JP6190696B2 - Effervescent skin external preparation - Google Patents

Description

  The present invention relates to an effervescent skin external preparation characterized by having excellent foamability and increased permeability of carbon dioxide gas to the skin, and more particularly, an acidic substance, carbon dioxide gas that reacts with the acidic substance and reacts with the acidic substance. Carbon dioxide foaming skin characterized by containing squalane as a carbon dioxide skin absorption enhancer in a solid, granular or powdery carbon dioxide foaming skin external preparation containing a carbon dioxide generating substance that generates carbon dioxide It relates to an external preparation.

Since ancient times, it has been known for a long time that carbon dioxide has various effects, and it is widely used for spa therapy. The effects of carbon dioxide include, for example, increased blood flow, moisturizing effect, anti-inflammatory effect, etc., and clinical effects on diseases such as fatigue recovery, hemorrhoids, pressure ulcers, peripheral arterial occlusive disease, and hypertension have been recognized (patented) Reference 1).

In anticipation of such effects, various effervescent skin external preparations using carbon dioxide gas have been proposed. For example, a granular material containing a water-soluble acid (first agent), carbonate, water, and a thickener. Effervescent skin external preparation (see Patent Document 2) containing a viscous composition (second agent) containing a foaming pack (Patent Document 3) containing a carbonate, an organic acid, a pyrogen, and a foam stabilizer For example).

However, in the above-mentioned external preparation for effervescent skin, the characteristics based on the dosage form such as physical irritation to the skin of carbon dioxide gas, effervescence, effervescence persistence, dripping, extensibility, elasticity, stickiness, and flexibility are not Although it has been made, no study has been made on the percutaneous absorption effect of permeating carbon dioxide into the skin.

Japanese Patent Laid-Open No. 4-200512 JP 2013-014532 A JP-A-8-268828

  Therefore, in the present invention, a percutaneous absorption enhancer having an excellent effect of promoting percutaneous absorption of carbon dioxide gas is found, and blended with a solid, granular, fine granular or powdery carbon dioxide foaming external preparation for skin. Thus, an object of the present invention is to provide a carbon dioxide foaming topical skin preparation that has an enhanced effect of absorbing carbon dioxide into the skin and mucous membranes.

  The present inventors, in a solid, granular or powdery carbon dioxide foaming skin external preparation containing an acidic substance, a carbon dioxide generating substance that reacts with the acidic substance to generate carbon dioxide and a thickener, In order to find a percutaneous absorption enhancer excellent in the percutaneous absorption promotion effect of carbon dioxide gas, the percutaneous absorption action of carbon dioxide gas was investigated for various substances. As a result, they found a carbon dioxide gas percutaneous absorption promoting action excellent in squalane, and completed the present invention. That is, the present invention comprises an acidic substance, a carbon dioxide generating substance that reacts with the acidic substance to generate carbon dioxide, and a transdermal absorption promoter for carbon dioxide, characterized in that it is solid, granular, fine granular Or it is a powdery carbon dioxide foaming topical skin preparation, wherein the carbon dioxide transdermal absorption enhancer is squalane. The present invention also includes an acidic substance, a carbon dioxide generating substance that reacts with the acidic substance to generate carbon dioxide, a thickener, and a carbon dioxide percutaneous absorption enhancer. The present invention relates to a carbon dioxide foaming topical skin preparation, characterized in that the carbon dioxide foaming topical skin preparation is in the form of a fine particle or powder, and the percutaneous absorption enhancer of carbon dioxide is squalane.

  ADVANTAGE OF THE INVENTION According to this invention, the foamable skin external preparation characterized by having the outstanding foamability and having improved the permeability | transmittance of the carbon dioxide gas to the skin can be provided. In particular, solid, granular, fine or powdery carbon dioxide foaming skin containing an acidic substance, a carbon dioxide generating substance that reacts with the acidic substance to generate carbon dioxide and a transdermal absorption promoter for carbon dioxide. In the preparation for external use, the permeability of carbon dioxide to the skin can be enhanced by blending squalane as a skin absorption promoter for carbon dioxide.

  The present invention comprises an acidic substance, a carbon dioxide generating substance that reacts with the acidic substance to generate carbon dioxide, and a transdermal absorption promoter for carbon dioxide, characterized in that it is solid, granular, fine granular or powder The carbon dioxide foaming topical skin preparation, characterized in that the carbon dioxide transdermal absorption enhancer is squalane.

