JP7258325B2 - Skin external composition and bath agent composition containing lipolysis accelerator and lipolysis accelerator - Google Patents

Description

TECHNICAL FIELD The present invention relates to a lipolysis accelerator and a composition for external use on the skin and a bath agent composition containing the lipolysis accelerator.

Since obesity causes various adult diseases, there is a demand for a solution for it.
Conventionally, oral administration of caffeine, citric acid, and other components has been performed as a composition used to eliminate obesity, but from the point of view of safety, its practicality is limited and satisfactory effects have not been obtained. It was difficult. Therefore, the obesity-relieving action of plant extracts has been studied.
For example, in Patent Document 1, by transdermal administration of Chinese ginseng extract, valerian extract, hawthorn extract, dead nettle extract, etc., vascular endothelial growth factor C (VEGFC) expression is induced and activation of lymphatic function is promoted. An anti-obesity agent is described. Patent Document 2 describes a percutaneously administered obesity-improving agent with the same mechanism as Patent Document 1, containing rose oxide, citronellyl acetate and niaouli oil as components.

In addition, Patent Document 3 describes saw palmetto, eleuthero, acai, cardamom, angelica, guava, kokushiri, nut gummy, neem, hemp, elderberry, sedge, chabot diatom, sakuna, anise, carrot, ashwagandha, calluna, and eucalyptus. Oral or percutaneous administration of peroxisome proliferator-activated receptor (PPAR) ligand agents containing plant extracts of hawthorn, linseed, agitake, locust, and manchurianthorn increases lipid metabolism and prevents and treats obesity. has been described to be effective.

In Patent Document 4, the extracts of grape seeds, persimmon leaves, pu-erh tea, St. John's wort, apples, cod, oak, banaba leaves, red-clawed wisteria, Japanese cornel, sycamore, and eucommia leaf extracts are orally administered to treat carbohydrates and lipids. have been described as anti-obesity agents by inhibiting the digestion and absorption of lipids and by inhibiting α-amylase and lipase.

JP 2008-189609 A WO2014/051113 WO2009/054504 JP-A-9-227398

Here, elimination of obesity includes not only prevention of fat accumulation but also reduction of already accumulated fat, and the two are clearly different.
Obesity refers to a condition in which excess neutral fat (triglycerides) accumulates in adipose tissue and the adipose tissue increases. In the prevention of obesity, this accumulation is suppressed, but it does not reduce the accumulated adipose tissue, and slimming cannot be achieved. In other words, in order to shrink the excessively accumulated adipose tissue, it is necessary to decompose and consume the neutral fat stored as lipid droplets in the white adipocytes. important as the first step in reducing the Decomposition of triglycerides in the first stage results in smaller lipid droplets, leading to a reduction in the size of white adipocytes, which ultimately results in a reduction in the volume of adipose tissue, resulting in slimming.

However, in Patent Literatures 1 to 4, the decomposition of fat was not confirmed. In particular, Patent Document 4 only inhibits and suppresses the digestion and absorption of nutritional ingredients by α-amylase inhibitory action or lipase inhibitory action, and only has the effect of preventing fat accumulation. It did not break down accumulated fat and was not useful for slimming. In addition, since it is administered orally, it is not possible to achieve local slimming in areas where fat is accumulated, and it is necessary to consider systemic side effects.
Accordingly, an object of the present invention is to provide a lipolysis promoter for decomposing fat accumulated in the body.

The present invention has, for example, the following configurations.
[1] Promotes lipolysis, containing as an active ingredient an extract of at least one plant selected from the group consisting of Hypericum perforatum, Tsurushikimi, Amomum tsaoko, broad-leaved tea tree and hawthorn agent.
[2] The lipolysis accelerator of [1], which contains as an active ingredient an extract of at least one plant selected from the group consisting of Hypericum perforatum, Tsurushikimi and Amomum tsaoko.
[3] A composition for external use on the skin containing the lipolysis promoter of [1] or [2].
[4] A bath agent composition containing the lipolysis promoter of [1] or [2].
[5] The external skin composition of [3], which is applied to at least a part of the body and used in a hot bath.

