JP6142255B2 - Effervescent skin external preparation - Google Patents

Description

  The present invention relates to a foamable skin external preparation.

  Conventionally, a foamable skin external preparation containing a synthetic or natural extract having a blood circulation promoting action on the skin has been used.

  These extracts are not effective in a small amount of formulation, and for a large amount of formulation, the skin irritation is too great. Proposals have been made. Many of these substances generate carbon dioxide by the reaction between acidic substances and carbonates. From the standpoint of improving stability during storage, foaming skin preparations are separated from acidic substances and carbonates separately. A method has been adopted in which two agents that can be stored as agents are mixed and foamed during use. As the form of the two agents, for example, it has been proposed to use an aqueous solution and a solid (Patent Document 1), both using a viscous substance (Patent Document 2), a solid and a viscous substance (Patent Document 3), etc. The handling by the user is not always sufficient.

  Furthermore, even when the two-part foaming skin external preparation is used as described above, there are additives (active ingredients, etc.) reactive to either the acidic substance or carbonate in the same agent. Then, an acidic substance or carbonate may react gradually at the time of storage, and stability at the time of storage may fall.

  On the other hand, there is also a proposal of a two-part foaming skin external preparation in which a solid acidic substance and a solid carbonate coexist in the same agent (Patent Document 4), but depending on the conditions during production, the solid acidic substance And solid carbonate may react to generate carbon dioxide gas, or both may gradually react during storage to cause trouble such as carbon dioxide gas generation. However, there is no specific solution for this problem.

  In addition, in the two-pack type foamable cosmetic material disclosed in Patent Document 1 composed of an aqueous solution and a solid material, the solid material is coated with polyethylene glycol which is solid at room temperature. The coating with polyethylene glycol is intended to obtain a suitable sustained release property of carbon dioxide gas when the two agents are mixed at the time of use.

JP-A-63-310807 JP 05-229933 A International Publication No. 99/24043 JP 2010-275322 A

  The present invention has been made in view of the above circumstances, and a first object of the present invention is an effervescent skin external preparation containing an acidic substance and a carbon dioxide generating substance that reacts with the acidic substance to generate carbon dioxide. Another object of the present invention is to provide a foaming skin external preparation excellent in stability and durability, which does not cause problems such as unexpected generation of carbon dioxide gas during production or storage of the foamable skin external preparation. A second object of the present invention is to provide an effervescent skin external preparation that is easy to handle.

  The inventors include an acidic substance and a carbon dioxide generating substance that generates carbon dioxide by reacting with the acidic substance in the same agent so that the acidic substance and the carbon dioxide generating substance do not come into physical contact with each other. It was found that the above-mentioned problems can be solved by blending in, or not containing moisture in the same agent containing the acidic substance and the carbon dioxide generating substance, and the present invention has been completed. . Specifically, the present invention provides the following.

(1) Carbon dioxide gas which is a one-component type or multi-component type foamable skin external preparation of two or more types, and generates carbon dioxide gas by reacting at least an acidic substance and the acidic substance in any one of the same agent A foamable skin external preparation characterized by containing a generating substance and coexisting so that the acidic substance and the carbon dioxide generating substance do not contact each other.
(2) The foamable skin external preparation according to (1), wherein the acidic substance and / or the carbon dioxide generating substance has a coat layer.
(3) The foamable skin external preparation according to (2), wherein the coating layer contains at least one selected from the group consisting of carbohydrates, water-soluble polymers, organic acid salts, oils and fats, and hydrocarbon waxes. It is.
(4) The foamable external preparation for skin according to any one of (1) to (3), further containing a polysaccharide or metal soap in the same agent.
(5) The foamable external preparation for skin according to (4), wherein the polysaccharide is dextrin and / or starch, and the metal soap is calcium stearate.
(6) The foamable skin external preparation according to any one of (1) to (5), which is stored in a sealed container.
(7) The foamable external preparation for skin according to (6), wherein the gas in the sealed container is treated so as not to contain moisture.
(8) The foamable skin external preparation according to any one of (1) to (7), wherein the carbon dioxide generating substance is a carbonate.
(9) The foamable skin external preparation according to any one of (1) to (8), wherein the acidic substance and / or the carbon dioxide generating substance is solid.

  According to the present invention, even when an acidic substance and a carbon dioxide generating substance that reacts with the acidic substance to generate carbon dioxide are present in the same agent, the foaming skin external preparation is produced or stored. It is possible to provide a foamable skin external preparation excellent in stability and durability, which does not cause the problem of unexpected carbon dioxide generation. Furthermore, since a foamable skin external preparation can be made into one agent, packaging and the like can be simplified, manufacturing costs can be reduced, and the user can easily handle the foamable skin external preparation. Become. Furthermore, even when an additive such as an active ingredient having reactivity with each other is contained in the same agent, it is possible to obtain a foamable skin external preparation excellent in stability and durability.

It is a figure for demonstrating the coat layer formed in an acidic substance and / or a carbon dioxide generating substance.

  An aspect of the present invention is one or more types of foaming skin external preparation, wherein at least an acidic substance and a carbon dioxide generating substance that reacts with the acidic substance to generate carbon dioxide in the same agent are in contact with each other It is blended so that it does not occur, or water is not contained in the same agent. The dosage form of the foamable external skin preparation of the present invention as a whole may be a one-drug type, a two-drug type, or a multi-drug type higher than that.

  Mixing the acidic substance and the carbon dioxide generating substance in the same agent so that they do not come into contact with each other, or by containing no moisture in the same agent, one agent for foaming skin external preparation Can be more than a mold or two-part type. From the viewpoint of ease of handling, it is particularly preferable to use a one-pack type.

  Hereinafter, each component of the foamable skin external preparation of the present invention and a method for producing the external preparation will be described.

1. Acidic substance The acidic substance used in the present invention may be either an organic acid or an inorganic acid, and one or more of these are used. Further, these may be solid, gaseous or liquid, and are not particularly limited, but the reaction of carbon dioxide gas is likely to occur quickly, and the generation of carbon dioxide gas can be easily controlled by adjusting the amount. It is preferable to employ a solid material.

