JP4291177B2 - Cosmetic or dermatological pharmaceutical composition having a slimming effect and method of use thereof - Google Patents

Description

The present invention relates to a cosmetic or dermatological composition having a slimming effect and a method for using the same.
Specifically, a cosmetic or dermopharmaceutical composition having a slimming effect, comprising at least one diterpene selected from cafe stall, carweol and chemical derivatives thereof in a human safe medium Related to things.
Further, as described above, at least one diterpene is contained in a human-safe medium, and apart from the diterpene, xanthine derivatives such as caffeine and theobromine are considered to be particularly advantageous. The present invention also relates to a cosmetic or dermatological pharmaceutical composition having a slimming effect.
Furthermore, the present invention also relates to a method of using the composition by topical application for slimming prevention of overweight of the thigh and lumbar region, tightening of the skin, and especially prevention and treatment of cellulite and orange skin and / or tightening of the facial contour. .

  The cosmetics industry is constantly searching for new ingredients that have full-fledged activity against the slimming effect and can be used locally by general consumers.

Skin sagging and dullness have been a concern for women for a long time, and it has become the main cause of the development of various slimming cosmetics. However, in order to respond to changes in the overall approach to local meat problems, it is now necessary to target a wider audience. Certainly, women have always cared about their own bodies even when they are young and at a certain age, but men also have diets, disturbed eating habits, and lack of exercise. There are many examples of muscle training centered on the waist, waist and abdomen that are extremely sensitive to the cumulative effects of lifestyle and aging.
After the development of a slimming active ingredient (for example, caffeine) that directly activates lipolysis by inhibiting phosphodiesterase, as a more advanced ingredient, activation of membrane receptors (G protein) and inhibition (Alpha receptor and neuropeptide Y (NPY)) appeared. These approaches attempt to activate glycerol release through hormone sensitive lipase (HSL) in adipocytes. This reduces intracellular lipid accumulation and thus reduces cell volume.
By the way, apart from this, there seems to be an original and complementary method. In other words, in addition to activating the fat accumulation reduction by fat cells, it is a method of cutting off the supply source to cells through receptors that take in fat.
After ingesting a meal, fat cells accumulate lipids supplied with blood circulation by the action of a special receptor called a clathrin receptor.
After meals, cholesterol, triglycerides and other lipids are carried in the blood as kilomicrons. After partial hydrolysis, kilomicrons produce various carriers that constitute a transfer system to various cellular tissues (see Non-Patent Document 1).
For adipocytes, the transfer system is mainly composed of LDL (low density lipoprotein) and VLDL (very low density lipoprotein). At present, it is known that fat cells carry nutrients necessary for their maturation via LDL and VLDL, and accumulation of triglycerides is associated with fatty acids released by VLDL (see Non-Patent Document 2).
After the lipoprotein adheres to the clathrin receptor and the complex of the LDL receptor and the VLDL receptor is taken up, the triglyceride content and the transported cholesterol are released in the fat cells.

VALET and RICHARD, “Les lipides et la cellule adipeuse”, France, NATHAN Publishing, 1997, p. 23-24 YANO et al., “Atherosclerosis”, Vol. 135, No. 1, UK, ELSEVIER Publishing, 1997, p57

The present inventors have studied the effects of diterpenes such as caffe stall, carweol and their chemical derivatives on the regulation of LDL and VLDL receptor expression, while suppressing the development of preadipocyte cell lines and the accumulation of lipids in adipocytes. We found that we can suppress.
Accordingly, the present inventors have found that diterpenes selected from cafestall, carweol and their chemical derivatives, when applied topically, prevent slimming of the thighs and waists, and tighten the skin. And especially for the prevention and treatment of cellulite and orange skin and / or the tightening of facial contours, it has been found to have an excellent cosmetic effect as a slimming ingredient.
Therefore, the object of this patent application is that it has been discovered that diterpenes selected from cafe stall, carweol and their chemical derivatives are a new means as a slimming component.

Accordingly, one of the objects of the present invention is to provide a product that has an effect as a slimming component and has no side effects.
Based on the above, the present invention relates to a cosmetic or skin having a slimming effect, comprising at least one diterpene selected from cafe stall, carweol and chemical derivatives thereof in a human-safe medium. It is an object of the present invention to provide a medicinal composition and a method of use.

