JP2002255883A - New compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new substance which is contained in propolis, orally has antitumor activity and is usable for a perfume and toiletries. SOLUTION: This compound is represented by general formula 1 or its salt. This method for producing the new compound comprises subjecting propolis to steam distillation and isolating the compound from distilled essential oil.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel substance contained in propolis.

[0002]

2. Description of the Related Art Propolis is a glue-like substance formed by mixing tree sap, plant sprout, exudate and the like collected by honeybees with beeswax. Honeybees repair nests with propolis. . It is famous that propolis was used as a natural antibacterial ingredient in mummies in ancient Egypt, but in addition to it, it has been widely used for anti-inflammatory drugs, analgesics, etc. It has been used for a long time as a folk medicine when taken internally. recent years,
Research has evolved to elucidate the various physiological actions and the like, and has been attracting attention as a raw material for health foods and functional foods intended to prevent, improve, and treat lifestyle-related diseases and other diseases.
Propolis is said to exert various effects when taken orally.For example, propolis is widely used as a raw material for health foods, etc., with the expectation of effects such as antibacterial, antioxidant, antitumor, carcinogenic, and immunostimulatory effects. It has become.

[0003]

However, as mentioned above, propolis is a mixture of various substances such as sap and resin of trees, various medicinal plants, pollen, beeswax, etc. as a source plant, and is contained in propolis. The substance has not been sufficiently elucidated, but rather the substance contained in the propolis has not been elucidated or identified. Therefore, an object of the present invention is to isolate and identify useful new substances contained in propolis.

[0004]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems and found that useful distillate oil obtained by distilling propolis contained a useful novel substance. Thus, the present invention has been completed.

That is, the present invention provides

Embedded image (Hereinafter, referred to as “the present compound”) and salts thereof. Since the present compound has a fragrance that is slightly refreshing and sweet and calms down when it is smelled, it is expected that the compound and its salt have the purpose of using the fragrance and its chemical structure. Activities related to tumor activity can be used for purposes.

Further, the present invention is an oral composition containing the present compound or an orally ingestible salt thereof (hereinafter, referred to as “the present oral composition”). The present oral composition includes those used for the purpose of the aroma possessed by the present compound or the activity related to the antitumor activity expected to be possessed by the present compound and its orally ingestible salt. .

Further, the present invention is a perfume composition containing the present compound (hereinafter referred to as “the present perfume composition”).
The present fragrance composition includes those used for the purpose of fragrance possessed by the present compound.

The present invention relates to a toilet article containing the present compound or a salt thereof (hereinafter referred to as “the toilet article”).
That. ). The toiletries include those used for the purpose of the aroma possessed by the present compound or the activity associated with the antitumor activity expected to be possessed by the present compound and salts thereof. The "toiletries" here
The term includes cosmetics, detergents, fragrances, and the like, as described below.

Further, the present invention is characterized in that the present compound or a salt thereof is isolated from the essential oil (hereinafter referred to as "the essential oil") obtained by steam distillation of propolis. (Hereinafter referred to as “the present compound production method”). Since the present compound production method is based on steam distillation of propolis, the present compound or its salt can be efficiently produced without lowering the distillation temperature (than ordinary distillation) and thermally denaturing the present compound or its salt in propolis. can do.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION The present compound and salts thereof The compound of the present invention (the present compound) has a structure represented by the above formula (1). The present invention includes the present compound itself and salts of the present compound. Here, the salt of the present compound is not particularly limited, and examples thereof include a metal salt formed by a phenolic hydroxyl group (for example, a sodium salt and a potassium salt). The present compound or a salt thereof can be used for various purposes. For example, since the present compound has a fragrance that is subtly refreshing and sweet and calms down when you smell it, the purpose of using the fragrance, or the present compound or a salt thereof, is based on the chemical structure of the present compound or The activity associated with the antitumor activity expected to be possessed by the salt can be used for the purpose.