  Organic acids include linear fatty acids such as formic acid, acetic acid, propionic acid, butyric acid, valeric acid, oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, fumaric acid, maleic acid, phthalic acid, isophthalic acid Acids, dicarboxylic acids such as terephthalic acid, acidic amino acids such as glutamic acid and aspartic acid, glycolic acid, malic acid, tartaric acid, citric acid, lactic acid, hydroxyacrylic acid, α-oxybutyric acid, glyceric acid, tartronic acid, salicylic acid, gallic acid And oxyacids such as tropic acid, ascorbic acid and gluconic acid. Of these, citric acid, ascorbic acid, malic acid, and succinic acid are preferable from the viewpoints of safety and solubility in water.

2. Carbon Dioxide Generating Substance Various carbon dioxide generating substances that generate carbon dioxide by reacting with the acid used in the present invention can be used without any particular limitation. The carbon dioxide generating substance is preferably a carbonate such as sodium carbonate, calcium carbonate, potassium carbonate, magnesium carbonate, ammonium hydrogen carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, lithium hydrogen carbonate, cesium hydrogen carbonate, magnesium hydrogen carbonate. , Hydrogen carbonates such as calcium hydrogen carbonate and magnesium carbonate hydroxide, and the like, and one or more of these are used. Among these, sodium hydrogen carbonate is more preferable, and sodium hydrogen carbonate is more preferable in that a moderate foaming power can be realized. These may be solid or liquid, and are not particularly limited. However, the reaction of carbon dioxide is likely to occur quickly, and the generation of carbon dioxide is easily controlled by adjusting the amount. It is preferable to employ one.

  The acidic substance and the carbon dioxide generating substance may be a single powder or a granular substance, or may be a powder or a granule composed of a mixture with other components such as an excipient and a granulating agent. Anything that is powdery is acceptable.

3. Compounding substances Examples of other components that can be contained in the powder or granule include powders such as lactose, powdered sugar, starch, xylitol, D-sorbitol, glucose, D-mannitol, fructose, sucrose, sucrose, urea, etc. It can be used alone or in combination of two or more.

  Here, when granulating the acidic substance or the mixture of the carbon dioxide generating substance and other components to obtain granules of the acidic substance or the carbon dioxide generating substance, other components (however, the acidic substance or the The content of the coating layer covering the carbon dioxide generating substance is not particularly limited, but is preferably less than 80% by mass in the granule. When other components are present in a content exceeding 80% by mass, foaming properties are lowered, which is not preferable.

4). Granulation method The method for producing the above powder or granule is not limited to this example, dry crushing granulation method or wet crushing granulation method, fluidized bed granulation method, high-speed stirring granulation method, extrusion granulation It can be produced according to conventional methods such as law.

  For example, when a low melting point compound is used as a granulating agent as a matrix base, it is sufficient to add the acidic substance or the carbon dioxide generating substance to the low melting point granulating agent melted by heating in a container such as a beaker. Stir and mix. You may add an appropriate additive to this as needed. The mixture is further stirred while being cooled at room temperature, and left to solidify. If it hardens to some extent, it may be cooled rapidly in a refrigerator or the like.

  Further, for example, the above materials may be put into a fluidized bed granulator, mixed by airflow for several minutes, and then granulated by spraying water.

  When a low melting point compound is not used for the matrix base, the granulating agent is dissolved or dispersed in a suitable solvent such as water or ethanol in a container such as a beaker, and the carbon dioxide generating substance is dissolved or dispersed in this. After thoroughly mixing, heat in an oven to remove the solvent and dry. When it is completely hardened, it is pulverized and sieved to make the size of the granules, and then granulated.

  As the shape of the acidic substance or the carbon dioxide generating substance, for example, an irregular shape, a planar shape, a polyhedron shape, a spherical shape, a drop shape, a fiber shape, a columnar shape, a fine powder shape, and the like can be employed without particular limitation. Moreover, the thing of the wide range can be used without a restriction | limiting especially as the particle size. In particular, those having a particle size distribution of about 1,000 μm or less are more preferable from the viewpoint of ease of handling and ease of mixing with the viscous composition. The particle size distribution in the present invention can be determined by a normal laser diffraction / scattering method.

5). Means for Coexistence of Acidic Substance and Carbon Dioxide Generating Substance in the Same Agent The aspect of the present invention includes the acidic substance and the carbon dioxide generating substance in the same agent, and the acidic substance and the carbon dioxide gas in the same agent It is necessary that the generated substances are blended so that they do not come into physical contact with each other and coexist, or that the same agent does not contain moisture, but the coexistence means is not particularly limited and can be widely applied. Is possible.

  When blending so that the acidic substance and the carbon dioxide generating substance do not come into physical contact with each other, for example, a coating layer is provided on either or both of the acidic substance and the carbon dioxide generating substance. Alternatively, either one or both of the acidic substance and the carbon dioxide generating substance may be encapsulated. Further, a layer that does not contain the acidic substance and the carbon dioxide generating substance may be sandwiched between the acidic substance and the carbon dioxide generating substance so as not to be in direct contact with each other, and compression-molded to obtain a solid state.

  In addition, even if the acidic substance and the carbon dioxide generating substance are contained in the same agent, if the moisture is not included in the same agent, the problem of unexpected carbon dioxide generation may occur. Can be prevented. For example, as a component contained in the same agent containing the acidic substance and the carbon dioxide generating substance, powder, oil, non-aqueous solvent or the like is used, or the preservation thereof is performed in a sealed container without moisture permeability. It is feasible. Further, during storage, it is also preferable to perform treatment (for example, vacuum treatment or filling with an inert gas) so that the gas in the sealed container does not contain moisture, or use a desiccant or the like.

Hereinafter, the coexistence means of the acidic substance and the carbon dioxide generating substance in the same agent will be specifically described, but the invention is not limited thereto.

(1) First co-agent coexistence means First, the first co-agent coexistence means will be described in detail. That is, it is a method of “mixing and coexisting so that the acidic substance and the carbon dioxide generating substance do not come into physical contact with each other”.

