JP2006321732A - Removal of abnormal protein, and composition for suppressing increase of 8-hydroxy-2'-deoxyguanosine - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition for removing abnormal proteins comprising a highly effective abnormal protein-removing component, and to provide an anti-ageing composition contributing to prevention and treatments of diseases caused by abnormal proteolysis using the abnormal protein-removing component. <P>SOLUTION: The composition comprises α-lipoic acid as the abnormal protein-removing component. Health foods and beauty foods comprising the same are also provided. The composition for suppressing the increase of 8-hydroxy-2'-deoxyguanosine comprises α-lipoic acid. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an abnormal protein removal composition characterized by containing α-lipoic acid, a disease associated with abnormal protein accumulation, a disease involving production of 8-hydroxy 2′-deoxyguanosine, which is an oxidized base compound, and skin moisture. The present invention relates to a composition that is effective for the prevention and improvement of diseases accompanied by a decrease in the amount.

An abnormal protein refers to a protein that has undergone oxidation, saccharification, or aldehyde modification with aging, and in the present invention, refers to a carbonylated protein.
Abnormal protein increases with age, and diseases or disorders caused by abnormal protein accumulated in the body due to abnormal proteolysis (Alzheimer's disease, Parkinson's disease, Lewy body disease, triplet repeat disease, amyotrophic lateral sclerosis, It has been revealed that it is involved in many diseases such as cataract, arteriosclerosis, diabetic nephropathy, photoaging of skin, wrinkles in skin, etc. (Non-patent Documents 1 and 2). Even when young, if excessive amounts of active oxygen are chronically generated in the living body due to excessive stress, ultraviolet rays, etc., accumulation of abnormal proteins is accelerated.
Currently, the prevention and treatment of diseases caused by abnormal protein degradation has become a major issue. However, in the prevention and treatment research for these diseases, oxidative modification of proteins has been applied to prevent the accumulation of abnormal proteins in vivo. Research has been done from the point of view of defense. That is, it is an attempt to suppress the oxidation of proteins by erasing the active oxygen generated by oxidative stress to a level that cannot be handled by the biological defense mechanism by ingesting antioxidant substances. Typical antioxidants include tocophenols and carotenoids, and polyphenols contained in various plants.

However, the intake of antioxidants contributes to the elimination of active oxygen generated in the living body, but does not contribute to the removal of already accumulated abnormal proteins. Accordingly, removal of abnormal proteins is essential for the prevention and treatment of various diseases involving abnormal proteins accumulated in the living body with aging. As a result of searching for a component that removes abnormal proteins, soybean saponin (Patent Document 1) and kale (Patent Document 2) have been found to be effective.
In addition, 8-hydroxy 2′-deoxyguanosine, which is known as the most major purine base modification product, is known to increase in skin tissues due to oxidative stress such as ultraviolet rays. An increase in 8-hydroxy-2′-deoxyguanosine in the keratinocytes constituting the epidermis can contribute to skin cancer, accompanied by an increase in p53 expression and cyclothymidine dimer, a pyrimidine base modification product. In addition, 8-hydroxy 2′-deoxyguanosine in the DNA base acts on melanocytes to promote melanin production. Therefore, melanin production is suppressed by suppressing the production | generation of 8-hydroxy 2'-deoxyguanosine by ultraviolet irradiation. In addition, suppressing the production of 8-hydroxy-2′-deoxyguanosine suppresses the damage to the DNA of the cells, and collagen production is promoted in fibroblasts. It is expected to lead to improvement (Patent Document 3).

  It is known that the amount of carbonyl oxide and 8-hydroxy-2'-deoxyguanosine increase with age in a short-lived species such as house fly (Non-patent Document 3). In addition, when a single oxidative stress is applied to a living body, the increase in the amount of carbonyl oxide and the amount of 8-hydroxy-2′-deoxyguanosine is such that 8-hydroxy-2′-deoxyguanosine increases faster than carbonyl oxide. Is known (Non-Patent Document 4). As a result of earnest study based on the viewpoint that suppressing the abnormal increase of 8-hydroxy-2'-deoxyguanosine predicted from these leads to the effect of removing abnormal protein, the effects of improving skin aging and improving skin water content It has been discovered that it can be used to prevent and treat various diseases caused by abnormal protein accumulation.

