JPH11130656A - Adiposity inhibitor and preparation for external use for skin containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject inhibitor useful for preparations for external use for skin, exhibiting excellent effect of preventing accumulation of an excessive quantity of fat by controlling increase in number of fat cells and also excellent slimming effect by including an ω-3-based polyunsaturated fatty acid. SOLUTION: This preparation contains an ω-3-based polyunsaturated fatty acid and/or its derivative (e.g. eicosapentaenoic acid, docosahexaenoic acid and α-linolenic acid) at 0.0001 to 10 wt.%, preferably 0.01 to 5 wt.%, and also preferably contains at least one agent selected from the group consisting of a phosphodiesterase activity inhibitor (e.g. caffeine and theophyline), cyclic AMP and/or its derivative, plant extract containing cyclic AMP (e.g. Jujube extract), β-adrenergic stimulant and/or α<2> -adrenergic inhibitor (e.g. isoproterenol), astringent (e.g. aloe extract), blood circulation accelerant (e.g. tocopherol), and lipase activity accelerant (Fucus extract).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a fat accumulation inhibitor, and more particularly to a fat accumulation inhibitor useful for suppressing or preventing obesity, reducing local or systemic fat tissue, and an external skin containing the same. Agent.

[0002]

2. Description of the Related Art Obesity is caused by excessive intake of energy with respect to consumed energy, which is accumulated as neutral fat in white fat cells, and is a serious problem for men and women from the viewpoint of medical care and beauty. ing. There are two types of such obesity. One is a type in which the number of fat cells does not change, and fat is accommodated by expanding the capacity of the existing fat cells (fat cell capacity expansion type obesity), and the other is a type in which the number of fat cells increases This is a type that accommodates fat that increases due to fat (adipocyte-increased obesity). The latter adiposity-increasing obesity does not significantly increase the adipocyte capacity, but has a drawback in that it is more resistant to obesity treatment than the former adipocyte-enlargement obesity. The reduction in fat cell volume occurs relatively easily, but the reduction in fat cell number does not occur except in special cases.

[0003] Conventionally, in order to suppress, prevent and improve obesity, in addition to dietary restrictions, taking of drugs and the like and appropriate exercise, use of cosmetics such as massage gels and creams for promoting metabolism in the body has been used. It has been known. As an example, cosmetics intended for slimming effects have been attempted to incorporate medicinal ingredients such as caffeine, western ivy extract, hamamelis extract, green tea extract, black tea extract, oolong tea extract, and seaweed extract. I was

[0004]

However, in the skin external preparation containing the above-mentioned medicinal components, the effect of the medicinal components is not sufficient, or if a sufficient amount is obtained to obtain the medicinal effects, the feeling of use becomes poor. There are problems such as being damaged, and improvement thereof has been desired. In addition, the future medicinal ingredients,
It acts on fat cell capacity expansion type obesity by the phosphodiesterase activity inhibitory action and astringent action which are one step of lipid metabolism, decomposes fat and tightens the body, and increases fat cells by focusing on suppressing the number of fat cells. At present, components that act on type obesity are not well known. Therefore, there has been a strong demand for the development of a medicinal component having a sufficient effect while suppressing an increase in the number of fat cells to prevent accumulation of excessive fat.

[0005]