According to the present invention, lipolysis is promoted, and fat accumulated in the body is decomposed.

1 is a graph showing the lipolysis promoting effect of the plant extract of the present invention.

The present invention provides a lipolytic composition comprising, as an active ingredient, an extract of at least one plant selected from the group consisting of Hypericum perforatum, Tsurushikimi, Amomum tsaoko, broad-leaved tea tree and hawthorn. Regarding accelerators.

1. Plant The plant used for the plant extract, which is the active ingredient of the lipolysis accelerator, is at least one selected from the group consisting of the following plants.
Hypericum erectum (scientific name: Hypericum erectum), Tsurushikimi (scientific name: Skimmia japonica (Thunb.) var. intermedia Komatsu f. repens), Amomum tsao-ko (scientific name: Amomum tsao-ko), broad-leaved tea tree ) (Melaleuca quinquenervia) and Hawthorn (Crataegus oxyacantha).
Among these, Hypericum perforatum, Tsurushikimi and Amomumu tsaoko are preferred, and Hypericum perforatum is more preferred.
These may be used individually by 1 type, or may be used in combination of 2 or more types.

Although not particularly limited, it is preferable to use the aerial part of Hypericum perforatum, it is preferable to use the whole plant part of Tsurushikimi, it is preferable to use the fruit part of Amomumu Tsaoko, Broad-leaved tea The tree preferably uses leaf parts, and the hawthorn preferably uses leaf parts. The plant may be used as it is or dried. Also, it may be appropriately cut, crushed, or pulverized so as to be suitable for extraction.

2. Extract Production Method The plant is used as an extract.
Solvents used for extraction include water, organic solvents, and the like, and may be used in combination. Examples of organic solvents include aliphatic alcohols such as methanol, ethanol, propanol and butanol, esters such as ethyl acetate and butyl acetate, and ketones such as acetone and methyl ethyl ketone. These may be used individually by 1 type, or may be used in combination of 2 or more types.

As the extraction method, a known extraction method can be used, and the plant may be immersed in the solvent as it is, or may be stirred, refluxed, or the like. The extraction temperature and extraction time are also appropriately set according to the extraction solvent and extraction target.
After extraction, if necessary, the extraction residue may be separated by filtration, centrifugation, or the like.

The above plant extract is obtained by extracting a plant with water or an organic solvent by the above method, or by adding the extract to a mixture of ethyl acetate or butanol and water for liquid layer partitioning. It is a thing that was given. The liquid layer distribution method is not particularly limited, and known methods can be used. Further, these may be dried or freeze-dried and used as powder, diluted with a solvent for use, or concentrated.

3. Lipolysis accelerator The lipolysis accelerator referred to in the present invention means an agent that has the effect of reducing the volume of lipid droplets.
Lipid droplets are cell organelles that store lipids such as triglycerides and cholesterol, and lipids such as neutral lipids (triglycerides) are present inside the phospholipid monolayer.

When the triglycerides in the lipid droplets are hydrolyzed into fatty acids and glycerol, both are released into the blood and circulate in the body, and then the fatty acids are taken up by the mitochondria in muscle cells such as skeletal muscle and decomposed to be used as energy. released. In this way, the neutral fat inside the lipid droplets is decomposed into fatty acids and glycerol and released to the outside of the lipid droplets, thereby reducing the volume of the lipid droplets.

The plant extract used in the present invention was found to have the effect of reducing the volume of these lipid droplets. As described above, the decrease in the volume of lipid droplets means that the neutral fat in the lipid droplets was decomposed into fatty acids and glycerol, the size of white adipocytes decreased, and the volume of adipose tissue This leads to elimination of obesity, slimming, and the like.

