JP2005162663A - Skin base - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a therapeutic agent for skin, a skin cleansing agent, an ointment, an adhesive, which is excellent in applicability to the skin and a feeling of use, and gives a proper moist feeling and flexibility to the skin and is safe It is to provide a skin base useful for drugs, nasal preparations, ear drops, eye drops, skin cosmetics and the like.
The present invention provides a skin characterized by containing β-glucan having a weight average molecular weight of 1,000 to 4,600,000 and a viscosity of 1% by weight aqueous solution at 36 ° C. of 0.5 to 10,000 mPa · S. A base for use is provided.

Description

  TECHNICAL FIELD The present invention relates to a skin base, and more specifically, a therapeutic agent for skin, a skin cleansing agent, an ointment, a patch, a nasal preparation, an ear drop, an eye drop, and a skin makeup, which are excellent in applicability to the skin. The present invention relates to a dermatological base useful for preparations.

  Skin cosmetics, skin treatment agents, skin cleansing agents, cosmetics for the skin such as nasal preparations, pharmaceuticals, and the like contain a skin base in order to facilitate application to the skin in addition to the drug. This base for skin gives moderate viscosity, can be applied uniformly and smoothly to the skin, does not easily flow off the skin, has good retention on the skin, has no unpleasant stickiness, and is excellent In addition to having excellent usability, it is necessary for the medicinal ingredients to permeate into the skin, and without causing rough skin or damage to the skin, giving the skin appropriate moistness and flexibility. ing.

  Therefore, the use of various thickeners has been proposed. For example, the use of hydrophilic compound gels such as agar and carrageenan (Patent Document 1) and the use of agar that gives a specific viscosity (Patent Document 2) have been proposed. However, none of these have sufficient performance, and the development of an excellent skin base has been awaited.

JP 2001-342451 A JP 2003-128588 A

  An object of the present invention is to provide a safe skin base that is excellent in applicability to the skin and a feeling of use, and that gives an appropriate wet feeling and flexibility to the skin.

  The present inventors have found that a skin base having excellent performance can be obtained by using a specific β-glucan.

  That is, the present invention includes a skin base characterized by containing β-glucan having a weight average molecular weight of 1,000 to 4,600,000 and a viscosity of 1% by weight aqueous solution at 36 ° C. of 0.5 to 10,000 mPa · S. Is to provide.

  The present invention further provides the above skin base, wherein the 1 g% aqueous solution is β-glucan having a viscosity at 10 ° C. of 1.0 to 50000 mPa · S.

  The present invention further provides the above-mentioned base for skin, which contains mevalonic acid.

  The present invention also provides a therapeutic agent for skin, a skin cleanser, an ointment, a patch, a nasal preparation, an ear drop, an eye drop or a skin cosmetic containing the above-mentioned skin base.

  ADVANTAGE OF THE INVENTION According to this invention, the safe base for skin which is excellent in the applicability | paintability to a skin, and a usability | use_condition, and also gives moderate wet feeling and a softness | flexibility to skin can be provided.

Hereinafter, the present invention will be described in detail.
The skin base of the present invention contains β-glucan. Β-glucan referred to in the present invention is a kind of polysaccharide, and it is a 1-2β-D-glucopyranose bond, 1-3-β-D-glucopyranose bond, and 1-4-4-β-D-glucopyranose bond. , 1-6-β-D-glucopyranose bond, at least two kinds of bonds selected from the group of cereal-derived β-glucan, microorganism-derived β-glucan, basidiomycetous-derived β-glucan Or 2 or more types are mentioned as a preferable example.

  First, the cereal-derived β-glucan is described. As the cereal, a gramineous plant is preferable. Examples of gramineous plants include cereals such as rice, wheat, corn, sorghum, millet, millet, millet, barley, oats (crown) and rye it can. In particular, β-glucan obtained by extraction from these grasses is preferred. In the present invention, β-glucan obtained by this extraction is also referred to as extracted β-glucan.

  The extraction method of β-glucan extracted from this gramineous plant is not particularly limited, and it may be extracted by adding an extraction solvent to the gramineous plant as an extraction raw material. Also, the purity of the extract itself after solid-liquid separation, or a liquid or solid obtained by concentrating β-glucan extracted from the extract by a known method, or purified from the extract by a known method Any of the liquids, solids, etc. obtained by any manufacturing method, any form, and any purity can be used. Of course, a mixture of extracted components other than β-glucan may be used. In the present invention, these are all referred to as β-glucan extracted from the grass family.

  For extraction, the whole plant can be used as a raw material, but it is preferable to use seeds having a relatively high β-glucan content. Any of crushed powder (whole grain), cocoon, bran, malt, germ, and endosperm obtained in the grain refining process may be used. Preferably, it is an endosperm portion obtained by scouring whole grains and grains of barley and oats from the outer periphery, and rice bran, rice bran, wheat and corn bran and germs, and more preferably barley and oats. It is the endosperm part which refined the whole grain flour and grain of the kind from the outer peripheral part, and the cocoon which generate | occur | produces in that case.

  In addition, β-glucan extracted from gramineous plants has a 1-2β-D-glucopyranose bond, a 1-3β-D-glucopyranose bond, a 1-4β-D-glucopyranose bond, Β-glucan having at least two kinds of -6-β-D-glucopyranose bonds is preferable, and β-glucan composed of 1-3,1-4-β-D-glucopyranose bonds is preferably contained.

  Explaining the method for extracting β-glucan from the grass family, β-glucan in the grass family can be dissolved as an aqueous solution as a water-soluble polymer. For example, water, warm water, hot water is added to the grain powder of the grass family. Alternatively, extraction can be performed at an arbitrary temperature for an arbitrary time using a salt solution, an acid, an alkaline aqueous solution, an organic solvent, etc., with a solvent 2 to 100 times the amount of the powder. Furthermore, β-glucan can be obtained by solid-liquid separation of the extract. Among these, β-glucan extracted with water, warm water or hot water is preferable, and β-glucan extracted with warm water having a temperature of 80 ° C. or lower and 4 ° C. or higher is more preferable. Further, an extraction accelerator or the like may be added during extraction.

  Specifically, as a method for obtaining high molecular weight β-glucan from barley, for example, a method of producing a waxy barley as a raw material by water extraction (Japanese Patent Publication No. 4-11197), or barley, oats A method for obtaining β-glucan having a weight average molecular weight of 100,000 to 1,000,000 by alkali extraction, neutralization and alcohol precipitation (Japanese Patent Publication No. 6-83652), and barley koji with a yield of 82% or less as a raw material , Β-glucan obtained by extraction of β-glucan with hot water at 80 to 90 ° C. (Japanese Patent Laid-Open No. 11-225706), and β-glucan obtained by these production methods are further obtained by known methods. Low molecular weight β-glucan. For example, as a method for reducing the molecular weight, any known hydrolysis reaction of polysaccharides can be used. For example, it is known that water-soluble polysaccharides are hydrolyzed by heating under pressure in the presence of an acid, and this can be used to reduce the molecular weight. Further, it is also effective to reduce the molecular weight using an enzymatic hydrolysis reaction. As the enzyme, 1,3-β glucanase or the like can be used. Furthermore, β-glucan obtained by direct extraction from raw material grains by methods such as WO98 / 13056 and JP-A-2002-97203 can also be used. Moreover, you may use the extraction promoter etc. which are described in Unexamined-Japanese-Patent No. 2002-105103.

Next, the microorganism-derived β-glucan used in the present invention will be described.
Since microorganisms contain a large amount of β-glucan in their cell walls, β-glucan derived from microorganisms is a culture obtained by inoculating microorganisms into their respective growth media and growing the cells. The cultured cell wall residue obtained by disrupting the cultured cells and removing the contents as they are can be used. In addition, any of the cultured cells or the β-glucan extracted from the cultured cell wall residue can be used as it is, or purified of the extracted β-glucan. It is also possible to utilize β-glucan secreted and produced outside the cells by culturing microorganisms. In this case, the culture solution after completion of the culture can be isolated or purified from the culture solution as it is. Β-glucan can be used.

  Of these, if cultured cells obtained by inoculating microorganisms in each growth medium and growing the cells are used as they are, the cell contents may cause the quality of the skin base to deteriorate. It is preferable to use a cultured cell wall residue obtained by crushing the cultured cells and removing the contents, and further, the cultured cells or β-glucan extracted from the cultured cell wall residues may be used as they are or after purification. More preferably, it is most preferable to use β-glucan secreted and produced outside the cells together with the culture solution or purified from the culture solution.

