Collagen hydrogel film forming agent

Abstract

To provide a collagen hydrogel film forming agent.SOLUTION: A collagen hydrogel film forming agent comprises 1 mass%-5 mass% of collagen, 0.1 mass%-20 mass% of a thickener, 7 mass%-25 mass% of a humectant, and 70 mass% or more of water.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a collagen hydrogel film-forming agent. [Background technology]

[0002] Topical preparations (film-forming agents) that form an artificial film (second skin) when applied to the skin are capable of penetrating into minute irregularities in the skin surface tissue that are difficult to contact with mask packs such as nonwoven fabric sheets and bandages. As such, they are expected to be used in cosmetics for moisturizing and protecting purposes, as well as in pharmaceuticals used as wound dressings and as topical preparations containing medicinal drugs for treatment.

[0003] Among film-forming agents, those containing natural polymeric materials derived from animals have characteristics similar to the texture of skin tissue, do not interfere with metabolism on the skin, are less irritating when applied to the skin, and are water-soluble and can be washed off without concern of damaging the skin when peeled off, compared to film-forming agents containing synthetic polymeric compounds.

[0004] Patent Document 1 and Non-Patent Document 1 describe collagen-containing creams that contain bovine collagen and / or chitosan, which are natural animal-derived polymers, and lanolin, polysorbate 60, or polysorbate 80, which are emulsifiers. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Indian Patent Application Publication No. 18 / 2017 (Indian Patent Application No. 3554 / DEL / 2015) [Non-patent literature]

[0006] [Non-Patent Document 1] Sivalingam Udhayakumar, et al., “Biomaterials Science”, 2017, vol. 5, p1868―1883 Summary of the Invention [Problem to be solved by the invention]

[0007] Collagen, a representative animal-derived natural polymer, forms three-dimensional crosslinks in vivo. It is also known that collagen fibers artificially crosslinked ex vivo have high moisturizing, protective and wound-healing properties. However, collagen materials for general skin care applications lose their fibrosis ability due to heat treatment and / or strong base treatment during the manufacturing process. On the other hand, collagen gels near its isoelectric point, but because of its fragile structure, it must be used as a cream with an emulsifier added to stabilize the film, and cannot be used as a collagen hydrogel film-forming agent.

[0008] Furthermore, the present inventors have found a new problem with hydrogel coating-forming agents that use collagen isolated in a state where fibrosis ability is maintained without heat treatment or strong base treatment during the collagen extraction process and the collagen hydrogel coating-forming agent manufacturing process, in that even when a collagen hydrogel coating-forming agent is prepared that contains a moisturizing agent such as glycerin in addition to collagen, the morphology of the coating that is formed is unstable.

[0009] Therefore, an object of the present invention is to provide a collagen hydrogel coating forming agent which contains collagen that maintains its fibrosis ability and which forms a hydrogel coating with a stable morphology. [Means for solving the problem]

[0010] The present inventors conducted extensive research to solve the above problems, and discovered that a collagen hydrogel coating former containing collagen isolated without heat treatment or strong base treatment, a moisturizer such as glycerin, and a thickener can form a hydrogel coating having a stable shape without further adding an emulsifier.

[0011] Furthermore, the present inventors have found that a collagen hydrogel film-forming agent, which contains a thickener in addition to a moisturizer, forms a collagen hydrogel film when applied to the skin and is useful as a cosmetic having effects such as improving skin wrinkles, improving skin texture, reducing porphyrin, and improving dry skin, as well as a pharmaceutical having therapeutic effects such as improving acne vulgaris, thereby completing the present invention.

[0012] That is, the present invention relates to the following [1] to

[18] . [1] A collagen hydrogel coating former comprising 1% by mass to 5% by mass of collagen, 0.1% by mass to 20% by mass of a thickener, 7% by mass to 25% by mass of a moisturizer, and 70% by mass or more of water. [2] The coating agent according to [1], wherein the thickener comprises one or more thickeners selected from the group consisting of xanthan gum, locust bean gum, carrageenan and hydroxyethyl cellulose. [3] The coating agent according to [1], wherein the thickener is one or more thickeners selected from the group consisting of xanthan gum, locust bean gum and carrageenan. [4] The coating agent according to [1], wherein the thickener is xanthan gum. [5] The coating agent according to any one of [1] to [4], wherein the total content of lanolin, polysorbate 60 and polysorbate 80 is 10 mass% or less. [6] The coating agent according to any one of [1] to [5], wherein the content of the emulsifier is 10 mass % or less. [7] The coating agent according to any one of [1] to [6], which does not contain an emulsifier. [8] The film-forming agent according to any one of [1] to [7], wherein the moisturizer is one or more moisturizers selected from the group consisting of glycerin, sorbitol, and propylene glycol. [9] The film-forming agent according to any one of [1] to [8], wherein the moisturizer is glycerin.

[10] The coating agent according to any one of [1] to [9], which has a pH of 5.0 to 8.0.