A suitable amount of the above plant extract as a lipolysis promoter is not particularly limited, but a suitable range includes the following ranges from the viewpoint of sufficiently exhibiting lipolysis promotion and suppressing toxicity. The concentration below indicates the concentration of the plant extract per medium in Example 1, which will be described later.
Hypericum perforatum is preferably 0.001 mg/ml to 1 mg/ml, more preferably 0.01 mg/ml to 0.2 mg/ml. Tsurushikimi is preferably 0.001 mg/ml to 1 mg/ml, more preferably 0.005 mg/ml to 0.1 mg/ml. Amomum Tsaoko is preferably 0.001 mg/ml to 1 mg/ml, more preferably 0.01 mg/ml to 0.2 mg/ml. Broad-leaved tea tree is preferably 0.001 mg/ml to 1 mg/ml, more preferably 0.005 mg/ml to 0.1 mg/ml. Hawthorn is preferably 0.001 mg/ml to 1 mg/ml or more, more preferably 0.01 mg/ml to 0.2 mg/ml or more.

4. Composition The lipolysis-promoting agent can be used as a composition together with other ingredients. This composition can be used for slimming, lipolysis, improving obesity, anti-obesity, preventing obesity, preventing obesity, suppressing obesity, etc., preferably for slimming, lipolysis, or anti-obesity. It can be used for weight loss, and more preferably for slimming.
It is also preferred to optionally add other anti-obesity ingredients to the composition.

Other anti-obesity ingredients include plant extracts other than the above-mentioned essential plant extracts, derivatives of hydroxycitric acid such as citric acid, hydroxycitric acid and hydroxycitric palmitic acid (HCAP (registered trademark)), theophylline, xanthine derivatives such as caffeine, β-adrenergic stimulants such as butopamine and isoproterenol, α2-adrenergic inhibitors such as yohimbine and ergotoxin, bipyridine derivatives such as milrinone and amrinone, tea extracts, carnitine and Hi-carnitine, etc. and at least one selected from the group consisting of carnitine derivatives.
These may be used individually by 1 type, or may be used in combination of 2 or more types.

Examples of the plant extracts of the optional components include iris (scientific name: Iris florentina), ginger (scientific name: Zingiber officinale) and thyme (scientific name: Thymus serpyllum). For iris, the root part is preferably used, for ginger, the root part is preferably used, and for thyme, the above-ground part is preferably used. The method for producing these plant extracts is the same as the above-described method for producing the plant extract.
The concentration of these plant extracts per medium in Example 1, which will be described later, is preferably 0.001 mg/ml to 1 mg/ml, more preferably 0.01 mg/ml to 0.2 mg/ml, for iris. Ginger is preferably 0.001 mg/ml to 1 mg/ml or more, more preferably 0.005 mg/ml to 0.1 mg/ml or more. Thyme is preferably 0.001 mg/ml to 1 mg/ml, more preferably 0.01 mg/ml to 0.2 mg/ml.

<Composition for external use on the skin>
When the above composition is used as a composition for external use on the skin, effects such as tightening of the applied site can be obtained.
In addition to the anti-obesity component, the composition for external use on the skin may optionally contain a pharmaceutically acceptable additive or an additive that can be applied to the skin.
For example, moisturizing agents, oily ingredients, ultraviolet absorbers, surfactants, thickeners, alcohols, powder ingredients, scrubs, coloring agents, aqueous ingredients, water, anti-inflammatory agents, disinfectants, antioxidants, preservatives, A skin nutrient etc. are mentioned.

The content of the plant extract, which is an essential ingredient in the external composition for skin, is not particularly limited, but is preferably 0.0001 to 10% by mass, more preferably 0.001 to 1% by mass, relative to the entire external composition for skin. .
The dosage form of this external composition for skin is not particularly limited, but liquids such as lotions and milky lotions, creams, gels, ointments, packs, sticks, sheets, poultices, powders, granules and the like.

The method of using the external composition for skin is not particularly limited as long as it is applied to the skin. The site to be applied is not particularly limited, but is preferably applied to a site where fat accumulation is to be reduced, such as around the abdomen, upper arms, thighs, calves, face, and the like. After application to the skin, it is preferred to warm at least the site of application, and it is also preferred to massage the site of application.

A more preferred method of use includes applying the composition for external use on the skin to at least a part of the body and taking a warm bath. This is because direct application to the skin makes it possible to locally deliver a high-concentration lipolysis-promoting agent to adipose tissue, and to heat the area to which the external composition for skin is applied by a warm bath. . When the lipolysis accelerator contains an oily plant extract, it has poor compatibility with water and is fat-soluble, so it is easily absorbed into the body even in water, so it is preferably used in this usage.

