JPH07330624A - Anti-inflammatory, anti-itch agent - Google Patents

Abstract

(57) [Summary] [Purpose] To develop a highly active and highly safe anti-inflammatory and anti-itch external preparation. [PROBLEMS] To provide an anti-inflammatory and anti-itch external composition containing an extract from a steam distillation residue of mint grass as an active ingredient. [Effect] It is possible to provide an anti-inflammatory and anti-itch external preparation with good effect and high safety.

Description

Detailed Description of the Invention

[0001]

The present invention relates to an anti-inflammatory and anti-itch agent,
More specifically, an active ingredient is a certain ingredient obtained from a plant of the genus Mentha (Lamiaceae), which is excellent in anti-inflammatory, itching prevention, suppression, wound healing, skin roughness prevention, and skin roughness improvement. And an external preparation useful as a cosmetic, a medicine, and a quasi drug.

[0002]

2. Description of the Related Art Diseases associated with itch include atopic dermatitis and pruritus syrup such as senile pruritus. Such skin disorders cause mental distress to the patient and cause symptoms when scratched. Aggravate. In order to prevent or treat these skin diseases, various kinds of external preparations have been conventionally proposed. Of these, in particular, those having a crude drug as a main component have been attracting attention in consideration of a mild action on the skin (for example, JP-A-1-319424). However, even crude drug components are not always preferable because they act on the skin. From such a point of view, up to now, no external preparation has been found that has a satisfactory effect on itch-related diseases. In view of this situation,
The present inventors have conducted extensive studies to provide a natural product-based anti-inflammatory and anti-itch agent which has a strong activity against inflammation and is safe in terms of safety.

That is, itching is caused by applying a stimulus to the upper layer of the skin, and histamine is well known as a chemical substance that causes the itch. Histamine is released in the tissue by degranulation from mast cells and causes itching, which is an early reaction that causes inflammation (Atsushi Kubota et al., Edited by Contemporary Dermatology System 3C, Yasumasa Ishibashi, et al. Edited: strongly itchy) Skin diseases), the present inventors have found that various plant extracts have histamine release inhibitory action (in vitro) and inflammatory agent.
(compound 48/80) was investigated using the anti-inflammatory effect (in vivo) as an index. As a result, they found that there is a component having a strong anti-inflammatory effect in the residue generated by steam distillation when collecting the essential oil of a plant of the genus Mentha (hereinafter referred to as mint grass) of the Labiatae family, and thus the present invention is completed. Came to.
Mint leaves contain menthol as an essential oil component, and are widely used as a peppermint flavor for cosmetics, dentistry, and cooking. In addition, whole plants and oils have been used as aromatic stimulants, carminatives, antiseptics and antispasmodics. However, regarding the portion excluding the essential oil component, that is, the steam distillation residue, a method for producing a deodorant substance (JP-A-59-6056-6058).
No. JP-B No. 64-1145) and oral compositions (JP-A No. 62-155210) are known, and their physiological activities, anti-inflammatory and anti-itch effects have not yet been reported.

[0004]

The present invention provides an anti-inflammatory and anti-itch agent which comprises, as an active ingredient, a solvent extract of a steam distillation residue of a plant belonging to the genus Mentha (Mentha). It is a thing. The present invention also provides a solvent-extracted extract of a steam distillation residue of a certain Lamiaceae mentha plant, which is useful as an active ingredient of such anti-inflammatory and anti-itch agents.

The mint grass to be subjected to steam distillation is not particularly limited, and it is usually used for collecting essential oils for cosmetics, medicines, foods, etc.
a aquatica L.), Mentha piperita
L.), Penile Royal mint (Mentha pulegium L.), Malva mint (Mentha rotundifolia (L.) Huds.), Dutch mint (Mentha spicata L.) or Bergamot mint
(Mentha citrata (Ehrh.) Briq.) And their varieties. Further, steam distillation of mint grass is not particularly limited, and may be one used for collecting essential oil,
The residue can be used as it is or after drying.

The active ingredient of the present invention can be obtained by solvent-extracting the steam distillation residue of mint grass and distilling the solvent off from the extract. Examples of the extraction solvent include water, benzene, diethyl ether, chloroform, methylene chloride, ethyl acetate, butyl acetate, acetone, methanol, ethanol, butanol and 1,3.
-A solvent selected from butylene glycol may be mentioned, and these may be used alone or in combination of two or more kinds. Preferred solvents include water, methanol, ethanol and mixed solvents thereof, and are particularly preferable because they contain a component having a strong anti-inflammatory effect on the ethanol extract extract and its purified product.

