JP5702961B2 - Glutathione production promoter and pharmaceutical having glutathione production promotion action - Google Patents

Description

  The present invention relates to a glutathione production promoter and a pharmaceutical product having a glutathione production promotion action.

  Glutathione is a tripeptide composed of three amino acids, glutamic acid, cysteine, and glycine. It is an antioxidant that is widely distributed in the living body. It captures radicals, regulates cell functions by redox, and serves as an SH donor for various enzymes. Its role and involvement in detoxification metabolism are known.

  Decreased intracellular glutathione levels can lead to cell damage due to UV exposure, inflammation, acute or chronic alcohol liver damage, liver disease, Parkinson's disease, Alzheimer's disease, gastric ulcer, immunodeficiency, acquired immune deficiency syndrome, physiological aging It is known to lead to accompanying aging phenomenon, canceration and the like.

  Therefore, if the amount of glutathione in the cell can be increased, it can be expected to suppress a decrease in oxidative stress response that decreases with aging, and prevention of skin aging, spots and freckles associated with oxidative stress such as ultraviolet irradiation. Can be expected. In addition, it can be expected to prevent various functional declines caused by deficiency of glutathione.

  Conventionally, as those having a production promoting action of glutathione, butcher bloom, coxnohagashi, himalayan raspberry, rosemary, jujuak, licorice, gayo, auren, arnica, oolong tea, cucumber, grasshopper, wildflower, lavender, ginseng, ginkgo, Extraction from one or more natural products selected from the group consisting of moon peach, star fruit, royal jelly, oxon, aloe ferrox, yeast, diau, peony, sorghum, persian baboon, ginseng, maronier, hops and emmelio A glutathione production promoter containing a product as an active ingredient is known (see, for example, cited document 1).

  On the other hand, it is known that extracts from plants belonging to the genus Saussurea are used in skin cosmetics as collagen production promoters or as estrogen-like agents (see, for example, Reference 2). In addition, it is also known that an extract from Saussurea laniceps Hand.-Mazz. Among plants belonging to the genus Saussurea is used as a tyrosinase inhibitor or melanin production inhibitor in whitening cosmetics. (For example, see cited document 3.) In recent years, with the progress of research on extracts from plants belonging to the genus Saussurea, it is also known that extracts from plants belonging to the genus Saussurea are used in cosmetics (for example, cited document 4). And 5).

  However, an extract from a plant belonging to the genus Saussurea, a predetermined component fractionated from an extract from a plant belonging to the genus Saussurea, or a dihydrodehydrocostus contained in a plant belonging to the genus Saussurea It is not known to use lactone (Dihydrodehydrocostuslactone) as a glutathione production promoter.

JP 2009-132661 A JP 2001-316240 A Japanese Patent No. 3658548 JP 2004-331546 A JP 2004-331547 A

  An object of the present invention is to provide a “glutathione production promoter using components obtained from a highly safe natural product”. Another object is to provide a “pharmaceutical, food or cosmetic containing the glutathione production promoter and having a glutathione production promoting effect”.

  As a result of diligent research on substances having a glutathione production promoting action, the present inventors have conventionally used “South Rare (collagen production promoters, estrogen-like agents, tyrosinase inhibitors, melanin production inhibitors or cosmetics”. The extract from plants belonging to the genus Saussurea ”is effective as a glutathione production promoter, and“ predetermined components fractionated from the extract from plants belonging to the genus Saussurea ”and“ dihydrodehydroco It has been found that "sustuslactone" is also effective as a glutathione production promoter, and the present invention has been completed. The present invention includes the following items.

[1] A glutathione production promoter containing, as an active ingredient, an extract from a plant belonging to the genus Saussurea.

[2] Plants belonging to the genus Saussurea are Saussurea involucrata (Kar. Et Kir.) Sch.Blp., Saussurea medusa Maxim. And Saussurea laniceps Hand. .-Mazz.) The glutathione production promoter according to [1] above, which is one or more plants selected from the group consisting of.

[3] When a solution in which an extract from a plant belonging to the genus Saussurea is dissolved in 30% (V / V) methanol is passed through a column using a porous polystyrene resin as a carrier, the porous polystyrene A glutathione production promoter containing a component adsorbed on a resin as an active ingredient.

[4] The plants belonging to the genus Saussurea are Saussurea involucrata (Kar. Et Kir.) Sch.Blp., Saussurea medusa Maxim. And Saussurea laniceps Hand. .-Mazz.) The glutathione production promoter according to [3] above, which is one or more plants selected from the group consisting of.

[5] A solution obtained by dissolving an extract from a plant belonging to the genus Saussurea in 30% (V / V) methanol is passed through a column using a porous polystyrene resin as a carrier, and then 50% (V / V). V) A glutathione production promoter containing, as an active ingredient, a component adsorbed on the porous polystyrene resin when methanol is passed through the column.

[6] Plants belonging to the genus Saussurea are Saussurea involucrata (Kar. Et Kir.) Sch.Blp., Saussurea medusa Maxim. And Saussurea laniceps Hand. .-Mazz.) The glutathione production promoter according to [5] above, which is one or more plants selected from the group consisting of.

[7] A solution obtained by dissolving an extract from a plant belonging to the genus Saussurea in 30% (V / V) methanol is passed through a column using a porous polystyrene resin as a carrier, and then 50% (V / V). V) A glutathione production promoter containing, as an active ingredient, a component that is eluted from the column by methanol when methanol is passed through the column and then methanol is passed through the column.

[8] The plants belonging to the genus Saussurea are Saussurea involucrata (Kar. Et Kir.) Sch.Blp., Saussurea medusa Maxim. And Saussurea laniceps Hand. .-Mazz.) The glutathione production promoter according to the above [7], which is at least one plant selected from the group consisting of:

[9] A glutathione production promoter containing dihydrodehydrocostus lactone represented by the following formula (1) as an active ingredient.

[10] A pharmaceutical, food or cosmetic having a glutathione production promoting action, comprising the glutathione production promoter according to [1] or [2] above.

[11] A pharmaceutical, food or cosmetic having a glutathione production promoting action, comprising the glutathione production promoter according to [3] or [4] above.

[12] A pharmaceutical, food or cosmetic having a glutathione production promoting action, comprising the glutathione production promoter according to [5] or [6] above.

[13] A pharmaceutical, food or cosmetic having a glutathione production promoting action, comprising the glutathione production promoter according to [7] or [8] above.

[14] A pharmaceutical, food or cosmetic having a glutathione production promoting action, comprising the glutathione production promoter according to [9] above.

  According to the present invention, as can be seen from the test examples to be described later, “a glutathione production promoter using a component obtained from a highly safe natural product” and “glutathione production promoting action containing the glutathione production promoter”. Possessed pharmaceuticals, foods or cosmetics ".

