JP2003064360A - Antioxidant - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an antioxidant having high antioxidizing actions and scarcely causing gastrointestinal injuries. SOLUTION: This antioxidant comprises rosemary, curcumin, astaxanthin and tocotrienol.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an antioxidant which has an excellent antioxidant effect and is less likely to cause gastrointestinal disorders.

[0002]

2. Description of the Related Art Oxygen is an essential element for animals and is used to generate energy and sustain life. On the other hand, part of the oxygen taken in the body is converted into highly toxic active oxygen. It is known that the active oxygen and free radicals cause damage to tissues in a living body and thus cause arteriosclerosis, cancer, cataract and the like. It is also closely related to aging and damages proteins, lipids, DNA, etc. in the body and is said to promote aging.

The body has a defense mechanism against active oxygen, and catalase, superoxide dismutase and glutathione peroxidase are typical examples. In recent years, protection against active oxygen has been emphasized, and as one of them, intake of food having antioxidant activity is recommended. As antioxidant components in foods, there are innumerable substances such as tocopherol, vitamin C, carotene, flavonoids, etc., and health foods that can efficiently ingest these substances are also commercially available. Although it is good for the health to have a proper diet every day, it is often difficult in the modern lifestyle, and these health foods have a great role for health.

Under these circumstances, it is important for health foods containing antioxidants to be used in a combination that can efficiently capture active oxygen and free radicals even in a small amount and has high antioxidant power. However, although there are fat-soluble and water-soluble antioxidants, the fat-soluble substances are frequently used, and ingestion may cause stomach upset and the like. In particular,
In elderly people whose antioxidant capacity is diminished and need antioxidants,
At the same time, the digestive function is also deteriorated, so that a formulation that is unlikely to cause gastrointestinal disorders is desired.

[0005]

SUMMARY OF THE INVENTION Therefore, an object of the present invention is to provide an antioxidant which has a high antioxidant power and is less likely to cause gastrointestinal disorders.

[0006]

Under such circumstances, as a result of intensive studies, the present inventors have found that among the conventionally known substances having an antioxidant action, if four specific types are used in combination. Further, they have found that an antioxidant having high antioxidative activity and less likely to cause gastrointestinal disorders such as gastric lean can be obtained, and thus completed the present invention.

That is, the present invention provides an antioxidant containing rosemary, curcumin, astaxanthin and tocotrienol.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The antioxidant of the present invention suppresses oxidation due to active oxygen and free radicals in the body, and as a result, protects against tissue damage due to oxidation reaction in the body.

The rosemary used in the present invention is obtained by extracting rosemary leaves, flowers and the like with a solvent such as ethanol, water, acetone, hexane, methyl ethyl ketone, ethyl acetate, diethyl ether and carbon dioxide. You can Rosemary is present in the total composition as dry solids of the extract in an amount of 0.05 to 30% by weight, in particular 0.5.
It is preferable to add 10 to 10% by weight. As curcumin, for example, one extracted from the rhizome of turmeric in the ginger family can be used. Curcumin is preferably added in an amount of 0.1 to 30% by weight, particularly 0.5 to 10% by weight, based on the total composition. As the astaxanthin, for example, extracts of Haematococcus alga, krill, shrimp, crab, salmon and the like can be used. Astaxanthin was added in the total composition of 0.
It is preferable to add 001 to 20% by weight, particularly 0.01 to 5% by weight. Tocotrienols are α, β, γ, σ-
Any of the isomers, or a mixture thereof,
Extracts such as wheat germ oil, palm oil, rice bran oil, malt and oat can also be used. Tocotrienol is contained in an amount of 0.01 to 50% by weight, especially 0.1 to 1% by weight in the total composition.
It is preferable to add 0% by weight.

The antioxidant of the present invention further includes lycopene, lutein, β, among the conventionally used antioxidants.
-One or two or more kinds selected from seven kinds of carotene, α-carotene, zeaxanthin, selenium and ascorbic acid can be blended in combination with the above four components, and higher antioxidant power can be obtained.

Lycopene is one of carotenoids present in red pigments of tomatoes and ripe fruits. For example, tomato extract, watermelon extract and the like can be used. Lycopene is contained in an amount of 0.001 to 20% by weight in the total composition, and particularly 0.1.
It is preferable that the content is 01 to 5% by weight. Lutein (xanthophyll) is one of carotenoid alcohols, and for example, marigold extract, egg yolk extract, pumpkin extract and the like can be used. Lutein is 0.001 to 15% by weight, especially 0.01 to 4% by weight in the total composition.
It is preferable to mix them. As β-carotene and α-carotene, for example, palm oil extract, carrot extract, Dunaliella extract and the like can be used. β-carotene and α-carotene are 0.001 to 10 in the total composition, respectively.
It is preferable to add the composition in an amount of 0.01% by weight, particularly 0.01 to 4% by weight.

