TW201201865A - Glutathione production promoter, and pharmaceuticals, food, and cosmetic material having glutathione production promoting function - Google Patents

Abstract

This invention provides a glutathione production promoter with high-safety ingredients obtained from natural product, and also provides pharmaceuticals, food, and cosmetic material that contain glutathione production promoter and have clutathione production promoting function. The glutathione production promoter contains the extract of plants belong to the Saussurea genus, especially the extract of one or more of plants selected from the group consisting of Saussurea involucrate (Kar. Et Kir.) Sch.Blp., Saussurea Medusa Maxim, and Saussurea laniceps Hand.-Mazz as the active ingredients.

Description

201201865 VI. Description of the Invention: [Technical Fields of the Invention] [0001] The present invention relates to a glutathion production promoter (glutathic) T1 (a promoter of a ie Pro action) and a glutathione production-promoting medicine Products, food or cosmetics. [Prior Art] [0002]

Glutathione is a tripeptide composed of giutamic, cysteine, and giicine t3 amino acids. Antioxidants (in vivo) are known to capture radicals, regulate cell functions by redox, and act as SH-based donors of various enzymes. Participate in detoxification metabolism, etc. [0003] It is known that a decrease in the amount of glutathione in the cell leads to cell damage, inflammation, acute diffuse alcoholic liver damage, liver disease, and exposure to ultraviolet rays. Parkinson's disease, Alzheimer's disease, gastric ulceration, immunodeficiency, Acquired Immune Deficiency Syndrome, physiologic ageing ( Physiological aging), canceration, etc. [0004] Therefore, if the amount of glutathione in the cell is increased, it is expected to suppress the oxidative stress reaction which is lowered due to aging. The reduction in oxidative stress response can be expected to prevent skin aging, stains, and freckles associated with oxidative stress, such as ultraviolet radiation. Moreover, it can be 100124696, Form No. A0101, Page 3 of 51, 1002041805-0 201201865 It is expected to prevent various functional reductions caused by the lack of glutathione. [0006] In the past, a substance having a glutathione-promoting action is known to contain a surface sucrose containing the following extract as an active ingredient. Peptide production promoter: from butcher's broom, Mallotus philippensis, Himalayan raspberry, rosemary, H〇uttuynia herb, licorice Iicorice), outer galea, coptis, Arnica, oolong tea, Sophora root 'Phellodendron bark, Swertia herb, wild thyme , lavender, ginseng (Panax ginseng), ginkgo, moon 1 (Shel 1 ginger), carambola, royal jelly (r〇yai jeiiy), scutellaria root, good Aloe ferox, yeast (yeast), Rehmannia root, peony, Achillea millefolium, mulberry bark, Artemisiae capillaris flos An extract of one or two or more natural products selected from the group consisting of horse chestnut, hop, and Isodon japonicus (see, for example, Patent Document 1). On the other hand, it is known that an extract derived from a plant belonging to the genus Saussurea is used as a collagen (col lagen) production promoter or an estrogenic agent for skin cosmetics (for example, reference to a patent) Literature 2). Moreover, it is known that an extract from Saussurea 1 aniceps Hand. - Mazz. among plants belonging to the genus Saussurea is used as a tyrosinase inhibitor 100124696 Form No. A0101 Page 4 / A total of 51 pages 1002041805-0 201201865 (tyrosinaseinhibit〇r) or a melanin production inhibitor (raelanin production inhibit〇r) are used for whitening cosmetics (for example, refer to Patent Document 3). Furthermore, it has been known in recent years that there is also an advancement in the study of extracts from plants belonging to the genus Saussurea 'the use of extracts from plants belonging to the genus Saussurea for cosmetics (for example, refer to the patent literature) 4 and patent document 5). [000Ή but 疋' is a predetermined ingredient derived from an extract belonging to a plant belonging to the genus Saussurea, an extract from a plant belonging to the genus Saussurea or included in the genus Aoki It is not known that Dihydrodehydrocostus lactone, a plant of the genus (Saussurea), is used as a promoter for the production of a glutathione. [Patent Document 1] 曰 特 2009 2009 2009 - 2009 2009 2009 0009 0009 0009 0009 0009 0009 〇〇 〇〇 〇〇 〇〇 〇〇 〇〇 〇〇 〇〇 〇〇 〇〇 〇〇 〇〇 〇〇 〇〇 〇〇 〇〇 658 658 658 658 658 658 658 658 658 658 658 658 658 658 658 658 658 658 658 658 658 658 [Patent Document 4] Japanese Laid-Open Patent Publication No. 2004-331 546 [Patent Document 5] 曰 National Patent Publication No. 2004-331547

SUMMARY OF THE INVENTION [0013] An object of the present invention is to provide a [glutathione production promoter using a component obtained from a natural product having high safety]. Further, it is an object of the invention to provide a medical product, a food or a cosmetic containing the glutathione production promoting agent and having a glutathione production promoting effect. [0014] The present inventors focused on substances having a glutathione-promoting effect 100124696 Form No. A0101 Page 5 of 51 1002041805-0 201201865 Dedicated to the results of the study, found to be used as a collagen production promoter, female A hormonal agent, a tyrosinase inhibitor, a melanin production inhibitor or a cosmetic material [an extract derived from a plant belonging to the genus Saussurea] is effective as a glutathione production promoter, and, [ It is also effective to use a predetermined component after the extract from the extract of the plant belonging to the genus Saussurea] and [dihydrodehydrogenated eucalyptus vinegar] as a chymotrypsin production promoter, thus achieving the completion of the present invention. Invention "The present invention consists of the following matters. [1] A cholestyramine production promoter comprising an extract derived from a plant belonging to the genus Saussurea as an active ingredient (actiVe ingredient) [0016] [2], as described above [1] The glutathione production promoter described in the above, wherein the aforementioned plant belonging to the genus Saussurea is Saussurea involucrate (Kar. et Kir.) Sch. Blp., Saussurea medusa Maxim. And more than one plant selected from the group consisting of Saussurea lan iceps Hand.-Mazz. [3] A glutathione production promoting agent comprising the following component as an active ingredient: an extract derived from a plant belonging to the genus Saussurea is dissolved in 30% (V/V) 曱When the solution of the alcohol passes through a column of a porous polystyrene resin as a carrier, the component adsorbed by the porous polystyrene resin. [4] The glutathione production promoter according to the above [3], wherein the aforementioned 100124696 Form No. A0101 Page 6 / 51 page 1002041805-0 201201865 [0019] 〇 belongs to Moon Muxiang (Saussurea) The genus of plants is one selected from the group consisting of Saussurea involucrate (Kar. et Kir.) Sch.Blp., Saussurea medusa Maxim and Saussurea laniceps Hand.-Mazz. The above plants. [5] 'A glutathione production promoter containing an ingredient as an active ingredient: an extract from a plant belonging to the genus Saussurea is dissolved in 30% (V/V) sterol When the solution passes through a column in which a porous polystyrene resin is supported, and then 50% (V/V) of methanol is passed through the above-mentioned column, the component adsorbed by the porous polystyrene resin is used. [6] The vladigin production promoter according to the above [5], wherein the plant belonging to the genus Saussurea is a Saussurea involucrate (Kar. et Kir.) Sch. Blp. .), more than one plant selected from the group consisting of Saussurea medusa Maxim. and Saussurea laniceps Hand.-Mazz. 002 [0021] [7], a glutathione production promoter containing the following components as an active ingredient: an extract from a plant belonging to the genus Saussurea is dissolved at 30% (V/V) The methanol solution is passed through a column with a porous polystyrene resin as a carrier, and then 50% (V/V) methanol is passed through the column, and then methanol is further passed through the column, by the aforementioned sterol from the tube. The components eluted from the column. [8] The glutathione production promoter according to the above [7], wherein the aforementioned plant belonging to the genus Saussurea is Xinjiang Xuelian 100124696 Form No. A0101 Page 7 of 51 page 1002041805- 0 201201865 (Saussurea involucrate (Kar.et Kir.)

