JP2003081748A - Extension inhibitor of dendrite of melanocyte and cosmetic containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a preventing or ameliorating means effective for pigment anomaly accompanying inflammation and pigment anomaly such as freckle. SOLUTION: An excellent bleaching cosmetic for dealing with skin- melanization phenomena associated with a melanocyte and a macrophage is provided by making a skin care preparation such as the cosmetic contain an essence of Forsythia suspensa Thunb. vahl of Oleaceae, preferably the essence of a fruit, having excellent activities for inhibiting the extension of a dendrite of the melanocyte.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a dendritic growth inhibitor for melanocytes and a skin external preparation such as cosmetics. More specifically, the dendritic growth inhibitor for melanocytes suitable for whitening cosmetics provides Suitable for suppressing the interaction of macrophages with
The present invention relates to a skin external preparation for the treatment of skin phenomena involving melanocytes and macrophages.

[0002]

2. Description of the Related Art It is already known that melanocytes play a major role in pigment-related life phenomena in animals. However, how melanin, which is such a pigment, is produced in melanocytes Whether or not it migrates to cells is not yet known in detail, and it is only known that macrophages are often involved in the migration of such melanin granules. It has been pointed out that the involvement of such macrophages is made by producing the elongation factor (DEF) of melanocyte dendrites. However, it has been attempted to suppress the action of such elongation factors or by suppressing them. Suppressing the growth of melanocyte dendrites,
No attempt has been made to prevent the darkening of the skin by suppressing the migration of melanin granules by suppressing the elongation of the dendrites. Furthermore, it is not known at all that the essence of Forsythia suspensa Thunb. Vahl of the family Oleaceae, preferably the essence of fruit, has such a melanocyte elongation inhibitory action.

On the other hand, the solution of pigment abnormalities caused by abnormalities of melanin granules produced by melanocytes has been a long-standing problem for humankind to embody beautiful white skin. The results have been obtained, and various mechanisms have been obtained.However, no one has focused on the suppression of melanocyte dendrite elongation. Therefore, it is not known at all to be useful for the prevention and amelioration of pigmentation disorders associated with inflammation. In addition, as for pigment abnormalities such as freckles and inflammation-related pigment abnormalities, the effect of the well-known melanin production inhibitor such as ascorbic acid is another one, and it is a means of preventing or improving such pigment abnormalities. Development was desired.

Furthermore, the essence of the fruit of Forsythia suspensa Thunb. Vahl of the oleaceae family (Oleaceae) contains forcitol, oleanolic acid, sterol compounds and a large amount of vitamin P and has a detoxifying effect on heat. Is already known. In addition, forcitol, which is an active ingredient, has the strongest antibacterial activity against Staphylococcus aureus and Shigella group A, and also has a strong antibacterial effect against hemolytic Streptococcus, Streptococcus pneumoniae, and typhoid bacterium. It has a clear inhibitory effect on Mycobacterium tuberculosis and has a therapeutic effect on experimental mouse tuberculosis. In addition, oleanolic acid has a cardiotonic / diuretic effect. It is also an important drug for febrile / suppurative diseases in clinical applications. However,
It is not known at all that this thing has the effect of suppressing the dendrite extension of melanocytes, therefore,
Cosmetics and other external skin preparations containing this substance suppress dendrite elongation of melanocytes, and are therefore useful for preventing and improving pigment abnormalities caused by pigment abnormalities, in particular, light, and inflammation. Was nothing known at all.

[0005]

The present invention has been made under such circumstances, and is effective against pigment abnormalities such as freckles and pigment abnormalities that are particularly suitable for whitening the skin and are particularly associated with inflammation. It is an object of the present invention to provide a skin external preparation suitable as a preventive or improving means.

[0006]

