CN101277675B - Carnitine derivatives, salts thereof, external preparations for skin, and cosmetic materials - Google Patents

Abstract

The purpose of the invention is to provide novel carnitine derivatives and salts thereof that are resistant to hydrolysis in the presence of aqueous media, and also provide external skin preparations and cosmetics that are excellent in storage stability, product life, skin affinity and percutaneous absorption properties. In particular, to provide novel alpha-branched acyl carnitine derivatives and salts thereof, external skin preparations and cosmetics comprising specific alpha-branched acyl carnitine derivatives and/or salts thereof.

Description

Carnitine derivatives, salts thereof, external preparations for skin, and cosmetic materials

References to related applications

This application is an application filed pursuant to 35 U.S.C. §111(a), which requires provisional application No. 60 filed October 7, 2005 under 35 U.S.C. §111(b) under 35 U.S.C. §119(e) /724,276 and the filing date of No. 60/777,551 filed March 1, 2006.

field of invention

The present invention relates to skin external preparations and cosmetics. More particularly, the present invention relates to skin external preparations and cosmetics containing carnitine derivatives and/or salts thereof and promoting lipid metabolism. The present invention also relates to novel carnitine derivatives and salts thereof.

Background technique

Carnitine is known to play an important role in lipid metabolism in humans. In cells, carnitine is enzymatically bound to fatty acids from fat and transports the fatty acids into the mitochondria, the cell organelles where fat is burned. Therefore, carnitine has a function as a carrier of the fatty acid and is important for lipid metabolism. The fatty acids are β-oxidized in the mitochondria and converted into energy in the form of ATP in the living body.

The lipids are important not only as a source of energy but also as a body building block. All cell membranes are composed of said lipids. On a macroscopic scale, the lipids control the evaporation of moisture from the body in the form of sebum and intercellular fluid.

Excess lipids can lead to obesity due to the accumulation of subcutaneous fat and cause a number of cosmetic and QOL (quality of life) problems, including cellulite formation, shiny and oily skin from excess sebum, seborrheic dermatitis and the resulting Hair loss, acne, body odor, and skin aging due to decreased lipid metabolism.

As mentioned above, the lipid metabolism requires the transport of fatty acids into the mitochondria, which is the responsibility of carnitine. Therefore, the rate of lipid metabolism depends on the amount of carnitine in the cells. Increasing the concentration of carnitine in the target tissue promotes lipid metabolism and prevents and eliminates excess lipids and problems associated with them.

For this reason, various percutaneous absorption of carnitine-containing external preparations for skin to promote lipid metabolism have been studied and proposed (Patent Documents 1-4). However, these skin external preparations containing L-carnitine and its salts have not yet achieved satisfactory effects. The reason may be that L-carnitine and its salts are very easily hydrated, so their direct use would result in poor skin compatibility and percutaneous absorption properties, and sufficient carnitine can hardly reach the tissues where said lipid metabolism will be carried out .

Slimming skin external preparations have been proposed, which contain straight-chain acylcarnitine (in which carnitine is modified with straight-chain fatty acid residues) capable of higher dermatological effects than carnitine itself. For example, an external preparation for slimming skin contains palmitoyl-L-carnitine (L-carnitine palmitate), carnitine, caffeine, and coenzyme A (Patent Document 5).

[Patent Document 1] Japanese Patent No. 3434995

[Patent Document 2] JP-A-H07-309711

[Patent Document 3] JP-A-2000-16916

[Patent Document 4] JP-A-2001-64147

[Patent Document 5] French Patent No. 2694195

Contents of the invention

[Problems to be Solved by the Invention]

Linear acylcarnitines penetrate into the skin and produce an excellent lipid metabolism-stimulating effect. However, the straight-chain acyl group is easily hydrolyzed and easily decomposed in water-based preparations which are common forms of external preparations for skin, especially cosmetics. Therefore, the article has poor storage stability and a short lifespan.

The present invention is directed to solving the above-mentioned problems. It is therefore an object of the present invention to provide an external preparation for skin and a cosmetic which are excellent in storage stability, product life, skin affinity, and percutaneous absorption performance.

Another object of the present invention is to provide novel carnitine derivatives and salts thereof which are resistant to hydrolysis in the presence of aqueous media.

[means to solve the problem]

The present inventors diligently conducted research and found that α-branched acylcarnitine derivatives, particularly L-carnitine 2-hexyldecanoate, L-carnitine 2-methylpalmitate and L-carnitine 2- Butyl octanoate has excellent stability in the presence of aqueous media. The present invention has been accomplished based on this finding. The present invention relates to the following [1] to [26].

An external preparation for skin comprising a carnitine derivative represented by formula (1) and/or a salt of a carnitine derivative represented by formula (2):

wherein each ^of R and ^R is a saturated or unsaturated aliphatic hydrocarbon group of 1-18 carbon atoms which may have a branch;

Wherein R ¹ and R ² are as defined in formula (1), X ⁻ is an inorganic or organic anion that maintains electrical neutrality with the cationic portion of the carnitine derivative, and Y ⁺ is an ion that is electrically neutral with the carnitine derivative The anionic portion of the inorganic or organic cation remains electrically neutral.

The external preparation for skin as described in [1], wherein R ¹ and R ² in formulas (1) and (2) are each a saturated or unsaturated aliphatic hydrocarbon group of 3 to 16 carbon atoms which may have a branch.

The external preparation for skin as described in [1], wherein one of R ¹ and R ² in formulas (1) and (2) is a linear alkyl group of 6 carbon atoms, and the other is a linear alkyl group of 8 carbon atoms type alkyl.

The skin external preparation as described in [1], wherein one of R ¹ and R ² in the formulas (1) and (2) is a linear alkyl group of 4 carbon atoms, and the other is a linear alkyl group of 6 carbon atoms type alkyl.

The external preparation for skin as described in [1], wherein one of R ¹ and R ² in formulas (1) and (2) is a methyl group, and the other is a linear alkyl group of 14 carbon atoms.

The external preparation for skin as described in any one of [1]-[5], wherein ^X- in formula (2) is an anion selected from the group consisting of hydroxide ion, nitrate ion, sulfate ion, carbonate ion ions, bicarbonate ions, chloride ions, formate ions, acetate ions, citrate ions, tartrate ions, oxalate ions, fumarate ions, saturated or Unsaturated fatty acid anions, carnitine anions, carnitine derivative anions, ascorbate anions, ascorbylphosphate anions and ascorbylphosphate anions.

The skin external preparation according to any one of [1]-[6], wherein Y ⁺ in formula (2) is a cation selected from the group consisting of hydrogen ion, sodium ion, potassium ion, calcium ion, magnesium ion, Zinc ion, ammonium ion, carnitine cation and carnitine derivative cation.

The external preparation for skin according to any one of [1] to [7], wherein the carnitine derivative represented by formula (1) and/or the salt of the carnitine derivative represented by formula (2) 0.01-20% by mass of the skin external preparation.

A cosmetic comprising 0.01-20% by mass of the carnitine derivative and/or the salt of the carnitine derivative according to any one of [1]-[7].

The cosmetic according to [9], which is a cosmetic for promoting lipid metabolism.

Carnitine derivatives represented by formula (3):

Wherein ^one of R ^and R is a saturated aliphatic hydrocarbon group of 1-16 carbon atoms which may have a branch, and the other is a saturated aliphatic hydrocarbon group of 8-16 carbon atoms which may have a branch.

Salts of carnitine derivatives represented by formula (4):

wherein ^one of R ^and R is a saturated aliphatic hydrocarbon group of 1-16 carbon atoms which may have a branch, and the other is a saturated aliphatic hydrocarbon group of 8-16 carbon atoms which may have a branch, and X ^- is An inorganic or organic anion that is electrically neutral to the cationic portion of the carnitine derivative, and Y ⁺ is an inorganic or organic cation that is electrically neutral to the anionic portion of the carnitine derivative.

Carnitine derivatives represented by formula (5):

Wherein ^one of R ^and R is a saturated aliphatic hydrocarbon group of 2-7 carbon atoms which may have a branch, and the other is a saturated aliphatic hydrocarbon group of 3-7 carbon atoms which may have a branch.

Salts of carnitine derivatives represented by formula (6):

wherein ^one of R ^and R is a saturated aliphatic hydrocarbon group of 2-7 carbon atoms which may have a branch, and the other is a saturated aliphatic hydrocarbon group of 3-7 carbon atoms which may have a branch, and X ^- is An inorganic or organic anion that is electrically neutral to the cationic portion of the carnitine derivative, and Y ⁺ is an inorganic or organic cation that is electrically neutral to the anionic portion of the carnitine derivative.

Carnitine derivatives represented by formula (7):

Salts of carnitine derivatives represented by formula (8):

Wherein X ⁻ is an inorganic or organic anion that maintains electrical neutrality with the cationic portion of the carnitine derivative, and Y ⁺ is an inorganic or organic cation that maintains electrical neutrality with the anionic portion of the carnitine derivative.

The salt of a carnitine derivative as described in [16], wherein ^X- in the formula (8) is an anion selected from the group consisting of hydroxide ion, nitrate ion, sulfate ion, carbonate ion, bicarbonate ions, chloride ions, formate ions, acetate ions, citrate ions, tartrate ions, oxalate ions, fumarate ions, saturated or unsaturated fatty acid anions of 3-20 carbon atoms which may have branched chains , carnitine anion, carnitine derivative anion, ascorbate anion, phosphate ascorbate anion and phosphate ascorbate derivative anion.

The salt of a carnitine derivative as described in [16] or [17], wherein Y ⁺ in formula (8) is a cation selected from the group consisting of hydrogen ion, sodium ion, potassium ion, calcium ion, magnesium ion, zinc ion ions, ammonium ions, carnitine cations and carnitine derivative cations.

Carnitine derivatives represented by formula (9):

Salts of carnitine derivatives represented by formula (10):

Wherein X ⁻ is an inorganic or organic anion that maintains electrical neutrality with the cationic portion of the carnitine derivative, and Y ⁺ is an inorganic or organic cation that maintains electrical neutrality with the anionic portion of the carnitine derivative.

The salt of a carnitine derivative as described in [20], wherein ^X- in the formula (10) is an anion selected from the group consisting of hydroxide ion, nitrate ion, sulfate ion, carbonate ion, bicarbonate ions, chloride ions, formate ions, acetate ions, citrate ions, tartrate ions, oxalate ions, fumarate ions, saturated or unsaturated fatty acid anions of 3-20 carbon atoms which may have branched chains , carnitine anion, carnitine derivative anion, ascorbate anion, phosphate ascorbate anion and phosphate ascorbate derivative anion.

The salt of a carnitine derivative as described in [20] or [21], wherein Y ⁺ in formula (10) is a cation selected from the group consisting of hydrogen ion, sodium ion, potassium ion, calcium ion, magnesium ion, zinc ion ions, ammonium ions, carnitine cations and carnitine derivative cations.