  As microorganisms suitable for obtaining the β-glucan, microorganisms that have been conventionally used for food are highly safe and suitable. That is, yeast, lactic acid bacteria, natto bacteria, acetic acid bacteria, koji molds, algae such as chlorella and spirulina, microorganisms belonging to the genus Aureobasidium, and the like. These can use the said microorganisms isolate | separated from the environment (for example, foodstuff, soil, indoors, etc.). Moreover, the stock strain or isolate isolate | separated by single bacteria, Furthermore, the mutant strain which performed mutation operation in them by a conventional method can be used. Examples of the mutation operation include UV treatment, chemical treatment with nitrosoguanidine, ethidium bromide, ethyl methanesulfonate, sodium nitrite, and the like.

  Examples of the yeast include yeasts classified into the genus Saccharomyces used in alcoholic brewing and bread making processes such as beer, sparkling sake, shochu, sake, wine, whiskey, etc., for example, Saccharomyces cerevisiae (S. cerevisiae), Saccharomyces salmon (S.sake), Saccharomyces rosei (S.rosei), Others, Saccharomyces ruxii (S.rouxii), Saccharomyces bisporus, Saccharomyces bailii (S.baillii), Saccharomyces S. bayanus, S. capenisis, etc., and genus Syzosaccharomyces, such as S. pombe, Torulopsis, such as tolopsis etke R. (T.etchelsii), Tolropsis versatilis (T.versatilis), Truro T. holmii, Hanseniaspora, Hansenula, eg, H. subpelliculosa, Debaryomyces, eg, Debaryomyces Hanseni (D.hansenii), Saccharomycopsis genus For example, Saccharomycopsis fibrigera, Saccharomycodes genus, Pichia genus, Pachysolen genus, microorganism Examples include yeast of the genus Candida used for protein production, such as C. utilis, C. milleri, C. tropicalis, C. maltosa and C. lipolytica. In addition, Rhodotorula yeast.

  Examples of the lactic acid bacteria include genus Lactobacillus, Bifidobacterium, cocci, Leuconostoc, Pediococcus, Streptococcus, and Lactococcus. ) Lactic acid bacteria are usually used, but other genus Enterococcus genus, Vagococcus genus, Carnobacterium genus, Aerococcus genus, Tetragenococcus genus lactic acid bacteria Can be used. Specific Lactobacillus strains include Lactobacillus bulgaricus, L. helveticus, L. acidophilus, L. lactis, L. lactis, Lactobacillus casei (L. casei), Lactobacillus brevis (L. brevis), Lactobacillus plantarum (L. plantarum), Lactobacillus salmon (L.sake), Streptococcus thermophilus (Streptococcus thermophilus), Streptococcus thermophilus (S. lactis), Streptococcus cremoris, Bifidobacterium longum, B. bifidum, B. breve, B. Phytobacterium infantis (B.infantis), Leuconostoc cremoris, Leuconostoc Mecenteroides (Ln.mesenteroides), Leuconostococcus (Ln.ocnos), Pediococcus acidilactici (Pediococcus acidilactici), Pediococcus cerevisiae (P.cerevisiae), Pediococcus spentaseseus (P.pentosaceus) One kind or two or more kinds of conventionally used lactic acid bacteria can be used. These may be used alone or in combination of two or more. Further, the culture of lactic acid bacteria belonging to the genus Bifidobacterium and the culture of other lactic acid bacteria may be performed separately, and these may be mixed.

  The microorganism belonging to the genus Aureobasidium may be any microorganism as long as it is a strain that produces a glucose polymer having a β bond outside the bacterial cell by culturing the microorganism, and examples thereof include Aureobasidium. A strain of Aureobasidium pullulans, specifically, IFO4464, IFO4466, IFO6353, IFO7757, ATCC9348, ATCC3092, ATCC42023, ATCC433023, FERM BP-8391 and the like can be used. In addition, the microorganisms separated in the environment (for example, food, soil, indoors, etc.) can be used. Moreover, the stock strain or isolate isolate | separated by single bacteria, Furthermore, the mutant strain which performed mutation operation in them by a conventional method can be used. Examples of the mutation operation include UV treatment, chemical treatment with nitrosoguanidine, ethidium bromide, ethyl methanesulfonate, sodium nitrite, and the like.

  Other strains of the genus Bacillus genus Bacillus, strains of the genus Acetobactor acetic acid bacteria, strains of the Aspergillus genus and Penicillium genus, chlorella and spirulina Algae, dried chlorella powder, Aureobasidium genus strain known to secrete and produce pullulan out of the cell, and other polysaccharides used as food additives Xanthomonas, Aeromonas, Azotobactor, Alcaligenes, Erwinia, Enterobactor, Sclerotium, Pseudomonas ), Agrobacterium, and Macrohomopsis strains can be used.

Next, β-glucan derived from basidiomycetes used in the present invention will be described.
Basidiomycetes contain a large amount of β-glucan in the nuclei of fruit bodies and mycelia assembled in a lump, so that the fruit bodies and mycelia are finely pulverized, or the extract extracted from the pulverized product, or extracted Any of these can be used as a basidiomycete-derived β-glucan such as a product obtained by purifying β-glucan from a product. In addition, germination of basidiomycetous spores, inoculating mycelium in each growth medium and growing the bacterial cells, the cultured cells were obtained as they were, and the cultured cells were crushed and the contents were removed. Cultured cell wall residue can be used. In addition, any of the β-glucan extracted from the cultured cells or the cultured cell wall residue can be used as it is or purified from the extracted β-glucan. It is also possible to utilize β-glucan secreted and produced outside the bacterial cells by culturing basidiomycetes. In this case, the culture solution after completion of the culture is used as it is or separated and purified from the culture solution. β-glucan can be used as β-glucan derived from basidiomycetes.

  Among these, if the cultured cells obtained by inoculating spores and mycelium into each growth medium and growing the cells are used as they are, with the pulverized fruit bodies and mycelia being crushed, the cell contents However, since there is a possibility that the quality of the skin base may be deteriorated, it is preferable to use a cultured cell wall residue obtained by crushing the cultured cells and removing the contents, and further using the cultured cells or the cultured cells. It is more preferable to use β-glucan extracted from the cell wall residue as it is or after purification, and it is further preferable to use β-glucan secreted and produced outside the cells together with the culture solution or purified from the culture solution. Most preferred.

  As the basidiomycetes, cultivars are most preferable, but β-glucans from basidiomycetes that are not subjected to commercial production can also be used in the present invention. Examples include Agaricus blazei, Agaricus mushrooms, Agaricus mushrooms, Ezoharitake, Enokitake, Kanzotake, Mushroom, Kinugasatake, Agaricus, Salmonella mushroom, Sakerihi Toyotake, Sangohatake, Shitaketake, Shirotaketa Winter summer grass, sea cucumber, aratake, naratakemodoki, niboshimeji, nikawaurokotake, nikawaharitake, numerisugitake, numerisugitaketake, mushroom, oyster mushrooms, bullflower, owl, bamboo shoots, mushrooms, mushrooms, mushrooms , Mukitake, Murasakishiji, Yamadoritake, Yamabushitake, Willow Matsutake, Hanabiratake, Meshimako Etc. The.

  As a method for isolating cultured cell wall residues of the above microorganisms and basidiomycetes as β-glucan, an appropriate amount of solvent is added to the cultured microorganisms, the cultured mycelium, the cultivated mycorrhiza or fruiting body, and self-digestion Alternatively, there is a method of isolating the cultured cell wall residue as β-glucan by destroying a part of the cell wall by adding hydrolase, allowing the contents to flow away, and recovering the residual components. Also, a method of obtaining β-glucan by damaging microorganisms or basidiomycetous cells by physical force such as French press or ultrasonic crusher, destroying part of the cells, removing the contents, and collecting the residue There is also.

  The extraction method of β-glucan is not particularly limited, and it may be extracted by adding an extraction solvent to microorganisms or basidiomycetes that are extraction raw materials. As the extraction solvent, one or two or more mixed solvents such as water, a salt solution, an aqueous acid solution, an aqueous alkaline solution, and an organic solvent can be used. Moreover, extraction efficiency can be improved by using together the enzyme which decomposes | disassembles a cell wall. The extract can be purified by purifying the extract itself in a solid-liquid separation, or a liquid or solid obtained by concentrating β-glucan extracted from the extract by a known method, or purifying the extract by a known method. Any of the liquids, solids, etc. obtained by any manufacturing method, any form, and any purity can be used. Of course, it is also possible to use a mixture of extracted components other than β-glucan. In the present invention, all of these are referred to as β-glucan extracted from microorganisms or basidiomycetes.

