JP2006016383A - Skin care preparation for slender body and cosmetic comprising the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin care preparation for slender body and a cosmetic comprising the same excellent in skin affinity and percutaneous absorbability, containing a carnitine derivative that has the activity of promoting lipid metabolism and acts as a lipid decomposition promoter promoting the lipid metabolism of systemic or local subcutaneous adipose tissue, thus capable of eliminating, suppressing or preventing obesity. <P>SOLUTION: The skin care preparation for slender body contains a specific carnitine derivative and also preferably other body-slenderizing ingredient(s) or skin care ingredient(s). <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a skin external preparation for slimming and a skin cosmetic containing the same. Specifically, the present invention relates to an external preparation for skin and a cosmetic that contain a carnitine derivative and have an effect of promoting the decomposition of subcutaneous fat.

  The present invention also relates to a slimming skin external preparation and a cosmetic containing a carnitine derivative and further containing other slimming ingredients and skin care ingredients.

  Most of the fats in the body are those in which excessive intake energy relative to metabolic energy is accumulated as neutral fat in the white fat cells. Obesity is an excessive accumulation of fat as body fat, which may cause diseases such as arteriosclerosis, which is undesirable for health, and excessive accumulation of subcutaneous fat is undesirable in appearance. Therefore, there is a tendency that a body with less body fat and tightening is desired. However, at present, obesity is increasing due to satiety, overeating, lack of exercise, stress, etc., and the reduction or prevention of subcutaneous fat has become an important issue regardless of age. For this reason, attempts have been made to eliminate obesity by various methods such as dietary restrictions, exercise, massage, etc. or intake of digestion absorption-suppressing foods, but subcutaneous fat, which greatly affects appearance, is easily suppressed or reduced. Thus, a lipolysis-promoting external preparation and a slimming cosmetic composition having a satisfactory effect have not been found.

  By the way, fat is converted to energy by fatty acid being β-oxidized in mitochondria and metabolized, and when fatty acid is taken into mitochondria, it is essential to bind carnitine, The rate of fatty acid metabolism depends on the amount of carnitine present. Therefore, increasing the concentration of carnitine in the tissue that wants to promote fatty acid metabolism is considered to be effective for fat breakdown and hence slimming. For this reason, various investigations and proposals have been made to formulate carnitine or the like in a skin external preparation and absorb it transdermally to promote the metabolism of subcutaneous fat (see Patent Documents 1 to 4). However, these were all using L-carnitine or a salt thereof, and a satisfactory slimming effect was not obtained. This is because carnitine and its salts have very high hydration properties, and as such, skin affinity and transdermal absorbability are insufficient, and it is not possible to reach a sufficient amount to the tissue that performs fat metabolism. This is considered to be difficult.

For this reason, there has been a demand for the appearance of a slimming skin external preparation that is excellent in transdermal absorbability, reaches a sufficient amount in a tissue that performs fat metabolism, and has an effect of promoting fat metabolism.
In addition, it has been proposed that palmitoyl-L-carnitine, which is a derivative of carnitine, is blended into cosmetics for the purpose of slimming together with caffeine (see Patent Documents 5 and 6).

  In addition to carnitine, active research has been conducted on components involved in fat metabolism or fat synthesis. For example, inhibition of synthesis of intracellular cAMP, which is a second messenger of lipolysis, such as hydroxycitric acid and its derivatives known as inhibitors of the fat synthesis pathway from the citric acid cycle (see Non-Patent Documents 1 and 2 and Patent Document 7) A component that suppresses the action of α2 adrenergic having an action (see Non-Patent Document 3 and Non-Patent Document 4), a β-adrenergic stimulant having an action of promoting the synthesis of intracellular cAMP (see Non-Patent Document 3 and Patent Document 8), Inhibitors of phosphodiesterase having an action of degrading intracellular cAMP (see Patent Document 9).

On the other hand, even if fat metabolism is promoted and obesity is resolved, if fat metabolism is excessively promoted, skin tension may be impaired due to lack of subcutaneous fat or sebum, dry skin, rough skin, etc. May cause problems.

Accordingly, there has been a demand for the appearance of a slimming skin external preparation and cosmetic that not only has a high effect of promoting fat metabolism, but can also keep the skin healthy at the same time.
Japanese Patent No. 3434995 Japanese Patent Laid-Open No. 7-309711 JP 2000-16916 A JP 2001-64147 A French Patent Invention No. 2694195 International Publication No. 2004/002435 Pamphlet JP-A-9-176004 JP 59-155313 A Japanese Patent Laid-Open No. 10-182347 Sullivan AC et al. Lipids 9 (2) 12, 121-128, 1974 Watson YA et al., Arch. Biochem. Biophys. 135 (1), 209-217, 1969 Lafontan, M., M. Berlan. Fat cell adrenergic receptors and the control of white and brown fat cell function.J. Lipid Res. 34: 1057-1091, 1993, Greenway FL et al., Regional fat loss from the thigh in obese women after adrenergic modulation.Clinical Theraputics 9 (6), 663-669, 1987

  The present invention contains a carnitine derivative that has excellent skin affinity and transdermal absorbability and has an action of promoting fat metabolism, and acts as a lipolysis promoter that promotes fat metabolism of systemic or local subcutaneous adipose tissue. Another object of the present invention is to provide a skin external preparation for slimming and a cosmetic that can eliminate, suppress or prevent obesity.

Another object of the present invention is to provide a slimming skin external preparation and a cosmetic material, which contain other slimming components in addition to the carnitine derivative and specifically enhance the slimming effect.
Furthermore, this invention makes it the subject to provide the skin external preparation for slimming and cosmetics which have not only a high slimming effect but the moisturizing and skin care effect with respect to skin.

  As a result of diligent research in view of the above circumstances, the present inventors have found that (1) specific carnitine derivatives such as acylcarnitine derivatives, alcohol carnitine ester derivatives, or carnitine derivatives that are combinations thereof have skin affinity and transdermal absorption. Highly capable of easily reaching the tissues where fat metabolism is performed, and can suitably promote fat metabolism, (2) In addition to the above specific carnitine derivatives, it contains ingredients involved in fat metabolism and synthesis pathways (3) In addition to the specific carnitine derivative, a specific skin care component is added to the skin while promoting fat metabolism. As a result, the present invention has been completed.

That is, the present invention relates to the following items [1] to [62].
[1] A slimming skin external preparation containing a carnitine derivative represented by the following general formula (1);

(In the formula (1), R ¹ represents a hydrogen atom or an acyl group having 2 to 30 carbon atoms which may have a branched or unsaturated bond,
R ² is a hydrogen atom or a carbon number of 1 to 22 which may have a branched or unsaturated bond
(Wherein R ¹ and R ² are not hydrogen atoms at the same time),
Me represents a methyl group,
X ⁻ represents an inorganic anion or an organic anion that is electrically neutral with the cation moiety of the carnitine derivative. ).
[2] In the formula (1), R ¹ may have a branched or unsaturated bond having 4 to 4 carbon atoms.
The slimming skin external preparation according to [1], which is 22 acyl groups.
[3] In the formula (1), R ¹ may have a branched or unsaturated bond and has 14 carbon atoms.
The slimming skin external preparation according to [1], which is an acyl group of ˜22.
[4] In the formula (1), R ² is a hydrogen atom or a hydrocarbon group having 1 to 18 carbon atoms which may have a branched or unsaturated bond [1] The slimming skin external preparation in any one of-[3].
[5] In the formula (1), R ¹ is a hydrogen atom,
The slimming skin external preparation as described in [1], wherein R ² is a hydrocarbon group having 1 to 18 carbon atoms which may have a branched or unsaturated bond.
[6] In the formula (1), R ² may have a branched or unsaturated bond having 4 to 4 carbon atoms.
The slimming skin external preparation according to any one of [1] to [3], which is 10 hydrocarbon groups.
[7] In the formula (1), R ¹ may have a branched or unsaturated bond having 4 to 4 carbon atoms.
22 acyl groups;
The slimming skin external preparation as described in [1], wherein R ² is a hydrogen atom.
[8] The slimming skin external preparation according to any one of [1] to [7], wherein the carnitine derivative is contained in an amount of 0.01% by mass to 20% by mass.
[9] The method according to any one of [1] to [8], further comprising at least one selected from the group consisting of hydroxycitric acid, derivatives thereof, and pharmacologically acceptable salts thereof. For slimming skin.
[10] The slimming skin external preparation as described in [9], wherein the hydroxycitric acid is obtained from a Garcinia Cambodian extract.
[11] The slimming skin external preparation according to [9] or [10], wherein the hydroxycitric acid derivative is a hydroxycitric acid derivative represented by the following formula (2):

(In the formula (2), R ¹¹ and R ¹² each independently represent a hydrogen atom or any group that can be removed by a bioenzymatic reaction selected from the group represented by the following formula (3). R ¹¹ and R ¹² do not simultaneously become hydrogen atoms.), X ^{1 to} X ³ each independently represent a nitrogen or oxygen atom, and R ³ , R ⁴ , R ⁵ , R ^{3 ′} , R ^{4 ′.} , R ^{5 ′} each independently represents a hydrogen atom or a chain hydrocarbon group having 1 to 30 carbon atoms which may have a branched or unsaturated bond (provided that X ¹
, X ² and X ³ are each an oxygen atom, the corresponding R ^{3 ′} , R ^{4 ′} and R ^{5 ′} do not exist. )

(In Formula (3), R < ⁶ > -R < ⁸ > is a hydrogen atom, an aryl group, or a C1-C30 linear hydrocarbon group which may have a branch, an unsaturated bond, or a substituent each independently. Represents.)
[12] In the formula (3), R ⁶ is a chain hydrocarbon group having ^{7 to} 23 carbon atoms which may have a branch, an unsaturated bond or a substituent, and R ⁷ and R ⁸ are And each independently a hydrogen atom, or a chain hydrocarbon group having 8 to 24 carbon atoms, which may have a branch, an unsaturated bond, or a substituent, according to [11] Skin external preparation.
[13] In the formula (2), R ^{3 to} R ⁵ are each independently a hydrogen atom or a chain hydrocarbon group having 1 to 30 carbon atoms which may have a branched or unsaturated bond. , X ^{1 to} X ³ are all oxygen atoms, and
In the above formula (3), R ⁶ is, branched, may have an unsaturated bond or a substituent, a chain hydrocarbon group having 7 to 23 carbon atoms, R ⁷ and R ⁸ are each independently Or a chain hydrocarbon group having 8 to 24 carbon atoms, which may have a hydrogen atom, a branched, unsaturated bond or a substituent, for external application for slimming skin according to [11] Agent.
[14] In the formula (2), R ¹² is a hydrogen atom, R ^{3 to} R ⁵ are all hydrogen atoms, X ^{1 to} X ³ are all oxygen atoms, and
[11], wherein in the formula (3), R ⁶ is a chain hydrocarbon group having 13 to 21 carbon atoms which may have a branch, an unsaturated bond or a substituent. For slimming skin.
[15] In the formula (2), R ¹² is a hydrogen atom, and R ^{3 to} R ⁵ are each independently a hydrogen atom, or may have a branched or unsaturated bond, having 1 to 30 carbon atoms. A chain hydrocarbon group (provided that R ^{3 to} R ⁵ do not simultaneously become hydrogen atoms), X ^{1 to} X ³ are all oxygen atoms, and
In the above formula (3), R ⁶ is a chain hydrocarbon group having 13 to 21 carbon atoms which may have a branch, an unsaturated bond or a substituent, [11] For slimming skin.
[16] It contains at least one selected from the group consisting of the hydroxycitric acid, its derivatives, and pharmacologically acceptable salts thereof in an amount of 0.01 to 20% by mass [9] The slimming skin external preparation in any one of-[15].
[17] The slimming skin external preparation according to any one of [1] to [8], further comprising an α2 adrenergic inhibitor.
[18] The α2 adrenergic inhibitor is yohimbine, phentolamine, phenoxybenzamine, trazoline, ergotamine, ergotoxin, dihydroergotamine, ergomethrin, methylergomethrin, dihydroergotoxin, laurucine, piperoxane, and derivatives thereof. The slimming skin external preparation as described in [17], which is at least one selected from the group consisting of pharmacologically acceptable salts.
[19] The slimming skin external preparation as described in [17], wherein the α2 adrenergic inhibitor is obtained from a plant extract.
[20] The [2], wherein the α2 adrenergic inhibitor is obtained from at least one selected from the group consisting of ginkgo biloba extract, ivy extract, and horse chestnut extract. For slimming skin.
[21] The slimming skin external preparation according to any one of [17] to [20], comprising the α2 adrenergic inhibitor in an amount of 0.0001 to 10% by mass.
[22] The slimming skin external preparation according to any one of [1] to [8], further comprising a β-adrenergic stimulant.
[23] The β-adrenergic stimulant is isoproterenol, epinephrine, norepinephrine, dobutamine, dopamine, butopamine, salbutamol, terbutaline, isoetarine, protokilol, fenoterol, metaproterenol, chlorprenalin, hexoprenaline, trimethquinol , Procaterol hydrochloride, prenalterol, forskolin, disodium (R, R) -5- [2-[[2- (3-chlorophenyl) -2-hydroxyethyl] -amino] propyl] -1,3-benzodio Xol-2,2-dicarboxylate, (R, R) -4- [2-({2-[(3-chlorophenyl) -2-hydroxyethyl] amino} propyl) phenyl] phenoxyacetic acid, {2- Hydroxy-5- [2-({2-hydroxy-3 [4- (1-Methyl-4-trifluoromethyl) -1H-imidazol-2-yl] phenoxy} propyl) amino] ethoxy} -benzamide monomethanesulfonate, erythro-DL-1- (7-methylindane [14] characterized in that it is at least one selected from the group consisting of -4-yloxy) -3-isopropylaminobutan-2-ol, derivatives thereof, and pharmacologically acceptable salts thereof. The skin external preparation for slimming as described.
[24] The slimming skin external preparation as described in [22], wherein the β-adrenergic stimulant is obtained from a plant extract.
[25] The β-adrenergic stimulant is an extract of Coleus forskohlii (forskolin), Ipomoea hederacea extract, Ipomoea batata extract, Sage (Salvia officinalis) extract, The slimming skin external application according to [22], which is obtained from at least one selected from the group consisting of a tanjin (Salvia miltiorrhiza) extract and a mannenrou (Rosmarinus officinalis; rosemary) extract Agent.
[26] The slimming skin external preparation according to any one of [22] to [25], comprising the β-adrenergic stimulant in an amount of 0.0001 to 10% by mass.
[27] The slimming skin external preparation according to any one of [1] to [8], further comprising a phosphodiesterase inhibitor.
[28] The phosphodiesterase inhibitor is a group consisting of theophylline, theobromine, aminophylline, xanthine, isobutylmethylxanthine, apigenin, amentoflavone, vilobetine, cyanadopiticin, ginkgonetine, derivatives thereof, and pharmacologically acceptable salts thereof. The slimming skin external preparation as described in [27], which is at least one selected from the above.
[29] The slimming skin external preparation as described in [27], wherein the phosphodiesterase inhibitor is obtained from a plant extract.
[30] The phosphodiesterase inhibitor is extracted from tea extract, coffee extract, guarana extract, yerba mate extract, cola extract, ginkgo biloba extract, sequoia mesgi extract, yew extract, and hydrangea extract. The slimming skin external preparation as described in [27], which is obtained from at least one selected from the group consisting of:
[31] The slimming skin external preparation according to any one of [27] to [30], comprising the phosphodiesterase inhibitor in an amount of 0.0001 to 10% by mass.
[32] Furthermore, it includes a saturated or unsaturated fatty acid having 12 to 22 carbon atoms and / or a pharmacologically acceptable salt thereof which may have a branch [1] to [8] The slimming skin external preparation according to any one of the above.
[33] The fatty acid is at least one selected from the group consisting of lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, isostearic acid, 12-hydroxystearic acid, undecylenic acid, and hexyldecanoic acid. [14] The slimming skin external preparation as described in [32].
[34] The slimming skin external preparation as described in [32], wherein the fatty acid is a coconut oil fatty acid.
[35] The saturated or unsaturated fatty acid having 12 to 22 carbon atoms and / or pharmacologically acceptable salt thereof, which may have a branch, is contained in an amount of 0.001 to 20% by mass. The skin external preparation for slimming according to any one of [32] to [34].
[36] The method according to any one of [1] to [8], further comprising at least one selected from the group consisting of ascorbic acid, derivatives thereof, and pharmacologically acceptable salts thereof. An external preparation for slimming skin.
[37] The slimming skin external preparation as described in [36], wherein the ascorbic acid is L-ascorbic acid.
[38] The slimming skin external application according to [36] or [37], wherein the pharmacologically acceptable salt of ascorbic acid is sodium L-ascorbate and / or magnesium L-ascorbate Agent.
[39] The ascorbic acid derivative is selected from the group consisting of L-ascorbyl stearate, L-ascorbyl palmitate, L-ascorbyl dipalmitate, L-ascorbyl tetraisopalmitate, L-ascorbic acid-2-glucoside. The slimming skin external preparation according to any one of [36] to [38], which is at least one kind.
[40] The slimming skin external preparation according to any one of [36] to [38], wherein the pharmacologically acceptable salt of the ascorbic acid derivative is L-ascorbic acid sulfate disodium salt. .
[41] The ascorbic acid derivative is an ascorbyl 2-phosphate ester and / or a higher fatty acid ester of ascorbyl 2-phosphate ester represented by the following formula (4) [36] -The slimming skin external preparation in any one of-[38];