Zeaxanthin is an isomer of lutein,
For example, marigold extract, mango extract, papaya extract, pumpkin extract and the like can be used. Zeaxanthin is preferably added in an amount of 0.0001 to 10% by weight, particularly 0.001 to 4% by weight, based on the total composition.
As selenium, for example, selenium-containing yeast can be used. Selenium is preferably added in an amount of 0.00001 to 0.5% by weight, particularly 0.001 to 0.1% by weight, based on the total composition. Ascorbic acid can be used as vitamin C, or can be used which is isolated and extracted from, for example, citrus fruits. Ascorbic acid is preferably added in an amount of 1 to 50% by weight, particularly 10 to 30% by weight, based on the total composition.

The antioxidant of the present invention may further contain vitamins, minerals, antioxidants other than the above, and the like within a range that does not impair the effects of the present invention.

The antioxidant of the present invention can be made into a dosage form such as a soft capsule, a liquid preparation, a granule, a tablet, etc. In any case, it can be produced by a usual method.

[0015]

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

Example 1 Antioxidant soft capsules having the composition shown below (40 tablets per capsule)
0 mg, content weight 250 mg) was prepared by a conventional method. The following components were used in the composition. (1) Carotene mix oil is a mixture of marigold extract, tomato extract, Dunaliella extract, palm oil extract and carrot extract, about 4% by weight of lycopene, about 4% by weight of lutein, β -Carotene about 2
%, Α-carotene about 1% by weight, and zeaxanthin about 0.2% by weight. (2) Selenium-containing yeast is baker's yeast (Saccharomyces Cerevisiae) cultivated in a medium containing selenium dioxide, and contains about 0.1% by weight of selenium. (3) Turmeric extract crushed the rhizome of Curcumelon ga L.,
90% by weight of curcumin extracted with acetone
contains. (4) The Haematococcus alga extract is a Hematococcus alga extracted with acetone, and contains about 5% by weight of astaxanthin. (5) Palm oil extract is palm palm (Elaeis guineensi)
The pulp of s) was extracted with hexane and contained about 40% by weight of tocotrienol. (6) The rosemary extract was obtained by drying 10 parts by weight of leaves of Rosmarinus officinalis, crushing it, and extracting it with 50 parts by weight of acetone to obtain 1 part by weight (dry extract).

(Composition) Carotene mix oil 12.5 mg Selenium-containing yeast 10 mg Turmeric extract 6 mg Haematococcus algal extract 20 mg Palm oil extract 15 mg Rosemary extract 5 mg Vitamin C 50 mg Glycerin fatty acid ester 15 mg Beeswax 15 mg 250 mg in total

Test Example 1 (Measurement of Autoxidation Inhibitory Action Using Unsaturated Fatty Acid) 4 mg of docosahexaenoic acid (DHA) was dissolved in 1 mL of ethanol. 20 μL of that is taken in a test tube, and the test substance of 0.
Add 20 μL of ethanol solution containing 35 μg or 20 μL of ethanol as a control, and add 60 at 80 ℃.
Heated for minutes. After cooling, 200 μL of 20 mM butylhydroxytoluene (BHT), 200 μL of 8% sodium dodecyl sulfate (SDS) aqueous solution and 400 μL of distilled water were added and mixed. Further, 3.2 mL of 0.8% thiobarbituric acid (TBA) solution was added and mixed, and after sealing,
Heated at 95 ° C for 15 minutes. After cooling, 4 mL of ethyl acetate was added and mixed, and the mixture was centrifuged at 2000 rpm for 10 minutes.
The ethyl acetate layer was measured at an excitation light wavelength of 515 nm and a fluorescence wavelength of 555 nm, and the resulting malondialdehyde (MD
A) The amount was calculated, and the autoxidation inhibition rate of the test substance relative to the control was determined by the following formula. The results are shown in Table 1.

[0019]

[Equation 1]

[0020]

[Table 1]

From the results shown in Table 1, the inhibitory rate of dl-α-tocopherol, which is conventionally known as an antioxidant, was 6.9%, but the antioxidant of the present invention was 84.6%.
And showed a very high inhibition rate.

Test Example 2 (Antioxidation Test Using Rabbit Erythrocyte Membrane Ghost) (1) Purification of Rabbit Erythrocyte Membrane Ghost: 100 mL of rabbit stored blood wasotonic with 10 mM phosphate buffer (Na ₂ HPO ₄ / K).
H ₂ PO ₄₎ -152mMNaCl solution, pH 7.4) 100 m
After adding L and shaking, the mixture was centrifuged at 1,500 × g for 20 minutes to remove the supernatant. Repeat this operation 3 times,
The resulting erythrocytes were hypotonic (10 mM phosphate buffer (Na ₂ HPO
100 mL of ₄ / KH ₂ PO ₄ ), pH 7.4) was added, shaken and then centrifuged at 20,000 × g for 40 minutes to remove the supernatant. To the obtained residue, 100 mL of a hypotonic solution was added, shaken, and then similarly centrifuged. This operation was repeated 3 to 5 times to obtain white or pale pink erythrocyte membrane ghost.

(2) Measurement of protein content of erythrocyte membrane ghost: Measurement was carried out by the bicinchoninic acid (BCA) method, and protein content was calculated from a calibration curve prepared using bovine serum albumin. The erythrocyte membrane ghost obtained was adjusted to 50 mg (protein amount) / mL with 50 mM phosphate buffer (Na
₂ HPO ₄ / KH ₂ PO ₄ , pH 7.4) and suspended in erythrocyte membrane ghost test.