[11] The coating agent according to any one of [1] to

[10] , further comprising a buffer.

[12] The coating agent according to any one of [1] to

[11] , which contains an acid.

[13] The coating agent according to any one of [1] to

[12] , which contains a preservative.

[14] The coating agent according to any one of [1] to

[13] , wherein the temperature of the collagen-containing solution is kept at 33°C or lower and the pH is kept at 10.0 or lower during the process of extracting the collagen and the process of producing and storing the collagen hydrogel coating agent.

[15] The coating agent according to any one of [1] to

[14] , which does not contain chitosan.

[16] A collagen hydrogel coating former comprising 1% by mass to 5% by mass of atelocollagen, 0.14% by mass to 2% by mass of xanthan gum, 7% by mass to 11% by mass of glycerin, and 76% by mass or more of water, and containing an emulsifier in an amount of 10% by mass or less.

[17] A method for producing a collagen hydrogel coating-forming agent containing 1% by mass to 5% by mass of collagen, 0.1% by mass to 20% by mass of a thickener, 7% by mass to 25% by mass of a moisturizer, and 70% by mass or more of water, wherein the collagen is extracted under conditions in which the pH of a solution containing the collagen is maintained at 10.0 or less and the temperature of the solution is maintained at 33° C. or less during the extraction process, and the pH of the solution containing the collagen is maintained at 10.0 or less and the temperature of the solution is maintained at 33° C. or less during the production and storage of the collagen hydrogel coating-forming agent.

[18] The method according to

[17] , wherein the collagen hydrogel coating agent further contains a buffer and an acid. Effect of the Invention

[0013] According to the collagen hydrogel coating forming agent of the present invention, it is possible to form a hydrogel coating having a stable shape without further containing an emulsifier.

[0014] In addition, the collagen hydrogel coating agent of the present invention forms a collagen hydrogel coating when applied to the skin, and has skin care effects such as improving skin wrinkles, improving skin texture, reducing porphyrin, and improving dry skin, as well as therapeutic effects such as improving acne vulgaris. [Brief description of the drawings]

[0015] [Figure 1] FIG. 13 is a diagram showing the morphological stability of the formed hydrogel coating when the collagen hydrogel coating forming agent contains a thickener or not. [Diagram 2] FIG. 13 is a diagram showing the results of a use example of the skin care effect when a collagen hydrogel film-forming agent is applied to the skin. [Diagram 3] FIG. 13 is a diagram showing the results of a use example of the effect of improving dry skin when the collagen hydrogel film-forming agent is applied to the dry palm of the hand. [Figure 4] FIG. 13 is a diagram showing the results of an example of the acne care effect when a collagen hydrogel film-forming agent is used in combination with a quasi-drug. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] The collagen hydrogel coating forming agent of the present invention contains 1% to 5% by mass of collagen, 0.1% to 20% by mass of a thickener, 7% to 25% by mass of a moisturizer, and 70% or more by mass of water.

[0017] The collagen hydrogel film-forming agent of the present invention contains collagen. Collagen is the main component of the extracellular matrix in vertebrates, including humans, and is a fibrous protein that forms connective tissues such as skin, joints, and bones. In the present invention, collagen gels when the film-forming agent of the present invention is applied to the skin, and has a moisturizing and protective effect, and also plays a role of supporting the components of the film-forming agent containing collagen at the application site. The role of supporting the components of the film-forming agent containing collagen at the application site contributes to, for example, adjusting the pH of the attachment site when a buffer is added to the film-forming agent, and to direct delivery and sustained release of a drug to the affected site when a drug is added. When a film-forming agent containing collagen is applied to a wound site as a wound dressing, it has an effect of normalizing the wound site and the tissue environment surrounding it as an extracellular matrix, and plays a role of inducing the adhesion and aggregation reaction of platelets by contacting with platelets, contributing to the initiation of a series of wound healing cascades starting from blood coagulation.

[0018] The type, origin, etc. of collagen used in the present invention are not particularly limited, and may be, for example, collagen extracted from placenta collected from mammals, dermis, tendons, bones, or cartilage collected from mammals, reptiles, and birds, or collagen-containing tissues such as fish scales, skin, and swim bladder extracted from fish.

[0019] In a preferred embodiment of the collagen hydrogel film-forming agent of the present invention, the collagen is atelocollagen.

[0020] Atelocollagen is a protein from which the non-helical regions called telopeptides at the N-terminus and C-terminus of collagen have been removed (hereinafter also referred to as "atelosylated"). Telopeptides are known to have large species differences and high antigenicity, and removal of telopeptides is expected to significantly reduce antigenicity. There are no particular limitations on the method for atelosylation of collagen, but it is generally performed by treatment with an enzyme such as pepsin, and more generally, it is performed at the same time as collagen extraction from collagen-containing tissues.