Japanese Patent Laid-Open No. 2002-179592 JP 2004-91398 A JP 2003-2819 A BIO clinica, Vol.11, No.5, 1996 The FASEB Journal, Vol. 9, 1173-1182, 1995 Proc Natl Acad Sci U S A. 91, 25, 1994, 12332-5 Free Radic Biol Med.; 30, 6, 2001, 613-24

  An object of the present invention is to identify an abnormal protein removing component that is more effective and to provide a composition for removing an abnormal protein containing the component, and to use this abnormal protein removing component to prevent a disease caused by abnormal proteolysis. It is to provide an anti-aging composition that contributes to prevention and treatment.

In order to achieve the above object, the present inventor searched for a component that removes an abnormal protein using α-lipoic acid. As a result, an effect required for α-lipoic acid was found and the present invention was completed.
The main configuration of the present invention is as follows.
(1) A composition for removing abnormal protein, comprising α-lipoic acid.
(2) A composition for suppressing increase in 8-hydroxy-2′-deoxyguanosine, which comprises α-lipoic acid.
(3) A composition for anti-aging, comprising α-lipoic acid.
(4) A composition for improving skin moisture content, comprising α-lipoic acid.
(5) A composition for preventing UV damage, comprising α-lipoic acid.
(6) A composition for suppressing dullness of the skin, comprising α-lipoic acid.
(7) A composition for suppressing wrinkles, comprising α-lipoic acid.
(8) A food comprising the composition according to any one of (1) to (7).
(9) The food according to (8), wherein the intake of α-lipoic acid is 50 mg / day or more.

By using the abnormal protein accumulation inhibitor and the 8-hydroxy 2′-deoxyguanosine increase inhibitor of the present invention, accumulation of abnormal protein can be suppressed. Therefore, the preparation of the present invention is a disease or disorder caused by abnormal protein degradation (Alzheimer's disease, Parkinson's disease, Lewy body disease, triplet repeat disease, amyotrophic lateral sclerosis, cataract, arteriosclerosis, diabetic nephropathy, skin It is effective in preventing or treating diseases caused by abnormal protein degradation such as photoaging of the skin and wrinkles in the skin).
By providing α-lipoic acid as an active ingredient for removing abnormal protein, the intaker can obtain a high effect of removing abnormal protein just by ingesting a non-burden amount. Disability prevention and treatment can be performed. Furthermore, it is useful as a food for anti-aging.
Examples of cosmetic anti-aging effects include a reduction in skin water content and prevention of wrinkles and dullness. That is, the composition of the present invention can be used as an anti-aging and anti-aging health food, anti-aging beauty food, rust prevention and anti-rust health food. The composition for removing abnormal protein of the present invention exhibits an excellent effect on mammals and is highly safe.
The non-hemolytic composition of the present invention can be applied parenterally, such as administration as an injection. It can also be taken orally as a pharmaceutical or a food such as a health food.

The present invention is described in detail below.
Alpha lipoic acid is a vitamin-like active substance discovered as a sulfur-containing factor that promotes the growth of microorganisms in liver and yeast extract in the mid 1940s, and was isolated and crystallized from the liver of cattle and pigs in the early 1950s. The chemical structure was determined. Lipoic acid is widely present in the animal and microbial worlds, but what is currently marketed is not a natural product, but almost a product made by chemical synthesis. Several methods have been developed for the synthesis of α-lipoic acid and its derivatives. Currently used exclusively is a synthetic method starting from adipic acid. Natural α-lipoic acid is in D-form, but α-lipoic acid generally used is a 1: 1 mixture of synthesized optical isomers (DL-type, racemic). .

