JP3499616B2 - Application to hydroxytyrosol, melanin production inhibitor or lipid peroxide production inhibitor - Google Patents

Description

Detailed Description of the Invention

The present invention relates to hydroxytyrosol (3,4-dihydroxyphenylethanol) represented by the following structural formula (Formula 1).
For blending new skin external preparations or bath agents
Melanin production inhibitor and lipid peroxide production inhibitor
It

[Chemical 1]

[0002]

FIELD OF INDUSTRIAL APPLICABILITY
Is a melanin production inhibitor for the formulation of bath agents and lipid peroxide
The growth inhibitor can be applied to all external preparations for the purpose of preventing or improving pigmentation such as spots and freckles, and skin problems such as rough skin and dryness .
You can Specifically, liquid, emulsion, cream,
Ointment, gel, powder, granules, solid, or foamy, 1) external medicines, 2) quasi-drugs, 3) topical or systemic skin cosmetics, 4) bath water The bath agents etc. to be used can be raised.

[0003]

2. Description of the Related Art Pigmentation of the skin such as liver spots (spots), freckles (freckles) and senile mollusks is a condition often observed by exposure to ultraviolet rays, cosmetic rashes, contact dermatitis, etc. , Is one of the major worries for women. The melanin pigments caused by these are organelles called premelanosomes formed in the cytoplasm of melanocytes distributed in the epidermal basal cell layer of skin,
It is generated under a certain genetically defined active order. Normally, the mature melanosomes filled with this melanin pigment reach the body surface along with the keratinization process, and finally they are exfoliated and excreted outside the body.However, due to various factors, the balance between the production and excretion of melanosomes is high. It has been clarified that a collapse occurs, and when it is excessively accumulated in epidermal cells, the symptoms as described above appear. By the way, until now, many researchers have developed an active ingredient applicable as an external preparation for the prevention or treatment of such pigment abnormalities, and some have already been put to practical use.

When these are systematically summarized, the following three factors are considered to be the main causes of pigmentation. (1) Formation of melanin pigment exceeding the normal level (2) Deposition of melanin pigment on tissue cells (3) Decrease in melanin pigment elimination (excretion) function And, as a countermeasure against (1), blocking / absorption of ultraviolet rays , Suppression of active oxygen production, suppression of lipid peroxide production, Tyro
Inhibition of sinase activity (suppression of melanin pigment production), etc., and in response to (2) and (3), it exerts actions and effects such as reduction / degradation of melanin pigment, promotion of turnover, and repair of damaged cells. Ingredients and the like have been searched for, and for example, applied to daily-used cosmetics and the like for consideration. Table 1 is an example of the effective ingredients that have been proposed so far.

[Table 1]

On the other hand, not only melasma and melasma, but aging of the skin (skin atrophy, wrinkles, dry skin symptoms, abnormal keratinization of skin, etc.),
The number of people suffering from skin diseases such as primary irritant dermatitis, senile pigment spots, and rough skin is also increasing year by year. It is believed that all of these phenomena are due to the accumulation of harmful effects of lipid peroxides. According to previous research reports, the relationship between lipid peroxide and skin diseases is as follows.
Two phenomena have been pointed out. One is a phenomenon in which lipid peroxide directly forms a complex with a membrane protein of epidermal and dermal cells to cause cell degeneration and bring about an adverse effect. For example, it is explained that lipid contained in cosmetics is oxidized by long-term storage, and as a result, the increased lipid peroxide irritates the skin and causes dermatitis, pigmentation and the like. Also,
Secondly, peroxyl radicals are induced from fatty acids in sebum by exposure to ultraviolet rays, resulting in continuous autoxidation of sebum, causing degenerative destruction of epidermal cells, or atrophy of skin proteins and decreased elasticity. It is a theory that causes wrinkles and increases wrinkles in the epidermis.