[0021] A preferred example of collagen that can be used in the present invention is collagen obtained by pretreating the above-mentioned collagen-containing tissue homogenate and then extracting it. That is, a preferred example of collagen that can be used in the present invention is collagen obtained from the above-mentioned collagen-containing tissue homogenate through a pretreatment process and an extraction process.

[0022] Pretreatment of collagen-containing tissue fragments may include decellularization treatment using a high-concentration aqueous sodium chloride solution, a surfactant solution, etc., defatting treatment using an organic solvent, etc., decomposition treatment of impurity proteins using a base, etc., and decalcification treatment using an acid or a chelator, etc., and one or more of these may be used in any combination and order.

[0023] The collagen extraction method is not particularly limited. For example, collagen obtained by salting out with the addition of sodium chloride or the like, extraction with an acid such as hydrochloric acid, and extraction with an enzyme such as pepsin can be used. From the viewpoint of maintaining collagen's fibrosis ability and extracting it at a high yield, extraction with an acid such as hydrochloric acid or extraction with an enzyme such as pepsin is preferred, and from the viewpoint of ateloforming collagen and suppressing antigenicity, extraction with an enzyme such as pepsin is more preferred, and extraction with an enzyme such as pepsin under acidic conditions is particularly preferred.

[0024] The collagen content may be 1% by mass to 5% by mass, preferably 2% by mass to 4% by mass, and more preferably 3% by mass to 4% by mass, based on the total mass of the collagen hydrogel coating agent. If the collagen content is less than 1% by mass, it may be difficult to form a coating.

[0025] In one embodiment, the collagen hydrogel coating agent of the present invention does not contain chitosan. Chitosan is an animal-derived natural polymeric material derived from the connective tissue of invertebrates (arthropods, fungi, crustaceans, etc.), but it is also an allergen for crustacean allergies, and cases of contact dermatitis have been reported when people with crustacean allergies use products such as chitosan-containing creams. Therefore, by not containing chitosan, it is expected that the user is not limited and the onset of allergies due to potential crustacean allergies is suppressed.

[0026] The thickener plays a role of supporting the components of the film-forming agent at the application site when applied to the skin by increasing the viscosity of the collagen hydrogel film-forming agent of the present invention. The thickener is not particularly limited as long as it has the effect of increasing viscosity, and examples thereof include xanthan gum, locust bean gum, tragacanth gum, carrageenan, sodium alginate, hydroxyethyl cellulose, carboxymethyl cellulose, methyl cellulose, starch, soluble starch, acrylates copolymer, polyacrylic acid, polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl methacrylate, and silicone rubber, and one of these may be used alone or two or more may be used in combination. From the viewpoint of promoting gelation after application to the skin, it is preferable to use one or more thickeners selected from the group consisting of xanthan gum, locust bean gum, carrageenan, and hydroxyethyl cellulose, more preferably to use one or more thickeners selected from the group consisting of xanthan gum, locust bean gum, and carrageenan, and particularly preferably to use xanthan gum.

[0027] The content of the thickener may be 0.1% by mass to 20% by mass, preferably 0.11% by mass to 8% by mass, more preferably 0.12% by mass to 4% by mass, even more preferably 0.13% by mass to 2% by mass, even more preferably 0.14% by mass to 2% by mass, and particularly preferably 0.14% by mass to 1% by mass, based on the total mass of the collagen hydrogel coating agent.

[0028] The moisturizing agent plays a role of moisturizing the application site when the collagen hydrogel film-forming agent of the present invention forms a film on the skin. The moisturizing agent is not particularly limited as long as it has a moisturizing effect, and examples thereof include glycerin, ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, sorbitol, erythritol, xylitol, and maltitol, and one of these may be used alone or two or more may be used in combination. From the viewpoint of exerting a high moisturizing effect, it is preferable to use one or more moisturizing agents selected from the group consisting of glycerin, propylene glycol, and sorbitol, and it is more preferable to use glycerin.

[0029] The content of the moisturizer may be 7% by mass to 25% by mass, preferably 7% by mass to 20% by mass, more preferably 7% by mass to 16% by mass, even more preferably 7% by mass to 13% by mass, and particularly preferably 7% by mass to 11% by mass, based on the total mass of the collagen hydrogel coating agent.

[0030] The collagen hydrogel coating agent of the present invention contains water. Water not only distributes throughout the coating to exert a moisturizing effect, but also plays a role in directly delivering the drug in a sustained manner, particularly when the drug is contained in the gel for use as a medicine, by diffusing the contained drug in the gel, thereby providing an efficient and long-lasting healing effect. The water is preferably purified water.

[0031] The water content is 70% by mass or more, preferably 73% by mass to 91% by mass, more preferably 76% by mass to 90% by mass, even more preferably 79% by mass to 89% by mass, and particularly preferably 82% by mass to 88% by mass, based on the total mass of the collagen hydrogel coating agent. When the water content is equal to or less than the upper limit, the gel tends to maintain its shape when applied to the skin.

