JP2003081807A5 - - Google Patents

Description

[Claims]
(1)
Deng calendula calendula plant belonging to the genus of the Asteraceae (Compositae) (Calendula) (Calendula
officinalis L.) , a melanocyte dendrite elongation inhibitor containing an essence extracted from a flower head with a polar solvent .
(2)
Calendula of Calendula, a member of the family Asteraceae (Compositae)
officinalis L.), a macrophage-derived dendrite elongation promoting factor inhibitor containing essence extracted with a polar solvent.

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to Dendorai preparative elongation inhibitor melanocytes.

On the other hand, resolving pigment abnormalities caused by abnormal melanin granules produced by melanocytes is a long-standing problem for humankind to embody beautiful white skin, and for this reason, various efforts have been made and many results have been achieved. Although various mechanisms have been obtained, none of them focused on the suppression of dendritic elongation of melanocytes. Of the essence extracted with a polar solvent from the head flower of Calendula offspring (Calendula officinalis L.) of the Calendula plant of the family Asteraceae (Compositae) for prevention and improvement of pigmentation disorders associated with Not known at all. In addition, the effect of a well-known melanin production inhibitor such as ascorbic acid on pigment abnormalities such as inflammation and pigment abnormalities such as freckles is only one, and there is no means of preventing or improving such pigment abnormalities. Development was desired.

Furthermore, extracts of Calendula officinalis L. of the family Asteraceae (Compositae) include essential oils, bitter substances, resins, and rubber substances called calendulin, are used as aromatic bitter medicines, and are also used for trauma. Dried head flowers were also used as carminative and stimulants, and were used as folk medicine such as stomach and anthelmintic. The young shoots and leaves became edible and used for feed. However, it is not known at all that this essence has an action of suppressing the elongation of melanocyte dendrite, and therefore, a skin external preparation such as a cosmetic containing the same has the effect of suppressing the elongation of melanocyte dendrite . It is known that it is not useful for preventing and improving pigment abnormalities, which are associated with pigment abnormalities, particularly, light, and are accompanied by inflammation.

[0005]
[Problems to be solved by the invention]
The present invention, all SANYO was made under such circumstances, the elongation inhibitors suitable melanocyte dendrites as effective prophylactic or improvement measures against pigmentation disorders, such as abnormal pigmentation and freckles accompanied by inflammation The task is to provide.

[0006]
[Means for solving the problem]
In view of such a situation, the present inventors have intensively studied for effective prevention or improvement measures for pigment abnormality accompanied by inflammation and pigment abnormality such as freckles. tow calendula) (to Heading the extension inhibitory effect of dendrite of excellent melanocytes to Essen vinegar calendula officinalis L.), it has led to the completion of the inventions. That is, the present invention relates to the following technology.
(1) A melanocyte dendrite elongation inhibitor comprising an essence extracted from a flower of a calendula offspring (Calendula officinalis L.) of a calendula plant of the family Asteraceae (Compositae) with a polar solvent .
(2) An inhibitor of a macrophage-derived dendrite elongation promoting factor, comprising an essence extracted from a flower of a calendula offspring (Calendula officinalis L.) of a calendula plant of the family Asteraceae (Compositae) with a polar solvent.
Hereinafter, the present invention will be described in detail focusing on embodiments.