Carnitine derivatives represented by formula (11):

Salts of carnitine derivatives represented by formula (12):

Wherein X ⁻ is an inorganic or organic anion that maintains electrical neutrality with the cationic portion of the carnitine derivative, and Y ⁺ is an inorganic or organic cation that maintains electrical neutrality with the anionic portion of the carnitine derivative.

The salt of a carnitine derivative as described in [24], wherein ^X- in the formula (12) is an anion selected from the group consisting of hydroxide ion, nitrate ion, sulfate ion, carbonate ion, bicarbonate ions, chloride ions, formate ions, acetate ions, citrate ions, tartrate ions, oxalate ions, fumarate ions, saturated or unsaturated fatty acid anions of 3-20 carbon atoms which may have branched chains , carnitine anion, carnitine derivative anion, ascorbate anion, phosphate ascorbate anion and phosphate ascorbate derivative anion.

The salt of a carnitine derivative as described in [24] or [25], wherein Y ⁺ in formula (12) is a cation selected from the group consisting of hydrogen ion, sodium ion, potassium ion, calcium ion, magnesium ion, zinc ion ions, ammonium ions, carnitine cations and carnitine derivative cations.

[Invention effect]

Since the carnitine derivative is resistant to decomposition in the presence of an aqueous medium, the external preparation for skin and cosmetics of the present invention have a long life. Therefore, the carnitine derivative in the product and the carnitine derivative derived from the carnitine derivative salt produce excellent effects (skin affinity, transdermal absorption property, and promotion in tissues) stably for a long period of time. activity in lipid metabolism).

Therefore, the skin external preparations and cosmetics can be suitably used to promote lipid metabolism.

The novel carnitine derivatives and salts thereof of the present invention are hardly hydrolyzed in the presence of an aqueous medium.

Brief description of the drawings

Figure 1 is a graph showing the concentrations of free carnitine and carnitine derivatives derived from test substances delivered to the lateral compartment of the dermis after 24 hours in Example 1; and

FIG. 2 is a graph showing changes over time in the residual ratio of carnitine derivatives derived from test substances in the aqueous solution of Example 2. FIG.

Preferred Embodiments of the Invention

The present invention will be described in detail below.

The skin external preparations and cosmetics of the present invention contain specific carnitine derivatives and/or salts thereof. That is, the external preparations for skin and cosmetics may contain either one or both of specific carnitine derivatives and salts thereof.

<Carnitine Derivatives>

The carnitine derivative used in the skin external preparation and cosmetics of the present invention is represented by formula (1):

wherein each ^of R and ^R is a saturated or unsaturated aliphatic hydrocarbon group of 1-18 carbon atoms which may have a branch. Preferably, ^one of R ^and R is a saturated or unsaturated aliphatic hydrocarbon group of 1-16 carbon atoms which may have branched chains, while the other is a saturated or unsaturated aliphatic hydrocarbon group of 3-16 carbon atoms which may have branched chains. Unsaturated aliphatic hydrocarbon group. More preferably, each of R ¹ and R ² is a saturated or unsaturated aliphatic hydrocarbon group of 3-16 carbon atoms which may have a branch. Still preferably, each of ^R1 and ^R2 is a saturated or unsaturated aliphatic hydrocarbon group of 4-12 carbon atoms which may have a branch.

The carnitine moiety in the carnitine derivatives is usually in the L-form. The carnitine derivatives comprise an α-branched acyl group with ^R1 and ^R2 . When R ¹ and R ² are different, the α-carbon atom at the branch point is an asymmetric carbon atom, and an optical isomer is produced. There is no particular limitation on the optical isomers. Any optical isomers and mixtures of said isomers can be used in the present invention.

The carnitine derivatives can remain stable for a long time, probably because they contain an α-branched acyl group with ^R and ^R , which reduces the electron donating effect on the ester bond so that the acyl group in the presence of aqueous media difficult to hydrolyze.

Examples of the saturated aliphatic hydrocarbon group include linear or branched alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl Base, n-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2-ethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4 -Methylhexyl, 2-ethylpentyl, 3-ethylpentyl, n-octyl, 2-methylheptyl, 3-methylheptyl, 4-methylheptyl, 5-methylheptyl , 6-methylheptyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-propylpentyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl Alkyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl and isostearyl.

Examples of the unsaturated aliphatic hydrocarbon group include linear or branched alkenyl such as 10-undecenyl, 9-hexadecenyl, cis-9-octadecenyl, 11-octadecenyl Carbenyl, cis, cis-9,12-octadecadienyl, 9,12,15-octadecatrienyl, 6,9,12-octadecatrienyl and 9,11 , 13-octadecatrienyl.

Preferred combinations of R ^{and R} include methyl/methyl, methyl/ethyl, methyl/n-propyl, methyl/isopropyl, methyl/n-butyl, methyl/n-pentyl, methyl Base/n-hexyl, methyl/n-octyl, methyl/n-decyl, methyl/n-tetradecyl, methyl/n-hexadecyl, ethyl/ethyl, ethyl/n-propyl, Ethyl/isopropyl, ethyl/n-butyl, ethyl/isopropyl, ethyl/n-butyl, ethyl/n-pentyl, ethyl/n-hexyl, ethyl/n-octyl, ethyl /n-decyl, ethyl/n-tetradecyl, ethyl/n-hexadecyl, n-propyl/n-propyl, n-propyl/n-butyl, n-propyl/n-pentyl, n-propyl /n-hexyl, n-butyl/n-hexyl, n-butyl/n-octyl and n-hexyl/n-octyl. The skin external preparations and cosmetics of the present invention may contain one or more carnitine derivatives having different combinations of ^R1 and ^R2 .

Embodiments of the carnitine derivative represented by formula (1) include known compounds and novel compounds. Representative novel carnitine derivatives will be described below.

The novel carnitine derivatives include compounds represented by formula (3):

Wherein ^one of R ^and R is a saturated aliphatic hydrocarbon group of 1-16 carbon atoms which may have a branch, and the other is a saturated aliphatic hydrocarbon group of 8-16 carbon atoms which may have a branch.

Examples of saturated aliphatic hydrocarbon groups of 1 to 16 carbon atoms include linear or branched alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl Base, n-pentyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2-ethylbutyl, n-heptyl, 2-methylhexyl, 3-methylpentyl Hexyl, 4-methylhexyl, 2-ethylpentyl, 3-ethylpentyl, n-octyl, 2-methylheptyl, 3-methylheptyl, 4-methylheptyl, 5- Methylheptyl, 6-methylheptyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-propylpentyl, n-nonyl, n-decyl, n-undecyl , n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl and n-hexadecyl. Examples of saturated aliphatic hydrocarbon groups of 8 to 16 carbon atoms include linear or branched alkyl groups such as n-octyl, 2-methylheptyl, 3-methylheptyl, 4-methylheptyl, 5-methylheptyl, Heptyl, 6-methylheptyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-propylpentyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl and n-hexadecyl.

Various embodiments of the novel carnitine derivatives include compounds represented by formula (5):

Wherein ^one of R ^and R is a saturated aliphatic hydrocarbon group of 2-7 carbon atoms which may have a branch, and the other is a saturated aliphatic hydrocarbon group of 3-7 carbon atoms which may have a branch.

Examples of saturated aliphatic hydrocarbon groups of 2 to 7 carbon atoms include linear or branched alkyl groups such as ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n- Pentyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2-ethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 2-ethylpentyl and 3-ethylpentyl. Examples of saturated aliphatic hydrocarbon groups of 3 to 7 carbon atoms include linear or branched alkyl groups such as n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2-ethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methyl ylhexyl, 2-ethylpentyl and 3-ethylpentyl.

Considering excellent skin affinity, preferred combinations of ^R5 and ^R6 include ethyl/n-pentyl, ethyl/n-hexyl, ethyl/n-heptyl, n-propyl/n-butyl, n-propyl/ n-pentyl, n-propyl/n-hexyl, n-propyl/n-heptyl, n-butyl/n-butyl, n-butyl/n-pentyl, n-butyl/n-hexyl, n-butyl/n-heptyl, n-pentyl/n-pentyl, n-pentyl/n-hexyl, n-pentyl/n-heptyl, n-hexyl/n-hexyl, n-hexyl/n-heptyl and n-heptyl/n-heptyl.

Preferably, one of ^R1 and ^R2 in formula (1), or one of ^R3 and ^R4 in formula (3) is a linear alkyl group of 6 carbon atoms, and the other is 8 carbon atoms linear alkyl. That is, a carnitine derivative having a combination of n-hexyl and n-octyl, specifically L-carnitine 2-hexyldecanoate represented by the following formula (7), is particularly preferred. The carnitine derivatives are exceptionally stable in the presence of aqueous media.

Also preferably, one of R and R in formula ( ¹ ), or one of R ^and R in formula (3) is ^a methyl group, and the other is a linear alkyl group of ¹⁴ carbon atoms ( n-tetradecyl). Specifically, L-carnitine 2-methyl palmitate represented by the following formula (9) is preferable. Also preferably, one of R and R in formula ( ¹ ), or one of R ^and R in formula ( ⁵ ) ^, is a linear alkyl group of 4 carbon atoms, while the other is a 6-carbon Atoms of linear alkyl groups. That is, carnitine derivatives having a combination of n-butyl and n-hexyl groups, specifically L-carnitine 2-butyloctanoate represented by the following formula (11), are preferred.

<Salts of Carnitine Derivatives>

The salt of the carnitine derivative used in the skin external preparation and cosmetics of the present invention is represented by formula (2):

In the formula (2), X ^- is an inorganic or organic anion maintaining electrical neutrality with the cationic portion of the carnitine derivative. Medically acceptable anions are preferable, and examples thereof include inorganic ions such as hydroxide ions, nitrate ions, sulfate ions, carbonate ions, bicarbonate ions, and chloride ions; and organic ions such as formate ions, acetate ions, Citrate ion, tartrate ion, oxalate ion, fumarate ion, saturated or unsaturated fatty acid anion of 3-20 carbon atoms which may have a branched chain, carnitine anion, carnitine derivative anion, ascorbate anion , ascorbyl phosphate anion and ascorbyl phosphate derivative anion. Among them, hydroxide ions, chloride ions, citrate ions, carnitine anions, and carnitine derivative anions are preferable in view of compatibility in external preparations for skin, especially cosmetics.

In formula (2), Y ⁺ is an inorganic or organic cation maintaining electrical neutrality with the anion portion of the carnitine derivative. Medically acceptable cations are preferable, and examples thereof include hydrogen ions, sodium ions, potassium ions, calcium ions, magnesium ions, zinc ions, ammonium ions, carnitine cations, and carnitine derivative cations. Among them, hydrogen ions, sodium ions, potassium ions, carnitine cations, and carnitine derivative cations are preferable in view of compatibility in skin external preparations, especially cosmetics.