  Further, a method for extracting β-glucan from microorganisms or basidiomycetes will be described. Β-glucan used in the present invention can be dissolved in a solvent such as water as a water-soluble polymer, and is generally commercially available as basidiomycetes. Dry, pulverized mushrooms, water, warm water, hot water or salt solution, further using acid, alkaline aqueous solution, organic solvent, etc. Can be extracted at any temperature for a period of time. Furthermore, β-glucan can be obtained by solid-liquid separation of the extract. Among these, β-glucan extracted with water, hot water or hot water is preferable, and β-glucan extracted with water having a temperature of 90 ° C. or lower and 4 ° C. or higher is more preferable. Furthermore, you may add extraction promoters, such as an enzyme solution, at the time of extraction.

  Β-glucan used in the present invention has 1-2β-D-glucopyranose bond, 1-3β-D-glucopyranose bond, 1-4-β-D-glucopyranose bond, 1-6-β. Β-glucan having at least two kinds of -D-glucopyranose bonds is preferred, and in particular β-glucan composed of 1-3-β-D-glucopyranose bond and 1-4-β-D-glucopyranose bond, 1-3 β-glucan composed of β-D-glucopyranose bond and 1-6-β-D-glucopyranose bond, 1-3-β-D-glucopyranose bond, 1-4-β-D-glucopyranose bond and 1- It is preferable to contain β-glucan consisting of a 6-β-D-glucopyranose bond.

  In addition, when the extract from microorganisms or basidiomycetes is used without purification, or the extract obtained by pulverizing and solidifying only is used as it is, the purity of β-glucan in the component is 1-100%, preferably 10-100%, more preferably 20-100%, and the higher the purity, the better.

  The β-glucan used in the present invention has a weight average molecular weight of 1,000 to 4,600,000, and more preferably 2,000 to 500,000 in order to obtain good coatability. If it is less than 1000, the fluidity increases and a problem arises in the retention of the drug on the skin. Conversely, if it exceeds 500,000, the viscosity increases and it becomes difficult to apply to the skin. The target molecular weight β-glucan may be obtained directly from cereals, microorganisms and basidiomycetes by extraction, or may be obtained by reducing the molecular weight of β-glucan by a known method.

  The β-glucan of the present invention has water solubility, and the viscosity at 36 ° C. of a 1% by weight aqueous solution is 0.5 to 10000 mPa · S, preferably 0.6 to 8000 mPa · S. If it is less than 0.5 mPa · S, the fluidity increases and a problem arises in the retention of the drug on the skin. Conversely, if it exceeds 10,000 mPa · S, the viscosity increases and it becomes difficult to apply to the skin. More preferably, the viscosity at 10 ° C. of a 1 wt% aqueous solution is 1.0 to 50000 mPa · S. Further, the ratio of the viscosity at 10 ° C. to the viscosity at 36 ° C. is preferably 1.6 or more and 1: As a result, the skin base of the present invention has a viscosity suitable for storage during storage, and has a viscosity suitable for application when applied to the skin that is affected by the normal body temperature of about 36 ° C. Thus, the storage stability and usability are excellent.

The content of β-glucan of the present invention is preferably 0.001 to 50% by weight in the skin base,
0.01 to 10% by weight is preferred. If it is less than 0.001% by weight, the effect of the present invention is not sufficiently exhibited, and if it exceeds 50% by weight, the viscosity may increase and it may be difficult to use.

  The skin base of the present invention is characterized by high safety because it uses β-glucan extracted from natural grains, microorganisms, basidiomycetes and the like.

  The skin base of the present invention can further preferably contain mevalonic acid. By blending mevalonic acid, a moist feeling and flexibility can be imparted to the skin.

  The mevalonic acid referred to in the present invention is involved in the biosynthesis metabolism of isoprenoid-related substances in a large number of organisms in nature. Mevalonolactone is in the lactone form, and mevalonolactone is mevalonic acid in aqueous solution. Exists. In this specification, mevalonic acid and mevalonolactone are treated as synonyms.

  As a method for mass production of mevalonic acid, for example, methods of producing from microorganisms are known (Japanese Patent Publication No. 7-89938, Japanese Patent Publication No. 7-89939, Japanese Patent Publication No. 7-89940, Japanese Patent Publication No. 7- In this method, R-mevalonic acid which is a natural type can be obtained.

  In addition, mevalonic acid obtained by chemical synthesis has two optical isomers, R-mevalonic acid and S-mevalonic acid. In the present invention, these racemates can be used as they are, Only natural R-mevalonic acid can be divided and used. Of course, it is also possible to divide and use only S-mevalonic acid.

  The mevalonic acid used in the present invention is preferably natural R-mevalonic acid from the viewpoints of biocompatibility and safety.

  In the present invention, as the mevalonic acid, a monovalent or divalent metal salt of mevalonic acid, for example, a salt of sodium, potassium, calcium or the like, or an alcohol, for example, methyl alcohol, ethyl alcohol, butyl alcohol, propylene glycol Esters with glycerin, isopropyl alcohol and the like can also be used. R-mevalonate and S-mevalonate are present in the salt, and R-mevalonate and S-mevalonate are present in the ester, and these racemates can be used as they are. From the viewpoint of safety and safety, natural R-mevalonate and R-mevalonate are preferred.

  In the skin base of the present invention, the content of mevalonic acid is preferably 0.001 to 20% by weight, and preferably 0.01 to 5% by weight. If the amount is less than 0.001% by weight, the effect may not be obtained. Even if the amount exceeds 20% by weight, an effect commensurate with the increase in the amount may not be expected.

  In addition to the β-glucan and mevalonic acid, the skin base of the present invention may further contain a substance that imparts some physiological activity to the skin when applied to the skin. For example, whitening ingredients, anti-inflammatory agents, anti-aging agents, slimming agents, tanning agents, antioxidants, hair growth agents, hair growth agents, blood circulation promoters, moisturizing ingredients other than polyhydric alcohols or sugars, drying agents, cooling agents , Warming sensates, amino acids, wound healing promoters, stimulation relieving agents, analgesics, cell activators, enzyme components, and the like.

  Examples of the above-mentioned substances that give physiological activity to the skin include physiologically active components of naturally-derived components such as animal and plant extract components, seaweed extract components, and herbal medicine components. For example, Ashitaba extract, Avocado extract, Achacha extract, Altea extract, Arnica extract , Aloe extract, apricot extract, apricot kernel extract, ginkgo biloba extract, fennel extract, turmeric extract, oolong tea extract, AGES extract, Echinacea leaf extract, Ogon extract, Oat extract, Ouren extract, barley extract, Hypericum extract, Odrioptera extract, Dutch mustard Extract, orange extract, dried seawater, seaweed extract, hydrolyzed elastin, hydrolyzed wheat powder, hydrolyzed silk, chamomile extract, carrot extract, kawara mugi extract, licorice extract, oil-soluble licorice extract, calcadede Extract Fermented extract, rice germ oil, comfrey extract, collagen, bilberry extract, saicin extract, psychic extract, saitai extract, salvia extract, savanna extract, sasa extract, hawthorn extract, salamander extract, shiitake extract, shikon extract, shikon extract, perilla extract , Linden extract, citrus extract, peony extract, ginger root extract, birch extract, Japanese horse chestnut extract, Kizuta extract, Sosa Extract, elderberry extract, yarrow extract, mint extract, sage extract, mallow extract, nematode extract, senbu extract, soybean extract, taisu extract, thyme extract, tea extract, clove extract, chigaya extract, chimpi extract, toki extract, toshinsen extract , Tonin extract, Spruce extract, Dokudami extract, Tomato extract, Natto extract, Carrot extract, Garlic extract, Novara extract, Hibiscus extract, Bacmond extract, Parsley extract, Honey, Hamamelis extract, Parietalia extract, Hikikoshi extract, Bisabolol, Biwa extract, Japanese dandelion extract, Japanese quince extract, Bukuryo extract, Butcher bloom extract, Grape extract, Placenta extract, Propolis , Loofah extract, safflower extract, peppermint extract, body sage extract, button extract, hop extract, pine extract, maroni extract, honeysuckle extract, mugwort extract, melissa extract, peach extract, cornflower extract, eucalyptus extract, yukinoshita extract, yuzu extract, yokiinin extract, mugwort An extract, a lavender extract, an apple extract, a lettuce extract, a lemon extract, a forsythia extract, a rose extract, a rosemary extract, a Roman chamomile extract, a royal jelly extract and the like can be mentioned.

