JP4300105B2 - Antioxidant - Google Patents

Description

  The present invention relates to an antioxidant containing a colloidal solution of a binary metal cluster, and a composition containing the antioxidant as an active ingredient.

  In order to protect the skin from damage caused by reactive oxygen species such as superoxide, hydroxy radical, hydrogen peroxide and singlet oxygen, many antioxidants have been developed and incorporated in skin external preparations and cosmetics. However, most antioxidants have the disadvantage of being auto-oxidized and altered. Therefore, it is desired to develop an antioxidant that has sufficient antioxidant ability and has no problems such as coloring, discoloration, and precipitation.

  A metal colloid liquid is used as an anti-oxidant agent that is difficult to change in skin external preparations. For example, a colloidal solution of platinum has a high singlet oxygen scavenging ability, and the inventors of the present invention described in Japanese Patent Application No. 2003-298188 as an agent for maintaining good singlet oxygen scavenging ability for a long period of time. A singlet oxygen scavenger comprising a colloidal liquid is provided. However, in general, it is difficult to prepare a colloidal liquid of metal with good dispersibility, and precipitation may occur.

  An object of the present invention is to provide an antioxidant with little alteration and good dispersibility.

  As a result of intensive studies to solve the above problems, the present inventors have found that the dispersibility of the metal is improved by combining the platinum group metal and gold. The present invention has been completed based on this finding.

  That is, the present invention provides an antioxidant containing a binary metal cluster containing a platinum group metal and gold, and an antioxidant containing a colloidal solution of a binary metal cluster containing a platinum group metal and gold. According to a preferred embodiment of the present invention, the above-mentioned antioxidant in which the gold is the core and the platinum group metal is the shell in the binary metal cluster; the core metal relative to the total moles (100%) of the platinum group metal and gold. There is provided the above-mentioned antioxidant having a mol% of 5% or more and 75% or less; the above-mentioned antioxidant in which the platinum group metal is platinum; and any one of the above-mentioned antioxidants used as a skin external preparation.

From another viewpoint, a composition containing any of the above antioxidants as an active ingredient is provided. From another viewpoint, the above-mentioned composition that is an external preparation for skin is provided.
From another aspect, a method of using a colloidal solution of a binary metal cluster containing a platinum group metal and gold as an antioxidant; a method of using the antioxidant as a skin external preparation; a platinum group for producing an antioxidant Use of a colloidal solution of a binary metal cluster containing metal and gold; Use of a colloidal solution of a binary metal cluster containing a platinum group metal and gold for the manufacture of a skin external preparation is provided.

The antioxidant of the present invention comprises a bimetallic cluster comprising a platinum group metal and gold. The platinum group metal is a generic name for transition metals composed of ruthenium, osmium, rhodium, iridium, palladium, and platinum. Any of these may be used as the platinum group metal used in the antioxidant of the present invention, but it is preferable to use platinum.
In the present specification, the “binary metal cluster” refers to particles in which a kind of metal serves as a core and another metal forms a shell around it. The core may be a platinum group metal or gold, but gold is preferably the core and the platinum group metal is a shell.

  The colloidal solution of a binary metal cluster means a state in which the above-mentioned binary metal cluster is dispersed in a liquid phase. It may be a colloidal liquid of a kind of binary metal cluster or a colloidal liquid containing two or more kinds of binary metal clusters. Among these, a colloidal liquid of a single binary metal cluster is preferable, and a colloidal liquid of a binary metal cluster in which gold is a core and a platinum group metal is a shell is preferable.

  In order to obtain a stable colloidal state, the binary metal cluster is preferably one having a large specific surface area and excellent surface reactivity. The particle size of the binary metal cluster is not particularly limited, but is preferably 50 nm or less, more preferably 20 nm or less, still more preferably 10 nm or less, and particularly preferably about 1 to 6 nm. The average particle size of the colloidal particles can be determined by observing with a transmission electron microscope.

