JP2003146870A - Lipid degradation promoter and method of slimming body - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a lipid degradation promoter that is very effective for improvement of the obese constitution by reducing fatty tissues of the whole body or local parts thereof, or for inhibiting and preventing the obesity by inhibiting the lipid tissues from being increased. SOLUTION: The lipid degradation promoter is a compound represented by general formula (1). The lipid decomposition promoter is used by adding to external preparations for skin and to drink and food.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to improvement of the obesity constitution by promoting a decrease in systemic or local adipose tissue, or promotion of lipolysis effective in suppressing or preventing obesity by preventing the increase of the adipose tissue. And an external preparation for skin and a food and drink composition.

[0002]

2. Description of the Related Art Fat in the body is a product in which excess amount of ingested energy with respect to consumed energy is accumulated as neutral fat of white adipocytes. Obesity, which is highly accumulated as body fat, is not only cosmetically unfavorable but also causes various diseases such as arteriosclerosis. Recently, obesity due to overeating, lack of exercise, stress, etc. is increasing, but on the other hand, especially women tend to long for a slim body. Further, accumulation of subcutaneous fat and the like is unfavorable for health, and reduction of subcutaneous fat or prevention of accumulation is an important issue.

Capsaicin, which is contained in capsicum as a substance having an obesity-preventing action, binds to albumin in the blood, secretes hormones that promote metabolism of the adrenal gland, and acts on the liver and adipocytes to activate energy metabolism. It is known (Kazuo Iwai and Yanji Nakatani, Food functions of spice ingredients, page 97, 1989). However, since capsaicins have a strong stimulus, there is a problem that their use and usage amount are limited.

It is difficult to eliminate the fat cells that have once accumulated, and it is a quick way to make the fat cells as small as possible.
For that purpose, we thought that it was necessary to decompose the oil droplets in the fat. Oil drops are decomposed by an enzyme (phospholipase C) like proteins, but because they are covered with a water-repelling phospholipid membrane, they are in a mass of water called parcels around oil drops. Enzymes are inaccessible. On the other hand, by exercising to activate the sympathetic nerve, a lipolytic hormone is secreted. It is believed that this hormone promotes lipolysis by removing the phospholipid membrane and increasing the affinity between the enzyme and oil droplets. Therefore, it was considered necessary to find a substance that acts to increase the affinity between the oil droplet and the enzyme, like this hormone.

The present inventors have found that raspberry ketone, zingerone and their derivatives promote the decomposition of fat accumulated in adipose tissue, and are effective in suppressing obesity or improving obesity constitution (Japanese Patent Laid-Open No. 2004-242242). 2000-169325). However, since raspberry ketone and zingerone have unique fragrances, they were not satisfactory in terms of compounding amount and versatility.

On the other hand, 3, which is contained in sesame seeds and olives,
It is known that 4-dihydroxyphenethyl alcohol (hydroxytyrosol) has an excellent immunosuppressive effect and active oxygen scavenging effect (JP-A-2-306971).
JP-A No. 7-223940), there is no description or suggestion that this substance has a lipolysis promoting action.

Therefore, there is a demand for a lipolysis promoter and a slimming method which are more versatile and have a satisfactory effect of suppressing or reducing subcutaneous fat and the like. Therefore, the present invention has excellent general-purpose properties, and improves the obesity constitution by promoting the reduction of systemic or local adipose tissue, or promotes lipolysis effective in suppressing or preventing obesity by preventing the increase of the same tissue. It is intended to provide a drug and a slimming method.

[0008]

In order to achieve the above object, the inventors of the present invention have conducted extensive studies on a substance having an action of acting on adipocytes and promoting lipolysis, and as a result, the following general formula (1) It was found that the compound shown has the above-mentioned effects, promotes the decomposition of fat accumulated in adipose tissue, is effective in suppressing obesity or improving obesity constitution, and completed the present invention.

[0009]

[Chemical 4]

That is, the present invention resides in a lipolysis promoter comprising hydroxytyrosol represented by the above general formula (1) and a skin external preparation and a food / beverage composition for slimming containing the compound. .

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below.
The hydroxytyrosol represented by the general formula (1) used in the present invention can be easily obtained by extraction from sesame seeds as described in JP-A-7-223940. Further, it can be used by extracting from olives and / or vegetation water produced in the olive oil production process with a suitable solvent, and if necessary, concentrating, drying, and purifying by a known method.