In view of such a situation, the inventors of the present invention have conducted earnest studies for a preventive or ameliorating means effective for pigment abnormalities associated with inflammation and pigment abnormalities such as freckles. As a result, forsythia (Fo) of the oleaceae (Oleaceae)
rsythia suspensa Thunb. vahl) found an excellent inhibitory effect on melanocyte dendrite elongation,
By including a substance having such an action in a skin external preparation, it was found that such a skin external preparation is useful for the prevention and amelioration of pigment abnormalities accompanied by inflammation and pigment abnormalities such as freckles, and completed the invention. Came to let. That is, the present invention relates to the following technology. (1) A melanocyte elongation inhibitor comprising the essence of a Forsythia plant of the family Oleaceae. (2) The melanocyte elongation inhibitor according to (1), wherein the Forsythia plant (Forsythia) is Forsythia (Forsythia suspensa Thunb. Vahl). (3) The elongation inhibitor for melanocyte dendrites according to (1) or (2), wherein the essence is an extract of a polar solvent of fruit. (4) The melanocyte elongation inhibitor according to any one of (1) to (3), wherein the dendrite elongation suppression is caused by the inhibitory action of a macrophage-derived dendrite elongation promoting factor. (5) An external preparation for skin, which contains the melanocyte elongation inhibitor according to any one of (1) to (4) and which corresponds to a skin phenomenon involving melanocytes and macrophages. (6) The external preparation for skin according to claim 5, which is a cosmetic, and which is used to cope with a skin phenomenon involving melanocytes and macrophages. (7) For the skin phenomenon related to melanocytes and macrophages according to (5) or (6), the skin phenomenon related to melanocytes and macrophages is a skin darkening phenomenon or freckles with inflammation caused by light. Skin external preparation. (8) Forsyt of the oleaceae (Oleaceae)
hia suspensa Thunb. vahl) essence,
Cosmetics for whitening. (9) Forsyt (Forsyt) of the oleaceae (Oleaceae)
The cosmetic for whitening according to (8), characterized in that the essence of hia suspensa Thunb. vahl) is a polar solvent extract of fruit. (10) The whitening cosmetic composition according to (8) or (9), characterized in that the whitening action has a mechanism of a dendrite elongation inhibiting action in melanocytes. Less than,
The present invention will be described in detail focusing on the embodiments.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION (1) Elongation inhibitor for melanocyte dendrites of the present invention The elongation inhibitor for melanocyte dendrites of the present invention is
Forsythia (Forsythi) of the Oleaceae family
It consists of the essence of a). Forsythia (Forsyth
ia) forsythia (Forsythia suspensa Thunb. va
hl), Chinese Forsythia (Forsythia viridissima Lindl
y), Forsythia korena Naka
i), Yamatorenkyo (Forsythia japonica Makino),
There are Hirosyenkyo (Forsythia ovata Nakai) etc.,
Any substance that suppresses the elongation of dendrites of the present invention is included. Therefore, any of these plants can be used as the essence of the present invention. However, it is preferable to use forsythia (Forsythia suspensa Thunb.) To extract the extract of the melanocyte dendrite elongation inhibitor. This is because a large amount of dendrite growth inhibitory substances of melanocytes are contained. Here, the essence means the plant body of such a plant itself,
Processed product obtained by processing the plant by drying, shredding, crushing, etc., extract obtained by extracting the plant or the processed product with a solvent, solvent-removed product obtained by removing the solvent of the extract, extract or its solvent-removed product Means a generic term for purified fractions obtained by column chromatography and liquid-liquid extraction. The essence can be extracted from the whole plant grass. Among these, as an elongation inhibitor of the melanocyte dendrite of the present invention, in the case of Forsythia plants (Forsythia),
A solvent extract of fruit or a solvent-removed product thereof can be preferably exemplified, and as such a solvent, a polar solvent can be particularly preferably exemplified. Examples of such a polar solvent include water, alcohols such as ethanol, methanol, 1,3-butanediol and propylene glycol, esters such as ethyl acetate and methyl formate, ketones such as acetone and methyl ethyl ketone, chloroform and One or more selected from halogenated hydrocarbons such as methylene chloride, nitriles such as acetonitrile, and ethers such as diethyl ether and tetrahydrofuran can be preferably exemplified. Of these, water and alcohol are particularly preferable. To prepare such an extract, 1 to 10 times the amount of the solvent is added to the plant or its processed product, and the mixture may be immersed for several days at room temperature and for several hours at a temperature near the boiling point. After that, the insoluble matter can be removed by filtration and the solvent can be removed by concentration under reduced pressure or freeze-drying, if necessary. Forsyt of the oleaceae (Oleaceae)
In the case of fruits of Hia suspensa Thunb. This is because the fruit portion contains a large amount of melanocyte dendrite elongation-inhibiting components, which is particularly preferable. The thus-obtained melanocyte dendrite elongation inhibitor of the present invention, Oleaceae (Ol
eaceae) forsythia (Forsythia suspensa Thunb. va
hl) fruit essence has an excellent effect of suppressing melanocyte elongation of dendrites, and thus suppresses the transfer of melanin granules from melanocytes to the skin tissue, and the movement of such melanin granules is a mechanism. To do
It has the effect of preventing or ameliorating pigment abnormalities such as blackening and freckles with inflammation that occur upon light irradiation. It is considered that such an action has a mechanism of inhibiting the elongation factor of melanocyte dendrite released by macrophages from acting on melanocyte. Of course, since the pigment abnormality takes such a route in the production of melanin granules, the melanocyte dendrite elongation inhibitor of the present invention also suppresses melanization accompanied by inflammation due to light irradiation and pigment abnormality other than freckles. Since such pigment abnormalities can be prevented or ameliorated by other means, the feature of the effect of the present invention is to prevent or ameliorate pigment abnormalities such as blackening and freckles with inflammation that occur during the light irradiation. It can be said that the action. Further, since such an essence also contains a substance having a tyrosinase activity inhibitory effect or a melanin production inhibitory effect, it can be contained in a whitening cosmetic composition for such an effect. Since such an action works synergistically or additively with the dendrite elongation inhibitory action of the present invention, it is also within the technical scope of the present invention to incorporate these essences into a cosmetic to obtain a whitening cosmetic. Belong to.

