JP2001322932A - Active oxygen scavenger and active oxygen scavenging composition containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an active oxygen scavenging agent having excellent scavenging action on active oxygen, especially singlet oxygen and provide a composition containing the agent such as cosmetics, foods or pharmaceuticals. SOLUTION: Kojic acid having excellent singlet oxygen scavenging action or its physiologically permissible salt is included in cosmetics, foods or pharmaceuticals.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an active oxygen scavenger and a composition containing the active oxygen scavenger for scavenging active oxygen.

[0002]

2. Description of the Related Art The generation of active oxygen in a living body has important physiological activities such as elimination of foreign substances and removal of pathogenic microorganisms, but also causes tissue damage, inflammation and aging. It has various adverse effects on living organisms, and its control is an important theme in maintaining normal life activity. To eliminate active oxygen such as superoxide, singlet oxygen, and hydroxyl radicals that are excessively expressed, metal chelating agents are used to suppress the generation of active oxygen generated by using metal ions as catalysts. Is secondary, not so high, and it has been desired to develop an active oxygen scavenger having excellent active oxygen scavenging ability. Furthermore, it has been pointed out that such active oxygens are a cause of these diseases in atopic dermatitis and chemical hypersensitivity, for which the cause and treatment method have not been determined. Is effective in preventing the onset of cholera, in addition to controlling the exacerbation after the onset of such a disease, and also efficiently eliminating and controlling the active oxygen. The recognition that is important is shared. Furthermore, in the formation of wrinkles caused by light and the like, it is said that, in addition to active oxygen generated by light, inflammation caused by light irradiation is also synergistically involved. Active oxygen scavengers that do not degrade are thought to be very beneficial in preventing such wrinkles, but such active oxygen scavengers have not yet been obtained. Among various active oxygen, singlet active oxygen is
It is easy to occur at the site irradiated with light or ischemic site,
It is said that this generation raises the nitric oxide generation mechanism and triggers various active oxygen generation systems.To minimize the effect of the generated active oxygen on the living body, it is necessary to erase this. It is said to be important.

On the other hand, kojic acid is a compound having a structure represented by the chemical formula 1, which is already commercially available as a raw material for cosmetics. It is already known that such kojic acid and its salts are incorporated into cosmetics and the like for the purpose of suppressing melanin production. However, these substances are active oxygen, and in particular, a single substance that triggers the generation of active oxygen. It is also excellent in terminating oxygen, and it can be used in inflamed areas by including such kojic acids in compositions such as cosmetics, and is useful for preventing wrinkles from forming due to light. It was not known at all that a composition could be obtained.

[0004]

Embedded image Chemical formula 1

[0005]

SUMMARY OF THE INVENTION The present invention has been made under such circumstances, and an active oxygen scavenger having excellent active oxygen scavenging ability and a composition for scavenging active oxygen containing the same are disclosed. The task is to provide.

[0006]

DISCLOSURE OF THE INVENTION In view of the above-mentioned circumstances, the present inventors have made intensive research efforts for an active oxygen scavenger having excellent active oxygen scavenging ability. And completed the invention. Furthermore, as a result of repeated studies, it has been found that by containing these kojic acids in a composition for eliminating active oxygen, the compound exhibits an action of suppressing an undesirable biological reaction derived from active oxygen, thereby completing the invention. Reached. That is, the present invention relates to the following technology. (1) An active oxygen scavenger comprising kojic acid and / or a physiologically acceptable salt thereof. (2) the active oxygen is singlet oxygen,
The active oxygen scavenger according to (1). (3) A composition for scavenging active oxygen, comprising the active oxygen scavenger according to (1) or (2). (4) The composition for eliminating active oxygen according to (3), which is a cosmetic. (5) for use in inflamed areas, (4)
The composition for elimination of active oxygen according to the above. (6) The composition for erasing active oxygen according to (4) or (5), which is used for forming wrinkles derived from light. (7) Cosmetic acid and / or a salt thereof, which is a cosmetic for light-derived wrinkles. (8) The cosmetic according to (7), which is used for an inflammatory site. Hereinafter, the present invention will be described in more detail focusing on embodiments.

