JPH05320048A - Antioxidant - Google Patents

Abstract

PURPOSE:To provide a highly safe antioxidant composition free from problems in terms of toxicity, usable as a raw material for foods, cosmetics, or medicines, formulated with a combination of a tocopherol of natural origin and sphingosin. CONSTITUTION:This antioxidant composition formulated with a combination of pref. each 0.001-1wt.% of (A) a tocopherol (pref. delta-tocopherol) and (B) a sphingosin (e.g. extracted from bovine brain). This combination potentiates the antioxidizing power synergistically. Incorporation of this composition in cosmetics formulated with fatty oil can prevent the fatty oil from oxidation. This composition can be used in biological systems to prevent the systems from lipid peroxidation.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel antioxidant composition having excellent antioxidant activity.

[0002]

2. Description of the Related Art Conventionally, dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), as antioxidants for foods and cosmetics containing oils and fats,
Tocopherols are used. But BHT, B
Synthetic antioxidants such as HA have a safety problem and their addition amount is limited. Therefore, natural antioxidants have been desired, but tocopherols have a slightly inferior antioxidant power, and improvement of their effects has been desired. The present invention has been made in response to such conventional circumstances, has a high effect as an antioxidant, has no toxicity problem, and can be used as foods, cosmetics, pharmaceutical raw materials, etc. It is an object of the present invention to provide an antioxidant composition having high activity.

[0003]

In order to achieve the above object, the present invention has been earnestly studied centering on natural products or antioxidants derived from natural products. As a result, the composition containing tocopherols and sphingosine is an antioxidant. It was found to be effective and effective as. That is, the present invention is an antioxidant composition comprising tocopherols and sphingosine.

As tocopherols, α-, β-, γ-, δ-forms of natural products, or a mixture thereof can be used. As a synthetic product, dl-α tocopherol can be used. Further, a natural product and a synthetic product can be mixed and used. Among the tocopherols, δ-tocopherol is particularly preferable from the viewpoint of antioxidant power. As sphingosine, for example, one extracted from bovine brain can be used. The compounding amount is 0.001-1 in each case
Weight percent is suitable. If it is less than 0.001% by weight, the antioxidant power is insufficient, and if it is used in excess of 1% by weight, it is unnecessary from the viewpoint of the antioxidant power. On the other hand, the product smells and the usability deteriorates. However, it is not practical.

By using the composition of the present invention, it becomes possible to stably incorporate even a substance having poor oxidation stability and difficult to be incorporated into the system. For example, when applied to cosmetics, it is expected to have an emollient effect. Turtle oil, mink oil, etc. have poor oxidative stability and their use has been limited, but cosmetics containing these oils and fats have a tocopherol of the present invention. By adding a composition consisting of and sphingosine, fats and oils can be prevented from being oxidized, and these fats and oils can be effectively incorporated into cosmetics. Recently, with the aim of preventing lipid peroxidation in biological systems,
Although application of an antioxidant has been proposed, the composition of the present invention can of course be used in a biological system.

[0006]

The combined use of tocopherols and sphingosine synergistically increases the antioxidant activity, as confirmed by the following experiments by the present inventors.

(1) Perilla oil, which is a highly unsaturated oil, is applied to a dry column of activated alumina to remove tocopherols, and 1000 ppm of tocopherols and 500 ppm of sphingolipids (sphingosine,
Sphingomyelin or cerebroside) was added. About 1 g of the oil thus prepared was incubated at 40 ° C. in the dark, and after a predetermined time, the change in peroxide value (POV) was measured daily. The details of the sample used are described below.

Sphingosine; Sigma (from beef brain cerebroside) Sphingomyelin; Sigma (from beef brain) Cerebroside; Sigma (from beef brain) α-tocopherol; Sigma (natural product) δ-tocopherol; Sigma Manufactured (natural product) dl-α tocopherol; manufactured by Eisai (synthetic product) Experimental results are shown in Table 1. In the table, dl-α-Toc. Is dl-α tocopherol, δ-Toc. Is δ-tocopherol, SPH. Indicates sphingosine.

