JP2007070228A - Tyrosinase inhibitor, bleaching ingredient, bleaching cosmetic and bleaching food and beverage - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a tyrosinase inhibitor, a bleaching ingredient, a bleaching cosmetic and a bleaching food and beverage effective for preventing and ameliorating pigmentation/stains/freckles after suntan. <P>SOLUTION: The tyrosinase inhibitor is obtained by using at least one kind of Crepidiastrum lanceolatum and its extract as a main component. The bleaching ingredient is obtained by using at least one kind of Crepidiastrum lanceolatum and its extract as a main component. The bleaching cosmetic is obtained by using at least one kind of Crepidiastrum lanceolatum and its extract as a main component. The bleaching food and beverage is obtained by using at least one kind of Crepidiastrum lanceolatum and its extract as a main component. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a tyrosinase inhibitor, a whitening agent, a whitening cosmetic, and a whitening food or drink.

  Although there are some unclear points about the mechanism of skin spots and freckles, melanin pigments are generally formed due to hormonal abnormalities or the stimulation of ultraviolet rays from sunlight. It is thought to be generated by deposition.

This melanin pigment, which causes skin coloring, is produced in the melanosomes in the melanocytes between the epidermis and dermis, and the produced melanin pigment diffuses to neighboring cells.
And it is estimated that the biochemical reaction in this melanocyte is as follows.

That is, tyrosine, which is an essential amino acid, becomes dopaquinone by the action of the enzyme tyrosinase, which changes to black melanin by enzymatic or non-enzymatic oxidation. This process is a melanin pigment formation process.
Therefore, suppressing the action of tyrosinase in the first stage of the reaction is important for suppressing the production of melanin pigment.

  By the way, conventionally, for the prevention and treatment of pigmentation, stains, freckles, etc., a whitening agent containing a chemically synthesized product such as hydroquinone as an active ingredient, for example, 0.01 to 10% by weight of hydroquinone based on the total amount of cosmetics. Cosmetics (Patent Document 1) containing at least one kind of saccharide and a herbal medicine or herbal extract having a whitening effect have been used.

However, chemically synthesized products such as hydroquinone are at risk of side effects such as skin irritation and allergies. Therefore, it is desired to develop a whitening agent containing a highly safe natural raw material as an active ingredient.
JP-A-5-139950

  The present invention solves the above-mentioned problems, and it is possible to obtain a pigmentation prevention effect and a whitening effect by inhibiting the activity of tyrosinase involved in the production of melanin pigments that cause pigmentation, spots, freckles, etc. Another object of the present invention is to provide a whitening agent, a whitening cosmetic, and a whitening food or drink containing a plant-derived tyrosinase inhibitor, and a substance having a tyrosinase inhibitory effect derived from food.

In order to solve the above-mentioned problems, the inventors of the present application conducted research and investigation on substances derived from various plants, conducted experiments, and found that Hosovawadan, a perennial plant belonging to the genus Asteraceae that grows naturally in the south of Honshu Shimane Prefecture. (Nigana) and its extract were found to have tyrosinase inhibitory activity.
Further experiments and examinations were conducted to complete the present invention.

  That is, the tyrosinase inhibitor of the present invention (Claim 1) is characterized by containing at least one of Hosoubadan and Hosoubadan extract.

  Further, the whitening agent of the present invention (Claim 2) is characterized by containing at least one of Hosovawadan and Hosobabadan extract.

  Moreover, the whitening cosmetic of the present invention (Claim 3) is characterized by containing at least one of Hosoubadan and Hosoubadan extract.

  The whitening food or drink of the present invention (Claim 4) is characterized in that it contains at least one of Hoso Bawadan and Hoso Baba Dan extract.

  The tyrosinase inhibitor obtained by the invention of the present application (Claim 1) contains Hosovawadan (Nigana), which is a vegetable that is eaten daily, or an extract obtained by extracting an active ingredient from Hosovawadan. It is possible to obtain an anti-pigmentation effect and a whitening effect by inhibiting tyrosinase activity involved in melanin production that causes pigmentation, spots, buckwheat, and the like.

