JP2007277134A - Interleukin-6 production inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an interleukin-6 production inhibitor. <P>SOLUTION: The interleukin-6 production inhibitor comprises pyridoxine 3,4'-cyclic phosphoric acid or a physiologically permissible salt thereof as an active ingredient. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an interleukin-6 production inhibitor and a cosmetic for the prevention and / or treatment of inflammatory diseases including the inhibitor, and a cosmetic for the suppression and / or improvement of skin disorders and the like.

  Cytokines including interleukin-6 (hereinafter sometimes abbreviated as “IL-6” in the present specification) are produced from cells in order to maintain tissue homeostasis. In skin that has been exposed to time or continuous stimulation from the outside or inside, excessive production of cytokines from epidermal keratinocytes causes damage to the skin tissue. In particular, overproduction of interleukin 6 is deeply involved in the proliferation of keratinocytes, the production of collagen and proteoglycans from fibroblasts, and the promotion of collagenase secretion, and causes skin disorders such as skin inflammation and skin thickening. (See Acta Derm. Venereol., 71, pp.93-98, 1991, etc.).

  Several attempts have been proposed to prevent or treat skin disorders such as skin inflammation and skin thickening by suppressing the action and production of interleukin-6. For example, Japanese Patent Laid-Open No. 2005-263645 discloses that the release of inflammatory cytokines such as interleukin-6 is inhibited and blocked by the action of an ATP receptor antagonist on the cellular ATP receptor to block the inflammation. A method and a composition for suppression are disclosed, and a pharmaceutical composition or a cosmetic composition for suppressing and improving skin inflammation caused by an external stimulus such as ultraviolet irradiation has been proposed. In addition, active vitamin D, glucocorticoids, and the like are said to be effective in suppressing excessive production of interleukin-6 involved in skin disorders (J. Immunopathol. Pharmacol., 8, pp.199- 207, 1996; Skin Pharmacol. Appl. Skin. Physiol., 13, pp. 93-103, 2000). However, for example, active vitamin D, which is a fat-soluble vitamin, may cause accumulation in adipose tissue and the like, and it is a safety problem to administer these substances over a long period of time. Therefore, it is safe to replace these substances. The provision of an active ingredient is desired.

  On the other hand, pyridoxine is a substance with vitamin B6 action, which is metabolized to pyridoxal 5'-phosphate in the body and plays an important role in the metabolism of proteins in the body, and also acts as a coenzyme for fat metabolism. Yes. Insufficient vitamin B6 is known to cause skin inflammation, swelling, hair loss, etc. (Fragrance Journal, 17 (3), 96-100 (1989), JP 2002-265368 A). As an external preparation for skin, an external preparation containing vitamin B6 derivatives such as pyridoxine hydrochloride has been used for the treatment and prevention of skin irritations, acne, sunburn, hot flashes caused by snowburn, itching due to inflammation, and dandruff due to dry seborrhea. It has been. For example, JP 2001-354579 discloses that antipyretic and antiallergic effects are achieved by combining pyridoxine hydrochloride and pyridoxine glycyrrhetinate with a solvent extract of Lamiaceae as an anti-inflammatory agent, and atopic dermatitis in the skin. It is disclosed that a cosmetic that exhibits an improving effect on skin inflammatory diseases such as acne and rough skin can be provided.

Pyridoxine and its hydrochloride are known to be very unstable to light, and its derivatives pyridoxal, pyridoxamine, and pyridoxal 5'-phosphate are also very unstable to light. For this reason, there is a problem that even when these substances are blended into a skin external preparation, a sufficient effect as vitamin B6 cannot be obtained. In order to solve this problem, several vitamin B6 derivatives with improved light stability have been proposed. For example, International Publication WO2005 / 033123 discloses that a compound in which 3-position of vitamin B6 is glycosylated and pyridoxine 3,4′-cyclic phosphate are excellent in photostability, and these substances are used as active ingredients. Cosmetics, medicines, foods, and the like are proposed. It is also disclosed that a cosmetic composition containing these substances as an active ingredient is effective as a whitening agent, an anti-aging agent, and / or an inhibitor of wrinkle formation due to exposure to ultraviolet rays. However, the above publications do not suggest or teach that pyridoxine 3,4'-cyclic phosphate among these vitamin B6 derivatives has an interleukin-6 production inhibitory action.
Acta Derm. Venereol., 71, pp. 93-98, 1991 J. Immunopathol. Pharmacol., 8, pp.199-207, 1996 Skin Pharmacol. Appl. Skin. Physiol., 13, pp.93-103, 2000 Fragrance Journal, 17, pp.96-100, 1989 JP 2002-265368 A International Publication WO2005 / 033123

