JP2007161630A - Sebum inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a sebum inhibitor having a high sebum secretion suppressing effect which is effective for treatment or prophylaxis to increase in dandruff, alopecia, dermatitis or pimple, etc., by suppressing excessive secretion of sebum from sebaceous gland of the skin. <P>SOLUTION: The sebum inhibitor optionally comprises a hydrolyzate of a plant body obtained by removing sugar, low molecular lipid component and wax component, a salt obtained by salt substitution treatment of the hydrolyzate, an ester a product of esterification of the hydrolyzate or an amide a product of amidation. The sebum inhibitor optionally comprises a trihydroxy fatty acid, a salt of the trihydroxy fatty acid, an ester or an amide of the trihydroxy fatty acid as the active component. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a sebum inhibitor. The sebum inhibitor of the present invention suppresses excessive sebum secretion from the sebaceous glands, and is effective in preventing or treating dandruff or acne.

  Sebum secreted from the sebaceous glands of the skin and scalp is important for protecting the skin and hair, and also plays a role in preventing water loss. However, excessive sebaceous gland activity causes increased dandruff, hair loss, dermatitis, or acne. For this reason, it has been conventional to remove sebum by washing with soap or the like, but since this effect is temporary, a compound having a sebum synthesis inhibitory effect has been studied in order to obtain a sustained effect. Has been. For example, a sebum inhibitor containing a compound such as monohydroxycarboxylic acid or dihydroxycarboxylic acid has been reported as having an effect (Patent Document 1).

  In addition to this, extracts from Raijin, Asteraceae, or a baker's yeast have been reported as having an effect of suppressing sebum secretion (Patent Document 2, Patent Document 3, and Patent Document). 4).

  However, the effect of the reported sebum inhibitor is not yet satisfactory, and there has been a demand for a sebum inhibitor that is more effective.

JP-A-8-48625 JP 2005-187422 A JP 2000-169332 A JP-A-8-188517

  The inventors of the present invention have eagerly studied the active ingredient of the sebum inhibitor that is more effective than the active ingredient of the conventional sebum inhibitor. It was found that a product obtained by extracting a fraction and hydrolyzing this fraction (hereinafter referred to as a hydrolysis-treated product) has sebum secretion inhibitory activity. The present inventors further provide a product obtained by subjecting the hydrolysis treatment product to salt conversion treatment (hereinafter referred to as a salt transformation treatment product), a product obtained by esterification treatment (hereinafter referred to as esterification). It was found that the sebum synthesis inhibitory activity was also obtained in the product (hereinafter referred to as the treated product) or the product obtained by the amidation treatment (hereinafter referred to as the amidated product).

Furthermore, the present inventors include the hydrolysis treatment product as follows:
Formula (I):
HO—CH ₂ —R—COOH (I)
(In the formula, R is a linear or branched saturated or unsaturated hydrocarbon group having 10 to 20 carbon atoms substituted with two hydroxyl groups)
It was found that even this compound alone has sebum synthesis inhibitory activity. Moreover, it discovered that the salt, ester, or amide of this compound has the same sebum secretion suppression activity.
The present invention is based on such knowledge.

Therefore, the present invention
(1) A water-insoluble fraction is obtained by removing a water-soluble fraction from a plant body, a soluble fraction of a polar organic solvent is removed from the water-insoluble fraction to obtain an insoluble fraction of a polar organic solvent, and the polar organic The insoluble fraction of the nonpolar organic solvent is obtained by removing the insoluble fraction of the nonpolar organic solvent from the insoluble fraction of the solvent, and the hydrolyzed product obtained by hydrolyzing the insoluble fraction of the nonpolar organic solvent. object,
(2) a salt of the hydrolysis treatment product,
(3) an ester of the hydrolysis treatment product, or (4) an amide of the hydrolysis treatment product,
It is related with the sebum inhibitor characterized by containing at least 1 sort (s) or more as an active ingredient.
In a preferred embodiment of the sebum inhibitor of the present invention, the polar organic solvent is a halogenated saturated aliphatic hydrocarbon compound / lower alcohol mixture having 1 to 6 carbon atoms, particularly chloroform / methanol.
In another preferred embodiment of the sebum inhibitor of the present invention, the nonpolar organic solvent is a saturated aliphatic hydrocarbon compound or ether having 1 to 10 carbon atoms, particularly heptane.
In still another preferred embodiment of the sebum inhibitor of the present invention, the plant body is grape fruit, sugar cane or bell pepper.
In another preferred embodiment of the sebum inhibitor of the present invention, the plant is an industrial waste derived from a plant.

