WO2014112220A1 - Préparation à usage externe pour la peau - Google Patents

Préparation à usage externe pour la peau Download PDF

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Publication number
WO2014112220A1
WO2014112220A1 PCT/JP2013/082379 JP2013082379W WO2014112220A1 WO 2014112220 A1 WO2014112220 A1 WO 2014112220A1 JP 2013082379 W JP2013082379 W JP 2013082379W WO 2014112220 A1 WO2014112220 A1 WO 2014112220A1
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WIPO (PCT)
Prior art keywords
acid
skin
external preparation
emulsion
mass
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PCT/JP2013/082379
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English (en)
Japanese (ja)
Inventor
田代　朋子
幹永 森
荒河　純
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富士フイルム株式会社
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Priority to CN201380055295.6A priority Critical patent/CN104755071A/zh
Publication of WO2014112220A1 publication Critical patent/WO2014112220A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35—Ketones, e.g. benzophenone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37—Esters of carboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/63—Steroids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/006—Antidandruff preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth

Definitions

  • the present invention relates to an external preparation for skin.
  • Triterpene compounds are broadly classified into triterpene compounds such as danmarans, hopanes, onoselans, lanostanes, oleananes, and cycloartanes, depending on the ring bonding mode.
  • triterpene compounds oleanane-based triterpene compounds are known as the main components of plant extracts that exhibit functions such as anti-inflammatory, moisturizing, whitening, anti-wrinkle, and antibacterial when blended in an external preparation for skin.
  • oleanane triterpene compounds that are pentacyclic and have a carboxyl group as a substituent are known to have particularly useful functions as cosmetics (Tanaka Shingo, triterpene and triterpene saponins, natural product chemistry) 6th revised edition, Nanedo (1985), p130-p140).
  • glycyrrhetinic acid As such an oleanane triterpene compound having a pentacyclic group and a carboxyl group, glycyrrhetinic acid and the like are known. Glycyrrhetinic acid is widely blended in various compositions such as a scalp composition as an oil-soluble drug having an anti-inflammatory effect (Japanese Patent Application Laid-Open No. 2008-201767).
  • carotenoids such as xanthophylls including astaxanthin are known to have an anti-dandruff action and an anti-itch action.
  • astaxanthin is known to have excellent hair restoration and hair growth effects (see JP 2009-179628 A and JP 2008-273874 A).
  • Glycyrrhetinic acid is excellent in functionality such as suppression of rough skin, but is hardly soluble in water and has low solubility in oil. Therefore, conventionally, glycyrrhetinic acid has been solubilized using a sufficient amount of ethanol and blended into an external preparation for skin. However, since there are some users who are sensitive to ethanol, an external preparation for skin having an ethanol-free composition is desired. The present inventors have found that an emulsion containing glycyrrhetinic acid is used as one of the measures for incorporating a desired amount of glycyrrhetic acid into a skin external preparation without using ethanol. However, skin external preparations that do not contain ethanol tend to be inferior in antiseptic properties. On the other hand, when antiseptic
  • This invention is made
  • Means for solving the above problems are as follows.
  • the present invention it is possible to provide a skin external preparation excellent in rough skin suppression, antiseptic properties, and emulsion stability.
  • a numerical range indicated by using “to” indicates a range including the numerical values described before and after “to” as the minimum value and the maximum value, respectively.
  • the amount of each component in the composition means the total amount of the plurality of substances present in the composition unless there is a specific notice when there are a plurality of substances corresponding to each component in the composition.
  • aqueous phase is used as a term for “oil phase” regardless of the type of solvent.
  • the term “process” is not limited to an independent process, and is included in the term if the intended purpose of this process is achieved even when it cannot be clearly distinguished from other processes. .
  • the emulsion in the present invention is an oil-in-water emulsion (O / W emulsion) comprising an oil phase composed of an oily composition containing an oily component and an aqueous phase composed of an aqueous composition containing an aqueous component. It is preferable that As described later, the emulsion in the present invention is preferably obtained by emulsifying and mixing an aqueous composition containing an aqueous component and an oily composition containing an oily component.
  • the average particle diameter of the emulsion in the present invention means the volume average particle diameter of the emulsion.
  • the average particle size of the emulsion in the present invention can be determined by a known method such as an electron microscope, a centrifugal sedimentation method, a liquid exclusion chromatography method, a laser scattering diffraction method, or a dynamic light scattering method. In view of accuracy and simplicity of measurement, the average particle size of the emulsion in the present invention is preferably measured using a dynamic light scattering method.
  • Examples of commercially available measuring devices using the dynamic light scattering method include dense particle size analyzer FPAR-1000 (Otsuka Electronics Co., Ltd.), Nanotrack UPA (Nikkiso Co., Ltd.), Nanosizer (manufactured by Malvern), etc. It is done.
  • the particle diameter in the present invention a value measured at 25 ° C. using Nanotrac UPA is adopted.
  • the average particle size of the emulsion is adjusted by factors such as the stirring conditions (shearing force, temperature, pressure) in the production method and the ratio of the oil phase to the water phase.
  • the skin external preparation of the present invention has an emulsion containing glycyrrhetinic acid, at least one selected from the group consisting of astaxanthin and an astaxanthin derivative, an I / O value of 1.5 or less, and an alkyl group Or a preservative having an alkyl chain length of 5 or less and having a linear or branched alkyl group, and a skin external preparation substantially free of ethanol.
  • an antiseptic having an I / O value of 1.5 or less and having no alkyl group or having an alkyl chain length of 5 or less and having a linear or branched alkyl group is appropriately selected as “ It is called “specific preservative”.
  • the group consisting of astaxanthin and astaxanthin derivatives may be collectively referred to using the term “astaxanthins”.
  • the present invention contains an emulsion containing glycyrrhetinic acid and a specific preservative in combination, and does not contain ethanol or has an ethanol content of 1% by mass or less, so that it has an excellent inhibitory effect on rough skin.
  • preservative property and emulsion stability can be provided.
  • the external preparation for skin of the present invention can contain glycyrrhetic acid stably in the system without using ethanol by containing glycyrrhetic acid in the form of an emulsion. Furthermore, the skin external preparation of this invention can suppress skin inflammation synergistically by containing both glycyrrhetic acid and astaxanthins. For this reason, according to this invention, the skin external preparation which has the outstanding rough skin inhibitory effect can be provided. In addition, the specific preservative in the present invention suppresses emulsion breakage with respect to an emulsion containing glycyrrhetinic acid and the like, and improves the antiseptic properties of the external preparation for skin while effectively maintaining the stability of the emulsion.
  • the inventors of the present invention have noticeably caused the emulsion breakage due to the preservative when the preservative having a hydrophilic part and a hydrophobic part and having a structure close to the emulsifier is used. It is presumed that this is caused by the hydrophobic part possessed by adsorbing on the surface of the emulsion containing an oily component such as glycyrrhetinic acid and aggregating the emulsion.
  • an oily component such as glycyrrhetinic acid and aggregating the emulsion.
  • a specific preservative having a specific structure and low polarity is selectively contained, so that both the preservative and the emulsion can be stabilized. The present inventors speculate.