In formula (2), R ¹ and R ² are as defined in formula (1).

The skin external preparation and cosmetic of the present invention may contain one or more salts of carnitine derivatives having different combinations of X ⁻ , Y ⁺ , R ¹ and R ² .

The salts of carnitine derivatives represented by formula (2) include known compounds and novel compounds. Salts of representative novel carnitine derivatives will be described below.

Embodiments of the salts of neocarnitine derivatives include compounds represented by formula (4):

wherein R ³ and R ⁴ are as defined in formula (3), and X ⁻ and Y ⁺ are as defined in formula (2).

Various embodiments of the novel salts of carnitine derivatives include compounds represented by formula (6):

wherein R ⁵ and R ⁶ are as defined in formula (5), and X ⁻ and Y ⁺ are as defined in formula (2).

Preferably, one of ^R1 and ^R2 in formula (2), or one of ^R3 and R4 in formula ( ⁴ ) is a linear alkyl group of 6 carbon atoms, and the other is a linear alkyl group of 8 carbon atoms linear alkyl. That is, a salt of a carnitine derivative having a combination of n-hexyl and n-octyl, specifically, a salt of L-carnitine 2-hexyldecanoate represented by the following formula (8) is particularly preferred. Carnitine derivatives derived from this salt are exceptionally stable in the presence of aqueous media.

wherein X ⁻ and Y ⁺ are as defined in formula (2).

Also preferably, one of R ^and R in formula ( ² ), or one of R ^and R in formula ( ⁴ ) is a methyl group, and the other is a linear alkyl group of 14 carbon atoms ( n-tetradecyl). Specifically, a salt of L-carnitine 2-methyl palmitate represented by the following formula (10) is preferable. Also preferably, one of R ^and R in formula ( ² ), or one of R ^and R in formula ( ⁶ ), is a linear alkyl group of 4 carbon atoms, while the other is a 6-carbon Atoms of linear alkyl groups. That is, salts of carnitine derivatives having a combination of n-butyl and n-hexyl groups, specifically, salts of L-carnitine 2-butyl octanoate represented by the following formula (12) are preferred.

where X ⁻ and Y ⁺ are as defined in formula (2).

<Preparation of Carnitine Derivatives and Salts>

The carnitine derivatives and salts thereof used in the skin external preparations and cosmetics of the present invention can be synthesized from commercially available L-carnitines, for example, by reaction of L-carnitines and fatty acid chlorides.

For example, the synthesis of L-carnitine 2-hexyldecanoate hydrochloride will be described below. L-carnitine and 2-hexyldecanoic acid chloride were mixed in trifluoroacetic acid, followed by heating and stirring at 50-80°C to conduct a reaction. Thereafter, trifluoroacetic acid was distilled off by evaporation and recovered by adding petroleum ether to the residue, and water was added to the residue to quench the acid chloride. Then, ethanol and diethyl ether were added to the residue to extract it, and a water-ethanol phase was separated. The water-ethanol phase was combined with n-butanol and washed with water if necessary. n-Butanol was distilled off to obtain L-carnitine 2-hexyldecanoate hydrochloride.

Examples of carnitine as a raw material for producing the carnitine derivative and its salt include internal salts, inorganic salts such as hydrochloride and sodium salts, and organic salts such as oxalate, tartrate and fumarate.

<External skin preparations and cosmetics>

The skin external preparations and cosmetics, especially cosmetics for improving lipid metabolism, contain the above-mentioned carnitine derivatives and/or salts thereof. The lipid metabolism-improving cosmetic is a cosmetic aimed at improving and preventing skin problems and aging and obesity related to excess lipid and decreased lipid metabolism. Examples of the desired effects of the cosmetics include weight loss, prevention of cellulite, skin tightening, prevention of oily and oily skin due to excess sebum and smeared makeup, improvement and prevention of seborrheic dermatitis and This causes hair loss, prevents acne, prevents body odor, and anti-aging, revitalizes and cares for the skin by promoting the conversion of lipids into energy.

The content of the carnitine derivative and/or its salt is usually 0.01-20% by mass, preferably 0.05-12% by mass, more preferably 0.1-5% by mass in the total amount of the external preparation for skin. The amount indicates its content when any one of the carnitine derivatives or salts thereof is used alone, and their content when the carnitine derivatives and salts thereof are used in combination.

When the external preparation for skin contains the above-mentioned amount of the carnitine derivative and/or its salt, the carnitine derivative and/or its salt quickly penetrates into the skin and acts as desired.

The cosmetics and lipid metabolism-improving cosmetics desirably contain the carnitine derivative and/or its salt in the above-mentioned amount for external preparations for skin.

The skin external preparations and cosmetics may contain other components commonly used in general skin external preparations and cosmetics while still achieving the effects of the present invention.

The components include:

Hydrocarbons, such as ozokerite, α-olefin oligomers, light isoparaffins, light liquid isoparaffins, squalene, squalane, synthetic squalane, plant squalane, ozokerite ( ceresin), paraffin, polyethylene powder, polybutene, microcrystalline wax, liquid isoparaffin, liquid paraffin, mineral oil and petrolatum;

Natural fats and oils, such as natural waxes, which include jojoba oil, carnauba wax, candelilla wax, rice wax, shellac, lanolin, mink wax, spermaceti, sugarcane wax, spermaceti, beeswax, and lignite 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 germ oil, peach kernel oil, palm kernel Oil, Palm Oil, Castor Oil, Grapeseed Oil, Cottonseed Oil, Coconut Oil, Hydrogenated Coconut Oil, Tallow, Hydrogenated Oil, Horse Oil, Mink Oil, Egg Butter, Egg Yolk Fat Oil, Rose Hip Oil, Kiwi Oil, Evening Primrose oil, wheat germ oil, peanut oil, camellia oil, camellia oil, cocoa butter, wood wax, tallow, beef hoof fat, lard, horse tallow, suet, shea butter, macadamia oil, and meadowfoam oil;

Fatty acids such as lauric, myristic, palmitic, stearic, behenic, oleic, isostearic, 12-hydroxystearic, undecylenic and coconut fatty acids;

Higher alcohols such as isostearyl alcohol, octyldodecanol, hexyldecanol, cholesterol, phytosterol, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, behenyl alcohol, and cetostearyl alcohol Alcohol mixture;

Alkyl glyceryl ethers such as batyl alcohol, chimeryl alcohol, batyl alcohol, and isostearyl glyceryl ether;

Esters such as isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, butyl stearate, ethyl oleate, ethyl linoleate, isolinoleate Propyl ester, cetyl caprylate, hexyl laurate, isooctyl myristate, decyl myristate, myristyl myristate, cetyl myristate, octadecyl myristate Cetyl Palmitate, Stearyl Stearate, Decyl Oleate, Oleyl Oleate, Cetyl Ricinoleate, Isostearyl Laurate, Myristate Isotridecyl myristate, Isocetyl myristate, Isostearyl myristate, Octyldodecyl myristate, 2-Ethylhexyl palmitate, Isodedecyl palmitate Hexaalkyl Esters, Isostearyl Palmitate, 2-Ethylhexyl Stearate, Isocetyl Stearate, Isodecyl Oleate, Octyldodecyl Oleate, Castor Octyldodecyl Alkylate,

Ethyl Isostearate, Isopropyl Isostearate, Cetyl 2-Ethylhexanoate, Cetyl Stearyl 2-Ethylhexanoate, Stearyl 2-Ethylhexanoate Hexyl Isostearate, Ethylene Glycol Dicaprylate, Ethylene Glycol Dioleate, Propylene Glycol Dicaprylate, Propylene Glycol Dicaprylate, Propylene Glycol Dicaprate, Propylene Glycol Dioleate , neopentyl glycol dicaprate, neopentyl glycol dicaprylate, glyceryl tricaprylate, glyceryl tri-2-ethylhexanoate, glyceryl tri(caprylate caprate), tri(stearyl caprylate Glyceryl tri(undecanoate), Glyceryl triisopalmitate, Glyceryl triisostearate, Trimethylolpropane tri-2-ethylhexanoate, Triisostearic acid Trimethylolpropane, Pentaerythritol Tetra-2-Ethylhexanoate, Pentaerythritol Tetramyristate,

Pentaerythritol Tetraisostearate, Diglyceryl Tetraisostearate, Octyldodecyl Neopentanoate, Isocetyl Caprylate, Isostearyl Caprylate, 2-Ethylhexyl Isonononanoate Esters, Hexyldecyl Dimethyl Octanoate, Octyl Dodecyl Dimethyl Octanoate, 2-Ethylhexyl Isopalmitate, Isocetyl Isostearate, Isostearyl Isostearate octyl dodecyl isostearate, lauryl lactate, myristyl lactate, cetyl lactate, octyl dodecyl lactate, triethyl citrate, acetyl citrate Triethyl Ester, Acetyl Tributyl Citrate, Trioctyl Citrate, Triisohexadecyl Citrate, Trioctyldodecyl Citrate, Diisostearyl Malate, Hydroxyhard 2-Ethylhexyl Fatty Acid, Di-2-Ethylhexyl Succinate, Diisopropyl Adipate, Diisobutyl Adipate, Dioctyl Adipate, Diheptyl Deca Adipate Monoalkyl ester, diethyl sebacate, diisopropyl sebacate, dioctyl sebacate,

Cholesteryl Stearate, Cholesteryl Isostearate, Cholesteryl Hydroxystearate, Cholesteryl Oleate, Dihydrocholesteryl Oleate, Phytosteryl Isostearate, Phytosteryl Oleate , 12-stearyl hydroxystearic acid isocetyl ester, 12-stearyl hydroxystearic acid stearyl ester, 12-stearyl hydroxystearic acid isostearyl ester, polyoxyethylene ( 3) Polyoxypropylene (1) cetyl ether acetate, polyoxyethylene (3) polyoxypropylene (1) isocetyl ether acetate, isononyl isononanoate, octyl isononanoate , tridecyl isononanoate and isotridecyl isononanoate;

Silicone oils such as methylpolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, methylcyclopolysiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane Oxane, Dodecamethylcyclohexasiloxane, Octamethyltrisiloxane, Decamethyltetrasiloxane, Tetramethylhexasiloxane, Highly polymerized methylpolysiloxane, Dimethicone Polysiloxane/methyl(polyoxyethylene)siloxane/methyl(polyoxypropylene)siloxane copolymer, dimethylsiloxane/methyl(polyoxyethylene)siloxane copolymer, dimethicone Methylsiloxane/Methyl(polyoxypropylene)siloxane Copolymer, Dimethicone/Methylhexadecyloxysiloxane Copolymer, Dimethicone/Methylstearin Oxy-siloxane copolymers, polyether-modified silicone resins, alcohol-modified silicone resins, alkyl-modified silicone resins, and amino-modified silicone resins;