The present invention also provides a compound represented by the general formula (I):
HO—CH ₂ —R—COOH (I)
(Wherein R is a linear or branched saturated or unsaturated hydrocarbon group having 10 to 20 carbon atoms substituted with two hydroxyl groups), the trihydroxy fatty acid Further, the present invention relates to a sebum inhibitor, characterized in that it contains at least one of a salt of the above, an ester of the trihydroxy fatty acid, or an amide of the trihydroxy fatty acid as an active ingredient.
In a preferred embodiment of the sebum inhibitor of the present invention, the trihydroxy fatty acid represented by the general formula (I) is 9,10,18-trihydroxyoctadecanoic acid or 9,10,18-trihydroxyoctadecenoic acid. is there.

  The hydrolyzed product or derivative thereof (for example, salt, ester, or amide), which is an active ingredient of the sebum inhibitor of the present invention, or the compound represented by the general formula (I) or derivative thereof (for example, , Salts, esters, or amides) have higher sebum synthesis inhibitory activity than the active ingredients contained in conventional sebum inhibitors. Therefore, the sebum inhibitor of the present invention has an effect of suppressing sebum secretion on the skin, and is effective in preventing or treating dandruff, hair loss, dermatitis, or acne. In addition, the sebum inhibitor of the present invention is less irritating to the skin and has a good feeling of use as compared with conventional sebum inhibitors. Furthermore, the active ingredient of the sebum inhibitor of the present invention is produced from industrial wastes derived from plants that have been conventionally discarded, such as residues obtained by extracting grape juice from grape fruits and / or residues obtained by extracting sugar juice from sugarcane. Therefore, it is excellent in terms of effective use of industrial waste, and is advantageous in terms of manufacturing cost.

Hereinafter, the present invention will be described in detail.
The sebum inhibitor of this invention can contain the hydrolysis treatment product of the fraction extracted from a plant body as an active ingredient. Moreover, the sebum inhibitor of this invention can contain the salt which carried out the salt conversion process of the said hydrolysis process product as an active ingredient, the ester which carried out the esterification process, or the amide which carried out the amidation process. Moreover, the sebum inhibitor of this invention can contain the trihydroxy fatty acid, the salt of a trihydroxy fatty acid, the ester of a trihydroxy fatty acid, or the amide of a trihydroxy fatty acid as an active ingredient.

  In order to obtain the hydrolysis product, first, a fraction containing a large amount of cutin and suberin, which are polyester polymers of fatty acids, is extracted from the plant body. The extraction method is not particularly limited, and any known method can be used. For example, a fraction containing a large amount of cutin and suberin by removing sugars, low molecular weight lipids, and wax components from a plant. Can be extracted.

  Although the plant body for obtaining the active ingredient of the sebum inhibitor of the present invention is not particularly limited, a plant body containing a large amount of cutin and suberin is desirable. Kuching is a polyester polymer of fatty acids present in the plant body so as to cover the epidermis cells of the plant tissue, and suberin is a polyester polymer of fatty acid present in the epidermis cells of the plant body. Examples of plants rich in cutin and suberin include bell peppers, grapes, and sugar cane. In particular, a residue obtained by extracting grape juice from grape fruits and a residue obtained by extracting sugar juice from sugarcane have been conventionally discarded as industrial waste and have no utility value. However, the residue obtained by collecting the moisture of the plant body contains a large amount of cutin and suberin existing in the epidermal cells of the plant tissue and in the vicinity of the epidermal cells. These residues can be effectively used as a starting material for obtaining an active ingredient of the sebum inhibitor of the present invention.

  Any known method can be used as a method for extracting a fraction rich in cutin and suberin. By removing sugars, low molecular weight lipids and wax components from the plant body, an extract fraction containing a large amount of cutin and suberin, which are polyester polymers of fatty acids, can be obtained. A well-known method can also be used as a method for removing sugar from a plant, and sugar can be removed by removing a water-soluble component from a plant. Also, known methods can be used for separating low molecular weight lipids, and low molecular weight lipids can be removed by extraction with a solvent that dissolves low molecular weight lipids and does not solubilize polyester polymers of fatty acids. Can do. Further, a known method can be used for separating the wax component, and the wax component can be separated by solubilizing the wax component and extracting with a solvent that does not solubilize the fatty acid polyester polymer. Further, the order of removing sugar, low molecular weight lipid and wax component is not limited as long as each component can be sufficiently separated, but it is desirable to separate the order of sugar, low molecular weight lipid and wax component. .