  • the skin external preparation of this invention does not contain ethanol substantially, it becomes possible to include the user sensitive to ethanol in the object of use.
  • the skin external preparation of the present invention does not contain ethanol or the ethanol content is 1% by mass or less.
  • the content of ethanol is preferably 0.5% by mass or less, more preferably 0.1% by mass or less, based on the total mass of the skin external preparation. Inclusion of more than 1% by mass of ethanol in the external preparation for skin reduces the anti-inflammatory effect of the combined use of glycyrrhetinic acid and astaxanthins. It is preferable that the external preparation for skin of the present invention does not contain ethanol.
  • the external preparation for skin of the present invention contains glycyrrhetinic acid.
  • Glycyrrhetinic acid is one of oleanane-based pentacyclic triterpene compounds obtained by, for example, hydrolyzing glycyrrhizic acid, which is a component contained in licorice root.
  • Glycyrrhetinic acid can be blended in cosmetics or quasi-drugs for anti-aging care and the like in anticipation of anti-inflammatory action, antioxidant action and anti-aging action in the cosmetics field.
  • glycyrrhetinic acid is said to have a remarkable effect on acute or chronic dermatitis, and has effects such as anti-inflammatory effect, anti-allergic action, and bacterial (such as Staphylococcus aureus, Diphtheria, Salmonella) growth inhibition It has been known. Moreover, glycyrrhetinic acid is excellent in effects such as reducing skin inflammation and suppressing sebum secretion, and is used in many skin care products, lipsticks and the like. In addition, since glycyrrhetinic acid also has effects such as hair loss prevention effects, dandruff or itching suppression, it is often used in scalp care products.
  • Glycyrrhetinic acid may be an extract from a natural product or a purified product thereof, or may be a synthetic product synthesized according to a known synthesis method. Glycyrrhetinic acid is also available as a commercial product, and examples of commercially available products include ⁇ -glycyrrhetinic acid manufactured by Maruzen Pharmaceutical Co., Ltd., Alps Pharmaceutical, and Kaneka. Glycyrrhetinic acid may be used individually by 1 type, and may be used in combination of 2 or more type.
  • Glycyrrhetinic acid is contained in the external preparation for skin of the present invention in the form of an emulsion.
  • the emulsion containing glycyrrhetinic acid preferably contains an emulsifier. From the viewpoint of stability, it is more preferable that the emulsion containing glycyrrhetinic acid contains an emulsifier containing phospholipid. Details of the emulsifier suitably used in the present invention will be described later.
  • the content of glycyrrhetinic acid in the external preparation for skin of the present invention is preferably 0.0001% by mass to 0.5% by mass, and 0.001% by mass to 0% from the viewpoint of obtaining the rough skin inhibiting effect expected for glycyrrhetic acid. More preferably, it is more preferably 0.005% by mass to 0.2% by mass. If the content of glycyrrhetinic acid is 0.0001% by mass or more, for example, the effects expected of glycyrrhetic acid such as rough skin suppression effect (anti-inflammatory effect) tend to be sufficiently obtained, and 0.5% by mass If it is below, it tends to suppress the precipitation of glycyrrhetinic acid.
  • the external preparation for skin of the present invention contains at least one selected from the group consisting of astaxanthin and astaxanthin derivatives (astaxanthins). Astaxanthin derivatives include esters of astaxanthin. As the components included in the astaxanthins, one kind may be used alone, or two or more kinds may be used in combination.
  • Astaxanthin may be contained in the skin external preparation of the present invention as a component in an astaxanthin-containing oil that is an extract separated or extracted from a natural product containing astaxanthin. Astaxanthins may be obtained by appropriately purifying, as necessary, extracts extracted or extracted from natural products. Astaxanthins may be synthetic products.
  • Astaxanthins can be used as long as they are obtained according to a conventional method in addition to those obtained from natural products such as plants, algae, crustaceans and bacteria.
  • examples of astaxanthins that are natural products include red yeast Phaffia, Haematococcus algae, marine bacteria, krill, and the like.
  • examples of the astaxanthins include extracts from natural cultures, and extracts extracted from Haematococcus algae (also referred to as Haematococcus algae extract) and pigments derived from krill. Particularly preferred from the viewpoints of quality and productivity.
  • a widely commercially available Haematococcus alga extract may be used as the astaxanthins.
  • hematococcus algae extracts examples include ASTOTS-S, ASTOTS-2.5 O, ASTOTS-5 O, and ASTOTS-10 O manufactured by Takeda Paper Instruments Co., Ltd. 50F, Asteryl Oil 5F, etc., such as BioAstin SCE7 manufactured by Toyo Enzyme Chemical Co., Ltd.
  • a krill extract Astax ST and the like can be obtained.
  • the content of astaxanthin as a pure pigment content is preferably 0.001% by mass to 50% by mass from the viewpoint of handling during composition production. More preferably, the content is 0.01% by mass to 25% by mass.
  • astaxanthins may be contained in a form solubilized with a solubilizer or the like, or may be contained in the form of an emulsion containing astaxanthins. From the viewpoint of skin permeability, astaxanthins are preferably contained in the external preparation for skin of the present invention in the form of an emulsion.
  • the emulsion containing astaxanthins preferably contains an emulsifier, and more preferably contains an emulsifier containing a phospholipid from the viewpoint of the stability of the astaxanthins. Details of the emulsifier suitably used in the present invention will be described later.
  • the content of at least one selected from the group consisting of astaxanthin and its derivatives in the external preparation for skin of the present invention is 0.000001% by mass to 0.001% from the viewpoint of obtaining the anti-inflammatory effect expected of astaxanthin or its derivatives.
  • 01 mass% is preferable, 0.00001 mass% to 0.0075 mass% is more preferable, and 0.0001 mass% to 0.005 mass% is still more preferable.
  • the external preparation for skin of the present invention has an I / O value of 1.5 or less and has no alkyl group or an alkyl chain length of 5 or less and has a linear or branched alkyl group ( Contains a specific preservative).
  • the compound used as the specific preservative in the present invention includes (1) an I / O value of 1.5 or less, (2) no alkyl group or an alkyl chain length of 5 or less, and a straight chain Alternatively, it is necessary to have a molecular structure having a branched alkyl group and (3) to have antiseptic properties.
  • the external preparation for skin of the present invention may contain other preservatives other than the specific preservative, but more preferably contains only the specific preservative.
  • the I / O value is a parameter serving as an index that represents a measure of hydrophilicity / hydrophobicity exhibited by a compound based on a ratio between an organic group and an inorganic group.
  • I represents inorganicity
  • O represents organicity
  • the I / O value is described in detail in “Organic Conceptual Diagram” (by Yoshio Koda, Sankyo Publishing, 1984).
  • the antiseptic property obtained by the preservative depends on the nature of the site contributing to the antiseptic property of the compound used as the preservative and the hydrophilicity / hydrophobicity of the compound, and the necessary amount of the preservative is determined in consideration of these. .
  • Preservatives having an I / O value exceeding 1.5 have high hydrophilicity, and in order to obtain antiseptic properties with such preservatives, it is necessary to add a larger amount of preservatives.
  • Preservatives with an I / O value exceeding 1.5 cause stickiness due to the addition of a large amount of preservatives in a topical skin preparation containing an emulsion containing glycyrrhetinic acid.