Polymers such as sodium alginate, carrageenan, agar, furcelleran, cyamoposis gum, quince seeds, konjac mannan, tamarind gum, tara gum, dextrin , locust bean gum, gum arabic, ghatti gum, karaya gum, tragacanth gum, arabinogalactan, pectin, marmelo, chitosan, starch, curdlan , xanthan gum, gellan gum, cyclodextrin, dextran, pullulan, microcrystalline cellulose, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl cellulose Carboxymethyl cellulose, carboxymethyl cellulose, carboxylated starch, cationized cellulose, phosphate starch, cationized guar gum, carboxymethyl/hydroxypropylated guar gum, hydroxypropylated guar gum, white Egg white, casein, gelatin, sodium polyacrylate, polyacrylamide, carboxyvinyl polymer, polyethyleneimine,

Highly polymerized polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl ether, polyacrylamide, acrylic acid copolymer, methacrylic acid copolymer, maleic acid copolymer, vinylpyridine copolymer, ethylene/acrylic acid Copolymers, vinylpyrrolidone polymers, vinyl alcohol/vinylpyrrolidone copolymers, nitrogen-substituted acrylamide polymers, amino-modified siloxanes, cationic polymers, ammonium dimethacrylammonium polymers, acrylic-based anions polymers, methacrylic anionic polymers, modified siloxanes, acrylic/methacrylic acid alkyl (C _10-30 ) ester copolymers and polyoxyethylene/polyoxypropylene copolymers;

lower alcohols such as ethanol, isopropanol, 1-butanol, 2-butanol and benzyl alcohol;

Polyols such as ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, glycerin, diglycerol, polyglycerol, 1,3-butanediol, triethylene glycol, dipropylene glycol, 3-methanol Base-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 and 1,6-hexanediol;

Anionic surfactants such as potassium cocoate, sodium cocoate, triethanolamine cocoate, potassium laurate, sodium laurate, triethanolamine laurate, potassium myristate, sodium myristate, isopropyl myristate Alcoholamine, Potassium Palmitate, Sodium Palmitate, Isopropanolamine Palmitate, Potassium Stearate, Sodium Stearate, Triethanolamine Stearate, Potassium Oleate, Sodium Oleate, Sodium Castor Oil Fatty Acid, Undecyl Zinc enoate, Zinc laurate, Zinc myristate, Magnesium myristate, Zinc palmitate, Zinc stearate, Calcium stearate, Magnesium stearate, Aluminum stearate, Calcium myristate, Myristic acid Magnesium, Aluminum Dimyristate, Aluminum Isostearate,

Polyoxyethylene lauryl ether acetic acid, polyoxyethylene lauryl ether sodium acetate, polyoxyethylene tridecyl ether acetic acid, polyoxyethylene tridecyl ether sodium acetate, sodium stearoyl lactylate, isostearyl Sodium Lactylate, Sodium Lauroyl Sarcosine, Cocoyl Sarcosine, Sodium Cocoyl Sarcosinate, Sarcosine Triethanolamine Coconut Fatty Acid, Lauroyl Sarcosine, Lauroyl Sarcosine Potassium Acid, Lauroyl Sarcosine Triethanolamine, Oleoyl Sarcosine, Sodium Myristoyl Sarcosinate, Sodium Stearoyl Glutamate, Coconut Fatty Acid Acyl Glutamate, Coconut Fatty Acid Acyl Glutamate Potassium , Sodium coconut fatty acid acyl glutamate, triethanolamine coconut fatty acid acyl glutamate, lauroyl acyl glutamate, potassium lauroyl acyl glutamate, sodium lauroyl acyl glutamate, triethanolamine lauroyl acyl glutamate Ethanolamine, Myristoyl Glutamate, Myristoyl Glutamate Potassium, Myristoyl Glutamate Sodium, Stearoyl Glutamate, Stearoyl Glutamate Potassium, Stearoyl Glutamate Disodium Amino Acid, Sodium Hydrogenated Tallow Acyl Glutamate, Coconut Fatty Acid/Sodium Hydrogenated Tallow Acyl Glutamate, Sodium Coco Fatty Acid Methylalanine, Lauroyl Methylalanine, Lauroyl Methylalanine Sodium lauroyl methylalanine, triethanolamine lauroyl methylalanine, sodium myristoyl methylalanine, sodium lauroyl methyl taurate, potassium coconut fatty acid methyl taurate, coconut fatty acid methyl taurate Sodium Taurate, Magnesium Coco Fatty Acid Methyl Taurate, Sodium Myristoyl Methyl Taurate, Sodium Palmitoyl Methyl Taurate, Sodium Stearoyl Methyl Taurate, Oleoyl Methyl Taurate sodium alkane sulfonate, sodium tetradecene sulfonate, dioctyl sodium sulfosuccinate, disodium lauryl sulfosuccinate, sodium coco fatty acid ethyl ester sulfonate, sodium lauryl sulfate, lauryl Triethanolamine Sulfate, Sodium Cetyl Sulfate, Triethanolamine Alkyl Sulfate (11, 13, 15), Sodium Alkyl Sulfate (12, 13), Triethanolamine Alkyl Sulfate (12, 13), Alkyl Ammonium Sulfate (12, 14, 16), Diethanolamine Alkyl Sulfate (12, 13), Triethanolamine Alkyl Sulfate (12-14), Triethanolamine Alkyl Sulfate (12-15), Triethanolamine Coconut Oil Alkyl Magnesium Sulfate, Ammonium Lauryl Sulfate, Potassium Lauryl Sulfate, Magnesium Lauryl Sulfate, Monoethanolamine Lauryl Sulfate, Diethanolamine Lauryl Sulfate,

Sodium Myristyl Sulfate, Sodium Stearyl Sulfate, Sodium Oleyl Sulfate, Triethanolamine Oleyl Sulfate, Sodium Polyoxyethylene Lauryl Ether Sulfate, Triethanolamine Polyoxyethylene Lauryl Ether Sulfate, Polyoxyethylene(1) Sodium Alkyl (11, 13, 15) Ether Sulfate, Triethanolamine Polyoxyethylene (1) Alkyl (11, 13, 15) Ether Sulfate, Sodium Polyoxyethylene (3) Alkyl (11-15) Ether Sulfate , Polyoxyethylene (2) Alkyl (12,13) Ether Sodium Sulfate, Polyoxyethylene (3) Alkyl (12-14) Ether Sodium Sulfate, Polyoxyethylene (3) Alkyl (12-15) Ether Sulfate Sodium, polyoxyethylene (2) sodium lauryl ether sulfate, polyoxyethylene (3) sodium myristyl ether sulfate, higher fatty acid alkanolamide sodium sulfate, lauryl phosphoric acid, sodium lauryl phosphate,

Potassium cetyl phosphate, diethanolamine cetyl phosphate, polyoxyethylene oleyl ether phosphoric acid, polyoxyethylene lauryl ether phosphoric acid, sodium polyoxyethylene lauryl ether phosphate, polyoxyethylene cetyl ether phosphoric acid, Sodium polyoxyethylene cetyl ether phosphate, polyoxyethylene stearyl ether phosphoric acid, polyoxyethylene oleyl ether phosphoric acid, polyoxyethylene oleyl ether sodium phosphate, polyoxyethylene alkylphenyl ether phosphoric acid, polyoxyethylene Sodium Alkyl Phenyl Ether Phosphate, Triethanolamine Polyoxyethylene Alkyl Phenyl Ether Phosphate, Polyoxyethylene Octyl Ether Phosphate, Polyoxyethylene (10) Alkyl (12,13) Ether Phosphate, Polyoxyethylene Alkyl ( 12-15) Ether phosphoric acid, polyoxyethylene alkyl (12-16) ether phosphoric acid, polyoxyethylene lauryl ether phosphate triethanolamine and polyoxyethylene oleyl ether phosphate diethanolamine;

Cationic surfactants such as Dioctylamine, Dimethylstearylamine, Trilaurylamine, Diethylaminoacetamide Stearate, Lauryltrimethylammonium Chloride, Cetyltrimethyl Ammonium Chloride, Cetyl Trimethyl Ammonium Bromide, Cetyl Trimethyl Ammonium Saccharinate, Stearyl Trimethyl Ammonium Chloride, Alkyl(20-22) Trimethyl Ammonium Chloride, Laurel Trimethylammonium Bromide, Trimethylammonium Alkyl (16, 18) Chloride, Trimethylammonium Stearyl ammonium chloride, di(polyoxyethylene) oleyl methyl ammonium chloride (2EO), dipolyoxyethylene stearyl methyl ammonium chloride, polyoxyethylene (1) polyoxypropylene (25) diethylmethyl Ammonium Chloride, Tris(polyoxyethylene)stearyl Ammonium Chloride (5EO), Distearyl Dimethyl Ammonium Chloride,

Dialkyl (12-15) dimethyl ammonium chloride, dialkyl (12-18) dimethyl ammonium chloride, dialkyl (14-18) dimethyl ammonium chloride, dicocoyl di Methyl Ammonium Chloride, Dicetyl Dimethyl Ammonium Chloride, Isostearyl Lauryl Dimonium Chloride, Benzalkonium Chloride, Myristyl Dimethyl Benzyl Ammonium Chloride, Lauryl Dimethyl Ammonium Chloride Dimethyl(ethylbenzyl)ammonium chloride, stearyldimethylbenzylammonium chloride, laurylpyridinium chloride, hexadecylpyridinium chloride, lauroylcholecarbamoylmethyl chloride pyridinium chloride, stearyl cholcarbamoylmethyl pyridinium chloride, alkyl isoquinolinium bromide, benzethonium chloride and benzethonium chloride;

Amphoteric surfactants such as 2-Alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaines, alkyldiaminoethylglycine hydrochloride, sodium lauryldiaminoethylglycinate, undecyl Sodium Alkyl Hydroxyethylimidazolium Betaine, Undecyl-N-Carboxymethylimidazolium Betaine, Acyl-N-Carboxyethyl-N-Hydroxyethyl Ethylenediamine Disodium Coco Fatty Acid Ester, Acyl-N-carboxyethoxyethyl-N-carboxymethylethylenediamine disodium coco fatty acid ester, acyl-N-carboxymethoxyethyl-N-carboxymethylethylenediamine disodium coconut oil Fatty acid esters, sodium lauryl aminopropionate, sodium lauryl aminopropionate, triethanolamine lauryl aminopropionate, acyl-N-carboxyethyl-N-hydroxyethyl ethylenediamine sodium palm oil fatty acid ester , Betaine Lauryl Dimethyl Glycine, Betaine Cocoalkyl Dimethyl Glycine, Betaine Stearyl Dimethyl Glycine, Sodium Stearyl Dimethyl Betaine, Amidopropyl Betaine Coco Fatty Acid Ester, Amidopropyl Betaine Palm Olein Fatty Ester, Amidopropyl Betaine Lauryl Propyl Acetate, Amidopropyl Betaine Ricinoleate, Stearyl Dihydroxyethyl betaine and lauryl hydroxysultaine;