  The shape of the plant body as a starting material is not particularly limited, and it may be in a dry state or still containing moisture. Further, finely crushed or non-crushed may be used, but in order to efficiently extract each component of sugar, low molecular weight lipid and wax, it is preferable to extract from finely crushed.

  Next, a specific embodiment for removing sugars, low molecular weight lipids and wax from the plant body in order to obtain the hydrolyzed product will be described by taking a method using a Soxhlet extractor as an example. For example, the plant body is first dried and pulverized using a mixer or the like. Using a Soxhlet extractor, the pulverized product is refluxed with water to obtain a water-insoluble fraction A which is a residual residue. Next, the water-insoluble fraction A is converted into a polar organic solvent [preferably a halogenated saturated aliphatic hydrocarbon compound having 1 to 6 carbon atoms / lower alcohol mixture such as chloroform: methyl alcohol mixture (especially 2: 1 mixture), etc. Is obtained] to obtain a polar organic solvent insoluble fraction B which is a residual residue. The polar organic solvent insoluble fraction B is then refluxed with a nonpolar organic solvent (preferably a saturated aliphatic hydrocarbon compound or ether having 1 to 6 carbon atoms, for example, heptane), and is a residual residue. A non-polar organic solvent insoluble fraction C is obtained.

  Examples of the halogenated saturated aliphatic hydrocarbon compound having 1 to 6 carbon atoms include chloroform. Examples of the lower alcohol include methyl alcohol and ethyl alcohol. The mixing ratio of the halogenated saturated aliphatic hydrocarbon compound having 1 to 6 carbon atoms / the lower alcohol mixture is not particularly limited as long as it is a mixing ratio in which the low molecular weight lipid is dissolved. To 1: 1, more preferably 1: 0.2 to 1: 0.8, and most preferably 1: 0.4 to 1: 0.6. Furthermore, examples of the saturated aliphatic hydrocarbon compound having 1 to 6 carbon atoms include pentane, hexane, heptane, and octane. The reflux is performed at room temperature, but can also be performed at 10 to 60 ° C. The extraction method is not limited to a method using a Soxhlet extractor, and a method capable of separating the soluble fraction and the insoluble fraction (residue) of each solvent, for example, a method using centrifugation or filtration is also possible. is there.

  By hydrolyzing the non-polar organic solvent insoluble fraction C obtained from the plant body, a hydrolysis treatment product using the active ingredient of the sebum inhibitor of the present invention can be obtained. Hydrolysis is promoted by adding an acid or alkali as a catalyst. For example, hydrolysis is performed by hydrolysis in 10% (w / v) KOH / 95% (v / v) methyl alcohol. Can be obtained. Preferably, the obtained hydrolyzed product is made acidic (preferably pH 3 or lower) with hydrochloric acid or the like, and then treated with the nonpolar organic solvent to remove the soluble fraction.

The hydrolysis treatment product is
Formula (I):
HO—CH ₂ —R—COOH (I)
(Wherein R is a linear or branched saturated or unsaturated hydrocarbon group having 10 to 20 carbon atoms substituted with two hydroxyl groups)
The trihydroxy fatty acid represented by these is included as a main component, and this trihydroxy fatty acid can be used alone as an active ingredient of the sebum inhibitor of the present invention.

  Such a trihydroxy fatty acid is not particularly limited as long as it is a trihydroxy fatty acid represented by the above general formula (I), but R has 14 carbon atoms substituted with two hydroxyl groups. It is preferably a trihydroxy fatty acid which is a saturated or unsaturated linear hydrocarbon group of -18. The unsaturated hydrocarbon group preferably has 1 to 4 double bonds, and specifically, for example, 9,10,18-trihydroxyoctadecanoic acid or 9,10,18-trihydroxyoctadecenoic acid Can be illustrated as a more preferable example.

