WO2005089783A1

WO2005089783A1 - Lipoprotein lipase activity inhibitor

Info

Publication number: WO2005089783A1
Application number: PCT/JP2004/003853
Authority: WO
Inventors: Toshihiko Seki; Eiichiro Yagi
Original assignee: Shiseido Co., Ltd.
Priority date: 2004-03-22
Filing date: 2004-03-22
Publication date: 2005-09-29

Abstract

A lipoprotein lipase activity inhibitor which inhibits fat accumulation in fat cells. Namely, an enzyme lipoprotein lipase (LPL), which is regenerated by fat cells and secreted into peripheral vessels in epithelial cells by exocytose, decomposes fat having been absorbed into the vessels as foods into fatty acids and glycerol. Then the fatty acids and glycerol migrate into fat cells in the subcutaneous fat tissue and fat is finally synthesized in the fat cells. By applying the above-described lipoprotein lipase activity inhibitor to the skin as an external skin preparation for slimming, therefore, the action of the enzyme lipoprotein lipase (LPL) can be inhibited in peripheral vessels in epithelial cells. As a result, the decomposition of fat into fatty acid and glycerol can be inhibited and the synthesis of new fat in fat cells can be finally prevented. Thus, slimming effect can be established.

Description

Description Lipoprotein lipase activity inhibitor Technical field

The present invention relates to a lipop-mouth tin lipase activity inhibitor comprising as an active ingredient an extract of the plant of Hawthorn and Z or Odricoso, and provides an external preparation for slimming skin.

The lipop-mouth tin lipase activity inhibitor of the present invention exerts a slimming effect by preventing fat in blood from being decomposed by lipop-mouth tin lipase and preventing the decomposed product from becoming fat in fat cells. It is. Background art

To provide cosmetics intended for slimming, plant extracts that suppress lipoprotein lipase activity have been incorporated into cosmetics. For example, Patent Literature 1 discloses extraction of brown algae extract, Darus. Palmaria. Palmate extract, wheat protein extract, spirulina extract, Skazura extract, and a specific vine plant (Un cariat omentosa) native to South America. Liquids and the like are incorporated into cosmetics as substances that prevent fat accumulation.

On the other hand, Patent Literature 2 discloses that many plant extracts such as kingin power (Honeysuckle family) and hawthorn (Hawthorn parasitoid) are used as accelerators to increase the utilization of glycogen / fat in the body. It is added to food. However, Patent Document 2 merely discloses a combination of a plant extract in foods such as candy and the like and tablets, and does not suggest application to cosmetics for slimming.

`` Patent Document 1 ''

JP 2002-157071 `` Patent Document 2 J

DISCLOSURE OF THE INVENTION The present inventors have newly found that extracts of S. hawthorn and odricososo from many plants have an excellent lipoprotein lipase activity inhibitory effect. An object of the present invention is to provide a novel lipoprotein lipase activity inhibitor containing these plant extracts as an active ingredient. The lipoprotein lipase activity inhibitor of the present invention can provide an excellent skin external preparation for slimming. Disclosure of the invention

The present invention provides a lipoprotein lipase activity inhibitor comprising an extract of a plant of Hawthorn and / or Odricoso as an active ingredient.

The present invention also provides a slimming skin external preparation comprising the above lipoprotein lipase activity inhibitor as an active ingredient. Brief Description of Drawings

FIG. 1 is a graph showing the inhibitory effect of the extract of the hawthorn on the lipop mouth tin lipase activity.

FIG. 2 is a graph showing the inhibitory effect of the extract of Adricos solanii on lipoprotein lipase activity. BEST MODE FOR CARRYING OUT THE INVENTION

The hawthorn used in the present invention is the following plant

Study: Crataegus leavigata Dc. Family name: Parasaceae Hawthorn

English name: Hawthorn (May flower, May Bush)

Hawthorn is a deciduous shrub native to Europe and West Asia and North Africa. It is also used as a garden tree and has many horticultural varieties. As a medicine, this herb is very important and has been used in Europe for a very long time as a mild sedative for the nervous system. It is also used as a Japanese sensation in the treatment of hypertension in orthodox medicine, and its medicinal effects are known.

