JPH11286442A - Inflammatory factor activation inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject inhibitor useful for the prevention, improvement and treatment of inflammatory skin injury and disorder caused by ultraviolet rays by including N-acetylcysteine. SOLUTION: This inhibitor is obtained by including N-acetylcysteine preferably N-acetyl-L-cysteine or N-acetyl-DL-cysteine as an active ingredient. The above-mentioned N-acetylcysteine is preferably added at 0.01-10 wt.% as an active ingredient to a cosmetic for the prevention and improvement of inflammatory skin injury caused by ultraviolet rays and 0.01-50 wt.% as an active ingredient to a preparation for external use for skin for the prevention and treatment of inflammatory disorder caused by ultraviolet rays. The above-mentioned cosmetic or preparation for external use for skin has no restriction in its dosage form and can be used in the form of a solution, paste, gel or the like and also as an oil, lotion, cutaneous aging preventive/improver or rough skin inhibitor/ improver.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an ultraviolet-induced inflammatory factor activation inhibitor useful for the prevention, improvement or treatment of inflammatory skin damage or disease caused by ultraviolet rays, and a skin external preparation containing the same. Related to cosmetics.

[0002]

2. Description of the Related Art In recent years, a large number of injuries and illnesses to the skin caused by sunlight, particularly ultraviolet rays, have been reported. For example, aging,
In canceration, pigmentation, inflammation, etc.,
It is known that inflammatory cytokines such as L-1α and TNF-α are deeply involved (for example, “Oxidative
Stress in Dermatology, Marcel Dekker, Inc., 187
２０５205, 1993). Regulation of gene expression is mainly performed at the transcription level of the gene, and the expression of inflammatory cytokines is regulated by transcriptional regulators such as NF-κB and AP-1 (for example,
"Reactive oxygen and signal transduction," Kodansha Scientific, pp. 37-46, 1996). It has been reported that these transcription factors are readily activated by ultraviolet light, resulting in the expression of inflammatory cytokines (eg, Ge
ne & Development, 9, 2723-2735, 19
1995). Therefore, if it is possible to suppress the expression of inflammatory cytokines and the activation of transcriptional regulators related thereto due to ultraviolet rays, it is expected that injury and disease to the skin will be prevented.

[0003] For example, it has been shown that antioxidants such as N-acetyl-L-cysteine and pyrrolidinedithiocarbamate suppress NF-κB activation by active oxygen and the like (for example, “signal transmission with active oxygen”). Kodansha Scientific, pp. 37-46, 1996). However, it is not clear about the inhibitory effect on UV-induced NF-κB activation or inflammatory cytokine expression. In addition, these compounds also have a problem in use sensation, such as giving the skin a squeaky feeling when applied to the skin.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to provide an ultraviolet-induced inflammatory factor activation inhibitor which suppresses the expression of inflammatory cytokines by ultraviolet light and the activation of gene transcription regulators involved in the expression.

[0005]

Means for Solving the Problems The present inventors have conducted intensive studies to achieve the above object, and as a result, have found that the above object can be achieved by containing N-acetylcysteine or a salt thereof. The present invention has been completed.

That is, the present invention provides an ultraviolet-induced inflammatory factor activation inhibitor characterized by containing one or more of N-acetylcysteine or a salt thereof, and an ultraviolet-induced inflammation comprising the same. The present invention relates to an agent for preventing and treating diseases and an external preparation for skin. Further, the present invention provides a cosmetic additive comprising one or more of N-acetylcysteine or a salt thereof, or a cosmetic additive comprising the cosmetic additive, preferably 0.01 to
The present invention relates to a cosmetic containing 10% by weight, more preferably 0.1 to 5% by weight. The skin external preparation or cosmetic of the present invention is, in addition to the compound of the present invention, an oily raw material,
One or two or more selected from a surfactant, a solvent, a humectant, a polymer substance, a powder substance, a dye, and a fragrance may be contained.

[0007]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail.

[0008] The N-acetylcysteine of the present invention may be either optically active or racemic, but N-acetyl-L-cysteine or N-acetyl-DL-cysteine is preferred. Examples of the salt include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as magnesium and calcium, inorganic bases such as ammonia, monoethanolamine, diethanolamine, triethanolamine and 2-amino-2-methyl-1. Organic amine salts such as -propanol, 2-amino-2-methyl-1,3-propanediol, lysine, ornithine and arginine. These salts may be used in combination of two or more. These may be blended as an N-acetylcysteine salt, or a component that forms a salt with N-acetylcysteine may be separately blended to form an N-acetylcysteine salt in the composition.