Furthermore, derivatives such as salts, esters, or amides of the hydrolysis treatment product can also be used as active ingredients of the sebum inhibitor of the present invention. The salt of the hydrolyzed product can be obtained by a reaction that can convert the free acid to its corresponding salt. In this conversion reaction, for example, NaOH as a base may be added to the acid in the hydrolysis treatment product. The method for esterifying the hydrolysis treatment product is not limited as long as it is a method of dehydrating acid and alcohol or phenol to produce an ester, and the produced ester is also particularly limited. Although it is not a thing, it produces | generates, for example by adding methanol as an alcohol to the acid in the said hydrolysis treatment product, and heating. The heating is not particularly limited as long as it is a temperature at which an ester is produced. Furthermore, the method for amidating the hydrolysis-treated product is not particularly limited as long as it is a method for producing an amide by reacting an acid group with an amino group, and the produced amide is not limited. For example, it can be produced by adding a primary amine having an amino group (—NH ₂ ), for example, diethanolamine, to the acid in the hydrolysis treatment product and heating. The heating is not particularly limited as long as it is a temperature at which an amide is generated.

  Furthermore, the salt, ester or amide obtained by subjecting the trihydroxy fatty acid represented by the general formula (I) to salt conversion treatment, esterification treatment or amidation treatment is also effective for the sebum inhibitor of the present invention. It is an ingredient.

In addition, as a base for converting the hydrolysis product into a salt, alkali metal base such as sodium base or potassium base, alkaline earth metal base such as calcium base or magnesium base, ammonium base, trimethylamine base Or an alkylamine base such as triethylamine base, an alkanolamine base such as trimethanolamine base, triethanolamine base, or triisopropanolamine base, an amino acid base such as lysine base, or arginine base, a guanidine base, or a glucosamine base. Examples thereof include sugar amine bases.
Moreover, the said base can be used as a base for converting the trihydroxy fatty acid represented by the said general formula (I) into a salt.

In addition, as alcohol or phenol for esterifying the hydrolysis treatment product, methyl alcohol, alcohol having an alkyl group such as ethyl alcohol, hydrocarbon having an aryl group such as benzene, glycerin, propylene glycol, or Examples thereof include polyhydric alcohols such as polyethylene glycol.
Examples of the alcohol or phenol for esterifying the trihydroxy fatty acid represented by the general formula (I) include the alcohol having an alkyl group, the hydrocarbon having an aryl group, or a polyhydric alcohol. it can.

Examples of the compound for amidating the hydrolysis-treated product include ammonia, an amine having an alkyl group, such as methylamine, ethylamine, or propylamine, an amine having a hydroxy group, such as monoethanolamine, or Examples include diethanolamine, amino acids such as glycine or phenylalanine.
Moreover, the said compound can be illustrated also as a compound for amidating the trihydroxy fatty acid represented by the said general formula (I).

  The method for producing the trihydroxy fatty acid represented by the general formula (I) is not limited in any way. For example, the crude purified non-polar organic solvent insoluble fraction C extracted from the plant body is hydrolyzed and purified. The manufacturing method which obtains a thing may be sufficient. Further, chemical synthesis may be used in order to obtain a highly purified trihydroxy fatty acid. Further, the production method of the compound selected from the salt, ester or amide of the trihydroxy fatty acid of the general formula (I) is not limited in any way, and the above-mentioned hydrolysis product of the plant having a low degree of purification is used. It may be produced from a highly purified trihydroxy fatty acid obtained by chemical synthesis. However, from the viewpoint of safety to the skin or scalp, it is preferable to use a trihydroxy fatty acid produced from a non-polar organic solvent-insoluble fraction C derived from a cutin and / or suberin of a plant, or a derivative thereof. .

  About the hydrolyzed product obtained by hydrolyzing the non-polar organic solvent insoluble fraction C from the plant body, or the salt, ester or amide of this hydrolyzed product, an enzyme involved in sebum synthesis After examining the inhibitory activity of a certain acetyl CoA carboxylase, a test for confirming the effect by a monitor test was conducted. A high sebum synthesis inhibitory effect was confirmed for all the products and derivatives thereof. This effect was very high even when compared with the monohydroxy fatty acid which has been reported to have sebum synthesis inhibiting activity. In addition, 9,10,18-trihydroxyoctadecanoic acid or 9,10,18-trihydroxyoctadecenoic acid, which is a main compound contained in the hydrolysis-treated product, can also inhibit sebum synthesis by itself. Was confirmed.

  The sebum inhibitor of the present invention can contain other components as desired in addition to the above-mentioned active ingredients, as long as the carrier does not impair the effects of the present invention. As other components, those conventionally known to be usable as carriers and additives for pharmaceuticals or cosmetics can be used. For example, surfactant, oil, moisturizer, refreshing agent, antioxidant, alcohol, chelating agent, pH adjuster, antiseptic, viscosity adjuster, dye, fragrance, anti-inflammatory agent, kerato, antibacterial agent, Or a disinfectant etc. can be mentioned. These components may be used alone or in combination of two or more.