(In formula (4), R represents a hydrogen atom or an acyl residue of a higher fatty acid).
[42] The slimming skin according to [41], wherein in the formula (4), R is an acyl residue of lauric acid, myristic acid, palmitic acid, stearic acid, or 2-hexyldecanoic acid Topical agent.
[43] A pharmacologically acceptable salt of the ascorbic acid derivative is an ascorbic acid-2-phosphate ester represented by the following formula (4) and / or a higher fatty acid ester of ascorbic acid-2-phosphate ester: Skin external preparation for slimming according to any one of [36] to [38] and [41] to [42], which is a sodium salt, potassium salt, magnesium salt or zinc salt;

(In formula (4), R represents a hydrogen atom or an acyl residue of a higher fatty acid).
[44] The slimming skin according to [43], wherein in the formula (4), R is an acyl residue of lauric acid, myristic acid, palmitic acid, stearic acid, or 2-hexyldecanoic acid Topical agent.
[45] It contains at least one selected from the group consisting of the ascorbic acid, derivatives thereof, and pharmacologically acceptable salts thereof in an amount of 0.01 to 20% by mass [36] to [44] The slimming skin external preparation according to any one of [44].
[46] The slimming according to any one of [1] to [8], further comprising at least one selected from the group consisting of tocopherol, a derivative thereof, and a pharmacologically acceptable salt thereof. Skin external preparation.
[47] The slimming skin external preparation according to [46], wherein the tocopherol is at least one selected from the group consisting of α-tocopherol, β-tocopherol, γ-tocopherol and δ-tocopherol.
[48] The [46] or [47], wherein the tocopherol derivative is at least one selected from the group consisting of an α-tocopherol derivative, a β-tocopherol derivative, a γ-tocopherol derivative and a δ-tocopherol derivative. The slimming skin external preparation described in 1.
[49] The slimming skin external preparation as described in [48], wherein the tocopherol derivative is a tocopherol phosphate.
[50] The slimming skin external preparation as described in [49], wherein the tocopherol phosphate is a compound represented by the following formula (5):

(In formula (5), R ²¹ , R ²² and R ²³ each independently represents a hydrogen atom or a methyl group).
[51] The slimming skin external preparation as described in [48], wherein the tocopherol derivative is a tocopherol aminoalkylcarboxylate ester.
[52] The slimming skin external preparation according to [51], wherein the tocopherol aminoalkylcarboxylic acid ester is a compound represented by the following formula (6):

(In formula (6), R ³¹ and R ³² represent the same or different lower alkyl groups or hydrogen atoms, R ³³ and R ³⁴ each independently represent a hydrogen atom or a methyl group, and Z has a substituent. Represents a branched or linear alkylene group which may be present.
[53] The aminoalkylcarboxylic acid of the tocopherol aminoalkylcarboxylic acid ester is glycine, alanine, β-alanine, valine, leucine, isoleucine, phenylalanine, methionine, cysteine, serine, threonine, tyrosine, thyroxine, histidine, proline, 4 -Slimming skin external preparation as described in [51] or [52], which is a compound selected from hydroxyproline, aspartic acid, glutamic acid, and their N-alkyl derivatives or N, N-dialkyl derivatives.
[54] It contains at least one selected from the group consisting of the tocopherol, derivatives thereof, and pharmacologically acceptable salts thereof in an amount of 0.01 to 10% by mass. 53]. The slimming skin external preparation according to any one of [53].
[55] A cosmetic comprising the skin external preparation for slimming according to any one of [1] to [8]. [56] A cosmetic comprising the slimming skin external preparation according to any one of [9] to [16].
[57] A cosmetic comprising the slimming skin external preparation according to any one of [17] to [21].
[58] A cosmetic comprising the slimming skin external preparation according to any one of [22] to [26].
[59] A cosmetic comprising the slimming skin external preparation according to any one of [27] to [31].
[60] A cosmetic comprising the skin external preparation for slimming according to any one of [32] to [35].
[61] A cosmetic comprising the skin external preparation for slimming according to any one of [36] to [45].
[62] A cosmetic comprising the slimming skin external preparation according to any one of [46] to [54].

  The slimming skin external preparation and cosmetics of the present invention contain a specific carnitine derivative that has better skin affinity and transdermal absorbability than L-carnitine or a salt thereof, and has a sufficient action to promote fat metabolism. Therefore, a specific carnitine derivative, which is an active ingredient, can easily reach the subcutaneous adipose tissue where fat metabolism is performed and can act as a lipolysis promoter that promotes fat metabolism in the whole body or local subcutaneous adipose tissue. It can be suitably used as a slimming skin external preparation and cosmetic for relieving, suppressing or preventing obesity at the site.

  Further, when the slimming skin external preparation and cosmetics of the present invention contain other slimming components in addition to the specific carnitine derivative, the effect of promoting fat metabolism is improved by various actions, and the slimming effect is improved. Can be increased specifically.

  Further, when the skin external preparation for slimming and cosmetics of the present invention contain a skin care ingredient in addition to the specific carnitine derivative, not only the high slimming effect due to the carnitine derivative, but also the moisture retention and skin care effect on the skin. Can also be used to keep the skin healthy.

Hereinafter, the present invention will be specifically described.
The slimming skin external preparation and cosmetic of the present invention contain a specific carnitine derivative.
Carnitine derivative The carnitine derivative used in the present invention is a compound represented by the following general formula (1).

(In the formula (1), R ¹ represents a hydrogen atom or an acyl group having 2 to 30 carbon atoms which may have a branched or unsaturated bond,
R ² is a hydrogen atom or a carbon number of 1 to 22 which may have a branched or unsaturated bond
(Wherein R ¹ and R ² are not hydrogen atoms at the same time),
Me represents a methyl group,
X ⁻ represents an inorganic anion or an organic anion that is electrically neutral with the cation moiety of the carnitine derivative. ).

  Examples of such carnitine derivatives include acyl carnitine derivatives, alcohol carnitine ester derivatives, or carnitine derivatives that are combinations thereof.

In the acylcarnitine derivative used as the carnitine derivative according to the present invention, R ¹ in the general formula (1) is an acyl group having 2 to 30 carbon atoms which may have a branched or unsaturated bond, A compound in which R ² is a hydrogen atom. That is, in the acylcarnitine derivative that can be used in the present invention, R ¹ has 2 to 30 carbon atoms, preferably 4 to 22 carbon atoms, more preferably 14 to 22 carbon atoms, and the carbon chain is branched. It is a carnitine derivative which may be an acyl group which may have an unsaturated bond, and R ² is a hydrogen atom.

Specifically, such acylcarnitine derivatives include R ¹ in the general formula (1).
Are hexanoyl group, 2-methylpentanoyl group, 3-methylpentanoyl group, 4-methylpentanoyl group, 2-ethylbutanoyl group, heptanoyl group, 2-methylhexanoyl group, 3-methylhexanoyl group, 4-methylhexanoyl group, 2-ethylpentanoyl group, 3-ethylpentanoyl group, octanoyl group, 2-methylheptanoyl group, 3-methylheptanoyl group, 4-methylheptanoyl group, 5-methylheptanoyl group Group, 6-methylheptanoyl group, 2-ethylhexanoyl group, 3-ethylhexanoyl group, 4-ethylhexanoyl group, 2-propylpentanoyl group, nonanoyl group, decanoyl group, undecanoyl group, 10-undecenoyl group , Dodecanoyl group, tridecanoyl group, tetradecanoyl group, pentadecanoyl group, Sadecanoyl group, 9-hexadecenoyl group, heptadecanoyl group, octadecanoyl group, isostearyl group, cis-9-octadecenoyl group, 11-octadecenoyl group, cis, cis-9,12-octadecadienoyl group, 9,12, 15-octadecatrienoyl group, 6,9,12-octadecatrienoyl group, 9,11,13-octadecatrienoyl group, nonadecanoyl group, 2,6,10,14-tetramethylpentadecanoyl group, Icosanoyl group, 8,11-icosadienoyl group, 5,8,11-icosatrienoyl group, 5,8,11,14-icosatetraenoyl group, 3,7,11,15-tetramethylhexadecanoyl group, A compound in which R ² is a hydrogen atom, which is an acyl group such as a henicosanoyl group or a docosanoyl group Is mentioned.

In the carnitine ester derivative of alcohol used as the carnitine derivative according to the present invention, R ¹ in the general formula (1) is a hydrogen atom, and R ² may have a branched or unsaturated bond. It is a compound which is a hydrocarbon group of ~ 22. That is, in the carnitine ester derivative of alcohol that can be used in the present invention, R ¹ is a hydrogen atom, R ² has 1 to 22 carbon atoms, preferably 1 to 18 carbon atoms, and the carbon chain is It is a carnitine derivative which is a hydrocarbon group which may be branched and may have an unsaturated bond.

Specifically, as such a carnitine ester derivative of alcohol, R ¹ in the general formula (1) is a hydrogen atom, and R ² is a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group. 1-methylpropyl group, 2-methylpropyl group, pentyl group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 1-ethylpropyl group, hexyl group, 1-methylpentyl group, 2-methylpentyl Group, 3-methylpentyl group, 4-methylpentyl group, 1-ethylbutyl group, 2-ethylbutyl group, heptyl group, 1-methylhexyl group, 2-methylhexyl group, 3-methylhexyl group, 4-methylhexyl group 5-methylhexyl group, 1-ethylpentyl group, 2-ethylpentyl group, 3-ethylpentyl group, octyl group, 1-methylheptyl group Til, 2-methylheptyl, 3-methylheptyl, 4-methylheptyl, 5-methylheptyl, 6-methylheptyl, 1-ethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4- Ethylhexyl group, 1-propylpentyl group, 2-propylpentyl group, nonyl group, decyl group, undecyl group, 10-undecenyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, hexadecyl group, 9-hexadecenyl group, heptadecyl group Group, octadecyl group, isostearyl group, cis-9-octadecenyl group, 11-octadecenyl group, cis, cis-9,12-octadecadienyl group, 9,12,15-octadecatrienyl group, 6,9 , 12-octadecatrienyl group, 9,11,13-octadecatrienyl , Nonadecyl group, 2, 6,
10,14-tetramethylpentadecyl group, icosanyl group, 8,11-icosadienyl group, 5,8,11-icosatrienyl group, 5,8,11,14-icosatetraenyl group, 3,7,11,15 -A compound which is any one of hydrocarbon groups such as a tetramethylhexadecyl group, a heicosanyl group and a docosanyl group.

The carnitine derivative according to the present invention is a carnitine derivative that is a combination of the above-described acylcarnitine derivative and a carnitine ester derivative of an alcohol, that is, in the above formula (1), both R ¹ and R ² are not hydrogen atoms. When the group is a carnitine derivative, the carnitine derivative is an acyl group having 2 to 30 carbon atoms in which R ¹ in the general formula (1) may have a branched or unsaturated bond, ^A compound in which 2 is a hydrocarbon group having 1 to 22 carbon atoms which may have a branched or unsaturated bond.

As such a carnitine derivative in which R ¹ and R ² in the general formula (1) are groups other than hydrogen atoms, R ¹ is an acyl group having 2 to 30 carbon atoms, and R ² is 1 carbon atom. ~ 22 hydrocarbon group compounds, preferably R ¹ is an acyl group having 4 to 22 carbon atoms, R ² is a hydrocarbon group compound having 1 to 18 carbon atoms, more preferably R ¹ is 14 to carbon atoms. And a compound having 22 acyl groups and R ² is a hydrocarbon group having 4 to 10 carbon atoms. Here, each of R ¹ and R ² may have a branched carbon chain or may have an unsaturated bond.

Specifically, as such a carnitine derivative, R ¹ in the general formula (1) is acetyl group, propionoyl group, butanoyl group, pentanoyl group, hexanoyl group, 2-methylpentanoyl group, 3-methyl. Pentanoyl group, 4-methylpentanoyl group, 2-ethylbutanoyl group, heptanoyl group, 2-methylhexanoyl group, 3-methylhexanoyl group, 4-methylhexanoyl group, 2-ethylpentanoyl group, 3 -Ethylpentanoyl group, octanoyl group, 2-methylheptanoyl group, 3-methylheptanoyl group, 4-methylheptanoyl group, 5-methylheptanoyl group, 6-methylheptanoyl group, 2-ethylhexanoyl group 3-ethylhexanoyl group, 4-ethylhexanoyl group, 2-propylpentanoyl group, nonanoyl group, Canoyl group, undecanoyl group, 10-undecenoyl group, dodecanoyl group, tridecanoyl group, tetradecanoyl group, pentadecanoyl group, hexadecanoyl group, 9-hexadecenoyl group, heptadecanoyl group, octadecanoyl group, isostearyl group, cis -9-octadecenoyl group, 11-octadecenoyl group, cis, cis-9,12-octadecadienoyl group, 9,12,15-octadecatrienoyl group, 6,9,12-octadecaterienoyl group, 9 , 11,13-octadecatrienoyl group, nonadecanoyl group, 2,6,10,14-tetramethylpentadecanoyl group, icosanoyl group, 8,11-icosadienoyl group, 5,8,11-icosatrienoyl group, 5,8,11,14-icosatetraenoyl group, 3,7,11, Any one of acyl groups such as 15-tetramethylhexadecanoyl group, henicosanoyl group, docosanoyl group, and R ² is methyl group, ethyl group, propyl group, isopropyl group, butyl group, 1-methylpropyl; Group, 2-methylpropyl group, pentyl group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 1-ethylpropyl group, hexyl group, 1-methylpentyl group, 2-methylpentyl group, 3-methyl Pentyl group, 4-methylpentyl group, 1-ethylbutyl group, 2-ethylbutyl group, heptyl group, 1-methylhexyl group, 2-methylhexyl group, 3-methylhexyl group, 4-methylhexyl group, 5-methylhexyl Group, 1-ethylpentyl group, 2-ethylpentyl group, 3-ethylpentyl group, octyl group, 1-methyl Butyl group, 2-methylheptyl group, 3-methylheptyl group, 4-methylheptyl group, 5-methylheptyl group, 6-methylheptyl group, 1-ethylhexyl group, 2-ethylhexyl group, 3-ethylhexyl group, 4- Ethylhexyl group, 1-propylpentyl group, 2-propylpentyl group, nonyl group, decyl group, undecyl group, 10-undecenyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, hexadecyl group, 9-hexadecenyl group, heptadecyl group Group, octadecyl group, isostearyl group, cis-9-octadecenyl group, 11-octadecenyl group, cis, cis-9,12-octadecadienyl group, 9,12,15-octadecatrienyl group, 6,9 , 12-octadecatrienyl group, 9,11,13-octadecatrieniy Group, nonadecyl group, 2,6,10,14-tetramethylpentadecyl group, icosanyl group, 8,11-icosadienyl group, 5,8,11-icosatrienyl group, 5,8,11,14-icosatetra Examples thereof include compounds which are any one of hydrocarbon groups such as an enyl group, 3,7,11,15-tetramethylhexadecyl group, heicosanyl group and docosanyl group.