N-acetylcysteine is described in the literature (for example, J. Org. Chem., Vol. 30, pages 2839-2840,
1965), it can be easily derived by a method of reacting cysteine with acetic anhydride.

[0010] N-acetylcysteine or a salt thereof is
It is used by direct administration to the UV-induced inflammatory factor activation system, but is usually used by blending it into a cosmetic or a skin external preparation. For example, when it is incorporated into cosmetics as an active ingredient for preventing or improving ultraviolet-induced inflammatory skin damage, it is 0.01 to 10% by weight, preferably 0.01 to 5% by weight.
What is necessary is just to add by weight%. When it is incorporated into an external preparation for skin as an active ingredient for the prevention and treatment of ultraviolet-induced inflammatory diseases, it is suitably added in an amount of 0.01 to 50% by weight, preferably 0.1 to 20% by weight. If the amount is less than 0.01% by weight, the ability to suppress the activation of ultraviolet-induced inflammatory factor is not sufficiently exhibited, which is not preferable. If it exceeds 50% by weight, there is a problem in the feeling of use such as squeaking feeling on the skin, which is not preferable.

The cosmetic or external preparation for skin of the present invention includes:
In addition to N-acetylcysteine and perfume, components generally used as cosmetics or external preparations for the skin can be added as long as the effects of the present invention are not impaired.
Ingredients generally used in cosmetics or external preparations for the skin include oily raw materials, surfactants, solvents, humectants, polymer substances, powder substances, pigments, fragrances and the like.

Oily raw materials include oils and fats such as animal and vegetable oils,
Waxes such as lanolin, hydrocarbons such as paraffin, higher alcohols such as cetanol, higher fatty acids such as stearic acid, sterols, phospholipids such as lecithin, synthetic esters such as myristic acid, metal soaps, silicone oils, etc. Can be mentioned.

Examples of the surfactant include an anionic surfactant, a cationic surfactant, an amphoteric surfactant, a nonionic surfactant, and an emulsifying / solubilizing agent.

Examples of the solvent include lower alcohols such as ethanol, ethers, glycerins, liquid nonionic surfactants, liquid oily raw materials, other organic solvents, water and the like.

Examples of the humectant include polyhydric alcohols such as glycerin, organic acid salts such as pyrrolidone carboxylic acid, mucopolysaccharides such as urea and hyaluronic acid, and amino acid salts such as proline.

Examples of the high molecular substance include natural high molecular compounds such as collagen, semi-synthetic high molecular compounds such as partially deacetylated chitin, and synthetic high molecular compounds such as carboxymethyl cellulose.

As the powdery substance, inorganic pigments such as talc,
Functional pigments such as synthetic mica, fine particle composite powder (hybrid fine powder), pearlescent pigments such as titanium dioxide-coated mica, polymer powders such as photochromic pigments, nylon powders, and organic powders such as Nε-lauroyl lysine And the like.

The dyes include legal tar dyes of the first kind,
Legal tar dyes II, legal tar dyes III, hair dyes, natural dyes, mineral dyes and the like can be mentioned.

As the flavor, animal flavors such as musk,
Vegetable flavors such as jasmine oil; synthetic flavors such as α-amylcinnamaldehyde;

The dosage form of the cosmetic or external preparation for skin of the present invention is not particularly limited, and may take any dosage form such as a solution, a paste, a gel, a solid, and a powder. Further, the cosmetic or external preparation for skin of the present invention includes oils, lotions, creams, emulsions, gels, shampoos, hair rinses,
Hair conditioner, enamel, foundation,
Lipstick, towel, pack, ointment, perfume, powder, cologne, dentifrice, soap, aerosol, cleansing foam, etc., skin aging preventive improver, skin inflammation preventive improver, bath agent, hair restorer, skin serum, sun protection It can be used as an agent, an agent for preventing and improving photosensitivity, an agent for preventing and improving photoallergy, an agent for preventing and improving photoimmune suppression, and an agent for preventing and improving skin roughness due to trauma, cracks, cracks and the like.

Further, other common components in cosmetics or external preparations for skin can be added to the cosmetics or external preparations for skin of the present invention as long as the effects of the present invention are not impaired. Other commonly used ingredients in cosmetics or external preparations for the skin include preservatives / disinfectants, antioxidants, ultraviolet absorbers, chelating agents, antifading agents, buffers, acne agents,
Anti-dandruff, itching inhibitor, antiperspirant deodorant, burn agent, anti-mite / lice agent, keratin softener, xerosis agent, antiviral agent, transdermal absorption enhancer, hormones, vitamins, amino acids / peptides , Proteins, astringents, anti-inflammatory agents,
Examples include refreshing / stimulating agents, components derived from animals and plants, melanin synthesis inhibitors (whitening agents), antibiotics, antifungal agents, hair restorers, and the like.

