JP2008081440A - Aromatase activity promoter - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an aromatase activity promoter excellent in an aromatase activity-promoting effect. <P>SOLUTION: This aromatase activity promoter is characterized by containing one or more selected from Hibiscusrosa-sinensis, Casuarina plants, Sasa kurilensis, Aralia cordata, Osmunda japonica Thunb., Matteuccia struthiopteris (L.)Todaro, Centaurea Cyannus L., Eryobotrya japonica (Thunb.)Lindl., Prunus speciosa, Calophyllum inophyllum, Cyathea spinulosa, and Suillus grevillei as an active ingredient. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an aromatase activity promoter.

In vivo, aromatase is an enzyme that biosynthesizes estrogen from testosterone. Conventionally, when estrogen secretion decreases due to aging, autonomic ataxia (hot flashes, hyperhidrosis, etc.), osteoporosis (low back pain, fractures, etc.), cardiovascular diseases (arteriosclerosis, increased cholesterol level, cerebrovascular disease, etc.) ), Neuropsychiatric symptoms (depression, insomnia, etc.), genitourinary tract (dysuria, vaginitis, intercourse disorders, etc.), skin dryness, dementia, etc. are known to appear.
Then, although it is disclosed regarding the plant which improves said symptom by accelerating | stimulating the activity of aromatase (refer patent documents 1-3), the effect by these is not enough and more effective aromatase activation. The drug was expected.

As for Bushou, there are known glycosidase inhibitory effect (see Patent Document 4), hyaluronidase activity inhibitory effect (see Patent Document 5), lipolysis promoting effect (see Patent Document 6), etc., but Bushroom has aromatase activity promoting effect. It has never been known to have.
As for the use of the asteraceae plant, the composition for oral cavity containing a humus extract as a glucose transferase inhibitor (see Patent Document 7), and a baked product obtained by calcination of cinnamon ash and graphite silica are included as active ingredients. Plant growth agent, skin agent, plant freshness-preserving agent (see Patent Documents 8 to 10), hair restorer (see Patent Document 11) containing ellagitannin contained in the genus Mokumao as an active ingredient, lipase inhibitory activity and antioxidant activity An anti-obesity agent (see Patent Document 12) and the like, which contains an extract of cinnamon having an active ingredient as an active ingredient, is known, but it has not been known so far that euphorus has an aromatase activity promoting effect.
In addition to using larvae as an edible, Nemagaridake is known to have a keratinase inhibitory effect (see Patent Document 13) and the like, but it has not been known that Nemagaridake has an aromatase activity promoting effect.
In addition to edible shoots, udo is known to have a lipase inhibitory effect (see Patent Document 14), a hair-growth effect (see Patent Document 15), etc., but it has been known so far that Udo has an aromatase activity promoting effect. It wasn't.
Although cornflower has an antibacterial effect (see Patent Document 16), a hair nourishing effect (see Patent Document 17) and the like, it has not been known that cornflower has an aromatase activity promoting effect.
In addition to using flesh as an edible, loquat has been used as a herbal medicine. Loquat is known to have an anti-acne effect (see Patent Document 18), an elastase inhibitory action (see Patent Document 19), and the like, but it has never been known that loquat has an aromatase activity promoting effect.
Sakura has known hyaluronidase inhibitory action (see Patent Document 20), deodorant / antibacterial action (see Patent Document 21), and the like, but it has not been known so far that Sakura has an aromatase activity promoting effect.
Terihaboku is known to have a matrix metalloprotease inhibitory action (see Patent Document 22), an antiallergic action (see Patent Document 23) and the like, but it has not been known that Terihaboku has an aromatase activity promoting effect.
Hego is known to have a skin-beautifying action, a whitening action (see Patent Document 24) and the like, but it has not been known that hego has an aromatase activity promoting effect.
Hanaiguchi has known α-glucosidase inhibitory action (see Patent Document 25), moisturizing / whitening action (see Patent Document 26), vascular endothelial cell proliferation promoting action (see Patent Document 27), and the like. It has not been known so far to have a promoting effect.
Young shoots found in springs of spring and kogomi are widely used for food, but it has not been known that springs and kogomi have an aromatase activity promoting effect.

