TW201201825A - Melanin production inhibitor, and pharmaceuticals, food, or cosmetic material with inhibition function of melanin production - Google Patents

Abstract

This invention is to provide a safe and excellent melanin production inhibitor without side effect, and pharmaceuticals, food, or cosmetic material containing the same and having inhibition function of melanin production. The solution of this invention is a melanin production inhibitor that contains the extract of Saussurea involucrate (Kar.et Kir) Sch. Blp; and the ingredients obtained from the extract by column fraction or the dihydrodehydrocostuslactone is the active ingredient. The invention also provides pharmaceuticals, food, or cosmetic material containing melanin production inhibitor and having inhibition function of melanin production.

Description

201201825 VI. Description of the Invention: [Technology, Food, or Cosmetics having a melanin production inhibitor (me 1 aninproduct ion inh i b i tor ) and a melanin production inhibitory effect] [0001] The present invention relates to a melanin production inhibitor (me 1 aninproduct ion inh i b i tor ). [Prior Art] [0002] Melanin is a function of tyrosinase present in melanocytes (by tyrosine) via dopa (dopa) (3,4- (3, nu 4-dihydroxyphenyialanine) is produced by enzymatic or non-enzymatic oxidation reacti〇ns. Pigmentation, which considers skin spots, freckles, etc., is caused by abnormal secretion of hormones or ultraviolet exposure, causing excessive production of melanin and sequestration on the skin. In the past, whitening agents (whitening cosmetics) for the prevention or treatment of pigmentation such as pigmentation and freckles have been mixed with hydroquinone, L-ascorbic acid and hydrazine. Derivative, kojic acid, arbutin, etc. (for example, refer to Patent Document 1). [0003] However, the stability or solubility of these substances in the prescription system may be discolored or produced over time. If the concentration of the whitening effect is determined, it will be produced in safety. The problem is therefore unsatisfactory. [0004] On the other hand, an extract derived from a plant belonging to the genus Saussurea is known as a collagen production promoter (collagen pro-100124698, Form No. A0101, Page 3 of 42204204807-0 201201825 duct ion promoter) or an estrogenic agent is used for a skin cosmetic (for example, refer to Patent Document 2). Moreover, it is known that an extract from Saussurea laniceps Hand.-Mazz. among plants belonging to the genus Saussurea is regarded as a tyrosinase inhibitor or a melanin production inhibitor. It is used for whitening cosmetics (for example, refer to Patent Document 3). Furthermore, in recent years, it is known that an extract from a plant belonging to the genus Saussurea is used for cosmetics by progress in research on an extract belonging to a plant belonging to the genus Saussurea (for example, refer to the patent document) 4 and patent document 5). [00〇5] However, the extract from the plant belonging to the genus Saussurea comes from the extract of Saussurea involucrate (Kar. et Kir.) Sch.Blp., from Saussurea involucrate. (Kar.et Kir.)

Sch. Blp.) The specified composition after extract fractionation (fracti〇n) or dihydrodehydrocostus lactone contained in Saussurea involucrate (Kar. et Kir.) Sch.Blp. Dihydrodehydrocostuslactone) has no significant effect on the inhibition of melanin production. [Patent Document 1] 曰 特 200 200 9 9 9 9 9 0007 0007 0007 0007 0007 0007 0007 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 200 658 658 658 658 658 658 658 658 658 [Patent Document 4] [Patent Document 4] 曰 特 20 20 20 04-331 546 [0010] 100124698 [Patent Document 5] Form No. A0101 曰 National Special Publication No. 2004-331 547, No. 4 / Total 42 pages 1002041807-0 201201825 SUMMARY OF THE INVENTION The object of the present invention is to provide a [melanin production inhibitor which is safe and has a significant melanin production inhibitory effect]. Further, it is intended to provide a pharmaceutical, food or cosmetic having a melanin production inhibitory action containing the melanin production inhibitor. [0012] The present inventors focused on the results of research on melanin production-inhibiting substances, and found that it was not known to have significant melanin production inhibition [from Xinjiang Snow Lotus (Sa·surea inv〇lucrate (Kar·· et Kir· ) Sch. Β1ρ·) extract] is effective as a melanin production inhibitor' and [by the extract from Saussurea involucrate (Kar. et Kir·) Sch. Blp.) The prescribed component] and [dihydrodehydrocostus lactone] are also effective as melanin production inhibitors, and thus the present invention has been accomplished. The present invention consists of the following matters. [1] A melanin production inhibitor containing an extract derived from Saussurea involucrate (Kar. et Kir.) Q Sch. Blp. as an active ingredient [0014] [2] ], a melanin production inhibitor containing the following ingredients as an active ingredient: an extract from Saussurea involucrate (Kar. et Kir.) Sch. Blp. will be dissolved at 3〇% (V/V) When the solution of methanol passes through a column of a porous polystyrene resin as a carrier, it is adsorbed by the porous polystyrene resin. [0015] [3], a melanin production inhibitor containing the following ingredients as effective 100124698 Form No. A0101 Page 5 of 42 1002041807-0 201201825 Composition: Will make from Saussurea involucrate (Kar.et Kir .) Sch.Blp.) The solution of the extract dissolved in 30% (V/V) methanol is passed through a column supported on a porous polystyrene resin, and then used as a solvent for dissolving 50% (V/V). a component which is adsorbed by the porous polystyrene resin when the sterol passes through the column. [4] A melanin production inhibitor comprising the following components as an active ingredient: an extract from Saussurea involucrate (Kar. et Kir.) Sch. Blp. is dissolved at 30% ( V/V) The solution of sterol is passed through a column supported on a porous polystyrene resin, and then 50% (V/V) methanol, which is a solvent for dissolution, is passed through the above-mentioned column, and then used as a dissolution. When the methanol of the solvent passes through the column, the component which is eluted from the column by the sterol is used. [5] A melanin production inhibitor comprising dihydrodehydrocostus lactone represented by the following formula (1). [Chemical Formula 1]

