JPH09255546A - 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, disturbance of skin texture, pigmentation, denaturation and destruction, of corium-constituting component and itchiness. SOLUTION: This preparation contains 0.000001-10wt.%, preferably 0.0001-1wt.% (based on the preparation) of a substance for suppressing the adhesion of vascular endothelial cell and lymphocyte. The substance for suppressing the abhesion of vascular endothelial cell and lymphocyte is a nonprotein substance such as benzoic acid anilide derivative, benzene derivative, vegetable extract, galloyl tannin and peptide. The preparation is further compounded with 0.01-20wt.% of conventional 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 from among antibacterial agent, fungicide, anti-inflammatory agent, antipruritic and antianthemic agent, antiviral agent, keratolytic agent, anti-free rabical 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 this situation, the present inventor, in the process of studying the properties of the skin and its changes, and the role of cell adhesion molecules in the skin,
Skin that does not exhibit features of inflammation such as redness, swelling, and fever,
That is, even in the skin that is healthy and does not have an inflammatory symptom in appearance, white blood cells, especially lymphocytes, may infiltrate a large amount into the skin tissue, and further, these infiltrating lymphocytes cause the formation of spots on the skin, rough skin, and skin peeling. , Thickening of skin, disorder of texture, degeneration and destruction of dermal components are found to have an extremely large effect, and lymphocytes are suppressed by suppressing adhesion between lymphocytes and vascular endothelial cells. The substance that suppresses the infiltration of skin into the skin tissue (cell adhesion inhibitory substance) is used to form spots on the skin, rough skin, skin peeling,
The inventors have found that thickening, texture disorder, and degeneration and destruction of dermal components can be effectively prevented, and have completed the present invention.

That is, the present invention contains a substance that suppresses adhesion between vascular endothelial cells and lymphocytes, and prevents skin peeling, thickening, rough skin, irregular texture, pigmentation, denaturation / destruction of dermal constituents, and itching. An object is to provide an improving external skin preparation.

[0012]

DESCRIPTION OF THE PREFERRED EMBODIMENTS In recent years, molecular-level research on various diseases has progressed, and in immune and inflammatory diseases, intercellular adhesion between leukocytes and vascular endothelial cells and subsequent infiltration of leukocytes have been reported. It has been found to be largely involved ["Regulation of expression of adhesion molecules and clinical application" (Medical View, 1991), Nature, Vol. 364, 149-155 (1993), Sc.
ience, Vol.247, 456-459 (1990), Annual Review Immune 198
9,175-185, Trends in Glycoscience and Glycotechnol
ogy, Vol.4, No.19,405-414 (1992), Experimental Medicine Vol.10, No.1
1,1402-1413 (1992), Experimental Medicine Vol.11, No.16, 2168-2175
(1993), Science, Vol. 255, 1125-1127 (1992), etc.]. It has also been found that cell surface adhesion molecules such as ICAM-1, ELAM-1, and VCAM-1 are involved in cell-cell adhesion [Annu
al Review Immunity 1989,175-185, Infection / Inflammation / Immunity Vol.19
(2), 129-153 (1989), Infection / Inflammation / Immunity Vol.24 (3), 158-
165 (1994)].

That is, when an external stimulus is applied to the living body, a large number of leukocytes infiltrate the site, so-called inflammatory reaction occurs, and when the leukocytes infiltrate from the blood vessel into the tissue,
Leukocytes and vascular endothelial cells adhere to each other via specific cell adhesion molecules on their cell surfaces, and most of the adhered leukocytes directly destroy the basement membrane of blood vessels and leak out of the blood vessels. It turns out. Inflammation is also a local reaction to damage to living tissues, resulting in bacterial infection, trauma,
When the tissue is damaged by physical stimuli such as heat, cold, radiation, electricity and chemical substances, the regeneration of chemical mediators, the enhancement of vascular permeability, the migration, infiltration and granulation of leukocytes such as neutrophils and macrophages, The main signs of inflammation such as redness, swelling, fever, and pain appear clinically following the process of tissue production and healing.

As described above, it has been conventionally known that cell adhesion between vascular endothelial cells and leukocytes and subsequent leukocyte infiltration are extremely important steps in immune and inflammatory diseases. It is not yet known that cell adhesion between vascular endothelial cells and leukocytes, particularly lymphocytes, and infiltration of lymphocytes are involved in various skin troubles that are not accompanied by the main signs of inflammation. The external preparation for skin of the present invention containing a substance capable of suppressing the infiltration of lymphocytes (cell adhesion suppressor) by suppressing the above has not yet been proposed.