  The main component of the liquid phase in which the binary metal cluster is dispersed is preferably water. An organic solvent may be contained as long as the colloidal state is not destabilized. Examples of the organic solvent include alcohols such as methanol and ethyl alcohol; polyhydric alcohols such as glycerin, diglycerin, 1,3-butylene glycol and dipropylene glycol.

Various methods for producing binary metal clusters are known. For example, there is a method of producing by simultaneous reduction of two kinds of metals using an ethanol reduction method, but there are cases where sodium hydroxide is added to promote the reduction reaction. . Further, NaBH ₄ may be used as a reducing agent. (Reference: New J. Chem., 22, 1179-1201, 1998 Naoki Toshima and Tetsu Yonezawa) When such a method is used, a metal that is easier to reduce forms a core, so platinum and gold are used. , Gold is reduced first to form the core. In order to form a “reverse core / shell” in which gold becomes a shell, for example, a sacrificial hydrogen reduction method (Eur. Phys. JD, 16: 209-212, 2001) may be used.

  The molar ratio of the platinum group metal to gold is not particularly limited, but the molar ratio of the core metal is preferably 5% to 75% with respect to the total mole (100%) of the platinum group metal and gold.

  It is preferable to use a protective agent to produce a stable binary metal cluster. Although the kind of protective agent is not particularly limited, for example, polyvinylpyrrolidone (PVP) or polyacrylic acid (PAA) is preferable, and poly (1-vinyl-2-pyrrolidone) is particularly preferable. The concentration ratio of platinum group metal and gold as a unit chemical formula amount is preferably metal: protectant = 1: 40 to 1: 200. It is also possible to use various surfactants (for example, surfactants such as anionic, cationic, amphoteric, nonionic, or fat-soluble). When the reduction is performed using alcohol, ethyl alcohol, n-propyl alcohol, n-butyl alcohol, n-amyl alcohol, ethylene glycol, or the like is used. These protective agents and surfactants contribute to stabilization of the colloidal state as protective colloid agents after the formation of a binary metal cluster in the liquid phase. However, the method for preparing the binary metal cluster is not limited to the method described above.

  You may use the binary metal cluster produced | generated in the liquid phase for the preparation of the antioxidant of this invention, without isolate | separating from a liquid phase as it is. For example, if desired, after passing through an appropriate purification step (for example, a step of distilling off the organic solvent used in the metal salt reduction reaction step under reduced pressure), an arbitrary amount of water is added, or an arbitrary amount By removing an amount of water, an antioxidant composed of a stable colloidal solution can be prepared. If desired, a surfactant, a dispersing agent or the like that contributes to stabilization of the colloidal state may be added. Of course, the method for preparing the antioxidant of the present invention is not limited to this. For example, the produced binary metal cluster is once separated from the liquid phase and then dispersed again in the liquid phase containing water as a main component. You can also

  The concentration of the binary metal cluster in the colloidal liquid as the mother liquor used for the preparation of the final product is not particularly limited as long as it does not impair the stability of the colloidal state. In general, the stability is maintained if it is about 1 nmol / L to 1 mmol / L, but the stability of the colloidal state is different for each metal and is not limited to this range. A preferable range of the concentration of the binary metal cluster in the composition as the final product will be described later.

The antioxidant of the present invention or the composition containing the antioxidant of the present invention and one or more additives is used for various purposes such as pharmaceuticals, quasi-drugs, cosmetics, and foods. be able to.
Active oxygen is abundant on the skin surface that is constantly in contact with oxygen and exposed to ultraviolet light. Moreover, since sebum and a photosensitizer are present in the skin, oxidative damage due to active oxygen is likely to occur. In addition, there are reports that damage due to active oxygen accumulates even in dermal components such as collagen and elastin, which are closely related to skin aging. The antioxidant of the present invention and the composition containing the antioxidant as an active ingredient are more useful as an external preparation for skin because they can suppress the damage and injury caused by active oxygen in the skin as described above. Can be used for prevention, whitening and skin beautification.