(1) [0020] [6], a pharmaceutical product having a melanin production inhibitory effect, food or food 100124698 Form No. A0101 Page 6 of 42 1002041807-0 201201825 A cosmetic material containing melanin produced as described in [i] above Inhibitor. [0 (β1] [7], a pharmaceutical, food or cosmetic having a melanin production inhibitory action, comprising the melanin production inhibitor according to [2] above [8], a melanin production inhibitor The pharmaceutical product, the food or the cosmetic, which contains the melanin production inhibitor of the above [3], [9], a pharmaceutical, food or cosmetic having a melanin production inhibitory action, as described above [4] A melanin production inhibitor according to the above [5], which is a melanin production inhibitor having the melanin production-inhibiting action, and the melanin production inhibitor according to the above [5]. [Effects] According to the present invention, it is also known from the test examples described later that a melanin production inhibitor having no side effects, a safe and significant melanin production inhibitory effect, and [having a melanin production inhibitory effect] can be provided. [Pharmaceuticals, Foods, or Cosmetics] [Embodiment] [0019] Hereinafter, the [melanin production inhibitor] of the present invention and [having melanin production inhibition] will be described in more detail based on the embodiments. [0028] Fig. 1 is a flow chart for explaining the first to fifth embodiments. [0029] 100124698 The melanin production inhibitor of the present invention contains the following components as an active ingredient: [Extract from Saussurea involucrate (Kar.et Kir·) Sch.Blp.], [will make, Saussurea involucrate VRar·et Kir.) Form No. A0101 Page 7 of 42 Page 1002041807-0 201201825

The extract of Sch. Blp.) is a component which is dissolved in a porous polystyrene resin when a solution of methanol in a volume of 3〇% (V/V) is passed through a column made of a porous polystyrene resin], [will A solution obtained by dissolving an extract from Saussurea involucrate (Kar. et Kir.) Sch. Blp. in 30% (V/V) sterol through a column of porous polystyrene resin as a carrier When 50% (V/V) methanol is passed through the column, the component adsorbed by the porous polystyrene resin], [will be made from Xinjiang Snow Lotus (Saussurea involucrate (Kar.et Kir.)

The extract of Sch. Blp.) is dissolved in 30% (V/V) methanol through a column of porous polystyrene resin, and then 5% (v/V) sterol is passed through the column. Further, when methanol is passed through the column, the component which is eluted from the column by methanol or [dihydrodehydrocostus lactone] (see FIG. 1 and FIG. 2 described later). [〇〇3〇] Hereinafter, the above-mentioned respective active ingredients are described by the first to fifth embodiments. [0031] [Embodiment 1] [0032] The melanin production inhibitor according to the first embodiment contains [from Xinjiang] Saussurea involucrate (Kar. et Kir.)

The extract of Sch. Blp.) is an active ingredient (refer to Fig. 1). [0033] Among the melanin production inhibitors related to the first embodiment, [the extract from Saussurea involucrate (Kar. et Kir.) Sch. Blp.] contains Saussurea involucrate (Kar). .et Kir.) Sch.Blp.) The extract obtained by the extraction treatment, the dilution or concentrate of the extract, and the extract 100124698 Form No. A0101 Page 8 of 42 1002041807-0 201201825 Any of the crude or purified substances of the obtained materials or materials. [0034] In the extraction treatment, Xinjiang Xuelian (7) (10) "叮 (10) i nvoluc- (Kar. et Kir.) Sch. Blp.) (sometimes also known as the big snow lotus or Tianshan snow lotus or Xinjiang snow lotus) as extraction Raw material. Although the whole raw material can be used as a whole piant, it is preferable to use a ground segment. [0035] ^r^mmcsaussurea involucrate (Kar. et Kir.) 0 Sch.Blp.) is mainly distributed in Herbaceous herbs of the Xinjiang Autonomous Region, Sichuan Province, Hongfen Mountain, and various provinces and regions in Tibet have been used for joint rheumatism, sun therapy, menstrual irregularities, uterine withdrawal, and cold and pain in the lower abdomen of women. Colorless vaginal discharge, kidney deficiency and snow blindness (s_blindness) can be used for traumatic bleeding. [0036] ^fUSmcSaussurea involucrate (Kar. et Kir.) Sch. Blp.) can be obtained in Xinjiang, China, etc. 〇[0037] Saussurea involucrate (Kar. et Kir.) Sch. Blp., which is used as an extraction material, is dried and pulverized immediately after collection. Drying can also be carried out under sunlight, and it is carried out using a commonly used dryer. Also available. [0038] in extraction It is preferred to use a polar solvent for the extractant in the treatment. The component having a melanin production inhibitory effect can be easily used by Xinjiang Snow Lotus (Saussurea involucrate (Kar. et Kir.) by extraction treatment using a polar solvent.

Sch· Blp·) extracted. 100124698 Form No. A0101 Page 9 of 42 1002041807-0 201201825 [0039] Specific examples of the polar solvent may, for example, be water, a water-soluble organic solvent, or the like, and may be used alone or in combination. The above water, water-soluble organic solvent. The extracting agent is preferably one of water, a water-soluble organic solvent or an aqueous water-soluble organic solvent among the polar solvents. [0040] In addition to pure water, tap water, well water, mineral water, mineral water, hot spring water, spring water, fresh water, etc., the water that can be used as an extractant also includes such pure water, tap water, well water, Mineral water, mineral water, hot spring water, spring water, and fresh water are applied to various processors. The various treatments include, for example, heating, bactericidal, sterilizing &, 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. Further, 'the extractant can also be used as a treatment for adjusting the osmotic pressure of various waters, buffering, etc. (physiological saline, phosphate buffer, acid buffered physiological salt) Water (PBS: Phosphate Buffered Saline), etc. ο [0042] A water-soluble organic solvent which can be used as an extractant can be exemplified by a lower aliphatic alcohol, an 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 100124698 Form No. A0101 Page 10 of 42 page 1002041807-0 201201825 [00445] [0045] [0045]

