WO2017094916A1 - GLYCEROL PRODUCTION PROMOTER DERIVED FROM Staphylococcus Epidermidis, ANTIMICROBIAL PEPTIDE PRODUCTION PROMOTER DERIVED FROM SKIN EPIDERMAL KERATINOCYTES, AND UTILIZATION THEREOF IN EXTERNAL PREPARATION FOR SKIN PROTECTION - Google Patents

GLYCEROL PRODUCTION PROMOTER DERIVED FROM Staphylococcus Epidermidis, ANTIMICROBIAL PEPTIDE PRODUCTION PROMOTER DERIVED FROM SKIN EPIDERMAL KERATINOCYTES, AND UTILIZATION THEREOF IN EXTERNAL PREPARATION FOR SKIN PROTECTION Download PDF

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WO2017094916A1
WO2017094916A1 PCT/JP2016/086094 JP2016086094W WO2017094916A1 WO 2017094916 A1 WO2017094916 A1 WO 2017094916A1 JP 2016086094 W JP2016086094 W JP 2016086094W WO 2017094916 A1 WO2017094916 A1 WO 2017094916A1
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genus
skin
production promoter
lactic acid
promoter derived
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PCT/JP2016/086094
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French (fr)
Inventor
Kazue Takayama
Yuko MAKIOKA
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Ichimaru Pharcos Co., Ltd.
Combi Corporation
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Priority to KR1020187002720A priority Critical patent/KR20180084729A/en
Priority to CN201680044943.1A priority patent/CN107922956A/en
Publication of WO2017094916A1 publication Critical patent/WO2017094916A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A61K38/1729—Cationic antimicrobial peptides, e.g. defensins
    • 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
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • 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
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/99—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
    • 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
    • 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
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • 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
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/10—General cosmetic use