There are many religious stories in the legend of the plant. As a particularly famous legend, it is said that the crown when Christ was crucified was Seohawthorn, and that the blood of Christ sanctified the hawthorn. For this reason, it was used as an amulet in old times. The flower language is “hope”. It has not been known so far that Hawthorn has a lipop-mouth tin lipase activity inhibitory effect, and the present inventors have found it for the first time. In addition, the extract of Hawthorn cultivar has never been used as a lipop-mouth tin lipase activity inhibitor incorporated in an external preparation for slimming skin.

The extract of the wild hawthorn used in the present invention is obtained by extracting an organic solvent such as water, ethanol, propylene glycol, 1,3-butylene glycol or the like from a flower, a leaf, or a fruit, alone or in combination. Obtained. The extract obtained by extraction can be used as it is. Alternatively, the concentrated extract is adsorbed on a column of a porous polymer (for example, Amberlite XAD-2) after removal of impurities using an adsorption method such as ion exchange resin, and then methanol or ethanol. Eluted and concentrated ones can also be used.

The plants used in the present invention are the following plants.

Family name: Lamiaceae

Scientific name: Lamium album L. Odricoso is a perennial plant that is widely distributed in the temperate zone from Hokkaido to Kyushu and East Asia, and prefers half-shade on the roadside of mountains. The leaves contain tanyun, essential oils, ascorbic acid, carotenoid saponin, etc., and the flowers contain flavonoid polysaccharides, essential oils, saponin, etc. It is used as an astringent, expectorant, diuretic, wound, and anti-inflammatory.

Until now, it has not been known that odricosodi has an effect of suppressing lipoprotein lipase activity, and it was found by the present inventors for the first time. Odorikoso extract has never been used as a lipoprotein lipase activity inhibitor incorporated in a skin external preparation for slimming.

The extract of odricosodium used in the present invention is obtained by extracting an organic solvent such as water, ethanol, propylene glycol, 1,3-butylendalycol from a flower, a stem, or a leaf, alone or in combination with each other. can get. The extract obtained by extraction can be used as it is. Alternatively, a concentrated extract may be adsorbed on a column of a porous polymer (for example, Amberlite XAD-2) after removing impurities using an adsorption method such as an ion exchange resin, and then methanol or Eluted with ethanol and concentrated can also be used. The present invention is a lipop-mouth tin lipase activity inhibitor comprising the above plant extract as an active ingredient, and is used as a slimming active ingredient to be incorporated into a skin external preparation for slimming. In other words, it is a drug that is incorporated into a skin external preparation such as a cosmetic as a fat synthesis inhibitor. Then, it is blended with any skin external preparation to provide a skin external preparation for slimming. It is also preferable to mix both the extract of the hawthorn and the extract of the sorghum.

The amount of the extract is preferably 0.01 to 20% by mass, more preferably 0.05 to 1% by mass, as a concentrated extract extract in the total amount of the external preparation. If the amount is less than 0.01% by mass, the slimming effect due to the inhibition of lipoprotein lipase activity is not sufficiently exerted. Meanwhile, 20 mass. / Greater effect even if blended beyond ₀ Above is not recognized, and formulation becomes difficult.

When the lipop-mouth tin lipase activity inhibitor of the present invention is blended into a skin external preparation for slimming, other components usually used in skin external preparations such as cosmetics and pharmaceuticals, for example, as long as the effects of the present invention are not impaired, for example, Moisturizers, antioxidants, oily components, UV absorbers, emulsifiers, surfactants, thickeners, alcohols, powder components, coloring materials, aqueous components, water, various skin nutrients, etc. as needed Can be blended.

In addition, sequestering agents such as disodium edetate, trisodium edetate, sodium taenoate, sodium polyphosphate, sodium metaphosphate, dalconic acid, malic acid, caffeine, tannin, verapamil, tranexamic acid and the like Derivatives, licorice extract, hot water extract of grabradine, karin fruit, various crude drugs, drugs such as tocopherol acetate, glycyrrhizic acid and its derivatives or salts thereof, vitamin c, magnesium ascorbate phosphate, darcoside ascorbate, arbutin , Whitening agents such as kojic acid, sugars such as glucose, fructose, mannose, sucrose and trehalose, and vitamin A derivatives such as retinoic acid, retinol, retinol acetate, retinol palmitate, etc. .