  The subject of this invention is providing the production inhibitor of interleukin-6. Another object of the present invention is to provide an interleukin-6 production inhibitor that can be safely used as an active ingredient in medicines and cosmetics and has excellent stability.

  As a result of intensive studies to solve the above problems, the present inventors have found that pyridoxine 3,4′-cyclic phosphate described in International Publication WO2005 / 033123 has an action of suppressing the production of interleukin-6. The present inventors have found that it can be used as an active ingredient such as pharmaceuticals and cosmetics as an interleukin-6 production inhibitor excellent in safety and stability. The present invention has been completed based on the above findings.

That is, the present invention provides an interleukin-6 production inhibitor containing pyridoxine 3,4′-cyclic phosphate or a physiologically acceptable salt thereof as an active ingredient.
In addition, according to the present invention, there is provided a medicine or cosmetic containing the interleukin-6 production inhibitor. This medicine is useful as a medicine for the prevention and / or treatment of diseases caused by overproduction of interleukin-6, and the above cosmetics are caused by overproduction of interleukin-6 when applied to the skin or the like. Skin disorders such as dermatitis and skin thickening can be suppressed and / or improved.

  From another aspect, the use of pyridoxine 3,4′-cyclic phosphate or a physiologically acceptable salt thereof for the production of the above-mentioned interleukin-6 production inhibitor; Use of pyridoxine 3,4'-cyclic phosphate or physiologically acceptable salts thereof for inhibiting the production of interleukin-6 in vivo in a mammal, comprising pyridoxine 3,4'-cyclic A method comprising administering to a mammal, including a human, an effective amount of phosphoric acid or a physiologically acceptable salt thereof; and a method for inhibiting and / or ameliorating skin damage in a mammal, comprising pyridoxine 3,4 Provided by the present invention is a method comprising the step of applying an effective amount of '-cyclic phosphate or a physiologically acceptable salt thereof to the skin of a mammal, including a human.

  The interleukin-6 production inhibitor of the present invention has an action of remarkably suppressing the production of interleukin-6 in the living body or skin, and prevents inflammatory diseases caused by overproduction of interleukin-6. And / or can be used as a pharmaceutical for treatment and cosmetics for suppressing and / or improving skin disorders, etc.

  Pyridoxine 3,4'-cyclic phosphate, which is an active ingredient of the interleukin-6 production inhibitor of the present invention, is a substance described in Example 6 in the examples of International Publication WO2005 / 033123. It can be easily produced according to the method described in the publication. As an active ingredient of the inhibitor of the present invention, a salt of pyridoxine 3,4′-cyclic phosphate may be used. The salt is preferably a physiologically acceptable base addition salt. Examples thereof include metal salts such as lithium salt, sodium salt, potassium salt, magnesium salt, and calcium salt, or ammonium salts such as ammonium salt, methylammonium salt, dimethylammonium salt, trimethylammonium salt, and dicyclohexylammonium salt. It may form a salt with an amino acid such as glycine. The method for producing such a base addition salt is described in Examples 6 (c) and 7 of the above-mentioned International Publication, and those skilled in the art can easily produce a base addition salt according to the method described in the above publication. it can. Moreover, you may use the hydrate or solvate of pyridoxine 3,4'- cyclic phosphate or its physiologically acceptable salt as an active ingredient of the inhibitor of this invention.