In any of these carnitine derivatives, X ⁻ in the general formula (1) represents an inorganic or organic anion that is electrically neutral with the cation portion of the carnitine derivative. That is, X ⁻ is an inorganic anion or an organic anion that is electrically neutral with the cation of the carnitine derivative, for example, an inorganic anion such as chlorine ion, nitrate ion, sulfate ion, carbonate ion, or bicarbonate ion; Examples thereof include organic anions obtained by ionizing organic acid compounds such as formic acid, acetic acid, glycine, oxalic acid, tartaric acid and fumaric acid.

These carnitine derivatives that can be used in the present invention can be produced from commercially available L-carnitines. For example, the acylcarnitine derivative described above can be produced by the method described in Analyst (1990, 115 (5), 511-516). Moreover, the above-mentioned carnitine ester derivatives of alcohol can be produced by the method described in Journal of Organic Chemistry (1995, 60 (25), 8318-8319). Furthermore, a carnitine derivative having both functional groups of an acyl group and an ester group, in which R ¹ and R ^{2 in} the above general formula (1) are groups other than hydrogen atoms, can be appropriately combined by combining these methods. It can also be produced by the method described in JP-A-8-295616. According to these methods, as the raw material carnitine, any of an inner salt, an inorganic salt such as hydrochloride or sodium salt, or an organic salt such as oxalate, tartrate or fumarate can be used. Good.
≪Slimming skin external preparation, cosmetics≫
The slimming skin external preparation and cosmetics of the present invention contain the specific carnitine derivative described above.

  In the slimming skin external preparation of the present invention, the amount of the carnitine derivative is usually 0.01 to 20% by mass, more preferably 0.05 to 12% by mass, based on the total amount of the external skin preparation. When the carnitine derivative is contained in such an amount in the external preparation for skin, the transfer to the skin is quick, and the efficacy effect required for the external preparation for skin can be exhibited. Also in the cosmetic of the present invention, the amount of the carnitine derivative is desirably the same as that of the slimming skin external preparation of the present invention, but is not limited thereto.

The slimming skin external preparation and cosmetics of the present invention may further contain other slimming ingredients and skin care ingredients in addition to the carnitine derivatives described above.
Slimming component The above-mentioned action of carnitine derivatives is thought to increase the intracellular tissue concentration of carnitine, which is a mediator during fatty acid uptake into mitochondria, so that other than fatty acid uptake into mitochondria, It is expected that a high slimming effect can be obtained synergistically by combining components involved in various stages of the metabolic pathway or synthetic pathway as the slimming component with the carnitine derivative.
( Fat synthesis pathway inhibitor )
As one of such slimming components, at least one selected from the group consisting of hydroxycitric acid known as an inhibitor of the fat synthesis pathway from the citric acid cycle, derivatives thereof and pharmacologically acceptable salts thereof is Can be mentioned. These are expected to have an effect of suppressing fat accumulation.

The hydroxycitric acid is abundant in plant extracts such as Garcinia Cambodia, and may be obtained from the plant extract or may be chemically synthesized.
The hydroxycitric acid derivative is preferably a compound represented by the following formula (2) from the viewpoint of excellent transdermal absorbability.

In the formula (2), R ¹¹ and R ¹² each independently represent a hydrogen atom or any group capable of leaving by a biological enzyme reaction selected from the group represented by the following formula (3) ( However, R ¹¹ and R ¹² do not become a hydrogen atom at the same time.)

Specifically, at least one of the R ¹¹ and R ¹² is preferably any group capable of being released in vivo enzymatic reaction selected from the group represented by the formula (3), R ¹¹ and One of R ¹² may be these groups, and both may be these groups. Among these, an embodiment in which one of R ¹¹ and R ¹² is these groups is preferable, and in particular, any one of which R ¹¹ can be removed by a bioenzymatic reaction selected from the group represented by the above formula (3). The embodiment in which R ¹² is a hydrogen atom is more preferred.

In said formula (3), R < ⁶ > -R < ⁸ > is a hydrogen atom, an aryl group, or a C1-C30 linear hydrocarbon group which may have a branch, an unsaturated bond, or a substituent each independently. Represents. Here, the group capable of leaving by a biological enzyme reaction means a group that can be hydrolyzed by a hydrolase such as esterase existing in the living body and R ¹¹ and R ¹² can be hydrogen atoms.

Examples of the aryl group include a phenyl group, a naphthyl group, a furyl group, a thienyl group, and a pyridyl group. Examples of the chain hydrocarbon group having 1 to 30 carbon atoms which may have a branch, an unsaturated bond or a substituent include, for example, a part of acyl groups described later as examples of R ¹¹ and / or R ^12. The constituents are listed.

Among these, R ^{6 to} R ⁸ are each independently a hydrogen atom, or a chain hydrocarbon group having 1 to 30 carbon atoms, which may have a branched, unsaturated bond or substituent. preferable.

More specifically, R ⁶ is a branched hydrocarbon group having 7 to 23 carbon atoms, preferably 13 to 21 carbon atoms, more preferably branched, optionally having a branch, an unsaturated bond, or a substituent. An optionally substituted alkyl group having 13 to 21 carbon atoms, wherein R ⁷ and R ⁸ are each independently a hydrogen atom, a branched, unsaturated bond, or a substituent. 8 to 24, preferably a hydrogen atom or a chain hydrocarbon group of 14 to 22, more preferably a hydrogen atom.

  Among these, any group that can be eliminated by a biological enzyme reaction selected from the group represented by the above formula (3) is a group having 8 to 24 carbon atoms, preferably 14 to 22 carbon atoms. desirable.

Here, as a substituent, a halogen atom, an amino group, a cyano group, an alkoxy group, a nitro group etc. are mentioned, for example.
Specific examples of the derivative in which the hydroxyl group in the molecule is modified include, specifically, R ¹¹ and / or R ^{12 in} the above formula (2) is a hexanoyl group, a 2-methylpentanoyl group, or a 3-methylpentanoyl group. Group, 4-methylpentanoyl group, 2-ethylbutanoyl group, heptanoyl group, 2-methylhexanoyl group, 3-methylhexanoyl group, 4-methylhexanoyl group, 2-ethylpentanoyl group, 3-ethyl Pentanoyl group, octanoyl group, 2-methylheptanoyl group, 3-methylheptanoyl group, 4-methylheptanoyl group, 5-methylheptanoyl group, 6-methylheptanoyl group, 2-ethylhexanoyl group, 3 -Ethylhexanoyl group, 4-ethylhexanoyl group, 2-propylpentanoyl group, nonanoyl group, decanoyl group, undecanoyl group, 10 Undecenoyl group, dodecanoyl group, tridecanoyl group, tetradecanoyl group, pentadecanoyl group, hexadecanoyl group, 9-hexadecenoyl group, heptadecanoyl group, octadecanoyl group, isostearyl group, cis-9-octadecenoyl group, 11- Octadecenoyl group, cis, cis-9,12-octadecadienoyl group, 9,12,15-octadecatrienoyl group, 6,9,12-octadecatrienoyl group, 9,11,13-octadecatrie Noyl group, nonadecanoyl group, 2,6,10,14-tetramethylpentadecanoyl group, icosanoyl group, 8,11-icosadenoyl group, 5,8,11-icosatrienoyl group, 5,8,11,14- Eicosatetraenoyl group, 3,7,11,15-tetramethylhexadecanoyl , Hen'ikosanoiru group include compounds is either docosanoyl group.

Of these, as preferred examples, R ¹¹ and / or R ¹² in the formula (2) is an octanoyl group, a decanoyl group, an undecanoyl group, a dodecanoyl group, a hexadecanoyl group, an octadecanoyl group, or an isostearyl group. A compound that is any of them is mentioned.

More preferred examples include compounds in which R ¹¹ is any one of an octanoyl group, a decanoyl group, an undecanoyl group, a dodecanoyl group, a hexadecanoyl group, an octadecanoyl group, and an isostearyl group, and R ¹² is a hydrogen atom. Can be mentioned.

Next, in the formula (2), X ^{1 to} X ³ each independently represent a nitrogen or oxygen atom, R ³ ,
R ⁴ , R ⁵ , R ^{3 ′} , R ^{4 ′} and R ^{5 ′} are each independently a hydrogen atom, or a chain hydrocarbon group having 1 to 30 carbon atoms, which may have a branched or unsaturated bond. (However, when X ¹ , X ² and X ³ are each an oxygen atom, the corresponding R ^{3 ′} , R ^{4 ′} and R ^{5 ′} do not exist.)

When any of X ^{1 to} X ³ is a nitrogen atom, —CONR ^m R ^{m ′} (m and m ′ are X ^{1 to} X ³
Corresponding to any one of 3, 4 and 5. ) Represents a degradable substituted or unsubstituted amide group in vivo enzymatic reaction, also -COOR ^m (m in the case of any of X ¹ to X ³ is an oxygen atom
Represents a number of 3, 4 or 5 corresponding to X ^{1 to} X ³ . ) Represents a carboxyl group or an ester group decomposable by a biological enzyme reaction.

Here, the substituted or unsubstituted amide group decomposable by a biological enzyme reaction is a substituted or unsubstituted amide group that can be hydrolyzed by a hydrolase such as amidase existing in the living body to become a carboxyl group. Means that.

  The ester group decomposable by a biological enzyme reaction means an ester group that can be hydrolyzed by a hydrolase such as esterase existing in the living body to become a carboxyl group.

R ³ , R ⁴ , R ⁵ , R ^{3 ′} , R ^{4 ′} and R ^{5 ′} are each independently a hydrogen atom or 1 to 30 carbon atoms, preferably 8 to 8 provided that the above proviso is satisfied. 24, more preferably a chain hydrocarbon group which may have a branched or unsaturated bond of 14 to 22, more preferably a hydrogen atom or an alkyl which may have a branch of 14 to 22 carbon atoms It is a group. In addition, sugar residues derived from monosaccharides and polysaccharides may be used.

Specifically, R ³ , R ⁴ , R ⁵ , R ^{3 ′} , R ^{4 ′} and R ^{5 ′} are each independently a hydrogen atom, methyl group, ethyl group, propyl group, isopropyl group, butyl group, 1-methylpropyl group, 2-methylpropyl group, pentyl group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 1-ethylpropyl group, hexyl group, 1-methylpentyl group, 2-methylpentyl group 3-methylpentyl group, 4-methylpentyl group, 1-ethylbutyl group, 2-ethylbutyl group, heptyl group, 1-methylhexyl group, 2-methylhexyl group, 3-methylhexyl group, 4-methylhexyl group, 5-methylhexyl group, 1-ethylpentyl group, 2-ethylpentyl group, 3-ethylpentyl group, octyl group, 1-methylheptyl group, 2-methylheptyl group, 3 Methylheptyl group, 4-methylheptyl group, 5-methylheptyl group, 6-methylheptyl group, 1-ethylhexyl group, 2-ethylhexyl group, 3-ethylhexyl group, 4-ethylhexyl group, 1-propylpentyl group, 2- Propylpentyl group, nonyl group, decyl group, undecyl group, 10-undecenyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, hexadecyl group, 9-hexadecenyl group, heptadecyl group, octadecyl group, isostearyl group, cis- 9-octadecenyl group, 11-octadecenyl group, cis, cis-9,12-octadecadienyl group, 9,12,15-octadecatrienyl group, 6,9,12-octadecatrienyl group, 9, 11,13-octadecatrienyl group, nonadecyl group, 2,6,10,1 4-tetramethylpentadecyl group, icosanyl group, 8,11-icosadienyl group, 5,8,11-icosatrienyl group, 5,8,11,14-icosatetraenyl group, 3,7,11,15-tetra Any of a methylhexadecyl group, a heicosanyl group, and a docosanyl group can be mentioned.

Among these, as preferable examples, R ³ , R ⁴ , R ⁵ , R ^{3 ′} , R ^{4 ′} , and R ^{5 ′} are each independently a hydrogen atom, a methyl group, provided that the above proviso is satisfied. Any of ethyl, propyl, isopropyl, butyl, hexyl, octyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, isostearyl The aspect which is is mentioned.

As more preferred examples, 1 to 2 of R ³ , R ⁴ , R ⁵ , R ^{3 ′} , R ^{4 ′} and R ^{5 ′} are methyl group, ethyl group, propyl group, isopropyl group, butyl group, hexyl group. An octyl group, a decyl group, an undecyl group, a dodecyl group, a tridecyl group, a tetradecyl group, a pentadecyl group, a hexadecyl group, a heptadecyl group, an octadecyl group, or an isostearyl group, and the other is a hydrogen atom. .

X ^{1 to} X ³ are each independently a nitrogen atom or an oxygen atom, but all of them may be the same atom or a mixture thereof. Preferred examples are the same atom, and more preferred examples are oxygen atoms.

When X ^{1 to} X ³ are all oxygen atoms, the modified carboxyl group moiety is —COOR ^m (m is any number of 3, 4, and 5 corresponding to X ^{1 to} X ^3. Represents a carboxyl group or an ester group decomposable by a biological enzyme reaction. In this case, R ^{3 ′} , R ^{4 ′} and R ^{5 ′} do not exist.

That is, the hydroxycitric acid derivative that can be used in the present invention includes a compound in which at least one hydroxyl group is modified and the carboxyl group is not modified as described above, and at least one hydroxyl group as described above. And a compound in which at least one of the carboxyl groups is modified. Specific examples of these compounds include compounds obtained by combining the above examples of R ¹¹ , R ¹² , X ^{1 to} X ³ , R ³ , R ⁴ , R ⁵ , R ^{3 ′} , R ^{4 ′} , and R ^{5 ′.} Preferably mentioned.

As described above, the functional groups in the molecule can be modified in various combinations. In particular, R ¹² is a hydrogen atom, R ^{3 to} R ⁵ are all hydrogen atoms, and X ^{1 to} X ³ are A compound represented by the following formula (2-1) which is an oxygen atom (for example, hydroxycitric acid-2-palmitate), or
R ¹² is a hydrogen atom, and R ^{3 to} R ⁵ are each independently a hydrogen atom or a chain hydrocarbon group having 1 to 30 carbon atoms, which may have a branched or unsaturated bond (provided that R ^{3 to} R ⁵ are not hydrogen atoms at the same time.) And a compound represented by the following formula (2-2) in which X ^{1 to} X ³ are all oxygen atoms is a preferred example.

  Specific examples of the hydroxycitric acid derivative include hydroxycitric acid-2-octanoate, hydroxycitric acid-2-caprate, hydroxycitric acid-2-laurate, hydroxycitric acid-2-myristate, hydroxycitric acid-2- Palmitate, hydroxycitric acid-2-stearate, hydroxycitric acid-2-behenoate, hydroxycitrate-2-isopalmitate, hydroxycitrate-2-isostearate, hydroxycitrate-2-hexyldecanoate, hydroxycitrate Acid-2-linoleate, hydroxycitric acid monomethyl ester-2-myristate, hydroxycitric acid monomethyl ester-2-palmitate, hydroxycitric acid monomethyl ester-2-stearate, and salts thereof That.

  Among these, preferred examples include hydroxycitric acid-2-laurate, hydroxycitric acid-2-myristate, hydroxycitric acid-2-palmitate, hydroxycitric acid-2-stearate, hydroxycitric acid-2-behenoate , Hydroxycitric acid-2-isopalmitate, hydroxycitric acid-2-isostearate, hydroxycitric acid-2-hexyldecanoate, hydroxycitric acid-2-linoleate and their salts.

  Further preferred examples include hydroxycitric acid-2-myristate, hydroxycitric acid-2-palmitate, hydroxycitric acid-2-stearate, and salts thereof.