  • the preservative has an I / O value of 1.5 or less, it can exhibit antiseptic properties even in a small amount.
  • the preservative has an I / O value of 1.5 or less, depending on the molecular structure, there are those that deteriorate the emulsion stability in the external preparation for skin including the emulsion containing glycyrrhetinic acid. If it does not have an alkyl group or has an alkyl chain length of 5 or less and a linear or branched alkyl group, the stability of the emulsion is maintained well.
  • the I / O value of the specific preservative is 1.5 or less, preferably 1.4 or less, and more preferably 1.3 or less.
  • the specific preservative does not have an alkyl group or has an alkyl chain length of 5 or less and a linear or branched alkyl group, and further has an aromatic group (for example, a phenyl group). May be.
  • the compound has an I / O value of 1.5 or less and has no alkyl group or an alkyl chain length of 5 or less and a linear or branched alkyl group, Used without limitation.
  • Specified preservatives may be used alone or in combination of two or more.
  • Suitable examples of the specific preservative include at least one preservative selected from the group consisting of phenoxyethanol, parabens, and propynyl butylcarbamate iodide.
  • the specific preservative it is preferable to use a combination of two or more selected from the group consisting of phenoxyethanol, parabens, and propynyl iodide butylcarbamate from the viewpoint of antiseptic properties.
  • parabens examples include methyl paraben (methyl paraoxybenzoate), ethyl paraben (ethyl paraoxybenzoate), propyl paraben (propyl paraoxybenzoate), and the like.
  • the content of the specific preservative in the external preparation for skin of the present invention can be appropriately set in consideration of the molecular structure and physical properties of the compound used as the specific preservative. Below, although content of the specific compound applied suitably for this invention is shown, the kind of specific preservative in this invention and its content are not limited to these.
  • the content of phenoxyethanol is preferably 0.001% by mass to 1% by mass, and preferably 0.001% by mass to 0.7% by mass with respect to the total mass of the external preparation for skin. More preferred is 0.001% by mass to 0.5% by mass.
  • the content of methylparaben is preferably 0.001% by mass to 0.5% by mass, and 0.001% by mass to 0.3% by mass with respect to the total mass of the external preparation for skin. %, More preferably 0.001% by mass to 0.2% by mass.
  • the content of ethyl paraben is preferably 0.001% by mass to 0.5% by mass, and 0.001% by mass to 0.00% by mass with respect to the total mass of the external preparation for skin. It is more preferably 3% by mass, and further preferably 0.001% by mass to 0.2% by mass.
  • propynyl butylcarbamate is used, the content of propynyl butylcarbamate is preferably 0.0001% by mass to 0.02% by mass with respect to the total mass of the external preparation for skin, The content is more preferably 0.001% by mass to 0.015% by mass, and still more preferably 0.002% by mass to 0.01% by mass.
  • MIC minimum inhibitory concentration
  • the minimum growth inhibitory concentration means a necessary minimum amount (% by mass) of a preservative for inhibiting the growth of specific bacteria.
  • the smaller the MIC value the stronger the antiseptic effect of the compound.
  • the larger the value the greater the amount required to satisfy a certain standard of antiseptic effect.
  • the MIC is determined by the “Microbial Limit Test Method” in the General Test Method in the “Japanese Pharmacopoeia Fifteenth Revision (2006)”.
  • the microbial limit test method there are a membrane filter method, a platen plate mixing method, a platen plate surface smearing method, and a liquid medium serial dilution method.
  • a membrane filter method As the microbial limit test method, there are a membrane filter method, a platen plate mixing method, a platen plate surface smearing method, and a liquid medium serial dilution method.
  • the MIC in the present invention a value obtained by a liquid medium serial dilution method is used.
  • MIC Erichia coli
  • Methyl paraben methyl paraoxybenzoate
  • Phenoxyethanol MIC: 0.4% by mass
  • Ethylparaben ethyl paraoxybenzoate
  • Butynyl carbamate propynyl iodide MIC: 0.01 mass
  • Ethylhexylglycerin MIC: 0.2% by mass
  • Caprylyl glycol MIC: 0.2% by mass
  • Pentylene glycol MIC: 2.65% by mass
  • the skin external preparation of the present invention preferably contains an N-acylamino acid monoester.
  • the N-acylamino acid monoester is preferably contained in the oil phase in the emulsion containing glycyrrhetinic acid contained in the external preparation for skin of the present invention.
  • the N-acyl amino acid monoester may be synthesized by a chemical reaction between an acyl group, a neutral amino acid, and an alcohol that forms an ester site.
  • a method for synthesizing the N-acylamino acid monoester the methods described in paragraph numbers [0047] to [0053] of JP-A No. 11-246841 can be exemplified.
  • the acyl group is preferably a saturated or unsaturated hydrocarbon having a straight or branched chain having 6 to 22 carbon atoms, such as capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenine.
  • An acyl group that can be derived from acid, linoleic acid, linolenic acid, oleic acid, isostearic acid, 2-ethylhexanoic acid, coconut oil fatty acid, beef tallow fatty acid, hardened tallow fatty acid and the like is preferable.
  • Preferred acyl groups include caproyl group, lauroyl group, myristyl group, palmitoyl group, stearoyl group, behenoyl group, cocoyl group and the like.
  • Neutral amino acids include glycine, alanine, ⁇ -alanine, aminobutyric acid, aminopropionic acid, sarcosine, N-methyl- ⁇ -alanine, and preferably glycine, alanine, valine, leucine, isoleucine, serine, threonine , Proline, ⁇ -alanine, aminobutyric acid, sarcosine, and N-methyl- ⁇ -alanine, particularly preferably sarcosine, alanine, glycine, and N-methyl- ⁇ -alanine.
  • These amino acids may be either optically active or racemic.
  • Examples of alcohols constituting the ester moiety include linear or branched chains having 1 to 40 carbon atoms and cyclic alcohols having 3 to 30 carbon atoms.
  • Examples of the straight chain or branched chain having 1 to 40 carbon atoms include lower alcohols having 1 to 5 carbon atoms and higher alcohols having 6 to 20 carbon atoms.
  • the alcohols constituting the ester moiety are preferably alcohols having a branched or straight chain alkyl or alkenyl group having 1 to 10 carbon atoms in the molecule. Alcohols having an alkyl group in the molecule are more preferred.
  • cyclic alcohol having 3 to 30 carbon atoms examples include cyclopropanol, cyclobutanol, cyclopentanol, and cyclohexanol.
  • alcohols constituting the ester moiety also include sterols such as cholesterol, dihydrocholesterol, and phytosterol.
  • alcohols constituting the ester moiety include methanol, ethanol, propanol, isopropanol, butanol, t-butanol, isobutanol, 3-methyl-1-butanol, 2-methyl-1-butanol, pentanol, hexanol, Examples include cyclohexanol, octanol, 2-ethyl-hexanol, decanol, fusel oil and the like. Among them, alcohols having a branched or straight chain alkyl group having 2 to 8 carbon atoms in the molecule are preferable, and isopropanol is most preferable.