[0032] In one embodiment, the collagen hydrogel coating agent of the present invention contains an acid. Collagen is easily dissolved in water under acidic conditions, but is easily gelled under neutral conditions, and cannot maintain a dissolved state, particularly under physiological temperature and neutral conditions. Therefore, by including an acid in the coating agent of the present invention and providing acidic conditions for extraction and / or dissolution of collagen during the production process, collagen can be dissolved.

[0033] The acid is not particularly limited, and examples thereof include formic acid, hydrochloric acid, sulfuric acid, nitric acid, acetic acid, nitric acid, citric acid, propionic acid, adipic acid, lactic acid, phosphoric acid, tartaric acid, methanesulfonic acid, maleic acid, fumaric acid, calcium chloride, and ammonium chloride, among which one kind may be used alone or two or more kinds may be used in combination. In one embodiment, the acid is hydrochloric acid.

[0034] In one embodiment, the collagen hydrogel coating agent of the present invention contains a buffer. By containing a buffer and maintaining the pH at a range from weakly acidic to near neutral, the skin irritation of the collagen hydrogel coating agent can be reduced. Furthermore, particularly when collagen is dissolved under acidic conditions during extraction and / or dissolution during the manufacturing process, the pH of the coating agent can be set to a range from weakly acidic to near neutral while maintaining the collagen in a dissolved state by neutralizing the collagen with a buffer after dissolution.

[0035] The buffer is not particularly limited, and examples thereof include borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, Tris buffer, aspartic acid, aspartate salt, and epsilon-aminocaproic acid, among which one kind may be used alone or two or more kinds may be used in combination. In one embodiment, the buffer is a phosphate buffer.

[0036] The pH of the collagen hydrogel coating forming agent of the present invention is preferably 4.0 to 9.0, and more preferably 5.0 to 8.0, from the viewpoint of achieving both reduced skin irritation and dissolution of collagen.

[0037] In one embodiment, the collagen hydrogel coating agent of the present invention contains a preservative. The preservative is not particularly limited, and examples thereof include 2-phenoxyethanol, polyaminopropyl biguanide aqueous solution, butylene glycol, propanediol, hexanediol, butylparaben, methylparaben, propylparaben, and sodium benzoate, among which one kind may be used alone or two or more kinds may be used in combination. In one embodiment, the preservative is 2-phenoxyethanol.

[0038] The collagen hydrogel coating forming agent of the present invention may contain, in addition to the above-mentioned components, a plasticizer, a stabilizer, a cooling agent, an absorption promoter, a fragrance, a physiologically active substance, and the like.

[0039] In one embodiment, the collagen hydrogel film-forming agent of the present invention does not contain an emulsifier in an amount exceeding 14% by mass. Emulsifiers play a role in emulsification, in particular in creams and the like among film-forming agents, to enhance the dispersibility of components in the film-forming agent, and to enhance the solubility of poorly soluble active ingredients, and the like. A low content of emulsifier in the collagen hydrogel film-forming agent can reduce skin irritation.

[0040] In one embodiment, the collagen hydrogel coating-forming agent of the present invention has a total content of lanolin, polysorbate 60, and polysorbate 80 as emulsifiers of 14% by mass or less, and may be 13% by mass or less, 12% by mass or less, 11% by mass or less, 10% by mass or less, 9% by mass or less, 8% by mass or less, 7% by mass or less, 6% by mass or less, 5% by mass or less, 4% by mass or less, 3% by mass or less, 2% by mass or less, or 1% by mass or less, based on the total mass of the coating-forming agent. In one embodiment, the collagen hydrogel coating-forming agent of the present invention does not contain any of lanolin, polysorbate 60, and polysorbate 80.

[0041] Furthermore, in one embodiment, the collagen hydrogel coating agent of the present invention has an emulsifier content of 14% by mass or less, and may be 13% by mass or less, 12% by mass or less, 11% by mass or less, 10% by mass or less, 9% by mass or less, 8% by mass or less, 7% by mass or less, 6% by mass or less, 5% by mass or less, 4% by mass or less, 3% by mass or less, 2% by mass or less, or 1% by mass or less, based on the total mass of the coating agent. In one embodiment, the collagen hydrogel coating agent of the present invention does not contain an emulsifier.

[0042] The method and conditions for producing the collagen hydrogel film-forming agent of the present invention are not particularly limited, but in a preferred embodiment, the collagen-containing solution is not heated and maintained at a low temperature during the process of collagen extraction and the production and storage of the collagen hydrogel film-forming agent. Since collagen is easily denatured by heating and denatured collagen is difficult to gel, it is preferable that the solution is not heated and maintained at a low temperature during the production process. Furthermore, since collagen is easily gelled under neutral conditions and at a temperature of about human body temperature, a solution placed under neutral and high temperature conditions before application to the skin will gel collagen in the solution and cannot be used as a collagen hydrogel film-forming agent. The collagen-containing solution of the collagen hydrogel film-forming agent of the present invention is preferably kept at a temperature of 40°C or lower, more preferably at a temperature of 36°C or lower, even more preferably at a temperature of 33°C or lower, even more preferably at a temperature of 30°C or lower, and particularly preferably at a temperature of 25°C or lower.