It is a flowchart shown in order to demonstrate Embodiment 1-5. It is a flowchart shown in order to demonstrate the preparation examples of sample df and a comparative sample. It is a graph which shows the result of Experimental example 1 (The glutathione production promotion effect with respect to a human skin fibroblast). It is a graph which shows the result of Experimental example 2 (The glutathione production promotion effect with respect to a normal human epidermal keratinocyte).

  Hereinafter, the “glutathione production promoter” and the “pharmaceutical, food, or cosmetic containing glutathione production promoter and having a glutathione production promoter” of the present invention will be described in more detail based on embodiments.

FIG. 1 is a flowchart for explaining the first to fifth embodiments.
The glutathione production promoter of the present invention was prepared by dissolving an extract from a plant belonging to the genus Saussurea and an extract from a plant belonging to the genus Saussurea in 30% (V / V) methanol. When the solution is passed through a column using a porous polystyrene resin as a carrier, 30% (V / V) of an extract from a plant belonging to the genus Saussurea, “components adsorbed on the porous polystyrene resin” The component dissolved in methanol is passed through a column using porous polystyrene resin as a carrier, and then 50% (V / V) methanol is passed through the column. A solution prepared by dissolving an extract from a plant belonging to the genus Saussurea in 30% (V / V) methanol is passed through a column using a porous polystyrene resin as a carrier. Thereafter, when 50% (V / V) methanol is passed through the column and then methanol is passed through the column, it contains “the component eluted from the column by methanol” or “dihydrodehydrocostoslactone” as an active ingredient. (See FIG. 1 and FIG. 2 described later.)
Hereinafter, each above-mentioned active ingredient is demonstrated by Embodiment 1-5.

[Embodiment 1]
The glutathione production promoter according to Embodiment 1 contains “an extract from a plant belonging to the genus Saussurea” as an active ingredient (see FIG. 1).

  In the glutathione production promoter according to Embodiment 1, the “extract from a plant belonging to the genus Saussurea” includes an extract obtained by extraction from a plant belonging to the genus Saussurea, and dilution of the extract A liquid or a concentrated liquid, a dried product obtained by drying the extract, or a crude purified product or a purified product thereof are included.

  In the extraction process, a plant belonging to the genus Southus (Saussurea) is used as an extraction raw material. As the extraction raw material, whole grass can be used, but it is preferable to use the above-ground part.

  As a specific example of plants belonging to the genus Southus (Saussurea), Southusia involucrata (Kar. Et Kir.) Sch.Blp. (Chinese name: Xinjiang Snow Lotus or Tianshan Snow Lotus) .), Saussurea medusa Maxim. (Chinese name: Mian Snow Lotus), Saussurea laniceps Hand.-Mazz. (Chinese name: Cotton Head Snow Lotus), Saussurea gnaphaloides (Royle) Sch.-Bip.), Southarea Stella Maxim., Southarea Tridactyla Sch.-Bip.ex Hook.f., Southarea Namikawae (Saussurea namikawae Kitam.), Southarea Gossipora (Saussurea) gossypiphora D.Don, Southlea Nisshiokae (Saussurea nishiokae Kitam.), Southrea Leucoma (Saussurea leucoma Diels), Southlea Querquifo Saussurea quercifolia WWSmith, Saussurea eriocephala Franch., Southrea Kingi (Saussurea kingii JRDrumm.ex CECFisch.), Saussurea simpsoniana (Field.et Gardn.) Lipsch. Saussurea obvallata (DC.) Edgew., Saussurea wettsteiniana Hand.-Mazz., Saussurea globosa Chen, Saussurea longifolia Franch. It can be illustrated.

  As an extraction raw material, the plants belonging to the genus Saussurea can be used alone, or two or more different ones can be used in combination. As the raw material for extraction, one of Saussurea involucrata (Kar.et Kir.) Sch.Blp., Saussurea medusa Maxim. And Saussurea laniceps Hand.-Mazz. It is preferable to use more than one species, and it is more preferable to use Saussurea involucrata (Kar. Et Kir.) Sch. Blp.

  Saussurea involucrata (Kar.et Kir.) Sch.Blp., Saussurea medusa Maxim., And Saussurea laniceps Hand.-Mazz. Are mainly located in Xinjiang Autonomous Region of China. A herb of the family Asteraceae distributed in Sichuan Province, Ulsan and Tibet provinces, etc., so far rheumatoid arthritis, impotence, irregular menstrual flow, uterine bleeding, coldness and pain in the lower abdomen of women, colorless belt, renal failure It has been known that it can be used externally for wound bleeding. Saussurea involucrata (Kar.et Kir.) Sch.Blp., Saussurea medusa Maxim. And Saussurea laniceps Hand.-Mazz. ”,“ Mother Snow Lotus Flower ”and“ Cotton Snow Lotus Flower ”.

  Among the plants belonging to the genus Saussurea, Saussurea involucrata (Kar. Et Kir.) Sch.Blp. Is an example of the Xinjiang Autonomous Region of China, and the Southus gnaphaloides (Royle) Sch.- Bip.) Is Sichuan Province, Tibet Autonomous Region, etc. in China, and Southrea Stella (Saussurea stella Maxim.) Is China's Qinghai Province, Gansu Province, Sichuan Province, Tibet Autonomous Region, etc. In China, Sichuan, Yunnan, Qinghai, Tibet Autonomous Region, Hong Kong, Nepal, etc., South Rare Sunnyssu (Saussurea laniceps Hand.-Mazz.) Is in China's Sichuan Province, Tibet Autonomous Region, etc., South Rare Tridactyla Sch .-Bip.ex Hook.f.) is Tibet Autonomous Region in China, and Southus Namikawae Kitam. Is Tibet Autonomous Region in China・ Saussurea gossypiphora D.Don is in Nepal etc., South Rhea Nisiokae (Saussurea nishiokae Kitam.) Is in Nepal, etc. Saussurea quercifolia WWSmith) is in Sichuan, Yunnan, etc. in China, Saussurea eriocephala Franch. Is in Yunnan, China, and Southusia Kingii JRDrumm.ex CECFisch. In Tibet Autonomous Region, etc., Saussurea simpsoniana (Field.et Gardn.) Lipsch. Is in Nepal, etc., and Southus Ouarata (Saussurea obvallata (DC.) Edgew.) Is in Yunnan, Sichuan and Tibet provinces in China. For example, Saussurea wettsteiniana Hand.-Mazz. Is located in Yunnan Province, China. Bosa (Saussurea globosa Chen) in Sichuan Province, etc. of China, Sausurea-longifolia (Saussurea longifolia Franch.) Is available in China, Yunnan, and the like.

  The plant belonging to the genus Southus (Saussurea) as the raw material for extraction is suitably dried and pulverized immediately after collection. Drying may be performed in the sun or using a commonly used dryer.