[0009]

[Table 1] Changes in POV [meq / kg] ─────────────────────────────── Number of days 4 days 8 days ── ───────────────────────────── Control 71.0 167.5 dl-α-Toc. (1000 ppm) 65.3 108.7 δ-Toc. (1000ppm) 32.0 97.7 SPH. (500ppm) 48.0 110.5 dl-α-Toc. (1000ppm) ＋ SPH. (500ppm) 51.0 99.6 δ-Toc. (1000ppm) ＋ SPH. (500ppm) 8.7 13.3 Sphingomyelin (500ppm) 88.5 145.7 Cerebroside (500ppm) 97.7 157.6 ── ─────────────────────────────

As shown in Table 1, it was discovered for the first time that sphingosine and δ-tocopherol, in particular, had a synergistically strong antioxidant effect.

(2) A liver (10 g) was extracted from an SD rat (12 weeks old) and 90 ml of a buffer solution (0.
25M sucrose, 0.1M EDTA, 5mM Tris-H
Homogenized with Cl, pH 7.4). The homogenate was centrifuged at 7,000 G for 10 minutes, and the supernatant was further centrifuged at 105,000 G for 60 minutes to obtain microsomes. The resulting microsomes were treated with 50 mM Tri
It was washed with s-hydrochloric acid buffer (pH 7.4) and stored at -80 ° C until used in the experiment. Microsomes (1 to 3 mg / protein) prepared as described above were added to 1.7 mM ADP
And 0.1 mM FeCl ₃ in 50 mM Tris-hydrochloric acid buffer (pH 7.4). This was supplemented with sphingosine at concentrations of 8.0 and 800 μM, and 8.
Α-Toc was added to 0 μM. 0.1 mM NADPH was added to these to initiate the peroxidation reaction, and the mixture was incubated at 37 ° C. for 20 minutes. The degree of lipid peroxidation was determined by the quantification of phospholipid hydroperoxide by the TBA method and CL-HPLC method. The change in the amount of tocopherol was determined by the fluorescence-HPLC method (CL-HPLC method: T. Miyazawa, K. Yasuda, K. Fujimo.
to, Anal. Lett., 20 , 915 (1987)).

Table 3 shows the antioxidant effect of sphingosine and the consumption of α-tocopherol when α-tocopherol was added to NADPH-dependent rat liver microsomal lipid peroxidation. α tocopherol 8.0 μM and sphingosine 80
It was found that the addition of 0 μM significantly suppressed the decrease in tocopherol associated with lipid peroxidation. This result demonstrates that sphingosine synergizes with tocopherol to exhibit an antioxidant effect.

[0013]

TABLE 2 consumption antioxidant effect and α-tocopherol sphingosine upon α-tocopherol added pressure in the NADPH-dependent rat liver microsomes lipid peroxidation n = 4 ───────────────── ────────────────── PCOOH PEOOH α Tocopherol [pmol / mg protein] [nmolMDA / mg protein] ───────────────── ─────────────────── Control 65.9 19.7 <0.1 8.0 μM α tocopherol 29.4 9.8 1.8 8.0 μM α tocopherol +8.0 μM sphingosine 28.4 9.0 2.3 8.0 μM α tocopherol +800 μM sphingosine 10.0 4.2 4.2 ───────────────────────────────────

[0014]

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 (Emulsion) Stearic acid 2.5 (% by weight) Cetyl alcohol 1.5 Vaseline 5.0 Liquid paraffin 7.0 Turtle oil 3.0 Polyoxyethylene (10 mol) monooleate 2. 0 Polyethylene glycol 1500 3.0 Triethanolamine 1.0 Sphingosine 0.01 δ-Tocopherol 0.02 Perfume Suitable amount Preservative Suitable amount Purified water Residual

Example 2 (Cream) Beeswax 10.0 (wt%) Cetyl alcohol 5.0 Hydrogenated lanolin 5.0 Squalane 37.5 Mink oil 3.0 Glyceryl monostearate 2.0 Polyoxyethylene (20 Mol) sorbitan monolaurate 2.0 propylene glycol 5.0 sphingosine 0.01 δ-tocopherol 0.02 perfume appropriate amount preservative appropriate amount purified water residual

From Examples 1 and 2 sphingosine and δ
-Comparative examples 1 and 2 having a formulation excluding tocopherol were prepared. After the preparation, it was left at 50 ° C. for one month and then the odor was judged. Judgment is made by 3 expert panelists. The results are shown in Table 4.

