JPH06183987A - Lipoperoxide formation inhibitor and composition containing the same - Google Patents

Abstract

PURPOSE:To obtain a lipoperoxide formation inhibitor having high capturing and scavenging action on active oxygen, excellent inhibitory effect on lipoperoxide formation, high stability and safety. CONSTITUTION:A lipoperoxide formation inhibitor is mixed with an extract of a plant of the genus Pelargonium. This lipoperoxide formation inhibitor is blended with a composition such as a cosmetic, food or medicine.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a lipid peroxide production inhibitor and a composition containing the same, and more particularly to a lipid peroxide production inhibitor containing an extract of a plant of the genus Pelargonium and the lipid peroxide production thereof. It relates to a composition containing an inhibitor.

[0002]

2. Description of the Related Art In recent years, active oxygen produced in the living body has become
It has become clear that it reacts with unsaturated fatty acids to produce lipid peroxides, which adversely affects the human body. For example, lipid peroxides and their oxidative degradation products act on nucleic acids and proteins, causing vascular disorders due to arteriosclerosis, liver dysfunction, retinopathy, cataracts, etc., and being involved in carcinogenesis, aging, etc. It has been known.

Particularly, the skin, which is easily affected by environmental factors directly from the outside, is easily attacked by ultraviolet rays, natural radiation, etc., and active oxygen is easily generated by these actions, which is a biological membrane phospholipid or Reacts with the unsaturated fatty acids of sebum to produce a large amount of lipid peroxide. As a result, abnormal pigmentation such as spots, freckles, inflammation, edema,
It is prone to problems such as necrosis, wrinkles and aging.

Many cosmetics, pharmaceuticals, foods and drinks contain a large amount of fats and oils, which react with active oxygen during storage and use to produce lipid peroxides, which leads to quality deterioration and The expression of toxicity to the human body has become a big problem.

[0005] For this reason, exploratory research on drugs for improving abnormal lipid peroxides in vivo has been widely conducted. Typical examples include fat-soluble tocopherol (vitamin E) and water-soluble ascorbic acid (vitamin C) as natural products, and BHT as a synthetic compound.
Examples include (3,5-tert-butyl-4-hydroxytoluene) and BHA (2 (3) -tert-butyl-hydroxyanisole), but the effects were not satisfactory.

[0006] On the other hand, many attempts have been made to obtain a lipid peroxide production inhibitory substance which is highly effective in improving abnormal lipid peroxides in vivo, and various crude drug extracts have been disclosed (for example, Japanese Patent Laid-Open No. 2000-242242). JP-A-60-224629, JP-A-61-24522, JP-A-2-193930, JP-A-2-243632, JP-A-2-264727, JP-A-3-153629, JP-A-3-221587,
JP-A-4-69343, JP-A-4-202138,
JP-A-4-247010).

[0007]

However, the above herbal medicine extract has the following problems compared with tocopherol and ascorbic acid.
Although the lipid peroxide abnormally improving effect to some extent is obtained, it does not yet have a sufficient lipid peroxide production suppressing effect. In addition, the synthetic compounds BHT and BHA have problems such as suspected carcinogenicity. Therefore, a substance that is excellent in the effect of suppressing the production of lipid peroxide and has high safety is desired.

In order to suppress the production of lipid peroxide,
In addition to its antioxidant effect that suppresses lipid oxidation, it also has the effect of supplementing and removing active oxygen itself, but superoxide dismutase, catalase, etc., which have a conventionally known action of supplementing and removing active oxygen, have extremely low stability. , Is not practical. If a stable substance having an action of supplementing and removing active oxygen is obtained, it is expected that a higher inhibitory effect on lipid peroxide production will be obtained by the combined use with an antioxidant.

[0009] The present invention has been made from the above viewpoint, and provides a lipid peroxide production inhibitor which has a high action of capturing and removing active oxygen, is excellent in the lipid peroxide production inhibitory effect, and is highly stable and safe. It is an object of the present invention to provide a composition that does not easily produce lipid peroxide containing the same.

[0010]

Means for Solving the Problems In order to solve the above problems, the present inventor has conducted an earnest search for a component having an action of trapping and removing active oxygen and an action of inhibiting lipid peroxide production, and as a result, an extract of a plant of the genus Pelargonium was obtained. It was found that a component having a strong active oxygen trapping and removing action is present, and the present invention has been completed. That is, the present invention relates to a lipid peroxide production inhibitor containing an extract of a plant of the genus Pelargonium and its peroxidation. A composition for cosmetics, foods, pharmaceuticals, etc., which contains an adipogenesis inhibitor. Hereinafter, the present invention will be described in detail.