Method for Producing the Present Compound The method for obtaining the present compound or a salt thereof is not particularly limited.
It may be chemically synthesized, or may be physically or chemically isolated from propolis because it is contained in propolis. In particular, according to the method for producing the present compound or its salt by isolating the present compound or its salt from the essential oil (the present essential oil) obtained by steam distillation of propolis and distilling it (the present compound producing method), Is preferable because it can be safely derived from natural products, and the present compound or a salt thereof can be efficiently produced. In addition,
The method of steam distillation of propolis can be any method that reduces the partial pressure of the distillate by lowering the partial pressure of the distillate (than ordinary distillation) by entraining the distillate vapor with steam. For example, a method in which an aqueous phase is present in a distillation still and a method in which distillation is performed while blowing water vapor can be exemplified. Further, the conditions for performing steam distillation may be any conditions as long as the present compound or a salt thereof can be obtained, and is not particularly limited. For example, published in Hirokawa Shoten, "13th Revised Japanese Pharmacopoeia Commentary" According to the method for testing the essential oil content in "Shinpakusho Test Method B-223", steam distillation may be performed by heating at an oil bath temperature of 120C for 5 hours. Furthermore, it goes without saying that the method of steam distillation of propolis may be steam distillation under reduced pressure (that is, steam distillation and vacuum distillation are performed together).

In order to isolate the present compound or a salt thereof from the distillate essential oil (essential oil), it is necessary to separate the present compound or a salt thereof from other compounds. Various methods known as separation methods may be used. For example, the present compound or its salt can be obtained by subjecting the essential oil to chromatography such as column chromatography or thin-layer chromatography, or separation operation such as distillation and extraction such as vacuum distillation or steam distillation. May be isolated. In addition, in a case where isolation of the present compound or a salt thereof is hindered by containing water in the present essential oil, the present essential oil may be brought into contact with a dehydrating agent.

The present oral composition The present invention provides an oral composition (the present oral composition) containing the present compound or an orally ingestible salt thereof. Here, the orally ingestible salt of the present compound is not particularly limited, and examples thereof include a metal salt formed with a phenolic hydroxyl group (for example, a sodium salt and a potassium salt). In addition, the present oral composition is not limited to one produced by mixing the isolated present compound or an orally ingestible salt thereof, and a mixture containing the present compound or an orally ingestible salt thereof ( For example, it may be manufactured by blending the present essential oil). The compound has a fragrance that is slightly refreshing and sweet and calms down when it is smelled, and its chemical structure indicates that the compound or its orally ingestible salt is associated with antitumor activity Since it is expected to have physiological activity, the present oral composition containing the present compound or an orally ingestible salt thereof includes those used for the purpose related to aroma and antitumor activity. (For example, ingestion for the purpose of imparting aroma to food, antitumor-related effects, and ingestion for the purpose of preventing tumors and the like).

The present oral composition is prepared by mixing the present compound or an orally ingestible salt thereof with a carrier such as an extender or an excipient which is acceptable as an oral composition, and solidifying such as tablets and pills. Or a syrup or the like prepared in a liquid form, or the compound or an orally ingestible salt thereof, for example, in the form of a drink (soft drink (coffee, cocoa, juice, mineral drink, tea drink, etc.) , Green tea, black tea, oolong tea, etc.),
Milk drinks, lactic acid drinks, yogurt drinks, carbonated drinks, alcoholic beverages (sake, Western wine (wine, honey wine (mead))
), Fruit liquor, etc.), spreads (custard cream,
Butter cream, peanut cream, chocolate cream, cheese cream, etc.), paste (fruit paste, vegetable paste, sesame paste, seaweed paste, etc.),
Western confectionery (chocolate, donut, pie, cream puff, eclair, muffin, waffle, gum, gummy, jelly, candy, cookies, crackers, biscuits,
Snacks, cakes, puddings, etc.), Japanese sweets (candy, rice crackers, Karinto, hail, dumplings, rice balls, Daifuku, soybean paste, mochi, bean paste, buns, castella, anmitsu, sheep, etc.),
Frozen snacks (ice cream, popsicles, sorbet, shaved ice, etc.), retort foods (curry, beef bowl, Chinese rice bowl, porridge, rice porridge, miso soup, soup, meat sauce, demiglace sauce, meatball, hamburger, oden seeds, red rice, yakitori, teacup steamed) Etc.), instant food (instant noodles, instant udon, instant soba, instant yakisoba, instant spaghetti, instant wonton noodles, instant shiruko, miso soup, powdered soup, powdered juice, hot cake mix, etc.) Canned foods, jelly foods (jelly, agar, terrine, jelly drinks, etc.), seasonings (salts, natural salt, soy sauce, mirin, vinegar (grain vinegar, honey vinegar, etc.), sugar, honey, miso, dressing, umami seasoning Ingredients, complex seasonings, sauces, mayonnaise, ketchup, sprinkle, Tentsuyu, Noodle soup, Dashi-no-Matsu, Chinese soup Pu, Chinese porcelain (mapo tofu, chinjaorose), bouillon, grilled meat sauce, cold shabu sauce, curry roux, stew roux, etc.), beekeeping products (honey, royal jelly, propolis, pollen load) Pollen dumplings), bee pups, etc.), dairy products (milk, cheese, yogurt, fresh cream, etc.), processed fruits (jam, marmalade, syrup pickles, dried fruits, etc.),
Processed vegetables (vegetable jam, etc.), cereal processed foods (noodles, pasta, bread, rice noodles, etc.), pickles (takuan, nara pickles, kimchi pickles, fukugami pickles, rakkyo pickles, Chinese cabbage pickles, mustard pickles, shibazuke pickles, light pickles , Pickles, etc.), pickles (instant pickles, kimchi, etc.), fish products (kamaboko, chikuwa, hampan, etc.), meat products (ham, sausage, salami, bacon, etc.), delicacies (saki) Sardines, cod, sea urchin, sea squid, squid, octopus, kawahagi mirinboshi, pufferfish mirinboshi, smoked squid, salted konowata, etc., dried food (seasoned laver, etc.), side dishes ( Fish, fried, stir-fried, grilled, boiled, vinegared, etc., frozen foods (fried shrimp, croquettes, spring rolls, tonkatsu, shomai,
Dumplings, hamburgers, takoyaki, imagawa-yaki (rotary-yaki),
It may be added and blended to meat bean, anman bean, etc., fats and oils foods (salad oil, margarine, butter) and the like, or foods (including drinking water) containing the present compound or an orally ingestible salt thereof. )).

