JPH09241637A - Composition for removing active oxygen free radical and removal thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a composition capable of removing active oxygen free radicals causing injurious actions such as cytotoxicity and preventing and reducing various disorders such as oxidative stress or aging by combining an active oxygen free radical scavenger with a specific component. SOLUTION: This composition comprises (A) an active oxygen free radical scavenger (e.g. preferably catechins or a tannin-polyphenol) and (B) one or more substances selected from uronic acids (e.g. D-glucuronic acid), uronides (e.g. polyuronide-polysaccharides), mucopolysaccharides (e.g. hyaluronic acid) and amino acid-peptides (e.g. an oligopeptide comprising about 2 to several amino acids).

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a highly sensitive and efficient method for promoting removal of active oxygen radicals, its composition, and use of the composition.

[0002]

2. Description of the Related Art Active oxygen radicals are simply called active oxygen or free radicals and are highly reactive atoms or molecules having unstable unpaired electrons. Further, one electron must be incorporated or given in reverse. Tries to maintain stability. Generally, superoxide (· O ₂ ^-), hydroxy radical (HO ·), hydrogen peroxide (H ₂ O _2), are called active oxygen refers to four singlet oxygen ⁽¹ O _2). In addition, hydroperoxy radical (HOO
.), Peroxy radicals (LOO.), Alkoxy radicals (LO.), Etc. are also considered to be active oxygen in a broad sense, and these are called active oxygen species and radical species.

New active oxygen radicals are secondarily and tertiaryly produced from the active oxygen radicals and increase at an accelerating rate, causing damage to cells and DNA, lipid peroxidation and the like and participating in many diseases. It has become clear in recent years. Among them, the hydroxyl radical (HO.) Is the most reactive and has been shown to be an active oxygen radical that has a great damaging effect on cell damage (Etsuo Futaki (19)
88) Mebio. , 5 , 22-26). UV rays (U
It has been confirmed that hydroxy radical (HO.) Production and its involvement are also involved in the occurrence of inflammation on skin and the like due to V).
Viral infections also produce deleterious effects of reactive oxygen radicals, which are more than necessary to maintain biological balance, as a result of an excessive immune response in the infected individual (T. Oda et al. (1989) Science, 244 , 974). -97
6).

[0004] Superoxide desmutase (SO
D) and enzymes such as catalase, and removal methods using antioxidant components such as ascorbic acid and glutathione have been widely studied from a pharmacological point of view.
Many reports have been made.

It is well known that active oxygen radicals not only adversely affect the living body but also trigger or accelerate deterioration of quality of foods and the like.

Recently, regarding so-called active oxygen radical scavenger components for removing active oxygen radicals, various flavonoids and their related components (catechin, quercetin, kaempferol, myricetin, rutin, anthocyanins, polyphenols, etc.), saponins, etc. ,
Much attention and expectation has been gathered in research on natural ingredients derived from food materials that have not been neglected until now.

[0007] For example, in flavan-3-ol type catechins, which are natural components of green tea and have a galloyl residue in the chemical structure, destruction of DNA by active oxygen radicals (T. Nakayama et al.
3) Biosci. Biotech. Bioche
m. , 57 , 174-176), lipid peroxidation (TA)
Riga et al. (1990) Agric. Biol. Che
m. , 54 , 2499-2504), oxidative cell injury (T. Nakayama et al. (1993) Bioche.
m. Pharmacol. , 45 , 265-267), each of which has an inhibitory effect, and therefore has a radical scavenger action.

However, with respect to the radical scavenger action of these catechins, a large discrepancy in effect and a contradictory negative evaluation have also been reported (for example,
F. H. Stich (1991) Mutat. Re
s. , 259 , 307-324). That is, in v
According to an in vitro experiment, while it has a radical scavenger action, it seems that active oxygen radicals that have not been completely processed or have been taken up are released in reverse.
This is because it has been observed that at some point, it rather goes around the promotion of disorders (accelerators).

[0009] Catechins have been continuously drunk as a main component of green tea by many people in a wide area such as Japan and China since ancient times, and those that have been widely used with good utility until now have been in vitro experiments. However, since the aspect as a bad guy was shown, the present inventors have made diligent efforts to elucidate the mechanism of action as the "double-edged sword" and solve the problem. It has been empirically said that individual effects are additively or synergistically enhanced by combining a plurality of antioxidant components such as vitamin C and E, β-carotene and lycopene,
Also in these components, the aspect as a “double-edged sword” similar to that of catechins has come to be known, and the mechanism of action has not yet been elucidated.

[0010]

On the other hand, the present inventors have
We have been working on the development of a method that can analyze the disappearance reaction of active oxygen radicals easily and accurately. The method is based on a highly sensitive measurement of photon emission, which is observed as if faint light emission occurs when active oxygen radicals disappear.
It has a high accuracy comparable to that of the recent ESR-trapping method and enzyme method, but is extremely simpler than these methods and is not easily affected by confusing similar reactions such as antioxidative effect or coexisting other components ( Y. Yoshi
ki et al. (1995) Phytochemistry, 3
9 , 225-229).