That is, the invention according to claim 1 includes a phosphodiesterase inhibitor selected from a natural extract containing methylxanthine in addition to at least one diterpene selected from cafestall, carweol and acetic acid cafestol. The present invention relates to a cosmetic or dermatological pharmaceutical composition for topical application for slimming, characterized in that it is contained in a medium safe for the human body.
The invention according to claim 2 relates to a cosmetic or dermatological pharmaceutical composition for topical application for slimming according to claim 1, wherein the above-mentioned diterpene is derived from a plant extract.
Invention belongs to the plant extract Arabic Coffea (Coffea arabica L.), Coffea canephora (Coffea robusta L.) and co Hinoki genus selected from Liberia Coffea (Coffea liberica B.) (Coffea L. ) according to claim 3 3. The cosmetic or dermatological pharmaceutical composition for topical application for slimming according to claim 2, which is a raw seed (green coffee bean) extract before roasting the plant .
The invention according to claim 4 is characterized in that the above-mentioned diterpene occupies 0.0001 ppm to 50% of the total weight of the composition, or the cosmetic for topical application for slimming according to any one of claims 1 to 3 The present invention relates to a pharmaceutical composition for skin.
The invention according to claim 5 is for topical application for slimming according to any one of claims 1 to 4 , wherein the phosphodiesterase inhibitor accounts for 0.0001 to 20% of the total weight of the composition. The present invention relates to a cosmetic or dermatological pharmaceutical composition.
The invention according to claim 6 relates to a cosmetic or dermopharmaceutical composition for topical application for slimming according to claim 1 , wherein the natural extract containing methylxanthine is a mate (Yerba Mate) extract.
The invention according to claim 7, characterized in that it comprises also components which act on the microcirculation system, at least one supplementary component selected from tightening components and / or anti-glycation ingredients and mixtures thereof, according to claim The cosmetic or dermatological pharmaceutical composition for topical application for slimming according to any one of 1 to 6 .
In the invention according to claim 8 , diterpene is used in the form of a solution, dispersion, emulsion, paste or powder as a simple substance or a premix, or as a simple substance or a premix, a macro, micro or nanocapsule, liposome or kilo microns, macro, or transported by a vector selected from the micro or nano-particles or microspheres Pont di, powdered organic polymers, talc, and characterized by being adsorbed on the bentonite and other mineral medium, according to claim 1 to 7 The cosmetic or dermatological pharmaceutical composition for topical application for slimming according to any one of the above.
The invention according to claim 9, diterpene is, emollient lotion, milky lotion or cream, skin care lotion or cream, cleansing cream, Russia Shon, foundation base, sunscreen lotions, artificial tanning lotion or cream, after-shave lotion, in each species dosage form selected from the mouth red, alone or wherein the suitable being used in the form of premix with excipients, slimming topical application according to any one of claims 1 to 8 The present invention relates to a cosmetic or dermatological pharmaceutical composition.
The invention according to claim 10 includes an organic solvent or a water-soluble glycol solvent, an extracted or synthetic oil, an ionic or nonionic thickener, a softening agent, a turbidity agent, a stabilizer, an emollient, silicone, α -Hydroxy acids, antifoaming agents, moisturizers, vitamins, fragrances, preservatives, sequestering agents, coloring agents, gelling and thickening polymers, surfactants and emulsifiers, other water-soluble or fat-soluble active ingredients , plant extracts Characterized in that it contains one or more ingredients selected from tissue extracts, marine extracts, UV absorbers, antioxidants and commonly used in cosmetics in a human safe mixture The present invention relates to a cosmetic or dermatological pharmaceutical composition for topical application for slimming according to any one of claims 1 to 9 .
The invention according to claim 11, and thigh and overweight slimming measures the waist, the tightening of the tightening及beauty cell Ruraito and prevention and treatment of orange skin and / or the face contour of the skin intended claim 1 The cosmetic or dermatological composition for slimming according to any one of 10 is used for cosmetic application by topical application.
The invention according to claim 12, and thigh and overweight slimming measures the waist, the tightening of the tightening及beauty cell Ruraito and prevention and treatment of orange skin and / or the face contour of the skin intended claim 1 of a composition according to any one of 10, on how to obtain a cosmetic or dermatological agent composition is for slimming topical application.
The invention according to claim 13 is directed to slimming measures for overweight of the thigh and waist, tightening of the skin and prevention / treatment of cellulite and orange skin and / or tightening of the contour of the face. The present invention relates to a method of using any one of the compositions described above in producing a cosmetic or dermatological pharmaceutical composition for topical application for slimming.
The invention according to claim 14 includes topical application of the slimming cosmetic or dermatological composition according to any one of claims 1 to 10 , and includes prevention and treatment of cellulite and orange skin and / or body weight The present invention relates to a usage method for tightening and slimming a facial contour.
The invention according to claim 15, aimed thigh and overweight slimming measures the waist, the fit Hikishima contour of prevention, treatment and / or the face of the tightening及beauty cell Ruraito and orange skin skin, skin care medicament It is related with the utilization method of the cosmetics or dermatological pharmaceutical composition for the topical application | coating for slimming in any one of Claims 1-10 in preparation of this.

The cosmetic or dermatological pharmaceutical composition having a slimming effect of the present invention has the effect of slimming the upper thigh and lower back, tightening the skin and, in particular, preventing and treating cellulite and orange skin and / or tightening the facial contour. can get.
Further, the cosmetic or dermatological pharmaceutical composition having a slimming effect of the present invention can provide a product having no particular side effect while having an effect as a slimming component.

ここにおいて、
（１）Ｒ及びＲ'は、同一でも異なっていても良く、それぞれ水素原子、直鎖状または枝分かれ状の炭化水素基、アリール基、アラルキル基、アシル基、スルホニル基または糖類を表している。
（２）シーケンスＸ−ＹはＣＨ_２−ＣＨ_２、ＣＨ＝ＣＨ、ＣＲ^１Ｒ^２−ＣＲ^２Ｒ^４またはＣＲ^５＝ＣＲ^６のいずれかに対応し、これらの式中Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ｒ^５、Ｒ^６は、同一でも異なっていても良く、それぞれ水素原子、直鎖状または枝分かれ状の炭化水素基、アリール基、アラルキル基、アシル基、スルホニル基または糖類を表している。
「直鎖状または枝分かれ状の炭化水素基」とは、本発明においては、（アルコール、カルボン酸、アミンなどで）置換されていても良く、飽和または不飽和の、１〜２０個の炭素原子を有する炭化水素基を意味する。特に、アルキル基としてはメチル基がある。
「アリール基」とは、本発明においては、各々５〜８個の炭素原子を有し、連結または融合され、置換基を有することもある１または複数の芳香環を意味する。特にアリール基としては、フェニル基やナフチル基があり、置換基としてはハロゲン原子、アルコキシ基、上述の直鎖状または枝分かれ状の炭化水素基やニトロ基がある。
「アラルキル基」とは、本発明においては、上述の直鎖状または枝分かれ状の炭化水素基を介して結合された上述のアリール基を意味する。特にアラルキル基としてはベンジル基がある。
「アシル基」とは、本発明においては、Ｒ^７が上述の直鎖状または枝分かれ状の炭化水素基、アリール基、アラルキル基やアミン基である−Ｃ＝ＯＲ^７基を意味する。特にアシル基としてはアセチル基（Ｒ^７＝ −ＣＨ_３）がある。
「アミン基」とは、本発明においては、Ｒ^８及びＲ^９が同一または異なっていても良く、それぞれ、水素原子、上述の直鎖状または枝分かれ状の炭化水素基、アリール基、アラルキル基、アシル基、スルホニル基、糖類である−ＮＲ^８Ｒ^９基を意味する。
「スルホニル基」とは、本発明においては、Ｒ^１０が上述の直鎖状または枝分かれ状の炭化水素基、アリール基、アラルキル基、アルコキシ基、アミン基である−ＳＯ_２Ｒ^１０基を意味する。特にスルホニル基としては、メシル基（Ｒ^１０ ＝ −ＣＨ_３）、トリフリル基（Ｒ^１０ ＝ −ＣＦ_３）やトシル基（Ｒ^１０ ＝ −Ｐｈ−ＣＨ_３）がある。
「アルコキシ基」とは、本発明においては、Ｒ^１１が上述の直鎖状または枝分かれ状の炭化水素基、アリール基、アラルキル基、アシル基、スルホニル基、糖類である−ＯＲ^１１基を意味する。
「糖類」とは、本発明においては、ヘキソース、単糖及び配糖体を意味する。特に糖類としては、グルコース、アラビノース、フルクトース、ガラクトース、マンノース、マルトース、ラクトース、サッカロース、セロビオースがある。 The cosmetic or dermatological medicinal composition having a slimming effect of the present invention contains at least one diterpene represented by the formula 2 (Chemical Formula 2) in a medium safe to human body.