  Specific examples of preferable physiologically active components such as other naturally derived components include deoxyribonucleic acid, ribonucleic acid, raffinose, mucopolysaccharide, hyaluronic acid or a salt thereof such as sodium hyaluronate, chondroitin sulfate sodium, collagen, elastin, Biopolymers such as chitin, chitosan, hydrolyzed eggshell membranes; amino acid derivatives such as amino acids, sarcosine, N-methyl-L-serine; multivalents such as ethyl glucose, sodium lactate, urea, sodium pyrrolidonecarboxylate, betaine, whey Moisturizing ingredients other than alcohol or saccharides; oily ingredients such as sphingolipids, ceramides, cholesterol, cholesterol derivatives, phospholipids; anti-flames such as ε-aminocaproic acid, glycyrrhizic acid, β-glycyrrhetinic acid, lysozyme chloride, guaiazulene, hydrocortisone Vitamin A, B2, B6, D, vitamins such as calcium pantothenate, biotin, nicotinamide, vitamin E; active ingredients such as allantoin, diisopropylamine dichloroacetic acid, 4-aminomethylcyclohexanecarboxylic acid; carotenoid, Antioxidants such as flavonoids, tannins, lignans, saponins; cell activators such as α-hydroxy acids and β-hydroxy acids, blood circulation promoters such as γ-oryzanol, wound healing agents such as retinol and retinol derivatives; ascorbic acids, Whitening agents such as arbutin, kojic acid, placenta extract, sulfur, ellagic acid, linoleic acid, tranexamic acid, glutathione; cephalanthin, licorice extract, red pepper tincture, hinokitiol, garlic iodide extract, pyridoxine hydrochloride, nicotinic acid, nicotinic acid derivative , Calcium pantothenate, D-pantothenyl alcohol, acetyl pantothenyl ethyl ether, biotin, allantoin, isopropylmethylphenol, estradiol, ethinylesteradiol, capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, takanal, camphor, salicylic acid, nonyl acid Vanillylamide, nonanoic acid vanillylamide, piroctone olamine, glyceryl pentadecanoate, l-menthol, mononitroguaiacol, resorcin, γ-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin, female hormone, cantharis tincture, cyclosporine, zinc pyrithione, hydrocortisone , Minoxidil, polyoxyethylene sorbitan monostearate, mint oil, Sasanishiki Hair tonic and the like; beta-glucan, and the like having a molecular weight and viscosity outside the range of the present invention.

  Examples of the ascorbic acids include ascorbic acid, ascorbic acid sulfate, ascorbic acid phosphate, ascorbic acid higher fatty acid ester, and salts thereof. These salts are sodium salt, potassium salt, magnesium salt, calcium salt, barium salt, ammonium salt, monoethanolamine salt, diethanolamine salt, triethanolamine salt, monoisopropanolamine salt, diisopropanolamine salt, triisopropanolamine. Examples include salts. Examples of the ascorbic acid sulfate include ascorbic acid-2-sulfate and ascorbic acid-3-sulfate, and examples of the ascorbic acid phosphate include ascorbic acid-2-phosphate and ascorbic acid. -3-phosphate esters, which are known substances and are described in JP-B-44-31237 and JP-B-54-21415. Examples of higher fatty acid esters of ascorbic acid include ascorbic acid-2-palmitic acid monoester, ascorbic acid-2,6-palmitic acid diester, ascorbic acid-2-stearic acid ester, and the like.

  The amount of a component that gives some physiological activity to the skin when applied to the skin as described above depends on the concentration of the active ingredient's effect, but is 0.05 to 90 weight% is preferable, More preferably, it is 0.1 to 50 weight%.

  In addition to the above components, the skin base of the present invention includes oils, powders (pigments, pigments, resins), fluorine compounds, resins, surfactants, solubilizers, and the like that are commonly used in skin bases. Components such as thickeners, preservatives, fragrances, antibacterial agents, bactericides, salts, solvents, chelating agents, neutralizing agents, pH adjusting agents, preservatives, buffering agents, insect repellents and the like can be used.

  Examples of the above powders include dyes such as red 104, red 201, yellow 4, blue 1, black 401, rake dyes such as yellow 4 Al lake, yellow 203 Ba rake; nylon powder , Silk powder, urethane powder, Teflon (registered trademark) powder, silicone powder, polymethyl methacrylate powder, cellulose powder, silicone elastomer spherical powder, polyethylene powder, etc .; yellow iron oxide, red iron oxide, black iron oxide Colored pigments such as chromium oxide, carbon black, ultramarine, and bitumen; white pigments such as zinc oxide, titanium oxide, and cerium oxide; extender pigments such as talc, mica, sericite, kaolin, and plate-like barium sulfate; Pearl pigment; barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, silicate mug Metal salts such as Siumu; silica, inorganic powder such as alumina; bentonite, smectite, boron nitride, and the like. These powders have a spherical shape, a rod shape, a needle shape, a plate shape, an indefinite shape, a flake shape, a spindle shape, and the like.

  These powders are conventionally known surface treatments such as fluorine compound treatment, silicone treatment, silicone resin treatment, pendant treatment, silane coupling agent treatment, titanium coupling agent treatment, oil agent treatment, N-acylated lysine treatment, The surface treatment may or may not be performed in advance by polyacrylic acid treatment, metal soap treatment, amino acid treatment, inorganic compound treatment, plasma treatment, mechanochemical treatment, or the like.

  Among these powders, silicone elastomer spherical powder, polyethylene powder, polypropylene powder, Teflon (registered trademark) powder, silicone rubber, urethane powder, polyalkylsilsesquioxane, nylon, silica beads, alumina beads, apatite, allyl Spherical powders (including hollow resin powders) such as fluorinated acrylic beads are preferably blended because they retain the physiologically active component and are excellent in sustained release effect.

  Examples of the oil agent include volatile and non-volatile oil agents and solvents and resins that are usually used for skin bases, and they may be liquids, pastes, or solids at room temperature, but liquids that are excellent in handling are preferable. Examples of oil agents include, for example, higher alcohols such as cetyl alcohol, isostearyl alcohol, lauryl alcohol, hexadecyl alcohol, octyldodecanol; fatty acids such as isostearic acid, undecylenic acid, oleic acid; glycerin, sorbitol, ethylene glycol, propylene Polyols and sugars such as glycol and polyethylene glycol; myristyl myristate, hexyl laurate, decyl oleate, isopropyl myristate, hexyl decyl dimethyloctanoate, glyceryl monostearate, diethyl phthalate, ethylene glycol monostearate, oxy Esters such as octyl stearate; Hydrocarbons such as liquid paraffin, petroleum jelly and squalane; Waxes such as lanolin, reduced lanolin and carnauba wax Include ethylene-alpha-olefin co-oligomer; mink oil, cacao butter, coconut oil, palm kernel oil, camellia oil, sesame oil, castor oil, oils such as olive.

  Examples of other forms of oil include, for example, dimethylpolysiloxane, methylhydrogenpolysiloxane, methylphenylpolysiloxane, polyether-modified organopolysiloxane, fluoroalkyl / polyoxyalkylene co-modified organopolysiloxane, alkyl-modified Silicone compounds such as organopolysiloxane, terminal-modified organopolysiloxane, fluorine-modified organopolysiloxane, amodimethicone, amino-modified organopolysiloxane, silicone gel, acrylic silicone, trimethylsiloxysilicate, silicone RTV rubber; perfluoropolyether, fluorinated Fluorine compounds such as pitch, fluorocarbon, fluoroalcohol and the like can be mentioned.

  Examples of the solvent include purified water, cyclic silicone, ethanol, isopropanol, light liquid isoparaffin, lower alcohol, ethers, LPG, fluorocarbon, N-methylpyrrolidone, fluoroalcohol, volatile linear silicone, next-generation fluorocarbon, etc. Can be mentioned.

  As the surfactant, for example, an anionic surfactant, a cationic surfactant, a nonionic surfactant, or a betaine surfactant can be used.

  Examples of thickeners and resins include sodium polyacrylate, cellulose ether, calcium alginate, carboxyvinyl polymer, ethylene / acrylic acid copolymer, vinyl pyrrolidone polymer, vinyl alcohol / vinyl pyrrolidone copolymer, nitrogen-substituted acrylamide -Based polymer, polyacrylamide, cationic polymer such as cationized gar gum, dimethylacrylammonium-based polymer, acrylic acid / methacrylic acid acrylic copolymer, POE / POP copolymer, polyvinyl alcohol, pullulan, agar, gelatin, tamarind seed polysaccharide , Xanthan gum, carrageenan, high methoxyl pectin, low methoxyl pectin, gar gum, gum arabic, crystalline cellulose, arabinogalactan, caraya gum, gum tragacanth, argy Acid, albumin, casein, curdlan, gellan gum, dextran, cellulose, polyethyleneimine, highly polymerized polyethylene glycol, cationized silicone polymer, synthetic latex, and the like.