<Bath agent composition>
The above composition can be used as a bath agent composition. In addition to the anti-obesity component, the bath agent composition may contain optional components known as components of bath agent compositions.
Such optional ingredients include surfactants, carbonates, organic acids, inorganic pigments, humectants, preservatives, fragrances, inorganic salts, oily components, lubricants, water-soluble polymers, clouding agents, colorants, and the like. can be exemplified.

The content of the plant extract, which is an essential ingredient in the bath agent composition, is not particularly limited, but is preferably 0.0001 to 10% by mass, more preferably 0.001 to 1% by mass, relative to the entire bath agent composition. .

As for the method of using the bathing agent, any ordinary method of using the bathing agent, such as dissolving it in water (hot water) and using it, can be adopted without limitation. As a bathing method, it is used for a full body bath, a half body bath, a foot bath, and the like. The amount used is not particularly limited, but the amount of the bath agent composition per 200 liters of water is preferably 20 to 200 g.

The form of the bath agent is not particularly limited, but powders, granules, liquids, tablets, briquettes, flakes and the like can be mentioned.

Specific examples of the optional components of the external skin composition and bath agent composition include the following.

Examples of surfactants include nonionic surfactants, anionic surfactants and cationic surfactants.

Carbonates include, for example, sodium carbonate, sodium hydrogen carbonate, magnesium carbonate, potassium carbonate, potassium hydrogen carbonate, sodium sesquicarbonate, ammonium carbonate, calcium carbonate, etc. Organic acids include, for example, succinic acid, fumaric acid, apple acid, adipic acid, tartaric acid, citric acid, malonic acid, maleic acid and the like. One or more kinds of these carbonates and organic acids can be used, respectively, and effervescent granules obtained by combining both can also be used.

Examples of inorganic pigments include titanium oxide, calcium carbonate, magnesium carbonate, zinc oxide (zinc white), talc, calcium silicate, silicic anhydride, kaolin, bentonite, and titanium mica.

Examples of moisturizing agents include sugars such as sorbitol, xylitol, maltitol, dextrin, glucose, maltose, lactose, saccharose, xylose, fructose, mannitol, and lactitol; ethylene glycol, propylene glycol, 3-methyl-1,3-butane. Polyhydric alcohols such as diols, glycerin and 1,3-butylene glycol; amino acids such as sodium pyrrolidonecarboxylate and sodium glutamate; urea; plant-derived extracts;

Examples of preservatives include paraoxybenzoic acid esters (eg, methylparaben), benzoic acid, benzoates, and phenoxyethanol.

Examples of fragrances include natural fragrances such as lavender oil and jasmine oil, and synthetic fragrances such as geraniol and phenethyl alcohol.

Examples of inorganic salts include sodium sulfate, magnesium sulfate, sodium chloride, potassium chloride, sodium thiosulfate, magnesium oxide, aluminum sulfate, alum, and metasilicate.

Examples of oily components include natural oils such as soybean oil, jojoba oil, avocado oil, almond oil, olive oil, cocoa butter, sesame oil, persic oil, castor oil, coconut oil, rice bran oil, mink oil, beef tallow, and lard. Hydrogenated oils obtained by hydrogenating these natural fats and oils, synthetic glycerides such as myristic acid glycerides and 2-ethylhexanoic acid glycerides, fats and oils such as diglycerides; waxes such as carnauba wax, spermaceti wax, beeswax and lanolin; liquid paraffin Hydrocarbons such as , petrolatum, paraffin, microcrystalline wax, ceresin, squalane, pristane; lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, lanolin fatty acid, isostearic acid, etc. Lauryl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, cholesterol, higher alcohols such as 2-hexyldecanol; cetyl octanoate, myristyl lactate, cetyl lactate, isopropyl myristate, isopropyl palmitate, isopropyl adipate, esters such as butyl stearate, decyl oleate and cholesterol isostearate; essential oils; and silicone oils.