JP 2004-189609 A JP 2005-338772 A JP 2005-343873 A JP 2000-239164 A Japanese Patent Laid-Open No. 2003-12489 Japanese Patent Laid-Open No. 2005-60366 JP 59-152313 A JP 2002-238351 A Japanese Patent Laid-Open No. 2003-300088 JP 2003-250438 A JP 2004-091390 A JP-A-2005-060334 JP 2004-161621 A JP-A-5-255100 Japanese Patent Laid-Open No. 10-218737 JP 2000-44419 A JP 2001-163734 A JP-A-10-265364 Japanese Patent Laid-Open No. 11-171758 JP 2003-012489 A JP-A-2005-198854 JP 2001-192317 A JP 2005-272326 A JP 2003-95910 A JP 2000-063281 A JP-A-9-227333 JP 2000-212059 A

  The objective of this invention is providing the aromatase activity promoter excellent in the aromatase activity promotion effect.

  The present invention provides an aromatase activity promoter comprising, as an active ingredient, one or more selected from Bushouge, Mokumau, Nemagari-dake, Udo, Wind-up spring, Kogomi, Cornflower, Biwa, Sakura, Terihaboku, Hegoh, Hanaiguchi. Is.

  According to the present invention, it exhibits an excellent aromatase activity promoting effect, including autonomic ataxia (hot flashes, hyperhidrosis, etc.), osteoporosis (back pain, fractures, etc.), cardiovascular disease (arteriosclerosis, increased cholesterol level, Prevent or improve symptoms caused by estrogen deficiency, such as cerebral apoplexy), neuropsychiatric symptoms (depression, insomnia, etc.), genitourinary tract (dysuria, vaginitis, sexual intercourse, etc.), dry skin, dementia, etc. To do.

  The active ingredients of the aromatase activity promoter of the present invention will be introduced respectively.

Bushsouge ( Hibiscus rosa-sinensis ) is a plant belonging to the family Malvaceae and Hibiscus , and in addition to those naturally occurring, varieties for horticulture and cultivation may be used. Bushsouge can use whole parts such as whole grass, above-ground parts, roots, stems, leaves, flowers, and fruits, but it is preferable to use leaves from the viewpoint of effectiveness.

The Casuarina, using a plant belonging to the casuarinaceae (Casuarinaceae) Casuarina species (Casuarina). Examples of such genus Eucalyptus plants include Casuarina equisetifolia L., Mokumau (also known as Mauahiba Casuarina stricta Ait .; Casuarina quadrivalvis Labill.), Casuarina sumatrana Jungh., Casuarina collina Pos Yamamokumaou (Casuarina junghuhniana Miq.), Rose Mok ephedra (Casuarina torulosa Ait.), Kasuarina-Papuana (Casuarina papuana S. Moore), River Oak (Casuarina cunninghamiana), swamp oak (Casuarina glauca), Shidaremokumaou (Casuarina rumphiana), Examples are Casuarina suberosa and the like. You can use any part of the tree, branches, leaves, flowers, seeds, bark, sap, roots, stems, buds, etc. It is good to use branches and leaves from the point of effectiveness.

Sasa kurilensis belongs to the genus Sasa. Nemagaridake may use any part such as a stem, a leaf, a young stalk, and a skin, but a young stalk may be used from the viewpoint of effectiveness.

Udo ( Aralia cordata ) belongs to the genus Arachnaceae. Although the use site | part of Udo is not specifically limited, From a point of effectiveness, it is good to use a young shoot and a rhizome.

Wind-up spring ( Osmunda japonica Thunb.) Is a fern plant belonging to the spring-fly family. The use part of the mainspring is not particularly limited, but it is preferable to use young shoots found in spring from the viewpoint of effectiveness.