Means for Solving the Problems As a result of intensive studies, the present inventors have found that ω-3 polyunsaturated fatty acids and / or derivatives thereof have an excellent fat accumulation inhibitory effect,
Fat accumulation is synergistically suppressed by combining specific medicinal ingredients.Furthermore, by combining a medicinal agent having these fat accumulation suppressing effects, a skin external preparation excellent in slimming effect can be obtained. And completed the present invention. That is, the present invention provides a fat accumulation inhibitor containing an ω-3 polyunsaturated fatty acid and / or a derivative thereof, and a ω-3 polyunsaturated fatty acid and / or a derivative thereof, a phosphodiesterase activity inhibitor, a cyclic AMP and / or a derivative thereof, a salt, a plant extract containing cyclic AMP, a β-adrenergic stimulant and / or an α ² -adrenergic inhibitor, an astringent, a blood circulation promoter, or a lipase activity promoter. A fat accumulation inhibitor containing one or two or more kinds, and an external preparation for skin containing these fat accumulation inhibitors. The details will be described below.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The ω-3 polyunsaturated fatty acid and / or its derivative used in the present invention has 18 carbon atoms.
To 22 and a free fatty acid having 3 or more unsaturated bonds and / or a derivative thereof. These free fatty acids include, for example, α-linolenic acid, stearidonic acid, eicosatetraenoic acid, eicosapentaenoic acid, docosahexaenoic acid, and the like. Examples of the derivatives include salts and esters.Examples of the salts include metal salts such as sodium and potassium, and amine salts such as triethanolamine and monoethanolamine.Examples of the ester include glycerin And mono-, di- and triglycerides. These can be isolated and blended alone, or can be used as a mixture.Fats and oils containing a large amount of these, such as tuna oil, sardine oil, fish oil such as saury oil and perilla oil, etc. are used as they are. can do.

In the present invention, one or more of the above-mentioned ω-3 polyunsaturated fatty acids and / or their derivatives can be appropriately selected and used according to the purpose. Among them, eicosapentaenoic acid (hereinafter referred to as “EP
A "), docosahexaenoic acid (hereinafter referred to as" DH
A "), α-linolenic acid is preferred.

The content of the ω-3 polyunsaturated fatty acid and / or a derivative thereof in the composition of the present invention is not particularly limited, but is preferably 0.0001 to 10% by weight (hereinafter, referred to as “the content”).
Simply expressed as “%”), and more preferably 0.01%.
~ 5%. In the case of using an oil / fat having a low purity of the ω-3 type highly unsaturated fatty acid and / or its derivative, the substantial content may be within the above range. When the content of the ω-3 polyunsaturated fatty acid and / or its derivative is less than 0.0001%, a sufficient effect may not be obtained,
If the content is more than 10%, there may be a problem in the preparation, such as coloring, odor generation, or precipitation depending on the dosage form.

Further, by combining the above-mentioned ω-3 polyunsaturated fatty acid and / or a derivative thereof with a specific medicinal ingredient, the effect of suppressing fat accumulation becomes more remarkable. Specific medicinal ingredients include a phosphodiesterase activity inhibitor, cyclic AMP and / or a derivative thereof and a salt, a plant extract containing cyclic AMP, β-
Adrenergic stimulants and / or α ₂ -adrenergic inhibitors Astringents, blood circulation enhancers and lipase activity enhancers are one or a combination of two or more thereof. What is shown is mentioned.

(Phosphodiesterase activity inhibitor) Examples of the phosphodiesterase activity inhibitor include xanthine derivatives represented by caffeine, theophylline, theobromine, aminophylline and the like, salts thereof, citric acid, black tea extract, green tea extract, oolong tea Extracts and the like can be mentioned, and one or more of these can be appropriately selected and blended.

Among these phosphodiesterase activity inhibitors, particularly preferred are caffeine and its derivatives and salts thereof, theophylline and its derivatives and their salts, black tea extract, green tea extract and oolong tea extract. .

(Cyclic AMP and / or Derivative and Salt and Plant Extract Containing Cyclic AMP) The cyclic AMP and / or its derivative and salt include cyclic AMP and dibutyryl cyclic AMP and the like. And a salt of cyclic AMP sodium and the like. Examples of the plant extract containing cyclic AMP include a daisy extract, and one or more of these can be appropriately selected and blended.
Of these, cyclic AMP is particularly preferable.
It is a Chinese radish extract.

(Β-Adrenergic stimulant and / or α ₂ -adrenergic inhibitor) Astringents of β-adrenergic stimulant and / or α ₂ -adrenergic inhibitor include isoproterenol, dobutamine, Salbutamol, yohimbine, phentolamine, ergotamine and the like can be mentioned, and one or more of these can be appropriately selected and blended.