[0043] In a preferred embodiment, strong basic treatment is not performed during the process of collagen extraction and the production and storage of the collagen hydrogel coating-forming agent. That is, in a preferred embodiment, the collagen-containing solution is not exposed to strong basic conditions during the process of collagen extraction and the production and storage of the collagen hydrogel coating-forming agent. The collagen-containing solution of the collagen hydrogel coating-forming agent of the present invention is preferably kept at pH 11.0 or less, more preferably at pH 10.5 or less, even more preferably at pH 10.0 or less, even more preferably at pH 9.5 or less, and particularly preferably at pH 9.0 or less.

[0044] The method of application of the collagen hydrogel coating agent according to the collagen hydrogel coating agent of the present invention is not particularly limited, and may be, for example, coating or rubbing. In one embodiment, the coating agent contained in a container is sucked up by a pump dispenser and discharged onto the skin in the form of a liquid, mist or foam, and then coated or rubbed. In yet another embodiment, a foam formed by an inert gas such as carbon dioxide is coated or rubbed.

[0045] The collagen hydrogel film-forming agent of the present invention can be used for, for example, cosmetics and pharmaceuticals.

[0046] Examples of cosmetic applications include:

[0047] For example, it may be applied to the skin for the purpose of overall skin care such as improving skin texture, wrinkle improvement, and porphyrin reduction. The moisturizing, protective, and pH adjusting effects of collagen on the attachment site can contribute to this application. In addition, in this application, the collagen fiber-based hydrogel coating has a certain adsorption and evaporation effect on metabolic products on the skin, and therefore can exert a moisturizing effect without completely blocking metabolism on the skin, unlike the coating formed by a coating agent using synthetic polymers or oils and fats, which produces a moisturizing effect by blocking water evaporation and sebum secretion on the skin. In addition, in this application, the collagen fiber-based hydrogel coating functions as a support for active ingredients such as beauty ingredients, and can be expected to have a sustained release effect of the active ingredients.

[0048] In addition, it can be applied to dry skin for the purpose of improving dry skin, for which the moisturizing effect of collagen and the effect of carrying the components of the film-forming agent at the application site can be utilized.

[0049] In addition, it can be used for treating and preventing sensitive skin and rough skin caused by masks by applying it to skin that shows these symptoms. In this application, the collagen and film-forming agent components that have a moisturizing and protective effect on the skin can be carried to the application site.

[0050] In addition, for the purpose of maintaining the fragrance and suppressing deterioration of the scent, it can be used in combination with fragrance-containing perfumes, cosmetics, lip creams, hand creams, hair creams, etc. Collagen's effect of adjusting the pH of the attachment site and its effect of carrying the components of the film-forming agent at the application site can contribute to this use.

[0051] In addition, the film-forming agent can be used as a makeup base by further containing a pigment. The moisturizing effect of collagen and the effect of carrying the components of the film-forming agent at the application site can contribute to this use. Furthermore, since the collagen hydrogel film-forming agent of the present invention can be used for skin care and wound healing, in addition to the use as a general makeup base, it can also be used as a cosmetic (care cosmetic, care makeup product) that has skin care and treatment effects.

[0052] Other examples of uses include care applications for preventing or alleviating rough hands caused by dry winter conditions or working around water, etc. The moisturizing and protective effects of collagen can contribute to these uses.

[0053] In addition, it can be applied to the facial skin before applying makeup in order to improve the compatibility of cosmetics with the skin (makeup application) by suppressing unevenness such as wrinkles and pores on the facial skin and making it closer to a flat surface. In this application, the moisturizing effect of collagen and the effect of carrying the components of the film-forming agent to the application site can contribute.

[0054] Examples of pharmaceutical applications include the following:

[0055] For example, it may be applied to the site of cosmetic surgery after the treatment in order to shorten the time (downtime) until symptoms such as redness, internal bleeding, and swelling that frequently occur at the site of cosmetic surgery are improved and to protect the site of surgery. The moisturizing effect, protective effect, effect of normalizing the surrounding tissue environment as an extracellular matrix, effect of initiating the wound healing cascade, etc., of collagen can contribute to this use.

[0056] In addition, the use of collagen as a wound healing promoter that serves as a wound dressing for minor burns and abrasions can be mentioned. In this use, the moisturizing effect of collagen, the effect of normalizing the surrounding tissue environment as an extracellular matrix, and the effect of initiating the wound healing cascade can be contributed. Furthermore, when the film-forming agent contains drugs such as antibacterial drugs and steroids, the components of the film-forming agent containing collagen are supported at the application site, and the drugs can be directly delivered to the affected area and slowly released, and the use of the film-forming agent as a wound healing promoter with a higher healing effect can be mentioned.