Examples of the pharmacologically acceptable salt of the hydroxycitric acid derivative include the alkali metal salts and alkaline earth metal salts of the hydroxycitrate derivative described above.
Examples of the alkali metal salt include sodium salt and potassium salt, and examples of the alkaline earth metal salt include calcium salt.

  There is no restriction | limiting in particular in the manufacturing method of hydroxycitrate derivative or its salt mentioned above, Hydroxycitric acid and / or its alkali metal salt and / or its alkaline earth metal salt, and the carboxylic acid derivative or It can be produced by reacting a phosphoric acid derivative or a sulfonic acid derivative in an appropriate solvent.

The hydroxycitric acid, its derivatives, and pharmacologically acceptable salts thereof may be used alone or in combination of two or more.
At least one selected from the group consisting of the hydroxycitric acid, derivatives thereof, and pharmacologically acceptable salts thereof is usually 0.01 to 20% by mass in the slimming skin external preparation of the present invention, preferably It is desirable to be contained in an amount of 0.05 to 10% by mass.
( Α2 adrenergic inhibitor )
Further, as one of the slimming components, a component that suppresses the action of α2 adrenaline having an action of suppressing the synthesis of intracellular cAMP, which is a second messenger of lipolysis can be used. That is, since α2 adrenaline suppresses lipolysis, a secondary effect of promoting lipolysis can be expected by suppressing the action of α2 adrenaline.

  Examples of the α2 adrenergic inhibitor include yohimbine, phentolamine, phenoxybenzamine, tolazoline, ergotamine, ergotoxin, dihydroergotamine, ergomethrin, methylergomethrin, dihydroergotoxin, laurucine, piperoxane, derivatives thereof, and pharmacological agents thereof. In addition to salts that are acceptable, natural extracts having an α2 adrenergic inhibitory action, particularly extracts of plants such as ginkgo, ivy, horse chestnut and the like can be used. These pharmacologically acceptable salts include these inorganic acid salts, such as hydrochloride salts. These may be used alone or in combination of two or more.

The α2 adrenergic inhibitor is usually contained in the slimming skin external preparation of the present invention in an amount of usually 0.0001 to 10% by mass, preferably 0.0005 to 5% by mass.
( Β-adrenergic stimulant )
Further, as one of the slimming components, a β-adrenergic stimulant having an action of promoting the synthesis of intracellular cAMP which is a second messenger of lipolysis can be used. The β-adrenergic stimulant is expected to have an effect of suppressing fat accumulation.

Examples of this β-adrenergic stimulant include isoproterenol, epinephrine, norepinephrine, dobutamine, dopamine, butopamine, salbutamol, terbutaline, isoethalin, protokilol, fenoterol, metaproterenol, chlorprenalin, hexoprenalin, trimethquinol, hydrochloric acid Procaterol, prenalterol, forskolin, disodium (R, R) -5- [2-[[2- (3-chlorophenyl) -2-hydroxyethyl] -amino] propyl] -1,3-benzodioxole -2,2-dicarboxylate, (R, R) -4- [2-({2-[(3-chlorophenyl) -2-hydroxyethyl] amino} propyl) phenyl] phenoxyacetic acid, {2-hydroxy- 5- [2-({2-hydroxy-3- 4- (1-methyl-4-trifluoromethyl) -1H-imidazol-2-yl] phenoxy} propyl) amino] ethoxy} -benzamide monomethanesulfonate, erythro-DL-1- (7-methylindan- 4-Iroxy) -3-isopropylaminobutan-2-ol, derivatives thereof, and pharmacologically acceptable salts thereof, as well as natural products having β-adrenergic stimulant action, in particular Coleus forskohlii ) Extract (Forskolin), Ipomoea hederacea extract, Sweet potato (Ipomoea batata) extract, Sage (Salvia officinalis), Tanjin (Salvia miltiorrhiza), Mannenro (Rosmarinus officinalis; Rosemary), etc. Plant extracts can be used. In addition, as these pharmacologically acceptable salts, these inorganic acid salts, such as hydrochlorides, can be mentioned. These may be used alone or in combination of two or more.

The β-adrenergic stimulant is usually contained in the slimming skin external preparation of the present invention in an amount of usually 0.0001 to 10% by mass, preferably 0.0005 to 5% by mass.
( Phosphodiesterase inhibitor )
Moreover, as one of the slimming components, an inhibitor of phosphodiesterase having an action of degrading intracellular cAMP which is a second messenger of lipolysis can be used. Phosphodiesterase suppresses lipolysis by lowering intracellular cAMP concentration and decreasing hormone-sensitive lipase activity. Therefore, by suppressing the action of phosphodiesterase, the suppression of lipolysis can be canceled and a secondary effect of promoting lipolysis can be expected.

  Examples of the phosphodiesterase inhibitor include caffeine, theophylline, theobromine, aminophylline, xanthine, isobutylmethylxanthine, apigenin, amentoflavone, vilobetine, cyanadopiticin, ginkgonetin, derivatives thereof, and pharmacologically acceptable salts thereof. Extracts of natural products having phosphodiesterase inhibitor activity, particularly tea, coffee, guarana, Yerba Mate, cola, ginkgo, sequoia mulberry, yew, caster, etc. can be used. These pharmacologically acceptable salts include alkali metal salts, alkaline earth metal salts and the like. Examples of the alkali metal salt include a sodium salt, and examples of the alkaline earth metal salt include a calcium salt. These may be used alone or in combination of two or more.

The phosphodiesterase inhibitor is usually contained in the slimming skin external preparation of the present invention in an amount of usually 0.0001 to 10% by mass, preferably 0.0005 to 5% by mass.
Skin care component The action of the carnitine derivative described above is to increase the concentration of carnitine in the cellular tissue that becomes a mediator when fatty acids are taken into the mitochondria and promote fat metabolism, but if fat metabolism is excessively promoted, The shortage of subcutaneous fat and sebum may damage the skin tension and may cause problems such as dry skin and rough skin.

On the other hand, in addition to the carnitine derivative, a skin care external preparation for slimming that has a skin care action that promotes lipolysis of the skin and at the same time keeps the skin healthy by further blending certain skin care ingredients. Obtainable.
( Fatty acids )
One such skin care ingredient can include fatty acids.

When an agent containing the carnitine derivative and fatty acids is administered transdermally, the carnitine derivative promotes lipolysis and provides a slimming effect deep in the skin, and supplies fatty acids as appropriate nutrients on the skin surface. Thereby, the outstanding slimming effect | action can be given, keeping the moisture retention of skin. Examples of such fatty acids include a saturated or unsaturated fatty acid having 12 to 22 carbon atoms and / or a pharmacologically acceptable salt thereof, which may have a branch,
Contains these fatty acids in addition to lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, isostearic acid, 12-hydroxystearic acid, undecylenic acid, hexyldecanoic acid and their pharmacologically acceptable salts A natural product-derived fatty acid such as coconut oil fatty acid can be preferably used. These pharmacologically acceptable salts include these alkali metal salts. Examples of the alkali metal salt include sodium salt and potassium salt. These may be used singly or in combination of two or more.

The saturated or unsaturated fatty acid having 12 to 22 carbon atoms and / or pharmacologically acceptable salt thereof which may have a branch is usually 0.001 to 20 in the slimming skin external preparation of the present invention. It is desirable to be contained in an amount of mass%, preferably 0.005 to 10 mass%.
( Ascorbic acids and ascorbic acid derivatives )
Moreover, as one of the said skin care components, at least 1 sort (s) chosen from the group which consists of ascorbic acid, its derivative (s), and these pharmacologically acceptable salts can be mentioned. The skin care action derived from the promotion of collagen synthesis and the action of eliminating active oxygen has been known for a long time and has been used in many cosmetics.

Examples of the ascorbic acid include L-ascorbic acid. Examples of the pharmacologically acceptable salt of ascorbic acid include sodium L-ascorbate and / or magnesium L-ascorbate.

Examples of the ascorbic acid derivative include L-ascorbyl stearate, L-ascorbyl palmitate, L-ascorbyl dipalmitate, L-ascorbyl tetraisopalmitate, L-ascorbic acid-2-glucoside, and the following formula (4) And higher fatty acid esters of ascorbic acid-2-phosphate and / or ascorbic acid-2-phosphate.

(In formula (4), R represents a hydrogen atom or an acyl residue of a higher fatty acid).
Examples of the pharmacologically acceptable salt of the ascorbic acid derivative include L-ascorbic acid sulfate disodium, ascorbic acid-2-phosphate and / or ascorbic acid represented by the above formula (4). Examples include sodium salts, potassium salts, magnesium salts, and zinc salts of higher fatty acid esters of 2-phosphate esters.

These can be used alone or in combination of two or more.
Among these, higher fatty acid esters of ascorbic acid-2-phosphate represented by the above formula (4) or sodium salts, potassium salts, magnesium salts or zinc salts thereof are preferable, and in the above formula (4) R represents an acyl residue of lauric acid, myristic acid, palmitic acid, stearic acid, or 2-hexyldecanoic acid, a higher fatty acid ester of ascorbic acid-2-phosphate, or a sodium salt, potassium salt, magnesium salt thereof Or zinc salt is used more preferably.

At least one selected from the group consisting of the ascorbic acid, derivatives thereof, and pharmacologically acceptable salts thereof is usually 0.01 to 20% by mass, preferably 0, in the slimming skin external preparation of the present invention. It is desirable to be included in an amount of 0.05 to 10% by mass.
( Tocopherols, tocopherol derivatives )
Moreover, as one of the said skin care components, at least 1 sort (s) chosen from the group which consists of a tocopherol, its derivative (s), and these pharmacologically acceptable salts can be mentioned. Tocopherol is known as vitamin E, and has an antioxidant action, a biological membrane stabilization action, an immunostimulatory action, a blood circulation promoting action, and the like, and cosmetics using such actions are known.

Examples of tocopherol include α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol.
Examples of tocopherol derivatives include α-tocopherol derivatives, β-tocopherol derivatives, γ-tocopherol derivatives, and δ-tocopherol derivatives, and preferred examples thereof include phosphoric acid esters and aminoalkylcarboxylic acid esters. These can be used alone or in combination of two or more.

  As the tocopherol phosphate ester, the following formula (5)

(In formula (5), R ²¹ , R ^22, and R ²³ each independently represents a hydrogen atom or a methyl group.) Tocopherol phosphates represented by formula (5) are preferred.
Moreover, as a tocopherol aminoalkyl carboxylic acid ester, following formula (6)

(In formula (6), R ³¹ and R ³² represent the same or different lower alkyl groups or hydrogen atoms, R ³³ and R ³⁴ each independently represent a hydrogen atom or a methyl group, and Z has a substituent. And a tocopherol aminoalkylcarboxylic acid ester represented by the following formula: Further, the aminoalkylcarboxylic acid of the tocopherol aminoalkylcarboxylic acid ester is glycine, alanine, β-alanine, valine, leucine, isoleucine, phenylalanine, methionine, cysteine, serine, threonine, tyrosine, thyroxine, histidine, proline, 4- More preferably, it is selected from hydroxyproline, aspartic acid, glutamic acid, N-alkyl derivatives or N, N-dialkyl derivatives thereof.

  Examples of these pharmacologically acceptable salts include inorganic salts and alkali metal salts of the tocopherol or tocopherol derivative. Examples of the inorganic acid salt include hydrochloride, and examples of the alkali metal salt include sodium salt and potassium salt.

At least one selected from the group consisting of the tocopherol, derivatives thereof, and pharmacologically acceptable salts thereof is usually 0.01 to 10% by mass, preferably 0.00% in the slimming skin external preparation of the present invention. It is desirable to be contained in an amount of 05 to 5% by mass.
Other components In addition to the above-mentioned carnitine derivatives, the slimming skin external preparation and cosmetic of the present invention can be used in place of the above-described slimming component and / or skin care component, or in addition to the above-described slimming component and / or skin care component. In addition, it is possible to mix components generally used in external preparations for skin or cosmetics in an amount that does not impair the effects of the present invention (in the case where the slimming component or skin care component described above overlaps with the component described below) Are treated as slimming and skin care ingredients.)

Although it can mix | blend as a component which can be mix | blended, For example, the following components are mentioned.
Hydrocarbons: for example, ozokerite, α-olefin oligomer, light isoparaffin, light liquid isoparaffin, squalene, squalane, synthetic squalane, vegetable squalane, ceresin, paraffin, polyethylene powder, polybutene, microcrystalline wax, liquid isoparaffin, liquid paraffin, Mineral oil, petrolatum etc.

  Natural fats and oils: For example, jojoba oil, carnauba wax, candelilla wax, rice bran wax, shellac, lanolin, mink sebum wax, whale wax, sugarcane wax, sperm whale oil, beeswax, montan wax and other natural waxes, avocado oil, almond oil, Olive oil, extra virgin olive oil, sesame oil, rice bran oil, rice oil, rice germ oil, corn oil, soybean oil, corn oil, persic oil, palm kernel oil, palm oil, castor oil, grape seed oil, cottonseed oil, palm oil, water Palm oil, beef tallow, hydrogenated oil, horse oil, mink oil, egg yolk oil, egg yolk fat oil, rosehip oil, kukui nut oil, evening primrose oil, wheat germ oil, peanut oil, camellia oil, sasanca oil, cacao butter, moclaw, Beef bone fat, beef leg oil, pork fat, horse fat, sheep fat, shea butter, macadamia nut oil, Meadow home oil, etc.

  Fatty acids: For example, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, isostearic acid, 12-hydroxystearic acid, undecylenic acid, coconut oil fatty acid and the like.

Higher monoalcohols: for example, isostearyl alcohol, octyldodecanol, hexyldecanol, cholesterol, phytosterol, lauryl alcohol, myristyl alcohol, cetanol, stearyl alcohol, oleyl alcohol, behenyl alcohol, cetostearyl alcohol and the like.

Alkyl glyceryl ethers: For example, batyl alcohol, chimyl alcohol, seraalkyl alcohol, isostearyl glyceryl ether and the like.
Esters: for example, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, butyl stearate, ethyl oleate, ethyl linoleate, isopropyl linoleate, cetyl caprylate, hexyl laurate, isooctyl myristate, myristine Decyl acid, myristyl myristate, cetyl myristate, octadecyl myristate, cetyl palmitate, stearyl stearate, decyl oleate, oleyl oleate, cetyl ricinoleate, isostearyl myristate, isotridecyl myristate, isocetyl myristate, myristic acid Isostearyl, octyldodecyl myristate, 2-ethylhexyl palmitate, isocetyl palmitate, isostearyl palmitate 2-ethylhexyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate, octyldodecyl ricinoleate, ethyl isostearate, isopropyl isostearate, cetyl 2-ethylhexanoate, cetostearyl 2-ethylhexanoate, 2- Stearyl ethylhexanoate,

Hexyl isostearate, ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol dicaprylate, propylene glycol di (capryl / capric acid), propylene glycol dicaprate, propylene glycol dioleate, neopentyl glycol dicaprate, neopentyl glycol dioctanoate Glyceryl tricaprylate, glyceryl tri-2-ethylhexanoate, tri (caprylic / capric acid) glyceryl, tri (caprylic acid / capric acid / stearic acid) glyceryl, glyceryl triundecylate, glyceryl triisopalmitate, glyceryl triisostearate, Tri-2-ethylhexanoic acid trimethylolpropane, triisostearic acid trimethylolpropane, tetra-2-ethylhexa Pentaerythrityl acid, pentaerythrityl tetramyristic acid, pentaerythrityl tetraisostearate, diglyceryl tetraisostearate, octyldodecyl neopentanoate, isocetyl octoate, isostearyl octoate, 2-ethylhexyl isoperargonate, dimethyloctanoic acid Hexyldecyl, octyldodecyl dimethyloctanoate, 2-ethylhexyl isopalmitate, isocetyl isostearate, isostearyl isostearate, octyldodecyl isostearate, lauryl lactate, myristyl lactate, cetyl lactate, octyldodecyl lactate, triethyl citrate, acetyl citrate Triethyl, acetyl tributyl citrate, trioctyl citrate, triisocetyl citrate, trioctyldodecyl citrate Diisostearyl malate, hydroxystearic acid 2-ethylhexyl, succinate di-2-ethylhexyl,

Diisopropyl adipate, diisobutyl adipate, dioctyl adipate, diheptyl undecyl adipate, diethyl sebacate, diisopropyl sebacate, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, oleic acid Dihydrocholesteryl, phytosteryl isostearate, phytosteryl oleate, isocetyl 12-stearoylhydroxystearate, stearyl 12-stearoylhydroxystearate, isostearyl 12-stearoylhydroxystearate, polyoxyethylene acetate (3) polyoxypropylene (1) cetyl Ether, polyoxyethylene acetate (3) polyoxypropylene (1) iso Chirueteru, isononyl isononanoate, octyl isononanoate, tridecyl isononanoate, isotridecyl like isononanoate.