[0006]

As shown in Table 1, many components effective for preventing or improving pigmentation or suppressing lipid peroxide production have been proposed so far. However, some of these have extremely strong effects, whitening ingredients that may cause permanent bleaching effects, those that are effective against each but exhibit cytotoxicity, or are safe but in a test system. There were many things that were not expected in practical use as much as the effect of. In addition, even if it is recognized as safe and effective to some extent,
Some are extremely poor in stability, or have problems with odor, color tone, solubility, etc., and some of them have the drawback that they cannot be applied unless some measures or ingenuity are applied in the formulation. At present, only a few of them are effective active ingredients.

The inventors of the present invention have conducted intensive studies for the purpose of developing a new cosmetic ingredient which is highly effective and practical. As a result, hydroxytyrosol ( 3,4-
It has been found that dihydroxyphenylethanol ) has a strong melanin production inhibitory action and a lipid peroxide production inhibitory action, and at the same time is an extremely useful component which can solve the above problems. Then, by applying the above-mentioned components to external preparations for skin and bath agents, it is effective in preventing and improving spots, freckles, etc., as well as preventing and improving rough skin and dryness, and smoothing the texture of the skin (skin The inventors have completed the present invention, knowing that an excellent skin beautifying effect such as improvement in quality itself) can be obtained.

[0008]

Means for Solving the Problems The present invention is composed of the following two inventions. 1. A melanin production inhibitor for use in the formulation of a skin external preparation or a bath agent, which contains hydroxytyrosol as an active ingredient. 2. A lipid peroxide production inhibitor containing hydroxytyrosol as an active ingredient for blending an external preparation for skin or blending a bath agent.

Active ingredient of the present invention: Hydroxytyrosol is a natural product (for example, Olea europaea Linne (Oleaceae)).
The fruit may be any of those extracted from the above), those further purified therefrom, or those chemically synthesized. Further, the melanin production inhibitor or lipid peroxide production inhibitor for external skin agent formulation or bath agent formulation, oily hydroxytyrosol as it is, or in the form of an extract of natural products containing it, or Various bases, additives and the like used in cosmetics described below are added to them to be provided in a prepared form.

The melanin production inhibitor according to the present invention or
A skin external preparation or bath preparation containing a lipid peroxide production inhibitor is manufactured by formulating it with a base or additive usually used in cosmetics. For example, oils include animal and vegetable oils, mineral oils, ester oils, wax oils, higher alcohols, fatty acids, silicone oils, phospholipids and the like. As the surfactant, an anionic surfactant, a cationic surfactant, an amphoteric surfactant, a nonionic surfactant and the like are used. Others, p-aminobenzoic acid, anthranil derivative, salicylic acid derivative, coumarin derivative, amino acid compound, benzotriazole derivative, tetrazole derivative, imidazoline derivative, pyrimidine derivative, dioxane derivative, camphor derivative, furan derivative, pyrone derivative, nucleic acid derivative, allantoin UV absorbers such as derivatives, nicotinic acid derivatives, shikonin, vitamin B ₆ derivatives, ascorbic acid and its salts, stearic acid ester, tocopherol and its ester derivatives, nordihydroguaselethenoic acid, butylhydroxytoluene (BHT), butylhydroxy Antioxidants such as anisole (BHA), para-hydroxyanisole, propyl gallate, hydroxyethyl cellulose, methyl cellulose, ethyl cellulose, carbo Shi cellulose, carboxyethyl cellulose, gum arabic, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl methacrylate, polyacrylic acid salts, carboxyvinyl polymers, carrageenan, pectin, alginic acid and salts thereof, casein, thickeners such as gelatin,
Glycerin, propylene glycol, 1,3-butylene glycol, hyaluronic acid and its salts, polyethylene glycol, chondroitin sulfate and its salts, water-soluble chitin or chitosan derivatives, humectants such as sodium lactate, lower alcohols, polyhydric alcohols, water-soluble High molecular,
pH adjuster, chelating agent, antiseptic / antifungal agent, fragrance, colorant, cooling agent, stabilizer, extract derived from animals and plants,
Animal / vegetable proteins and their degradation products, animal / vegetable polysaccharides and their degradation products, animal / vegetable glycoproteins and their degradation products, blood flow promoters, anti-inflammatory / anti-inflammatory agents, cell activating agents, vitamins, Amino acids and salts thereof, keratolytic agents, astringent agents, wound healing agents, foam increasing agents, deodorant / deodorant agents, etc. may be used in combination as necessary to produce the above-mentioned various products.