According to this measurement method, hydrogen peroxide (H ₂ O ₂ ) as a representative example of active oxygen radicals or hydroxy radicals (HO.) Generated by the Fenton reaction are considered to remove active oxygen radicals. As a representative example, various flavonoids and their related components were made to act in an aqueous phase system, and the intensity of photon emission was investigated. Flavonoids are a generic term for phenolic compounds having C6-C3-C6 as a basic skeleton, and are said to exceed 4,000 species. Catechin, quercetin, kaempferol, myricetin, rutin, anthocyanin, and the like have C-3 chemical structure. ,-
5, -7, and C- of the benzene ring called B-ring
Those having a hydroxyl group at the 3 ', -4', -5 'positions or further having a sugar or the like bound thereto are more likely to release photons when they are made to act on the active oxygen radical, and therefore have a removing action on the active oxygen radical. The inventors of the present invention have already announced that they tend to have a high tendency (Y. Yoshiki et al.
5) Phytochemistry, 39 , 225-2.
29).

The inventors of the present invention have developed these studies, and the above-mentioned compound (active oxygen radical scavenger), which is considered to remove active oxygen radicals, is difficult to recognize the action of removing aldehydes and amino acids, It was observed that coexistence with substances such as uronic acid (acid saccharide) significantly increased photon emission. And, it was confirmed that these remarkable increases were due to the large promotion of the removal of active oxygen radicals.

[0013] The inventors of the present invention have conducted further verifications, and found that active oxygen radical scavengers have a considerable amount of radical scavenger action capable of self-digesting active oxygen radicals. If the specific component coexists, it is presumed that the active oxygen radicals attracted by themselves are positively transferred to such a specific component, so that they are present as so-called catalyst species. Further, the above specific component alone has a poor direct working ability to process the active oxygen radical by itself, but can be easily received and processed if the active oxygen radical is catalytically delivered from the active oxygen radical scavenger. It is presumed that it is a recipient species.

According to these assumptions, more combinations of various types and concentrations of active oxygen radicals, active oxygen radical scavengers as catalyst species and specific components as acceptor species, concentration, pH, etc. are investigated, and photon emission in each is investigated. Based on the results of the measurement, the effect of scavenging active oxygen radicals was evaluated and the mechanism of action was analyzed.

As a result, it was clarified that there is a combination of an active oxygen radical scavenger and a specific component having a role of processing the active oxygen radical transferred from the active oxygen radical scavenger in the reaction of eliminating the active oxygen radical.

Furthermore, we have discovered a new law between photons and the following relational expression. Formula [P] = k [X] [Y] f (Z) where [X] is the active oxygen radical scavenger concentration, and [Y] is the active oxygen radical scavenger concentration. The concentration of a specific component that plays a role in processing the delivered active oxygen radical, [P] is the intensity of photon emission observed as if faint light emission occurs during the disappearance reaction of the active oxygen radical, and k is the photon constant (mainly (Refers to the active oxygen radical scavenger and the ability to process active oxygen radicals due to the combination of specific components having a role of processing active oxygen radicals transferred from the active oxygen radical scavenger).

[0017]

By utilizing a combination of an active oxygen radical scavenger satisfying the correlation of the above law and a specific component having a role of processing the active oxygen radical transferred from the active oxygen radical scavenger, The ability to remove active oxygen radicals is significantly enhanced, and it is possible to avoid or significantly reduce the negative side as a "double-edged sword" of the radical scavenger action that tends to occur when the active oxygen radical scavenger is alone. Found and completed the present invention.

It is an object of the present invention to provide a composition having excellent ability to treat active oxygen radicals, and a method for removing active oxygen radicals using this composition.

That is, the present invention comprises a composition containing an active oxygen radical scavenger and one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides. I will provide a.

The present invention also contains an active oxygen radical scavenger and one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides. Provided is a composition for removing radicals.

Furthermore, the present invention uses an active oxygen radical scavenger and one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides. A method for removing radicals is provided.

Further, the present invention comprises an active oxygen radical scavenger and one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides, and an antioxidant. , Anti-aging agent, quality deterioration preventing agent, antiseptic agent, antifouling agent, deodorant and freshness-retaining agent.

Furthermore, the present invention uses a composition containing an active oxygen radical scavenger and one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides. Characteristic oxidation prevention method, aging prevention method, quality deterioration prevention method,
A method for preventing decay, a method for preventing pollution, a method for deodorizing, and a method for maintaining freshness are provided.

The involvement of active oxygen radicals in oxidation, aging, quality deterioration, decay, pollution, deodorization and deterioration of freshness is
It has been pointed out as one of the important factors of these expression and malignant transformation mechanism, and as a result, health disorders, disease onset, physiological function decline, cosmetic appearance deterioration, product value decline, productivity decline,
It gives an opportunity to cause serious damage such as pollution of living environment and natural environment. This also contributes to anxiety that diseases are likely to occur and is difficult to cure, medical cost increase, and industrial loss such as loss in production and distribution and high cost. Examples where it would be desirable to have active oxygen radicals rather involved are in the cases of sterilization, disinfection and bleaching, which are very limited and in most cases have harmful consequences. The present invention provides a means for solving the problems caused by these active oxygen radicals most efficiently, at low cost, and in a wide range of applications.

In the living body, examples of sudden or large exposure to active oxygen radicals include rapid blood recirculation during surgery,
In a limited number of cases, such as a large-scale systemic burn and emphysema that rapidly emerges during diving, in most cases, a small amount becomes a burn and eventually increases and causes harm.