(2) Skin external preparation for skin phenomenon involving melanocytes and macrophages of the present invention The melanocyte dendrite elongation inhibitor of the present invention prevents melanocyte dendrite elongation factors released by macrophages from acting on melanocytes. Since the mechanism is to inhibit, it is possible to suppress the life phenomenon in which melanocytes and macrophages work in concert, and by including such a dendrite elongation inhibitor of melanocytes in an external preparation for skin, melanocytes and It can respond to skin phenomena involving macrophages. That is, the external preparation for skin of the present invention is for treating skin phenomena involving melanocytes and macrophages, and is characterized by containing the dendrite elongation inhibitor for melanocytes of the present invention. Here, the external preparation for skin referred to in the present invention is a general term for compositions that are externally applied to the skin, and a skin external medicine containing a patch and a cosmetic containing a detergent can be preferably exemplified. Then, it is particularly preferable that it is a cosmetic. This is because the melanocyte dendrite elongation inhibitor of the present invention has high safety and a mild action. As the skin phenomenon in which melanocytes and macrophages are involved, it is particularly preferable that the above-mentioned blackening and pigment abnormalities such as freckles with inflammation due to light irradiation are the most important issues, but other inflammatory reactions are also included. . In the skin external preparation for skin phenomena involving melanocytes and macrophages of the present invention, the preferable content of the dendrite elongation inhibitor of melanocytes is 0.001% by weight to 10% by weight with respect to the total amount of the skin external preparation. And more preferably 0.01 to 5% by weight.
This is because if the amount is too small, the dendrite elongation-inhibiting effect may not be exerted, and if the amount is too large, the effect may reach the ceiling and the flexibility of other prescription components may be impaired.

The external skin preparation for the skin phenomenon involving melanocytes and macrophages of the present invention is a known anti-inflammatory agent, and if prednisolone, hydrocortisone, dexamethasone, indomethacin, diclofenac sodium, etc. are added, they are synergistically affected by sunlight. Meaningful for melanosis with inflammation. In addition to the above-mentioned essential components, any components usually used in cosmetics and external medicines for skin can be contained. Examples of such optional components include hydrocarbons such as squalane, petrolatum, microcrystalline wax, jojoba oil, carnauba wax, esters such as octyldodecyl oleate, triglycerides such as olive oil, beef tallow, and coconut oil, stearic acid. , Fatty acids such as oleic acid and lithinoleic acid, higher alcohols such as oleyl alcohol, stearyl alcohol and octyldodecanol, anionic surfactants such as sulfosuccinate and sodium polyoxyethylene alkylsulfate, amphoteric surfactants such as alkyl betaine salts Agents, cationic surfactants such as dialkylammonium salts, sorbitan fatty acid esters, fatty acid monoglycerides, polyoxyethylene adducts thereof, polyoxyethylene alkyl ethers, polyoxyethylene Nonionic surfactants such as fatty acid esters, polyhydric alcohols such as polyethylene glycol, glycerin and 1,3-butanediol, thickening / gelling agents, antioxidants, ultraviolet absorbers, coloring agents, preservatives , Powder, etc. can be contained. Of course, it is advantageous that the conventional melanin production inhibitor, hydroquinone such as ascorbic acid or arbutin, may exert a synergistic effect.

[0010]

EXAMPLES The present invention will be described in more detail below with reference to Examples, but it goes without saying that the present invention is not limited to these Examples.