  The action of the interleukin-6 production inhibitor of the present invention is to measure the production inhibitory effect on interleukin-6 produced by ultraviolet irradiation using keratinocytes of human normal skin, for example, as shown in the following examples. Thus, it can be easily confirmed by those skilled in the art. However, it is easily understood by those skilled in the art that the inhibitory action of the inhibitor of the present invention can be easily confirmed by other well-known methods, and the interleukin of the inhibitor of the present invention can be easily understood. It is also easily understood by those skilled in the art that the production inhibitory action is not limited to the inhibitory action on the production of interleukin-6 in photoaging.

  The inhibitor of the present invention is a pharmaceutical that can achieve prevention and / or treatment of diseases such as inflammatory diseases caused by overproduction of interleukin-6, based on the action of suppressing production of interleukin-6. Can be applied as In particular, for the skin, based on the action of suppressing the production of interleukin-6, it can be applied as a medicament as an external preparation for dermatitis, and it can be applied to the skin caused by external or internal irritation. It can also be applied as a cosmetic for having an action of suppressing and / or improving various skin disorders such as inflammation and skin thickening.

  The interleukin-6 production inhibitor of this invention can be mix | blended as an active ingredient of a pharmaceutical or cosmetics, for example. As a medicine, a pharmaceutical composition can be preferably used. In addition to a pharmaceutical composition used for the prevention, diagnosis and treatment of human illnesses, a so-called quasi-drug, multivitamin, non-human The pharmaceutical composition used for the disease of other mammals is included. Examples of the pharmaceutical composition include powders, granules, fine granules, tablets (for example, uncoated tablets, film-coated tablets, thin-layer sugar-coated tablets, sugar-coated tablets, chewable tablets, double-layer tablets, etc.), capsules, powder inhalants, Examples thereof include liquid preparations, external preparations, and in-use injections provided in a dry powder form. The cosmetic is preferably a cosmetic composition in the form of a cream, solution, or emulsion, and can be provided as, for example, a powder, a foundation, a lotion, or a shampoo, but is not limited thereto. The compounding amount of the interleukin-6 production inhibitor in the above pharmaceutical composition or cosmetic composition is not particularly limited, and can be appropriately selected according to the type of composition and intended use. For example, application to skin The amount of the inhibitor to be added in the external preparation for the purpose of, for example, is about 0.001 to 10 mass percent, preferably about 0.01 to 2 mass percent with respect to the total mass of the composition. Moreover, in order for the interleukin-6 production inhibitor of this invention to exhibit the inhibitory effect stably, it is preferable that the pH of a composition is the range of 5.0-8.0.

  Arbitrary components other than the interleukin-6 production inhibitor of this invention can be mix | blended with said pharmaceutical composition or cosmetics. Examples of such components include, but are not limited to, physiologically active substances such as amino acids, lipids, sugars, hormones, enzymes, and nucleic acids. Since International Publication WO2005 / 033123 discloses various compositions including additives for pharmaceutical preparations, those skilled in the art can use appropriate compositions containing the interleukin-6 production inhibitor of the present invention and other physiologically active substances. Can be easily prepared. The entire disclosures of the above publications are incorporated herein by reference. In the production of a skin external preparation or cosmetic intended for whitening, anti-aging, or suppression of wrinkle formation by exposure to ultraviolet rays, the cosmetic, quasi-drug, skin external preparation, etc. Components usually used in production, such as water (purified water, hot spring water, deep water, etc.), oil agent, surfactant, metal soap, gelling agent, powder, alcohols, water-soluble polymer, film-forming agent , Resin, clathrate, antibacterial agent, fragrance, deodorant, salt, pH adjuster, freshener, plant / animal / microbe extract, active oxygen remover, blood circulation promoter, astringent, antiseborrhea Agents, moisturizers, chelating agents, keratolytic agents, enzymes, hormones, other vitamins and the like can be used as necessary.

  In addition, it is known that the above-mentioned action can be exhibited within the range of not impairing the effects of the present invention in producing a skin external preparation or cosmetic intended for whitening, anti-aging, or suppression of wrinkle formation by exposure to ultraviolet rays. These active ingredients can also be blended in the composition. Examples of such active ingredients include, but are not limited to, UV protection agents, antibacterial agents, whitening agents, anti-inflammatory agents, cell activators, active oxygen scavengers, and moisturizers. Absent.