Metabolic processes of the living body, accumulation of waste products, exposure to direct sunlight, ultraviolet rays and radiation, contact with carcinogenic and mutagenic substances and heavy metals, burns and viral infections, cuts and There are various opportunities to activate oxygen and oxygen molecule-containing compounds in a normal state or an inactive state, such as when cells are destroyed, and further to be radicalized. Also, when exposed to foods and drinks with active oxygen radicals, smoke of cigarettes, soot exhaust gas, chlorine-based organic solvents, etc., they are not only directly radically acted by them but also active on the living body side. Generation of oxygen radicals is triggered or induced. Although the amount of active oxygen radicals produced at the beginning is extremely small and partial, it gradually and acceleratedly increases as the production continues beyond the normal range or remains unremoved after production. Then, the adverse effects as in the above example begin to appear.

Therefore, active oxygen radicals are damaged in comparison with ordinary chemical reactions (non-radical reactions) such as redox reactions and enzymatic reactions in that their production and influence increase in a chain. Different. In other words, in many cases, the process in which the physiological function deterioration, degeneration, and the like infiltrates unknowingly and then rapidly and with great damage as if they suddenly appear at some point.

Taking human diseases as an example, diabetes (particularly insulin-independent type), liver cirrhosis (particularly fatty liver type),
In cardiovascular diseases such as angina (particularly arteriosclerotic type), dementia (particularly cerebral infarction type), and malignant tumors (mainly chemical carcinogenesis), chronic oxidative stress load due to active oxygen radicals is involved in the onset mechanism. It is said to be a major factor that has been recognized in many chronic diseases. In addition, aging (aging) and deterioration of physiological functions due to exhaustion of physical strength, abnormal metabolic and respiratory abnormalities due to continuous violent movements, excessive or insufficient nutritional balance and intake, lack of sleep and exercise, and aging and degeneration or fatigue. It appears as a phenomenon. In these, it is observed that metabolic waste products are likely to be accumulated, and that the generation or residual accumulation of active oxygen radicals is increased along with poor regeneration and functional deterioration of cell tissues, skin, etc. It is a major factor.

Taking non-human animals and plants as examples, excessive production of oxygen radicals, residual accumulation or exposure not only lead to various health and growth disorders as in humans, but also As a result, in the livestock breeding, pet breeding, aquaculture and plant cultivation industries, milking volume declines, meat quality and fattening rate decline, egg laying rate decline, hair loss such as hair loss, breeding and breeding efficiency decline, pest damage damage increases. It also leads to a decrease in productivity and a decrease in commercial value, such as a decrease in appreciation value, a decrease in cultivation yield, the amount of aquaculture landing and the quality thereof.

Taking foods and feeds themselves as an example,
The production of active oxygen radicals by exposure to ultraviolet rays, mixing of raw materials bearing active oxygen radicals, etc., and the presence of hydrogen peroxide, which is a raw material of active oxygen radicals and is used for sterilization and bleaching in the manufacturing process, results in nutrition such as vitamins. Decomposition of ingredients and food ingredients, decomposition of oils and fats and emulsion disintegration for those containing and used oils, fading and discoloration for those containing pigments and used, deterioration due to wounds, etc. for fresh products, and accompanying unpleasant odors. Acceleration of deterioration of taste and texture,
Significant quality degradation will result.

Taking the environment as an example, the presence of floating substances liable or liable to have active oxygen radicals creates an environment in which an unpleasant odor or allergy or inflammation is likely to occur in the living space or working space, and water quality change is promoted. To be done.

Many of the damages as in these examples are likely to occur without the involvement of active oxygen radicals. However, in most of the cases where active oxygen radicals are involved, they are greatly promoted and accelerated with the lapse of time. In terms of increase, it is different from the case without involvement.

When the active oxygen radicals are involved in the increase in damage, conventional types of antioxidants, antioxidants, quality deterioration inhibitors, antiseptic agents, antifouling agents, deodorants and freshness-retaining agents are used. It is difficult to prevent or suppress satisfactorily, and the method for removing active oxygen radicals and the composition having the function according to the present invention are required.

The composition and the method for removing active oxygen radicals according to the present invention have a high safety and a high removal efficiency because they exhibit a great effect with an extremely small amount compared with the conventional active oxygen radical scavenger. It was difficult to solve the problem with products, but poor solubility and insolubilization due to the large amount used, deterioration of flavor and color tone, destruction of physical properties, cost increase, concern about secondary infection, etc. Many problems can be solved.

Since the method for removing active oxygen radicals according to the present invention is less influenced by pH as shown in the following examples, unlike the case of using enzymes, antioxidants, etc., it is possible to change from acidic to alkaline. Widely applicable,
Moreover, by exhibiting a high effect at room temperature, it is extremely industrially useful in a wide range of fields including the food field and pharmaceutical field.

[0036]

BEST MODE FOR CARRYING OUT THE INVENTION The active oxygen radicals to be embodied in the present invention are all applicable if the reaction of their disappearance is measured as photons and complies with the above relational expression. That is, superoxide (· O ₂ ^-), hydroxy radical (HO ·), hydrogen peroxide (H ₂ O _2), is not limited to singlet oxygen ⁽¹ O _2), hydroperoxy radicals (HOO ·), peroxy All active oxygen radicals in a broad sense, including radicals (LOO.) And alkoxy radicals (LO.), Are the subject of the present invention.

Examples of the active oxygen radical scavenger used in the present invention include catechins, tannins,
Examples include polyphenols, anthocyanins, flavonoids, saponins, and their respective related components. These ingredients are distributed in plants, and Chinese herbal medicine and folk medicine,
Not a little contained in western herbs, plant foods (beans, grains, vegetables, fruits, etc.) and animal feed (grass, bran, etc.). It has also been confirmed that many of these components, even though weak, exhibit a radical scavenger action or an antioxidant action alone. Each component will be described below.