  The carbon dioxide foaming external preparation for skin according to the present invention is a one-part type carbon dioxide gas containing an acidic substance, a carbon dioxide generating substance that reacts with the acidic substance to generate carbon dioxide, and a carbon dioxide percutaneous absorption enhancer. It is an effervescent skin external preparation, and is used by dissolving in a water-soluble component such as water at the time of use. By dissolving the carbon dioxide foaming topical skin preparation according to the present invention in a water-soluble component such as water, the acidic substance reacts with the carbon dioxide generating substance to generate carbon dioxide, which is converted into the skin (mucosa, scalp and When applied to hair (including hair), the percutaneous absorption enhancer of carbon dioxide absorbs a sufficient amount of carbon dioxide into the skin and contains a percutaneous absorption enhancer. Compared with the carbon dioxide-foaming skin external preparation which does not, the effect of the carbon dioxide gas outstanding can be acquired.

  The carbon dioxide foaming external preparation for skin according to the present invention is characterized by being in a solid form, granule form, fine grain form or powder form, and by making these forms, squalane can be stably used as a transdermal absorption enhancer. It can be blended, has excellent solubility in water-soluble components such as water, and is excellent in storage stability and portability. Moreover, it is preferable that water is not included substantially from a viewpoint of storage stability.

  The carbon dioxide foaming external preparation for skin according to the present invention is in the form of powder when the raw materials are blended as it is, but is granulated or granulated by granulating using a general matrix base. Can do. The method for producing the powder or granule is not limited to this example, and includes dry crushing granulation method, wet crushing granulation method, fluidized bed granulation method, high-speed stirring granulation method, extrusion granulation method, etc. It can be produced according to a conventional method. Moreover, the carbon dioxide foaming external preparation for skin according to the present invention can be made into a solid form by compression molding or the like using a common excipient.

  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. Moreover, it is preferable that the acidic substance to be used is a solid form, a granule form, a fine grain form, and a powder form from a soluble viewpoint.

  Examples of organic acids include linear fatty acids such as formic acid, acetic acid, propionic acid, butyric acid and valeric acid or salts thereof, oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, fumaric acid, maleic acid, phthalic acid Acids, dicarboxylic acids such as isophthalic acid and terephthalic acid or salts thereof, acidic amino acids such as glutamic acid and aspartic acid or salts thereof, glycolic acid, malic acid, tartaric acid, citric acid, lactic acid, hydroxyacrylic acid, α-oxybutyric acid, glycerin Examples include acids, tartronic acid, salicylic acid, gallic acid, tropic acid, ascorbic acid, gluconic acid and other oxyacids or salts thereof, and inorganic acids include phosphoric acid, sulfurous acid and other inorganic acids or salts thereof, These 1 type (s) or 2 or more types can be used. Among these, from the viewpoints of safety and solubility, citric acid or a salt thereof, ascorbic acid or a salt thereof, malic acid or a salt thereof, succinic acid or a salt thereof is preferable, and citric acid or a salt thereof is more preferable.

  As the carbon dioxide generating substance used in the present invention, various substances can be used without any particular limitation. Moreover, it is preferable that the carbon dioxide generating substance to be used is solid, granule, fine granule, or powder from the viewpoint of solubility.

  Examples of the carbon dioxide generating substance include carbonates such as sodium carbonate, calcium carbonate, potassium carbonate, magnesium carbonate, sodium sesquicarbonate, ammonium hydrogen carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, lithium hydrogen carbonate, cesium hydrogen carbonate, magnesium hydrogen carbonate And hydrogen carbonates such as calcium hydrogen carbonate, and one or more of these are used. Among these, sodium hydrogen carbonate or sodium hydrogen carbonate can be preferably used, and sodium hydrogen carbonate is more preferable in terms of achieving an appropriate foaming power.

  In the present invention, the acidic substance and the carbon dioxide generating substance may be blended as they are, but it is preferable from the viewpoint of storage stability that they are blended so that they do not physically contact each other and coexist. The coexistence means is not particularly limited and can be widely applied.

  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. In addition, 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 that they do not come into direct contact with each other, and compression molding may be performed.

  The means for coexisting the acidic substance and the carbon dioxide generating substance in the same agent will be specifically described below, but is not limited thereto.

