JP3290291B2 - Active oxygen scavenger and composition containing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an active oxygen scavenger and a cosmetic, pharmaceutical or edible composition containing the same, and more particularly to an active oxygen scavenger comprising a hydrolyzate of lignin and containing the same. The present invention relates to a cosmetic, a pharmaceutical composition, and an edible composition.

[0002]

2. Description of the Related Art In general, the effects of active oxygen on living organisms include cross-linking of collagen fibers, partial cleavage of DNA helix, and tissue damage due to the generation of chain radicals. Aging of the living body, loss of elasticity, hair loss, induction of allergic reactions such as bronchial asthma and inflammation due to histamine release, damage of smooth muscle in myocardial infarction which is an ischemic disease, exacerbation of diseases such as liver damage, It is known that destruction of tissues causes dementia and the like. Furthermore, although the detailed cause is unknown, it is said that active oxygen is also involved in the onset of rheumatism.

[0003] Therefore, suppressing the generation of active oxygen in the living body is very important in treating or preventing these diseases. The search for substances that act has been widely practiced.

[0004] For example, as drugs having such an action, those which have been conventionally used include those derived from natural products, such as fat-soluble tocopherol (vitamin E),
Water-soluble ascorbic acid (vitamin C); synthetic compounds such as BHT (butylhydroxytoluene),
BHA (butylhydroxyanisole) and the like. However, these agents are not effective in scavenging active oxygen, and BHT and BHA are suspected to be carcinogenic in synthetic compounds, and none of them is practical as active oxygen scavengers.

[0005] Recently, many attempts have been made to obtain a substance having an active oxygen scavenging effect from a crude drug extract in order to obtain sufficient drug efficacy and safety. For example, Japanese Patent Application Laid-Open No. 60-224629. JP-A-61-24522,
JP-A-2-193930, JP-A-2-243632
JP-A-2-264727, JP-A-3-15362
9, JP-A-3-221587, JP-A-4-6934
No. 3, JP-A-4-202138, JP-A-4-2470
The inventions described in each publication of No. 10 each utilize a substance having an active oxygen scavenging action derived from a crude drug. However, although these crude drug extracts have no problem in safety, sufficient extracts have not yet been obtained in terms of active oxygen scavenging action.

[0006] Further, 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. However, since SOD is a protein, Not only is it difficult to obtain, but also because it is digested, oral administration is impossible, and in administration by injection,
The blood half-life was short and not satisfactory.

On the other hand, lignin is one of the main components of woody plants such as wood, bamboo and straw, and is a reticulated high molecular compound. However, since lignin itself is a high molecular compound, its bioavailability is low. It was not used industrially. Attempts have been made to increase the bioavailability of lignin by improving the water solubility by hydrolyzing lignin.

However, in addition to the above lignin,
Even for a lignin hydrolyzate obtained by hydrolyzing it, no action of eliminating active oxygen was known. Furthermore, no attempt has been made to use them for preventing or treating the above-mentioned various diseases, preventing or improving aging by incorporating them into cosmetics, pharmaceuticals or foods.

[0009]

DISCLOSURE OF THE INVENTION The present invention has been made in view of the above point of view, and has an active oxygen scavenger which has a sufficient effect of eliminating active oxygen generated in a living body and has high safety. It is an object of the present invention to provide a cosmetic, pharmaceutical, food or other composition containing the composition.

[0010]

Means for Solving the Problems In order to solve the above problems, the present inventors have screened a wide range of compounds derived from various plants using the active oxygen scavenging action as an index. They have found that they have an erasing effect, and have completed the present invention.

That is, the present invention relates to an active oxygen scavenger comprising a hydrolyzate of lignin, and a cosmetic, pharmaceutical or edible composition containing the same. 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 hydrolyzate of lignin. Lignin is a network polymer compound contained in woody plants such as wood, bamboo and straw, and in the present invention, lignin obtained by decomposing such plants can be used by hydrolyzing. . In addition, lignin can be taken out from the plant as a hydrolyzate and used as it is in the present invention.