Definitions

  • the present invention relates to drug agents and an external preparation for skin protection, which protect the skin from external stresses such as drying and harmful bacteria through a function of promoting one or a series of the production of glycerol derived from skin resident bacteria, namely Staphylococcus epidermidis that is a useful bacterium, and the production ofantimicrobial peptides derived from skin epidermal keratinocytes.
  • Background Art glycerol derived from skin resident bacteria, namely Staphylococcus epidermidis that is a useful bacterium, and the production ofantimicrobial peptides derived from skin epidermal keratinocytes.
  • Non-patent Document 1 On the human skin, commensal microorganisms form a group as a skin resident bacterial flora.
  • skin resident bacteria Staphylococcus epidermidis, Staphylococcus aureus, corynebacteria and the like inhabit the skin, and the protective function of the skin against the outside world is maintained by the balance of these bacteria.
  • the balance of the flora of these bacteria is impaired and such protective function is thus compromised by an environmental factor such as a rapid temperature change, dryness or a strong detergent or chemical agent, or by a physical/mental factor such as injury, emotional stress or poor systemic condition due to a disease (Non-patent Document 1).
  • Staphylococcus epidermidis known as a useful bacterium of the skin breaks down serum to produce glycerol and thereby plays a role in physical protective functions, such as inhibition of dry skin and suppression of propagation of saprophytic bacteria by adjusting the skin surface pH. Accordingly, when the ratio of Staphylococcus epidermidis decreases, these protective functions may no longer be demonstrated and this may cause a skin disease.
  • moisturizing agents, antibacterial agents, disinfectant components and the like are widely used in skin external preparations; however, depending on the drug components, there is a concern that the protective functions provided by Staphylococcus epidermidis, which is an aerobic bacterium, may also be inhibited.
  • Staphylococcus epidermidis also plays a role in enhancing the biological protective functions of living body by stimulating skin epidermal keratinocytes and promoting the production of antimicrobial peptides therefrom.
  • antimicrobial peptides produced by skin epidermal keratinocytes human ⁇ -defensin-2 (hBD2) and human ⁇ -defensin-3 (hBD3) are known, and it has been reported that these antimicrobial peptides show an antibacterial action against Staphylococcus aureus, which is a harmful bacterium, and serve as a biological barrier to protect the skin from such harmful bacteria (Non-patent Document 2).
  • saccharides such as glucooligosaccharides have been used as assimilable sources (Patent Document 1); however, since not only useful Staphylococcus epidermidis but also other harmful bacteria such as Staphylococcus aureus assimilate such saccharides, a skin protective function is not attained in some cases. In addition, many saccharides give a sticky feel when applied to the skin, and this presents another problem of the difficulty in formulation in terms of the feel.
  • Staphylococcus aureus is known to exist in a large number on the skin of people having dry skin or rough skin and atopic dermatitis patients. It is also known that toxins produced by Staphylococcus aureus cause a further deterioration of the skin condition. For keeping the skin surface condition healthy, it is thus believed to be important to effectively kill Staphylococcus aureus and to maintain Staphylococcus epidermidis having a skin protective function.
  • Staphylococcus epidermidis on the skin are similar to those of lactic acid bacteria and bifidobacteria that are useful intestinal bacteria. These useful intestinal bacteria are known to adjust the intestinal pH, inhibit the proliferation of harmful bacteria such as Clostridium perfringens and Escherichia coli, and have a protective function in the intestinal tract.
  • useful bacteria such as lactic acid bacteria and bifidobacteria are taken into the intestinal tract; however, generally, in order to allow these useful bacteria to reach the intestine alive and colonize there, it is required to select acid-resistant strains and to encapsulate them into an enteric coated-type capsule.
  • a method of ingesting a food or drink containing dietary fibers and various oligosaccharides that are selectively assimilated by the useful bacteria has also been employed. Yet, depending on the individual constitution, these methods sometimes cause excessive intestinal fermentation and diarrhea.
  • Patent Document 2 the use of heat-killed cells of a lactococcus bacterium has been proposed (Patent Document 2).
  • Ingestion of heat-killed cells of Enterococcus faecalis in the form of a food or drink enables to facilitate the proliferation of bifidobacteria in the intestinal tract and to thereby suppress the proliferation of harmful bacteria and improve the intestinal protective function. Furthermore, since the dead bacterial cells are easily processed as a food or drink, unnecessary fermentation does not proceed, so that the storage stability of the food or drink is hardly affected.
  • Preferred examples of heat-killed cells of a lactic acid bacterium include those of a microbe classified as Enterococcus faecalis, and it is particularly preferred to use Enterococcus faecalis EC-12 strain (accession No. FERM BP-10284), whose 16S rDNA has been registered as "AB15482" at the National Institute of Genetics.
  • Enterococcus faecalis EC-12 strain accession No. FERM BP-10284
  • Patent Document 1 Japanese Laid-open Patent Application (Kokai) No. 2005-002087
  • Patent Document 2 Japanese Laid-open Patent Application (Kokai) No. 2004-051530 NON-PATENT DOCUMENTS
  • Non-patent Document 1 Gallo, R.L. et al., Journal of Investigative Dermatology 131:1974-1980 (2011)
  • Non-patent Document 2 Kisich, K.O. et al., Journal of Investigative Dermatology 127:2368-2380 (2007) SUMMARY OF THE INVENTION Problems to be Solved by the Invention
  • An object of the present invention is to provide drug agents and an external preparation for skin protection, which protect the skin from external stresses such as drying and harmful bacteria through a function of promoting one or a series of the production of glycerol derived from Staphylococcus epidermidis and the production of antimicrobial peptides derived from skin epidermal keratinocytes against harmful bacteria such as Staphylococcus aureus.
  • the present inventors investigated a variety of lactic acid bacteria and conducted intensive studies to discover that cells of a lactococcus bacterium, Enterococcus faecalis EC-12, particularly heat-killed cells of Enterococcus faecalis EC-12 have an action of promoting the production of glycerol derived from Staphylococcus epidermidis and the production of antimicrobial peptides derived from skin epidermal keratinocytes.
  • heat-killed cells of Enterococcus faecalis EC-12 give an excellent silky feel when applied to the skin and provides a feeling-improving effect in any of aqueous-type, oil-type, milky lotion-type and powder-type external preparations.
  • the present invention includes the following items.
  • a glycerol production promoter derived from Staphylococcus epidermidis the promoter comprising a lactic acid bacterium belonging to the genus Enterococcus as an effective ingredient.
  • the antimicrobial peptide production promoter derived from skin epidermal keratinocytes according to any one of [6] to [9], wherein the lactic acid bacterium belonging to the genus Enterococcus is heat-killed.
  • the drug agents and the external preparation for skin protection according to the present invention are capable of promoting the production of glycerol derived from Staphylococcus epidermidis and the production of human ⁇ -defensin-2 and human ⁇ -defensin-3, which are antimicrobial peptides derived from skin epidermal keratinocytes against Staphylococcus aureus. That is, dry skin is inhibited by promotion of the glycerol production, and controlling the skin surface pH enhances the protective functions of the skin, such as suppression of the proliferation of saprophytic bacteria.
  • the skin can be protected from harmful bacteria existing thereon. Consequently, the skin surface condition can be maintained healthy through one or a series of these promoting functions. Furthermore, the drug agents and the external preparation for skin protection according to the present invention give excellent silky feel when applied to the skin and provide a feeling-improving effect in any of aqueous-type, oil-type, milky lotion-type and powder-type external preparations.
  • FIG. 1 shows the results of quantifying the glycerol production after adding heat-killed cells of Enterococcus faecalis EC-12 and Aloe vera polysaccharides as plant polysaccharides to culture solutions of Staphylococcus epidermidis type strain (ATCC 12228).
  • FIG. 2 shows the results of quantifying the glycerol production after adding heat-killed cells of Enterococcus faecalis EC-12 to culture solutions of skin resident bacteria collected from a glabellar area of human.
  • FIG. 3 shows the results of quantifying the amount of glycerol collected from human cheek in a human monitor test where a softening lotion containing heat-killed cells of Enterococcus faecalis EC-12 was used.
  • FIG. 4 shows the results of measuring the expression levels of human ⁇ -defensin-2 (hBD2) and human ⁇ -defensin-3 (hBD3) mRNAs after culturing human normal keratinocytes in a culture medium containing heat-killed cells of Enterococcus faecalis EC-12 and extracting RNAs therefrom.
  • hBD2 human ⁇ -defensin-2
  • hBD3 human ⁇ -defensin-3
  • the glycerol production promoter derived from Staphylococcus epidermidis, the antimicrobial peptide production promoter derived from skin epidermal keratinocytes and the external preparation for skin protection according to the present invention comprise a lactic acid bacterium belonging to the genus Enterococcus as an effective ingredient.
  • the lactic acid bacterium belonging to the genus Enterococcus is Enterococcus faecalis, particularly heat-killed Enterococcus faecalis EC-12.
  • the drug agents and the external preparation for skin protection have the following characteristics of: 1. promoting the production of glycerol derived from Staphylococcus epidermidis; 2. synergistically promoting the production of glycerol derived from Staphylococcus epidermidis by further comprising plant polysaccharides in combination; 3. promoting the production of antimicrobial peptides derived from skin epidermal keratinocytes against harmful bacteria such as Staphylococcus aureus; 4. enhancing the function of protecting the skin from external stresses such as drying and harmful bacteria through one or a series of the above-described promoting functions; and 5. giving an excellent silky feel when applied to the skin and is capable of providing a feeling-improving effect in any of aqueous-type, oil-type, milky lotion-type and powder-type external preparations.
  • the method of culturing the lactic acid bacterium belonging to the genus Enterococcus is not particularly restricted including conventionally known culturing methods of lactic acid bacteria, and heat-killed cells thereof can be produced by the following method.
  • bacterial cells are recovered by a method such as filtration or centrifugation and, after subsequently washing the recovered cells with water, the cells are suspended in water or the like, heat-treated and then, as required, concentrated and dried, whereby heat-killed cells of the lactic acid bacterium belonging to the genus Enterococcus can be prepared.
  • a normally used spray dryer, freeze dryer or the like may be employed.
  • the recovered cells may also be subjected to a treatment with an enzyme, a treatment with a surfactant and/or a grinding/pulverization treatment, and resultants of such treatments are also included in the killed bacterial cells or treated products thereof according to the present invention.
  • Examples of water used for the washing and suspending include pure water, tap water, well water, mineral spring water, mineralized water, hot-spring water, spring water and fresh water, as well as a variety of treatment products thereof.
  • Examples of a water treatment include purification, heating, sterilization, filtration, ion exchange, osmotic adjustment and buffering.
  • examples of water that can be used as an extraction solvent in the present invention also include purified water, heated water, ion-exchanged water, physiological saline and various buffers.
  • the lactic acid bacterium belonging to the genus Enterococcus obtained in the above-described manner can be used as a glycerol production promoter derived from Staphylococcus epidermidis, a skin epidermal keratinocyte-derived antimicrobial peptide production promoter against harmful bacteria such as Staphylococcus aureus, or an external preparation for skin protection which maintains the skin surface condition healthy through one or a series of these promoting functions.
  • the above-described heat-killed bacterial cells be suspended and adjusted such that they are contained in an amount of not less than 5 ⁇ 10 11 cells, particularly preferably not less than 5 ⁇ 10 12 cells, per 1 gram of each promoter. Further, in a routinely used external preparation for skin protection, it is preferred that the heat-killed bacterial cells be incorporated and adjusted such that one-third to an equivalent of the above-described amount is applied per use.
  • the external preparation for skin protection may take a form that is appropriate for application such as ampule, capsule, powder, granule, liquid, gel, foam, emulsion, sheet, mist or spray, and examples such external preparation include 1) pharmaceutical preparations; 2) quasi drugs; 3) topical or systemic skin external preparations (e.g., basic cosmetics such as cosmetic solutions, milky lotions, creams, ointments, lotions, oils and facial packs; facial and skin cleansers such as bar soaps, liquid soaps and handwashes; massaging agents; cleansing agents; hair-removing agents; depilatories; shaving agents; after-shave lotions; pre-shave lotions; shaving creams; make-up cosmetics such as foundations, lipsticks, rouges, eye shadows, eyeliners and mascaras; perfumes; manicures; manicure enamels; manicure enamel removers; cataplasms; plasters; tapes; sheets; patches; and aerosols); 4) medical and/
  • these external preparations for skin protection can be produced by arbitrarily selecting, and using those components and additives exemplified below in combination as required.
  • the amount thereof to be incorporated into these formulation systems is not particularly prescribed here; however, normally, it is believed to be preferably about 0.0001 to 50%.
  • oils and fats include avocado oil, almond oil, fennel oil, perilla oil, olive oil, orange oil, orange roughy oil, sesame oil, cacao butter, camomile oil, carrot oil, cucumber oil, beef tallow fatty acid, kukui nut oil, safflower oil, shea butter, liquid shea butter, soybean oil, camellia oil, corn oil, rapeseed oil, persic oil, castor oil, cottonseed oil, peanut oil, turtle oil, mink oil, egg-yolk oil, palm oil, palm kernel oil, haze wax, coconut oil, beef tallow, lard, squalene, squalane, pristane, and hydrogenation products (e.g., hardened oil) of these oils and fats.
  • avocado oil almond oil, fennel oil, perilla oil, olive oil, orange oil, orange roughy oil, sesame oil, cacao butter, camomile oil, carrot oil, cucumber oil, beef tallow fatty acid, kukui
  • waxes examples include beeswax, carnauba wax, spermaceti, lanolin, liquid lanolin, reduced lanolin, hard lanolin, candelilla wax, montan wax, shellac wax, and rice wax.
  • mineral oils examples include liquid paraffins, vaseline, paraffins, ozokerite, ceresin, and microcrystalline waxes.
  • fatty acids include natural fatty acids, such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, 12-hydroxy stearic acid, undecylenic acid, tall oil and lanolin fatty acid; and synthetic fatty acids, such as isononanoic acid, caproic acid, 2-ethylbutanoic acid, isopentanoic acid, 2-methylpentanoic acid, 2-ethylhexanoic acid and isopentanoic acid.
  • natural fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, docosahexaenoic acid, eicosapenta
  • Alcohols examples include natural alcohols, such as ethanol, isopropanol, lauryl alcohols, cetanol, stearyl alcohols, oleyl alcohols, lanolin alcohols, cholesterols, phytosterols and phenoxyethanol; and synthetic alcohols, such as 2-hexyl decanol, isostearyl alcohols and 2-octyl dodecanol.
  • natural alcohols such as ethanol, isopropanol, lauryl alcohols, cetanol, stearyl alcohols, oleyl alcohols, lanolin alcohols, cholesterols, phytosterols and phenoxyethanol
  • synthetic alcohols such as 2-hexyl decanol, isostearyl alcohols and 2-octyl dodecanol.
  • polyhydric alcohols examples include ethylene oxide, ethylene glycol, diethylene glycol, triethylene glycol, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, polyethylene glycol, propylene oxide, propylene glycol, polypropylene glycol, 1,3-butylene glycol, pentyl glycol, glycerin, pentaerythritol, threitol, arabitol, xylitol, ribitol, galactitol, sorbitol, mannitol, lactitol, and maltitol.
  • esters examples include isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, oleyl oleate, decyl oleate, octyldodecyl myristate, hexyldecyl dimethyloctanoate, cetyl lactate, myristyl lactate, diethyl phthalate, dibutyl phthalate, acetylated lanolin, ethylene glycol monostearate, propylene glycol monostearate, and propylene glycol dioleate.
  • Metal Soaps examples include aluminum stearate, magnesium stearate, zinc stearate, calcium stearate, zinc palmitate, magnesium myristate, zinc laurate, and zinc undecylenate.
  • gum substances, saccharides and water-soluble polymer compounds include gum arabic, gum benzoin, gum dammar, guaiac resin, Irish moss, karaya gum, gum tragacanth, gum carob, quince seed, agar, casein, lactose, fructose, sucrose and its ester, trehalose and its derivatives, dextrin, gelatin, pectin, starch, carrageenan, carboxymethyl chitin and chitosan, alkylene (C 2 to C 4 ) oxide (e.g., ethylene oxide)-added hydroxyalkyl (C 2 to C 4 ) chitin and chitosan, low-molecular-weight chitin and chitosan, chitosan salts, sulfated chitin and chitosan, phosphorylated chitin and chitos
  • surfactants examples include anionic surfactants (alkyl carboxylates, alkyl sulfonates, alkyl sulfates and alkyl phosphates); cationic surfactants (alkylamine salts and alkyl quaternary ammonium salts); amphoteric surfactants, such as carboxylic acid-type amphoteric surfactants (amino-type and betaine-type); sulfate-type amphoteric surfactants; sulfonic acid-type amphoteric surfactants; phosphate-type amphoteric surfactants; nonionic surfactants (ether-type nonionic surfactants, ether ester-type nonionic surfactants, ester-type nonionic surfactants, block polymer-type nonionic surfactants and nitrogen-containing nonionic surfactants); and other surfactants (natural surfactants, protein hydrolysate derivatives, polymeric surfactants, titanium-silicon-containing surfactants).
  • vitamins include vitamin A group, such as retinol, retinal (vitamin A1), dehydroretinal (vitamin A2), carotene and lycopene (provitamin A); vitamin B group, such as thiamine hydrochloride, thiamine sulfate (vitamin B1), riboflavin (vitamin B2), pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), folic acid, nicotinic acid, pantothenic acid, biotin, choline, and inositol; vitamin C group, such as vitamin C acid and derivatives thereof; vitamin D group, such as ergocalciferol (vitamin D2), cholecalciferol (vitamin D3) and dihydrotachysterol; vitamin E group, such as vitamin E, derivatives thereof and ubiquinones; vitamin K group, such as phytonadione (vitamin K1), menaquinone (vitamin K1), menaquinone
  • amino acids include valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxylysine, arginine, ornithine, histidine, and amino acid derivatives such as sulfates, phosphates, nitrates, citrates and pyrrolidonecarboxylic acid of the above-described amino acids.
  • additive(s) derived from a plant or animal material(s) is/are arbitrarily selected and incorporated after subjecting them to a processing that is performed by a conventional method (e.g., a combination of treatments arbitrarily selected from grinding, milling, washing, hydrolysis, fermentation, purification, squeezing, extraction, fractionation, filtration, drying, powderization, granulation, dissolution, sterilization, pH adjustment, deodorization, decolorization and the like) in accordance with the type and mode of the product to which the additive(s) is/are added.
  • a conventional method e.g., a combination of treatments arbitrarily selected from grinding, milling, washing, hydrolysis, fermentation, purification, squeezing, extraction, fractionation, filtration, drying, powderization, granulation, dissolution, sterilization, pH adjustment, deodorization, decolorization and the like
  • the solvent used for extraction may be selected with consideration of the intended use and type of the product to which the additive(s) is/are added as well as the processing/treatment to be performed subsequently and the like, and it is usually desirable to use one or a mixture of two or more selected from lower alcohols (e.g., water, methanol, ethanol, propyl alcohols, isopropyl alcohols, butanol, isobutanol), water-containing lower alcohols, polyhydric alcohols (e.g., propylene glycol, 1,3-butylene glycol, glycerin), water-containing polyhydric alcohols and various organic solvents (e.g., acetone, ethyl acetate).
  • lower alcohols e.g., water, methanol, ethanol, propyl alcohols, isopropyl alcohols, butanol, isobutanol
  • polyhydric alcohols e.g., propylene glycol, 1,3-butylene glycol, g
  • Incorporation of an additive derived from a plant or animal material into a systemic or topical external preparation or a cosmetic product is expected to exert not only cosmetic effects such as protection of skin and hair, moisturization, improvement of feel and texture, provision of flexibility, stimulus relief, relaxation of stress by fragrance, cell activation (cellular anti-aging), suppression of inflammation, improvement of skin and hair conditions, inhibition and improvement of rough skin, hair generation, promotion of hair growth, inhibition of hair loss, glossing, cleansing effect, fatigue relief, blood-flow facilitation and bathing effect, but also other effects such as fragrancing, deodorization, thickening, antiseptic effect and buffering.
  • cosmetic effects such as protection of skin and hair, moisturization, improvement of feel and texture, provision of flexibility, stimulus relief, relaxation of stress by fragrance, cell activation (cellular anti-aging), suppression of inflammation, improvement of skin and hair conditions, inhibition and improvement of rough skin, hair generation, promotion of hair growth, inhibition of hair loss, glossing, cleansing effect, fatigue relief, blood-flow facilitation and bathing effect, but also other effects such
  • Specific plants (crude drugs) for raw materials are, for example, almond (tonsil), Persicaria tinctoria (Polygonum tinctorium Lour), Sabia japonica (Sinomenium acutum Rehder et Wilson), Aucuba japonica, Chinese parasol tree or Firmiana simplex, Cocculus trilobus (Cocculus trilobus DC.), Gastrodia elata Blume f.
  • Amaranthus blitum (Amaranthus viridis), Oryza sativa "seed, seed coat", Anethum graveolens “seed”, Thymus quinquecostatus, Urtica thunbergiana, Cananga odorata, Conandron ramondioides, Selaginella tamariscina or Selaginella tamariscina, Phaseolus vulgaris, oolong tea, Foeniculum vulgare, Huito (Genipa americana), Scirpus fluviatilis, Lonicera gracilipes "fruit", Carum carvi, Curcuma longa, Spirodela polyrhiza (Lemna minor), Asarum sieboldii or Asarum heterotropoides var.
  • Gray Hydrangea macrophylla, Cinnamomum cassia, Broussonetia papyrifera (Broussonetia kazinoki "fruit"), Curcuma zedoaria, Quercus dentata, Croton eluteria, Rhamnus purshiana, Gypsophila elegans, Inula salicina, Lygodium (Lygodium japonicum), kaniwa, Dianthus caryophyllus, Valeriana fauriei (Valeriana fauriei Briquet), Betula, Betula or Betula platyphylla var. japonica.
  • japonica Trichosanthes cucumeroides
  • Pinellia ternata Avena fatua, Paullinia cupana "seed", Magnolia officinalis, karaya, Cerasus spachiana Lavalee ex H.Otto var. spachiana forma ascendens, Pseudocydonia sinensis (Chaenomeles speciosa), Garcinia cowa, Agastache rugosa, Potentilla chinensis (Potentilla, Potentilla discolor), Veronica undulata, Trametes versicolor, Dianthus superbus var.
  • melanolasius Fragaria, Rubus phoenicolasius, Rubus parvifolius, Rubus palmatus var. coptophyllus, Rubus idaeus), Actinidia chinensis "fruit, leaf”, Trichosanthes kirilowii (Trichosanthes kirilowii MAXIM.), Platycodon grandiflorus (Platycodon grandiflorus, Platycodon Root), Chrysanthemum morifolium (Chrysanthemum indicum, Chrysanthemum zawadskii var.
  • japonica Agrimonia pilosa
  • Cephalanthera falcata Cephalanthera erecta
  • Cymbidium floribundum Lucuma laurifolia
  • Psidium guajava "fruit” Parthenium argentatum
  • Quercus infectoria gall
  • Aleurites moluccanus Cephalanthera longifolia, Lycium barbarum (Lycium chinense, lycii fructus, lycii folium, Lycii root), Asparagus (Asparagi radix), Pueraria montana (Puerariae Radix), Cinnamomum camphora, gooseberry "fruit", Artemisia annua (Artemisia annua leaf), P.
  • Mandshurica (Neottia nidus-avis), Clematis chinensis (Wei-ling-xian), Cerasus (Prunus speciosa, Prunus serrulata, Prunus sargentii, Prunus pendula Maxim. form. ascendens Ohwi, Prunus incisa, Prunus maximowiczii, Prunus yedoensis, Prunus nipponica, Prunus leveilleana Koene, Prunus subhirtella, Prunus lannesiana var.
  • Prunus campanulata leaf, flower, fruit, bark (cherry bark)
  • cherry Punica granatum
  • Sasa Cephalanthera longibracteata
  • Camellia sasanqua Alisma plantago-aquatica var.
  • frutescens var. crispa f. crispa or Perilla frutescens var. crispa 'Discolor' perilla herb, sisosi
  • red sandal tree Tilia japonica
  • Magnolia officinalis Forsythia viridissima Lindl.
  • Lyophyllum decastes (Lyophyllum shimeji, Lyophyllum fumosum, Lyophyllum decastes, Lyophyllum connatum, Hypsizygus tessellatus, Lyophyllum shimeji, Hypsozogus ulmarius), Magnolia liliiflora (Magnolia kobus), Filipendula, Solanum tuberosum, Adenophora polymorpha root, Jasminum (Jasminum sambac), Ophiopogon japonicus, Vigna unguiculata ssp.
  • Fagopyrum esculentum "seed” Dioscorea rhipogonoides, Vicia faba, Rheum, Raphanus sativus var. longipinnatus, Glycine max, Citrus aurantium (wild orange peel, orange pease), E.quantisii, Eclipta prostrata, Euphorbia pekinensis (Knoxia root), Dicksoniaceae (Cibotium rhizome), dark sweet cherry "fruit", Alcea rosea, T. vulgaris L. (Thymus, Thymus quinquecostatus), Dioscorea gracillima Miq.
  • Phyllostachys bambusoides Phyllostachysis caulis
  • Pogostemon cablin Mentha (Mentha, mint leaf), Mucuna pruriens, Coix lacryma-jobi var. ma-yuen (Coix Seed), Anemarrhena asphodeloides (Anemarrhenae Rhizoma), banana, oregano, Eschscholzia californica (Tribulus terrestris), Vanilla Beans, papaya, Gnaphalium affine, adjobobo, Senna occidentalis "whole plant, cauline, leaf", Paprika, E. helleborine var.
  • Vitex rotundifolia or Vitex trifolia L. (Vitex rotundifolia fruit), Cyperus rotundus (Cyperi Rhizoma), Tribulus terrestris, Rosa rugosa (maikai flower), Glehnia littoralis, Hamamelis japonica, palm, rose (rose), balata, Hevea brasiliensis, Agaricus campestris (Agaricus arvensis, Agaricus abruptibulbus), Aspidistra elatior, Paliurus spina-christi, Parietaria, Cymbidium nishiuchianum cv.
  • fauriei (achyranthis radix, Orchis chidori, Chamaecyparis obtusa, Thujopsis dolabrata, Ricinus communis L., Sunflower, Capsicum annuum Group, Semiaquilegia adoxoides, Typha domingensis (Typha orientalis Presl), Agaricus subrufescens (Agaricus blazei Murrill, Hilo matsutake), Neottia acuminata, Pimenta "fruit", juniper, Bletilla striata, Amaranthaceae “fruit”, Cicer arietinum, Lens culinaris, Althaea officinalis, Anemone chinensis (Pulsatilla root), Eriobotrya japonica "fruit, leaf, cauline", Areca catechu (Areca nut), Pu-erh tea (Camellia assamica (Mast.) Chang), Piper kads
  • viride Mentha spicata L., Mimosa, Zingiber mioga, Synsepalum dulcificum "fruit", Commiphora myrrha, Terminalia chebula, Xerochrysum bracteatum, Hibiscus syriacus (althea), Aphananthe aspera, Sapindus mukorossi, Munya, Lithospermum purpurocaeruleum (Lithospermum root), Callicarpa japonica or Callicarpa japonica var. luxurians.
  • sibirica, Morella rubra Myrica bark
  • Artemisia tridentata Eucalyptus
  • Saxifraga stolonifera Saxifraga leaf
  • Yucca or Brevifolia Citrus junos "fruit", Lilium, Angelica dahurica, Artemisia (Artemisia princeps leaf), Omphalia lapidescens (raigan), Lime "fruit”, Secale cereale, Siraitia grosvenorii "fruit”, raspberry “leaf, fruit”, Latania (Krameriaceae), Allium chinense or shallot (Allium chinese bulb), lavender, Dimocarpus longan (Longan Aril), Agave, (Agave americana, American aloe), Camellia sinensis L.
  • seaweeds include seaweeds [green algae: Chlorella vulgaris, Chlorella pyrenoidsa, Chlorella ellipsoidea, Green laver (Enteromorpha linza, Enteromorpha prolifera, Enteromorpha compressa, Enteromorpha intestinalis, Enteromorpha clathrata), Ulva pertusa (sea lettuce)], seaweeds [brown algae: Laminariaceae (Saccharina japonica, Saccharina japonica var. ochotensis, Saccharina japonica var.
  • seaweeds also include other algae, for example, green algae (Genus Chlamydomonas: Chlamydomonas reinhardtii, Chlamydomonas nivalis, Genus Dunaliella: Dunaliella salina, Genus Chlorococcum: Chlorococcum sp., Genus Pandorina: Pandorina morum, Genus Volvox: Volvox carteri, Volvox sp., Genus Palmella, Genus Tetraspora, Genus Spirogyra, Mougeotia sp., Spirogyra, Genus Draparnaldia, Genus Ulothrix: Ulothrix flacca, Genus Ulva: Ulva pertusa, Ulva reticulata, Ulva arasakii, Genus Prasiola: Prasiola japonica, Genus Fritschiella, Genus Cladophora: Cladophora japonica,
  • Genus Bryopsis Genus Codium: Codium fragile, Codium subtubulosum, Codium contractum, Codium cylindricum, Codium latum, Genus Acetabularia: Acetabularia ryukyuensis, Genus Chaetomorpha: Chaetomorpha spiralis, Chaetomorpha moniligera, Chaetomorpha okamurai, Genus Closterium, Genus Korekaete, Genus Cosmarium, Genus Dictyosphaeria: Dictyosphaeria cavernosa, Genus Monostroma: Monostroma nitidum, Monostroma latissimum, Monostroma grevillei, Kornmannia leptoderma, Genus Oedogonium, Genus Pediastrum, Genus Trentepohla: Trentepohla aurea
  • Genus Pylaiella Pilayella littoralis
  • Genus Ectocarpus Hincksia indica
  • Genus Botrytella Botrytella parva
  • Genus Ralfsia Ralfsia fungiformis
  • Genus Sphacelaria Sphacelaria tribuloides
  • Genus Halopteris Halopteris filicina
  • Genus Cutleria Cutleria cylindrica
  • Cutleria adspersa Genus Dictyota: Dictyota dichotoma
  • Dictyota dilatata Genus Pachydictyon
  • Dictyota coriacea Rugulopteryx okamurae
  • Genus Spatoglossum Spatoglossum pacificum
  • Genus Dictyopteris Dictyopteris divaricata
  • Genus Kjellmaniella Saccharina gyrata
  • Genus Eckloniopsis Eckloniopsis radicosa
  • Genus Ecklonia Ecklonia cava
  • Ecklonia stolonifera Ecklonia kurome
  • Genus Thalassiophyllum Thalassiophyllum clathrus
  • Genus Streptophyllum Streptophyllum sp.
  • Genus Streptophyllopsis Streptophyllopsis kuroshioensis
  • Genus Arthrothamnus Arthrothamnus bifidus
  • Genus Eisenia Eisenia bicyclis
  • Genus Alaria Alaria praelonga
  • Alaria crassifolia Eualaria fistulosa
  • Genus Silvetia Genus Eisenia bicyclis
  • Genus Bangia Bangia fuscopurpurea, Bangia gloiopeltidicola
  • Genus Pyropia Pyropia tenera, Pyropia yezoensis, Pyropia pseudolinearis, Pyropia dentata, Wildemania occidentalis, Wildemania variegata, Wildemania amplissima, Genus Rhodochorton: Acrochaetium howei, Genus Trichogloea: Trichogloea requienii, Genus Liagora: Yamadaella caenomyce, Liagora japonica, Liagora ceranoides f.
  • Genus Nemalion Nemalion vermiculare, Nemalion multifidum, Dermonema pulvinatum, Genus Helminthocladia: Helminthocladia australis, Helminthocladia yendoana, Genus Dermonema: Dermonema virens, Genus Scinaia: Scinaia japonica, Genus Pseudogloiophloea: Pseudogloiophloea okamurai, Genus Actinotrichia: Actinotrichia fragilis, Genus Tricleocarpa: Tricleocarpa jejuensis, Dichotomaria falcata, Genus Ptilonia: Ptilonia okadae, Genus Delisea: Delisea japonica, Genus Asparagopsis: Bonnemaisonia hamifera, Asparagopsis taxiformis, Genus Gelidium:
  • Examples of materials of animal origin include cockscomb extract; bovine, swine or human placental extracts; bovine or swine stomach, duodenum, intestine and spleen extracts and decomposition products thereof; bovine or swine brain tissue extracts; collagen derivatives, such as bovine, swine or fish collagen hydrolysates (treated with an acid, an alkali, an enzyme or the like), water-soluble collagens and acylated collagens; bovine or swine elastin, hydrolysates thereof (treated with an acid, an alkali, an enzyme or the like) and water-soluble elastin derivatives; keratin, decomposition products thereof, and derivatives thereof; silk proteins, decomposition products thereof, and derivatives thereof; decomposition products of swine or bovine hemocyte proteins (globin peptide); decomposition products of bovine or swine hemoglobins (e.g., hemin, hematin, heme,
  • arbitrary parts, cells, tissues, organs, metabolites and the like that are derived from genetically modified organisms and cell fusion products can be used as well.
  • undifferentiated cell colonies and colonies of differentiating cells which are obtained by cell-culturing an arbitrary part, cell, tissue, organ or the like, can also be used.
  • Marine Components examples include seawater such as deep sea water, for example, sea salts and dried sea water; inorganic salts obtained from the sea water of the Dead Sea, Atlantic Ocean or Pacific Ocean (e.g., sodium chloride, magnesium chloride and potassium chloride); sea sludge and mud (fango) of various places, such as Italian fango, German fango, Eifel fango and Koch fango (ingredients: silicon dioxide, titanium dioxide, aluminum oxide, iron oxide, manganese oxide, sodium oxide, potassium oxide, magnesium oxide, calcium oxide, strontium oxide, sodium, potassium, magnesium, calcium, chromium, iron, copper, nickel, zinc, lead, manganese, arsenic and water); and Shotoku stone.
  • seawater such as deep sea water, for example, sea salts and dried sea water
  • inorganic salts obtained from the sea water of the Dead Sea, Atlantic Ocean or Pacific Ocean e.g., sodium chloride, magnesium chloride and potassium chloride
  • sea sludge and mud fango of various places, such as
  • Microbial Culture Metabolites examples include yeast metabolites; yeast extract; bacterial metabolites; bacterial extracts; fungal and actinomycete metabolites; fungal and actinomycete extracts; Bacillus natto metabolites; fermented soybean extract; fermented rice extract; fermented rice bran (red bran and white bran) extract; euglena extract, decomposition products thereof, and water-soluble derivatives thereof; trehalose and its derivatives; lactic acid fermentation products of raw milk and skim milk powder; lactic acid bacteria fermentation products of plants belonging to the family Leguminosae; and lactic acid bacteria fermentation products of plants belonging to the genus Cocos.
  • ⁇ -hydroxy Acids examples include glycolic acid, citric acid, malic acid, tartaric acid, and lactic acid.
  • inorganic pigments examples include silicic anhydride, magnesium silicate, talc, kaolin, bentonite, mica, mica-titanium, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, calcium carbonate, magnesium carbonate, yellow iron oxide, red iron oxide, black iron oxide, ultramarine, chromium oxide, chromium hydroxide, carbon black, and calamine.
  • ultraviolet absorbers and blocking agents examples include benzophenone derivatives (e.g., 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate, dihydroxydimethoxybenzophenone, sodium dihydroxydimethoxybenzophenone-sulfonate, 2,4-dihydroxybenzophenone and tetrahydroxybenzophenone), p-aminobenzoic acid derivatives (e.g., p-aminobenzoic acid, ethyl p-aminobenzoate, glyceryl p-monobenzoate, amyl p-aminobenzoate and octyl p-aminobenzoate), methoxycinnamic acid derivatives (e.g., ethyl p-methoxycinnamate),
  • Skin-whitening Agents examples include p-aminobenzoic acid derivatives, salicylic acid derivatives, anthranilic acid derivatives, coumarin derivatives, amino acid compounds, benzotriazole derivatives, tetrazole derivatives, imidazoline derivatives, pyrimidine derivatives, dioxane derivatives, camphor derivatives, furan derivatives, pyrone derivatives, nucleic acid derivatives, allantoin derivatives, nicotinic acid derivatives, vitamin C and its derivatives (e.g., magnesium salt of vitamin C phosphate, and vitamin C glucoside), vitamin E and its derivatives, kojic acid and its derivatives, oxybenzone, benzophenone, arbutin, guaiazulene, shikonin, baicalin, baicalein, berberine, placenta extract, ellagic acid, and Rucinol.
  • p-aminobenzoic acid derivatives examples include p-aminobenzoic acid
  • tyrosinase activity inhibitors include vitamin C and its derivatives (e.g., magnesium salt of vitamin C phosphate, and vitamin C glucoside), hydroquinone and its derivatives (e.g., hydroquinone benzyl ether), kojic acid and its derivatives, vitamin E and its derivatives, N-acetyltyrosine and its derivatives, glutathione, hydrogen peroxide, zinc peroxide, placenta extract, ellagic acid, arbutin, Rucinol, silk extract, and plant extracts (e.g., chamomile, mulberry, common gardenia, Japanese angelica root, burnet, shrubby sophora, mugwort, Japanese honeysuckle, phellodendron bark, houttuyniae herba, hoelen, Job's tears, white-dead nettle, hop, Japanese hawthorn, eucalyptus,
  • melanin pigment reducing/decomposing substance examples include phenylmercuric hexachlorophene, mercuric oxide, mercurous chloride, hydrogen peroxide, zinc peroxide, and hydroquinone and its derivatives (e.g., hydroquinone benzyl ether).
  • turnover-promoting/cell-activating substances include hydroquinone, lactic acid bacteria extracts, placenta extract, reishi mushroom extract, vitamin A, vitamin E, allantoin, spleen extract, thymus extract, yeast extract, fermented milk extract, and plant extracts (e.g., aloe, scutellaria root, horsetail, gentian, burdock, lithospermum root, carrot, hamamelis, hop, coix seed, white-dead nettle, swertia herb, Japanese angelica root, pot marigold, sweet hydrangea leaf, hypericum, cucumber, thyme, rosemary, and parsley).
  • plant extracts e.g., aloe, scutellaria root, horsetail, gentian, burdock, lithospermum root, carrot, hamamelis, hop, coix seed, white-dead nettle, swertia herb, Japanese angelica root, pot marigold, sweet hydrange
  • Astringents examples include succinic acid, allantoin, zinc chloride, zinc sulfate, zinc oxide, calamine, zinc p-phenol sulfonate, aluminum potassium sulfate, resorcin, ferric chloride, and tannic acid (including catechin compound).
  • Active Oxygen Scavengers examples include SOD, catalase, and glutathione peroxidase.
  • Anti-oxidants examples include vitamin C salts thereof, stearic acid esters, vitamin E and salts thereof, nordihydroguaiaretic acid, butylhydroxytoluene (BHT), butylhydroxyanisole (BHA), hydroxytyrosol, p-hydroxyanisole, propyl gallate, sesamol, sesamolin, gossypol, and propolis.
  • lipid peroxide production inhibitors examples include ⁇ -carotene and plant extracts (e.g., sesame cultured cells, sweet hydrangea leaf, hypericum, hamamelis, clove, melissa, isodon herb, white birch, scarlet sage, rosemary, heavenly bamboo fruit, rose fruit, ginkgo, and green tea).
  • plant extracts e.g., sesame cultured cells, sweet hydrangea leaf, hypericum, hamamelis, clove, melissa, isodon herb, white birch, scarlet sage, rosemary, heavenly bamboo fruit, rose fruit, ginkgo, and green tea.
  • Anti-inflammatory agents include ichthammol, indomethacin, kaolin, salicylic acid, sodium salicylate, methyl salicylate, acetylsalicylic acid, diphenhydramine hydrochloride, d-camphor, dl-camphor, hydrocortisone, guaiazulen, chamazulene, chlorpheniramine maleate, glycyrrhizic acid and salts thereof, glycyrrhetinic acid and salts thereof, glycyrrhiza extract, lithospermum root extract, rose fruit extract, and propolis.
  • antibacterial agents examples include acrinol, sulfur, calcium gluconate, chlorhexidine gluconate, sulfamine, mercurochrome, lactoferrin and its hydrolysate, alkyldiaminoethylglycine chloride solutions, triclosan, sodium hypochlorite, chloramine T, bleaching powder, iodine compounds, iodoform, sorbic acid and salts thereof, propionic acid and salts thereof, salicylic acid, dehydroacetic acid, p-hydroxybenzoic acid esters, undecylenic acid, thiamine lauryl sulfate, thiamine lauryl nitrate, phenol, cresol, p-chlorophenol, p-chloro-m-xylenol, p-chloro-m-cresol, thymol, phenethyl alcohol
  • Moisturizing Agents examples include glycerin, propylene glycol, 1,3-butylene glycol, hyaluronic acid and salts thereof, polyethylene glycol, chondroitin sulfate and salts thereof, water-soluble chitin derivatives, water-soluble chitosan derivatives, pyrrolidonecarboxylic acid and salts thereof, sodium lactate, mini-Sasanishiki extract, Bacillus natto metabolites, fermented soybean extract, loofah water, and saps of white birch and Japanese red pine.
  • Elastase Activity Inhibitors examples include diisopropyl fluorophosphate, plant extracts (e.g., scutellaria root, hypericum, sophora root, mulberry leaf, cinnamon bark, geranium herb, comfrey, scarlet sage, elder, linden and moutan bark), and seaweed extracts.
  • plant extracts e.g., scutellaria root, hypericum, sophora root, mulberry leaf, cinnamon bark, geranium herb, comfrey, scarlet sage, elder, linden and moutan bark
  • seaweed extracts examples include diisopropyl fluorophosphate, plant extracts (e.g., scutellaria root, hypericum, sophora root, mulberry leaf, cinnamon bark, geranium herb, comfrey, scarlet sage, elder, linden and moutan bark), and seaweed extracts.
  • hair-care agents include selenium disulfide, alkylisoquinolium bromide solutions, zinc pyrithione, biphenamine, thianthol, castoreum tincture, ginger tincture, capsicum tincture, quinine hydrochloride, strong aqueous ammonia, potassium bromate, sodium bromate, and thioglycolic acid.
  • Antiandrogen Agents examples include estrogens (e.g., estrone, estradiol and ethinyl estradiol), isoflavone, and oxendolone.
  • peripheral blood flow promoters include vitamin E and its derivatives, swertia herb extract, garlic extract, ginseng extract, aloe extract, gentian extract, angelica root extract, cepharanthine, carpronium chloride, and minoxidil.
  • stimulating agents include capsicum tincture, nonylic acid vanillylamide, cantharides tincture, ginger tincture, peppermint oil, 1-menthol, camphor, and benzyl nicotinate.
  • Metabolic Activators examples include photosensitizer 301, hinokitiol, pantothenic acid and its derivatives, allantoin, placenta extract, biotin, and pentadecanoic acid glyceride.
  • Antiseborrheic Agents examples include pyridoxine and its derivatives, sulfur, and vitamin B6.
  • Keratolytic Agents examples include resorcin, salicylic acid, lactic acid, and urea.
  • Oxidizing Agents examples include hydrogen peroxide, sodium persulfate, ammonium persulfate, sodium perborate, urea peroxide, sodium percarbonate, sodium tripolyphosphate peroxide, sodium bromate, potassium bromate, sodium pyrophosphate peroxide, sodium orthophosphate peroxide, sodium silicate-hydrogen peroxide adduct, sodium sulfate-hydrogen peroxide adduct, sodium chloride-hydrogen peroxide adduct, ⁇ -tyrosinase solution, and mushroom extract.
  • hair-removing agents include inorganic reducing agents such as strontium sulfate, sodium sulfide, barium sulfide and calcium sulfide; and thioglycolic acid and salts thereof (e.g., calcium thioglycollate, sodium thioglycollate, lithium thioglycollate, magnesium thioglycollate and strontium thioglycollate).
  • inorganic reducing agents such as strontium sulfate, sodium sulfide, barium sulfide and calcium sulfide
  • thioglycolic acid and salts thereof e.g., calcium thioglycollate, sodium thioglycollate, lithium thioglycollate, magnesium thioglycollate and strontium thioglycollate.
  • hair-swelling agents examples include ethanolamine, urea, and guanidine.
  • dyes include 5-amino-o-cresol, 2-amino-4-nitrophenol, 2-amino-5-nitrophenol, 1-amino-4-methylaminoanthraquinone, 3,3'-iminodiphenol, 2,4-diaminophenoxyethanol hydrochloride, 2,4-diaminophenol hydrochloride, toluene-2,5-diamine hydrochloride, nitro-p-phenylenediamine hydrochloride, p-phenylenediamine hydrochloride, N-phenyl-p-phenylenediamine hydrochloride, m-phenylenediamine hydrochloride, o-aminophenol, N-phenyl-p-phenylenediamine acetate, 1,4-diaminoanthraquinone, 2,6-diaminopyridine, 1,5-dihydroxynaphthalene, toluene-2,5-diamine, tol
  • fragrance agents include natural animal fragrance agents such as musk, civet, castoreum and ambergris; plant fragrance agents such as anise essential oil, angelica essential oil, ylang-ylang essential oil, iris essential oil, fennel essential oil, orange essential oil, cananga essential oil, caraway essential oil, cardamom essential oil, guaiacwood essential oil, cumin essential oil, lindera essential oil, cassia essential oil, cinnamon essential oil, geranium essential oil, copaiba balsam essential oil, coriander essential oil, perilla essential oil, cedar wood essential oil, citronella essential oil, jasmine essential oil, ginger-grass essential oil, Japanese cedar essential oil, spearmint essential oil, peppermint essential oil, star anise essential oil, tuberose essential oil, clove essential oil, neroli essential oil, wintergreen essential oil, tolu balsam essential oil, patchouli essential oil, rose essential oil, palmarosa essential oil, Japanese cypress essential oils, anise essential oil,
  • pigments and coloring agents examples include red cabbage pigment, red-kerneled rice pigment, madder pigment, annatto pigment, sepia pigment, turmeric pigment, sophora pigment, krill pigment, persimmon pigment, caramel, gold, silver, gardenia pigment, corn pigment, onion pigment, tamarind pigment, spirulina pigment, buckwheat herb pigment, cherry pigment, laver pigment, hibiscus pigment, grape juice pigment, marigold pigment, purple sweet potato pigment, purple yam pigment, lac pigment, and rutin.
  • additives examples include hormones, metal ion-blocking agents, pH adjusting agents, chelating agents, antiseptic/antifungal agents, refrigerants, stabilizing agents, emulsifying agents, animal/plant proteins and decomposition products thereof, animal/plant polysaccharides and decomposition products thereof, animal/plant glycoproteins and decomposition products thereof, blood-flow promoters, anti-inflammatory/anti-phlogistic agents, anti-allergic agents, wound-healing agents, foaming agents, thickening agents, enzymes, purified water (including electronic water, microcluster water and the like), oral-care agents, deodorants, bittering agents, and seasonings.
  • the use of these additives in combination can be expected to additively or synergistically improve the effects of the present invention or other cosmetic effects.
  • the bacterium used as an effective ingredient is one belonging to the genus Enterococcus.
  • the bacterium is more preferably Enterococcus faecalis.
  • strains such as Enterococcus faecalis EC-12 (accession No. FERM BP-10284), ATCC 19433, ATCC 14508, ATCC 23655, IFO 16803 and IFO 16804, and variants thereof can be exemplified. Thereamong, the EC-12 strain is most preferred as the bacterium used as an effective ingredient.
  • variants used herein is meant to encompass ones that are obtained by those of ordinary skill in the art through mutation of a specific strain within such a range that does not modify the properties of the specific strain in accordance with a method well-known to those of ordinary skill in the art, as well as ones that can be confirmed to be equivalent thereto by those of ordinary skill in the art.
  • Enterococcus faecalis EC-12 (accession No. FERM BP-10284) was purchased from Combi Corporation.
  • Aloe vera polysaccharides were produced. Aloe vera leaves in an amount of 100 g were ground and subsequently subjected to squeezing, extraction and filtration, after which ethanol or isopropanol was added to the thus obtained filtrate, followed by stirring. Then, the resulting precipitates were recovered and washed by again adding thereto ethanol or isopropanol, and the thus washed precipitates were dried to obtain Aloe vera polysaccharide powder.
  • Skin resident bacteria were collected by rubbing three times in the vertical direction and three times in the lateral direction of a 3 cm-square glabellar area with a sterile swab. The swab was subsequently washed in 10 mL of phosphate buffered physiological saline to recover the bacteria.
  • a 3 cm-square area on each cheek was rubbed with a sterile swab three times in the vertical direction and three times in the lateral direction to collect glycerol on the skin surface. Then, the swab was washed in 200 ⁇ L of phosphate buffered physiological saline to disperse metabolites.
  • a culture medium for epidermal cells Humedia KG2, manufactured by Kurabo Industries Ltd.
  • human epidermal keratinocytes manufactured by Kurabo Industries Ltd.
  • the human epidermal keratinocytes were further cultured in a differentiation-inducing culture medium, which was prepared by adding calcium to Humedia KG2, for 3 days at 37°C in the presence of 5%CO 2 , after which the culture medium was replaced with a fresh one.
  • PCR was performed using the thus obtained cDNAs.
  • the primers shown in Table 3 were prepared based on the cDNA sequence of human ⁇ -defensin-2 (accession No. NG_023301) and the cDNA sequence of human ⁇ -defensin-3 (accession No. NC_000008), and TAKARA Human Housekeeping Gene Primer Set Human ACTB Primer was used as the primer for ⁇ -actin utilized as an internal standard.
  • PCR was performed using One Step SYBRR PrimeScript TM RT-PCR Kit (manufactured by TAKARA Bio Inc.), and real-time PCR analysis was performed in accordance with a conventional method using TaKaRa PCR Thermal Cycler Dice.
  • the real-time PCR analysis the mRNA amount was relatively quantified for human ⁇ -defensin-2, human ⁇ -defensin-3 and ⁇ -actin.
  • the cooling method was performed by, for example, a method of slowly cooling the resultant under stirring with a refrigerantinjected into the jacket of the production pot or a method of cooling the resultant using a heat exchanger.
  • Cream (W/O-type) (A Phase) t-butylmethoxydibenzoyl methane 3.0% Hexyl diethylaminohydroxybenzoyl benzoate 2.0% Dimethicone and caprylyl dimethicone ethoxy glucoside 20.0% Glyceryl tri(behenate/isostearate/eicosandioate) 1.0% Stearyl dimethicone 1.0% Tocopherol acetate 0.05% Benzoic acid 0.3% Diisopropyl sebacate 7.0% Octocrylene 8.0% Talc, yellow iron oxide, Mg stearate, titanium dioxide, mica, Al hydroxide, stearic acid 1.4% (B Phase) Titanium dioxide, Mg stearate, talc, black iron oxide, Al hydroxide, mica, stearic acid 1.13% Red and brown iron oxide, Mg stearate, titanium dioxide, mica, water, Al oxide, stearic acid 0.85% Titanium dioxide, talc
  • the B phase was then added to the A phase with stirring, and the resultant was stirred to homogeneity.
  • the materials of the C phase were mixed with stirring and heated to 70 to 75°C, and the C phase was slowly added to the A-B mixed phase with stirring (over a period of about 5 minutes), after which the resultant was stirred for about 3 minutes and then naturally cooled.
  • the D phase was added thereto and stirred for about 1 minute, after which the E phase was added and stirred for about 5 minutes and the F phase was further added and stirred for about 1 minute, followed by addition of the G phase and subsequent stirring for about 1 minute.
  • the H phase was added and stirred for about 2 minutes, after which the resultant was naturally cooled to room temperature.
  • Xanthan gum and Na polyacrylate were dispersed using a batch-type dispersion apparatus or the like, and the A phase was added to the B phase at 75°C. The resultant was homogenized for several minutes and then cooled with gentle stirring, and the C phase was added thereto once the temperature dropped to 40°C (methanol was dissolved in ethanol in advance).
  • a Phase Mineral oil 8.0% Red pigment 1.0% Yellow pigment 0.3% Enterococcus lactic acid bacterium 0.01 to 1% (appropriate amount)
  • B Phase Caprylic/capric triglyceride balance to 100 Ethylhexyl methoxycinnamate 3.0% Isopropyl myristate 10.0%
  • C Phase Alkyl (C26-28) methicone 9.0% Cetanol 1.6%
  • D Phase Mixture of PEG-8, tocopherol, ascorbyl palmitate, ascorbic acid and citric acid 0.1% Propylparaben 0.1%
  • E Phase Fragrance agent 0.2% Mixture of mica and titanium oxide 18.4% Mixture of mica, titanium oxide and iron oxide 7.0% Silica 0.5% (Production Method) The A phase was uniformly premixed and then uniformly mixed with the B phase.
  • the C phase was further added thereto, and the resultant was heated to 78 to 80°C with gentle stirring, after which the D phase and the E phase were added thereto little by little and the resultant was uniformly stirred, poured into a mold and then naturally cooled to normal temperature.
  • Cream Foundation (W/O-type) (Oil Phase) Decamethylcyclopentasiloxane 15.0% Liquid paraffin 5.0% p-methoxy cinnamate 3.0% Polyether-modified dimethylsiloxane 2.0% (Aqueous Phase) Purified water balance to 100 Glycerin 5.0% Aqueous antiseptic agent appropriate amount (Powder) Titanium oxide 10.0% Talc 3.8% Color pigment appropriate amount Enterococcus lactic acid bacterium 0.01 to 1% (appropriate amount) (Other Component) Fragrance agent appropriate amount
  • Moisturizing Cream (O/W-type) (A Phase) Shea butter 1.5% Alkyl (C12-15) benzoate 1.3% Alkyl (C26-28) dimethicone 6.5% Glyceryl stearate 1.5% Mixture of glyceryl stearate and PEG-100 stearate 3.0% Hexyl laurate 1.3% Isododecane 1.3% Isohexadecane 1.3% Isopropyl palmitate 1.3% Tocopherol acetate 0.5% Heat-killed cells of Enterococcus lactic acid bacterium 0.01 to 1 (appropriate amount) (B Phase) Purified water balance to 100 Carbomer 0.3% Glycerin 2.0% Propylene glycol 2.0% (C Phase) Fragrance agent 0.5% Mixture of phenoxyethanol, methylparaben, ethylparaben, butylparaben, propylparaben and isobutylparaben 0.5% Tetrahydroxypropyl ethylened
  • the lactic acid bacterium belonging to the genus Enterococcus according to the present invention facilitates the production of glycerol derived from Staphylococcus epidermidis, which is a skin resident bacterium useful on the skin, and the production of antimicrobial peptides derived from skin epidermal keratinocytes.
  • the lactic acid bacterium belonging to the genus Enterococcus according to the present invention gives an excellent silky feel when applied to the skin and imparts good touch feeling to any of the aqueous type, oil-type, milky lotion-type and powder-type external preparations for skin protection. Therefore, the lactic acid bacterium belonging to the genus Enterococcus according to the present invention is extremely applicable to skin-protecting agents and external preparations for skin protection that normalize the skin condition or maintain the normality thereof.