  In the extraction process, it is preferable to use a polar solvent as the extraction solvent. A component having a glutathione production promoting action can be easily extracted from a plant belonging to the genus Southus (Saussurea) by an extraction treatment using a polar solvent.

  Specific examples of the polar solvent include water and water-soluble organic solvents, and these may be used alone or in combination of two or more. Of these polar solvents, water, a water-soluble organic solvent, or a water-containing water-soluble organic solvent is preferably used as the extraction solvent.

Water that can be used as the extraction solvent includes pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and the like, as well as those subjected to various treatments. Examples of various treatments include heating, sterilization, sterilization, filtration, and ion exchange. Accordingly, the water that can be used as the extraction solvent in the present invention includes hot water, ion-exchanged water, and the like.
Further, as the extraction solvent, various waters subjected to treatments such as adjustment of osmotic pressure and buffering (physiological saline, phosphate buffer, phosphate buffered saline, etc.) can also be used.

  Examples of water-soluble organic solvents that can be used as the extraction solvent include lower aliphatic alcohols and acetone. Specific examples of the lower aliphatic alcohol include monohydric alcohols such as methanol, ethanol, propanol and butanol, and polyvalents such as 1,3-butylene glycol, propylene glycol, 1,3-propanediol, pentylene glycol and isoprene glycol. Alcohol can be illustrated.

  When using the liquid mixture of 2 or more types of polar solvents as an extraction solvent, the mixing ratio can be adjusted suitably. For example, when a water-containing water-soluble organic solvent is used as the extraction solvent, a water-containing water-soluble organic solvent preferably containing 50% by weight or more of a monohydric alcohol, a polyhydric alcohol, acetone or the like can be used.

  An intermediate polar solvent such as ethyl acetate or butyl acetate may be used as the extraction solvent.

  As the extraction solvent, 50% (V / V) ethanol and 80% (V / V) ethanol can be suitably used.

  The extraction treatment is not particularly limited as long as soluble components contained in plants belonging to the genus Southus (Saussurea) can be eluted in the extraction solvent, and can be performed according to a conventional method. In the extraction process, it is not necessary to adopt a special extraction method, and any apparatus can be used at room temperature or under reflux heating.

  Extraction methods include extraction by immersing the extraction raw material in the extraction solvent at room temperature for a long time, extraction with heating to a temperature below the boiling point of the extraction solvent and stirring, or heating to reflux near the boiling point of the extraction solvent. The method of extracting below can be illustrated. At this time, the amount of the extraction solvent is usually 5 to 50 times (weight ratio), preferably 5 to 15 times (weight ratio) of the extraction raw material, and the extraction time is usually 1 to 10 hours, preferably 1 to 1. It is 4 hours, and the extraction temperature is usually 50 to 95 ° C, preferably 80 to 95 ° C.

  In the extraction process, before performing the extraction with the polar solvent, a degreasing process using a nonpolar solvent such as pentane, hexane, heptane, octane, petroleum ether or the like may be performed. Can be efficiently performed.

  After the soluble component is eluted by the extraction treatment, an extraction liquid can be obtained by performing a treatment such as filtration or centrifugation to remove the extraction residue. The obtained extract is diluted, concentrated, dried, purified, etc. according to a conventional method in order to obtain a diluted or concentrated solution of the extract, a dried product of the extract, or a crude purified product or a purified product thereof. Processing may be performed.

  Extracts from plants belonging to the genus Saussurea have a specific odor and taste, and may be purified for decolorization, deodorization, and the like. Specifically, purification can be performed by activated carbon treatment adsorption resin treatment, ion exchange resin treatment, etc., and these treatments cause a decrease in glutathione production promoting action in extracts from plants belonging to the genus Southus (Saussurea). Do as much as possible.

[Embodiment 2]
The glutathione production promoter according to the second embodiment is a solution in which a solution obtained by dissolving an extract from a plant belonging to the genus Saussurea in 30% (V / V) methanol is applied to a column using a porous polystyrene resin as a carrier. The “component that is adsorbed to the porous polystyrene resin when passed through” is contained as an active ingredient (see FIG. 1).

  “An extract from a plant belonging to the genus Saussurea” can be obtained by the method described in the first embodiment.

  Examples of the porous polystyrene resin used as the carrier include Diaion (registered trademark of Mitsubishi Chemical Corporation) HP20 and HP21, and Sepabeads (registered trademark of Mitsubishi Chemical Corporation) SP850, SP700 and SP70.

  In Embodiment 2, the component adsorbed on the porous polystyrene resin is eluted by passing a solution of 30% (V / V) methanol in the column and then passing a relatively low-polarity solvent through the column. can do. Examples of the solvent that can be used for elution of the component include intermediate polar solvents such as lower aliphatic alcohols, acetone and ethyl acetate, and nonpolar solvents such as hexane. Of these solvents, methanol can be particularly preferably used.

In the present specification, “when a solution in which an extract from a plant belonging to the genus Saussurea is dissolved in 30% (V / V) methanol is passed through a column using a porous polystyrene resin as a carrier, The component that is adsorbed on the polystyrene resin is referred to as “adsorption component”.
Further, when a solution obtained by dissolving an extract from a plant belonging to the genus Saussurea in 30% (V / V) methanol is passed through a column using a porous polystyrene resin as a carrier, 30% (V / V V) A component eluted from the column with methanol is referred to as a “non-adsorbed component”.

[Embodiment 3]
The glutathione production promoter according to Embodiment 3 is a solution in which a solution in which an extract from a plant belonging to the genus Saussurea is dissolved in 30% (V / V) methanol is applied to a column using a porous polystyrene resin as a carrier. Then, when 50% (V / V) methanol is passed through the column, it contains “the component adsorbed on the porous polystyrene resin” as an active ingredient (see FIG. 1).

  “An extract from a plant belonging to the genus Saussurea” can be obtained by the method described in the first embodiment.

  Examples of the porous polystyrene resin used as the carrier include Diaion (registered trademark of Mitsubishi Chemical Corporation) HP20 and HP21, and Sepabeads (registered trademark of Mitsubishi Chemical Corporation) SP850, SP700 and SP70.

  In Embodiment 3, the component adsorbed on the porous polystyrene resin can be eluted by passing 50% (V / V) methanol through the column and then passing a lower polarity solvent through the column. Examples of the solvent that can be used for elution of the component include intermediate polar solvents such as lower aliphatic alcohols, acetone and ethyl acetate, and nonpolar solvents such as hexane. Of these solvents, methanol can be particularly preferably used.

[Embodiment 4]
The glutathione production promoter according to Embodiment 4 is a solution in which a solution obtained by dissolving an extract from a plant belonging to the genus Saussurea in 30% (V / V) methanol is applied to a column using a porous polystyrene resin as a carrier. Then, 50% (V / V) methanol is passed through the column, and then, when methanol is passed through the column, the component “eluting from the column with methanol” is contained as an active ingredient (see FIG. 1). .