Nonionic surfactants such as polyoxyethylene (10) alkyl (12, 13) ether, polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene oil Polyoxyethylene (3,7,12) alkyl (12-14) ether, polyoxyethylene tridecyl ether, polyoxyethylene myristyl ether, polyoxyethylene-secondary alkyl (14) ether , polyoxyethylene isocetyl ether, polyoxyethylene hexadecyl/stearyl ether, polyoxyethylene (2, 10, 20) isostearyl ether, polyoxyethylene oleyl cetyl ether, Polyoxyethylene (20) peanut ether, polyoxyethylene octyl lauryl ether, polyoxyethylene behenyl ether, polyoxyethylene octyl phenyl ether,

Polyoxyethylene nonylphenyl ether, polyoxyethylene dinonylphenyl ether, polyoxyethylene (1) polyoxypropylene (1, 2, 4, 8) hexadecyl ether, polyoxyethylene (5) polyoxyethylene Oxypropylene (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) polyoxypropylene (34) stearyl ether, polyoxyethylene (4) polyoxyethylene Propylene (30) stearyl ether, polyoxyethylene (34) polyoxypropylene (23) stearyl ether, polyoxyethylene polyoxypropylene cetyl ether, polyoxyethylene polyoxypropylene decyltetradecyl ether,

Polyethylene glycol monolaurate, polyethylene glycol monostearate, polyethylene glycol monostearate, polyethylene glycol monooleate, ethylene glycol fatty acid ester, self-emulsifiable ethylene glycol Alcohol Monostearate, Diethylene Glycol Laurate, Macrogol Myristate, Macrogol Palmitate, Diethylene Glycol Stearate, Self-Emulsifiable Polyethylene Glycol (2) Monostearate, Macrogol Isostearate, Polyethylene Glycol Dicaprylate, Diethylene Glycol Dilaurate, Macrogol Dilaurate, Macrogol (150) Dipalmum Ethylene Glycol Distearate, Diethylene Glycol Distearate, Polyethylene Glycol Distearate, Ethylene Glycol Dioleate, Polyethylene Glycol Dioleate,

Polyethylene glycol diricinoleate, polyoxyethylene(20) sorbitan monolaurate, polyoxyethylene(20) sorbitan monopalmitate, polyoxyethylene(6) sorbitan Alcohol monostearate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan tristearate, polyoxyethylene (6) sorbitan monostearate Oleate, polyoxyethylene (20) sorbitan monooleate, polyoxyethylene (20) sorbitan trioleate, sorbitan polyoxyethylene (20) coco fatty acid ester, Polyoxyethylene (10-80) sorbitan monolaurate, polyoxyethylene sorbitan tristearate, polyoxyethylene (20) sorbitan isostearate, polyoxyethylene ( 150) Sorbitan tristearate,

Polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene (10) hydrogenated castor oil, polyoxyethylene (20) hydrogenated castor oil, polyoxyethylene (40) hydrogenated castor oil, polyoxyethylene (50) hydrogenated Castor Oil, Polyoxyethylene (60) Hydrogenated Castor Oil, Lipophilic Glyceryl Monostearate, Lipophilic Glyceryl Monooleate, Self-Emulsifiable Glyceryl Monostearate, Coco Fatty Acid Glycerides, Glyceryl Laurate Glyceryl Myristate, Glyceryl Isostearate, Glyceryl Ricinoleate, Glyceryl Monohydroxystearate, Glyceryl Oleate, Glyceryl Linoleate, Glyceryl Erucate, Glyceryl Behenate Esters, wheat germ oil fatty acid glycerides, safflower oil fatty acid glycerides, hydrogenated soybean oil fatty acid glycerides, saturated fatty acid glycerides,

Cottonseed Oil Fatty Acid Glycerides, Glyceryl Monoisostearate Monomyristate, Monotallow Glycerides, Monoglyceryl Lanolin Fatty Acid, Glyceryl Sesquioleate, Glyceryl Distearate, Glyceryl Di Isostearate, Glyceryl Diarachidate, Sorbitan Monolaurate, Sorbitan Monopalmitate, Sorbitan Monostearate, Sorbitan Monoisostearate Esters, Sorbitan Monooleate, Sorbitan Sesquistearate, Sorbitan Sesquioleate, Sorbitan Tristearate, Sorbitan Trioleate , Sorbitan Coco Fatty Acid Ester, Sorbitan Isostearate, Sorbitan Sesquiisostearate, Sorbitan Distearate, Diglyceryl Isopalmitate Esters, Poly(4-10) Glyceryl Monolaurate, Poly(10) Glyceryl Monomyristate, Poly(2-10) Glyceryl Monostearate, Poly(2-10) Glyceryl Monoisohard fatty acid ester, poly(2-10) glyceryl monooleate, diglyceryl sesquioleate,

Poly(2-10) Glyceryl Diisostearate, Poly(6-10) Glyceryl Distearate, Diglyceryl Triisostearate, Poly(10) Glyceryl Tristearate ester, poly(10) glyceryl trioleate, poly(2) glyceryl tetraisostearate, decaglyceryl pentastearate, poly(6-10) glyceryl pentaoleate, poly( 10) Glyceryl heptastearate, decaglyceryl decastearate, poly(10) glyceryl decaoleate, condensed poly(6) glyceryl ricinoleate, sucrose fatty acid esters, sucrose Coco fatty acid esters, alkyl glucoside, coco alkyl dimethyl amine oxide, lauryl dimethyl amine oxide, dihydroxyethyl lauryl dimethyl amine oxide, stearyl dimethyl amine oxide, Oleyl dimethylamine oxide and polyoxyethylene cocoalkyl dimethylamine oxide;

Natural surfactants such as saponin, lecithin, soy lecithin, hydrogenated soy lecithin, soy lysophospholipid, hydrogenated soy lysophospholipid, egg yolk lecithin, hydrogenated egg yolk lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, phospholipids Acylserine, sphingomyelin, sphingomyelin, ganglioside, bile acid, cholic acid, deoxycholic acid, sodium cholate, sodium deoxycholate, spiculisporic acid, rhamnolipid, seaweed glycolipids, sophorolipids and mannose erythritol lipids;

UV absorbers, including p-aminobenzoic acid, p-aminobenzoic acid derivatives such as ethyl p-aminobenzoate, glyceryl p-aminobenzoate, amyl p-dimethylaminobenzoate and p-dimethylaminobenzoic acid2 - Ethylhexyl ester, cinnamic acid derivatives such as benzyl cinnamate, glyceryl di-p-methoxycinnamate mono-2-ethylhexanoate, 2,4-diisopropyl cinnamate methyl ester, 2, Ethyl 4-diisopropylcinnamate, Potassium p-methoxycinnamate, Sodium p-methoxycinnamate, Isopropyl p-methoxycinnamate, 2-Ethylhexyl p-methoxycinnamate, 2-Ethoxyethyl p-methoxylactone and ethyl p-ethoxycinnamate, urocanic acid, urocanic acid derivatives such as ethyl urocanate,

Benzophenone derivatives such as 2,4-dihydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 2-hydroxy-4-methoxy-5-sulfodi Sodium benzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, 2-hydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4,4' - Sodium dimethoxybenzophenone and 2,2'-dihydroxy-4,4'-dimethoxy-5-sulfobenzophenone, salicylic acid derivatives such as ethylene glycol salicylate ester, 2-ethylhexyl salicylate, phenyl salicylate, benzyl salicylate, p-tert-butylphenyl salicylate, homomentyl salicylate and 3,3,5-trisalicylate Methylcyclohexyl ester, 2-(2'-hydroxy-5'-methoxyphenyl)benzotriazole and 4-tert-butyl-4'-methoxybenzoylmethane;

Powder and colored materials such as kaolin, silicic anhydride, aluminum magnesium silicate, sericite, talc, boron nitride, mica, montmorillonite, hemp cellulose powder, wheat starch, silk powder, corn starch, nitro dyes, Azo dyes, nitroso dyes, triphenylmethane dyes, xanthane dyes, quinoline dyes, anthraquinone dyes, indigo dyes, pyrene dyes, phthalocyanine dyes,

Natural dyes including flavonoids, quinones, porphyrins, annatto, squid ink powder, caramel, guaiazulene, gardenia blue, gardenia yellow, carmine carmine, shikonin, copper Sodium chlorophyllin, capsanthin dye, safflower red, safflower yellow, lac acid and riboflavin butyrate, carbon black, yellow iron oxide, black iron oxide, red iron oxide, iron blue, ultramarine blue, zinc oxide , chromium oxide, titanium oxide, black titanium oxide, zirconium oxide, chromium hydroxide, aluminum oxide, magnesium oxide, barium sulfate, aluminum hydroxide, calcium carbonate, lithium cobalt titanate, manganese violet and pearlescent pigments;

Plant extracts such as ashitaba extract, palm catechu extract, avocado extract, hydrangea serrata leaf extract, Jiaogulan extract, aescin extract, arnica extract , Oil-soluble Arnica Extract, Almond Extract, Aloe Vera Extract, Benzoin Resin Extract, Ginkgo Biloba Extract, Nettle Extract, Orris Root Extract, Fennel Extract, Turmeric Extract, Rosehip Extract, Pine Fruit chrysanthemum leaf extract, Scutellaria baicalensis root extract, Phellodendron bark extract, Coptis rhizome extract, barley germ seed extract, okra extract, hypericum erectum extract, oil-soluble forsythia extract Extract, Sesame Flower Extract, Oil-soluble Sesame Flower Extract, Mangosteen Flower Extract, Watercress (nasturtium officinale) Extract, Orange Flower Water, Kaki Tannin, Pueraria Root Extract, Valerian root extract, cattail extract, chamomile extract, oil-soluble chamomile extract, chamomile water, oat extract, carrot extract, oil-soluble carrot extract, carrot oil, capillary extract, licorice extract Extract, licorice extract powder, licorice flavonoids, cantharidin tincture, raspberry extract, kiwi fruit extract, cinchona bark extract,