Silicone oils: for example, methylpolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, methylcyclopolysiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, octamethyltrisiloxane, deca Methyltetrasiloxane, tetradecamethylhexasiloxane, highly polymerized methylpolysiloxane, dimethylsiloxane / methyl (polyoxyethylene) siloxane / methyl (polyoxypropylene) siloxane copolymer, dimethylsiloxane / methyl (polyoxyethylene) siloxane copolymer Polymer, dimethylsiloxane / methyl (polyoxypropylene) siloxane copolymer, dimethylsiloxane / methylcetyloxysiloxane copolymer Body, dimethyl siloxane-methyl stearoxysiloxane copolymer, polyether-modified silicones, alcohol-modified silicones, alkyl-modified silicones, amino-modified silicones.

Polymers: for example, sodium alginate, carrageenan, agar, fur celeran, guar gum, quince seed, konjac mannan, tamarind gum, tara gum, dextrin, starch, locust bean gum, gum arabic, gati gum, caraya gum, tragacanth gum, arabinogalactan, pectin Quince, chitosan, starch, curdlan, xanthan gum, gellan gum, cyclodextrin, dextran, pullulan, microcrystalline cellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxystarch, cationized cellulose, Starch phosphate ester, cationized guar gum, Ruboxymethyl hydroxypropylated guar gum, hydroxypropylated guar gum, albumin, casein, gelatin, sodium polyacrylate, polyacrylate amide, carboxyvinyl polymer, polyethyleneimine, highly polymerized polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl ether, poly Acrylamide, acrylic acid copolymer, methacrylic acid copolymer, maleic acid copolymer, vinylpyridine copolymer, ethylene / acrylic acid copolymer, vinylpyrrolidone polymer, vinyl alcohol / vinylpyrrolidone copolymer, nitrogen substitution Acrylamide polymer, amino-modified silicone, cationized polymer, dimethylacrylammonium polymer, acrylic acid anion polymer, methacrylic acid Anionic polymers, modified silicones, alkyl methacrylate acrylate acid (C ₁₀ ~ ₃₀₎ copolymers, polyoxyethylene / polyoxypropylene copolymers.

Lower monoalcohols: for example, ethanol, isopropyl alcohol, 1-butanol, 2-butanol, benzyl alcohol and the like.
Polyhydric alcohols: for example, ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, 1,3-butanediol, triethylene glycol, dipropylene glycol, 3-methyl-1, 3-butanediol, 1,2-pentanediol, 1,4-pentanediol, 1,5-pentanediol, 2,4-pentanediol, 2-methyl-2,4-pentanediol, 3-methyl-1,5 -Pentanediol, 1,2
-Hexanediol, 1,6-hexanediol and the like.

Anionic surfactant: For example, coconut oil fatty acid potassium, coconut oil fatty acid sodium, coconut oil fatty acid triethanolamine, potassium laurate, sodium laurate, triethanolamine laurate, potassium myristate, sodium myristate, myristic acid Isopropanolamine, potassium palmitate, sodium palmitate, isopropanolamine palmitate, potassium stearate, sodium stearate, triethanolamine stearate, potassium oleate, sodium oleate, sodium castor oil fatty acid, zinc undecylenate, zinc laurate , Zinc myristate, magnesium myristate, zinc palmitate, zinc stearate, calcium stearate, magnesium stearate, Alin aluminum, calcium myristate, magnesium myristate, dimyristate, aluminum isostearate,
Polyoxyethylene lauryl ether acetic acid, sodium polyoxyethylene lauryl ether acetate, polyoxyethylene tridecyl ether acetic acid, sodium polyoxyethylene tridecyl ether acetate, sodium stearoyl lactate, sodium isostearoyl lactate, sodium lauroyl sarcosine, coconut oil fatty acid sarcosine, Coconut oil fatty acid sarcosine sodium, coconut oil fatty acid sarcosine triethanolamine, lauroyl sarcosine,

Lauroyl sarcosine potassium, lauroyl sarcosine triethanolamine, oleoyl sarcosine, myristoyl sarcosine sodium, sodium stearoyl glutamate, coconut oil fatty acid acyl glutamate, coconut oil fatty acid acyl glutamate potassium, coconut oil fatty acid sodium acyl glutamate, coconut oil fatty acyl glutamate triethanolamine , Lauroyl acyl glutamate, potassium lauroyl acyl glutamate, sodium lauroyl acyl glutamate, triethanolamine lauroyl acyl glutamate, myristoyl acyl glutamate, potassium myristoyl acyl glutamate, sodium myristoyl acyl glutamate, stearoyl acyl glutamate, stearoyl acyl glutamate Um, stearoyl acyl glutamate disodium, hydrogenated beef tallow fatty acid acyl glutamate sodium, coconut oil fatty acid / hardened tallow fatty acid acyl glutamate sodium, coconut oil fatty acid sodium methylalanine, lauroylmethylalanine, lauroylmethylalanine sodium, lauroylmethylalanine triethanolamine, myristoyl Sodium methylalanine, sodium lauroylmethyltaurine,

Palm oil fatty acid methyl taurine potassium, coconut oil fatty acid methyl taurine sodium, palm oil fatty acid methyl taurine magnesium, myristoyl methyl taurine sodium, palmitoyl methyl taurine sodium, stearoyl methyl taurine sodium, oleoyl methyl taurine sodium, sodium alkane sulfonate, tetradecene sulfone Sodium sulfate, dioctyl sodium sulfosuccinate, disodium lauryl sulfosuccinate, sodium coconut oil fatty acid ethyl ester sulfonate, sodium lauryl sulfate, lauryl sulfate triethanolamine, sodium cetyl sulfate, alkyl (11,13,15) triethanolamine sulfate, Alkyl (12,13) sodium sulfate, alkyl (12,13) triethanolamine sulfate, alkyl (1 , 14, 16) sulfate, alkyl (12-13) diethanolamine sulfate, alkyl (12-14) sulfate, triethanolamine alkyl (
12-15) Triethanolamine sulfate, palm oil alkyl magnesium sulfate / triethanolamine, ammonium lauryl sulfate, potassium lauryl sulfate, magnesium lauryl sulfate, monoethanolamine lauryl sulfate, diethanolamine lauryl sulfate, sodium myristyl sulfate, sodium stearyl sulfate, oleyl sulfate Sodium, oleyl sulfate triethanolamine, polyoxyethylene lauryl ether sodium sulfate,

Polyoxyethylene lauryl ether sulfate triethanolamine, polyoxyethylene (1) alkyl (11, 13, 15) ether sodium sulfate, polyoxyethylene (1) alkyl (11, 13, 15) ether triethanolamine sulfate, polyoxy Ethylene (3) alkyl (11-15) ether sodium sulfate, polyoxyethylene (2) alkyl (12,13) sodium ether sulfate, polyoxyethylene (3) alkyl (12-14) ether sodium sulfate, polyoxyethylene ( 3) Sodium alkyl (12-15) ether sulfate, polyoxyethylene (2) sodium lauryl ether sulfate, polyoxyethylene (3) sodium myristyl ether sulfate, higher fatty acid alkanolamide sulfate sodium salt Lauryl phosphate, sodium lauryl phosphate, potassium cetyl phosphate, diethanolamine cetyl phosphate, polyoxyethylene oleyl ether phosphate, polyoxyethylene lauryl ether phosphate, sodium polyoxyethylene lauryl ether phosphate, polyoxyethylene cetyl ether phosphate, Polyoxyethylene cetyl ether sodium phosphate, polyoxyethylene stearyl ether phosphate, polyoxyethylene oleyl ether phosphate, polyoxyethylene oleyl ether sodium phosphate, polyoxyethylene alkylphenyl ether phosphate, polyoxyethylene alkylphenyl ether phosphorus Acid sodium, polyoxyethylene alkyl phenyl ether triethanolamine phosphate, polyoxyethylene octyl Ether phosphoric acid, polyoxyethylene (10) alkyl (12,13) ether phosphoric acid, polyoxyethylene alkyl (12-15) ether phosphoric acid, polyoxyethylene alkyl (12-16) ether phosphoric acid, polyoxyethylene lauryl Ether phosphate triethanolamine, polyoxyethylene oleyl ether phosphate diethanolamine, etc.

  Cationic surfactants: for example, dioctylamine, dimethylstearylamine, trilaurylamine, diethylaminoethylamide stearate, lauryltrimethylammonium chloride, cetyltrimethylammonium chloride, cetyltrimethylammonium bromide, cetyltrimethylammonium saccharin, stearyltrimethyl chloride Ammonium, alkyl chloride (20-22) trimethyl ammonium, lauryl trimethyl ammonium bromide, alkyl (16,18) trimethyl ammonium chloride, stearyl trimethyl ammonium bromide, stearyl trimethyl ammonium saccharin, alkyl chloride (28) trimethyl ammonium chloride, di ( Polyoxyethylene) oleylmethylammonium (2EO), dipolyoxyethylene chloride N-stearylmethylammonium chloride, polyoxyethylene chloride (1) polyoxypropylene (25) diethylmethylammonium chloride, tri (polyoxyethylene) stearylammonium chloride (5EO), distearyldimethylammonium chloride, dialkyl (12-15) dimethylammonium chloride Dialkyl (12-18) dimethylammonium chloride, dialkyl (14-18) dimethylammonium chloride, dicocoyldimethylammonium chloride, dicetyldimethylammonium chloride, isostearyl lauryldimethylammonium chloride, benzalkonium chloride, myristyldimethylbenzylammonium chloride , Lauryldimethyl (ethylbenzyl) ammonium chloride, stearyldimethylbenzylammonium chloride, laurylpyridinyl chloride Um, cetylpyridinium chloride, lauroylcoraminoformylmethylpyridinium chloride, stearoylcoraminoformylmethylpyridinium chloride, alkylisoquinolium bromide, methylbenzethonium chloride, benzethonium chloride and the like.

  Amphoteric surfactants: for example 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, alkyldiaminoethylglycine hydrochloride, sodium lauryldiaminoethylglycine, undecylhydroxyethylimidazolium betaine sodium, undecyl-N -Carboxymethylimidazolium betaine, coconut oil fatty acid acyl-N-carboxyethyl-N-hydroxyethylethylenediamine disodium, coconut oil fatty acid acyl-N-carboxyethoxyethyl-N-carboxyethylethylenediamine disodium, coconut oil fatty acid acyl- N-carboxymethoxyethyl-N-carboxymethylethylenediamine disodium, sodium laurylaminopropionate, sodium laurylaminodipropionate Lithium, laurylaminopropionic acid triethanolamine, palm oil fatty acid acyl-N-carboxyethyl-N-hydroxyethylethylenediamine sodium, lauryldimethylaminoacetic acid betaine, coconut oil alkyldimethylaminoacetic acid betaine, stearyldimethylaminoacetic acid betaine, stearyldimethylbetaine Sodium, coconut oil fatty acid amidopropyl betaine, palm oil fatty acid amidopropyl betaine, lauric acid amidopropyl acetic acid betaine, ricinoleic acid amidopropyl betaine, stearyl dihydroxyethyl betaine, lauryl hydroxysulfobetaine and the like.

Nonionic surfactant: For example, polyoxyethylene (10) alkyl (12,13) ether, polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene oleyl ether, polyoxyethylene (3, 7, 12) alkyl (12-14) ether, polyoxyethylene tridecyl ether, polyoxyethylene myristyl ether, polyoxyethylene-s
ec-alkyl (14) ether, polyoxyethylene isocetyl ether, polyoxyethylene cetostearyl ether, polyoxyethylene (2,10,20) isostearyl ether, polyoxyethylene oleyl cetyl ether, polyoxyethylene (20) arachi Ether, polyoxyethylene octyldodecyl ether, polyoxyethylene behenyl ether, polyoxyethylene octyl phenyl ether, polyoxyethylene nonyl phenyl ether, polyoxyethylene dinonyl phenyl ether, polyoxyethylene (1) polyoxypropylene (1,2 , 4,8) cetyl ether, polyoxyethylene (5) polyoxypropylene (1,2,4,8) cetyl ether, polyoxyethylene (10) polyoxypropylene (1,2,4,8) cetyl ether, polyoxyethylene (20) polyoxypropylene (1,2,4,8) cetyl ether, polyoxyethylene polyoxypropylene lauryl ether, polyoxyethylene (3) poly Oxypropylene (34) stearyl ether, polyoxyethylene (4) polyoxypropylene (30) stearyl ether, polyoxyethylene (34) polyoxypropylene (23) stearyl ether, polyoxyethylene polyoxypropylene cetyl ether,

Polyoxyethylene polyoxypropylene decyl tetradecyl ether, polyethylene glycol monolaurate, ethylene glycol monostearate, polyethylene glycol monostearate, polyethylene glycol monooleate, ethylene glycol fatty acid ester, self-emulsifying ethylene glycol monostearate, lauric acid Diethylene glycol, polyethylene glycol myristate, polyethylene glycol palmitate, diethylene glycol stearate, self-emulsifying polyethylene glycol monostearate (2), polyethylene glycol isostearate, ethylene glycol dioctanoate, diethylene glycol dilaurate, polyethylene glycol dilaurate, dipalmitate Polyethylene glycol (150), ethylene glycol distearate, diethylene glycol distearate, polyethylene glycol distearate, ethylene glycol dioleate, polyethylene glycol dioleate, polyethylene glycol diricinoleate, polyoxyethylene monolaurate (20) sorbitan, polyoxy monopalmitate Ethylene (20) sorbitan, polyoxyethylene (6) sorbitan monostearate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan tristearate, polyoxyethylene (6) sorbitan monooleate, Polyoxyethylene (20) sorbitan monooleate, polyoxyethylene (20) sorbitan trioleate, polyoxyethylene Down (20) coconut oil fatty acid sorbitan,

Polyoxyethylene (10-80) sorbitan monolaurate, polyoxyethylene sorbitan tristearate, polyoxyethylene (20) sorbitan isostearate, polyoxyethylene (150) sorbitan tristearate, polyoxyethylene castor oil, polyoxyethylene Hardened castor oil, polyoxyethylene (10) hardened castor oil, polyoxyethylene (20) hardened castor oil, polyoxyethylene (40) hardened castor oil, polyoxyethylene (50) hardened castor oil, polyoxyethylene (60) Hydrogenated castor oil, lipophilic glyceryl monostearate, lipophilic glyceryl monooleate, self-emulsifying glyceryl monostearate, glyceryl coconut oil fatty acid, glyceryl laurate, glyceryl myristate, isostearic acid Seryl, glyceryl ricinoleate, glyceryl monohydroxystearate, glyceryl oleate, glyceryl linoleate, glyceryl erucate, glyceryl behenate, wheat germ oil fatty acid glyceride, safflower oil fatty acid glyceryl, hydrogenated soybean fatty acid glyceryl, saturated fatty acid glyceride, Cottonseed oil fatty acid glyceryl, monoisostearate glyceryl monomystearate, mono-bovine fatty acid glyceride, monolanolin fatty acid glyceryl, glyceryl sesquioleate, glyceryl distearate, glyceryl diisostearate, glyceryl diarachiate, sorbitan monolaurate,

Sorbitan monopalmitate, sorbitan monostearate, sorbitan monoisostearate, sorbitan monooleate, sorbitan sesquistearate, sorbitan sesquioleate, sorbitan tristearate, sorbitan tristearate, coconut fatty acid sorbitan, sorbitan isostearate, sesqui Sorbitan isostearate, sorbitan distearate, diglyceryl isopalmitate, poly (4-10) glyceryl monolaurate, poly (10) glyceryl monomyristate, poly (2-10) glyceryl monostearate, poly (2 -10) glyceryl, poly (2-10) glyceryl monooleate, diglyceryl sesquioleate, poly (2-10) glyceryl diisostearate, diste Poly (6-10) glyceryl phosphate, diglyceryl triisostearate, poly (10) glyceryl tristearate, poly (10) glyceryl trioleate, poly (2) glyceryl tetraisostearate, decaglyceryl pentastearate, penta Poly (6-10) glyceryl oleate, poly (10) glyceryl heptearate, decaglyceryl decastearate, poly (10) glyceryl decaoleate, condensed poly (6) glyceryl ricinoleate, sucrose fatty acid ester, coconut oil fatty acid Sucrose ester, alkyl glucoside, coconut oil alkyl dimethylamine oxide, lauryl dimethylamine oxide, dihydroxyethyl lauryl dimethylamine oxide, stearyl dimethylamine oxide, oleyl dimethylamine Oxide, polyoxyethylene coconut oil alkyldimethylamine oxide, and the like.