The substance for suppressing cell adhesion between vascular endothelial cells and lymphocytes 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, For example, a benzoic acid anilide derivative previously reported by the applicant (Japanese Patent Application No. 6-325340).
No.), gallic acid derivative (Japanese Patent Application No. 7-86617), benzene derivative (Japanese Patent Application No. 7-86619), plant extracts (Japanese Patent Application No. 6-325334), galloyl tannins, known peptides. (J. Biological Chem., 270 (36) 21
129-21136, 1995), pentoxifylline (J. Invest Derm
atol, 104,824-828,1995), 3-deazaadenosine (J. Im
munology, 144 (2) 653-661, 1990), carboxamide derivative (J. Medicinal Chem., 37 (6) 717-718, 1994), inositol polyamines (J. Biological Chem., 269 (21) 15060-15).
066, 1994), sialyl Lewis X and its derivatives, triterpenic acid derivatives (US Pat. No. 943356), lactose and lactosamine derivatives (US Pat. No. 800557), and the like.

The amount of such cell adhesion-suppressing substance used is
In the external preparation for skin, 0.000001 to 10% by weight is preferable, and 0.0001 to 1% by weight is particularly preferable.

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-absorbing 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 agents 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 the 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.

[0026]

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.

[0027]

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 Cell Adhesion Inhibitors on Skin Peeling: 1 after shaving the back of white guinea pigs
A cell adhesion inhibitor (100 mM: 10 μl) was applied to cm ^2, and 2 hours later, a patch test seal containing 30% of 1% SDS (sodium dodecyl sulfate) solution was soaked.
The test substance was applied again after application for a minute. 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.

[0029]

[Table 1]

Test Example 2 Effect of Cell Adhesion Inhibitor on Texture Disorder: A cell adhesion inhibitor (0.1%: 15 μl) was applied to 1 cm ² of human skin, and 2 hours later, dry nitrogen gas was applied to the site. It was sprayed for 30 minutes. 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.

[0031]

[Table 2]

Test Example 3 Effect of Cell Adhesion Inhibitor on Pruritus: A cell adhesion inhibitor (100 mM: 15 μl) was applied to the back of Balb / c mice, and 2 hours later, an histamine solution was intradermally injected, followed by 1 hour. The behavior of the mouse was recorded over a period of time. 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.

[0033]

[Table 3]

Test Example 4 Effect of Cell Adhesion Inhibitor on Pigmentation: Brown guinea pig back hair was carefully shaved with a hair clipper and a shaver, and then the hair was divided into eight 1.5 cm squares. UV rays in the UVB region were irradiated with 0.3 times the minimum erythema dose (MED) in order to promote pigmentation, and after UV irradiation, each sample was evaluated (0.1 to 1% / ethanol solution, 20 μl). Was applied. 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 a color difference meter, the L * value was calculated from the obtained Munsell value, and the value obtained by 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.

[0036]

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

[0037]

[Table 4]

Test Example 5 Effect of Adhesion Inhibitor on Destruction of Dermal Component: The back of hairless rats is irradiated with ultraviolet rays in the UVB region at 0.3 times the minimum erythemal dose (MED) in order to accelerate the denaturation of the dermal component. Then, an evaluation sample (0.1-1% / ethanol solution, 20 μl per 1 × 1 cm square)
) Was applied. After repeating this operation for 20 days, the material was collected, 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.

[0039]

[Table 5]

The skin external preparations of Examples 1 to 19 were prepared according to a conventional method.