[0046] alcohol [0047]. When a mixture of two or more kinds of 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, a propylene 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 Xinjiang Xuelian (8811331^63丨1^〇1-ucrate (Kar.et Kir.) Sch.Blp.) can be dissolved in the extractant. Can be carried out according to the usual methods. In the extraction treatment, it is not necessary to adopt a special extraction method, and any method can be used at room temperature or even under reflux heating. The extraction method can exemplify a method of immersing the extraction raw material in an extractant at a normal temperature for a long time and extracting, or A method of extracting to a temperature equal to or lower than the boiling point of the extractant while stirring, or extracting at a temperature near the boiling point of the extractant under heating and reflux. In this case, the extraction dose 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 4 hours. The extraction temperature is usually 50 to 95 ° C, preferably 80 to 95 ° C. In the extraction treatment, before the extraction with the polar solvent is carried out, the use of pentane, hexane, gamma, cinnabar, petroleum ether 100124698, form number A0101, page 11 / total page 42, 204101807-0 [0048] The degreasing treatment of a non-polar solvent (n〇np〇lar s〇l vent) such as 201201825 may be performed, and the pre-application treatment may be performed to efficiently perform extraction treatment using a polar solvent. After the soluble component is dissolved by the extraction treatment, the extract can be obtained by subjecting to a treatment such as filtration, centrifugal separation, or the like, and removing the extraction residue. The obtained extract may be subjected to a treatment such as dilution, concentration, drying, purification or the like according to a usual method in order to obtain a diluted solution or a concentrated solution of the extract, a dried product of the extract, or a crude purified product or a purified product thereof. [0050] Because of the snow lotus from Xinjiang (Saussurea involucrate (Kar. et

The extract of Kir· ) Sch.Blp.) has a unique odor and taste, so purification for the purpose of decolorization, deodorization, and the like can also be performed. Purification can be carried out in particular by activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, etc., which are not caused by Xinjiang Saussurea involucrate. The range of reduction in melanin production inhibition in the extract of (Kar. et Kir.) Sch. Blp.) was carried out. [Embodiment 2] [0052] The melanin production inhibitor according to the second embodiment contains [will be made from Xinjiang Snow Lotus (Saussurea involucrate (Kar. et Kir.)]

The extract of Sch. Blp.) is dissolved in a 30% (V/V) methanol solution, and the component adsorbed by the porous polystyrene resin is an active ingredient when passing through a column of a porous polystyrene resin. Refer to Figure 1). 100124698 Form No. A0I01 Page 12 of 42 1002041807-0 201201825 [0053] [SaussUrea inv〇iucrate (Karet)

The extract of Kir·) Sch'Blp.) can be obtained by the method described in the first embodiment. [0054] Examples of the porous polystyrene resin to be a carrier include Diaiqn (registered trademark of Mitsubishi Chemical Corporation) Hp2 {^Hp2i*sEpA_ BEADS (registered trademark of Mitsubishi Chemical Corporation) SP850, SP700 and SP70. [0055] The component adsorbed by the porous polystyrene resin in θ 〜'/杨态二 can be obtained by using Saussurea involuc_ rate (Kar.et Kir, c, ·) Sch.Blp. After the extract is dissolved in 30% (V/V) methanol, the solution passes through the column, and the less polar solvent is dissolved through the column. Erodible The solvent used for dissolving the component can be exemplified by a lower aliphatic alcohol, an intermediate polar solvent such as _^, ethyl acetate or the like; These towels can be made suitable for use with methanol. [0056] ❹ In this specification, it is said that [SauSsurea in-volucrate (Kar. et Kir.) Sch.Blp ^ ^^ will be passed through a porous polystyrene resin. When the column of the carrier is used, the component adsorbed by the porous polystyrene resin is [adsorbed component]. [0057] Moreover, it is said that L will be from Xinjiang Xuelian ("Cai (4) _ 〇 1 town heart (Kar.et Kir . ) Sch.Blp.) The extract is dissolved in a 3 % (v / v) methanol solution through a column of porous polystyrene resin - by m (v / m alcohol by the column The component to be eluted] is [non-adsorbed into 100124698, Form No. A0101, Page 13 of 42, 1002041807-0 201201825]. [0058] [Embodiment 3] [0〇59] Melanin production inhibition related to the third embodiment Agent containing [will make from Saussurea involucrate (Kar.et Kir.)

The extract of Sch. Blp.) is dissolved in a solution of 3〇% (ν/ν) sterol through a column supported on a porous polystyrene resin, and then 50% (V/V) sterol is passed through the column. In the case, the component adsorbed by the porous polystyrene resin is an active ingredient (see FIG. 1). [0086] [Saussurea involucrate (Kar. et from Xinjiang) [0060]

The extract of Kir.) Sch. Blp.) can be obtained by the method described in the first embodiment. [0061] The porous polystyrene resin to be a carrier is, for example, IAI 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, in the third embodiment, the component adsorbed by the porous polystyrene resin 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 which can be used for dissolving the component can be exemplified by an intermediate polar solvent such as a lower aliphatic alcohol, a glycerin I or an ethyl acetate, or the like; a nonpolar solvent such as hexane or the like. Among these solvents, methanol can be particularly suitably used. [Embodiment 4] The melanin production inhibitor associated with the fourth embodiment is contained in [Sassurea involucrate (Kar.) from Form No. 1001698 Form No. A0101 Page 14/42 Page 1002041807-0 201201825 Xinjiang Snow Lotus (Kar. Et Kir.) Sch. Blp·) The solution of the extract dissolved in 30% (V/V) sterol passed through a column of porous polystyrene resin, and then 5〇% (v/V)曱When the alcohol passes through the column and then the methanol is passed through the column, the component which is eluted from the column by the sterol is an active ingredient (refer to FIG. 1). [0065] [Saussurea involucrate (Kar. et from Xinjiang)

The extract of Kir.) Sch. Blp.) can be obtained by the method described in the first embodiment.多孔 [0066] The porous polystyrene resin to be a carrier is, for example, IAION (registered trademark of Mitsubishi Chemical Corporation) HP20 and HP21 or SEPA-BEADS (registered trademark of Mitsubishi Chemical Corporation) από, SP700 and SP70. [〇〇67] In this specification, [the solution from Saussurea in_volucrate (Kar. et Kir.) Sch.Blp.) is dissolved in 30% (V/V) methanol to pass through the porous a polystyrene-based vinyl resin as a carrier column, then 50% (V/V) methanol is passed through the column, and then the methanol is passed through the column, and the component which is eluted from the tube sheet by methanol is [methanol dissolution]. section]. [Embodiment 5] The melanin production inhibitor according to the fifth embodiment contains dihydrodehydrocostus lactone represented by the following formula (1) as an active ingredient. [Chemical Formula 1] 1002041807-0 100124698 Form No. A0101 Page 15 of 42 - (1) 201201825 [0071]

Dihydrodehydrocostine lactone is shown in the preparation example described later, and is contained in Saussurea involucrate (Kar. et Kir.).

