JP2006213660A - Singlet oxygen eliminating agent, and external preparation for skin using the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new agent having a singlet oxygen-eliminating ability, and to provide an external preparation for skin. <P>SOLUTION: This singlet oxygen eliminating agent comprises coenzyme Q<SB>10</SB>, and the external preparation for skin contains the same as an active ingredient. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a novel singlet oxygen scavenger and a skin external preparation containing the same as an active ingredient.

  Conventionally, as active oxygen species in a broad sense, superoxide, hydroxy radicals, hydrogen peroxide and singlet oxygen, and reaction products of these metals and lipids are known. However, some reactive oxygen species have different numbers of electrons from, for example, ground state oxygen, such as superoxide, hydrogen peroxide, and hydroxy radicals. However, there are also singlet oxygens that are excited molecular species that are in an excited state, and each has unique characteristics that cannot be captured by the framework of reactive oxygen species based on the difference in the electronic state. Conventionally, electron spin resonance (ESR) has been widely used to detect reactive oxygen species (for example, Patent Document 1). ESR is effective for detecting radical species such as superoxide and hydroxy radical, but cannot detect singlet oxygen that is not a radical species. In addition, the lifetime of singlet oxygen in water is as short as about 4 μsec, and detection methods having both sensitivity and specificity are limited (for example, Patent Document 2). Therefore, in the past, those that have been reported as reactions involving active oxygen species in a broad sense and those that have been reported as effective agents for capturing active oxygen species are considered singlet when their detection methods are examined. Most of the oxygen is not clear.

  In recent years, the reactivity of each reactive oxygen species has been studied, and it has been found that each of the reactive oxygen species exhibits a specific reactivity. For example, superoxide and hydroxy radicals react with proteins and easily cause their fragmentation. On the other hand, singlet oxygen has a unique reactivity that is completely different from superoxide or the like, in which a protein is cross-linked and polymerized (for example, Non-Patent Document 1). It has also been clarified that singlet oxygen is generated on the surface of healthy skin by irradiation with ultraviolet rays and causes peroxidation of sebum that causes various skin troubles (for example, Non-Patent Document 2). ). Against this background, the contribution of singlet oxygen has been regarded as important for diseases and aging that have been said to involve active oxygen species. Therefore, if there is an agent capable of eliminating singlet oxygen, it is effective in preventing these diseases and aging. In addition, conventionally known singlet oxygen scavengers are often deteriorated during storage over time due to the poor chemical stability of the substance itself, and the singlet oxygen scavenging ability is often reduced. Improvement is desired in terms of sustainability.

On the other hand, it has been proposed that cosmetics containing a coenzyme Q _10, the inside, coenzyme Q ₁₀ has been disclosed to exhibit antioxidant action (for example, Patent Documents 3 and 4). However, there is no description about the relationship with singlet oxygen.

Japanese Patent Laid-Open No. 2001-10954 (page 5, Example 9) JP 7-159325 A JP-A-6-199687 JP 2004-107262 A J. et al. Soc. Cosmet. Chem. Japan. Vol. 28, no. 2 1994, p. 163-171. Journal of the Japan Cosmetic Science Society vol. 19 No. 1 1995, p. 1-6.

  An object of the present invention is to provide an agent that maintains good singlet oxygen scavenging ability for a long period of time. Another object of the present invention is to provide a singlet oxygen scavenger and a composition capable of suppressing various reactions caused by singlet oxygen. In addition, the present invention can be applied to the skin to prevent singlet oxygen extinction, which can prevent skin aging, skin blackening, skin damage, and the like caused by a reaction involving singlet oxygen. It is an object to provide a preparation and an external preparation for skin.

The present invention for solving the above problems, to provide a singlet oxygen quencher made of coenzyme Q _10. As one embodiment of the present invention, there is provided the above singlet oxygen scavenger having a singlet oxygen scavenging constant of 1.0 × 10 ⁷ M ⁻¹ s ⁻¹ or more. The singlet oxygen scavenger of the present invention or an external preparation for skin containing the same as an active ingredient can be used to suppress various reactions involving singlet oxygen, collagen crosslink formation inhibitor, immediate blackening It can be used as an inhibitor, an enzyme deactivation inhibitor, a lipid peroxidation inhibitor, a cell aging inhibitor or a dye fading inhibitor.

From another point of view, according to the present invention, by applying to the skin a skin external preparation containing the singlet oxygen scavenger as an active ingredient; the singlet oxygen scavenger or a composition containing the singlet oxygen scavenger as an active ingredient. , A method of suppressing any of collagen cross-linking formation, immediate blackening, enzyme deactivation, lipid peroxidation, cell aging and pigment fading; applying the above singlet oxygen scavenger or a composition containing this as an active ingredient to the skin by a method for preventing skin aging; method of preparing the external preparation for skin comprising the step of adding a coenzyme Q _10; is provided.

  ADVANTAGE OF THE INVENTION According to this invention, the singlet oxygen scavenger which maintains a favorable singlet oxygen scavenging ability for a long term can be provided. In addition, according to the present invention, it is possible to provide a singlet oxygen scavenger and a composition that can suppress various reactions caused by singlet oxygen. In addition, according to the present invention, singlet that can prevent skin aging, skin blackening, skin damage, and the like caused by a reaction involving singlet oxygen due to application to the skin. Oxygen scavengers and compositions can be provided.