put it here,
(1) R and R ′ may be the same or different and each represents a hydrogen atom, a linear or branched hydrocarbon group, an aryl group, an aralkyl group, an acyl group, a sulfonyl group, or a saccharide.
(2) The sequence XY corresponds to either CH ₂ —CH ₂ , CH═CH, CR ¹ R ² —CR ² R ⁴ or CR ⁵ = CR ⁶ , wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , and R ⁶ may be the same or different, and each represents a hydrogen atom, a linear or branched hydrocarbon group, an aryl group, an aralkyl group, an acyl group, a sulfonyl group, or a saccharide. Represents.
“Straight or branched hydrocarbon group” in the present invention is an optionally substituted (alcohol, carboxylic acid, amine, etc.), saturated or unsaturated, 1-20 carbon atom. Means a hydrocarbon group having In particular, the alkyl group includes a methyl group.
The “aryl group” in the present invention means one or more aromatic rings each having 5 to 8 carbon atoms, which are linked or fused and may have a substituent. In particular, the aryl group includes a phenyl group and a naphthyl group, and the substituent includes a halogen atom, an alkoxy group, the above-described linear or branched hydrocarbon group, and a nitro group.
The “aralkyl group” means, in the present invention, the above-described aryl group bonded through the above-described linear or branched hydrocarbon group. In particular, aralkyl groups include benzyl groups.
The “acyl group” in the present invention means a —C═OR ⁷ group in which R ⁷ is the above-mentioned linear or branched hydrocarbon group, aryl group, aralkyl group or amine group. In particular, an acyl group includes an acetyl group (R ⁷ = —CH ₃ ).
In the present invention, the “amine group” may be the same or different for R ⁸ and R ⁹ , and each represents a hydrogen atom, the above-mentioned linear or branched hydrocarbon group, an aryl group, an aralkyl group, The -NR < ⁸ > R < ⁹ > group which is an acyl group, a sulfonyl group, and saccharides is meant.
The “sulfonyl group” in the present invention means a —SO ₂ R ¹⁰ group in which R ¹⁰ is the above-described linear or branched hydrocarbon group, aryl group, aralkyl group, alkoxy group, or amine group. . Particularly sulfonyl group, mesyl group ^(R 10 = _-CH 3), there is a triflyl group ^(R 10 = -CF ₃₎ or a tosyl group _{^{(R 10 = -Ph-CH 3}} ).
The “alkoxy group” in the present invention means an —OR ¹¹ group in which R ¹¹ is the above-mentioned linear or branched hydrocarbon group, aryl group, aralkyl group, acyl group, sulfonyl group, or saccharide. .
In the present invention, “saccharide” means hexose, monosaccharide and glycoside. In particular, saccharides include glucose, arabinose, fructose, galactose, mannose, maltose, lactose, saccharose, and cellobiose.

The cosmetic or dermatological pharmaceutical composition having a slimming effect of the present invention contains at least one diterpene selected from cafe stall, carweol and chemical derivatives thereof in a human-safe medium.
In addition, the cosmetic or dermatological pharmaceutical composition having a slimming effect of the present invention contains at least one diterpene in a human-safe medium as described above, and separately from the diterpene, xanthines such as caffeine and theobromine. It also contains at least one lipolytic component, where the derivative is considered particularly advantageous.

  The diterpenes according to the present invention may have a plurality of asymmetric centers and therefore may exist as optical isomers. The present invention includes such isomers, either alone or in a mixture.

Examples of the diterpene according to the present invention include cafe stall (in formula 2, R = R ′ = H, XY = CH ₂ —CH ₂ ), carweol (in formula 2, R = R ′ = H, XY = CH = CH) and acetic acid caffe stall (in formula 2, R = —COCH ₃ R ′ = H, X—Y = CH ₂ —CH ₂ ) are preferred.