  • Examples of combinations of acyl groups, neutral amino acids, and alcohols that create ester sites used in the synthesis of N-acyl amino acid monoesters include “lauroyl group, sarcosine and isopropanol”, “myristoyl group, ⁇ -alanine and phytosterol” Or a combination such as “a caproyl group, glycine and isobutanol”.
  • a combination of a lauroyl group, a sarcosine group and isopropanol is preferable from the viewpoint of solubility of glycyrrhetinic acid.
  • N-acylamino acid monoester in the present invention can be synthesized according to the above-described known synthesis method, or a commercially available product may be used.
  • commercially available products include N-lauroyl sarcosine isopropyl (trade name: Erdeu SL-205) manufactured by Ajinomoto Co., Inc., N-myristoyl-N-methyl ⁇ -alanine phytosteryl-decyltetradecyl (trade name: El Deu APS307), Japan Examples include emulsion myristoylmethylaminopropionate hexyldecyl (trade name: AMITER MA-HD).
  • N-acylamino acid monoester an amino acid selected from the group consisting of sarcosine, alanine, glycine and N-methyl- ⁇ -alanine is converted to N-caproylation, N-lauroylation, N-myristylation, N-palmitoylation N-stearoylated, N-behenoylated, or N-cocoylated partial structure, and a branched or linear partial structure obtained by alkyl esterification and having an alkyl chain length of 2 to 8 carbon atoms. What has is preferable.
  • N-lauroyl sarcosine isopropyl is more preferable in the present invention.
  • N-acyl amino acid monoesters can be used alone or in combination of two or more.
  • N-acylamino acid monoester is a component capable of dissolving glycyrrhetic acid at a high concentration sufficient to exert the function expected of glycyrrhetinic acid.
  • the emulsion containing glycyrrhetinic acid in the present invention preferably contains an N-acyl amino acid monoester, and more preferably contains N-lauroyl sarcosine isopropyl.
  • the content of the N-acylamino acid monoester in the external preparation for skin of the present invention is preferably 2-fold to 200-fold, more preferably 5-fold to 100-fold, based on the weight of the total mass of glycyrrhetinic acid.
  • the amount of 10 times to 50 times is more preferable.
  • the content of the N-acylamino acid monoester is in the range of 2 to 200 times by mass based on the total mass of glycyrrhetinic acid, the stability of the emulsion containing glycyrrhetinic acid is good. It is preferable.
  • the external preparation for skin of the present invention preferably contains an emulsifier.
  • the emulsifier can be added to either the aqueous phase composition or the oil phase composition in accordance with the properties of the respective emulsifiers when the emulsion is prepared in the present invention.
  • an emulsifier any of a nonionic surfactant and an ionic surfactant may be sufficient.
  • the emulsifier containing a phospholipid is mentioned.
  • Nonionic surfactant examples include polyglycerin fatty acid esters, glycerin fatty acid esters, organic acid monoglycerides, polyglycerin fatty acid ethers, propylene glycol fatty acid esters, polyoxyethylene alkyl ethers, polyoxyethylene polyoxypropylene alkyl ethers, polyols
  • nonionic surfactants include polyglycerin fatty acid esters, glycerin fatty acid esters, organic acid monoglycerides, polyglycerin fatty acid ethers, propylene glycol fatty acid esters, polyoxyethylene alkyl ethers, polyoxyethylene polyoxypropylene alkyl ethers, polyols
  • examples include xylene sterol, polyoxyethylene hydrogenated castor oil, polyglycerin condensed ricinoleic acid ester, sorbitan fatty acid ester, sucrose fatty acid ester, and polyoxyethylene sorbitan fatty acid ester. Of these
  • the total amount of the nonionic surfactant is preferably 20% by mass or less, more preferably 2% by mass to 15% by mass, and further preferably 5% by mass to 10% by mass with respect to the total mass of the emulsion. It is.
  • the polyglycerol fatty acid ester preferably has an HLB of 10 to 16, more preferably 11 to 15.
  • M w of the hydrophilic group M 0 is the molecular weight of the hydrophobic group.
  • an emulsifier having an arbitrary HLB value can be obtained by utilizing the additivity of HLB.
  • polyglycerin fatty acid esters include hexaglycerin monomyristic acid ester, hexaglycerin monolauric acid ester, decaglycerin monooleic acid ester, decaglycerin monostearic acid ester, decaglycerin monoisostearic acid ester, decaglycerin monopalmitic acid ester , Decaglycerin monomyristic acid ester, decaglycerin monolauric acid ester, decaglycerin monolinoleic acid ester, decaglycerin diisostearic acid ester and the like.
  • decaglycerin monooleate decaglycerin monostearate, decaglycerin monoisostearate, decaglycerin monopalmitate, decaglycerin monomyristate, decaglycerin monooleate, decaglycerin are preferred.
  • Monostearic acid ester and decaglycerin monoisostearic acid ester are particularly preferred.
  • a polyglycerol fatty acid ester you may use a commercial item.
  • sucrose fatty acid ester Preferable examples of the sucrose fatty acid ester include sucrose myristic acid ester, sucrose palmitic acid ester, sucrose stearic acid ester, sucrose oleic acid ester sucrose erucic acid ester and the like. Moreover, you may use a commercial item as sucrose fatty acid ester. These sucrose fatty acid esters can be used singly or in combination.
  • any of an anionic surfactant, a cationic surfactant, and an amphoteric surfactant may be sufficient.
  • the ionic surfactant include alkyl sulfonates, alkyl sulfates, monoalkyl phosphates, fatty acid salts and the like.
  • the salts sodium chloride, sodium citrate, sodium ascorbate and the like are used.
  • These ionic surfactants can be used singly or in combination.
  • these ionic surfactants can be used in combination at any ratio with respect to the total mass of the emulsion contained in the present invention.
  • One preferred embodiment of the emulsifier in the present invention includes an emulsifier containing a phospholipid.
  • an emulsifier containing phospholipid lecithin is preferable.
  • Lecithin is an emulsifier exhibiting good emulsifying power for oil phase compositions containing N-acyl amino acid monoesters, and is particularly preferred as an emulsifier when N-acyl amino acid monoesters are used in the present invention.
  • lecithin is not limited to phosphatidylcholine (PC), but means a lipid mixture mainly composed of various phospholipids.
  • lipids include phosphatidic acid, phosphatidylglycerin, phosphatidylinositol, phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylcholine, phosphatidylserine, bisphosphatidic acid, disulfide
  • glycerolecithin such as phosphatidylglycerin (cardiolipin); sphingolecithin such as sphingomyelin.
  • Lecithin is often used as an emulsifier for foods and cosmetics because of its safety and emulsifying ability to make an emulsion by dispersing oil in water.
  • osmotic action that permeates and absorbs substances from the skin and mucous membranes is used, and it is used as a material for pharmaceutical liposomes, fat emulsions for intravenous injections, therapeutic agents for wrinkles and skin diseases.
  • Soy lecithin is often used for food or cosmetic applications mainly from the viewpoint of cost.
  • Lecithin is a kind of glycerophospholipid, which is present in all cells of natural animals and plants, and is a major component of biological membranes.
  • Examples of lecithin derived from natural products that can be used include lecithin derived from soybeans, lecithin derived from egg yolk, and lecithin derived from animals and plants.