  “An extract from a plant belonging to the genus Saussurea” can be obtained by the method described in the first embodiment.

  Examples of the porous polystyrene resin used as the carrier include Diaion (registered trademark of Mitsubishi Chemical Corporation) HP20 and HP21, and Sepabeads (registered trademark of Mitsubishi Chemical Corporation) SP850, SP700 and SP70.

  In the present specification, “a solution obtained by dissolving an extract from a plant belonging to the genus Saussurea in 30% (V / V) methanol is passed through a column using a porous polystyrene resin as a carrier, % (V / V) methanol is passed through the column, and when methanol is further passed through the column, “the component eluted from the column by methanol” is referred to as “methanol elution fraction”.

[Embodiment 5]
The glutathione production promoter according to Embodiment 5 contains dihydrodehydrocostus lactone represented by the following formula (1) as an active ingredient.

  Dihydrodehydrocostus lactone is contained in an extract from a plant belonging to the genus Saussurea as shown in Preparation Example 4 described later (see FIG. 2 described later). The dihydrodehydrocostus lactone used for the glutathione production promoter may be a product separated from an extract from a plant belonging to the genus Southus (Saussurea), or may be a natural product other than a plant belonging to the genus Southus (Saussurea). And what was isolate | separated from the natural product containing dihydrodehydrocostus lactone may be used, and a commercial item and a synthetic product may be used.

  The glutathione production promoter according to Embodiments 1 to 5 above (that is, the glutathione production promoter of the present invention) can be expected to suppress a decrease in oxidative stress response that decreases due to aging through its glutathione production promoting action, It can be expected to prevent, treat or improve skin aging, spots or freckles associated with oxidative stress such as ultraviolet irradiation. However, the glutathione production promoter of the present invention can be used for all purposes other than these uses that are meaningful for exerting the glutathione production promoting action.

  In addition, the glutathione production promoter of the present invention has a glutathione production promoting action, thereby causing a disease related to deficiency of glutathione (for example, cell damage due to UV exposure, inflammation, acute or chronic alcohol liver disorder, liver disease, Parkinson's disease, Alzheimer's disease). It is also expected to be used as an active ingredient of preventive, therapeutic or ameliorating agents for gastric ulcer, immunodeficiency, acquired immune deficiency syndrome, aging with physiological aging, canceration, etc.). Furthermore, since the glutathione production promoter of the present invention can increase the intracellular concentration of glutathione using its action, it can also be used as an active ingredient of a prophylactic, therapeutic or ameliorating agent for sleep disorders such as insomnia. Can be expected to use. In addition, the glutathione production promoter of the present invention may contain any one of the active ingredients in Embodiments 1 to 5, or two or more of the active ingredients in Embodiments 1 to 5. You may contain. In the case where two or more of the active ingredients in Embodiments 1 to 5 are contained, their blending ratio may be appropriately determined according to the degree of their action.

  The glutathione production promoter of the present invention can be used as a pharmaceutical, food, or cosmetic containing glutathione production promoter and having glutathione production promoting action.

  The route of administration of the “internal medicine having glutathione production promoting effect” of the present invention is not particularly limited, but for example, enteral administration such as oral administration and rectal administration, mucosal administration such as nasal administration, and intravenous administration・ Injection administration such as subcutaneous administration can be given. The dosage form of the internal medicine of the present invention can be in the form of a formulation suitable for the administration method, for example, tablet, powder, fine granule, granule, capsule, powder, pill, troche And liquids such as solid preparations, solutions, suspensions, emulsions, syrups, injections, and gel preparations. A pure product, purified product, crude product, etc. of the glutathione production promoter of the present invention may be administered as it is, but may be administered together with a pharmacologically acceptable excipient. As the excipient, any monosaccharides, second class, polysaccharides, inorganic salts, fats and oils, distilled water, etc. that can be generally used as preparations can be used. In formulating, additives such as binders, lubricants, dispersants, suspending agents, emulsifiers, diluents, buffers, antioxidants, and bacterial inhibitors can be used.

  The content of the glutathione production promoter in the internal medicine of the present invention can be set to an optimum amount for each dosage form based on the dosage form, effective dosage, and dosage data as the dosage form.

  The form of the “food having glutathione production promoting action” of the present invention includes a pure product of the glutathione production promoter of the present invention, a partially purified product thereof, and a crude extraction of the compound from a plant containing the glutathione production promoter. Products, pastes containing the glutathione production promoter, foods containing the glutathione production promoter, and the like. In other words, drinks, jellies, biscuits, tea, tablets, pills, soft capsules, hard capsules, powders, fine granules, granules, etc. are provided as normal foods in the form of “foods that promote glutathione production” Any form can be used as long as it is possible. Additives such as excipients, binders, lubricants, dispersants, suspending agents, emulsifiers, diluents, buffers, antioxidants, and bacterial inhibitors can also be used as auxiliary materials.

  Examples of the form of the “external medicine or cosmetic having a glutathione production promoting effect” of the present invention are not particularly limited.

  Examples of the form of external medicine include ointments, creams, cloths, tapes, and external preparations. The pharmaceutical preparation for external use of the present invention can contain other pharmaceutical ingredients as necessary in the glutathione production promoter of the present invention, and also includes a binder, a dispersant, a suspending agent, an emulsifier, a diluent, and a buffer. Additives such as antioxidants and bacteria inhibitors may be used.

  As the form of the cosmetic, any form that can be used as an external preparation / cosmetic preparation such as lotion, cosmetic liquid, milky lotion, cream, gel, pack, cosmetic powder, facial cleansing foam, bath preparation, etc. can be used. In addition to the glutathione production promoter of the present invention, the cosmetic preparation may contain components blended into the cosmetic preparation as necessary. Examples of the ingredients include solid oil, semi-solid oil, liquid oil, low molecular moisturizer, polymer moisturizer, fat-soluble moisturizer, emollient, surfactant, preservative, antioxidant, pH adjuster, Ethanol, water, etc. can be raised.

  The pharmaceuticals, foods and cosmetics of the present invention can be expected to suppress a decrease in oxidative stress response that decreases with aging through the glutathione production promoting action of the glutathione production promoter of the present invention. It can be expected to prevent, treat or improve skin aging and spots and freckles related to the above. However, the pharmaceuticals, foods, and cosmetics of the present invention can be used for all purposes that are meaningful for exerting the glutathione production promoting action in addition to these uses.

  In addition, the pharmaceutical, food and cosmetics of the present invention have a glutathione production-promoting action of a glutathione production-promoting agent, thereby causing diseases associated with deficiency of glutathione (for example, cell damage, inflammation, acute or chronic alcohol liver damage caused by UV exposure, Hepatic disease, Parkinson's disease, Alzheimer's disease, gastric ulcer, immune deficiency, acquired immune deficiency syndrome, aging with physiological aging, canceration, etc.) can be expected to prevent, treat or improve, Since the intracellular concentration of glutathione can be increased, it can be expected to prevent, treat or improve sleep disorders such as insomnia.