A slimming skin external preparation is any composition that can be applied to the skin. Preferably, it is a cosmetic for personal use. For the dosage form, any dosage form such as a solution type, a solubilizing type, an emulsifying type, a powder dispersing type, a water-oil-two-layer system, a water-oil-one powder three-layer system, an ointment, a diel, and the like can be applied. In addition, the form of use is arbitrary. For example, it can be used as a facial cosmetic such as a lotion, an emulsion, a cream, a pack, a makeup cosmetic such as a foundation, or a bath agent.

"Flesh synthesis suppression mechanism of slimming effect according to the present invention"

The theory of the slimming effect according to the present invention will be described below.

`` Fat synthesis suppression mechanism '' The lipoprotein lipase activity inhibitor of the present invention suppresses fat accumulation in adipocytes. That is, the enzyme lipoprotein lipase (LPL), which is regenerated by fat cells and secreted by exocytose in the capillaries of epithelial cells, and fat absorbed into blood vessels as food is broken down into fatty acids and glycerin. The fatty acids and glycerin move from the capillaries into the fat cells of the subcutaneous fat, and finally fat is synthesized in the fat cells. Therefore, by applying the lipoprotein lipase activity inhibitor of the present invention to the skin as an external preparation for slimming, it is possible to suppress the action of the enzyme lipoprotein lipase (LPL) in the capillaries of epithelial cells. It becomes possible. As a result, it suppresses fat from being broken down into fatty acids and glycerin in the capillaries of epithelial cells, and eventually prevents fat synthesis in fat cells, thereby suppressing obesity and slimming effects. The fruit is exerted.

As described above, the slimming effect according to the present invention is achieved by a mechanism fundamentally different from that of the conventional slimming method based on the “intracellular neutral fat burning” theory. In other words, it does not burn fat in fat cells, but fundamentally eliminates fatty acids, which are necessary for fat synthesis, which causes fat accumulation, thereby preventing fat synthesis in cells. By doing so, it has a remarkable slimming effect.

The above-mentioned lipoprotein lipase activity inhibitory effect was measured by the LPL activity measurement kit (Lipoprotein Lipase Activity Kit, Cat.ff RB-LPL: Roar Biomedical Inc., Columbia University, Audubon Biomedical Center, 3960 Broadway, New York, NY 10032). USA) to determine the effect of suppressing LPL activity. A specific evaluation method will be described in detail in Examples.

In addition, according to this evaluation method, screening of various plant extracts and various drugs is superior to lipoprotein tin lipase activity inhibitory effect of Pseudomonas cerevisiae and Podricososium, and thus a more excellent lipoprotein lipase activity is obtained. Sex inhibitors can be searched for. Example

Next, the present invention will be described in more detail with reference to examples. The present invention is not limited to only these examples. The compounding amount represents mass%.

The hawthorn extract is an extract obtained by extracting the flowers, leaves, and fruits of the hawthorn with a 50% aqueous solution of 1,3-butylendalcol.

Odricosodium extract is an extract obtained by extracting the flowers, leaves, and stems of odricosodium with a 40% aqueous solution of propylenedaricol.

Various test drugs were screened by the following method to find out the effect of the extract of T. cerevisiae and Odricosodium II on lipop-mouth tin lipase activity and applied to the present invention.

"Evaluation method of LPL (lipoprotein lipase) activity inhibitory effect"

Using the LPL activity measurement kit (Lipoprotein Lipase Activity Kit, Cat. # RB-LPL: Roar Biomedical Inc., Columbia University, Audubon Biomedical Center, 3960 Broadway, New York, NY 10032 USA) at 96 Uenoref ⁰ rate The LPL activity inhibitory effects of various test drugs were measured. 0.15 ° 0.3 ° 0.6 ° 1.5% 3%, 15% 30% (final concentration 0.05 ° 0.1%, 0.2% 0.5 %, 1%, 5%, 10% v / v) diluted with the solvent of the drug substance solution of the test drug (for hawthorn extract, 50% 1,3-Butylene Glycol aqueous solution. Then, 40% Propylene Glycol aqueous solution). The number of samples was n = 3-5.