The extract of Sch. Blp.) (see Figure i and Figure 2, which will be described later). Dihydrodehydrocostus lactone used in the black pigment production inhibitor is used by Saussurea involucrate (Kar·et Kir.)

The extract of Sch. Blp.) can also be used, and is used by Saussurea involucrate (Kar.et Kir.)

The natural product other than Sch. Blp.) and containing dihydrodehydro-lactolactone may be used as a separator, and a commercially available product or a synthetic product may be used. The melanin production inhibitor (i.e., the melanin production inhibitor of the present invention) which is related to the above-described addition form 5 is expected to prevent, treat or improve pigmentation such as stains and freckles through melanin production inhibition. Further, since the melanin production inhibitor of the present invention is effective in the formation of a natural product contained in a natural product which has been used for a long time as a folk medicine, it has become a safer [with no side effects]. Pigment production inhibitor]. Further, the melanin production inhibitor of the present invention is known as a test case described later as "100124698 Form No. A010 having a significant melanin production inhibitory effect." Page 16 of 42 page 1002041807-0 201201825 Melanin production inhibitor]. In addition, the melanin production inhibitor of the present invention may contain any one of the active ingredients in the above-mentioned Embodiments - five, and may contain two or more of the active ingredients in the above-described first to fifth embodiments. When two or more of the active ingredients in the above-described first to fifth embodiments are contained, the compounding ratio of the active ingredients may be appropriately determined according to the degree of action of the active ingredients. [0075] The melanin production inhibitor of the present invention can be used as a pharmaceutical, food or cosmetic having a melanin production inhibitory action containing the melanin production inhibitor. The route of administration of the [medicine for internal use having a melanin production inhibitory action] of the present invention is not particularly limited, and examples thereof include enteral administration such as oral administration and intrarectal administration. Injectable administration such as mucosal administration, intravenous administration, subcutaneous administration or the like of a drug or nasal administration. The dosage form of the internal pharmaceutical of the present invention can be in the form of a preparation suitable for the administration method, and examples thereof include a tablet (table 1 et al), a powder, a fine granule, a granule, a capsule, a powder, and a pill. A solid agent such as a troche; a solution such as a solution, a suspension, an emulsion, a syrup, or an injection; a gel-form preparation or the like. The pure product, the purified product, the crude purified product or the like of the melanin production inhibitor of the present invention may be administered as it is, or may be administered together with a pharmacologically acceptable excipient. The excipient can be used as a preparation if it is a monosaccharide, a disaccharide, a polysaccharide, an inorganic salt, a fat or oil, or distilled water. For formulation, binders, lubricants, dispersants, suspensions, etc., may also be used. Additives, emulsifiers, thinners, buffers, antioxidants, etc., 100124698 Form No. A0101 Page 17 of 42 1002041807-0 201201825. 、 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ The amount which is most suitable for each administration form is set to the next time. In the present invention, the melanin production (four) ^ (tetra) state of the present invention may be a purified product or a food containing the mesochrome production inhibitor of the black (1) producing (tetra) compound. That is, the form of the "food for black use" is a form of food, such as a health drink, a fruit production inhibitor, a pill, a soft capsule, a hard capsule, a powder, a tea, a key, etc. :: The auxiliary material may also be an additive such as an excipient, a binder, a lubricant, an emulsifier, a diluent, a buffer, an antioxidant, a J suspension, etc. ' _ inhibits the melanin production inhibitory action of the present invention The example of the form of the external pharmaceutical material is not particularly limited. Examples of the form of the external pharmaceutical product include a soft agent, a powdered mud (CataPlaSm), a tape, an external preparation, etc. The external medicine of the present invention is required. The melanin production inhibitor of the present invention contains other medical treatments and can also use a knotting agent, a dispersing agent, a suspending agent, an emulsifier, a diluent, a buffering agent, an additive, a chemical agent, a bacterial inhibitor, etc. 100124698 [0081] The form of the cosmetic can also use lotion, beauty lotion, page 18 of 42 lotion, cream form number A0101 1002041807-0 201201825 Ο [0082] am), gel, mask (pack) The cosmetic powder preparation or the like can be used as any form of the external seal or cosmetic preparation. The second preparation: the cosmetic preparation is in addition to the melanin production inhibitor of the present invention: A field a* mouth knife W Φ solid oil, semi-solid oil, liquid oil, low-molecular polymer ^ ^ ^ ~ fool, fat-soluble moisturizer, lubricant (em〇1Uent), surfactant (chemical agent unt Active agent), preservative, anti-oxidation, water (also called dant), pH adjuster (PHadjuster), ethanol, medicinal sigma pigment production of the present invention, ° ° α and cosmetics can be expected to pass through the black of the present invention It has a melanin production inhibitory effect, and it is used to prevent, treat or improve the color of spots such as freckles by using melanin. [0083] ❹ Moreover, the sputum of the present invention, the medical product, the food and the cosmetic Contains [melanin-producing inhibitor with no side effects and significant melanin production inhibition], & becomes a drug, food or makeup that has no side effects, is safe, and has significant melanin production inhibitory effects. The present invention will be described in more detail below with reference to [1, a sample preparation example] and [2, a melanin production inhibition effect], but the present invention is not limited by such examples. 0085] 1. Preparation example of sample [0086] (Preparation example of sample a in preparation example D [0087] Preparation example 1 is used for purification by Saussurea involucrate 100124698 (Kar. et Kir.) Sch Mp Water Form No. A0101 Page 19 of 42 Preparation of 1002041807-0 201201825 (purified water) Extract (sample a (water extract)). [0088] Saussurea involucrate (Kar.et Kir.) in the plant belonging to the genus Saussurea

Sch. Blp.) The ground part of the pulverized material 3 〇. 3g of the solution obtained by heat extraction (80 ° C ~ 90t:, 2 hours) using 45 〇 mL (ml) of purified water (using qualitative solution) The extract was obtained by using two types of paper (purchased by ADVANTEC Toyo Co., Ltd.). The obtained extract was concentrated under reduced pressure and lyophilized to give 8.3 g of sample a (water extract). The solid yield was 27.3%. [Modulation Example 2] Preparation Example of Sample b [0090] Modulation Example 2 is for utilization of 5 % by Saussurea i nvo 1 ucrate (Kar. et Kir.) Sch. Blp. (v/v) Preparation example of ethanol extract (sample b (50% ethanol extract)). [Surface] in the Saussurea involucrate (Kar.et Kir.) of the plant belonging to the genus Saussurea