Kogomi ( Matteuccia struthiopteris (L.) Todaro) is a fern plant belonging to the genus Kusotatsu. . Although the use site | part of kogomi is not specifically limited, From the point of effectiveness, it is good to use the young bud seen in spring.

Cornflower ( Centaurea Cyannus L.) is a dicotyledonous plant belonging to the genus Cornaceae . Although the use part of a cornflower is not specifically limited, It is good to use a flower from the point of effectiveness.

Biwa ( Eryobotrya japonica (Thunb.) Lindl .; Mespilus japonica Thunb.) Is an evergreen tree belonging to the genus Biwa. The use site of loquat is not particularly limited, but leaves may be used from the viewpoint of effectiveness.

Sakura ( Prunus speciosa ) is a deciduous tree belonging to the genus Rosaceae. In the present invention, it is preferable to use a cultivar called Yoshino Yoshino. The site of cherry blossom use is not particularly limited, but leaves may be used from the viewpoint of effectiveness.

As Terihaboku, a plant belonging to the genus Terihaboku of Hypericaceae is used. Such Calophyllum inophyllum plant of the genus Calophyllum inophyllum (Calophyllum inophyllum), Calophyllum-Ino film (Calophyllum inophyllum), Calophyllum-Neoebudikumu (Calophyllum neoebudicum), Calophyllum-Burashiriensu and its variants, (Calophyllum brasiliense;. Calophyllum brasiliense var antillanum ; Calophyllum brasiliense var. Rekoi ), Calophyllum antillanum , Calophyllum calaba , Calophyllum jacquinii , Calophyllum lucidum , Calophyllum lucidum , Calophyllum pialoum piaroanum ) and Calophylum chiapense . Although the use site of Terihaboku is not particularly limited, it is better to use leaves from the viewpoint of effectiveness.

As the hego, a fern plant belonging to the genus Hegoaceae is used. Such cyathea plants Hego (Cyathea spinulosa; Cyathea fauriei; Alsophila fauriei), Kusamaruhachi (Cyathea hancockii), GORE to Mori (Gore to shade) (Cyathea lepifera), Maruhachi (Cyathea mertensiana), GORE into bantams (Cyathea Metteniana ), Mehego ( Cyathea ogurae ), Blackhego ( Onihego ) ( Cyathea podophylla ), Edauchi Hegogo ( Cyathea tuyamae ), and variants thereof. Although the use site | part of a hego is not specifically limited, From the point of effectiveness, it is good to use a leaf.

As the honey beetle, a basidiomycete belonging to the genus Nyuriguchi is used. Such Suillus luteus genus Basidiomycetes, suillus grevillei (Suillus grevillei), safflower Iguchi (Suillus pictus), Kinoboriiguchi (Suillus spectabilis), white slime Iguchi (Suillus laricinus), Kinumeriiguchi (Suillus americanus), slime Tsubai croaker (Suillus subluteus), Goyouiguchi Examples include ( Suillus placidus ), scallop ( Suillus luteus ), spotted bamboo ( Suillus granulatus ), cotton scallop ( Suillus tomentosus ), agaric ( Suillus bovinus ), and variants thereof. There are no particular restrictions on the use site of the honey bees, but a fruiting body may be used in terms of effectiveness.

  When using the above plants and the like, they can be pulverized as they are, but it is preferable to use an extract. For extraction, any part of a plant such as a trunk, a branch, a leaf, a flower, a seed, a bark, a sap, a root, a stem, a bud, a fruiting body, a mycelium, or a spore may be used. In the extraction, the raw material may be used as it is. However, in consideration of the extraction efficiency, it is preferable to perform the extraction after performing processing such as shredding, drying, and pulverization. The extraction can be performed by immersing in an extraction solvent or by an extraction method using a supercritical fluid or a subcritical fluid. In order to increase the extraction efficiency, homogenization may be performed in stirring or an extraction solvent. The extraction temperature is suitably about 5 ° C. to the boiling point of the extraction solvent. The extraction time varies depending on the type of extraction solvent and the extraction temperature, but it is appropriate to set it to about 1 hour to 14 days.