[Coat layer formation]
As a coating layer forming method, for example, a method of forming a coating layer in at least one of an acidic substance and a carbon dioxide generating substance may be used. By providing a coat layer, even if it coexists with the acidic substance, the carbon dioxide generating substance and other components in the same agent, there is no risk of unexpected carbon dioxide generation during its production or storage, so stability, It is preferable from the viewpoint of durability.

  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. For example, fats and oils, fatty acids, fatty acid salts, acetylcellulose, hydroxyethylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, sodium polyacrylate, hydroxypropylmethylcellulose, methyl methacrylate-methacrylic acid copolymer, ethyl acrylate-methacrylic acid Examples thereof include a copolymer, gum arabic, sodium alginate, soluble starch, hydroxypropyl cellulose, wheat starch, sugars (for example, sucrose, lactose, etc.), citrate and the like.

  The amount of the coating agent used for the acidic substance and the carbon dioxide generating substance is preferably 1 to 20% by weight, more preferably 1 to 10% by weight, based on the acidic substance or the carbon dioxide generating substance.

  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.

  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.

  The acidic substance and the carbon dioxide generating substance are preferably contained in the carbon dioxide foaming topical skin preparation at a weight ratio of 1: 0.1 to 1:40 from the viewpoint of irritation to the skin. : It is more preferable to contain in the ratio of 0.5-1: 20, and it is still more preferable to contain in the ratio of 1: 1-1: 10. If the above range is exceeded, the pH when used as an external preparation for foaming skin becomes strongly acidic or strongly basic. Is preferably within the above range.

  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 cosmetics, pharmaceuticals, quasi drugs, etc., synthetic polymers, semi-synthetic polymers, natural polymers, Clay minerals can be used.

  Synthetic polymers include carboxyvinyl polymer, polyvinyl alcohol, acrylic acid / alkyl methacrylate copolymer, acrylates / alkyl acrylate crosspolymer, polyacrylic acid, polyacrylamide, polyalkylacrylamide / polyacrylamide copolymer, carboxymethylcellulose, cation And hydrophilic synthetic polymers such as fluorinated cellulose and pluronic.

  Examples of the semisynthetic polymer include cellulose derivatives such as carboxymethylcellulose or salts thereof, methylcellulose, ethylcellulose, propylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, and sulfonated cellulose derivatives. Examples of other semi-synthetic polymers include propylene glycol alginate, ethylene glycol alginate, dextrin fatty acid ester, gelatin fatty acid ester, gelatin fatty acid amide, and the like.

  Natural polymers include polysaccharides and derivatives thereof, such as xanthan gum, succinoglycan, carrageenan, guar gum, locust bean gum, celluloses, galactan, gum arabic, tragacanth gum, mannan, curdlan, alginic acid or salts thereof, gum arabic Pectin, quinseed, starch, alge colloid, chondroitin sulfate or salts thereof, chito acid and derivatives thereof. Examples of other natural polymers include nucleic acids or salts thereof, ribonucleic acids or salts thereof, albumin, gelatin, silk fibroin and the like.

  Examples of the clay mineral include laponite, bentonite, smectite kaolinite, and montmorillonite.

  Among the above thickeners, it is preferable to use a thickener that can be uniformly dissolved without causing lumps in water-soluble components such as water, and that can reduce the feeling of rough skin caused by undissolved components.

  Examples of such a thickener include carboxyvinyl polymer, carboxymethyl cellulose or salts thereof, polyvinyl alcohol, sodium polyacrylate, acrylic acid / alkyl methacrylate copolymer, xanthan gum, succinoglycan, carrageenan, guar gum, locust Examples include bean gum, celluloses, galactan, gum arabic, tragacanth gum, mannan, curdlan, alginic acid or salts thereof, albumin, carboxymethyl cellulose cellulose or salts thereof, hydroxypropyl cellulose, locust bean gum, sodium alginate, xanthan gum. Carrageenan, starch and albumin are preferably used. These thickeners can be used alone, but it is preferable from the viewpoint of stability to use two or more kinds.

  The thickener is preferably contained at 0.1 to 50% by weight, more preferably 3 to 30% by weight, in the carbon dioxide foaming external preparation for skin. If the content is small, dripping may be easily caused during use, or a rough feeling may be liable to occur during dissolution. On the other hand, if the content of the thickener exceeds the above range, the thickener that cannot be dissolved may be generated or the washing out may be deteriorated.

