensional measurement of PRIMOS is that the parallel projection stripes projected on the skin are changed by the height difference of the skin surface, and the degree of this change is calculated quantitatively by computer.

Eye wrinkle images measured by PRIMOS were matched with the measurement site using 3D matching.

In the value of the eye wrinkle parameter from the roughness analysis, the average roughness (Ra) is the average of the absolute values of the lengths from the center line to the cross-sectional curve of the surface when the center line is drawn at the roughness height of the cross section, and Rmax (Maximum roughness depth) Represents the difference between the highest acid and the lowest valley within a single measurement range. In addition, when one or more measured values of the surface roughness variables Ra and Rmax decrease, it means that the eye wrinkles are temporarily covered.

The temporary eye wrinkle coverage by PRIMOS High Resolution was calculated using the following formula.

(3) Statistical Analysis

According to the normality test results, the paired t-test confirmed the significance between the sample application and the sample application at the 95% confidence interval. Statistical analysis program used IBM SPSS Statistics 21.0 (SPSS, Chicago, IL, USA).

5-2. Eye wrinkles Coverage  Evaluation results

The measurement result and the reduction rate for each wrinkled surface roughness parameter using PRIMOS High Resolution are shown in Table 10, and the statistical analysis results are shown in Table 11 (FIGS. 13 and 14).

As a result of analyzing the measured value of eye wrinkle surface roughness variable using PRIMOS High Resolution, the Ra value decreased 9.926% immediately after application to a statistically significant level (p <0.01) compared to before application, and the Rmax value was lower than before application. Statistically significant level (p <0.01), decreased by 8.784% immediately after application.

6. Artificial Skin  Experimental application of the composition-makeup lasting

The human efficacy of the makeup skin uniformity persistence of the composition for forming an artificial skin film prepared in the above examples was confirmed. Sample names and the like of the artificial skin film forming composition used were the same as those used in the eye wrinkle coverage test.

The subjects were based on those with 20 eyes of 30 to 55 years old healthy females with wrinkles around the eyes corresponding to the optical damage score of 2 to 6. One week before the start of the experiment, the use of treatments, cosmetics, quasi-drugs, and medical treatments and massages for the purpose of skin improvement that could affect the evaluation results were prohibited. The experiment was carried out a total of three times (before sample application, immediately after sample application, and after 3 hours of sample application).

First, in the case of the skin uniformity persistence experiment, the first cream of the composition for artificial skin film formation is reduced by the size of a bean pill and evenly spread on the folds of the eye area, which is the designated sample application site, and then the second cream is applied in the same amount as the first agent The sample was allowed to dry for 3 to 5 minutes after being applied to the same site.

6-1. How to evaluate makeup uniformity lasting

(1) photographing facial part using Visia-CR

Both sides of the subject were photographed in cross-polarized mode using the Visia-CR (Canfield Imaging System, USA). Each measurement was performed after fixing shooting conditions using a strobe mounted inside the apparatus.

(2) Digital Color Management with ElleadSys Pro

ElleadSys Pro is an integrated image processor for consistently managing the shooting environment, conditions, analysis and record keeping of images. Ellead ColorMap consists of 40 color patches by adding 14 kinds of skin tone references to 26 standard colors. By using the device to implement the skin color of the various images taken with the digital device closest to the actual skin color can improve the accuracy and reliability of the image analysis. All images of the sustainability experiment were analyzed after applying ElleadSys Pro.

(3) Evaluation of makeup uniformity persistence using Visia-CR photo and image analysis software

In order to evaluate makeup skin uniformity persistence, image analysis software (Image-Pro Plus, USA) was used to derive the standard deviation (S.D.) of S (Saturation) of the test site under the same threshold conditions. The S value is a saturation factor, and when the standard deviation value of S (saturation) is not statistically significant even after the measurement time is compared with the value immediately after application, it was evaluated that the makeup skin uniformity was sustained. Makeup skin uniformity persistence was calculated using the following formula:

(4) Statistical Analysis

According to the normality test results, the significance of between before / after sample application and immediately after / after sample application and 3 hours after application in 95% confidence interval and the homogeneity between sample application / non-application group were confirmed by the corresponding sample t-test. In addition, the significance between groups was confirmed by the Wilcoxon signed rank test. Statistical analysis program used IBM SPSS Statistics 21.0 (SPSS, Chicago, IL, USA).

6-2. Makeup Sustainability Evaluation Results

Table 12 shows the results of the standard deviation measurement of S (Saturation) using facial imaging and image analysis software using VISIA-CR, the results of the statistical analysis in Table 13, and the results of the persistence in Table 14 (Fig. 15). And FIG. 16).

As a result of analyzing the standard deviation values of S using facial imaging using VISIA-CR and image analysis software, the sample application area and the non-application area were reduced statistically significant level (p <0.001) immediately after application. Indicated. In addition, the standard deviation value of S of the sample application site did not show a statistically significant level difference after 3 hours of application compared to immediately after the sample application (Table 12 and Table 13). The sample application site had a sustained rate of 43.149% and there was no statistically significant difference between the sample application site and the non-application site (Table 14).

As a result of analyzing the measured values of the surface roughness parameters of the eye wrinkle area using PRIMOS High Resolution, the Ra value was reduced by 9.926% immediately after application to a statistically significant level (p <0.01). Rmax value decreased 8.784% immediately after application to a statistically significant level (p <0.01) compared to before application. Therefore, the composition for artificial skin film formation (first agent, S-S002) and the composition for artificial skin film formation (second agent, S-S003) are judged to help temporary eye wrinkle cover immediately after application.

