JPH09255547A - Skin preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin preparation for external use useful for the prevention and amelioration of various skin troubles such as skin peeling, pachyderma, chapped skin and pigmentation. SOLUTION: This preparation contains 0.000001-10wt.%, preferably 0.0001-1 wt.%(based on the preparation) of an NFκ activation suppressing substance. The substance for suppressing the activation of NFκ B prevents the formation of skin spot, skin peeling, pachyderma, chapped skin, disturbance of skin texture, denaturation and destruction of corium component and itchiness. The substance is e.g. N-acetylcysteine, pyrrolidine dithiocarbonate, benzoquinone derivative, vanadium complex or cyclic imide derivative. The preparation is further compounded with conventional gelling agent, water-absorbing oleophilic active component, antiseptic agent, antioxidant, solvent, perfume, filler, coloring substance, etc. It is further incorporated with one or more agents selected form among antibacterial agent, fungicide, anti-inflammatory agent, antipruritic and antianthemic agent, antiviral agent, keratolytic agent, anti-free radical agent, antioxidant, antisebum agent, antidandruff agent, antiacne agent and humectant.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to skin peeling, thickening,
The present invention relates to a skin external preparation useful for prevention and improvement of various skin problems such as rough skin and pigmentation.

[0002]

2. Description of the Related Art In recent years, keeping healthy and beautiful skin has become a serious concern for men and women of all ages. However, the skin is subtly affected by temperature, humidity, ultraviolet rays, aging, illness, stress, eating habits, etc., so that various functions of the skin decline,
Aging of the skin, various troubles occur, and various changes in appearance are caused, which may further cause mental stress to people. Further, one of the typical types of skin aging is the formation of "stain (pigmentation)", which is one of the major cosmetic problems especially for women.

The skin is anatomically classified into the epidermis, the dermis, and the subcutaneous tissue in order from the surface. Most of the epidermis consists of keratinocytes, and pigment cells (melanocytes), Langerhans cells, etc. are mixed therein. Under an optical microscope, the epidermis is divided into four layers: basal layer, spinous layer, granular layer, and stratum corneum. Keratinocytes divide in the bottom layer, the basal layer, in an almost constant cycle and are sequentially pushed up from the basal layer (keratinization). With this process, the keratinocytes gradually flatten and become a thin plate-like structure in the stratum corneum. Then, the outermost stratum corneum gradually peels off as so-called dirt.

On the other hand, fibroblasts and mast cells are present in the dermis, which is located under the epidermis, in a form surrounded by proteins called extracellular matrix such as collagen and elastin. In addition, the dermis contains many intricate microvessels. In the skin, the cells and proteins described above are closely linked to maintain healthy and beautiful skin. But,
Due to aging and the external environment, the skin gradually changes its function, properties, structure, appearance, etc., and it is sensuously hypersensitivity, itching, and an increase in appearance of stains (pigmentation). Disorders of texture or rough skin due to keratinization may occur. These diseases are different from diseases and do not hinder daily life by themselves, but they are extremely serious problems from a cosmetic or psychological point of view and maintain youthful and healthy skin forever. It is what everyone wants.

Daily skin hypersensitivity and itching etc. are caused by various factors such as soap, shampoo, rinse, shaving,
Since it can be caused by rubbing, drying, temperature change, sunlight, etc., and it is not a disease, it has not been given much importance so far. Antihistamines, steroids, and antipyretic analgesics such as ibuprofen, which have been conventionally used as medicines, are used for excessive itching and fever. Recently, it has been reported that a substance P antagonist is effective for sensitive skin (Japanese Patent Laid-Open No. 7-304649).

Although there is no strict definition of "texture of the skin", this does not appear to have deep irregularities on the skin, such as wrinkles, but a fine disturbance of the stratum corneum occurs in the epidermis, As a result, it can be generally understood that the gloss and feel of the skin are affected. One of the causes of such irregular skin texture and rough skin due to abnormal keratinization is that the proliferation and keratinization cycle of epidermal keratinocytes changes due to any of the above-mentioned endogenous or environmental factors of the living body. it is conceivable that.