In addition, plant extracts which are already said to have various skin-beautifying effects such as melanin production inhibitory action, lipid peroxide production inhibitory action, anti-inflammatory and anti-allergic action (usually,
Water, ethanol, 1,3-butylene glycol, propylene glycol, or any mixture thereof obtained in combination with) or animal components, or safe with known pigmentation preventing components as shown in Table 1. The combined use within the range can be expected to enhance the effect of the present invention. Examples of plants or herbal medicines that are said to have various skin beautifying effects include, for example, Acenyak (Asenyaku), Ashitaba, Altea, Arnica, Avocado, Amacha (sweet tea), Aloe, Angelica, Pomegranate, Nettle, Ginkgo (Ginkgo biloba). Leaves, ginkgo), fennel (incense), turmeric (spicy), usubasaishin (spicy), hemlock, ume (karameme), white-tailed oak, noibara (commercial), Hikiokoshi (prolonged life grass), Ougi, Scutellaria baicalensis (Ogon), yellowfin. (Yellow oak), Yamazakura (cherry bark), Coptis chinensis (yellow ream), Panax ginseng (carrot), Hypericum perforatum (younger brother cut grass), Odorikosou, Dutch pepper, orange, Onami fir, Onji, Kakushitsu, Kagosou, Tsudukudami (nosed crow), Gajutsu (mudder) ,
Kudzu (Kakkon), valerian (Yoshikusa), birch, chamomile, sagebrush (Inchinko), licorice (liquorice), raspberry, kiwi fruit, Kikarasuri, chrysanthemum (Chrysanthemum), Kikyo (Kikyo), Kisage (Azusa fruit), cucumber , Wolfberry (ground bone skin, bracts, clover leaves), clara (bitter ginseng), camphor, gardenia (yamaboshi), kumazasa, mulberry (mulberry bark, mulberry leaves), kayga, ebisugusa (Keimeiko),
Gentian, Gensho, honoki, safflower, safflower, kohone, kohone, goshuyu, kotsusaiho, gobaishi, burdock, dwarf garlic, cornbill, cornflower ), Saffron, soapless,
Salvia, hawthorn, hawthorn (sansho), hawthorn carrot (37 ginseng), sanchisou, shiitake mushroom, dio (ground yellow), shikunshi (shikushi), purple (purple root), perilla (shiso leaf, perilla spp), oyster ( Persimmon), linden, striped peony, peony, plantain (carrot), waremokou (gem), ginger (ginger), ginger (iris), spruce moth (female child), citrus cypress, zebra, moss, moss (Flower, Shinobi winter), Horsetail, Ivy, Horse chestnut, Elderflower, St. John's wort, Sturgeon radix,
Senkyu, sendan, senburi (our drug), rhubarb,
Dates, soybeans, pearl oysters, cod, thyme, dandelion, ginseng (bamboo ginseng), green tea, tea, cloves (cloves), citrus peels, camellia, camellia, twabuki, touka, toki (this) Return), quince, daidai (orange peel), corn (nanban fur), Eucommia ulmoides (Duchu, Duzhong leaf) horsetail, dokudami (ten medicines), tomatoes, trolloioi, nanten (southern nut), elderberry, garlic (garden), Thistle, parsley, sesame, hamamelis, roses, hiss, loquat (loquat leaf), juniper, butterbur, butterbur dandelion, fujibakama, matsuhodo (bukuro), bodaiju, hop, maikai (maikai), button (peony skin), pine needles, mannenrow, Horse chestnut, myrrh, sparrow, merlot
Melissa, bokeh (peach melon), peach (peach kernels, peach leaves), Japanese cedar (irradiated), cornflower, mistletoe, moss lice, eucalyptus, yukinoshita (tiger ear grass), bayberry (pick ume bark),
Examples include pearl barley (Yokuinin), yomena, mugwort (moth leaf), lavender, gentian, forsythia, ganoderma lucidum, rosemary, and Roman chamomile.