<1> Lipid Peroxide Production Inhibitor of the Present Invention (1) Extract of Pelargonium Plants The lipid peroxide production inhibitor of the present invention contains an extract of pelargonium plants.

First, the plant of the genus Pelargonium used in the present invention is a plant belonging to the genus Pelargonium of the family Furosoaceae, for example, Pelargonium zonale, Pelargonium inquinans, and Pelargonium xantherae, which are native to South Africa. hortorum), Pelargonium grossularioides, Pelargonium odoratissimum (Pelargonium odoratissim)
um) and the like.

Incidentally, these plants are JJA Van der W
alt & PJ Vorster, Pelargoniums of Southern Afri
ca Vol.1-4, National Botanic Gardens Kirstenbosch
(1988).

The above-mentioned plant of the genus Pelargonium contains a component having a function of scavenging and deactivating active oxygen which is a factor causing the production of lipid peroxide harmful to the human body, and crushed leaves can be used as they are. However, it is preferable to use the extract of the above components as an active ingredient of the lipid peroxide production inhibitor of the present invention.

An example of a method for extracting a component having an active oxygen trapping and removing action from a plant of the genus Pelargonium will be described below. First, the leaves of a pelargonium plant are crushed. At this time, in order to facilitate the crushing of the leaves, for example, pretreatment such as freezing with liquid nitrogen may be performed. Next, crushed pelargonium plants are put in an extraction solvent for extraction, and then, if necessary, concentrated to dryness.

The solvent used for extraction may be one or more selected from water, alcohol, acetone and ethyl acetate, preferably an ethanol aqueous solution of 30 to 99.5 vol%, more preferably 40 to. 80 vo
A 1% aqueous ethanol solution is used. For example, 80v
Extract with an ol% ethanol solution at room temperature overnight,
Concentrate to dryness.

If necessary, a component having an action of capturing and removing active oxygen is further extracted. For example, the dry solid is dissolved in a mixed solution of equal amounts of ethyl acetate and water. Next, this mixed solution is separated into an ethyl acetate layer and an aqueous layer using a separating funnel or the like, the ethyl acetate solution is concentrated, and a component having a high active oxygen trapping and removing action is taken out as a dry solid. The dried product thus obtained has a green color and is water-soluble, but it may become difficult to dissolve in water when completely dried, and therefore, when used in an aqueous system, it may be stored in a slightly wet state.

(2) Extraction Examples of Pelargonium Plant Extracts Next, examples of extraction from pelargonium plants with various solvents will be shown. 1 g of dried leaves of pelargonium zonare is frozen in liquid nitrogen and then crushed and extracted with water, 40% ethanol aqueous solution, 80% ethanol aqueous solution, 99.5% ethanol aqueous solution, acetone, ethyl acetate (20 ml each) at room temperature for 5 hours. After that, the same solvent was added to each to make 50 ml.

The extract thus obtained was used as a sample to evaluate the action of capturing and removing active oxygen. This evaluation is performed by measuring stoichiometry of model radical inactivation by each sample (measurement of radical scavenging ability).
I went there. That is, a stable free radical, α, α-diphenyl-β-picrylhydrazyl (DPPH.) Was used as a model of active oxygen, and at a constant ratio with the sample,
After reacting for a certain period of time, the amount of radicals reduced thereby was measured as the amount of decrease in absorbance at 517 nm.

10 μl of each extraction solution was placed in each test tube,
2 ml each of 99.5% ethanol aqueous solution, 0.1M
Acetate buffer (pH 5.5) 2 ml, 0.5 mM α, α
-Diphenyl-β-picrylhydrazyl (DPPH.)
1 ml of an ethanol solution (manufactured by Nacalai Textile Co., Ltd.) was added, and 30 minutes later, the amount of decrease in absorbance at 517 nm was measured. The measurement was performed according to Kenji Fukuzawa and Junji Terao, “Chemistry and Biological Experiment Line 2, Lipid Peroxidation Experimental Method” p79.

The results are shown in Table 1. The amount of decrease in absorbance is 0 when the absorbance does not decrease at all and 0 when the absorbance is 0.
When the decrease amount is 1, the decrease amount of the free radicals is larger as the decrease amount of the absorbance is larger.

[0022]

[Table 1]

From these results, a component having a sufficient active oxygen scavenging and removing action was extracted regardless of which solvent was used.
It can be seen that 0-80% ethanol aqueous solution is preferable.