<Example 1> To 500 g of forsythia fruits of the Astragaliaceae, 5 liters of 50% ethanol was added, heated with stirring at 90 ° C for 2 hours, cooled to room temperature, and then filtered to remove insoluble matter. It was further concentrated under reduced pressure and then freeze-dried. The essence 1 of forsythia, which is the melanocyte dendrite elongation inhibitor of the present invention,
Got

<Example 2> To 500 g of forsythia fruits of the Astragaliaceae, 5 l of 50% ethanol was added, and at room temperature,
After extraction for 1 week, insoluble matter was removed by filtration, further concentrated under reduced pressure, and then freeze-dried. Then, forsythia essence 2 which is a melanocyte dendrite elongation inhibitor of the present invention was obtained.

Example 3 Using the melanocyte dendrite elongation inhibitors of Examples 1 and 2, the dendrite elongation inhibitory action was examined. That is, according to a conventional method, macrophages were collected from mouse abdominal cavity and diluted with 10% FBS-added Eagle's minimum medium to prepare a macrophage solution having a concentration of 2 × 10 6 cells / ml. This one 9
Dispense 0 μl each into a 35 mm Petri dish and add 0.05
Ultraviolet irradiation was carried out for 20 minutes at mW / cm 2. 0.005% by dry weight of Forsythia essences 1 and 2 which are dendrite elongation inhibitors for these melanocytes
The resulting solution was dissolved in DMSO and added, and the mixture was cultured at 37 ° C. overnight. On the other hand, the tail of the mouse is cut off, the epidermis of the tail is finely chopped, placed in a petri dish, and treated with 0.5% trypsin at 37 ° C. overnight, separated into epidermis and dermis using tweezers, and only epidermis is collected. , 0.5% trypsin at 37 ° C. for 20 minutes, and filtered to collect only melanocytes as a filtrate. The filtrate containing this melanocyte was added to Eagle's minimal medium with 10% FBS, 10-4M IBMX and 1%.
The cells were cultured in a medium containing 0 ng / ml TPA at 37 ° C. for 48 hours. This was suspended in the same medium, 1000 cells / well were dispensed into 96-wells, and cultured overnight at 37 ° C. The melanocyte medium was discarded, washed 3 times with PBS, and then replaced with 35 μl of a minimum medium containing 10% FBS Eagle. 35 μl of the culture supernatant of macrophages containing the above-mentioned sample was added thereto, and the mixture was cultured at 37 ° C. for two nights and photographed under an optical microscope, and the length of dendrite was measured from this photograph. The results are shown in Table 1. From this, it is understood that the effect of suppressing the dendrite elongation by the essences 1 and 2 of forsythia which is the melanocyte dendrite elongation inhibitor of the present invention is excellent. (Sample) 1) UV irradiation + DMSO solution (0.005%) of forsythia essence 1, 2 which is a dendrite elongation inhibitor for melanocytes (0.005%) 2) UV irradiation only (positive control) 3) UV non-irradiation only (negative control)

[0014]

[Table 1]

<Example 4> A lotion was prepared according to the following formulation. That is, the prescription ingredients were stirred and solubilized at room temperature to obtain a lotion. About this lotion, 3 panelists from 1 group suffering from blemishes and freckles used it twice a day for 1 month in the morning and evening to evaluate the preventive and improving effects of the blemishes and freckles. The evaluation criteria are as follows: score 2: marked improvement, score 1:
Clear improvement, score 0.5: slight improvement, score 0: no improvement. The average score was 0.79. It was confirmed that the lotion containing the forsythia essence 1 having the melanocyte dendrite elongation suppressing effect of the present invention is effective in improving spots and freckles. 4. Forsythia essence of Example 1 1 1.0 parts by weight 1,3 butanediol 5. 0 parts by weight glycerin 3. 0 parts by weight sodium citrate 0.1 parts by weight methylparaben 0.2 parts by weight ethanol 8 parts by weight water 82. 7 parts by weight

<Example 5> A lotion was prepared according to the following formulation. That is, the prescription ingredients were stirred and solubilized at room temperature to obtain a lotion. About this lotion, 3 panelists from 1 group suffering from blemishes and freckles used it twice a day for 1 month in the morning and evening to evaluate the preventive and improving effects of the blemishes and freckles. The evaluation criteria are as follows: score 2: marked improvement, score 1:
Clear improvement, score 0.5: slight improvement, score 0: no improvement. The average score was 0.87. It was found that the lotion containing the forsythia essence 2 having the melanocyte dendrite elongation suppressing effect of the present invention is effective in improving spots and freckles. Forsythia essence of Example 2 21 parts by weight 1,3 butanediol 5 parts by weight Glycerin 3 parts by weight Sodium citrate 0.1 parts by weight Methylparaben 0.2 parts by weight Ethanol 8 parts by weight Water 82.7 parts by weight

