JPH08259438A - Scavenger for active oxygen - Google Patents

Abstract

PURPOSE: To obtain a medicine containing α- and γ-thujaplicins as active ingredients and capable of suppressing the release of active oxygen or removing the released active oxygen species. CONSTITUTION: This scavenger for active oxygen contains at least one comprising α-thujaplicin and its salt and γ-thujaplicin and its salt as active ingredients. The ingredients are good in stability and excellent in persistence without any side effects. The α-thujaplicin or its salt is excellent in scavenging actions, especially on hydrogen peroxide and singlet oxygen. The scavenger can be prepared into a peroral agent, a suppository, a parenteral injection, etc., and further a lotion, a cream, an ointment, etc., by suitably blending a filler, an extender, a binder, a humectant, a disintegrating agent, a surfactant, a lubricant, etc., therewith. The scavenger has preventing and lowering actions on in vivo production of peroxylipids and is effective in preventing and treating diseases due to blood platelet aggregation, inflammation, arteriosclerosis, etc. The daily dose thereof is 1-10mg/kg α- and γ-thujaplicins.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to an active oxygen scavenger.

[0002]

2. Description of the Related Art Oxygen is indispensable for living organisms such as energy production and metabolism to maintain life. The oxygen is a reaction in the energy production system,
Oxygen anion radicals, peroxide ions, hydroxy radicals, hydrogen peroxide, hypochlorite ions, singlet oxygen, and other so-called active oxygen species are formed by reactions such as enzymatic reactions, ultraviolet rays, and radiation. The reactive oxygen species are useful for living organisms such as oxygenase and bactericidal action of leukocytes, but on the other hand, unsaturated substances that form phospholipids of biological membranes such as oleic acid, linoleic acid, linolenic acid and arachidonic acid which are abundant in living organisms It promotes the peroxidation of fatty acids and forms lipid peroxides. This lipid peroxide is
Like the above-mentioned reactive oxygen species, it induces the generation of alkoxy radicals and hydroxy radicals, attacks biological membranes, and causes membrane damage and deactivation of various useful enzymes [metabolism, 15 (1
0), see 1978 Special Feature Active Oxygen]. However, in the living body, for example, superoxide dismutase (SO
D), catalase, glutathione peroxidase, and other enzymes involved in metabolic deactivation of the above reactive oxygen species, and vitamins having various antioxidant abilities, including α-tocopherol (vitamin E) Is present, and normal living body maintenance is performed by such actions, but for some reason the appropriate defense mechanism is deficient due to the enzymes, vitamins, etc., or the ability of the defense mechanism is It is often observed that the generation of reactive oxygen species exceeding the range and the production and accumulation of lipid peroxide occur. When such a deficiency of defense mechanism occurs, various disorders such as various disorders due to chain reaction progression of peroxidation reaction such as platelet aggregation, inflammation, liver disorder, arteriosclerosis, hemolysis, aging or senile dementia, Retinopathy, lung injury, heart and lung injury due to certain drugs, ischemic vascular disease, etc. occur.

[0003] Among the active oxygen species, O ₂ generated from the O ₂ by xanthine oxidase enzymes such as ^-
It is known that OH generated by the reaction between H ₂ O ₂ and H ₂ O ₂ gives a great obstacle to the living body. As a compound that eliminates H ₂ O ₂ , an enzyme called catalase is known. No other useful compound has been found.

The object of the present invention is to remove active oxygen species (scavenging), which are considered to be the main cause of the above-mentioned various disorders, and to prevent or reduce the production / accumulation of lipid peroxide in the living body. To provide.

[0005]

The present inventor has conducted extensive studies to provide a new drug having an activity of suppressing the release of active oxygen species or removing active oxygen species, and as a result, α-tsuyapricin It was also found that such a salt, and γ-tsuyapricin or a salt thereof exhibit such activity, and these components have good stability, excellent sustainability, and no side effects. In addition, among these components, α
-Tsyapricin or its salts are especially suitable for hydrogen peroxide (H ₂
It was found that the scavenging action of O ₂ ) and singlet oxygen ( ¹ O ₂ ) is very excellent, and the present invention has been completed here.

That is, the present invention relates to an active oxygen scavenger containing, as an active ingredient, at least one component selected from α-tsuyapurisin and its salt, and γ-tsuyapurisin and its salt.