Diterpene derivatives such as cafe stall, carweol and their chemical derivatives can be obtained by chemical synthesis, especially by extracting plant extracts using some plant such as green coffee beans and other coffee beans. Can do. Extraction from any plant can be performed based on classical extraction methods.
Extraction solvents include water, propylene glycol, butylene glycol, glycerin, PEG-6 (capryl / capric acid) glyceryl, polyethylene glycol, methyl and / or ethyl ether of diglycols, cyclic polyols, ethoxyl groups or propoxyl groups In addition to diglycol, alcohol (methanol, ethanol, propanol, butanol), a mixture of these solvents can be selected.
For the extraction of green coffee beans, for example, dipping, brewing, leaching, reflux extraction, supercritical extraction, ultrasonic or microwave extraction, or countercurrent technology can be used, but not limited thereto. .

The “green coffee bean” in the present invention means a raw seed before roasting a plant belonging to the genus Coffea L .. Examples of plants belonging to the genus Coffea L. include Arabic coffee (Coffea arabica L.), Robusta coffee (Coffea robusta L.), and Liberia coffee (Coffea liberica B.).
The term “coffee beans” simply refers to a roasted seed of a plant belonging to the genus Coffea L.

  The amount of diterpene utilized in accordance with the present invention will of course vary depending on what effect is sought, but must be effective in promoting the slimming effect. For example, diterpenes may be from 0.1 ppm to 50% based on the total weight of the composition, generally from 1 ppm to 10%, preferably from 10 ppm to 1% based on the total weight of the composition.

In a particularly preferred embodiment of the present invention, a cosmetic or dermatological pharmaceutical composition having a slimming effect comprising a diterpene selected from cafestall, carweol and chemical derivatives thereof in a human-safe medium. In addition to the diterpene, the product contains a lipolytic component and / or an adipogenesis-suppressing component.
For example, complementation of effects can be added by stimulating the re-degradation of triglycerides already present in the cells to compensate for “nutrient decline” of adipocytes.

  The first method of stimulating triglyceride re-degradation is the usual method of amplifying cAMP by inhibiting phosphodiesterase. Examples of the phosphodiesterase inhibitor include xanthine derivatives and natural extracts containing the same. Examples of xanthine derivatives include caffeine and derivatives thereof, theophylline and derivatives thereof, theobromine, aminophylline, and xanthine. These xanthine derivatives can be used alone or in combination. Examples of natural extracts containing xanthine derivatives include tea, coffee, guarana, mate (Yerba Mate) and cola extracts.

  Other lipolytic components that can be used in the present invention include certain plant extracts and marine extracts that do not contain caffeine.

  In addition to the phosphodiesterase inhibitor, the lipolytic component contains an α-2 blocker, β-adrenergic agonist and antagonist, β receptor and / or G protein that blocks the α-2 receptor on the adipocyte surface. Choose from activating compounds, glucose transport blockers, neuropeptide Y (NPY) antagonists that block NPY receptors on the adipocyte surface, components that improve fatty acid transport, lipolytic peptides and lipolytic proteins be able to.

The above-mentioned methylxanthine can be obtained by either chemical synthesis or plant extraction using various plants including mate (Yerba Mate). Matecha (Yerba Mate) is a plant native to the Andes Plateau, and is rich in methylxanthine and used as a raw material for common beverages with stimulating effects. Among methylxanthines, caffeine and theobromine are the most abundant, and it has been confirmed that these components have an effect of promoting re-degradation of triglycerides.
In the plant extraction method, as an extraction solvent, water, propylene glycol, butylene glycol, glycerin, polyethylene glycol, methyl and / or ethyl ether of diglycols, cyclic polyol, diglycol containing ethoxyl group or propoxyl group, alcohol ( In addition to glyceryl (methanol, ethanol, propanol, butanol), PEG-6 (capryl / capric acid), a mixture of these solvents can be used.
In addition, when extracting a material (Yerba Mate), for example, immersion, decoction, leaching, reflux extraction, supercritical extraction, ultrasonic or microwave extraction, or countercurrent technology can be used. It is not necessarily done.
The natural extract containing a xanthine derivative such as methylxanthine is preferably a mate (Yerba Mate) extract containing a large amount of caffeine and theobromine.

  The amount of the lipolysis component or adipogenesis-inhibiting component contained in the composition according to the present invention other than diterpene varies greatly depending on the case, but is generally 0.0001 to 20%, preferably 0.001 to 10% of the composition weight. And

Particularly preferred forms of the present invention include a green coffee bean extract containing a large amount of diterpenes (especially cafe stall and carweol), and a material containing a large amount of caffeine, theobromine, aminophylline, theophylline and xanthine among methylxanthines (Yerba Mate) and extract. This combination induces complementarity of effects, leading to an overall reduction in fat mass through the reduction of fat cells by inhibiting the uptake of LDL and VLDL by fat cells and promoting the re-degradation of triglycerides contained in fat cells. It is burned.
The combination of the above components exhibits a synergistic effect in the slimming action.

According to a particularly advantageous embodiment, the composition having a slimming effect according to the invention also comprises at least one supplementary ingredient chosen from:
Minor, such as flavonoids, ginnan extract, ruscogenin, natural or synthetic escrosides, escin, nicotinate, hesperidin methylchalcone, ruscus (nagida), lavender or rosemary essential oils, Ammi visnaga extract Active ingredients that act on the circulatory system (vasoprotectants or vasodilators).
Centella asiatica and Siegesbeckia extracts, silicon, amadoline, ergothioneine and derivatives thereof, hydroxystilbene derivatives including hydroxystilbene and resveratrol, azalea plant extracts including blueberries, vitamin C and Tightening ingredients such as its derivatives, retinol and its derivatives and / or anti-glycation ingredients (preventing saccharides from sticking to collagen fibers).

  The blending amount of the supplemental component is not particularly limited, but is 0.01 to 20%, preferably 0.05 to 10% of the total weight of the composition.

  The composition which is the subject of the present invention comprises a medium that is safe for the human body and cosmetically or dermatologically unproblematic, ie compatible with the skin tissue. Therefore, the composition can be applied to various parts of the human body including mucous membranes and skin appendages.