(1-1) Coat Layer Formation The acidic substance and the carbon dioxide generating substance used in the present invention can be used without any particular limitation as long as they are described above, but at least one of them has a coat layer. By providing a coat layer, even if the acidic substance, the carbon dioxide generating substance and other components coexist in the same agent, there is no risk of unexpected carbon dioxide generation during the production or storage, so stability, It is preferable from the viewpoint of durability.

  FIG. 1 conceptually shows how the coat layer is formed. The coat layer indicated by reference numeral 2 in the figure is formed so as to cover all (see A) or part (see B) the surface of the acidic substance or carbon dioxide generating substance indicated by reference numeral 1. In the embodiment shown in A, since the entire surface of the acidic substance or carbon dioxide generating substance 1 is covered with the coat layer 2, the physical contact between the acidic substance and the carbon dioxide generating substance can be completely eliminated theoretically.

  The coating layer 2 covers only a part of the surface of the acidic substance or the carbon dioxide generating substance 1 as shown in B as long as physical contact between the acidic substance and the carbon dioxide generating substance can be suppressed. Also good. In this embodiment, a portion (exposed portion) that is not covered with the coat layer 2 exists on the surface of the acidic substance or the carbon dioxide generating substance 1. For this reason, when mixed with water during the use of the foamable skin external preparation, the water comes into contact with the exposed portion of the acidic substance or carbon dioxide generating substance 1 and quickly dissolves the acidic substance or carbon dioxide generating substance 1, Sufficient foaming can be obtained in a short time.

  A preferable coating agent for constituting the coating layer can be used without particular limitation as long as it has low reactivity with the acidic substance or the carbon dioxide generating substance. As the coating agent, any one or more selected from the group consisting of saccharides, water-soluble polymers, organic acid salts, fatty acids, polymers, oils and fats that dissolve at a certain temperature or higher by heating, and hydrocarbon waxes are used. be able to. Among these, saccharides, water-soluble polymers, organic acid salts and oils are preferred.

Examples of sugars include disaccharides such as lactose (lactose), sucrose (sucrose), maltose (malt sugar), and trehalose; oligosaccharides or oligosaccharides having three or more sugars; sucrose; sugar alcohols such as mannitol, sorbitol, and xylitol. Can be mentioned.
Examples of the water-soluble polymer include cellulose derivatives such as starch and cellulose gum, xanthan gum, carrageenan, pectin, and dextrin. Examples of the cellulose derivative include methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl hydroxyethyl cellulose, methyl hydroxypropyl cellulose, and carboxymethyl cellulose in addition to cellulose gum (carboxymethyl cellulose).
Among these, lactose, sucrose, trehalose and mannitol are preferable for saccharides, and starch, cellulose gum, xanthan gum and dextrin are preferable for water-soluble polymers.

  Examples of the organic acid salt include citrate, tartrate, succinate, adipate, fumarate, malate, malonic acid, and pyrrolidonecarboxylate. Among these, citrate is preferable.

Examples of the fatty acids include fatty acids having 12 to 22 carbon atoms, such as lauric acid, myristic acid, palmitic acid, stearic acid, and behenic acid.

Examples of the polymer include N-vinyl-2-pyrrolidone polymers such as polyvinyl pyrrolidone and copolymers of vinyl pyrrolidone and vinyl acetate. Polymers of ethylene glycol such as polyethylene glycol are not preferable from the viewpoint of stability and durability.

  Examples of the fats and oils include rapeseed oil, castor oil, coconut oil, and beef tallow, and hydrogenated hydrogenated oils can also be used. Further, higher alcohols such as behenyl alcohol, cetyl alcohol, myristyl alcohol and stearyl alcohol, and waxes such as beeswax and carnauba wax can also be used.

  Examples of the hydrocarbon wax include petrolatum, paraffin wax, and microcrystalline wax. Solid dosage forms are more suitable for coating.

  These coating agents can be used alone or in combination of two or more. In particular, when an acidic substance such as citric acid is coated, it is preferable to employ an organic acid salt such as calcium citrate.

  The amount of the coating agent used for the acidic substance and / or carbon dioxide generating substance is 1 to 100% (w / w) with respect to the acidic substance or carbon dioxide generating substance (acidic substance or carbon dioxide generating substance: coating agent = 100 : 1 to 100: 100), preferably 1 to 67% (100: 1 to 60:40), more preferably 1 to 43% (100: 1 to 70:30), and 1 to 25% (100: 1 to 100: 100). 80:20).

  The coating layer may be coated by any method as long as it is usually used for coating particles. For example, it may be coated at the same time as granulation by spray granulation or tumbling granulation, etc., and the powder or granulated product is coated with oil and fat, granulation coating, transport layer method, pan coating, rolling coating, fluid coating or You may coat | cover using methods, such as dry coating. When excessive heat or physical force is applied during coating, the acidic substance or the carbon dioxide generating substance is destroyed and the generated film is broken, and the surface of the acidic substance or the carbon dioxide generating substance is broken. Not only is it difficult to uniformly coat the lipid powder on the whole, but the acidic substance or the carbon dioxide generating substance leaks out on the surface and solidifies due to moisture absorption, or it may cause adverse effects on other components during compounding. The coating conditions must be such that the coating layer and the coating object are not destroyed.

  In the case of the coating layer of the embodiment shown in FIG. 1A, for example, an acidic substance or a carbon dioxide gas generating substance is added to a coating agent (such as fats and oils) dissolved under a certain condition, and the mixture is uniformly mixed and then cooled. Thereby, the coating layer which coat | covers the whole surface of an acidic substance or a carbon dioxide generating substance can be formed.

  In the case of the coating layer of the embodiment shown in FIG. 1B, for example, an acidic substance or a carbon dioxide generating substance is moistened, and a coating agent (sugar, water-soluble polymer, organic acid salt, fat or the like) is sprayed and attached. And let it dry. Thereby, the coat layer which coat | covers the surface of an acidic substance or a carbon dioxide generating substance partially can be formed.