The plant used in the present invention includes:
There is no particular limitation as long as it contains lignin, and in terms of availability, conifers such as cedar and pine, deciduous broad-leaved trees such as oak and oak, and lauan can be mentioned.

The above method for obtaining a lignin hydrolyzate from a lignin-containing plant may be carried out by a conventional method. For example, if necessary, the plant may be subjected to grinding to increase the surface area. After performing an appropriate pretreatment, an alkali is used as a catalyst in an aqueous alkali solution such as sodium hydroxide, or a heat treatment is performed in a mixture of water and dioxane to hydrolyze lignin in the plant, Examples of the method include elution into a solution. Lignin can also be hydrolyzed by an enzymatic method using a lignin-degrading enzyme.

As a specific method for obtaining a lignin hydrolyzate by the above method, for example, a lignified plant such as Lauan is ground with a grinder or the like, and an aqueous solution of 1,3-dioxane is added thereto, followed by autoclaving. And heating under pressure at 150 to 200 ° C. for 1 to 3 hours.

The solution containing the hydrolyzate of lignin thus obtained is adjusted to a necessary pH to remove insolubles, and then the solvent is removed to obtain a concentrate.
A fractionation operation may be performed by column chromatography, liquid-liquid extraction, or the like, to obtain a fraction containing a component having an active oxygen eliminating action at a high concentration in the hydrolyzate.

Here, the lignin hydrolyzate used in the present invention may be any of the above-mentioned lignin hydrolyzate solution, its pH-adjusted product, fractionated product, and concentrate thereof, or a mixture thereof. .

<2> Composition containing active oxygen scavenger of the present invention The composition of the present invention is obtained by blending one or more of the above active oxygen scavengers by a conventional method. Examples include cosmetics, pharmaceuticals, foods, and the like.

(1) Cosmetic The cosmetic of the present invention contains the active oxygen scavenger described above for the purpose of preventing and improving wrinkles and hair loss, and preventing the generation of undesirable odors such as body odor. .

The amount of the active oxygen scavenger of the present invention in the above-mentioned cosmetics is not particularly limited, but is preferably in the range of 0.01 to 10% by weight based on the total amount of the cosmetics. More preferably, it is blended in the range of 1 to 1% by weight. If the amount of the active oxygen scavenger is less than 0.01%, the active oxygen scavenger has improved wrinkles, improved hair removal,
In some cases, effects such as body odor improvement may not be sufficiently obtained.
Even if it is added in excess of weight%, the effect tends to level off and is often not economical.

The cosmetics to which the present invention is applied are not particularly limited in dosage form, and include, for example, basic cosmetics such as lotions, emulsions, creams, and the like, makeup cosmetics such as foundations, under-make-ups, and white powders; Hair tonic,
Cosmetics for hair such as hair liquid, shampoo, and rinse can be mentioned. These cosmetics can be produced in the same manner as ordinary cosmetics, except that the active oxygen scavenger is blended.

In addition to the active oxygen scavenger, the cosmetic of the present invention contains various components generally used in cosmetics, for example, hydrocarbons such as petrolatum and liquid paraffin, jojoba oil, carnauba wax and the like. Esters, olive oil,
Triglycerides such as tallow, stearyl alcohol,
Higher alcohols such as behenyl alcohol, fatty acids such as stearic acid and behenic acid, nonionic surfactants such as glyceryl monostearate, polyoxyethylene stearic acid, polyoxyethylene hydrogenated castor oil, polyoxyethylene stearyl ether, soap, and sulfuric acid Anionic surfactants such as esters, cationic surfactants such as stearylamine, amphoteric surfactants such as alkyl betaine, glycerin, polyhydric alcohols such as propylene glycol,
Various powder components, humectants, thickeners, coloring agents, fragrances, antioxidants, pH adjusters, chelating agents, preservatives, or ultraviolet protective agents, anti-inflammatory agents, whitening agents, and the like can be added.