(3) Lipid Peroxide Production Inhibitor The lipid peroxide production inhibitor of the present invention contains the extract of the above-mentioned plant of the genus Pelargonium, and contains the extract of two or more plants belonging to the genus of Pelargonium. You may mix and use it. Further, the extract itself may be used, or may be mixed with various bases, if necessary, together with other lipid peroxide inhibiting substances.

The compounding amount and the kind of the base are not particularly limited and may be set appropriately. Examples of other lipid peroxide inhibiting substances include substances that have been conventionally used such as tocopherol and ascorbic acid.

<2> Composition Containing Lipid Peroxide Production Inhibitor of the Present Invention The composition of the present invention contains the above lipid peroxide production inhibitor, and contains a lipid that easily produces lipid peroxide. It can be applied as long as it includes, for example, cosmetics, food,
Examples include medicines and quasi drugs.

As the cosmetics to which the present invention is applied, the dosage form is not particularly limited, and examples thereof include base materials such as emulsion, cream and water-based gel, and finishing agents such as foundation and control color. You can These cosmetics can be produced in the same manner as ordinary cosmetics except that the above-mentioned lipid peroxide production inhibitor is added.

The blending amount of the above lipid peroxide production inhibitor is not particularly limited, but it is preferably blended in cosmetics in the range of 0.005 to 1% by weight. Further, the cosmetics of the present invention include various components generally used in cosmetics, that is, an aqueous component, an oily component, a powder component, a surfactant, a moisturizer, a thickener, a coloring agent, a fragrance, an antioxidant, and a pH adjusting agent. , Chelating agent,
An antiseptic, an ultraviolet protective agent, an anti-inflammatory agent, a whitening agent, etc. can be added.

When the above-mentioned lipid peroxide production inhibitor is used in food, it is used as a general food by adding the required amount of extract to each food material and processing and producing it by a usual production method. As foods and functional foods, plants and extracts can be used as they are or in an easy-to-eat state. Generally, the amount of the above-mentioned lipid peroxide production inhibitor added to food is preferably in the range of 0.01 to 2% by weight.

When the lipid peroxide production inhibitor of the present invention is used in a medicine, the dosage form is not particularly limited, but it is generally a pharmaceutically acceptable harmless one or several kinds of vehicles, carriers,
Mixtures with excipients, integrants, preservatives, stabilizers, flavors, etc., tablets, granules, capsules, internal preparations such as drenches, ointments, creams, external preparations such as liquid preparations, sterile solutions It may be an injection such as a drug or suspension. These can be manufactured using a conventionally known technique.

For example, the above-mentioned lipid peroxide production inhibitor and an integrant such as corn starch and gelatin, an excipient such as microcrystalline cellulose, a potato starch, a puffing agent such as sodium alginate, a sweetener such as lactose and sucrose, etc. To the powder,
It can be a tablet, granule, or capsule. Also,
In the case of an injection, distilled water for injection, polyethylene glycol or the like is used as a solvent, or a dispersant, a buffer, a preservative, an antioxidant or the like may be added thereto as required. When used as an external preparation, petrolatum, paraffin, oils and fats, lanolin and the like are used as a base.

The dose varies depending on the age of the patient, the type of disease, the symptoms, etc., but in general, the amount of lipid peroxide inhibitor is 0.005-1% by weight in oral administration, and 0 in the case of injection. 0.001-1% by weight, and as an external preparation, 0.001.
By using it in the range of 005 to 1% by weight, the expected effect can be expected.

Since the plant of the genus Pelargonium is used as a herb in South Africa in foods and the like, there is no problem in safety.

[0034]

EXAMPLES Examples of the present invention will be described below. The percentages used below are weight percentages unless otherwise specified.

First, examples of the lipid peroxide production inhibitor of the present invention are shown below.

[0036]

Example 1 Lipid Peroxide Production Inhibitor Pelargonium zonare leaves (10 g) were frozen with liquid nitrogen, crushed, and then immersed in 200 ml of 80% ethanol aqueous solution for extraction overnight. The extract was filtered through a Buchner funnel, concentrated to dryness using a rotary evaporator,
1.31 g of dried product was obtained.

This was added to 100 ml of a mixed solution of equal amounts of water and ethyl acetate and dissolved. The mixed solution was fractionated with a separating funnel to separate the ethyl acetate layer, which was concentrated to dryness with a rotary evaporator, and a green dry matter of 0.
72 g was obtained and used as a lipid peroxide production inhibitor.

[0038]

Example 2 Lipid Peroxide Production Inhibitor An equivalent weight of dl to the final concentrated dry solid obtained in Example
-Α-Tocopherol (manufactured by Nakarai Textile Co., Ltd.) was mixed to obtain a lipid peroxide production inhibitor.