The coating layer prevents unexpected carbon dioxide generation by preventing physical contact between the acidic substance and carbon dioxide generating material during manufacture and storage, while at the time of use (when mixed with a liquid containing moisture). It is necessary that the acidic substance and the carbon dioxide generating substance react appropriately to generate a desired amount of carbon dioxide. Therefore, when using the coating agent which does not melt | dissolve in water, such as fats and oils, the coat layer of the aspect shown to FIG. 1A is preferable. When a water-soluble coating agent is used, FIG. 1A,
Any of the coating layers shown in B can be employed.

(1-2) Encapsulation The method for encapsulating the acidic substance and / or carbon dioxide generating substance of the present invention is not particularly limited, and a known method can be adopted.

  As the encapsulation method, a known method can be applied without any particular limitation. Examples of the encapsulation material include gelatin, starch, gum arabic, methylcellulose, acrylic acid ester, methacrylic acid ester, vinyl acetate, Polyvinyl alcohol, silicone resin, solid wax, polyethylene, fatty acid, higher alcohol, and the like, and those formed with a multilayer of surfactants such as liposomes are included, but can be widely used without being limited thereto. For example, the basic structure of the capsule is composed of a homopolymer or copolymer formed from one or more monomers selected from acrylic acid ester, methacrylic acid ester, vinyl acetate, and styrene, or the monomer and acrylic acid, methacrylic acid, divinyl A resin capsule made of a copolymer formed from a monomer selected from benzene and ethylene glycol dimethacrylate is also preferable. In such a microcapsule, the contents and the polymer constituent monomer constituting the capsule shell are emulsified in a reaction solvent such as water, and polymerization of azobisisobutyronitrile, benzoyl peroxide, etc. is started. What is necessary is just to add an agent and to perform emulsion polymerization. As a surface active component used for such emulsification, for example, hexlite sold under the name of “Laponite XLG” can be suitably exemplified. The produced microcapsules are separated by means such as centrifugation, and if desired, the microcapsules of the present invention can be produced by washing.

(1-3) Solidification In the present invention, the acidic substance and the carbon dioxide gas are generated so that they do not directly contact between the first layer containing the acidic substance and the second layer containing the carbon dioxide generating substance. It is also one of useful methods to sandwich a third layer made of a substance other than the substance (for example, excipient, thickener, etc.) and to solidify it by compression molding. The solidified dosage form may be any dosage form as long as it is solid, such as a tablet, a sphere, and a plate. Here, the acidic substance to be used and the carbon dioxide generating substance may be used as they are, or the acidic substance in which a coating layer is provided by the above-described method on either one of the first layer and the second layer, or A carbon dioxide generating substance, the encapsulated acidic substance or the carbon dioxide generating substance may be used. As a solidification method, a known method can be applied without any particular limitation.

  The acidic substance and the carbon dioxide generating substance contained in the first layer and the second layer may be used as they are, or in addition, excipients, thickeners and the like may be mixed and used. . As the excipient, thickener and the like used for the first layer, the second layer and the third layer, those described in the description of the granule can be used without any particular limitation.

(1-4) Auxiliary means for coexisting means in the first same agent The foamable external preparation for skin according to the present invention contains polysaccharides, metal soap, etc. in addition to the above-mentioned acidic substances and carbon dioxide generating substances. It is preferable to contain. By adding polysaccharides, metal soap, etc. to the acidic substance and carbon dioxide generating substance at least one of which is coated, encapsulated or solidified, the effect of preventing the generation of unexpected carbon dioxide can be enhanced. The addition amount of polysaccharides and the like is, for example, about 1 to 20% (w / w), preferably 5 to 10% (w / w) with respect to the entire same agent containing the acidic substance and the carbon dioxide generating substance. It is said to be about. In addition, the polysaccharide etc. which are added should just be a solid form, for example, may be a powder form and a granular form.

Examples of polysaccharides and derivatives thereof include, for example, dextrin, maltodextrin, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl hydroxyethyl cellulose, methyl hydroxypropyl cellulose, carboxymethyl cellulose, guar gum, hydroxypropyl guar gum, hydroxyethyl guar gum, carboxymethyl guar gum, Examples thereof include cationized guar gum, locust bean gum, tamarind gum, tragacanth gum, pectin, glucomannan, schizophyllan, carrageenan, alginic acid, agar, agarose, starch, xanthan gum, dextran, curdlan, pullulan, inulin and the like. Of these, dextrin and starch are preferred.

  Examples of the metal soap include calcium salts such as calcium stearate, calcium myristate, and calcium palmitate, and magnesium salts such as magnesium stearate, magnesium myristate, and magnesium palmitate. Among these, calcium stearate is preferable.

(1-5) Carbon dioxide generator for effervescent skin external preparation In the present invention, the acidic substance and the carbon dioxide generator are blended, at least one of which has a coating layer, and at least one of them is encapsulated. A solidified layer formed between the first layer containing the acidic substance and the second layer containing the carbon dioxide generating substance is supplied as a carbon dioxide generator for the foamable skin external preparation. May be. The carbon dioxide gas generating agent for foamable external preparation for skin preferably contains polysaccharides, metal soap and the like.

(2) Second means for coexisting in the same agent Next, the second means for coexisting in the same agent will be described in detail. That is, it is a method of “not containing water in the same agent”. In the same agent containing the acidic substance and the carbon dioxide generating substance, it is preferable not to contain water that promotes at least the reaction between them.

  In this invention, the water | moisture content in a foamable skin external preparation contains the water | moisture content released | released by a time-dependent change from all the components mix | blended with a foamable skin external preparation in addition to a liquid or gaseous thing. By not containing these moisture in the same agent, even if the acidic substance and the carbon dioxide generating substance are in direct contact with each other, the problem of unexpected carbon dioxide generation can be prevented.

  Therefore, it is necessary to appropriately select other components contained in the agent containing the acidic substance and the carbon dioxide generating substance so as not to contain moisture. Furthermore, by preventing moisture from entering the foamable external preparation for the skin from the environment and removing moisture released over time from the contained components, a state in which no moisture is contained in the agent is obtained. It is important to maintain.