(1) Catechins and related components thereof: Catechins are a group of flavan-3-ol skeletons having a plurality of phenolic hydroxyl groups at C ₆ -C ₃ -C ₆ . What used to be called tea tannins and classified as other polyphenol compounds was classified into an independent group. Broadly speaking, it corresponds to flavanols (flavanols) in flavonoid compounds in a broad classification. .

Among the Camellia plants, it is contained in a wide variety of tea leaves (10 to 15% in green tea), and it is sometimes called tea catechins and sometimes distinguished from other sources. Compared to some fruits such as apples, ume, grapes and olives (mostly unripe fruits with strong astringency), cacao, hops, etc., and herbal medicines such as Asenyak (Asenyaku), Rhubarb (Daio) and Keihi (Cinnamon). Many are included.

Typical components of catechins are catechin, catechin gallate, epicatechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, gallocatechin, and gallocatechin gallate, and all of them are radical scavengers. It has been confirmed that it exhibits an action or an antioxidant action.

A radical scavenger action or an antioxidant action is also recognized in gallates such as gallic acid whose B ring portion is liberated by the hydrolysis of catechins.

Both catechins and their related components are included in the active oxygen radical scavenger of the present invention.

(2) Tannin polyphenols and related components thereof: Tannins are gallic acid or its derivatives to which various phenol compounds are bound, and are a main substance group in the polyphenol compound, and hydrolyzable tannin (hydrolysable). tanni
n) and condensed tannin (condensed tann)
in).

The hydrolyzable tannin is one which produces gallic acid or ellagic acid of this bimolecular polymerization by hydrolysis.
Tannins of gallics and quintiles obtained from the worms of oak and Nurde (up to 5 gallic acids and ellagic acids are bound to one molecule of sugar; 50-70% included), Kakishibu tannins (Sibuol in which gallic acid and phloroglucin are bonded; Kakishibu) (Including 1 to 2%)
Is a typical example, and the radical scavenger action or antioxidant action has been confirmed as the main component.

Condensed tannin is a catechin having a flavan-3-ol skeleton polycondensed (mostly several molecules to several tens of tens), and is used in foods such as tea leaves and apples (especially unripe fruits). In crude drugs, it is abundantly contained in Genshosho, Uchimura (Bearberry), Keihi, Clove, etc., and its radical scavenger action or antioxidant action has been confirmed as a main component.

Tannin polyphenols and any of their related components are included in the active oxygen radical scavenger of the present invention.

(3) Anthocyanins and related components thereof: Anthocyanins have anthocyanidins (flavilium compounds) consisting of C ₆ -C ₃ -C ₆ skeleton as aglycones (non-sugar components), and various sugars ( It is a water-soluble plant pigment mainly composed of glucose, galactose, and arabinose), which is mainly present in flowers, fruits, and leaves, and exhibits red to purple to blue to black purple depending on pH and the like. Broadly, it is classified into a group of flavonoid compounds.

Depending on the type of aglycone, cyanidin glycosides (cyanine, shisonine, chrysanthemin, etc.), delphinidin glycosides (nasinine, hyacin, berylamine, etc.), belargonidin glycosides (beralgonine, flagarine, etc.), malvidin glycosides ( Oenin, negretin, etc.)
4 strains are major anthocyanins.

A radical scavenger action or an antioxidant action has been confirmed for each main component.

Any of the anthocyanins and their related components are included in the active oxygen radical scavenger of the present invention.

(4) Flavonoids and related components thereof: Flavonoids are compounds (chromone derivatives) having a flavone structure consisting of a C ₆ -C ₃ -C ₆ skeleton, and are almost free from various plants as glycosides. It is a water-soluble plant pigment that is present in all tissues and exhibits colorless to pale yellow color depending on pH and other factors. In a broad sense, it is classified into a group of flavonoid compounds.

Flavones (luteolin, abigenin, etc.), isoflavones (genistin, daidzein, etc.),
Five major flavonoids are flavanones (hesperidin, naringenin, citronetin, etc.), flavonols (rutin, quercetin, myricetin, kaempferol, etc.), and flavanars (dihydroquercetin, etc.).

A radical scavenger action or an antioxidant action has been confirmed for each main component.

Any of the flavonoids and their related components are included in the active oxygen radical scavenger of the present invention.

(5) Saponins and related components thereof: Saponins are often glycosides composed of triterpenoid-type and steroid-type aglycones (sapogenins), and classified into other glycosides. Used.

The triterpenoid saponins are widely distributed in plants and often have a weak hemolytic effect, and most of the saponins belong to this system. It is well known that foods include soybean, adzuki bean, kidney bean, spinach, sugar beet, etc., and herbal medicines include kyoto (root), licorice (rhizome), senega (Himehagi; root), kiraya (bark), etc. .

The steroidal saponin is a lily family (240
Genus 4,000 species), yam family (10 genera 650 species),
Most of the plants belonging to the digitalis genus (40 species) of the sesameaceae family are ubiquitously distributed, and many of them have a dramatic pharmacological action such as hemolytic toxicity and cardiotonic action. Of these plants, the foodstuffs are potatoes,
Edible lily (red lily bulb), leek, leek, lacquer,
Garlic and other substances whose content is extremely small and which have no other problems such as alkaloids are edible. There are many examples of utilizing the dramatic pharmacological action of crude drugs, and it is well known that they are contained in digitalis (leaf), onidokoro (rhizome), salsa (root), and chimo (root of hemlock).

A radical scavenger action or an antioxidant action has been confirmed for each main component.