Abstract

Provided are: a skin-protecting agent and an external preparation for skin protection, which not only synergistically work in combination with a plant polysaccharide but also has an effect of promoting the production of glycerol derived from Staphylococcus epidermidis, which is a skin resident bacterium useful on the skin, and the production of antimicrobial peptides derived from skin epidermal keratinocytes and exhibits excellent effect of improving the touch feeling when applied to the skin.　More specifically, the present invention provides a skin protective agent and an external preparation for skin protection, which comprise a lactic acid bacterium belonging to the genus Enterococcus.

Description

GLYCEROL PRODUCTION PROMOTER DERIVED FROM Staphylococcus Epidermidis, ANTIMICROBIAL PEPTIDE PRODUCTION PROMOTER DERIVED FROM SKIN EPIDERMAL KERATINOCYTES, AND UTILIZATION THEREOF IN EXTERNAL PREPARATION FOR SKIN PROTECTION
Field of the Invention
　　　 The present invention relates to drug agents and an external preparation for skin protection, which protect the skin from external stresses such as drying and harmful bacteria through a function of promoting one or a series of the production of glycerol derived from skin resident bacteria, namely Staphylococcus epidermidis that is a useful bacterium, and the production ofantimicrobial peptides derived from skin epidermal keratinocytes.
Background Art
　　　 On the human skin, commensal microorganisms form a group as a skin resident bacterial flora.　As skin resident bacteria, Staphylococcus epidermidis, Staphylococcus aureus, corynebacteria and the like inhabit the skin, and the protective function of the skin against the outside world is maintained by the balance of these bacteria.　However, it is known that the balance of the flora of these bacteria is impaired and such protective function is thus compromised by an environmental factor such as a rapid temperature change, dryness or a strong detergent or chemical agent, or by a physical/mental factor such as injury, emotional stress or poor systemic condition due to a disease (Non-patent Document 1).
　　　 For example, Staphylococcus epidermidis known as a useful bacterium of the skin breaks down serum to produce glycerol and thereby plays a role in physical protective functions, such as inhibition of dry skin and suppression of propagation of saprophytic bacteria by adjusting the skin surface pH.　Accordingly, when the ratio of Staphylococcus epidermidis decreases, these protective functions may no longer be demonstrated and this may cause a skin disease.　In order to inhibit such a skin disease, moisturizing agents, antibacterial agents, disinfectant components and the like are widely used in skin external preparations; however, depending on the drug components, there is a concern that the protective functions provided by Staphylococcus epidermidis, which is an aerobic bacterium, may also be inhibited.
　　　 Moreover, Staphylococcus epidermidis also plays a role in enhancing the biological protective functions of living body by stimulating skin epidermal keratinocytes and promoting the production of antimicrobial peptides therefrom.　As the antimicrobial peptides produced by skin epidermal keratinocytes, human β-defensin-2 (hBD2) and human β-defensin-3 (hBD3) are known, and it has been reported that these antimicrobial peptides show an antibacterial action against Staphylococcus aureus, which is a harmful bacterium, and serve as a biological barrier to protect the skin from such harmful bacteria (Non-patent Document 2).
　　　 Conventionally, for the purpose of promoting the proliferation of Staphylococcus epidermidis, saccharides such as glucooligosaccharides have been used as assimilable sources (Patent Document 1); however, since not only useful Staphylococcus epidermidis but also other harmful bacteria such as Staphylococcus aureus assimilate such saccharides, a skin protective function is not attained in some cases.　In addition, many saccharides give a sticky feel when applied to the skin, and this presents another problem of the difficulty in formulation in terms of the feel.
　　　 Staphylococcus aureus is known to exist in a large number on the skin of people having dry skin or rough skin and atopic dermatitis patients.　It is also known that toxins produced by Staphylococcus aureus cause a further deterioration of the skin condition.　For keeping the skin surface condition healthy, it is thus believed to be important to effectively kill Staphylococcus aureus and to maintain Staphylococcus epidermidis having a skin protective function.
　　　 The roles of Staphylococcus epidermidis on the skin are similar to those of lactic acid bacteria and bifidobacteria that are useful intestinal bacteria.　These useful intestinal bacteria are known to adjust the intestinal pH, inhibit the proliferation of harmful bacteria such as Clostridium perfringens and Escherichia coli, and have a protective function in the intestinal tract.
　　　 For improvement of the intestinal environment, useful bacteria such as lactic acid bacteria and bifidobacteria are taken into the intestinal tract; however, generally, in order to allow these useful bacteria to reach the intestine alive and colonize there, it is required to select acid-resistant strains and to encapsulate them into an enteric coated-type capsule.　In addition, in order to increase the number of useful bacteria in the intestine, a method of ingesting a food or drink containing dietary fibers and various oligosaccharides that are selectively assimilated by the useful bacteria has also been employed.　Yet, depending on the individual constitution, these methods sometimes cause excessive intestinal fermentation and diarrhea.　As a method, which solves such a problem, the use of heat-killed cells of a lactococcus bacterium has been proposed (Patent Document 2).
　　　 Ingestion of heat-killed cells of Enterococcus faecalis in the form of a food or drink enables to facilitate the proliferation of bifidobacteria in the intestinal tract and to thereby suppress the proliferation of harmful bacteria and improve the intestinal protective function.　Furthermore, since the dead bacterial cells are easily processed as a food or drink, unnecessary fermentation does not proceed, so that the storage stability of the food or drink is hardly affected.
　　　 Preferred examples of heat-killed cells of a lactic acid bacterium include those of a microbe classified as Enterococcus faecalis, and it is particularly preferred to use Enterococcus faecalis EC-12 strain (accession No. FERM BP-10284), whose 16S rDNA has been registered as "AB15482" at the National Institute of Genetics.
PRIOR ART REFERENCES
PATENT DOCUMENTS
　　　 [Patent Document 1] Japanese Laid-open Patent Application (Kokai) No. 2005-002087
　　　 [Patent Document 2] Japanese Laid-open Patent Application (Kokai) No. 2004-051530
NON-PATENT DOCUMENTS
　　　 [Non-patent Document 1] Gallo, R.L. et al., Journal of Investigative Dermatology 131:1974-1980 (2011)
　　　 [Non-patent Document 2] Kisich, K.O. et al., Journal of Investigative Dermatology 127:2368-2380 (2007)