  In addition, the tyrosinase inhibitor of the present invention has high safety because it is mainly composed of an extract obtained from Hosoubadan (Nigana), which is a vegetable that is eaten daily, or Hosoubadan. There is little risk of side effects such as skin irritation and allergies.

  In addition, the whitening agent of the present invention (Claim 2) contains at least one of Hosoubadan and Hosoubadan extract, so it is excellent in safety, has few side effects such as skin irritation and allergy, and prevents pigmentation. A whitening agent having an effect and a whitening effect can be provided.

  In addition, since the whitening cosmetic composition of the present invention (Claim 3) is formulated with at least one of Hoso Bawadan and Hoso Baba Dan extract, it is possible to suppress or prevent pigmentation, stains, buckwheat etc. Therefore, it is possible to provide a highly safe whitening cosmetic with less risk of side effects such as skin irritation and allergies.

  Moreover, since the food for whitening of the present invention (Claim 4) is mixed with Hoso Bawadan (Nigana) or Hoso Baba Dan extract, which is a vegetable that is eaten on a daily basis, it is safe to eat and drink, There is little risk of side effects such as allergies, and it is possible to provide a whitening food or drink having an effect of preventing pigmentation and a whitening effect.

  As described above, according to the present invention, a highly safe natural product, Hosoubadan (Nigana), or an extract having an inhibitory action on tyrosinase extracted from Hosoubadan, is highly safe and can be used for allergies. It becomes possible to provide a tyrosinase inhibitor, a whitening agent, a whitening cosmetic, and a whitening food and drink with less risk of side effects.

  The tyrosinase inhibitor of the present invention is made from Hosovawadan, a perennial plant belonging to the genus Asteraceae that grows naturally in the south of Honshu Shimane Prefecture. This Hosovawadan is a plant called scientific name: Crepidiastrum lanceolatum, Japanese name: Hosovawadan, and is called Njana or Nigana in the Okinawa dialect name.

  Hosobawadan (Nigana) is a plant that has long been eaten raw in Okinawa or eaten through fire in Okinawa, and the safety of this plant and its extract components has been confirmed. Therefore, according to the present invention, it is possible to provide a tyrosinase inhibitor having a tyrosinase inhibitory activity that can be substituted for a chemically synthesized product and using a natural product having excellent safety as a raw material.

  In addition, by using the tyrosinase inhibitor of the present invention made from natural products, it is possible to obtain an anti-pigmentation effect and a whitening effect, and it is highly safe and may cause side effects such as skin irritation and allergy. It is possible to provide a whitening agent, a whitening cosmetic and a whitening food / beverage.

  In the present invention, it is possible to use at least one of flowers, stems, leaves, rhizomes, roots and seeds of Hosoubadan, and whole plants can be used as a raw material for Hosoubadan. However, preferably leaves and stems are used. This is due to the high content of substances having a tyrosinase inhibitory action in leaves and stems.

Moreover, when using Hoso Bawadan as a raw material, it can be used in the state which grind | pulverized, for example.
When pulverizing Hoso Bawadan, it can be easily made into a fine powder using a blender in a state of ventilation drying or freeze drying, for example.

  Moreover, the Hoso Bawadan extract extracted from the Hoso Bawadan can be used. By performing the extraction, the active ingredient of Hosoubadan (the substance having a tyrosinase inhibitory action) can be obtained with high purity. And the effect of the tyrosinase inhibitor which is a product can be heightened by using the extract with which the active ingredient was concentrated as a raw material. In addition, also when extracting and using the active ingredient of Hosouba dan, it is preferable to use a leaf and a stem as an extraction raw material.

In the present invention, “Hosobabadan extract” means an extract obtained using Hosobawadan as an extraction raw material as described above.
In addition, the “hosobawadan extract” includes an extract obtained from hosoubadan as an extraction raw material, a diluted or concentrated solution of the corresponding extract, a dried product obtained by drying the extract, or a crudely purified product thereof, Purified product is included.

As the extraction solvent, water, an acid such as hydrochloric acid, sulfuric acid, citric acid, and acetic acid or an aqueous alkali solution such as sodium hydroxide and potassium hydroxide can be used.
In addition, organic solvents such as alcohols (for example, absolute ethanol, ethanol, propylene glycol, 1,3-butylene glycol, etc.), ketones such as acetone, esters such as diethyl ether, dioxane, and ethyl acetate are used. it can.
These solvents can be used alone or in any combination of two or more.
Moreover, the extract by each solvent can be combined and used as a Hoso Bawadan extract.