[0007]
BEST MODE FOR CARRYING OUT THE INVENTION
(1) The melanocyte dendrite elongation inhibitor of the present invention The melanocyte dendrite elongation inhibitor of the present invention is obtained from the head flower of Calendula officinalis L. of a calendula plant of the family Asteraceae (Compositae). containing essences extracted with a polar solvent. In here, the essence, extract according polar organic solvents head flower such plants, solvent extracts was removed, the solvent removed substance, or the purification of the solvent removed substance by column chromatography or liquid-liquid extraction Generic name such as purified fractions. The polar solvent such as this, for example, water, ethanol, methanol, 1,3-butanediol, alcohols such as propylene glycol, esters such as ethyl acetate and methyl formate, ketones such as acetone and methyl ethyl ketone, chloroform Preferred examples include one or more selected from halogenated hydrocarbons such as methane and methylene chloride, nitriles such as acetonitrile, and ethers such as diethyl ether and tetrahydrofuran. Of these, water and alcohol are particularly preferred. In order to prepare such an extract, a 1 to 10-fold amount of a solvent is added to the plant or its processed product, and immersed for several days at room temperature or several hours at a temperature near the boiling point. Thereafter, insolubles are removed by filtration or the like, and if necessary, the solvent can be removed by concentration under reduced pressure or lyophilization. If head flower toe calendula Asteraceae (Compositae) (Calendula officinalis L.) , after the parts 50% ethanol extraction, filtration, vacuum concentrated, and particularly preferred as essence of lyophilized some cases. This is because the head flower portion is particularly preferable because it contains a large amount of a melanocyte dendrite elongation inhibitory component. The essence of the head flower of Calendula officinalis L. of the family Asteraceae (Compositae), which is the melanocyte dendrite elongation inhibitor of the present invention thus obtained, suppresses the melanocyte elongation of dendrite. It inhibits the movement of melanin granules from melanocytes to skin tissue, and the mechanism of such movement of melanin granules causes pigmentation abnormalities such as inflammation-induced blackening and freckles caused by light irradiation. Has the effect of preventing or improving It is considered that such an action has a mechanism of inhibiting the action of a dendritic elongation factor of melanocytes released by macrophages on melanocytes. 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 pigmentation abnormalities other than blackening and freckles accompanied by inflammation by light irradiation. 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 inflammation-induced blackening and freckles that occur during light irradiation. It can be said that it works. Further, since such an essence contains a substance having an inhibitory action on tyrosinase activity or melanin production, it can be contained in a whitening cosmetic for the purpose of such an action .

(2) elongation inhibitor dendrites of melanocytes applications present invention to the skin external preparation of the elongation inhibitor melanocyte dendrites of the present invention, elongation factor dendrites of melanocytes macrophages release to inhibit the act on melanocytes because it is a mechanism that, it is possible to suppress the life phenomenon in which the melanocytes and the macrophages work cooperatively, the extension inhibitor of dendrite of such melanocytes, skin for skin phenomenon eyes Ranosaito and macrophages are involved It is preferably used as an external preparation. Here, the external preparation for skin of the present invention is a skin phenomenon corresponding to melanocytes and macrophages are involved, characterized in that it contains a stretch inhibitor dendrites of melanocytes present invention. Here, the external preparation for skin referred to in the present invention is a generic name of a composition applied externally to the skin, and a skin external medicine including a patch and a cosmetic including a cleansing agent can be preferably exemplified. Then, it is particularly preferred that the composition is a cosmetic. This high safety extension inhibitor dendrites of melanocytes present invention, because the action is moderate. As skin phenomena involving melanocytes and macrophages, particularly preferably pigmentation abnormalities such as blackening and freckles accompanied by inflammation by light irradiation are mentioned as the most important issues, but also include other inflammatory reactions . The preferred content of melanocytes and macrophages in the skin external agent for the skin phenomena corresponding involved, melanocyte dendrite elongation inhibitor according to the present invention, relative to the total amount of the skin treatment composition, 0.001% to 10 %, More preferably 0.01% to 5% by weight. This is because if the amount is too small, the effect of suppressing dendrite elongation may not be exhibited, and if the amount is too large, the effect may reach a plateau and the degree of freedom of other formulation components may be impaired.