The composition of the test drug of the hawthorn extract is “hawthorn extract: 1 to 3%, 1,3 Butylene Glycol: 50 ° /., Water: residue”.

In addition, the composition of the test drug of odricosodium extract is: "odricosodium extract:;! ~ 3%, Propylene Glycol: 40 ° /., Water: residue". Sigma LPL (Cat. # L2254) was used as the enzyme LPL, and diluted with a TNE buffer solution at 2ωΰΐ / 50 μl (final concentration 0.67 unit / 150 1). LPL measurement After thoroughly mixing the substrate emulsion of the kit, 2 μl of the substrate emulsion was diluted with 48 μl of TNE buffer per 1 μl, and added to each well of the 96 μl plate as 501 to prepare in advance. After adding 50 μl of the test drug and control that had been added and 50 μl of the prepared LPL enzyme solution, the mixture was incubated at 37 ° C for 60 minutes, and the fluorescence intensity was measured using a microplate reader. (Excitation light: 370 nm, fluorescence: 450 nm) At the same time, using the pre-hydrolyzed substrate (75.7 moles / ml) attached to the above kit, prepare a dilution series and use it in place of the substrate emulsion. The linearity of LPL activity was confirmed.

The results are shown in FIGS. 1 and 2.

"Consideration of Fig. 1"

FIG. 1 shows the results of evaluating the inhibitory effect of the hawthorn extract on the lipop-mouth tin lipase activity. This bar graph shows the LPL activity of each diluted solution of the hawthorn extract assuming the LPL activity value of the control solvent (50% 1,3-Butylene Glycol aqueous solution: 50% 1,3—BG) as 100%. It shows the degree of activity suppression, and is concentration-dependent, and its LPL activity suppression is significantly retained up to 0.05% concentration.

From this, it can be seen that the extract of Hawthorn has a remarkable inhibitory effect on lipoprotein lipase activity. Therefore, an external preparation for skin prepared by incorporating the hawthorn extract as a lipo-mouth tin lipase activity inhibitor exhibits an excellent slimming effect as an external preparation for slimming skin.

"Consideration of Fig. 2"

Fig. 2 shows the effect of Odricosodium extract on the lipop-mouth tin lipase activity. The result of the evaluation is shown. This bar graph shows the degree of inhibition of LPL activity for each diluted solution of Odricosodium extract, with the LPL activity value of the control solvent (40% aqueous solution of Propylene Glycol: indicated as 40% PG) as 100%. Dependency is 0.05. /. Up to the concentration, its suppression of LPL activity is significantly retained. From this, it can be seen that Adricos soybean extract has a remarkable inhibitory effect on lipoprotein lipase activity. Therefore, an external preparation for skin containing odricosodi extract as a lipoprotein lipase activity inhibitor exhibits an excellent slimming effect as an external preparation for slimming. The following is a formulation example of the lipoprotein lipase activity inhibitor of the present invention, that is, an example of a slimming cosmetic.

Example 1: Slimming lotion

Ethyl alcohol 5.0 Glycerin 2.0 Dipropylene dalicol 6.0 Polyoxyethylene polyoxypropylene des'oletetratetracinoleate

0.2 Sodium hexametaphosphate 0.03 Sodium polyaspartate 0.1 α-Tocopherol 2-L-ascorbic acid diester phosphate

0.1 Isostearyl alcohol 1.0 Caffeine 0.2 Dokudami extract 0.1 Podricosodium extract 0.1 Western heart extract 0.1 Hexametaphosphoric acid 0.1 Carboxybule polymer 0.05 Hydrogen hydroxide 0.02 Phenoxyethanol

Example 2: OW type emulsion for slimming

Dimethylpolysiloxane 4.0 Decamethinoresin pentasiloxane 3.0 Ethanol 15.0 Glycerin 3.0

1,3-butylene glycol 5.0 polyoxyethylene methyl darcoside 3.0 squalane 1.0 isostearyl alcohol 5.0 diisopropyl sebacate 0.5 sodium hydroxide 0.1 sodium hexamethaphosphate 0.0 5 Force phene 1.0 Saw hawthorn extract 0.5 0.5 Potassium glycyrrhizinate 0.05