  Examples of α-lipoic acid that can be used in the present invention include D-form, L-form, racemate, and their oil and fat coatings. Examples of the salt of lipoic acid include amine salts and ammonium salts in addition to alkali metal salts such as sodium salts and potassium salts. Examples of the derivatives of lipoic acid that can be used in the present invention include alkyl or alkenyl esters, amides, dihydrolipoic acid that is a reduced form, alkyl or alkenyl esters and amides thereof, and the like. In the present invention, one type or two or more types are selected and used from the above. The amount added to the base or carrier is suitably about 0.001 to 5.0% by weight in the total amount.

The abnormal protein removing composition of the present invention can contain a compound having an antioxidant action in addition to α-lipoic acid. To provide an anti-aging composition having an anti-aging action, a composition containing an abnormal protein-removing action and a compound having an anti-oxidation action, having an anti-aging action and an abnormal protein removing function. Can do.
The compound exhibiting an antioxidant action is not particularly limited, but various vitamins such as vitamin E and tocotrienol, various carotenoids such as astaxanthin and lycopene, and various polyphenols such as silymarin and catechin. , Various sulfur-containing compounds such as cysteine and glutathione, or coenzyme Q10 and natural components containing them.

  The composition having an abnormal protein removing action of the present invention can be used as a health food or a beauty food for anti-aging. Examples of cosmetic anti-aging effects include a reduction in skin water content and prevention of wrinkles and dullness. That is, the composition of the present invention can be used as an anti-aging and anti-aging health food, anti-aging beauty food, rust prevention and anti-rust health food. The composition for removing abnormal protein of the present invention exhibits an excellent effect on mammals and is highly safe.

The non-hemolytic composition of the present invention can be applied parenterally, such as administration as an injection. It can also be taken orally as a pharmaceutical or a food such as a health food.
The composition of the present invention can be applied in the form of, for example, a solution such as an aqueous solution, an oil, an emulsion, a suspension, a semi-solid agent such as a gel or a cream, a solid agent such as a powder, a granule, a tablet, or a capsule. . It can be prepared in these forms by a conventionally known method to form various dosage forms.
When making the composition of this invention into the form of a foodstuff, additive components, such as starch normally used in the field | area of a foodstuff, can be mix | blended. It can be in the form of granules, tablets, powders, capsules, and liquids, and such preparations can be produced by commonly used formulation techniques.

  The abnormal protein removing composition of the present invention can contain α-lipoic acid as an active ingredient and, if necessary, additives such as a pharmaceutically acceptable diluent or carrier. Moreover, the composition of this invention can contain the other pharmacologically active ingredient as needed.

EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to these Examples etc.
Hereinafter, the present invention will be described in detail based on various test examples.

[Test Example 1: Measurement of radical scavenging ability derived from lipid peroxide]
Various antioxidants including α-lipoic acid were measured and compared for their ability to eliminate radicals derived from lipid peroxide generated by ultraviolet irradiation of oleic acid.
The following components (1) to (5) were mixed at 50 ° C., and the total amount was adjusted to 500 mg with water to obtain a 25% (w / w) oleic acid-containing micelle solution containing various antioxidants. As an antioxidant, alpha lipoic acid, dihydro alpha lipoic acid, L-cysteine, glutathione (reduced form), and glutathione (oxidized form) were mixed in the micelle solution.
(1) Hydrogenated lecithin (Resinol S-10 manufactured by Nikko Chemical Co., Ltd.) 10.75 mg
(2) PBS (pH 7.4) 100 μM
(3) Antioxidant / 1,3-butylene glycol: glycerol (1: 1; w / w) The antioxidant concentration was arbitrarily set between 100 μM and 2000 μM.
(4) αPBN (α-Phenyl N-Butylnitrone / 1,3-butylene glycol: glycerol (1: 1; w / w)) 100 mM
(5) Oleic acid 125mg