  Examples of solubilizers that are added when a drug or other additive is poorly water-soluble include, for example, polysorbate 80, polyoxyethylene hydrogenated castor oil 60, polyethylene glycol, 1,3-butylene glycol, macrogol 200, macrogol. 300, macro goal 400, macro goal 1500, macro goal 4000, macro goal 6000, and the like.

  Examples of the pH adjuster include acids such as hydrochloric acid, sulfuric acid, boric acid, phosphoric acid and acetic acid, and bases such as sodium hydroxide, monoethanolamine, diethanolamine and triethanolamine.

  Preservatives include inverse soaps such as benzalkonium chloride, benzethonium chloride and chlorhexidine gluconate, parabens such as methylparaben, ethylparaben, propylparaben and butylparaben, alcohols such as chlorobutanol, phenylethyl alcohol and benzyl alcohol Organic acids such as sodium dehydroacetate, sorbic acid and sodium sorbate, and salts thereof.

  It is also preferable to impart an ultraviolet protective effect to the skin base of the present invention. In this case, it is preferable to use an ultraviolet protective agent (also referred to as an ultraviolet absorber) as shown below. As a compounding quantity of a ultraviolet protective agent, 0.005 to 50 weight% is preferable with respect to the skin base whole quantity, More preferably, it is 0.01 to 40 weight%.

  Buffering agents include alkali metal salts of acids such as phosphoric acid, boric acid, acetic acid, tartaric acid, lactic acid and carbonic acid, amino acids such as glutamic acid, epsilon aminocaproic acid, aspartic acid, glycyl, arginine and lysine, taurine, trisaminomethane, etc. Is mentioned.

  Examples of the ultraviolet protective agent (including organic and inorganic types, which may correspond to either UV-A or B) include fine particle titanium oxide and fine particle zinc oxide. Examples of the organic ultraviolet protective agent include 2-methoxyhexyl paramethoxycinnamate, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfate, and 2,2′-dihydroxy-4- Methoxybenzophenone, p-methoxyhydrocinnamic acid diethanolamine salt, paraaminobenzoic acid (hereinafter abbreviated as PABA), ethyldihydroxypropyl PABA, glyceryl PABA, homomenthyl salicylate, methyl-O-aminobenzoate, 2-ethylhexyl-2-cyano- 3,3-diphenyl acrylate, octyl dimethyl PABA, octyl methoxycinnamate, octyl salicylate, 2-phenyl-benzimidazole-5-sulfate, triethanolamine salicylate, 3- (4-methylbenzidine Den) camphor, 2,4-dihydroxybenzophenine, 2,2 ', 4,4'-tetrahydroxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 2-hydroxy-4-N- Octoxybenzophenone, 4-isopropyldibenzoylmethane, butylmethoxydibenzoylmethane, 4-tert-butyl-4'-methoxydibenzoylmethane, 4- (3,4-dimethoxyphenylmethylene) -2,5-dioxo-1 -Imidazolidinepropionate 2-ethylhexyl, polymer derivatives thereof, silane derivatives and the like. Furthermore, what sealed these in the polymer may be used.

  The skin base of the present invention may be used by blending a medicinal component having a medicinal component and any other component into the skin base.

  Ingredients that can be blended as drugs having medicinal properties are not particularly limited, but not only the physiologically active substances, but also hypnotic sedation such as glutethimide, chloral hydrate, nitrazebam, amovalpital, phenovalpital, etc. Agents: Antipyretic analgesics such as aspirin, acetaminophen, ibuprofen, flurpiprofen, indomethacin, ketoprofen, diclofenac sodium, thearamide hydrochloride, piroxicam, flufenamic acid, mefenamic acid, bentazosin, etc .: topical methylbenzoate methyl, lidocaine, etc. Anesthetic agents: Naphazoline nitrate, tetrizoline nitrate, oxymethasone hydrochloride, tramazoline hydrochloride, and other local vasoconstrictors: chlorpheniramine maleate, sodium cromoglycate, oxatomide, azelastine hydrochloride, Antiallergic agents such as ketotifen sulfate, traxanox sodium, amlexanox: bactericides such as benzethonium chloride, cardiotonic agents such as dopamine hydrochloride, nihidecarenone: arrhythmic agents such as propranolol hydrochloride, pindolol, phenytoin, disopyramide: isosorbide nitrate, nifedipine, Coronary vasodilators such as diltiazem hydrochloride and dipyridamole: Gastrointestinal agents such as domperidone: Adrenocortical hormones such as triamcinolone acetonide, dexamethasone, sodium betamethasone phosphate, hydrocortisone acetate, prednisolone acetate, fluocinonide, pecromethasone propionate, flunisolide, etc .: Antiplasmin agents such as tranexamic acid: Antifungal agents such as clotrimazole, miconazole nitrate, ketoconazole: tefgafur, fluorouracil, Antineoplastic agents such as lucaptopurine: Amoxiline, ampicillin, cephalexin, cephalotin sodium, ceftizoxime sodium, nirisromycin, oxytetracycline hydrochloride, etc. Antibiotics: insulin, nakacalcitonin, chicken calcitonin, calcitonins such as chicken calcitonin, urokinase, Physiologically active peptides such as TPA, interferon: Antiviral agents such as acyclovir, valacyclovir, ganciclovir, penciclovir, fanciclovir, vidarabine, cydarabine: vaccines such as influenza vaccine, swine pordeterra infection prevention vaccine, hepatitis B vaccine, etc. Can be mentioned.

  To further illustrate, examples of parasitic skin disease agents include bifonazole, siccanin, bisdecalinium acetate, clotrimazole, and salicylic acid, and suppurative diseases agents include sulfamethoxazole sodium, erythromycin, and gentamicin sulfate. Anti-inflammatory analgesics include indomethacin, ketoprofen, benmethazone valerate and fluocinolone acetonide, antipruritics include diphenhydramine, etc., local anesthetics include procaine hydrochloride and lidocaine hydrochloride Examples of the disinfectant for skin include iodine, povidone iodine, benzalkonium chloride, and chlorhexidine gluconate.

  Further, the skin base of the present invention can be applied not only to the body surface such as so-called outer skin but also to body cavities, that is, rectum, urethra, nasal cavity, vagina, ear canal, oral cavity or fossa, and examples of drugs that can be used for these. Is shown below. Of course, they may be used on the skin.

  Examples include antihistamines such as diphenhydramine hydrochloride and chlorpheniramine maleate, and reproductive organs such as clotrimazole, nafazolyl nitrate, ketotifen fumarate, and miconazole nitrate. Tetrizoline hydrochloride and the like, bronchodilators such as aminophylline, antimetabolites such as fluorouracin, hypnotic sedatives such as diazepam, and antipyretic analgesic and anti-inflammatory agents as aspirin. , Indomethacin, sulindac, phenylbutazone and ibuprofen, etc., adrenal hormone agents include dexamethasone, triamcinolone and hydrocortisone, and local anesthetic agents include lidocaine hydrochloride. , Purulent sulfisoxazole as a disease for agents, kanamycin, include such tobramycin and erythromycin, as a synthetic antibacterial agent norfloxacin, etc. gatifloxacin and nalidixic acid.

  In addition, anti-corticosteroids such as hydrocortisone, prednisone, prednisolone, triamcinolone, triamcinolone acetonide, dexamethasone, betamethasone, beclomethasone, beclomethasone dipropionate, halopredon acetate, acetaminophen, phenacetin, aspirin, aminopyrine, sulpyrine, phenylbutazone, Analgesics such as flufenamic acid, iffenac, ibuprofen, alclofenac, diclofenac sodium, indomethacin, colchicine, probenecid, and other anti-inflammatory enzymes such as chymotrypsin, bromelain serrapeptase, difuenhydramine hydrochloride, maleinchlorpheniramine, etc. Antihistamines, sodium cromoglycate, codeine phosphate, isopropyl chloride Antitussive asthma drugs such as Renol, tetracycline hydrochloride, leucomycin, fradiomycin, penicillin and its derivatives, antibiotics and fungicides such as erythromycin, chemotherapeutic drugs such as sulfathiazole and nitrofurazone, local anesthetics such as benzocaine, Vasoconstrictors such as phenylephrine hydrochloride, tetrahydrozoline hydrochloride, naphthazoline nitrate, oximenozolin hydrochloride, tramazoline hydrochloride, cardiotonic agents such as digitalis and digoxin, vasodilators such as nitroglycerin and papaverine hydrochloride, chlorhexidine hydrochloride, hexylresorcin, tepotridine chloride, ethacridine, etc. Antibacterial agents, enzymes such as lysozyme chloride, dextranase, hypoglycemic agents such as insulin, other hemostatic agents, sex hormones, antihypertensive agents, sedatives, anti-neoplastic agents It is.