Furthermore, the cosmetic of the present invention contains SOD in addition to the hydrolyzate of lignin which is the active oxygen scavenger of the present invention.
A substance having an active oxygen scavenging action such as

(2) Pharmaceuticals When the active oxygen scavenger of the present invention is formulated as a pharmaceutical, the dosage form is not particularly limited. For example, injections, powders, granules, tablets, capsules, liquids and the like are usually used. Into various preparations according to the usual method. In addition, at the time of formulation, in addition to the active oxygen scavenger, excipients, binders, disintegrants, lubricants, flavoring agents, bulking agents, optional ingredients commonly used in pharmaceuticals such as coating agents are optional. Can be used.

The dosage of the above-mentioned medicines varies depending on the type and condition of the disease, the age of the patient, the weight, etc.
The amount of active oxygen scavenger per person per day is 10mg ~ 1
It is appropriate to administer 000 mg orally in one or several divided doses, or to administer 5 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.

(3) Foods When the active oxygen scavenger of the present invention is incorporated into foods, it can be incorporated into various foods together with optional components commonly used in foods. For example, sweets such as candy, gummy and jelly, drinks such as juice, and staple foods such as bread. The compounding amount varies depending on the type of food, but is preferably 0.01 to 10% by weight without impairing the taste of the food, and at which a sufficient effect of eliminating active oxygen can be expected.
More preferably, it is 0.1 to 1% by weight.

[0027]

The active oxygen scavenger of the present invention and the compositions containing it, such as cosmetics, medicines and foods, have excellent active oxygen scavenging action of the hydrolyzate of lignin, which is the active ingredient, as described above. It is said that active oxygen is involved in the formation of wrinkles, generation of body odor, hair loss, inflammation, senile dementia, ischemic diseases such as myocardial infarction, or allergic diseases, liver disorders, rheumatism and various other diseases. It effectively works for treatment and improvement of living body aging such as skin.

The active oxygen scavenger of the present invention and the cosmetic, pharmaceutical, food and other compositions containing it can also be effectively used for preventing the above-mentioned diseases and aging of the living body. this is,
This is because, by pre-existing a component having an active oxygen scavenging action in a living body, active oxygen generated in the living body can be quickly eliminated and detoxified.

[0029]

Embodiments of the present invention will be described below. First, examples of the active oxygen scavenger of the present invention will be described.

[0030]

Example 1 500 g of Lauan was powdered with a grinder, 4 L of a 50% aqueous solution of 1,3-dioxane was added to the powder, and the mixture was placed in an autoclave and heated at 180 ° C. for 2 hours. Thereafter, the solution was taken out of the autoclave and cooled, and then insolubles were removed by filtration. The solvent was removed from the obtained filtrate by distillation under reduced pressure, and 211 g of the solvent was removed.
Of lignin was obtained. This was used as an active oxygen scavenger 1 as it was.

The lignin hydrolyzate obtained above was separated with 1 L of normal hexane and 1 L of an 80% aqueous methanol solution, and the normal hexane layer was discarded to perform degreasing. The remaining 80% aqueous methanol solution layer was concentrated under reduced pressure to obtain 156 g.
Of the lignin hydrolyzate in 80% methanol aqueous solution was obtained. This was used as an active oxygen scavenger 2 as it was.

An 80% aqueous methanol solution of the lignin hydrolyzate was solubilized and dispersed in 1 L of purified water, charged to column chromatography filled with Diaion HP-20 (manufactured by Mitsubishi Kasei), and charged with 2 L of purified water. 2L 2
A 0% aqueous ethanol solution and 2 L of ethanol were sequentially flowed. Each of the obtained fractions was concentrated under reduced pressure to obtain 92 g of a water fraction,
19 g of a 20% ethanol fraction and 23 g of an ethanol fraction were obtained. These were designated as active oxygen scavenger 3, active oxygen scavenger 4, and active oxygen scavenger 5, respectively.