[0018]

[Table 3] ────────────────────────────── Example 1 Example 2 Comparative Example 1 Comparative Example 2 ──── ────────────────────────── Odor judgment ○ ○ × △ ─────────────────── ──────────── ○: No rancid odor △: Slight rancid odor ×: Rancid odor

Example 3 (Cream) cetostearyl alcohol 3.5 (wt%) 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 delta-tocopherol 0.01 sphingosine 0.01 fragrance 0.03 1,3-butylene glycol 5.0 glycerin 5.0 sodium hyaluronate 0.05 purified water residual

(Production method) Heat-dissolved cetostearyl alcohol, squalane, beeswax, reduced lanolin, ethylparaben, polyoxyethylene (20 mol) sorbitan monopalmitate, stearic acid monoglycoside, δ-tocopherol, sphingosine and a fragrance, 75
What was kept at ℃ is added to 1,3-butylene glycol, glycerin, sodium hyaluronate and purified water heated at 75 ℃ 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 4 (Emulsion) α-tocopherol 0.02 (% by weight) Sphingosine 0.01 Stearic acid 1.5 Cetyl alcohol 0.5 Beeswax 2.0 Polyoxyethylene (10 mol) Monooleate 1. 0 Stearic acid monoglycoside 1.0 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, sphingosine, and flavor 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). Other components except the quince seed extract are mixed, heated and dissolved to maintain the temperature at 70 ° C (oil phase). The oil phase is added to the aqueous phase to carry out preliminary emulsification, and homogenize 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.

[0023]

As described above, according to the present invention,
It can exhibit a remarkable antioxidant effect as compared with conventional antioxidants. Further, by using the composition of the present invention, it becomes possible to stably mix even a substance that has been poor in oxidative stability and difficult to be mixed into the system, and can be used in a wide range such as cosmetics and foods. There is expected.

[Procedure amendment]

[Submission date] July 15, 1993

[Procedure Amendment 1]

[Document name to be amended] Statement

[Name of item to be corrected] Full text

[Correction method] Change

[Correction content]

[Document name] Statement

[Title of Invention] Antioxidant

[Claims]

Detailed Description of the Invention

[0001]

The present invention relates, in the novel and relates to an antioxidant having excellent antioxidant effect.

[0002]

2. Description of the Related Art Conventionally, dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), as antioxidants for foods and cosmetics containing oils and fats,
Tocopherols are used. But BHT, B
Synthetic antioxidants such as HA have a safety problem and their addition amount is limited. Therefore, natural antioxidants have been desired, but tocopherols have a slightly inferior antioxidant power, and improvement of their effects has been desired. The present invention has been made in response to such conventional circumstances, has a high effect as an antioxidant, has no toxicity problem, and can be used as foods, cosmetics, pharmaceutical raw materials, etc. The purpose of the present invention is to provide an antioxidant with high activity .

[0003]

Since the present inventors SUMMARY OF THE INVENTION The above objects achieved, derived from a natural product or natural product antioxidant result of intensive studies centered on, the tocopherols and sphingosine
It has been found that the formulation is effective and effective as an antioxidant. That is, the present invention, antioxidant, characterized in that by blending tocopherols and sphingosine
It is an agent . Also, it is special that it contains this antioxidant.
It is an external preparation for skin.

As tocopherols, α-, β-, γ-, δ-forms of natural products, or a mixture thereof can be used. As a synthetic product, dl-α tocopherol can be used. Further, a natural product and a synthetic product can be mixed and used. Among the tocopherols, δ-tocopherol is particularly preferable from the viewpoint of antioxidant power. As sphingosine, for example, one extracted from bovine brain can be used. The compounding amount is 0.001-1 in each case
Weight percent is suitable. If it is less than 0.001% by weight, the antioxidant power is insufficient, and if it is used in excess of 1% by weight, it is unnecessary from the viewpoint of the antioxidant power. On the other hand, the product smells and the usability deteriorates. However, it is not practical.

By using the antioxidant of the present invention, even a substance which has been difficult to be compounded due to poor oxidation stability can be stably compounded in the system. For example, when applied to cosmetics, it is expected to have an emollient effect. Turtle oil, mink oil, etc. have poor oxidative stability and their use has been limited, but cosmetics containing these oils and fats have a tocopherol of the present invention. By adding an antioxidant composed of and sphingosine, fats and oils can be prevented from being oxidized, and these fats and oils can be effectively incorporated into cosmetics. The purpose of lipid peroxidation preventing in biological systems has recently have been proposed for applying antioxidants, anti-acids of the present invention
Of course , the agent can also be used for biological systems.