  In addition, although there are no special restrictions in extraction conditions, such as extraction temperature and extraction time, for example, an active ingredient can be extracted by immersing Hosoubadan in the above-mentioned extraction solvent for a long time at normal temperature. In addition, the time required for extraction can be shortened by heating.

Hosovawadan extract can be used as a tyrosinase inhibitor as it is, but it can be concentrated to form a solution, paste, or powder to increase the content and increase the tyrosinase inhibitory effect. .
In addition, various general methods, such as concentration under reduced pressure and freeze-drying, can be used for concentration of the Hoso Bawadan extract.

  In addition, Hosovawadan extract can be used as it is as a tyrosinase inhibitor, but it can enhance the effect of inhibiting tyrosinase by purification. In addition, in this invention, the refined | purified material which refine | purified the Hosoubadan extract is the concept contained in the Hosoubadan extract.

  For the purification of Hoso Bawadan extract, a general method such as transfer to an organic solvent or use of an adsorbent can be used. For example, a highly active extract and purified product can be obtained by transferring a hot water extract of Hosoubadan to an organic solvent.

  The extract can be purified using an adsorbent. Examples of the adsorbent include silica gel, polyvinylpolypyrrolidone, polyvinylpyrrolidone, styrene-divinylbenzene copolymer, methacrylate polymer, crosslinked dextran. Gels, hydrophilic vinyl polymers, and the like can be used.

  In the tyrosinase inhibitor according to the present invention, the concentration of Hosovawadan extract or purified product can be in the range of 0.01 to 100% by weight as the solid content, but preferably in the range of 0.5 to 50% by weight. is there. By setting the content concentration of the Hoso Bawadan extract or purified product to be in the range of about 0.5 to 50% by weight, good usability and effects can be obtained.

  As described above, hosoubadan and hosoubadan extract (or a purified product thereof) have a tyrosinase inhibitory action, and thus can be used as active ingredients of tyrosinase inhibitors.

  In addition, by blending Hoso Bawadan and / or Hoso Bawadan extract, it is possible to obtain anti-pigmentation effect and whitening effect by inhibiting tyrosinase activity involved in melanin production that causes pigmentation, spots, buckwheat etc. In addition, it is possible to provide a whitening agent, a whitening cosmetic, and a whitening food and drink that have high safety and are less likely to cause side effects such as skin irritation and allergy.

Further, Hosoubadan and Hosoubadan extract can be used as they are as a tyrosinase inhibitor, a whitening agent, a whitening cosmetic, and a whitening food or drink, but can also be formulated and used according to a conventional method.
In the case of formulating, a pharmaceutically acceptable carrier such as dextrin and cyclodextrin and other optional auxiliaries can be added for easy storage and handling.
Hosoubadan and Hosoubadan extract can be made into arbitrary dosage forms such as powder, granules and tablets by formulation.

  The tyrosinase inhibitor of the present invention includes components usually used in external preparations for skin such as cosmetics and pharmaceuticals, for example, other whitening agents, moisturizers, antioxidants, oily components, ultraviolet absorbers, surfactants, thickeners. Agents, alcohols, powder components, colorants, aqueous components, water, various skin nutrients, and the like can be blended as needed.

In particular, Hoso Bawadan and Hoso Bawadan extract are excellent in safety when applied to the skin and are therefore suitable for blending into skin cosmetics. Further, skin cosmetics (whitening cosmetics) containing at least one of Hosovawadan and Hosovawadan extract are given a whitening effect derived from Hosovawadan, and are highly safe cosmetics having a whitening effect. Can be used.
The “whitening cosmetic” in the present invention is a skin cosmetic used for the purpose of whitening, and the type thereof is not particularly limited. For example, lotion, cream, emulsion, pack, lipstick, lip Cream can be given.

  In addition, Hoso Bawadan and Hoso Bawadan extract are suitable for blending in foods and drinks because they can be taken orally. A whitening effect is imparted to foods and drinks containing at least one of Hosovawadan and Hosobawadan extract, and can be used as foods for whitening. “Whitening food / beverage” is a food / beverage used for the purpose of whitening, and there is no particular limitation on the type thereof.