  Common liquid oils used in cosmetics, pharmaceuticals, and quasi drugs include olive oil, avocado oil, camellia oil, macadamia nut oil, evening primrose oil, jojoba oil, rapeseed oil, egg yolk oil, sesame oil, castor oil, safflower Oil, cottonseed oil, soybean oil, tea seed oil, rice bran oil, wheat germ oil, germ oil, peanut oil, sunflower oil, almond oil, corn oil, turtle oil, mink oil, persic oil, southern oil, linseed oil, eno oil , Kaya oil, Nippon Kiri oil, Medhufoam oil, Squalene, Squalane, Vegetable squalane, Jojoba alcohol, Liquid paraffin, Polybutene, Hydrogenated polyisobutene, Isocetyl isostearate, Bisethoxydiglycol, cyclohexanedicarboxylate, Di-2-ethylhexane Ethylene glycol, cetyl 2-ethylhexanoate, tri- -Trimethylolpropane ethylhexanoate, pentaerythritol tetra-2-ethylhexanoate, cetyl octanoate, pentaerythryl tetraoctanoate, glyceride tri-2-heptylundecanoate, diisobutyl adipate, 2-hexyldecyl sebacate, Glycerol trioctanoate, glyceryl triisopalmitate, diisostearyl malate, isopropyl myristate, 2-octyldodecyl oleate, hexyldecyl dimethyloctanoate, 2-hexyldecyl myristate, myristyl myristate, octyldodecyl myristate, palmitic Isopropyl 2-ethylhexyl palmitate, 2-hexyl decyl palmitate, 2-heptyl undecyl palmitate, butyl stearate, iso-stearate Chill, decyl oleate, dodecyl oleate, oleyl oleate, myristyl lactate, cetyl lactate, cholesteryl 12-hydroxystearylate, castor oil fatty acid methyl ester, 2-ethylhexyl succinate, 2-hexyldecyl adipate, di-adipate 2-heptylundecyl, diisopropyl sebacate, di-2-ethylhexyl sebacate, neopentyl glycol dicaprate, neopentyl glycol dioctanoate, glyceryl trimyristate, glyceride tri-2-heptylundecanoate, trimethylolpropane triisostearate , Glyceryl tri-2-ethylhexanoate, dimethicone, dimethylpolysiloxane, methylphenylpolysiloxane, octamethylcyclotetrasiloxane, decamethylcyclopen Tasiloxane, glyceryl trioctanoate, glyceryl triisopalmitate, triglycerin, oleic acid, tall oil fatty acid, isostearic acid, lauryl alcohol, oleyl alcohol, isostearyl alcohol, octyldodecanol, methylpolysiloxane, methylphenylpolysiloxane, methyl Hydrogen polysiloxane, cyclic polysiloxane, isopropyl myristate, isopropyl palmitate, hexyl laurate, oleyl oleate, decyl oleate, octyldodecyl myristate, hexyldecyl dimethyloctanoate, diethyl phthalate, dibutyl phthalate, succinate Liquids such as dioctyl acid, fluorine-modified oil, trioctanoin, and tripropylene glycol dipivalate are known at 25 ° C. From the point of skin absorption promoting action, vegetable oils such as jojoba oil, natural hydrocarbon oils such as squalane, synthetic ester oils such as bisethoxydiglycol cyclohexanedicarboxylate, cetyl 2-ethylhexanoate and glyceryl tri-2-ethylhexanoate, It is preferable to use silicone oil such as methylpolysiloxane, and it is particularly preferable to use a squara. The percutaneous absorption enhancer is preferably contained at 0.001 to 10% by weight, particularly preferably 0.01 to 5% by weight, in the carbon dioxide foaming external preparation for skin.

  In addition to the above components, the carbon dioxide foaming topical skin preparation according to the present invention includes various active ingredients, pH adjusters, fats and oils, fragrances, colorants, antioxidants, antibacterial and antifungal agents, alcohols, depending on applications and purposes. Ingredients that are usually used in external preparations for skin, such as nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, inorganic salts, lubricants and solvents can be blended.