Lubricants include, for example, kaolin, polyethylene glycol, talc, magnesium stearate, calcium stearate, silicone oils, oily ingredients, starch and the like.

Examples of water-soluble polymers include cornstarch, glue, gelatin, collagen, casein, sodium alginate, carrageenan, furcelleran, tamarind gum, pectin, gum arabic, guar gum, xanthan gum, tragacanth gum, locust bean gum, dextran, dextrin, agar, Natural water-soluble polymers such as starch; semi-synthetic water-soluble polymers such as carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, cellulose acetate phthalate, propylene glycol alginate, oxidized starch, esterified starch, etherified starch, and cationic starch Polymer; synthetic water-soluble polymers such as sodium polyacrylate, polyethyleneimine, polyvinyl alcohol, polyethylene glycol, polyvinylpyrrolidone, carboxyvinyl polymer, and the like.

Examples of the clouding agent include dextrin-coated titanium oxide, carboxymethylcellulose sodium-coated titanium oxide, and the like.

These can be used individually by 1 type or in combination of 2 or more types.
The composition for external use on the skin and the bath agent composition can be produced by mixing the lipolysis promoter of the present invention with any of the anti-obesity ingredients and other ingredients according to a conventional method.

EXAMPLES The present invention will be described in more detail below with reference to Examples and Comparative Examples, but the present invention is not limited to these Examples.
The concentrations of plant extracts and the like in the examples are the concentrations per volume of the medium.

[Preparation of accumulation sample of lipid droplets]
Preadipocyte cells (3T3-L1, manufactured by Dainippon Pharmaceutical Co., Ltd.) were spread on a 96-well black plate (manufactured by Greiner Bio One Co., Ltd.) at 1 × 10 cells/well, and added with 10% fetal bovine serum (FBS). (manufactured by Hyclone) in a DMEM medium (low glucose) (manufactured by Wako Pure Chemical Industries, Ltd.) and cultured in a 37° C.-5% CO ₂ incubator to proliferate. After culturing for 24 hours, the medium was changed to medium containing 0.25 μM dexamethasone, 0.5 mM 1-methyl-3-isobutylxanthine and 1 μg/ml insulin. After inducing adipocyte differentiation for 48 hours, the medium was changed to medium containing 10% fetal bovine serum (FBS) and 1 μg/ml insulin, and thereafter the medium was replaced with 10% fetal bovine serum every other day. The medium was replaced with a medium containing serum (FBS) and 1 μg/ml insulin, cultured for 4 days, and used as a lipid droplet accumulation sample.
Accumulation of lipid droplets in the cells was confirmed visually at a magnification of 100 under an optical microscope (DIAPHOT, manufactured by Nikon Corporation).

After completion of the culture, the medium was replaced with phosphate-buffered saline (PBS), and AdipoRed (registered trademark) assay reagent (manufactured by Lonza) was added to stain the lipid droplets. The fluorescence intensity of the stained lipid droplets was measured at 572 nm using a fluorometer (EnSpire, manufactured by PerkinElmer), and the value obtained in the control (untreated) group was used as the initial value.

[Preparation of extract]
Table 1 below shows the plants used in the examples and the parts used. The details of the extraction method are as follows. For the extraction, dried pulverized parts of each plant were used.

Extraction method 20 g of the pulverized material shown in Table 1 above was immersed in 200 ml of 50% by volume ethanol (10 (W/V) times the volume), heated under reflux for 2 hours, and filtered to obtain an extract. After concentrating the whole extract, it was freeze-dried, dissolved or suspended in 80 ml of distilled water, added with 40 ml of ethyl acetate and stirred to obtain a separated extract. The resulting extract was concentrated, lyophilized and tested.

[Example 1]
The medium of the lipid droplet accumulation samples was changed daily to a medium containing 10 μg/ml insulin and 0.025 mg/ml broad-leaved tea tree extract, and cultured for 3 days.
After completion of the culture, the medium was replaced with phosphate-buffered saline (PBS), and AdipoRed (registered trademark) assay reagent (manufactured by Lonza) was added to stain the lipid droplets. The fluorescence intensity of the stained lipid droplets was measured at 572 nm using a fluorometer (EnSpire, manufactured by PerkinElmer). The value (%) relative to the initial value of the obtained measured value was obtained, and the value obtained by subtracting the value from 100 (%) was defined as the volume reduction rate of the lipid droplets.