When the hydroxytyrosol represented by the above general formula (1) is used as a lipolysis promoter in a skin external preparation or a slimming food / beverage composition, the compounding amount varies depending on the form of the preparation. However, for example, 0.001 to 20% by mass is preferable, and 0.01 to 10% by mass is more preferable. If the amount is less than 0.001% by mass, the effect of the present invention may not be exhibited, and if the amount exceeds 20% by mass, the effect corresponding to the compounded amount may not be obtained.

When the lipolysis-promoting agent of the present invention is used as a skin external preparation for slimming, oils, pigments, surfactants, humectants, ultraviolet absorbers, anti-inflammatory agents used in ordinary skin external preparations are used. In addition to bactericides, preservatives, pigments, butadamine, isoproterenol, and other β-adrenergic stimulants, yohimbine, ergotoxin, and other α2-adrenergic inhibitors, theophylline, caffeine, and other xanthine derivatives, milrinone, amrinone Raspberry ketone, zingerone, 3,4-dihydroxyphenyl-2-, which has an action of suppressing or preventing obesity, such as bipyridine derivatives
Known substances such as butanone and synephrine may be added.

When the lipolysis-promoting agent of the present invention is used in a slimming food / beverage composition, sugars, flavors, emulsifiers, dairy products, proteins, stabilizers, colorants, which are used in ordinary food / beverage compositions, Acidulant, oil, cereal, egg, gum base,
Xanthine derivatives such as caffeine, hydroxycitric acid, known substances such as capsaicin, raspberry ketone, zingerone, 3-4-dihydroxyphenyl-2-butanone and synephrine, which have an obesity-suppressing or preventing action, can be added.

The lipolysis promoter of the present invention can be incorporated into, for example, foods, orally administered drugs, skin cosmetics, etc.
The dosage form is not particularly limited, and in the case of an external preparation for skin such as slimming skin cosmetics, cream for skin application, bath, cleaning etc., emulsion, gel, stick, sheet, pap, powder, liquid , Granules and the like, in the case of food and drink composition, chewing gum, chocolate, candy, gummy jelly,
It can be added to beverages, soups, ice creams, noodles, bakery foods and the like.

[0016]

EXAMPLES The present invention will be described in detail below based on examples and comparative examples. The lipolysis promoting effect was evaluated by the following lipolysis test and subcutaneous lipolysis test.

[Lipolysis test method] Rodbell method [R
odbell, M .; J. Biol. Chem. , 23
9, 375 (1964)], free adipocytes were prepared from epididymal adipose tissue of male Wistar rats (body weight: 150 to 200 g) using a collagenase solution. The above cells were added to a Hanks buffer solution containing bovine serum albumin and norepinephrine (final concentration 0.05 μg / mL) prepared so that the concentration of the test substance was a predetermined amount, and the cells were allowed to stand at 37 ° C. for 1 hour.
Reacted for hours. The liberated fatty acid was extracted, and the amount of fatty acid was quantified with a copper reagent and a coloring reagent.

[0018] Lipolysis promotion rate (%) = [A / B] × 100 A: Fatty acid amount when the test substance was added B: Amount of fatty acid in control (without addition of test substance)

Example 1 (Production of hydroxytyrosol fraction) 20 liters of vegetation water obtained by removing squeezed lees such as seeds from the aqueous layer produced in the production process of olive oil made in South France was washed with an equal amount of hexane. After that, the polyphenol fraction containing hydroxytyrosol was extracted with 20 liters of ethyl acetate. The extraction solvent was removed by a conventional method to obtain about 60 g of a lipolysis promoter used in the present invention. It was confirmed by GC-MS that the lipolysis promoter obtained as shown in FIG. 1 contained about 25% hydroxytyrosol.

Example 2 (Separation and purification of hydroxytyrosol) 10 g of the lipolysis promoter obtained in Example 1 was purified by silica gel column chromatography (developing solvent; petroleum ether / ethyl acetate = 1/1). 3.5 g of hydroxytyrosol was obtained. It was confirmed by GC analysis that the purity was 95% or higher.

Examples 3 and 4 and Comparative Examples 1 and 2 The results of evaluation of the various lipolysis promoters in the above lipolysis test are shown below.

[0022] Lipolysis promoter Test concentration Lipolysis promotion rate (%)                                                                    Example 3   Hydroxytyrosol of Example 2 0.05% 163.4 ± 3.5                                                     p <0.001                                                                    Example 4   Hydroxytyrosol of Example 2 0.50% 182.9 ± 12.1                                                     p <0.001                                                                    Comparative Example 1   Raspberry ketone 0.02% 118.3 ± 11.6                                                         n. s.                                                                    Comparative example 2   Raspberry ketone 0.20% 143.6 ± 8.1                                                     p <0.001

The lipolysis-promoting agent (hydroxytyrosol) obtained in Example 2 had a lipolysis-promoting rate higher than that of the raspberry ketone used in Comparative Examples (known to have a lipolytic action in JP-A 2000-169325). It was clarified that the effect of promoting lipolysis was much higher.