Animal components include human or bovine placenta extract, collagen or elastin or their hydrolysates, silk peptides, glycoproteins such as mucin, or their degradation products. Others, yeast extract,
The combined use of selenium-containing yeast extract, rice fermentation extract, fermented milk extract, etc. is also considered to be effective.

Melanin production inhibitor or peracid according to the present invention
Incorporation of phospholipid production inhibitor into skin external preparations or bath preparations
In this case , the content of hydroxytyrosol is not particularly specified, but in the case of aiming at improvement of skin troubles such as pigmentation and dullness of skin in a short period of time, it is usually 0.5 to 5 It may be contained in any proportion within the range of% by weight. On the other hand, for such various skin problems, in a product form for the purpose of merely preventive or gradually improving by cumulative effect, the usual prescribed amount (0.0001 ~ If it is contained at about 1.0% by weight), the desired effect is expected.
Further, in the case of a bath agent, it may be added to 200 to 300 liters of bath water so as to consider the prescription so as to obtain the same concentration or adjust the amount used. A more specific description will be given below based on examples.

[0014]

EXAMPLES Production Example 1: Extraction from Natural Products Hydroxytyrosol is a component that is abundantly contained in olive oil and the like. For example, a high content extract can be obtained by the following method. Hexane (100 mL) was added to olive oil (100 g), and 50-70% methanol aqueous solution (60
(mL) and extracted 2 to 3 times to collect the extract, and 40 to 5 under reduced pressure.
The solvent is distilled off at 0 ° C. If necessary, the residue is subjected to silica gel column chromatography (eluent solvent / ethyl acetate: petroleum ether = 1: 1) to purify the hydroxytyrosol fraction.

[0015]

EXAMPLES Production Example 2: Chemical Synthesis Hydroxytyrosol was synthesized according to the synthetic process (Formula 2) shown below.

[Chemical 2]

1) 3,4-dihydroxyphenylacetic acid [2]
Of synthetic red phosphorus (0.2 g) and 55% hydriodic acid (100 mL) were heated to reflux until the brown color disappeared, then cooled and cooled under a stream of nitrogen with 3,4-dimethoxyphenylacetic.
Acid [1] (19.6 g, 0.10 mol) was added and the mixture was heated under reflux for 3 hours. Then, the reaction solution is cooled to room temperature, concentrated under reduced pressure, water (150 mL) is added to the obtained residue, shaken well, and concentrated again under reduced pressure. After repeating this operation 2-3 times, hot water (100 mL) was added to the residue, red phosphorus was removed by filtration, and the obtained filtrate was made into a saturated solution of sodium chloride and added to ethyl acetate (75 mL). The extraction operation is performed 3 to 4 times. The extracted ethyl acetate layer is collected, washed several times with 4N-sodium hydrogensulfate aqueous solution (25 mL), dried over anhydrous sodium sulfate, further treated with activated carbon, and concentrated under reduced pressure to obtain a solid dried product. Next, the target product [2] (15.8 g, yield 94%) is purified by recrystallizing this solid dried material from a mixed solution of ethyl acetate-cyclohexane (1: 1).