Any of the saponins and their related components are included in the active oxygen radical scavenger of the present invention.

Examples of specific components used in the present invention for processing the active oxygen radicals transferred from the active oxygen radical scavenger include uronic acids, uronanides, mucopolysaccharides, amino acids / peptides, and these. Each related component is mentioned. These components are widely found in animals, plants and microorganisms. Although these components have almost no to weak radical scavenger action or antioxidant action alone, they show a large increase or promotion of radical scavenger action by combining with the above-mentioned active oxygen radical scavenger. It was These components will be described below.

(1) Uronic Acids (uronic aci)
ds) and related components thereof: Uronic acid is a general term for derivatives of sugars having a reducing carbonyl group and a carboxyl group. D-glucuronic acid, D-galacturonic acid, D-mannuronic acid, L-iduronic acid and the like are representative ones that naturally exist.

Further, these salts (--Na, --K, --C)
a, —Mg salt and the like; for example, D-glucuronic acid sodium salt), amide state (—NH ₂ ; for example, D-glucuronic acid amide), lactone form (1,4-monolactone, 6,
3-mono-lactone, 1,4-6,3-dilactone and the like; for example, D-glucuronolactone, sugar acids (for example, D-glucosugar acid, D-glucosugar acid lactone, L-gulonic acid, L -Gulono-γ-lactone), oligo and polyuronic acids (acidic oligosaccharides and acidic polysaccharides; for example, poly-D-galacturonic acid, which is a skeletal component of pectic acid, and main components of brown algae such as kelp, L-glucuronic acid and D -Alginic acid consisting of mannuronic acid) and the like.

Both uronic acids and their related components are included in the specific components of the present invention, which have a role of treating active oxygen radicals transferred from the active oxygen radical scavenger.

(2) Uronides
And their related components: Uronide is a combination of uronic acid and aglycone (non-sugar component) or other sugar. In their biosynthesis, UDP-D-glucuronic acid serves as a precursor, and an enzymatically catalyzed reaction causes the D-glucuronic acid residue to bind to an aglycone or the like with a uronide,
Also, isomerization to other uronic acids such as D-mannuronic acid has been carried out.

Glucuronic acid glycosides (eg flavonoid-type or triterpenoid-type glucuronides) containing a polycyclic compound as an aglycone, D-glucuronic acid or a plant gum or a viscous substance in which its polymer is bound to other sugar chains such as hemicellulose. Pesticides (for example, polyuronide polysaccharides such as gum arabic) are typical uronans widely distributed in the plant kingdom, such as vegetables, seeds and crude drugs.

Any of the uronates and their related components are included in the specific components of the present invention that have the role of treating the active oxygen radicals passed from the active oxygen radical scavenger.

(3) Mucopolysaccharide
(Ccharides) and their related components: Mucopolysaccharides are widely present in the animal kingdom mainly in connective tissues such as bone, cartilage, skin, cell membranes, blood vessels, organs and collagen, and hexosamine (N-acetyl-D-glucosamine or N-).
Acetyl-D-galactosamine) and, with a few exceptions, most are uronic acids (D-glucuronic acid or L-iduronic acid), which are polysaccharides mainly composed of a disaccharide repeating structure. Most of them are acidic due to the sulfate group bound to hexosamine and the carboxyl group of uronic acid, and are also called acidic mucopolysaccharides.

The most typical mucopolysaccharides having uronic acid as a constituent sugar include hyaluronic acid (D-glucuronic acid + N-acetyl-D-glucosamine) and chondroitin sulfate (D-).
Glucuronic acid + N-acetyl-D-galactosamine),
Dermatan sulfate (L-iduronic acid + N-acetyl-D-
Galactosamine), hevalan sulfate (D-glucuronic acid +
There are 5 types of N-acetyl-D-glucosamine), heparin (a repeating structure of D-glucuronic acid + N-acetyl-D-glucosamine and L-iduronic acid + N-acetyl-D-glucosamine), and these are mucopolysaccharides. Account for most of the.

Most mucopolysaccharides in the living body of animals exist as proteins and partly as peptide bonds (proteoglycans and peptidoglycans), and may be enzymatically decomposed into mucooligosaccharides.

Any of the mucopolysaccharides having uronic acid as a constituent sugar and their related components are included in the specific component of the present invention having a role of treating the active oxygen radicals transferred from the active oxygen radical scavenger. .

(4) Amino acids / peptides and their related components: Among amino acids, 23 kinds of constituent amino acids involved in the formation of proteins / peptides, and existing in a free state or as a constituent component of a specific compound without forming them About 20 types of special amino acids, including about 50 types in total, are known. In the present invention, various constituent amino acids such as glycine and alanine, ornithine, citrulline, and γ-
When special amino acids such as aminobutyric acid are combined with the components of the active oxygen radical scavenger, a strong radical scavenger action is exerted in each case, and the active oxygen radicals transferred from the active oxygen radical scavenger are absorbed. A high function as a specific component having a processing role was confirmed in these amino acids. Similarly, other special amino acids such as β-alanine and betaine were confirmed to have high functions as specific components having a role of processing the active oxygen radicals transferred from the active oxygen radical scavenger.

In the action of the radical scavenger as a specific component having a role of processing the active oxygen radicals transferred from the active oxygen radical scavenger, constituent amino acids and special amino acids, individual amino acids in each, and acidic / neutral / alkaline Since no clear difference in superiority or inferiority was observed between the respective environmental pH values, the properties of the carboxyl group or amino group, which is a common basic structure as an amino acid, and the properties of the ampholyte are largely involved, and the properties of the side chains that differ depending on each Seemed to contribute less.