The cosmetic or dermatological pharmaceutical composition can take any commonly used form depending on the application method.
For example, emollient lotion, milk or cream, skin care or hair care milk, spray or cream, cleansing cream, lotion or milk, foundation foundation, sunscreen lotion, milk or cream, artificial sun lotion, milk or cream, shave Cream or mousse, aftershave lotion, shampoo, lipstick, mascara or nail polish.
Such compositions may take the form of lipsticks, eye makeup products, funny or foundations to prevent lip coloring and cracking.
A mousse composition or aerosol composition containing a propellant can also be considered.
The diterpene is then used in the above form, alone or in the form of a premix of a suitable diluent.

When the composition according to the invention takes the form of an oil-in-water or water-in-oil type emulsion, the oil phase is essentially extracted or synthesized into a mixture of fats and oils and optionally Will be added with other fats and oils. The oil phase of the emulsion is not particularly limited, but is preferably 5 to 60 wt% of the total weight of the emulsion.
The water phase weight of the emulsion is not particularly limited, but is preferably 30 to 85 wt% of the total weight of the emulsion. The proportion of the emulsifier is preferably 1 to 20 wt% of the total weight of the emulsion, more preferably 2 to 12 wt%.

  When the composition according to the present invention is a lotion containing oil, oily alcohol or aqueous alcohol, for example, it becomes a sunscreen lotion or skin softening lotion containing an ultraviolet absorber. The oil lotion can constitute foaming oil, oil for bath, etc. containing an oil-soluble surfactant.

  The main additives that can be used in the cosmetic or dermatological composition according to the present invention include organic solvents such as MP-diol and polyglycerin, water-soluble glycol solvents, extraction or synthetic oils, ionicity Or nonionic thickener, softener, turbidity agent, stabilizer, emollient, silicone, α- or β-hydroxy acid, antifoaming agent, moisturizer, vitamin, fragrance, preservative, sequestering agent, coloring Agents, gelling and thickening polymers, surfactants and emulsifiers, other water-soluble or oil-soluble active ingredients, plant extracts, tissue extracts, marine extracts, UV absorbers, antioxidants, etc. One or more ingredients that are typically utilized in selected cosmetic products can be incorporated into a human safe mixture.

  Cosmetic or dermatological compositions having a slimming effect may contain, in addition to diterpenes, in particular the Yerba Mate extract and / or the green coffee bean extract.

  Of the alcohols, mono- or polyalcohols are particularly preferred, for example ethanol, isopropanol, propylene glycol, glycerol and sorbitol.

  As for oils and fats, petroleum oils can be mentioned as mineral oils. Animal oils include whale oil, camellia oil, seal oil, herring oil, halibut liver oil, cod oil, tuna oil, turtle oil, cow leg oil, horse leg oil, sheep leg oil, mink oil, otter oil, marmot oil, etc. Examples of vegetable oils include almond oil, wheat germ oil, jojoba oil, sesame oil, sunflower oil, palm oil, walnut oil, shea fat, dipterocarp oil, macadamia nut oil, and cassis seed oil.

Examples of fatty acid esters include C _{12 to} C ₂₂ saturated or unsaturated fatty acid esters, lower alcohol esters such as isopropanol and glycerol, or C _{8 to} C ₂₂ linear or branched saturated or unsaturated higher alcohol esters, C ₁₀ -C ₂₂ alkanediol-1,2 esters can be used.

  Moreover, as oils and fats, petrolatum, paraffin, lanolin, hydrogenated lanolin, tallow, lanolin acetate, and silicone oil can be used.

  Waxes include Sipollo, Lanolin wax, Beeswax, Candelilla wax, Monocrystalline wax, Carnauba wax, Whale wax, Cocoa butter, Shea butter, Silicone wax, Hydrogenated oil that solidifies at 25 ° C, Scroglyceride, and oleic acid , Myristic acid, linolenic acid and calcium stearate, magnesium and aluminum.

Higher alcohols include lauryl, cetyl, myristyl, stearyl, palmityl and oleyl alcohol, as well as Guerbet alcohols such as 2-decyltetradecanol or 2-hexidecanol. Regarding the emulsifier, polyoxyethylene fatty alcohols include lauryl, cetyl, stearyl and oleyl alcohols containing 2 to 20 mol of ethylene oxide, and alkyl ethers of glycerol are C ₁₂ to 2 to 10 mol of glycerol. There are _C18 alcohols. In addition, a viscous agent such as a cellulose derivative, a polyacrylic acid derivative, guar gum, locust bean gum, or xanthan gum can also be used.

  The composition according to the present invention may contain additives usually used in cosmetics and skin treatments, such as moisturizers, softeners, skin drugs, UV absorbers, bactericides, and colorants. , Preservatives, fragrances and propellants.

  When the composition according to the present invention is a dispersion, there is an aqueous dispersion of lecithin containing a surfactant or an aqueous dispersion of lipid globules consisting of an organized molecular membrane with an encapsulated aqueous phase. In this regard, lipid compounds include long-chain alcohols and diols, sterols such as cholesterol, phospholipids, sulfuric acid and cholesteryl phosphate, long-chain amines and their quaternary ammonium derivatives, dihydroxyalkylamines, polyoxyethylene fatty amines, Long chain aminoalcohol esters and salts thereof and quaternary ammonium derivatives, fatty alcohol phosphates such as dicetyl phosphate or its sodium salt, alkyl sulfates such as sodium cetyl sulfate, fatty acid salts and French Patent No. 2 315 Mention may be made of certain types of lipids described in 991, 1 477 048 and 2 091 516 or international patent applications WO 83/01 571 and WO 92/08 685.