  More specifically, examples of the UV protection agent include paramethoxycinnamate-2-ethylhexyl, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sodium sulfate, 4-t -Butyl-4'-methoxydibenzoylmethane, 2-phenyl-benzimidazole-5-sulfuric acid, titanium oxide, zinc oxide and the like.

  Examples of the antibacterial agent include benzoic acid, sodium benzoate, p-hydroxybenzoate ester, benzalkonium chloride, phenoxyethanol, isopropylmethylphenol, and the like.

  Whitening agents have the effect of preventing the occurrence of darkening of the skin caused by sunburn, etc., stains caused by pigmentation, buckwheat, etc., such as arbutin, ellagic acid, linoleic acid, vitamin C and its derivatives, vitamin E And derivatives thereof, glycyrrhizic acid and derivatives thereof, tranexamic acid, placenta extract, chamomile extract, licorice extract, ages extract, seaweed extract, sea cucumber extract, cucumber extract, gokahi extract, rice bran extract Extract, Wheat germ extract, Saisin extract, Hawthorn extract, Sunpens extract, Shirayuri extract, Peonies extract, Sempukuka extract, Soy extract, Tea extract, Molasses extract, Byaclen extract, Grape extract , Hop extract, Mikaika extract, Mokka extract, Yukinoshita extract, Yokuinin extract Etc. The.

  Anti-inflammatory agents have the effect of suppressing inflammation such as hot flashes and erythema after sunburn. For example, sulfur and its derivatives, glycyrrhizic acid and its derivatives, glycyrrhetinic acid and its derivatives, aloe extract, altea extraction , Ashitaba extract, Arnica extract, Ginseng extract, nettle extract, Duckweed extract, Hypericum extract, Chamomile extract, Snapdragon extract, Watercress extract, Comfrey extract, Salvia extract, Bamboo extract , Perilla extract, birch extract, gentian extract and the like.

  Cell activators are used for the purpose of improving rough skin, such as caffeine, chicken crown extract, shell extract, shell extract, royal jelly, silk protein and its degradation products or derivatives thereof, lactoferrin or degradation products thereof. , Mucopolysaccharides such as chondroitin sulfate and hyaluronic acid or their salts, collagen, yeast extract, lactic acid bacteria extract, bifidobacteria extract, fermentation metabolic extract, ginkgo biloba extract, barley extract, assembly extract, lysium extract Products, carrot extract, rosemary extract, glycolic acid, citric acid, lactic acid, malic acid, tartaric acid, succinic acid and the like.

  The active oxygen scavenger has an action such as suppression of lipid peroxide production. For example, superoxide dismutase, mannitol, quercetin, catechin and derivatives thereof, rutin and derivatives thereof, button pi extract, yashajitsu extract, melissa extract , Lanahan fruit extract, retinol and its derivatives, vitamin A such as carotenoid, thiamine and its derivative, riboflavin and its derivative, pyridoxine and its derivative, vitamin B such as nicotinic acid and its derivative, tocopherol and its derivative, etc. Vitamin E, dibutylhydroxytoluene, butylhydroxyanisole, etc. are mentioned.

  Examples of the humectant include proteins such as elastin and keratin or derivatives thereof, hydrolysates and salts thereof, amino acids such as glycine, serine, aspartic acid, glutamic acid, arginine and theanine and derivatives thereof, sorbitol, erythritol, Trehalose, inositol, glucose, sucrose and derivatives thereof, dextrin and derivatives thereof, saccharides such as honey, D-panthenol and derivatives thereof, urea, phospholipid, ceramide, auren extract, ginger extract, diautum extract, sensyu extract Product, mallow extract, gypsophila extract, dokudami extract, hamamelis extract, bodaige extract, maronier extract, quince extract and the like.