[0007]

DESCRIPTION OF THE PREFERRED EMBODIMENTS (1) Active oxygen scavenger of the present invention The active oxygen scavenger of the present invention comprises kojic acid and / or a salt thereof. Here, as the salt of kojic acid that can be used in the present invention, any physiologically acceptable salt can be used without any particular limitation. Examples thereof include alkali metal salts such as sodium and potassium, and alkaline earth salts such as calcium and magnesium. Preferable examples include metal salts, ammonium salts, organic amine salts such as triethanolamine and triethylamine, and basic amino acid salts such as arginine and lysine. The active oxygen scavenger of the present invention, among various active oxygen,
It has the effect of characteristically eliminating singlet oxygen, suppressing the biological injury reaction caused by active oxygen within the initial stage, and preventing the damage caused by active oxygen from becoming serious. Examples of such a biological injury reaction include an inflammation reaction caused by singlet oxygen, a fragmentation reaction of collagen fibers constituting a collagen fiber bundle of skin, and a disconnection reaction of nucleic acids. Further, since the active oxygen scavenger of the present invention also has an action of suppressing inflammation, it can be used for inflamed sites,
By using it for an inflammation site, an undesirable biological reaction in which inflammation and singlet oxygen work synergistically can be effectively suppressed. Preferable examples of such a biological reaction include a wrinkle forming reaction caused by light irradiation. The preferred content of the active oxygen scavenger and the active oxygen scavenging composition of the present invention is 0.001 to 10% by weight.
And more preferably 0.05 to 5% by weight.
This is because if the amount is too small, the effect may not be exhibited, and if the amount is too large, the effect reaches a peak.

(2) Composition for Eliminating Active Oxygen of the Present Invention The composition for erasing active oxygen of the present invention is characterized by containing the active oxygen scavenger of the present invention. Preferred examples of the composition for scavenging active oxygen of the present invention include skin external preparations such as foods, pharmaceuticals, and cosmetics. Among them, cosmetics can be exemplified as a suitable composition. This means that the dermal toxicity of the active oxygen scavenger of the present invention is extremely low,
This is because hydrogen peroxide appears on the skin in places such as inflammation and has an unfavorable effect on the skin, so that the effect of eliminating it in the skin is extremely large. Particularly, in the case of cosmetics, administration of such an active oxygen scavenger to an inflamed site is particularly preferable since it exerts an action of suppressing inflammation. Examples of such inflammation include sun burns, atopic dermatitis, chemical sensitivity, and the like.

The composition of the present invention may contain, in addition to the active oxygen scavenger of the present invention, optional components usually used in foods, medicines or cosmetics. As such optional components, in the case of foods and orally administered drugs, excipients, coating agents, binders, disintegrants, lubricants, bulking agents, coloring agents, stabilizers, emulsifiers, dispersants, and the like can be preferably exemplified. And topical skin medicines, hydrocarbons such as squalane, petrolatum, microcrystalline wax, jojoba oil, carnauba wax, esters such as octyldodecyl oleate, triglycerides such as olive oil, tallow, coconut oil, stearin Acid, oleic acid, fatty acids such as ritinoleic acid, oleyl alcohol, stearyl alcohol,
Higher alcohols such as octyldodecanol; anionic surfactants such as sulfosuccinates and sodium polyoxyethylene alkyl sulfate; amphoteric surfactants such as alkyl betaine salts; cationic surfactants such as dialkylammonium salts; sorbitan fatty acids Nonionic surfactants such as esters, fatty acid monoglycerides, their polyoxyethylene adducts, polyoxyethylene alkyl ethers, polyoxyethylene fatty acid esters, and polyhydric alcohols such as polyethylene glycol, glycerin, and 1,3-butanediol , A thickening / gelling agent, an antioxidant, an ultraviolet absorber, a coloring material, a preservative, a powder, and the like. Among these, particularly preferred are polyhydric alcohols in skin external preparations such as cosmetics and skin external pharmaceutical compositions. This is because the properties of the skin, whose barrier function has been impaired by inflammation, can be preferably maintained. The preferred content of these polyhydric alcohols is 0.5 to 10% by weight, more preferably 1 to 5% by weight, based on the total amount of the cosmetic. It is also very advantageous to include a conventionally known anti-inflammatory component in order to effectively suppress the inflammation that has already occurred. As such anti-inflammatory component, anti-inflammatory agents such as indomethacin, suprofen, ketoprofen, ketotifen and the like can be suitably exemplified in the case of crude drug components such as birch extract and burdock extract, and external medicines for skin. The preferred content of the components is 0.001 to 1% by weight,
A more preferred content is 0.01 to 0.1% by weight.
The external preparation for skin such as the cosmetic and the external medicine for skin of the present invention can be produced by treating such essential components and optional components according to a conventional method. As the dosage form of the external preparation for skin of the present invention, any of emulsions, creams, lotions, and gels can be applied.
(000-20,000 centistokes) An emulsified type of essence is particularly preferred because it is easy to administer locally. The skin external preparation for use in the presence of inflammation of the present invention thus obtained has an action of relieving inflammation caused by active oxygen generated in the body such as atopic dermatitis and chemical hypersensitivity. It has the effect of preventing, suppressing and improving the care of the underlying skin and the sedation of such inflammation. Further, it is possible to prevent wrinkles and loss of elasticity caused by inflammation caused by such active oxygen.
In addition, active oxygen and inflammation have a particularly favorable preventive effect on wrinkles caused by irradiation with light in which synergism is involved in their formation. A preferred optional component of the composition for oral administration is an enteric coating agent capable of maintaining the action time of the active oxygen scavenger of the present invention, and such a coating agent is an extract of lac shell shellworm. Zein which is an insoluble protein contained in grains such as shellac, wheat and corn is preferably exemplified. The preferred content of these is 20 to 50% by weight based on the total amount of the composition. Such a composition for oral administration can also be produced by treating an arbitrary component and an essential component according to a conventional method.