The present oral composition can be used for so-called health foods, functional foods, dietary supplements, supplements, foods for specified health use (one of the Ministry of Health, Labor and Welfare, health foods), and nutritional foods (the Ministry of Health, Labor and Welfare, health foods 1), food for the sick / combined food for the sick (Ministry of Health, Labor and Welfare, a type of special use food) or food for the elderly (Ministry of Health, Labor and Welfare, a type of special use food) If present, plain tablets, sugar-coated tablets, granules, powders, tablets, capsules (including both hard capsules and soft capsules), chewable types, syrup types and the like can be used. Since the present compound or its orally ingestible salt is contained in the essential oil distilled by steam distillation of propolis (this essential oil), it is safe to use it as a component of the oral composition. There is no problem. Examples of the orally ingestible salt include, for example, a metal salt (for example, a sodium salt) formed by a phenolic hydroxyl group, and the like.

The compounding ratio of the present compound or the orally ingestible salt thereof in the present oral composition is not particularly limited and may be appropriately selected from a wide range. The amount of the present compound is usually 100% by weight of the present oral composition. % In the range of about 1 × 10 ^{−4 to} 95% by weight. The oral intake of the present oral composition is not particularly limited as long as the desired improvement, therapeutic or prophylactic effect is obtained, and usually the embodiment, the age of the patient,
It is appropriately selected according to gender, constitution, other conditions, type of disease and its degree. Usually, about 1 × 10 ^{−5 to} 85 mg / kg per day as the active compound of the present compound.
It can be taken in 1 to 4 times a day. In addition, the present oral composition may be used as a functional food, a health food, a health-oriented food, and the like.

The present fragrance composition The present invention further provides a fragrance composition (the present fragrance composition) containing the present compound. In addition, the present fragrance composition is not only manufactured by mixing the isolated present compound, but also manufactured by mixing a mixture containing the present compound (for example, the essential oil). Good. As described above, the present compound has a fragrance that is subtly refreshing and sweet, and has a calming sensation when smelling it, so that the composition containing the present compound is a fragrance composition utilizing the fragrance of the present compound. Can be used as