Although the mechanism of aging is not clear, since the skin is located in the outermost layer of the living body and plays a frontier role in the defense of the body, accumulation of damage due to environmental factors promotes the skin aging phenomenon. It is thought to have a large effect on the.
Stain-like pigmentation, which is one of the typical symptoms of skin aging, occurs due to an increase in melanin pigment synthesized by melanocytes in the epidermis. It has been pointed out that the factors are involved, but it has not been clarified yet. Therefore, until now, drugs for the purpose of suppressing the production of melanin and reducing existing melanin have been studied as whitening agents, and until now, arbutin, kojic acid, vitamin C,
Licorice extract (JP-A-63-23809, JP-A-1)
No. 149706), parentheses (JP-A-64-16)
709) and hydroxystilbene (Japanese Patent Laid-Open No. 64-64-
No. 38,093), 3-hydroxychromone (JP-A-55-111410, JP-A-55-143908), isoflavone (JP-A-58-22504), and the like.

The dermis located in the lower layer of the epidermis is affected by both intrinsic and extrinsic factors, so that the dermis component D
NA-protein crosslinks (crosslinks), obstacles and degeneration of protein crosslinks such as collagen and elastin, S
It causes inactivation of antioxidant enzymes such as OD (superoxide dismutase), membrane lipid peroxidation of cell components and consequent deterioration of cell function, and as a result, it also affects the function and properties of the entire skin and appearance. Therefore, it is considered that maintaining a healthy dermis condition leads to maintaining a healthy skin in appearance and function.

[0009]

SUMMARY OF THE INVENTION Accordingly, the object of the present invention is to remove skin, thicken, rough skin, disturb texture, pigmentation,
(EN) It is intended to provide an external preparation for skin which is useful for preventing or improving denaturation / destruction of dermis constituents or itch.

[0010]

In such an actual situation, the present inventor, in the process of advancing research on the properties and functions of the skin, skin that does not exhibit the characteristics of inflammation such as redness, swelling, and fever, That is, activation of NFκB has a very large effect on the formation of spots, exfoliation, thickening, rough skin, irregular texture, and degeneration and destruction of dermal components in healthy skin that is not accompanied by inflammation. In addition, the substance that suppresses the activation of NFκB (NFκB activation inhibitor) causes the formation of stains on the skin, skin peeling, thickening, rough skin, disordered texture, degeneration and destruction of dermal components. They have found that it can be effectively prevented, and have completed the present invention.

That is, the present invention provides a skin external preparation for preventing and improving skin peeling, thickening, rough skin, rough texture, pigmentation, denaturation / destruction of dermis constituents or itch, which contains an NFκB activation inhibiting substance. To provide.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION Higher order life phenomena such as development, differentiation, proliferation and maintenance of homeostasis are accurately performed according to a specific genetic program, which is the expression of specific genes in individual cells. It is regulated by activation, differentiation and proliferation at the cellular level through regulation. These changes begin when cells that should express genetic information are stimulated by cytokines and hormones from the outside and bind to receptors on the cell membrane, and eventually undergo nuclear reactions through various biochemical reactions. Signal transduction to cause changes in gene expression. It is known that such control of gene expression is mainly performed at the transcription level of the gene.

The gene group whose expression is induced by stimulation from the outside is in a state where it can be rapidly reactivated by stimulation. Which gene is selectively activated is determined by the specific nucleotide sequence present in the expression control region of the gene and the presence or absence of a transcription regulatory factor that specifically binds to these cis elements. That is, it is considered that gene expression occurs when a transcription regulatory factor is quantitatively or qualitatively activated by an external stimulus.