More than one plant selected from the group consisting of Sch. Blp.), Saussurea medusa Maxim. and Saussurea lan iceps Hand. - Mazz. [00] [9] [9] A glutathione production promoter comprising dihydrodehydrocostus lactone represented by the following formula (j) As an active ingredient. [Chemical Formula 1]

[10] A pharmaceutical, food or cosmetic having a glutathione production-promoting action, comprising the glutathione production promoter according to the above [丨] or [2]. [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 glucagon production-promoting agent according to [5] or [6] above. 100124696 Form No. A0101 Page 8 of 51 1002041805-0 201201865 [0029] [0032] [0033] [0035] [13], a glutathione production promotion The medicinal product, the food or the cosmetic which acts, contains the glutathione production promoter described in the above [7] or [8]. [14] A pharmaceutical, food or cosmetic having a glutathione-promoting action, comprising the vacin-stimulating agent according to [9] above. [Effects of the Invention] According to the present invention, it is also known from the test examples described later that a [Glutathione production promoter using a component derived from a natural product of a female whole sex] can be provided and the glucagon can be contained. [Pharmaceutical, food or cosmetic having a bran demannin production promoting effect] which produces an accelerator. BEST MODE FOR CARRYING OUT THE INVENTION The glutathione production promoter of the present invention and the glutathione production-promoting drug, food or cosmetic containing the glutathione production promoter are described in more detail below. ]. Fig. 1 is a flow chart for explaining the embodiment - five. The glutathione production promoter of the present invention contains the following components as an active ingredient: [from an extract belonging to a plant belonging to the genus Saussurea], [will be extracted from a plant belonging to the genus Saussurea] When a solution in which methanol is dissolved in 3 〇% (V/V) is passed through a column of a porous polystyrene resin, the component adsorbed by the porous polystyrene resin], [will be derived from Azuzu (Saussurea) The extract of the genus plant is dissolved in a 30% (V/V) sterol solution through a column of porous polystyrene resin, and then 50% (V/V) methanol is passed through the column. The component adsorbed by the porous polystyrene resin], [the extract from the plant belonging to the genus Aoki 100124696 Form No. A0101 Page 9 / 51 page 1002041805-0 201201865 (Saussurea) will be dissolved in 3〇% (v/ v) a solution of sterol is passed through a column with a porous polystyrene resin as a carrier, then 50% (V/V) sterol is passed through the column, and then methanol is passed through the column, by methanol from the column Dissolved component] or [dihydrodehydrocostus lactone] (refer to Figure 1 and later) FIG 2). [0036] Hereinafter, the above-mentioned respective active ingredients are described by the first to fifth embodiments. [0037] [Embodiment 1] [0038] The glutathione production promoter contained in the first embodiment contains [from The extract of the plant of the genus Saussurea is an active ingredient (refer to Fig. 1). In the glutathione production promoter according to the first embodiment, the extract from the plant belonging to the genus A. sinensis contains the plant belonging to the genus Saussurea. The extract obtained by the extraction treatment, the diluted solution or concentrate of the extract, the dried product obtained by drying the extract, or any of the crude purified or purified product of the substance [0040] in the extraction treatment Plants belonging to the genus Saussurea are used as extraction materials. Although a whole plant can be used for extracting the raw material, it is preferable to use a ground segment. [0041] Specific examples of plants belonging to the genus Saussurea can be exemplified: Saussurea involucrate (Kar. et Kir)

Sch. Bip.) (sometimes also known as the big snow lotus or the Tianshan snow lotus), the jellyfish snow lotus (Saussurea medusa Maxim.), the cotton head snow lotus 100124696 Form No. A010] Page 10 of 51 1002041805-0 201201865

(Saussurea laniceps Hand.-Mazz.), Saussurea gnaphaloides (Royle) Sch.-Bip., Saussurea Stella Maxim., Saussurea tridactyla Sch.-Bip.ex Hook.f.), Saussurea namikawae Kitam., Saussurea gossypiphora D.Don., Saussurea nishiokae Kitarn., Saussurea leucoma Diels, Saussurea quercifolia WW Smith, Saussurea eriocephala French. Saussurea kingii JRDrumm.ex CECFisch., small fruit snow bunny ($8113811^3 81111 mouth 5011 ana (Field.et Gardn.) Lipsch.), Saussurea obvallata (Saussurea obvallata ( DC.) Edgew.), Saussurea wettsteiniana Hand.-Mazz., Saussurea globosa Chen, Saussurea longifolia Franch.

The above-mentioned plants belonging to the genus Saussurea can also be used singly as the extracting raw materials, and two or more different plants belonging to the genus Saussurea can also be used in combination. The extracting material is preferably one or more of Saussurea involucrate (Kar. et Kir.) Sch. Blp., Saussurea medusa Maxim., and Saussurea laniceps Hand.-Mazz. It is better to use Xinjiang Snow Lotus (88115511^3丨1^〇1-ucrate (Kar.et Kir.) Sch.Blp.). [0043] Xinjiang Saussurea is known (Saussurea involucrate (Kar. et 100124696 Form No. A0101 Page 11 of 51 1002041805-0 201201865

Kir.) Sch.Blp.), Saussurea medusa Maxim. and Saussurea laniceps Hand. -Mazz· are mainly distributed in the Xinjiang Autonomous Region, Sichuan Province, Kunlun Mountain and Tibetan provinces in China. Herbaceous herbs have been used so far in Guanlang rheumatism, sunburn, menstrual irregularities, uterine outflows, chills and pain in women's lower abdomen, colorless vaginal discharge, kidney deficiency and snow blindness (sn〇w blindness) External for traumatic bleeding. In addition, Xinjiang Snow Lotus (Saussurea involucrate (Kar.et Kir.)

Sch.Blp.), Saussurea medusa Maxim. and Saussurea laniceps Hand.-Mazz. are sometimes referred to as [Xinjiang Snow Lotus], [Jellyfish Snow Lotus] and [Miantou Snow]. lotus]. [0044] Among the above-mentioned plants belonging to the genus Saussurea, Saussurea involucrate (Kar. et Kir)