Cucumber extract, apricot kernel (apricot kernel) extract, quince seed extract, Mastiff extract, mountain white bamboo extract, sophora angustifolia extract, walnut shell extract, clematis extract, Brown sugar extract, chlorella extract, mulberry tree extract, cinnamon bark extract, gentian extract, geranium herb extract, tea leaf extract, water lily extract, burdock root extract, oil-soluble burdock root extract, wheat Germ extract, hydrolyzed wheat flour, rice bran extract, fermented rice bran extract, comfrey plant extract, asiasarum root extract, saffron extract, soapwort extract, oil-soluble sage extract , Crataegus cuneata Fruit Extract, Xanthoxylum Extract, Shiitake Mushroom Extract, Shiitake Mushroom Extract Powder, Rehmannia Rehmannia Extract, Aphrodisiac Aegypti Extract, Oil-Soluble Aphrodite Aphrodisiac Extract, Japanese Basil Extract extract, linden extract, oil-soluble linden extract, filipendula multijuga extract, crude drug extract, coix seed extract, ginger extract, oil-soluble ginger extract, ginger tincture, Calamus root extract, birch bud extract, oil-soluble birch bud extract, birch bud liquid, honeysuckle extract, quince extract, oil-soluble quince extract,

Essence booster, stevia extract, ivy extract, thorny hawthorn extract, elderflower extract, juniper extract, yarrow extract, oil-soluble yarrow extract, peppermint extract, Sage extract, oil-soluble sage extract, sage water, mallow extract, celery extract, cnidium officinale extract, chuanxiong water, swertia japonica extract, Soybean extract, jujube extract, thyme extract, camellia tea extract, camellia dry distillate, camellia seed extract, lilac flower extract, citrus extract, camellia seed extract, centella asiatica extract, oil-soluble walnut Extract, duke cherry (duke) extract, terminalia tree extract, dong angelica extract, oil soluble dong ang gui extract, dong dong gui water, calendula extract, oil soluble calendula extract, soybean milk powder, Peach extract, bitter orange extract, Houttuynia cordata extract, tomato extract, Potentilla root extract, natto extract, ginseng extract, oil-soluble ginseng extract, garlic extract, rose hip extract,

Oil soluble rosehip extract, malt extract, malt root extract, Ophiopogon japonicus extract, parsley extract, barley leaf juice concentrate, distilled peppermint water, witch hazel water, witch hazel extract, Rosa centifolia (rosa centifolia) flower extract, wallweed extract, Prunella vulgaris (isodonis japonicus) extract, loquat leaf extract, oil-soluble loquat leaf extract, coltsfoot flower extract, Poria cocos extract, pseudophyllum root extract, pseudophyllum root extract Grape Extract Powder, Grape Extract, Grape Leaf Extract, Grape Water, Dried Flower Extract, Luffa Cylindrical Fruit Extract, Luffa Cylindrical Fruit Water, Safflower Extract, Oil Soluble Linden Flower Extract, Linden Flower Water, peony root extract, hops extract, oil soluble hops extract, scabbard pine fruit extract, milk thistle fruit extract, horse chestnut extract, oil soluble horse chestnut extract, Sapindus bark extract Extract, lemon balm extract, sweet rhinoceros extract, peach leaf extract, oil-soluble peach leaf extract, bean sprouts extract, cornflower flower extract, cornflower flower water, eucalyptus extract, saxifrage extract , Lily Bulb Extract, Coix Seed Extract, Oil-soluble Coix Seed Extract, Artemisia annua Extract, Artemisia Artemisiae Water, Lavender Extract, Lavender Water, Apple Extract, Ganoderma Lucidum Extract, Lettuce Extract, Milk Vetch Extract extract, rose water, rosemary extract, oil soluble rosemary extract, chamomile flower extract and burnet root extract;

Amino acids and peptides such as glycine, valine, leucine, isoleucine, serine, threonine, phenylalanine, tyrosine, tryptophan, cystine, cysteine, methionine , hydroxyproline, aspartic acid, asparagine, glutamic acid, glutamine, histidine, γ-aminobutyric acid, DL-pyrrolidone carboxylic acid, ε-aminocaproic acid, hydrolyzed elastin, Water-soluble elastin, hydrolyzed collagen, water-soluble collagen, casein, glutathione, wheat peptide and soybean peptide;

Vitamins and vitamin-active agents, including vitamin A such as retinol, retinal, retinoic acid, retinyl acetate and retinyl palmitate, carotenoids such as alpha-carotene, beta-carotene, gamma -carotene, delta-carotene, lycopene, zeaxanthin, cryptoxanthin, echinenone and astaxanthin, vitamin B1 such as thiamine, vitamin B2 such as riboflavin, vitamin B6 such as pyridoxine, pyridoxine Pyridoxal and pyridoxamine, vitamin B12 such as cyanocobalamin,

Folic Acid, Niacin, Niacinamide, Pantothenic Acid, Biotin, Vitamin C such as L-Ascorbic Acid, Sodium L-Ascorbate, L-Ascorbyl Stearate, L-Ascorbyl Palmitate, L-Ascorbyl Dipalmitate, Tetraiso L-Ascorbyl Palmitate, Disodium L-Ascorbyl Sulfate, Magnesium L-Ascorbate, Sodium L-Ascorbyl Phosphate, Ascorbyl-2-Phosphate and L-Ascorbyl-2-Glucoside, Vitamin D such as Ergocalciferol and Cholecalciferol, vitamin E such as d-alpha-tocopherol, DL-alpha-tocopherol, dl-alpha-tocopheryl acetate, dl-alpha-tocopheryl succinate, beta-tocopherol, gamma-tocopherol and d-delta-tocopherol, ubiquinones, vitamin K, carnitine, ferulic acid, gamma-oryzanol, alpha-lipoic acid, and orotic acid;

Preservatives such as benzoic acid, sodium benzoate, undecylenic acid, salicylic acid, sorbic acid, potassium sorbate, dehydroacetic acid, sodium dehydroacetate, isobutylparaben, isopropylparaben Esters, Ethylparaben, Butylparaben, Propylparaben, Benzylparaben, Methylparaben, Sodium Methylparaben, Phenoxyethanol, Photosensitizer No.101, Photosensitizer No.201 and Photosensitizer No.401;

Antioxidants such as butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, erythorbic acid, sodium erythorbate, p-hydroxyanisole, and octyl gallate;

Sequestering agents including metal ion compounds such as trisodium EDTA, EDTA, disodium EDTA, trisodium EDTA, tetrasodium EDTA Sodium, sodium citrate, gluconic acid, phytic acid, sodium polyphosphate and sodium metaphosphate;

Moisturizers such as hyaluronic acid, sodium hyaluronate, sodium chondroitin sulfate, sodium lactate, sodium pyrrolidone carboxylate, betaine, lactic acid bacteria broth, yeast extract, and ceramide;

Anti-inflammatory agents such as glycyrrhizic acid, trisodium glycyrrhizinate, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, beta-glycyrrhetinic acid, glyceryl glycyrrhetinate, stearyl glycyrrhetinate, lysozyme chloride, hydrocortisone pine and allantoin;

pH adjusters such as sodium hydroxide, potassium hydroxide and triethanolamine;

Salts such as sodium chloride, potassium chloride, magnesium chloride and sodium sulfate;

alpha-hydroxy acids such as citric, glycolic, tartaric, and lactic acids;

Whitening agents such as arbutin, alpha-arbutin and placenta extract;

Essential oils such as angelica oil, ylang-ylang essential oil, elemi oil, German chamomile oil, chamomile oil, cardamom oil, calamus oil, galbanum oil, camphor oil, carrot seed oil, sweet sage oil, clove oil, cinnamon oil, Coriander Oil, Cypress Oil, Sandalwood Oil, Fir Oil, Citronella Oil, Laurel Leaf Oil, Jasmine Absolute, Juniper Oil, Ginger Extract, Peppermint Oil, Clary Sage Oil, Cedar Oil, Geranium Oil, Thyme Oil , Tea Tree Oil, Nutmeg Oil, Neroli Oil, Neroli Oil, Pine Oil, Basil Oil, Peppermint Oil, Patchouli Oil, Palmarosa Oil, Fennel Oil, Orange Leaf Oil, Black Pepper Oil, Lantan Oil, Vetiver Herb oil, peppermint oil, bergamot oil, benzoin oil, aniba rosaeodora oil, marjoram oil, myrrh oil, melissa oil, eucalyptus oil, ravensara oil, lavender Herb oil, lavender oil, lindane oil, rose oil, rosewood oil, rosemary oil and angelica muscatel oil;

Terpenes such as pinene, terpinene, terpinolene, myrcene and longifolene;

spices and water.

The formulations and forms of the external preparations for skin and cosmetics are not particularly limited as long as they are used directly on the skin. It is more preferable to apply the skin external preparations and cosmetics to the skin in the vicinity of the desired subcutaneous fat metabolism. In a broad sense, the topical skin preparations and cosmetics include any formulations used directly on the skin, such as milk body lotions, skin creams, foundation creams, massage creams, cleansing creams, shaving creams, cleansing foams, toners, lotions, Packs, lipsticks, lipsticks, eye shadows, nail polishes, soaps, body shampoos, hand soaps, shampoos, conditioners, hair tonics, treatment conditioners, hair creams, hair gels, hair tonics, anti-hair loss agents, hair dyes, Styling gels, depilatory agents, anti-dandruff agents, toothpaste, dental adhesives, mouthwashes, hair perms, curling agents, styling agents, ointments, resurfacing adhesives, sizing agents, body washes, antiperspirants, and sunscreens. The skin external preparation and cosmetic can be used regardless of the sex and age of the user, and can be used for animal skin as well as human skin.

The skin external preparations and cosmetics of the present invention may be in any form including solid, liquid, semi-solid, gas, powder, granule, tablet, gel and foam.

Although not required, it is preferred to select formulations and forms that include an aqueous medium, since the present invention is particularly effective in ameliorating the poor stability of conventional carnitine derivatives and their salts in aqueous formulations. In this case, water may suitably account for 0.01-99.99% by mass of the skin external preparation or cosmetic.

The cosmetics of the present invention may additionally contain existing cosmetic ingredients other than the above-mentioned components while still achieving the effects of the present invention. Examples of the ingredients include those listed in: The Japanese Standards of Cosmetic Ingredients (The Japanese Standards of Cosmetic Ingredients) 2nd Edition (edited by the Japanese Pharmacopoeia Association and published by Yakuji Nippo, Ltd. (1984)), Japanese Cosmetic Ingredients Catalog (The Japanese Cosmetic Ingredients Codex) (edited by Ministry of Health and Welfare, Pharmaceutical Examination Division (Ministry of Health and Welfare Medicine Review Department) and published by Yakuji Nippo, Ltd. (1993)), Supplement to The Japanese Cosmetic Ingredient Catalog Ingredients Codex) (edited by Ministry of Health and Welfare, Pharmaceutical Examination Division (Ministry of Health and Welfare Medical Review Department) and published by Yakuji Nippo, Ltd. (1993)), Cosmetics Comprehensive Licensing Standards (The Comprehensive Licensing Standards of Cosmetics by Category) (by Ministry of Health and Welfare, Pharmaceutical Examination Division (Ministry of Health and Welfare Pharmaceutical Examination Division) edited and published by Yakuji Nippo, Ltd. (1993)), The Japanese Cosmetic Ingredients Codex by Category (by Ministry of Health and Welfare, Pharmaceutical Examination Division ( Ministry of Health, Welfare, Medical Examination Department) edited and published by Yakuji Nippo, Ltd. (1997), Dictionary of Cosmetic Ingredients (Dictionary of Cosmetic Ingredients) (Nikko Chemicals, Co. Ltd. (1991)), and 300 Latest Cosmetic Functional Materials (300Latest Cosmetic Functional Materials ) (CMS Publishing Co., Ltd. (2002)).