Among transcriptional regulatory factors, NFκB is a protein consisting of two types of subunits, p50 and p65,
When unstimulated, it is present in the cytoplasm by binding to the inhibitory protein I-κB, but when stimulated by IL-1 or TNF-α, the kinase activated thereby causes I-
It is believed that κB is inactivated and the released NFκB translocates to the nucleus to activate transcription.

Genes that are activated by NFκB, that is, have a cis element that binds NFκB to the expression control sequence are IL-1, IL-6, IL-8, IFN-.
It is known that many are related to cytokines and adhesion molecules involved in immune / inflammatory reactions such as β, ELAM-1, and ICAM-1. In addition, human immunodeficiency virus (HIV) and human T-cell leukemia virus (HTLV-
I), cytomegalovirus (CMV), adenovirus, etc. are considered to be activated by the transcription of NFκB in the host cell, which promotes the growth of virus and spread of infection. , HIV, H
It is expected to be effective in treating viral infections such as TLV-I, CMV, and adenovirus (Experimental Medicine:
Volume 9, Issue 16, 68-, 1991: Annu. Rev. Immunol .: Volume 12, 141-, 199
4, Advances in Immunology: 58, 1-).

From the viewpoint of such disease control, a gallic acid derivative (Japanese Patent Application No. 7-215983) previously reported by the applicant of the present invention has been searched for a substance which suppresses the activation of NFκB. , N-acetyl cysteine and pyrrolidine dithiocarbonate (The Journal of Immunolog
y, 1994,153: 2681-), aspirin and sodium salicylate (Science, 1994,265 (12): 956-), benzoquinone derivatives (JP7291860, JP7291859), vanadium complex (DE4336642), pervanadate (J. Biological che
m., 270 (18) 10631-10639,1995), phenylarsine oxide (J. Biological chem., 270 (18) 10631-10639,199).
5), cyclic imide derivatives (WO9501348), tosylphenyl chloromethyl ketone, diisocoumarin, α-tocopheryl succinate, pentoxifylline and the like have been reported. However, it is not yet known that activation of NFκB is involved in various skin troubles, and therefore, the external preparation for skin of the present invention containing an NFκB activation inhibitor has not been proposed yet.

The NFκB activation inhibitor used in the present invention is not limited to a specific substance, but in view of transdermal absorbability, a non-protein substance is particularly preferable. In addition to the reported gallic acid derivatives (Japanese Patent Application No. 7-215983), known substances such as N-acetyl cysteine, pyrrolidine dithiocarbonate, benzoquinone derivative, vanadium complex, cyclic imide derivative, and tosyl. Examples thereof include phenylchloromethyl ketone, diisocoumarin, α-tocopheryl succinate, and pentoxifylline.

The amount of such NFκB activation-inhibiting substance used is preferably 0.000001 to 10% by weight, and particularly preferably 0.0001 to 1% by weight in the external preparation for skin.

The external preparation for skin of the present invention contains additives that are usually added to the external preparation for skin, such as water-absorbing gelling agent, lipophilic gelling agent, water-absorbing active ingredient, lipophilic active ingredient, and antiseptic. Agents, antioxidants, solvents, fragrances, fillers and coloring substances can be added. The blending amount thereof is an amount usually used in an external preparation and can be 0.01 to 20% by weight in the external preparation for skin.

Examples of oils include mineral oils (petroleum jelly oil, etc.), vegetable oils (sunflower oil, etc.), animal oils, synthetic oils (purserine oil, etc.), silicone-containing oils, and fluorinated oils (perfluoropolyether, etc.). Can be mentioned. Also,
A fatty alcohol and a fatty acid (such as stearic acid) can be used in combination with these oils.

As the emulsifier, glycerol stearate, polysorbate 60, PEG-6 / PEG-32 /
Glycol Stearate Mixture (Gattefosse
Company: Trade name Tefose) and the like. Examples of the solvent include lower alcohols, and ethanol and isopropanol are particularly preferable. Examples of water-absorbent gelling agents include carboxyvinyl polymers, acrylic copolymers, polyacrylamides, polysaccharides and natural rubber. Examples of the lipophilic gelling agent include modified clay, fatty acid metal salts, and hydrophobic silica.