2) Hydroxytyrosol (3,4-dihydroxy)
Synthesis of phenylethanol [3]) Tetrahydrofuran THF (200 mL) and lithium aluminum hydride LiAlH ₄ (5.12 g, 0.13 mol)
After cooling to ℃ and stirring, 3,4-dihydroxyphenylacetic ac
After id [2] (7.6 g, 0.045 mol) was added over 20 to 30 minutes, the temperature was gradually raised and refluxed for 6 hours. After allowing the reaction solution to cool, it is filtered through a glass filter covered with Celite, and purified water (100 mL) and 10% hydrochloric acid (100 mL) are added to the filtrate to stop the reaction. Then, with ethyl acetate (100 mL) 3 ~
The extracted ethyl acetate layer is extracted 4 times and dried over anhydrous magnesium sulfate, and then the solvent is distilled off under reduced pressure to obtain a gel.
This gel was subjected to silica gel column chromatography (eluent solvent / ethyl acetate: petroleum ether = 1: 1) to purify oily 3,4-dihydroxyphenylethanol [3] (4.5 g, yield 66%).

[0018]

[Example] Melanin production inhibition test C57BL mice (8 weeks old, male) were exposed to ultraviolet rays (Toshiba ultraviolet ray FL2
0-SE lamp) was irradiated continuously at 15.2 mJ / cm ² once a day for 3 days. One week after the final irradiation day, the auricle was collected, the cartilage was removed, and the skin of the outer ear was immersed in a 2N-NaBr solution at 37 ° C for 2 hours. After that, the epidermis was peeled off from the straight skin, and this epidermis was removed with 0.
1% L-DOPA solution (0.1M phosphate buffer, pH = 7.2) at 37 ℃,
It was soaked for 3 hours and stained with DOPA. In addition, the samples obtained in Production Examples 1 and 2 were previously prepared using dimethyl sulfoxide (DMS
O) and purified water, and adjust each concentration ( ^W /
_W ), and as a control, the same amount of the solvent used during sample preparation was added. Further, as Comparative Example 1, 4-hydroxyphenyl-β-D-glucopyranoside was tested, and as Comparative Example 2, kojic acid was tested. Judgment is based on the fixed part (5
The number of melanocytes in mm ² ) was measured with a microscope, the number of cells per 1 mm ² was determined, and the inhibition rate was calculated with the number of subjects being 100.

The test results are shown in Table 2. When the melanocytes of the epidermis of colored mouse auricles activated by ultraviolet rays were specifically stained with DOPA solution, the samples obtained in Production Examples 1 and 2 were 4-hydroxyphenyl-β-D-
It was confirmed that it has a higher melanin production inhibitory action than glucopyranoside and kojic acid.

[Table 2]

[0020]

[Example] Lipid peroxide production inhibition test (TBA method) 0.1% linolenic acid was added to 0.8% sodium lauryl sulfate aqueous solution to dissolve, and this solution (3.9 mL) was placed in a 10 mL transparent glass screw bottle. Sample solution (0.1 mL) adjusted with ethanol to each concentration was added to this, and ultraviolet rays (Toshiba: FL-20SE lamp, FL-20SBL lamp, 3 lamps each in parallel arrangement,
After irradiation for 1 hour at a distance of 15 cm), take 1 mL of this solution,
Add 1 mL of a mixture of 0.67% thiobarbituric acid aqueous solution and 15% acetic acid aqueous solution (pH 3.5) and 20 μL of 4.5% dibutylhydroxytoluene, and heat at 95 ° C for 1 hour. After cooling
Add 4 mL of a mixture of methanol / n-butanol (15:85), shake well, and then centrifuge. Next, the absorbance of this n-butanol layer at 534 nm was measured and used as the amount of lipid peroxide. The amount of lipid peroxide when a sample was added and irradiated with ultraviolet light was a, the amount of lipid peroxide when a sample was added and not irradiated with ultraviolet light was b, and the amount of lipid peroxide when ethanol was added instead of the sample and irradiated with ultraviolet light. The inhibition rate was calculated by the following equation (Equation 1), where a'is the oxidized lipid amount and b'is the amount of lipid peroxide in the case where ethanol was added instead of the sample and ultraviolet irradiation was not performed.