　　　　　　　　　　　SUMMARY OF THE INVENTION
Problems to be Solved by the Invention
　　　 For maintenance of a healthy skin surface condition, a means and a method for protecting the skin from external stresses such as drying and harmful bacteria are indispensable.　An object of the present invention is to provide drug agents and an external preparation for skin protection, which protect the skin from external stresses such as drying and harmful bacteria through a function of promoting one or a series of the production of glycerol derived from Staphylococcus epidermidis and the production of antimicrobial peptides derived from skin epidermal keratinocytes against harmful bacteria such as Staphylococcus aureus.
Means for Solving the Problems
　　　 The present inventors investigated a variety of lactic acid bacteria and conducted intensive studies to discover that cells of a lactococcus bacterium, Enterococcus faecalis EC-12, particularly heat-killed cells of Enterococcus faecalis EC-12 have an action of promoting the production of glycerol derived from Staphylococcus epidermidis and the production of antimicrobial peptides derived from skin epidermal keratinocytes.　In addition, it was also discovered that heat-killed cells of Enterococcus faecalis EC-12 give an excellent silky feel when applied to the skin and provides a feeling-improving effect in any of aqueous-type, oil-type, milky lotion-type and powder-type external preparations.
　　　 That is, the present invention includes the following items.
　　　 [1] A glycerol production promoter derived from Staphylococcus epidermidis, the promoter comprising a lactic acid bacterium belonging to the genus Enterococcus as an effective ingredient.
　　　 [2] The glycerol production promoter derived from Staphylococcus epidermidis according to [1], wherein the lactic acid bacterium belonging to the genus Enterococcus is Enterococcus faecalis.
　　　 [3] The glycerol production promoter derived from Staphylococcus epidermidis according to [1] or [2], wherein the lactic acid bacterium belonging to the genus Enterococcus is Enterococcus faecalis EC-12 (accession No. FERM BP-10284).
　　　 [4] The glycerol production promoter derived from Staphylococcus epidermidis according to any one of [1] to [3], wherein the lactic acid bacterium belonging to the genus Enterococcus is killed.
　　　 [5] The glycerol production promoter derived from Staphylococcus epidermidis according to any one of [1] to [4], wherein the lactic acid bacterium belonging to the genus Enterococcus is heat-killed.
　　　 [6] An antimicrobial peptide production promoter derived from skin epidermal keratinocytes, the promoter comprising a lactic acid bacterium belonging to the genus Enterococcus as an effective ingredient.
　　　 [7] The antimicrobial peptide production promoter derived from skin epidermal keratinocytes according to [6], wherein the lactic acid bacterium belonging to the genus Enterococcus is Enterococcus faecalis.
　　　 [8] The antimicrobial peptide production promoter derived from skin epidermal keratinocytes according to [6] or [7], wherein the lactic acid bacterium belonging to the genus Enterococcus is Enterococcus faecalis EC-12 (accession No. FERM BP-10284).
　　　 [9] The antimicrobial peptide production promoter derived from skin epidermal keratinocytes according to any one of [6] to [8], wherein the lactic acid bacterium belonging to the genus Enterococcus is killed.
　　　 [10] The antimicrobial peptide production promoter derived from skin epidermal keratinocytes according to any one of [6] to [9], wherein the lactic acid bacterium belonging to the genus Enterococcus is heat-killed.
　　　 [11] The antimicrobial peptide production promoter according to any one of [6] to [10], wherein the antimicrobial peptide is human β-defensin-2 (hBD2) or human β-defensin-3 (hBD3).
　　　 [12] An external preparation for skin protection, comprising the glycerol production promoter derived from Staphylococcus epidermidis or the antimicrobial peptide production promoter derived from skin epidermal keratinocytes according to any one of [1] to [11].
Effects of the Invention
　　　 The drug agents and the external preparation for skin protection according to the present invention are capable of promoting the production of glycerol derived from Staphylococcus epidermidis and the production of human β-defensin-2 and human β-defensin-3, which are antimicrobial peptides derived from skin epidermal keratinocytes against Staphylococcus aureus.　That is, dry skin is inhibited by promotion of the glycerol production, and controlling the skin surface pH enhances the protective functions of the skin, such as suppression of the proliferation of saprophytic bacteria.　Meanwhile, by promoting the production of antimicrobial peptides from skin epidermal keratinocytes against Staphylococcus aureus, the skin can be protected from harmful bacteria existing thereon.　Consequently, the skin surface condition can be maintained healthy through one or a series of these promoting functions.　Furthermore, the drug agents and the external preparation for skin protection according to the present invention give excellent silky feel when applied to the skin and provide a feeling-improving effect in any of aqueous-type, oil-type, milky lotion-type and powder-type external preparations.
FIG. 1 shows the results of quantifying the glycerol production after adding heat-killed cells of Enterococcus faecalis EC-12 and Aloe vera polysaccharides as plant polysaccharides to culture solutions of Staphylococcus epidermidis type strain (ATCC 12228). FIG. 2 shows the results of quantifying the glycerol production after adding heat-killed cells of Enterococcus faecalis EC-12 to culture solutions of skin resident bacteria collected from a glabellar area of human. FIG. 3 shows the results of quantifying the amount of glycerol collected from human cheek in a human monitor test where a softening lotion containing heat-killed cells of Enterococcus faecalis EC-12 was used. FIG. 4 shows the results of measuring the expression levels of human β-defensin-2 (hBD2) and human β-defensin-3 (hBD3) mRNAs after culturing human normal keratinocytes in a culture medium containing heat-killed cells of Enterococcus faecalis EC-12 and extracting RNAs therefrom.
Mode for Carrying Out the Invention
　　　 The glycerol production promoter derived from Staphylococcus epidermidis, the antimicrobial peptide production promoter derived from skin epidermal keratinocytes and the external preparation for skin protection according to the present invention comprise a lactic acid bacterium belonging to the genus Enterococcus as an effective ingredient.　In a preferred mode, the lactic acid bacterium belonging to the genus Enterococcus is Enterococcus faecalis, particularly heat-killed Enterococcus faecalis EC-12.
　　　 The drug agents and the external preparation for skin protection according to the present invention have the following characteristics of:
　　　 1. promoting the production of glycerol derived from Staphylococcus epidermidis;
　　　 2. synergistically promoting the production of glycerol derived from Staphylococcus epidermidis by further comprising plant polysaccharides in combination;
　　　 3. promoting the production of antimicrobial peptides derived from skin epidermal keratinocytes against harmful bacteria such as Staphylococcus aureus;
　　　 4. enhancing the function of protecting the skin from external stresses such as drying and harmful bacteria through one or a series of the above-described promoting functions; and
　　　 5. giving an excellent silky feel when applied to the skin and is capable of providing a feeling-improving effect in any of aqueous-type, oil-type, milky lotion-type and powder-type external preparations.
　　　 The method of culturing the lactic acid bacterium belonging to the genus Enterococcus is not particularly restricted including conventionally known culturing methods of lactic acid bacteria, and heat-killed cells thereof can be produced by the following method.　From a culture of the lactic acid bacterium belonging to the genus Enterococcus obtained by a conventional method, bacterial cells are recovered by a method such as filtration or centrifugation and, after subsequently washing the recovered cells with water, the cells are suspended in water or the like, heat-treated and then, as required, concentrated and dried, whereby heat-killed cells of the lactic acid bacterium belonging to the genus Enterococcus can be prepared.　A normally used spray dryer, freeze dryer or the like may be employed.　Depending on the case, before or after a sterilization treatment by heating or the like, or before or after a drying treatment, the recovered cells may also be subjected to a treatment with an enzyme, a treatment with a surfactant and/or a grinding/pulverization treatment, and resultants of such treatments are also included in the killed bacterial cells or treated products thereof according to the present invention.
　　　 Examples of water used for the washing and suspending include pure water, tap water, well water, mineral spring water, mineralized water, hot-spring water, spring water and fresh water, as well as a variety of treatment products thereof.　Examples of a water treatment include purification, heating, sterilization, filtration, ion exchange, osmotic adjustment and buffering.　Accordingly, examples of water that can be used as an extraction solvent in the present invention also include purified water, heated water, ion-exchanged water, physiological saline and various buffers.
　　　 The lactic acid bacterium belonging to the genus Enterococcus obtained in the above-described manner can be used as a glycerol production promoter derived from Staphylococcus epidermidis, a skin epidermal keratinocyte-derived antimicrobial peptide production promoter against harmful bacteria such as Staphylococcus aureus, or an external preparation for skin protection which maintains the skin surface condition healthy through one or a series of these promoting functions.
　　　 In the glycerol production promoter derived from Staphylococcus epidermidis and the antimicrobial peptide production promoter derived from skin epidermal keratinocytes according to the present invention, it is preferred that the above-described heat-killed bacterial cells be suspended and adjusted such that they are contained in an amount of not less than 5 × 1011 cells, particularly preferably not less than 5 × 1012 cells, per 1 gram of each promoter.　Further, in a routinely used external preparation for skin protection, it is preferred that the heat-killed bacterial cells be incorporated and adjusted such that one-third to an equivalent of the above-described amount is applied per use.
(Form of External Preparation for Skin Protection)
　　　 The external preparation for skin protection according to the present invention may take a form that is appropriate for application such as ampule, capsule, powder, granule, liquid, gel, foam, emulsion, sheet, mist or spray, and examples such external preparation include 1) pharmaceutical preparations; 2) quasi drugs; 3) topical or systemic skin external preparations (e.g., basic cosmetics such as cosmetic solutions, milky lotions, creams, ointments, lotions, oils and facial packs; facial and skin cleansers such as bar soaps, liquid soaps and handwashes; massaging agents; cleansing agents; hair-removing agents; depilatories; shaving agents; after-shave lotions; pre-shave lotions; shaving creams; make-up cosmetics such as foundations, lipsticks, rouges, eye shadows, eyeliners and mascaras; perfumes; manicures; manicure enamels; manicure enamel removers; cataplasms; plasters; tapes; sheets; patches; and aerosols); 4) medical and/or cosmetic preparations applied to scalp and hair (e.g., shampoos, rinses, hair treatment agents, pre-hair treatment agents, permanent solutions, hair dyes, hair dressings, hair tonics, hair-growth/restoration stimulants, cataplasms, plasters, tapes, sheets and aerosols); 5) bath agents to be put into bath; and 6) other preparations such as underarm deodorants, deodorizers, antiperspirants, sanitary goods, sanitary cottons and wet tissue papers.
(Constituents of External Preparation for Skin Protection)
　　　 Further, these external preparations for skin protection can be produced by arbitrarily selecting, and using those components and additives exemplified below in combination as required.　The amount thereof to be incorporated into these formulation systems is not particularly prescribed here; however, normally, it is believed to be preferably about 0.0001 to 50%.
(1) Various Oils and Fats
　　　 Examples of oils and fats include avocado oil, almond oil, fennel oil, perilla oil, olive oil, orange oil, orange roughy oil, sesame oil, cacao butter, camomile oil, carrot oil, cucumber oil, beef tallow fatty acid, kukui nut oil, safflower oil, shea butter, liquid shea butter, soybean oil, camellia oil, corn oil, rapeseed oil, persic oil, castor oil, cottonseed oil, peanut oil, turtle oil, mink oil, egg-yolk oil, palm oil, palm kernel oil, haze wax, coconut oil, beef tallow, lard, squalene, squalane, pristane, and hydrogenation products (e.g., hardened oil) of these oils and fats.
(2) Waxes
　　　 Examples of waxes include beeswax, carnauba wax, spermaceti, lanolin, liquid lanolin, reduced lanolin, hard lanolin, candelilla wax, montan wax, shellac wax, and rice wax.
(3) Mineral Oils
　　　 Examples of mineral oils include liquid paraffins, vaseline, paraffins, ozokerite, ceresin, and microcrystalline waxes.
(4) Fatty Acids
　　　 Examples of fatty acids include natural fatty acids, such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, 12-hydroxy stearic acid, undecylenic acid, tall oil and lanolin fatty acid; and synthetic fatty acids, such as isononanoic acid, caproic acid, 2-ethylbutanoic acid, isopentanoic acid, 2-methylpentanoic acid, 2-ethylhexanoic acid and isopentanoic acid.
(5) Alcohols
　　　 Examples of alcohols include natural alcohols, such as ethanol, isopropanol, lauryl alcohols, cetanol, stearyl alcohols, oleyl alcohols, lanolin alcohols, cholesterols, phytosterols and phenoxyethanol; and synthetic alcohols, such as 2-hexyl decanol, isostearyl alcohols and 2-octyl dodecanol.
(6) Polyhydric Alcohols
　　　 Examples of polyhydric alcohols include ethylene oxide, ethylene glycol, diethylene glycol, triethylene glycol, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, polyethylene glycol, propylene oxide, propylene glycol, polypropylene glycol, 1,3-butylene glycol, pentyl glycol, glycerin, pentaerythritol, threitol, arabitol, xylitol, ribitol, galactitol, sorbitol, mannitol, lactitol, and maltitol.
(7) Esters
　　　 Examples of esters include isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, oleyl oleate, decyl oleate, octyldodecyl myristate, hexyldecyl dimethyloctanoate, cetyl lactate, myristyl lactate, diethyl phthalate, dibutyl phthalate, acetylated lanolin, ethylene glycol monostearate, propylene glycol monostearate, and propylene glycol dioleate.
(8) Metal Soaps
　　　 Examples of metal soaps include aluminum stearate, magnesium stearate, zinc stearate, calcium stearate, zinc palmitate, magnesium myristate, zinc laurate, and zinc undecylenate.
(9) Gum Substances, Saccharides and Water-soluble Polymer Compounds
　　　 Examples of gum substances, saccharides and water-soluble polymer compounds include gum arabic, gum benzoin, gum dammar, guaiac resin, Irish moss, karaya gum, gum tragacanth, gum carob, quince seed, agar, casein, lactose, fructose, sucrose and its ester, trehalose and its derivatives, dextrin, gelatin, pectin, starch, carrageenan, carboxymethyl chitin and chitosan, alkylene (C2 to C4) oxide (e.g., ethylene oxide)-added hydroxyalkyl (C2 to C4) chitin and chitosan, low-molecular-weight chitin and chitosan, chitosan salts, sulfated chitin and chitosan, phosphorylated chitin and chitosan, alginic acid and salts thereof, hyaluronic acid and salts thereof, chondroitin sulfate and salts thereof, heparin, ethyl cellulose, methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, sodium carboxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, nitrocellulose, crystalline cellulose, polyvinyl alcohols, polyvinylmethyl ether, polyvinylpyrrolidone, polyvinyl methacrylate, polyacrylate, polyalkylene oxides such as polyethylene oxide and polypropylene oxide, crosslinked polymers thereof, carboxyvinyl polymers, and polyethyleneimines.
(10) Surfactants
　　　 Examples of surfactants include anionic surfactants (alkyl carboxylates, alkyl sulfonates, alkyl sulfates and alkyl phosphates); cationic surfactants (alkylamine salts and alkyl quaternary ammonium salts); amphoteric surfactants, such as carboxylic acid-type amphoteric surfactants (amino-type and betaine-type); sulfate-type amphoteric surfactants; sulfonic acid-type amphoteric surfactants; phosphate-type amphoteric surfactants; nonionic surfactants (ether-type nonionic surfactants, ether ester-type nonionic surfactants, ester-type nonionic surfactants, block polymer-type nonionic surfactants and nitrogen-containing nonionic surfactants); and other surfactants (natural surfactants, protein hydrolysate derivatives, polymeric surfactants, titanium-silicon-containing surfactants and fluorocarbon-based surfactants).
(11) Various Vitamins
　　　 Examples of vitamins include vitamin A group, such as retinol, retinal (vitamin A1), dehydroretinal (vitamin A2), carotene and lycopene (provitamin A); vitamin B group, such as thiamine hydrochloride, thiamine sulfate (vitamin B1), riboflavin (vitamin B2), pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), folic acid, nicotinic acid, pantothenic acid, biotin, choline, and inositol; vitamin C group, such as vitamin C acid and derivatives thereof; vitamin D group, such as ergocalciferol (vitamin D2), cholecalciferol (vitamin D3) and dihydrotachysterol; vitamin E group, such as vitamin E, derivatives thereof and ubiquinones; vitamin K group, such as phytonadione (vitamin K1), menaquinone (vitamin K2), menadione (vitamin K3) and menadiol (vitamin K4); and essential fatty acid (vitamin F), carnitine, ferulic acid, γ-oryzanol, orotic acid, vitamin P group (rutin, eriocitrin and hesperidin), and vitamin U.
(12) Various Amino Acids
　　　 Examples of amino acids include valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxylysine, arginine, ornithine, histidine, and amino acid derivatives such as sulfates, phosphates, nitrates, citrates and pyrrolidonecarboxylic acid of the above-described amino acids.
(13) Various Additives Derived from Plant or Animal Materials
　　　 An additive(s) derived from a plant or animal material(s) is/are arbitrarily selected and incorporated after subjecting them to a processing that is performed by a conventional method (e.g., a combination of treatments arbitrarily selected from grinding, milling, washing, hydrolysis, fermentation, purification, squeezing, extraction, fractionation, filtration, drying, powderization, granulation, dissolution, sterilization, pH adjustment, deodorization, decolorization and the like) in accordance with the type and mode of the product to which the additive(s) is/are added.
　　　 The solvent used for extraction may be selected with consideration of the intended use and type of the product to which the additive(s) is/are added as well as the processing/treatment to be performed subsequently and the like, and it is usually desirable to use one or a mixture of two or more selected from lower alcohols (e.g., water, methanol, ethanol, propyl alcohols, isopropyl alcohols, butanol, isobutanol), water-containing lower alcohols, polyhydric alcohols (e.g., propylene glycol, 1,3-butylene glycol, glycerin), water-containing polyhydric alcohols and various organic solvents (e.g., acetone, ethyl acetate).　However, when the use of an organic solvent is not preferred depending on the application, water may be used alone or ethanol that is easily removable after the extraction may be used alone or in an arbitrary mixture with water, or the additive(s) may be extracted by squeezing.
　　　 Incorporation of an additive derived from a plant or animal material into a systemic or topical external preparation or a cosmetic product is expected to exert not only cosmetic effects such as protection of skin and hair, moisturization, improvement of feel and texture, provision of flexibility, stimulus relief, relaxation of stress by fragrance, cell activation (cellular anti-aging), suppression of inflammation, improvement of skin and hair conditions, inhibition and improvement of rough skin, hair generation, promotion of hair growth, inhibition of hair loss, glossing, cleansing effect, fatigue relief, blood-flow facilitation and bathing effect, but also other effects such as fragrancing, deodorization, thickening, antiseptic effect and buffering.
　　　 Furthermore, with an expectation of previously known various cosmetic and pharmaceutical effects of the respective raw materials, by also using such materials in combination, the intended effects of the present invention can be enhanced and a product expected to show multifunctional effects can be obtained.
　　　 Specific plants (crude drugs) for raw materials are, for example, almond (tonsil), Persicaria tinctoria (Polygonum tinctorium Lour), Sabia japonica (Sinomenium acutum Rehder et Wilson), Aucuba japonica, Chinese parasol tree or Firmiana simplex, Cocculus trilobus (Cocculus trilobus DC.), Gastrodia elata Blume f. viridis (Makino) Makino ex Tuyama, Acacia, Astilbe thunbergii, Ribes rubrum "fruit", red clover, Vitis vinifera, Ternstroemia gymnantheria (Logwood), Mallotus japonicus, Rubia cordifolia or Rubia tinctorum or Rubia cordifola L. (R. cordifolia H. Hara), Rehmannia glutinosa or Rehmannia glutinosa Libos., Ferula assa-foetida, Thalictrum minus L. var. hypoleucum (Siebold et Zuccarini) Miquel., Ulmus parvifolia, P. gardneriana, Mauritia flexuosa, Akebia quinata, Cannabis (Cannabis sativa seed), Ipomoea purpurea or Ipomoea nil (Pharbitidis Semen), Hydrangea macrophylla, Angelica keiskei, Vigna angularis, Thujopsis, Malpighia emarginata, Uncaria gambir, Achira (Canna edulis), Pimpinella anisum, Abiu, Abiurana, Brassica, Quercus variabilis "fruit", avocado, Linum usitatissimum, Hydrangea serrata, Gynostemma pentaphyllum, Polygonatum odoratum, Amana (Amana edulis), Amaranthus (Amaranthaceae, Amaranthus gangeticus, Amaranthus caudatus, Amaranthus caudatus, Amaranthus cruentus, Amaranthus hybridus, Amaranthus retroflexus, Amaranthus spinosus, Epipactis helleborine, Amaranthus-hypochondriacus), Fritillaria verticillata or Fritillaria, Alstroemeria (Alstroemeriaceae), Alkanna tinctoria, Algarrobo (Prosopis julifera), Althaea, Arnica, Alpinia or Alpinia katsumadai Hayata (Alpinia katsumadai), Aloe (Aloe), Aloe vera, Angelica, Prunus armeniaca or Prunus armeniaca, Styrax benzoin, Lucuma salicifolia, Pseudelephantopus spicatus, Epimedium grandiflorum or Epimedium grandiflorum var. grandiflorum (Epimedium), Juncus effusus, Fallopia japonica (Polygonum cuspidatum), Taxus cuspidata, Fragaria, Ficus carica Ficus (Ficus carica Ficus "fruit, leaf"), Iris tectorum, Abutilon theophrasti (Abutilon avicennae), Pyrola japonica, Ginkgo biloba (Ginkgo biloba "seed, leaf"), Polygala tenuifolia, Ceratonia, Draba nemorosa (Draba nemorosa. L), Amaranthus blitum (Amaranthus viridis), Oryza sativa "seed, seed coat", Anethum graveolens "seed", Thymus quinquecostatus, Urtica thunbergiana, Cananga odorata, Conandron ramondioides, Selaginella tamariscina or Selaginella tamariscina, Phaseolus vulgaris, oolong tea, Foeniculum vulgare, Huito (Genipa americana), Scirpus fluviatilis, Lonicera gracilipes "fruit", Carum carvi, Curcuma longa, Spirodela polyrhiza (Lemna minor), Asarum sieboldii or Asarum heterotropoides var. mandshuricum or Asarum europaeum (Asarum sieboldii), Malva sylvestris, Althaea officinalis, Ponerorchis graminifolia, Prunella vulgaris, Aralia cordata or Angelica (Notopterygium incisum, Aralia cordata, Angelica), Uncaria Tomentosa (Uncaria, Uncaria tomentosa), Uva, Prunus mume (Japanese apricot "seed, fruit pulp"), Quercus stenophylla, Arctostaphylos (Arctostaphylos uva-ursi), Citrus unshiu, Styrax obassia, Artemisia dracunculus, Eleutherococcus senticosus, Epipactis papillosa, Echinacea purpurea, Cytisus scoparius, Flammulina velutipes, Senna obtusifolia or Cassia tora (Senna obtusifolia), Gentianella alborosea, Elderberry "fruit", Canarium luzonicum, eryngii or Pleurotus eryngii, Styphnolobium japonicum (sophora flower, sophora flower), Pisum sativum, Astragalus membranaceus or Astragalus propinquus, Polygonatum falcatum or Polygonatum sibiricum, A. filifera Salm. cv. Compacta or Agave victoriae-reginae, Coptis japonica, Opuntia ficus-indica, Trichosanthes bracteata, Inula helenium, Sinomenium acutum (Menispermaceae), Plantago asiatica Plantago asiatica, Plantago asiatica), Stemmacantha uniflora (Rhaponticum uniflorum, Anemone chinensis), Corylus heterophylla (Corylus sieboldiana Bl), Carnegiea gigantes Br. et R., Atractylodes macrocephala or Atractylodes japonica, Lagerstroemia speciosa (Banaba), Alnus sieboldiana "fruit", Eriocaulon buergerianum, Pouteria sapotae, Crataegus pinnatifida var. major or Crataegus cuneata, Lodoicea, Hordeum vulgare, Oxalis tuberosa, Cnidium monnieri, CnidAbelmoschus esculentus "fruit", Inula (Inula), Echinops latifolius (Echinops latifolius Tausch, Echinops sphaerocephalus), Panax ginseng or Panax (Daucus carota subsp. sativus), Hypericum erectum or Hypericum perforatum var. angustifolium or Hypericum perforatum (Hypericum erectum), Lamium album (Lamium album var. barbatum), Xanthium (Xanthium occldentale), Juglans ailantifolia, Dioscorea tokoro Makino or Dioscorea or Dioscorea tokoro (ioscorea tokoro), Gastrodia (Gastrodia elata), Lilium lancifolium or Lilium japonicum or Lilium longiflorum (Lilium), Orchis fauriei, Ononis, Ulmus laciniata, Patrinia scabiosifolia (Patrinia villosa), Olluco, Nasturtium officinale (cresson), Petroselinum crispum, Psoralea corylifolia, Apium graveolens var. dulce, Olea europaea "fruit pulp, seed, leaf", Origanum vulgare, Citrus sinensis "fruit, pericarp", Rehmannia glutinosa Libos. var. hueichingensis (Rehmannia glutinosa), Theobroma cacao "fruit, pericarp, seed", Diospyros kaki (sitei "leaf"), Uncaria rhynchophylla, Glechoma hederacea or Glechoma hederacea subsp. grandis (Glechoma hederacea var. grandis), Epipactis thunbergii A. Gray, Hydrangea macrophylla, Cinnamomum cassia, Broussonetia papyrifera (Broussonetia kazinoki "fruit"), Curcuma zedoaria, Quercus dentata, Croton eluteria, Rhamnus purshiana, Gypsophila elegans, Inula salicina, Lygodium (Lygodium japonicum), kaniwa, Dianthus caryophyllus, Valeriana fauriei (Valeriana fauriei Briquet), Betula, Betula or Betula platyphylla var. japonica. (Betula pendula), Gerbera, Cucurbita, Ceiba pentandra "seed", Zanthoxylum bungeanum, Typha latifolia L. (Typha angustifolia pollen), Matricaria chamomilla or Roman chamomile, Tetrapanax papyrifer (Akebia quinata), Myrciaria dubia (Camocamo), Calla, Fumaria officinalis, Trichosanthes cucumeroides or Trichosanthes kirilowii var. japonica (Trichosanthes cucumeroides), Pinellia ternata, Avena fatua, Paullinia cupana "seed", Magnolia officinalis, karaya, Cerasus spachiana Lavalee ex H.Otto var. spachiana forma ascendens, Pseudocydonia sinensis (Chaenomeles speciosa), Garcinia cowa, Agastache rugosa, Potentilla chinensis (Potentilla, Potentilla discolor), Veronica undulata, Trametes versicolor, Dianthus superbus var. longicalycinus (Dianthus chinensis) or Dianthus superbus (Dianthus superbus L. var. longicalycinus, Dianthus chinensis L.), Artemisia apiacea (Artemisia carvifolia), Artemisia capillaris (Artemisiae Capillaris Herba decoction), Euphorbia kansui, Glycyrrhiza (Glycyrrhiza), A. cantara, Euphorbia antisyphilitica Zuccarini, Tussilago farfara, Canna, Cymbidium kanran, Rubus (Rubus idaeus subsp. melanolasius., Fragaria, Rubus phoenicolasius, Rubus parvifolius, Rubus palmatus var. coptophyllus, Rubus idaeus), Actinidia chinensis "fruit, leaf", Trichosanthes kirilowii (Trichosanthes kirilowii MAXIM.), Platycodon grandiflorus (Platycodon grandiflorus, Platycodon Root), Chrysanthemum morifolium (Chrysanthemum indicum, Chrysanthemum zawadskii var. latilobum), Dendranthema lavandulifolium, Catalpa ovata, Rumex japonicus, Citrus aurantium L., Hedera rhombea, Aloe arborescens, Satureja hortensis, Cinchona, Cinchona officinalis (Cinchona, Cinchona pubescens), Cinchona pubescens (Quinoa), Phellodendron amurense, Cajanus cajan, Gymnema sylvestre, Cereus peruvianus, Brassica oleracea var. capitata, cabbage-turnip "unripe fruit", Carum carvi, Cucumis sativus, Tamarix (Tamarix tenuissima, Tamarix chinensis), Quillaja saponalia, Quillaja, Ajuga (Ajuga decumbens), Fortunella "fruit", Pithecellobium dulce, Primula sieboldii 'Ginsekai', Opuntia tuna, Piper betle, Agrimonia pilosa var. japonica (Agrimonia pilosa), Cephalanthera falcata, Cephalanthera erecta, Cymbidium floribundum, Lucuma laurifolia, Psidium guajava "fruit", Parthenium argentatum, Quercus infectoria (gall), Aleurites moluccanus, Cephalanthera longifolia, Lycium barbarum (Lycium chinense, lycii fructus, lycii folium, Lycii root), Asparagus (Asparagi radix), Pueraria montana (Puerariae Radix), Cinnamomum camphora, gooseberry "fruit", Artemisia annua (Artemisia annua leaf), P. macrophylla, Gardenia jasminoides (gardeniae fructus), Quercus acutissima, Theobroma grandiflorum, Piper cubeba, Sasa veitchii, Verbena officinalis, Sophora flavescens (sophorae radix), cranberry "fruit", Castanea crenata "seed, fruit pulp, astringent skin", Curcurigo latifolia "fruit", grapefruit "fruit, leaf", Rhamnaceae, Ilex rotunda, Plectranthus kameba or Isodon trichocarpus or Isodon japonicus, Syzygium aromaticum (caryophyllus, Clove), Thlaspi arvense, Schizonepeta (schizonepeta herb, schizonepeta herb), Celosia argentea (keikanka, Celosia argentea), Epiphyllum oxypetalum, Laurus nobilis, Smilax glabra (smilax rhizome, smilacis rhizoma), Gentiana lutea, Geranium thunbergii (Geranium), Hovenia dulcis (Stachyurus praecox), Dendrobium nobile, Citrus kinokuni (Citrus leiocarpa, Citrus reticulata, Citrus reticulata, C tumida Hort.ex Tanaka, Citrus fumida, Citrus tangerina, Ponkan Suntara Santra (Citrus peel)), Rosa chinensis (Rosa chinensis flower), Melissa officinalis, Broussonetia kazinoki "fruit", Camellia sinensis (black tea), Nuphar japonica (Nuphar Rhizome), Ligusticum (Nothosmyrnium japonicum, Nothosmyrnium japonicum), Sorghum vulgare, Alpinia officinarum, Coriandrum "fruit", Picrorhiza kurrooa (Picrorhiza kurroa rhizome), Scutellaria baicalensis (Scutellaria root), Vaccinium vitis-idaea (Vaccinium vitis-idaea leaf), Cocos nucifera "fruit", Tetradium ruticarpum (Evodiae fructus), Rubus chingii (Rubus idaeus), Piper nigrum, Cosmos, Copaifera officinalis, Coffea robusta "seed, leaf", Magnolia kobus or Magnolia liliiflora (Magnolia salicifolia), Arctium lappa (clotbur, Arctii fructus), Clematis apiifolia var. biternata, Sesamum indicum, Scrophularia (Scrophularia buergerian
a root), Schisandra chinensis or Kadsura japonica or Schisandraceae, Triticum (wheat), rice or rice bran "outer bran, white rice bran", rice oil, Cola acuminata "seed", Cola Bella "seed", Excelsa, Trigonella foenum-graecum "fruit", Jateorhiza palmata, Marsdenia cundurango, Laminariaceae, Amorphophallus konjac, Comfrey (Symphytum officinale), sisal (Agave sisalana), Cremastra appendiculata, Neottia nidus-avis var. mandshurica (Neottia nidus-avis), Clematis chinensis (Wei-ling-xian), Cerasus (Prunus speciosa, Prunus serrulata, Prunus sargentii, Prunus pendula Maxim. form. ascendens Ohwi, Prunus incisa, Prunus maximowiczii, Prunus yedoensis, Prunus nipponica, Prunus leveilleana Koene, Prunus subhirtella, Prunus lannesiana var. lannesiana, Prunus campanulata "leaf, flower, fruit, bark (cherry bark)"), cherry, Punica granatum, Sasa, Cephalanthera longibracteata, Camellia sasanqua, Alisma plantago-aquatica var. orientale (Alisma Rhizome), Ipomoea batatas, Saccharum officinarum, sugar beet, Zizyphus vulgaris (Zizyphi Spinosi Semen), Crocus sativus (xihonghua), Manilkara zapota, Pouteria campechiana, Citrus maxima "fruit", Saponaria officinalis, Salmonberry "fruit", Actaea simplex (Cimicifugae rhizoma), Echinops gmelinii, Salvia (Salvia officinalis), Lobelia sessilifolia (Lobelia sessilifolia Lamb.), Pterocarya, Hylocereus, Sangre de grado (Croton), Epimedium grandiflorum, Panax notoginseng, Cornus officinalis (corni fructus), Zanthoxylum piperitum, Sophora subprostrata, Busyrospernum parkii, Tilia japonica "fruit", Lentinula edodes (Lentinula edodes), Aster tataricus, winged bean, Digitalis, Combretaceae (Combretum indicum), Perilla frutescens or P. frutescens var. crispa f. crispa or Perilla frutescens var. crispa 'Discolor' (perilla herb, sisosi), red sandal tree, Tilia japonica, Magnolia officinalis, Forsythia viridissima Lindl. (Forsythia suspensa), Lyophyllum decastes (Lyophyllum shimeji, Lyophyllum fumosum, Lyophyllum decastes, Lyophyllum connatum, Hypsizygus tessellatus, Lyophyllum shimeji, Hypsozogus ulmarius), Magnolia liliiflora (Magnolia kobus), Filipendula, Solanum tuberosum, Adenophora polymorpha root, Jasminum (Jasminum sambac), Ophiopogon japonicus, Vigna unguiculata ssp. sesquipedalis, Gypsophila paniculata, Hedychium coronarium (Amomum villosum, Amomum xanthioides), Coix lacryma-jobi, Trachycarpus "fruit", Cymbidium goeringii, Queen Palm, Zingiber officinale (ginger), Dichroa febrifuga (Dichroa root), sweet flag (sword lily, sweet flag), Elettaria cardamomum "fruit", Quercus myrsinifolia "seed", Bletilla striata, Sesbania grandiflora "seed", Trifolium repens (Trifolium), Abrus fruticulosus (Abrus cantoniensis), Iris florentina L.,
