JPH05320036A - Composition for eliminating singlet oxygen - Google Patents

Abstract

PURPOSE:To provide a composition capable of suppressing the peroxidation reaction of lipid, etc., on the skin caused by singlet oxygen. CONSTITUTION:This singlet oxygen-eliminating composition having the above effects can be produced by compounding a singlet oxygen-eliminating agent such as carotenoid (e.g. alpha-, beta- or gamma-carotene, lycopene, cryptoxanthin, lutein, zeaxanthin, isozeaxanthin, rhodoxanthin, capsanthin and crosetin), 1,4 diazacyclooctane, 2,5-dimethylfuran, 2-methylfuran, 2,5-diphenylfuran, 1,3- diphenylbenzofuran, alpha-, beta-, gamma- or gamma-tocopherol, histidine, tryptophan, methionine, alanine or its alkyl ester as an essential component. The above reactions caused by an excessive amount of active oxygen on the skin can be suppressed by using the above composition in combination with a chain transfer-inhibiting antioxidant such as dibutylhydroxytoluene, dibutylhydroxyanisole or gallic acid ester.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a singlet oxygen scavenging composition, and more particularly to a substance having a singlet oxygen scavenging action generated in the skin and consequently suppressing the peroxidation reaction of skin components. A composition comprising.

[0002]

2. Description of the Related Art There have been many references to the existence of so-called active oxygen in the skin and proposals for a composition for removing the active oxygen (for example, JP-A-4-69343). However, as the reactive oxygen species, superoxide dismutase (SOD) and SO for superoxide, OH radical, radical generated from hydroperoxide, etc. are targeted.
Most of the substances are D-like substances or chain-breaking substances, and no substance for singlet oxygen has been proposed.

On the other hand, singlet oxygen is a type of active oxygen that is activated by ground-state triplet oxygen (normal oxygen in the air) and is highly reactive. The reaction produces hydroperoxide or the like, for example, lipid peroxide. (Tetsuo Niki: Special issue: Basic and clinical studies on free radicals, Japanese clinical practice, 46, No. 10, 15 (2125) ~ 19
(2129), 1988). However, since it is not a chain reaction, it was previously thought that singlet oxygen contributes little to oxygen damage in vivo. For example, when it comes to the relationship between the skin and singlet oxygen, it has long been said that porphyria is involved, but for healthy general skin, there is no academic mention of this involvement. I didn't. However, the present inventors have found that singlet oxygen is actually generated in healthy human skin, and that this singlet oxygen promotes the peroxidation reaction of skin components, and it has been proposed so far. It was noted that the active oxygen removing composition is not sufficient to remove all active oxygen including singlet oxygen, and is not always satisfactory as a composition for external use on the skin.

Therefore, the present invention provides a composition capable of suppressing the peroxidation reaction of lipids and the like on the skin caused by singlet oxygen by containing a singlet oxygen scavenging agent, and a chain It is an object of the present invention to provide a composition capable of suppressing the peroxidation reaction of lipids and the like caused by a larger amount of active oxygen on the skin by using a cleaving antioxidant together.

[0005]

The first aspect of the present invention is a singlet oxygen scavenging composition containing a singlet oxygen scavenger. The second of the present invention is a singlet oxygen scavenger,
A singlet oxygen scavenging composition comprising a chain-breaking antioxidant.

In the present invention, the singlet oxygen scavenger means
What reacts with singlet oxygen to lose its energy,
Alternatively, it refers to a substance that produces an adduct with singlet oxygen and consequently loses its energy, or a substance that has both of these actions.

As a singlet oxygen scavenger, α-carotene,
β-carotene, γ-carotene, lycopene, cryptoxanthin, lutein, zeaxanthin, isozeaxanthin,
Carotenoids such as rhodoxanthin, capsanthin, and crocetin, 1,4-diazadicyclooctane, 2,5-dimethylfuran, 2-methylfuran, 2,5-diphenylfuran, 1,3-diphenylisobenzofuran, α-tocopherol, Examples include β-tocopherol, γ-tocopherol, δ-tocopherol, histidine, tryptophan, methionine or alanine. That these compounds are good singlet oxygen scavengers include, for example:
Kunio Yagi, Minoru Nakano, supervised by Oxygen, Tokyo, Ito Denryaku Publishing Co., Ltd. (1987). The compounding amount of the singlet oxygen scavenger is preferably 0.005 to 1% by weight.

Next, as chain-breaking antioxidants, dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), gallic acid esters, ascorbic acid, tannic acid, epicatechin, epigallocatechin, epicatechin gallate , Tannins such as epigallocatechin gart, and flavonoids such as rutin.
The fact that these compounds are highly effective chain-breaking antioxidants is described in, for example, Japan Oil Chemistry Association: Oil Chemistry Handbook, Maruzen Co., Ltd. (1990). The amount of the chain-breaking antioxidant to be blended is preferably 0.005 to 1% by weight.