The prepared micelle solution containing oleic acid was added to a commercially available 24-well plate, and an ultraviolet A wave (FL32SBL / DMR: manufactured by Clinical Supply Co., Ltd.) with an integrated amount of 100 kJ / m ² (20 minutes at an ultraviolet intensity of 50 W / m ² ). Was irradiated to the solution to induce peroxidation of oleic acid, and radicals derived from lipid peroxide were generated.
Since radicals derived from lipid peroxide are trapped by αPBN in an oleic acid-containing micelle solution and PBN spin adduct is formed, it can be detected as ESR signal intensity. The ESR signal was measured using JES-TE200 (manufactured by JEOL). The ESR signal intensity in each test condition is Sn, the radical scavenging rate is Q (%), the IC50 concentration is calculated from the magnitude of the ESR signal using the following formula, and the peroxide scavenging ability of various antioxidants Compared.

Q (%) = 1 − {(Sn [sample] −Sn [blank])
/ (Sn [control] -Sn [blank])}
sample = various antioxidants
blank = UV-A wave non-irradiation and no antioxidant added
control = UV-A wave 100 kJ / m ² irradiation, and no antioxidant added radical scavenging factor F: F = Q / 100 is calculated from radical scavenging rate Q (%),
A linear curve of [antioxidant concentration] vs [F / 1-F] at an arbitrary antioxidant concentration was determined.

This linear curve is
[Antioxidant concentration] vs [S / s-1]
* S / s-1 (S: ESR signal intensity in the absence of antioxidant)
(s: ESR signal intensity in the presence of antioxidant)
It corresponds to.
x-axis → [antioxidant concentration] y-axis → [F / 1−F] and then IC50 concentration from x value (concentration) for y = 1, ie F = 0.5 and Q = 50% Was calculated.
Table 1 shows the lipid peroxide-derived radical scavenging ability (IC50 concentration) of various antioxidants.

  As shown in FIG. 1 and Table 1, the radical-erasing ability generated by ultraviolet irradiation changes depending on the concentration of α-lipoic acid, and the elimination of UV-induced radicals of α-lipoic acid, compared to other antioxidants. I can understand that it is excellent.

[Test Example 2: Effect test of α-lipoic acid on the skin of UV-irradiated mice]
In a test system in which hairless mice were irradiated with UVA waves and UVB waves to form wrinkles, α-lipoic acid was orally ingested to examine wrinkle suppression and skin aging suppression effects.
The test was conducted using hairless mice (Hos: HR-1 female) 6 weeks old at the time of introduction under the following conditions 1) to 9).

1) Preparation and administration of test object In the grouping of hairless mice, animals having good general condition were divided into 5 groups per group so that there was no difference between groups on the day of the start of administration. Each individual was raised at 1 gauge / group.
In Examples 2 and 3, the feed NF for mice (manufactured by Oriental Bioservice) was subjected to a mixing treatment so that α-lipoic acid was uniformly mixed, and allowed to be freely ingested by mixed feed. In the mixing process, sterilization is performed by irradiating 30 kGy of γ-ray, but α lipoic acid is not decomposed. DTNB method (Archives of Biochemistry and Biophysics, Vol. 120, Issue 1, 1967, p.1922-197) ).

  As a comparative control, in Comparative Examples 7 and 8, β-carotene, which is a kind of carotenoids, and mouse feed NF (manufactured by Oriental Bioservice) were uniformly mixed and allowed to freely ingest by mixing. Moreover, as a control group of this test, Comparative Examples 5 and 6 were fed with a feed not mixed with α-lipoic acid and β-carotene, Comparative Example 5 was not irradiated with UV, and Comparative Example 6 was irradiated with UV. Table 2 shows a list of administration groups.

2) Skin morphology observation Photographing of the surface of the skin and determination of the collected replica were performed. The score was scored according to the criteria shown in Table 3 using the degree of wrinkle formation as an index.

  However, when the judgment is difficult, judgment of 0.5 points, 1.5 points, and 2.5 points is allowed.

3) Measurement of skin moisture content The moisture content was measured using a moisture checker, measuring 3 cm from the tail of the back to the neck, 2 cm, and 0.5 cm from the lumbar spine to the right, and calculating the average. The measurement date was 4 weeks after UV irradiation and the date of dissection as the test start date and the intermediate observation date.