Sch. Blp·) The ground part of the pulverized material 3〇·5g was extracted by heating with 45〇1 (^50% (V/V) ethanol (80〇c~9{rc, 2 hours), and then filtered. 4的的样本1) (50) The extract was obtained by a qualitative analysis using two kinds of filter paper (purchased by ADVANTEC Toyo Co., Ltd.). The obtained extract was concentrated under reduced pressure and lyophilized to obtain 7.4 g of sample 1) (50 % ethanol extract). The solid yield was 24.2%. [Modulation Example 3] Preparation example of sample c 100124698 Form No. A0101 Page 20 / Total 42 page 1002041807-0 201201825 [0093] Modulation Example 3 is for the preparation of Saussurea inv〇iucrate (Kar. Et Kir. ) Sch. Blp.) A preparation example of an extract (sample c (80% ethanol extract)) using 80% (v/v) ethanol was obtained. [0094] Saussurea involucrate (Kar.et Kir.) in the plant belonging to the genus Sau ssurea

Sch. Blp.) Ground material pulverized material 3〇. 7g was heated and extracted with 450mL of 80% (V/V) ethanol (8°°〇90°C for 2 hours), and the obtained solution was filtered (used For qualitative analysis, two types of filter paper (purchased by ADVANTEC Toyo Co., Ltd.) were used to obtain an extract. The obtained extract mash was sequentially concentrated under reduced pressure and lyophilized to obtain 5. 4 g of a sample c (80% ethanol extract). 5%。 The solid yield was 17.5%. (Preparation Example 4) Preparation Example of Samples d to f and Comparative Sample 1 [0096] FIG. 2 is a flow chart for explaining a preparation example of a sample and a comparative sample 1 " [0097] Modulation Example 4 is to obtain a comparative sample 丨 (non-adsorbed component), sample d (adsorbed component), and sample e (methanol elution) from Saussurea inv〇iucrate 〇 (Kar. et Kir.) Sch. Blp. Part) and Example of Preparation of Sample F (Dihydrodehydrocostinelactone) This preparation example was carried out in accordance with the flow shown in FIG. [0098] In the snow lotus of Xinjiang (Saussurea involucrate (Kar. et

Kir. ) Sch. Blp.) 4 kg of ground material was subjected to two times of extraction with 80 L of 80% (V/V) ethanol (80 ° C, 2 hours), and the resulting solution was filtered. (The extract was obtained by qualitative analysis using two types of filter paper (purchased by ADVANTEC Toyo Co., Ltd.)).于于100124698 Form No. A0101 Page 21 of 42 1002041807-0 201201825 6 0 T: The extract was concentrated under reduced pressure and dried (normal temperature, 1 hr) to obtain 680 g of an extract. Next, the extract was dissolved in 30% (V/V) methanol (3 L, 40 ° C) as a solution, and the solution was passed in advance to pass