[0010]

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

Example 1 Singlet oxygen scavenging activity was investigated using kojic acid, an active oxygen scavenger of the present invention.
That is, hematoporphyrin (0.25 mM; 50 μl)
-With respect to singlet oxygen generated in an ultraviolet ray (30 seconds) system, kojic acid is added at a different dose, and the amount of superoxide thus erased is measured by an ESR spin trap method (trapping agent: 2, 2, 6, 6). -Tetramethyl-4-piperidone hydrochloride (TMPD)), and the IC50 value was calculated from a plot of the erased value and the dose. For comparison, arbutin, kojic acid, ascorbic acid glucoside and L-ascorbic acid were also examined for this effect. Table 1 shows the results. This indicates that kojic acid, which is the active oxygen scavenger of the present invention, is excellent in the action of scavenging singlet oxygen among the excellent active oxygen.

[Table 1]

Example 2 Five groups of hairless mice were used to examine the effect of ultraviolet rays on the formation of wrinkles in a wrinkle model. That is, a hairless mouse was prepared by adding 0.1 ml of a 50% aqueous ethanol solution containing 0.1% of the active oxygen scavenger of the present invention.
After coating and processing, the amount of ultraviolet light (B
(LB lamp; manufactured by Toshiba Corporation). This work
Performed 24 times at a rate of 5 times / week for 24 weeks, and the state of wrinkles on the skin was compared with the average level of the control group that was irradiated with ultraviolet rays and was not subjected to sample administration.
+: Clearly reduced wrinkles are recognized, ±: Somewhat less wrinkles are felt,-: Evaluated based on the same level of wrinkles. Table 2 shows the results. This indicates that the active oxygen scavenger of the present invention and the ultraviolet wrinkle model have an effect of preventing wrinkle formation.

[0013]

[Table 2]

Example 3 Effect on Inflammation Hartley white guinea pig (female, 300 to 350)
g) The back of 60 animals was shaved, and an irradiation site of 3 cm × 3 cm was provided. Was irradiated with ultraviolet light to cause inflammation. (M
24 hours after the irradiation) The skin reaction was evaluated 24 hours after irradiation by the criteria of Draize (++: reaction with edema, +: reaction with obvious erythema, ±: reaction with weak erythema,
−: No response), and 25 + animals having almost the same response level were selected. The selected animals were divided into two groups of 5 animals. One group received 0.05 ml of a 0.1% by weight 50% ethanol solution of kojic acid, and two groups received 0.05 ml of 50% ethanol. Was administered. Twenty-four hours after administration, the skin reaction was determined again based on the Draize standard.
The results are shown in Table 3 as the number of appearance cases. This indicates that the active oxygen scavenger of the present invention tends to suppress inflammation. Therefore, it can be seen that administration of the active oxygen scavenger of the present invention to an inflamed site does not worsen inflammation, and that administration to such an inflamed site is possible.