  The glutathione production promoter, pharmaceuticals, foods and cosmetics of the present invention are preferably applied to humans, but as long as the respective effects are exhibited, they are applied to animals other than humans. You can also

  Hereinafter, the present invention will be described in more detail with reference to “1. Sample preparation example” and “2. Test example of glutathione production promoting action”, but the present invention is not limited thereto.

1. Sample Preparation Example (Preparation Example 1) Sample Preparation Example Preparation Example 1 is an extract of purified water from Saussurea involucrata (Kar. Et Kir.) Sch.Blp. (Sample a (water extract) )) Is a preparation example.
Heat extraction with 450 mL (milliliter) of purified water for 30.3 g of ground product of Saussurea involucrata (Kar. Et Kir.) Sch.Blp., A plant belonging to the genus Saussurea (After 80 degreeC-90 degreeC, 2 hours), the obtained solution was filtered (2 types of filter paper for qualitative analysis (purchased from Advantech Toyo Co., Ltd.) was used.) An extract was obtained. The obtained extract was concentrated under reduced pressure and lyophilized in order to obtain 8.3 g of sample a (water extract). The solid yield was 27.3%.

(Preparation Example 2) Preparation Example of Sample b Preparation Example 2 is an extract from Saussurea involucrata (Kar. Et Kir.) Sch. Blp. With 50% (V / V) ethanol (sample b (50 % Ethanol extract))).
450 mL of 50% (V / V) ethanol for 30.5 g of ground pulverized product of Saussurea involucrata (Kar. Et Kir. Sch.Blp.), A plant belonging to the genus Saussurea After heating extraction (80 ° C. to 90 ° C., 2 hours) by filtration, the resulting solution was filtered (uses two types of filter paper for qualitative analysis (purchased from Advantech Toyo Co., Ltd.)) to obtain an extract. . The obtained extract was concentrated under reduced pressure and freeze-dried sequentially to obtain 7.4 g of sample b (50% ethanol extract). The solid yield was 24.2%.

(Preparation Example 3) Preparation Example of Sample c Preparation Example 3 is an extract from Saussurea involucrata (Kar. Et Kir. Sch. Blp.) With 80% (V / V) ethanol (sample c (80 % Ethanol extract))).
450 mL of 80% (V / V) ethanol with respect to 30.7 g of ground pulverized product of Saussurea involucrata (Kar. Et Kir. Sch.Blp.), A plant belonging to the genus Saussurea After heating extraction (80 ° C. to 90 ° C., 2 hours) by filtration, the resulting solution was filtered (uses two types of filter paper for qualitative analysis (purchased from Advantech Toyo Co., Ltd.)) to obtain an extract. . The obtained extract was concentrated under reduced pressure and freeze-dried sequentially to obtain 5.4 g of sample c (80% ethanol extract). The solid yield was 17.5%.

(Preparation Example 4) Preparation Examples of Samples df and Comparative Sample FIG. 2 is a flowchart shown for explaining preparation examples of samples df and comparative samples.
Preparation Example 4 is a comparative sample (non-adsorbed component), sample d (adsorbed component), sample e (methanol-eluted fraction) and sample from Southus involucrata (Kar. Et Kir.) Sch. Blp. This is a preparation example for obtaining f (dihydrodehydrocostus lactone). The preparation example was performed according to the flow shown in FIG.

  Saussurea involucrata (Kar. Et Kir.) Sch.Blp. 4 kg ground ground was digested with 80% (V / V) ethanol (80 ° C, 2 hours). After performing twice, the resulting solution was filtered (uses two types of filter paper for qualitative analysis (purchased from Advantech Toyo Co., Ltd.)) to obtain an extract. Further, the extract was concentrated under reduced pressure at 60 ° C. and dried (normal temperature, 10 hours) to obtain 680 g of an extract. Next, the extract was dissolved in 30% (V / V) methanol (3 L, 40 ° C.) to form a solution, and the solution was preliminarily equilibrated with 30% (V / V) methanol, Diaion HP20 (1500 g, (Purchased from Mitsubishi Chemical Corporation) was passed through a column packed as a carrier. Thereafter, elution was performed with 6 L of 30% (V / V) methanol, and the 30% (V / V) methanol elution fraction was recovered as a non-adsorbed component (comparative sample). Subsequently, elution was performed successively with 7 L of 50% (V / V) methanol, 6 L of methanol, 5 L of ethanol, 5 L of ethyl acetate and 5 L of hexane, and the elution fractions were collected. Each elution fraction was dried to remove the solvent, and 399 g of non-adsorbed component (comparative sample), 38 g of 50% (V / V) methanol elution fraction, 100 g of methanol elution fraction (sample e), 21 g Ethanol elution fraction, 18 g ethyl acetate elution fraction and 0.11 g hexane elution fraction were obtained. The total of the elution fractions other than the non-adsorbed component was defined as the adsorbed component (sample d), and the total weight of each elution fraction other than the non-adsorbed component (that is, the adsorbed component) was 177.11 g. .

Among these, the methanol elution fraction (sample e) (100 g) was subjected to silica gel column chromatography (80 mmφ × 350 mm, purchased from Fuji Silysia Chemical Ltd.) using chloroform / methanol / water as an elution solvent. That is, elution was performed while sequentially changing the ratio of the elution solvent from 90: 10: 0, 40: 10: 1, and 30: 10: 1 (both chloroform: methanol: water), and the eluate was 150 mL per fraction. The fractions were collected one by one, and these fractions were combined to obtain 8 fractions A to H. Among these, the solvent was removed from the eluate containing fraction A (elution amount: 450 mL to 1200 mL) to obtain a dry solid, and 40.9 g of fraction A was obtained.
Next, fraction A (40.9 g) was subjected to silica gel column chromatography (60 mmφ × 250 mm, purchased from Fuji Silysia Chemical Ltd.) using hexane / acetone as an elution solvent. That is, elution was carried out while sequentially changing the elution solvent ratio to 9: 1, 6: 1, 4: 1, 2: 1 (both hexane: acetone), and 60 mL of the eluate was fractionated. These fractions were combined to obtain 8 fractions AA to AH. Among these, the solvent was removed from the eluate containing fraction AB to obtain a dry solid, and 13.1 g of fraction AB (elution amount: 180 mL to 600 mL) was obtained.
Further, fraction AB (13.1 g) was subjected to ODS silica gel column chromatography (60 mmφ × 150 mm, purchased from Nacalai Tesque, Inc.) using methanol / water as an elution solvent. That is, elution was carried out while sequentially changing the elution solvent ratios to 7: 3, 8: 2, 9: 1 (both methanol: water), and the eluate was fractionated 40 mL per fraction, and these fractions were combined. Ten fractions of AB-1 to AB-10 were obtained. Among these, the solvent was removed from the eluate containing fraction AB-3 (elution amount: 1200 mL to 1440 mL) to obtain a dry solid to obtain 2.1 g of fraction AB-3.
Further, fraction AB-3 (2.1 g) was subjected to silica gel column chromatography (60 mmφ × 150 mm, purchased from Fuji Silysia Chemical Ltd.) using hexane / ethyl acetate as an elution solvent. That is, elution was carried out while sequentially changing the elution solvent ratio to 19: 1 and 9: 1 (both hexane: ethyl acetate), and the eluate was fractionated 40 mL per fraction, containing dihydrodehydrocostus lactone. Eluate (elution amount: 1240 mL to 1520 mL) was obtained. The solvent was removed from the eluate to obtain a dry solid, and 161 mg of dihydrodehydrocostus lactone (sample f) was obtained.