IOION HP20 (1500 g, purchased from Mitsubishi Chemical Corporation) after 30% (V/V) methanol balance (equi 1 ibrate) was packed 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 1). Subsequently, 7 L of 50% (V/V) methanol, 6 L of decyl alcohol, 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 portions was regarded as a dry solid' to obtain 399 g of a non-adsorbed component (Comparative Sample 1), 38 g of a 50% (v/v) methanol-soluble fraction, and 100 g of a sterol-soluble fraction (sample e). 21 g of the ethanol-dissolved fraction, 18 g of the ethyl acetate-soluble fraction, and 0.1 g of the hexane-soluble fraction. Ll. 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 Wherein 'methanol elution fraction (sample e) (100 g) was added to a silica gel column chromatography (silica gej c〇) using trimethyl sulphide / sulphate / decyl alcohol / water as a solvent for dissolution. Iumn chromatography ) (80mm x 350mm, purchased by Fuji SILYSIA Chemical Co., Ltd.). That is, while changing the ratio of the dissolved solvent to 90:10: 〇, 40: 10. 1, 30: ι〇: ι (all three gas methane: decyl alcohol: water) while dissolving 'per part' ( Fractional fractionation solution 〇luent)i5〇mL, add these parts together to get 8 100124698 form number Α0101 page 22 / total page 422041807-0 201201825 part of a~η. The portion A of 40.9 g is obtained by removing the solvent as a dry solid by the solution of the portion A (dissolved amount: 450 mL to 1 200 mL). [0100] ο [0102] 100124698 then 'Part A (40. 9g) was added to the hexane/acetone as the solvent for the separation of the gel column chromatography (6〇111115 Shanghai><25〇 Legs, purchased by Fuji 511^51 into Chemical Co., Ltd.). In other words, the ratio of the solvent to the solvent 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. Here, the solvent was removed from the solution containing a portion of AB as a dry solid' to obtain a portion AB of 13. g (dissolved amount: 180 mL to 600 mL). Further, a part of AB (13.lg) was added to ODS® rubber column chromatography (60 mm <^xl5 mm, purchased from NACALAI TESQUE Co., Ltd.) using methanol/water as a solvent. That is, while the ratio of the solvent to be dissolved is sequentially changed to 7:3, 8:2, 9:1 (all of which are decyl alcohol: water), the solution is dissolved, and each part is fractionated and dissolved in 4 〇mL, and the portions are added. Get 1 part of AB-1~AB-10 together. The LB portion AB_3 is obtained by removing the solvent from the solution containing a portion of AB-3 (dissolved amount: 1 200 raL to 144 Å|nL) as a dry solid. 8. Hexa hexane/ethyl acetate as the solvent (4) Hose column chromatography (6G_xl5Gmm, purchased by Fuji SILYSIA Chemical Co., Ltd.). That is, the ratio of the field agent is sequentially changed to 19:1, 9. w. 9.1 (all hexane: acetic acid, hydrazine) while dissolving, each minute is separated from the liquid 4 〇mL, to obtain a溶 There is a solution of dinitrogenated detoxification vinegar (dissolved amount:, ~&. Solvent removed from the eluent. Form No. 1 Page 23 / Total 42 pages of granules to 1002041807-0 201201825 161 mg Dihydrodehydrocostine lactone (Sample f). [0103] Dihydrodehydrocostus lactone (sample f) which was fractionated and isolated by the above method (isfiati〇n) Using the nuclear magnetic resonance spectroscopy to obtain 1H-NMR spectral data and 13C-NMR spectral data, the following peaks were observed, and the literature (Journal of Natural Products, Vol. 62) The value of the 27th page '1999' is roughly the same. In addition, the formula of 'diazepine azlactone (sample f) is C Η 0 . 1 5 2 0 2 [0104] ^-NMR (CDC13 » 400MHz ) 6 : 1. 23 ( 3H - d * J = 7.0Hz 'Me-12), 1.30 (lH, m, H-8), 1.85 (1H, m, H-2), 1.94 (2H'm, H- 2, H-7), 2. 〇 4 (lH, m, H-9), 2.10 ( lH, m, H-3), 2.21 (lH, m, H-ll), 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 ( 1H, br s ' H-15b) ' 5. 04 ( 1H ' d, J = 2. 0Hz, H-14a) 5. 19 ( 1H,d,J = 2. 0Hz ' Η-14b o [0105] 13C-NMR (CDC13 ^ 100MHz) 6 : 13. 22 ( C-1 2 ), 30.17 (C-2), 32.48 (C-3, 8), 37.65 (C-9), 42.04 ( C-ll), 47.04 (C-1), 49.85 (C-7), 51.93 (C-5), 85.28 (C-6), 109.15 (C-14), 111.81 (015), 149.94 (C-10 ), 151.70 (C-4), 178. 70 (C-13). 100124698 Form No. A0101 Page 24 of 42 1002041807-0 201201825 [0106] Moreover, mass spectrometry (mass spectr〇) was performed on dihydro degassed woody vinegar (sample f) divided and separated by the above method. Oximetry), the results obtained are obtained, and the measured mass is approximately the same as the mass estimated by the molecular formula. HR-ESI-TOF-MS m/z: 233. 1550 [M+H]+ (Calcd f〇r [0108] C15H2Q〇2: 233. 1 542). Further, in the above, a general experimental apparatus and an experimental apparatus were used using the column chromatography of DIAION HP20, Shi Xisheng column chromatography, and 0DS tantalum column chromatography. Further, the nuclear magnetic resonance spectroscopy apparatus was a Brukei 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 Melanin Production Inhibition Effect A test example of melanin production inhibitory action was carried out by measuring the effect of inhibiting Q on melanin production of B16 mouse melanoma cel Is. (A), Test Method [0113] 10% (V/V) fetal bovine serum (FBS, by GIBC0-) was added using Dulbecco's modi fied Eagle's medium (DMEM, purchased from GIBCO-BRL). BRL mouse melanoma cells (B16 melanoma 4A5, purchased by RIKEN BioResource Center) were broadcast as 1004001807-0 100124698 A0101 Page 25 of 42 201201825 (disseminate) in 6 wells (we 11 pi ate) (purchased by NUNC), 3.5成3.5父105〇6115/评611, to (:〇2 incubator (incubator) ( Incubate at 37 ° C, 5% carbon dioxide, 95% air). After 24 hours, the medium was changed to a sample containing 〇nmoi/L α containing a specified concentration (20 gg/mL or ΙΟ/zg/mL). - MSH (melanocyte-stimulating hormone, purchased from SIGMA) DMEM medium supplemented with 10% FBS, further cultured for 48 hours. [0114] Sample was used sample a (water extract) , refer to the above preparation example 1, concentration 20 〇 eg / mL) Sample b (50% ethanol extract, reference to Preparation Example 2, concentration 200 #g/mL), sample c (80% ethanol extract, refer to the above Preparation Example 3 'concentration 200 " g/mL), test Sample d (adsorption component, reference to Preparation Example 4, concentration 20 Mg/mL), sample e (methanol elution portion, see Preparation Example 4, concentration 20 /zg/mL), and sample ί (dihydrodehydrogenated wood) The lactones were tested according to the above-mentioned Preparation Example 4, concentration 2 〇 "g/mL), and for comparison, for the comparative sample 2 (non-adsorbed component 'refer to the above-mentioned preparation example 4, concentration 2 〇〇vg/mL) and comparative sample 2 (4-hydroxyphenyl-AD-glucopyranoside), purchased from SIGMA at a concentration of 20/zg/ 5mL的离心离心管 (microtube), the cells were also recovered by the usual method (trypsinization), the cells were recovered from each well (weii). Then the recovered cells were transferred to a 1.5 mL microcentrifuge tube (microtube) ), pellets were obtained by centrifugation (800 G, 10 minutes). 20 〇eL of 1 mol/L NaOH aqueous solution was added to the granules, and heated at 80 ° C. 100124698 Form No. A0101 Page 26 / Total 42 Pages 1002041807 201201825 1 5 minutes to dissolve the absorbance at the measuring wavelength of 4 7 5 nm (absorbance) ) (blank: lm〇1/LNa〇H aqueous solution). While performing the assay, 'count i 〇 y count count try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try try In the evaluation, the amount of melanin was calculated by comparing the amount of melanin per living cell in the case where the medium to which no sample was added was used (an index when the amount of melanin per living cell when the sample was not added was 100%). (B), Test Results 〇 [0117] The test results are shown in Table 1 and FIG. Table 1 is a table showing the results of the test examples (inhibition of melanin production by B16 mouse melanoma cells). Fig. 3 is a graph showing the results of a test case (inhibition of melanin production in B16 mouse melanoma cells). [0118] [Table 1] [0119] The relative space of the B1 fi small cavern in the fine running of the music. Volume·