  The dosage form of the sebum suppressant of the present invention is a dosage form that can be applied to the skin. It can be a hair nourishing agent.

In the sebum inhibitor of the present invention, the hydrolyzed product of the fraction extracted from the plant, at least one of its salt, ester or amide, or at least one of trihydroxy fatty acid, its salt, ester or amide What is necessary is just to make a sebum inhibitor contain 1 type as an active ingredient. The content of the active ingredient is not particularly limited, and an effective amount that can suppress sebum secretion may be used. The ratio of the general formula (I) is applied to the skin or scalp. Preferably, the content of trihydroxy fatty acid is preferably 0.05 to 20% by mass, more preferably 0.1 to 10% by mass. When the content is less than 0.05% by mass, the sebum secretion inhibitor tends to have a poor sebum-inhibiting effect. Conversely, when the content exceeds 20% by mass, an increase in the effect is virtually impossible and sebum secretion is not expected. It tends to be difficult to add to the inhibitor.
Moreover, the said active ingredient may be contained by 1 type in the sebum inhibitor of this invention, and may be contained as a 2 or more types of mixture.

  The sebum inhibitor of the present invention containing the product or compound or a derivative thereof as an active ingredient was prepared as an emulsion. This emulsion was actually used to examine the feeling of use on the skin. As a result, it was found that there was no irritation to the skin and a very good usability when compared with conventional emulsions containing monohydroxy fatty acids reported as compounds having a sebum-suppressing effect.

  When the hydrolyzed product of the cutin / suberin extract fraction from the plant body, or a salt, ester or amide thereof as an active ingredient is contained in the sebum inhibitor of the present invention, it is represented by the general formula (I). Hydroxy fatty acids other than trihydroxy fatty acids (for example, dihydroxy fatty acids or monohydroxy fatty acids), other fatty acids, and the like, but the trihydroxy fatty acids represented by the general formula (I) are If it is contained with the content of, it may be contained other fatty acids. Of course, it goes without saying that the product derived from the extract fraction may be purified to purify the trihydroxy fatty acid and used as the purified product.

  EXAMPLES Hereinafter, the present invention will be specifically described by way of examples, but these do not limit the scope of the present invention.

<< Preparation Example 1 >>
The residue after squeezing grape juice from the grape fruit was dried and then pulverized with a mixer. 100 g of the obtained powder was put into a stainless steel container, and 1 L of water was added and boiled for 2 hours. The water extraction residue obtained by filtration was inserted into an extraction tube of a Soxhlet extractor, and extracted with 1 L of chloroform: methanol (2: 1) for 20 hours under reflux. Next, the extraction solvent was changed to heptane, and Soxhlet extraction treatment was performed in the same manner. About 65 g of heptane extraction residue remaining in the extraction tube was taken out.
By the above extraction treatment with water, chloroform: methanol (2: 1), and heptane, sugars, low molecular lipids and wax components were removed, respectively. To 60 g of the heptane extraction residue, 200 mL of 10% (w / v) KOH / 95% (v / v) methanol was added and refluxed for 24 hours for hydrolysis (saponification decomposition). The treatment liquid was filtered off, and the resulting filtrate was acidified with hydrochloric acid, followed by extraction with dimethyl ether to remove ether-soluble components. Under reduced pressure, the solvent was distilled off to obtain 16 g of a hydrolyzed product.

  The obtained hydrolyzed product was analyzed by gas chromatography (GC). As a result, the hydrolyzed product was composed of 42% by mass of 9,10,18-trihydroxyoctadecenoic acid, 15% by mass of 9,10,18-trihydroxyoctadecanoic acid, and 10,18-dihydroxyoctadecanoic acid. An amount of 11% by weight was included. The trihydroxy fatty acid content represented by the general formula (I) was 57% by mass. This hydrolysis treatment product was designated as hydrolysis treatment product A.

<< Preparation Example 2 >>
The residue after squeezing sugar juice from sugarcane was dried, and then 200 g of this dry powder was extracted with water, Soxhlet extraction using chloroform: methanol (2: 1) as an extraction solvent, and heptane, as in Preparation Example 1. Soxhlet extraction was sequentially performed using a solvent as a solvent, and about 110 g of a heptane extraction residue was taken out. To 55 g of the heptane extraction residue, 200 mL of 10% (w / v) KOH / 95% (v / v) methanol was added and refluxed for 24 hours for hydrolysis (saponification decomposition). The treatment liquid was filtered off, and the resulting filtrate was acidified with hydrochloric acid, followed by extraction with dimethyl ether to remove ether-soluble components. Under reduced pressure, the solvent was distilled off to obtain 4 g of a hydrolyzed product.