6). Effervescent skin external preparation In addition to the acidic substance and the carbon dioxide generating substance, the effervescent skin external preparation of the present invention includes an active ingredient, a thickener, a pH adjuster, fats and oils, a fragrance, a colorant, an antioxidant, It is usually used in skin external preparations such as fungicides, alcohols, polyhydric alcohols, nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, inorganic salts, lubricants and solvents. It can be mixed with one or more of the above components to form a one-part foamable skin external preparation. The carbon dioxide gas generating agent for effervescent skin external preparation can also be used when preparing a one-pack type effervescent skin external preparation.

  In addition, a two-part foaming skin external preparation comprising at least the first agent containing the acidic substance and the carbon dioxide generating substance and a second agent containing at least water may be used. Is possible. Also at this time, when preparing the first agent, a carbon dioxide gas generating agent for foamable skin external preparation can be used.

When it is a two-part foaming external preparation for skin, active ingredients, thickeners, pH adjusters, fats and oils, fragrances, colorants, antioxidants, antibacterial and fungicides, alcohol, polyhydric alcohols, nonionic surface activity Agent,
One or more components selected from an anionic surfactant, a cationic surfactant, an amphoteric surfactant, an inorganic salt, a lubricant, a solvent, and the like can be mixed in the first agent or the second agent.

  As a liquid that can be added in the same agent containing the acidic substance and the carbon dioxide generating substance, it is preferable to use a non-aqueous solution in the liquid, for example, a liquid oil such as hydrocarbon oil, fat, ester oil, silicone oil, Examples include polyhydric alcohols such as propylene glycol, essential oils, fragrances, non-aqueous solvents such as glycol ethers, nonionic surfactants, and the like. On the other hand, examples of solids include excipients such as lactose, oligosaccharides and starches, desiccants and the like. Furthermore, examples of the desiccant include chemical desiccants such as calcium chloride, magnesium perchlorate, and anhydrous sodium sulfate, and physical desiccants such as silica gel, aluminum oxide, molecular sieve, and zeolite.

  The foamable skin external preparation of the present invention can be made into a multi-drug form of three or more types by appropriately changing the mode of the two-part foamable external skin preparation. On the other hand, it is preferable to make the foamable skin external preparation of the present invention into a one-pack type because packaging can be simplified and the production cost can be reduced.

  Hereinafter, representative components that can be used in addition to the acidic substance and the carbon dioxide generating substance contained in the foamable skin external preparation of the present invention will be further described.

  The active ingredient used in the present invention is not particularly limited, and drugs and plants that are usually used in cosmetics, external medicines, quasi drugs, and the like can be used depending on the purpose. Typical examples include glycyrrhizic acid or derivatives thereof, whitening agents such as placenta extract, moisturizing ingredients such as propylene glycol, polyethylene glycol, sorbitol, sodium lactate, sodium pyrrolidonecarboxylate, and plant ingredients such as licorice. It is done. As plant components, the whole plant, leaves (leaf blades, petiole, etc.), fruits (mature, immature, etc.), seeds, flowers (petals, ovary, etc.), stems, rhizomes, roots, tuberous roots, etc., are used as they are. These can be used after being cut, crushed, pulverized, exploited, or dried or powdered.

  The thickener used in the present invention is not particularly limited as long as it is a water-soluble component that can be used in the fields of cosmetics, external medicines, and quasi drugs. Polyacrylic acid, polyacrylamide, polyalkylacrylamide / Hydrophilic synthetic polymers such as polyacrylamide copolymer, carboxymethylcellulose, cationized cellulose, and hydrophilic natural polymers such as xanthan gum, succinoglycan, guar gum, locust bean gum, laponite, bentonite, smectite Examples thereof include hydrophilic thickening compounds such as hydrophilic clay minerals. Among these, it is preferable to use a hydrophilic thickener having a large interaction with moisture contained in the external preparation for skin. On the other hand, when a normal thickener used in cosmetics or the like is used, when the acidic substance is contained, the viscosity is lowered, which may cause dripping.

  In the case of a one-part foamable skin external preparation, foaming is caused by mixing a liquid containing moisture and the one-part foamable skin external preparation, whereas in the case of a two-part foamable skin external preparation, two parts Foaming can be started by mixing. The water-containing liquid used in the present invention is not limited to any liquid as long as it is a liquid containing water in addition to water used in cosmetics, pharmaceuticals, etc., water used in general households. be able to. For example, tap water, distilled water, membrane filtered water, ion exchange water, deep ocean water, sake, wine such as sake, soy milk, drink yogurt, acerola juice, sports drink, carbonated water drink, rice tofu, etc. Is mentioned. These can be used alone or in combination of two or more.

The amount of water-containing liquid used is not particularly limited and can be used in a wide range, but it is preferably added in an amount of 1 to 5 times by weight with respect to the external preparation for skin, and 2 to 4 times. It is more preferable to add the amount. By adding more than 1 times the amount of liquid, the external preparation for skin can be quickly dissolved, and a sufficient amount of carbon dioxide gas can be generated. On the other hand, dripping due to a decrease in viscosity of the external preparation for skin can be prevented by adding the liquid within 5 times the amount.

  The temperature of the liquid containing the moisture used is not particularly limited and can be used in a wide range. However, since the action of the active ingredient contained in the one-part skin external preparation is enhanced, it is particularly useful to cool it in advance. preferable. The usable temperature range is preferably water at about room temperature or tap water from the viewpoint of usability during application and user convenience.

7). Form of use of foamable skin external preparation In the case of the one-part foamable skin external preparation of the present invention, foaming is caused by mixing with a liquid containing moisture on the palm or in the container. In the case of a two-part foaming external preparation for skin, foaming is caused by mixing the two parts on the palm or in a container during use.