Examples of the water-absorptive active ingredient include proteins, protein hydrolysates, amino acids, polyalcohols, ureas, allantoin, sugars and their derivatives, vitamins, hydroxy acids and the like. Examples of lipophilic active ingredients include retinol and its derivatives, tocopherol and its derivatives, essential fatty acids, ceramides, essential oils, salicylic acid and its derivatives and the like.

Examples of the drug include antibacterial agents, antibacterial agents,
One or more selected from anti-inflammatory agents, anti-pruritic agents, anti-viral agents, keratolytic agents, anti-free radical agents, antioxidants, anti-sebum agents, anti-dandruff agents, anti-acne agents and moisturizers. To be Examples of antibacterial agents include clindamycin phosphate, erythromycin, and tetracycline antibiotics. Examples of the antibacterial agent include imidazole type compounds such as econazole, ketoconazole, miconazole and salts thereof; polyene compounds such as amphotericin B; and arisamines such as terbinafine and octopirox. As an anti-inflammatory agent,
Steroid agents such as hydrocortisone and betamethasone; ibuprofen and its salts, acetylsalicylic acid, acetaminophen, glycyrrhizinic acid and the like. Examples of antipruritic agents include tenaldine, trimeprazine, cyproheptadine and the like. Examples of antiviral agents include acyclovir and the like.

Examples of the keratolytic agent include α-hydroxycarboxylic acid and salts thereof, β-hydroxycarboxylic acid and salts thereof, β-ketocarboxylic acid and salts thereof, amides and esters such as glycolic acid, lactic acid, salicylic acid and citric acid. Hydroxy acids; fruit acid, n-octanoyl-5-
Salicylic acid and the like can be mentioned. Examples of the anti-free radical agent include α-tocopherol and its esters, superoxide dismutases, metal chelating agents, ascorbic acid and its esters, and the like.

Examples of antisebum agents include progesterone. Examples of the antidandruff agent include octopirox and zinc pyrithione. As an anti-acne agent,
Examples thereof include retinoic acid and benzoyl peroxide. Moisturizers include natural and synthetic ceramides, hyaluronic acid,
Cholesterol and its salts, collagens, etc. are mentioned.

The external preparation for skin of the present invention can be in the same form as a conventional external preparation for skin and can be prepared according to a conventional method. As the form of the skin external preparation,
Aqueous or water-alcoholic solution such as lotion; water-in-oil liquid or semi-liquid emulsion prepared by dispersion (H / E) of fatty phase (E) in aqueous phase (H), reverse phase (E) / H) oil-in-water liquid or semi-liquid emulsions; cream-type or gel-type emulsions having a flexible consistency; microemulsions; aqueous gel dispersions, anhydrous gel dispersions, vesicular dispersions, etc. Can be mentioned. The proportion of the fatty phase in the emulsion is preferably 5 to 80% by weight in the external preparation for skin of the present invention, particularly 5 to
50% by weight is preferred.

The external preparation for skin of the present invention is a cream for cleaning, protecting, treating or care of face, hands, feet or body (for example, day and night cream, makeup removing cream, foundation cream, sunscreen cream). , Liquid foundation, make-up removing lotion, skin care body lotion, sunscreen lotion, skin care lotion, gel or foam and the like depending on the application.

[0028]

The external preparation for skin of the present invention is useful for preventing and improving skin peeling, thickening, rough skin, irregular texture, pigmentation, denaturation / destruction of dermis constituents, and itching.

[0029]

Next, the present invention will be described with reference to examples, but the present invention is not limited to these examples.