When ¹ H-NMR spectrum data and ¹³ C-NMR spectrum data were obtained by nuclear magnetic resonance spectroscopy for dihydrodehydrocostus lactone (sample f) fractionated and isolated by the above method, the following peaks were observed. It almost agreed with the value in the literature (Journal of Natural Products, Vol. 62, page 27, 1999). The molecular formula of dihydrodehydrocostus lactone (sample f) is C ₁₅ H ₂₀ O ₂ .

¹ H-NMR (CDCl ₃ , 400 MHz) δ: 1.23 (3H, d, J = 7.0 Hz, Me-12), 1.30 (1H, m, H-8), 1.85 (1H, m, H-2), 1.94 (2H, m, H-2, H-7), 2.04 (1H, m, H-9), 2.10 (1H, m, H-3), 2.21 (1H, m, H-11), 2.50 (3H, m, H-3, H-8, H-9), 2.79 (1H, dd, J = 8.9, 8. 9 Hz, H-5), 2.87 (1H, m, H-1), 3.91 (1H, dd, J = 9.3, 9.3 Hz, H-6), 4.77 (1H, br) s, H-15a), 4.87 (1H, br s, H-15b), 5.04 (1H, d, J = 2.0 Hz, H-14a) 5.19 (1H, d, J = 2) .0Hz, H-14b).

¹³ C-NMR (CDCl ₃ , 100 MHz) δ: 13.22 (C-12), 30.17 (C-2), 32.48 (C-3, 8), 37.65 (C-9), 42.04 (C-11), 47.04 (C-1), 49.85 (C-7), 51.93 (C-5), 85.28 (C-6), 109.15 (C -14), 111.81 (C-15), 149.94 (C-10), 151.70 (C-4), 178.70 (C-13).

  Further, when mass spectrometry was performed on the dihydrodehydrocostus lactone (sample f) fractionated and isolated by the above method, the following results were obtained, and the measured mass was approximately the same as the mass estimated from the molecular formula did.

HR-ESI-TOF-MS m / z: 233.1550 [M + H] ⁺ (Calcd for C ₁₅ H ₂₀ O ₂ : 233.1542).

  In the above, general-purpose laboratory instruments and experimental apparatuses were used for column chromatography with Diaion HP20, silica gel column chromatography, and ODS silica gel column chromatography. As a nuclear magnetic resonance spectrum apparatus, a Bruker DRX-400 type nuclear magnetic resonance spectrum apparatus (manufactured by Bruker BioSpin Corporation) was used. As a mass spectrometer, a Waters-Micromass LCT mass spectrometer (manufactured by Waters) was used.

2. Test Example of Glutathione Production Promoting Action A test example of glutathione production promoting action was performed by measuring glutathione production activity on human skin fibroblasts and normal human epidermal keratinocytes.

(Test Example 1) Test example of glutathione production promoting action on human dermal fibroblasts (a) Test method Minimum essential medium α containing 10% (V / V) fetal bovine serum (FBS, purchased from Nichirei Bioscience) as a medium MEMα (purchased from GIBCO) and seeded human skin fibroblasts (NB1RGB; purchased from RIKEN BioResource Center) in a 24-well plate (purchased from NUNC) at 1.0 × 10 ⁵ cells / well. The cells were cultured in a CO ₂ incubator (37 ° C., 5% carbon dioxide, 95% air). After 24 hours, the medium was replaced with a sample-added medium adjusted to contain the sample at a predetermined concentration (200 μg / mL or 20 μg / mL), and further cultured for 24 hours.
As samples, sample a (water extract, see Preparation Example 1 above, concentration 200 μg / mL), sample b (50% ethanol extract, see Preparation Example 2 above, concentration 200 μg / mL), sample c (80 % Ethanol extract, see Preparation Example 3. Concentration 200 μg / mL), sample d (Adsorption component. See Preparation Example 4 above, concentration 20 μg / mL), sample e (Methanol elution fraction. Preparation Example 4 above) Reference: concentration 20 μg / mL) and sample f (dihydrodehydrocostus lactone, see Preparation Example 4 above, concentration 20 μg / mL) were tested for each. For comparison, a test was also conducted on a comparative sample (non-adsorbed component, see Preparation Example 4 above, concentration 200 μg / mL).

  Next, trypsin treatment was performed by a conventional method, and cells were collected from each well. Thereafter, the cells were washed with Dulbecco's phosphate buffer, and then 80 μL of 10 mM hydrochloric acid was added, followed by cell membrane disruption treatment by freeze-thawing (twice). 20 μL of 5% (W / V) sulfosalicylic acid was added to the treatment solution after cell membrane disruption treatment, and after centrifugation (8000 G, 10 minutes), the resulting supernatant was used for measurement. The amount of glutathione in the supernatant was measured by an enzyme recycling method using Total Glutathione Quantification Kit (purchased from Dojindo), and the total amount of glutathione was calculated. At the same time as measuring the total amount of glutathione, the number of viable cells without trypan blue was counted using a hemocytometer to calculate the amount of glutathione per live cell, and glutathione per live cell when using a medium without sample. The relative amount of glutathione (an index when the amount of glutathione per living cell when no sample was added was taken as 100%) was calculated by comparing with the amount.