  The method for preserving the effervescent skin external preparation is not particularly limited as long as it is stored while blocking moisture in both cases of the one-part type effervescent skin external preparation and the two-part type effervescent skin external preparation. Therefore, these are preferably stored in a sealed state in a storage container. The shape of the storage container to be used can be appropriately selected according to the purpose, and examples thereof include cup shape, tube shape, bag shape, bottle shape, stick shape, pump shape, jar shape, and canned shape. Moreover, the material which comprises a storage container can use metals, such as plastic, glass, aluminum, paper, various polymers, etc. individually or in 2 types or more, It can use widely, without being limited to these.

  Specific examples of containers include: aluminum sticks laminated with polyethylene terephthalate on the inner surface, storage bags such as aluminum bags, stand pouch with chuck, polyethylene terephthalate on the inner surface in terms of hermeticity, storage stability of contents, manufacturing cost, etc. A storage container made of polyethylene terephthalate in which the lid is heat-sealed with an aluminum film or the like laminated with is preferable.

  Furthermore, in order to block moisture, the inside of the sealed container to be used is preferably evacuated or filled with dry nitrogen or the like.

8). Use of effervescent skin external preparation The effervescent skin external preparation of the present invention promotes an increase in skin blood flow, and is intended for whitening, skin quality improvement, freckles improvement, skin rejuvenation, skin tightening, and partial skin thinning. It can be suitably used not only for cosmetics such as cosmetics, emulsions, creams, packs, and peeling agents, but also for quasi-drugs such as hair, cleaning agents, bathing agents, and pharmaceuticals such as drugs. .

1. Stability evaluation test I
<Example 1>
Carbonate for effervescent skin external preparation using 0.2 g (2 parts by mass) of citric acid powder having a coating layer as an acidic substance and 0.8 g (8 parts by mass) of sodium bicarbonate powder as a carbon dioxide generating substance A gas generating agent was prepared. The coating layer is formed on the citric acid powder by moistening 0.19 g (95 parts by mass) of the citric acid powder, spraying and adhering 0.01 g (5 parts by mass) of calcium citrate thereto, and then drying. Went by.

The citric acid powder on which the coating layer was formed and the sodium hydrogen carbonate powder were housed in an aluminum film bag whose inner surface was laminated with polyethylene terephthalate and sealed. It was stored at 40 ° C., 50 ° C. or 60 ° C. for 17 to 27 days, and during the storage period, the presence or absence of carbon dioxide gas was observed using the presence or absence of bag expansion as an index.

<Example 2>
Evaluation was performed in the same manner as in Example 1 except that 1% w / w dextrin powder was added to the carbon dioxide gas generating agent for foamable external skin preparation of Example 1.

<Examples 3 to 6>
Evaluation was carried out in the same manner as in Example 2 except that the amount of dextrin added to the carbon dioxide gas generating agent for an effervescent skin external preparation was changed to 2.5, 5, 7.5, and 10% w / w.

<Comparative Example 1>
0.19 g (2 parts by mass) of citric acid powder and 0.8 g (8 parts by mass) of sodium hydrogen carbonate powder were placed in an aluminum film bag without forming a coating layer and sealed. The presence or absence of carbon dioxide gas generation was observed in the same manner as in Example 1.

  The results are shown in “Table 1”. In the table, “None” indicates that carbon dioxide gas was not generated during the storage period (17 to 27 days). “Yes” indicates that carbon dioxide gas was generated, and the numbers in parentheses indicate the number of storage days in which foaming was observed.

  In Comparative Example 1 in which no coat layer was formed, generation of carbon dioxide gas was confirmed after one day at any storage temperature of 40 ° C., 50 ° C., and 60 ° C. On the other hand, in Example 1 in which a coat layer of calcium citrate was formed on the citric acid powder, generation of carbon dioxide gas was not observed over the entire period of observation under storage conditions of 40 ° C., and storage at 50 ° C. and 60 ° C. Even under the conditions, the generation of carbon dioxide gas was 7 days later and 3 days later, respectively. From this result, it was shown that the formation of a coat layer can prevent the generation of unexpected carbon dioxide during storage.

  In Examples 2 to 6 in which dextrin was further added to the carbon dioxide generating agent for effervescent skin external preparation, generation of carbon dioxide during the storage period could be more effectively prevented. When the addition amount of dextrin was 1%, 2.5%, 5%, 7.5%, the stability of the external preparation for skin was improved in a concentration-dependent manner, and the effect of significantly delaying the generation of carbon dioxide gas was achieved. In addition, in the test conducted by changing the powder to be added to the carbon dioxide gas generating agent for effervescent skin external preparations from dextrin to starch, the effect of preventing the generation of carbon dioxide during the storage period was obtained, similar to dextrin. It was.

<Example 7>
Evaluation was performed in the same manner as in Example 1 except that 3% w / w calcium stearate powder was added to the carbon dioxide gas generating agent for effervescent skin external preparation.

<Example 8>
Evaluation was performed in the same manner as in Example 7 except that the amount of calcium stearate added to the carbon dioxide generating agent for foamable external skin preparation was changed to 5% w / w.

  The results are shown in “Table 2”.

  In Examples 7 and 8 in which calcium stearate was added to a carbon dioxide gas generating agent for an effervescent skin external preparation, Comparative Example 1 in which no coating layer was formed and Example 1 in which only a coating layer was formed with calcium citrate (Table) 1)), the generation of carbon dioxide was significantly delayed. From these results, it was shown that the stability of the external preparation for skin can be improved by adding calcium stearate to the carbon dioxide generating agent for foamable external preparation for skin. Although the mechanism by which calcium stearate and the above dextrin and starch delay the generation of carbon dioxide gas is not clear, the possibility of contributing to the stabilization of the coating layer was considered.

2. Stability evaluation test II
<Example 9>
Using 0.18 g of citric acid powder (citric acid equivalent, 2 parts by mass) and 0.8 g (8 parts by mass) of sodium bicarbonate powder on which a calcium citrate coat layer is formed, for an effervescent skin external preparation A carbon dioxide generator was prepared. The coating layer was formed on the citric acid powder in the same manner as in Example 1 except that the mass part ratio of the citric acid powder and calcium citrate was 9: 1.