  The content of the drug that can be blended varies depending on the type of the drug, but generally it is preferably within the range of about 0.001 to 10% by weight.

  The skin base of the present invention can also be used for eye drops. By using it as an eye drop, the intraocular transfer to a drug can be improved. This eye drop is not limited with respect to its target disease, and effectively acts on each disease by containing a drug suitable for the treatment of dry eye syndrome, glaucoma, cataract, inflammation, hay fever, and the like. In particular, mevalonic acid can be preferably blended.

  The types of drugs that can be incorporated into eye drops are not particularly limited. For example, antibacterial agents (quinolone antibacterial agents, cephalosporins, sulfacetamide sodium, sulfamethoxazole, etc.), anti-inflammatory agents (hydrocortisone, dexamethasone, Prezonisolone, betamethasone, diclofenac, indomethacin, fluorometholone, pranoprofen, dipotassium glycyrrhizinate, epsilon-aminocaproic acid, etc., antihistamines (chlorpheniramine maleate, diphenhydramine hydrochloride, etc.), antiglaucoma agents (prostaglandin derivatives, carbonic acid) Dehydrase inhibitors, etc.), antiallergic agents (such as sodium cromoglycate) and the like.

  Examples of immunosuppressants and antimetabolites include methotrexate, cyclophosphamide, cyclosporine, 6-mercaptopurine, azathioprine, fluorouracil, and tegafur. Further, a mixture of the above compounds such as neomycin sulfate and dexamethasone sodium phosphate Mixtures such as combinations of antibiotic / anti-inflammatory agents such as combinations, etc., can be mentioned, but other drugs can also be used to treat eye symptoms and lesions.

  The amount of these drugs added is preferably 0.001 to 10% by weight, but is not particularly limited as long as it is a concentration at which a therapeutic effect is exhibited.

  When used in eye drops, in addition to the above components, as additives, isotonic agents, buffers, pH adjusters, solubilizers, stabilizers, preservatives and the like can be appropriately blended.

  Examples of isotonic agents include glycerin, propylene glycol, sodium chloride, potassium chloride, sorbitol, mannitol and the like.

  Examples of the buffer include phosphoric acid, phosphate, citric acid, acetic acid, ε-aminocaproic acid, trometamol, and the like.

  Examples of the pH adjuster include hydrochloric acid, citric acid, phosphoric acid, acetic acid, sodium hydroxide, potassium hydroxide, boric acid, borax, sodium carbonate, sodium hydrogen carbonate and the like.

  Examples of solubilizers added when the drug or other additives are poorly water soluble include polysorbate 80, polyoxyethylene hydrogenated castor oil 60, macrogol 4000, and the like.

  Examples of the stabilizer include edetic acid and sodium edetate.

  Examples of the preservative include sorbic acid, potassium sorbate, benzalkonium chloride, benzethonium chloride, methyl paraoxybenzoate, propyl paraoxybenzoate, chlorobutanol, and the like, and these preservatives can be used in combination.

  The skin base of the present invention may be used by blending β-glucan, preferably mevalonic acid, and the above-mentioned optional components and drug components in water or a solvent.

  The skin base of the present invention can be easily formulated with a poorly water-soluble drug due to the effect of β-glucan.

  The skin base of the present invention is expected to have the above-mentioned medicinal ingredients, medicinal ingredients, therapeutic agents for skin, skin cleansing agents, ointments, patches, haptics, adhesive plasters, coating agents, nasal preparations, point Can be used for ear drops, eye drops, skin cosmetics, etc.

  Specific examples of these products include, for example, lotion, emulsion, skin milk, cream, ointment, lotion, calamine lotion, sunscreen agent, suntan agent, after-shave lotion, pre-shave lotion, makeup base material, pack material, cleansing Cosmetics, face wash, anti-acne cosmetics, essence and other basic cosmetics; makeup cosmetics such as foundation, white powder, eye shadow, eyeliner, eyebrow, teak, lipstick and nail color; shampoo, rinse, conditioner, hair color , Hair tonic, Set agent, Hair conditioner, Hair conditioner, Body powder, Deodorant, Hair remover, Soap, Body shampoo, Hand soap, Perfume, Toothpaste, Oral care product, Bathing agent, Esthetic agent, Massage agent, Sunburn Inhibitors, children's diapers Diapers for the elderly, bedsore treatment agents, bedsore prevention agents, bedsore recovery agents, sanitary products, various skin treatment agents, nasal preparations, nasal irrigation agents, intranasal inflammation inhibitors, nasal obstruction prevention or treatment agents, eye drops, muscle pain Drugs, hot compresses, cold compresses, patches, haps, plasters, coatings, adhesive bandages, medicated tapes, allergy prevention or treatment agents for allergic dermatitis, wounds and artifacts, warts, octopuses, fish eyes Remedies, insect repellents, insect repellents, acne preventives, acne remedies, athlete's foot remedies, heat from illness and exercise, and the surface of a squirrel that comes into contact with the skin. These products may be manufactured by a conventionally known method. In addition, when used for adhesives, haptics, adhesive bandages, medicated tapes, diapers, hoods, etc., the skin base of the present invention is made of cloth, non-woven fabric, gauze, knit, paper, synthetic resin, film, pad. It may be applied, impregnated, or soaked into a part, or a part that comes into contact with the skin or an adhesive part.

  Hereinafter, the present invention will be described with reference to examples. “Parts” and “%” are based on weight unless otherwise specified.

Test Example 1 Measurement of Grain-Derived β-Glucan Content Grain-derived β-glucan was analyzed by McClary method (enzymatic method) using a β-glucan measurement kit manufactured by Megazyme. First, when the measurement sample was powder, it was passed through a 500 μm (30 mesh) sieve, the water content was measured, 100 mg of the sample was taken in a 17 ml tube, and 200 μl of a 50% ethanol solution was added and dispersed. Next, 4 ml of 20 mM phosphate buffer (pH 6.5) was added and mixed well, and then heated in a boiling water bath for 1 minute. Mix well and heat in hot water bath for another 2 minutes. After cooling to 50 ° C. and allowing to stand for 5 minutes, add 200 μl (10 U) of the lichenase enzyme solution (diluted with 20 ml of 20 mM phosphate buffer, the remaining amount is stored frozen) to each tube, The reaction was carried out at 50 ° C. for 1 hour. 5 ml of 200 mM acetate buffer (pH 4.0) was added to the tube and mixed gently. It was left to stand at room temperature for 5 minutes, and the supernatant was obtained by centrifugation. Take 100 μl in three tubes, one with 100 μl 50 mM acetate buffer (pH 4.0), the other two with 100 μl (0.2 U) β-glucosidase solution (20 ml of vial attached to kit) Diluted with 50 mM acetic acid buffer solution, and the remaining amount was stored frozen), and reacted at 50 ° C. for 10 minutes. 3 ml of glucose oxidase / beloxidase solution was added and reacted at 50 ° C. for 20 minutes, and the absorbance (EA) at 510 nm of each sample was measured. β-glucan content was determined by the following formula.

βglucan (%, W / W) = (EA) × (F / W) × 8.46
F = (100) / (absorbance of glucose 100 μg)
W = calculated anhydride weight (mg)

  In addition, when the measurement sample is an extract (liquid) from which β-glucan is extracted, the content may be measured after preparing the extract (solid or powder) as follows. That is, after adding twice the amount of ethanol to the β-glucan extract and mixing well, the precipitate was collected by centrifugation, dried well and pulverized to obtain a β-glucan extract (solid). The β-glucan extract was analyzed by McCleary method (enzyme method) using a β-glucan measurement kit manufactured by Megazyme after measuring the water content. 50 mg of each precipitated sample was taken in a 17 ml tube, and 200 μl of 50% ethanol solution was added and dispersed. After that, it measured similarly to the above.

[Test Example 2] Measurement of β-glucan content derived from microorganisms or basidiomycetes β-glucan analysis was performed by measuring the total amount of polysaccharide precipitated by alcohol by the phenol-sulfuric acid method, followed by β-glucan in the precipitated polysaccharide. Confirmation and quantification were performed using a detection and measurement kit for β-glucan containing (1-3) -β-D-bond from Seikagaku Corporation. First, the total polysaccharide amount in the measurement sample was measured by the phenol sulfuric acid method. That is, 30 μl of distilled water was added to 30 μl of the sample solution, 120 μl of phosphate buffer (pH 6.9) containing 300 mM NaCl was added thereto, 540 μl (3 times volume) of ethanol was added, and the mixture was added to −15 ° C. for 10 minutes. The polysaccharide was left to stand. After removing the supernatant, 100 μl of distilled water was added and dissolved. 100 μl of 5% phenol aqueous solution and 500 μl of sulfuric acid were added and reacted. Absorbance at 490 nm was measured using a blank obtained by adding a phenol solution and sulfuric acid to 100 μl of distilled water without adding a sample. A calibration curve was prepared using a 2-fold dilution series prepared from pullulan 10 mg / ml as a standard sample, and the amount of polysaccharide was quantified.