Example 5, Comparative Examples 3 to 4 (Chewing Gum) Each chewing gum having the following composition was blended with an active ingredient, and 2
When 30 women with a body fat percentage of 35% or more in their 0s took 5 chewing gums (15 g / sheet) daily for 1 month each day, and the body fat percentage decreased by 5% or more from the original body fat percentage, It was evaluated as a person with reduced body fat. Example 5 Comparative Example 3 Comparative Example 4 Gum base 20 20 20 Maltitol 73.5 74.5 70.5 Reduced starch syrup 4 4 4 Apple fragrance 0.5 0.5 0.5 0.5 Garcinia extract * 1 1 1 5 Hydroxytyroso -(Example 2) 1 --- Evaluation Number of persons with reduced body fat (person) 23 11 20 * 1 Garcinia extract: "Citrimax HCA-500-F" (hydroxycitric acid (HCA) 47.5, manufactured by Interhealth) (Mass% included)

Example 6 (tablet confectionery) A tablet confectionery was prepared with the following composition, and 3 tablets (0.5 g / tablet) were ingested daily and evaluated in the same manner as in Example 5. Composition Sorbitol 82.9 Sucrose fatty acid ester 4 Raspberry fragrance 0.1 Garcinia extract * 1 3 Lipolysis accelerator of Example 1 10 Evaluation Body fat reducer (person) 25

As described above, Examples 5 and 6 were food / beverage compositions suitable for continuous eating, in which the effect of significantly lowering the body fat percentage was observed, and the composition did not become tired even after long-term intake.

Examples 7 to 8 and Comparative Example 5 (Gel-like slimming skin cosmetics) In the following composition, components A and B were individually mixed and dissolved by a conventional method, and then component B was added to component A. The gel cosmetic for slimming was prepared by stirring.

[0028] Ingredients (mass%) Example 7 Example 8 Comparative Example 5 (A component) Lipolysis promoter of Example 1 3.0 − − Of Example 2   Hydroxytyrosol-1.0- Glycerin 10.0 10.0 10.0 10.0 Carboxy vinyl polymer 0.3 0.3 0.3 Edetate disodium 0.1 0.1 0.1 Purified water Residual amount Residual amount Diisopropanolamine 1.0 1.0 1.0 Squalane 10.0 10.0 10.0 (B component) Polyoxyethylene (60) 0.8 0.8 0.8       Hydrogenated castor oil Carrageenan 3.0 3.0 3.0 3.0 Xanthan gum 3.0 3.0 3.0 Polyvinyl alcohol 2.0 2.0 2.0 Ethanol 45.0 45.0 45.0 Menthol 0.1 0.1 0.1 Perfume Suitable amount Suitable amount Suitable amount

Example 5 was applied to the above gel-like slimming skin cosmetic composition.
After the continuous application of 2 g to the abdomen and thighs of the panel of Example 2 twice a day for 3 weeks, the results of the questionnaire about the slimming effect, the panel using Examples 7 and 8 showed that the abdomen was tightened. Much more than 5.

[0030]

INDUSTRIAL APPLICABILITY The present invention is characterized by using a lipolysis promoter which is effective in reducing systemic or local adipose tissue, suppressing or preventing obesity, and improving obesity constitution, and the lipolysis promoter. It is clear that a slimming method can be provided.

   ─────────────────────────────────────────────────── ─── Continued front page    F-term (reference) 4B018 LB01 MD08 ME01                 4C083 AC022 AC102 AC122 AC432                       AC471 AC532 AC542 AD092                       AD112 AD352 BB41 CC02                       DD41 EE10 EE12 EE50                 4C206 AA01 AA02 CA19 KA01 MA72                       MA83 NA14 ZA70

Claims (6)

[Claims] 1. The following general formula (1): Lipolysis promoter consisting of. 2. A skin external preparation containing a compound represented by the following general formula (1). [Chemical 2] 3. The external skin preparation is a skin cosmetic.
The skin external preparation described. 4. The skin external preparation according to claim 2, which is a skin cosmetic for slimming. 5. A slimming method, which comprises using the lipolysis promoter according to claim 1 or the external skin preparation according to claim 2. 6. A slimming food / beverage composition comprising a compound represented by the following general formula (1). [Chemical 3]