Parthenocissus tricuspidata "flower", Lupinus albus, Nandina domestica var. leucocarpa (Nandina domestica fruit), Cinchona succirubra, Daphne odora, Cinnamomum verum, Cinnamomum cassia (Chinese cinnamon), Citrullus lanatus (Citrullus), Lonicera japonica (lonicerae flos), Rumex acetosa (garden sorrel), swim-berry "fruit", Chrysophyllum cainito, Stevia rebaudiana, strawberry "fruit", Vincetoxicum paniculatum (Cynanchum paniculatum root), Equisetum arvense, Portulaca oleracea, Prunus salicina "fruit", Cymbidium ensifolium, Pinus sylvestris "strobile", Larix decidua, Hedera helix, Juglans regia, Crataegus laevigata, Taraxacum officinale, Aesculus hippocastanum (marronnier), Pyrus communis "fruit", Filipendula ulmaria, Sambucus nigra (Elder), Juniperus communis (Juniper, Juniperus seed), Achillea millefolium (Milfoil), Rosa, Capparis spinosa, European mistletoe, Mentha piperita L. or Melissa officinalis, Armoracia rusticana, Acorus gramineus, Dendrobium moniliforme (Dendrobium linawianum, Dendrobium nobile, D. okinawense Hatusima et Ida, Dendrobium officinale, Dendrobium phalaenopsis, D.tetragonum A. Cunn., Dendrobium tosaense) (Dendrobium, Dendrobium moniliforme Sw.), Lippia Citriodora (Aloysia citrodora), Malva, P. senega var. latifolia, Polygala senega, Oenanthe javanica, Apium graveolens, Ligusticum striatum, Andrographis paniculata, Melia azedarach, Opuntia stricta, Senna alexandrina "fruit, leaf", Clematis terniflora, Swertia japonica (Swertia Herb), senboku, Amomum tsao-ko, Lemaireocereus griseus B. et R., Chimonanthus praecox f. concolor., Fagopyrum esculentum "seed", Dioscorea rhipogonoides, Vicia faba, Rheum, Raphanus sativus var. longipinnatus, Glycine max, Citrus aurantium (wild orange peel, orange pease), E. grijisii, Eclipta prostrata, Euphorbia pekinensis (Knoxia root), Dicksoniaceae (Cibotium rhizome), dark sweet cherry "fruit", Alcea rosea, T. vulgaris L. (Thymus, Thymus quinquecostatus), Dioscorea gracillima Miq. (Dioscorea tokoro Makino), Salix subfragilis, Tamarindus indica "seed", Allium cepa, Magnolia salicifolia, Aralia elata "fruit, leaf, root bark", Ilex latifolia (Ilex latifolia Thunb., Ilex kudingcha C. J. Tseng), Dahlia (Dahlia hybrida), Lupinus mutabilis, Rhynchosia volubilis, Opuntia vulgaris, Salvia miltiorrhiza, Taraxacum or Taraxacum albidum or Taraxacum mongolicum Hand.-Mazz., dammar, cherry "fruit", Imperata cylindrica "fruit, root, bud", Panax japonicus, Cichorium intybus, Phyllanthus niruri, Tulipa, choko-no-stei, globe artichoke (Cynara scolymus), Rheum officinale (Rheum), U. macrocarpa, Artemisia argyi (Artemisia vulgaris), Polyporus umbellatus (chuling), Stachys affinis, Oenothera tetraptera, Neottia kiusiana, Agaricus bisporus (mushroom), Cyrtosia septentrionalis, Camellia japonica, Centella asiatica, Sagina japonica (Sagina herb), Commelina communis, Vigna angularis (Small red-been), Cyrtosia septentrionalis, Fallopia multiflora (polygoni radix), Tetragonia tetragonioides, Codonopsis lanceolata, Glycine soja, Farfugium japonicum, Erythrina variegata, Juglans regia var. orientis, dewberry "fruit", Gelidiaceae, Rubus suavissimus, Lindera aggregata (Benzoin strychnifolium), Benincasa hispida (Benincasa seed), Uncaria sinensis, Capsicum annuum (Capsicum fruit), Angelica acutiloba, Calendula officinalis (Tagetes), Gleditsia Linn, D. asper, Zea mays or Zea mays L., Ligustrum lucidum (Ligustrum japonicum), Gentiana scabra or Japanese Gentian, Equisetum hyemale, Houttuynia cordata (Houttuyniae herba), Carapichea ipecacuanha, Cuscuta chinensis or Cuscuta, Eucommia ulmoides (Eucommia ulmoides "bark, leaf, root"), Fraxinus (Fraxini bark), Solanum lycopersicum, tragacanth, triacanthos "seed", grandiflorum, Potentilla tormentilla Schrk, Populus suaveolens, Abelmoschus manihot, Coumarouna odorata, nigeria berry "fruit", Dioscorea polystachya or Dioscorea japonica (Dioscoreae rhizoma), Ruscus aculeatus, Elsholtzia ciliata, Capsella bursa-pastoris, Brassica napus, Canavalia gladiata or Canavalia gladiata, Citrus natsudaidai, Zizyphus jujuba Mill. (zizyphi fructus), Rosa laevigata, Dipsacus japonicus (Dipsacus japonicus root), Pholiota nameko, Arachis hypogaea (peanut), Nandina domestica (Nandina domestica fruit), false nettle (ramie), Viola odorata, Picrasma quassioides (quassia wood), Artemisia absinthium (wormwood), Myristica fragrans, Cinnamomum cassia Bl. or Cinnamomum cassia or Cinnamomum verum or Cinnamomum pedunculatum (Chinese cinnamon) or Cinnamomum, Orchis joo-iokiana, Allium tuberosum (Oriental garlic), Sambucus sieboldiana (Sambucus williamsii stem "fruit, flower, cauline, leaf"), Allium sativum (garlic), Rhus chinensis (Japanese gall), Allium, Albizia julibrissin or Albizzia bark or nebi or Albizia julibrissin or Lycoris radiata Herb (Albizzia bark), Cirsium japonicum (Cirsium nipponense), Rosa multiflora (dog rose fruit), Campsis grandiflora (trumpet creeper), Celosia argentea, Achillea millefolium, Angelica decursiva (praeruptorum root), Rosa multiflora, Prunus persica, pineapple "fruit", Hibiscus (Hibiscus rosa-sinensis, Chinese hibiscus, Hibiscus sabdariffa), Gentiana decumbens, Acer japonicum, Pau Dausset, Drynaria fortunei (Drynaria herb), Mucuna birdwoodiana Tutcher, Dactylorhiza aristata, Dictamnus (Dictamnus dasycarpus), huckleberry "fruit", Stellaria (Stellaria holostea), Corylus (Corylus sieboldiana Bl.), Scopolia japonica (Scopolia rhizome), Ocimum basilicum, Nelumbo nucifera (Nelumbo nucifera fruit), parsley (Petroselinum crispum), Naked barley, batata, Phyllostachys nigra var. henonis or Phyllostachys bambusoides (Phyllostachysis caulis), Pogostemon cablin, Mentha (Mentha, mint leaf), Mucuna pruriens, Coix lacryma-jobi var. ma-yuen (Coix Seed), Anemarrhena asphodeloides (Anemarrhenae Rhizoma), banana, oregano, Eschscholzia californica (Tribulus terrestris), Vanilla Beans, papaya, Gnaphalium affine, paharobobo, Senna occidentalis "whole plant, cauline, leaf", Paprika, E. helleborine var. sayekiana, Vitex rotundifolia or Vitex trifolia L. (Vitex rotundifolia fruit), Cyperus rotundus (Cyperi Rhizoma), Tribulus terrestris, Rosa rugosa (maikai flower), Glehnia littoralis, Hamamelis japonica, palm, rose (rose), balata, Hevea brasiliensis, Agaricus campestris (Agaricus arvensis, Agaricus abruptibulbus), Aspidistra elatior, Paliurus spina-christi, Parietaria, Cymbidium nishiuchianum cv. Shoshun, Momordica charantia (Momordica), Ulmus davidiana var. japonica (Elm bark, Elm white bark, Elm leaf), Dioscorea mexicana, Gentiana thunbergii, Sterculia scaphigera WALL, Artocarpus altilis, Iris domestica (Belamcanda chinensis rhizome), Codonopsis pilosula, Pecan nut, Lycoris radiata (Lycoris radiata bulb, Lycoris radiata), Dahlia coccinea, Echinops, Trapa natans (Trapa fructus), Pistacia vera, beet, Pyrrosia lingua (Pyrrosia herb), Genista tinctoria, Bellis perennis (daisy), Achyranthes bidentata var. fauriei (achyranthis radix, Orchis chidori, Chamaecyparis obtusa, Thujopsis dolabrata, Ricinus communis L., Sunflower, Capsicum annuum Group,
Semiaquilegia adoxoides, Typha domingensis (Typha orientalis Presl), Agaricus subrufescens (Agaricus blazei Murrill, Hilo matsutake), Neottia acuminata, Pimenta "fruit", juniper, Bletilla striata, Amaranthaceae "fruit", Cicer arietinum, Lens culinaris, Althaea officinalis, Anemone chinensis (Pulsatilla root), Eriobotrya japonica "fruit, leaf, cauline", Areca catechu (Areca nut), Pu-erh tea (Camellia assamica (Mast.) Chang), Piper kadsura (Piper wallichii), Petasites japonicus, Tussilago farfara (Tussilago farfara bud), Eupatorium japonicum (Eupatorium fortunei), Lablab purpureus (henzu), Daphne genkwa (Prunus apetara, Daphne genkwa bud), Grape "fruit, pericarp, seed, leaf", Fagus crenata, Cordyceps sinensis (vegetable wasp and plant worm), Periandra dulcis MART., Pfaffia paniculata, Butia capitata, Attalea funifera Mart., Blackcurrant "fruit", Blackberry, Pradosia lactescens, Plum "fruit", Genus Furcellaria, blueberry (Vaccinium myrtillus L.), prune, flora blanca, Blond psyllium, Phaseolus radiatus (mung bean), Hazelnut, Luffa aegyptiaca, Cymbidium dayanum, Carthamus tinctorius, henequen, Atropa belladonna, berry "fruit", Persea, Pell Lesbian Berg, Pereskia grandifolia, Crassulaceae or Hylotelephium erythrostictum (Crassulaceae), Boysenberry "fruit", Bassia scoparia or Kochia scoparia or Belvedere or Bassia scoparia (Kochia scoparia), Cymbidium sinense, Impatiens balsamina (Phrymaceae), Pouteria sapota, Pouteria lucuma, Magnolia obovata, Saposhnikovia divaricata, Spinach, Physalis alkekengi, Magnolia obovata (Magnolia Bark), Chaenomeles speciosa, Chrysanthemum lavandulifolium, subsp. linariaefolia, Atractylodis lanceae rhizoma, Aizoon Stonecrop (Sedum Spetabile), Echinacea angustifolia, Tilia miqueliana, Paeonia suffruticosa (Paeonia suffruticosa "flower, leaf, cauline, bark"), Paeonia suffruticosa Andrews, Humulus lupulus, Simmondsia chinensis, Borage (Borago officinalis), Bordeaux, whortleberry "fruit", Cistanche salsa (Boschniakia rossica, cistanchis herba), Dendrobium officinale, Arisaema heterophyllum Blume (Arisaema), Grifola frondosa, Ephedra sinica, Lepidium meyenii, Macadamia integrifolia, Marguerite (Argyranthemum frutescens), Digenea simplex, Morus alba (Morus bombycis "bark, leaf"), Magnolia sprengeri var. diva., M. excelsa, masaranzuba-do-seara, Sideroxylon rugosum, Tropaeolum tuberosum (tuber nasturtium, nasturtium), Actinidia polygama, pinecone, Pinus "leaf, bark, root", Pouteria salicifolia, Wolfiporia extensa (Hoelen), Piper aduncum, marjoram (Origanum vulgare L.), Adenophora coronopifolia (sophorae radix), Mulberry "fruit", marmelo, Mullein (Verbascum thapsus), Mangifera indica, Garcinia mangostana, manzana (Andes camomile), Juglans mandshurica, Mandarin "fruit", Ganodermataceae (shelf fungus), Citrus aurantium L. (orange pease "fruit"), Bupleurum scorzonerifolium (bupleuri radix), Ottelia alismoides (Ottelia japonica), Lobelia chinensis, Lythrum anceps, Polygonum aviculare or Polygonum aviculare (Avicularin), Menyanthes, Cryptotaenia japonica, C. viride, Mentha spicata L., Mimosa, Zingiber mioga, Synsepalum dulcificum "fruit", Commiphora myrrha, Terminalia chebula, Xerochrysum bracteatum, Hibiscus syriacus (althea), Aphananthe aspera, Sapindus mukorossi, Munya, Lithospermum purpurocaeruleum (Lithospermum root), Callicarpa japonica or Callicarpa japonica var. luxurians. (Callicarpa), Purple corn, Millettia reticulata, Megakansa-Opuntika, Leonurus japonicus (Leonurus sibiricus herb), Ocimum basilicum, Melaleuca, Melissa, Melilot, Cucumis melo "fruit", Artemisia mongolia, Phyllostachys edulis, Pereskia aculeata, Molle (Schinus molle), Aquifoliaceae, Saussurea costus (Saussureae radix), Rheum palmatum, Prunus persica (peach "leaf, seed, flower, fruit"), Sprout, Prunus cerasus "fruit", Corchorus olitorius (jute), yakawa-purple sweet potato, Alpinia oxyphylla (bitter seed cardamon), Rodgersia podophylla (Centaurea cyanus), Monarda fistulosa, Smallanthus sonchifolius, Alnus firma (Centaurea cyanus) or Alnus pendula or Alnus sieboldiana "fruit, pericarp, ear of fruit", Myrica gale, Fatsia japonica (Fatsia japonica leaf), Viscum album (Taxillus delavayi), Salix (Salix gilgiana, Salix subfragilis, Salix babylonica, Salix chaenomeloides, Salix gracilistyla, Salix integra, Salix kinuyanagi, Salix koriyanagi, Salix matsudana var. tortuosa, Salix reinii, Arecaceae, Salix sieboldiana, Toisusu urbaniana, Salix viminalis, Salix vulpina, Populus suaveolens), Persicaria hydropiper "leaf, cauline", Cayratia japonica, Ardisia japonica, Carpesium abrotanoides L. (Lappula, Carpesium abrotanoides), Phytolacca americana (Phytolacca esculenta root), Alnus hirsuta var. sibirica, Morella rubra (Myrica bark), Artemisia tridentata, Eucalyptus, Saxifraga stolonifera (Saxifraga leaf), Yucca or Brevifolia, Citrus junos "fruit", Lilium, Angelica dahurica, Artemisia (Artemisia princeps leaf), Omphalia lapidescens (raigan), Lime "fruit", Secale cereale, Siraitia grosvenorii "fruit", raspberry "leaf, fruit", Latania (Krameriaceae), Allium chinense or shallot (Allium chinese bulb), lavender, Dimocarpus longan (Longan Aril), Agave, (Agave americana, American aloe), Camellia sinensis L. (Green tea), Apple "fruit, seed, leaf, root", Gentiana scabra, Rubus or Suabishimusu (ten-ryou), Echinops ritro, Litchi chinensis, Lettuce (Lactuca sativa), Redcurrant "fruit", dragon fruit, lemon "fruit", Lemon grass, Forsythia or Forsythia viridissima (Forsythia), Astragalus sinicus, Chimonanthus praecox (Wintersweet), wax palm, Rhizoma Phragmitis (Phragmites australis, Phragmites communis), loganberry "fruit", rosemary (Rosmarinus officinalis), rose hip (Rosa multiflora), Eutrema japonicum, Buddle jaofficinalis, Sanguisorba officinalis, or the like.
　　　 Representative examples of seaweeds include seaweeds [green algae: Chlorella vulgaris, Chlorella pyrenoidsa, Chlorella ellipsoidea, Green laver (Enteromorpha linza, Enteromorpha prolifera, Enteromorpha compressa, Enteromorpha intestinalis, Enteromorpha clathrata), Ulva pertusa (sea lettuce)], seaweeds [brown algae: Laminariaceae (Saccharina japonica, Saccharina japonica var. ochotensis, Saccharina japonica var. religiosa, Saccharina angustata), Undaria pinnatifida, Undaria undarioides, Undaria peterseniana, Giant Kelp (Macrocystis pyrifera, Macrocystis integrifolia, Nereocystis luetkeana), Sargassum fusiforme, Fucus distichus, Padina arborescens, Padina australis, Padina australis var. cuneata, Padina boryana, Padina crassa, Padina japonica, Padina minor, Padina stipitata], seaweeds [red algae: Cyrtymenia sparsa, Gelidium elegans (Gelidiaceae), Ptilophora subcostata, Gelidium japonicum, Pterocladiella tenuis, Pterocladiella capillacea, Yatabella hirsuta, Acanthopeltis japonica, Gelidiella acerosa, Meristotheca papulosa, Eucheuma serra, Eucheuma amakusaense, Eucheuma denticulatum, Eucheuma arnoldii, Chondrus ocellatus, Chondrus giganteus, Chondrus crispus (Chondrus ocellatus), Chondrus yendoi, Chondrus pinnulatus f.armatus, Chondrus pinnulatus, Chondrus elatus, Chondrus verrucosus, Chondrus nipponicus, Chondrus pinnulatus, Chondracanthus tenellus, Chondracanthus teedii, Chondracanthus intermedius, Acrosorium flabellatum, Acrosorium venulosum, Acrosorium polyneurum, Acrosorium yendoi, red algae], and the like.
　　　 In addition, representative examples of seaweeds also include other algae, for example, green algae (Genus Chlamydomonas: Chlamydomonas reinhardtii, Chlamydomonas nivalis, Genus Dunaliella: Dunaliella salina, Genus Chlorococcum: Chlorococcum sp., Genus Pandorina: Pandorina morum, Genus Volvox: Volvox carteri, Volvox sp., Genus Palmella, Genus Tetraspora, Genus Spirogyra, Mougeotia sp., Spirogyra, Genus Draparnaldia, Genus Ulothrix: Ulothrix flacca, Genus Ulva: Ulva pertusa, Ulva reticulata, Ulva arasakii, Genus Prasiola: Prasiola japonica, Genus Fritschiella, Genus Cladophora: Cladophora japonica, Cladophora sakaii, Cladophora glomerata, Aegagropila linnaei, Genus Valonia: Valonia macrophysa, Valonia aegagropila, Genus Boergesenia: Boergesenia forbesii, Genus Caulepra: Caulerpa okamurae, Caulerpa racemosa var. laete-virens, Caulerpa brachypus, Caulerpa scalpelliformis var. intermedia, Genus Bryopsis, Genus Codium: Codium fragile, Codium subtubulosum, Codium contractum, Codium cylindricum, Codium latum, Genus Acetabularia: Acetabularia ryukyuensis, Genus Chaetomorpha: Chaetomorpha spiralis, Chaetomorpha moniligera, Chaetomorpha okamurai, Genus Closterium, Genus Korekaete, Genus Cosmarium, Genus Dictyosphaeria: Dictyosphaeria cavernosa, Genus Monostroma: Monostroma nitidum, Monostroma latissimum, Monostroma grevillei, Kornmannia leptoderma, Genus Oedogonium, Genus Pediastrum, Genus Trentepohla: Trentepohla aurea, Genus Zygnema, Genus Vaucheria, etc.);
　　　 Blue algae (Genus Aphanothece: Aphanothece sacrum, Genus Microcystis, Genus Nostoc: Nostoc verrucosum, Nostoc commune, Nostoc commune var. flagelliforme, Genus Oscillatoria, Genus Spirulina (Arthrospira): Arthrospira platensis, Genus Trichodesmium (Trichodesmium), etc.);
　　　 Blown algae (Genus Pylaiella: Pilayella littoralis, Genus Ectocarpus: Hincksia indica, Genus Botrytella: Botrytella parva, Genus Ralfsia: Ralfsia fungiformis, Genus Sphacelaria: Sphacelaria tribuloides, Genus Halopteris: Halopteris filicina, Genus Cutleria: Cutleria cylindrica, Cutleria multifida, Cutleria adspersa, Genus Dictyota: Dictyota dichotoma, Dictyota dilatata, Genus Pachydictyon, Dictyota coriacea, Rugulopteryx okamurae, Genus Spatoglossum: Spatoglossum pacificum, Genus Dictyopteris: Dictyopteris divaricata, Dictyopteris latiuscula, Dictyopteris polypodioides, Genus Stypopodium: Stypopodium zonale, Genus Padina: Padina arborescens, Padina crassa, Padina boryana,Genus Elachista: Elachista taeniaeformis, Genus Halothrix, Halothrix ambigua, Genus Leathesia: Leathesia difformis, Genus Saundersella: Saundersella simplex, Genus Analipus: Analipus japonicus, Genus Chordaria: Chordaria flagelliformis, Genus Cladosiphon: Cladosiphon okamuranus, Genus Eudesme: Eudesme virescens, Genus Tinocladia: Tinocladia crassa, Genus Sphaerotrichia: Sphaerotrichia divaricata, Genus Papenfussiella: Papenfussiella kuromo, Genus Acrothrix: Acrothrix pacifica, Genus Nemacystus: Nemacystus decipiens, Genus Ishige: Ishige okamurae, Ishige foliacea, Genus Carpomitra: Carpomitra costata, Genus Sporochnus: Sporochnus radiciformis, Genus Nereia: Nereia intricata, Genus Desmarestia: Desmarestia ligulata, Desmarestia viridis, Desmarestia tabacoides, Genus Akkesiphycus: Akkesiphycus lubricus, Genus Punctaria: Punctaria latifolia, Genus Endarachne: Endarachne binghamiae, Genus Petalonia: Petalonia fascia, Genus Asperococcus: Asperococcus bullosus, Genus Coilodesme: Coilodesme japonica, Genus Colpomenia: Colpomenia sinuosa, Colpomenia bullosa, Genus Soranthera: Soranthera sp., Genus Hydroclathrus: Hydroclathrus clathratus, Genus Chnoospora: Chnoospora implexa, Genus Stictyosiphon: Stictyosiphon soriferus, Genus Cassiope: Cassiope lycopodioides, Genus Striaria: Striaria attenuata, Genus Scytosiphon: Scytosiphon lomentaria, Genus Dictyosiphon: Dictyosiphon foeniculaceus, Genus Chorda: Chorda asiatica, Genus Agarum: Agarum clathratum, Genus Costaria: Costaria costata, Genus Cymathaere: Cymathaere japonica, Saccharina kulilensis, Genus Saccharina: Saccharina coriacea, Saccharina longipedalis, Saccharina japonica var. diabolica, Laminaria yezoensis, Saccharina longissima, Saccharina yendoana, Saccharina cichorioides, Genus Kjellmaniella: Saccharina gyrata, Genus Eckloniopsis: Eckloniopsis radicosa, Genus Ecklonia: Ecklonia cava, Ecklonia stolonifera, Ecklonia kurome, Genus Thalassiophyllum: Thalassiophyllum clathrus, Genus Streptophyllum: Streptophyllum sp., Genus Streptophyllopsis: Streptophyllopsis kuroshioensis, Genus Arthrothamnus: Arthrothamnus bifidus, Genus Eisenia: Eisenia bicyclis, Genus Alaria: Alaria praelonga, Alaria crassifolia, Eualaria fistulosa, Genus Silvetia: Silvetia babingtonii, Genus Hormophysa: Hormophysa cuneiformis, Genus Turbinaria: Turbinaria ornata, Genus Myagropsis: Cystoseira hakodatensis, Myagropsis myagroides, Myagropsis yendoi, Genus Sargassum: Sargassum nipponicum, Sargassum hemiphyllum, Sargassum segii, Sargassum horneri, Sargassum filicinum, Sargassum fulvellum, Sargassum sagamianum, Sargassum nigrifolium, Sargassum piluliferum, Sargassum tosaense, Sargassum patens, Sargassum thunbergii, Sargassum ringgoldianum Harvey ssp. ringgoldianum, Sargassum confusum, Sargassum kjellmanianum, Sargassum micracanthum, Sargassum siliquastrum, Sargassum macrocarpum, Sargassum giganteifolium, Genus Coccophora: Coccophora langsdorfii, Genus Macrocystis: Macrocystis pylifera, Genus Nereocystis: Nereocystis luetkeana, Genus Scytosiphon: Scytosiphon lomentaria, etc.);
　　　 Red algae (Genus Bangia: Bangia fuscopurpurea, Bangia gloiopeltidicola, Genus Pyropia: Pyropia tenera, Pyropia yezoensis, Pyropia pseudolinearis, Pyropia dentata, Wildemania occidentalis, Wildemania variegata, Wildemania amplissima, Genus Rhodochorton: Acrochaetium howei, Genus Trichogloea: Trichogloea requienii, Genus Liagora: Yamadaella caenomyce, Liagora japonica, Liagora ceranoides f. leprosa, Genus Nemalion: Nemalion vermiculare, Nemalion multifidum, Dermonema pulvinatum, Genus Helminthocladia: Helminthocladia australis, Helminthocladia yendoana, Genus Dermonema: Dermonema virens, Genus Scinaia: Scinaia japonica, Genus Pseudogloiophloea: Pseudogloiophloea okamurai, Genus Actinotrichia: Actinotrichia fragilis, Genus Tricleocarpa: Tricleocarpa jejuensis, Dichotomaria falcata, Genus Ptilonia: Ptilonia okadae, Genus Delisea: Delisea japonica, Genus Asparagopsis: Bonnemaisonia hamifera, Asparagopsis taxiformis, Genus Gelidium: Gelidium freshwateri, Gelidium crinale, Gelidium pacificum, Gelidium subfastigiatum, Gelidium tenue, Yohira, Gelidium linoides, Genus Dudresnaya: Dudresnaya japonica, Dudresnaya minima, Genus Hyalosiphonia: Hyalosiphonia caespitosa, Genus Pikea: Pikea yoshizakii, Genus Dumontia: Dumontia contorta, Dumontia simplex, Genus Masudaphycus: Masudaphycus irregularis, Genus Constantinea: Constantinea subulifera, Genus Neodilsea: Neodilsea yendoana, Neodilsea tenuipes, Genus Portieria: Portieria hornemannii, Portieria japonica, Genus Stylaster: Rhodopeltis borealis, Genus Contarinia: Contarinia okamurae, Genus Peyssonnelia: Peyssonnelia caulifera, Genus Cruoriopsis: Cruoriopsis japonica, Genus Amphiroa: Amphiroa anceps, Genus Corallina: Corallina officinalis, Genus Grateloupia: Grateloupia asiatica, Grateloupia ramosissima, Grateloupia divaricata, Grateloupia livida, Polyopes lancifolius, Grateloupia imbricata, Grateloupia carnosa, Grateloupia elliptica, Grateloupia turuturu, Grateloupia lanceolata, Grateloupia kurogii, Genus Halymenia: Sebdenia flabellata, Halymenia polydactyla, Grateloupia acuminata, Genus Prionitis: Prionitis patens, Genus Polyopes: Polyopes polyideoides, Genus Carpopeltis: Carpopeltis rigida, Carpopeltis angusta, Carpopeltis affinis, Carpopeltis flabellata, Carpopeltis crispata, Carpopeltis divaricata, Grateloupia articulata, Grateloupia cornea, Grateloupia elata, Grateloupia ramosissima, Genus Cryptonemia: Grateloupia schmitziana, Genus Gloiosiphonia: Gloiosiphonia capillaris, Genus Schimmelmannia: Schimmelmannia plumosa, Genus Gloiopeltis: Gloiopeltis complanata, Gloiopeltis furcata, Gloiopeltis tenax, Genus Tichocarpus: Tichocarpus crinitus, Genus Callophyllis: Callophyllis japonica, Callophyllis crispata, Callophyllis palmata, Callophyllis adhaerens, Callophyllis adnata, Euthora cristata, Callophyllis hayamensis, Callophyllis mageshimensis, Callophyllis rhynchocarpa, Genus Callophyllis: Callophyllis okamurae, Genus Cirrulicarpus: Cirrulicarpus gmelini, Genus Kallymenia: Kallymenia sessilis, Kallymenia sagamiana, Kallymenia callophylloides, Genus Schmitzia: Schmitzia japonica, Genus Tsengia: Tsengia nakamurae, Tsengia lancifolia, Genus Platoma: Platoma izunosimensis, Genus Schizymenia: Schizymenia dubyi, Genus Halarachnion: Halarachnion latissimum, Genus Sebdenia: Sebdenia yamadai, Genus Solieria: Solieria robusta, Solieria tenuis, Genus Meristotheca: Meristotheca coacta, Genus Turnerella: Turnerella mertensiana, Genus Catenella: Catenella caespitosa, Genus Plocamium: Plocamium telfairiae, Plocamium cartilagineum, Genus Hypnea: Hypnea asiatica, Hypnea saidana, Hypnea variabilis, Hypnea japonica, Genus Phacelocarpus: Phacelocarpus japonicus, Genus Caulacanthus: Caulacanthus ustulatus, Genus Sarcodia: Sarcodia ceylanica, Genus Gracilaria: Gracilaria vermiculophylla, Gracilariopsis chorda, Gracilaria parvispora, Gracilaria gigas, Gracilaria incurvata, Gracilaria textorii, Gracilaria rhodocaudata, Gracilaria salicornia, Gracilaria srilankia, Gracilaria sublittoralis, Gracilaria vieillardii, Hydropuntia edulis, Hydropuntia eucheumatoides, Gracilariopsis lemaneiformis, Gracilaria punctata, Gracilaria arcuata, Gracilaria blodgettii, Hydropuntia sp., Gracilaria cuneifolia, Genus Gelidiopsis: Ceratodictyon hachijoense, Genus Gracilaria : Gracilaria salicornia, Genus Tylotus: Tylotus lichenoides, Genus Ceratodictyon: Ceratodictyon spongiosum, Genus Ahnfeltiopsis: Ahnfeltiopsis flabelliformis, Genus Ahnfeltiopsis: Ahnfeltia plicata, Ahnfeltiopsis concinna, Ahnfeltia paradoxa, Genus Stenogramma: Stenogramma interrupta, Genus Chondracanthus: Mastocarpus yendoi, Gigartina ochotensis, Mastocarpus pacificus, Genus Chondrus: Chondrus yendoi, Genus Mazzaella: Mazzaella japonica, Genus Gloioderma: Gloioderma japonica, Genus Gloiocladia: Gloiocladia spinulosa, Gloiocladia stipitata, Genus Chrysymenia: Chrysymenia wrightii, Chrysymenia okamurae, Genus Coelarthrum: Coelarthrum opuntia, Chamaebotrys boergesenii, Genus Botryocladia: Botryocladia leptopoda, Genus Cryptarachne: Cryptarachne polyglandulosa, Genus Palmaria: Palmaria palmata, Rhodymenia intricata, Sparlingia pertusa, Genus Halichrysis: Halichrysis micans, Genus Devaleraea: Devaleraea yendoi, Genus Lomentaria: Lomentaria catenata, Lomentaria pinnata, Lomentaria okamurae, Genus Champia: Champia bifida, Champia expansa, Genus Ceramium: Ceramium kondoi, Ceramium tenerrimum, Ceramium paniculatum, Ceramium japonicum, Ceramium boydenii, Genus Campylaephora: Campylaephora hypnaeoides, Campylaephora crassa, Microcladia: Microcladia elegans, Genus Reinboldiella: Reinboldiella schmitziana, Family Delesseriaceae: Marionella schmitziana, Congregatocarpus kurilensis, Neoholmesia japonica, Genus Sorella: Sorella repens, Genus Polyneura: Polyneura japonica, Genus Neohypophyllum: Neohypophyllum middendorfii, Genus Myriogramme: Myriogramme polyneura, Hideophyllum yezoense, Genus Acrosorium: Acrosorium venulosum, Acrosorium flabellatum, Acrosorium polyneurum, Acrosorium yendoi, Genus Hymenena: Hymenena tenuis, Genus Martensia: Martensia fragilis, Genus Caloglossa: Caloglossa continua, Genus Dasya: Dasya sessilis, Genus Heterosiphonia: Heterosiphonia japonica, Heterosiphonia pulchra, Genus Rhodoptilum: Rhodoptilum plumosum, Genus Polysiphonia: Polysiphonia morrowii, Polysiphonia crassa, Genus Digenea: Digenea simplex, Genus Chondria: Chondria armata, Chondria crassicaulis, Chondria dasyphylla, Chondria intertexta, Chondria ryukyuensis, Chondria expansa, Chondria lancifolia, Genus Laurencia: Palisada intermedia, Chondrophycus undulatus, Laurencia pinnata, Laurencia brongniartii, Genus Pterosiphonia: Pterosiphonia pinnulata, Kintarosiphonia fibrillosa, Genus Symphyocladia: Symphyocladia marchantioides, Symphyocladia latiuscula, Symphyocladia linearis, Genus Herposiphonia: Herposiphonia fissidentoides, Herposiphonia subdisticha, Genus　Amansia: Amansia rhodantha, Amansia japonica, Amansia mitsuii, Genus Enantiocladia: Enantiocladia okamurae, Genus Aneurianna: Aneurianna lorentzii, Genus Neurymenia: Neurymenia fraxinifolia, Genus Neorhodomela: Neorhodomela aculeata, Genus Odonthalia: Odonthalia corymbifera, Genus Batrachospermum: Batrachospermum gelatinosum, Batrachospermum virgatum, Batrachospermum gallaei, Genus Cyanidium: Cyanidium caldarium, Genus Nemalionopsis: Nemalionopsis tortuosa, Genus Polysiphonia, Genus Porphyridium: Porphyridium purpureum, Genus Thorea: Thorea okadae, etc.);
　　　 Charophyta (Genus Chara, Genus Lamprothamnium, Genus Nitellopsis: Nitellopsis obtusa, Genus Lychnothamnus, Genus Nitella: Nitella flexilis var. flexilis, Nitella acuminata var. capitulifera, Genus Tolypella, etc.); and golden algae (Genus Chromophyton: Chromophyton rosanoffii, etc.).
　　　 Examples of materials of animal origin include cockscomb extract; bovine, swine or human placental extracts; bovine or swine stomach, duodenum, intestine and spleen extracts and decomposition products thereof; bovine or swine brain tissue extracts; collagen derivatives, such as bovine, swine or fish collagen hydrolysates (treated with an acid, an alkali, an enzyme or the like), water-soluble collagens and acylated collagens; bovine or swine elastin, hydrolysates thereof (treated with an acid, an alkali, an enzyme or the like) and water-soluble elastin derivatives; keratin, decomposition products thereof, and derivatives thereof; silk proteins, decomposition products thereof, and derivatives thereof; decomposition products of swine or bovine hemocyte proteins (globin peptide); decomposition products of bovine or swine hemoglobins (e.g., hemin, hematin, heme, protoheme and heme iron); milk, casein, decomposition products thereof, and derivatives thereof; skim milk powder, decomposition products thereof, and derivatives thereof; lactoferrin and decomposition products thereof; hen egg components; decomposition products of fish meat; and nucleic acid-related substances (e.g., ribonucleic acid and deoxyribonucleic acid).
　　　 As materials of plant or animal origin, arbitrary parts, cells, tissues, organs, metabolites and the like that are derived from genetically modified organisms and cell fusion products can be used as well.　Moreover, for example, undifferentiated cell colonies and colonies of differentiating cells, which are obtained by cell-culturing an arbitrary part, cell, tissue, organ or the like, can also be used.
(14) Marine Components
　　　 Examples of marine components include seawater such as deep sea water, for example, sea salts and dried sea water; inorganic salts obtained from the sea water of the Dead Sea, Atlantic Ocean or Pacific Ocean (e.g., sodium chloride, magnesium chloride and potassium chloride); sea sludge and mud (fango) of various places, such as Italian fango, German fango, Eifel fango and Freiburg fango (ingredients: silicon dioxide, titanium dioxide, aluminum oxide, iron oxide, manganese oxide, sodium oxide, potassium oxide, magnesium oxide, calcium oxide, strontium oxide, sodium, potassium, magnesium, calcium, chromium, iron, copper, nickel, zinc, lead, manganese, arsenic and water); and Shotoku stone.
(15) Microbial Culture Metabolites
　　　 Examples of microbial culture metabolites include yeast metabolites; yeast extract; bacterial metabolites; bacterial extracts; fungal and actinomycete metabolites; fungal and actinomycete extracts; Bacillus natto metabolites; fermented soybean extract; fermented rice extract; fermented rice bran (red bran and white bran) extract; euglena extract, decomposition products thereof, and water-soluble derivatives thereof; trehalose and its derivatives; lactic acid fermentation products of raw milk and skim milk powder; lactic acid bacteria fermentation products of plants belonging to the family Leguminosae; and lactic acid bacteria fermentation products of plants belonging to the genus Cocos.
(16) α-hydroxy Acids
　　　 Examples of α-hydroxy acids include glycolic acid, citric acid, malic acid, tartaric acid, and lactic acid.
(17) Inorganic Pigments
　　　 Examples of inorganic pigments include silicic anhydride, magnesium silicate, talc, kaolin, bentonite, mica, mica-titanium, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, calcium carbonate, magnesium carbonate, yellow iron oxide, red iron oxide, black iron oxide, ultramarine, chromium oxide, chromium hydroxide, carbon black, and calamine.
(18) Ultraviolet Absorbers and Blocking Agents
　　　 Examples of ultraviolet absorbers and blocking agents include benzophenone derivatives (e.g., 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate, dihydroxydimethoxybenzophenone, sodium dihydroxydimethoxybenzophenone-sulfonate, 2,4-dihydroxybenzophenone and tetrahydroxybenzophenone), p-aminobenzoic acid derivatives (e.g., p-aminobenzoic acid, ethyl p-aminobenzoate, glyceryl p-monobenzoate, amyl p-aminobenzoate and octyl p-aminobenzoate), methoxycinnamic acid derivatives (e.g., ethyl p-methoxycinnamate, isopropyl p-methoxycinnamate, octyl p-methoxycinnamate, 2-ethoxyethyl p-methoxycinnamate, sodium p-methoxycinnamate, potassium p-methoxycinnamate and glyceryl di-p-methoxycinnamate mono-2-ethylhexanoate), salicylic acid derivatives (e.g., octyl salicylate, phenyl salicylate, homomenthyl salicylate, dipropylene glycol salicylate, ethylene glycol salicylate, myristyl salicylate and methyl salicylate), anthranilic acid derivatives (e.g., methyl anthranilate), urocanic acid derivatives (e.g., urocanic acid and ethyl urocanate), coumarin derivatives, amino acid compounds, benzotriazole derivatives, tetrazole derivatives, imidazoline derivatives, pyrimidine derivatives, dioxane derivatives, camphor derivatives, furan derivatives, pyrone derivatives, nucleic acid derivatives, allantoin derivatives, nicotinic acid derivatives, vitamin B6 derivatives, umbelliferone, esculin, benzyl cinnamate, cinoxate, oxybenzone, dioxybenzone, octabenzone, sulisobenzone, benzoresorcinol, arbutin, guaiazulene, shikonin, baicalin, baicalein, berberine, Neo Heliopan, Escalol, zinc oxide, talc, and kaolin.
(19) Skin-whitening Agents
　　　 Examples of skin-whitening agents include p-aminobenzoic acid derivatives, salicylic acid derivatives, anthranilic acid derivatives, coumarin derivatives, amino acid compounds, benzotriazole derivatives, tetrazole derivatives, imidazoline derivatives, pyrimidine derivatives, dioxane derivatives, camphor derivatives, furan derivatives, pyrone derivatives, nucleic acid derivatives, allantoin derivatives, nicotinic acid derivatives, vitamin C and its derivatives (e.g., magnesium salt of vitamin C phosphate, and vitamin C glucoside), vitamin E and its derivatives, kojic acid and its derivatives, oxybenzone, benzophenone, arbutin, guaiazulene, shikonin, baicalin, baicalein, berberine, placenta extract, ellagic acid, and Rucinol.
(20) Tyrosinase Activity Inhibitors
　　　 Examples of tyrosinase activity inhibitors include vitamin C and its derivatives (e.g., magnesium salt of vitamin C phosphate, and vitamin C glucoside), hydroquinone and its derivatives (e.g., hydroquinone benzyl ether), kojic acid and its derivatives, vitamin E and its derivatives, N-acetyltyrosine and its derivatives, glutathione, hydrogen peroxide, zinc peroxide, placenta extract, ellagic acid, arbutin, Rucinol, silk extract, and plant extracts (e.g., chamomile, mulberry, common gardenia, Japanese angelica root, burnet, shrubby sophora, mugwort, Japanese honeysuckle, phellodendron bark, houttuyniae herba, hoelen, Job's tears, white-dead nettle, hop, Japanese hawthorn, eucalyptus, yarrow, marshmallow, cinnamon bark, beach vitex fruit, hamamelis, Japanese mulberry, isodon herb, Chinese bellflower, dodder seed, caper spurge seed, leopard flower, ephedra, cnidium rhizome, aralia rhizome, bupleurum root, saposhnikovia root, glehnia root, scutellaria root, moutan bark, peony root, geranium herb, pueraria root, glycyrrhiza, sumac gallnut, aloe, cimicifuga rhizome, safflower, green tea, black tea, and gambir).
(21) Melanin Pigment Reducing/Decomposing Substances
　　　 Examples of melanin pigment reducing/decomposing substance include phenylmercuric hexachlorophene, mercuric oxide, mercurous chloride, hydrogen peroxide, zinc peroxide, and hydroquinone and its derivatives (e.g., hydroquinone benzyl ether).
(22) Turnover-promoting/Cell-activating Substances
　　　 Examples of turnover-promoting/cell-activating substances include hydroquinone, lactic acid bacteria extracts, placenta extract, reishi mushroom extract, vitamin A, vitamin E, allantoin, spleen extract, thymus extract, yeast extract, fermented milk extract, and plant extracts (e.g., aloe, scutellaria root, horsetail, gentian, burdock, lithospermum root, carrot, hamamelis, hop, coix seed, white-dead nettle, swertia herb, Japanese angelica root, pot marigold, sweet hydrangea leaf, hypericum, cucumber, thyme, rosemary, and parsley).
(23) Astringents
　　　 Examples of astringents include succinic acid, allantoin, zinc chloride, zinc sulfate, zinc oxide, calamine, zinc p-phenol sulfonate, aluminum potassium sulfate, resorcin, ferric chloride, and tannic acid (including catechin compound).
(24) Active Oxygen Scavengers
　　　 Examples of active oxygen scavengers include SOD, catalase, and glutathione peroxidase.
(25) Anti-oxidants
