JPH09208484A - Active oxygen-eliminator and composition containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an active oxygen-eliminator containing the essence of a plant belonging to the genus Hippophae in the family Elaeagnaceae, capable of sufficiently eliminating active oxygen generated in living bodies, and high in safety. SOLUTION: This active oxygen-eliminating agent contains the essence of a a plant (e.g, Hippophae rhamnoides) belonging to the genus Hippophae (generally called as 'saci') in the family Elaeagnaceae. The plant essence includes a processed plant product obtained e.g. by drying, grinding or kneading the plant itself into a paste, an extraction solution obtained by extracting the plant or the processed plant with a solvent, an extract obtained by removing the solvent from the extraction solution, and its purified product. The active oxygen-eliminating agent may be prepared into compositions such as medicines, foods, beverages or cosmetics. The active oxygen- eliminating agent is suitable for treating and preventing ageing, allergies, cardiac infarction, hepatopathy, dementia, rheumatism, etc. The content of the active oxygen- eliminating agent in the cosmetic or food is preferably 0.1-1wt.%, and the active oxygen-eliminating agent as the medicine is orally administered at a daily dose of 10-100mg for an adult in one to several portions or injected at a daily dose of 5-500mg for an adult.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an active oxygen scavenger and a composition for external use for skin, foods, pharmaceuticals, etc. containing the same.

[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
JP-A-2-264727, JP-A-3-15362
No. 9, JP-A-3-221587, JP-A-4-6934.
No. 3, JP-A-4-202138, 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, the genus Hippophae
Although it was known that the plant of the plant e) contained a component having an action of treating or preventing cancer, it was not known at all that it had an action 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.

[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]

In order to solve the above problems, the present inventors extensively screened compounds derived from various plants with active oxygen scavenging activity as an index, and as a result, the essence of plants of the genus Hippophae was excellent. It has been found that it has an active oxygen scavenging effect, and has completed the present invention. Here, the essence referred to in the present invention, the plant itself is dried, crushed, processed into paste, etc., the processed product of the plant, the plant or the processed product of the plant was extracted with a solvent,
Alternatively, it means an extract obtained by removing the solvent from them, a product containing a purified product obtained by purifying the extract by column chromatography, liquid-liquid extraction, ultrafiltration and the like.

(1) Active Oxygen Scavenger of the Present Invention The active oxygen scavenger of the present invention comprises an essence of a plant of the Hippophae genus plant of the family Gumidae, which is generally called "search. The plants of the genus Hippophae genus are Salicifolia (H.salicifolia), Tibetana (H.thibetana), Neurocorpa (H.neurocorpa), Rhamnoides (H.rhamnoid).
es), etc., and any of these can be used in the present invention. The most common of these is Rhamnoides (H.
rhamnoides). These may be used alone,
Two or more kinds may be used in combination. To obtain an extract from these plants, 1 to 1
A 10-fold amount of the solvent may be added, and it may be immersed for several days at room temperature and for several hours at a temperature near the boiling point. As the solvent, polar solvents are preferable, alcohols such as methanol and ethanol, esters such as ethyl acetate and methyl formate, nitriles such as acetonitrile, ethers such as diethyl ether and tetrahydrofuran, halogenation such as chloroform and methylene chloride. Examples include hydrocarbons, ketones such as acetone and methyl ethyl ketone, and one or more selected from these may be used. The active oxygen scavenger of the present invention is a plant, a processed product of a plant, an extract of a plant,
It consists of a purified product of the extract. The part of the plant is not particularly limited, but fruits are most preferable. The most preferred of these is the fruit water extract. The active oxygen scavenger of the present invention made from fruits is expected to have high safety because the fruits are edible.

(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, thereby preventing wrinkles caused by collagen cross-linking caused by UV irradiation, preventing hair loss, body odor, etc. It has the effect of preventing the generation of unpleasant odor. 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
１1% by weight.

When the active oxygen scavenger of the present invention is formulated as a medicine, the dosage form is not particularly limited, but 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 pharmaceuticals, 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 can be added to various foods together with optional components used in 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 a salt thereof which is the active ingredient thereof, wrinkles caused by ultraviolet irradiation-induced collagen cross-linking, which is said to involve active oxygen as described above. Formation, generation of body odor, hair loss,
It is effective for treating various diseases such as inflammation, senile dementia, myocardial infarction and other ischemic diseases, allergic diseases, liver disorders, rheumatism and improving aging of skin and the like.

Further, 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.

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described in detail below with reference to examples, but it goes without saying that the present invention is not limited to these examples.

Example 1 Production Example 1 kg of the flesh of search fruit was crushed with a food processor, and the extract was squeezed with a filto press to freeze-dry it. Water (1 liter) was added to this, and the filtrate was freeze-dried to obtain 51 g of active oxygen scavenger 1 as a brown powder.

Example 2 Production Example 1 kg of the flesh of search fruit was crushed with a food processor, and the extract was squeezed with a filto press to freeze-dry it. To this, 1 liter of 50% aqueous ethanol solution was added, and after filtration, the filtrate was freeze-dried to obtain 47 g of active oxygen scavenger 2 as a brown powder.