  The resulting product was analyzed by gas chromatography (GC). As a result, the hydrolysis product has an amount of 9,10,18-trihydroxyoctadecanoic acid 20% by mass, 18-hydroxyoctadecenoic acid 19% by mass, and 9,15-dihydroxyoctadecenoic acid 16% by mass. And included. The trihydroxy fatty acid content represented by the general formula (I) was 20% by mass. This hydrolysis treatment product was designated as hydrolysis treatment product B.

<< Preparation Example 3 >>
The hydrolysis treatment product B obtained in Preparation Example 2 was neutralized with sodium hydroxide to give a sodium salt. Specifically, 50 g of the hydrolyzed product B was dissolved in 200 mL of ethanol, neutralized by adding 60 mL of 10% sodium hydroxide solution, and then the solvent was distilled off under reduced pressure. By this treatment, 53 g of the salt conversion treatment product of the hydrolysis treatment product B was obtained. This product was designated as salt conversion product C.

<< Preparation Example 4 >>
100 g of the hydrolysis-treated product B obtained in Preparation Example 2 was mixed with 200 g of propylene glycol and 0.4 g of sodium hydroxide, and reacted by heating to 170 ° C. under a reduced pressure of 40 mmHg. 108 g of a fatty acid esterification product was obtained. This product was designated as an esterification product D.

<< Adjustment Example 5 >>
160 g of the hydrolysis-treated product B obtained in Preparation Example 2 was mixed with 100 g of diethanolamine and 0.6 g of sodium hydroxide, reacted at 140 ° C. under a reduced pressure of 40 mmHg, and reacted with fatty acid amide by diethanolamine. 248 g of the chemical treatment product was obtained. This product was designated as amidation product E.

<< Preparation Example 6 >>
After drying the pepper skin, 50 g of this dry powder was extracted with water, Soxhlet extraction with chloroform: methanol (2: 1) as the extraction solvent, and Soxhlet extraction with heptane as the solvent, as in Preparation Example 1. Sequentially, about 32 g of heptane extraction residue was taken out. To 55 g of the heptane extraction residue, 200 mL of 10% (w / v) KOH / 95% (v / v) methanol was added and refluxed for 24 hours for hydrolysis (saponification decomposition). The treatment liquid was filtered off, and the resulting filtrate was acidified with hydrochloric acid, followed by extraction with dimethyl ether to remove ether-soluble components. Under reduced pressure, the solvent was distilled off to obtain 6 g of a hydrolyzed product.

  The resulting product was analyzed by gas chromatography (GC). As a result, the hydrolysis product contained 9,10,18-trihydroxyoctadecanoic acid at 13% by mass, 9,10,18-trihydroxyoctadecenoic acid at 10% by mass, and 10,16-dihydroxyoctadecenoic acid. Contained in an amount of 75% by weight. The trihydroxy fatty acid content represented by the general formula (I) was 23% by mass. This product was designated as hydrolysis product F.

《Pharmacological test example: Sebum synthesis inhibition test》
The sebum synthesis inhibitory ability was evaluated using monohydroxy fatty acid (sodium 11-hydroxyundecanoate) for each product obtained in Preparation Examples 1 to 6 and for comparison.
The sebum synthesis inhibitory ability was determined from the inhibitory activity of acetyl CoA carboxylase, an enzyme involved in sebum synthesis, according to a report by Tanab et al. [Methods in Enzymology, 71, 5 (1981)]. The measuring method is as follows.

[1] Preparation of acetyl CoA carboxylase solution (1) Preparation of crude enzyme solution After fasting male rats weighing 250-300 g for 48 hours, feeding [56% glucose, 22% vitamin-free casein, 6% mineral (AIN -93G), 4% vitamin (AIN-93-VX), 12% cellulose] for 48 hours. The rat was decapitated, the liver was excised, 0.25M sucrose solution 2.5 times the liver weight was added, and the mixture was crushed with a homogenizer under ice cooling. Furthermore, the supernatant obtained by centrifugation (100,000 × g) was used as a crude enzyme solution.