L-Sodium glutamate 0.05 Lavender oil 0.1 Diodiextract 0.1 Dimorpholinopyridazinone 0.1 Mentone 1.0 1.0 Xanthan gum 0.1 Canolepoxybininole polymer 0.1 Atarilic acid 'alkyl methacrylate copolymer (ぺ Mullen TR-1)

0.1 Color material Proper weight Norabene Proper amount Fragrance Proper amount Purified water residue Example 3 OZW emulsion for slimming

Dimethylpolysiloxane 2.0 Behenenoleanorecone 1.0 Batyl alcohol 0.5 Glycerin 8.0 Dipropyleneglycoreno 5.0 Xylitol 3.0 Hardened oil 3.0 Squalane 6.0 Isostearyl alcohol 5. 0 Pentaerythritite tetra-2-ethylhexanoate 2.0 Polyoxyethylene glyceryl isostearate 1.0 Polyoxyethylene glyceryl monostearate 1.0 Caffeine 0.0 1 Odricoso ゥ extract 1.0 Potassium potassium hydroxide Sodium edetate 0.05 Appropriate amount of phenoxyethanol compound Canoleboxybininole polymer 0.1 Appropriate amount of fragrance Purified water residue Example 4: O / W type cream for slimming

Squalane 8.0 Serine 2.0 Dimethylpolysiloxane 1.0 Stearyl alcohol 1.8 Behenyl alcohol 1.6 Glycerin 8.0 Dipropylene glycol 5.0 Macadamia nut oil 2.0 Hardened oil 3.0 Stearic acid 2.0 0 Cholesterinol hydroxystearate 0.5

Cetyl 2-ethylhexanoate 4.0 Polyoxyethylene hydrogenated castor oil '0.5 Self-emulsifying glyceryl monostearate 3.0 Hydroxide power 0.15 Sodium hexametaphosphate 0.05 α-Toco Ferronole 2-L-ascorbic acid phosphate diester

1 • 0 Caffeine 0.5 Cranberry hawthorn extract 0.5 Tocopherol acetate 0.1 Paraben qs sodium edetate 0.05

4-t-butyl-1 4'-methoxydibenzoylmethane 0.05 di-para-methoxycinnamic acid mono-2-glycyl hexylhexanoate 0.05 colorant qs Carboxyvinyl / repolymer 0.05 purified water Residue

Example 5: W / O type cream for slimming

Glycerin 3.0 Erythritol 2.0 Cyclomethicone 20.0 Isostearyl lanorecol 1 0.0 Tripropylene glycol dineopentanoate 1.0 Diisopropyl sebacate 1.0 Trioctanoin 3.0 Cetananol 0.1 Dimethicone coco Polyol 2.5 quanta 1-18 hectrite 1.5 caffeine 1.0 paraben

Colorant

Spice

Odricoso extract. 0.1 purified water

Industrial applicability

The lipoprotein lipase activity inhibitor of the present invention suppresses fat accumulation in adipocytes. In other words, the enzyme lipoprotein lipase, which is regenerated by fat cells and is secreted by exocytoses into the capillary blood vessels of epithelial cells

(L P L) breaks down the fat absorbed into the blood vessels as food, into fatty acids and glycerin. The fatty acids and glycerin move from the capillaries into the fat cells of the subcutaneous fat, and finally fat is synthesized in the fat cells. Therefore, the activity of the enzyme lipoprotein lipase (LPL) in the capillaries of epithelial cells can be suppressed by applying the lipoprotein lipase activity inhibitor of the present invention to skin as an external preparation for slimming skin. Becomes possible. As a result, in the capillaries of the epithelial cells, fat is suppressed from being broken down into fatty acids and glycerin, and finally the synthesis of new fats in fat cells is prevented, thereby exerting a slimming effect. Obesity can be prevented.

The lipop-mouth tin lipase activity inhibitor of the present invention provides an excellent external preparation for slimming skin by such a mechanism.

Claims

The scope of the claims

1. A lipoprotein lipase activity inhibitor comprising an extract of hawthorn and / or odorososin as an active ingredient.

2. An external preparation for slimming skin, comprising the lipoprotein lipase activity inhibitor according to claim 1 as an active ingredient.