The skin external preparation and cosmetics of the present invention can be produced by a conventional method according to the formulation, for example, by dissolving, mixing or dispersing the above-mentioned ingredients in predetermined amounts.

Hereinafter, the present invention will be described in more detail by way of examples. However, it should be construed that the present invention is not limited to the examples. In the examples, % is by mass unless mentioned otherwise.

Example

[Synthesis Example 1]

Synthesis of L-carnitine 2-hexyldecanoate hydrochloride

In an ice bath, 45.6 g (0.283 mol) of L-carnitine were dissolved in 150 ml of trifluoroacetic acid. To the resulting solution, 116.6 g (0.425 mol) of 2-hexyldecanoyl chloride was added dropwise over 10 minutes, followed by heating and stirring at 80°C for 4 hours. The solvent was distilled off under reduced pressure. The obtained dark brown oily substance weighing 264.6 g was washed 3 times with 200 ml of n-hexane, and 200 ml of black oily substance was collected. 3.0 g of this oily substance was extracted with 20 ml of ethanol, 30 ml of n-butanol and 60 ml of water. The organic phase obtained was washed with 60 ml of water and with a mixture of 20 ml of ethanol and 60 ml of water. The organic phases were washed with 60 ml of water, collected and dried. Distillation of the solvent yielded 2.0 g of L-carnitine 2-hexyldecanoate hydrochloride.

The structures of the obtained compounds were identified by NMR, liquid chromatography-mass spectrometry (LC/MS) and elemental analysis.

<NMR>

¹ H-NMR (CDCl ₃ ): 0.90ppm (6H, t, 7.0Hz), 1.29-1.62ppm (24H, m), 2.41ppm (1H, m), 2.76ppm (2H, d, 6.0Hz), 3.21 ppm (9H, s), 3.75ppm (1H, d, 14.6Hz), 3.92ppm (1H, dd, 8.2, 14.6Hz), 5.60-5.64ppm (1H, m)

NMR equipment: Burker Advance 500

Sample concentration: 40mg sample/422mg heavy chloroform

Temperature: ambient temperature

<Liquid Chromatography-Mass Spectrometry (LC/MS)>

MS (ESI) m/z: 400.5 [M ⁺ ] (LC/MS)

Liquid chromatography (LC): Agilent 1100 series

Chromatographic column: Shodex silica C8-5B

Column temperature: 40°C

Elution solution: 20mM ammonium acetate aqueous solution/acetonitrile (30/70)

Flow rate: 1.0ml/min

Sample concentration and injection volume: 10μg×5mg/ml eluting solution

Detection: Photodiode array UV 200-700nm

Mass spectrometry (MS): Thermoquest LCQ Advantage

Ionization method: ESI (electrospray ionization)

Scanning range: m/z 50-1000 (alternating positive and negative charges)

MS/MS Collision Energy: 40%

<Elemental analysis>

Elemental analysis: C: 62.8%, H: 10.6%, N: 3.5%, O: 14.9%, Cl: 8.2%

C, H, N, and O: Organic element analyzer CHNS-932 and oxygen analysis option VTF-900 (manufactured by LECO)

Reference substance: symmetrical diphenylthiourea (for the analysis of C, H and N), p-nitroaniline (for the analysis of O)

Cl: Ion Chromatography (mix exactly 1 mg of the sample with the eluting solution (1.8 mM Na ₂ CO ₃ +1.7 mM NaHCO ₃ ) to a constant volume of 100 ml, and analyze with anion chromatography (DIONEX DX-500) to determine the Cl.)

Column: Shodex SI-904E

Flow rate: 1.0ml/min

Injection volume: 25μL

Detector: Conductivity detector

Suppressor: ASRS-I

[Synthesis Example 2]

Synthesis of L-carnitine 2-methyl palmitate hydrochloride

In an ice bath, 45.6 g (0.283 mol) of L-carnitine were dissolved in 150 ml of trifluoroacetic acid. To the resulting solution, 122.4 g (0.425 mol) of 2-methylpalmitoyl chloride was added dropwise over 10 minutes, followed by heating and stirring at 80° C. for 4 hours. The solvent was distilled off under reduced pressure. The obtained dark brown oily substance weighing 278.0 g was washed 3 times with 200 ml of n-hexane, and 200 ml of black oily substance was collected. 3.0 g of this oily substance was extracted with 20 ml of ethanol, 30 ml of n-butanol and 60 ml of water. The organic phase obtained was washed with 60 ml of water and with a mixture of 20 ml of ethanol and 60 ml of water. The organic phases were washed with 60 ml of water, collected and dried. Distillation of the solvent yielded 2.2 g of L-carnitine 2-methylpalmitate hydrochloride.

The structure of the obtained compound was identified by NMR, liquid chromatography-mass spectrometry (LC/MS) and elemental analysis as described in Synthesis Example 1.

<NMR>

¹ H-NMR (CDCl ₃ ): 2.50ppm (1H, m), 2.75ppm (1H, dd, 6.2, 1.5Hz), 2.80ppm (1H, m), 3.73ppm (1H, d, 14.4Hz), 3.91 ppm (1H, dd, 14.4, 8.5Hz), 5.61-5.65ppm (1H, m)

<Liquid Chromatography-Mass Spectrometry (LC/MS)>

MS (ESI) m/z: 414.5 [M ⁺ ]

<Elemental analysis>

Elemental analysis: C: 64.3%, H: 10.3%, N: 3.2%, O: 14.2%, Cl: 8.0%

[Synthesis Example 3]

Synthesis of L-carnitine 2-butyl octanoate hydrochloride

In an ice bath, 45.6 g (0.283 mol) of L-carnitine were dissolved in 150 ml of trifluoroacetic acid. To the resulting solution, 92.7 g (0.425 mol) of 2-butyloctanoyl chloride was added dropwise over 10 minutes, followed by heating and stirring at 80°C for 4 hours. The solvent was distilled off under reduced pressure. The obtained dark brown oily substance weighing 250.0 g was washed 3 times with 200 ml of n-hexane, and 200 ml of black oily substance was collected. 3.0 g of this oily substance was extracted with 20 ml of ethanol, 30 ml of n-butanol and 60 ml of water. The organic phase obtained was washed with 60 ml of water and with a mixture of 20 ml of ethanol and 60 ml of water. The organic phases were washed with 60 ml of water, collected and dried. Distillation of the solvent yielded 1.6 g of L-carnitine 2-butyl octanoate hydrochloride.

The structure of the obtained compound was identified by NMR, liquid chromatography-mass spectrometry (LC/MS) and elemental analysis as described in Synthesis Example 1.

<NMR>

¹ H-NMR (CDCl ₃ ): 2.76ppm (1H, d, 6.0Hz), 2.80ppm (1H, m), 3.76ppm (1H, d, 14.4Hz), 3.94ppm (1H, dd, 14.4, 8.2Hz ), 5.60-5.64ppm (1H, m)

<Liquid Chromatography-Mass Spectrometry (LC/MS)>

MS (ESI) m/z: 344.5 [M ⁺ ]

<Elemental analysis>

Elemental analysis: C: 60.1%, H: 9.5%, N: 3.5%, O: 16.7%, Cl: 10.2%

[Example 1]

Percutaneous absorption performance

The following 5 substances are tested:

1) L-Carnitine hydrochloride (Sigma-Aldrich)

2) L-Carnitine Palmitate Hydrochloride (Sigma-Aldrich)

3) L-carnitine 2-hexyl caprate hydrochloride (synthesis example 1)

4) L-carnitine 2-methyl palmitate hydrochloride (synthesis example 2)

5) L-carnitine 2-butyl octanoate hydrochloride (synthesis example 3)

Test substances (1) and (2) are standard reference substances.

The test substances were each dissolved in Dulbecco's PBS(-) containing 5% by mass of 1,2-hexanediol, followed by adding 1N NaOH to adjust the pH to 7. As a result, a 0.3% by mass solution of the test substance was prepared. The two chambers were separated by a three-dimensional model of human skin tissue (TESTSKIN ^™ LSD-d, obtained from TOYOBO CO., LTD.). 3 ml of each test substance solution was put into the epidermis-side chamber and 3 ml of Dulbecco's PBS(-) into the dermis-side chamber. They were stirred at 35°C for 24 hours with a magnetic stirrer.

After 24 hours, 1 ml of the buffer solution in the dermal side chamber was collected and 0.5 ml of the collected solution was analyzed to determine free carnitine. The remainder of the collected solution was adjusted to pH 11 with 1 N NaOH, packaged in 1.5 ml screw vials, and left at 80°C for 6 hours, followed by cooling. The pH of the solution was adjusted to 7 with 1N HCl, thereby decomposing all acylcarnitine derivatives to free carnitine. Each of these solutions was mixed with 0.02 ml of 1N hydrochloric acid, 0.1 ml of 1.6 mass % 1-aminoanthracene in acetone and 0.1 ml of 16 mass % EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiethylene amine hydrochloride) aqueous solutions were combined, followed by thorough stirring. The solution was allowed to stand at room temperature for 20 minutes and washed with 3 ml diethyl ether. The aqueous phase was filtered and analyzed by reverse phase high performance liquid chromatography (RPHPLC) (column: Phenomenex Synergi-RP, eluent solution: 45% acetonitrile, flow rate: 1.0 ml/min) to determine the 1-aminoanthracene modification The peak intensity of carnitine (excitation wavelength: 248nm, fluorescence wavelength: 418nm). The concentrations of the test substance-derived carnitine derivative and free carnitine in the solution in the dermal side chamber were calculated and determined from the above peak intensities. The alkali and heat treated samples indicated the combined free carnitine and carnitine derivative concentrations. Untreated samples indicated the concentration of free carnitine.

The results are shown in Figure 1.

Figure 1 shows that L-carnitine 2-hexyldecanoate, L-carnitine 2-methyl palmitate and L-carnitine 2-butyl octanoate pass through the skin and reach Equivalent or higher L-carnitine concentrations than those obtained with esters.