Sch.Blp·) can be obtained in the Xinjiang Autonomous Region of China, etc. Saussurea gnaphaloides (Royle) Sch.-Bip. can be obtained in Sichuan Province, Tibet Autonomous Region, etc. in China, Saussurea Stella Maxim.) can be obtained in China's Qinghai Province, Gansu Province 'Sichuan Province' Tibet Autonomous Region, etc. Saussurea medusa Maxim. can be found in China's Sichuan Province, Yunnan Province, Qinghai Province, Tibet Autonomous Region 'Hong Kong, Nepal Obtained in other places, Saussurea laniceps Hand.-Mazz. can be obtained in China's Sichuan Province, Tibet Autonomous Region, etc., Saussurea tridactyla Sch'-Bip.ex H〇〇kf is available in China. The Tibet Autonomous Region and other places have obtained 'Jellyfish Snow Lotus (Saussurea 100124696 Form No. A0101 Page 12 / 51 pages 1002041805-0 201201865 Ο ο naraikawae Kitam.) can be obtained in China's Tibet Autonomous Region, etc., 4 rabbits (Saussurea g〇SSyPiph〇ra D.Don.) is available in Nepal and other places. Saussurea nishiokae Kitam. is available in Nepal and other places. Saussurea leucoma Diels is available in Yunnan Province, China. Acquired, Saussurea quefcif〇lia wWSmith can be obtained in China's Sichuan Province, Yunnan Province, etc., Saussurea eri〇cephala ch. can be obtained in Yunnan Province, China, etc., saussurea king" J. R. Drumm. ex CEC Fisch. Available in the Tibet Autonomous Region of China and other places, 'Saussurea simpsoniana (Field.et Gardn.) Lipsch.) is available in Nepal and other places, Saussurea obvallata (DC.) Edgew.) can be obtained in Yunnan, Sichuan, Tibet and other places in China. Saussurea wettsteiniana Hand·-Mazz. can be obtained in Yunnan Province, China, etc. Saussilrea Globosa Chen) can be obtained in Sichuan Province and other places in China, and Saussurea longifolia Franch. can be obtained in Yunnan Province and other places in China. [0045] The plants belonging to the genus Saussurea, which are used as extraction raw materials, are dried and pulverized immediately after collection. Drying can also be carried out under sunlight, and it can also be carried out using a dryer which is usually used. [0046] It is preferred to use a polar solvent as the extractant in the extraction treatment. The component having a glutathione-promoting action can be easily extracted from a plant belonging to the genus Saussurea by extraction treatment using a polar solvent. 100124696 Form No. A0101 Page 13 of 51 1002041805-0 201201865 [0049] [0050] Specific examples of the polar solvent may, for example, be water, a water-soluble organic solvent, or the like. It is also possible to use two or more of these water-soluble organic solvents in isolation or in combination. The extracting agent is preferably one of water, a water-soluble organic solvent or an aqueous water-soluble organic solvent among the polar solvents. In addition to pure water, tap water, well water, mineral water, spring water, spring water, fresh water, etc., the water that can be used as an extractant also contains such pure water, tap water, well water, mineral water, mineral water. Hot spring water, spring water, and fresh water are applied to various processors. Various treatments include, for example, heating, bactericidal, extinction, transition, ion exchange, and the like. Therefore, the water which can be used as the extractant in the present invention also contains hot water, ion exchanged water or the like. Furthermore, 'the extractant can also be used for the treatment of osmotic pressure (〇sm〇i: ic pressure), buffering, etc. (physiological saline, phosphate buffer, phosphate buffer physiology) Saline (PBS: Phosphate Buffered Saline), etc. ο A water-soluble organic solvent which can be used as an extractant can be exemplified by a lower aliphatic alcohol, acetone or the like. Specific examples of the lower aliphatic alcohols include exemplified by monohydric alcohols such as methanol, ethanol, propanol and butanol; 1, 3-butylene glycol and propylene glycol; , 1,3-propanediol, pentylene glycol, isoprene glycol, etc. (polyhydric 100124696 Form No. A0101 Page 14 of 51 page 1002041805-0 201201865 [0054] alcohol [0054] alcohol) ° When a mixture of two or more polar solvents is used as an extractant, the mixing ratio thereof can be appropriately adjusted. For example, when an aqueous water-soluble organic solvent is used as the extracting agent, it is preferred to use an aqueous water-soluble organic solvent containing 50% by weight or more of a monohydric alcohol, a polyhydric alcohol, acetone or the like. As the extracting agent, an intermediate polar solvent such as ethyl acetate or butyl acetate may be used. Further, the extractant may be suitably used with 50% (V/V) ethanol and 80% (V/V) ethanol. The extraction treatment is not particularly limited as long as the soluble component contained in the plant belonging to the genus Saussurea can be dissolved, and it can be carried out according to a usual method. No special extraction method is required for the extraction treatment, and any device can be used at room temperature or even under reflux. [0055] 萃取 The extraction method can exemplify a method of immersing the extraction raw material in an extraction sword and extracting it at a normal temperature for a long time, or heating to a temperature below the boiling point of the extractant and extracting while stirring, or in extraction A method of extracting near the boiling point of the agent under heating under reflux. In this case, the extraction dose is usually 5 to 50 times (weight ratio), preferably 5 to 15 times (weight ratio), and the extraction time is usually 1-10 hours, preferably 1 to 4 hours. The extraction temperature is usually 50 to 95 ° C, preferably 80 to 95. (: [0056] Before the extraction treatment, a nonpolar solvent (nonpolar sol vent) such as pentyl, hexazepine, hexazone, cinnabar, petroleum ether or the like is applied before the extraction with the polar solvent is performed. The degreasing treatment can also be 100124696 Form No. A0101 Page 15 / 51 page 1002041805-0 201201865 The extraction treatment with a polar solvent can be efficiently performed by pre-application treatment. [0057] Soluble components are obtained by extraction treatment After the dissolution, the extraction residue can be obtained by a treatment such as filtration or centrifugation to remove the extraction residue. The known extract is obtained by diluting or concentrating the extract. The liquid, the dried product of the extract or a crude purified product or purified product thereof may be subjected to a treatment such as dilution, concentration, drying, purification, etc. according to a usual method. [0058] Due to a plant belonging to the genus Saussurea The extract has a unique odor and taste, so it can also be purified for the purpose of decolorization, deodorization, etc. Purification can be specifically treated by activated carbon (activa Ted carbon treatment), adsorption resin treatment (ads〇rpti〇n resin treatment), ion exchange resin treatment (i〇n ex_ change resin treatment), etc., which do not incur a genus from the genus Saussurea The range of the reduction of the glutathione production promoting action in the extract of the plant is carried out. [Embodiment 2] The glutathione production promoter related to the second embodiment contains [will be derived from A component of a plant of the genus Saussurea is dissolved in a 30% (V/V) methanol solution, and a component adsorbed by a porous polystyrene resin is a component which is adsorbed by a porous polystyrene resin. It is an active ingredient (refer FIG. 1). [The extract from the plant belonging to the genus Saussurea] is obtained by the method as described in the above-mentioned Embodiment 1. 100124696 Form No. A0101 Page 16/ 51 页 〇 〇 〇 〇 〇 〇 01 01 01 01 01 01 01 01 01 多孔 多孔 [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ Registrar Standards ΗΡ20 and ΗΡ21 or SEPA-BEADS (registered trademark of Mitsubishi Chemical Corporation) SP850, SP700 and SP70. Further, the component adsorbed by the porous polystyrene resin in the second embodiment can pass the solvent having a lower polarity through the column after passing the solution dissolved in 30% (V/V) methanol through the tube. Dissolve. The solvent for dissolving the component can be exemplified by an intermediate polar solvent such as a lower aliphatic alcohol, acetone or ethyl acetate; a nonpolar solvent such as hexane. Among these solvents, methanol can be particularly suitably used. In the present specification, it is said that [a solution in which an extract derived from a plant belonging to the genus Saussurea is dissolved in 30% (V/V) methanol is perforated by a column which is supported by a porous polystyrene resin. The component adsorbed by the polystyrene resin is [adsorbed component]. Further, it is said that [the solution from the plant belonging to the genus Saussurea is dissolved in 30% (V/V) methanol through a column of porous polystyrene resin as a carrier, by 30% (V/V) The component in which the sterol is eluted from the column] is [non-adsorbed component]. [Embodiment 3] The facial flavonoid production promoter according to the second embodiment contains [a solution in which an extract derived from a plant belonging to the genus Saussurea is dissolved in 30% (V/V) methanol is passed. When the porous polystyrene resin serves as a carrier column and then 509 KV/V sterol is passed through the column, the component adsorbed by the porous polystyrene resin is an active ingredient (see FIG. 1). 100124696 Form No. A0101 Page 17 of 51 1002041805-0 201201865 [0069] [0073] [0074] [0074] 100124696 [from plants belonging to the genus Saussurea The extract] can be obtained by the method described in the first embodiment. Examples of the porous polystyrene resin to be a carrier include DIAI ON (registered trademark of Mitsubishi Chemical Corporation) HP20 and HP21 or SEPA-BEADS (registered trademark of Mitsubishi Chemical Corporation) SP85〇, SP700 and SP70. Further, the component adsorbed by the porous polystyrene resin in the third embodiment can be dissolved by passing a solvent having a lower polarity through the column after passing 50% (v/v) of methanol through the column. The solvent for dissolving the component can be exemplified by an intermediate aliphatic solvent such as a lower aliphatic alcohol, acetone or ethyl acetate; a nonpolar solvent such as hexane; Among these solvents, decyl alcohol is particularly suitable. [Fourth Embodiment] The glutathione production promoter according to the fourth embodiment contains [a solution in which an extract derived from a plant belonging to the genus Saussurea is dissolved in 30% (V/V) methanol; The porous polystyrene resin is used as a carrier column, and then 50% (V/V) methanol is passed through the column, and then, when the methanol is passed through the column, the component which is dissolved by the column by the sterol is used as an active ingredient. (Refer to Figure 1). [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 to be a carrier include DIAION (registered trademark of Mitsubishi Chemical Corporation) HP20 and HP21 or SEPA-BEADS (registered trademark of Mitsubishi Chemical Corporation) SP850 'Form No. A0101 Page 18 / 51 pages 1002041805-0 201201865 [0075] [0077] [0079] [0079] SP700 and SP70. In the present specification, [a solution in which an extract derived from a plant belonging to the genus Saussurea is dissolved in 30% (V/V) methanol is passed through a column with a porous polystyrene resin as a carrier, and then 5 When 〇% (V/V) methanol passes through the column, and then the sterol is passed through the column, the component which is dissolved by the oxime by the hydrazine is [methanol elution portion]. [Fiveth embodiment] The glutathione production promoter according to the fifth embodiment contains dihydrodehydrocostus lactone represented by the following formula (1) as an active ingredient. [Chemical Formula 1] ❹ [0080]