Example 6 A skin external pharmaceutical composition was prepared according to the following formulation. That is, the formulation components were stirred and dispersed to obtain a skin external preparation. This product showed a remarkable effect on the blackening phenomenon of skin or freckles caused by light accompanied by inflammation by light. Forsythia essence of Example 1 10. 5 parts by weight Prednisolone 1 part by weight Vaseline 85 parts by weight

Example 7 A cream was prepared according to the following formulation. That is, (a), (b), and (c) were heated and dissolved at 80 ° C., and (a) and (b) were gradually added, and after further adding c to emulsify, the emulsified particles were homogenized with a homomixer and cooled to obtain a cream. This cream had an excellent effect in preventing and improving freckles and the like accompanied by inflammation. B) Squalane 10 parts by weight Cetanol 3 parts by weight Sorbitan sesquistearate 2 parts by weight Polyoxyethylene (20) behenyl ether 2 parts by weight Vitamin A acid 1 part by weight b) 1,3-butanediol 5 parts by weight Essence 21 parts by weight Carboxyvinyl polymer 0. 3 parts by weight Water 40 parts by weight C) Water 37.3 parts by weight Potassium hydroxide 0.2 parts by weight

<Example 8> A skin external pharmaceutical composition was prepared according to the following formulation. That is, the formulation components were stirred and dispersed to obtain a skin external preparation. This product showed a remarkable effect on the blackening phenomenon of skin or freckles caused by light accompanied by inflammation by light. Forsythia essence of Example 2 20. 5 parts by weight Dexamethasone 1 part by weight Vaseline 85 parts by weight

[0020]

According to the present invention, it is possible to provide an effective preventive or ameliorating means for pigment abnormalities associated with inflammation and pigment abnormalities such as freckles.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Kazuko Nishikawa             560 POLA, Kashio-cho, Totsuka-ku, Yokohama-shi, Kanagawa             Chemical Industry Co., Ltd. Pola Totsuka Research Center (72) Inventor Satoshi Suzuki             560 POLA, Kashio-cho, Totsuka-ku, Yokohama-shi, Kanagawa             Chemical Industry Co., Ltd. Pola Totsuka Research Center (72) Inventor Yuko Saito             560 POLA, Kashio-cho, Totsuka-ku, Yokohama-shi, Kanagawa             Chemical Industry Co., Ltd. Pola Totsuka Research Center F-term (reference) 4C083 AA111 AA112 AB032 AC012                       AC102 AC122 AC182 AC302                       AC442 AC482 AD092 AD492                       AD622 CC02 CC04 CC05                       EE16 FF01                 4C086 AA01 AA02 DA08 MA01 MA17                       MA28 MA63 NA14 ZA89                 4C088 AB64 AC04 BA08 CA04 MA02                       MA28 MA63 NA14 ZA89

Claims (10)

[Claims] 1. A melanocyte elongation inhibitor comprising the essence of a plant of the genus Forsythia of the family Oleaceae. 2. The melanocyte elongation inhibitor according to claim 1, wherein the Forsythia plant (Forsythia) is Forsythia (Forsythia suspensa Thunb. Vahl). 3. The elongation inhibitor for melanocyte dendrites according to claim 1, wherein the essence is an extract of a fruit with a polar solvent. 4. The melanocyte elongation inhibitor according to any one of claims 1 to 3, wherein the dendrite elongation suppression is caused by an inhibitory action of a macrophage-derived dendrite elongation promoting factor. 5. A skin external preparation for dermatological phenomena involving melanocytes and macrophages, comprising the melanocyte elongation inhibitor according to any one of claims 1 to 4. 6. The external preparation for skin according to claim 5, which is a cosmetic, and which is used for coping with a skin phenomenon involving melanocytes and macrophages. 7. The skin phenomenon involving melanocytes and macrophages according to claim 5 or 6, wherein the skin phenomenon involving melanocytes and macrophages is a skin darkening phenomenon or freckles with inflammation caused by light. Skin external preparation. 8. A whitening cosmetic containing the essence of Forsythia suspensa Thunb. Vahl of the family Oleaceae. 9. The whitening cosmetic composition according to claim 8, wherein the essence of Forsythia suspensa Thunb. Vahl of the family Oleaceae is a polar solvent extract of fruits. 10. The whitening cosmetic composition according to claim 8 or 9, wherein the whitening action has a mechanism of inhibiting dendrite elongation in melanocytes.