(2) Ammonium sulfate precipitation (first time)
After adding solid ammonium sulfate (ammonium sulfate) to the crude enzyme solution obtained in (1) so as to be 30% saturated, the resulting precipitate was collected by centrifugation and 300 mL of 10 mM phosphate buffer (pH 7.4). Dissolved in. Unless otherwise specified, a phosphate buffer containing 5 mM 2-mercaptoethanol and 1 mM EDTA was used.

(3) Calcium-phosphate gel fractionation and ammonium sulfate precipitation (second time)
The solution obtained in (2) above was added to 170 mL of calcium phosphate gel suspension with stirring, and the mixture was stirred as it was for 20 minutes, followed by centrifugation to remove the supernatant. 33 mM phosphate buffer solution (pH 7.5) was added to the precipitation part, and washing of the precipitate was repeated three times. Next, 120 mL of 0.2 M phosphate buffer (pH 7.4) was added to the precipitate to elute the protein (enzyme). After this operation was repeated twice, ammonium sulfate precipitation was performed on the solution in the same manner as in (2) above, and the resulting precipitate was dissolved in 10 mM phosphate buffer (pH 7.4).

(4) DEAE-cellulose column chromatography The solution obtained in (3) above was applied to a DEAE-cellulose (DEAE-sephacel, Amersham) column equilibrated with 10 mM phosphate buffer (pH 7.4). After washing the column with 10 mM phosphate buffer, gradient elution was performed with a salt gradient between 10 mM and 50 mM phosphate concentration. The eluate when the salt concentration reached about 150 mM was collected, and a saturated ammonium sulfate solution was added in an amount 0.66 times that of the eluate, and the resulting precipitate was collected by centrifugation.

(5) Sepharose 2B column chromatography The precipitate obtained in (4) above was dissolved in 0.1 M phosphate buffer (pH 7.4) containing 10 mM potassium citrate and 0.25 M sucrose. The resulting solution was passed through a Sepharose 2B column equilibrated with the same buffer and eluted with the same buffer. The eluate was dialyzed against 0.1 M phosphate buffer to which 0.25 M sucrose and an amount of ammonium sulphate so as to equilibrate at 50% saturation was added. The produced precipitate was collected by centrifugation, and then dissolved in 0.1 M phosphate buffer containing 0.25 M sucrose to obtain an enzyme solution.

[2] Preparation of Sample Solution The hydrolysis product A was dissolved in ethanol so that the concentration of the trihydroxy fatty acid represented by the general formula (I) was 1.05M. Similarly, the hydrolysis products B and C were also dissolved in ethanol so that the concentration of the trihydroxy fatty acid represented by the general formula (I) was 1.05M. The salt conversion product C, esterification product D, and amidation product E are represented by the general formula (I) of the hydrolysis product B before each treatment. The trihydroxy fatty acid was dissolved in ethanol to a concentration of 1.05M.

[3] Measurement of acetyl CoA carboxylase inhibitory activity 10 mM magnesium chloride, 3.75 mM glutathione, 0.75 mg / mL bovine serum albumin, 0.125 mM acetyl CoA, 0.5 mM in 50 mM Tris-HCl buffer (pH 7.5) Potassium phosphoenolpyruvate, 0.125 mM NADH, 15 μg / mL pyruvate kinase, and 6 μg / mL lactate dehydrogenase were added, and the enzyme solution prepared in the above step [1] was added to 5 mU of acetyl CoA carboxylase. . 760 μL of the solution thus obtained was transferred to a spectrophotometer cell, and Triton-X100 was added and dissolved in an amount of 4 μL, and then 40 μL of the sample solution prepared in the above step [2] was added. After incubating at 37 ° C. for 10 minutes, 20 μL of 150 mM ATP and 20 μL of 1M potassium bicarbonate were added to start the reaction, and absorbance at 340 nm (decrease in absorbance due to oxidation of NADH) was measured over time. The acetyl CoA carboxylase activity was determined from the amount of change in absorbance. The enzyme activity was defined as 1 U in which 1 μmol of NADH was oxidized per minute. At this time, a sample obtained by adding ethanol in place of the sample solution was used as a blank, and compared with the case where the trihydroxy fatty acid represented by the general formula (I) was contained in the reaction solution in an amount of 50 mM, The acetyl-CoA carboxylase inhibitory activity was determined according to formula (2).
X (%) = 100− (A / B) × 100 (2)
X in the general formula (2) is the enzyme activity inhibition rate (%), A is the enzyme activity in the presence of the sample, and B is the enzyme activity in the absence of the sample.
The results are shown in Table 1.