[0022]

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples. In addition, in this Example, the compounding amount was represented by weight%.

Test Example 1 UV-induced NF-κB Activation Inhibition Test A test compound was added in a concentration range that did not damage human epidermal cells that reached confluence in a culture plate.
After a lapse of time, the culture solution was replaced with a phenol red-free medium. Ultraviolet rays (UVB: 50 mJ / cm ² ) were applied to the cells using Dermalei M-DMR-80 (manufactured by Toshiba Medical Supplies), and after 4 to 5 hours, the cells were collected and the nuclear protein was extracted by a conventional method. NF-κB activated in the obtained nuclear protein was detected by gel shift assay. Quantification of NF-κB was performed by measuring the radioactivity value of the NF-κB band using a bioimaging analyzer BAS2000 (manufactured by Fuji Film Co., Ltd.). The NF-κB activation inhibition rate of the test compound was calculated by the following formula (I). Table 1 shows the results.

(Equation 1)

[0024]

[Table 1]

As shown in Table 1, active oxygen-induced NF-κ
B activation inhibitor desferrioxamine (for example,
AIDS Research and Human Retroviruses, 11, 10
49-1061 (1995)) and pyrrolidinedithiocarbamate which is a phorbol ester-induced NF-κB activation inhibitor (for example, Immunology, 90, 455-4).
60, 1997)) showed no inhibitory activity in this test, whereas this product showed an inhibitory activity. This product has the ability to suppress the activation of UV-induced inflammatory factor.

Test Example 2 Test for IL-1α Expression Inhibition A test compound was added to human epidermal cells that had reached confluence in the culture plate, and after 18 hours, the culture was replaced with a phenol red-free medium. Dermalei M-DM
The cells were exposed to ultraviolet light (UVB: 50 mJ / cm ² ) using R-80 (manufactured by Toshiba Medical Supplies), and after 24 hours, the culture was recovered and the IL-1α concentration in the culture was adjusted to IL-1α · E
The measurement was performed using a LISA system (Amersham). The inhibition rate of IL-1α expression of the test compound was determined by the following formula (II)
Was calculated by Table 2 shows the results.

(Equation 2)

[0027]

[Table 2]

As shown in Table 2, this product is an ultraviolet-induced IL
It has the ability to suppress the expression of -1α and has a high ability to suppress the activation of ultraviolet-induced inflammatory factor.

Test Example 3 Sensory test The feeling of use as a cosmetic was evaluated by sensory evaluation of panelists of 10 men and women. Table 3 shows the evaluation criteria for each evaluation item. At the time of the sensory evaluation, the formulations shown in Table 4 were prepared.

[0030]

[Table 3]

[0031]

[Table 4]

As shown in Table 4, none of the products had a feeling of creaking on the skin, and the feeling of use was sufficiently satisfactory.

The cosmetics or skin external preparations of Examples 5 to 14 were prepared by a conventional method. This product did not show a squeaky feeling on the skin, and the feeling of use was sufficiently satisfactory.

Example 5 Facial Wash Cream N-acetyl-L-cysteine 1.0% by weight Lauric acid 4.0 Myristic acid 12.0 Palmitic acid 10.0 Stearic acid 10.0 Cetanol 1.5 Lanolin 1.0 Glycerin 18 6.0 Potassium hydroxide 6.0 Buffer appropriate amount Perfume appropriate amount Preservative appropriate amount Purified water balance

Example 6 Thickening Lotion N-acetyl-L-cysteine 2.0% by weight Ethanol 15.0 Sorbit 2.0 1,3-butylene glycol 2.0 Polyethylene glycol (1500) 1.0 Polyoxyethylene (20) Oleyl ether 2.0 Pectin 0.5 Dye proper amount Chelating agent proper amount UV absorber proper amount buffer proper amount perfume proper amount preservative proper amount purified water balance

Example 7 Emollient Cream N-acetyl-L-cysteine 0.1% by weight Cetanol 5.0 Stearic acid 3.0 Vaseline 5.0 Squalane 10.0 Tri (2-ethylhexanoic acid) glyceryl 7.0 Di Propylene glycol 5.0 Glycerin 5.0 Propylene glycol monostearate 3.0 Polyoxyethylene (20) cetyl ether 3.0 Triethanolamine 1.0 Antioxidant proper amount Fragrance proper amount Preservative proper amount Purified water balance