[Equation 1]

The test results are shown in Table 3. Production example 1
It was confirmed that the samples obtained in 2 and 2 both showed a stronger lipid peroxide production inhibitory action than d, l-α-tocopherol of the comparative example.

[Table 3]

[0022]

[Examples] Safety test 1) Primary skin irritation test Hartley guinea pigs (5 mice / group, body weight: 310 g) with the back removed from the natural extract obtained in Production Examples 1-2 and the synthesized hydroxytyrosol Before and after) was applied to the skin. The evaluation was performed 24 hours after application by using the erythema and edema as indices by the primary irritant scoring method. As a result, in all animals, no erythema or edema was observed in any of the samples, and it was determined to be negative.

[0023]

[Examples] Safety test 2) Cumulative skin irritation test Hartley guinea pigs (female, 5 animals per group) from which the natural extracts obtained in Production Examples 1 and 2 and the synthesized hydroxytyrosol were depilated , Body weight of about 320 g) was applied once a day at a frequency of 0.5 mL / animal 5 times a week. The application was carried out for 4 weeks and the hair removal was performed on the last application day of each week. Judgment was performed on the day after the last day of each week by the scoring method for primary irritation, using erythema and edema as indexes. As a result, all samples were negative in all animals from 1 to 4 weeks after application without any erythema or edema.

[0024]

[Examples] Safety test 3) Acute toxicity test The natural extracts obtained in Production Examples 1-2 and the synthesized hydroxytyrosol were fasted for 4 hours before the test.
2,000 mg / kg for y strain mice (female, 5 mice per group, weight 28 g)
The amount was orally administered, and the onset and degree of toxicity were observed over time. As a result, no abnormality was observed in all mice for 14 days, and there was no abnormality in the autopsy result. LD ₅₀
Was determined to be 2,000 mg / kg or more.

[0025]

[Example] Use test of ointment The sample obtained in Production Example 2 was added to the hydrophilic ointment of the Japanese Pharmacopoeia, and 1 was applied to male and female panelists (total 12 people) suffering from spots and freckles.
They were asked to use it 3 times a day for 3 consecutive weeks, and the effect was evaluated. In addition, the ointment was prepared by adjusting three types of sample concentrations of 1%, 3%, and 5%, and changing the adaptation site for each type. The results are shown in the following table (Table 4).

[Table 4]

[0026]

Examples Production of various external preparations According to the above evaluation results, various external preparations containing hydroxytyrosol were produced. The formulation examples are shown below, but the external preparation for skin according to the present invention is not limited thereto.

1) Example of production of lotion A lotion was manufactured according to the following formulation.                                                             weight%         1. Sorbit 2         2.1,3-butylene glycol 2         3. Polyethylene glycol 1000 1         4. Polyoxyethylene oleyl ether (25E.O.) 2         5. Ethanol 20         6. Hydroxytyrosol (Production Example 1) 0.3         7. pH adjusting agent         8. Preservative Suitable amount         9. Residue of purified water 100

2) Example of production of emulsion An emulsion was prepared according to the following formulation.                                                             weight%         1. Squalane 3         2. Vaseline 1         3. Stearyl alcohol 0.3         4. Sorbitan monostearate 1.5         5. Polyoxyethylene (20) sorbitan monooleate 3         6.1,3-butylene glycol 5         7. Hydroxytyrosol (Production Example 2) 0.5         8. Preservative Suitable amount         9. Residue of purified water 100

3) Cream production example A cream was produced according to the following formulation.                                                             weight%         1. Squalane 20         2. Beeswax 5         3. Refined jojoba oil 5         4. Glycerin monostearate 2         5. Sorbitan monostearate 2         6. Polyoxyethylene (20) sorbitan monostearate 2         7. Glycerin 5         8. Hydroxytyrosol (Production Example 1) 0.5         9. Preservative Suitable amount         Ten. Residue of purified water 100