Hereinafter, the present invention will be described more specifically with reference to examples. However, the scope of the present invention is not limited to the following examples. The pyridoxine 3,4-cyclic sodium phosphate and pyridoxine 3,4-cyclic magnesium phosphate used in the following examples were synthesized by the methods described in Examples 6 and 7 of International Publication WO2005 / 033123, respectively.
Example 1: Cleansing cream (ingredient) (%)
(1) Stearic acid 2.0
(2) Stearyl alcohol 3.0
(3) Lipophilic glyceryl monostearate 2.0
(4) Beeswax 1.5
(5) Vaseline 6.0
(7) Liquid paraffin 40.0
(8) Dimethylpolysiloxane (100CS) 0.5
(9) Sorbitan sesquioleate 1.0
(10) Preservative appropriate amount (11) Triethanolamine 1.0
(12) Propylene glycol 10.0
(13) Polyethylene glycol 20000 0.5
(14) Carboxyvinyl polymer 0.05
(15) Purified water Residual amount (16) Pyridoxine 3,4-cyclic sodium phosphate 0.05
(17) Perfume appropriate amount (production method)
A. Ingredients (1) to (10) are dissolved by heating and maintained at 70 ° C.
B. Ingredients (11) to (15) are dissolved by heating and maintained at 70 ° C.
C. A is added to B and emulsified.
D. After cooling C, components (16) and (17) were added and mixed to obtain a cleansing cream.
The obtained cleansing cream was a gentle cleansing cream that spreads lightly and has good makeup stains, and suppresses inflammation and thickening of the skin and smoothes the skin.

Example 2: Face wash (component) (%)
(1) Lauric acid 5.0
(2) Myristic acid 18.5
(3) Stearic acid 6.0
(4) Glycerin 12.0
(5) Polyethylene glycol 1500 5.0
(6) Potassium hydroxide 6.5
(7) Purified water remaining amount (8) Palm oil fatty acid diethanolamide 5.0
(9) Palm oil fatty acid methyl taurine sodium 1.8
(10) Polyoxyethylene (7.5E.O.) lauryl ether 2.0
(11) Ethylene glycol distearate 1.0
(12) Hydroxypropyl methylcellulose 1% aqueous solution 5.0
(13) Pyridoxine 3,4-cyclic sodium phosphate 0.1
(14) Perfume appropriate amount (production method)
A. Components (1) to (7) are dissolved by heating.
B. Components (8) to (11) are dissolved by heating.
C. Add B to A and mix.
D. After cooling C, components (12) to (14) are added and mixed to obtain a face wash.
The obtained facial cleanser had a fine and rich foaming and a refreshing feeling of use, and was a facial cleanser that smoothed the skin by suppressing inflammation and thickening of the skin.

Example 3: Lotion 1
(Ingredient) (%)
(1) Citric acid 0.05
(2) Sodium citrate 0.2
(3) Sodium pyrrolidonecarboxylate (50%) solution * 1 0.5
(4) Glycerin 3.0
(5) 1,3-butylene glycol 8.0
(6) L-ascorbic acid 2-glucoside * 2 2.0
(7) Sodium hydroxide 0.25
(8) Pyridoxine 3,4-cyclic sodium phosphate 0.2
(9) Purified water remaining amount (10) ethyl alcohol 10.0
(11) Perfume Appropriate amount (12) Preservative Appropriate amount (13) Polyoxyethylene monooleate (20E.O.)
Sorbitan 0.5
* 1: Made by Ajinomoto Co. * 2: Made by Hayashibara Biochemical Research Institute (production method)
A. Components (1) to (9) are mixed and dissolved.
B. Components (10) to (13) are mixed and dissolved.
C. B was added to A and mixed to obtain a skin lotion.
The obtained lotion 1 had a fresh and refreshing feeling of use, and was a lotion that suppressed skin inflammation and skin thickening, kept the skin fresh and smoothed the skin.