The extraction conditions can be set arbitrarily. For example, extraction can be carried out simply by immersing the steam distillation residue of mint grass in an extraction solvent having a volume of about 1 to 30 times at room temperature or under heating. The extract may be used by itself after removing the solid matter by filtration or centrifugation to remove the solid matter by a suitable method known per se, or may be used after being concentrated or dried. it can. If desired, the above extract may be decolorized with activated carbon, or purified by treatment with a resin such as a synthetic polymer adsorbent. However, since the anti-inflammatory and anti-itch effects of the active ingredient strongly appear even in the form of the extract, high-level purification is not usually required unless there is a problem in terms of color, smell and stability.

The compounding amount of the active ingredient in the anti-inflammatory and anti-itch agent of the present invention varies depending on the formulation form, expected inflammation, degree of itch-suppressing effect and the like, but usually, the ingredient is added based on the total amount of the agent. 0.01 to 1 in terms of extract solids
0.0 wt%, preferably 0.1-5.0 wt% is suitable.

In the anti-inflammatory and anti-itch agents of the present invention, in addition to the above-mentioned active ingredients, if desired, a base (eg petrolatum, liquid paraffin etc.), a thickener (eg carboxyethyl cellulose, hyaluronic acid etc.), Additives such as surfactants (eg polyoxyethylene hydrogenated castor oil, sodium lauryl sulfate, etc.), diluents (eg water, ethanol, etc.), carrier for formulation of fragrances, excipients, additives, etc. can do. The anti-inflammatory and anti-itch agents of the present invention can be formulated into external preparations such as ointments, emulsifiers, creams, lotions, powders and packs by a method known per se, and are used as cosmetics, medicines and quasi drugs. It can be used for the prevention and control of inflammation and itch, wound healing, skin roughness prevention, and skin roughness improvement.

[0010]

EXAMPLES The present invention will be described in more detail with reference to Reference Examples, Test Examples and Examples, but the present invention is not limited thereto. (1) Preparation of Mint Grass Extract Reference Example 1 Mint grass (Mentha minna) steam distillation residue dried product 5
00 g was extracted twice with 4 liters of ethanol. Then, the combined solution of the two extracts was concentrated under reduced pressure and then dried.
23 g of the extract was obtained (yield 4.6%).

Reference Example 2 Dried product 5 of steam distillation residue of mint grass
00 g was extracted twice with 4 liters of methanol. Then, the combined solution of the two extracts was concentrated under reduced pressure and then dried.
30 g of the extract was obtained (6% yield).

Reference Example 3 Steam-distilled residue dried product 4 of mint grass
00 g was extracted twice with 4 liters of 50% ethanol. Then, the combined liquid of the two extracts was concentrated under reduced pressure and then dried to obtain 108 g of the extract (yield 27%).

Reference Example 4 Steam-dried residue dried product 400 of mint grass
g was extracted twice with 4 liters of water. Then, the combined liquid of the two extracts was concentrated under reduced pressure and then dried to obtain Extract 1
13 g was obtained (yield 28.3%).

(2) Histamine Release Inhibition Test Test Example 1 Test method: Rats (Wistar / ST system, body weight about 250 g) were intraperitoneally injected with 0.1% BSA phosphate buffer, and obesity was determined according to a conventional method. The cells were collected and a cell suspension was prepared.
The test substance was added to this suspension (2 ml), and after 10 minutes, an inflammatory agent (compound48 / 80) was added, and the amount of free and intracellular histamine for 10 minutes was quantified by the fluorescence method, and the formula shown in Formula 1 was used. The release inhibition rate (%) was calculated in accordance with.

[Equation 1] Results: The results are shown in Table 1. The release rate of only the inflammatory agent was 51.
9%, release rate of mint grass water extract is 50 μg / ml
Was 25.2% and 100 μg / ml was 3.5%, showing release inhibition rates of 51.4% and 93.3%, respectively.
Further, the release suppressing effect was also observed in the extracts extracted with other solvents.

[0015]

[Table 1]

(3) Paw edema inhibitory test by a inflammatory agent Test Example 2 Test substance: Macrogol ointment (Maruishi Pharmaceutical Co., Ltd.) with 5% of mint grass extract (Reference Examples 1 to 4) uniformly dispersed in the ointment positive Control substance: Restamine Kowa ointment (Kowa Co., Ltd.) Test method: Rat (Wister / ST system, body weight around 150 g) A test substance 5% mixed ointment was applied to the right hind paw, and after 4 hours, the test substance was wiped subcutaneously in the right footpad. 0.1m of inflammatory agent (compound 48/80) (100μg / ml) dissolved in physiological saline
1 subcutaneously. 60 minutes after the administration of the inflammatory agent, the measurement was performed using a paw volume measuring device, and the edema rate was calculated according to the following formula (2). In addition, the inhibition rate was calculated according to the formula shown in Formula 3 by comparison with the control group (placebo).