  Examples of the present invention will be shown below, and the features thereof will be described in more detail.

100 g of fresh nigana (Hosobabadan) leaves commercially available as vegetables,
(1-1) 80% by weight ethanol (the rest is water): 0.4 L,
(1-2) 50 wt% ethanol (the rest is water): 0.4 L,
(1-3) Water: 0.4L
Were extracted under the conditions of room temperature for 90 days, and the following extracts 1-1 to 1-3 were obtained.
Moreover, extraction was performed under the conditions of 80 ° C. for 1 hour using the extraction solvent (1-1) to obtain the following extract 1-4.
Extraction liquid 1-1 (extraction for 90 days with 80 wt% ethanol at room temperature)
Extract liquid 1-2 (extracted with 50 wt% ethanol at room temperature for 90 days))
Extract 1-3 (normal temperature with water, extraction for 90 days))
Extraction liquid 1-4 (extraction at 80 ° C. for 1 hour with 80 wt% ethanol)
And the obtained extract 1-1-1-4 were concentrate | evaporated under reduced pressure, and the Hosoubadan extract was obtained.

100 g of lyophilized and pulverized leaves of Japanese leek (Hosobawadan) marketed as vegetables,
(2-1) 80% by weight ethanol (the rest is water): 1.5 L,
(2-2) 50% by weight ethanol (the rest is water): 1.5 L,
(2-3) Water: 1.5L
(2-4) 1N hydrochloric acid aqueous solution: 1.5 L
In the case of using 80 wt% ethanol: 1.5 L of the above (2-1) and the case of using 50 wt% ethanol: 1.5 L of the above (2-2) Is heated to 80 ° C, and when using the water of (2-3) above and when using the 1N hydrochloric acid aqueous solution of (2-4) above, heating to 100 ° C and extracting for 1 hour each And the following extracts 2-1 to 2-4 were obtained.
Extract 2-1 (extraction with 80 wt% ethanol at 80 ° C. for 1 hour)
Extract liquid 2-2 (extraction at 50 ° C. for 1 hour with 50 wt% ethanol)
Extract 2-3 (extraction with water at 100 ° C. for 1 hour)
Extract 2-4 (Extraction with 1N aqueous hydrochloric acid at 100 ° C. for 1 hour)
Then, the obtained extract liquids 2-1 to 2-4 were concentrated under reduced pressure to obtain a Hosoubadan extract.

  Of each of the Hoso Babadan extracts obtained in Examples 1 and 2, Hoso Babadan extract of Extract 1-4 (extraction solvent: 80 wt% ethanol) of Example 1, and Extract 2- of Example 2 1 (extraction solvent: 80 wt% ethanol), extract 2-2 (extraction solvent: 50 wt% ethanol) and extract 2-4 (extraction solvent: 1N aqueous hydrochloric acid) The tyrosinase inhibitory activity was measured by the following method.

In this example, when the Hosoubadan extract was dissolved in the solvent, the solid content of the Hosoubadan extract obtained in each extraction step was measured, and 1 ml of the Hosoubadan extract solution obtained by dissolving the solid in the solvent was measured. The concentration was adjusted so that 2.5 mg of the solid (Hosobabadan extract) was dissolved therein.
Specifically, the amount of Hosovawadan extract (solid material) extracted from 100 g of Hosovawadan extract raw material (fresh Hosoubadan or raw material obtained by freeze-drying and grinding fresh Hosoubadan)
In extract 1-4, 1.7g
30 g for Extract 2-1
30 g for Extract 2-2
46 g for extract 2-4
Met.
Therefore, in the tyrosinase inhibitory activity test that was conducted, 1 mg of Hosoubadan extract (solid content) was added to the reaction solution.