The present fragrance composition may contain components other than the present compound, and examples thereof include other fragrance compounds, solvents, and preservatives. And what adds this perfume composition is not specifically limited,
It can be added to various things for fragrance purposes, for example,
Can be added to toiletries. The "toiletries" herein include cosmetics, detergents and fragrances. The cosmetics included in the “toiletries” include, for example, (1) creams, milky lotions, lotions, serums, whitening agents, beauty packs, makeup base creams, foundations (base makeup, for example, Powder type, liquid type), control color, concealer, cheek color, eye color, eye liner, eyebrow, mascara, highlight color, shadow color, eye mask, eye cream, lipstick (lip color), lip balm, lip gloss, Lip lacquer, lip liner, sun cream, sun cream, calming lotion, body lotion, body lotion, shaving lotion, shaving cream, peeling agent, exfoliating pack, keratotic plug pack, body slimming gel, Eye makeup Ba, lip color remover, wipe lotion, skin care cosmetics including baby powder, etc., (2) hair (for hair) gels, hair (for hair) spray, hair liquid, hair tonic,
Hair mousse, pomade, tic, hair cream, hair wax, hair oil, hair (for hair) rinse, hair conditioner, hair (for hair) treatment,
Hair cosmetics, including hair repair agents, hair perm agents, hair manicure agents, hair dyes, hair bleaching agents, hair restorers, hair restorers, etc., (3) shampoos for hair, body shampoos, hand soaps, Soap (including solid, liquid and powder), cosmetic cleansing gel, cosmetic cleansing cream, cosmetic cleansing oil, cold cream, facial cleanser (facial cleansing foam, facial cleansing gel, cleansing wash, etc.), toothpaste (toothpaste, solid toothpaste) , Powdered toothpaste, water toothpaste, lubricated toothpaste, medicated toothpaste),
Body wash containing mouthwash, gargle, etc.
(4) Bath cosmetics including bath additives, bath oils, bath salts, hot springs, etc., (5) Nourishing cream for nails, nail polish (including base coat, top coat, nail color, etc.), remover, solvent (Nail polish diluent) and the like, nail cosmetics, (6) massage oil (oil applied to the body when massaging the body), and the like. Further, the detergent contained in the “toiletry product” referred to herein includes laundry detergent (including any of solid, liquid and powder),
Laundry detergent including laundry softener, laundry bleach, etc., dish detergent, polishing powder, bleach, bathroom cleaner, glass cleaner,
Residential detergents including carpet cleaners, floor cleaners and the like are included. Furthermore, the fragrance contained in the "toiletries" here includes a house fragrance (for example,
Includes indoor fragrance, car fragrance, toilet fragrance, refrigerator fragrance, etc. ), Perfume (parfum), eau de toilette (parfand toilet), eau de cologne, deodorant colon, deodorant spray, deodorant gel,
Colon spray, colon lotion, solid perfume, paste, perfume spray, aroma spray, air cleaning spray, deodorant spray, aroma oil, essential oil (essential oil), incense, incense, aroma candle, potpourri oil and the like are included. In addition, the present perfume composition can be added to the aforementioned oral composition for the purpose of flavoring.

The concentration of the present compound in the present fragrance composition and the amount of the present fragrance composition added to the fragrance composition for the purpose of flavoring may be determined by the type of the fragrance composition to be added, the method of use and the purpose. It may be appropriately determined depending on, but are not particularly limited, in terms of the amount of the compound of the perfume composition is contained in what is added, 1 × 10 ^{- 4}
９５95% by weight. In addition, since this compound is contained in the essential oil (this essential oil) distilled out by steam distillation of propolis, there is no safety problem even if it is used for various purposes.

The present toiletry article In addition, the present invention provides a toiletry article (the present toiletry article) containing the present compound or a salt thereof. In addition, the present toiletry product is manufactured not only by mixing the isolated present compound or a salt thereof, but also by mixing a mixture containing the compound or a salt thereof (eg, the essential oil). It may be something. Further, as described above, the salt of the present compound is not particularly limited, and examples thereof include a metal salt formed by a phenolic hydroxyl group (for example, a sodium salt and a potassium salt).
As described above, the present compound has a fragrance that is slightly refreshing and sweet, and has a calming sensation when it is smelled, and its chemical structure indicates that the present compound or a salt thereof has an activity related to antitumor activity. Therefore, the present toiletries containing the present compound or a salt thereof may be used for the activity related to the aroma or antitumor activity of the present compound (for example, use for the purpose of antitumor related effect). , For the purpose of preventing the occurrence of tumors, etc.).