  Other lipids include lipophilic long chains with 12-30 carbon atoms, saturated or unsaturated, linear or branched, such as olein, lanolin, tetradecyl, hexadecyl, isostearyl, laurin Alternatively, lipids having a long alkylphenyl chain can be used. These lipophilic groups of lipids may be ionic or nonionic. Nonionic lipophilic groups include polyethylene glycol derivatives. As the lipid forming the lamellar phase, polyglycerol ethers described in French Patent Nos. 1 477 048, 2 091 516, 2 465 780 and 2 482 128 can also be used effectively.

  As the ionic lipophilic group, amphoteric, anionic and cationic ones can be used effectively.

  Other lipids described in International Patent Application WO 83/01 571 as being usable for vesicle formation include glycolipids such as lactosylceramide, galactocerebroside, ganglioside and trihexosylceramide, phosphatidylglycerol and phosphati There are phospholipids such as diluinositol.

The active ingredient is an ingredient effective as a pharmaceutical or food or a cosmetically active ingredient. The water-soluble active ingredient is in an aqueous phase that is uniformly dissolved or enclosed in a vesicle. The water-soluble component having activity as a cosmetic and / or pharmaceutical product may be a product for caring for or treating skin or hair, and includes the following. Moisturizing ingredients such as glycerin, sorbitol, pentaerythritol, pyrrolidone carboxylic acid and their salts: artificial tans that may be used in combination with colorants such as dihydroxyacetone, erythritol, glyceraldehyde, and tartaric aldehyde. Ingredients: Water-soluble UV absorbers: antiperspirants, deodorants, astrins, refreshing agents, stimulants, healing agents, keratin softeners, hair removal agents, aromatic waters: polysaccharides and other plant tissue extracts: water-soluble colorants: anti-dandruff Agent: Anti-seborrheic agent, oxidizing agent such as hydrogen peroxide and other decoloring agents: reducing agent such as thioglycolic acid and its salts.
In addition, vitamins, hormones, enzymes such as superoxide dismutase, vaccines, anti-inflammatory agents such as hydrocortisone, antibiotics, bactericides, cytotoxic agents and antitumor agents can be mentioned.

  If the active ingredient is fat-soluble, it can be placed in the vesicle membrane. Fat-soluble active ingredients include fat-soluble UV absorbers, ingredients that improve skin drying and aging, tocopherol, vitamin E, F or A and esters thereof, retinoic acid, antioxidants, essential fatty acids, glycyrrhetinic acid, keratin softener And carotenoids can be selected.

  The diterpene can be used in the cosmetic or dermatological pharmaceutical composition according to the present invention as a single substance or as a premix, separately added or previously mixed with an appropriate excipient, and used as a solution, dispersion, emulsion, paste. Alternatively, it can be used in the form of powder. It can also be transported with cosmetic vectors such as macro, micro or nano capsules, liposomes or kilomicrons, macro, micro or nano particles or micro sponges. It can also be adsorbed on powdered organic polymers, talc, bentonite and other mineral media.

  Diterpenes can be worn in any form or in the day or night, including synthetic and natural fibers, wool, in macro, micro, or nanoparticle or macro, micro, or nanocapsule binding, addition, absorption, or adsorption forms. Can be used in the manufacture of clothes and underwear. Direct contact with the skin such as stockings, underwear, handkerchiefs, wet tissues, etc., can exert a cosmetic effect through contact between the fibers and the skin, and can perform continuous local delivery It can be used to process any material.

  In addition, the cosmetic or dermatological composition according to the present invention is intended to prevent slimming of the thighs and waists and to tighten the skin, and especially to prevent and treat cellulite and orange skin and / or tighten the facial contour. It also relates to the use of cosmetic or dermatological compositions according to the invention for cosmetic purposes by topical application.

  Furthermore, the cosmetic or dermatological pharmaceutical composition according to the present invention is intended for slimming measures for overweight of the thighs and lower back, tightening of the skin and especially prevention / treatment of cellulite and orange skin and / or tightening of the facial contour. It also relates to the use of the composition according to the invention as a cosmetic or dermatological pharmaceutical composition or for its manufacture.

  In addition to the above, the present invention includes topical application of a cosmetic or dermatological composition based on the present invention, and is intended for the prevention and treatment of cellulite and orange skin and / or tightening and slimming of the body and facial contours. It also covers beauty methods.

  The composition according to the present invention can be applied topically to the face or body to be tightened, such as the waist, buttocks, thighs, abdomen and facial contours. One of the major advantages of the present invention is that, thanks to the topical application, a very local and selective “gentle” treatment can be performed as needed or desired.

  The present invention also provides a skin, mucous membrane and skin appendage for the purpose of anti-overweight slimming of the thigh and waist, tightening of the skin, and especially prevention / treatment of cellulite and orange skin and / or tightening of facial contours. It also relates to the use of the composition according to the invention in the preparation of skin care medicines for care and the like.

For reference, although not limited to the following, some examples of use of the present invention will be introduced.
[Prescription Example 1: Slimming preparation (PA1)]
Yerba Mate Extract 30.0
Butylene glycol 15.0
Green coffee bean extract 10.0
Crobol A70 5.0
Glycerin 5.0
Cetyl hydroxyethyl cellulose 1.5
Water, preservative
Total 100wt%
Formulation PA1 contains the following amounts of active ingredients.
Active ingredient wt% of total weight of PA1
Cafe stall 0.05-0.07wt%
Caffeine 0.9 to 1 wt%
Theobromine 0.09 ~ 0.11wt%
Formulation PA1 is the most preferred embodiment of the present invention. The amount of the preparation PA1 in the cosmetic composition varies greatly depending on the case, but is generally 0.001 to 20 wt%, preferably 0.01 to 10 wt% of the total weight of the cosmetic composition. Formulation PA1 is used as a slimming effectiveness in the products shown below.