100124696 Dihydrodehydrocostine lactone is contained in an extract derived from a plant belonging to the genus Saussurea (see Fig. 2 to be described later) as shown in Preparation Example 4 to be described later. The dihydrodehydrocostus lactone used in the glutathione production promoter can also be used as an extract from an extract belonging to the genus Saussurea, and the plant belonging to the genus Saussurea can also be used. A natural product other than dihydrodehydro-lactolactone may be used as a separator, and a commercially available product or a synthetic product may be used. Form No. A0101 Page 19/51 Page 1002041805-0 201201865 [0082] The glutathione production promoter (that is, the (four) glutathione production line (IV) of the present invention) can be expected. It is expected to prevent, treat, or improve skin aging, stains, and freckles caused by oxidative stress, such as ultraviolet irradiation, by a sucrose-like growth promoting effect. However, the noodle depletion production promoter of the present invention can be used for all purposes which are useful for promoting the production of cuquitin in addition to these uses. Moreover, the lysin production of the present invention promotes the promotion of glutathione through the action of glutathione, as a disease associated with the lack of surface vesicles (IV) (eg, cell damage, inflammation, acute or chronic alcohol caused by exposure to ultraviolet light). Preventive agents and therapeutic agents for liver damage, liver disease, Parkinson's disease, Alzheimer's disease, gastric ulcer, immunodeficiency, acquired immunodeficiency syndrome, aging phenomenon associated with physiological age, cancer, etc. Or use the active ingredient of the improver. In addition, since the glutathione production promoter of the present invention can increase the intracellular concentration of cubbly-like cells by its action, it is expected to prevent sleep disorders such as insomnia (sieep dis_order). The active ingredient of the agent, therapeutic agent or improving agent is used. In addition, the glutathione production promoter of the present invention may contain any one of the active ingredients in the above-described embodiment __5, and may contain two or more of the active ingredients in the above-described embodiments. . When two or more of the active ingredients in the above-described first to fifth embodiments are contained, the compounding ratio of the effective ingredients may be appropriately determined depending on the degree of action of the effective components. The vladipeptide gene production promoter of the present invention can be used as a pharmaceutical product having a glucagon production-promoting action containing the vappaine production-promoting agent, food product 100124696 Form No. A0101 Page 20 of 51 page 1002041805-0 [0083] 201201865 or cosmetic use. The [medicine for internal use having a glycopeptide production-promoting effect] of the present invention. The drug L is not particularly limited, for example, enteral administration such as oral administration or intrarectal administration, dry film administration such as nasal administration, intravenous administration, and the like. Injectable preparations such as subcutaneous administration, etc. The dosage form of the internal pharmaceutical of the present invention can be in a form suitable for administration and preparation, for example, a tablet (tabl et) a solid agent such as a powder, a granule, a granule, a capsule, a powder, a pill, a troche, a solution, a suspension, an emulsion, a syrup, an injection, etc.; a gel preparation; . The pure product, the purified product, the crude purified product and the like of the glutathione production promoter of the present invention can be administered as it is, or can be combined with a pharmacologically acceptable excipient. The preparation may be used as a preparation if it is monosaccharide, double domain (dlSaCCharide), polysaccharide (polysaccharide), inorganic salt, oily glutinous rice, distilled water or the like. When the formulation is formulated, an additive such as a reducing agent, a lining agent, a dispersing agent, a suspending agent, an emulsifier, a diluent, a buffer, an antioxidant, a bacterial inhibitor, or the like may be used. [0086] 100124696 The internal medicine of the present invention The content of the glutathione production promoter in the preparation can be set in an amount suitable for each administration form in accordance with the form of the preparation, the effective administration amount, and the amount of the preparation to be administered. The form of the [food having a 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 of the compounds, and a glutathione containing the same. Crude extract of the compound of the plant producing the promoter, Form No. containing the glutathione production promoter Α0101 Page 21 of 51 1002041805-0 201201865 Paste, with the glutathione production promoter Food, etc. That is, the form of [food having glutathione-promoting action] is health drink = fruit / east, biscuit, tea, lozenge, pill, soft capsule, hard capsule powder, fine granule, granule, etc. Usually available as a form of food, it can be used in any form. As the auxiliary raw material, an additive such as an excipient, a binder, a lubricant, a dispersing agent, an m-floating agent, an emulsifier, a diluent, a buffer, an antioxidant, a bacterial inhibitor or the like can also be used. [0088] The example of the form of the [medicinal preparation or cosmetic preparation having a vagiginin-promoting action] of the present invention is not particularly limited. Examples of the form of the external pharmaceuticals include ointments, ointments, cataplasms, tapes, and external preparations. The external pharmaceutical of the present invention may contain other pharmaceutical ingredients in the glutathione production promoter of the present invention as needed, and may also use a binder, a dispersing agent, a suspending agent, an emulsifier, a diluent, a buffer, and an anti-drug. An additive such as an oxidizing agent or a bacterial inhibitor. The form of the cosmetic may be any form which can be used as an external preparation or a cosmetic preparation, such as a lotion, a cosmetic liquid, an emulsion, a cream, a gel, a pack, a cosmetic powder, and a facial cleanser. In addition to the glutathione production promoter of the present invention, the above cosmetic preparation may contain a component to be blended in a cosmetic preparation as needed. Examples of the compounding component include solid oil 'semi-solid oil, liquid oil, low molecular weight humectant, molecular humectant, fat-soluble humectant, lubricant (em〇llient), surface active agent, and preservative. , antioxidants, pH adjusters, ethanol, water, etc. 100124696 Form No. A0101 Page 22 of 51 1002041805-0 201201865 [0090] [0091] [0095] [0095] 100124696 The pharmaceutical, food and cosmetic of the present invention can be expected to pass through this The glutathione production-promoting action of the glutathione production-promoting agent of the invention suppresses the decrease of the oxidative stress reaction due to aging, and can be expected to prevent, (7) treat or improve the preparation and the external ray irradiation. Force related skin aging or stains, freckles. However, the pharmaceuticals, foods, and cosmetics of the present invention can be used for all purposes that are meaningful for the promotion of caspase production in addition to these uses. Further, the pharmaceutical, food, and cosmetic of the present invention can be expected to promote the action of the glutathione-promoting action of the glutathione-promoting agent, and prevent, treat or ameliorate diseases associated with lack of glutathione (for example, exposure). Cell damage, inflammation, acute or chronic alcoholic liver damage, liver disease, Parkinson's disease, Alzheimer's disease, gastric ulcer, immune insufficiency, acquired immunodeficiency syndrome, physiologic ageing In addition, since the intracellular concentration of the glucagon can be increased, it is expected that prevention, treatment, or improvement of sleep disorders such as insomnia, and the glutathione production promoter of the present invention. Although pharmaceuticals, foods, and cosmetics are suitable for humans, they can be applied to animals other than humans as long as their respective effects are achieved. Hereinafter, the present invention will be described in more detail by way of [1, a preparation example of a sample] and [2, a test example of promoting the action of glutathione production], but the present invention is not limited by these examples. 1. Preparation Example of Sample (Modulation Example 1) Preparation Example of Sample a No. A0101 Page 23/51 Page 1002041805-0 201201865 [Modulation Example 1 is for the preparation of Saussurea involucrate (Kar.) Et Kir. ) Sch. Blp.) A preparation example of an extract (sample a (water extract)) using purified water was obtained. [0097] In the Xinjiang Xuelian (Saussurea involucrate (Kar. et Kir.) belonging to the genus Saussurea

Sch. Blp·) Ground pulverized material 30. 3g After heating extraction (80 ° C ~ 90 ° C, 2 hours) with 45 〇 mL (ml) of purified water, the solution obtained by hydrazine (using qualitative The extract was obtained by using two types of filter paper (purchased by ADVANTEC Toyo Co., Ltd.). The obtained extract was concentrated under reduced pressure and cooled, and dried in the east (17 〇1^1丨231; 丨011) to obtain 8.3 g of sample a (water extract). 3%。 Solid yield (solid yield) was 27.3%. (Preparation Example 2) Preparation Example of Sample b [0099] Modulation Example 2 is for obtaining 50% (V/V) ethanol from Saussurea involucrate (Kar. et Kir.) Sch. Blp. Preparation example of the extract (sample b (50% ethanol extract)). [0100] Saussurea involucrate (Kar.et Kir.) in the plant belonging to the genus Saussurea