The properties derived from this common basic structure are 2 to
It seems that an oligopeptide consisting of several amino acids can be expected sufficiently. In addition, depending on the type and three-dimensional structure of the constituent amino acids, it may be possible to have a peptide in which more amino acids are connected.

Any of the amino acids / peptides and their related components are included in the specific component of the present invention having a role of processing the active oxygen radicals transferred from the active oxygen radical scavenger.

The combination of the above-mentioned active oxygen radical scavenger and the specific component having a role of treating the active oxygen radicals transferred from the active oxygen radical scavenger markedly increases (or promotes) the radical scavenger action, and the active oxygen radical scavenger is activated. 1,000 times or more compared with the case of only (Comparison with photon constant k value / Difference of 3 or more when converted with log k value)
It was possible in the present invention to bring out the effect (measurement is by photon analysis method).

In carrying out the method according to the present invention, uronic acids, uronates, mucopolysaccharides and amino acids, which are specific components having a role of treating active oxygen radical scavengers and active oxygen radicals transferred from the active oxygen radical scavengers in advance. -In addition to being used as a so-called composition in which one or more kinds of substances selected from peptides are combined, an active oxygen radical scavenger or uronic acids, uronates, mucopolysaccharides and amino acids / peptides The above relational expression [P] = k [X] [Y] f by supplementing either or both of one or more substances selected from
It can also be performed by a so-called complementary method that satisfies (Z).

The active oxygen radical scavenger used in the present invention and one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides, and combinations thereof, require treatment. The type of active oxygen radicals to be used, and the elimination reaction thereof are measured as photons and are selected according to the above-mentioned relational expression according to the industrial application field,
There is no particular limitation. Although the photon constant k reflects the magnitude of the radical scavenger action promoting effect, the lower limit and the upper limit are set uniformly because the criteria required for each case, such as the purpose of use and target, differ. That is not appropriate.

Vitamin C and Vitamin E, which are generally known as antioxidants, can be used as an active oxygen radical scavenger, or a specific component having a role of processing the active oxygen radicals transferred from the active oxygen radical scavenger. No photon emission was observed, and therefore it was not a photon-type active oxygen radical scavenger satisfying at least the above relation.

[0079]

INDUSTRIAL APPLICABILITY The method and composition for combining the active oxygen radical scavenger with one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides according to the present invention are active oxygen radicals. In contrast, a wide pH range from acidic to alkaline
Excellent removal function in the range and at room temperature.

Therefore, the composition of the present invention and the method for removing active oxygen radicals are induced by the involvement of active oxygen radicals in the physiological activity of humans, non-human animals, plants, fermenting microorganisms, cultured cells and other living organisms. For prevention or improvement of various disorders such as oxidative stress and aging that are easily affected, and also in breeding, aquaculture, cultivation, fermentation, culture, processing, preservation, etc. It is expected to be used especially in the fields where it is required to prevent quality deterioration and activity deterioration such as deterioration of freshness, deterioration of efficacy and efficiency.

Therefore, foods, feeds, medical and medical supplies, quasi-drugs, cosmetics, detergents, deodorants, hygiene products, clothing products, freshness-maintaining materials and packaging containers, animal breeding, aquaculture,
Most useful in various industrial fields such as plant cultivation, fermentation and culture.

Further, regarding some specific forms which can be provided to the user so that the usefulness of the present invention can be easily exhibited and utilized, some examples are shown from the product group in these industries. Is.

For example, in the food field, the composition of the present invention is used as an active ingredient for improving the quality and shelf life of processed foods and maintaining freshness in fresh foods as a food additive having a high function of removing active oxygen radicals. By providing foods for specified health use and health foods, they can be utilized for health maintenance and disease prevention. In the feed field, it can be used as a feed additive and pet food for health management and improving feed efficiency and productivity.

In the fields of pharmaceuticals, quasi drugs, cosmetics, and medical devices as prescribed in each item of Article 2 of the Pharmaceutical Affairs Law, they can be used as pharmaceutical additives or cosmetic additives to improve the quality of the formulation. In addition, it can be used as an active ingredient for treating and preventing diseases, improving physical condition, maintaining and improving beauty, and ensuring hygiene and a comfortable environment. Among them, in pharmaceuticals, therapeutic drugs for diseases that cause onset or delayed recovery or worsening of symptoms due to the involvement of active oxygen radicals, and for general use, nourishing tonic health drugs, gastrointestinal drugs, cold remedies, drugs for oral rhinitis, and integuments. Particularly useful in the field of medicinal products. For quasi-drugs, medicated toothpaste, mouthwash, medicated cosmetics, hair preparation, bath preparation,
In the field of axillary odor control agents and physiological treatment products, and in cosmetics, hair cosmetics, hair wash cosmetics, lotions, cream emulsions, packs, foundations, lipsticks,
It is highly useful in the fields of facial cleansers, soaps and toothpastes.

In addition to the above examples, it is possible to provide the composition of the present invention and the method for removing active oxygen radicals in a concrete form in various ways. It is not limited.

[0086]

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.

In each of the examples, the measurement conditions and analysis methods described below were followed.

1. Concentration : (1) Active oxygen radical (here, H ₂ O ₂ ) ... Final concentration at the time of measurement is 0.01 to 20 mM (2) Active oxygen radical scavenger (here (−)-epigallocatechin) ... -The final concentration at the time of measurement is 0.01 to 20 mM (3) Specific components (here, amino acids and saccharides) that play a role in processing the active oxygen radicals transferred from the active oxygen radical scavenger ... Final concentration at the time of measurement Is 0.01
˜20 mM Various combinations of these three at various concentrations were provided for measurement.