Example 1
An emulsion was prepared according to the formulation shown in Table 2 using the hydrolysis treatment product A obtained in Preparation Example 1 as an active ingredient. The hydrolyzed product A was added in an amount of 1% by mass as the trihydroxy fatty acid represented by the general formula (I).

Example 2
An emulsion was prepared by repeating the same operation as in Example 1 except that the hydrolysis treatment product B obtained in Preparation Example 2 was used in place of the hydrolysis treatment product A.

Example 3
An emulsion was prepared by repeating the same operation as in Example 1 except that the salt conversion product C obtained in Preparation Example 3 was used instead of the hydrolysis product A.

Example 4
An emulsion was prepared by repeating the same operation as in Example 1 except that the esterification product D obtained in Preparation Example 4 was used instead of the hydrolysis product A.

Example 5
An emulsion was prepared by repeating the same operation as in Example 1 except that the amidation product E obtained in Preparation Example 5 was used instead of the hydrolysis product A.

Example 6
An emulsion was prepared by repeating the same operation as in Example 1 except that the hydrolysis treatment product F obtained in Preparation Example 6 was used in place of the hydrolysis treatment product A.

<< Comparative Example 1 >>
An emulsion was prepared by repeating the same operation as in Example 1 except that sodium 11-hydroxyundecanoate was used in place of the hydrolysis treatment product A.

《Usability test》
The emulsions prepared in Examples 1 to 6 and Comparative Example 1 were applied to the forehead of 10 adult male and female panelists, and the usability was tested. Evaluation was performed in the following three stages.
Good usability: 2 points Somewhat unpleasant usability: 1 point Unpleasant usability: 0 points.
Specifically, the evaluation of feeling uncomfortable is a case such as “the skin is irritated” or “the skin becomes red”. Table 3 shows the total points of 20 panelists.

  The emulsions of Examples 1 to 6 were less irritating than the emulsion of Comparative Example 1, and good usability was obtained.

  The sebum inhibitor of the present invention has a sebum synthesis inhibitory effect, suppresses excessive activity of the sebaceous glands, and is useful for the prevention or treatment of dandruff, hair loss, dermatitis, acne and the like.

Claims (9)

(1) A water-insoluble fraction is obtained by removing a water-soluble fraction from a plant body, a soluble fraction of a polar organic solvent is removed from the water-insoluble fraction to obtain an insoluble fraction of a polar organic solvent, and the polar organic The insoluble fraction of the nonpolar organic solvent is obtained by removing the insoluble fraction of the nonpolar organic solvent from the insoluble fraction of the solvent, and the hydrolyzed product obtained by hydrolyzing the insoluble fraction of the nonpolar organic solvent. object,
(2) a salt of the hydrolysis treatment product,
(3) an ester of the hydrolysis treatment product, or (4) an amide of the hydrolysis treatment product,
A sebum inhibitor, comprising at least one or more active ingredients.   The sebum inhibitor according to claim 1, wherein the polar organic solvent is a halogenated saturated aliphatic hydrocarbon compound / lower alcohol mixture having 1 to 6 carbon atoms.   The sebum inhibitor according to claim 2, wherein the polar organic solvent is a chloroform / methanol mixture.   The sebum inhibitor according to any one of claims 1 to 3, wherein the nonpolar organic solvent is a saturated aliphatic hydrocarbon compound or ether having 1 to 10 carbon atoms.   The sebum inhibitor according to claim 4, wherein the nonpolar organic solvent is heptane.   The sebum inhibitor according to any one of claims 1 to 5, wherein the plant body is grape fruit, sugarcane or bell pepper.   The sebum inhibitor as described in any one of Claims 1-5 whose said plant body is industrial waste derived from a plant body. Formula (I):
HO—CH ₂ —R—COOH (I)
(In the formula, R is a linear or branched saturated or unsaturated hydrocarbon group having 10 to 20 carbon atoms substituted with two hydroxyl groups)
A sebum inhibitor, comprising as an active ingredient at least one of a trihydroxy fatty acid represented by formula (1), a salt of the trihydroxy fatty acid, an ester of the trihydroxy fatty acid, or an amide of the trihydroxy fatty acid.   The sebum inhibitor according to claim 8, wherein the trihydroxy fatty acid represented by the general formula (I) is 9,10,18-trihydroxyoctadecanoic acid or 9,10,18-trihydroxyoctadecenoic acid.