[0033]

Example 2 500 g of cedar was immersed in 2 L of normal hexane for 1 day to degrease, then powdered with a grinder, 4 L of a 50% aqueous solution of 1,3-dioxane was added, and the mixture was placed in an autoclave at 180 ° C. for 2 hours. Heated. Thereafter, the solution was taken out of the autoclave and cooled, and then insolubles were removed by filtration. The solvent was removed from the obtained filtrate by distillation under reduced pressure to obtain 134 g of a solvent.
Of lignin was obtained. This was used as an active oxygen scavenger 6 as it was.

[0034]

Example 3 500 g of Kunugi was immersed in 2 L of normal hexane for 24 hours to degrease, then powdered with a grinder, 4 L of a 50% 1,3-dioxane aqueous solution was added, and the mixture was heated in an autoclave at 180 ° C for 2 hours. . Thereafter, the solution was taken out of the autoclave and cooled, and then insolubles were removed by filtration. The solvent was removed from the obtained filtrate by distillation under reduced pressure to obtain 82 g of a lignin hydrolyzate. This was used as an active oxygen scavenger 7 as it was.

<Evaluation of Active Oxygen Scavenger of the Present Invention> The active oxygen scavenger obtained in each of the above Examples was evaluated for safety and active oxygen scavenging action.

(1) Acute toxicity test (intraperitoneal administration) 7 groups of 5 ICR male mice (body weight: 25 to 30 g)
In each group of, the active oxygen scavenger 1 ~ obtained in each of the above examples
7 was dissolved in physiological saline and administered intraperitoneally at a rate of 1000 mg / kg. On the 14th day after the administration, survival was determined, but no death was observed in any of the groups. Thus, LD ₅₀ by intraperitoneal administration of the active oxygen scavenger of the present invention.
The value is larger than 1000 mg / kg, which indicates that the safety is excellent.

(2) Acute toxicity test (oral administration) 7 groups of 6 ICR male mice (body weight: 25 to 30 g)
In each group of, the active oxygen scavenger 1 ~ obtained in each of the above examples
7 was dissolved in physiological saline and orally administered at a rate of 1000 mg / kg. On the 14th day after administration, survival was judged, but no death was observed in any of the groups. This indicates that the oral administration of the active oxygen scavenger of the present invention resulted in an LD ₅₀ value of more than 1000 mg / kg, indicating excellent safety.

(3) Measurement of scavenging activity of active oxygen Based on the reaction formula shown in Chemical formula 1, a superoxide anion (O ₂ ⁻ ), which is one of active oxygens, is generated by a xanthine-xanthine oxidase (XOD) system and generated. and O ₂ was ^- measured production rate by nitrous acid method, was determined active oxygen scavenging action value by correcting the value with xanthine oxidase inhibition percentage value.

[0039]

Embedded image 0.1 mL of the active oxygen scavenger aqueous solution containing various concentrations of the active oxygen scavengers 1 to 7 obtained in each of the above examples was added to 6
5 mM potassium dihydrogen phosphate, 35 mM sodium borate, 0.2 mM aqueous 0.5 mM EDTA (hereinafter referred to as buffer A), 0.2 mL of 0.5 mM xanthine solution, 0.1 mL of 10 mM aqueous solution of hydroxylamine hydrochloride, 0 mL of pure water .2 mL of the mixed solution and stirred well to obtain a test solution. Similarly, a control solution was prepared using 0.1 mL of pure water instead of the active oxygen scavenger.

To the test solution and the control solution, 0.2 mL of a buffer A containing 1 μL / mL of xanthine oxidase was added and stirred, followed by incubation at 37 ° C. for 30 minutes. As a blank, a solution treated in the same manner as above was prepared by adding 0.2 mL of buffer A containing no xanthine oxidase to the test solution and control solution prepared in the same manner as described above.

To each of the thus obtained solutions, 2 mL of a mixture 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.