  The citric acid powder on which the coat layer was formed and the sodium hydrogen carbonate powder were housed in an aluminum film bag whose inner surface was laminated with polyethylene terephthalate and sealed. It was stored at 40 ° C., 50 ° C. or 60 ° C. for 20 days, and during the storage period, the presence or absence of carbon dioxide gas was observed using the presence or absence of bag expansion as an index. As the carbon dioxide gas generating agent for effervescent skin external preparation which is a reference for evaluation, the above-mentioned Example 1 was also tested.

<Example 10>
Evaluation was performed in the same manner as in Example 9 except that 6% of dextrin powder was added to the carbon dioxide gas generating agent for foamable skin external preparation of Example 9 with respect to the total weight.

<Example 11>
Using 0.18 g of citric acid powder (citric acid equivalent, 2 parts by mass) and 0.8 g of sodium hydrogen carbonate powder (8 parts by mass) on which a coating layer of fat (rapeseed oil) is formed A carbon dioxide gas generating agent was prepared. The coating layer was formed on the citric acid powder by moistening 0.16 g (8 parts by mass) of the citric acid powder, spraying and attaching 0.04 g (2 parts by mass) of rapeseed oil, and then drying. .

<Example 12>
Evaluation was performed in the same manner as in Example 11 except that 6% of the dextrin powder was added to the carbon dioxide gas generating agent for foamable external skin preparation of Example 11 with respect to the total weight.

<Example 13>
Using 0.18 g (2 parts by mass) of citric acid powder and 0.8 g of sodium hydrogencarbonate powder (sodium hydrogen carbonate equivalent, 8 parts by mass) on which a coating layer of fat (oiled rapeseed oil) was formed, A carbon dioxide generating agent for an external preparation for skin was prepared. Formation of the coating layer on the sodium carbonate powder was carried out in the same manner as in Example 11 except that the mass part ratio between the sodium carbonate powder and the oil was 9: 1.

<Example 14>
Evaluation was performed in the same manner as in Example 13 except that 6% of the dextrin powder was added to the carbon dioxide gas generating agent for foamable external skin preparation of Example 15 with respect to the total weight.

<Example 15>
0.18 g of citric acid powder with a calcium citrate coating layer (citric acid equivalent, 2 parts by mass), 0.8 g of sodium hydrogen carbonate powder with a coating layer of fat (rapeseed rapeseed oil) (hydrogen carbonate) Sodium equivalent, 8 parts by mass) was used to prepare a carbon dioxide gas generating agent for effervescent skin external preparation. Formation of the coat layer on the citric acid powder was performed according to the method described in Example 1. The same thing as Example 13 was used for the sodium hydrogen carbonate in which the coating layer of rapeseed oil was formed.

<Example 16>
Evaluation was performed in the same manner as in Example 15 except that 6% of the dextrin powder was added to the carbon dioxide gas generating agent for foamable external skin preparation of Example 17 with respect to the total weight.

<Comparative example 2>
Foaming using 0.18 g of citric acid powder (citric acid equivalent, 2 parts by mass) and 0.8 g (8 parts by mass) of sodium bicarbonate powder on which a coating layer of polyethylene glycol (molecular weight 4,000) was formed. A carbon dioxide generator for a topical skin external preparation was prepared. Formation of the coating layer on the citric acid powder was performed in the same manner as in Example 1 except that 1/10 part by mass of polyethylene glycol was used with respect to the citric acid powder.

<Comparative Example 3>
Using 0.18 g (2 parts by mass) of citric acid powder and 0.8 g of sodium bicarbonate powder (sodium bicarbonate equivalent, 8 parts by mass) on which a coating layer of polyethylene glycol (molecular weight 4,000) was formed, A carbon dioxide generator for a foamable external preparation for skin was prepared. Formation of the coating layer on the sodium carbonate powder was carried out in the same manner as in Example 11 except that 1/10 parts by mass of polyethylene glycol was used with respect to the sodium carbonate powder.

<Comparative example 4>
The same coated citric acid powder 0.18 g (citric acid equivalent, 2 parts by mass) as in Comparative Example 2 and the same coated sodium bicarbonate powder 0.8 g (sodium bicarbonate equivalent, 8 masses) as in Comparative Example 3. Part) was used to prepare a carbon dioxide gas generating agent for effervescent skin external preparation.

  The results are shown in “Table 4”. In the table, “None” indicates that carbon dioxide gas was not generated during the storage period (20 days). “Yes” indicates that carbon dioxide gas was generated, and the numbers in parentheses indicate the number of storage days in which foaming was observed.

  In Examples 9 to 16, generation of carbon dioxide gas could be prevented or delayed as compared with Example 1 which was used as a reference for evaluation. On the other hand, in Comparative Examples 2 to 4, generation of carbon dioxide gas was confirmed after one day at any storage temperature of 40 ° C., 50 ° C., and 60 ° C.

3. Stability evaluation test III
Using a citric acid powder having a coating layer formed of various coating agents, it was mixed with sodium hydrogen carbonate to prepare a carbon dioxide gas generating agent for an effervescent skin external preparation. The carbon dioxide generating agent for effervescent skin external preparation was accommodated in an aluminum film bag having an inner surface laminated with polyethylene terephthalate and sealed. It was stored at 40 ° C. for 1 day, and the presence or absence of carbon dioxide was observed using the presence or absence of bag expansion as an index.

  As the coating agent, lactose, sucrose, trehalose, mannitol, dextrin, potato starch, cellulose gum, xanthan gum, stearic acid, polyethylene glycol (molecular weights 400, 1,500, 4,000, 20,000) were used.

  To 8 g of citric acid powder, 0.3 g of purified water was added, and the whole was moistened while mixing well. 2 g of the coating agent was added to the moistened citric acid powder, and the mixture was thoroughly coated until uniform, and then dried at 60 ° C. for 2 to 3 hours. The citric acid powder (2 parts by mass) on which the coating layer was formed was mixed with sodium hydrogen carbonate powder (8 parts by mass).