4) Example of manufacturing body soap A body soap was manufactured according to the following formulation.                                                             weight%         1. Potassium laurate 15         2. Potassium myristate 5         3. Propylene glycol 5         4. Hydroxytyrosol (Production Example 1) 1         5. pH adjusting agent         6. Preservative Suitable amount         7. Residue of purified water 100

5) Production example of ointment An ointment was produced according to the following formulation.                                                             weight%         1. White vaseline 24         2. Stearyl alcohol 20         3. Propylene glycol 12         4. Polyoxyethylene hydrogenated castor oil 60 4         5. Glycerin monostearate 1         6. Hydroxytyrosol (Production Example 1) 1         7. Preservative Suitable amount         8. Residue of purified water 100

6) Cream foundation A cream foundation was manufactured according to the following formulation.                                                             weight%         1. Stearic acid 5         2. Hydrophilic glyceryl monostearate 2         3. Seto Stearieu Alcohol 1         4. Propylene glycol monolaurate 3         5. Liquid paraffin 6         6. Isopropyl myristate 8         7. Hydroxytyrosol (Production Example 2) 0.5         8. Triethanolamine 1         9. Sorbit 3         Ten. Titanium oxide 8         11. Kaolin 5         12. Talc 2         13. Ben Knight 1         14. Preservative Suitable amount         15. Residue of purified water 100

7) Example of production of bath agent A bath agent was prepared according to the following formulation.                                                             weight%         1. Hydroxytyrosol (Production Example 1) 20         2. Polyoxysorbitan monolaurate 20         3. Glycerin monostearate 5         4. Lauric acid diethanolamide 3         5. Residue of purified water 100

[0034]

Example: Use test of emulsion and bath agent The emulsion and bath agent produced in the example were tested by male and female panelists (total 20
Name) to use it freely for one month and asked for a questionnaire survey on its effect and feeling of use. In addition, the panelists were divided into two groups of 10 people, and the group in charge of emulsion and the group in charge of bath agent were assigned. The results are shown in the following table (Table 5).

[Table 5]

[0035]

The hydroxytyrosol according to the present invention is
It has excellent melanin production inhibitory action and lipid peroxide production inhibitory action, and since it has no irritation to the skin, it is suitable for application to external preparations for skin and bath agents. In the skin external preparation or bath preparation containing hydroxytyrosol,
The continuous use of it has the effect of preventing and improving skin spots, freckles, dullness, or rough skin, and is also effective in improving the skin quality (adjusting the texture). Was shown. Many people suffer from pigmentation diseases such as spots and freckles, or skin troubles such as rough skin and bulkiness, and it is said that such mental stress may exacerbate the symptoms especially in people with sensitive skin. The present invention is a novel and safe external preparation for external use or bath preparation , which can prevent or improve these skin troubles, adjust the texture of the skin and keep it healthy.
The present invention provides a melanin production inhibitor and a lipid peroxide production inhibitor for blending .

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁷ Identification symbol FI A61P 17/00 A61P 17/00 43/00 105 43/00 105 111 111 (72) Inventor Kazuhiko Yamashita Okawa, Kanagawa-gun, Okochi-cho 451 (72) Inventor Kazue Dotari 1101 Shinmachi, Hayashida-cho, Himeji-shi, Hyogo 1F Sakaguchi Apert (56) Reference JP-A-7-215837 (JP, A) (58) Fields investigated (Int.Cl. ⁷ , DB name) A61K 7/00-7/50

Claims (2)

(57) [Claims] 1. A melanin production inhibitor for the external use of a skin agent or a bath agent, which contains hydroxytyrosol as an active ingredient. 2. A lipid peroxide production inhibitor for use in the formulation of a skin external preparation or a bath agent, which comprises hydroxytyrosol as an active ingredient.