Such toiletries include, but are not limited to, cosmetics, detergents and fragrances. The cosmetics included in the present toiletry products include, for example, (1) creams, milky lotions, lotions, serums,
Whitening agent, beauty pack agent, makeup base cream, foundation (base makeup agent, for example, powder type, liquid type), control color, concealer, teak color, eye color, eyeliner, eyebrow,
Mascara, highlight color, shadow color, eye mask, eye cream, lipstick, lip balm, lip gloss, lip lacquer, lip liner, tan cream, sun cream, calming lotion, body lotion, body lotion, mustache Shaving lotion, shaving cream, peeling agent, exfoliating pack, keratotic plug removing pack, body slimming gel,
Eye makeup remover, lip color remover, wiping lotion, skin cosmetics including baby powder, etc. (2) Hair (for hair) gel, hair (for hair) spray, hair liquid, hair tonic, hair mousse, pomade, tic , Hair cream, hair wax, hair oil, hair (for hair) rinse, hair conditioner, hair (for hair) treatment, hair repair, hair (hair) perm, hair (hair) nail polish, hair dye , Hair cosmetics including hair bleaching agents, hair tonics, hair restorers, etc., (3) hair shampoos, body shampoos, hand soaps, soaps (including solids, liquids and powders), cosmetic cleansing gels, cosmetic cleansing creams , Cosmetic cleansing oil, cold cream,
Body wash including face wash (face wash foam, face wash gel, cleansing wash, etc.), toothpaste (toothpaste, solid toothpaste, powder toothpaste, water toothpaste, lubricating toothpaste, medicated toothpaste), mouthwash, gargle, etc. (4) )Bath additive,
Bath cosmetics including bath oil, bath salt, hot spring source, etc. (5) Nourishing cream for nails, nail polish (including base coat, top coat, nail color, etc.), remover, solvent (manicure thinner), etc. And (6) massage oil (oil applied to the body when massaging the body) and the like. In addition, the detergent contained in the toiletries herein includes laundry detergents (including any of solid, liquid and powder), laundry detergents including laundry softeners, laundry bleaching agents, dishwashing detergents, and polishing powders. , Bleaching agents, bathroom cleaners, household cleaners, including glass cleaners, carpet cleaners, floor cleaners and the like.
Further, the fragrance contained in the toiletry product referred to herein includes house fragrances (eg, indoor fragrances, car fragrances, toilet fragrances, refrigerator fragrances, etc.), and perfumes (parfum). , Eau de Toilette (Palfand Wallet), Cologne, Deodorant Cologne, Deodorant Spray, Deodorant Gel, Cologne Spray, Cologne Lotion, Solid Perfume, Mixture, Powder Perfume, Aroma Spray, Air Cleaning Spray, Deodorant Spray, Aroma Oil, Essential Oil ( Essential oils), incense, incense,
Aroma candles, potpourri oil, etc. are included. Among the toiletry products that come into contact with the skin (for example, the cosmetics), the present compound or a salt thereof can be continuously held or adhered to the surface of the skin. Can exhibit the activity related to the antitumor activity expected to have for a long period of time.

The amount of the compound of the present invention, its salt or essential oil to be added to the toiletry product may be appropriately determined according to the type of the toiletry product, the method of use and the purpose, and is not particularly limited. Is usually 1 × 10 in terms of the amount of the present compound contained in toiletries.
^{-4 to} 95% by weight. In addition, since this compound or its salt is contained in the essential oil (this essential oil) distilled by steam distillation of propolis, there is no safety issue even if it is used for various toiletry products.

[0023]

EXAMPLES Examples and test examples will be given below to specifically explain the present invention. However, the present invention is not limited by the embodiments and the like.

Example 1 Steam Distillation Experiment Propolis (used by honey bees in an environment where alexin (plant) is present) was used as a crude drug in "13th revised Japanese Pharmacopoeia Manual" published by Hirokawa Shoten. Steam distillation was performed according to the test method for essential oil content in Test Method B-223. Specifically, first,
After pulverizing about 99.42 g of propolis, the pulverized propolis powder and 500 ml of distilled water were put into a 1000 ml round bottom flask. Attached to the round bottom flask was an essential oil meter (FIG. 1 shown in the above manual B-224).
At the upper end of the essential oil meter, a reflux condenser (the above manual B-22)
4) shown in FIG. 4 was installed. The scale tube of the essential oil meter was filled with water up to a reference line.

Next, the round bottom flask was placed in an oil bath for 12 hours.
Heat to 0 ° C. (oil bath temperature: 120 ° C.) and boil the contents of the round bottom flask (steam distillation). After boiling for 5 hours, stop heating and leave for a while (about 2-3 minutes)
did. Thereafter, the stopcock of the essential oil meter was opened, water was allowed to slowly flow out, and the oil layer (essential oil) was separated. The separated oil layer was completely dissolved in 50 ml of diethyl ether, and 2 g of anhydrous sodium sulfate was added to the diethyl ether solution, and left for about 1 day to remove water contained in the diethyl ether solution. Sodium sulfate was removed from the diethyl ether solution by filtration with a folded filter paper, and diethyl ether was distilled off from the diethyl ether solution under reduced pressure by an evaporator to obtain an essential oil (hereinafter, simply referred to as "essential oil"). When the essential oil was weighed, it was 5
At 32 mg, the essential oil was a transparent, low-viscosity oil with a light green tint, and emitted an extremely good aroma (a refreshing and sweet aroma that would calm down when you smell it) in a very small amount.