[0006]

The combined use of tocopherols and sphingosine synergistically increases the antioxidant activity, as confirmed by the following experiments by the present inventors.

(1) Perilla oil, which is a highly unsaturated oil, is applied to a dry column of activated alumina to remove tocopherols, and 1000 ppm of tocopherols and 500 ppm of sphingolipids (sphingosine,
Sphingomyelin or cerebroside) was added. About 1 g of the oil thus prepared was incubated at 40 ° C. in the dark, and after a predetermined time, the change in peroxide value (POV) was measured daily. The details of the sample used are described below.

Sphingosine; Sigma (from beef brain cerebroside) Sphingomyelin; Sigma (from beef brain) Cerebroside; Sigma (from beef brain) α-tocopherol; Sigma (natural product) δ-tocopherol; Sigma Manufactured (natural product) dl-α tocopherol; manufactured by Eisai (synthetic product) Experimental results are shown in Table 1. In the table, dl-α-Toc. Is dl-α tocopherol, δ-Toc. Is δ-tocopherol, SPH. Indicates sphingosine.

[0009]

[Table 1] Changes in POV [meq / kg] ─────────────────────────────── Number of days 4 days 8 days ── ───────────────────────────── Control 71.0 167.5 dl-α-Toc. (1000 ppm) 65.3 108.7 δ-Toc. (1000ppm) 32.0 97.7 SPH. (500ppm) 48.0 110.5 dl-α-Toc. (1000ppm) ＋ SPH. (500ppm) 51.0 99.6 δ-Toc. (1000ppm) ＋ SPH. (500ppm) 8.7 13.3 Sphingomyelin (500ppm) 88.5 145.7 Cerebroside (500ppm) 97.7 157.6 ── ─────────────────────────────

As shown in Table 1, it was discovered for the first time that sphingosine and δ-tocopherol, in particular, had a synergistically strong antioxidant effect.

(2) A liver (10 g) was extracted from an SD rat (12 weeks old) and 90 ml of a buffer solution (0.
25M sucrose, 0.1M EDTA, 5mM Tris-H
Homogenized with Cl, pH 7.4). The homogenate was centrifuged at 7,000 G for 10 minutes, and the supernatant was further centrifuged at 105,000 G for 60 minutes to obtain microsomes. The resulting microsomes were treated with 50 mM Tri
It was washed with s-hydrochloric acid buffer (pH 7.4) and stored at -80 ° C until used in the experiment. Microsomes (1 to 3 mg / protein) prepared as described above were added to 1.7 mM ADP
And 0.1 mM FeCl ₃ in 50 mM Tris-hydrochloric acid buffer (pH 7.4). This was supplemented with sphingosine at concentrations of 8.0 and 800 μM, and 8.
Α-Toc was added to 0 μM. 0.1 mM NADPH was added to these to initiate the peroxidation reaction, and the mixture was incubated at 37 ° C. for 20 minutes. The degree of lipid peroxidation was determined by the quantification of phospholipid hydroperoxide by the TBA method and CL-HPLC method. The change in the amount of tocopherol was determined by the fluorescence-HPLC method (CL-HPLC method: T. Miyazawa, K. Yasuda, K. Fujimo.
to, Anal. Lett., 20 , 915 (1987)).

Table 2 shows the antioxidant effect of sphingosine and the consumption of α-tocopherol when α-tocopherol was added to NADPH-dependent rat liver microsomal lipid peroxidation. α tocopherol 8.0 μM and sphingosine 80
It was found that the addition of 0 μM significantly suppressed the decrease in tocopherol associated with lipid peroxidation. This result demonstrates that sphingosine synergizes with tocopherol to exhibit an antioxidant effect.