[0017]

[Equation 2]

[Equation 3]

Results: The results are shown in Table 2. For example, in the control group, the edema rate was 51.8%, the edema rate of the mint grass ethanol extract was 29.3%, and the edema inhibitory effect of 43.4% was observed. In addition, edema-suppressing action was also observed in extracts extracted with other solvents. The inhibition rate of 14.9% was obtained with the restamine Kowa ointment used as a positive control.
Therefore, the edema suppressive effect was recognized by the mint grass ethanol extract.

[0019]

[Table 2]

(4) Analysis of active ingredient Test Example 3 150 g of the mint grass ethanol extract obtained in Reference Example 1
Was liquid-liquid distributed with hexane / hydrous ethanol (4 liters each), the hydrous ethanol layer was collected and concentrated under reduced pressure to 90 g.
I got an extract. This extract was subjected to column chromatography (390 g: φ50 × 300 mm) of Diaion (manufactured by Mitsubishi Kasei Co., Ltd., DIAION HP-20) with water, 50% ethanol, ethanol, and acetone (3.5 liters each). The fractions were sequentially eluted, and 50% ethanol-eluted fractions were collected and concentrated under reduced pressure to obtain 30 g of extract. This extract was subjected to silica gel column chromatography (250
g: φ38 × 510 mm) and eluted using a linear gradient of chloroform-methanol (9: 1, 8 liters) -methanol (0.5 liters), 100 m
Fractions of 1 were fractionated. The 41st to 51st fractions were collected, concentrated, and again subjected to the same silica gel column column chromatography, and chloroform-methanol (7: 1, 1 liter) -chloroform-
Elution was performed using a linear gradient of methanol (4: 1, 1 liter) and fractionation was carried out in 50 ml fractions. The 11th to 14th fractions were collected and dried under reduced pressure to obtain 1.2 g of powder. The result of the histamine release inhibition test of this powder according to Test Example 1 above showed a concentration of 10
Release rate of 0 μg / ml 34.0% (inhibition rate 34.5%)
And showed strong anti-inflammatory and anti-itch effects. This active ingredient had the following physical properties.

(A) Infrared absorption spectrum (KBr) ν
_max : 3400, 2930, 1650, 1060 cm
^-1 (See FIG. 1) (b) Ultraviolet absorption spectrum (H ₂ O) λ _max : 260,2
80 nm (see FIG. 2) (c) Solubility: readily soluble in water, insoluble in benzene, ether, chloroform. (D) Color reaction: A yellowish brown color is obtained when heated after spraying sulfuric acid on a TLC plate. It turns red with metallic magnesium and hydrochloric acid. It turns brown with ferric chloride and shows a deep yellow color when alkali is added. (E) Thin layer chromatography (TLC): Chloroform: methanol = 2: 1 shows an Rf value of 0.25 in a developing solvent.

Example 1: Ointment

[Table 3] The extract obtained in Reference Example 1 was propylene glycol # 400.
After being uniformly dispersed in the mixture, macrogol ointment was added and mixed to obtain an ointment.

Example 2: Lotion

[Table 4] Glycerin, citric acid, sodium citrate in purified water,
The extract obtained in Reference Example 4 was dissolved. Polyoxyethylene hydrogenated castor oil (60.E.
O. ), Methylparaben, and fragrance were dissolved and added to the above aqueous solution for solubilization, and filtered to obtain a lotion.

Example 3: Cosmetic oil

[Table 5] Other ingredients were uniformly dissolved in squalane to obtain a cosmetic oil.

Example 4: Cream

[Table 6] The component (A) is melted by heating to 80 ° C. Separately, the component (B) excluding the fragrance was melted by heating and kept at 80 ° C., and the above component (A) was added thereto with stirring and thoroughly mixed. Further, the mixture was cooled with stirring to add a flavor, and further cooled to obtain a cream.

Example 5: Emulsion

[Table 7] Ingredient (A) is dissolved by heating at 80 ° C and heated separately (80
(° C.) The component (B) excluding the dissolved fragrance was cooled with stirring, the fragrance was added, and further cooled to obtain an emulsion.

Example 6: Pack

[Table 8] The extract, ethylparaben, fragrance and ethanol obtained in Reference Example 2 were uniformly dissolved. This was added to a mixture of vinyl acetate / styrene copolymer, polyvinyl alcohol, and sorbit to obtain a pack.

Example 7: Powder

[Table 9] The extract obtained in Reference Example 4 and decaglyceryl stearate were dissolved by heating, and this was gradually added to a dextrin and talc mixture with stirring to obtain a powder.

[0029]

EFFECT OF THE INVENTION By applying the anti-inflammatory and anti-itch external use composition of the present invention, anti-inflammatory and anti-itch prevention and inhibition,
In addition to wound healing, it has excellent effects in preventing and improving rough skin.