[0120] mm__dense i_relative black_color 帚[0121] sample a (water extract) 40 β g/mL 79. 5% [0122] sample b (50% ethanol extract) 40 βg/ mL 82. 2% [0123] Sample c (80% ethanol extract) 40 βg/mL 84. 7% [0124] Sample d (adsorbed component) 20 βg/mL 76. 6% [0125] Sample e (Methanol-soluble fraction) 20 βg/mL 67. 6% [0126] Sample f (dihydrode-saponin) 10 /zg/mL 73. 5% Form No. A0101 Page 27 / Total 42 Pages 100124698 1002041807 -0 201201825 [0127] Comparative sample 1 (non-adsorbed component) 20/zg/mL 101. 0% [0128] Comparative sample 2 (arbutin) 20/zg/mL 80.3% [0129] No test was added (挂照)_二_100. 0°/〇[0130] (a), for samples a~c [0131] As shown in Table 1 and Figure 3, it can be confirmed from Xinjiang Saussurea involucrata (Kar. Any extract of et Kir.) Sch.Blp.) (samples a to c) showed melanin production inhibition in B16 mouse melanoma cells. (b), for the sample d [0133] As shown in Table 1 and FIG. 3, it was confirmed from the comparison with the non-added sample and the comparative sample 1 (non-adsorbed component) that the sample d was confirmed. (Adsorbed component) shows a clear inhibition of melanin production. Further, it was confirmed that the sample d (adsorbed component) showed a higher melanin production inhibitory effect than the comparative sample 2 (arbutin). (c), for the sample e [0135] As shown in Table 1 and FIG. 3, it was confirmed that the sample e (melanol-dissolved portion) showed higher melanin production inhibition than the sample d (adsorbed component). effect. (d), for sample f [0137] As shown in Table 1 and FIG. 3, it was confirmed that the sample f (dihydrodehydrocostus lactone) was compared with the comparative sample 2 (arbutin) A low concentration (10 V g/mL) at a concentration (20//g/mL) also showed a higher inhibition of melanin production. 1002041807-0 100124698 Form No. A0101 Page 28/Total 42 Page 201201825 [Examples] [0139] Production of a sneak η, a recording example [0140] Using the sample [(Modulation Example 1) according to the above] Preparation Example] The water extract prepared by the method described above was prepared into a tablet (50 〇mg per amount) by the following prescription. Water extract (Preparation Example 1) l〇mg [0142] Lactose 470 mg Ο

Dry corn starch l 〇 mg [0144] talc (talc) 9 mg [0145] calcium stearate ling [0146] (modulation method) [0147] water extract (2 g), dried corn starch (2 g), Talc (1.8 g), calcium stearate (G. 2 g) was added to lactose (94 g) and mixed with β. Next, a tablet was prepared by a conventional method using a single stroke tablet press. [0148] : The 50% ethanol extract prepared by the method described in [Modulation Example 2] Preparation of Sample b] Hard capsules (360 mg per capsule) were prepared by the following prescription. 50% ethanol extract (Preparation Example 2) 5 mg [0151] Lactose 220 mg 1002041807-0 100124698 Form nickname A0101 Page 29/Total 42 page 201201825 11 Omg [0152] Jade starch [0153] propyl fiber Hydroxypropy 1 cellulose 25mg [Modulation method] [0155] Lactose (220g) and corn starch (ii〇g) were added to 5〇% ethanol extract (5g) and mixed to form hydroxypropyl fiber An aqueous solution of a phenol (25 g) was added thereto and kneading was carried out. Next, pellets were produced by a usual method using an extrusion granulator. A hard capsule is prepared by filling the granules into a gelatin hard capsule. [Example 3] The 80% ethanol extract prepared by the method described in [Modulation Example 3> Preparation Example of Sample c] is used as follows. Formulated soft capsules (170 mg per capsule) [0158] 80% ethanol extract (Preparation Example 3) 5 mg [0159] Soybean oil 165 mg [0160] (Modulation method) [0161] 80% ethanol extract ( 5 g) was added to soybean oil (l65 g) and subjected to / kneading. Then, soft capsules were prepared by filling into soft capsules according to a usual method by using a rotary die automatic molding machine. [0162] Example 4 Preparation of the Pills [0163] Using the adsorption component prepared by the method described in the above [(Preparation Example 4) Samples d to f and Comparative Example 1 Preparation Example], a pellet was prepared by the following prescription ( 1 0 〇mg ) 100124698 Form No. A0101 Page 30 / Total 42 Page 1002041807-0 201201825 [0164] Adsorption component (Preparation Example 4) 0. 5mg [0165] Taiwan jute (corchorus 〇1 itorius) powder 20. Omg [0166] Starch 30.Omg [0167] Molasses 20.Omg [0168] Tea extract 15.Omg [0169] Soy fiber 14.Omg [0170] Shellac (shel lac) 0. 5mg [0171] (Preparation method) [0172] The above materials are mixed and mixed, and an appropriate amount of water is added, and a homogenous kneaded product is produced by a kneader. The kneaded product was rolled, and pelletized by a pelletizer, and dried to prepare a pellet. [0173] Production Example 5: Preparation of a sputum [0174] A preparation example of the sample a according to the above [(Preparation Example 1)] was used. The water extract prepared by the method described above was prepared into a jelly (l〇〇g) by the following method. [0175] Water extract (Preparation Example 1) 0. 02g [0176] Gelatin 2. OOg Orange juice 20.00g [0178] Water 77.98g [Modulation method] Form No. A0101 Page 31 of 42

100124698 1002041807-0 201201825 [0180] The above ingredients were mixed and heated to 9 (TC. Filled in a container after confirming dissolution of gelatin) to be cooled. The jelly was solidified by gelatinization. [0181] Example 6, #膏的卞二 [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( An ointment (100 g) was prepared by a usual method. [0183] (Oil phase component) [0184] Dihydrodehydrogeninolide (Preparation Example 4) O.Olg [0185] White Vaseline 20.00 g [ 0186] mineral oil (mineral oi 1 ) 20. 00g [0187] stearyl alcohol 5. OOg [0188] stearyl-2 (steareth-2) 3. OOg [0189] benzoic acid Propyl ester (propylparaben) 0.10 g [0190] Natural vitamin E 0.10 g [0191] (aqueous phase component) [0192] 1,3-butylene glycol (1,3-butylene glycol) 5. OOg [0193 ] phenoxyethanol 0. 40g 100124698 Form No. A0101 Page 32 of 42 1002041807-0 201201825 Ο