　　　 Examples of anti-oxidants include vitamin C salts thereof, stearic acid esters, vitamin E and salts thereof, nordihydroguaiaretic acid, butylhydroxytoluene (BHT), butylhydroxyanisole (BHA), hydroxytyrosol, p-hydroxyanisole, propyl gallate, sesamol, sesamolin, gossypol, and propolis.
(26) Lipid Peroxide Production Inhibitors
　　　 Examples of lipid peroxide production inhibitors include β-carotene and plant extracts (e.g., sesame cultured cells, sweet hydrangea leaf, hypericum, hamamelis, clove, melissa, isodon herb, white birch, scarlet sage, rosemary, heavenly bamboo fruit, rose fruit, ginkgo, and green tea).
(27) Anti-inflammatory Agents
　　　 Examples of anti-inflammatory agents include ichthammol, indomethacin, kaolin, salicylic acid, sodium salicylate, methyl salicylate, acetylsalicylic acid, diphenhydramine hydrochloride, d-camphor, dl-camphor, hydrocortisone, guaiazulen, chamazulene, chlorpheniramine maleate, glycyrrhizic acid and salts thereof, glycyrrhetinic acid and salts thereof, glycyrrhiza extract, lithospermum root extract, rose fruit extract, and propolis.
(28) Antibacterial Agents, Sterilizers and Disinfectants
　　　 Examples of antibacterial agents, sterilizers and disinfectants include acrinol, sulfur, calcium gluconate, chlorhexidine gluconate, sulfamine, mercurochrome, lactoferrin and its hydrolysate, alkyldiaminoethylglycine chloride solutions, triclosan, sodium hypochlorite, chloramine T, bleaching powder, iodine compounds, iodoform, sorbic acid and salts thereof, propionic acid and salts thereof, salicylic acid, dehydroacetic acid, p-hydroxybenzoic acid esters, undecylenic acid, thiamine lauryl sulfate, thiamine lauryl nitrate, phenol, cresol, p-chlorophenol, p-chloro-m-xylenol, p-chloro-m-cresol, thymol, phenethyl alcohols, O-phenylphenol, Irgasan CH3565, halocarban, hexachlorophene, chlorhexidine, ethanol, methanol, isopropyl alcohols, benzyl alcohols, ethylene glycol, propylene glycol, 2-phenoxyethanol, 1,2-pentanediol, zinc pyrithione, chlorobutanol, isopropylmethylphenol, nonionic surfactants (e.g., polyoxyethylene lauryl ether, polyoxyethylene nonylphenyl ether, and polyoxyethylene octylphenyl ether), amphoteric surfactants, anionic surfactants (e.g., sodium lauryl sulfate and potassium lauroyl sarcosinate), cationic surfactants (e.g., cetyltrimethylammonium bromide, benzalkonium chloride, benzethonium chloride and methylrosaniline chloride), formaldehyde, hexamine, brilliant green, malachite green, crystal violet, Germall, photosensitizer 101, photosensitizer 201, photosensitizer 401, an N-long-chain acyl basic amino acid derivatives and acid addition salts thereof, zinc oxide, hinokitiol, sophora root, and propolis.
(29) Moisturizing Agents
　　　 Examples of moisturizing agents include glycerin, propylene glycol, 1,3-butylene glycol, hyaluronic acid and salts thereof, polyethylene glycol, chondroitin sulfate and salts thereof, water-soluble chitin derivatives, water-soluble chitosan derivatives, pyrrolidonecarboxylic acid and salts thereof, sodium lactate, mini-Sasanishiki extract, Bacillus natto metabolites, fermented soybean extract, loofah water, and saps of white birch and Japanese red pine.
(30) Elastase Activity Inhibitors
　　　 Examples of elastase activity inhibitors include diisopropyl fluorophosphate, plant extracts (e.g., scutellaria root, hypericum, sophora root, mulberry leaf, cinnamon bark, geranium herb, comfrey, scarlet sage, elder, linden and moutan bark), and seaweed extracts.
(31) Hair-care Agents
　　　 Examples of hair-care agents include selenium disulfide, alkylisoquinolium bromide solutions, zinc pyrithione, biphenamine, thianthol, castoreum tincture, ginger tincture, capsicum tincture, quinine hydrochloride, strong aqueous ammonia, potassium bromate, sodium bromate, and thioglycolic acid.
(32) Antiandrogen Agents
　　　 Examples of antiandrogen agents include estrogens (e.g., estrone, estradiol and ethinyl estradiol), isoflavone, and oxendolone.
(33) Peripheral Blood Flow Promoters
　　　 Examples of peripheral blood flow promoters include vitamin E and its derivatives, swertia herb extract, garlic extract, ginseng extract, aloe extract, gentian extract, angelica root extract, cepharanthine, carpronium chloride, and minoxidil.
(34) Stimulating Agents
　　　 Examples of stimulating agents include capsicum tincture, nonylic acid vanillylamide, cantharides tincture, ginger tincture, peppermint oil, 1-menthol, camphor, and benzyl nicotinate.
(35) Metabolic Activators
　　　 Examples of metabolic activators include photosensitizer 301, hinokitiol, pantothenic acid and its derivatives, allantoin, placenta extract, biotin, and pentadecanoic acid glyceride.
(36) Antiseborrheic Agents
　　　 Examples of antiseborrheic agents include pyridoxine and its derivatives, sulfur, and vitamin B6.
(37) Keratolytic Agents
　　　 Examples of keratolytic agents include resorcin, salicylic acid, lactic acid, and urea.
(38) Oxidizing Agents
　　　 Examples of oxidizing agents include hydrogen peroxide, sodium persulfate, ammonium persulfate, sodium perborate, urea peroxide, sodium percarbonate, sodium tripolyphosphate peroxide, sodium bromate, potassium bromate, sodium pyrophosphate peroxide, sodium orthophosphate peroxide, sodium silicate-hydrogen peroxide adduct, sodium sulfate-hydrogen peroxide adduct, sodium chloride-hydrogen peroxide adduct, β-tyrosinase solution, and mushroom extract.
(39) Hair-removing Agents
　　　 Examples of hair-removing agents include inorganic reducing agents such as strontium sulfate, sodium sulfide, barium sulfide and calcium sulfide; and thioglycolic acid and salts thereof (e.g., calcium thioglycollate, sodium thioglycollate, lithium thioglycollate, magnesium thioglycollate and strontium thioglycollate).
(40) Hair-swelling Agents
　　　 Examples of hair-swelling agents include ethanolamine, urea, and guanidine.
(41) Dyes
　　　 Examples of dyes include 5-amino-o-cresol, 2-amino-4-nitrophenol, 2-amino-5-nitrophenol, 1-amino-4-methylaminoanthraquinone, 3,3'-iminodiphenol, 2,4-diaminophenoxyethanol hydrochloride, 2,4-diaminophenol hydrochloride, toluene-2,5-diamine hydrochloride, nitro-p-phenylenediamine hydrochloride, p-phenylenediamine hydrochloride, N-phenyl-p-phenylenediamine hydrochloride, m-phenylenediamine hydrochloride, o-aminophenol, N-phenyl-p-phenylenediamine acetate, 1,4-diaminoanthraquinone, 2,6-diaminopyridine, 1,5-dihydroxynaphthalene, toluene-2,5-diamine, toluene-3,4-diamine, nitro-p-phenylenediamine, p-aminophenol, p-nitro-o-phenylenediamine, p-phenylenediamine, p-methylaminophenol, picramic acid, sodium picramate, N,N'-bis(4-aminophenyl)-2,5-diamino-1,4-quinonediimine, 5-(2-hydroxyethylamino)-2-methylphenol, N-phenyl p-phenylenediamine, m-aminophenol, m-phenylenediamine, 5-amino-o-cresol sulfate, 2-amino-5-nitrophenol sulfate, o-aminophenol sulfate, o-chloro-p-phenylenediamine sulfate, 4,4'-diaminodiphenylamine sulfate, 2,4-diaminophenol sulfate, toluene-2,5-diamine sulfate, nitro-p-phenylenediamine sulfate, p-aminophenol sulfate, p-nitro-o-phenylenediamine sulfate, p-nitro-m-phenylenediamine sulfate, p-phenylenediamine sulfate, p-methylaminophenol sulfate, m-aminophenol sulfate, m-phenylenediamine sulfate, catechol, diphenylamine, α-naphthol, hydroquinone, pyrogallol, phloroglucinol, gallic acid, resorcin, tannic acid, sodium 2-hydroxy-5-nitro-2',4'-diaminoazobenzene-5'-sulfonate, and hematein.
(42) Fragrance Agents
　　　 Examples of fragrance agents include natural animal fragrance agents such as musk, civet, castoreum and ambergris; plant fragrance agents such as anise essential oil, angelica essential oil, ylang-ylang essential oil, iris essential oil, fennel essential oil, orange essential oil, cananga essential oil, caraway essential oil, cardamom essential oil, guaiacwood essential oil, cumin essential oil, lindera essential oil, cassia essential oil, cinnamon essential oil, geranium essential oil, copaiba balsam essential oil, coriander essential oil, perilla essential oil, cedar wood essential oil, citronella essential oil, jasmine essential oil, ginger-grass essential oil, Japanese cedar essential oil, spearmint essential oil, peppermint essential oil, star anise essential oil, tuberose essential oil, clove essential oil, neroli essential oil, wintergreen essential oil, tolu balsam essential oil, patchouli essential oil, rose essential oil, palmarosa essential oil, Japanese cypress essential oil, cedar essential oil, sandalwood essential oil, petitgrain essential oil, bay essential oil, vetiver essential oil, bergamot essential oil, Peru balsam essential oil, bois de rose essential oil, Ho-leaf essential oil, mandarin essential oil, eucalyptus essential oil, lime essential oil, lavender essential oil, linaloe essential oil, lemongrass essential oil, lemon essential oil, rosemary essential oil and Japanese peppermint essential oil; and other synthetic fragrance agents.
(43) Pigments and Coloring Agents
　　　 Examples of pigments and coloring agents include red cabbage pigment, red-kerneled rice pigment, madder pigment, annatto pigment, sepia pigment, turmeric pigment, sophora pigment, krill pigment, persimmon pigment, caramel, gold, silver, gardenia pigment, corn pigment, onion pigment, tamarind pigment, spirulina pigment, buckwheat herb pigment, cherry pigment, laver pigment, hibiscus pigment, grape juice pigment, marigold pigment, purple sweet potato pigment, purple yam pigment, lac pigment, and rutin.
(44) Other Additives
　　　 Examples of other additives include hormones, metal ion-blocking agents, pH adjusting agents, chelating agents, antiseptic/antifungal agents, refrigerants, stabilizing agents, emulsifying agents, animal/plant proteins and decomposition products thereof, animal/plant polysaccharides and decomposition products thereof, animal/plant glycoproteins and decomposition products thereof, blood-flow promoters, anti-inflammatory/anti-phlogistic agents, anti-allergic agents, wound-healing agents, foaming agents, thickening agents, enzymes, purified water (including electronic water, microcluster water and the like), oral-care agents, deodorants, bittering agents, and seasonings.　The use of these additives in combination can be expected to additively or synergistically improve the effects of the present invention or other cosmetic effects.
　　　　　　　　　　　　　　　EXAMPLES
　　　 Examples where Enterococcus faecalis EC-12, which most prominently showed the intended effects of the present invention, was used as a lactic acid bacterium belonging to the genus Enterococcus will now be described; however, the present invention is not restricted to the following examples and the like.
(Deposition of Microorganism)
　　　 Enterococcus faecalis EC-12 has been deposited with the International Patent Organism Depositary, National Institute of Advanced Industrial Science and Technology (AIST Tsukuba Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki, Japan) as of February 25, 2005 under accession No. FERM BP-10284 (original deposit date).
　　　 According to a preferred mode of the present invention, the bacterium used as an effective ingredient is one belonging to the genus Enterococcus.　The bacterium is more preferably Enterococcus faecalis.
　　　 As Enterococcus faecalis, strains such as Enterococcus faecalis EC-12 (accession No. FERM BP-10284), ATCC 19433, ATCC 14508, ATCC 23655, IFO 16803 and IFO 16804, and variants thereof can be exemplified.　Thereamong, the EC-12 strain is most preferred as the bacterium used as an effective ingredient.
　　　 The term "variants" used herein is meant to encompass ones that are obtained by those of ordinary skill in the art through mutation of a specific strain within such a range that does not modify the properties of the specific strain in accordance with a method well-known to those of ordinary skill in the art, as well as ones that can be confirmed to be equivalent thereto by those of ordinary skill in the art.
(Acquisition of Lactic Acid Bacterium Belonging to the Genus Enterococcus and Heat-killed Cells Thereof)
　　　 Enterococcus faecalis EC-12 (accession No. FERM BP-10284) was purchased from Combi Corporation.
(Production of Plant Polysaccharides)
　　　 As plant polysaccharides, Aloe vera polysaccharides were produced.　Aloe vera leaves in an amount of 100 g were ground and subsequently subjected to squeezing, extraction and filtration, after which ethanol or isopropanol was added to the thus obtained filtrate, followed by stirring.　Then, the resulting precipitates were recovered and washed by again adding thereto ethanol or isopropanol, and the thus washed precipitates were dried to obtain Aloe vera polysaccharide powder.
(Preparation of Samples)
　　　 The thus produced heat-killed cells of Enterococcus lactic acid bacterium and Aloe vera polysaccharides were mixed to prepare samples 1 to 4 as shown in Table 1 (culture medium-added final concentration).
Figure JPOXMLDOC01-appb-T000001
(Culturing of Staphylococcus epidermidis Type Strain)
　　　 As a culture medium, Nutrient Broth No. 2 (manufactured by Nissui Pharmaceutical Co., Ltd.) was used.　To this culture medium, the samples 1 to 4 (values shown in Table: culture medium final concentration, %) were each added.　Then, Staphylococcus epidermidis type strain (ATCC 12228) was inoculated into the culture medium at 1 to 5 × 103 CFU/μL and cultured at 37°C for 24 hours.　As a control, a sample without addition of the heat-killed cells of Enterococcus lactic acid bacterium was used (sample 1).
(Method of Recovering Human Skin Resident Bacteria)
　　　 Skin resident bacteria were collected by rubbing three times in the vertical direction and three times in the lateral direction of a 3 cm-square glabellar area with a sterile swab.　The swab was subsequently washed in 10 mL of phosphate buffered physiological saline to recover the bacteria.
(Culturing of Human Skin Resident Bacteria)
　　　 As a culture medium, Nutrient Broth No. 2 (manufactured by Nissui Pharmaceutical Co., Ltd.) was used.　To this culture medium, the heat-killed cells of Enterococcus lactic acid bacterium were added at a final concentration of 0.25, 0.5 or 1.0 w/w%.　Then, the skin resident bacteria recovered by the above-described method were inoculated into 100 μL of each culture medium, which was subsequently cultured at 37°C for 24 hours.　As a control, the culture medium with no addition of heat-killed bacterial cells was used.
(Measurement of Glycerol Amount)
　　　 The resulting cultures of the Staphylococcus epidermidis type strain (ATCC 12228) and human skin resident bacteria were each fractionated.　These cultures were stirred using a vortex mixer, and the amount of glycerol was measured in accordance with a conventional method using Glycerol Assay Kit (manufactured by Cayman Chemical).
(Glycerol Amount Measurement Results)
　　　 The results are shown in FIGs. 1 and 2.　The addition of the heat-killed cells of Enterococcus lactic acid bacterium resulted in a significantincrease in the glycerol production of the Staphylococcus epidermidis type strain (ATCC 12228) (FIG. 1).　An about 10-fold glycerol production-promoting effect was observed when the addition to the culture medium was made at a final concentration of 1.0 w/w% (sample 2).　Further, when the Aloe vera polysaccharides (0.1 w/w%) were added in combination (sample 4), the glycerol production of the Staphylococcus epidermidis type strain was synergistically increased.　An increase in the glycerol production by an addition of heat-killed cells of Enterococcus lactic acid bacterium was also observed for the cultures of human skin resident bacteria (FIG. 2).
(Human Monitor Test)
　　　 Male and female panelists (a total of 18 test subjects) performed prebed facial cleansing and subsequently applied a softening lotion containing the heat-killed cells of Enterococcus lactic acid bacterium (beauty lotion A) on the right cheek and a placebo softening lotion containing no heat-killed cell of Enterococcus lactic acid bacterium (beauty lotion B) as a control on the left cheek every day for 7 consecutive days (the formulations of these softening lotions are shown below).　After waking up on the 8th day, a 3 cm-square area on each cheek was rubbed with a sterile swab three times in the vertical direction and three times in the lateral direction to collect glycerol on the skin surface.　Then, the swab was washed in 200 μL of phosphate buffered physiological saline to disperse metabolites.
(Softening Lotion)
　　　 Heat-killed cells of Enterococcus lactic acid bacterium
　　　　　　　　　　　　　　　　　　　　　　 0 or 0.1 w/v%
　　　 Ethanol　　　　　　　　　　 5.0%
　　　 1,3-butylene glycol　　　　　　　　　8.0%
　　　 PEG-60 hydrogenated castor oil　　　　0.2%
　　　 Fragrance agent　　　　　　　　　　　0.01%
　　　 Methylparaben　　　　　　　　 0.15%
　　　 Citric acid　　　　　　　　　　　　　0.02%
　　　 3Na citrate　　　　　　　　　　　　　0.08%
　　　 EDTA-2Na　　　　　　　　　　　　　　0.03%
　　　 Water　　　　　　　　　　　　　　　balance to 100
　　　 The above components were uniformly mixed in accordance with a conventional method to obtain the softening lotions (beauty lotion A and beauty lotion B).
(Measurement of Glycerol Amount)
　　　 The thus obtained dispersion was stirred using a vortex mixer, and the amount of glycerol was measured in accordance with a conventional method using Glycerol Assay Kit (manufactured by Cayman Chemical).
(Glycerol Amount Measurement Results)
　　　 The results are shown in FIG. 3.　The use of the softening lotion containing the heat-killed cells of Enterococcus lactic acid bacterium resulted in a significantincrease in the amount of glycerol on the skin surface of the human monitors as compared to the use of the control softening lotion.
(Sensory Evaluation in Human Monitor Test)
　　　 The male and female panelists (a total of 18 test subjects) who participated in the human monitor test was given a questionnaire survey with regard to the use feeling of the tested softening lotions and the skin condition before and after the test.　The answers thereof are shown in Table 2.
Figure JPOXMLDOC01-appb-T000002
(Human β-defensin-2 (hBD2) and Human β-defensin-3 (hBD3): Quantitative Analysis of mRNA)
　　　 Using a 24-well plate with a culture medium for epidermal cells (Humedia KG2, manufactured by Kurabo Industries Ltd.), human epidermal keratinocytes (manufactured by Kurabo Industries Ltd.) were cultured to sub-confluency.　The human epidermal keratinocytes were further cultured in a differentiation-inducing culture medium, which was prepared by adding calcium to Humedia KG2, for 3 days at 37°C in the presence of 5%CO2, after which the culture medium was replaced with a fresh one.　To this culture medium, the heat-killed cells of Enterococcus lactic acid bacterium were added at a final concentration of 0.25, 0.5 or 1.0 w/w%.　As a positive control, Staphylococcus epidermidis type strain was added at a concentration of about 1 × 104 cells/mL.　After 6 hours of culturing, total RNA was extracted from the human epidermal keratinocytes using RNeasy (manufactured by QIAGEN).　Using each of the thus extracted RNAs as a template, cDNAs were prepared by performing reverse transcription reaction in accordance with a conventional method using SuperScript VILO (manufactured by Invitrogen).
　　　 PCR was performed using the thus obtained cDNAs.　As for the PCR conditions, the primers shown in Table 3 were prepared based on the cDNA sequence of human β-defensin-2 (accession No. NG_023301) and the cDNA sequence of human β-defensin-3 (accession No. NC_000008), and TAKARA Human Housekeeping Gene Primer Set Human ACTB Primer was used as the primer for β-actin utilized as an internal standard.
Figure JPOXMLDOC01-appb-T000003
　　　 PCR was performed using One Step SYBRR PrimeScriptTM RT-PCR Kit (manufactured by TAKARA Bio Inc.), and real-time PCR analysis was performed in accordance with a conventional method using TaKaRa PCR Thermal Cycler Dice.　By the real-time PCR analysis, the mRNA amount was relatively quantified for human β-defensin-2, human β-defensin-3 and β-actin.
(Method of Evaluating mRNA Amounts of Human β-defensin-2, Human β-defensin-3 and β-actin)
　　　 The mRNA amounts of human β-defensin-2, human β-defensin-3 and β-actin were evaluated in terms of percentage with respect to the mRNA amount of β-actin used as an internal standard.
　　　 Relative expression level of human β-defensin-2 or human β-defensin-3 mRNA (% of control) = (Amount of human β-defensin-2 or human β-defensin-3 mRNA)/(Amount of β-actin mRNA) × 100
(Results of Quantitative Analysis of Human β-defensin-2 and Human β-defensin-3 mRNAs)
　　　 The results are shown in Fig. 4.　The addition of the heat-killed cells of Enterococcus lactic acid bacterium also resulted in an increase in the expression levels of β-defensin-2 and β-defensin-3 mRNAs in the human epidermal keratinocytes (FIG. 4).
(Production Examples of Various External Preparations for Skin Protection)
1. Sunscreen Cream (O/W Cream-type)
(Oil Phase)
　　　 2-ethylhexyl p-methoxycinnamate　　　 5.0%
　　　 4-t-butyl-4'-methoxydibenzoylbutane　 1.0%
　　　 Squalane　　　　　　　　　　　　　　　　　 10.0%
　　　 Vaseline　　　　　　　　　　　　　　　　　 5.0%
　　　 Stearyl alcohol　　　　　　　　　　　　　　 3.0%
　　　 Stearic acid　　　　　　　　　　　　　　　 3.0%
　　　 Glyceryl monostearate　　　　　　　　3.0%
　　　 Polyacrylic acid　　　　　　　　　　　　　 1.0%
　　　 Anti-oxidant　　　　　　　　　　　　appropriate amount
　　　 Antiseptic agent　　　　　　　　　　appropriate amount
　　　 Fragrance agent　　　　　　　　　　　appropriate amount
　　　 Heat-killed cells of Enterococcus lactic acid bacterium
　　　　　　　　　　　　　　　0.01 to 1% (appropriate amount)
(Aqueous Phase)
　　　 Purified water　　　　　　　　　　　balance to 100
　　　 Dipropylene glycol　　　　　　　　　　　　 7.0%
　　　 Titanium dioxide (surface-treated with alumina)
　　　　　　　　　　　　　　　　　　　　　　　　　　5.0%
　　　 Disodium edetate　　　　　　　　　　　　　 0.05%
　　　 Triethanolamine　　　　　　　　　　　　　　 1.0%
(Production Method)
　　　 The oil phase and the aqueous phase were each heated to 70°C to dissolve the components.　In the aqueous phase, titanium dioxide was thoroughly dispersed and, after adding thereto the oil phase and homogenizing emulsified particles using a homomixer, the resultant was degassed, filtered, cooled and then recovered.　As for the cooling method, the cooling was performed by, for example, a method of slowly cooling the resultant under stirring with a refrigerantinjected into the jacket of the production pot or a method of cooling the resultant using a heat exchanger.
2. Sunscreen Milky Lotion (W/O-type Milky Lotion)
(Oil Phase)
　　　 2-ethylhexyl p-methoxycinnamate　　　 5.0%
　　　 Titanium dioxide (hydrophobized)　　　5.0%
　　　 Zinc oxide (hydrophobized)　　　　　　9.0%
　　　 Squalane　　　　　　　　　　　　　　　　　 20.0%
　　　 Silicone oil　　　　　　　　　　　　　　　 23.0%
　　　 Silicone resin　　　　　　　　　　　　　　 2.0%
　　　 Glycerin diisostearate　　　　　　　2.0%
　　　 Organically modified montmorillonite　0.5%
　　　 Antiseptic agent　　　　　　　　　　appropriate amount
　　　 Fragrance agent　　　　　　　　　　　appropriate amount
　　　 Enterococcus lactic acid bacterium
　　　　　　　　　　　　　　　0.01 to 1% (appropriate amount)
(Aqueous Phase)
　　　 Purified water　　　　　　　　　　　balance to 100
　　　 1,3-butylene glycol　　　　　　　　　　　　 5.0%
(Production Method)
　　　 The oil phase and the aqueous phase were each heated to 60°C to dissolve the components.　In the oil phase, titanium dioxide and zinc oxide were thoroughly dispersed and, after adding thereto the aqueous phase and homogenizing emulsified particles using a homomixer, the resultant was degassed, filtered, cooled and then recovered.
3. Sun Oil
　　　 2-ethylhexyl p-methoxycinnamate　　　 2.0%
　　　 Liquid paraffin　　　　　　　　　　　　　　 56.0%
　　　 Isopropyl myristate　　　　　　　　　　　　 10.0%
　　　 Silicone oil　　　　　　　　　　　　　　　 30.0%
　　　 Silicone resin　　　　　　　　　　　　　　 2.0%
　　　 Anti-oxidant　　　　　　　　　　　　appropriate amount
　　　 Fragrance agent　　　　　　　　　　　appropriate amount
　　　 Heat-killed cells of Enterococcus lactic acid bacterium
　　　　　　　　　　　　　　　0.01 to 1% (appropriate amount)
(Production Method)
　　　 The silicone resin was added to and dissolved in silicone oil.　Then, isopropyl myristate was added and the resultant was thoroughly mixed with stirring, after which the remaining components were added and the resultant was stirred.
4. Powder-type Foundation
(Powder)
　　　 Zinc myristate-treated talc　　　　　　　　 20.0%
　　　 Sericite　　　　　　　　　　　　　　　　　 34.6%
　　　 Titanium oxide　　　　　　　　　　　10.0%
　　　 Red iron oxide　　　　　　　　　　　1.0%
　　　 Yellow iron oxide　　　　　　　　　　　　　 4.0%
　　　 Black iron oxide　　　　　　　　　　　　　 0.4%
　　　 Mica surface treated with titanium oxide and aluminum oxide　　　　　　　　　　　 　　　　　　　　　　 15.0%
　　　 Nylon powder　　　　　　　　　　　　5.0%
　　　 Enterococcus lactic acid bacterium
　　　　　　　　　　　　　　　0.01 to 1% (appropriate amount)
(Base Materials)
　　　 Squalane　　　　　　　　　　　　　　　　　 3.0%
　　　 Octyldodecyl myristate　　　　　　　3.5%
　　　 Vaseline　　　　　　　　　　　　　　　　　 2.5%
(Other Components)
　　　 Antiseptic agent　　　　　　　　　　appropriate amount
　　　 Fragrance agent　　　　　　　　　　　appropriate amount
(Production Method)
　　　 The powder components were mixed using a mixer such as a high-speed fluid-type mixer and further made into fine particles using a grinder.　Then, the base materials were added to the fine particles and thoroughly mixed using a vertical screw mixer or the like.　Further, the resultant was pulverized and granulated using a hammer mill or the like and subsequently compression-molded.
5. Two-way Foundation
(Powder)
　　　 Silicon-treated titanium oxide　　　　　　　 10.0%
　　　 Talc　　　　　　　　　　　　　　　　　　　 30.0%
　　　 Sericite　　　　　　　　　　　　　　　　　 39.6%
　　　 Red iron oxide　　　　　　　　　　　1.5%
　　　 Yellow iron oxide　　　　　　　　　　　　　 5.5%
　　　 Black iron oxide　　　　　　　　　　　　　 0.4%
　　　 Methyl methacrylate powder　　　　　　3.0%
　　　 Heat-killed cells of Enterococcus lactic acid bacterium
　　　　　　　　　　　　　　　0.01 to 1 (appropriate amount)
(Base Materials)
　　　 Squalane　　　　　　　　　　　　　　　　　 3.0%
　　　 Dimethylpolysiloxane　　　　　　　　2.0%
　　　 Glycerin triisooctanoate　　　　　　　　　　 3.0%
　　　 Ethyl p-aminobenzoate　　　　　　　　2.0%
(Other Components)
　　　 Antiseptic agent　　　　　　　　　　appropriate amount
　　　 Fragrance agent　　　　　　　　　　　appropriate amount
6. Cream (W/O-type)
(A Phase)
　　　 t-butylmethoxydibenzoyl methane　　　 3.0%
　　　 Hexyl diethylaminohydroxybenzoyl benzoate
　　　　　　　　　　　　　　　　　　　　　　　　　　2.0%
　　　 Dimethicone and caprylyl dimethicone ethoxy glucoside
　　　　　　　　　　　　　　　　　　　　　　　　　　20.0%
　　　 Glyceryl tri(behenate/isostearate/eicosandioate)
　　　　　　　　　　　　　　　　　　　　　　　　　　1.0%
　　　 Stearyl dimethicone　　　　　　　　　　　　 1.0%
　　　 Tocopherol acetate　　　　　　　　　　　　 0.05%
　　　 Benzoic acid　　　　　　　　　　　　　　　 0.3%
　　　 Diisopropyl sebacate　　　　　　　　7.0%
　　　 Octocrylene　　　　　　　　　　　　　　　　 8.0%
　　　 Talc, yellow iron oxide, Mg stearate, titanium dioxide, mica, Al hydroxide, stearic acid 　　　　　　　　　　 1.4%
(B Phase)
　　　 Titanium dioxide, Mg stearate, talc, black iron oxide, Al hydroxide, mica, stearic acid 　　　　　　　　　　 1.13%
　　　 Red and brown iron oxide, Mg stearate, titanium dioxide, mica, water, Al oxide, stearic acid 　　　　　　　0.85%
　　　 Titanium dioxide, talc, Mg stearate, Al hydroxide, mica, stearic acid　　　　　　　 　　　　　　　　　　　　　　3.9%
(C Phase)
　　　 Water　　　　　　　　　　　　　　　　　　 balance to 100
　　　 Mg sulfate　　　　　　　　　　　　　　　　 0.7%
　　　 Betaine　　　　　　　　　　　　　　1.0%
　　　 Na hyaluronate　　　　　　　　　　　0.1%
　　　 Glycerin　　　　　　　　　　　　　　　　　 1.0%
(D Phase)
　　　 Phenoxyethanol　　　　　　　　　　　0.4%
(E Phase)
　　　 Titanium dioxide, glycerin, alumina　 3.5%
(F Phase)
　　　 Dimethyl silylated silica　　　　　　　　　 1.0%
(G Phase)
　　　 Cyclopentasiloxane, (dimethicone/vinyltrimethyl siloxysilicate) cross-polymer　　　 　　　　　　　1.0%
　　　 Heat-killed cells of Enterococcus lactic acid bacterium
　　　　　　　　　　　　　　　0.01 to 1 (appropriate amount)
(H Phase)
　　　 Fragrance agent　　　　　　　　　　　　　　 0.3%
(Production Method)
　　　 The materials of the A phase were mixed with stirring and heated to 70 to 75°C.　The B phase was then added to the A phase with stirring, and the resultant was stirred to homogeneity.　In a separate container, the materials of the C phase were mixed with stirring and heated to 70 to 75°C, and the C phase was slowly added to the A-B mixed phase with stirring (over a period of about 5 minutes), after which the resultant was stirred for about 3 minutes and then naturally cooled.　Once the resultant was cooled to a temperature of 40°C or lower, the D phase was added thereto and stirred for about 1 minute, after which the E phase was added and stirred for about 5 minutes and the F phase was further added and stirred for about 1 minute, followed by addition of the G phase and subsequent stirring for about 1 minute.　Lastly, the H phase was added and stirred for about 2 minutes, after which the resultant was naturally cooled to room temperature.
7. Moisturizing Gel (Beauty Solution)
(A Phase)
　　　 Cetearyl olivate + sorbitan olivate　 3.5%
　　　 Unsaponified olive oil　　　　　　　0.5%
　　　 Dicaprylyl carbonate　　　　　　　　3.0%
　　　 Shea butter　　　　　　　　　　　　　　　　 0.5%
　　　 Wheat germ oil　　　　　　　　　　　0.5%
　　　 Cyclomethicone　　　　　　　　　　　6.0%
　　　 Dimethicone　　　　　　　　　　　　　　　　 1.0%
(B Phase)
　　　 Water　　　　　　　　　　　　　　　　　　 balance to 100
　　　 Glycerin　　　　　　　　　　　　　　　　　 1.5%
　　　 Propylene glycol　　　　　　　　　　　　　 1.5%
　　　 Na polyacrylate　　　　　　　　　　　　　　 0.7%
　　　 Xanthan gum　　　　　　　　　　　　　　　　 0.1%
(C Phase)
　　　 Antiseptic agent　　　　　　　　　　appropriate amount
　　　 Fragrance agent　　　　　　　　　　　appropriate amount
　　　 Menthol　　　　　　　　　　　　　　0.3%
　　　 Ethanol　　　　　　　　　　　　　　3.0%
　　　 Heat-killed cells of Enterococcus lactic acid bacterium
　　　　　　　　　　　　　　　0.01 to 1 (appropriate amount)
(Production Method)
　　　 The A phase and the B phase were each prepared by mixing the respective materials.　Xanthan gum and Na polyacrylate were dispersed using a batch-type dispersion apparatus or the like, and the A phase was added to the B phase at 75°C.　The resultant was homogenized for several minutes and then cooled with gentle stirring, and the C phase was added thereto once the temperature dropped to 40°C (methanol was dissolved in ethanol in advance).
8. Lip Cream
(A Phase)
　　　 Mineral oil　　　　　　　　　　　　　　　　 8.0%
　　　 Red pigment　　　　　　　　　　　　　　　　 1.0%
　　　 Yellow pigment　　　　　　　　　　　0.3%
　　　 Enterococcus lactic acid bacterium
　　　　　　　　　　　　　　　0.01 to 1% (appropriate amount)
(B Phase)
　　　 Caprylic/capric triglyceride　　　　　　　　 balance to 100
　　　 Ethylhexyl methoxycinnamate　　　　　3.0%
　　　 Isopropyl myristate　　　　　　　　　　　　 10.0%
(C Phase)
　　　 Alkyl (C26-28) methicone　　　　　　　　　　 9.0%
　　　 Cetanol　　　　　　　　　　　　　　1.6%
(D Phase)
　　　 Mixture of PEG-8, tocopherol, ascorbyl palmitate, ascorbic acid and citric acid　　 　　　　　　　0.1%
　　　 Propylparaben　　　　　　　　　　　　0.1%
(E Phase)
　　　 Fragrance agent　　　　　　　　　　　　　　 0.2%
　　　 Mixture of mica and titanium oxide　　18.4%
　　　 Mixture of mica, titanium oxide and iron oxide
　　　　　　　　　　　　　　　　　　　　　　　　　　7.0%
　　　 Silica　　　　　　　　　　　　　　　　　　 0.5%
(Production Method)
　　　 The A phase was uniformly premixed and then uniformly mixed with the B phase.　The C phase was further added thereto, and the resultant was heated to 78 to 80°C with gentle stirring, after which the D phase and the E phase were added thereto little by little and the resultant was uniformly stirred, poured into a mold and then naturally cooled to normal temperature.
9. Liquid Foundation (O/W-type)
(Oil Phase)
　　　 Stearic acid　　　　　　　　　　　　　　　 2.4%
　　　 Propylene glycol monostearate　　　　2.0%
　　　 Cetostearyl alcohol　　　　　　　　　　　　 0.2%
　　　 Liquid lanolin　　　　　　　　　　　　　　 2.0%
　　　 Liquid paraffin　　　　　　　　　　　　　　 3.0%
　　　 Isopropyl myristate　　　　　　　　　　　　 8.5%
　　　 Oil-soluble antiseptic agent　appropriate amount
(Aqueous Phase)
　　　 Purified water　　　　　　　　　　　balance to 100
　　　 Sodium carboxymethyl cellulose　　　　　　　 0.2%
　　　 Bentonite　　　　　　　　　　　　　　　　　 0.5%
　　　 Dipropylene glycol　　　　　　　　　　　　 4.0%
　　　 Triethanolamine　　　　　　　　　　　　　　 1.1%
　　　 Aqueous antiseptic agent　　　　　　　appropriate amount
(Powder)
　　　 Titanium oxide　　　　　　　　　　　8.0%
　　　 Talc　　　　　　　　　　　　　　　　　　　 4.0%
　　　 Color pigment　　　　　　　　 appropriate amount
　　　 Heat-killed cells of Enterococcus lactic acid bacterium
　　　　　　　　　　　　　　　0.01 to 1 (appropriate amount)
(Other Component)
　　　 Fragrance agent　　　　　　　　　　　appropriate amount
(Production Method)
　　　 The powder was pulverized and then mixed with the aqueous phase.　To this mixture, the oil phase and the fragrance agent were added with stirring and subsequently emulsified and dispersed using a homomixer, and the resultant was cooled to room temperature.
10. Cream Foundation (W/O-type)
(Oil Phase)
　　　 Decamethylcyclopentasiloxane　　　　　15.0%
　　　 Liquid paraffin　　　　　　　　　　　　　　 5.0%
　　　 p-methoxy cinnamate　　　　　　　　　3.0%
　　　 Polyether-modified dimethylsiloxane　 2.0%
(Aqueous Phase)
　　　 Purified water　　　　　　　　　　　balance to 100
　　　 Glycerin　　　　　　　　　　　　　　　　　 5.0%
　　　 Aqueous antiseptic agent　　　　　　　appropriate amount
(Powder)
　　　 Titanium oxide　　　　　　　　　　　10.0%
　　　 Talc　　　　　　　　　　　　　　　　　　　 3.8%
　　　 Color pigment　　　　　　　　 appropriate amount
　　　 Enterococcus lactic acid bacterium
　　　　　　　　　　　　　　　0.01 to 1% (appropriate amount)
(Other Component)
　　　 Fragrance agent　　　　　　　　　　　appropriate amount
11. Moisturizing Cream (O/W-type)
(A Phase)
　　　 Shea butter　　　　　　　　　　　　　　　　 1.5%
　　　 Alkyl (C12-15) benzoate　　　　　　　　　　 1.3%
　　　 Alkyl (C26-28) dimethicone　　　　　　6.5%
　　　 Glyceryl stearate　　　　　　　　　　　　　 1.5%
　　　 Mixture of glyceryl stearate and PEG-100 stearate
　　　　　　　　　　　　　　　　　　　　　　　　　　3.0%
　　　 Hexyl laurate　　　　　　　　　　　　　　　 1.3%
　　　 Isododecane　　　　　　　　　　　　　　　　 1.3%
　　　 Isohexadecane　　　　　　　　　　　　1.3%
　　　 Isopropyl palmitate　　　　　　　　　　　　 1.3%
　　　 Tocopherol acetate　　　　　　　　　　　　 0.5%
　　　 Heat-killed cells of Enterococcus lactic acid bacterium
　　　　　　　　　　　　　　　0.01 to 1 (appropriate amount)
(B Phase)
　　　 Purified water　　　　　　　　　　　balance to 100
　　　 Carbomer　　　　　　　　　　　　　　　　　 0.3%
　　　 Glycerin　　　　　　　　　　　　　　　　　 2.0%
　　　 Propylene glycol　　　　　　　　　　　　　 2.0%
(C Phase)
　　　 Fragrance agent　　　　　　　　　　　　　　 0.5%
　　　 Mixture of phenoxyethanol, methylparaben, ethylparaben, butylparaben, propylparaben and isobutylparaben
　　　　　　　　　　　　　　　　　　　　　　　　　　0.5%
　　　 Tetrahydroxypropyl ethylenediamine　　0.7%
(Production Method)
　　　 After heating the A phase and the B phase to 70°C in separate containers, the A phase was added to the B phase, and the resulting mixture was homogenized using a batch-type dispersion apparatus or the like and then naturally cooled to 40°C with stirring.　Thereafter, the C phase was added to the mixture, and the resultant was further homogenized and cooled to room temperature.
INDUSTRIAL AVAILABILITY
　　　 The lactic acid bacterium belonging to the genus Enterococcus according to the present invention facilitates the production of glycerol derived from Staphylococcus epidermidis, which is a skin resident bacterium useful on the skin, and the production of antimicrobial peptides derived from skin epidermal keratinocytes.　Moreover, the lactic acid bacterium belonging to the genus Enterococcus according to the present invention gives an excellent silky feel when applied to the skin and imparts good touch feeling to any of the aqueous type, oil-type, milky lotion-type and powder-type external preparations for skin protection.　Therefore, the lactic acid bacterium belonging to the genus Enterococcus according to the present invention is extremely applicable to skin-protecting agents and external preparations for skin protection that normalize the skin condition or maintain the normality thereof.