Next, a solution having a total polysaccharide amount of about 1 to 0.1 mg / ml is first diluted 10-fold with 0.5 M NaOH, and then diluted with β-glucan-free distilled water, and diluted to 10 ⁻¹⁰ Was prepared. 50 μl of β-glucan diluted solution was taken in a tube, 50 μl of the main reaction reagent was added, and incubated at 37 ° C. for 30 minutes. Subsequently, 50 μl of sodium nitrite solution, 50 μl of ammonium sulfamate, and 50 μl of N-methyl 2-pyrrolidone solution were added and reacted, and then the absorbance of the solution was measured at 545 nm (target wavelength: 630 nm). A calibration curve was obtained with a β-glucan solution of 7.5-60 pg / ml with the attached β-glucan standard, and the concentration of each β-glucan solution was calculated.

[Test Example 3] Measurement of β-glucan molecular weight The molecular weight of β-glucan was measured as follows. That is, 5 mg of the extract was taken in a tube, 0.5 ml of distilled water was added and dissolved in boiling water. A sample for HPLC was obtained through a 0.22 μm filter. For separation, Shodex packed column KS-805 (manufactured by Showa Denko KK), which is an HPLC gel filtration column, was used at a flow rate of 0.6 ml / min. The temperature was 50 ° C., the detection was performed with an RI detector, and the separation solvent was water. The molecular weight marker was measured using Shodex pullulan standard solution P-82 (manufactured by Showa Denko KK).

  When the extracted β-glucan was an extract (liquid), first, twice the amount of ethanol was added, cooled to −20 ° C. and allowed to stand for 1 hour to obtain a precipitate. 5 mg of the obtained precipitate was taken in a tube, and the molecular weight was measured by operating in the same manner as in the case of the extract.

[Preparation of grain-derived β-glucan raw material and production of extraction accelerator]
The glutinous bare barley was shaved with a grinding mill and refined to a yield of 82%. The soot that occurred at this time was designated 糠 -1. The barley that had been milled to a yield of 82% was further shaved by a grinding mill, and was milled to a yield of 55%. The soot generated at this time was designated as pulverized product-1. 20 L of tap water was added to the container (50 L), and the temperature was adjusted to 15 ° C. while stirring. 6 kg of Vase-1 was added to this, and the mixture was stirred and extracted for 2 hours. After solid-liquid separation with a continuous centrifuge, the supernatant was freeze-dried to obtain 450 g of an extraction accelerator.

Production Example 1 [Extraction example of β-glucan derived from cereal]
30 L of tap water was added to a container (70 L), 150 g of the extraction accelerator was added with stirring, and after dissolution, 7.5 kg of the pulverized product-1 was added. After stirring and extracting at 50 ° C. for 2 hours, the supernatant was obtained after solid-liquid separation with a continuous centrifuge. The obtained supernatant was boiled, and after cooling, 15 L of a slightly viscous β-glucan solution was obtained. Two times the amount of ethanol was added to the obtained β-glucan solution, and the precipitate was collected and dried to obtain 460 g of β-glucan (sample 1). As a result of analysis according to Test Example 1, the purity of β-glucan was 91%. As a result of analysis according to Test Example 2, the extract was detected at a molecular weight of 200,000 to 10,000, and the maximum peak was a molecular weight of 40,000. The maximum peak was confirmed to be β-glucan by the method of Test Example 1. The viscosity at 36 ° C. of 1% by weight of β-glucan of Sample 1 was 2.51 mPa · S, and the viscosity at 10 ° C. was 4.71 mPa · S.

Production Example 2 [Production of Basidiomycete-derived β-glucan]
The fruit body of Kawariharatake was crushed and pulverized, 50 liters of hot water was added to 10 kg of the pulverized product, and hot water extraction was performed for 3 hours with gentle stirring under boiling conditions. After the hot water extraction treatment, the solution was centrifuged to obtain the separated solution. Three times the amount of 99% ethyl alcohol was added to the separated liquid to obtain a precipitate, which was freeze-dried to obtain 1200 g of β-glucan (sample 2). The amount of β-glucan contained in 1 g of Sample 3 was calculated to be 860 mg. The maximum peak molecular weight was 450,000. The viscosity at 36 ° C. of 1% by weight of β-glucan of Sample 2 was 4 mPa · S, and the viscosity at 10 ° C. was 7.8 mPa · S.

Production Example 3 [Production of Microbe-Derived β-Glucan]
1 L of 2% sodium hydroxide was added to 100 g of a cell wall (yeast cell wall E) prepared from commercially available pressed bread yeast, and the mixture was stirred and extracted at 4 ° C. for 24 hours. The centrifuged extract was neutralized with HCl and precipitated with twice the amount of ethanol to obtain 20 g of β-glucan (sample 3). The amount of β-glucan contained in 10 mg of Sample 4 was calculated to be 4.2 mg. The maximum peak molecular weight was 400,000. The viscosity at 36 ° C. of 1% by weight of β-glucan of Sample 3 was 20 mPa · S, and the viscosity at 10 ° C. was 43 mPa · S.

Production Example 4 [Production of R-mevalonic acid]
R-mevalonic acid (sample 4) was produced according to the method described in JP-B-7-89940, page 3, left column, line 11 to page 4, right column, line 4.

  Using the β-glucan obtained in Production Examples 1 to 3 and mevalonic acid obtained in Production Example 4, the following skin base is produced, and using the following therapeutic agents for skin, ear drops, Eye drops, nasal preparations, and skin cosmetics were produced.

[Example 1] Skin base-1
The following formulation components were mixed, dissolved by heating, and cooled to prepare skin base-1. The viscosity of skin base-1 after standing for 1 day was 36 ° C. and 250 mPa · S at 10 ° C. and 580 mPa · S.

[Combination]
β-glucan (Sample 1 obtained in Production Example 1) 30 g
1000g of purified water

[Example 2] Skin base-2
The following ingredients were mixed and dissolved to prepare skin base-2. The viscosity of the base for skin-2 was 36 ° C, 0.81 mPa · S, and 1.77 mPa · S at 10 ° C.

[Combination]
β glucan (Sample 2 obtained in Production Example 2) 1 g
2000 g of purified water

[Example 3] Skin base-3
The following ingredients were mixed and dissolved to prepare skin base-3. The viscosity of the base for skin-3 was 36 ° C., 10500 mPa · S, and 32000 mPa · S at 10 ° C.

[Combination]
β-glucan (Sample 3 obtained in Production Example 3) 20 g
80g of purified water

[Example 4] Skin base-4
The following ingredients were mixed and dissolved by heating to prepare skin base-4. After standing at 4 ° C. for 8 hours, the viscosity of the base for skin-4 was 36 ° C., 14200 mPa · S, and 10 ° C., 30050 mPa · S.

[Combination]
β glucan (Sample 1 obtained in Production Example 1) 10 g
0.1 g of R-mevalonic acid (Sample 4 obtained in Production Example 4)
40g of purified water

[Example 5] Skin base-5
The following ingredients were mixed and dissolved to prepare skin base-5. The viscosity of the base for skin-5 was 36 ° C., 2.6 mPa · S, and 5.1 mPa · S at 10 ° C.

[Combination]
β glucan (Sample 3 obtained in Production Example 3) 1 g
R-mevalonic acid (Sample 4 obtained in Production Example 4) 0.5 g
1000g of purified water

[Comparative Example 1] Comparative Base for Skin-1
Comparative product skin base-1 was prepared in the same manner as in Example 1 except that agar (reagent grade: Wako Pure Chemical Industries, Ltd.) was used instead of β-glucan. The comparative skin base-1 formed a strong gel at 36 ° C. and had a viscosity of 100,000 mPa · S or more, which was the detection limit.

[Comparative Example 2] Comparative Base for Skin-2
A comparative skin base-2 was prepared in the same manner as in Example 1 except that agarose (manufactured by Wako Pure Chemical Industries, Ltd.) purified from agar was used instead of β-glucan. Comparative Base for Skin-2 was formed at 36 ° C., forming a firm gel, and having a viscosity of 100,000 mPa · S or more, which was the detection limit.