2. pH : (1) Acidic is 50 mM citric acid-HCl at pH 2.6.
Buffer solution (containing 50% methanol) (2) Neutral: 25 mM phosphate buffer solution (pH 5) (5%
(0% methanol content) (3) Alkaline is 25 mM Na ₂ B _{4 of} pH 9.0
O ₇ -HCl buffer (containing 50% methanol) All were (−)-epigallocatechin (hereinafter, referred to as “EG
Abbreviated as "C") to maintain the complete dissolution of
Contains 0% (the active oxygen radicals used and the specific component that plays a role in processing the active oxygen radicals delivered from the active oxygen radical scavenger are completely dissolved without methanol), and the solution is microfiltered (pore size 0.22). Micron) to remove contaminants that interfere with the measurement and ensure a high degree of clarity.

3. Temperature : In all cases, room temperature (23 ° C
At a fixed place).

4. Method of measuring photon intensity P : Photon emitted from the reaction mixture as if emitting faint light,
It measured using the photon measurement spectrophotometer with a filter (Tohoku Denshi Kogyo Co., Ltd. CLD-110 type | mold). This equipment is equipped with a micro pump (Waters 510 type) and a micro injector (Waters).
U6K type), and a specific component (uronic acids, uronans, mucopolysaccharides) that plays a role in processing active oxygen radicals, active oxygen radical scavengers, and active oxygen radicals transferred from active oxygen radical scavengers in a flow cell. And one or more substances selected from amino acids and peptides) were mixed, and the liquid flow was immediately stopped so that the photon release immediately after mixing could be measured with time. The lattice scattered light was detected by a phototube with an image sensor in the measurement system. Since the photon emission is observed in a wide range of wavelengths of 300 to 650 nm, the number of counts detected from all the wavelengths is automatically integrated, and the maximum emission peak value is defined as the photon intensity P.

[0092]

Example 1 A combination of H ₂ O _{2 as} an active oxygen radical, EGC as an active oxygen radical scavenger, and amino acids as specific components having a role of processing an active oxygen radical transferred from an active oxygen radical scavenger. In p, acidic, neutral, and alkaline
The photon constant k at H was measured as described above.

Amino acids (both L-type) are glycine,
16 kinds of alanine, leucine, isoleucine, valine, homoserine, threonine, methionine, cysteine, phenylalanine, proline, histidine hydrochloride, arginine hydrochloride, ornithine hydrochloride, citrulline and γ-aminobutyric acid were used.

No photon emission was observed for any of the 16 amino acids, either alone or in combination with EGC in the absence of H ₂ O ₂ . Also, EGC
Even in combination with H ₂ O ₂ in the absence, photon emission was only weak. However, when the three were combined, photons were strongly expressed, and a large promotion of the active oxygen radical scavenger action was observed.

Table 1 shows the photon constant k at pH 2.6, 7.0 and 9.0. All 16 kinds of amino acids showed high values around 3 (however, log k value) at each pH. Therefore, 16 kinds of amino acids in a reaction liquid mixture system composed of active oxygen radicals, active oxygen radical scavengers, and specific components having a role of processing active oxygen radicals transferred from active oxygen radical scavengers. Was identified as acting as a specific component for processing the active oxygen radicals transferred from the active oxygen radical scavenger.

[0096]

[Table 1]

[0097]

Example 2 Of H ₂ O ₂ (active oxygen radical), EGC (active oxygen radical scavenger), neutral and acidic saccharides (specific component having a role of processing active oxygen radicals transferred from the active oxygen radical scavenger) Acidic, neutral, and alkaline p in each of the three combinations
The photon constant k at H was measured in the same manner as in Example 1.

Sugars (both D-type) are glucose, sucrose, glucuronic acid, sodium glucuronate,
Six types of glucuronic acid amide and glucuronolactone were used.

[0099] In the neutral sugar glucose and sucrose is, these components only, combination of of H ₂ O ₂ under EGC absence combination with EGC under H ₂ O ₂ absent, also 3
No photon emission was observed and no active oxygen radical scavenger action was observed in any of the combinations.

Acid sugar (also referred to as uronic acid) and its related components glucuronic acid, sodium glucuronate,
With glucuronic acid amide and glucuronolactone, no photon emission was observed when these components alone were combined with EGC in the absence of H ₂ O ₂ . Further, even in the combination with H ₂ O ₂ in the absence of EGC, the photon emission was only weak. However, when the three were combined, photons were strongly expressed, and a large promotion of the active oxygen radical scavenger action was observed.

In Table 2, the photon constant k at pH 2.6, 7.0 and 9.0 is shown. For each of the four types of acidic sugar and its related components, at around pH 3 (however,
The gk value) was high.

Therefore, it was used in a reaction mixture system composed of active oxygen radicals, active oxygen radical scavengers, and specific components having a role of treating active oxygen radicals transferred from the active oxygen radical scavengers. It was recognized that all of the four types of acidic sugars and the related components thereof act as specific components having a role of processing the active oxygen radicals transferred from the active oxygen radical scavenger.

[0103]

[Table 2]

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display location A61K 38/00 A61K 45/06 45/06 B01J 20/22 Z B01J 20/22 C09K 3/00 S C09K 3/00 A61K 37/02

Claims (34)

[Claims] 1. An active oxygen radical scavenger, uronic acids, uronanides, mucopolysaccharides and amino acids.
A composition comprising one or more substances selected from peptides. 2. The composition according to claim 1, wherein the active oxygen radical scavenger is one or more substances selected from catechins, tannin / polyphenols, anthocyanins, flavonoids and saponins. 3. An active oxygen radical scavenger and uronic acids, uronans, mucopolysaccharides and amino acids.
A composition for removing active oxygen radicals, comprising one or more substances selected from peptides. 4. The active oxygen radical scavenger according to claim 3, wherein the active oxygen radical scavenger is one or more substances selected from catechins, tannin / polyphenols, anthocyanins, flavonoids and saponins. Composition. 5. An active oxygen radical scavenger and uronic acids, uronanides, mucopolysaccharides and amino acids.
A method for removing active oxygen radicals, which comprises using one or more substances selected from peptides. 6. The removal of active oxygen radicals according to claim 5, wherein the active oxygen radical scavenger is one or more substances selected from catechins, tannin / polyphenols, anthocyanins, flavonoids and saponins. Method. 7. An active oxygen radical scavenger and uronic acids, uronanides, mucopolysaccharides and amino acids.
An antioxidant comprising one or more substances selected from peptides. 8. The antioxidant according to claim 7, wherein the active oxygen radical scavenger is one or more substances selected from catechins, tannin / polyphenols, anthocyanins, flavonoids and saponins. 9. An active oxygen radical scavenger, uronic acids, uronanides, mucopolysaccharides and amino acids.
A method for preventing oxidation, which comprises using a composition containing one or more substances selected from peptides. 10. An active oxygen radical scavenger selected from catechins, tannin / polyphenols, anthocyanins, flavonoids and saponins.
The antioxidant method according to claim 9, which is one kind or two or more kinds of substances. 11. An active oxygen radical scavenger,
An anti-aging agent comprising one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides. 12. An active oxygen radical scavenger selected from catechins, tannin polyphenols, anthocyanins, flavonoids and saponins.
The anti-aging agent according to claim 11, which is one kind or two or more kinds of substances. 13. An active oxygen radical scavenger,
A method for preventing aging, which comprises using a composition containing one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides. 14. An active oxygen radical scavenger selected from catechins, tannin polyphenols, anthocyanins, flavonoids and saponins.
14. The method for preventing aging according to claim 13, which is one kind or two or more kinds of materials. 15. An active oxygen radical scavenger,
An agent for preventing quality deterioration, which comprises one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides. 16. An active oxygen radical scavenger selected from catechins, tannin / polyphenols, anthocyanins, flavonoids and saponins.
The quality deterioration inhibitor according to claim 15, which is one kind or two or more kinds of substances. 17. An active oxygen radical scavenger,
A method for preventing quality deterioration, which comprises using a composition containing one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides. 18. An active oxygen radical scavenger selected from catechins, tannin polyphenols, anthocyanins, flavonoids and saponins.
18. The method for preventing deterioration of quality according to claim 17, wherein the method is one kind or two or more kinds of materials. 19. An active oxygen radical scavenger,
An antiseptic agent, which comprises one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides. 20. The active oxygen radical scavenger selected from catechins, tannin / polyphenols, anthocyanins, flavonoids and saponins.
The antiseptic agent according to claim 19, which is one kind or two or more kinds of substances. 21. An active oxygen radical scavenger,
A method for preventing decay, which comprises using a composition containing one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides. 22. A reactive oxygen radical scavenger selected from catechins, tannin / polyphenols, anthocyanins, flavonoids and saponins.
22. The method for preventing decay according to claim 21, which is one kind or two or more kinds of substances. 23. An active oxygen radical scavenger,
An antifouling agent comprising one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides. 24. A reactive oxygen radical scavenger selected from catechins, tannin / polyphenols, anthocyanins, flavonoids and saponins.
The antifouling agent according to claim 23, which is one kind or two or more kinds of substances. 25. An active oxygen radical scavenger,
A method for preventing pollution, which comprises using a composition containing one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides. 26. A reactive oxygen radical scavenger selected from catechins, tannin / polyphenols, anthocyanins, flavonoids and saponins.
26. The pollution control method according to claim 25, which is one kind or two or more kinds of substances. 27. An active oxygen radical scavenger,
A deodorant comprising one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides. 28. The active oxygen radical scavenger selected from catechins, tannin polyphenols, anthocyanins, flavonoids and saponins.
The deodorant according to claim 27, which is one kind or two or more kinds of substances. 29. An active oxygen radical scavenger,
A deodorizing method comprising using a composition containing one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides. 30. An active oxygen radical scavenger selected from catechins, tannin / polyphenols, anthocyanins, flavonoids and saponins.
30. The deodorizing method according to claim 29, which is one kind or two or more kinds of substances. 31. An active oxygen radical scavenger,
A freshness-retaining agent containing one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides. 32. A reactive oxygen radical scavenger selected from catechins, tannin / polyphenols, anthocyanins, flavonoids and saponins.
The freshness-retaining agent according to claim 31, which is one kind or two or more kinds of materials. 33. An active oxygen radical scavenger,
A method for maintaining freshness, which comprises using a composition containing one or more substances selected from uronic acids, uronanides, mucopolysaccharides and amino acids / peptides. 34. The active oxygen radical scavenger selected from catechins, tannin / polyphenols, anthocyanins, flavonoids and saponins.
34. The freshness keeping method according to claim 33, which is one kind or two or more kinds of materials.