Claims (12)

  1. A glycerol production promoter derived from Staphylococcus epidermidis, said promoter comprising a lactic acid bacterium belonging to the genus Enterococcus as an effective ingredient.
  2. The glycerol production promoter derived from Staphylococcus epidermidis according to claim 1, wherein said lactic acid bacterium belonging to the genus Enterococcus is Enterococcus faecalis.
  3. The glycerol production promoter derived from Staphylococcus epidermidis according to claim 1 or 2, wherein said lactic acid bacterium belonging to the genus Enterococcus is Enterococcus faecalis EC-12 (accession No. FERM BP-10284).
  4. The glycerol production promoter derived from Staphylococcus epidermidis according to any one of claims 1 to 3, wherein said lactic acid bacterium belonging to the genus Enterococcus is killed.
  5. The glycerol production promoter derived from Staphylococcus epidermidis according to any one of claims 1 to 4, wherein said lactic acid bacterium belonging to the genus Enterococcus is heat-killed.
  6. An antimicrobial peptide production promoter derived from skin epidermal keratinocytes, said promoter comprising a lactic acid bacterium belonging to the genus Enterococcus as an effective ingredient.
  7. The antimicrobial peptide production promoter derived from skin epidermal keratinocytes according to claim 6, wherein said lactic acid bacterium belonging to the genus Enterococcus is Enterococcus faecalis.
  8. The antimicrobial peptide production promoter derived from skin epidermal keratinocytes according to claim 6 or 7, wherein said lactic acid bacterium belonging to the genus Enterococcus is Enterococcus faecalis EC-12 (accession No. FERM BP-10284).
  9. The antimicrobial peptide production promoter derived from skin epidermal keratinocytes according to any one of claims 6 to 8, wherein said lactic acid bacterium belonging to the genus Enterococcus is killed.
  10. The antimicrobial peptide production promoter derived from skin epidermal keratinocytes according to any one of claims 6 to 9, wherein said lactic acid bacterium belonging to the genus Enterococcus is heat-killed.
  11. The antimicrobial peptide production promoter according to any one of claims 6 to 10, wherein said antimicrobial peptide is human β-defensin-2 (hBD2) or human β-defensin-3 (hBD3).
  12. An external preparation for skin protection, comprising the glycerol production promoter derived from Staphylococcus epidermidis or the antimicrobial peptide production promoter derived from skin epidermal keratinocytes according to any one of claims 1 to 11.
PCT/JP2016/086094 2015-12-04 2016-12-05 GLYCEROL PRODUCTION PROMOTER DERIVED FROM Staphylococcus Epidermidis, ANTIMICROBIAL PEPTIDE PRODUCTION PROMOTER DERIVED FROM SKIN EPIDERMAL KERATINOCYTES, AND UTILIZATION THEREOF IN EXTERNAL PREPARATION FOR SKIN PROTECTION WO2017094916A1 (en)