As a result of analyzing the standard deviation value of S (Saturation) in the area around the eyes using Visia-CR photographs and image analysis, it decreased to a statistically significant level (p <0.001) immediately after application compared to before application. In addition, the standard deviation value of S of the sample application site did not show a statistically significant level difference after 3 hours of application compared to immediately after the sample application. Sample application sites had a sustained rate of 43.149%.

Therefore, it is judged that the composition for artificial skin film formation (part 1, S-S002) and the composition for artificial skin film formation (part 2, S-S003) help to sustain makeup skin uniformity after 3 hours of application.

7. Human Application Experiment of Artificial Skin Membrane Composition-Skin Abnormality

The presence or absence of skin abnormalities in the test subjects was closely observed and grades were expressed as none (0), weakness (1), moderateness (2), and severeness (3). Assessment of adverse reactions may include erythema, edema, scaling, itching, stinging, burning, stiffness and prickling. It judged together. As a result of the determination, when the adverse reaction was confirmed, the adverse reaction evaluation by the dermatologist was further performed in accordance with the adverse reaction treatment regulations.

As a result of adverse reaction evaluation, no special symptoms related to skin adverse reactions were observed during the experiment.

The above description of the present application is intended for illustration, and it will be understood by those skilled in the art that the present invention may be easily modified in other specific forms without changing the technical spirit or essential features of the present application. Therefore, it should be understood that the embodiments described above are exemplary in all respects and not restrictive. 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 above description, and it should be construed that all changes or modifications derived from the meaning and scope of the claims and their equivalents are included in the scope of the present application.

Claims (20)

An agent comprising an organopolysiloxane unit; And,
A second agent comprising nanoparticles coated with a hydrophobic material and a platinum catalyst supported on the nanoparticles
Comprising, artificial skin film forming composition.
The method of claim 1,
The platinum catalyst is adsorbed on the surface of the nanoparticles coated with the hydrophobic material, artificial skin film forming composition.
The method of claim 1,
The hydrophobic material is polydimethylsiloxane, gelatin, polyethylene glycol, hydroxypropyl methyl cellulose, methyl cellulose, polyvinylpyrrolidone, starch, ethyl cellulose, alginate, carboxymethyl cellulose, gum arabic, trigacanth rubber, and these Comprising one selected from the group consisting of combinations, artificial skin film forming composition.
The method of claim 1,
The nanoparticles are biocompatible nanoparticles or biodegradable nanoparticles, artificial skin film forming composition.
The method of claim 1,
The nanoparticles, silica, titanium oxide, zinc oxide, and the composition comprising the one selected from the group consisting of a combination thereof.
The method of claim 1,
The platinum catalyst includes one selected from the group consisting of platinum carbonyl cyclovinylmethylsiloxane complex, platinum divinyltetramethyldisiloxane complex, platinum cyclovinylmethylsiloxane complex, platinum octanealdehyde / octanol complex, and combinations thereof The composition for artificial skin film forming.
The method of claim 1,
The platinum content is in the range of 0.05% to 10% by weight relative to the total weight of the second agent, composition for artificial skin film formation.
The method of claim 1,
Nanoparticles coated with the hydrophobic material will further comprise a functional protein or drug, composition for artificial skin film formation.
Composition for artificial skin film forming according to any one of claims 1 to 8
Comprising, artificial skin film forming kit.
1 agent comprising organopolysiloxane units is applied to the skin, and
Applying a second agent comprising nanoparticles coated with a hydrophobic material and a platinum catalyst supported on the nanoparticles to the skin to form an artificial skin film comprising a polysiloxane polymer; or,
Applying to the skin a second agent comprising nanoparticles coated with a hydrophobic material and a platinum catalyst supported on the nanoparticles, and
Applying an agent comprising the organopolysiloxane unit to the skin to form an artificial skin film comprising the polysiloxane polymer
Comprising, artificial skin membrane production method.
The method of claim 10,
The second agent is prepared by mixing the solution containing the nanoparticles coated with the hydrophobic material and the solution containing the platinum catalyst and then ultrasonically reacted.
The method of claim 11,
The solvent of the solution containing the platinum catalyst is water, alcohol, or an organic solvent, artificial skin film manufacturing method.
The method of claim 10,
The platinum catalyst is adsorbed on the surface of the nanoparticles coated with the hydrophobic material, artificial skin film manufacturing method.
The method of claim 10,
The hydrophobic material is polydimethylsiloxane, gelatin, polyethylene glycol, hydroxypropyl methyl cellulose, methyl cellulose, polyvinylpyrrolidone, starch, ethyl cellulose, alginate, carboxymethyl cellulose, gum arabic, trigacanth rubber, and these The artificial skin membrane manufacturing method comprising the one selected from the group consisting of.
The method of claim 10,
The nanoparticles are biocompatible nanoparticles or biodegradable nanoparticles, artificial skin membrane manufacturing method.
The method of claim 10,
Wherein said nanoparticles are selected from the group consisting of silica, titanium oxide, zinc oxide, and combinations thereof.
The method of claim 10,
The platinum catalyst includes one selected from the group consisting of platinum carbonyl cyclovinylmethylsiloxane complex, platinum divinyltetramethyldisiloxane complex, platinum cyclovinylmethylsiloxane complex, platinum octanealdehyde / octanol complex, and combinations thereof What is artificial skin film production method.
The method of claim 10,
The content of the platinum catalyst is in the range of 0.05% to 20% relative to the total weight of the second agent, artificial skin film manufacturing method.
The method of claim 11,
The viscosity of the solution containing the platinum catalyst is in the range of 200 to 1,000 Cs, artificial skin membrane manufacturing method.
The method of claim 10,
Nanoparticles coated with the hydrophobic material will further comprise a functional protein or drug, artificial skin membrane manufacturing method.

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