The α-tsuyapurisin and salts thereof, and the γ-tsuyapurisin and salts thereof used as active ingredients in the present invention are known compounds, for example, JP-A-60-2.
Japanese Patent No. 28414 discloses that such tropolone derivatives and salts thereof can be used as a preventive / therapeutic agent for diseases caused by 12-lipoxygenase metabolites.

At least one component selected from α-tsuyapricin and a salt thereof, and γ-tsuyapricin and a salt thereof, which are used as active ingredients in the present invention, includes all components generally known as active oxygen species, for example,
The release of active oxygen species such as oxygen anion radicals, peroxide ions, hydroxy radicals, hydrogen peroxide, hypochlorite ion, and singlet oxygen is suppressed, or the released active oxygen species are removed, and lipid peroxide is added. It has the effect of preventing or reducing the in vivo generation. Therefore, the active oxygen scavenger of the present invention is used as a prophylactic and therapeutic agent for various disorders or diseases caused by excessive generation of reactive oxygen species, bioaccumulation of lipid peroxides, or lack of defense mechanism against, for example, anti-arteriosclerosis. Agents, carcinogenic agents, anticancer agents, anti-inflammatory agents, analgesics, therapeutic agents for autoimmune diseases,
It is useful as a drug such as a platelet aggregation inhibitor, antihypertensive agent, antihyperlipidemic agent, retinopathy of prematurity and cataract prevention and treatment agent. Further, the active oxygen scavenger of the present invention is a therapeutic agent for cardiac ischemic diseases such as myocardial infarction and arrhythmia, a liver and renal function improving agent for disorders such as transplantation and microcirculatory failure, and a treatment for gastrointestinal ulcers such as gastric ulcers. Agent, cerebral hemorrhage, cerebral infarction,
Therapeutic agent for transient cerebral ischemic disease, such as cutaneous vasculitis,
Skin diseases such as psoriasis, erythema multiforme, Behcet's disease, varicella dermatitis, cement dermatitis, sunburn, sunburn prevention, neurodermatitis, eczema, pruritus genitalis, dermatitis in humans, white blood cell reduction , Treatment of radiation exposure damage by radiation such as X-rays such as hair loss and redness of the skin, nausea, loss of appetite, α rays, β rays, γ rays, neutron rays, accelerated electron rays, mammals other than humans (dogs, cats) Skin diseases such as pets and cows, livestock such as horses, etc.,
Diabetes mellitus, ocular iron disease, retinitis, eye disease such as pigmentation, emphysema, adult respiratory distress syndrome, arthritis, malignant rheumatism, ulcerative colitis, Crohn's disease, Raynaud's disease, etc., stains, freckles and pigments It is useful as a drug for preventing deposition, burns, trauma, fatigue, etc. Furthermore, the active oxygen scavenger of the present invention is effective not only as the above-mentioned pharmaceuticals but also as an antioxidant or the like of oils and fats contained in processed foods.

Among the active ingredients of the active oxygen scavenger of the present invention, in particular, α-tsuyaprisin or a salt thereof is hydrogen peroxide (H ₂ O ₂ ) and singlet oxygen ( ¹ O) among active oxygen species.
₂ ) It has a very excellent activity of eliminating.

Examples of the salt of α-tsuyapricin and the salt of γ-tsuyapricin include alkali metal salts such as sodium and potassium salts, alkaline earth metal salts such as magnesium salts, and metal salts such as Cu salt and Zn salt. Inorganic salts, diethanolamine salts, 2-amino-2-ethyl-1,3-propanediol salts, alkanolamine salts such as triethanolamine salts, morpholine salts, piperazine salts, piperidine salts, etc., ammonium salts, arginine salts, lysine salts And organic salts such as basic amino acid salts such as histidine salts. As the basic amino acid, any of a D-form, an L-form or a mixture thereof can be used.

In the present invention, the components selected from α-tsuyapurisin and its salts, and γ-tsuyapurisin and its salts can be used alone or in admixture of two or more.

The active oxygen scavenger of the present invention is usually used in the form of a general pharmaceutical preparation. The preparation is prepared by using a diluent or excipient which is usually used such as a filler, a filler, a binder, a moisturizer, a disintegrant, a surface active agent and a lubricant. Various forms of this pharmaceutical preparation can be selected according to the therapeutic purpose, and typical examples thereof include tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, suppositories,
In addition to injections (solutions, suspensions, etc.), external preparations such as lotions, creams, ointments, etc. can be used.