[Brief description of drawings]

FIG. 1 is an infrared absorption spectrum of the active ingredient.

FIG. 2 is an ultraviolet absorption spectrum of the active ingredient.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Internal reference number FI Technical indication C07G 17/00 Z (72) Inventor Koji Nakata 3-46-7 Tsunoe-cho, Takatsuki-shi, Osaka ( 72) Inventor Ayumu Takahashi 11-27-10, Ohata-cho, Takatsuki-shi, Osaka Prefecture (72) Marina Watanabe 2-30-2-1 Oji, Takatsuki-shi, Osaka Prefecture (72) Inventor Kazumi Moji 1 Maruyama, Nara-shi, Nara Prefecture −1079−33 (72) Inventor Eiichi Naeshiro 6-15 Minamikusunosato-cho, Daito City, Osaka Prefecture

Claims (12)

[Claims] 1. A mentholaceae mentor (Menth) as an active ingredient.
a) An anti-inflammatory and anti-itch agent characterized by containing a solvent extract of a steam distillation residue of a genus plant. 2. A plant of the genus Mentha of the Labiatae family is Menthacea (Menth).
a aquatica L.), Mentha piperita
L.), Penile Royal mint (Mentha pulegium L.), Malva mint (Mentha rotundifolia (L.) Huds.), Dutch mint (Mentha spicata L) or Bergamot mint (M.
Entha citrata (Ehrh.) Briq.) and variants thereof, and the anti-inflammatory and anti-itch agents according to claim 1. 3. The solvent is one or more selected from water, benzene, diethyl ether, chloroform, methylene chloride, ethyl acetate, butyl acetate, acetone, methanol, ethanol, butanol and 1,3-butylene glycol. The anti-inflammatory and anti-itch agent according to claim 1, which is a solvent. 4. The anti-inflammatory and anti-itch agent according to claim 1, which comprises 0.01 to 10.0% by weight of the component based on the total amount of the composition in terms of extract solids. 5. The anti-inflammatory and anti-itch agent according to claim 1, which is a cosmetic. 6. The extract according to claim 1, which has the following physical properties.
The anti-inflammatory and anti-itch agents described. (A) Infrared absorption spectrum (KBr) ν _max : 340
0,2930,1650,1060 cm ⁻¹ (b) Ultraviolet absorption spectrum (H ₂ O) λ _max : 260,2
80 nm (c) Solubility: Soluble in water, insoluble in benzene, ether, chloroform. (D) Color reaction: A yellowish brown color is obtained when heated after spraying sulfuric acid on a TLC plate. It turns red with metallic magnesium and hydrochloric acid. It turns brown with ferric chloride and shows a deep yellow color when alkali is added. (E) Thin layer chromatography (TLC): Chloroform: methanol = 2: 1 shows an Rf value of 0.25 in a developing solvent. 7. A solvent-extracted extract of a mentha mentha plant having anti-inflammatory and anti-itch effects having the following physical properties. (A) Infrared absorption spectrum (KBr) ν _max : 340
0,2930,1650,1060 cm ⁻¹ (b) Ultraviolet absorption spectrum (H ₂ O) λ _max : 260,2
80 nm (c) Solubility: Soluble in water, insoluble in benzene, ether, chloroform. (D) Color reaction: A yellowish brown color is obtained when heated after spraying sulfuric acid on a TLC plate. It turns red with metallic magnesium and hydrochloric acid. It turns brown with ferric chloride and shows a deep yellow color when alkali is added. (E) Thin layer chromatography (TLC): Chloroform: methanol = 2: 1 shows an Rf value of 0.25 in a developing solvent. 8. A mint family plant belonging to the Labiatae family is Menthacea (Menth).
a aquatica L.), Mentha piperita
L.), Penile Royal mint (Mentha pulegium L.), Malva mint (Mentha rotundifolia (L.) Huds.), Dutch mint (Mentha spicata L) or Bergamot mint (M.
8. The extract according to claim 7, which is entha citrata (Ehrh.) Briq.) and variants thereof. 9. The solvent is one or more selected from water, benzene, diethyl ether, chloroform, methylene chloride, ethyl acetate, butyl acetate, acetone, methanol, ethanol, butanol and 1,3-butylene glycol. The extract according to claim 7, which is a solvent. 10. An ethanol-extracted extract of the steam distillation residue of a mentha mentha plant. 11. An extract which is distributed between hexane and hydrous ethanol and extracted into a hydrous ethanol layer. 12. A styrene-containing extract according to claim 11.
Extraction extract obtained by subjecting a divinylbenzene copolymer-based polymer adsorbent to column chromatography and eluting with 50% ethanol.