[0057] In addition, it can be used in combination with hair restorers to improve hair growth effects. In addition to the moisturizing and protective effects of collagen, this application is expected to contribute to the sustained release of drugs directly to the affected area. In addition, by using carbon dioxide gas to make the foam while carrying the drug, it is expected that the drug can be delivered by improving blood flow through cooling and stimulation.

[0058] Another application is as a gel matrix for sustained-release drugs in which a drug is further incorporated into a coating agent, with the aim of reducing the amount of drug with strong side effects or expensive drug used.

[0059] In addition, it can be applied to the skin of the hands and feet to improve dryness of the skin and nails of the hands and feet caused by hand-foot syndrome, which is one of the side effects of anticancer drugs, and to reduce numbness and pain. The moisturizing and protective effects of collagen can contribute to this use.

[0060] In addition, it can be applied to the skin after applying a sunscreen to reduce the number of times that it is necessary to reapply the sunscreen to maintain its effectiveness. In this application, the moisturizing effect of collagen and the effect of carrying the components of the film-forming agent at the application site can contribute.

[0061] In addition, the film-forming agent may be further supplemented with an antifungal drug or used in combination with an antifungal drug to treat infectious skin diseases such as athlete's foot. In this application, collagen is expected to contribute not only to its moisturizing and protective effects, but also to the sustained release of the drug directly to the affected area.

[0062] Further, the use thereof may be as an agent for treating skin diseases or promoting wound healing in animals belonging to the mammalian family, not limited to humans.

[0063] Since the collagen hydrogel coating agent of the present invention is in gel form, it delivers the active ingredient by infiltrating into minute irregularities in the skin surface tissue (fine wrinkles, pores, abrasions, etc.) that are difficult to contact with mask packs such as nonwoven fabric sheets and bandages, and the active ingredient is fixed and released gradually due to the gelling action of the collagen, so that the effect is evenly sustained at the target site and for a long time.

[0064] When the collagen hydrogel coating agent of the present invention is used after the completion of the care and healing of the skin tissue surface, the product is derived from animal fibrous tissue and has the properties of being low irritant to the skin tissue and not interfering with the sebum metabolism of the skin tissue, so that it maintains the normal state of the skin tissue surface and protects it from other irritants. In addition, the coating formed by the collagen hydrogel is similar to the properties of the skin, so the coating shape is maintained without collapsing when stretched. Furthermore, the collagen hydrogel coating can be washed off with lukewarm water and does not need to be peeled off for removal, so there is no concern about skin damage associated with coating peeling.

[0065] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these. EXAMPLES

[0066] [Example 1A] A collagen hydrogel coating agent having the composition shown in Table 1 was prepared using collagen derived from porcine placenta tissue.

[0067] The porcine placenta tissue was washed with tap water and finely chopped with a cutter of about 3 mm diameter using a meat grinder. The chopped placenta tissue was packed into a mesh bag and decellularized by repeatedly immersing and washing in a 25% sodium chloride solution for two days, and decalcified by repeatedly immersing and washing in a 2% ethylenediaminetetraacetic acid solution for two days. After the treatment, the placenta tissue was thoroughly washed with purified water.

[0068] The washed placental tissue obtained in the above step was suspended in about 25 times the amount of water. Approximately 20% pepsin was added relative to the solid content in the placental tissue, and the pH of the solution was adjusted to 1 to 2, followed by gentle stirring at 20 to 25°C for 48 hours. A filter aid was added to the stirred solution, which was then filtered through filter paper, and the resulting filtrate was further filtered through a 0.45 μm filter. The resulting filtrate was cooled to 5 to 10°C, and the pH was adjusted to 7.0 with a 0.3 N aqueous solution of sodium hydroxide to precipitate atelocollagen. The solution from which atelocollagen had precipitated was centrifuged or filtered, and the pellet was collected. The resulting pellet was freeze-dried to obtain atelocollagen powder.

[0069] The atelocollagen powder obtained in the above process was added to a mixed solution of 0.3 wt% hydrochloric acid and glycerin in the ratio shown in Table 1, and stirred at room temperature for about 10 minutes, and then left in a refrigerator at 4°C with a lid on for 72 hours to dissolve the atelocollagen. Similarly, the obtained solution was mixed with a 2 mass% xanthan gum aqueous solution in 0.3 mol / L phosphate buffer (pH 7.0) and stirred at room temperature for 20 minutes. Stirring was stopped once, 2-phenoxyethanol was added, and then the mixture was stirred again at room temperature for 10 minutes. The obtained solution was degassed by centrifugation to obtain a collagen hydrogel coating agent having the composition shown in Table 1. The obtained collagen hydrogel coating agent was stored in a refrigerator and used in the following examples.