In forming tablets, any of those widely used in the art as a carrier can be used, such as lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, and the like. Excipients such as kaolin, crystalline cellulose, silicic acid, water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, polyvinylpyrrolidone and other binders, drying Starch, sodium alginate, agar-free, laminaran powder, sodium hydrogen carbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, stearic acid monoglyceride, starch, disintegrants such as lactose, sucrose, stearin, mosquito Obata, disintegrating inhibitors such as hydrogenated oils, quaternary ammonium bases, absorption enhancers such as sodium lauryl sulfate, glycerin, a humectant such as starch,
Examples thereof include adsorbents such as starch, lactose, kaolin, bentonite, and colloidal silicic acid, refined talc, stearates, boric acid powders, and lubricants such as polyethylene glycol. In addition, tablets are tablets with a normal coating if necessary,
For example, a sugar-coated agent, a gelatin-coated tablet, an enteric-coated tablet, a film-coated tablet, a double tablet, or a multi-layer tablet can be used.

In the case of molding in the form of pills, those conventionally known in this field can be widely used as carriers, for example, excipients such as glucose, lactose, starch, cocoa butter, hydrogenated vegetable oil, kaolin, talc, and Arabic. Rubber powder, tragacanth powder, gelatin, binder such as ethanol, laminaran,
A disintegrating agent such as agar can be exemplified.

In the case of molding in the form of suppositories, conventionally known carriers can be widely used, and examples thereof include polyethylene glycol, cocoa butter, esters of higher alcohols, gelatin, and semisynthetic glycerides.

Further, when prepared as an injection, the solution, emulsion and suspension are preferably sterilized and isotonic with blood, and the solution, emulsion and suspension are formed into a form. At this time, all the diluents commonly used in this field can be used, and examples thereof include water, ethyl alcohol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, and polyoxyethylene sorbitan fatty acid esters. be able to. In this case, a sufficient amount of salt, glucose or glycerin for preparing an isotonic solution may be contained in the pharmaceutical preparation, and a usual solubilizing agent, buffer, soothing agent, etc. may be further added. If necessary, coloring agents, preservatives, fragrances, flavors, sweeteners and other pharmaceuticals may be contained in the preparation.

When the paste, cream or gel is formed, as a diluent, for example, white petrolatum,
Paraffin, glycerin, cellulose derivatives, polyethylene glycol, silicone, bentonite, etc. can be used.

The active oxygen scavenger of the present invention is applied to the skin as a cleansing cosmetic, lotion, cream, emulsion, makeup cream, cosmetic oil, basic cosmetics such as pack, foundation, Finishing cosmetics such as lipsticks, blushers, eyeliners, mascaras, eye shadows, nail polishes, and white powders, hair cosmetics such as hair styling agents and hair nourishing agents, bath agents, whitening agents, sunscreen agents, and acne agents. Can be prepared according to the methods conventionally used in this field. At that time, various known cosmetic bases can be used, and if necessary, various oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, ester oils, within a range that does not impair the effects of the present invention.
Raw materials for oils and fats such as metal soap, animal and plant extracts, medicinal agents such as vitamins and hormones, surfactants, pigments, dyes,
Pigments, fragrances, preservatives, bactericides, moisturizers, thickeners, antioxidants, sequestering agents, UV absorbers and other additives may be used in appropriate combination.

Α- contained in the active oxygen scavenger of the present invention
The amount of at least one component selected from tsuyapurisin and a salt thereof and γ-tsuyapurisin and a salt thereof is not particularly limited and is appropriately selected from a wide range, but is usually about 1 to 70% by weight in a pharmaceutical preparation. Is good.

The administration method of the active oxygen scavenger of the present invention is not particularly limited, and it may be administered according to various dosage forms, patient's age, sex and other conditions, degree of disease and the like. For example, tablets, pills, solutions, suspensions, emulsions, granules and capsules are orally administered. Further, in the case of an injection, it is administered alone or mixed with a normal replacement fluid such as glucose or amino acid, and then intravenously administered.
It is administered intradermally, subcutaneously or intraperitoneally. In the case of suppositories, they are administered rectally. Furthermore, in the case of external preparations such as lotions, creams and ointments, they are applied and administered.

The dose of the above-mentioned pharmaceutical preparation is appropriately selected according to the usage, the age of the patient, the sex and other conditions, the degree of the disease, etc., but usually, α-tsuyaprisin which is the active ingredient of the active oxygen scavenger of the present invention and its The amount of the salt and at least one component selected from γ-tsuyapurisin and its salt is 1
About 1 to 10 mg per 1 kg of body weight per day, preferably 2
The dose is preferably about 5 mg, and can be administered once or twice a day.