  • Soy lecithin is produced by drying and refining oil cake produced as a by-product in the soybean oil refining process.
  • Pasty lecithin having a phospholipid content of 70% or less is inexpensive because it contains about 30% crude soybean oil, and in the food field, this paste-like lecithin having a phospholipid content of 70% or less is used.
  • techniques such as high purification, fractionation, and modification have been added due to the physiological activity of phospholipids themselves and the need for more advanced emulsifiers, and various lecithin groups having different performance and functions have been created.
  • Highly purified lecithin is deoiled from the above-mentioned pasty lecithin using a solvent such as acetone and pulverized, and generally has a lecithin content of 90% or more.
  • a solvent such as acetone and pulverized
  • this highly purified lecithin include commercially available products such as Phospholipon 20 (Lipoid), Recion P (Riken Vitamin), SLP White (Tsubame Oil Co., Ltd.), Emmalmatic 300 (Lucas Meier Cosmetics).
  • Fractionated lecithin is obtained by increasing the content of specific phospholipids from the above highly purified lecithin by an operation utilizing the difference in solubility in various solvents, an operation such as distillation, etc. It is commercially available.
  • Examples of fractionated lecithin with increased PC content include Phospholipon 50 (PC 45%), Phosphopon 85G (PC 80%), Phosphopon 90G (PC 94%) (above, manufactured by Lipoid), Emmeletic 900 (PC 50%), Emmeletic 930 (PC 95%) (above, manufactured by Lucas Meyer Cosmetics), SLP-PC70, SLP-PC90 (above, manufactured by Sakai Oil Co., Ltd.) and the like are commercially available.
  • the modified lecithin can be roughly classified into hydrogenated lecithin and enzymatically decomposed lecithin.
  • hydrogenated lecithin is obtained by converting a fatty acid polyenoic acid in a lecithin structure into a saturated fatty acid by performing a hydrogenation treatment in order to oxidize or improve light stability.
  • This lecithin can be preferably used for cosmetics and pharmaceuticals.
  • Examples of hydrogenated lecithin include Emalmetic 320 (manufactured by Lucas Meyer Cosmetics), SLP White H (manufactured by Sakai Oil Co., Ltd.), and the like.
  • Emulmatik 950 manufactured by Lucas Meyer Cosmetics
  • SLP-PC92H manufactured by Sakai Oil
  • Phospholipon 90H manufactured by Lipoid
  • lysolecithin As the enzymatically degraded lecithin, an ester bond of the fatty acid at the 2-position bonded to glycerin is selectively decomposed by an enzyme, and what is called lysolecithin is used to distinguish it from normal lecithin. Lysolecithin has improved water solubility and generally improves emulsifying power as compared with lecithin before enzymatic degradation. This enzymatic decomposition treatment is usually performed on the first pasty lecithin and then highly purified, but the enzymatic decomposition treatment may be performed on the fractionated lecithin.
  • a typical example of lysolecithin is SLP white lyso (manufactured by Sakai Oil Co., Ltd.).
  • an enzyme-treated lecithin different from lysolecithin one that breaks the ester bond between phosphate and base has also been made. By performing this treatment, the base is removed from the phospholipid, and it becomes a phosphatidic acid form, thereby showing strong anionicity.
  • PA Nagase, lysophospholipid Nagase H both manufactured by Nagase ChemteX Corporation
  • the like are commercially available.
  • lecithins Any of the above-mentioned lecithins may be used, but from the viewpoint of maintaining the storage stability of the emulsion composition, soybean lecithin is preferred, and among them, highly purified lecithin and fractionated lecithin are more preferred.
  • the content of the emulsifier containing phospholipid is preferably 0.01% by mass to 30% by mass, more preferably 0.1% by mass to 20% by mass, with respect to the total mass of the emulsion. More preferably, it is 0.5 to 10% by mass.
  • sucrose fatty acid ester sucrose fatty acid ester, polyglycerin fatty acid ester or lecithin is preferable.
  • the emulsifiers described above may be used singly or in combination, depending on the application.
  • the external preparation for skin of the present invention preferably contains at least one oily component selected from the compound group consisting of phytosterol, cholesterol, phytosteryl ester, and cholesteryl ester (hereinafter referred to as “specific oil component” as appropriate). .
  • the specific oil component is preferably contained in the oil phase of the emulsion contained in the external preparation for skin.
  • Phytosterol is a kind of sterol, and is a component insoluble in white solid water, also called plant sterol.
  • phytosterols there are many types of phytosterols as natural products.
  • ⁇ -sitosterol, campesterol, stigmasterol, brush castrol and the like can be mentioned.
  • Phytosterol may be a natural product or a synthetic product, and can be obtained mainly from plants. Specifically, it can be obtained by extracting and purifying from pulp or the like using an organic solvent.
  • a commercial item may be used for phytosterol. Examples of commercially available products include Phytosterol (trade name) manufactured by Tama Seikagaku Co., and Generol 122N (trade name) manufactured by Henkel Japan. These phytosterols may be used alone or in combination.
  • Cholesterol (CAS registration number 57-88-5) is a kind of sterol, and is a component insoluble in white or slightly yellow solid water. Cholesterol may be either a natural product or a synthetic product, and can be obtained mainly from higher animal fats. Specifically, it can be obtained by purifying from wool fat. Moreover, you may use a commercial item for cholesterol. Examples of commercially available products include RIKEN Cholesterol (trade name) manufactured by Riken Vitamin Co., Ltd .; cholesterol (trade name) manufactured by Nippon Seika Co., Ltd., and the like.
  • the phytosteryl ester is obtained by an esterification reaction between a fatty acid and phytosterol.
  • the fatty acid include fatty acids having a total carbon number of 6 to 30.
  • Specific examples of fatty acids having 6 to 30 carbon atoms include caproic acid, caprylic acid, capric acid, lauric acid, palmitic acid, myristic acid, stearic acid, arachidic acid, behenic acid, isostearic acid, oleic acid, linoleic acid, Linolenic acid is mentioned. It may be a mixture extracted from natural products such as lanolinic acid and macadamia nut fatty acid.
  • amino acid derivatives such as hydroxyl fatty acids, such as hydroxystearic acid, and N-lauroyl glutamic acid
  • isostearic acid or N-lauroylglutamic acid is preferred from the viewpoint of improving the stability of the emulsion.
  • phytosteryl ester phytosteryl isostearate, N-lauroylglutamate di (phytosteryl / octyldodecyl), phytosteryl hydroxystearate and the like are preferable.
  • phytosteryl esters may be used singly or in combination.
  • Cholesteryl ester is obtained by esterification reaction of fatty acid and cholesterol.
  • the fatty acid include fatty acids having a total carbon number of 6 to 30. Fatty acids having a total carbon number of 6 to 30, specifically caproic acid, caprylic acid, capric acid, lauric acid, palmitic acid, myristic acid, stearic acid, arachidic acid, behenic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid An acid etc. are mentioned. It may be a fatty acid contained in a mixture extracted from a natural product, such as lanolinic acid or macadamia nut fatty acid.
  • the fatty acid examples include hydroxyl fatty acids such as hydroxystearic acid and amino acid derivatives such as N-lauroylglutamic acid.