Test Example 1 Effect of NFκB activation inhibitor on skin peeling: After the hair of the back of a white guinea pig was shaved, 1 cm ² of NFκB activation inhibitor (100 mM: 10
μl), and 2 hours after that, a patch test seal impregnated with a 1% SDS (sodium dodecyl sulfate) aqueous solution was applied for 30 minutes, and then the test substance was applied again. This operation was repeated for 7 days, and after 7 days, the skin was collected, stained with HE, photographed with a microscope, and the thickening and peeling state of the epidermis were measured and observed. The thickness of the epidermis was actually measured on a photograph, and the degree of peeling was evaluated by a relative comparison by visual observation, and was evaluated in four levels, where SDS untreated control was 1 and SDS treated (SDS + ethanol) was 4. . Table 1 shows the results.

[0031]

[Table 1]

Test Example 2 Effect of NFκB activation inhibitor on texture disorder: 1 cm ² of human skin was coated with NFκB activation inhibitor (100 mM: 15 μl), and 2 hours later, 30 minutes of dry nitrogen gas was applied to the site. I sprayed for a minute.
This operation was repeated for 10 days, and after 10 days, a replica of the skin was collected using a hydrophilic Exaflex hydrophilic vinyl silicone image-forming agent (manufactured by DCI Corporation). From this replica, the degree of texture of the skin was visually evaluated in 5 levels, with 1 being bad and 5 being good. Table 2 shows the results.

[0033]

[Table 2]

Test Example 3 Effect of NFκB Activation Inhibitor on Pruritus: Balb / c mouse was coated with NFκB activation inhibitor (100 mM: 15 μl), 2
Histamine solution was injected intradermally after hours, and the behavior of the mice was video-recorded for 1 hour thereafter. The time during which the mouse scratched the histamine-administered site was counted from the video image, and the effect on itching was evaluated. Table 3 shows the results.

[0035]

[Table 3]

Test Example 4 Effect of NFκB activation inhibitor on pigmentation: Brown guinea pig back hair was shaved carefully with a hair clipper and shaver, and then 1.5 cm square 8
Divided. An evaluation sample (100 mM / ethanol solution, 20 μl) was applied to each site, and 2 hours after that, the applied sample was wiped off with ethanol, and UV rays in the UVB region were adjusted to a minimum erythema dose (MED) of 0 to promote pigmentation. ．
It was irradiated with a triple amount, and after UV irradiation, the evaluation sample was applied again.
This operation was repeated for 7 days, and thereafter, only the sample was continuously applied for 1 week, and after 2 weeks, the pigmentation amount was examined. As a control, ethanol was applied instead of the sample to evaluate the effect. The results are shown in Table 4.

The evaluation was carried out by measuring with a color difference meter, calculating the L * value from the obtained Munsell value, and subtracting the L * value before UVB irradiation from the L * value 2 weeks after UVB irradiation (Δ
L *) was determined and the degree of pigmentation was compared. The larger the −ΔL * value, the stronger the degree of pigmentation.

[0038]

[Formula 1] ΔL * = (L * value after UVB irradiation) − (UVB
(L * value before irradiation)

[0039]

[Table 4]

Test Example 5 NFκ against destruction of dermal component
Effect of B activation inhibitor: back 1 × 1 of hairless rat
Evaluation sample per cm square (1% / ethanol solution, 20
μl), and after 2 hours, wipe off the applied sample with ethanol and use U to accelerate denaturation of dermal components.
The ultraviolet ray in the VB region was irradiated with 0.3 times the minimum erythema dose (MED), and after UV irradiation, the evaluation sample was applied again. After repeating this operation for 20 days, a sample was taken, stained with Masson's trichrome, and the ratio of collagen fibers stained in blue per unit area was analyzed using an image analyzer. The higher the degree of collagen fiber degeneration, the lower the proportion of blue color per unit area. As a control, ethanol was applied instead of the sample and evaluated. The results are shown in Table 5.

[0041]

[Table 5]

The skin external preparations of Examples 1 to 16 were prepared according to a conventional method.