[0022]

The active oxygen scavenger of the present invention suppresses the release of active oxygen or removes the released active oxygen species, and has the action of preventing or reducing the in vivo production of lipid peroxide.
Moreover, it has good stability, excellent sustainability, and no side effects.

Among the active oxygen scavengers of the present invention, active oxygen scavengers containing α-tsuyapricin or a salt thereof as an active ingredient are particularly hydrogen peroxide (H ₂ O ₂ ) and singlet oxygen ( ¹
It has an extremely excellent activity as an erasing agent for O ₂ ).

[0024]

EXAMPLES In order to explain the present invention in more detail, formulation examples of the active oxygen scavenger of the present invention will be given below, as well as test examples of active ingredient compounds.

Formulation Example 1 α-tsuyapurisin 150 g Avicel (trade name, manufactured by Asahi Kasei Co., Ltd.) 40 g Corn starch 30 g Magnesium stearate 2 g Hydroxypropyl methylcellulose 10 g Polyethylene glycol-6000 3 g Castor oil 40 g Ethanol 40 g α-tsuyapurisin, Avicel, corn starch and stearic acid After mixing and polishing magnesium, tableting is performed with sugar coated R 10 mm kine. The obtained tablets are hydroxypropylmethyl cellulose, polyethylene glycol-6000,
A film coating agent consisting of castor oil and ethanol is coated to produce a film coated tablet.

Formulation Example 2 α-tsuyapurisin 150 g Citric acid 1.0 g Lactose 33.5 g Dicalcium phosphate 70.0 g Pluronic F-68 30.0 g Sodium lauryl sulfate 15.0 g Polyvinylpyrrolidone 15.0 g Polyethylene glycol (Carbowax 1500 ) 4.5 g Polyethylene glycol (Carbowax 6000) 45.0 g Corn starch 30.0 g Dry sodium stearate 3.0 g Dry magnesium stearate 3.0 g Ethanol Appropriate amount α-tsuyapurisin, citric acid, lactose, dicalcium phosphate, pluronic Mix F-68 and sodium lauryl sulfate.

The above mixture is sieved through a No. 60 screen and wet granulated with an alcohol solution containing polyvinylpyrrolidone, Carbowax 1500 and 6000. Alcohol is added as needed to make the powder a pasty mass. Add corn starch and continue mixing until uniform particles are formed. The mixture is passed through a No. 10 screen, placed in a tray and placed in an oven at 100 ° C for 1
Dry for 2-14 hours. The dry particles are screened through a No. 16 screen, dry sodium lauryl sulfate and dry magnesium stearate are added and mixed and compressed into the desired shape on a tablet machine.

The core is treated with varnish and sprinkled with talc to prevent moisture absorption. The undercoat layer is coated around the core. Apply varnish a sufficient number of times for internal use. A further subbing layer and a smooth coating are applied to make the tablet completely round and smooth. Color coating is applied until the desired shade is obtained. After drying, the coated tablets are polished into tablets of uniform gloss.

Formulation Example 3 γ-tsuyapurisin 5 g polyethylene glycol (molecular weight: 4000) 0.3 g sodium chloride 0.9 g polyoxyethylene-sorbitan monooleate 0.4 g sodium metabisulfite 0.1 g methyl-paraben 0.18 g propyl- Paraben 0.02 g Distilled water for injection 10.0 ml The above parabens, sodium metabisulfite and sodium chloride are dissolved in about half of the above distilled water at 80 ° C with stirring. The resulting solution is cooled to 40 ° C. and γ-tsuyapricin, then polyethylene glycol and polyoxyethylene sorbitan monooleate are dissolved in the above solution. Next, distilled water for injection is added to the solution to make a final volume, and the solution is sterilized by sterilizing filtration using an appropriate filter paper to prepare an injection.

Next, formulation examples when the active oxygen scavenger of the present invention is used as a skin material are shown. In the following, "%" means "% by weight".

[0031] (A) The components (1) to (6) were heated to 80 to 85 ° C and uniformly dissolved.

(B) The components of (7) and (8) above and (1
The purified water of 1) was heated to 80 to 85 ° C and uniformly dissolved.

(C) Next, at 80 ° C., the above-mentioned (b) is added little by little to the above-mentioned (a), and the mixture is emulsified uniformly and then stirred under stirring.
Cooled to 5 ° C.

(D) In (c) at 45 ° C., the above (9) and (1)
After the mixture of (0) was added, the mixture was stirred uniformly and further cooled to room temperature with stirring.