  Extraction solvents include water, lower alcohols such as methanol, ethanol, propanol and isopropanol, polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, dipropylene glycol and glycerin, ethers such as ethyl ether and propyl ether. , Solvents such as esters such as butyl acetate and ethyl acetate, and ketones such as acetone and ethyl methyl ketone can be used, and one or more of these can be selected and used. Further, physiological saline, phosphate buffer, phosphate buffered saline, or the like may be used. Furthermore, you may use 1 type, or 2 or more types of supercritical fluids and subcritical fluids, such as water, a carbon dioxide, ethylene, propylene, ethanol, methanol, ammonia. It is also possible to extract under pressure using an autoclave or the like.

  The solvent extract can be used as it is, but the concentrated and dried product can be used again by dissolving it in water or a polar solvent. Alternatively, it may be used after a purification treatment such as desalting or a fractionation treatment by column chromatography or the like. The said extract, its processed material, and a fraction can be freeze-dried after each process and fractionation, and it can also be melt | dissolved and used for a solvent at the time of use.

  An aromatase activity promoter containing one or more selected from Bushouge, Mokumau, Negararidake, Udo, Wind-up, Kogomi, Cornflower, Biwa, Sakura, Terihaboku, Hego, Hanaiguchi, and aromatase activity promoter should be deficient in estrogen Autonomic ataxia caused by (hot flashes, hyperhidrosis, etc.), osteoporosis (low back pain, fractures, etc.), cardiovascular disease (arteriosclerosis, elevated cholesterol levels, stroke, etc.), neuropsychiatric symptoms (depression, insomnia, etc.), It is effective in preventing or improving symptoms such as genitourinary tract (dysuria, vaginitis, intercourse disorder), dry skin, and dementia.

  If the aromatase activity promoter of the present invention contains one or more selected from Bushouge, Mokumau, Nemagaridake, Udo, Wind-up spring, Kokomi, Cornflower, Biwa, Sakura, Terihaboku, Hego, Hanaiguchi The form is not limited, and can be used as, for example, foods and drinks such as health foods (special health foods, nutritional foods) and health foods, pharmaceuticals, cosmetics, quasi drugs, and the like.

  When used as a food or drink, it can be directly ingested as it is, or it can be ingested in a form that is easy to take, such as capsules, tablets, and granules, using known carriers and auxiliaries. The content of each extract in these molding agents is 0.01 to 10% by mass, preferably 0.1 to 5% by mass. In addition, mixed with food and drink ingredients, chewing gum, chocolate, candy, jelly, biscuits, crackers and other confectionery, ice cream, frozen desserts such as ice confectionery, tea, soft drinks, energy drinks, beauty drinks, and other udon noodles Noodles such as Chinese noodles, spaghetti, instant noodles, kneaded products such as rice cakes, bamboo rings, half pieces, seasonings such as dressing, mayonnaise, sauces, fats and oils such as margarine, butter, salad oil, bread, ham, soup, retort food, It can be used for all foods and drinks such as frozen foods. When ingesting these eating and drinking compositions, the intake is 0.01 to 1000 mg / kg body weight per adult day, preferably 0.1 to 100 mg / kg body weight in terms of each extract. Moreover, it can also be used as feed or pet food for livestock or pets, and its intake is preferably 0.001 to 1000 mg / kg body weight per day in terms of each extract.

  When used as a pharmaceutical, the dosage form is not particularly limited, and examples thereof include capsules, tablets, granules, liquids, injections, suppositories, and patches. In formulation, other pharmaceutically acceptable formulation materials such as excipients, disintegrants, lubricants, binders, antioxidants, colorants, anti-aggregation agents, absorption enhancers, solubilizers An agent, a stabilizer and the like can be added as appropriate. The dosage of these preparations is 0.01 to 1000 mg / kg body weight per adult day, preferably 0.1 to 100 mg / kg body weight per day in terms of each extract. Moreover, it can be used also as a pharmaceutical for livestock and pets, and its dosage is preferably 0.01 to 1000 mg / kg body weight per day in terms of each extract.