Example 4: Lotion 2
(Ingredient) (%)
(1) Meadow home oil 0.1
(2) Jojoba oil 0.05
(3) Perfume appropriate amount (4) preservative appropriate amount (5) polyoxyethylene monooleate (20E.O.)
Sorbitan 0.5
(6) Isostearic acid polyoxyethylene hydrogenated castor oil (50 EO) 1.0
(7) Ethyl alcohol 8.0
(8) Glycerin 5.0
(9) 1,3-butylene glycol 5.0
(10) Polyethylene glycol 1500 0.1
(11) Pyridoxine 3,4-cyclic sodium phosphate 0.1
(12) Remaining amount of purified water (production method)
A. Components (1) to (7) are mixed and dissolved.
B. Components (8) to (12) are mixed and dissolved.
C. A is added to B and mixed to obtain a skin lotion.
The obtained lotion 2 had a fresh and mellow feeling of use, and was a lotion that suppressed skin inflammation and thickening, kept the skin fresh and smoothed the skin.

Example 5: Lotion 3
(Ingredient) (%)
(1) Glyceryl tri-2-ethylhexanoate 0.08
(2) Squalane 0.02
(3) Sorbitan sesquioleate 0.05
(3) Polyoxyethylene monooleate (20E.O.)
Sorbitan 0.05
(4) Polyoxyethylene (8E.O.) alkylene (12-15)
Ether phosphoric acid 0.1
(5) Preservative appropriate amount (6) perfume appropriate amount (7) ethyl alcohol 8.0
(8) Dipropylene glycol 8.0
(9) Glycerin 4.0
(10) Pyridoxine 3,4-cyclic sodium phosphate 0.1
(11) Remaining amount of purified water (production method)
A. Components (1) to (7) are mixed and dissolved.
B. Components (8) to (11) are mixed and dissolved.
C. A is added to B and emulsified to obtain a skin lotion.
The obtained lotion 3 had a clean and light feeling of use, and was a lotion that suppresses inflammation and thickening of the skin, keeps the skin fresh and smoothes the skin.

Example 6: Latex (Ingredient) (%)
(1) Stearic acid 1.0
(2) Cetanol 0.5
(3) Lipophilic glyceryl monostearate 0.5
(4) Liquid paraffin 2.0
(5) Squalane 3.0
(6) Jojoba oil 3.0
(7) Cetyl palmitate 0.2
(8) Preservative appropriate amount (9) Sorbitan monostearate 0.3
(10) Polyoxyethylene monooleate (20E.O.)
Sorbitan 0.5
(11) Triethanolamine 0.5
(12) 1,3-butylene glycol 15.0
(13) Glycerin 3.0
(14) Polyethylene glycol 6000 0.5
(15) Purified water Remaining amount (16) Carboxyvinyl polymer 1% solution 8.0
(17) Dipotassium glycyrrhizinate * 1 0.1
(18) Pyridoxine 3,4-cyclic sodium phosphate 0.5
(19) Fragrance appropriate amount * 1: Made by Maruzen Pharmaceutical Co., Ltd. (production method)
A. Ingredients (1) to (10) are dissolved by heating and maintained at 70 ° C.
B. Ingredients (11) to (15) are dissolved by heating and maintained at 70 ° C.
C. B is added to A to emulsify, and components (16) to (17) are further added and mixed.
D. C is cooled, and components (18) and (19) are added and mixed to obtain an emulsion.
The obtained milky lotion had a smooth and mellow feeling of use, and was a milky lotion that softened the skin by suppressing skin irritation and thickening, giving the skin a moisturizing feeling and an appropriate emollient feeling.

Example 7: Cream (ingredient) (%)
(1) Stearic acid 2.5
(2) Cetanol 2.5
(3) Lipophilic glyceryl monostearate 2.0
(4) Vaseline 2.0
(5) Dipentaerythritol fatty acid ester * 1 2.0
(6) Isotridecyl myristate 5.0
(7) Liquid paraffin 8.0
(8) Squalane 5.0
(9) Beeswax 1.0
(10) Cetyl palmitate 2.0
(11) Sorbitan sesquioleate 0.5
(12) Polyoxyethylene monooleate (20E.O.)
Sorbitan 1.5
(13) Preservative appropriate amount (14) Triethanolamine 1.2
(15) 1,3-butylene glycol 8.0
(17) Glycerin 2.0
(17) Polyethylene glycol 20000 0.5
(18) Purified water Remaining amount (19) Carboxyvinyl polymer 1% aqueous solution 10.0
(20) Arbutin * 2 3.0
(21) Pyridoxine 3,4-cyclic sodium phosphate 1.0
(22) Perfume appropriate amount * 1: Cosmol 168AR (Nisshin Oillio Group)
* 2: Wako Pure Chemical Industries, Ltd. (production method)
A. Ingredients (1) to (13) are dissolved by heating and maintained at 70 ° C.
B. Ingredients (14) to (18) are dissolved by heating and maintained at 70 ° C.
C. B is added to A to emulsify, and component (19) is further added and mixed.
D. C is cooled, components (20), (21) and (22) are added and mixed to obtain a cream.
The obtained cream had a smooth and rich feeling of use, was a cream that suppressed skin inflammation and thickening, imparted a high emollient feeling to the skin, and softened the skin.