Sch.Blp.) Ground material pulverized material 3〇. 5g was heated and extracted (80°C to 90t, 2 hours) with 50% (V/V) ethanol of 仏^^匕, and the obtained solution was filtered ( The extract was obtained by qualitative analysis using two types of filter paper (purchased by ADVANTEC Toyo Co., Ltd.). The obtained extract was sequentially subjected to concentration under reduced pressure and cold-dried to obtain a sample of 7 · 4 g. 100124696 Form No. A0101 Page 24 of 51 1002041805-0 201201865 o b (50% ethanol extract). The solid yield was 24.2% [Modulation Example 3] Preparation Example of Sample c [0102] Modulation Example 3 was obtained by Saussurea involucrate (Kar. et Kir.) Sch. Blp. A preparation example using an extract of 80% (V/V) ethyl yeast (sample c (80% ethanol extract)). [0103] Saussurea involucrate (Kar.et Kir.) in the plant belonging to the genus Saussurea

Sch. Blp.) Ground material pulverized material 30. After heating extraction with 450 mL of O 80% (V/V) ethanol (80 ° C to 90 ° C for 2 hours), the obtained solution was filtered (using qualitative The extract was obtained by using two types of filter paper (purchased by ADVANTEC Toyo Co., Ltd.). The obtained extract was concentrated under reduced pressure and lyophilized to give 5. 4 g of sample c (80% ethanol extract). 5%。 The solid yield was 17.5%. (Preparation Example 4) Preparation Examples of Samples d to f and Comparative Samples [0105] FIG. 2 is a flow chart for explaining the preparation examples of the samples d to f and the comparative sample. [Modulation Example 4] is to obtain a comparative sample (non-adsorbed component), sample d (adsorbed component), and sample e (saussurea inv〇iucrate (Kar. et Kir.) Sch. Blp.) A preparation example of a sterol-dissolved portion) and a sample f (dihydrodehydro-lactolactone). This modulation example is carried out in accordance with the flow shown in Fig. 2 [0107] in Saussurea involucrate (Kar. et

Kir· ) Sch. Blp.) Ground part of the pulverized material 4kg was used twice. 100124696 Form No. A0101 Page 25/51 Page 1002041805-0 201201865 45L 80% (V/V) ethanol digestion extraction After (80 ° C, 2 hours), the obtained solution was filtered (using two kinds of filter papers for qualitative analysis (purchased from ADVANTEC Toyo Co., Ltd.)) to obtain an extract. The extract was concentrated under reduced pressure at 60 T: and dried (normal temperature, 1 hr) to obtain 680 g of an extract. Next, the extract was dissolved in 30% (V/V) of the fermentation (3 L, 40 ° C) as a solution, and the solution was passed through to pre-balance with 30% (V/V) sterol (equi 1 ibrate). The post-filled column of DIAI0N HP20 (1 500 g, purchased by Mitsubishi Chemical Corporation) was used as a carrier. Then, it was eluted by 6 L of 30% (V/V) methanol, and the 30% (V/V) methanol-dissolved portion was recovered as a non-adsorbed component (comparative sample). Subsequently, 7 L of 50% (V/V) decyl alcohol, 6 L of methanol, 5 L of ethanol, 5 L of ethyl acetate, and 5 L of hexane were successively eluted, and the eluted portions were each recovered. The solvent was removed, and each of the eluted fractions was used as a dry solid to obtain 399 g of a non-adsorbed component (comparative sample), 38 g of a 50% (v/v) methanol-soluble fraction, and 1 g of a methanol-soluble fraction (sample e). , a portion of the ethanol-dissolved portion of 21 g, an eluted portion of ethyl acetate of I8 g, and a partially dissolved portion of 0.11 g. When the respective eluted portions other than the non-adsorbed component were combined, the weight of each of the eluted fractions (i.e., the adsorbed component) other than the non-adsorbed component was 177.11 g as the adsorbed component (sample d). Wherein 'the sterol-dissolved fraction (sample e) (100 g) was added to silica gel column chromatography (80 mmφχ) using chloroform/methanol/water as the dissolution solvent. 350mm, purchased by Fuji SILYSIA Chemical Co., Ltd.). That is, while changing the ratio of the dissolved solvent to 90:10:0, 40:100124696 Form No. A0101 Page 26/51 Page 1002041805-0 201201865 [0109] θ [ΟΠΟ] ο [0111] iU: 1. 30: l〇: 1 (all chloroform: methanol: water) while dissolving the 'fraction' of each fraction of the eluent (eluent) 15 〇 mL, add these parts together to get A ~ Η 8 parts. The portion A of 40.9 g is obtained by removing the solvent from the solution containing a portion A (dissolved amount: 450 mL to 1 200 mL) as a dry solid. Then, Part A (40. 9 g) was added to a Shih Hose column chromatography (60 mmpx 250 mm, purchased from Fuji SILYSIA Chemical Co., Ltd.) using hexane/acetone as a solvent. In other words, the ratio of the solvent to be dissolved is changed to 9:1, 6:1, 4:1, and 2:1 (both hexane:acetone), and the solution is separated, and 60 mL of each of the fractions is separated. The parts are added together to get 8 parts of AA~AH. Wherein 'the solvent is removed from the solution containing part of AB as a dry solid to obtain a portion of 13. lg of AB (dissolved amount: 18 〇mL to 600 mL) » Further adding part of AB (13. lg) to methanol/water 0DS Dream Glue Column Chromatography (6 〇 nnnpxl 50 min, purchased from NACALAI TESQUE Co., Ltd.) as a solvent. In other words, while the ratio of the solvent to the solvent is sequentially changed to 7:3, 8:2, and 9:1 (all of which are decyl alcohol: water), the solution is separated, and 40 mL of each of the fractions is separated, and the portions are added together. Ten parts of AB-1 to AB-10 were obtained. Wherein the portion of the AB-3 is obtained by removing the solvent from the solution containing a portion of the AB-3 (dissolved amount: 1 200 mL to 14040 mL) as a dry solid. Further, a part of AB-3 (2. lg) was added to a ruthenium column chromatography (GOinmpxl 50 mm, purchased from Fuji SILYSIA Chemical Co., Ltd.) which was a solvent for the dissolution of hexane/acetic acid. That is, while the ratio of the solvent to be dissolved is sequentially changed to 19:1, 9:1 (all are burned: ethyl acetate 100124696, Form No. A0101, page 27/51 pages, 1002041805-0, 201201865), while dissolving, each part 4 mL of the dissolving liquid of each branch was obtained, and an eluate containing dihydrodehydro-hydrofuranyl lactone (dissolved amount: 1240 mL to 1 520 mL) was obtained. The solvent was removed from the solution as a dry solid to obtain 161 mg of dinitrogen dehydrated woody vinegar (sample f). [0112] 1 H-NMR spectral data was obtained by nuclear magnetic resonance spectroscopy for dihydrodehydrocostus lactone (sample f) which was fractionated and isolated by the above method. The 13C-NMR spectrum data showed that the following peaks were observed, which were substantially consistent with the values of the literature (Journal of Natural Products, Vol. 62, 27, 1999). Further, the molecular formula of dihydrodehydrogeninol (sample f) is.