4) Measurement of skin viscoelasticity (hardness) Using a skin viscoelasticity measuring device (Vesmeter: E-100S / manufactured by Wave Cyber), 3 cm from the tail of the back to the neck and 0.5 cm from the lumbar spine to the right The average of the hardness was obtained by measuring once. The measurement date was the dissection date.

5) Measurement of oxidized protein in skin tissue Oxidized protein, that is, carbonylated protein, labels carbonylated protein using 2,4-dinitrophenylhydrazine (DNPH) that specifically binds to the carbonyl group of the protein caused by oxidative damage. Subsequently, detection was performed using an anti-DNPH antibody that specifically binds to DNPH. A specific method is as follows. Cut 1 cm ² of the skin at the UV irradiation site, add 1 ml of 0.1 M Tris buffer (pH 7.5) containing PMSF at 4 ° C., homogenize, centrifuge at 12,000 g × 20 minutes, and filter the supernatant. And analyzed. The protein was converted to dinitrophenylhydrazine (DNPH) by a known method (Nakamura et al., Journal of Biochemistry, 119, 768-774, 1996). The DNPH protein was separated by SDS-PAGE, and transferred to a polyvinylidene difluoride (PVDF) membrane using a protein transfer device. After the transfer, the membrane was blocked at room temperature for 30 minutes in 5% skim at 4 ° C in a PBS (-) solution containing milk, washed with PBS (-), and reacted with anti-DNPH antibody at 4 ° C overnight. After washing, it was reacted with biotinylated anti-rabbit immunoglobulin G for 1 hour. After washing, the PVDF film was exposed using a fluorescence detection kit (ECL PLUS), and the image was transferred with a medical automatic developing device. Image analysis was performed using a transilluminator.

6) Measurement of 8-hydroxy 2'-deoxyguanosine in skin tissue 8-hydroxy 2'-deoxyguanosine was measured using an immunohistochemical technique. At the time of animal dissection, 2 cm from the caudal root of the back of the skin tissue toward the neck and 1 cm ² of the skin at a 0.5 cm site on the right side from the lumbar vertebra were cut out, fixed with Buan, and embedded in paraffin to preserve the skin tissue. A 3 μm-thick section was appropriately prepared, and deparaffinization and hydrophilization were performed based on known methods. Antigen activation was performed by microwave treatment for 5 minutes in 0.01 M citrate buffer (pH 6.0). After cooling to room temperature, the reaction was carried out with methanol containing 0.3% hydrogen peroxide at room temperature for 20 minutes to inhibit endogenous peroxidase. After washing with water and 10 mM PBS (−), microwave treatment was performed for 5 minutes with a diluted solution of goat serum 75 times 10 mM PBS (−) to block the serum, and the primary antibody (N45.1: manufactured by Nikken Zeil Co., Ltd.) was dropped. The antibody was reacted by microwave treatment at 5 μg / ml for 20 minutes. After washing twice with 10 mM PBS (−), a biotinylated secondary antibody (biotinylated goat immunoglobulin M; manufactured by DAKO) diluted 300-fold was reacted with the antibody by microwave treatment for 5 minutes. The plate was washed twice with 10 mM PBS (−) and reacted with an ABC reagent (ABC-HRP; manufactured by Vectastein) by microwave treatment for 5 minutes. The reaction was performed at room temperature for 3 minutes and 30 seconds using DAB (3,3-diaminobenzidine tetrahydrochloride: manufactured by DAKO) as a coloring reagent. After washing with water, dehydration and encapsulation were performed based on a known method. The staining state of the skin tissue was observed under a microscope, an image was taken in using Adobe Photoshop, and the stained portion in a certain area in the image was digitized by NIH Imaging.

7) UV irradiation At the time of UV irradiation, the animals were transferred to a dedicated PC cage, and each group was irradiated with UVB ²⁰ mJ / cm ² and UVA 14 J / cm ² . Irradiation was carried out every other day for 10 weeks.