Example 8: serum (component) (%)
(1) Glyceryl tri-2-ethylhexanoate 0.1
(2) Meadow Home Oil 0.05
(3) Jojoba oil 0.05
(4) Preservative appropriate amount (5) perfume appropriate amount (6) polyoxyethylene monooleate (20E.O.)
Sorbitan 0.5
(7) Polyoxyethylene hydrogenated isostearate castor oil (50 EO) 1.5
(8) Ethyl alcohol 5.0
(9) Glycerin 4.0
(10) Dipropylene glycol 8.0
(11) 1,3-butylene glycol 8.0
(12) Sodium lactate 0.5
(13) Sodium pyrrolidonecarboxylate (50%) solution * 1 0.5
(14) Hydroxyethyl cellulose 0.08
(15) Sodium alginate 0.05
(16) Pyridoxine 3,4-cyclic sodium phosphate 0.2
(17) Purified water remaining amount (production method)
* 1: A. Ajinomoto Co., Inc. Components (1) to (8) are mixed and dissolved.
B. Components (9) to (17) are mixed and dissolved.
C. A is added to B and mixed to obtain a serum.
The obtained cosmetic liquid had a mellow and mild feeling of use, was a cosmetic liquid that suppressed skin inflammation and thickening, imparted a high moisturizing feeling and emollient feeling to the skin, and made the skin fresh and soft.

Example 9: Pack (Peel-off type)
(Ingredient) (%)
(1) Polyvinyl alcohol 12.0
(2) Methylcellulose 0.1
(3) Glycerin 3.0
(4) 1,3-butylene glycol 5.0
(5) Purified water remaining amount (6) perfume appropriate amount (7) preservative appropriate amount (8) glyceryl tri-2-ethylhexanoate 0.1
(9) Polyoxyethylene monooleate (20E.O.)
Sorbitan 1.0
(10) Ethyl alcohol 13.0
(11) Pyridoxine 3,4-cyclic sodium phosphate 0.1
(Manufacturing method)
A. Components (1) to (5) are dissolved by heating.
B. Components (6) to (10) are mixed and dissolved.
C. After A is cooled, B and component (11) are added and mixed to obtain a pack.
The resulting pack has a moderate refreshing feeling and high tension, suppresses inflammation and thickening of the skin, imparts an appropriate moisturizing feeling and elasticity to the skin after packing, and softens the skin. Met.

Example 10: Massage cream (ingredient) (%)
(1) Stearic acid 2.0
(2) Stearyl alcohol 2.5
(3) Lipophilic glyceryl monostearate 2.0
(4) Sorbitan sesquioleate 1.0
(5) Cetyl palmitate 1.0
(6) Dipentaerythritol fatty acid ester * 1 4.0
(7) Vaseline 20.0
(8) Liquid paraffin 28.0
(9) Dimethylpolysiloxane (100CS) 0.5
(10) Sodium hydroxide 0.1
(11) Dipropylene glycol 7.0
(12) Carboxyvinyl polymer 0.1
(13) Purified water Residual amount (14) Pyridoxine 3,4-cyclic sodium phosphate 0.1
(15) Fragrance appropriate amount * 1: Cosmol 168AR (Nisshin Oillio Group)
(Manufacturing method)
A. Ingredients (1) to (9) are dissolved by heating and maintained at 70 ° C.
B. Components (10) to (13) are dissolved by heating and maintained at 70 ° C.
C. A is added to B and emulsified.
D. After cooling C, components (14) and (15) were added and mixed to obtain a massage cream.
The resulting massage cream has a rich and smooth feeling of use, has a high massage effect, suppresses inflammation and thickening of the skin, moisturizes the skin and gives it a smooth feel. there were.