Example 2 Column Chromatography of Essential Oil A total of 550 g of propolis (ambient environment: alexin) was subjected to steam distillation in the same manner as in Example 1, and a total of about 1.
8747 g of essential oil was obtained. This essential oil was fractionated by column chromatography. Column is Φ40mm × 5
BW-300 (Fuji
Silysia (Fuji Silysia Chemical Ltd.), N
o. 702210) was used. First, petroleum ether was used as the developing solvent, and fraction 1 (eluting residue after solvent evaporation: 378.9 m
g), fraction 2 (residual mass after evaporation of the solvent: 22.44 m)
g), fraction 3 (residual mass after distilling off the solvent: 45.23 m)
g), fraction 4 (residue mass after evaporation of the solvent: 5.38 m)
g), fraction 5 (residual mass after evaporation of the solvent: 1.21 m)
g), fraction 6 (residual mass after evaporation of the solvent: 0.53 m)
g), fraction 7 (residual mass after evaporation of the solvent: 3.51 m)
g), fraction 8 (residual mass after evaporation of the solvent: 5.25 m)
g), fraction 9 (residue mass after evaporation of the solvent: 1.74 mg)
Was fractionated. After elution of fraction 9, the developing solvent was changed to diethyl ether, and the eluted fraction was designated as fraction 10 (residual mass after evaporating the solvent: 1.2711 g).

Example 3 Column Chromatography of Fraction 10 Fraction 10 obtained in Example 2 was further fractionated by column chromatography. The column is Φ
BW-300 in a cylindrical glass cylinder of 30 mm x 65 cm
(No. 702210, manufactured by Fuji Silysia (Fuji Silysia Chemical Ltd.)) was used. In the fractionation, fraction 11 (residual mass after distilling off the solvent: 1.95 mg) and fraction 12 (residual mass after distilling off the solvent: 7) were detected while eluting components were detected by thin-layer chromatography. .85 mg), fraction 13 (mass of residue after solvent evaporation: 2.63 mg), fraction 14 (mass of residue after solvent evaporation: 0.82 mg), fraction 15 (residue after solvent evaporation). Fraction mass: 3.56 mg), fraction 16 (residual mass after distilling off the solvent: 14.54 mg), fraction 17 (residual mass after distilling off the solvent: 152.69 mg), fraction 18 (solvent distillation) Fraction 19 (residual weight after solvent evaporation: 56.66 mg), Fraction 20 (residual weight after solvent distillation: 155.29 mg), fraction 21 (residue mass after solvent evaporation: 21.57 mg), fraction 22 (residue mass after solvent evaporation: 80.21 mg), fraction 3 (residue weight after solvent evaporation: 119.47 mg), fraction 24 (residue weight after solvent distillation: 160.30 mg), fraction 25 (residue weight after solvent distillation: 21.57 mg) ) Was fractionated. As a developing solvent, n-hexane and ethyl acetate were used.
Hexane (volume): ethyl acetate (volume) ratio of 20
Column chromatography was performed with increasing proportions of ethyl acetate from 0: 1. The ratio of n-hexane (volume): ethyl acetate (volume) is 200: 1 → 20
The fraction was changed in the order of 0: 5 → 19: 1 → 9: 1 → 0: 1 while monitoring the fractionation status on thin layer chromatography (hereinafter, referred to as “TLC”), and the desired fraction was obtained. After confirming the release, the ratio was changed to the next solvent. Further, here, as TLC, Silic manufactured by Merck
Agel 60 F254 (No. 1.05715) was used, and the color was developed by spraying the anisaldehyde-sulfuric acid reagent on TLC and then heating.

(Example 4: Isolation of the present compound) Fraction 19 (about 56.7 mg) obtained in Example 3 was further developed and purified by preparative thin-layer chromatography (TLC). As TLC for detection, Silicagel 60 F254 manufactured by Merck (No. 1.0)
Using 5715), the color was developed by spraying the anisaldehyde-sulfuric acid reagent on TLC and then heating. As TLC for purification (for preparative), Merck 12
PLC plates silicagel 60 F
254 (No. 1.05717) was used. As a developing solvent, a 9: 1 mixture of n-hexane and ethyl acetate was used. By this condition, the mobility R of TLC
A portion of a spot appearing at f = 0.6 (n-hexane: ethyl acetate = 9: 1) is scraped, dissolved in ethyl acetate, and filtered to obtain an ethyl acetate solution, and the ethyl acetate is distilled off from the ethyl acetate solution. As a result, a wax-like substance (the present compound: 27.0 mg) was obtained. The resulting white wax-like substance had a fragrance that was faintly refreshing and sweet and calming when smelled.