[0043]

## EQU1 ## Active oxygen generation rate = [(A _550-3 −A _550-4 ) /
_{(A 550-1 -A 550-2)] ×} 100 urea generation 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 generation rate) × 100 where the symbols in the formula are the absorbance values of the solutions prepared under the conditions shown in Table 1. I do.

[0044]

[Table 1]

Further, the active oxygen scavenging activity value obtained by the above method was applied to a nonlinear least squares program to calculate an IC ₅₀ value (% by weight). Table 2 shows the results.

[0046]

[Table 2]

As is apparent from the results, the active oxygen scavenger of the present invention has an extremely low IC ₅₀ value and has excellent active oxygen scavenging activity even at a low concentration. Next, examples of compositions such as foods, medicines, and cosmetics containing the active oxygen scavenger obtained in each of the above examples will be described. The amounts used below are all parts by weight unless otherwise specified.

[0048]

Example 4 Candy The component A in Table 3 was heated and dissolved at 150 ° C. and cooled to 120 ° C. After that, the component B was added and stirred to make it uniform. This was molded and then cooled to obtain a candy.

[0049]

[Table 3]

[0050]

Example 5 Gummies The A component in Table 4 was heated and dissolved at 110 ° C., the separately swollen B component was added, the C component was further added, and the mixture was poured into a mold.
After standing all day and night, it was removed from the mold to obtain gummy.

[0051]

[Table 4]

[0052]

Examples 6 to 9 Juice The components shown in Table 5 were thoroughly stirred and solubilized, sterilized, aseptically filled, and sealed to produce juice.

[0053]

[Table 5]

[0054]

Example 10 Hot Cake The components shown in Table 6 were mixed well and baked in an oiled frying pan to prepare a hot cake.

[0055]

[Table 6]

[0056]

Example 11 Granules A component of Table 7 was mixed well, and 100 mL of 20%
The B component dissolved in the aqueous ethanol solution was gradually added while kneading, followed by granulation. This was air-dried at 40 ° C. for 2 days and night, sieved and sized to obtain granules.

[0057]

[Table 7]

[0058]

Example 12 Injection The components shown in Table 8 were dissolved, filtered, sterilized, aseptically filled in an ampoule and sealed to obtain an injection.

[0059]

[Table 8]

[0060]

Examples 13 and 14 Lotion The components shown in Table 9 were stirred and solubilized at room temperature to obtain a lotion.

[0061]

[Table 9]

[0062]

Examples 15 and 16 Emulsions The components A, B and C shown in Table 10 were each dissolved by heating at 80 ° C., the component B was added to the component A, the component C was further added, and the mixture was roughly emulsified and homogenized uniformly with a homogenizer. After cooling, an emulsion was obtained.

[0063]

[Table 10]

[0064]

Example 17 Cream A component, B component, and C component in Table 11 were each heated and dissolved at 80 ° C., B component was added to A component, and C component was further added.
Emulsification and cooling gave a cream.

[0065]

[Table 11]

[0066]

Examples 18 and 19 Hair tonic The components in Table 12 were stirred and solubilized at room temperature to obtain a hair tonic.

[0067]

[Table 12]

[0068]

The active oxygen scavenger of the present invention is excellent in active oxygen scavenging action and has high safety. Therefore, a composition such as a cosmetic, a pharmaceutical, a food, or a beverage containing the compound can be effectively used for a long period of time in the prevention and treatment of a disease involving active oxygen.

Continuation of the front page (51) Int.Cl. ⁷ identification code FI A61K 7/48 A61K 7/48 A61P 17/00 A61P 17/00 39/06 39/06 (58) Fields surveyed (Int.Cl. ⁷ , DB name) A61K 35/78 A23L 1/30 A61K 7/00 A61K 7/06 A61K 7/48 BIOSIS (DIALOG) CA (STN)

Claims (3)

(57) [Claims] 1. An active oxygen scavenger comprising a hydrolyzate of lignin. 2. A cosmetic comprising the active oxygen scavenger according to claim 1. 3. A pharmaceutical composition containing the active oxygen scavenger according to claim 1.