The compositions of the invention are particularly suitable for external skin application. As other additives to be added to such a composition, the components contained in ordinary skin external preparations can be added. For example, oils, surfactants, thickeners, neutralizers, preservatives, powder components, dyes, sequestering agents, fragrances, ultraviolet absorbers, medicinal agents, etc. Used.

[0010]

The effect of singlet oxygen on healthy human skin was confirmed by the present inventors as follows.

Confirmation of singlet oxygen reactant by ¹ HNMR measurement of squalene hydroperoxide (human skin surface) The inventors prepared squalene hydroperoxide by photosensitized oxidation reaction of purified squalene with methylene blue as a sensitizer. Then, the spectrum was measured. ¹ HNM
According to the R spectrum, the proton signal of the compound produced by attacking the squalene double bond by singlet oxygen could be identified as shown in the following chemical formulas 1 and 2.

[0012]

[Chemical 1]

[0013]

[Chemical 2]

The inventor collected sebum from the sun sulcus that received sunlight and fractionated the squalene hydroperoxide fraction using a reverse phase C ₁₈ column. Using this as a solvent for deuterated chloroform, ¹ H NMR spectrum was measured. This spectrum also has 1.3 ppm (a),
2.7 ppm (d), 4.3 ppm (3), 5.0 pp
Proton signals of m (1), 5.6 ppm (c), 7.2 ppm and 7.8 ppm (hydroperoxyl group protons) were observed. This is considered to be evidence of the presence of singlet oxygen on the skin surface.

The presence of singlet oxygen was confirmed by electron paramagnetic resonance (EPR) by in vitro human fibroblast (in vitro HFB) + UV. The inventors homogenized whole skin and epidermis, and A suspension of human fibroblasts in a buffer was used as an actual skin model. These were irradiated with UVA or UVB. In addition, 2,2,6,6-tetramethyl-4-piperidone (TMPD) was used as a spin scavenger for singlet oxygen, and the generated singlet oxygen was captured to obtain a stable EPR determination in the form of TMPD-nitrooxide. did. As a result, in the skin tissue, singlet oxygen was remarkably generated by UVA irradiation. In the cell homogenizing solution, UVB
Irradiation significantly generated singlet oxygen. That is, it is considered that singlet oxygen is generated both in the actual skin and inside the skin.

Next, since singlet oxygen was confirmed on human skin, whether or not the composition of the present invention, which is a singlet oxygen-scavenging composition, suppresses the peroxidation reaction in the skin was determined as follows. evaluated. Reduction of sebum peroxide The effect on sebum oxidation on human skin by a practical use test is shown below.

1. Test method Five healthy male subjects in their 20s to 40s were applied with lotion containing the formulation shown below to the groin area, 10 minutes later, the groin area was exposed to sunlight, and then sebum was applied from the groin area. Was sampled and the degree of oxidation of squalene in sebum was measured.

2. Practical use test Use lotion formulation Sample (add the substances in Table 1) 0.02% Citric acid 0.01% Sodium citrate 0.1% Alcohol unchanged 95% 7.0% Polyoxyethylene (20 mol) Oleyl alcohol 0.5% purified water residue

The results are summarized in Table 1. Here, the production amount of squalene hydroperoxide is 1 squalene in sebum.
The amount of squalene hydroperoxide per mole was measured using CL-HPL using a squalene hydroperoxide standard.
The average value of 5 people was recorded by the C method (Kono et al., Oil chemistry,
40 (9) P. 715 ('91)).

[0020]

[Table 1] ──────────────────────────────── Sample squalene hydroperoxide production ───────── ──────────────────────── Control Example 1 − 4.9 × 10 ⁻³ Control Example 2 SOD 4.7 × 10 ⁻³ Control Example 3 BHT 3.2 × 10 ^{− 3} Inventive Example 1 β-carotene 2.3 × 10 ⁻³ Inventive Example 2 Histidine 2.5 × 10 ⁻³ Inventive Example 3 dl-α tocopherol 1.8 × 10 ⁻³ Inventive Example 4 β-carotene (0.005%) + BHT (0.005) %) 1.9 × 10 ^-3 Inventive Example 5 β-carotene (0.01%) + BHT (0.01%) 1.0 × 10 ^-3 Inventive Example 6 Histidine (0.01%) + BHT (0.01%) 1.4 × 10 ^-3 ─── ─────────────────────────────

As can be seen from Table 1, even when the composition according to the present invention does not contain the chain-cutting antioxidant (Invention Examples 1 and 2), the chain-cutting antioxidant alone (Control Example 3) or It has a squalene hydroperoxide production inhibitory effect equivalent to or higher than that of SOD (Comparative Example 2), and is useful for reducing sebum peroxide.