In evaluating tyrosinase inhibitory activity,
(a) 0.4 ml (1 mg as a solid) of each of the above Hosoubadan extract extracts;
(b) 0.1 ml of a 25 mM phosphate buffer (pH 6.9) solution of 50 U / ml mushroom-derived tyrosinase;
(c) A 0.5 mg / ml L-Dopa 25 mM phosphate buffer (pH 6.9) solution (0.5 ml) was mixed and the change in absorbance (475 nm) for 5 minutes was measured, and the tyrosinase inhibition rate was controlled (extracted). This was performed by calculating the absorbance change of (no addition) as 100% and determining the tyrosinase inhibition rate. The tyrosinase inhibition rate indicates that the greater the value, the greater the tyrosinase inhibitory activity.
The results are shown in Table 1.

The unit of tyrosinase inhibition rate in Table 1, “1 mg extract / ml” represents the ratio of inhibiting tyrosinase activity when 1 mg equivalent of Hosoubadan extract (solid content) was present in 1 ml of reaction solution. Thus, it is a concept that means the specific activity of tyrosinase inhibitory ability for each extraction.
From Table 1, it was confirmed that the Hoso Bawadan extract (Hoso Bawadan extract solution) has tyrosinase inhibitory activity. In addition, in the conditions shown in Table 1, it turned out that the tyrosinase inhibition rate of the Hosovadadan extract extracted using 1N hydrochloric acid aqueous solution is high.

  In Examples 1 and 2, Hoso Bawadan extract not shown in Table 1 has also been confirmed to have tyrosinase inhibitory activity.

  Each Hosovawadan extract obtained in Examples 1 and 2 was used as an aqueous solution, and a neutralized Hosovawadan extract with a solid content concentration of 3.75% by weight was used as a sample, and each sample was applied. The safety when inspected.

For 10 men and women aged 20 to 50 years, acute reactions were visually observed and 4-day follow-up was conducted by questionnaire survey.
As a result, no acute reaction was observed in all subjects, and no skin troubles were observed in the subjects during the test period, confirming that there were no safety problems.

The skin external preparation (whitening cream) was produced by mix | blending Hoso Bawadan extract with the component shown in the following formulation examples.
(1) Stearic acid 8.0% by weight
(2) Stearyl alcohol 4.0% by weight
(3) Butyl stearate 6.0% by weight
(4) Propylene glycol 5.0% by weight
(5) 2.0% by weight of glyceryl monostearate
(6) Potassium hydroxide 0.4% by weight
(7) 74.1% by weight of purified water
To the above formulation, the extraction solvent of the above (2-4): Hosovawadan extract using 1N hydrochloric acid aqueous solution is added so that the final concentration as a solid is 0.5% by weight, and if necessary, antiseptic, oxidation After the prevention treatment, a cream (whitening cream) was obtained through an emulsification operation by a conventional method.
When the subject applied the whitening cream of this example to the skin and used it, it was confirmed that the whitening action was observed.

  In addition, when using the Hosoubadan extract of Example 1 and 2 other than the Hosoubadan extract of the above (2-4), the whitening effect as in the case of using the Hosoubadan extract of the above (2-4) A cream having whitening (whitening cream) can be obtained.

The skin external preparation (whitening gel) was produced by mix | blending Hoso Bawadan extract with the component shown in the following prescription examples.
(1) Dipropylene glycol 7.0% by weight
(2) PEG 1500 8.0 wt%
(3) Carboxyvinyl polymer 0.4% by weight
(4) Methylcellulose 0.2% by weight
(5) POE (15) oleyl alcohol ether 1.0% by weight
(6) Potassium hydroxide 0.1% by weight
(7) Purified water 81.3 wt%
To the above formulation, the extraction solvent of the above (2-4): Hoso Bawadan extract using 1N hydrochloric acid aqueous solution is added so that the final concentration as a solid is 2.0% by weight. After the prevention treatment, a chelating agent was added by a conventional method to obtain a gel.
When the test subject applied the whitening gel of this example to the skin, it was confirmed that the whitening action was observed.

  In addition, when using the Hosoubadan extract of Example 1 and 2 other than the Hosoubadan extract of the above (2-4), the whitening effect as in the case of using the Hosoubadan extract of the above (2-4) A gel having whitening (whitening gel) can be obtained.