1 ο ί υ L

h-NMR (CDC1, 40 ΜΗζ) δ : 1. 23 ( 3 Η > d > J = 7.0 Hz, Me-12), 1.30 (lH, m, H-8), 1.85 (1H, m, H-2), 1.94 (2H, m, H-2, H-7), 2.04 (lH, m, H-9), 2.10 (lH, m, H-3), 2.21 (lH, m, H-11), 2.50 (3H'm, H-3, H-8, H-9), 2.79 (lH, dd, J: 8.9, 8.9 Hz, H-5), 2.87 (lH, m, Hl) , 3. 91 (1H, dd, J = 9. 3, 9. 3Hz, H-6), 4. 77 (1H, br s'H-15a), 4.87 (lH, br s, H-15b), 5.04 ( 1H,d,J = 2. 0Hz, H-14a) 5. 19 ( 1H,d,J = 2. 0Hz , H-14b). 13C-NMR (CDC13, 100MHz) δ 13. 22 (C-12) ^ 30.17CC-2), 32.48 (C-3, 8), 37.65 (C-9), 42.04 (C-ll) ' 47.04 (Cl) ' 49.85 (C-7) > 51.93CC-5), 85.28 (C-6), 109.15 (C-14), 100124696 Form No. A0101 Page 28 of 51 1002041805-0 201201865 111.81 ( C-15), 149.94 (C-10) '151.70 (C-4), Π8·70 (C-13). Further, mass spectrometry was performed on the dihydrodehydrogenated viniferine (sample f) divided and separated by the above method, and the following results were obtained, and the measured mass was estimated from the molecular formula. The quality is roughly the same. HR-ESI-TOF-MS m/z: 233.1550 [M+H] + (Calcd for [0117] O r η [0118] C15H2 〇〇 2: 233· 1542). Further, in the above, a general experimental apparatus and an experimental apparatus were used by column chromatography of DIAION HP20, cartridge column chromatography, and 0DS cartridge column chromatography. Further, the nuclear magnetic resonance spectroscopy apparatus was a Bruker DRX-400 type nuclear magnetic resonance spectroscopy apparatus (manufactured by Bruker BioSpin Co., Ltd.). A mass spectrometer was a Waters-Micromass LCT mass spectrometer (manufactured by Waters Corporation). 2. Test Example of Glutathione Production Promoting Effect [0120] A test case in which the glutathione production promoting action is performed by measuring human skin fibroblast and normal human epidermal keratinization Test results of glutathione-producing activity of normal humanepidermal keratinocyte (β1) (Test Example 1) on the promotion of facial degammapeptide production by human skin fibroblasts [0122] (Α), test method [0123] Use of minimum essential medium containing 10% (v/v) fetal bovine serum 100124696 Form No. A0101 Page 29/51 Page 1002041805-0 201201865 (FBS 'purchased by NICHIREI, Inc.) Minimum essential medium)a (ΜΕΜα, purchased from GIBC0) was used as a medium to disseminate human skin fibroblasts (NB1RGB, purchased by RIKEN BioResource Center) on 24 well plates (well?13 6) (purchased by 1'11]!^), 俾1.〇\1〇5〇6115/ rating 611, with C〇2 incubator (37°C, 5% carbon dioxide, 95% air) Cultivate. After 24 hours, the medium was changed to a medium in which the sample was adjusted to contain a predetermined concentration (200; ag/mL or 20/zg/mL), and the culture was further carried out for 24 hours. [0124] The sample was sample A (water extract, see Preparation Example 1, concentration 200 #g/mL), sample b (50% ethanol extract, refer to the above preparation example 2, concentration 200 #g/ mL), sample c (80% ethanol extract, refer to the above preparation example 3, concentration 200 #g/mL), sample d (adsorption component, refer to the above preparation example 4, concentration 20 " g/mL), test Example e (melanol-dissolved portion, reference to the above-mentioned preparation example 4, concentration 20//g/mL) and sample f (dihydrodehydrocostus lactone, refer to the above-mentioned preparation example 4, concentration 20/zg/mL), Test it separately. Further, for comparison, a test was also conducted for a comparative sample (non-adsorbed component, reference to the above-mentioned preparation example 4, concentration: 200 /zg/mL). [013⁄4] Next, cells were recovered from each well by trypsinization by a usual method. Then, the cells were washed with Dulbecco's Phosphate Buffered Saline, and then added with 10 mM hydrochloric acid 80 to carry out the use of bundles to resolve; East (freezing and thawing) (100124696 Form No. A0101, page 30 / A total of 51 pages 1002041805-0 201201865 Ο 2 times) cell membrane disruption treatment. 5% (w/v) sulfosaiicylic acid 2 (^LM into the treatment solution after cell membrane disruption, centrifugation (8000G, 10 minutes), the resulting supernatant (supernatant liquid Provided to the assay. The glutathione in the supernatant was determined by the enZyme reCyCiing method using the T〇tal Glutathione Quan- tification Kit (purchased by Dojindo). The amount of peptide was calculated, and the total amount of glutathione was calculated. While measuring the total amount of glutathione, the number of viable cells was determined by using a hemocytometer (c〇unt) trypan blue non-stained cells (viable cen) Count) and the amount of facial glycoform of each living cell, by comparing the amount of glutasome per live cell in the case of using the medium without the sample added The index when the amount of glutathione per living cell was 100% when no sample was added) [0126] (B), test results [0127] The test results are shown in Table 1 and Figure 3. Table 1 shows Test Example 1 (Promoting the production of gSH in human 0 skin fibroblasts) Table 3. Fig. 3 is a graph showing the results of Test Example 1 (promoting effect on glutathione production by human dermal fibroblasts) [0128] [Table 1] [0129]相 晌 的 的 鞑 鞑 鞑 [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ 0 100124696 Form No. A0101 Page 31 / Total 51 Page 201201865 [0132] [0133] [0138] [0138] [0140] [0141] [0143] [0143] 0144] 100124696 Sample b (50% ethanol extract) 20 〇 Aig/mL 265.1% Sample c (80% ethanol extract) 200 /zg/mL 209.3% Sample d (adsorbed component) 20#g/mL 296 4% sample e (methanol elution part) 20"g/mL 362. 9% sample f (dihydrodehydrocostus lactone) 2〇eg/mL 163.8% Comparative sample (non-adsorbed component) 200 yg /mL 111. 8% No added sample (hanging) _=_Τ 〇ί) η % One (a), for samples a~c As shown in Table 1 and Figure 3, it can be confirmed from Xinjiang Snow Lotus (Saussurea Involucrata (Kar.et Kir.) Sch.Blp.) Any extract (samples a to c) on human skin fiber matrix The cells showed glutathione production promoting effects. Further, it was confirmed that in the samples a to c, the sample b (50% ethanol extract) and the sample c (80% ethanol extract) showed a high glutathione production promoting action. (b) For the sample d, as shown in Table 1 and Figure 3, it was confirmed that the sample d (adsorbed component) showed a significantly higher concentration than the high concentration (2〇vg/mL) (2〇〇eg) /mL) Comparative sample (non-adsorbed component), glutathione production promoting action c (C), and sample e, as shown in Table 1 and Fig. 3, it was confirmed that sample e (methanol eluted portion) was displayed. The glutathione production promoting effect is higher than that of the sample d (adsorbed component). Form No. _ 丨 32 pages / total 51 buy 1002041805-0 201201865 [0145] [0147] [0149] [0149] ❹ ❹ [0150] [0151] 100124696 (d), for the sample f as shown in Table 1 As shown in Fig. 3, it was confirmed that the sample f (dihydrodehydrocostus lactone) exhibited a high glutathione-promoting action even at a low concentration (2Qeg/mL). (Test Example 2) Test Example (A) for promoting cysteine-like growth of normal human epidermal keratinocytes 'The test method used EpiLife.KG2 (purchased from Kurashiki Textile Co., Ltd.) as a medium to normal human epidermis Keratinocytes (NHEK.F, purchased from Kurashiki Textile Co., Ltd.) were dispersed in 24 well plates (purchased from No. C), 俾 into 2. 5xl 〇 5ceUs/well, with C02 incubator (37〇c, 5%) Carbon dioxide, 95% air) was cultured. After 72 hours, the medium was changed to a medium in which the sample was adjusted to contain a predetermined concentration (1 〇 (4) mL or 5 #g/mL), and the culture was further carried out for 24 hours. Sample 疋 used sample a (water extract, refer to the above preparation example 1, concentration 200 / zg / mL), sample b (50% ethanol extract, refer to the above preparation example 2, concentration 20 〇 eg / mL), Sample c (8 〇 % ethanol extract, refer to the above Preparation Example 3 'concentration 2 〇〇 private g / mL), sample e (sterol elution portion 'refer to the above preparation example 4, concentration lOeg / mL) and sample f (dihydrodehydrocostus lactone, with reference to Preparation Example 4 above, concentration 5#g/mL), was tested separately. Secondly, cells were recovered from each well (weU) by trypsin treatment by a usual method. Then, the cells were washed with Dubecoside phosphate buffer, and the cell membrane was frozen and thawed (2 times) after adding 80 μL of 10 mM hydrochloric acid, Form No. A0101, page 33/51 pages, 1002041805-0 201201865. Broken processing. 5% (w/v) sulfosalicylic acid 2 〇/zL was added to the treatment solution after cell membrane disruption treatment, and centrifuged (8 〇〇〇g, 10 minutes) to obtain a supernatant. The amount of glutathione in the supernatant was measured by an enzyme recovery method using a total Glutathione Quantification Kit (purchased from Do j i ndo) to calculate the total amount of glutathione. While measuring the amount of total glutathione, the number of viable cells in the trypan blue non-staining was counted using a hemocytometer and the amount of pure cysts per viable cell was calculated, and each of the cases in which the medium was not added with the sample was used. The amount of the glutathione of the live blister was calculated from the amount of the glutathione (the index when the amount of glutathione of the mother-lived cells of the sputum was 100%). [0154] (B) Test Results The test results are shown in Table 2 and Figure 4.矣9β Ζ疋 shows a table showing the results of Test Example 2 (promoting the facial gonadotropin of normal human epidermal keratinocytes). Fig. 4 is a graph showing the results of Test Example 2 (promoting effect on cuczeptide production in non-human human epidermal keratinocytes). [Table 2] [0155] Just as a person’s thong