(Astringent) Astringents include zinc oxide, zinc paraphenol sulfonate, peppermint extract,
Oak extract, horse chestnut extract, aloe extract, hamamelis extract, rosemary extract, horsetail extract, western kizuta extract, clematis extract, sycamore extract, lavender extract, eucalyptus extract, hop extract, A birch extract, an Ibukitorano extract, a butcher bloom extract and the like can be mentioned, and one or more of these can be appropriately selected and blended.

Among these astringents, particularly preferred are aloe extract, hamamelis extract, rosemary extract, horsetail extract, western kizuta extract, clematis extract, sycamore extract, lavender extract, eucalyptus extract Extracts, hop extracts, birch extracts and Ibukitorano extract, marronnier extracts, butcher bloom extracts.

(Blood circulation enhancer) As blood circulation enhancers, tocopherol and its derivatives, nicotinic acid and its derivatives and salts thereof, γ-oryzanol, camphor, assembly extract, panax ginseng extract, hinokitiol,
A pepper extract, a ginkgo extract, an arnica extract, a safflower extract and the like can be mentioned, and one or more of these can be appropriately selected and blended.

Of these blood circulation promoting agents, particularly preferred are tocopherol and its derivatives, nicotinic acid and its derivatives and their salts, assembly extracts, panax ginseng extracts, hinokitiol, pepper extracts, ginkgo extracts and assembly extracts. , Arnica extract and safflower extract.

(Lipase activity enhancer) Examples of the lipase activity enhancer include hibamata extract, wakame extract, kelp extract, Aonori extract, chlorella extract, and the like.
One or more of these can be appropriately selected and blended. Among these lipase activity promoters, particularly preferred are Hibamata extract, Chlorella extract and Wakame extract.

The amount of the above-mentioned medicinal ingredient combined with the ω-3 polyunsaturated fatty acid and / or its derivative is not particularly limited, but is preferably 0.0001 to 10
%, More preferably 0.01 to 5%. Within this range, the effects of the present invention are more remarkably exhibited.

Examples of the external preparation for skin containing the above-mentioned fat accumulation inhibitor include cosmetics such as milky lotions, creams, lotions, packs, cleansers, massages and the like, cosmetics for the body, quasi-drugs or external medicines And so on.

The external preparation for skin of the present invention includes, in addition to the above-mentioned essential components, components to be added to ordinary external preparations for skin, for example, oils, powders, surfactants, purified water, polyhydric alcohols, lower grades. Alcohols, polymer compounds, gelling agents, ultraviolet absorbers, ultraviolet scattering agents, antioxidants, dyes, preservatives, fragrances, cosmetic ingredients, and the like can be appropriately selected and used as long as the effects of the present invention are not impaired. .

[0022]

EXAMPLES The present invention will be described in more detail with reference to Test Examples and Examples, which should not be construed as limiting the present invention.

Test Example 1 First, a test was conducted on the effect of ω-3 polyunsaturated fatty acids on adipocyte differentiation. Adipocytes are known to differentiate from fibroblasts called preadipocytes. Thus, the effect of ω3 highly unsaturated fatty acids on adipocyte differentiation was determined by adding a differentiation promoting agent to fibroblasts and using an enzyme that is specifically activated when differentiated into adipocytes as a differentiation expression marker. Was evaluated.

(Evaluation method) 0.5 × 10 ⁵ 3T3-L1 preadipocytes (fibroblasts) / ml were added to 10% FBS.
After culturing in DMEM medium for 2 days, the cells are differentiated with 0.5 mM 1-methyl-3-isobutylxanthine and 0.25 μM dexamethasone. At this time, ω−
The system 3 highly unsaturated fatty acids are added to the medium. 4 more
After 8 hours of culture, the cells were returned to 10% FBS-DMEM and seeded 9
After a day, glycerol-3-phosphate dehydrogenase (GPDH) activity was measured as a marker for differentiation expression into adipocytes, and at the same time, the protein was quantified by the Lowly method, and the specific activity (unit / mg) was calculated. Table 1 shows the relative values when the specific activity of the control is 100%.