  Natural surfactant: For example, saponin, lecithin, soybean phospholipid, hydrogenated soybean phospholipid, soybean lysophospholipid, hydrogenated soybean lysophospholipid, egg yolk lecithin, hydrogenated egg yolk lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, Sphingophospholipid, sphingomyelin, ganglioside, bile acid, cholic acid, deoxycholic acid, sodium cholate, sodium deoxycholate, spicrispolic acid, rhamnolipid, trehalose lipid, sophorolipid, mannosyl erythritol lipid, etc.

  UV absorbers: Paraaminobenzoic acid derivatives such as paraaminobenzoic acid, ethyl paraaminobenzoate, glyceryl paraaminobenzoate, amyl paradimethylaminobenzoate, 2-ethylhexyl paradimethylaminobenzoate, benzyl cinnamate, diparamethoxy Glyceryl mono-2-ethylhexanoate, methyl 2,4-diisopropylcinnamate, ethyl 2,4-diisopropylcinnamate, potassium paramethoxycinnamate, sodium paramethoxycinnamate, paramethoxycinnamate Cinnamic acid derivatives such as isopropyl acid, 2-methoxyhexyl paramethoxycinnamate, 2-ethoxyethyl paramethoxycinnamate, ethyl paraethoxycinnamate, urocanic acid derivatives such as urocanic acid, ethyl urocanate, 2, 4 -Dihydroxybenzo Enone, 2,2 ′, 4,4′-tetrahydroxybenzophenone, 2-hydroxy-4-methoxy-5-sulfobenzophenone sodium, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, 2-hydroxy-4- Benzophenone derivatives such as methoxybenzophenone, 2,2′-dihydroxy-4,4′-dimethoxybenzophenone, 2,2′-dihydroxy-4,4′-dimethoxy-5-sulfobenzophenone sodium, ethylene glycol salicylate, salicylic acid-2- Salicylic acid derivatives such as ethylhexyl, phenyl salicylate, benzyl salicylate, p-tert-butylphenyl salicylate, homomenthyl salicylate, salicylic acid-3,3,5-trimethylcyclohexyl, 2- (2'-hydroxy-5'-me Kishifeniru) benzotriazole, 4-tert-butyl-4'-methoxybenzoyl methane.

Powders and coloring materials: For example, kaolin, silicic anhydride, magnesium aluminum silicate, sericite, talc, boron nitride, mica, montmorillonite, hemp cellulose powder, wheat starch, silk powder, corn starch, nitro pigment, Azo dyes, nitroso dyes, triphenylmethane dyes, xanthene dyes, quinoline dyes, anthraquinone dyes, indigo dyes, pyrene dyes, phthalocyanine dyes, flavonoids, quinones, porphyrins, water-soluble anatos, Ikasumi powder , Caramel, guaiazulene, gardenia blue, gardenia yellow, cochineal, shikonin, copper chlorophyllin sodium, paprika dye, safflower red, safflower yellow, lacainate, riboflavin butyrate, carbon black, yellow iron oxide, black acid Iron, bengara, conger, ultramarine, zinc oxide, chromium oxide, titanium oxide, black titanium oxide, zirconium oxide, chromium hydroxide, alumina, magnesium oxide, barium sulfate, aluminum hydroxide, calcium carbonate, lithium cobalt titanate, manganese violet , Pearl pigments, etc.

  Plant extract: for example, Ashitaba extract, Asenyaku extract, Avocado extract, Achacha extract, Achachazul extract, Altea extract, Arnica extract, Oil-soluble Arnica extract, Almond extract, Aloe extract, Ansokkou extract, Ginkgo biloba extract, Nettle extract, Iris Root Extract, Fennel Extract, Turmeric Extract, Ages Extract, Echinacea Leaf Extract, Ogon Extract, Oat Extract, Auren Extract, Barley Extract, Okra Extract, Hypericum Extract, Oil-soluble Hypericum Extract, Otriculium Extract, Oil-soluble Otriculi Extract, Onion Extract, Dutch mustard extract, orange flower water, oyster tannins, cuckoo extract, valerian extract, cattail extract, chamomile extract, oil-soluble chamomile extract, chamomile water, Rasmuth extract, carrot extract, oil-soluble carrot extract, carrot oil, Chinese mugwort extract, licorice extract, licorice extract powder, licorice flavonoids, cantalis tincture, raspberry extract, kiwi extract, quina extract, cucumber extract, quincein extract, quince seed extract, gardenia extract , Kumazasa Extract, Clara Extract, Walnut Shell Extract, Clematis Extract, Brown Sugar Extract, Chlorella Extract, Mulberry Extract, Keihi Extract, Gentianana Extract, Genno Shoko Extract, Black Tea Extract, Kouhone Extract, Burdock Extract, Oil-soluble Burdock Extract, Wheat Germ Extract, Hydrolyzed wheat powder, rice bran extract, rice bran fermented extract, comfrey extract, saicin extract, saffron extract, savanna extract, oil-soluble salvia extract, Nzashiekisu, pepper extract, shiitake extract, shiitake extract powder, Rehmannia glutinosa, Shikonekisu, oil-soluble Shikonekisu, mint extract, linden extract, oil-soluble linden extract, Shimotsukesou extract,

Peonies extract, Juzudama extract, Pepper extract, oil-soluble Pepper extract, Pepper tincture, ginger root extract, birch extract, oil-soluble birch extract, birch sap, honeysuckle extract, Japanese horsetail extract, oil-soluble Japanese horse chestnut extract, scordinin, stevia extract , Kizuta extract, Hawthorn extract, Elderflower extract, Prunus extract, Yarrow extract, Oil-soluble Yarrow extract, Pepper extract, Sage extract, Oil-soluble sage extract, Sage water, Zeni mushroom extract, Celery extract, Senkyu extract, Senkyu Water, Assembly Extract, Soybean Extract, Taiso Extract, Thyme Extract, Tea Extract, Tea Distillate, Tea Seed Extract, Clove Extract, Chinpi Extract, Tsu Japanese quince extract, Japanese camellia extract, oil-soluble euglena extract, Duke extract, Terminaria extract, Japanese cypress extract, Japanese oil-soluble Japanese cypress extract, Japanese cypress extract, Japanese peanut extract, Japanese peanut extract Extract, Tormentilla extract, Natto extract, Carrot extract, Oil-soluble carrot extract, Garlic extract, Novara extract, Oil-soluble Novara extract, Bakuga extract, Bakuga root extract, Bakumondo extract, Parsley extract, Nectar leaf juice concentrate, Distilled mint water , Hamelis water, Hamelis extract, rose extract, parietalia extract, toad extract, loquat leaf extract, oil-soluble loquat leaf extract, dandelion extract, bukkuri pop extract, butcher bloom extract, butcher bull Muekisu the end,

Grape extract, grape leaf extract, grape water, hay flower extract, loofah extract, loofah water, safflower extract, oil-soluble bodai extract, bodaiju water, button extract, hop extract, oil-soluble hop extract, pine extract, maria thistle extract, maronier extract , Oil-soluble Maronnier extract, Mukuroji extract, Melissa extract, Melilot extract, Peach leaf extract, Oil-soluble Peach leaf extract, Prunus extract, Cornflower extract, Cornflower water, Eucalyptus extract, Yukinosita extract, Lily extract, Yokuinin extract, Oil-soluble Yokuinin extract, Artemisia extract, Artemisia water, Lavender extract, Lavender water, Apple extract, Ganoderma extract, Lettuce extract, Lotus root extract, Rose water, Rosemary extract, Oil-soluble rosemary extract, Roman chamomile Vinegar, burnet extract, and the like.

  Amino acids and peptides: glycine, valine, leucine, isoleucine, serine, threonine, phenylalanine, tyrosine, tryptophan, cystine, cysteine, methionine, hydroxyproline, aspartic acid, asparagine, glutamic acid, glutamine, histidine, γ-aminobutyric acid DL-pyrrolidonecarboxylic acid, ε-aminocaproic acid, hydrolyzed elastin, water-soluble elastin, hydrolyzed collagen, water-soluble collagen, casein, glutathione, wheat peptide, soybean peptide and the like.

  Vitamins and vitamin-like agents: for example, vitamin A such as retinol, retinal, retinoic acid, retinol acetate, retinol palmitate, α-carotene, β-carotene, γ-carotene, δ-carotene, lycopene, zeaxanthin, Carotenoids such as cryptoxanthine, echinenone, astaxanthin, vitamin B1 such as thiamine, vitamin B2 such as riboflavin, vitamin B6 such as pyridoxine, pyridoxal, pyridoxamine, vitamin B12 such as cyanocobalamin, folic acid, nicotinic acid, Nicotinamide, pantothenic acids, biotins, L-ascorbic acid, sodium L-ascorbate, L-ascorbyl stearate, L-ascorbyl palmitate, L-ascorbyl dipalmitate, tet Vitamin C such as L-ascorbyl isopalmitate, disodium L-ascorbate sulfate, magnesium L-ascorbate, sodium L-ascorbyl phosphate, ascorbyl 2-phosphate, L-ascorbic acid-2-glucoside , Vitamin D such as ergocalciferol, cholecalciferol, d-α-tocopherol, DL-α-tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol succinate, β-tocopherol, γ-tocopherol, Vitamin E such as d-δ-tocopherol, ubiquinones, vitamin K, carnitine, ferulic acid, γ-oryzanol, α-lipoic acid, orotic acid and the like.

  Preservatives: for example, benzoic acid, sodium benzoate, undecylenic acid, salicylic acid, sorbic acid, potassium sorbate, dehydroacetic acid, sodium dehydroacetate, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, ethyl paraoxybenzoate, butyl paraoxybenzoate Propyl paraoxybenzoate, benzyl paraoxybenzoate, methyl paraoxybenzoate, methyl sodium paraoxybenzoate, phenoxyethanol, Photosensitive Element 101, Photosensitive Element 201, Photosensitive Element 401, and the like.

  Antioxidants: For example, butylhydroxyanisole, butylhydroxytoluene, propyl gallate, erythorbic acid, sodium erythorbate, parahydroxyanisole, octyl gallate and the like.

  Blocking agent: for example, ethylenediaminehydroxyethyl triacetate trisodium, edetic acid, edetate disodium, edetate trisodium, edetate tetrasodium, sodium citrate, gluconic acid, phytic acid, sodium polyphosphate, sodium metaphosphate, etc. Metal ionic compounds.

  Moisturizer: for example, hyaluronic acid, sodium hyaluronate, sodium chondroitin sulfate, sodium lactate, sodium pyrrolidonecarboxylate, betaine, lactic acid bacteria culture solution, yeast extract, ceramide and the like.

  Anti-inflammatory agents: for example, glycyrrhizic acid, trisodium glycyrrhizinate, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, β-glycyrrhetinic acid, glyceryl retinoic acid, stearyl glycyrrhetinate, lysozyme chloride, hydrocortisone, allantoin and the like.

pH adjuster: For example, sodium hydroxide, potassium hydroxide, triethanolamine and the like.
Salts: For example, sodium chloride, potassium chloride, magnesium chloride, sodium sulfate and the like.

α-hydroxy acids: for example, citric acid, glycolic acid, tartaric acid, lactic acid and the like.
Whitening agents: for example, arbutin, α-arbutin, placenta extract and the like.
Essential oils: for example, angelica oil, ylang ylang oil, elemi oil, chamomile oil, roman chamomile oil, cardamom oil, calamus oil, galvanum oil, camphor oil, carrot seed oil, clary sage oil, clove oil, caihi oil, coriander oil, Cypress oil, sandalwood oil, cedarwood oil, citronella oil, cinnamon leaf oil, jasmine absolute, juniper berry oil, ginger extract, spearmint oil, sage oil, cedar oil, geranium oil, thyme oil, tea tree oil, nutmeg oil, Near-uri oil, neroli oil, pine oil, basil oil, peppermint oil, patchouli oil, palmarosa oil, fennel oil, petitgren oil, black pepper oil, frankincense oil, vetiver oil, peppermint oil, bergamot oil, benzoin oil, bo Dorozu oil, marjoram oil, myrrh oil, melissa oil, eucalyptus oil, Rabensara oil, lavandin oil, lavender oil, lindane oil, rose oil, rosewood oil, rosemary oil, lovage oil, and the like.

Terpenes: For example, pinene, terpinene, terpinolene, myrcene, longiferene and the like.
Ingredients such as fragrance, water, etc.

  The slimming skin external preparation of the present invention and the cosmetic containing the same may be in any dosage form and form as long as they are used in contact with the skin at the time of use, and in the vicinity of a site where metabolism of subcutaneous fat is desired. Those used in contact with the skin are more preferred. Specifically, for example, skin milk, skin cream, foundation cream, massage cream, cleansing cream, shaving cream, cleansing foam, lotion, lotion, pack, lipstick, blusher, eye shadow, nail polish, soap, body shampoo, hand Soap, shampoo, rinse, hair tonic, treatment, hair cream, hair spray, hair restorer, hair nourishing agent, hair dye, hair conditioner, hair removal agent, anti-dandruff agent, toothpaste, denture adhesive, gargle, permanent wave agent, curling Broadly includes agents, styling agents, ointments, poultices, tapes, bath agents, antiperspirants, sunscreen agents, etc. A form that can be used as a charge is preferred. Regardless of the gender and age of the user. Furthermore, in addition to humans, those that come into contact with animal skin are also included.

  Further, the slimming skin external preparation of the present invention and the cosmetic containing the same may be in any shape, in addition to solid, liquid, semi-solid, gas, powder, granule, tablet, gel, Although many forms, such as a foam form, are mentioned, it is not limited to this in particular.

In addition, the cosmetics of this invention can use what can generally be used as cosmetics among the other components mentioned above, In addition to these, the existing cosmetic raw material can also be used further. For example, Cosmetic Material Standards 2nd Edition Commentary, Japan Standards Association, 1984 (Pharmaceutical Daily Report), Cosmetic Raw Material Standards Independent Component Standards, Ministry of Health and Welfare Pharmaceutical Affairs Bureau Examination Division Supervision, 1993 (Pharmaceutical Daily Report), Cosmetic Raw Material Nonstandard Components Standards supplement, supervised by the Ministry of Health and Welfare Pharmacy Examination Division, 1993 (Pharmaceutical Daily), permission standards by cosmetics type, supervision by the Ministry of Health and Welfare Pharmacy Examination Division, 1993 (Pharmaceutical Daily Report), formulation standard by cosmetic variety, Ministry of Health and Welfare Pharmacy Examination Division All cosmetic raw materials described in Supervision, 1997 (Pharmaceutical Daily), Cosmetic Raw Material Dictionary, Heisei 3 (Nikko Chemicals), and new cosmetic functional materials 300, 2002 (CMC Publishing) can be used.