  Hereinafter, representative components other than the acidic substance, the carbon dioxide generating substance, and the thickener contained in the carbon dioxide foaming external preparation for skin according to the present invention will be further described.

  As an active ingredient used for this invention, the chemical | medical agent used for cosmetics, a pharmaceutical, a quasi-drug, a plant extract, etc. can be used according to the objective, without being specifically limited. Typical examples include glycyrrhizic acid or derivatives thereof, whitening agents such as placenta extract, plant components such as licorice, and the like. 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 dried or Although it can be used in powder form, it is common to use an extract extracted by a conventional method using a solvent such as water, ethanol, polyhydric alcohol or the like.

  There is no particular limitation on the method for preserving the carbon dioxide foaming topical skin preparation of the present invention, but a method for preserving cosmetics, pharmaceuticals, quasi drugs, etc. can be used, and it is stored in a state where moisture is cut off and not in contact It is good to have. 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.

  The carbon dioxide foaming topical skin preparation according to the present invention is excellent in transdermal absorbability of the generated carbon dioxide gas, and exhibits increased blood flow, moisturizing action, anti-inflammatory action, etc. by absorbing carbon dioxide into the skin. As a cosmetic, pharmaceutical, or quasi-drug for moisturizing, improving skin firmness, improving skin dullness, freckles, tightening skin, slimming, hair growth, wound healing, skin roughening, peeling, etc. Can be used.

  EXAMPLES Hereinafter, although an Example is shown and this invention is demonstrated further more concretely, the scope of the present invention is not limited to these Examples.

<Preparation of carbon dioxide foaming topical skin preparation>
According to the composition shown in Table 1, the carbon dioxide foaming topical skin preparation of the present invention was prepared.

<Confirmation test of transdermal absorption promotion effect>
Using the carbon dioxide foaming topical skin preparation prepared according to the above composition, a confirmation test was conducted on the percutaneous absorption promotion effect of carbon dioxide of various percutaneous absorption enhancers. 1 g of carbon dioxide foaming topical skin preparation prepared according to the above composition and 3 g of water were mixed in a container, and the whole amount was applied to the upper arm (4 cm × 4 cm) of the panel. 10 minutes after application, it was washed with running water. The skin color difference (a value) before and after application was measured with a CR-400 color difference meter (manufactured by Konica Minolta). Table 2 shows the change rate when the change rate of the color difference (a value: redness) before and after application in Comparative Example 1 in which no percutaneous absorption accelerator is blended is 1.

  From the results in Table 2, it was found that the percutaneous absorption enhancer according to the present invention was excellent in the effect of promoting the absorption of carbon dioxide into the skin.

  As is clear from the above study, according to the present invention, it is possible to provide a foamable skin external preparation characterized by having excellent foaming properties and enhancing the permeability of carbon dioxide gas to the skin. In particular, it contains a solid, granular, fine granular or powdery substance characterized by containing an acidic substance, a carbon dioxide generating substance that reacts with the acidic substance to generate carbon dioxide, and a transdermal absorption promoter for carbon dioxide. In the carbon dioxide foamable external preparation for skin, by incorporating squalane as a percutaneous absorption enhancer, it is possible to provide a foamable skin external preparation excellent in the effect of promoting absorption of carbon dioxide into the skin.

Claims (3)

An acidic substance, a carbon dioxide generating substance that reacts with the acidic substance to generate carbon dioxide, and a transdermal absorption accelerator for carbon dioxide, and a carbon dioxide foaming skin in the form of granules, fine particles, or powder The topical preparation for carbon dioxide foaming skin, wherein the percutaneous absorption enhancer for carbon dioxide is squalane (however, the acidic substance and the carbon dioxide generating substance are different agents, Excluding skin preparations and bath preparations to be mixed). An acidic substance, a carbon dioxide generating substance that reacts with the acidic substance to generate carbon dioxide, a thickener, and a carbon dioxide gas percutaneous absorption promoter. A gas foam skin external preparation, wherein the carbon dioxide transdermal absorption enhancer is squalane, wherein the carbon dioxide foam skin external preparation (however, the acidic substance and the carbon dioxide generating substance are separate agents) Yes, excluding skin preparations and bath preparations to be mixed during use). Content of squalane is 0.01 to 5.0 weight%, The carbon dioxide-foaming skin external preparation of any one of Claims 1-2 characterized by the above-mentioned.