[0025]

[Table 1]

As can be seen from the results in Table 1, DHA, E
In the group in which PA and α-linolenic acid were added to the ω-3 polyunsaturated fatty acids, GPDH activity, which is a differentiation expression marker for adipocytes, was reduced, so that the differentiation of preadipocytes into adipocytes was suppressed. It became clear.

Examples 1-4 and Comparative Examples 1-3 Cream Creams having the compositions shown in Table 2 were prepared and their slimming effects were evaluated.

[0028]

[Table 2]

(Preparation method) A: Components 1 to 8 and 11 are mixed and heated to 70 ° C. B: Heat component 13 to 70 ° C. C: Add B to A, emulsify and mix, then cool. D: Components 9 to 10 and 12 were added to C to obtain a cream.

(Evaluation method) 1 cream per test product
A panel of 15 women aged 8 to 28 years old.
Each time, an appropriate amount of the test cream was applied to the whole body for 12 weeks, and massaged sufficiently. The change in body fat percentage before and after the test period was measured using a body fat percentage meter (BFT-2000; manufactured by Kett Kagaku Co., Ltd.) to determine the rate of decrease in body fat percentage. Was evaluated. Table 2 also shows the obtained results.

As is evident from the results in Table 2, the cream containing the DHA-containing fat or oil according to the present invention, when applied to the skin, reduced the body fat percentage and had an excellent slimming effect. Further, the creams containing the DHA-containing fats and oils and the phosphodiesterase activity inhibitor, and the DHA-containing fats and fats and the blood circulation promoter, respectively, had more remarkable effects. On the other hand, the effect of the comparative example, which is a conventional technique in which a phosphodiesterase activity inhibitor or a blood circulation promoting agent was independently blended, was not sufficient.

Example 5 Lotion (Component) (%) Glycerin 3.0 2.1,3-butylene glycol 2.0 Polyoxyethylene (20EO) Sorbitan 1.0 Monolaurate 4. Ethyl alcohol 5.0 5. EPA (Note 1) 0.5 6. Panax ginseng extract (Note 2) 3.0 7. Preservative appropriate amount 8. Appropriate amount of flavor 9. Remaining purified water (Note 1) Sigma (Note 2) Panax ginseng root extracted with 90 v / v% ethanol.

(Production method) A: Components 3, 4, 5, 7 and 8 are mixed and dissolved. B: Components 1, 2, 6 and 9 are mixed and dissolved. C. A and B were mixed and made uniform to obtain a lotion. The lotion of Example 5 showed an excellent slimming effect.

Example 6 Emulsion (Component) (%) 1. Polyoxyethylene (10EO) sorbitan 1.0 monostearate 2. Polyoxyethylene (60EO) sorbitan 0.5 tetraoleate Glyceryl monostearate 1.0 4. Stearic acid 0.55. Behenyl alcohol 0.56. Squalane 8.0 7. α-linolenic acid (Note 1) 2.0 8. Caffeine (Note 2) 0.19. Tradition extract (Note 3) 0.1 10. Hibamata extract (Note 4) 0.1 11. Preservative appropriate amount 12. Carboxyvinyl polymer 0.1 13. Sodium hydroxide 0.05 14. Ethyl alcohol 5.0 15. Purified water balance 16. Perfume Appropriate amount (Note 1) Sigma Corporation (Note 2) Kanto Kagaku Co. (Note 3) Extract of daisies fruit with purified water. (Note 4) Extracted from 90% v / v ethanol of stems of a plant of the genus Hibamata.

(Preparation method) A: Components 8 to 15 are mixed by heating and maintained at 70 ° C. B: Components 1 to 7 are mixed by heating and maintained at 70 ° C. C: A is added to B and emulsified and mixed. D: After cooling C, component 16 was added and mixed uniformly to obtain an emulsion. The emulsion of Example 6 showed an excellent slimming effect.