Example 1 Skin Lotion: Cell Adhesion Inhibitor (Anilide Benzoate) 0.5% by Weight Glycerin Monostearate 1 Ethanol 15 Propylene Glycol 4 Isopropyl Palmitate 3 Lanolin 1 Methyl Paraoxybenzoate 0.1 Perfume, Trace Dye Purified water Remaining amount

Example 2 Packing Agent: Cell Adhesion Inhibitor (Pentoxifylline) 0.9% by Weight Polyvinyl Alcohol 20 Glycerin 5 Ethanol 16 Perfume, Pigment Traces Purified Water

Example 3 Face Care Gel: Cell Adhesion Inhibitor (Asunaro Extract) 1% by Weight Hydroxypropyl Cellulose 1 Antioxidant 0.05 Isopropanol 40 Preservative 0.3 Purified Water Remaining amount

Example 4 Face Care Cream: Cell Adhesion Inhibitor (Sialyl Lewis X) 0.2% by Weight Squalane 5 Stearic Acid 2 Glycerin Monostearate 10 Ethanol 2 Methyl Paraoxybenzoate 0.2 Cetanol 2 Olive Oil 3 Vaseline 5 Ceramide 1 Fragrance, pigment Trace amount of purified water Remaining amount

Example 5 Lotion: Cell adhesion inhibitor (butyl gallate) 0.05 wt% 1,3-butylene glycol 6.5 Polyoxyethylene sorbitan monolaurate ester 1.3 Ethanol 8 Preservative Trace fragrance Trace purified water Remaining amount

Example 6 Cream: Cell Adhesion Inhibitor (3-Deazaadenosine) 0.5% by Weight Cholesterol 0.5 Cholesterol Isostearate 1 Polyether Modified Silicone 1.5 Cyclic Silicone 20 Methylphenylpolysiloxane 2 Methylpoly Siloxane 2 Magnesium sulphate 0.5 Ethanol 3 Carboxymethyl chitin 0.5 Perfume, dye Trace amount of purified water Remaining amount

Example 7 Cream (oil-in-water emulsion): Cell adhesion inhibitor (methyl gallate) 0.1% by weight glycerol stearate 2 Tween 60 1 Stearic acid 1.4 Triethanolamine 0.7 Carbomer 0.4 Carite Liquid component of nut butter 11.5 Perhydrosqualene 12.5 Antioxidant 0.04 Fragrance Trace preservative Trace purified water Remaining amount

Example 8 Lotion: Cell adhesion suppressant (Asunaro extract) 0.50% by weight 10-Hydroxyundecanoic acid 0.75 9-Hydroxyundecanoic acid 0.20 8-Hydroxyundecanoic acid 0.05 Arginine 0.1. 4 Lysine 0.4 Polyoxyethylene hydrogenated castor oil (40EO) 1.5 Methyl polysiloxane-methyl (polyoxyethylene) siloxane copolymer (SH3775C, Toray Dow Corning) 0.6 Glycerin 5.0 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 Allantoin 0.01 Preservative proper amount Perfume proper amount Purification Water level

Example 9 Lotion: Cell adhesion inhibitor (Morgin) 0.50% 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 preservative proper amount perfume proper amount purified water remaining amount

Example 10 Gel: Cell Adhesion Inhibitor (Morgin) 0.5% by Weight 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 Carboxyvinyl polymer (Carbo (Paul 940, manufactured by Goodrich) 0.2 Dipotassium glycyrrhizinate 0.1 Potassium hydroxide 0.9 Allantoin 0.1 Tannic acid 0.2 Ethanol 20.0 Preservative A suitable amount Perfume Suitable amount Purified water Remaining amount

Example 11 Gel: Cell Adhesion Inhibitor (Asunaro Extract) 0.5% 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, Toray Dow Corning Co., Ltd.) 2.0 Methylpolysiloxane methyl (polyoxyethylene) siloxane copolymer (SH3775C, Toray Dow Corning Co., Ltd.) 1.0 Methylcellulose 0 .2 Hydroxyethyl cellulose hydroxypropyl trimethyl ammonium chloride ether Cello H-60, manufactured by Kao) 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 appropriate amount Purified water residue amount

Example 12 Emulsion: Cell adhesion inhibitor (ethyl gallate) 0.1% by weight 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 0.2 Thearoylmethyl taurine sodium 0.5 Cholesterol 0.8 Cholesterol isostearate 0.2 Alkenyl monocholesteryl succinate 0.8 Stearic acid 0.2 Palmitic acid 0.3 Myristic acid 0.1 Pentyl glycol dicaprate 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 Ceramide 0.3 Preservative proper amount Perfume proper amount Purified water Remaining amount

Example 13 Lotion: Cell adhesion inhibitor (Morgin) 0.05% by weight 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 0.01 Preservative appropriate amount Perfume appropriate amount Purified water residual amount