[0070] [Table 1]

[0071] [Example 1B] Using collagen derived from porcine dermis tissue, a collagen hydrogel coating-forming agent was prepared having the composition shown in Table 1. Collagen extraction and collagen hydrogel coating-forming agent production were performed in the same manner as in Example 1A, except for the origin of the collagen.

[0072] [Example 1C] Using collagen derived from human placenta tissue, a collagen hydrogel coating-forming agent was prepared having the composition shown in Table 1. Collagen extraction and collagen hydrogel coating-forming agent production were performed in the same manner as in Example 1A, except for the origin of the collagen.

[0073] [Example 2] A collagen hydrogel coating agent having the composition shown in Table 2 was prepared using fish-derived collagen.

[0074] The red sea bream scales were washed with city water and finely chopped with a cutter of about 3 mm diameter using a meat grinder. The pretreated red sea bream scales were suspended in about 100 times the amount of water. Approximately 20% pepsin was added to the solid matter of the fish scales, the pH of the solution was adjusted to 1-2, and then the solution was gently stirred at 20-25°C for 48 hours. A filter aid was added to the stirred solution, which was then filtered through filter paper, and the resulting filtrate was further filtered through a 0.45 μm filter. The resulting filtrate was cooled to 5-10°C and the pH was adjusted to 7.0 with a 0.3 N sodium hydroxide aqueous solution to precipitate atelocollagen. The solution containing the precipitated atelocollagen was centrifuged or filtered, and the pellets were collected. The resulting pellets were freeze-dried to obtain atelocollagen powder.

[0075] 20 g of the atelocollagen powder obtained in the above process was added to a mixed solution of 0.3 wt% hydrochloric acid and glycerin in the ratio shown in Table 2, and stirred at room temperature for about 10 minutes, and then the solution was left to stand in a refrigerator at 4°C for 72 hours with a lid on to dissolve the atelocollagen. Similarly, 0.3 mol / L phosphate buffer (pH 7.0) and 2 mass% xanthan gum aqueous solution were mixed with the obtained solution and stirred at room temperature for 20 minutes. Stirring was stopped once, 2-phenoxyethanol was added, and the mixture was stirred again at room temperature for 10 minutes. The obtained solution was degassed by centrifugation to obtain a collagen hydrogel coating agent having the composition shown in Table 2. The obtained collagen hydrogel coating agent was stored in a refrigerator and used in the following examples.

[0076] [Table 2]

[0077] [Example 3: Shape stability of collagen hydrogel coating against water with and without thickener] The morphological stability of the coating formed by the collagen hydrogel coating-forming agent of the present invention was evaluated. Specifically, a water-rich environment was assumed as an environment in which the hydrogel coating is likely to collapse, and the morphological stability of the hydrogel coating in such an environment was evaluated.

[0078] 1.0 g of the collagen hydrogel film-forming agent prepared in Example 1A (composition is the same as in Table 1) or the film-forming agent obtained by replacing the 2% by mass xanthan gum aqueous solution of the film-forming agent with a phosphate buffer solution (composition is shown in Table 3) was weighed out and spread evenly on the bottom surface of a petri dish. A collagen hydrogel film was formed by supplying hot air from a hair dryer, and then 10 mL of purified water was added to the petri dish. The morphological stability of the hydrogel film was examined by removing the hydrogel film in the presence of purified water. The results are shown in FIG. 1.

[0079] [Table 3]

[0080] The film formed by the collagen hydrogel film-forming agent according to the present invention, which contains xanthan gum as a thickener, can be taken out even in the presence of purified water, and the film-like form is stably maintained when lifted, whereas the film-forming agent without the addition of a thickener cannot take out the hydrogel film as a film from the water, and the film-like form is unstable. From the above, it was found that the collagen hydrogel film-forming agent according to the present invention can form a hydrogel film with a stable form by containing a thickener, without further containing an emulsifier.

[0081] [Example 4: Use of collagen hydrogel film-forming agent for skin care effects] The skin care effect of the collagen hydrogel film-forming agent prepared in Example 1A was examined.

[0082] Five women in their 30s to 50s and three men in their 20s to 40s were given 2 to 3 pushes (about 2 to 3 mL) of a collagen hydrogel film-forming agent (4% collagen) after washing their face every evening, and 2 to 3 pushes (about 2 to 3 mL) of a film-forming agent (2% collagen) obtained by diluting the collagen hydrogel film-forming agent twice with a commercially available lotion after washing their face every morning for one month (Application Example 1). During the test period, the use of basic cosmetics and supplements other than the collagen hydrogel film-forming agent was prohibited, and sunscreen was used in combination during the day. The area values ​​of wrinkles, texture, and porphyrin (metabolite of acne bacteria) were measured using a skin diagnostic device (VISIA (registered trademark) evolution, Integral Co., Ltd.) up to five times during the one month period before and after the start of use of the collagen hydrogel film-forming agent, and the improvement rate compared to before the start of use was calculated.