  • hydroxyl fatty acids such as hydroxystearic acid
  • amino acid derivatives such as N-lauroylglutamic acid.
  • isostearic acid or lauroylglutamic acid is preferable as the fatty acid.
  • cholesteryl ester cholesteryl isostearate, N-lauroylglutamate di (cholesteryl / octyldodecyl), cholesteryl hydroxystearate, lanolin fatty acid cholesteryl, macadamia nut fatty acid cholesteryl and the like are preferable.
  • cholesteryl esters may be used alone or in combination of two or more.
  • the specific oily component selected from the group consisting of phytosterol, cholesterol, phytosteryl ester and cholesteryl ester one kind may be used alone, or a plurality kinds may be used in combination.
  • the content of the specific oil component is preferably 1% by mass to 70% by mass, more preferably 2% by mass to 30% by mass with respect to the total mass of the oil component from the viewpoint of improving the stability of the emulsion. More preferably, it is 2% by mass to 25% by mass.
  • the external preparation for skin can contain any other components in addition to the above-described components as necessary.
  • the external preparation for skin can contain an antioxidant from the viewpoint of improving the stability of astaxanthins.
  • the antioxidant include ascorbic acid compounds, dibutylhydroxytoluene, tocopherol compounds and the like.
  • As the antioxidant at least one selected from ascorbic acid compounds is more preferable in that it significantly improves the stability of astaxanthins.
  • ascorbic acid compounds include ascorbic acid, sodium ascorbate, magnesium ascorbate, magnesium ascorbate sulfate, sodium ascorbate sulfate, magnesium ascorbate phosphate, sodium ascorbate phosphate, glucoside ascorbate, and ascorbyl palmitate. It is done.
  • Examples of the tocopherol compound include compounds selected from a compound group consisting of tocopherol and its derivatives, and a compound group consisting of tocotrienol and its derivatives.
  • the compound selected from these compound groups may be used individually by 1 type, or may be used in combination of multiple types. Moreover, you may use combining the compound each selected from the compound group which consists of a tocopherol and its derivative (s), and the compound group which consists of a tocotrienol and its derivative (s).
  • the compound group consisting of tocopherol and its derivatives includes dl- ⁇ -tocopherol, dl- ⁇ -tocopherol, dl- ⁇ -tocopherol, dl- ⁇ -tocopherol, dl- ⁇ -tocopherol acetate, nicotinic acid-dl- ⁇ -tocopherol Linoleic acid-dl- ⁇ -tocopherol, succinic acid dl- ⁇ -tocopherol and the like.
  • dl- ⁇ -tocopherol, dl- ⁇ -tocopherol, dl- ⁇ -tocopherol, dl- ⁇ -tocopherol, and a mixture thereof (mixed tocopherol) are more preferable.
  • tocopherol derivatives carboxylic acid esters of these tocopherols, particularly acetate esters, are preferably used.
  • the compound group consisting of tocotrienol and derivatives thereof includes ⁇ -tocotrienol, ⁇ -tocotrienol, ⁇ -tocotrienol, ⁇ -tocotrienol, and the like, and a group of compounds derived from these tocotrienols.
  • acetate esters of these tocotrienols are preferably used as tocotrienol derivatives.
  • the content of the antioxidant in the external preparation for skin can be 0.0001% by mass to 5% by mass, preferably 0.001% by mass to 3% by mass with respect to the total mass of the external preparation for skin. can do.
  • the skin external preparation can contain a functional oil component.
  • the functional oil component may be known as a functional oil component that can be expected to have various physiological activities.
  • the functional oily component can also be used as a solubilizer for carotenoids such as astaxanthins.
  • the functional oil component include, for example, ceramides such as natural ceramides and sugar-modified ceramides; fats and oils such as olive oil, camellia oil, macadamia nut oil, castor oil and coconut oil; ubiquinones such as coenzyme Q10; ⁇ -3 oils and fats such as EPA, DHA, linolenic acid; hydrocarbons such as liquid paraffin, paraffin, petrolatum, ceresin, microcrystalline wax, squalane; wax such as carnauba wax, candelilla wax, beeswax, lanolin; isopropyl myristate, Esters such as 2-octyldodecyl myristate, cetyl 2-ethylhexanoate, diisostearyl malate; fatty acids such as palmitic acid, stearic acid, isostearic acid; cetyl alcohol, stearyl alcohol, isostearyl alcohol, 2- Higher alcohols such as
  • the external preparation for skin can contain various extracts from natural products expected to exhibit various biological functions.
  • various extracts include, for example, carrot extract, assembly extract, aloe extract-1, arnica extract, nettle extract, Dutch mustard extract, mulberry white skin extract burdock extract, kizuta extract, garlic extract, pine extract, rose Marie extract, Onionis extract Roman chamomile extract, Altea extract, Ononis extract, Achillea millefolium extract, Tung leaf extract, Celery extract, Thyme extract-2, Salamander extract, Fuquisium poppo extract, Hop extract, Chimp extract Melissa extract, Sage extract, Eucalyptus Extract, jaundice extract, hypericum extract, chamomile extract, horsetail extract, salamander extract, peony extract, loquat leaf extract and the like.
  • the external preparation for skin can include nicotinic acid amide acetic acid DL- ⁇ -tocopherol pantotenyl ethyl ether benzyl nicotinate ⁇ -glycyrrhetinic acid 1-menthol and the like having a biological function other than the extract.
  • additive ingredients usually used for external preparations for skin particularly for external preparations for scalp may be appropriately added to the external preparation for skin according to the present invention.
  • additive components include, for example, polyhydric alcohols such as 1,3-butylene glycol; copper carrageenan, locust bean gum, guar gum, hydroxypropyl guar gum, xanthan gum, caraya gum, tamarind seed polysaccharide, gum arabic, tragacanth gum, hyaluronic acid, Monosaccharides or polysaccharides such as sodium hyaluronate, sodium chondroitin sulfate, dextrin; sugar alcohols such as sorbitol, mannitol, maltitol, lactose, maltotriitol, xylitol; vitamin B1 compounds such as thiamine; vitamin B2 compounds such as riboflavin; Vitamin B3 compounds such as nicotinic acid and nicotinic acid amide; vitamin B5 compounds such as niacin, pantothenic acid and pantothenyl ethyl ether; Min B6 compounds, vitamin
  • the external preparation for skin may contain other additive components based on its function, for example, as a functional component, an excipient, a viscosity modifier, a radical scavenger and the like.
  • additives such as various medicinal components, pH adjusters, pH buffering agents, ultraviolet absorbers, fragrances, and coloring agents can be used in combination. .
  • the method for producing the external preparation for skin of the present invention is not particularly limited, but is preferably produced by combining an emulsion containing glycyrrhetinic acid, astaxanthins, specific preservatives, and other desired components. .
  • glycyrrhetinic acid is contained as an emulsion containing glycyrrhetinic acid.
  • the emulsion containing glycyrrhetic acid is preferably prepared by emulsifying and mixing an oily composition prepared by dissolving glycyrrhetic acid in an oily component in which glycyrrhetinic acid is dissolved, and an aqueous composition containing an aqueous component.
  • the preparation method of the emulsion suitably applied to the present invention will be described later.