[Example 2: Slimming gel]
Carbopol 1342 0.3
Propylene glycol 2.0
Glycerin 1.0
White petrolatum 1.5
Cyclomethicone 6.0
Cetyl alcohol 0.5
Lyubragel MS 10.0
Trietanoramine 0.3
PA1 3.0
Water, preservative, fragrance
Total 100wt%

[Example 3: Slimming massage cream]
Ultrez 10 0.2
Butylene glycol 5.0
Stearic acid 1.5
Kurodamol GTCC 2.0
Petratum Oil 2.0
Kurodakor C90 0.5
Kurodafos CES 1.5
PA1 3.0
Water, preservative, fragrance
Total 100wt%

[Example 4: Effect of caffeol acetate acetate on mRNA of LDL and VLDL receptors]
(principle)
In order to clarify the transcriptional control (control of the RNA copy number of the gene encoding the protein to be examined), it is necessary to isolate synthetic messenger RNA (mRNA) by cell culture. Next, mRNA specific to the protein under consideration must be identified from the entire mRNA pool present in the cell.
The amplification / quantification method used is the reverse transcriptase polymerase chain reaction (RT-PCR) method, which is performed in real time using the latest apparatus, and enables quantitative measurement of the target mRNA online.

(Test procedure)
The preadipocyte cell line 3T3-L1 at the stage of differentiation into adipocytes (after the addition of an appropriate differentiation-inducing cocktail) was cultured for 24 hours with caffestol acetate.
At the end of the test, the adipocytes were degraded and the extracted mRNA was transcribed (by reverse transcriptase) into cDNA. The cDNA was then amplified (n copies per Taq-polymerase) to obtain a detectable signal.
Each time an amplicon (cDNA amplification product) was produced, it was quantified with an RT-PCR apparatus, and then electrophoresis was performed to visually confirm the results.

内部マーカーであるβ−アクチンにより標準化した値を、標準試料に対するパーセンテージで表した。３回行った試験の平均値である。 (Test results)

Values normalized by the internal marker β-actin were expressed as a percentage of the standard sample. It is the average value of the test performed 3 times.

(Conclusion)
Caffe stall acetate showed a clear effect on reducing mRNA expression, with a 33% reduction at 24 hours for the LDL receptor and a 10% reduction for the VLDL receptor.

(In vivo test)
[Example 5: Body cream used in clinical trial of female panel]
Ultrez 10 0.4
Glycerin 10.0
Crillet 1 2.0
Kurodamol OP 4.0
Dimethicone 3.0
Potassium sorbate 0.1
NaOH 38% 0.6
Ethanol 3.0
PA1 3.0
Water, preservative, fragrance
Total 100wt%

[Example 6: Massage cream used in clinical trial of male panel]
Ultrez 10 0.2
Butylene glycol 5.0
Kurodamol GTCC 2.0
Kurodamol C90 0.5
Dimethicone 1.5
DC345 2.0
Potassium sorbate 0.1
Stearic acid 1.5
NaOH 38% 0.5
Ethanol 3.0
PA1 3.0
Water, preservative, fragrance
Total 100wt%

The in vivo effect test of PA1 was performed for each set of female and male panels using an interference fringe detection method (FOITS) that analyzes the optical deformation of the laser interference fringe projection.
(principle)
The subject is located at a predetermined distance and is completely reproducible for each measurement. The analysis site is sequentially scanned with interference fringes of different widths.
Measurements are made on sites that are precisely positioned by natural landmarks, such as moles and clearly visible venules.
The recording of the deformation related to the state of the scanning surface is automatically performed while gradually projecting thin interference fringes. By automatically capturing the signal with the CCD camera, the scanned volume can be reproduced on the screen without directly touching the object.
The scanned volume is expressed in milliliters, and the decrease in local volume is measured by the change at the start and end of the test.

(Test procedure)
Volunteers of 15 male subjects and 12 female subjects applied cream containing 3% PA1 twice a day for 56 days.
Each subject became his / her own comparison standard, and a comparison was made between the cream application location and the non-application location. Thereby, it is possible to evaluate the volume change generated during the test due to environmental factors different from the effect of the cream application without causing a problem.

(Examination for female panel)
[Employment criteria]
Caucasian subjects aged 18 to 45 years. Cellulite on the thigh. Body mass index (BMI) is 20-26 kg / m ² . Weight is stable for at least 3 months. No diet has been available since 3 months before the test.
[Test results]
By collecting 3D data, the volume of the upper and lower thighs could be reproduced.
Thirteen volunteers with an average age of 28.7 ± 8 participated in the study.
The thigh volume before the start of the test (T0) and on the 56th day (T56) were compared.
The circumference of the thigh was represented by the perimeter of the upper cross section of the thigh, which becomes the boundary of the examination volume.
At T0, there was no significant difference in left and right thigh volumes.
Calculate the average volume increase / decrease after 56 days. Significance by Student's corresponding t-test (comparison between application and reference) and non-corresponding t-test (difference between T0 and T56 in each thigh) Judgment was made.
The test results are shown in Tables 3 and 4.

塗布５６日後、大腿部のボリュームと寸法はきわめて有意な変化を見せ、ボリュームは１０％減（Ｐ＜０．０１）、寸法は約１ｃｍ減（Ｐ＜０．０１）となっている。これと同じ期間において、クリームを塗布されなかった大腿部は有意の変化はまったく見せておらず、有意ではないがごく僅かな増加さえ見せている。

56 days after application, the volume and dimensions of the thigh showed a very significant change, the volume decreased by 10% (P <0.01), and the dimension decreased by about 1 cm (P <0.01). During this same period, the thigh that had not been applied with the cream showed no significant change, and even a slight but not significant increase.