[Examples 2 to 11]
The volume reduction rate of lipid droplets was determined in the same manner as in Example 1, except that the plant extract and the amount of addition shown in Table 2 were used instead of the broad-leaved tea tree extract.

[Comparative Example 1]
The volume reduction rate of lipid droplets was determined in the same manner as in Example 1, except that 0.05 mg/ml of hydroxycitric acid palmitate (HCAP) was used instead of the broad-leaved tea tree extract.

[Comparative Example 2]
The volume reduction rate of lipid droplets was determined in the same manner as in Example 1 except that 0.05 mg / ml of caffeine was used instead of the broad-leaved tea tree extract.

Table 2 shows the results of each example and comparative example.

From Table 2, a volume reduction rate of 10% or more was observed in all examples. In particular, Example 8 using St. John's wort shows a volume reduction rate of nearly 45% at a concentration of 0.05 mg/ml, and Example 9 shows a volume reduction rate of nearly 73% at a concentration of 0.1 mg/ml. As shown, the extract of Hypericum perforatum is particularly excellent in promoting lipolysis. Tsurusikimi is not preferable from the viewpoint of toxicity when used in large amounts, but as shown in Examples 4 and 5, it exhibits a high volume reduction rate at low concentrations.

Hereinafter, formulation examples of the lipolysis accelerator of the present invention are shown, but the implementation of the present invention is not limited to the following.
<External skin agent>
Ingredient Amount (% by mass)
Stearic acid 2.0%
Stearyl alcohol 3.0%
Deodorized lanolin 2.0%
Olive oil 15.0%
Glyceryl monostearate 2.0%
Tri(caprylic-capric)glyceryl 5.0%
1,3-butylene glycol 3.0%
Sorbitol 1.0%
Diglycerin 1.0%
Xanthan gum 0.25%
Carboxy vinyl polymer 0.1%
Hypericum extract 0.02%
Ginger extract 0.02%
Fragrance Trace purified water Remaining amount

<Bath salt>
Ingredient Amount (% by mass)
Sodium sulfate 69.2%
Sodium bicarbonate 23.3%
Silicic anhydride 0.5%
Calcium carbonate 1.0%
Perfume 0.8%
Hypericum extract 0.1%
Ginger extract 0.1%
Clouding agent ^* 5.0%
*Clouding agent Titanium oxide dextrin coating

<Bath salt>
Ingredient Amount (% by mass)
Liquid paraffin 30.0%
Rice bran oil 10.0%
POE cetyl ether 2.5%
Sorbitan monopalmitate 2.5%
Phenoxyethanol 0.3%
Perfume 0.5%
Hypericum extract 0.1%
Ginger extract 0.1%
Methyl paraoxybenzoate 0.2%
Remaining amount of purified water

<Bath salt>
Ingredient Amount (% by mass)
Fumaric acid 20.0%
Malic acid 18.0%
Sodium bicarbonate 21.0%
Sodium carbonate 20.0%
Sodium sulfate 18.58%
POE (caprylic-capric) glyceryl 0.2%
Ethylenediamine tetra POE/POP 0.02%
Soybean oil 0.3%
Polyvinylpyrrolidone 0.2%
PEG6000 0.5%
Hypericum extract 0.1%
Ginger extract 0.1%
Perfume 1.0%

Claims (4)

A slimming, lipolytic or anti-obesity composition comprising a Hypericum extract and a ginger extract (excluding fermented Hypericum extract and ginger extract ). A slimming, lipolytic or anti-obesity external skin composition comprising a Hypericum extract and a ginger extract ( excluding fermented Hypericum extract and ginger extract ). A slimming, lipolytic or anti-obesity bath composition comprising a Hypericum perforatum extract and a ginger extract ( excluding fermented Hypericum perforatum extract and ginger extract ). 3. The external composition for skin according to claim 2, which is applied to at least a part of the body and used in a hot bath.

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