(A) Test results The test results are shown in Table 1 and FIG. Table 1 is a table showing the results of Test Example 1 (promoting effect of glutathione production on human skin fibroblasts). FIG. 3 is a graph showing the results of Test Example 1 (promoting effect of glutathione production on human skin fibroblasts).
[Table 1]

Relative glutathione levels in human dermal fibroblasts
Sample concentration Relative glutathione level
Sample a (water extract) 200 μg / mL 129.5%
Sample b (50% ethanol extract) 200 μg / mL 265.1%
Sample c (80% ethanol extract) 200 μg / mL 209.3%
Sample d (adsorption component) 20 μg / mL 296.4%
Sample e (methanol elution fraction) 20 μg / mL 362.9%
Sample f (dihydrodehydrocostus lactone) 20 μg / mL 163.8%
Comparative sample (non-adsorbed component) 200 μg / mL 111.8%
No sample added (control)-100.0%

(A) About Samples a to c As shown in Table 1 and FIG. 3, any extract from Saussurea involucrata (Kar. Et Kir.) Sch. Blp. It was confirmed that glutathione production was promoted against human skin fibroblasts. In addition, among samples a to c, it was also confirmed that sample b (50% ethanol extract) and sample c (80% ethanol extract) exhibited a high glutathione production promoting action.

(B) Sample d As shown in Table 1 and FIG. 3, the sample d (adsorbed component) is a low concentration (20 μg / mL), but a high concentration (200 μg / mL) comparative sample (non-adsorbed component). It was confirmed that the glutathione production promoting action was significantly higher than

(C) Sample e As shown in Table 1 and FIG. 3, it was confirmed that sample e (methanol elution fraction) exhibited a higher glutathione production promoting effect than sample d (adsorbed component).

(D) Sample f As shown in Table 1 and FIG. 3, it can be confirmed that sample f (dihydrodehydrocostus lactone) exhibits a high glutathione production promoting action even at a low concentration (20 μg / mL). It was.

(Test Example 2) Test example of glutathione production promoting action on normal human epidermal keratinocytes (A) Test method Using EpiLife KG2 (purchased from Kurashiki Textile Co., Ltd.) as a medium, normal human epidermal keratinocytes (NHEK F. Purchased from Kurashiki Boseki Co., Ltd.) in a 24-well plate (purchased from NUNC) at 2.5 × 10 ⁵ cells / well, and CO ₂ incubator (37 ° C., 5% carbon dioxide, 95% air) ). After 72 hours, the medium was replaced with a sample-added medium adjusted to contain the sample at a predetermined concentration (200 μg / mL, 10 μg / mL, or 5 μg / mL), and further cultured for 24 hours.
As samples, sample a (water extract, see Preparation Example 1 above, concentration 200 μg / mL), sample b (50% ethanol extract, see Preparation Example 2 above, concentration 200 μg / mL), sample c (80 % Ethanol extract, see Preparation Example 3 above, concentration 200 μg / mL), sample e (methanol elution fraction, see Preparation Example 4 above, concentration 10 μg / mL) and sample f (dihydrodehydrocostus lactone, above preparation. See Example 4. Each was tested using a concentration of 5 μg / mL).

  Next, trypsin treatment was performed by a conventional method, and cells were collected from each well. Thereafter, the cells were washed with Dulbecco's phosphate buffer, and then 80 μL of 10 mM hydrochloric acid was added, followed by cell membrane disruption treatment by freeze-thawing (twice). 20 μL of 5% (W / V) sulfosalicylic acid was added to the treatment solution after the cell membrane disruption treatment, and after centrifugation (8000 G, 10 minutes), a supernatant was obtained. The amount of glutathione in the supernatant was measured by an enzyme recycling method using Total Glutathione Quantification Kit (purchased from Dojindo), and the total amount of glutathione was calculated. At the same time as measuring the total amount of glutathione, the number of viable cells without trypan blue was counted using a hemocytometer to calculate the amount of glutathione per live cell, and glutathione per live cell when using a medium without sample. The relative amount of glutathione (an index when the amount of glutathione per living cell when no sample was added was taken as 100%) was calculated by comparing with the amount.

(A) Test results The test results are shown in Table 2 and FIG. Table 2 is a table showing the results of Test Example 2 (promoting effect of glutathione production on normal human epidermal keratinocytes). FIG. 4 is a graph showing the results of Test Example 2 (promoting effect of glutathione production on normal human epidermal keratinocytes).
[Table 2]

Relative glutathione levels in normal human epidermal keratinocytes
Sample concentration Relative glutathione level
Sample a (water extract) 200 μg / mL 167.0%
Sample b (50% ethanol extract) 200 μg / mL 491.8%
Sample c (80% ethanol extract) 200 μg / mL 409.9%
Sample e (methanol elution fraction) 10 μg / mL 298.1%
Sample f (dihydrodehydrocostus lactone) 5 μg / mL 259.5%
No sample added (control)-100.0%

(A) About Samples a to c As shown in Table 2 and FIG. 4, any extract (samples a to c) from Saussurea involucrata (Kar. Et Kir.) Sch. It was confirmed that glutathione production was promoted to normal human epidermal keratinocytes. In addition, among samples a to c, it was also confirmed that sample b (50% ethanol extract) and sample c (80% ethanol extract) exhibited a high glutathione production promoting action.

(B) Sample e As shown in Table 2 and FIG. 4, it was confirmed that sample e (methanol elution fraction) exhibited a high glutathione production promoting action even at a low concentration (10 μg / mL). .

(C) Sample f As shown in Table 2 and FIG. 4, it can be confirmed that sample f (dihydrodehydrocostus lactone) exhibits a high glutathione production promoting action even at a low concentration (5 μg / mL). It was.

Example 1. Preparation of tablets Using the water extract prepared according to the method described in "Preparation example 1) Preparation example of sample a", tablets (500 mg per tablet) are prepared according to the following formulation.

Water extract (Preparation Example 1) 10mg
Lactose 470mg
10mg dried corn starch
Talc 9mg
Calcium stearate 1mg

(Preparation method)
Lactose (94 g) is mixed with water extract (2 g), dried corn starch (2 g), talc (1.8 g) and calcium stearate (0.2 g). Subsequently, a tablet is produced by a conventional method using a single-shot tablet press.

Example 2 Production of hard capsules Using the 50% ethanol extract prepared according to the method described in “Preparation Example 2) Preparation Example of Sample b” above, hard capsules (360 mg per capsule) are produced with the following formulation. .

50% ethanol extract (Preparation Example 2) 5mg
Lactose 220mg
Corn starch 110mg
Hydroxypropylcellulose 25mg

(Preparation method)
Lactose (220 g) and corn starch (110 g) are added to and mixed with 50% ethanol extract (5 g), and an aqueous solution of hydroxypropylcellulose (25 g) is added thereto and kneaded. Next, granules are produced by an ordinary method using an extrusion granulator. A hard capsule is prepared by filling the granule into a gelatin hard capsule.

Example 3 FIG. Production of soft capsules Using the 80% ethanol extract prepared according to the method described in “Preparation Example 3) Preparation Example of Sample c” above, soft capsules (170 mg per capsule) are produced according to the following formulation. .

80% ethanol extract (Preparation Example 3) 5mg
Soybean oil 165mg

(Preparation method)
Add 80% ethanol extract (5 g) to soybean oil (165 g) and mix. Next, soft capsules are prepared by filling the soft capsules using a rotary die type automatic molding machine according to a conventional method.