8) Dissection Each group was fasted for 18 hours from the day after the end of this breeding period, and then anesthesia was introduced by intraperitoneal administration of Nembutal (40 mg / kg) for dissection. 4) Skin sections were stored frozen for measurement of oxidized protein in skin tissue, and 5) skin sections were infiltrated into Buan solution for measurement of 8-hydroxy-2'-deoxyguanosine in skin tissue.

9) Statistical processing The test result was expressed as an average value ± standard deviation, and a significant difference test was performed by Excel statistical Student's t-test.

The results of Test Example 2 are sequentially shown below.
1. General condition observation From around the 4th week, light browning of the skin of the head, wrinkle depth of the neck and wrinkles of the back of the hind limbs became more noticeable in the UV irradiated animals than in the non-UV irradiated animals.
In the appearance observation at the time of dissection, wrinkles on the face, neck and back of the hind limbs were clearly confirmed in the UV-irradiated animals. The wrinkle depth was low, and the wrinkle color was observed lightly. In addition, animals with a high intake of α-lipoic acid had a moist feeling on the skin compared to the control group, and the symptom was particularly noticeable at a high concentration of UV + α-lipoic acid.

  As shown in FIG. 2, the formation of clear wrinkles was observed by ultraviolet irradiation, and the wrinkle-suppressing effect was significantly recognized in the α-lipoic acid mixed group under the same ultraviolet irradiation conditions in a concentration-dependent manner. On the other hand, in the β-carotene mixed group, the wrinkle-suppressing effect was negligible, and no concentration dependence was observed.

2. Body weight transition There was no significant difference in body weight transition between the groups.
3. Food intake There was no significant difference in food intake as with body weight changes.
4). Liver weight There was no significant difference in liver weight, and no abnormal symptoms were observed. No abnormalities were observed in other organs.

5. Skin moisture content The results are shown in FIG.
It can be inferred that the higher the numerical value of the skin moisture amount, the higher the moisture in the skin, that is, the higher the moisturizing power. It is generally known that the amount of moisture in the skin is reduced by UV irradiation. In this test, the amount of water on the intermediate observation day and the dissection day is lower in the UV irradiation group than in the control group. In the measurement of skin water content, the UV irradiation + α lipoic acid intake group showed a higher value on the intermediate observation day than the UV irradiation group. Also in the measurement of the dissection date, the UV irradiation + α-lipoic acid low concentration feeding group showed a high value although it was not significant compared with the UV irradiation group, and the UV irradiation + α-lipoic acid high concentration feeding group showed a high value in the average value. showed that.

6). Skin viscoelasticity (hardness)
As for the hardness known as an index of skin viscoelasticity, it is generally known that the higher the numerical value, the more the skin aging proceeds and the skin elasticity is lowered by UV irradiation. The result is shown in FIG. In the UV non-irradiated group, the elasticity of the UV irradiation + α lipoic acid intake group was significantly lower than that of the UV irradiation group.

7). Oxidized protein mass The results are shown in FIG. The oxidized protein mass is detected as the carbonylated protein mass. The lower the numerical value of the carbonylated protein, the smaller the accumulated amount in the organ. As is clear from FIG. 5, the amount of oxidized protein is significantly increased by UV irradiation as compared to non-irradiation, but is significantly decreased in the group administered with α lipoic acid in parallel with UV irradiation, and high purity α lipoic acid is obtained. Showed the effect of removing oxidized protein.

8). Measurement of 8-hydroxy 2′-deoxyguanosine in skin tissue The results are shown in FIGS. The skin tissue of the control group in FIG. 6 has only a slight staining of the basal layer cell nuclei, but the UV irradiation group in FIG. 7 clearly stains the upper layer nuclei than the epidermal basal cells. From this, it is clear that oxidative damage of the base has occurred. On the other hand, the skin tissue of the UV irradiation + α lipoic acid feeding group in FIG. 8 hardly undergoes staining of the epidermal tissue, and the staining level of the basal cells is not significantly different from the control group. FIG. 9 shows the result of quantifying the stained area by NIH Imaging. In contrast to the control group, the UV irradiation group has about 3-fold increased staining of 8-hydroxy 2′-deoxyguanosine, whereas the UV irradiation + α lipoic acid feeding group has an 8-hydroxy 2 ′ concentration dependently. -Suppression of deoxyguanosine production was observed.