  The antioxidant of the present invention can be used alone as a skin external preparation, or a skin external preparation can be prepared by mixing with one or more additives. The amount of the antioxidant of the present invention varies depending on the dosage form of the external preparation, the purpose of use, etc., as well as the antioxidant ability of the antioxidant, but in general, the concentration of the bimetallic cluster is the final composition. The content is preferably 0.01 nmol / L to 50 μmol / L, more preferably 1 nmol / L to 1 μmol / L. Within this range, the colloidal solution can be blended stably and can exhibit excellent medicinal effects.

  Additives added as necessary include water (purified water, hot spring water, deep water, etc.), alcohols, oils, surfactants, metals commonly used in skin cosmetics and pharmaceutical preparations for external use. Soap, gelling agent, powder, alcohol, water-soluble polymer, film-forming agent, resin, UV protection agent, inclusion compound, antibacterial agent, fragrance, deodorant, salt, pH adjuster, refresher, animal Microorganism-derived extracts, plant extracts, blood circulation promoters, astringents, antiseborrheic agents, whitening agents, anti-inflammatory agents, antioxidants other than the antioxidants of the present invention, cell activators, humectants, chelating agents , Keratolytic agents, enzymes, hormones, vitamins and the like. The external preparation for skin can be prepared according to a conventional method, and the blending amount of the additive can also be determined according to a conventional method as long as the effects of the present invention are not impaired.

  The form of the external preparation for skin is not limited, and forms belonging to skin cosmetics such as emulsions, creams, skin lotions, cosmetic liquids, packs, face wash, makeup cosmetics, shampoos, hair treatments, hair styling agents, It may be in any form relating to hair cosmetics such as hair nourishing agents and hair restorers; and forms of external pharmaceuticals such as dispersions, ointments, aerosols, patches, poultices, liniments and the like.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further more concretely, the scope of the present invention is not limited to the following Example.

[Example 1] Production example (example of 50% metal (gold) as a core)
Poly (1-vinyl-2-pyrrolidone) (K30, manufactured by Wako Pure Chemical Industries, Ltd., 0.147 g) was placed in a 100 mL two-necked eggplant type flask connected with an aryl condenser and a three-way cock, and dissolved in 23 mL of distilled water. After stirring this solution for 10 minutes, a 1.66 × 10 ⁻² M solution (1 mL) of tetrachloroauric acid tetrahydrate (H ₂ AuCl ₆ .4H ₂ O, manufactured by Wako Pure Chemical Industries, Ltd.) dissolved in distilled water. ) And hexachloroplatinic acid hexahydrate (H ₂ PtCl ₆ · 6H ₂ O, manufactured by Wako Pure Chemical Industries, Ltd.) in distilled water were added and a 1.66 × 10 ⁻² M solution (1 mL) was added, and the mixture was further stirred for 30 minutes. did. The reaction system was purged with nitrogen, and 25 mL of special grade ethanol was added and refluxed at 100 ° C. (temperature raising time 20 minutes) for 2 hours (including the temperature raising time) while maintaining a nitrogen atmosphere. It was confirmed that the color of the solution changed from pale yellow to colorless, red, and dark brown, and the reaction solution was air-cooled to near room temperature. The organic solvent was distilled off under reduced pressure while maintaining the temperature at 30 ° C. or lower. Thereafter, 33 ml of distilled water was added and dispersed and dispersed to obtain a dark brown and transparent colloidal solution (R = 40, 1 mM).