[0022]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Example 1 (Lotion) Alanine 1.0% by weight Tannic acid 0.1 Glycerin 4.0 1,3-Butylene glycol 4.0 Ethanol 7.0 Polyoxyethylene (20 mol) Oleyl alcohol 0.5 Methylparaben 0.05 Citric acid 0.01 Sodium citrate 0.1 Perfume 0.05 Purified water Residual

Manufacturing method Citric acid, sodium citrate, glycerin, 1,
Dissolve 3-butylene glycol, alanine and tannic acid. Separately, polyoxyethylene oleyl alcohol, a fragrance and methylparaben were dissolved in ethanol, and this was added to the above aqueous solution to solubilize it, followed by filtration to obtain a lotion.

Example 2 (Cream) Cetostearyl alcohol 3.5% by weight Squalane 40.0 Beeswax 3.0 Reduced lanolin 5.0 Ethylparaben 0.3 Polyoxyethylene (20 mol) Sorbitan monopalmitate 2.0 Stearic acid monoglycoside 2.0 β-carotene 0.01 BHT 0.01 Perfume 0.03 1,3-butylene glycol 5.0 Glycerin 5.0 Sodium hyaluronate 0.05 Purified water Residual

Manufacturing method : cetostearyl alcohol, squalane, beeswax, reduced lanolin, ethylparaben, polyoxyethylene (2
(0 mol) sorbitan monopalmitate, stearic acid monoglycoside, β-carotene, BHT and perfume which were heated and melted and kept at 75 ° C were heated to 75 ° C to give 1,3-butylene glycol, glycerin and hyaluronic acid. Add to sodium and purified water with stirring. After homogenizing with a homomixer to make the emulsified particles fine, the mixture was rapidly cooled with stirring to obtain a cream.

Example 3 (Emulsion) α-tocopherol 0.02% by weight Stearic acid 1.5 Cetyl alcohol 0.5 Beeswax 2.0 Polyoxyethylene (10 mol) monooleate 1.0 1.0 Stearate monoglycoside 1 0.0 Quinceseed extract (5% aqueous solution) 20.0 Propylene glycol 5.0 Ethanol 3.0 Ethylparaben 0.3 Methylparaben 0.05 Perfume 0.05 Purified water Residual

[ Production Method ] α-tocopherol and a fragrance are added to ethanol and dissolved (alcohol solution). Propylene glycol is added to purified water, dissolved by heating, and maintained at 70 ° C (aqueous phase). Mix other ingredients except quince seed extract, heat and dissolve to 70
Keep at ℃ (oil phase). Add the oil phase to the water phase and pre-emulsify,
Emulsify uniformly with a homomixer. While stirring this, an alcohol solution and a quince seed extract are added. Then, it was rapidly cooled to 30 ° C. with stirring to obtain an emulsion.

Example 4 (Foundation) Lycopene 0.01% by weight Tannic acid 0.01 Liquid paraffin 27.0 Lanolin 10.0 Solid paraffin 5.0 Sorbitan sesquioleate 5.0 Powder colorant 35.0 Perfume Suitable amount Preservative Suitable amount Purified water Residual

Manufacturing method The powder colorant and sorbitan sesquioleate are mixed and a part of liquid paraffin is added to form an oil phase in which the colorant is uniformly dispersed by an emulsifying machine. The lycopene and the rest of the oil phase are mixed and heated, melted and the previous oil phase is added and kept at 70 ° C. After adding purified water and tannic acid dissolved at 70 ° C. to the oil phase, the mixture is emulsified by a powerful emulsifier, stirred after cooling after emulsification, filled in a container at 40 ° C., and allowed to cool.

[0031]

INDUSTRIAL APPLICABILITY As described above, according to the present invention, by adding a component that removes singlet oxygen, which is one of the causative substances that induces the peroxidation reaction on the surface of healthy human skin, One of the causative substances of the reaction is removed, contributing to the reduction of sebum peroxide. In addition, by adding together a chain scission-type antioxidant together with a component for removing singlet oxygen, other substances responsible for the peroxidation reaction are also removed, which can further contribute to the reduction of sebum peroxide.

Claims (4)

[Claims] 1. A singlet oxygen scavenging composition comprising a singlet oxygen scavenger. 2. A singlet oxygen scavenging composition comprising a singlet oxygen scavenger and a chain-breaking antioxidant. 3. The singlet oxygen scavenger is α-carotene, β-carotene, γ-carotene, lycopene, cryptoxanthin,
Carotenoids such as lutein, zeaxanthin, isozeaxanthin, rhodoxanthin, capsanthin, crocetin, 1,4-diazadicyclooctane, 2,5-dimethylfuran, 2-methylfuran, 2,5-diphenylfuran, 1,3-diphenyl Isobenzofuran, α-tocopherol, β-tocopherol, γ-tocopherol,
The singlet oxygen-scavenging composition according to claim 1 or 2, which is δ-tocopherol, histidine, tryptophan, methionine, alanine or an alkyl ester thereof. 4. The singlet oxygen scavenger according to claim 2, wherein the chain-breaking antioxidant is dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), gallic acid esters, ascorbic acid, tannins or flavonoids. Composition.