[0013]

TABLE 2 consumption antioxidant effect and α-tocopherol sphingosine upon α-tocopherol added pressure in the NADPH-dependent rat liver microsomes lipid peroxidation n = 4 ───────────────── ────────────────── PCOOH PEOOH α tocopherol [pmol / mg protein] [ nmol / mg protein] ──────────────── ─────────────────── Control 65.9 19.7 <0.1 8.0 μM α tocopherol 29.4 9.8 1.8 8.0 μM α tocopherol +8.0 μM sphingosine 28.4 9.0 2.3 8.0 μM α tocopherol +800 μM sphingosine 10.0 4.2 4.2 ───────────────────────────────────

[0014]

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 (Emulsion) Stearic acid 2.5 (% by weight) Cetyl alcohol 1.5 Vaseline 5.0 Liquid paraffin 7.0 Turtle oil 3.0 Polyoxyethylene (10 mol) monooleate 2. 0 Polyethylene glycol 1500 3.0 Triethanolamine 1.0 Sphingosine 0.01 δ-Tocopherol 0.02 Perfume Suitable amount Preservative Suitable amount Purified water Residual

Example 2 (Cream) Beeswax 10.0 (wt%) Cetyl alcohol 5.0 Hydrogenated lanolin 5.0 Squalane 37.5 Mink oil 3.0 Glyceryl monostearate 2.0 Polyoxyethylene (20 Mol) sorbitan monolaurate 2.0 propylene glycol 5.0 sphingosine 0.01 δ-tocopherol 0.02 perfume appropriate amount preservative appropriate amount purified water residual

From Examples 1 and 2 sphingosine and δ
-Comparative examples 1 and 2 having a formulation excluding tocopherol were prepared. After the preparation, it was left at 50 ° C. for 1 month, and then the odor was evaluated. Judgment is made by 3 expert panelists. The results are shown in Table 3 .

[0018]

[Table 3] ────────────────────────────── Example 1 Example 2 Comparative Example 1 Comparative Example 2 ──── ────────────────────────── Odor judgment ○ ○ × △ ─────────────────── ──────────── ○: No rancid odor △: Slight rancid odor ×: Rancid odor

Example 3 (Cream) cetostearyl alcohol 3.5 (wt%) 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 delta-tocopherol 0.01 sphingosine 0.01 fragrance 0.03 1,3-butylene glycol 5.0 glycerin 5.0 sodium hyaluronate 0.05 purified water residual

(Production method) Heat-dissolved cetostearyl alcohol, squalane, beeswax, reduced lanolin, ethylparaben, polyoxyethylene (20 mol) sorbitan monopalmitate, stearic acid monoglycoside, δ-tocopherol, sphingosine and a fragrance, 75
What was kept at ℃ is added to 1,3-butylene glycol, glycerin, sodium hyaluronate and purified water heated at 75 ℃ 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 4 (Emulsion) α-tocopherol 0.02 (% by weight) Sphingosine 0.01 Stearic acid 1.5 Cetyl alcohol 0.5 Beeswax 2.0 Polyoxyethylene (10 mol) Monooleate 1. 0 Stearic acid monoglycoside 1.0 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, sphingosine, and flavor 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). Other components except the quince seed extract are mixed, heated and dissolved to maintain the temperature at 70 ° C (oil phase). The oil phase is added to the aqueous phase to carry out preliminary emulsification, and homogenize 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 5 (cream) beeswax 10.0 (weight
%) Cetyl alcohol 5.0 Hydrogenated lanolin 5.0 Squalane 37.5 Mink oil 3.0 Glyceryl monostearate 2.0 Polyoxyethylene (20 mol) sorbitan monolaurate 2.0 Propylene glycol 5.0 Sphingosine 0.001 δ-tocopherol 0.1 Fragrance Suitable amount Preservative Suitable amount Purified water Residual

Example 6 (health drink) Fructose-glucose liquid 17.9 (weight
%) Honey 0.1 citric acid 0.082 DL-malic acid 0.041 sodium L -aspartate 0.02 L-arginine 0.02 nicotinamide 0.01 sodium glutamate 0.001 thiamine NDS 0.00017 riboflavin 0 0.0025 Pyridoxine hydrochloride 0.0005 δ-tocopherol 0.05 Sphingosine 0.005 Ascorbic acid phosphate Mg salt 0.1 Purified water Residual fragrance Suitable amount

[0025]

As described above, according to the present invention,
It can exhibit a remarkable antioxidant effect as compared with conventional antioxidants. Further, by using the antioxidant of the present invention,
Even substances that are poor in oxidative stability and difficult to be compounded can be stably compounded in the system, and are expected to be used in a wide range of fields such as cosmetics and foods.

Claims (2)

[Claims] 1. An antioxidant composition comprising a mixture of tocopherols and sphingosine. 2. The antioxidant composition according to claim 1, wherein the tocopherols are δ-tocopherol.