[Example 2] Evaluation of antioxidant ability and colloidal dispersibility Antioxidant ability was evaluated by the rate at which the maximum absorption at 1,517 nm of 1,1-Diphenyl-2-picrylhydrazyl (DPPH) having a stable radical decreased when the sample was added. . The colloidal dispersibility was evaluated by “no precipitation (◯)” and “precipitation (×)” after standing overnight.
As a sample solution using platinum as a platinum group metal, a 5 mmol / L acetic acid buffer solution having a concentration of 2 μmol / L (metal concentration of gold and platinum combined) was prepared. The mixing ratio (mol) of platinum in gold and platinum is shown in Table 2. After adding 1 mL of the sample solution to 0.5 mL of 0.5 mmol / L DPPH solution and 1 mL of ethanol and reacting at room temperature for 20 minutes, the absorbance at 517 nm was measured (Abs (S)). Absorbance was measured in the same manner using 0.5 mL of DPPH solution, 1 mL of ethanol and 1 mL of acetate buffer as control solutions (Abs (C)).

(Formula 1)
Radical scavenging rate = [Abs (C) −Abs (S)] / Abs (C) × 100

The radical scavenging rate is represented by a value from 0 to 100, but the antioxidant ability was determined according to the following evaluation criteria.

結果を表2に示す。

The results are shown in Table 2.

以上の結果から、本発明の抗酸化剤は分散性および抗酸化能が共に良好であることがわかる。

From the above results, it can be seen that the antioxidant of the present invention has both good dispersibility and antioxidant ability.

[Example 3] Preparation of lotion A solution in which the following components (3), (4), and (8) to (10) are mixed and dissolved, and the following components (1), (2), (5) to (7) And the solution which mixed and dissolved (11) was mixed and it was made uniform, and the lotion was obtained.
(Ingredient) (%)
(1) Glycerin 5.0
(2) 1,3-butylene glycol 6.5
(3) Polyoxyethylene (20E.O.) sorbitan 1.2
Monolaurate (4) Ethyl alcohol 8.0
(5) Gold (core) / platinum colloid solution [gold: platinum = 1: 1, platinum concentration 100 nmol / L,
R = 40, protective agent: poly (1-vinyl-2-pyrrolidone)] 10.0
(6) Lactic acid 0.05
(7) Sodium lactate 0.1
(8) Paramethoxycinnamic acid-2-ethylhexyl 3.0
(9) Preservative appropriate amount (10) perfume appropriate amount (11) remaining amount of purified water

[Example 4] Preparation of emulsion The following components (8) to (9) were added to the component (12) and swollen, then the component (10) was added, mixed, heated and maintained at 70 ° C to prepare an aqueous phase. The following components (1) to (6) were heated and mixed at 70 ° C. and added to the aqueous phase to emulsify. The emulsion was cooled to room temperature, the following components (7), (11) and (13) were added and mixed uniformly to obtain an emulsion.
(Ingredient) (%)
(1) Polyoxyethylene (10E.O.) sorbitan 1.0
Monostearate (2) Polyoxyethylene (60EO) Sorbit 0.5
Tetraoleate (3) Glyceryl monostearate 1.0
(4) Stearic acid 0.5
(5) Behenyl alcohol 0.5
(6) Squalane 8.0
(7) Gold (core) / platinum colloid solution [gold: platinum = 1: 9, platinum concentration 1 μmol / L
R = 40, protective agent: poly (1-vinyl-2-pyrrolidone)] 5.0
(8) Preservative 0.1
(9) Carboxyvinyl polymer 0.1
(10) Sodium hydroxide 0.05
(11) Ethyl alcohol 5.0
(12) Purified water remaining amount (13) Perfume appropriate amount

  The prepared lotion and milky lot were free from discoloration / odor change and precipitates and were stable and applicable to the skin.

  According to the present invention, an antioxidant with little alteration and good dispersibility is provided. The antioxidant is useful as an active ingredient such as a skin external preparation.

Claims (4)

An antioxidant containing a colloidal solution of binary metal clusters with gold as the core and platinum as the shell. The antioxidant of Claim 1 which shows radical scavenging ability. 3. The antioxidant according to claim 1, wherein a mole percentage of gold is 5% or more and 75% or less with respect to a total mole (100%) of platinum and gold. The skin external preparation containing the antioxidant of any one of Claims 1-3.