Example 3: Production Example 1 kg of flesh of search fruit was crushed with a food processor, and then the extract was squeezed with a filto press and dried under vacuum at 48 ° C. Water (1 liter) was added to this, and the filtrate was freeze-dried to obtain 52 g of active oxygen scavenger 3 as a brown powder.

Example 4 (Candy) A candy was prepared according to the formulation shown in 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.

[0024]

[Table 1]

Example 5 (Gummy) The components shown in Table 2 were dissolved by heating at 110 ° C. and separately swollen 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.

[0026]

[Table 2]

Example 6 (Juice) The components shown in Table 3 were thoroughly solubilized with stirring, sterilized, aseptically filled, and sealed to prepare juice.

[0028]

[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.

[0030]

[Table 4]

Example 7 (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.

[0032]

[Table 5]

Example 8 (Injection) The components shown in Table 6 were dissolved, filtered, sterilized, and aseptically filled into an ampoule and sealed to obtain an injection.

[0034]

[Table 6]

Example 9 (Toilet lotion) The components shown in Table 7 were solubilized with stirring at room temperature to obtain a lotion.

[0036]

[Table 7]

Example 10 (Emulsion) A, B, and C in Table 8 were dissolved by heating at 80 ° C., B was added to A, and C was further added to coarsely emulsify, followed by homogenizing with a homogenizer and cooling to obtain an emulsion. Obtained.

[0038]

[Table 8]

Example 11 (Hair Tonic) The components of Table 9 were solubilized with stirring at room temperature to obtain a hair tonic.

[0040]

[Table 9]

Example 12 (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.

[0042]

[Table 10]

Example 13 (Jam) After the following ingredients were boiled in a pressure cooker for 30 minutes, they were evenly chopped with a food processor, sealed in a bottle, and sterilized to obtain a jam. Apple pulp 69 parts by weight Search pulp 10 parts by weight Sucrose 20 parts by weight Pectin 1 part by weight

Example 14 (Fruit Sauce) The following ingredients were boiled in a pressure cooker for 30 minutes, then finely chopped with a food processor, strained with a 200 # strainer, sealed in a bottle, sterilized, and fruited. Got the sauce. Strawberry pulp 50 parts by weight Active oxygen scavenger 1 10 parts by weight Sucrose 20 parts by weight Water 19 parts by weight Carboxymethyl cellulose 1 part by weight

[0045]

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 Acute toxicity test (intraperitoneal administration) Each group of 5 ICR male mice (body weight 25 to 30 g) was intraperitoneally injected with the active oxygen scavengers 1 to 3 obtained in Example 1 in 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 intraperitoneal administration is estimated to be higher than 1000 mg / Kg. Therefore, it is understood that all the active oxygen scavengers of the present invention are excellent in safety.

Example 2 Acute toxicity test (oral administration) Each group of 6 ICR male mice (body weight 25 to 30 g) was orally administered, and the active oxygen scavengers 1 to 3 obtained in Example 1 were physiological saline. The dissolved product 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 the active oxygen scavengers of the present invention are excellent in safety.

[0048] Example 3 Measurement of active oxygen scavenging action, based on the reaction formula shown in (in vitro) of 1, xanthine - superoxide anions which is one 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.

[0049]

Embedded image

0.1 ml of an active oxygen scavenger aqueous solution containing the active oxygen scavengers 1 to 3 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
A xanthine solution (0.2 ml), a 10 mM hydroxylamine hydrochloride aqueous solution (0.1 ml) and pure water (0.2 ml) were added to and mixed 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, followed by incubation at 37 ° C. for 30 minutes. As a blank, 0.2 ml of a buffer solution A containing no xanthine oxidase was added to the test solution and the control solution prepared as described above,
A solution treated as described 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 values obtained, 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 active oxygen scavenger of the present invention 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.

[0055]

[Table 11]

[0056]

[Table 12]

[0057]

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.

Continuation of the front page (51) Int.Cl. ⁶ Identification number Office reference number FI Technical indication location A61K 35/78 ACS A61K 35/78 ACS AGZ AGZ A23L 1/30 A23L 1/30 B A61K 7/00 A61K 7 / 00 kW 7/48 7/48 // A21D 2/36 A21D 2/36 A23G 3/00 101 A23G 3/00 101 A23L 1/06 A23L 1/06 2/38 2/38 C A61K 7/06 A61K 7 / 06 9/08 9/08 F

Claims (7)

[Claims] 1. An active oxygen scavenger consisting of an essence of a plant of the genus Hippophae of the family Gumidae. 2. The active oxygen scavenger according to claim 1, wherein the plant of the genus Hippophae of the family Gumaceae is search. 3. The active oxygen scavenger according to claim 1, wherein the plant is a fruit. 4. A composition containing the active oxygen scavenger according to claim 1. 5. The composition according to claim 4, which has a use in cosmetics. 6. The composition according to claim 4, which is used as a medicine. 7. The composition according to claim 4, wherein the use is food.