(Example 5: Identification of the present compound) The wax (wax) -like substance (white) obtained in Example 4 was analyzed by an electron impact mass spectrometer (EIMS: Electron Im).
When analyzed by Pact Mass Spectrometry), m / z (value obtained by dividing mass by electric charge) was obtained.
Shows a molecular ion peak at 256 (molecular weight 256),
69 shows the fragment ion peak of the prenyl group. In addition, GCMS-Q
P5050A (manufactured by Shimadzu Corporation) was used under the analysis conditions of an acceleration voltage of 70 eV (electron volt).

Further, the wax-like substance (white) obtained in Example 4 was subjected to ¹ H and ¹³ C nuclear magnetic resonance analysis (hereinafter, referred to as “NMR”). Table 1 shows the assignment of these ¹ H-NMR and ¹³ C-NMR peaks.
Shown in In addition, in both ¹ H-NMR and ¹³ C-NMR, Unity-50 manufactured by Varian (Varian) is used.
0 (500 MHz). ¹ H-NMR spectra were measured in CDCl ₃ at 500 MHz. Chemical shift δ (ppm) is expressed as CDCl ₃ (δH
7.24). ^{The 13} C-NMR spectrum was measured in CDCl ₃ at 125 MHz. Using TMS (tetramethylsilane) as an internal standard, the chemical shift δ (ppm) was calculated using CDCl ₃ (δC7
7.0).

(Table 1) Assignment of NMR peaks δH δC 1 5.36 (s, -OH) 152.6 2-127.2 3 7.03 (s) 125.8 4-130.05 7.03 (S) 125.8 6-127.2 7 6.60 (dd, J = 10.76, 17.62 Hz) 136.7 8 5.56 (d, J = 17.61, 0.91 Hz) 111. 1 5.07 (d, J = 0.91, 10.78 Hz) 9 3.33 (d, J = 7.32) 29.7 10 5.31 (m) 122.0 11-134.3 12 1 .77 (s) 17.8 13 1.77 (s) 25.8 14 3.33 (d, J = 7.32 Hz) 29.7 15 5.31 (m) 122.0 16-134.3 17 1.77 (s) 17.8 18 1.77 (s) 25.8

Further, the wack obtained according to Example 4
(IR) (IR absorption spectrum)
3612 cm)^-1To Fe
3087 cm with absorption based on phenolic hydroxyl group^-1, 1
662cm^-1, 908cm ^-1Absorption based on double bonds
Yield was observed. In addition, the IR analyzer is JASCO
Using FT / IR-410 manufactured by (JASCO Corporation)
Was.

The above EIMS, ¹ H-NMR, ¹³ C-
From the results of NMR and IR analysis, the wax (wax) -like substance (white) obtained in Example 4 had a molecular weight of 256.
And the molecular formula was C ₁₈ H ₂₄ O, which was confirmed to be the present compound.

(Example 6: Formulation 1 of oral composition) (1) The present compound (obtained in Example 4) 40 mg (2) Soybean oil 150 mg (3) Beeswax 20 mg (4) Glycerin fatty acid ester 30 mg The raw materials (1) to (4) were mixed according to a standard method and filled into soft gelatin capsules to obtain granular health food (the present oral composition). (1) This compound is used for the purpose of antitumor activity (prevention of tumor development), (2) soybean oil is used as diluent oil and antioxidant, and (3) beeswax is used as an intestinal medicine and granulating aid. And (4) glycerin fatty acid ester was blended as an excipient.