Example 8 Massage cream N-acetyl-L-cysteine 0.5% by weight Microcrystalline wax 9.0 Paraffin 2.0 Beeswax 3.0 Vaseline 5.0 Reduced lanolin 5.0 Squalane 34.0 Hexyl adipate Decyl 10.0 Propylene glycol 5.0 Glyceryl monooleate 3.5 Polyoxyethylene (20) sorbitan monooleate 1.0 Antioxidant qs Perfume qs Preservative qs Purified water Remainder

Example 9 Emulsion N-acetyl-L-cysteine 1.5% by weight Stearyl alcohol 0.5 Hardened palm oil 3.0 Liquid paraffin 35.0 Dipropylene glycol 6.0 Polyethylene glycol (400) 4.0 Sesuki Sorbitan oleate 1.5 Polyoxyethylene (20) oleyl ether 2.5 1% Carboxyvinyl polymer aqueous solution 15.0 Potassium hydroxide 0.1 Chelating agent Appropriate amount Perfume Appropriate preservative Appropriate amount Purified water Remainder

Example 10 Gel N-acetyl-L-cysteine 0.05% by weight Liquid paraffin 12.0 Tri (2-ethylhexanoic acid) glyceryl 50.0 Sorbit 10.0 Polyethylene glycol (400) 5.0 Acylmethyl Taurine 5.0 Polyoxyethylene (20) isocetyl ether 10.0 Appropriate amount of preservative Appropriate amount of preservative Purified water balance

Example 11 Serum N-acetyl-L-cysteine 0.5% by weight Dipropylene glycol 5.0 Polyethylene glycol (400) 5.0 Ethanol 10.0 Carboxyvinyl polymer 0.5 Sodium alginate 0.5 Water Potassium oxide 0.2 Polyoxyethylene monostearate (20) sorbitan 1.0 Sorbite monooleate 0.5 Oleyl alcohol 0.5 Placenta extract 0.2 dl-α-tocopherol acetate 0.2 Fragrance Appropriate amount Preservative Appropriate amount Fading Appropriate amount of inhibitor Purified water balance

Example 12 Pack N-acetyl-L-cysteine 3.0% by weight Polyvinyl alcohol 15.0 Carboxymethylcellulose 5.0 1,3-butylene glycol 5.0 Ethanol 12.0 Polyoxyethylene (20) oleyl ether 0.5 Appropriate amount of flavoring agent Preservatives appropriate amount Buffering agent appropriate amount Purified water balance

Example 13 Foundation N-acetyl-L-cysteine 5.0% by weight Liquid paraffin 10.0 Polyoxyethylene monooleate (20) sorbitan 3.5 Propylene glycol 3.0 Titanium oxide 9.0 Kaolin 24. 0 Talc 42.0 Color pigment 3.0 Fragrance appropriate amount Preservative appropriate amount Antioxidant appropriate amount

Example 14 Ointment N-acetyl-L-cysteine 1.0% by weight Urea 20.0 White petrolatum 15.0 Light liquid paraffin 6.0 Cetanol 3.0 Stearyl alcohol 3.0 Glyceryl monostearate 0 Appropriate amount of perfume Preservatives Appropriate buffer Buffer Appropriate amount Purified water balance

[0044]

Industrial Applicability N-acetyl-L-cysteine has an excellent inhibitory action on ultraviolet light-induced inflammatory factor activation. In addition, cosmetics or external preparations containing N-acetyl-L-cysteine, when applied to the skin, effectively remain on the skin and hardly fall off, and have a good feeling of use without giving a squeaky feeling to the skin. Things.

Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 7/48 A61K 7/48

Claims (6)

[Claims] 1. An ultraviolet-induced inflammatory factor activation inhibitor comprising one or more selected from N-acetylcysteine and salts thereof as an active ingredient. 2. A prophylactic / therapeutic agent for ultraviolet-induced inflammatory diseases comprising one or more of the compounds according to claim 1. 3. A cosmetic additive comprising one or more of the compounds according to claim 1. 4. An external preparation for skin, comprising the compound according to claim 1. 5. A cosmetic comprising the compound according to claim 1. 6. In addition to the compound according to claim 1, it contains one or more selected from oily raw materials, surfactants, solvents, humectants, polymeric substances, powdered substances, pigments and fragrances. The cosmetic according to claim 5, characterized in that: