JPH0967228A - Active oxygen-eliminating agent and composition containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an active oxygen-eliminating agent excellent in an eliminating action on active oxygen generated in a living body, high in safety, and capable of being used for foods, cosmetics, etc. SOLUTION: This active oxygen-eliminating agent comprises an oligogalacturonic acid-transition metal complex of the formula (M is a transition metal ion; (n), (o), (p) are each 0 or a natural number). The oligogalacturonic acid is obtained by hydrolyzing pectin with an enzyme, ultra-filtering the hydrolysate, and subsequently purifying the filtered product by a gel filtration method, etc., into fractions having different polymerization degrees, respectively, preferably a fraction having a polymerization degree of 1-5. The obtained oligogalacturonic acid is mixed with a transition metal (e.g. Fe) salt such as a hydrochloride or a nitrate to obtain the objective active oxygen-eliminating agent. The compound of the formula and the transition metal are composed in a ratio of 1:2 to 1:6. The active oxygen-eliminating agent is preferably compounded to a cosmetic in an amount of 0.01-10wt.%, and the agent is orally administered at a daily dose of 10-100mg for an adult divided in one to several portions or injected at a dose of 5-500mg in medicines.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an active oxygen scavenger and a composition containing the same, such as an external preparation for skin and food.

[0002]

2. Description of the Related Art Generally, the effects of active oxygen on the living body include cross-linking of collagen fibers, partial cleavage of DNA helix, and tissue damage due to generation of chained radicals, resulting in wrinkles and elasticity. Loss of skin, aging of skin and body such as hair loss, induction of allergic reaction such as bronchial asthma and inflammation due to histamine release, damage of smooth muscle in myocardial infarction which is an ischemic disease, deterioration of diseases such as liver damage, or It is known that destruction of brain tissue induces dementia and the like. Furthermore, although the detailed cause is unknown, it is said that active oxygen is involved in the onset of rheumatism.

Therefore, it is very important to suppress the generation of active oxygen in the living body in treating or preventing these diseases. Therefore, the active oxygen generated in the living body has hitherto been known. The search for a substance that has the effect of eliminating erythema has been widely carried out.

[0004] For example, as a drug having such an action, conventionally used are those derived from natural products such as fat-soluble tocopherol (vitamin E),
Examples include water-soluble ascorbic acid (vitamin C), and synthetic compounds include BHT (butylhydroxytoluene),
BHA (butyl hydroxyaniline) and the like can be mentioned.
However, these drugs do not have sufficient active oxygen scavenging action, and in synthetic compounds, both BHT and BHA are suspected to be carcinogenic, and it cannot be said that they are practical as active oxygen scavengers. It was

Recently, many attempts have been made to obtain a substance having an active oxygen scavenging action from a crude drug extract in search of sufficient medicinal effect and safety, for example, JP-A-60-224629. No. JP-A-61-24522,
JP-A-2-193930, JP-A-2-243632
No. 2, JP-A-2-264727, JP-A-3-15362
No. 9, JP-A-3-221587, JP-A-4-6934.
3, JP-A-4-202138, and JP-A-4-2470.
No. 10, etc. all utilize a substance having an active oxygen scavenging action derived from a crude drug. However, although there is no problem in safety with these crude drug extracts, from the viewpoint of active oxygen scavenging action, sufficient extracts have not yet been obtained.

[0006] Furthermore, attempts have been made to eliminate active oxygen generated in the living body by administering superoxide desmutase (SOD), one of the enzymes in the living body, but SOD is a protein. However, its oral administration is not possible because it is not only difficult to obtain, but it is also digested, and its half-life in blood is short and unsatisfactory even when administered by injection.

On the other hand, it has not been known at all that a complex of oligogalacturonic acid and a transition metal has a function of eliminating active oxygen. Furthermore, there has been no attempt to use it for the prevention or treatment of various diseases as described above, prevention of aging, or improvement by incorporating it into cosmetics, pharmaceuticals, foods, or the like. Also, it is well known that transition metals and their salts serve as oxidation catalysts, but it is unimaginable that such complexes containing transition metals have the opposite effect of scavenging active oxygen. Was that.

[0008]

SUMMARY OF THE INVENTION The present invention has been made in view of such a situation, and has an action of sufficiently eliminating active oxygen generated in the living body and having high safety. It is an object to provide an erasing agent and a composition containing the same.

[0009]

[Means for Solving the Problems] In order to solve the above problems, the present inventors extensively screened compounds derived from various plants using an active oxygen scavenging activity as an index, and as a result, a complex of oligogalacturonic acid and a transition metal was obtained. Was found to have an excellent active oxygen scavenging effect, and the present invention has been completed.

Hereinafter, the present invention will be described in detail.

(1) Active Oxygen Scavenger of the Present Invention The active oxygen scavenger of the present invention comprises a complex of oligogalacturonic acid represented by the general formula (I) and a transition metal. Of these, oligogalacturonic acid can be easily obtained by hydrolyzing pectin with an enzyme and separating it by ultrafiltration. Further, if this product is purified by gel filtration or the like, it can be separated and purified for each degree of polymerization.

[0012]

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The active oxygen scavenger of the present invention can be obtained by mixing the oligogalacturonic acid thus obtained with a salt of a transition metal such as hydrochloride or nitrate in a solution. The transition metal is not particularly limited, but iron, manganese, cobalt,
Nickel, copper, etc. can be exemplified, and among these, iron is most preferable. The composition ratio (equal ratio) of oligogalacturonic acid and transition metal in the complex is preferably 1: 2 to 1: 6, more preferably 1: 3 to 1: 5. This is because if it is biased toward either side, the active oxygen scavenging action is impaired.

(2) Composition Containing Active Oxygen Scavenger of the Present Invention The composition of the present invention contains the above active oxygen scavenger compounded by a conventional method. Examples thereof include foods and beverages.

When the active oxygen scavenger of the present invention is formulated into cosmetics, the cosmetic dosage form is not particularly limited, but basic cosmetics such as lotions, emulsions, creams, foundations, undermake-ups, and white powders. Make-up fees such as
Hair tonics, hair liquids, shampoos, rinses and other cosmetics for hair can be exemplified. These formulations can be obtained by formulating the active oxygen scavenger of the present invention and optional components for cosmetics by a conventional method. As the optional component, hydrocarbons such as petrolatum and liquid paraffin, esters such as jojoba oil and carnauba wax, triglycerides such as olive oil and beef tallow, alcohols such as stearyl alcohol and behenyl alcohol, fatty acids such as stearic acid and behenic acid. , Glyceryl monostearate, polyoxyethylene stearic acid, polyoxyethylene hydrogenated castor oil, nonionic surfactants such as polyoxyethylene stearyl ether, anionic surfactants such as soaps and sulfates, cationic surfactants such as stearylamine Agents, amphoteric surfactants such as alkylbetaine, polyhydric alcohols such as glycerin and propylene glycol, thickeners, preservatives, ultraviolet absorbers, and antioxidants. Furthermore,
A substance having an active oxygen scavenging action such as SOD may be blended with the active oxygen scavenger of the present invention.

In cosmetics, the active oxygen scavenger of the present invention eliminates active oxygen to prevent wrinkles, hair loss, and the generation of unpleasant odors such as body odor. Have an effect. The preferred content of the active oxygen scavenger of the present invention in cosmetics is 0.01 to 10% by weight, at which this effect is effectively exhibited. That is,
If the amount is less than 0.01%, these effects may not be exhibited, and if the amount is more than 10% by weight, the effect may reach the ceiling and it is not economical. More preferable content is 0.1
~ 1% by weight.

When the active oxygen scavenger of the present invention is formulated into a pharmaceutical product, the dosage form is not particularly limited, and for example, various commonly used agents such as injections, powders, granules, tablets, capsules and liquids. It can be formulated into a form according to a usual method together with optional ingredients usually used in pharmaceuticals such as an excipient, a binder, a disintegrating agent, a lubricant, a flavoring agent, a bulking agent, a clothing agent and the like.

Regarding the dose of the above-mentioned medicine, it depends on the type of disease, symptoms, age of patient, weight, etc.
As the amount of this compound per person per day, 10 mg to 100
Oral administration of 0 mg in 1 to several divided doses or 5
It is suitable to administer mg to 500 mg by injection. Examples of the method for administering the injection include intravenous administration, intraarterial administration, intraportal administration, intraperitoneal administration, intramuscular administration, and subcutaneous administration.

When the active oxygen scavenger of the present invention is added to foods, it is possible to add it to various foods together with optional components used in the foods without particular care. Examples thereof include candy, sweets such as gummy and jelly, drinks such as juice, and staple foods such as bread. Although the blending amount varies depending on the type of food, it is preferably 0.01 to 10% by weight, more preferably 0.1 to 1% by weight, which can expect an active oxygen scavenging action without impairing the taste of food.

(3) Action The active oxygen scavenger of the present invention and the composition containing the same are
Due to the excellent active oxygen scavenging action of the present compound and / or its salt, which is its active ingredient, it is said that active oxygen as described above is involved, formation of wrinkles, generation of body odor, hair loss, inflammation, and elderly people. It is effective for treating various diseases such as ischemic diseases such as sexual dementia and myocardial infarction, allergic diseases, liver disorders, rheumatism, and improving aging of the living body such as skin.

The active oxygen scavenger of the present invention and the composition containing the same can be effectively used for the prevention of the above-mentioned diseases and aging of living body. This is because by preliminarily presenting the present compound having an active oxygen scavenging action and / or a salt thereof in the living body, the active oxygen generated in the living body can be quickly erased and detoxified.

[0022]

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Example 1 (candy) A candy was prepared according to the prescription of Table 1. That is,
Component A is heated and dissolved at 150 ° C, cooled to 120 ° C, and then B
After adding the ingredients and stirring, the homogenized product was molded and cooled to obtain a candy.

[0023]

[Table 1]

Example 2 (Gummy) The components shown in Table 2 were dissolved by heating at 110 ° C. and swollen separately B
The ingredients were added, and further the ingredient C was added, and the mixture was poured into a mold, left for one day and night, and then removed from the mold to obtain a gummy.

[0025]

[Table 2]

Example 3 (Juice) The components shown in Table 3 were thoroughly solubilized by stirring, sterilized, aseptically filled, and sealed to produce juice.

[0027]

[Table 3]

Example 4 (Hot cake) The ingredients in Table 4 were mixed well and baked in an oiled frying pan to prepare a hot cake.

[0029]

[Table 4]

Example 5 (Granule) Ingredient A in Table 5 was mixed well and 100 ml of 20%
The component B dissolved in an aqueous ethanol solution was gradually added while kneading to increase the particle size. This was blow-dried at 40 ° C. for 2 days, sieved, and sized to obtain a granule.

[0031]

[Table 5]

Example 6 (Injection) The components shown in Table 6 were dissolved, filtered, sterilized, and aseptically filled into an ampoule and sealed to obtain an injection.

[0033]

[Table 6]

Example 7 (Toilet lotion) The components shown in Table 7 were solubilized with stirring at room temperature to obtain a lotion.

[0035]

[Table 7]

Example 8 (Emulsion) A, B, and C in Table 8 were heated and dissolved at 80 ° C., B was added to A, and C was added to coarsely emulsify, and the mixture was uniformly emulsified with a homogenizer and cooled to obtain an emulsion. Obtained.

[0037]

[Table 8]

Example 9 (hair tonic) The components of Table 9 were solubilized with stirring at room temperature to obtain a hair tonic.

[0039]

[Table 9]

Example 10 (Shampoo) A shampoo was prepared according to Table 10 below. That is, the prescription ingredients were weighed, dissolved by heating, and cooled to obtain a shampoo.

[0041]

[Table 10]

[0042]

The present invention will be described in more detail with reference to the following examples, but it goes without saying that the present invention is not limited to these examples.

Example 1 Production Example To 1 Kg of pectin, 5 liters of water and 5 g of pectinase were added and stirred at 37 ° C. for 2 hours for hydrolysis. This was ultrafiltered to obtain 123 g of oligogalacturonic acid (crude solution). This is gel filtered and concentrated to give 30 galacturonic acid.
g, dimer 11 g, trimer 8 g, tetramer 5 g, pentamer 7
g, hexamer 5 g, heptamer 4 g, and octamer 3 g were obtained. The same weight of ferrous chloride was added to these as a 5% aqueous solution, and the mixture was stirred at room temperature for 1 hour and then concentrated to give 59 g of each complex (iron oligogalacturonic acid complex,
Active oxygen agent 1), 21 g (oligogalacturonic acid dimer iron complex, active oxygen scavenger 2), 16 g (oligogalacturonic acid trimer iron complex, active oxygen scavenger 3), 8 g (oligogala) Caturonic acid tetramer iron complex, active oxygen scavenger 4), 13 g (oligogalacturonic acid pentamer iron complex, active oxygen scavenger 5), 10 g (oligogalacturonic acid hexamer iron complex, activity Oxygen scavenger 6), 8 g (oligogalacturonic acid heptameric iron complex, active oxygen scavenger 7), 5 g (oligogalacturonic acid octamer iron complex, active oxygen scavenger 8) were obtained.

Example 2 Acute Toxicity Test (Intraperitoneal Administration) One group of 5 ICR male mice (body weight 25 to 30 g) was intraperitoneally injected with the eight active oxygen scavengers obtained in Example 1 into physiological saline. The product dissolved in water was administered at a rate of 1000 mg / Kg. 14 days after the administration, life or death was judged, but no death was observed in any group. Therefore, the LD50 value by intraperitoneal administration is estimated to be higher than 1000 mg / Kg. Therefore, it is understood that the oligogalacturonic acid iron complex which is the active oxygen scavenger of the present invention is excellent in safety.

Example 3 Acute Toxicity Test (Oral Administration) Six ICR male mice (body weight: 25 to 30 g) per group were orally administered, and the eight active oxygen scavengers obtained in Example 1 were added to physiological saline. The solution dissolved in 1. was administered at a rate of 1000 mg / Kg. 14 days after the administration, life or death was judged, but no death was observed in any group. Therefore, the LD50 value by oral administration is estimated to be higher than 1000 mg / Kg. Therefore, it is understood that all of the oligogalacturonic acid iron complex which is the active oxygen scavenger of the present invention is excellent in safety.

[0046] Example 4 Measurement of reactive oxygen scavenging action based on the reaction formula shown in (in vitro) of 2, xanthine - is one superoxide anion of active oxygen by xanthine oxidase (XOD) system (O ₂ ^-) Was generated and the generation rate of the generated O ₂ ⁻ was measured by the nitrite method, and this value was corrected by the xanthine oxidase inhibition rate value to obtain the active oxygen scavenging action value.

[0047]

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0.1 ml of an active oxygen scavenger aqueous solution containing the eight kinds of active oxygen scavengers of the present invention obtained in Example 1 at various concentrations was added to 65 mM potassium dihydrogen phosphate, 35
mM sodium borate, 0.5 mM EDTA disodium aqueous solution (hereinafter referred to as buffer A) 0.2 ml, 0.5 mM
It was added to a mixed solution of 0.2 ml of a mM xanthine solution, 0.1 ml of a 10 mM aqueous solution of hydroxylamine hydrochloride, and 0.2 ml of pure water, and stirred well to prepare a test solution. Similarly, a control solution using 0.1 ml of pure water instead of the active oxygen scavenger was prepared.

To the above test solution and control solution, 0.2 ml of buffer solution A containing xanthine oxidase at a concentration of 1 μl / ml was added and stirred, and then incubated at 37 ° C. for 30 minutes. As a blank, 0.2 ml of buffer solution A containing no xanthine oxidase was added to the test solution and control solution prepared in the same manner as above,
A solution treated in the same manner as above was prepared.

To each of the solutions thus obtained, 2 ml of a mixed solution of 30 μM N-1-naphthylethylenediamine hydrochloride, 3 mM sulfanilic acid and 25% glacial acetic acid was added.
And left at room temperature for 30 minutes.
The amount of active oxygen generated was measured at an absorbance of 50 nm, and the amount of uric acid was measured at an absorbance of 295 nm.

Using the obtained values, based on the following equation,
The active oxygen scavenging activity value was calculated. This value was applied to a non-linear least squares program to calculate an IC50 value. The results are shown in Table 12. From this, it is understood that the oligogalacturonic acid iron complex has excellent active oxygen scavenging activity.

(Equation for determining active oxygen scavenging activity) Active oxygen generation rate = [(A _550-3 -A _550-4 ) / (A _550-1 -A _550-2 )] * 100 Urea production rate = [( A _295-3 -A _295-4 ) / (A _295-1 -A _295-2 )] * 100 Active oxygen scavenging activity = 100- (active oxygen generation rate / uric acid production rate) * 100 However, the symbol in the formula Is the absorbance value of each solution adjusted under the conditions shown in Table 11.

[0053]

[Table 11]

[0054]

[Table 12]

Example 5 Inhibitory Action of Lipid Peroxidation Production 1 group of 10 ICR mice (male, 5 weeks old) was orally administered with 1 ml of the juice of Example 3 a day, and after breeding for 24 months blood was collected by TBA method. The peroxide value of was measured. As a control, only fruit juice containing no oligogalacturonic acid iron complex was orally administered. Table 13 shows the results. From this, it is understood that the oligogalacturonic acid iron complex, which is the active oxygen scavenger of the present invention, suppresses the production of lipid peroxide. Further, it can be seen that foods containing them eliminate active oxygen produced in the body, suppress the production of lipid peroxide, and are useful for prevention and amelioration of aging and diseases.

[0056]

[Table 13]

Example 6 Evaluation of shampoo With respect to the shampoo of Example 10, the effect of improving the hair quality was determined by a questionnaire using 10 panelists per group for one consecutive month. Improvement effect is +: improved,
±: Slightly improved, −: Not improved or deteriorated. In addition, as a comparative example, water was used instead of the oligogalacturonic acid iron complex. The results are shown in Table 14. From this, it is understood that the active oxygen scavenger of the present invention prevents hair from being damaged by active oxygen generated by light or the like.

[0058]

[Table 14]

[0059]

The active oxygen scavenger of the present invention is excellent in active oxygen scavenging action and highly safe. Therefore, a composition such as a drug, a food, or a beverage containing this is very useful for the prevention and treatment of diseases involving active oxygen.

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[Chemical 12]

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display area A61K 7/06 A61K 7/075 7/075 7/48 7/48 31/70 AAM 31/70 AAM ABE ABE ABF ABF ABG ABG ABS ABS ACS ACS ACS AED AED 31/725 ADA 31/725 ADA C07H 3/06 C07H 3/06 7/033 7/033 7823-4B C12Q 1/26 // C12Q 1/26 A23L 2 / 00 F

Claims (7)

[Claims] 1. An active oxygen scavenger comprising a complex of oligogalacturonic acid and a transition metal. Embedded image 2. The degree of polymerization of oligogalacturonic acid is 1 to
5. The active oxygen scavenger according to claim 1, which is 5. 3. The active oxygen scavenger according to claim 1 or 2, wherein the transition metal is iron. 4. The activity according to claim 1, wherein the composition ratio (equal ratio) of oligogalacturonic acid and transition metal is 1: 2 to 1: 6. Oxygen scavenger. 5. A cosmetic containing the active oxygen scavenger according to claim 1. 6. A pharmaceutical composition containing the active oxygen scavenger according to claim 1. 7. A food grade composition containing the active oxygen scavenger according to claim 1.