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KR1020187002720A KR20180084729A (en) 2015-12-04 2016-12-05 A glycerol production promoter derived from Staphylococcus epidermidis, an antimicrobial peptide production promoter derived from keratinocyte keratinocyte, and a use thereof in a skin external preparation
CN201680044943.1A CN107922956A (en) 2015-12-04 2016-12-05 Glycerine derived from staphylococcus epidermis produces accelerating agent, the antimicrobial peptide derived from skin epidermis keratinocyte produces accelerating agent and their applications in skin sparing external preparation

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JP2015237848A JP6185041B2 (en) 2015-12-04 2015-12-04 Glycerol production promoter derived from Staphylococcus epidermidis, antibacterial peptide production promoter derived from skin epidermis keratinocytes, and their use as an external preparation for skin protection

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108208200A (en) * 2018-01-15 2018-06-29 吴礼顺 A kind of appetizing sesame oil and preparation method thereof
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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004269408A (en) * 2003-03-07 2004-09-30 Aureo Co Ltd Humectant for skin
JP2006028050A (en) * 2004-07-14 2006-02-02 Combi Corp Skin allergy suppressing composition
JP2007254333A (en) * 2006-03-22 2007-10-04 Kitasato Gakuen Microbial cell-containing composition having inflammation suppressive action
JP2008000121A (en) * 2006-06-20 2008-01-10 Bamen Kenichi Immunostimulating food, immunostimulating supplementary food, antitumor food, and antioxidative food
US20110182861A1 (en) * 2008-07-29 2011-07-28 Isabelle Castiel Cosmetic use of microorganisms for the treatment of oily skin
JP2011178683A (en) * 2010-02-26 2011-09-15 Combi Corp Composition having bedsore-relieving effect
US20150202136A1 (en) * 2012-02-14 2015-07-23 The Procter & Gamble Company Topical use of a skin-commensal prebiotic agent and compositions containing the same

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3795011B2 (en) * 2002-12-16 2006-07-12 株式会社ヤクルト本社 Moisturizer and cosmetics containing the same
KR100649855B1 (en) * 2003-03-07 2006-11-28 가부시키가이샤 아우레오 Composition containing ?-glucan and constipation-relieving drug, immunopotentiator and skin moistening agent using the composition
US7510734B2 (en) * 2004-03-04 2009-03-31 E-L Management Corporation Skin treatment method with Lactobacillus extract
JP5371169B2 (en) * 2004-09-24 2013-12-18 コンビ株式会社 Drug-resistant bacterial infection control agent
JP5340555B2 (en) * 2007-04-09 2013-11-13 コンビ株式会社 Villi extension agent
JP2011190217A (en) * 2010-03-15 2011-09-29 Combi Corp Human epidermal cell growth promoter, and skin care composition for external use and cosmetic each containing the same
JP4831711B1 (en) * 2010-09-11 2011-12-07 株式会社スリービー Anti-Candida fungi and prophylactic and / or therapeutic agents for candidiasis comprising Tamogitake extract as an active ingredient
US20140343034A1 (en) * 2013-04-25 2014-11-20 Japan Tobacco Inc. Skin barrier function improving agent

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004269408A (en) * 2003-03-07 2004-09-30 Aureo Co Ltd Humectant for skin
JP2006028050A (en) * 2004-07-14 2006-02-02 Combi Corp Skin allergy suppressing composition
JP2007254333A (en) * 2006-03-22 2007-10-04 Kitasato Gakuen Microbial cell-containing composition having inflammation suppressive action
JP2008000121A (en) * 2006-06-20 2008-01-10 Bamen Kenichi Immunostimulating food, immunostimulating supplementary food, antitumor food, and antioxidative food
US20110182861A1 (en) * 2008-07-29 2011-07-28 Isabelle Castiel Cosmetic use of microorganisms for the treatment of oily skin
JP2011178683A (en) * 2010-02-26 2011-09-15 Combi Corp Composition having bedsore-relieving effect
US20150202136A1 (en) * 2012-02-14 2015-07-23 The Procter & Gamble Company Topical use of a skin-commensal prebiotic agent and compositions containing the same

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108208200A (en) * 2018-01-15 2018-06-29 吴礼顺 A kind of appetizing sesame oil and preparation method thereof
DE102018219593B4 (en) * 2018-11-15 2021-01-07 Shanghai Pinmai Inter Tech Co., Ltd Chinese medical cosmetic composition
CN110859787A (en) * 2019-12-11 2020-03-06 广州环亚化妆品科技有限公司 Anti-saccharification traditional Chinese medicine composition and preparation method and application thereof
CN110859787B (en) * 2019-12-11 2022-02-11 广州环亚化妆品科技有限公司 Anti-saccharification traditional Chinese medicine composition and preparation method and application thereof
CN112121076A (en) * 2020-09-23 2020-12-25 北京农业生物技术研究中心 Chamomile essential oil and application thereof
WO2022146310A1 (en) * 2020-12-31 2022-07-07 Kastamonu Üni̇versi̇tesi̇ Rektörlüğü Wound healing mat from fruit, vegetable peel wastes as sources of vitamin c and e with anti-scar property
CN113827518A (en) * 2021-09-27 2021-12-24 广州市科能化妆品科研有限公司 Composition for inhibiting melanin generation, whitening composition, whitening emulsion and preparation thereof

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JP2017101006A (en) 2017-06-08
JP6185041B2 (en) 2017-08-23
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