  As a result, in the carbon dioxide generator for effervescent skin external preparations containing citric acid powder formed with a coat layer of lactose, sucrose, trehalose, mannitol, dextrin, potato starch, cellulose gum and xanthan gum, no carbon dioxide is generated. It was. On the other hand, carbon dioxide gas was generated in the foamable skin external preparation carbon dioxide generator containing citric acid powder having a coat layer formed of stearic acid and polyethylene glycol or citric acid powder having no coat layer formed.

  Even in an additional test in which the storage temperature was 50 ° C. or 60 ° C., lactose, dextrin, potato starch, cellulose gum and xanthan gum did not generate carbon dioxide on the seventh day of storage, and good stability was confirmed. In addition, using lactose as the coating agent, the mass ratio of the citric acid powder and the coating agent (citric acid powder: lactose) was changed from 8: 2 to 7: 3, 6: 4, or 5: 5. As a result, good stability could be confirmed in all cases (60 ° C., 5 days).

4). Efficacy evaluation test I
<Formulation example 1>
According to the following formulation, a two-part foamable skin external preparation consisting of granules and gels was prepared.
A: Granule (carbon dioxide generator for effervescent skin external preparation)
Calcium citrate coated citrate powder
: 0.2 g (citric acid equivalent)
Sodium bicarbonate powder: 0.8g
B: Gel agent Butylene glycol: 1.95 g
Xanthan gum: 0.13 g
Phenoxyethanol: 0.04g
Water: 10.88g

  A clinical trial was conducted using the prepared preparation. The subjects were four women in their 20s to 30s. After acclimation for 15 minutes after the face washing, the first measurement was carried out for (1) stratum corneum moisture content, (2) moisture transpiration rate, and (3) skin elasticity. The foaming skin external preparation was applied to the entire face and left for 15 minutes. After removing the effervescent skin external preparation with a spatula and rinsing, it was acclimated for 15 minutes, and then the second measurement was performed.

(1) The stratum corneum moisture content was measured using SKICON-200EX (IBS Corporation). (2) The moisture transpiration was measured using a Tevameter (registered trademark) TM300 (CK Corporation). (3) Skin elasticity was measured using a Cutometer (registered trademark) MPA580 (CK company).

<Formulation example 2>
Measurement was performed in the same manner as in Formulation Example 1 except that 1% w / w dextrin powder was added to the granule of Formulation Example 1.

<Comparative formulation example 1>
Measurement was performed in the same manner as in Formulation Example 1 except that the citric acid powder coated with the calcium citrate granule of Formulation Example 1 was changed to an uncoated citric acid powder.

<Comparative formulation example 2>
The measurement was performed in the same manner as Comparative Formulation Example 2, except that 1% w / w dextrin powder was added to the granule of Comparative Formulation Example 2.

  The results are shown in “Table 5” to “Table 7”. In each table, the first measurement value, the second measurement value, and the rate of change are shown as an average value ± standard deviation of four subjects.

(1) stratum corneum moisture content

(2) Moisture transpiration

(3) Skin elasticity

  In Formulation Examples 1 and 2, compared with Comparative Formulation Examples 1 and 2, (1) keratin water content and (3) skin elasticity after use were significantly increased. Further, in Formulation Examples 1 and 2, compared to Comparative Formulation Examples 1 and 2, (2) moisture transpiration after use could be significantly suppressed. From these results, it was confirmed that the foamable skin external preparation according to the present invention markedly improved the skin condition and exhibited an excellent cosmetic effect.

<Prescription example>
According to the following prescription examples 1-4, the one-pack type foaming external preparation for skin was prepared.

Formulation Example 1
Sodium bicarbonate: 0.5-40%
Coated citric acid Citric acid: 0.2-30%
Calcium citrate: 0.01-2%
Xanthan gum: 1-20%
Glucose: remaining amount

Formulation Example 2
Sodium bicarbonate: 0.5-40%
Coated citric acid Citric acid: 0.2-30%
Calcium citrate: 0.01-2%
Dextrin: 0.1-30%
Xanthan gum: 1-20%
Glucose: remaining amount

Formulation Example 3
Coated sodium hydrogen carbonate Sodium hydrogen carbonate: 0.5-40%
Oilseed rapeseed oil: 0.05-5%
Citric acid: 0.2-30%
Dextrin: 0.1-30%
Xanthan gum: 1-20%
Glucose: remaining amount

Formulation Example 4
Coated sodium hydrogen carbonate Sodium hydrogen carbonate: 0.5-40%
Oilseed rapeseed oil: 0.05-5%
Coated citric acid Citric acid: 0.2 to 30%
Calcium citrate: 0.01-2%
Dextrin: 0.1-30%
Xanthan gum: 1-20%
Glucose: remaining amount

Formulation Example 5
Sodium bicarbonate: 0.5-40%
Coated citric acid Citric acid: 0.2-30%
Lactose: 0.01-2%
Xanthan gum: 1-20%
Glucose: remaining amount

Formulation Example 6
Sodium bicarbonate: 0.5-40%
Coated citric acid Citric acid: 0.2-30%
Cellulose gum: 0.01-2%
Dextrin: 0.1-30%
Xanthan gum: 1-20%
Glucose: remaining amount

1: Acidic substance or carbon dioxide generating substance, 2: Coating agent

Claims (5)

A one-part type or two-part or more multi-form foamable skin external preparation, and at least one organic acid and a carbon dioxide generating substance that generates carbon dioxide by reacting with the organic acid in the same agent And the organic acid and the carbon dioxide generating substance coexist so as not to contact each other ,
The organic acid has a coating layer containing at least one selected from citrate, tartrate, succinate, adipate, fumarate, malate and malonate. Effervescent skin external preparation. Effervescent skin external preparation according to claim 1 in the same agent, which further contains a polysaccharide or a metal soap. The foamable skin external preparation according to claim 2 , wherein the polysaccharide is dextrin and / or starch, and the metal soap is calcium stearate. The foamable skin external preparation according to any one of claims 1 to 3 , wherein the carbon dioxide generating substance is a carbonate. The foamable skin external preparation according to any one of claims 1 to 4 , wherein the acidic substance and / or the carbon dioxide generating substance is solid.

Images