Example 11: Liquid foundation (ingredient) (%)
(1) Stearic acid 2.0
(2) Cetanol 0.5
(3) Behenyl alcohol 1.0
(4) Petrolatum 2.5
(5) Liquid paraffin 5.0
(6) Self-emulsifying glyceryl monostearate 1.0
(7) Preservative appropriate amount (8) Titanium oxide 6.0
(9) Color pigment 4.0
(10) Mica 2.0
(11) Talc 4.0
(12) Carboxymethylcellulose 0.2
(13) Bentonite 0.4
(14) Purified water remaining amount (15) Pyridoxine 3,4-cyclic magnesium phosphate 1.0
(16) Perfume appropriate amount (production method)
A. Components (1) to (7) are dissolved by heating.
B. Ingredients (8) to (11) are added to A, mixed uniformly, and kept at 70 ° C.
C. Ingredients (12) to (14) are dissolved by heating and maintained at 70 ° C.
D. B is added to C and emulsified.
E. After cooling D, components (15) and (16) were added and mixed to obtain a liquid foundation.
The obtained liquid foundation was a liquid foundation that had a light and expansive feeling of use, suppressed skin inflammation and thickening, and had a uniform and beautiful finish.

Test Example The interleukin-6 production inhibitory action of pyridoxine 3,4-cyclic phosphate was examined using as an index the production of interleukin-6 produced when keratinocytes were irradiated with ultraviolet rays.
Human normal skin keratinocytes were cultured, seeded in a 24-well plate at a density of 1 × 10 ⁴ / cm ² , and the culture was continued to a subconfluent state. KGM2 (manufactured by Kurabo Industries, 0.03% Ca) was used as a medium, and 100 μL of pyridoxine 3,4-cyclic phosphate was added to the medium at a final concentration of 25, 12.5, 6.25, 3.12, 1.56 mg / mL. For dilution of pyridoxine 3,4-cyclic phosphate, water was used and neutralized with 5N NaOH. Three hours later, after washing twice with phosphate buffered saline (PBS), 1 mL of Hanks' solution was added and irradiated with ultraviolet rays. UV-B (Dermaray) was used for ultraviolet irradiation, and 50 mJ was irradiated. After removing the Hanks solution, the medium was added and pyridoxine 3,4-cyclic phosphate was added again. After 24 hours, the medium was collected and centrifuged to remove cell components and the like, and interleukin-6 in the obtained medium was measured with an IL-6 measurement kit. Interleukin-6 [(h) IL-6] Human, ELISA Biotrak ™ System was used for the measurement. As a control, the same test was performed on pyridoxine 3,4-cyclic phosphate-untreated cells and UV-irradiated cells. The results are shown in FIG. From this result, it is clear that pyridoxine 3,4-cyclic phosphate significantly suppresses the production of interleukin-6 induced by ultraviolet irradiation.

It is the figure which showed the inhibitory effect of the pyridoxine 3, 4-cyclic phosphate with respect to the interleukin-6 production in the keratinocyte induced by ultraviolet irradiation. In the figure, UV + indicates the result of UV irradiation, and UV- indicates the result of no UV irradiation.

Claims (4)

An interleukin-6 production inhibitor comprising pyridoxine 3,4'-cyclic phosphate or a physiologically acceptable salt thereof as an active ingredient. A medicament for preventing and / or treating a disease caused by overproduction of interleukin-6, comprising the interleukin-6 production inhibitor according to claim 1. A cosmetic comprising an inhibitor of interleukin-6 production according to claim 1, which is a cosmetic having an action of suppressing and / or improving skin disorders caused by excessive production of interleukin-6. The cosmetic according to claim 3, wherein the skin disorder is dermatitis and / or skin thickening.