  • the particle size of the emulsified particles in the emulsion containing glycyrrhetinic acid is preferably 500 nm or less, and 200 nm or less. It is more preferable that it is 150 nm or less.
  • the details of the measuring method and measuring device of the particle size of the emulsion are as described above.
  • the emulsion containing glycyrrhetinic acid prepared in the method for producing a skin external preparation contains the desired amount of glycyrrhetinic acid capable of obtaining the effect expected to contain glycyrrhetinic acid in the final form of the skin external preparation of the present invention. What is necessary is just to prepare as an emulsion.
  • the preferred content of glycyrrhetinic acid contained in the external preparation for skin of the present invention is as described above.
  • a method for containing the astaxanthin in the external preparation for skin of the present invention (1) a method for solubilizing the astaxanthin with a solubilizer or the like and making it contained in the external preparation for skin, (2) an emulsion containing the astaxanthin And a method of containing the emulsion in an external preparation for skin.
  • the emulsion containing astaxanthin is preferably prepared by emulsifying and mixing an oily composition prepared by dissolving astaxanthin in an oily component in which astaxanthin dissolves, and an aqueous composition containing an aqueous component. .
  • the preparation method of the emulsion suitably applied to the present invention will be described later.
  • the emulsion containing astaxanthin may be an emulsion prepared separately from the emulsion containing glycyrrhetinic acid, or when preparing an emulsion containing glycyrrhetinic acid, both glycyrrhetinic acid and astaxanthin are used.
  • the emulsion prepared by using may be sufficient.
  • the particle diameter of the emulsion particles in the emulsion containing the astaxanthins is preferably 500 nm or less, and 200 nm or less. More preferably, it is more preferably 150 nm or less.
  • the details of the measuring method and measuring device of the particle size of the emulsion are as described above.
  • the content of astaxanthin or a derivative thereof in an emulsion containing astaxanthin or a derivative thereof is 0.0001% by mass to 10% with respect to the total mass of the emulsion from the viewpoint of obtaining the effect expected for the inclusion of astaxanthin or a derivative thereof.
  • the mass is preferably 0.001% by mass to 5% by mass, more preferably 0.005% by mass to 3% by mass.
  • the method for incorporating the specific preservative into the external preparation for skin of the present invention is not particularly limited.
  • a method for directly adding the specific preservative to the prepared external preparation for skin (ii) emulsification containing glycyrrhetinic acid
  • a method of adding a specific preservative to the aqueous phase composition may be mentioned.
  • the external preparation for skin of the present invention is prepared by preparing an emulsion containing glycyrrhetinic acid and an emulsion containing astaxanthins, and combining these emulsion with a specific preservative and other optional ingredients. It is more preferable.
  • the emulsion in the following description includes an emulsion containing glycyrrhetinic acid and an emulsion containing astaxanthins.
  • the emulsion applied to the present invention can be produced according to a known method.
  • the suitable manufacturing method of the emulsion applied to this invention is demonstrated in detail.
  • the emulsion applied to the present invention can be produced by mixing and emulsifying an oily composition containing a predetermined oily component and an aqueous composition.
  • the oily composition contains at least glycyrrhetinic acid, and further contains an N-acylamino acid monoester, an emulsifier, a specific oily component, and any desired oily component. Is preferred.
  • the oily composition preferably contains at least astaxanthins, and further contains an emulsifier and any desired oily component.
  • a uniform oily composition by mixing predetermined oily components and heating to 60 ° C to 90 ° C.
  • the oily composition may contain other oily components as necessary.
  • the prepared oily composition can be added and mixed with stirring into an aqueous composition containing a predetermined aqueous component heated to 40 ° C to 90 ° C.
  • the mixing ratio (mass) of the oily composition and the aqueous composition at this time is not particularly limited, but is 0.1 / 99.9 to 50 as the oily composition / aqueous composition ratio (mass%). / 50 is preferred, 0.5 / 99.5 to 30/70 is more preferred, and 1/99 to 20/80 is even more preferred.
  • the ratio of oily composition / aqueous composition is 0.1 / 99.9 or more, the amount of active ingredients such as glycyrrhetinic acid does not decrease, which is preferable because practical problems of the emulsion do not occur.
  • the oily composition / aqueous composition ratio is 50/50 or less because the emulsifier concentration does not become thin and the stability of the emulsion does not deteriorate.
  • an oily composition and an aqueous composition are mixed and emulsified, the oily composition and the aqueous composition are mixed to obtain a crude emulsion, and then refined using a fine emulsification means.
  • a means for obtaining a crude emulsion by mixing an oily composition and an aqueous composition any commercially available mixing means may be used.
  • a uniform coarse emulsion can be prepared by mixing and stirring an aqueous medium with a magnetic stirrer, household mixer, paddle mixer, impeller mixer or the like.
  • a stirring means having a strong shearing force that is, a homomixer, a dispermixer, an ultramixer or the like.
  • ultrasonic waves in addition to these stirring means.
  • the ultrasonic wave imparting means it is preferable to use an ultrasonic homogenizer.
  • ultrasonic homogenizer examples include ultrasonic homogenizers US-600, US-1200T, RUS-1200T, MUS-1200T (manufactured by Nippon Seiki Seisakusho Co., Ltd.), ultrasonic processors UIP2000, UIP-4000, UIP-8000. UIP-16000 (above, manufactured by Heelscher) and the like.
  • These high-power ultrasonic irradiation devices can be used at a frequency of 25 kHz or less, preferably 15 kHz to 20 kHz.
  • a static mixer, a microchannel, a micromixer, or the like that does not have an external stirring unit and requires only low energy can be used.
  • the rough emulsification treatment can be carried out at an arbitrary temperature of 20 ° C. or higher and 90 ° C. or lower, preferably 40 ° C. or higher and 80 ° C. or lower.
  • High-pressure homogenizers can be broadly classified into a chamber-type high-pressure homogenizer having a fixed throttle portion and a homogeneous valve-type high-pressure homogenizer that controls the opening of the throttle.
  • Examples of the former chamber type high-pressure homogenizer include microfluidizer (manufactured by Microfluidics), nanomizer (manufactured by Yoshida Kikai Kogyo Co., Ltd.), starburst (manufactured by Sugino Machine Co., Ltd.) and the like.
  • Examples of the latter homogeneous valve type high-pressure homogenizer include Gorin type homogenizer (manufactured by APV), Lanier type homogenizer (manufactured by Lanier), high-pressure homogenizer (manufactured by Niro Soavi), homogenizer (manufactured by Sanwa Machinery Co., Ltd.), high-pressure homogenizer ( Izumi Food Machinery Co., Ltd.), ultra-high pressure homogenizer (manufactured by Ika), and the like.
  • the high-pressure homogenizer is equipped with a very narrow chamber part and throttle part in the flow path, and a liquid is forcibly sent using a pump to the narrow flow path, creating a very large pressure difference before and after the throttle part, Using this pressure difference as driving energy, the liquid moves through a narrow pipe line at a speed comparable to the speed of sound, so a large shearing force is generated between the flow path walls and this becomes a dispersion force.