[0035] The components (1) to (11) above are added according to Formulation Example 4,
After appropriately heating, stirring and cooling, the desired cleansing cream was obtained.

[0036] The components (1) to (9) above are added according to Formulation Example 4,
After heating, stirring and cooling appropriately, the desired milk lotion was obtained.

[0037] The components (1) to (12) above are added according to Formulation Example 4,
After heating, stirring and cooling as appropriate, the desired makeup cream was obtained.

[0038] Add the above components (1) to (10) according to Formulation Example 4,
After heating, stirring and cooling as appropriate, the desired makeup cream was obtained.

[0039] The above components (1) to (8) are added according to Formulation Example 4,
After heating, stirring, and cooling as appropriate, the target W / O type cream was obtained.

[0040] After adding polyvinyl alcohol of component (1) and polyvinylpyrrolidone of component (2) moistened with some ethyl alcohol to the purified water of (6) above, the mixture was heated to 80 ° C. and uniformly mixed with occasional stirring. Leave at room temperature overnight. The next day, the rest of the components (4) and (5) and the component (6) were added, and the mixture was heated to 60 ° C. and uniformly mixed, and then cooled to room temperature with stirring to obtain a target pack.

[0041] (A) The components (2) to (4) were added to the ethyl alcohol and uniformly dissolved.

(B) The purified water of the above (9) is added to the above (5).
(7) was added and uniformly dissolved.

(C) Next, the above-mentioned (b) was added to the above-mentioned (a), uniformly mixed and solubilized, and then colored with the dye of the above-mentioned (8) to obtain a lotion.

[0044] The components (1) to (7) were uniformly mixed to obtain a white powder according to a conventional method.

[0045] Add the components (1) to (13) according to Formulation Example 4,
After appropriately heating, stirring and cooling, a desired sunscreen emulsion was obtained.

[0046] The components (1) to (10) were heated (85 ° C.) to obtain a uniform phase, which was then degassed and then poured into a mold and rapidly cooled to obtain a stick-like product.

[0047] After heating the above-mentioned components (1) to (4) and uniformly melting them, 7
The temperature was kept at 5 ° C., to which the above components (5) and (6) were dissolved in the above component (7) in advance, and then a liquid heated at 75 ° C. was added,
After uniformly stirring, the mixture was cooled with stirring to obtain the desired hydrophilic ointment.

[0048] (A) In the ethyl alcohol of (1) above, the above (2) to
The component (5) was added and uniformly dissolved.

(B) The above-mentioned (6) and (7) were added to the purified water of the above-mentioned (8), and they were uniformly dissolved.

(C) Next, the above-mentioned (b) was added to the above-mentioned (a) and mixed uniformly to obtain a desired hair tonic.

Pharmacological test (measurement of active oxygen scavenging activity by chemiluminescence method) 1. Method for preparing test solution 1) 1 mM α-tsuyapurisin NaOH aqueous solution α-tsuyapurisin (manufactured by Takasago International Corporation) 0.032
To 9 g, 2 ml of 0.1 M NaOH aqueous solution was accurately added, and after uniform mixing and dissolution, purified water was added to make exactly 200 ml.

2) 1 mM γ-tsuyapurisin NaOH aqueous solution γ-tsuyapurisin (manufactured by Takasago International Corporation) 0.032
To 9 g, 2 ml of 0.1 M NaOH aqueous solution was accurately added, and after uniform mixing and dissolution, purified water was added to make exactly 200 ml.

3) 100 mM α-tsuyapricin NaO
H aqueous solution α-tsuyapurisin (manufactured by Takasago International Corporation) 0.821
To 0 g, 5 ml of 1M NaOH aqueous solution was accurately added, and after uniform mixing and dissolution, purified water was added to make exactly 50 ml.

4) 100 mM γ-tsuyapricin NaO
H aqueous solution γ-tsuyapurisin (manufactured by Takasago International Corporation) 0.821
To 0 g, 5 ml of 1M NaOH aqueous solution was accurately added, and after uniform mixing and dissolution, purified water was added to make exactly 50 ml.