Example 1 Skin lotion: NFκB activation inhibitor (phenylarsine oxide) 0.5% by weight glycerin monostearate 1 ethanol 15 propylene glycol 4 isopropyl palmitate 3 lanolin 1 methyl paraoxybenzoate 0.1 fragrance, pigment Trace amount of purified water

Example 2 Packing agent: NFκB activation inhibitor (pentoxifylline) 0.9% by weight Polyvinyl alcohol 20 Glycerin 5 Ethanol 16 Fragrance, pigment Trace amount of purified water Remaining amount

Example 3 Face Care Gel: NFκB Activation Inhibitor (Diisocoumarin) 1% by Weight Hydroxypropyl Cellulose 1 Antioxidant 0.05 Isopropanol 40 Preservative 0.3 Purified Water Remainder

Example 4 Face Care Cream: NFκB activation inhibitor (pentyl gallate) 0.2 wt% squalane 5 stearic acid 2 glycerin monostearate 10 ethanol 2 paraoxybenzoate methyl 0.2 cetanol 2 olive oil 3 petrolatum 5 ceramide 1 Fragrance, pigment Trace amount of purified water Remaining amount

Example 5 Lotion: NFκB activation inhibitor (pyrrolidinedithiocarbonate) 0.1% by weight 1,3-butylene glycol 6.5 polyoxyethylene sorbitan monolaurate 1.3 ethanol 8 preservative trace perfume trace Purified water Remaining amount

Example 6 Cream: NFκB activation inhibitor (phenylarsine oxide) 0.5% by weight Cholesterol 0.5 Cholesterol isostearate 1 Polyether-modified silicone 1.5 Cyclic silicone 20 Methylphenylpolysiloxane 2 Methylpolysiloxane 2 Magnesium sulphate 0.5 Ethanol 3 Carboxymethyl chitin 0.5 Fragrance, dye Trace amount Purified water Remaining amount

Example 7 Cream (oil-in-water emulsion): NFκB activation inhibitor (heptyl gallate) 0.01% by weight NFκB activation inhibitor (pyrrolidinedithiocarbonate) 0.1 glycerol stearate 2 Tween 60 1 stearic acid 1 .4 Triethanolamine 0.7 Carbomer 0.4 Liquid component of calynut nut butter 11.5 Perhydrosqualene 12.5 Antioxidant 0.04 Perfume Trace preservative Trace purified water Remaining amount

Example 8 Skin Lotion: NFκB Activation Inhibitor (Phenylarsine Oxide) 0.5% by Weight NFκB Activation Inhibitor (Butyl Gallate) 0.05 Glycerin Monostearate 1 Ethanol 15 Propylene Glycol 4 Isopropyl Palmitate 3 Lanolin 1 Cholesterol isostearate 0.5 Dipotassium glycyrrhizinate 0.1 Ceramide 0.2 Methyl paraoxybenzoate 0.1 Fragrance, pigment Trace amount Purified water Remaining amount

Example 9 Lotion: NFκB activation inhibitor (α-tocopheryl succinate) 0.2% by weight 10-hydroxyundecanoic acid 0.75 9-hydroxyundecanoic acid 0.20 8-hydroxyundecanoic acid 0. 05 Arginine 0.4 Lysine 0.4 Polyoxyethylene hydrogenated castor oil (40EO) 1.5 Methyl polysiloxane methyl (polyoxyethylene) siloxane copolymer (SH3775C, manufactured by Toray Dow Corning) 0.6 Glycerin 5 0.0 1,3-butylene glycol 3.0 Glycine betaine 0.2 Trisodium citrate 0.9 Citric acid 0.4 Urea 0.5 ε-Aminocaproic acid 0.1 Ethanol 5.0 Preservative proper amount Perfume proper amount Purified water Remaining amount