  When used as a cosmetic or quasi-drug, the dosage form is arbitrary, and for example, it can be provided as a solubilizing system such as lotion, an emulsifying system such as cream or emulsion, or a dispersing system such as calamine lotion. Furthermore, it can also be provided in various dosage forms such as aerosols, ointments, powders and granules filled with a propellant.

  The cosmetics and quasi-drugs containing the aromatase activity promoter of the present invention are oily, which is usually blended in cosmetics, quasi-drugs, and detergents as needed in addition to the aromatase activity promoter. Ingredients, cell activators, antioxidants, moisturizers, powders, pigments, emulsifiers, solubilizers, detergents, UV absorbers, thickeners, drugs, fragrances, resins, antibacterial and antifungal agents, alcohols, etc. Can be appropriately blended.

  The blending amount when the aromatase activity promoter of the present invention is blended into cosmetics and quasi drugs can be adjusted depending on the type of skin cosmetics and quasi drugs, the purpose of use, etc. From the point, 0.0001-50.0 mass% is preferable with respect to the whole quantity, More preferably, it is 0.001-25.0 mass%.

  Hereinafter, production examples of extracts such as various plants that are active ingredients of aromatase activity promoters, tests for evaluating each action, prescription examples as skin preparations and foods, and usage tests will be described in more detail. The technical scope of the present invention is not limited thereby.

[Extraction method 1]
100 g of a dry pulverized product such as a plant was dispersed in 2.0 kg of a 50 vol% ethanol aqueous solution and extracted at room temperature for 2 hours with stirring. The extract supernatant was filtered off, concentrated under reduced pressure, and then lyophilized to obtain an extract.

[Extraction method 2]
100 g of a dry pulverized product such as a plant was dispersed in 2.0 kg of purified water and extracted by heating at 120 ° C. for 20 minutes. The extract supernatant was filtered and lyophilized to obtain an extract.

  Examples of aromatase activity promoters are summarized in Table 1.

  The aromatase activity promoting action of the above examples was evaluated.

[Aromatase activity promoting action]
To 4 μL of the sample solution prepared at each concentration, a mixed solution of NADP ⁺ , MgCl ₂ , glucose-6-phosphate, glucose-6-phosphate dehydrogenase, and control insect cell membrane protein (CPY19 / MFC high-throughput inhibitor screening kit (Hige Throughput Inhibitor Screening Kit) (manufactured by BD Biosciences) 96 μL was added and heated to 37 ° C. for 10 minutes. 15 mM CYP19 (aromatase), 100 μL of 50 μM 7-methoxy-4-trifluoromethylcoumarin (substrate) solution was added, and the mixture was heated to 37 ° C. for 30 minutes. The reaction was stopped by adding 75 μL of 100 mM Tris base.
Fluorescence measurement was performed at an excitation wavelength of 409 nm and an emission wavelength of 530 nm. Since 7-methoxy-4-trifluoromethylcoumarin is decomposed by CYP19 and 7-hydroxy-4-trifluoromethylcoumarin is generated to produce fluorescence, the aromatase activity promoting ability was quantified by fluorescence measurement.
The obtained results are shown in Tables 2 to 13 by relative values when the aromatase activity promoting action in the control without addition of the sample is taken as 100. Note that * and ** in the table indicate a significance probability of less than 5% (P <0.05) with respect to the significance probability P value in t-test, and the significance probability is less than 1% (P <0.01). Is represented by ** respectively.

  As is clear from Tables 2 to 13, all Examples of the present invention were found to have a high aromatase activity promoting effect.

Claims (1)

An aromatase activity promoter comprising one or more selected from Bushouge, Mokumau, Nemagari-dake, Udo, Wind-up, Kogomi, Cornflower, Biwa, Sakura, Terihaboku, Hego, Hanaiguchi.