G

Polysorbate 60 4. 50 g [0195] Purified water amount [0196] Total weight l〇〇g [0197] (Modulation method) [0198] The oil phase component and the water phase component are respectively Heating to 80 ° C and homogenizing, adding the aqueous phase to the oil phase while stirring, emulsification and cooling to make an ointment [0199] 眚 Example 7, 罄刽 罄刽 [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ In the methanol-dissolved portion prepared by the method described in (Preparation Example 4) Samples d to f and Preparation Example 1 of Comparative Sample 1, a tape (100 g) was prepared by a usual method using the following prescription. (Adhesive solvent) [0202] styrene-isopropylene-styrene block copolymer 7. 00 g [styrene-isopropylene-styrene block copolymer] [0204] Piccolyte 25.00 g [0205] isopropene rubber 5. 00g [0206] toluene 15.OOg [0207] ethyl acetate 14.20g [0208] hex Hyun 25.OOg Form No. 1010101 Page 33 / Total 42 Pages 100124698 1002041807-0 201201825 [0209] Pharmacological component) [0210] Methanol-soluble fraction (Preparation Example 4) O.Olg _1] Ethanol 7. 99 g [0212] (Transdermal absorption enhancer) [0213] Oleo alcohol 0. 80g [0214] Weight 100g [0215] (Preparation method) [0216] The adhesive solvent and the medicinal component are respectively made uniform, and the medicinal component and the percutaneous absorption enhancer are added to the adhesive solvent, and the composition is stirred at room temperature. The composition was stretched on a polyester film subjected to a silicone treatment, dried and cooled at 120 ° C, and then transferred to a polyethylene film (polyethylene film). Agent. Example 8: Preparation of the lotion Motion [0218] 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 lotion (100 g) was prepared in the usual manner. (Oil phase component) [0220] Polyoxyethylene (P〇1y〇xyethylene) (60 mol) hydrogenated castor oil [0221] (hydrogenated castor oil) 2. 〇g [0222] 1,3-butyl Alcohol 5.0g 100124698 Form No. A0101 Page 34 of 42 1002041807-0 201201825 [0223] (Water phase component) [0224] Water extract (Preparation Example 1) 0. lg [0225] Glycerin 5. Og [0226] Phenoxyethanol 0. 3g [0227] citric acid 0. lg [0228] sodium citrate 0. 2g [0229] ethanol 8. 0g [0230] purified water amount [0231] Weight 10 0 g [Modulation method] [0233] 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 and the wisdom of the sputum [0235] The 50% ethanol extract prepared by the method described in the above [(Preparation Example 2) Preparation of Sample b] was used, and the following The emulsion is prepared by a usual method (l〇〇g). [0236] Nippon oil 8. 00g [0237] Ethanol 5. 00g [0238] 100124698 yam (beheny 1 a 1 coho 1) Form No. A0101 Page 35 / Total 42 0. 50g 1002041807-0 201201825 [0239] ] citric acid o. l〇g [0240] Sodium citrate 0.20 g [0241] 50% ethanol extract (Preparation Example 2) 1. 50 g [0242] 1,3-butanediol 4.00 g [0243] Ethyl benzoate 〇.1〇g [0244] (ester para-hydroxybenzonate) [0246] edetate disodium 0.01g purified water amount [0247] total weight [0248] ( Modulation method) l〇〇g [0249] The above raw materials are stirred and mixed to prepare an emulsion. [Remuneration f 丨 丨 Q Q, 汸 汸 汸 [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ Example: An 80% ethanol extract prepared by the method described above was prepared into a cosmetic liquid (100 g) by a usual method by the following prescription. 80% ethanol extract (Preparation Example 3) 1. 5〇g tetamine ethylene chelate (carbazole XyVinyi p〇iymer) 〇.5〇珏 glycerol 6. 50g 1,3-butanediol acetoxyethanol form No. A0101 Page 36 of 42 7. 50g 0. 30g 1002041807-0 201201825 [0257] Potassium hydroxide 〇. 20g [0258] Hyaluronate sodium 0. 25g [0259] Shark (squalane) 0. 50g [0260] Vitamin E acetate 0. 05g [0261] Stearic acid 0. 20g [0262] Purified water amount [0263] The weight of the whole l〇〇g [0264] (Modulation method) [0265 The raw material is stirred, mixed, and dissolved to prepare a cosmetic liquid. [0266] [Brief Description of the Drawings] Fig. 1 is a flow chart for explaining the embodiment - -5. 2 is a flow chart for explaining a preparation example of the samples d to f and the comparative sample 1. 3 is a graph showing the results of a test example (inhibition of melanin production by B16 mouse melanoma cells). [Description of main component symbols] 100124698 Form No. A0101 Page 37 of 42 1002041807-0

Claims (1)

201201825 ' VII. Patent application scope: 1. A melanin production inhibitor containing an extract from Saussurea involucrate (Kar. et Kir.) Sch. Blp. as an active ingredient. 2. A melanin production inhibitor containing the following components as an active ingredient: The extract from Saussurea involucrate (Kar. et Kir.) Sch. Blp. will be dissolved at 30% (V/V). When the solution of sterol is passed through a column of a porous polystyrene resin as a carrier, the component adsorbed by the porous polystyrene resin. 3 · A melanin production inhibitor containing the following ingredients as an active ingredient: The extract from Saussurea involucrate (Kar. et Kir.) Sch.Blp· will be dissolved in 30% (V/V) When the methanol solution passes through a column of a porous polystyrene resin as a carrier, and then 50% (V/V) of methanol is passed through the column, the component adsorbed by the porous polystyrene resin. 4. A melanin production inhibitor containing the following components as an active ingredient: an extract from Saussurea involucrate (Kar. et Kir.) Sch. Blp. 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, and then 50% (V/V) is fermented through the column 'and then methanol is passed through the column' by the methanol The components eluted from the column. A melanin production inhibitor ‘ contains dihydrodehydrogen eucalyptus vinegar represented by the following formula (1). [Chemical Formula 1] 100124698 Form No. A0101 Page 38 of 42 1002041807-0 / 201201825 ο 6 . A pharmaceutical, food or cosmetic having a melanin production inhibitory effect, comprising a melanin production inhibitor according to claim 1 of the patent application. 7. A pharmaceutical, food or cosmetic having a melanin production inhibitory effect, comprising a melanin production inhibitor according to item 2 of the patent application. 8. A pharmaceutical, food or cosmetic having a melanin production inhibitory effect, comprising a melanin production inhibitor according to item 3 of the patent application. 9. A pharmaceutical, food or cosmetic having a melanin production inhibitory effect, comprising a melanin production inhibitor according to item 4 of the patent application. 10. A pharmaceutical, food or cosmetic having a melanin production inhibitory effect, comprising a melanin production inhibitor according to item 5 of the patent application. 100124698 Form NumberΑ0101 Page 39/Total 42 Page 1002041807-0