[0039]

Example 3 Lipid Peroxide Production Inhibitor Pelargonium zonare leaves (10 g) were shredded, dispersed in 200 ml of 40% ethanol aqueous solution, and extracted with a Soxhlet extractor for 3 hours. The extract was concentrated to dryness using a rotary evaporator to obtain 1.54 g of a green dry product. This was directly used as a lipid peroxide inhibitor.

[0040]

Example 4 Lipid Peroxide Production Inhibitor 10 g of leaves of pelargonium holtram were frozen in liquid nitrogen, crushed, immersed in 200 ml of acetone and extracted for 5 hours. After filtering this extract with a Buchner funnel,
Concentrate to dryness using a rotary evaporator to 1.3.
8 g of a green dry solid was obtained. This was directly used as a lipid peroxide inhibitor.

<Evaluation of Lipid Peroxide Production Inhibitor of the Present Invention>
With respect to the lipid peroxide production inhibitor of the present invention, the active oxygen trapping and removing action and the lipid peroxide production inhibiting effect were evaluated. still,
For comparison, the same evaluation was performed on dl-α-tocopherol (manufactured by Nacalai Techs Co., Ltd.).

Further, the storage stability and safety of the extract of the plant of the genus Pelargonium were also evaluated.

(1) Active oxygen trapping / removing action In a 20 ml screw tube, 99.5% of the lipid peroxide production inhibitor or dl-α-tocopherol of Example 1 was added.
Add 2 ml of a solution dissolved in ethanol and 2 ml of 0.1 M acetate buffer (pH 5.5), and add 0.5 mM DP.
Add 1 ml of PH / ethanol solution, and after 30 minutes 517
The decrease in absorbance at nm was measured. Further, the above experiment was conducted by changing the concentration of the sample variously.

The results are shown in FIG. EC showing the amount required to capture DPPH / half under the above conditions
₅₀ is 24.66μ of the lipid peroxide production inhibitor of Example 1.
The amount of g, dl-α-tocopherol was 42.27 μg. From this, it is understood that the active oxygen trapping and removing action of the lipid peroxide production inhibitor of Example 1 is about twice that of dl-α-tocopherol. Therefore, by using the lipid peroxide production inhibitor of Example 1, free radicals containing active oxygen can be effectively captured even at a concentration lower than that of dl-α-tocopherol.

(2) Lipid Peroxide Production Inhibition Effect A 20 ml screw tube was charged with 2.052 ml of linoleic acid diluted to 2.51% with an aqueous 99.5% ethanol solution.
Take 4 ml of 0.05 M phosphate buffer (pH 6.
0) was added, and further water was added to make 10 ml. To this, the lipid peroxide production inhibitor or dl-α-tocopherol of Example 1 was added in an amount of 0.01% by weight. This was maintained at 40 ° C. under dark conditions, and the amount of lipid peroxide produced by the TBA method was measured over time. Similarly, the amount of lipid peroxide produced was measured for the sample without the sample (standard).

According to the TBA method, 2 ml of a 20% aqueous solution of trichloroacetic acid was added to 2 ml of a sample, and then 1 m of an aqueous solution of 0.167% thiobarbituric acid (manufactured by Nacalai Techs Co., Ltd.)
l, and boiled in water at 100 ° C. for 10 minutes, immediately cooled with ice, centrifuged at 3000 rpm for 10 minutes, and 532n
Absorbance at m (R. Inatani et al, Agric.Bio
l. Chem., 47 [3], 521 (1983)). The higher the absorbance, the greater the amount of lipid peroxide produced.

The results are shown in FIG. In the case of dl-α-tocopherol, the production of lipid peroxide started after 6 days, whereas in the lipid peroxide production inhibitor of Example 1, it was 12
Almost no production of lipid peroxide was observed even after a lapse of days, which shows that the lipid peroxide production inhibitory effect is excellent.

(3) Lipid Peroxide Production Suppressing Effect under Oxidizing Conditions Next, the effect of using ferrous sulfate to inhibit lipid peroxide production under easily oxidizing conditions was examined.

Into a 20 ml screw tube, 2.052 ml of 2.51% squalene (manufactured by Nacalai Tex Co., Ltd.) in 99.5% ethanol aqueous solution was placed, and 4 ml of 0.05M phosphate buffer (pH 6.0) was added. ) Was further added, and ferrous sulfate and vitamin C were added so that each amount was 0.1 M, and water was added to make 10 ml. In addition to this, the lipid peroxide production inhibitor of Examples 1 and 2, or dl-
α-Tocopherol was added so as to be 0.01% by weight.