[Example 6] Ointment An ointment containing the base for skin-1 obtained in Example 1 and having the following composition was prepared by a conventional method. This ointment had flexibility and spreadability, and was excellent in applicability to the skin and feeling of use.

[Combination]
Hydrocortisone acetate (steroid anti-inflammatory agent) 0.05g
Polyoxyethylene (160) polyoxypropylene (30) glycol 3g
Macrogol 400 15g
Macrogol 4000 5g
Skin Base-1 60g
17 g of purified water

[Comparative Example 3]
A comparative ointment was obtained in the same manner as in Example 6 except that the comparative skin base-1 obtained in Comparative Example 1 was used instead of the skin base-1. The ointment of this comparative product was inferior in flexibility and spreadability and had an unpleasant stickiness.

[Example 7] Ointment An ointment having the following composition was prepared by a conventional method using the skin base-1 obtained in Example 1. This ointment had flexibility and spreadability, and was excellent in applicability to the skin and feeling of use.

[Combination]
Indomethacin (anti-inflammatory agent) 0.75g
Glycerin 1g
Macrogol 4000 3g
1,3-butylene glycol 20g
Skin Base-1 60g
Purified water 15g

[Example 8]
Using the skin base-1 obtained in Example 1, an ointment having the following composition was prepared by a conventional method. This ointment had flexibility and spreadability, and was excellent in applicability to the skin and feeling of use.

[Combination]
Lidocaine (local anesthetic) 0.5g
Glycyrrhetinic acid (anti-inflammatory agent) 0.3g
Benzalkonium chloride (bactericide) 0.01g
Glycerin 2g
Macrogol 400 10g
Macrogol 4000 3g
Polysorbate 80 3g
1 g of polyoxyethylene (160) polyoxypropylene (30) glycol
Skin Base-1 60g
20g of purified water

[Example 9]
Using the skin base-2 obtained in Example 2, an ointment having the following composition was prepared by a conventional method. This ointment had flexibility and spreadability, and was excellent in applicability to the skin and feeling of use.

[Combination]
Benzethonium chloride (antibacterial agent) 1g
1,3-butylene glycol 30g
Macrogol 4000 29g
Skin Base-2 40g

[Example 10]
Using the base for skin-3 obtained in Example 3, an ointment having the following composition was prepared by a conventional method. This ointment had flexibility and spreadability, and was excellent in applicability to the skin and feeling of use.

[Combination]
Miconazole nitrate (antifungal agent) 0.5g
Macrogol 400 59.5g
Macrogol 6000 10g
Skin Base-3 30g

[Comparative Example 4]
A comparative ointment product was obtained in the same manner as in Example 10 except that the comparative skin base-2 obtained in Comparative Example 2 was used instead of the skin base-3. The ointment of this comparative product was inferior in flexibility and spreadability and had an unpleasant stickiness.

[Example 11]
Using the skin base-1 obtained in Example 1, an ointment having the following composition was prepared by a conventional method. This ointment had flexibility and spreadability, and was excellent in applicability to the skin and feeling of use.

[Combination]
Acyclovir (antiviral agent) 5g
Macrogol 400 50g
Macrogol 4000 25g
Skin Base-1 20g

[Example 12]
Using the base for skin-4 obtained in Example 4, an ointment having the following composition was prepared by a conventional method. This ointment had flexibility and spreadability, and was excellent in applicability to the skin and feeling of use.

[Combination]
Chlorpheniramine maleate (antihistamine) 1g
Macrogol 400 69g
Macrogol 6000 10g
Skin Base-4 20g

[Example 13]
Using the skin base 5 obtained in Example 5, an ointment having the following composition was prepared by a conventional method. This ointment had flexibility and spreadability, and was excellent in applicability to the skin and feeling of use.

[Combination]
Indomethacin (anti-inflammatory agent) 1g
49 g of 1,3-butylene glycol
Macrogol 4000 25g
Skin Base-5 25g

[Example 14] Eye drops An eye drop was prepared by a conventional method using the base 1 for skin obtained in Example 1. The eye drops were adjusted to pH 7 with 0.1N sodium hydroxide or 0.1N hydrochloric acid. This ophthalmic solution had good liquid drainage and was excellent in feeling of instillation.

[Combination]
Skin base-1 50g
Planoprofen 0.5g
Concentrated glycerin 2.6g
1N sodium hydroxide appropriate amount 0.1N hydrochloric acid appropriate amount purified water 50g

[Comparative Example 5]
A comparative ophthalmic preparation was obtained in the same manner as in Example 14 except that the comparative skin base-1 obtained in Comparative Example 1 was used instead of the skin base-1. The eye drop of this comparative product was poor in liquid drainage and inferior in touch.

Example 15 Eye Drop An eye drop was prepared by a conventional method using the base for skin-4 obtained in Example 4. The eye drops were adjusted to pH 7 with 0.1N sodium hydroxide or 0.1N hydrochloric acid. This ophthalmic solution had good liquid drainage and was excellent in feeling of instillation.

[Combination]
Skin base-4 50g
Planoprofen 0.5g
Concentrated glycerin 2.6g
1N sodium hydroxide appropriate amount 0.1N hydrochloric acid appropriate amount purified water 50g

[Example 16] Eardrops Eardrops were produced by a conventional method using the base 1 for skin obtained in Example 1. This eardrop was easy to insert and was very excellent in spreadability, and did not cause dripping after the eardrop.

[Combination]
Gatifloxacin 0.5g
Sodium edetate 0.1g
Sodium chloride 0.9g
Skin Base-1 70.0g
28.5g of purified water

[Comparative Example 6]
A comparative product of eardrops was obtained in the same manner as in Example 16 except that the comparative skin base-1 obtained in Comparative Example 1 was used instead of the skin base-1. The ear product of this comparative product was inferior in spreadability.

[Example 17] Nasal preparation A nasal preparation was prepared in a conventional manner using the skin base-1 obtained in Example 1. The pH of the nasal preparation was adjusted to 7 with 0.1N sodium hydroxide or 0.1N hydrochloric acid. This agent for nasal cavity was easy to spray, and was very excellent in spreadability, and did not cause dripping after nasal drop.

[Combination]
Naphazoline hydrochloride 0.05g
Benzethonium chloride 0.02g
Chlorpheniramine maleate 0.5g
Lidocaine 0.5g
Concentrated glycerin 2.0g
0.01g sodium edetate
l-Menthol 0.008g
Polyoxyethylene hydrogenated castor oil 60 0.1 g
Skin Base-1 70.0g
0.1N hydrochloric acid appropriate amount 0.1N sodium hydroxide appropriate amount purified water 27g

[Comparative Example 7]
A comparative nasal preparation was obtained in the same manner as in Example 17 except that the comparative skin base-1 obtained in Comparative Example 1 was used instead of the skin base-1. The comparative product for nasal cavity was inferior in spreadability.

[Example 18] Skin cream A skin cream was produced in the usual manner using the skin base-5 obtained in Example 5. This skin cream had flexibility and spreadability, and was excellent in applicability to the skin and usability.

[Combination]
Beeswax 2.0g
Stearyl alcohol 5.0g
Stearic acid 8.0g
Squalane 10.0g
Self-emulsifying propylene glycol 3.0g
Monostearate polyoxyethylene cetyl ether (20E.O.) 1.0g
Fragrance 0.5g
Antiseptic appropriate amount antioxidant proper amount propylene glycol 7.8g
Glycerin 4.0g
Sodium hyaluronate 0.1g
Triethanolamine 1.0g
Skin Base-5 20.0g
37.5g of purified water

[Example 19]
Using the skin base-3 obtained in Example 3, a haptic agent was produced by a conventional method. The feeling of use of this haptic agent was good, and there was no rash.

[Combination]
Styrene-isoprene-styrene block copolymer 16g
Petroleum tackifier resin 20g
Liquid paraffin 12g
Sorbitan monooleate 5g
Calcium carbonate 12g
26.6g of purified water
1g methyl salicylate
l-Menthol 2g
Timor 0.3g
Sulfur 0.1g
Skin base-3 5g

Claims (4)

A skin base comprising a β-glucan having a weight average molecular weight of 1,000 to 4,600,000 and a 1% by weight aqueous solution having a viscosity at 36 ° C. of 0.5 to 10,000 mPa · S. Furthermore, the base for skin of Claim 1 which is the beta glucan whose viscosity in 10 degreeC of 1 weight% aqueous solution is 1.0-50000 mPa * S. Furthermore, mevalonic acid is contained, The base for skin of Claim 1 or 2 characterized by the above-mentioned. A therapeutic agent for skin, a skin cleanser, an ointment, a patch, a nasal preparation, an ear drop, an eye drop or a skin cosmetic comprising the skin base according to any one of claims 1 to 3.