(3) Antioxidant power measurement: antioxidant or dl-α
-Tocopherol 100mg dissolved in ethanol 100mL
Then, it was used as a test solution. Red blood cell membrane ghost 0.5 mg (tan
Mass, and 2,2'-azobis (2-
Amidinopropane) hydrochloride (AAPH) 25 μmol,
Add 25 μL of ethanol as a test solution or control.
E, 50 mM phosphate buffer (Na₂HPO_Four/ KH ₂PO_Four, PH 7.
4) Make 0.5 mL, and heat each solution at 37 ℃ for 30 minutes.
It was After heating, add 0.5 mL of each of these solutions to the test tube, 8.1.
% Sodium dodecyl sulfate (SDS) aqueous solution 0.2 mL,
Acetate buffer (pH 3.5) 1.5 mL, 0.8% butyl
50 μL of glacial acetic acid solution of droxytoluene (BHT),
0.8% thiobarbituric acid (TBA) aqueous solution 1.5m
L, 5 mM FeCl₃0.7 mL of aqueous solution was added in order. Shake well
After mixing, leave at 5 ° C for 60 minutes and then in a boiling water bath.
Heated for 60 minutes. After cooling, 1.0 mL of water, butanol-
Add 5.0 mL of pyridine mixture and shake to mix, 3,000 rp
After centrifuging at 10 m for 10 minutes, the supernatant is pumped at 515n wavelength.
m, fluorescence wavelength 553nm, TBA
The amount of reaction product is calculated as the amount of malondialdehyde (MDA)
I put it out. The standard is 1, 1, 3, 3
-Tetraethoxypropane 5 nmol / mL aqueous solution 500 μL
Was used in the same manner as above. The results are shown in Table 2.

Amount of MDA (nmol / mg Protein) = fluorescence intensity of test substance / fluorescence intensity of standard × 5 × 0.5 / 1
× 1 / 0.5

[0026]

[Table 2]

From the results shown in Table 2, the antioxidant of the present invention is M
It was confirmed that almost no DA was generated, and the oxidation of the erythrocyte membrane ghost was strongly suppressed.

Test Example 3 The load of the antioxidant on the gastrointestinal tract was evaluated. Ie age 4
Twenty men and women aged 0 to 65 years were divided into two groups, and the antioxidant of the present invention (Example 1) or a soft capsule of dl-α-tocopherol having the following composition (one capsule 400 mg, content weight 250)
mg) was taken between meals twice a day twice a day for 3 weeks. After the test was completed, a questionnaire was conducted regarding the presence / absence of a stomach leak. The results are shown in Table 3.

(Soft Capsule Composition of dl-α-tocopherol) dl-α-tocopherol 100 mg Soybean oil Appropriate amount Glycerin fatty acid ester 15 mg Beeswax 15 mg Total 250 mg

[0030]

[Table 3]

From the results shown in Table 3, the antioxidant of the present invention was
It was confirmed that stomach leaning was less likely to occur than the soft capsule of -α-tocopherol.

[0032]

The antioxidant of the present invention has high antioxidant power,
In addition, gastrointestinal disorders such as stomach upset are unlikely to occur. Therefore, it is suitable as a health food or the like for preventing tissue damage due to active oxygen and free radicals in the living body and for preventing arteriosclerosis, cancer, cataract, and the like.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 31/12 A61K 31/12 31/122 31/122 31/335 31/335 31/375 31/375 33 / 04 33/04 35/78 35/78 Q A61P 39/06 A61P 39/06 // A23L 1/302 A23L 1/302 1/304 1/304 (72) Inventor Yoko Fukazawa Shigeru Kitaminami, Yuki City, Ibaraki Prefecture 1075-2 NISSUI PHARMACEUTICAL CO., LTD.Institute (72) Inventor Tsuyoshi Kubota Ibaraki Prefecture Yuki City Kitaminami Moro 10755-2 Nissui PHARMACEUTICAL CO., LTD.Institute (72) Inventor Kozo Yatagai Ibaraki Prefecture Yuki City Kitaminami Mororo 1075- 2 In-house F-term (reference) 4B018 MD05 MD07 MD08 MD15 MD25 MD26 ME06 4C086 AA01 AA02 BA09 BA18 HA08 MA02 MA04 MA07 MA08 NA06 ZC37 ZC41 4C088 AB38 AB81 AC05 AC11 BA32 MA02 NA06 ZC37 ZC41 4C206 AA01 CA13 CA08 CA08 CA13 CA08 CB25 MA01 MA 02 MA04 MA11 NA06 ZC37 ZC41 4H025 AC05 BA04

Claims (2)

[Claims] 1. An antioxidant containing rosemary, curcumin, astaxanthin and tocotrienol. 2. The antioxidant according to claim 1, further comprising one or more selected from lycopene, lutein, β-carotene, α-carotene, zeaxanthin, selenium and ascorbic acid.