Hereinafter, the present invention will be described in detail.
The present invention relates to a singlet oxygen quencher made of coenzyme Q _10. Coenzyme Q ₁₀ used in the invention, the number of isoprenoid side chain of ubiquinone is a compound of 10, also known as ubiquinone 10, also called Yubidekanoren and coenzyme Q _10. In the present invention, a product extracted from a natural product or a synthetic product may be used.

The singlet oxygen scavenger of the present invention preferably has a singlet oxygen scavenging constant of 1.0 × 10 ⁷ M ⁻¹ s ⁻¹ or more, and 1.0 × 10 ⁸ M ⁻¹ s ⁻¹ or more. Is more preferable. In the present specification, the “singlet oxygen elimination constant” refers to a reaction rate constant (kq) of the Stern-Volmer formula (Io / I = 1 + kq · τ · Cq). Specifically, a singlet oxygen scavenger is added at various concentrations (Cq) to a system in which singlet oxygen is arbitrarily generated and light emission associated with the transition of singlet oxygen is observed. I) is measured, and the ratio (Io) / (I) to the emission intensity (Io) when not added is calculated and plotted against the respective concentrations (Cq), whereby the Stern-Volmer equation is calculated. It can be calculated from In the above formula, τ is the lifetime of singlet oxygen and is a constant that varies depending on the solvent of the system. The concentration Cq is the concentration of metal, and the unit is mol / L. As the experimental system and the luminescence detection device used for calculating the singlet oxygen elimination constant, those described in Japanese Patent No. 3356517 can be used.

  The singlet oxygen scavenger of the present invention can be used for applications that suppress reactions caused or promoted by the presence of singlet oxygen. For example, singlet oxygen is known to crosslink collagen, which is a constituent component of the dermis (J. Soc. Cosmet. Chem. Japan. Vol. 28, No. 2 1994, p. 163-171). Collagen crosslinking reduces skin elasticity and flexibility and contributes to skin aging. By applying the singlet oxygen scavenger of the present invention to the skin, it is possible to suppress the formation of collagen crosslinks, prevent skin aging, and maintain youthful skin. That is, the singlet oxygen scavenger of the present invention can be used as a collagen crosslinking inhibitor.

In addition, for example, singlet oxygen is frequently generated on the skin surface by UV-A irradiation, is involved in the immediate darkening that occurs non-enzymatically due to oxidation of dopa, and is involved in peroxidation of skin surface lipids. (Journal of Japan Fragrance Science Vol.19 No.1 1995, p.1-6). Therefore, by applying the singlet oxygen scavenger of the present invention to the skin, it can be used as an inhibitor that suppresses immediate darkening of the skin and peroxidation of the skin surface lipid. When the singlet oxygen scavenger of the present invention is used as an immediate blackening inhibitor, the singlet oxygen scavenger constant of the singlet oxygen scavenger is larger than dopa, that is, 6.8 × 10 ⁸ M ^−1. More preferably, it is s ⁻¹ or more. In addition, for example, singlet oxygen is known to cause or promote inactivation of many enzymes responsible for in vivo reactions. Therefore, the singlet oxygen scavenger of the present invention can be used as an enzyme deactivation inhibitor. In the case where the singlet oxygen scavenger of the present invention is used as an enzyme deactivation inhibitor, the singlet oxygen scavenging constant of the singlet oxygen scavenger is more preferably larger than the singlet oxygen scavenging constant of the enzyme. preferable.

  We have also reported that singlet oxygen is involved in cell senescence using a cell aging evaluation system to capture aging phenomena in living bodies (J. Jpn. Cosmet. Sci. Soc. Vol. 26, 2002, p. 79-85). In other words, when cells were exposed to singlet oxygen, a characteristic aging phenomenon was observed that shortened cell life. This phenomenon was suppressed by applying histidine, which is a singlet oxygen scavenger, to the cells. That is, it is suggested that the singlet oxygen scavenger has an effect of suppressing cell aging and consequently delaying aging of a living body. That is, the singlet oxygen scavenger of the present invention can be used as a cell aging inhibitor.

  In addition, singlet oxygen is known to cause or promote fading or discoloration of pigments such as plant extracts blended in cosmetics and foods. Even when there is no fading or discoloration, the presence of singlet oxygen may cause or accelerate the decomposition of a medicinal agent blended in a skin external preparation or the like. When the singlet oxygen scavenger of the present invention is blended, not only the singlet oxygen scavenging ability and the above-mentioned effects accompanying it can be obtained, but also the effect of suppressing the decomposition of other agents blended together can be obtained. That is, the singlet oxygen scavenger of the present invention can be used as an anti-fading agent, and can also be used as a preservative for other medicinal agents as well as fading.