  Based on the above results, the UV + α lipoic acid feeding group suppressed the decrease in water content against skin stress due to UV irradiation compared to the UV irradiation + β carotene feeding group and the control group. It was confirmed that the substance has the effect of preventing the generation of wrinkles and the like. In addition, the α lipoic acid intake group significantly reduced the amount of oxidized protein compared to the β carotene feeding group and the control group, and the effectiveness of the oxidized protein removal effect of α lipoic acid was shown. Furthermore, it has been clarified that skin elasticity is increased by administration of α-lipoic acid.

  The administration of α-lipoic acid to mice is as follows: when the amount of food consumed per day is 4 g, the body surface area conversion formula y = (3√x) 2 Equivalent to about 500 mg / 60 kg body weight with 1% free diet and about 50 mg / day / 60 kg body weight with 0.01% free dietary intake of α-lipoic acid. It is possible amount.

[Prescription example]
Formulation Example 1 A hard capsule containing lipoic acid as shown in Table 4.
Formulation Example 2 A soft capsule containing lipoic acid as shown in Table 4.
Formulation Example 3 A vegetable soft capsule containing lipoic acid as shown in Table 4.
Formulation Example 4 This is a soft capsule for antioxidant purposes containing lipoic acid as shown in Table 4.

It is the figure which showed the inhibitory effect of the lipid peroxidation radical by ultraviolet A wave irradiation in alpha lipoic acid presence. The ESR signal increased or decreased depending on the concentration of α-lipoic acid. It is the figure which showed the generation | occurrence | production degree of the wrinkle in UV irradiation test. The height of the graph is Means ± S. D (mean value ± standard deviation) was expressed. It is a figure showing the relationship between alpha lipoic acid feeding and skin water content in a UV irradiation test. The height of the graph is Means ± S. D (mean value ± standard deviation) was expressed. It is a figure showing the relationship between alpha lipoic acid feeding and skin elasticity (hardness) in a UV irradiation test. The height of the graph is Means ± S. D (mean value ± standard deviation) was expressed. It is a figure showing the relationship between alpha lipoic acid feeding and skin carbonylation protein in a UV irradiation test. The height of the graph is Means ± S. D (mean value ± standard deviation) was expressed. It is an immunochemical dyeing | staining figure of 8-hydroxy 2'-deoxy guanosine of the skin section of the control group in a UV irradiation test. It is an immunochemical staining figure of 8-hydroxy 2'-deoxyguanosine of the skin section of the UV irradiation group in the UV irradiation test. It is an immunochemical dyeing | staining figure of 8-hydroxy 2'-deoxyguanosine of the skin section of UV irradiation + alpha lipoic acid feeding group in a UV irradiation test. It is the figure which digitized the pigment | dye from the image uptake | capture of 8-hydroxy 2'-deoxyguanosine dyeing | staining in a UV irradiation test. The height of the graph is Means ± S. D (mean value ± standard deviation) was expressed.

Claims (9)

  A composition for removing abnormal protein, comprising α-lipoic acid.   A composition for suppressing the increase of 8-hydroxy-2'-deoxyguanosine, comprising α-lipoic acid.   An anti-aging composition comprising α-lipoic acid.   A composition for improving skin moisture content, comprising α-lipoic acid.   A composition for preventing UV damage, comprising α-lipoic acid.   A composition for suppressing dullness of the skin, comprising α-lipoic acid.   A composition for suppressing wrinkles, comprising α-lipoic acid.   A food comprising the composition according to claim 1.   The food according to claim 8, wherein the intake of α-lipoic acid is 50 mg / day or more.