Example 10 Lotion: NFκB activation inhibitor (ethyl gallate) 0.1% by weight 10-hydroxyundecanoic acid 0.89 9-hydroxyundecanoic acid 0.20 8-hydroxyundecanoic acid 0.02 triethanolamine 0.4 Potassium hydroxide 0.2 Polyoxyethylene isocetyl ether (20EO) 0.3 Polyoxyethylene oleyl ether phosphate sodium (8EO) 0.3 Polyoxyethylene dialkyl sodium phosphate (10EO) 0.1 Polyethylene glycol 1500 2.0 Polyoxyethylene methyl glucoside (10EO) 1.5 Dipropylene glycol 0.5 Disodium hydrogen phosphate 0.5 Succinic acid 0.3 Ethanol 10.0 Royal jelly extract 2.0 Ceramide 1.0 Preservative Suitable amount Fragrance Suitable amount Purified water Remaining amount

Example 11 Gel: NFκB activation inhibitor (α-tocopheryl succinate) 0.2 wt% 10-hydroxyundecanoic acid 1.7 9-hydroxyundecanoic acid 0.2 8-hydroxyundecanoic acid 0.1 Polyoxyethylene isocetyl ether (20EO) 1.0 Sodium polyoxyethylenetrialkylphosphate (10EO) 1.0 Sorbitol 0.5 1,3-Propanediol 0.5 Xanthan gum 0.5 Tuberose polysaccharide 3. 0 Carboxy vinyl polymer (Carbopol 940, manufactured by Goodrich Co.) 0.2 Dipotassium glycyrrhizinate 0.1 Potassium hydroxide 0.9 Allantoin 0.1 Tannic acid 0.2 Ethanol 20.0 Preservative proper amount Perfume proper amount Purified water residue amount

Example 12 Gel: NFκB activation inhibitor (pyridinedithiocarbonate) 0.05% by weight 10-hydroxyundecanoic acid 1.5 9-hydroxyundecanoic acid 0.4 8-hydroxyundecanoic acid 0.1 Silicone composition (KSG-17, manufactured by Shin-Etsu Chemical Co., Ltd.) 5.0 Methyl polysiloxane (KF96A-6cs, manufactured by Shin-Etsu Chemical Co., Ltd.) 15.0 Methyl polysiloxane (SH244, manufactured by Toray Dow Corning Co., Ltd.) 5.0 Methyl polysiloxane-methyl (Polyoxyethylene) siloxane copolymer (SH3771C, manufactured by Dow Corning Toray) 2.0 Methylpolysiloxane-methyl (polyoxyethylene) siloxane copolymer (SH3775C, manufactured by Dow Corning Toray) 1. 0 Methyl cellulose 0.2 Hydroxyethyl cellulose Hydroxypropyl trimethylammonium chloride Lido ether (Cathello H-60, manufactured by Kao Corporation) 0.02 Acetate dl-α-tocopherol 0.05 Isostearyl glycyrrhetinate 0.1 Isopropylmethylphenol 0.1 EDTA 0.1 Ethanol 5.0 Preservative proper amount Perfume proper amount Purification Water level

Example 13 Emulsion: NFκB activation inhibitor (butenyl gallate) 0.05 wt% 10-hydroxyundecanoic acid 1.07 9-hydroxyundecanoic acid 0.36 8-hydroxyundecanoic acid 0.07 N- (3- Hexadecyloxy-2-hydroxypropyl) -N-2-hydroxyethyldecanamid 0.5 N- (3-hexadecyloxy-2-hydroxypropyl) -N-2-hydroxyethylhexadecanamide 1.0 N- (3-tetradecyloxy-2-hydroxypropyl) -N-2-hydroxyethyl decanamide 0.5 Polyoxyethylene hydrogenated castor oil (10EO) 1.0 Methyl polysiloxane methyl (polyoxyethylene) siloxane Copolymer (SH3775C, Toray Dow Corning) 1.0 Sorbitan monostearate .2 sodium stearoylmethyltaurine 0.5 cholesterol 0.8 cholesterol isostearate 0.2 alkenyl succinate monocholesteryl 0.8 stearic acid 0.2 palmitic acid 0.3 myristic acid 0.1 dicapric acid pentyl glycol 4.0 Methyl polysiloxane (KF96A-500cs, manufactured by Shin-Etsu Chemical Co., Ltd.) 2.0 Isostearyl alcohol 1.2 Cetyl alcohol 1.0 Glycerin 3.5 Lactic acid 0.2 Sodium lactate 0.3 Preservatives proper amount Perfume appropriate amount Purified water remaining amount