[0158] [Abstract] 描 ipj· 胁 廿 廿 廿 skin sample a (water extract) 2 〇〇 sample b (50% ethanol extract) 2 〇〇 ^ g / mL 167. 0% ^ g/mL 491.8% 100124696 Form No. A0101 Page 34 / Total μ Page 1002041805-0 201201865 [0160] [0164] [0164] [0166] [0166] [0167] [0170] 100124696 Sample c (80% ethanol extract) 2〇〇#g/mL 409.9% Sample e (methanol elution fraction) 10//g/mL 298. 1% Sample f (dihydrodehydrocostitolide) 5eg/mL 259.5% No added 諕楛 ( oblique, _ 100.0% _ (a), for samples a~c as shown in Table 2 and Figure 4, It was confirmed that any extract (Sample a~c) from Saussurea involucrata (Kar. et Kir.) Sch. Blp. showed glutathione-promoting effect on normal human epidermal keratinocytes. It was also confirmed that in the samples a to c, the sample b (50% ethanol extract) and the sample c (80% ethanol extract) showed high glutathione production promoting effect. (b) e As shown in Table 2 and Figure 4, it can be confirmed that the sample e (melanol-dissolved portion) is degraded even if it is low (l Wg/mL) also showed a high surface degammam production promoting effect. (c) For the sample f, as shown in Table 2 and Figure 4, it was confirmed that the sample f (dihydrodehydrocostus lactone) even The low concentration (5eg/mL) also showed a high effect of promoting the production of the glutathione. [Examples] The use of the squirrel according to the above-mentioned preparation example 1) preparation example of sample a]

Form No. _ 帛35 _ 51 H The stated amount 1002041805-0 201201865 The water extract prepared by the method is 500 mg). A lozenge was prepared by the following formulation (each [0172] water extract (Preparation Example 1) 1 Omg [0173] Lactose 470 mg [0174] Dry corn starch 1 Omg [0175] Talc (ta 1 c) 9 mg [0176 Calcium stearate 1 mg [0177] (Preparation method) [0178] Water extract (2 g), dried corn starch (2 g), talc (1.8 g), calcium stearate (0.2 g) were added to lactose ( 94g) and mixing. Next, using a single stroke tablet press and making a key by a common method. [0179] f 丨2, 砀膜壹鲁丨's congratulatory work [0180] Using a 50% ethanol extract prepared according to the method described in [Modulation Example 2 Preparation Example b], a hard capsule (360 mg per capsule) was prepared by the following formulation: 5 mg 220 mg 1 Omg 50% ethanol extract (Preparation Example 2) [0182] Lactose [0183] Corn starch [0184] Propylcellulose (hydroxypropy 1 ce 1 1 u 1 ose ) 2 5 mg [0185] (Modulation method) 1002041805 -0 100124696 Form No. A0101 Page 36 of 51 201201865 [0186] Add lactose (22〇g) and cornstarch (llOg) to 5〇% (5 g) and mixing, a solution of light propyl cellulose (25 g) was added thereto and kneading was carried out. Then, water-soluble ethanol extraction was carried out by a conventional method using a masking granulator. The gelatin hard capsule was filled in a gelatin hard capsule to prepare a hard capsule. [Example 3] The preparation of the bismuth agent [0188] The method described in [Modulation Example of Sample c of Preparation Example 3] was used. Prepared 80% ethanol extract 'Prepared as a soft sac 0 dose (170 mg per capsule) by the following formula. [0189] 80% ethanol extract (Preparation Example 3) 5 mg [0190] Large and oil 16 5nig [Sun (Modulation method) 80% ethanol extract (5 g) was added to soybean oil (丨65 g) and mixed. Then, the soft capsule was filled in accordance with a usual method by using a rotary die automatic molding machine. The soft capsule was produced. [0193] The method of the above-mentioned [(Preparation Example 4) Samples d to f and the preparation example of the comparative sample] was used. The prepared ingredients and the ingredients were prepared by the following prescription (100 mg each). Adsorption component (Preparation Example 4) 〇5fflg Taiwanese jute (C〇rch〇rus〇Ut〇rius) powder 2〇.〇mg 100124696 Form No. A0101 Page 37/51 Page 1002041805-0 201201865 [0197] The starch is 3.Omg [0198] molasses 20.Omg [0199] tea extract 15.0 mg [0200] soybean fiber 14.0 mg [0201] insect knee (she 11 ac) 0. 5mg [0202] (modulation method) [ 0203] The raw materials were mixed by the above mixing, and a suitable amount of water was added to prepare a kneaded product, and the obtained kneaded product was rolled, pelletized by a pelletizer, and dried to prepare a pellet. [Example 5] The preparation of the fruit extract [0205] The water extract prepared by the method described in the above [(Preparation Example 1) Preparation of Sample a] was used, and the following prescription was used. The common method is to make jelly (l〇〇g).

Water extract (Preparation Example 1) 〇· 〇 2g [0207] Gelatin 2. 00g [0208] Orange juice 20. 00g [0209] Water 77.98g [Modulation method] [0211] Mixing the above ingredients, Heat to 90 ° C to the vessel for cooling. Jelly is made by curing gelatin. [0212] Example 6: Production of Aloe Vera 100124696 Form No. A0101 Page 38 of 51 1002041805-0 201201865 [0213] Using [(Modulation Example 4) sample d~f and comparative sample according to the above] The dihydrodehydrocostus lactone prepared by the method described in the preparation of the method described above was prepared by a usual method using an ointment (l〇〇g). (Oil phase composition) [03⁄45] Dihydrodehydrocostine lactone (Preparation Example 4) O.Olg 20.〇〇g [0216] White Vaseline