Example 14 Lotion: Cell adhesion inhibitor (anilide benzoate) 0.50% 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 Preservative proper amount Perfume proper amount Purified water Remaining amount

Example 15 Gel: Cell Adhesion Inhibitor (Asunaro Extract) 0.5% by Weight Ethyl 10-hydroxyundecanoate 1.9 Glyceryl 9-hydroxyundecanoate 0.2 Hydroxyethyl 8-hydroxyundecanoate 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) 0.2 Potassium hydroxide 0.9 Allantoin 0.1 Zinc sulfocarbolate 0.2 Ethanol 20.0 Preservative proper amount Perfume proper amount Purified water Remaining amount

Example 16 Gel: Cell adhesion inhibitor (Morgin) 0.5% by weight Isopropyl 9-hydroxydecanoate 1.5 Glycine 8-hydroxydecanoate 0.4 Ethyl 9-hydroxydodecanoate 0.1 Silicone composition (KSG-16, 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, Toray-Dow Corning Co., Ltd.) 2.0 Methylpolysiloxane-methyl (Polyoxyethylene) Siloxane Copolymer (SH3775C, Toray-Dow Corning Co., Ltd.) 1.0 Methylcellulose 0.2 Hydroxyethyl cellulose Hydroxypropyl trimethyl ammonium chloride (Catiscello H-60, manufactured by Kao Corporation) 0.02 Acetate dl-α-tocopherol 0.05 Isostearyl glycyrrhetinate 0.1 Isopropylmethylphenol 0.1 Zinc white 1.5 Ethanol 5.0 Preservative Suitable amount Perfume Suitable amount Purified water Remaining amount

Example 17 Emulsion: Cell adhesion inhibitor (3-deazaadenosine) 0.5% by weight Isostearyl 10-hydroxyundecanoate 1.25 Ethyl 9-hydroxyundecanoate 0.46 Glyceryl 8-hydroxyundecanoate 0 0.09 N- (3-hexadecyloxy-2-hydroxypropyl) -N-2-hydroxyethyl decanamide 0.5 N- (3-hexadecyloxy-2-hydroxypropyl) -N-2-hydroxyethyl Hexadecanamide 1.0 N- (3-tetradecyloxy-2-hydroxypropyl) -N-2-hydroxyethyl decanamide 0.5 Polyoxyethylene hydrogenated castor oil (10EO) 1.0 Methylpolysiloxane Methyl (polyoxyethylene) siloxane copolymer (SH3773C, Toray Dow Corning) 1. Sorbitan monostearate 0.2 Cholesterol 0.8 Cholesterol isostearate 0.2 Alkenyl succinate monocholesteryl 0.8 Stearic acid 0.5 Squalane 4.0 Methyl polysiloxane (KF96A-500cs, Shin-Etsu Chemical Co., Ltd.) 2. 0 2-Ethylhexyl paramethoxycinnamate (Persole MCX-SA, manufactured by Givaudan) 2.0 Cetyl alcohol 1.0 Glycerin 3.5 Lactic acid 0.2 Sodium lactate 0.3 Preservatives proper amount Perfume appropriate amount Purified water residual amount

Example 18 Pack: Cell Adhesion Inhibitor (Galoyl Glucose) 1.0% 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 Co., Ltd. 15.0 Aqueous carboxymethyl chitin solution (chitin liquid HV-10, manufactured by Ichimaru Falcos Co., Ltd.) 5.0 Triglucopolysaccharide (Pullulan PI-20, manufactured by Hayashibara Co., Ltd.) 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 0.0 Preservative Suitable amount Perfume Suitable amount Purification Water level

Example 19 Pack: Cell adhesion inhibitor (3-deazaadenosine) 0.5 wt% 10-hydroxyundecanoic acid 4.0 10-hydroxydodecanoic acid 0.85 7-hydroxydecanoic 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 Perfume Suitable amount Purified water Remaining amount

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Claims (3)

[Claims] 1. A skin peeling, thickening, rough skin, texture disorder, containing a substance for suppressing adhesion between vascular endothelial cells and lymphocytes,
Prevention of pigmentation, denaturation / destruction of dermal components or itching
External skin improvement agent. 2. The external preparation for skin according to claim 1, wherein the content of the substance for suppressing the adhesion between vascular endothelial cells and lymphocytes is 0.000001 to 10% by weight in the external preparation for skin. 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.