Example 14 Lotion: NFκB activation inhibitor (pyridinedithiocarbonate) 0.05 wt% 7-hydroxyoctanoic acid 0.75 7-hydroxynonanoic acid 0.20 7-hydroxydecanoic acid 0.05 arginine 0 .4 Lysine 0.4 Polyoxyethylene hydrogenated castor oil (40EO) 1.5 Methyl polysiloxane methyl (polyoxyethylene) siloxane copolymer (SH3775C, Toray Dow Corning) 0.6 Maltitol 5. 0 ethylene glycol monoethyl ether 0.2 trisodium citrate 0.9 succinic acid 0.4 urea 0.5 ε-aminocaproic acid 0.1 ethanol 5.0 dipotassium glycyrrhizinate 0.1 preservative proper amount perfume appropriate purified water residue amount

Example 15 Lotion: NFκB activation inhibitor (methyl gallate) 0.02% by weight 11-hydroxydodecanoic acid 0.73 11-hydroxytridecanoic acid 0.32 11-hydroxytetradecanoic acid 0.03 diisopropanol Amine 0.4 Potassium hydroxide 0.2 Polyoxyethylene isocetyl ether (20EO) 0.3 Polyoxyethylene oleyl ether sodium phosphate (8EO) 0.3 Polyoxyethylene dialkyl sodium phosphate (10EO) 0.1 Polyethylene Glycol 1500 2.0 Polyoxyethylene methyl glucoside (20EO) 1.5 Isoprene glycol 0.5 Disodium hydrogen phosphate 0.5 Succinic acid 0.3 Ethanol 0.0 Yeast extract 2.0 Aloe extract 0.2 Preservative Appropriate amount Perfume Appropriate amount Purified water Remaining amount

Example 16 Pack: NFκB activation inhibitor (cyclic imide derivative) 0.05% by weight 10-hydroxyundecanoic acid 4.0 9-hydroxyundecanoic acid 0.85 8-hydroxyundecanoic acid 0.15 polyvinyl alcohol (Gothenol EG-30, manufactured by Nippon Synthetic Chemical Industry) 15.0 Aqueous carboxymethyl chitin solution (Chitin Liquid HV-10, manufactured by Ichimaru Falcos) 5.0 Triglucopolysaccharide (Pullulan PI-20, manufactured by Hayashibara) 0.5 Xanthan gum 0.5 Sodium carboxymethyl cellulose 0.5 Titanium oxide 15.0 Aluminum magnesium silicate 1.0 1-Isostearoyl-3-myristoyl-glycerol 1.0 Diglycerin 1.5 Polyoxyethylene isocetyl ether (20EO) 1.0 Ethanol 5.0 Preservative Suitable amount Fragrance Appropriate amount Purified water Remaining amount

Continuation of the front page (51) Int.Cl. ⁶ Identification number Office reference number FI Technical display area A61K 7/00 A61K 7/00 W X

Claims (3)

[Claims] 1. An external skin preparation for preventing and improving skin peeling, thickening, rough skin, rough texture, pigmentation, denaturation / destruction of dermis constituents or itch, which contains an NFκB activation inhibitor. 2. The content of the NFκB activation inhibitor in the external preparation for skin is 0.000001 to 10% by weight.
The topical skin preparation according to the above. 3. An antibacterial agent, antibacterial agent, anti-inflammatory agent, antipruritic agent, antiviral agent, keratolytic agent, antifree radical agent, antioxidant, antisebum agent, antidandruff agent, antiacne agent. The external preparation for skin according to claim 1 or 2, which contains one or more kinds of agents selected from and a moisturizer.