The topical skin preparation for treating skin phenomena involving the melanocytes and macrophages according to the present invention is known as an anti-inflammatory agent, prednisolone, hydrocortisone, dexamethasone, indomethacin, diclofenac sodium, etc. Significant for accompanying melanosis. Further, in addition to the above essential components, any components usually used in cosmetics or external medicine for skin can be contained. Such optional components include, for example, hydrocarbons such as squalane, petrolatum, and microcrystalline wax, jojoba oil, carnauba wax, esters such as octyldodecyl oleate, triglycerides such as olive oil, tallow, coconut oil, and stearic acid. Oleic acid, fatty acids such as ritinoleic acid, higher alcohols such as oleyl alcohol, stearyl alcohol, and octyl dodecanol; anionic surfactants such as sulfosuccinates and sodium polyoxyethylene alkyl sulfate; and amphoteric surfactants such as alkyl betaine salts. Agents, cationic surfactants such as dialkylammonium salts, sorbitan fatty acid esters, fatty acid monoglycerides, their polyoxyethylene adducts, 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 and the like. Of course, the addition of hydroquinones such as ascorbic acids and arbutin, which are conventional melanin production inhibitors, may also exert a synergistic effect, which is advantageous.

<Example 1>
The essence of the head flower of Calendula officinalis L. of the family Asteraceae (Compositae) is obtained by adding 5 l of 50% ethanol to 500 g of the head flower, extracting with stirring for one week at room temperature, and filtering to remove insoluble matter. It was removed, further concentrated under reduced pressure, and then freeze-dried. Then, to obtain a honeysuckle essence 1 is elongated inhibitor dendrites of melanocytes present invention.

<Example 2>
The essence of the head flower of Calendula officinalis L. of the family Asteraceae (Compositae) is obtained by adding 5 l of 50% ethanol to 500 g of the head flower, heating at 90 ° C. for 2 hours with stirring, and cooling to room temperature. Then, the mixture was filtered to remove insolubles, further concentrated under reduced pressure, and then freeze-dried. Then, to obtain the essence 2 tow calendula is elongated inhibitor dendrites of melanocytes present invention.

<Example 3>
The essence of the head flower of Calendula officinalis L. of the family Asteraceae (Compositae) is obtained by adding 5 l of 50% methanol to 500 g of the head flower, heating at 90 ° C. for 2 hours with stirring, and cooling to room temperature. Then, the mixture was filtered to remove insolubles, further concentrated under reduced pressure, and then freeze-dried. Then, to obtain the essence 3 toe calendula is elongated inhibitor dendrites of melanocytes present invention.

<Example 4>
With elongation inhibitor dendrites of melanocytes of Example 1, 2 and 3 were examined dendrite outgrowth inhibition action. That is, macrophages were collected from the mouse abdominal cavity in advance and diluted with a minimal medium containing 10% FBS-added Eagle according to a conventional method to prepare a macrophage solution having a concentration of 2 × 10 ⁶ cells / ml. This was dispensed in 90 μl portions into a 35 mm petri dish, and this was irradiated with ultraviolet light at 0.05 mW / cm ² for 20 minutes. Essences 1, 2, and 3 of Calendula officinalis, which are inhibitors of elongation of melanocyte dendrite , were dissolved in DMSO to a dry weight percentage of 0.005%, and cultured at 37 ° C. overnight. On the other hand, the tail of the mouse was cut off, the epidermis of the tail was finely chopped, placed in a petri dish, treated with 0.5% trypsin at 37 ° C. overnight, separated into epidermis and dermis using forceps, and only the epidermis was collected. And 0.5% trypsin for 20 minutes at 37 ° C., and only melanocytes were collected as a filtrate by filtration. The filtrate containing the melanocytes was cultured at 37 ° C. for 48 hours in a medium in which 10% FBS, 10 ⁻⁴ M IBMX and 10 ng / ml TPA were added to Eagle's minimal medium. This was suspended in the same medium, dispensed into a 96-well well at a rate of 1000 cells / well, and cultured at 37 ° C. overnight. The melanocyte medium was discarded, washed three times with PBS, and then replaced with 35 μl of a minimum medium of Eagle supplemented with 10% FBS. To this, 35 μl of the culture supernatant of the macrophage containing the specimen was added, and the mixture was cultured at 37 ° C. for two nights, a photograph was taken under an optical microscope, and the length of the dendrite was measured from this photograph. Table 1 shows the results. From this, essences 1, 2 and 3 of the toe calendula is elongated inhibitor dendrites of melanocytes of the invention it can be seen that excellent inhibition of dendrite elongation.
(Sample)
1) of the tow calendula essence of 1 is elongated inhibitor dendrites of UV radiation + melanocytes DMSO solution (0.005%)
2) UV irradiation + DMSO solution of essence 2 of calendula officinalis, which is an inhibitor of melanocyte dendrite elongation (0.005%)
3) UV irradiation + DMSO solution of Essence 3 of calendula officinalis, which is an inhibitor of melanocyte dendrite elongation (0.005%)
4 ) UV irradiation only (positive control)
5 ) UV non-irradiation only (negative control)