2. Measuring device Chemiluminescence is produced by ALOKA, Luminescence Reader (LUMINESCENCE READE).
R) (BLR-201).

3. Test method (1) H ₂ O ₂ erasing activity 500 μM luminol 200 μl (pH 1
Dissolved in 1.0, 0.1 M borate buffer) and 150
200 μl of μM hematin (dissolved in the above buffer) was added and mixed, and left still for about 1 hour. 100 μl of test samples of various concentrations were added to this solution and mixed, and the mixture was mixed at 30 ° C.
Set to the measuring device whose temperature has been set to
10 μl of MH ₂ O ₂ (dissolved in the above buffer) was injected with a microsyringe, and chemiluminescence was measured. Immediately before measurement, the test sample was prepared by diluting the above-mentioned 1) 1 mM α-tsuyapurisin NaOH aqueous solution or the above-mentioned 2) 1 mM γ-tsuyapurisin NaOH aqueous solution with the above-mentioned buffer to various concentrations.

The measurement was performed three times for each concentration, and a graph was drawn using the average value as data (a graph including sample concentration 0). From this graph, the sample concentration at which the chemiluminescence at the sample concentration of 0 is eliminated by 50%, that is, IC
I asked ₅₀ .

[0058] carried out 3 times the same test, on average an IC ₅₀ obtained from three tests were the final an IC ₅₀ value.

(2) OH scavenging activity A) 250 μM luminol 100 μl (pH
(Dissolved in 7.8, 50 mM phosphate buffer) and allowed to stand for about 1 hour. 100μM ferrous sulfate 50μ in this solution
l (dissolved in distilled water, added 1M sulfuric acid 1V / V%), 2.
5 mM Diethylenetriamine-5-acetic acid (DTPA) 50μ
1 (dissolved in the above buffer), 300 μl of 50 mM phosphate buffer having a pH of 7.8, and 100 μl of test samples of various concentrations were mixed and set in a measuring device whose temperature had been set to 30 ° C., and 6 mMH ₂ O ₂ 10 μl
(Dissolved in the above buffer) was injected with a microsyringe, and chemiluminescence was measured. As a test sample, immediately before the measurement, 1 mM α-tsuyaprisin NaOH of 1) above was used.
Aqueous solution or 1 mM γ-tsuyapricin NaO of 2) above
The H aqueous solution was diluted with the above buffer and adjusted to various concentrations.

B) In the same manner as in A) above, pH 7.8.
Chemiluminescence was measured by adding 300 μl of ethanol in place of 300 μl of 50 mM phosphate buffer.

C) Data obtained by subtracting the measurement value of B) from the measurement value of A) was used.

The measurement was carried out three times for each concentration, and a graph was drawn using the average value as data (a graph including sample concentration 0). From this graph, the sample concentration at which the chemiluminescence at the sample concentration of 0 is eliminated by 50%, that is, IC
I asked ₅₀ .

[0063] carried out 3 times the same test, on average an IC ₅₀ obtained from three tests were the final an IC ₅₀ value.

(3) ¹ O ₂ scavenging activity 2.2 μM Cypridina miferrin (CLA) was added to a small test tube.
100 μl (pH 4.5, dissolved in 0.1 M acetic acid buffer), 5.5 mM DTPA 100 μl (dissolved in the above buffer), 400 mM H ₂ O ₂ 200 μl (dissolved in the above buffer), and 100 μl of test samples of various concentrations
1 l were mixed and set in a measuring device whose temperature was set to 30 ° C., and 10 M sodium hypochlorite (NaO) was added.
Cl) 10 μl (dissolved in the above buffer) was injected with a microsyringe, and chemiluminescence was measured. As a test sample, immediately before the measurement, 100 mM α-tsuyaprisin NaOH aqueous solution of 3) above or 100 mMγ of 4) above.
-A solution prepared by diluting an aqueous solution of tsuyapurisin NaOH with the above-mentioned buffer to have various concentrations was used.

The measurement was carried out three times for each concentration, and a graph was drawn using the average value as data (a graph including sample concentration 0). From this graph, the sample concentration at which the chemiluminescence at the sample concentration of 0 is eliminated by 50%, that is, IC
I asked ₅₀ .

[0066] carried out 3 times the same test, on average an IC ₅₀ obtained from three tests were the final an IC ₅₀ value.

The above results are shown in Table 1 below.

[0068]

[Table 1]

[0069]

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display location A61K 31/12 ABU A61K 31/12 ABU ABX ABX ACB ACB ADN ADN ADU ADU 7/00 7/00 C 7/02 7/02 A 7/025 7/025 7/06 7/06 7/42 7/42 7/48 7/48

Claims (1)

[Claims] 1. α-tsuyapricin and its salt, and γ-
An active oxygen scavenger containing, as an active ingredient, at least one component selected from tsuyapurisin and salts thereof.