[0083] Table 4 shows the improvement rate of wrinkles, skin texture and porphyrin after one month of use, and Fig. 2 shows examples of facial photographs of subjects before and after use. The improvement rate represents the average value of the reduction rate of wrinkles, skin texture and porphyrin area values ​​of each group of subjects based on the value before use, with Up representing a decrease in area and Down representing an increase in area. By applying the collagen hydrogel film-forming agent according to Application Example 1, both men and women showed improvement in wrinkles, skin texture and porphyrin. On the other hand, the only item that was observed to improve in subjects who applied commercially available cosmetics using the same application method was the skin texture of the male subjects.

[0084] [Table 4]

[0085] [Example 5: Use of collagen hydrogel film-forming agent in improving dry skin] The effect of the collagen hydrogel film-forming agent prepared in Example 1A on improving dry skin was examined.

[0086] A 68-year-old male applied one push (approximately 1 mL) of a collagen hydrogel film-forming agent (4% collagen) to the dry palms and backs of the hands of the subjects each day upon waking for a period of one minute.

[0087] Figure 3 shows pictures of the palms of the hands before and after use. Before use, there were many white peelings of keratin measuring a few millimeters in size on the palms of the hands, but after one week of daily application, the number of peelings had decreased significantly and the white areas had become smaller. In other words, a remarkable improvement in dry skin was observed.

[0088] [Example 6: Use of collagen hydrogel film-forming agent in acne care] The acne treatment effect of the collagen hydrogel film-forming agent prepared in Example 1A was examined.

[0089] A woman in her late 20s who regularly uses a commercially available acne care cream (a non-prescription drug) was given a collagen hydrogel film-forming agent (4% collagen) in addition to the non-prescription drug. She applied 2-3 pumps (2-3 mL) of the product to the affected areas of the face every day before going to bed for one week, spreading it over the affected areas over the course of about one minute.

[0090] Figure 4 shows photographs of the face before and after the combination. After starting the combination, inflammation was suppressed at an early stage and redness subsided. The occurrence of new acne was also suppressed more than with the quasi-drug alone. Before the combination, the skin was rough and inflamed even in areas other than the lacerations, but after the combination, the skin improved to normal.

Claims

1. A collagen hydrogel coating former comprising 1% by mass to 5% by mass of collagen, 0.1% by mass to 20% by mass of a thickener, 7% by mass to 25% by mass of a moisturizer, and 70% by mass or more of water.

2. 2. The film-forming agent according to claim 1, wherein the thickening agent comprises one or more thickening agents selected from the group consisting of xanthan gum, locust bean gum, carrageenan and hydroxyethyl cellulose.

3. The film-forming agent according to claim 1, wherein the thickening agent is one or more thickening agents selected from the group consisting of xanthan gum, locust bean gum and carrageenan.

4. The film-forming agent of claim 1 , wherein the thickening agent is xanthan gum.

5. The coating agent according to any one of claims 1 to 4, wherein the total content of lanolin, polysorbate 60 and polysorbate 80 is 10 mass% or less.

6. The coating agent according to claim 5, wherein the content of the emulsifier is 10% by mass or less.

7. The film-forming agent according to claim 6, which is free of an emulsifier.

8. The film-forming agent according to claim 7, wherein the moisturizing agent is one or more moisturizing agents selected from the group consisting of glycerin, sorbitol, and propylene glycol.

9. The film-forming agent according to claim 8 , wherein the humectant is glycerin.

10. The film-forming agent according to claim 9, which has a pH of 5.0 to 8.

0.

11. The film-forming agent of claim 10, further comprising a buffer.

12. The coating-forming agent according to claim 11, wherein the temperature of the collagen-containing solution is kept at 33° C. or lower and the pH of the solution is kept at 10.0 or lower during the process of extracting the collagen and the process of producing and storing the collagen hydrogel coating-forming agent.

13. A collagen hydrogel coating forming agent comprising 1% by mass to 5% by mass of atelocollagen, 0.14% by mass to 2% by mass of xanthan gum, 7% by mass to 11% by mass of glycerin, and 76% by mass or more of water, and containing an emulsifier in an amount of 10% by mass or less.

14. A method for producing a collagen hydrogel coating-forming agent, which contains 1% by mass to 5% by mass of collagen, 0.1% by mass to 20% by mass of a thickener, 7% by mass to 25% by mass of a moisturizer, and 70% by mass or more of water, wherein the collagen is extracted under conditions in which the pH of a solution containing the collagen is kept at 10.0 or less and the temperature of the solution is kept at 33° C. or less during the extraction process, and the pH of the solution containing the collagen is kept at 10.0 or less and the temperature of the solution is kept at 33° C. or less during the production and storage of the collagen hydrogel coating-forming agent.

15. The method according to claim 14 , wherein the collagen hydrogel film-forming agent further contains a buffer and an acid.

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