[0015]

[Table 3]

Example 4 A lotion was prepared according to the following formulation. That is, the ingredients were stirred and solubilized at room temperature to obtain a lotion. Using this lotion, one panel of three panelists suffering from wrinkles for a year was used twice a day for one month in the morning and evening to evaluate the effect of preventing and improving the wrinkles.
The evaluation criteria are rating 2: marked improvement, rating 1: obvious improvement, rating 0.5: slight improvement, rating 0: no improvement. The average score was 0.89. It was confirmed that the lotion containing the singlet oxygen scavenger of the present invention was effective in improving wrinkles. Kojic acid 0.1 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 83.7 parts by weight

Example 5 A lotion was prepared according to the following formulation. That is, the ingredients were stirred and solubilized at room temperature to obtain a lotion. Using this lotion, one panel of three panelists suffering from wrinkles for a year was used twice a day for one month in the morning and evening to evaluate the effect of preventing and improving the wrinkles.
The evaluation criteria are rating 2: marked improvement, rating 1: obvious improvement, rating 0.5: slight improvement, rating 0: no improvement. The average score was 0.77. It was confirmed that the lotion containing the singlet oxygen scavenger of the present invention was effective in improving wrinkles. Kojic acid 0.1 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 83.7 parts by weight

Example 6 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 atopic dermatitis. Kojic acid 0.1 part by weight Prednisolone 1 part by weight Vaseline 98.9 parts by weight

<Example 7> According to the following formula, a health food in the form of a sugar-coated tablet was prepared. That is, the part (a) was subjected to fluidized-bed granulation and then tableted to give an uncoated tablet. This was coated with enteric coating (b) and sugar-coated with the component (c) to prepare a food. I Hydroxypropylcellulose 10 parts by weight Kojic acid 1 part by weight Chorei extract 1 part by weight Royal jelly 1 part by weight Lactose 37 parts by weight Shellac 20 parts by weight Ethanol 1980 parts by weight C sucrose 25 parts by weight Gelatin 5 parts by weight

Example 8 According to the following formulation, a health food in the form of a sugar-coated tablet was prepared. That is, the part (a) was subjected to fluidized-bed granulation and then tableted to give an uncoated tablet. This was coated with enteric coating (b) and sugar-coated with the component (c) to prepare a food. I Hydroxypropylcellulose 10 parts by weight Kojic acid 1 part by weight Chorei extract 1 part by weight Royal jelly 1 part by weight Lactose 37 parts by weight Shellac 20 parts by weight Ethanol 1980 parts by weight C sucrose 25 parts by weight Gelatin 5 parts by weight

[0021]

According to the present invention, an active oxygen scavenger excellent in active oxygen scavenging ability, particularly an active oxygen scavenging ability for singlet oxygen, and a composition containing the active oxygen scavenger, such as cosmetics, food or medicine, are provided. Can be provided.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 17/02 A61P 17/02 17/16 17/16 39/06 39/06 // C07D 309/40 C07D 309/40 F term (reference) 4B018 LE01 MD08 ME06 4C062 DD08 DD13 4C083 AC012 AC102 AC122 AC302 AC482 AC841 AC842 AD592 CC02 CC04 DD23 EE10 EE12 EE13 EE17 4C086 BA07 MA01 MA04 MA63 NA14 ZA89 ZB11 ZC80

Claims (8)

[Claims] An active oxygen scavenger comprising kojic acid and / or a physiologically acceptable salt thereof. 2. The active oxygen scavenger according to claim 1, wherein the active oxygen is singlet oxygen. 3. A composition for scavenging active oxygen, comprising the active oxygen scavenger according to claim 1 or 2. 4. The composition for scavenging active oxygen according to claim 3, which is a cosmetic. 5. The composition for scavenging active oxygen according to claim 4, wherein the composition is used for an inflammatory site. 6. The composition for erasing active oxygen according to claim 4, wherein the composition is used for forming wrinkles derived from light. 7. A composition containing kojic acid and / or a salt thereof.
Cosmetic for wrinkles derived from light. 8. The cosmetic according to claim 7, which is used for an inflammatory site.