  • the applied pressure and the generated shear force are in a proportional relationship, and the higher the pressure applied, the higher the shear energy used for dispersion. However, not all shear force is used for dispersion, and it is known that the higher the pressure, the lower the energy efficiency and the greater the rate of conversion to heat. is there.
  • the pressure is 100 MPa or more, more preferably 150 MPa or more.
  • the limit on the high pressure side is preferably 300 MPa or less from the viewpoint of temperature rise and pressure resistance.
  • the number of high-pressure treatments may be one, but in order to improve the uniformity of the whole liquid, it is preferable to carry out two or more high-pressure treatments. More preferably, the high pressure treatment is performed 5 times.
  • the temperature before the high-pressure dispersion treatment is preferably set to 20 ° C. to 80 ° C., more preferably 40 ° C. to 70 ° C.
  • the pH of the external preparation for skin of the present invention is preferably from 5 to 8 from the viewpoint of improving the stability of both glycyrrhetinic acid and astaxanthins from the viewpoint of emulsion stability.
  • the pH can be adjusted by adjusting the amount of a component having pH adjusting ability such as various pH adjusting agents.
  • the skin external preparation of the present invention is particularly preferably used as a scalp cosmetic.
  • a scalp cosmetic in addition to the components described above, for example, an emollient agent, a treatment agent, a lubricant, a moisturizer, a hair restorer, a hair nourishing agent, a hair growth agent, an anti-whitening agent, Antibiotics, bactericides, anti-inflammatory agents, anti-allergic agents, anti-aging agents, fragrances, pigments, antiperspirants, cooling sensates, cooling agents, warming sensates and the like can be further added.
  • oily composition A This was dissolved with stirring to give oily composition A.
  • a mixed solution of 48.00 g of glycerin manufactured by Wako Pure Chemical Industries, Ltd.
  • 24.97 g of milli-Q water 70 An aqueous composition A was dissolved at ° C.
  • the aqueous composition A and the oily composition A prepared above were roughly emulsified with a TK homomixer (manufactured by Primemix) at 60 ° C. for 15 minutes at a rotation speed of 500 rpm.
  • This crude emulsion is passed through a Starburst mini machine (manufactured by Sugino Machine), an ultra-high pressure dispersion device, twice at a pressure of 200 MPa while being kept at 60 ° C. (oil-in-water type glycyrrhetic acid emulsion) Was prepared.
  • the average particle diameter of the emulsion was measured with Nanotrac UPA (manufactured by Nikkiso), and the volume average particle diameter (Mv) was obtained. .
  • the volume average particle diameter (Mv) of the emulsion was 80 ⁇ m.
  • the aqueous composition B obtained above was stirred with a homogenizer (model name: HP93, manufactured by SMT Co., Ltd.) while maintaining the temperature at 70 ° C. (10000 rpm), and the oily composition B was added to the aqueous composition B. A pre-emulsion was obtained. Subsequently, the obtained preliminary emulsion was cooled to about 40 ° C., and high-pressure emulsification was performed at 200 MPa using an optimizer HJP-25005 (manufactured by Sugino Machine Co., Ltd.). Then, it filtered with the micro filter with an average hole diameter of 1 micrometer, and prepared the astaxanthin emulsion (astaxanthin content rate: 0.3 mass%).
  • a homogenizer model name: HP93, manufactured by SMT Co., Ltd.
  • the obtained astaxanthin emulsion was diluted to 1% by mass with milliQ water, and the average particle size of the emulsion was measured using a particle size analyzer FPAR-1000 (Otsuka Electronics Co., Ltd.).
  • Examples 1 to Examples were prepared by mixing glycyrrhetinic acid emulsion, astaxanthin emulsion, preservative, and other components so that the types and content ratios of the blended components were the types and content ratios shown in Table 1. 5. External preparations for skin of Comparative Examples 1 to 8 were obtained.
  • the state of inflammation at the test site was visually observed, and the recovery of skin roughened by SDS was evaluated.
  • the evaluation criteria were evaluated as “C” for a sample that became red to the same extent as the site where water was applied, “B” for a sample that became slightly red, and “A” for a sample that did not remain red at all.
  • Emulsion stability For the purpose of evaluating the stability of the emulsion contained in the external preparation for skin by changing the particle size of the emulsion, the turbidity of the sample for evaluation was evaluated.
  • each sample for evaluation is stored at 50 ° C. for 1 week, and the turbidity of each sample after storage is measured with an optical density (OD) at 625 nm (1 cm cell, transmission measurement) using a UV-visible spectrophotometer. It was performed by using and measuring. Samples with turbidity exceeding 0.5 were evaluated as “C”, samples with turbidity exceeding 0.3 but not more than 0.5 were evaluated as “B”, and samples with turbidity not exceeding 0.3 were evaluated as “A”. .
  • the skin external preparations of Examples 1 to 5 containing both glycyrrhetinic acid and astaxanthins and a specific preservative have an effect of recovering rough skin by SDS. Furthermore, the skin external preparations of Examples 1 to 5 have sufficient antiseptic properties by containing a combination of two or more selected from the specific preservatives methylparaben, phenoxyethanol, ethylparaben, and propynyl iodide butylcarbamate. And the stability of the glycyrrhetic acid-containing emulsion and the astaxanthin emulsion was not deteriorated. On the other hand, the skin external preparation of Comparative Example 1 containing no preservative was found to have poor antiseptic properties and insufficient performance as a skin external preparation.
  • Example 6 A hair essence was prepared according to the following formulation.
  • the following numerical value means the mass% with respect to the total mass of prescription.
  • the glycyrrhetic acid emulsion and the astaxanthin emulsion it obtained by the above-mentioned method.
  • the hair essence of Example 6 has a sufficient scalp rough skin recovery effect, does not impair the stability of the glycyrrhetic acid-containing emulsion and the astaxanthin-containing emulsion, and has a sufficient antiseptic effect as described above. It confirmed by performing evaluation.

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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne une préparation à usage externe pour la peau qui comprend une émulsion contenant de l'acide glycyrrhétinique, au moins une substance choisie dans le groupe constitué de l'astaxanthine et de dérivés d'astaxanthine, et un conservateur qui a une valeur I/O de 1,5 ou moins, et qui n'a pas un groupe alkyle ou a un groupe alkyle linéaire ou ramifié ayant une longueur de chaîne alkyle de 5 ou moins. La préparation à usage externe ne comprend pas d'éthanol ou comprend 1 % en masse ou moins d'éthanol.
PCT/JP2013/082379 2013-01-21 2013-12-02 Préparation à usage externe pour la peau WO2014112220A1 (fr)

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JP2013-248315 2013-11-29

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JP2019131550A (ja) * 2018-02-01 2019-08-08 株式会社コーセー カロテノイドの安定化方法
JP2019131548A (ja) * 2018-02-01 2019-08-08 株式会社コーセー 組成物
JP7246987B2 (ja) * 2019-03-25 2023-03-28 日本精化株式会社 Ｏ／ｗ型乳化組成物
CN113729169A (zh) * 2021-08-12 2021-12-03 四川省食品发酵工业研究设计院有限公司 一种具有抑菌作用的肉类着色剂及制备方法
WO2023159476A1 (fr) * 2022-02-25 2023-08-31 L'oreal Composition pour le soin des matières kératiniques
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