(Example 7: Formulation 2 of oral composition) (1) The present compound (obtained in Example 4) 40 mg (2) Chamomile flower (dried product of chamomile flower) 1 pinch (3) Lavender (Dry herb) 1 knob Put the ingredients of (2) and (3) above in 300 ml of hot water and boil over low heat for 5 minutes. Take the broth in a cup and, while hot, wax (wax) like substance (1) above (white)
Was dropped and mixed to prepare a tea beverage (the present oral composition). This tea beverage was consumed while inhaling the rising steam while it was hot. In addition, (1) the present compound is used for the purpose of activity (tumor generation prevention) related to fragrance (fragrance) and antitumor properties, and (2)
Chamomile flowers are used for sedation, analgesic, anti-inflammatory and digestive effects, and (3) lavender is used for sedation, analgesic,
They were formulated for the purpose of improving insomnia and autonomic imbalance. (1) In addition to drinking the present compound, the present compound is volatilized by dropping and mixing the present compound into hot boiling broth, and the compound is absorbed from the intranasal mucosa by inhaling the vaporized vapor. Is expected.

(Example 8: Formulation 1 of toiletry product) (1) The present compound (obtained in Example 4) 40 mg (2) Grapefruit essential oil 100 μl (3) Jojoba oil 10 ml From the above (1) to (3) The above ingredients were mixed to give a whole body massage oil (this toiletry product). In addition,
(1) The compound is used for the purpose of antitumor activity (prevention of tumor development), fragrance (flavoring), (2) grapefruit essential oil is used for general pacing of massage, and (3) jojoba oil. Was formulated for the purpose of exhibiting high penetrative power and skin protection effect as an easy-to-handle base oil for dilution.

(Example 9: Formulation 2 of toiletries) (1) The present compound (obtained in Example 4) 80 mg (2) Sodium bicarbonate 20.0 g (3) Sodium sulfate 2.5 g (4) Honey 3.0 g (5) Royal jelly 0.5 g (6) Bergamot essential oil 100 μl The raw materials from (1) to (6) were mixed according to a conventional method to obtain a bath additive (this toiletry product) to be dissolved in 200 l of hot water. (1) The present compound is used for the purpose of perfume (perfume) and antitumor activity (prevention of tumor development).
(2) Sodium bicarbonate has the purpose of promoting blood circulation, (3) sodium sulfate has the purpose of promoting blood circulation, (4) honey has the purpose of moisturizing effect, and (5) royal jelly has the purpose of moisturizing effect and beautiful skin effect. And (6) bergamot essential oil was added for the purpose of fragrance (perfume), recovery from nervous breakdown, recovery from nervous fatigue, prevention of eczema and pimples on the back, and bactericidal effect.

(Example 10: Formulation of perfume composition) (1) The present compound 80 mg (2) 100% ethanol 100 ml (3) Surfactant 0.1 mg The above-mentioned raw materials (1) to (3) are mixed well. Then, the fragrance was gradually filled into a container capable of being diffused, and used as an indoor fragrance.

The oral compositions of Examples 6 and 7 and
In each of the toiletry product of No. 9 and the fragrance composition of Example 10, the present compound (obtained in Example 4)
Oral compositions, toiletries, and fragrance compositions were prepared in the same manner using the essential oil obtained in Example 1 in place of the above. In addition,
The essential oil obtained in Example 1 was 5% in the oral composition of Example 6.
0 μl, 10 μl for the oral composition of Example 7, 20 μl for the toiletry of Example 8, 100 μl for the toiletry of Example 9, and 50 μl for the fragrance composition of Example 10. Each was compounded in place of the present compound (obtained in Example 4).

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 31/05 A61K 31/05 A61P 35/00 A61P 35/00 C07C 37/76 C07C 37/76 C11B 9 / 00 C11B 9/00 D (72) Inventor Tomofumi Miyamoto 1-11-2, Aobadai, Munakata-shi, Fukuoka (72) Inventor Toshihide Kusunori 4-13-8-203 Hakozaki, Higashi-ku, Fukuoka, Fukuoka F-term (reference) 4B018 MD08 MD16 MD78 ME08 MF01 4C083 AA072 AA122 AB312 AB352 AC471 AC472 CC06 CC25 DD23 DD30 EE12 EE41 4C206 AA01 AA03 AA04 CA16 MA01 MA04 MA72 NA14 ZB26 4H006 AA01 AA02 AA03 AB12 AB14 AB28 AD14 FC52 FE13 4H0BA BA4509

Claims (5)

[Claims] (1) Formula (1) And a salt thereof. 2. An oral composition comprising the compound of claim 1 or an orally ingestible salt thereof. 3. A fragrance composition comprising the compound according to claim 1. 4. Toiletries containing the compound according to claim 1 or a salt thereof. 5. A process in which propolis is subjected to steam distillation and the distillate of essential oil is subjected to the formula: The method for producing a compound or a salt thereof according to claim 1, wherein the compound or a salt thereof is isolated.