[0217] mineral oil [0218] stearyl alcohol 20. 〇〇g 5. 〇〇g [0219] stearyl-2 (steareth-2) 3. 〇〇g [ 0220] propy lparaben 0.1〇g [0221] natural vitamin E 0.1 [0222] (aqueous phase component) [0223] 1,3-butanediol (1,3-butylene) Glycol ) 5. 〇〇g [0224] phenoxyethanol 0. 4〇g [0225] Polysorbate 60 (P〇lys〇rbate 60) 4. 5〇g [0226] Purified water amount 100124696 Form No. A0101 Page 39/51 Page 1002041805-0 201201865 [0227] Weight of the whole 1QQg [Modulation method] [0229] The oil phase component and the water phase component are respectively heated to 8 (TC and made uniform, borrowed The aqueous phase is added to the oil phase while stirring, and the emulsion is emulsified and cooled to prepare an ointment [0230]. 柞 、 、 、 、 023 023 023 023 023 023 023 023 023 023 023 023 023 023 023 023 023 023 023 023 023 023 023 023 023 023 023 023 023 023 The methanol-dissolved portion prepared by the method described in the preparation example of the comparative sample was prepared by a usual method by the following method. [0232] (Adhesive solvent) [0233] Styrene- different Alkene-styrene block copolymer 7. 〇〇g [0234] (styrene-isopropylene-^ + Ar»- L,, J styrene block copoly mer ) [0235] Piccolyte [0237] isopropene rubber [0237] (toluene) [0238] Ethyl acetate [0239] Hexane [0240] (Pharmaceutical ingredient) [0241] The sterol-dissolved portion (Preparation Example 4) [0242] Ethanol 25.00 g 5. 00 g 15.00 g 14.20 g 25. OOg 0. Olg 100124696 Form No. A0101 7. 99g Page 40/Total 5i Page 1002041805-0 201201865 [0243] (Transdermal absorption enhancer) 0. 80g l〇〇g [0244] Oleic alcohol (oleyl aicoh〇1: [0245] The weight of the whole [0246] (modulation method) |: 〇 247] (4) The solvent and the medicinal ingredients are added to the adhesive agent, and the medicinal ingredient and the percutaneous absorption enhancer are added to the adhesive solvent in the room. The composition was prepared by stirring under temperature. The composition was stretched on a polyester film (p〇iyester film) which was subjected to a cerium treatment (siHc〇ne treat_ ment), and after 12 rc was dried and cooled, the adhesive layer was transferred to a polyethylene film. (p〇lyethylene film) The tape preparation is used. [0248] The application example of the sample (a preparation example) is used in accordance with the above [(Modulation Example 1)] The water extract prepared by the method described above was prepared into a lotion (l〇〇g) by a usual method by the following prescription. _ [0250] (oil phase component) ❹ [0251] Polyoxyethylene (60 mol) hydrogenated castor oil [0252] (hydrogenated castor oil) 2. 〇g [0253] 1,3 - butanediol 5 0g [0254] (Aqueous phase component) [0255] Water extract (Preparation Example 1) 〇. lg [0256] Glycerol 5. 〇g Form No. A0101 Page 41 of 51 100124696 1002041805-0 201201865 [0257] Phenoxyethanol 0. 3g [0258] citric acid 0. lg [0259] sodium citrate 0. 2g [0260] ethanol 8. 0g [0261] purified water amount [0262] Weight 100 g [Modulation method] [0264] The oil phase component and the water phase component were uniformly dissolved, and the oil phase was added to the water phase while stirring to prepare a lotion. Example 9: Preparation of sputum [0266] 50°/modulated by the method described in [(Preparation Example 2) Preparation Example of Sample b] described above was used. The ethanol extract was prepared in the usual manner by the following formulation (l〇〇g). [0267] Oyster oil 8. 00g [0268] Ethanol 5. 00g [0269] behenyl alcohol 0.50g [0270] citric acid 0. l〇g [0271] sodium citrate 0 · 20g [0272 50% ethanol extract (Preparation Example 2) 1. 50g 100124696 Form No. A0101 Page 42 of 51 1002041805-0 201201865 [0273] 1,3-butanediol 4. OOg [0274] p-Hydroxybenzoic acid Ester 0. 10g [0275] (ester para-hydroxybenzonate) [0276] Edediate disodium O.Olg [0277] Purified water amount [0278] The weight of the whole l〇〇g [0279] ( Modulation method) Ο [0280] The above raw materials are stirred and mixed to prepare an emulsion. [Examples of the application of the method described in the above-mentioned [Modulation Example 3 Preparation Example c]] 80% ethanol extract was used. The following prescriptions are used to make a cosmetic solution (l〇〇g) in a usual manner. 80 g ethanol extract (Preparation Example 3) 1. 50 g 〇_] carboxyvinyl polymer 0.50 g [0285] glycerol 6. 50 g [0286] 1,3-butanediol 7. 50 g Phenoxyethanol 0.30 g [0288] Potassium hydroxide 0.20 g [0289] Hyaluronate sodium 0. 25g [0290] Shark entertainment>(s qua lane) 0. 50g 100124696 Form No. A0101 Page 43 / Total 51 pages 1002041805-0 201201865 [0291] Vitamin E acetic acid S (vitamin E acetate) 0. 05g [0292] Stearic acid 0. 20g [0293] Purified water amount [0294] The total weight l〇〇g [ 0295] (Preparation method) [0296] The raw materials were stirred, mixed, and dissolved to prepare a cosmetic liquid. BRIEF DESCRIPTION OF THE DRAWINGS [0297] FIG. 1 is a flow chart for explaining Embodiments 1 to 5. 2 is a flow chart for explaining the preparation examples of the samples d to f and the comparative sample. 3 is a graph showing the results of Test Example 1 (promoting effect on glutathione production of human skin fibroblasts). 4 is a graph showing the results of Test Example 2 (promoting effect on glutathione production of normal human epidermal keratinocytes). [Description of main component symbols] 100124696 Form No. A0101 Page 44 of 51 1002041805-0

Claims (1)

201201865 VII. Patent application scope: 1 2 Ο 3 • A vagirin production promoter containing an extract derived from a plant belonging to the genus Saussurea as an active ingredient. The glutathione production promoter according to claim 1 of the patent scope, wherein the plant belonging to the genus Saussurea is Saussurea involucrate (Kar. et Kir.) Sch. Blp., jellyfish snow lotus More than one plant selected from the group consisting of (Saussurea medusa Maxim.) and Saussurea laniceps Hand.-Mazz. A glutathione production promoter comprising an active ingredient: a solution in which an extract derived from a plant belonging to the genus Saussurea is dissolved in 30% (v/v) sterol is passed through When the polystyrene resin is a column of a carrier, the component adsorbed by the porous polystyrene resin. 4. The glutathione production promoter according to item 3 of the patent application, wherein the genus 65 6 100124696 is a plant of the genus Saussurea is manufactured by Saussurea involucrate (Kar. et Kir.) Sch. Blp.), more than one plant selected from the group consisting of Saussurea medusa Maxim. and Saussurea laniceps Hand.-Mazz. A glutathione production-promoting agent containing an active ingredient: a solution in which an extract derived from a plant belonging to the genus Saussurea is dissolved in 30% (v/v) sterol is passed through A polyphenylene styrene resin is a carrier column which is then adsorbed by the porous polystyrene resin when 50% (V/V) sterol is passed through the column. Such as the glutathione production promoter of claim 5, wherein the genus form number A0101 page 45 / 51 page 10021 201201865 The plant of the genus Saussurea is made of Xinjiang snow lotus (Saussurea involucrate (Kar .et Kir.) Sch. Blp.), more than one plant selected from the group consisting of Saussurea medusa Maxim. and Saussurea laniceps Hand.-Mazz. A glucagon production promoter comprising a component having an activity of dissolving an extract derived from a plant belonging to the genus Sauss urea in 30% (v/v) methanol; a column in which a porous polystyrene resin is used as a carrier, and then 50% (V/V) methanol is passed through the column, and then methanol is further passed through the column, and the component eluted from the column by the methanol . 8 · The glutathione production promoter according to item 7 of the patent application scope, wherein the plant belonging to the genus Saussurea is composed of Saussurea involucrate (Kar. et Kir.) Sch.Blp. More than one plant selected from the group consisting of Saussurea medusa Maxim. and Saussurea laniceps Hand.-Mazz. A caspase production promoter comprising dihydrodehydrocostus lactone represented by the following formula (1) as an active ingredient. [Chemical Formula 1] 100124696 Form No. A0101 Page 46 of 51 1002041805-0 201201865 ...(1) ίο . A pharmaceutical, food or cosmetic having a promoting effect on the production of glutathione, comprising a glutathione production promoter 第11 of claim 1 or 2. A pharmaceutical, food or cosmetic which promotes the production of a peptide, and a glutathione production promoter containing the third or fourth aspect of the patent application 〇12. A pharmaceutical and food having a promotion effect of glutathione production Or a cosmetic, a glutathione production promoter containing the fifth or sixth aspect of the patent application 〇13. A pharmaceutical, food or cosmetic having a glutathione-promoting effect, including a patent application scope 7 or 8 glutathione production promoting agent 〇14. A pharmaceutical, food or cosmetic having a glutathione-promoting action, comprising a surface glutathione production promoter of claim 9 . 100124696 Form No. A0101 Page 47 of 51 1002041805-0