Example 4 Using the adsorbate prepared according to the method described in Preparation above pills "(Preparation Example 4) Preparation of Sample d~f and comparative sample" pills by the following formulate (per one grain 100mg) Make it.

Adsorption component (Preparation Example 4) 0.5mg
Morohaya powder 20.0mg
Starch 30.0mg
Molasses 20.0mg
Tea extract 15.0mg
Soy fiber 14.0mg
Shellac 0.5mg

(Preparation method)
After mixing the raw materials with the above blending, adding a suitable amount of water, producing a homogeneous kneaded product with a kneader, rolling the kneaded product, making a round shape using a round machine and drying it to produce a pill To do.

Example 5 FIG. Preparation of Jelly Using the water extract prepared according to the method described in “(Preparation Example 1) Preparation Example of Sample a”, a jelly (100 g) is prepared by a conventional method with the following formulation.

Water extract (Preparation Example 1) 0.02g
2.00 g of gelatin
Orange juice 20.00g
77.98 g of water

(Preparation method)
The above ingredients are mixed and heated to 90 ° C. After confirming the dissolution of gelatin, fill the container and cool. A jelly is prepared by solidifying gelatin.

Example 6 Preparation of ointment Using the dihydrodehydrocostus lactone prepared according to the method described in "Preparation Example 4) Preparation Examples of Samples df and Comparative Samples" above, the ointment (100 g ).

(Oil phase component)
Dihydrodehydrocostus lactone (Preparation Example 4) 0.01 g
White petrolatum 20.00g
Mineral oil 20.00g
Stearyl alcohol 5.00g
Steareth-2 3.00g
Propylparaben 0.10g
Natural vitamin E 0.10g
(Aqueous phase component)
1,3-butylene glycol 5.00g
Phenoxyethanol 0.40g
Polysorbate 60 4.50g
Purified water
Total amount 100g

(Preparation method)
The oil phase component and the water phase component were each heated to 80 ° C. to be uniform, and the water phase was added to the oil phase while stirring, emulsified and cooled to prepare an ointment.

Example 7 Production of Tape Agent Using the methanol-eluted fraction prepared according to the method described in “Preparation Example 4) Preparation Examples of Samples df and Comparative Samples” above, tape preparation ( 100 g).

(Adhesive solvent)
Styrene-isopropylene-styrene block copolymer 7.00 g
Picolite 25.00g
Isopropylene rubber 5.00g
Toluene 15.00g
14.20 g of ethyl acetate
Hexane 25.00g
(Medicinal ingredients)
Methanol elution fraction (Preparation Example 4) 0.01 g
Ethanol 7.9g
(Transdermal absorption enhancer)
Oleyl alcohol 0.80g
Total amount 100g

(Preparation method)
The adhesive solvent and the medicinal component were made uniform, the medicinal component and the transdermal absorption accelerator were added to the adhesive solvent, and the mixture was stirred at room temperature to prepare a composition. This composition is spread on a silicone-treated polyester film, dried at 120 ° C. and cooled, and then the pressure-sensitive adhesive layer is transferred to a polyethylene film to produce a tape agent.

Example 8 FIG. Production of Lotion A lotion (100 g) is produced by a conventional method using the water extract prepared according to the method described in the above-mentioned “(Preparation Example 1) Preparation Example of Sample a”.

(Oil phase component)
Polyoxyethylene (60 mol) hydrogenated castor oil 2.0 g
1,3-butylene glycol 5.0 g
(Aqueous phase component)
Water extract (Preparation Example 1) 0.1g
Glycerin 5.0g
Phenoxyethanol 0.3g
Citric acid 0.1g
Sodium citrate 0.2g
Ethanol 8.0g
Purified water
Total amount 100g

(Preparation method)
An oil phase component and an aqueous phase component are uniformly dissolved, and the oil phase is added to the aqueous phase while stirring to prepare a skin lotion.

Example 9 Preparation of emulsion Using the 50% ethanol extract prepared according to the method described in the above-mentioned "(Preparation Example 2) Preparation Example of Sample b", an emulsion (100 g) is prepared in the usual manner with the following formulation.

Palm oil 8.00g
Ethanol 5.00g
Behenyl alcohol 0.50g
Citric acid 0.10g
Sodium citrate 0.20g
50% ethanol extract (Preparation Example 2) 1.50 g
1,3-butylene glycol 4.00 g
Paraoxybenzoic acid ester 0.10g
Edetic acid disodium 0.01g
Purified water
Total amount 100g

(Preparation method)
An emulsion is prepared by stirring and mixing the above materials.

Example 10 Preparation of cosmetic liquid Using the 80% ethanol extract prepared according to the method described in “Preparation Example 3) Preparation Example of Sample c” above, a cosmetic liquid (100 g) was prepared by the usual method with the following prescription. To do.

80% ethanol extract (Preparation Example 3) 1.50 g
Carboxy vinyl polymer 0.50g
Glycerin 6.50g
1,3-butylene glycol 7.50g
Phenoxyethanol 0.30g
Potassium hydroxide 0.20g
Sodium hyaluronate 0.25g
Squalane 0.50g
Vitamin E acetate 0.05g
Stearic acid 0.20g
Purified water
Total amount 100g

(Preparation method)
A cosmetic solution is prepared by stirring, mixing, and dissolving the above materials.

Claims (6)

A glutathione production promoter containing dihydrodehydrocostus lactone represented by the following formula (1) as an active ingredient.

  The glutathione production promoter according to claim 1, wherein the dihydrodehydrocostus lactone is contained in "an extract from Saussurea involucrata (Kar. Et Kir.) Sch. Blp." .   The dihydrodehydrocostus lactone is a porous polystyrene resin obtained by dissolving an extract from Saussurea involucrata (Kar. Et Kir. Sch. Blp.) In 30% (V / V) methanol. The glutathione production promoter according to claim 1, which is contained in the “component adsorbed on the porous polystyrene resin when passed through a column having a carrier as a carrier”.   The dihydrodehydrocostus lactone is a porous polystyrene resin obtained by dissolving an extract from Saussurea involucrata (Kar. Et Kir. Sch. Blp.) In 30% (V / V) methanol. The component contained in the component adsorbed by the porous polystyrene resin when 50% (V / V) methanol is passed through the column. The glutathione production promoter described in 1.   The dihydrodehydrocostus lactone is a porous polystyrene resin obtained by dissolving an extract from Saussurea involucrata (Kar. Et Kir. Sch. Blp.) In 30% (V / V) methanol. In a component that is eluted from the column by the methanol when 50% (V / V) methanol is passed through the column and then methanol is passed through the column. The glutathione production promoter according to claim 1, wherein   The pharmaceutical which has the glutathione production promotion effect | action which contains the glutathione production promoter in any one of Claims 1-5.

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