< Application Example 1 >
A lotion was prepared according to the following formulation. That is, the ingredients were stirred and solubilized at room temperature to obtain a lotion. This lotion, stain, using the panelists 1 group 3 people suffer from freckles, one month, the stains, were asked to evaluate the effect of preventing and improving freckles asked to use 2 times morning and evening daily. The evaluation criterion is a criterion of rating 2 : marked improvement, rating 1 : obvious improvement, rating 0.5 : slight improvement, rating 0 : no improvement. The average score was 0.91. Lotion containing essence 1 tow calendula with outgrowth inhibition effect of Dendorai bets melanocytes present invention, stain, to be effective in improving freckles were observed.
Calendula essence 1 of Example 1 1 part 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

< Application Example 2 >
A lotion was prepared according to the following formulation. That is, the ingredients were stirred and solubilized at room temperature to obtain a lotion. This lotion, stain, using the panelists 1 group 3 people suffer from freckles, one month, the stains, were asked to evaluate the effect of preventing and improving freckles asked to use 2 times morning and evening daily. The evaluation criterion is a criterion of rating 2 : marked improvement, rating 1 : obvious improvement, rating 0.5 : slight improvement, rating 0 : no improvement. The average score was 0.86. It was confirmed that the lotion containing the essence 2 of Calendula officinalis having the effect of suppressing the elongation of the melanocyte dendrites of the present invention was effective in improving spots and freckles.
Calendula essence 2 of Example 2 1 part by weight 1,3-butanediol 5 parts by weight Glycerin 3 parts by weight Sodium citrate 0.1 part by weight Methylparaben 0.2 parts by weight Ethanol 8 parts by weight Water 82.7 parts by weight

< Application 3 >
A pharmaceutical composition for external use on the skin was prepared according to the following formulation. That is, the prescription components were stirred and dispersed to obtain a skin external preparation. It showed a remarkable effect on light-induced skin blackening or freckles accompanied by light-induced inflammation.
Calendula essence 3 of Example 3 0.5 parts by weight Prednisolone 1 part by weight Vaseline 85 parts by weight

< Application Example 4 >
A cream was prepared according to the following recipe. That is, (a), (b), and (c) were each heated and dissolved at 80 ° C., (b) was gradually added to (a), and (c) was further added to emulsify the mixture. This cream was excellent in preventing and improving freckles with inflammation.
I)
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 of Calendula officinalis in Example 1 1 part by weight Carboxyvinyl polymer 0.3 part by weight Water 40 parts by weight c)
Water 37.3 parts by weight Potassium hydroxide 0.2 parts by weight

< Application Example 5 >
A pharmaceutical composition for external use on the skin was prepared according to the following formulation. That is, the prescription components were stirred and dispersed to obtain a skin external preparation. It showed a remarkable effect on light-induced skin blackening or freckles accompanied by light-induced inflammation.
Calendula essence 2 of Example 2 0.5 parts by weight Dexamethasone 1 part by weight Vaseline 85 parts by weight

[0021]
【The invention's effect】
According to the present invention, it is possible to provide a melanocyte dendrite elongation inhibitor that is effective against pigment abnormality accompanied by inflammation and pigment abnormality such as freckles.