  The slimming skin external preparation and cosmetics of the present invention can be produced by using the above-described components so as to have a predetermined content, and dissolving, mixing, or dispersing according to a conventional method according to the mode. it can.

Example
EXAMPLES Hereinafter, although this invention is demonstrated further more concretely based on an Example, this invention is not limited to these Examples.
Synthesis example 1
<Synthesis of hexadecanoyl-L-carnitine hydrochloride>
L-carnitine (1 mol) and trifluoroacetic acid (350 mL) were placed in a 500 mL four-necked flask equipped with a dropping funnel, thermometer and condenser, and dissolved with stirring while heating to 60 ° C. Hexadecanoyl chloride (1.1 mol) was added dropwise from the dropping funnel to the homogenized reaction solution over 30 minutes. After dropping, the reaction solution was stirred at 60 ° C. for 2 hours. Trifluoroacetic acid was distilled off using an evaporator. The obtained residue was dissolved in n-hexane (500 mL), water (500 mL) was added, and the mixture was stirred for 30 min. Further, ethanol (500 mL) -methyl-tert-butyl ether (500 mL) was added to this mixed solution for extraction. N-Butanol (500 mL) was added to the separated aqueous layer, and water (100 mL) was further added for extraction. The solvent was distilled off from the n-butanol layer obtained by liquid separation to obtain 201 g of a residue. The resulting residue was purified by recrystallization method with isopropanol to obtain 99% pure hexadecanoyl-L-carnitine hydrochloride (0.3 mol).
Synthesis example 2
<Synthesis of hexanoyl-L-carnitine hydrochloride, tetradecanoyl-L-carnitine hydrochloride, octadecanoyl-L-carnitine hydrochloride>
99% purity hexanoyl-L-carnitine hydrochloride in the same manner as in Synthesis Example 1 except that the same molar amount of hexanoyl chloride, tetradecanoyl chloride, and octadecanoyl chloride was used instead of hexadecanoyl chloride. Salt, tetradecanoyl-L-carnitine hydrochloride and octadecanoyl-L-carnitine hydrochloride were obtained.
Synthesis example 3
<Synthesis of hydroxycitric acid-2-palmitate>
(1) Synthesis of hydroxy citrate tribenzyl ester In a 200 mL eggplant flask, 2.96 g (10.1 mmol) of hydroxycitrate calcium salt, 5.86 g (30.8 mmol) of toluenesulfonic acid monohydrate, 10 g of benzyl alcohol (92 0.5 mmol) and 20 mL of toluene, and the mixture was stirred under reflux for 4 hours while removing azeotropic water. After allowing to cool, 50 mL of ethyl acetate was added and stirred well. This was added little by little to a 500 mL beaker containing 100 mL of 5% by mass aqueous sodium hydrogen carbonate solution. After removing insolubles and separating the aqueous layer, the organic layer was washed with water and further dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent and benzyl alcohol under reduced pressure was subjected to silica gel column chromatography and eluted with hexane: ethyl acetate (5: 1) to obtain 1.96 g (yield 40%) of the desired product as a white solid. It was.
(2) Synthesis of hydroxycitrate tribenzyl ester-2-palmitate In a 50 mL eggplant flask, 239 mg (0.50 mmol) of hydroxycitrate tribenzyl ester synthesized in (1) above, 5 mL of tetrahydrofuran (THF), 165 mg of palmitic acid chloride (0.60 mmol) was added, and a solution of 61 mg (0.60 mmol) of triethylamine dissolved in 2 mL of THF was added under ice cooling, followed by stirring at the same temperature for 30 minutes and at room temperature for 2 hours. Ethyl acetate (100 mL) and water (50 mL) were added to the reaction solution, and the organic layer was washed according to a conventional method, and then dried over anhydrous sodium sulfate. The residue obtained by evaporating the solvent under reduced pressure was subjected to silica gel column chromatography, and eluted with hexane: ethyl acetate (10: 1) to obtain 330 mg (yield 92%) of the desired product as a white solid.
(3) Synthesis of hydroxycitric acid-2-palmitate Into a 50 mL eggplant flask was charged 300 mg (0.42 mmol) of hydroxybenzyl tribenzyl ester-2-palmitate synthesized in (2) above, 5 mL of ethanol, dimethylformamide (DMF) 5 mL was added. 40 mg of 10% by mass palladium activated carbon was added as a catalyst, and catalytic reduction was performed for 2 hours. The catalyst was removed by filtration, the solvent was distilled off under reduced pressure, hexane was added to the resulting residue, and the precipitated solid was collected by filtration to obtain 175 mg (yield 84%) of the desired product as a white solid.

The structure of this target product was confirmed by the following ¹ H-NMR spectrum.
¹ H-NMR (270 MHz, DMSO-D6, ppm): 5.0 (s, 1H, CH), 3.2-3.8 (br, 4H, OH, COOH), 2.7-3.0 (dd, 2H, -CH ₂ COOH) , 2.0-2.2 (m, 2H, -CH 2 COOC -), 1.0-1.5 (m, 26H, - (CH 2) 13 -), 0.8-0.9 (t, 3H, CH 3 -).
Synthesis example 4
<Synthesis of dl-α-tocopherol N, N-dimethylglycine ester hydrochloride>
A solution prepared by dissolving 59.1 g of dicyclohexylcarbodiimide and 40.0 g of N, N-dimethylglycine hydrochloride in 320 g of pyridine and 60.0 g of dl-α-tocopherol in 240 g of pyridine was added. The reaction was stirred at room temperature for 8 hours, and pyridine was distilled off. 2000 ml of water and 1000 ml of ethyl acetate were added to the residue, and about 40 g of sodium carbonate was further added to adjust the pH to 7-8. The ethyl acetate layer was separated and the aqueous layer was extracted 3 times with 200 ml of ethyl acetate. Ethyl acetate was distilled off, ethyl acetate was further added, and the solid was filtered off after drying over anhydrous sodium sulfate. The concentration was adjusted so that dl-α-tocopherol dimethylglycine ester was 7-8%, and 20% dioxane solution was added in 1.5 times mole of dl-α-tocopherol dimethylglycine ester in terms of hydrochloric acid to neutralize. did. The obtained solid was collected by filtration and recrystallized with a methanol / acetone solvent to obtain 49.2 g of dl-α-tocopherol N, N-dimethylglycine ester hydrochloride.

(Comparison of transdermal absorption)
As a test substance,
1) L-carnitine (used as a comparative substance)
2) Hexanoyl-L-carnitine hydrochloride (Synthesis Example 2)
3) Tetradecanoyl-L-carnitine hydrochloride (Synthesis Example 2)
4) Hexadecanoyl-L-carnitine hydrochloride obtained in Synthesis Example 1 5) Octadecanoyl-L-carnitine hydrochloride (Synthesis Example 2)
5 types of carnitine and carnitine derivatives were used.

Each of the above test substances was dissolved in Dulbecco's PBS (−) to obtain 1% by mass of each test substance solution. Each test substance solution thus obtained was added to a human skin tissue three-dimensional model (TESTSKIN ^™ L).
SD-d, Toyobo Co., Ltd.) was placed on the surface of the tissue and cultured at 37 ° C. in the presence of 5% CO ₂ for 2 hours. Thereafter, each test substance solution was removed by suction, and further cultured at 37 ° C. in the presence of 5% CO _{2 for 2} , 6, 12 hours, and the skin model was sampled at each culture time. The skin model sampled at each incubation time was washed with Dulbecco's PBS (-), the tissue surface on which each test substance was placed was punched out with a 6 mm punch, homogenized in HEPES buffer (pH 7.2), and high-speed liquid Chromatography was used to quantitatively analyze carnitine in each skin model. (Measurement conditions are column: Shodex DE-413 (made by Showa Denko KK), temperature: 25 ° C., eluent: acetonitrile / 0.1 MH ₃ PO ₄ =
67/33, flow rate: 1.0 ml / min, detection: differential refractive index detector. In addition, the protein content in each skin model was quantitatively analyzed by the Lowry method.

  From these analysis values, the amount of carnitine (unit: nmol / mg skin protein) in the skin model at each test substance and each culture time was determined. The results are shown in Table 1.

  From this result, it was found that the administration of an acylated carnitine derivative can efficiently enrich the tissue concentration of carnitine for a long time immediately after administration, rather than administering L-carnitine. .

(Measurement of fat metabolic activity on mouse 3T3 adipocytes)
As test substances, the same five types of carnitine and carnitine derivatives 1) to 5) as used in Example 1 were used. When fat accumulated in fat cells is metabolized, glycerol and free fatty acids are released into the medium, and fat metabolism activity was measured and compared by quantifying glycerol in the medium.

Mouse 3T3 cells, which are preadipocytes, are each 1 × 10 ^{4 in} φ10 cm dishes.
Individually seeded and cultured in a DMEM medium (Invitrogen Corp.) containing 10% FCS in an atmosphere of 37 ° C. and 5% CO _{2 for} 1 week, and then the medium was 0.25 M dexamethasone, 0.5
The medium was replaced with a DMEM medium containing 10% FCS containing mM isobutylmethylxanthine and 10 μg / ml insulin, and further cultured for 2 days. After that, when the medium was returned to the normal DMEM medium containing 10% FCS and further cultured for one week, the preadipocytes differentiated into adipocytes. Here, the same medium as used in Example 1 was replaced with a normal medium containing 5 types of carnitine and carnitine derivatives of 1) to 5), and the medium was collected after 24 hours. The cells were recovered by washing with Dulbecco's PBS (-). As a control, one cultured under the condition where no test substance was added was used. Glycerol in the medium was quantified using Glycerol Test E Wako (Wako Pure Chemical Industries, Ltd.).

  Table 2 shows the amount of glycerol released in each test substance as a relative comparison value when the control is 100%.

  From this result, when the test substance was administered, the amount of glycerol released was higher than that of the subject, and in particular, when the acylated carnitine derivative was administered, the amount of glycerol released was larger, and fat metabolism was increased. It became clear that was promoted.

(Subcutaneous lipolysis test)
As test substances, the same five types of carnitine and carnitine derivatives 1) to 5) as used in Example 1 were used.

  After shaving the Wistar rats, male, 10-week-old abdomen, the skin was removed together with subcutaneous adipose tissue and mounted on a Franz diffusion cell. Fill the upper cell on the epidermis side with the test substance of Example 1 and fill the lower cell with Dulbecco's PBS (-) and keep it at 37 ° C. Then, the amount of glycerol released by the decomposition of fat was measured by glycerol test E Wako. The results are shown in Table 3. The measurement was performed three times, and the average value was shown.

  From this result, it was found that the amount of released glycerol was high when the test substance was administered, and the degradation promoting effect was sustained particularly when the acylated carnitine derivative was administered.

(Comparison of transdermal absorption)
As a test substance,
1) L-carnitine (used as a comparative substance)
6) L-carnitine The amount of carnitine in the skin model (unit: nmol / mg skin protein) was determined in the same manner as in Example 1 except that two types of L-carnitine hexadecyl ester hydrochloride were used. The results are shown in Table 4.

  From this result, it was found that the administration of the esterified carnitine derivative can efficiently enrich the tissue concentration of carnitine for a long time after the administration rather than the administration of L-carnitine.

(Measurement of fat metabolic activity on mouse 3T3 adipocytes)
When each test substance was used in the same manner as in Example 2, except that the same two types of carnitine and carnitine derivatives of 1) and 6) were used as test substances. The fat metabolic activity on mouse 3T3 adipocytes was measured by the amount of glycerol released. Table 5 shows the amount of glycerol released in each test substance as a relative comparison value when the control is 100%.

  From this result, it is clear that when the test substance is administered compared to the control, especially when the esterified carnitine derivative is administered, the amount of glycerol released is increased and the metabolism of fat is promoted. became.

(Subcutaneous lipolysis test)
As the test substance, it was released in each test substance in the same manner as in Example 3, except that the same two types of carnitine and carnitine derivatives of 1) and 6) as used in Example 4 were used. The amount of glycerol was measured. The results are shown in Table 6. The measurement was performed three times, and the average value was shown.

  From this result, it was found that the amount of released glycerol was high when the test substance was administered, and the degradation promoting effect was sustained particularly when the esterified carnitine derivative was administered.

(Comparison of transdermal absorption)
As a test substance,
1) L-carnitine (used as a comparative substance)
7) Hexadecanoyl-L-carnitine methyl ester hydrochloride 8) Hexadecanoyl-L-carnitine Hexadecyl ester hydrochloride was used in the same manner as in Example 1 except that three types of hexadecyl ester hydrochloride were used. The amount of carnitine (unit: nmol / mg skin protein) was determined. The results are shown in Table 7.

  From this result, it can be said that administration of an acylated and esterified carnitine derivative can efficiently enrich the tissue concentration for a long time immediately after administration, rather than administering L-carnitine. all right.

(Measurement of fat metabolic activity on mouse 3T3 adipocytes)
Each test substance was treated in the same manner as in Example 2 except that the same three types of carnitine and carnitine derivatives 1), 7) and 8) used in Example 7 were used as test substances. When used, fat metabolic activity on mouse 3T3 adipocytes was measured by the amount of glycerol released. Table 8 shows the amount of glycerol released in each test substance as a relative comparison value when the control is 100%.

  From this result, when the test substance was administered compared to the control, especially when the acylated and esterified carnitine derivative was administered, the amount of glycerol released was increased, and fat metabolism was promoted. It became clear.

(Subcutaneous lipolysis test)
Each test substance was the same as in Example 3 except that the same three types of carnitine and carnitine derivatives 1), 7) and 8) used in Example 7 were used as test substances. The amount of glycerol released was measured. The results are shown in Table 9. The measurement was performed three times, and the average value was shown.

  From this result, it was found that the amount of released glycerol was high when the test substance was administered, and the degradation promoting effect was sustained particularly when the acylated and esterified carnitine derivatives were administered. .

(Combination effect of acylcarnitine and other slimming ingredients)
Mouse 3T3-F442A cells (Dainippon Pharmaceutical Co., Ltd.) were seeded in a 96-well microplate and cultured in DMEM medium (manufactured by Invitrogen Corporation) containing 10% by mass FCS in an atmosphere of 37 ° C. and 5% CO _{2 for} 2 weeks. .

After microscopically confirming that most cells differentiated into fat cells, acylcarnitine (hexadecanoyl-L-carnitine hydrochloride, octadecanoyl-L-carnitine hydrochloride) as a base, and test The medium is replaced with a medium containing 50 μM of each additive listed in Table 10 below (However, Garcinia extract contains 70% by mass of hydroxycitric acid and is added in terms of hydroxycitric acid concentration, and only Ginkgo biloba extract is 30 μg / mL). The culture was further continued for 4 days. As a control, one cultured under conditions (without base) containing no test substance was used.

  After culturing for 4 days, the cells were washed 3 times with Dulbecco's PBS (-), and the amount of triglyceride accumulated in the cells was quantified by an oil red staining method. The amount of triglyceride accumulated in each test substance is shown in Table 10 as relative values when the control is 100.

From Table 10, when acylcarnitine is added alone or further carnitine is added in combination with a specific slimming component, that is, a hydroxycitrate derivative, an α2 adrenergic inhibitor, a β adrenergic stimulant, and a phosphodiesterase inhibitor. In comparison, it can be seen that a particularly high fat reducing action is obtained.

  A slimming skin external preparation was prepared according to each composition shown in Table 11 (Note that the source of the same compound as in Example 10 is the same as in Example 10). All of the obtained preparations were stable under storage at 25 ° C. for 1 month, and were suitable for external use.

(Skin care ingredients and effects on acylcarnitine slimming)
After culturing mouse 3T3-F442A cells as in Example 10 and confirming differentiation into adipocytes, acylcarnitine (hexadecanoyl-L-carnitine hydrochloride, octadecanoyl-L-carnitine hydrochloride) was used as a base. And a medium containing 50 μM of each additive listed in Table 12 below as a test substance, and further cultured for 4 days. As a control, those cultured under the condition that the test substance was not added (including the base) were used.