  The composition containing the singlet oxygen scavenger of the present invention as an active ingredient can be used for various purposes such as pharmaceuticals, quasi drugs, cosmetics and foods. Since singlet oxygen is always present on the skin surface that is always in contact with oxygen and exposed to ultraviolet rays, the composition containing the singlet oxygen scavenger of the present invention is more useful as an external preparation for skin. In addition, since the reaction suppressed by the elimination of singlet oxygen is a reaction that contributes to skin aging, skin blackening, and skin damage, the singlet oxygen elimination of the present invention that can suppress such reaction. The agent and the composition containing this as an active ingredient are particularly useful as a skin cosmetic for the purpose of preventing skin aging, whitening and skin.

A skin external preparation can be prepared by blending the singlet oxygen scavenger of the present invention alone or with one or more known external pharmaceutical additives or skin cosmetic additives according to a conventional method. . The amount of singlet oxygen quencher of the present invention, the dosage form of external preparations, other such purpose, varies depending singlet oxygen scavenging ability of singlet oxygen quencher, in general, the coenzyme Q ₁₀ The concentration in the final composition is preferably 1 μmol / L to 5 mmol / L, more preferably 10 μmol / L to 1 mmol / L. Within this range, it is possible to stably blended coenzyme Q _10, can exhibit superior efficacy.

  The singlet oxygen scavenger 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. 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 extract, plant extract, blood circulation promoter, astringent, anti-seborrheic agent, whitening agent, anti-inflammatory agent, active oxygen scavenger other than the singlet oxygen scavenger of the present invention, cell activator, moisturizer , 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 milky lotion, cream, lotion, cosmetic liquid, pack, face wash, makeup cosmetics; shampoo, hair treatment, hair styling agent, 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]
The singlet oxygen elimination constant of Coenzyme Q ₁₀ (manufactured by Sigma) was calculated by the method described above using the Stern-Volmer equation (Io / I = 1 + kq · τ · Cq). As the singlet oxygen detection device, the device described in Japanese Patent No. 3356517 (details are described in column 0026 of the same publication) was used. A 200 μM aqueous solution of Rose Bengal was circulated in the flow cell at a rate of 20 mL / min. When this cell was irradiated with a laser having a wavelength of 514.5 nm, which is an absorption wavelength of rose bengal, light emission accompanying the transition of singlet oxygen was observed, and the emission peak was 1268 nm. Then, a solution of coenzyme Q ₁₀ at various concentrations, respectively (solution solvent at a range of concentrations 100~1000μmol / L of ethanol of coenzyme Q _10), each measured emission intensity (I), additive-free The intensity ratio (Io) / (I) with the hourly emission intensity (I ₀ ) was calculated and plotted against the respective concentrations (Cq: concentration of coenzyme Q ₁₀ ). A singlet oxygen elimination constant (kq) was calculated from the Stern-Volmer equation. The results are shown below.
Singlet oxygen erasing constant of coenzyme ^{_{Q 10: 1.52 × 10 8 M}} -1 s -1

Conventionally, singlet oxygen scavenging constants were similarly calculated for various compounds known as reactive oxygen species scavengers or singlet oxygen scavengers. Ascorbic acid was found to be 8.3 × 10 ⁶ M ⁻¹ s ⁻¹ , Hipotaurine was 1 × 10 ⁶ M ⁻¹ s ⁻¹ , and mannitol was 1 × 10 ⁴ M ⁻¹ s ⁻¹ . From this result, coenzyme Q _10, as compared to compounds known as conventional active oxygen species scavenger or singlet oxygen quencher, it is demonstrated that show comparable or more excellent singlet oxygen scavenging ability It was.

[Example 2: lotion]
The following components (3), (4), and (8) to (10) were mixed and dissolved, and the following components (1), (2), (5) to (7), and (11) were mixed and dissolved. The solution was mixed and uniformed to obtain a skin lotion.
(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) Coenzyme Q ₁₀ * 1 0.05
(6) Lactic acid 0.05
(7) Sodium lactate 0.1
(8) Paramethoxycinnamic acid-2-ethylhexyl 3.0
(9) Preservative appropriate amount (10) Fragrance appropriate amount (11) Purified water remaining amount * 1: Sigma

[Example 3: Latex]
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) Coenzyme Q ₁₀ * 1 0.1
(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) Fragrance appropriate amount * 1: Sigma

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

  The singlet oxygen scavenger of the present invention or the external preparation for skin containing the same as an active ingredient has a singlet oxygen scavenging ability, and therefore, reactions involving singlet oxygen, particularly skin aging involving singlet oxygen. It is useful for suppressing various reactions that contribute to immediate blackening and skin damage.

Claims (4)

Singlet oxygen quencher made of coenzyme Q _10. 2. The singlet oxygen scavenger according to claim 1, wherein the singlet oxygen scavenging constant is 1.0 × 10 ⁷ M ⁻¹ s ⁻¹ or more. 3. The singlet oxygen scavenger used as a collagen crosslinking formation inhibitor, an immediate blackening inhibitor, an enzyme deactivation inhibitor, a lipid peroxidation inhibitor, a cell aging inhibitor or a pigment fading inhibitor. A skin external preparation containing the singlet oxygen scavenger according to any one of claims 1 to 3 as an active ingredient.