A skin external preparation (beauty liquid) was prepared by blending the Hoso Bawadan extract with the components shown in the following formulation examples.
(1) Sorbitol 8.0 wt%
(2) 1,3-butylene glycol 5.0% by weight
(3) PEG 1500 7.0% by weight
(4) Hyaluronic acid 0.1% by weight
(5) 7.0% by weight of ethanol
(6) POE oleyl alcohol ether 1.0% by weight
(7) Olive oil 0.2% by weight
(8) Purified water 69.7% by weight
To the above formulation, the extraction solvent of the above (2-4): Hoso Bawadan extract using 1N hydrochloric acid aqueous solution is added so that the final concentration as a solid is 2.0% by weight, and if necessary, preservative, oxidation After preventive treatment, it was solubilized by a conventional method to obtain a cosmetic liquid.
When the test liquid of this example was applied to the skin and used by a subject, it was confirmed that a whitening effect was observed.

  In addition, when using the Hosoubadan extract of Example 1 and 2 other than the Hosoubadan extract of the above (2-4), the whitening effect as in the case of using the Hosoubadan extract of the above (2-4) A cosmetic liquid having the above can be obtained.

(1) Soy milk 200g
(2) Cocoa 10g
In Example 8, the above component (2-4) extraction solvent: Hosoubadan extract using 1N hydrochloric acid aqueous solution was added to a final concentration of 5.0% by weight as a solid, and solubilized. And it was set as the drink after antiseptic treatment as needed.
When the subject continued to drink the beverage of this example, it was confirmed that a whitening effect was observed.

  In addition, when using the Hosoubadan extract of Example 1 and 2 other than the Hosoubadan extract of the above (2-4), the whitening effect as in the case of using the Hosoubadan extract of the above (2-4) Can be obtained.

(1) Buckwheat flour 100g
(2) 100g of flour
(3) Appropriate amount of egg In Example 9, the final concentration of Hosovawadan extract using the above component (2-4) extraction solvent: 1N hydrochloric acid aqueous solution as a solid substance is 5.0% by weight. In addition to the above, noodles were prepared.
When the subject ate the noodles of this example continuously, it was confirmed that a whitening effect was observed.

  In addition, when using the Hosoubadan extract of Example 1 and 2 other than the Hosoubadan extract of the above (2-4), the whitening effect as in the case of using the Hosoubadan extract of the above (2-4) Noodles (food) having the above can be obtained.

A jelly-like food was prepared by blending the Hoso Bawadan extract with the following ingredients.
(1) 60g sugar
(2) Soy protein 1g
(3) Pectin 1g
(4) Olive oil 1g
(5) Malic acid 1g
(6) Agar 1g
(7) Thickener and emulsifier Appropriate amount In Example 10, the final concentration of Hosovawadan extract using the above-described component (2-4) extraction solvent: 1N hydrochloric acid aqueous solution as a solid was 2.0. A jelly-like food was prepared in addition to the weight percent.
When the subject continued to eat the jelly-like food of this example, it was confirmed that a whitening effect was observed.

  In addition, when using the Hosoubadan extract of Example 1 and 2 other than the Hosoubadan extract of the above (2-4), the whitening effect as in the case of using the Hosoubadan extract of the above (2-4) It is possible to obtain a jelly-like food (food) having

  The invention of the present application is not limited to the above-mentioned examples, but coexisting substances other than at least one of Hosoubadan and Hosoubadan extract in tyrosinase inhibitors, whitening agents, whitening cosmetics, whitening foods and beverages Various applications and modifications can be made within the scope of the invention with respect to the types and ratios.

As described above, according to the present invention, it is possible to obtain a tyrosinase inhibitor with high safety to the human body, having excellent tyrosinase inhibitory activity using plant as a raw material, and high safety to the human body, And it becomes possible to provide the whitening agent which has the outstanding whitening effect | action, the cosmetics for whitening, and the food / beverage products for whitening.
Therefore, the present invention can be widely applied to the fields of tyrosinase inhibitors, whitening agents having a whitening effect, whitening cosmetics, and whitening foods and drinks.

Claims (4)

  A tyrosinase inhibitor characterized by containing at least one of hosoubadan and hosoubadan extract.   A whitening agent characterized by containing at least one of Hosovawadan and Hosovawadan extract.   A cosmetic for whitening, comprising at least one of Hoso Bawadan and Hoso Bawa Dan extract.   A whitening food or drink comprising at least one of Hosovawadan and Hosobawadan extract.