This was maintained at 40 ° C. under dark conditions, and the amount of lipid peroxide produced was measured over time by the TBA method. In the same manner, the lipid peroxide production inhibitory amount was measured for the sample without the sample (standard).

The results are shown in FIG. As is clear from this result, the lipid peroxide production inhibitors of Examples 1 and 2 can effectively inhibit the production of lipid peroxide even under the condition that they are very easily oxidized. It is also found that the combined use of the pelargonium genus extract and dl-α-tocopherol produces a higher effect.

(4) Storage stability 1 g of pelargonium zonare leaves was extracted with an 80% ethanol aqueous solution, and the extract was allowed to stand at room temperature without concentrating to dryness, and after 2 and 4 weeks, DPPH / radicals were removed. The activity of supplementing and removing active oxygen was investigated.

As a result, it was found that there was almost no difference between the measured values immediately after extraction and the measured values after 2 weeks and 4 weeks, indicating that the activity was not reduced. A slight amount of precipitate was observed.

Next, examples of the composition containing the lipid peroxide production inhibitor of the present invention will be described.

[0055]

Example 5 Cosmetic (Toilet lotion) The components of Table 2 were homogeneously mixed and dissolved at room temperature to obtain a lotion.

[0056]

[Table 2]

[0057]

Example 6 Cosmetic (Cream) Components A and B in Table 3 were each heated and dissolved at 70 ° C.
The component A was gradually added to the component A while stirring, the emulsion was inverted, and the mixture was cooled to 35 ° C. and the component C was added to obtain a cream.

[0058]

[Table 3]

[0059]

Example 7 Food (Cookie) Wheat flour containing 2% by weight of the lipid peroxide production inhibitor of Example 1 seasoned with salt, sucrose, butter, etc. was thoroughly stirred with an appropriate amount of water, Bake at 200 ° C for 30 minutes to make cookies.

[0060]

Example 8 Food (jelly) 12 g of agar was dissolved in 1 liter of water with stirring, and 40 parts of sucrose was added.
After adding 0 g, 150 g of starch syrup and a little salt and heating and dissolving with stirring, 2% by weight of the lipid peroxide production inhibitor of Example 1 and a fragrance are added, and the mixture is cooled to obtain a jelly.

[0061]

Example 9 Pharmaceuticals (Tablets, Capsules) The following components were uniformly mixed in the following parts by weight to give tablets or capsules. Lipid peroxide production inhibitor of Example 1 9.8 Lactose 80.0 Magnesium stearate 10.0 Hydroxypropylcellulose 0.2

[0062]

Example 10 Pharmaceuticals (Powder, Granule) The following components were uniformly mixed in the following parts by weight to give a powder or granule. Lipid peroxide production inhibitor of Example 3 10.0 Starch 35.0 Lactose 54.7 Hydroxypropyl cellulose 0.3

[0063]

Industrial Applicability The lipid peroxide production inhibitor of the present invention contains an extract of a plant of the genus Pelargonium as an active ingredient, and has a high active oxygen scavenging and removing action. As a result, the lipid peroxide production inhibitory effect is excellent and stable. It is highly safe and secure.

Further, the lipid peroxide production inhibitor of the present invention is
By including it in a composition containing fats and oils such as cosmetics, foods, pharmaceuticals, and quasi-drugs, a composition in which the production of lipid peroxide is suppressed can be obtained.

[Brief description of drawings]

FIG. 1 Pelargonium plant extract and dl-α-
The figure which shows the comparison of the amount of free radical reduction by tocopherol

FIG. 2 Pelargonium plant extract and dl-α-
Figure showing comparison of lipid peroxide production in the presence of tocopherol

FIG. 3 is a diagram showing a comparison of lipid peroxide production under oxidative conditions in the presence of a pelargonium plant extract, dl-α-tocopherol, and a mixture thereof.

Claims (4)

[Claims] 1. A lipid peroxide production inhibitor containing an extract of a plant belonging to the genus Pelargonium. 2. The lipid peroxide inhibitor according to claim 1, wherein the plant of the genus Pelargonium is one or more kinds selected from pelargonium zonare, pelargonium inquinans, pelargonium holtrum, pelargonium grossularioides, and pelargonium odoratisimum. . 3. The lipid peroxide production inhibitor according to claim 1, wherein the extraction solvent is one kind or two or more kinds selected from water, alcohol, acetone and ethyl acetate. 4. A composition containing the lipid peroxide production inhibitor according to claim 1.