Example 7 Massage Gel (Component) (%) Ethanol 10.0 2. 2. Polyoxyethylene (60) hydrogenated castor oil 0.5 Carboxyvinyl polymer 0.5 4. Triethanolamine 0.55. Glycerin 10.0 6. Dipropylene glycol 5.0 7. DHA-containing fats and oils (Note 1) 5.0 8. Isoproterolol (Note 2) 0.02 9. Preservative appropriate amount 10. Appropriate amount of fragrance 11. Appropriate amount of purified water (Note 1) Fish oil purified product with DHA content of 35% (Note 2) Sigma

(Preparation method) A: Components 1, 2, 9 and 10 are mixed by heating and kept at 75 ° C. B: Components 3 to 8 and Component 11 are mixed by heating and kept at 75 ° C. C: Add A to B. D: C was cooled to obtain a massage gel. The massage gel of Example 7 showed an excellent slimming effect.

Example 8 Pack (Ingredient) (%) Polyvinyl alcohol 20.0 2. Ethyl alcohol 20.0 3. Glycerin 5.0 4. Kaolin 6.0 5. 5. Fat containing EPA (Note 1) 1.0 6. Marronnier extract (Note 2) 3.0 7. Preservative appropriate amount 8. Appropriate amount of flavor 9. Remaining purified water (Note 1) Fish oil refined product with EPA content of 25% (Note 2) Dried fruit of horse chestnut is extracted with 1,3-butylene glycol.

(Preparation method) A: Components 1, 3, 4, 6, and 9 are mixed, heated to 70 ° C., and stirred. B: Components 2, 5, 7 and 8 are mixed. C: B was added to A, mixed, and cooled to obtain a pack. The pack of Example 8 showed an excellent slimming effect.

Example 9 Cleaning Fee (Component) (%) Stearic acid 10.0 2. 2. Palmitic acid 8.0 Myristic acid 12.0 4. Lauric acid 4.0 5. Oleyl alcohol 1.5 6. Purified lanolin 1.0 7. Appropriate amount of flavor 8. Preservative appropriate amount 9. Glycerin 18.0 10. Potassium hydroxide 6.0 11. 11. DHA-containing fats and oils (Note 1) 5.0 12. acetic acid-dl-α-tocopherol (Note 2) 0.05 Purified water Remaining (Note 1) Fish oil purified product with DHA content of 25% (Note 2) Tokyo Chemical Industry

(Preparation method) A: Components 9, 10 and 13 are mixed and heated to 70 ° C. B: Components 1 to 6, 8, 11, and 12 are mixed and heated to 70 ° C. C: B was added to A, kept at 70 ° C. for a while. After the saponification reaction was completed, the mixture was cooled to 50 ° C., Component 7 was added, and the mixture was cooled to obtain a detergent. The cleaning agent of Example 9 showed an excellent slimming effect.

[0042]

Industrial Applicability The fat accumulation inhibitor of the present invention has an excellent effect of suppressing the differentiation of preadipocytes into adipocytes, and suppresses an increase in the number of adipocytes to prevent excessive fat accumulation. Further, the external preparation for skin containing this fat accumulation inhibitor has an excellent slimming effect and is extremely useful in beauty and medicine.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 31/20 ADN A61K 31/20 ADN 31/23 31/23 45/00 45/00

Claims (3)

[Claims] 1. A fat accumulation inhibitor containing an ω-3 polyunsaturated fatty acid and / or a derivative thereof. 2. The composition according to claim 1, further comprising a phosphodiesterase activity inhibitor, cyclic AMP and / or
Or a derivative thereof, a salt thereof, a plant extract containing cyclic AMP, a β-adrenergic stimulant and / or α.
A fat accumulation inhibitor comprising one or more selected from ₂ -adrenergic action inhibitors, astringents, blood circulation promoters, and lipase activity promoters. 3. An external preparation for skin, comprising the fat accumulation inhibitor according to claim 1.