(Examination for male panel)
[Employment criteria]
White subjects over 30 years old. Body mass index (BMI) is 20-26 kg / m ² . Clear meat slack in the waist. Weight is stable for at least 3 months. I haven't been on a diet since 3 months before the test.
[Test results]
The outer surface and volume of the waist slack were reproduced by 3D data collection.
In this case (unlike the thigh, only the outer surface can be grasped), the available parameters are virtual volumes based on the average distance between the slack surface and the virtual cross section (which forms part of the upper body thickness). .
Thus, for each subject, the average increase / decrease in the amount of sag was evaluated in milliliters, but this could not be converted to a percentage.
15 volunteers with an average age of 42.3 ± 11 participated in the study. There was no significant difference in the volume of left and right sagging at T0.
Average increase / decrease in waist sagging after 56 days was confirmed, and the significance was determined by Student's paired t-test (comparison between application and reference) and unpaired t-test (difference between T0 and T56 for each sagging) Judgment was made.
The test results are shown in Table 5.

塗布５６日後において、腰部たるみ量の増減は、実質的に有意な１７．７ｍＬ減となっている。これと同じ期間において、クリームを塗布されなかった腰部は有意の変化をまったく示していない。

After 56 days of application, the increase or decrease in the amount of sag in the waist is substantially 17.7 mL. During this same period, the waist that had not been applied with the cream showed no significant changes.

Claims (15)

In addition to at least one diterpene selected from cafe stall, carweol and acetate cafe stall, a phosphodiesterase inhibitor selected from natural extracts containing methylxanthine is contained in a human safe medium. A cosmetic or dermatological pharmaceutical composition for topical application for slimming. The cosmetic or dermatological pharmaceutical composition for topical application for slimming according to claim 1, wherein the diterpene is derived from a plant extract. Plant extracts Arabic Coffea (Coffea arabica L.), Coffea canephora (Coffea robusta L.) and Liberia Coffea (Coffea liberica B.) co Hinoki genus selected from (Coffea L.) raw before roasting plants belonging A cosmetic or dermatological pharmaceutical composition for topical application for slimming according to claim 2, characterized in that it is a seed (green coffee bean) extract. The cosmetic or dermatological pharmaceutical composition for topical application for slimming according to any one of claims 1 to 3 , wherein the diterpene accounts for 0.0001 to 50% of the total weight of the composition. The cosmetic or dermatological pharmaceutical composition for topical application for slimming according to any one of claims 1 to 4 , wherein the phosphodiesterase inhibitor accounts for 0.0001 to 20% of the total weight of the composition. The cosmetic or dermatological pharmaceutical composition for topical application for slimming according to claim 1 , wherein the natural extract containing methylxanthine is a Yerba Mate extract. 7. The composition according to claim 1 , further comprising at least one supplemental component selected from components acting on the microcirculatory system, tightening component and / or anti-glycation component and mixtures thereof. A cosmetic or dermatological pharmaceutical composition for topical application for slimming. Diterpenes are used in the form of solutions, dispersions, emulsions, pastes or powders as a single or premix, or as macroscopic, micro or nanocapsules, liposomes or kilomicrons, macro, micro or nano particles as a single or premix or or transported by a vector selected from the microspheres Pont di, characterized in that it is adsorbed powdered organic polymers, talc, bentonite and other mineral medium, for slimming according to any one of claims 1 to 7 Cosmetic or dermatological pharmaceutical composition for topical application. Diterpene is, each seed agent selected emollient lotion, milky lotion or cream, skin care lotion or cream, cleansing cream, lotion down, foundation base, sunscreen lotions, artificial tanning lotion or cream, after-shave lotion, from the mouth red Cosmetic or dermatological agent for topical application for slimming according to any of claims 1 to 8 , characterized in that it is used in the form of a single or in the form of a premix with suitable excipients. Composition. Organic solvent or water-soluble glycol solvent, extraction or synthetic oil, ionic or nonionic thickener, softening agent, turbidity agent, stabilizer, emollient, silicone, α-hydroxy acid, antifoaming agent, Moisturizers, vitamins, fragrances, preservatives, sequestering agents, colorants, gelling and thickening polymers, surfactants and emulsifiers, other water-soluble or fat-soluble active ingredients , plant extracts, tissue extracts, marine extracts The composition according to claim 1 , comprising one or more ingredients selected from ultraviolet absorbers and antioxidants and commonly used in cosmetics in a human safe mixture. A cosmetic or dermatological pharmaceutical composition for topical application for slimming according to any one of the above. Thigh and overweight slimming measures the waist, and the prevention, treatment and / or facial contour tightening tightening及beauty cell Ruraito and orange skin skin for the purpose, slimming according to any one of claims 1 to 10 For cosmetic use by topical application of a cosmetic or dermatological pharmaceutical composition. Thigh and overweight slimming measures the waist, the tightening及beauty cell Ruraito and prevention and treatment of orange skin and / or the face of the tightening of the contour of the skin for the purpose, the composition according to any one of claims 1 to 10 the object, a method for utilization of a cosmetic or dermatological agent composition is for slimming topical application. The composition according to any one of claims 1 to 10, for the purpose of slimming measures for overweight of the thigh and waist, tightening of the skin and prevention / treatment of cellulite and orange skin and / or tightening of the facial contour. A method of use in the production of a cosmetic or dermatological pharmaceutical composition for topical application for slimming. A topical application of a cosmetic or dermatological pharmaceutical composition for slimming according to any one of claims 1 to 10 , and prevention and treatment of cellulite and orange skin and / or tightening and slimming of the body and facial contours Usage for the purpose. Thigh and overweight slimming measures the waist, the fit Hikishima contour of prevention, treatment and / or the face of the tightening及beauty cell Ruraito and orange skin skin aimed, in preparation of skin care pharmaceuticals claim 1 A method for using a cosmetic or dermatological composition for topical application for slimming according to any one of 10 .