  After culturing for 4 days, the cells were washed 3 times with Dulbecco's PBS (-), and the amount of triglyceride accumulated in the cells was quantified by an oil red staining method. The amount of triglyceride accumulated in each test substance is shown in Table 12 as relative comparison values when the control is 100%.

  According to Table 12, it can be seen that the amount of accumulated fat is slightly higher in the combination of acylcarnitine and glycerol. This means that the slimming action of acylcarnitine can be reduced when blended simultaneously as a preparation. In contrast, the combination of acylcarnitine and specific skin care ingredients, namely fatty acids, ascorbic acids, and tocopherol derivatives has little effect on fat accumulation and does not impair the slimming action of acylcarnitine as a skin care ingredient. It can be seen that this is a unique component that can be blended simultaneously.

  A slimming skin external preparation was prepared according to each composition of Table 13 below. All of the obtained preparations were stable without separation, precipitation, significant turbidity and the like under storage at 25 ° C. for 3 months, and were suitable for external use.

Claims (62)

A slimming skin external preparation comprising a carnitine derivative represented by the following general formula (1);

(In the formula (1), R ¹ represents a hydrogen atom or an acyl group having 2 to 30 carbon atoms which may have a branched or unsaturated bond,
R ² is a hydrogen atom or a carbon number of 1 to 22 which may have a branched or unsaturated bond
(Wherein R ¹ and R ² are not hydrogen atoms at the same time),
Me represents a methyl group,
X ⁻ represents an inorganic anion or an organic anion that is electrically neutral with the cation moiety of the carnitine derivative. ). The slimming skin external preparation according to claim 1, wherein R ¹ in the formula (1) is an acyl group having 4 to 22 carbon atoms which may have a branched or unsaturated bond. In the formula (1), R ¹ may have a branched or unsaturated bond and has 14 to 22 carbon atoms.
The skin external preparation for slimming according to claim 1, which is an acyl group of In the formula (1), R ² is a hydrogen atom or a hydrocarbon group having 1 to 18 carbon atoms which may have a branched or unsaturated bond. The slimming skin external preparation according to any one of the above. In the formula (1), R ¹ is a hydrogen atom,
The slimming skin external preparation according to claim 1, wherein R ² is a hydrocarbon group having 1 to 18 carbon atoms which may have a branched or unsaturated bond. In the formula (1), R ² is, according to any one of the preceding claims, characterized in that a hydrocarbon group branched or unsaturated bonds may 4-10 carbon atoms which may have a An external preparation for slimming skin. In the formula (1), R ¹ is an acyl group having 4 to 22 carbon atoms which may have a branched or unsaturated bond,
The slimming skin external preparation according to claim 1, wherein R ² is a hydrogen atom.   The skin external preparation for slimming according to any one of claims 1 to 7, wherein the carnitine derivative is contained in an amount of 0.01% by mass to 20% by mass.   The skin external preparation for slimming according to any one of claims 1 to 8, further comprising at least one selected from the group consisting of hydroxycitric acid, derivatives thereof, and pharmacologically acceptable salts thereof. Agent.   The slimming skin external preparation according to claim 9, wherein the hydroxycitric acid is obtained from a Garcinia Cambodian extract. The skin external preparation for slimming according to claim 9 or 10, wherein the hydroxycitric acid derivative is a hydroxycitric acid derivative represented by the following formula (2):

(In the formula (2), R ¹¹ and R ¹² each independently represent a hydrogen atom or any group that can be removed by a bioenzymatic reaction selected from the group represented by the following formula (3). R ¹¹ and R ¹² do not simultaneously become hydrogen atoms.), X ^{1 to} X ³ each independently represent a nitrogen or oxygen atom, and R ³ , R ⁴ , R ⁵ , R ^{3 ′} , R ^{4 ′.} , R ^{5 ′} each independently represents a hydrogen atom or a chain hydrocarbon group having 1 to 30 carbon atoms which may have a branched or unsaturated bond (provided that X ¹
, X ² and X ³ are each an oxygen atom, the corresponding R ^{3 ′} , R ^{4 ′} and R ^{5 ′} do not exist. )

(In Formula (3), R < ⁶ > -R < ⁸ > is a hydrogen atom, an aryl group, or a C1-C30 linear hydrocarbon group which may have a branch, an unsaturated bond, or a substituent each independently. Represents.) In the above formula (3), R ⁶ is, branched, may have an unsaturated bond or a substituent, a chain hydrocarbon group having 7 to 23 carbon atoms, R ⁷ and R ⁸ are each independently The skin external application for slimming according to claim 11, which is a hydrogen atom, or a chain hydrocarbon group having 8 to 24 carbon atoms, which may have a branched, unsaturated bond or substituent. Agent. In the formula (2), R ³ ~R ⁵ are each independently a hydrogen atom, or a branched or may have an unsaturated bond, a chain hydrocarbon group having 1 to 30 carbon atoms, X ¹ ~X ³ are all oxygen atom, and,
In the above formula (3), R ⁶ is, branched, may have an unsaturated bond or a substituent, a chain hydrocarbon group having 7 to 23 carbon atoms, R ⁷ and R ⁸ are each independently The skin external application for slimming according to claim 11, which is a hydrogen atom, or a chain hydrocarbon group having 8 to 24 carbon atoms, which may have a branched, unsaturated bond or substituent. Agent. In the formula (2), R ¹² is a hydrogen atom, R ^{3 to} R ⁵ are all hydrogen atoms, X ^{1 to} X ³ are all oxygen atoms, and
12. The formula (3), wherein R ⁶ is a chain hydrocarbon group having 13 to 21 carbon atoms, which may have a branch, an unsaturated bond or a substituent. For slimming skin. In the formula (2), R ¹² is a hydrogen atom, and R ^{3 to} R ⁵ are each independently a hydrogen atom, or a chain carbon atom having 1 to 30 carbon atoms which may have a branched or unsaturated bond. A hydrogen group (provided that R ^{3 to} R ⁵ are not simultaneously hydrogen atoms), X ^{1 to} X ³ are all oxygen atoms, and
In the formula (3), R ⁶ is a chain hydrocarbon group having 13 to 21 carbon atoms which may have a branch, an unsaturated bond, or a substituent. For slimming skin.   16. At least one selected from the group consisting of the hydroxycitric acid, derivatives thereof, and pharmacologically acceptable salts thereof is contained in an amount of 0.01 to 20% by mass. The slimming skin external preparation according to any one of the above.   The slimming skin external preparation according to any one of claims 1 to 8, further comprising an α2 adrenergic inhibitor.   The α2 adrenergic inhibitor is yohimbine, phentolamine, phenoxybenzamine, tolazoline, ergotamine, ergotoxin, dihydroergotamine, ergomethrin, methylergomethrin, dihydroergotoxin, laurucine, piperoxane, derivatives thereof, and pharmacologically thereof. 18. The slimming skin external preparation according to claim 17, wherein the preparation is at least one selected from the group consisting of acceptable salts.   The slimming skin external preparation according to claim 17, wherein the α2 adrenergic inhibitor is obtained from a plant extract.   18. The slimming product according to claim 17, wherein the α2 adrenergic inhibitor is obtained from at least one selected from the group consisting of ginkgo biloba extract, ivy extract, and horse chestnut extract. Skin external preparation.   The slimming skin external preparation according to any one of claims 17 to 20, comprising the α2 adrenergic inhibitor in an amount of 0.0001 to 10 mass%.   The slimming skin external preparation according to any one of claims 1 to 8, further comprising a β-adrenergic stimulant.   The β-adrenergic stimulant is isoproterenol, epinephrine, norepinephrine, dobutamine, dopamine, butopamine, salbutamol, terbutaline, isoetarine, protokilol, fenoterol, metaproterenol, chlorprenalin, hexoprenaline, trimethoquinol hydrochloride, procaterol , Prenalterol, forskolin, disodium (R, R) -5- [2-[[2- (3-chlorophenyl) -2-hydroxyethyl] -amino] propyl] -1,3-benzodioxole- 2,2-dicarboxylate, (R, R) -4- [2-({2-[(3-chlorophenyl) -2-hydroxyethyl] amino} propyl) phenyl] phenoxyacetic acid, {2-hydroxy-5 -[2-({2-hydroxy-3- [4- 1-methyl-4-trifluoromethyl) -1H-imidazol-2-yl] phenoxy} propyl) amino] ethoxy} -benzamide monomethanesulfonate, erythro-DL-1- (7-methylindan-4-iroxy 23) For slimming according to claim 22, which is at least one member selected from the group consisting of -3-isopropylaminobutan-2-ol, derivatives thereof, and pharmacologically acceptable salts thereof. Skin external preparation.   The skin external preparation for slimming according to claim 22, wherein the β-adrenergic stimulant is obtained from a plant extract. The β-adrenergic stimulant comprises Coleus forskohlii extract (forskolin), Ipomoea hederacea extract, sweet potato (Ipomoea batata) extract, sage (Salvia officinalis) extract, tangin (Salvia The skin external preparation for slimming according to claim 22, wherein the preparation is obtained from at least one selected from the group consisting of miltiorrhiza) extract and mannenrou (Rosmarinus officinalis; rosemary) extract.   The skin external preparation for slimming according to any one of claims 22 to 25, comprising the β-adrenergic stimulant in an amount of 0.0001 to 10 mass%.   The slimming skin external preparation according to any one of claims 1 to 8, further comprising a phosphodiesterase inhibitor.   The phosphodiesterase inhibitor is selected from the group consisting of theophylline, theobromine, aminophylline, xanthine, isobutylmethylxanthine, apigenin, amentoflavone, vilobetine, siadopiticin, ginkgonetine, derivatives thereof, and pharmacologically acceptable salts thereof. The skin external preparation for slimming according to claim 27, wherein the preparation is at least one kind.   The slimming skin external preparation according to claim 27, wherein the phosphodiesterase inhibitor is obtained from a plant extract.   The phosphodiesterase inhibitor is selected from the group consisting of tea extract, coffee extract, guarana extract, yerba mate extract, cola extract, ginkgo biloba extract, sequoia mesgi extract, yew extract, and hydrangea extract. 28. The slimming skin external preparation according to claim 27, which is obtained from at least one selected.   The skin external preparation for slimming according to any one of claims 27 to 30, comprising the phosphodiesterase inhibitor in an amount of 0.0001 to 10 mass%. Furthermore, the saturated or unsaturated C12-C22 fatty acid and / or its pharmacologically acceptable salt which may have a branch are included. For slimming skin.   The fatty acid is at least one selected from the group consisting of lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, isostearic acid, 12-hydroxystearic acid, undecylenic acid, and hexyldecanoic acid. The slimming skin external preparation according to claim 32, characterized in that it is characterized in that:   The skin external preparation for slimming according to claim 32, wherein the fatty acid is a coconut oil fatty acid. The saturated or unsaturated fatty acid having 12 to 22 carbon atoms and / or pharmacologically acceptable salt thereof, which may have a branch, is contained in an amount of 0.001 to 20% by mass. Item 35. A slimming skin external preparation according to any one of Items 32 to 34.   The skin external preparation for slimming according to any one of claims 1 to 8, further comprising at least one selected from the group consisting of ascorbic acid, derivatives thereof, and pharmacologically acceptable salts thereof. .   The skin external preparation for slimming according to claim 36, wherein the ascorbic acid is L-ascorbic acid. 38. The pharmacologically acceptable salt of ascorbic acid is sodium L-ascorbate and / or magnesium L-ascorbate.
The slimming skin external preparation described in 1.   The ascorbic acid derivative is at least one selected from the group consisting of L-ascorbyl stearate, L-ascorbyl palmitate, L-ascorbyl dipalmitate, L-ascorbyl tetraisopalmitate, L-ascorbic acid-2-glucoside. The slimming skin external preparation according to any one of claims 36 to 38, wherein:   The skin external preparation for slimming according to any one of claims 36 to 38, wherein the pharmacologically acceptable salt of the ascorbic acid derivative is L-ascorbic acid sulfate disodium salt. The ascorbic acid derivative is an ascorbic acid-2-phosphate ester and / or a higher fatty acid ester of ascorbic acid-2-phosphate represented by the following formula (4): The slimming skin external preparation according to any one of the above;

(In formula (4), R represents a hydrogen atom or an acyl residue of a higher fatty acid).   42. The slimming skin external preparation according to claim 41, wherein, in the formula (4), R is an acyl residue of lauric acid, myristic acid, palmitic acid, stearic acid, or 2-hexyldecanoic acid. A pharmacologically acceptable salt of the ascorbic acid derivative is a sodium salt of an ascorbic acid-2-phosphate ester and / or a higher fatty acid ester of ascorbic acid-2-phosphate ester represented by the following formula (4): The skin external preparation for slimming according to any one of claims 36 to 38 and 41 to 42, which is a potassium salt, a magnesium salt or a zinc salt;

(In formula (4), R represents a hydrogen atom or an acyl residue of a higher fatty acid).   44. The slimming skin external preparation according to claim 43, wherein, in the formula (4), R is an acyl residue of lauric acid, myristic acid, palmitic acid, stearic acid, or 2-hexyldecanoic acid.   45. The composition according to any one of claims 36 to 44, comprising at least one selected from the group consisting of the ascorbic acid, a derivative thereof, and a pharmacologically acceptable salt thereof in an amount of 0.01 to 20% by mass. The skin external preparation for slimming according to crab.   The slimming skin external preparation according to any one of claims 1 to 8, further comprising at least one selected from the group consisting of tocopherol, a derivative thereof, and a pharmacologically acceptable salt thereof.   The skin external preparation for slimming according to claim 46, wherein the tocopherol is at least one selected from the group consisting of α-tocopherol, β-tocopherol, γ-tocopherol and δ-tocopherol.   The slimming body according to claim 46 or 47, wherein the tocopherol derivative is at least one selected from the group consisting of an α-tocopherol derivative, a β-tocopherol derivative, a γ-tocopherol derivative, and a δ-tocopherol derivative. Skin external preparation.   49. The slimming skin external preparation according to claim 48, wherein the tocopherol derivative is a tocopherol phosphate ester. The slimming skin external preparation according to claim 49, wherein the tocopherol phosphate is a compound represented by the following formula (5):

(In formula (5), R ²¹ , R ²² and R ²³ each independently represents a hydrogen atom or a methyl group).   49. The slimming skin external preparation according to claim 48, wherein the tocopherol derivative is a tocopherol aminoalkylcarboxylic acid ester. 52. The slimming skin external preparation according to claim 51, wherein the tocopherol aminoalkylcarboxylic acid ester is a compound represented by the following formula (6):

(In formula (6), R ³¹ and R ³² represent the same or different lower alkyl groups or hydrogen atoms, R ³³ and R ³⁴ each independently represent a hydrogen atom or a methyl group, and Z has a substituent. Represents a branched or linear alkylene group which may be present.   The aminoalkylcarboxylic acid of the tocopherol aminoalkylcarboxylic acid ester is glycine, alanine, β-alanine, valine, leucine, isoleucine, phenylalanine, methionine, cysteine, serine, threonine, tyrosine, thyroxine, histidine, proline, 4-hydroxyproline. 53. A slimming skin external preparation according to claim 51 or 52, which is a compound selected from among aspartic acid, glutamic acid, and their N-alkyl derivatives or N, N-dialkyl derivatives.   54. The composition according to any one of claims 46 to 53, comprising at least one selected from the group consisting of the tocopherol, a derivative thereof, and a pharmacologically acceptable salt thereof in an amount of 0.01 to 10% by mass. The slimming skin external preparation described in 1.   Cosmetics containing the skin external preparation for slimming in any one of Claims 1-8.   Cosmetics containing the skin external preparation for slimming in any one of Claims 9-16.   Cosmetics containing the skin external preparation for slimming in any one of Claims 17-21.   A cosmetic comprising the slimming skin external preparation according to any one of claims 22 to 26.   Cosmetics containing the skin external preparation for slimming in any one of Claims 27-31.   Cosmetics containing the skin external preparation for slimming in any one of Claims 32-35.   A cosmetic comprising the slimming skin external preparation according to any one of claims 36 to 45.   A cosmetic comprising the slimming skin external preparation according to any one of claims 46 to 54.