[Example 2]

stability

The following 5 substances are tested:

1) Acetyl L-carnitine hydrochloride (Sigma-Aldrich)

2) L-Carnitine Palmitate Hydrochloride (Sigma-Aldrich)

3) L-carnitine 2-hexyl caprate hydrochloride (synthesis example 1)

4) L-carnitine 2-methyl palmitate hydrochloride (synthesis example 2)

5) L-carnitine 2-butyl octanoate hydrochloride (synthesis example 3)

Test substances (1) and (2) are standard reference substances.

The test substances were each dissolved in Dulbecco's PBS(-) containing 5% by mass of 1,2-hexanediol, followed by adding 1N NaOH to adjust the pH to 7. As a result, a 0.3% by mass solution of the test substance was prepared. The solution was tightly sealed in a glass vial and the temperature was controlled at 80°C in a water bath.

After a predetermined time elapsed, the solution was collected and analyzed by RPHPLC (column: Shodex C8-5B, eluting solution: 70% acetonitrile, flow rate: 1.0 ml/min). The residual carnitine derivative originating from the test substance was determined from the UV absorption intensity at 210 nm. Fig. 2 shows the time-dependent change in the residual ratio of carnitine derivatives derived from the test substances.

Figure 2 shows that carnitine derivatives with α-branched acyl groups: L-carnitine 2-hexyldecanoate, L-carnitine 2-methylpalmitate and L-carnitine 2-butyl octanoate showed a higher residual ratio and was exceptionally more stable in aqueous solution.

[Example 3]

lipolysis promotion

Human preadipocytes (obtained from TOYOBO CO., LTD.) were seeded on 96-well microplates and treated with human preadipocyte growth medium TAGM (obtained from TOYOBO CO., LTD.) at 37° C. and 5% CO ₂ Culture while refreshing the medium every other day. The growth medium was replaced with human adipocyte differentiation medium TADM (obtained from TOYOBO CO., LTD.), and culture was carried out for 5 days. Subsequently, the medium was changed to the evaluation medium shown in Table 1 below with or without 50 μM of any of the test substances described below. The cultivation was carried out for 5 days.

The following 5 substances are tested:

1) L-Carnitine hydrochloride (Sigma-Aldrich)

2) L-Carnitine Palmitate Hydrochloride (Sigma-Aldrich)

3) L-carnitine 2-hexyl caprate hydrochloride (synthesis example 1)

4) L-carnitine 2-methyl palmitate hydrochloride (synthesis example 2)

5) L-carnitine 2-butyl octanoate hydrochloride (synthesis example 3)

Test substances (1) and (2) are standard reference substances.

Table 1

(evaluation medium)

component Concentration (g/l) Calcium chloride dihydrate 0.265 Iron nitrate nonahydrate 0.0001 Magnesium Sulfate 0.09767 potassium chloride 0.4 Sodium carbonate 3.7 Sodium chloride 6.4 Sodium dihydrogen phosphate 0.109 L-Arginine Hydrochloride 0.084 L-cystine hydrochloride 0.0626 L-Glutamine 0.584 Glycine 0.030 L-Histidine Hydrochloride Hydrate 0.042 L-Isoleucine 0.105 L-leucine 0.105 L-Lysine Hydrochloride 0.146 L-Methionine 0.030 L-phenylalanine 0.066 L-serine 0.042 L-threonine 0.095 L-Tryptophan 0.016 L-Tyrosine Disodium Dihydrate 0.10379 L-valine 0.094 Choline hydrochloride 0.004 folic acid 0.004

Inositol 0.0072 Nicotinamide 0.004 Calcium D-pantothenate 0.004 Pyridoxine hydrochloride 0.004 riboflavin 0.0004 Thiamine hydrochloride 0.004 Sodium phenol red 0.0159 Sodium pyruvate 0.11 pH 7.3

The adipocytes were washed 3 times with Dulbecco's PBS(-) and fixed in formalin. The adipocytes were stained with an oil red/water-isopropanol (1/1) solution, and extracted with isopropanol. Triglycerides accumulated in the adipocytes were determined colorimetrically. Table 2 shows the triglyceride accumulation obtained by the test substances relative to untreated adipocytes (100).

Table 2

test substance Triglyceride accumulation not added 100 L-Carnitine Hydrochloride 98 L-Carnitine Palmitate Hydrochloride 87 L-Carnitine 2-Hexyldecanoate Hydrochloride 89 L-Carnitine 2-Methyl Palmitate Hydrochloride 89 L-Carnitine 2-Butyl Caprylate Hydrochloride 90

Table 2 shows that as acylcarnitine, L-carnitine 2-hexyl decanoate, L-carnitine 2-methyl palmitate and L-carnitine 2-butyl octanoate have good effects on promoting fat metabolism. Effect.

[Example 4]

Cosmetics containing L-carnitine 2-hexyldecanoate hydrochloride were made according to Table 3. The cosmetic was stored at 40°C for 3 months and proved to be stable without separation and precipitation.

table 3

component % Sodium chloride 0.2 Tetrasodium EDTA 0.2 1,2-Hexanediol 4.0 Dipotassium Glycyrrhizinate 0.1 1% sodium hyaluronate aqueous solution 4.0 L-Carnitine 2-Hexyldecanoate Hydrochloride 0.3 purify water Surplus

Note: Numerical values are % by mass relative to the total of 100%.

[Example 5]

Preparation of skin toner

Toners were prepared according to the following formulation examples 1-4, wherein the sum of components A and B was 100%.

(recipe embodiment 1)

a.

Dipotassium Glycyrrhizinate 0.2% L-Carnitine 2-Hexyldecanoate Hydrochloride 1.0% citric acid 0.1% Sodium citrate 0.3% purify water Surplus

b.

Polyoxyethylene sorbitan tetraoleate 0.9% Sorbitan Monooleate 0.1% olive oil 0.1% Dipropylene glycol 5.0%

Methylparaben 0.1% ethanol 10.0%

(recipe embodiment 2)

a.

Sodium citrate 0.1% Glycerin 8.0% Sodium pyrrolidone carboxylate 1.0% Trehalose 0.03% 1,3-Butanediol 5.0% purify water Surplus

b.

Polyoxyethylene polyoxypropylene decyl tetradecyl ether 0.6% Methylparaben 0.1% ethanol 10.0% L-Carnitine 2-Hexyldecanoate Hydrochloride 0.3%

(recipe embodiment 3)

a.

polyvinyl alcohol 0.1% carboxy vinyl polymer 0.2% Glycerin 3.0% Trisodium edetate 0.1% sodium hydroxide 0.05% 2-Amino-2-methyl-1-propanol 0.06% caffeine 0.1% purify water Surplus

b.

ethanol 20.0%

Polyoxyethylene oleyl ether 0.3% Methylparaben 0.1% Methanol 0.1% L-Carnitine 2-Methyl Palmitate Hydrochloride 0.1%

In Formulation Examples 1, 2 and 3, the ingredients of A and B were mixed together and heated at 50°C, respectively, to obtain solutions. Subsequently, with A being stirred, several small portions of B were added to A and dissolved therein. The resulting solution was cooled with stirring. When the temperature is 30°C, stop stirring and leave the solution to get toner.

(recipe embodiment 4)

a.

1,3-Butanediol 5.02% Bis(cholesteryl/behenyl/octyldodecyl)lauroyl glutamate 0.5% Trehalose 0.03% Glyceryl tricaprylate 0.03% PEG-58 Hydrogenated Castor Oil Isostearate 1.5% PEG-60 hydrogenated castor oil 0.5% Methylparaben 0.2% Propylparaben 0.01% Tocopherol 0.05% L-Carnitine 2-Butyl Caprylate Hydrochloride 0.3%

b.

Sodium malate 0.1% Malic acid Appropriate amount purify water Surplus

The ingredients of A and B were separately mixed together and heated at 60° C. to obtain solutions. Then, with A stirring, B is mixed with A and the mixture is cooled to form a homogeneous toner.

[Example 6]

Preparation of milk body lotion

Milk body lotions were prepared according to recipe examples 5-7. In formulation examples 5 and 6, the sum of components A and B is 100%. In formulation example 7, the sum of components A to C is 100%.

(recipe embodiment 5)

a.

squalane 10.0% Polyoxyethylene glyceryl isostearate 3.5% Polyoxyethylene hydrogenated castor oil triisostearate 6.5% Polyoxyethylene Hydrogenated Castor Oil Pyroglutamic Isostearate 12.0% Methylparaben 0.1%

b.

L-Carnitine 2-Hexyldecanoate Hydrochloride 0.5% purify water Surplus

The ingredients of A and B were mixed together, respectively, and A and B were heated at 70°C and 50°C, respectively, to obtain solutions. Subsequently, with stirring A, several small portions of B are added to A to form an emulsion. The emulsion was cooled under stirring to obtain an emulsified product, which was diluted 10 times with purified water to produce a milk body lotion.

(recipe embodiment 6)

a.

Liquid paraffin 10.6% Isopropyl myristate 0.6% oleyl alcohol 1.2% Polyoxyethylene stearyl ether 3.4% PEG distearate 1.9%

Polyoxyethylene polyoxypropylene myristyl ether 0.4% L-Carnitine 2-Hexyldecanoate Hydrochloride 0.3%

b.

Sodium Stearoyl Glutamate 0.1% Propylene Glycol 1.4% Methylparaben 0.1% PEG-400 0.2% purify water Surplus

The ingredients of A and B were mixed together, respectively, and A and B were heated at 70°C and 75°C, respectively, to obtain solutions. Subsequently, with stirring B, several small portions of A are added to B to form an emulsion. The emulsion is cooled with stirring to obtain a milk body lotion.

(recipe embodiment 7)

a.

Polyoxyethylene sorbitan monostearate 1.0% Polyoxyethylene sorbitan tetraoleate 0.5%  Sorbitan Monostearate 1.0% stearic acid 0.5% Behenyl alcohol 0.5% beeswax 0.5% squalane 10.0% Glyceryl tri-2-ethylhexanoate 10.0% Ten polyglyceryl decaoleate 3.0% 1,3-Butanediol 7.0% Methylparaben 0.1% L-Carnitine 2-Methyl Palmitate Hydrochloride 0.3%

b.

Xanthan gum 0.04% carboxy vinyl polymer 0.08% purify water Surplus

c.

Triethanolamine 0.05% purify water 4.95%

The ingredients of A, B and C were mixed together separately, and A and B were heated at 80°C to obtain a solution while C was homogenized at room temperature. Subsequently, with A being stirred, B was added to A to form an emulsion, and C was added thereto. Cooling with stirring formed a milky liquid at approximately 40°C. The milky liquid composition is cooled to room temperature to produce a milk body lotion.

[Example 7]

Gel preparation

Gels were prepared according to formulation examples 8-13. In formulation example 8, the sum of components A and B is 100%. In Formulation Example 9, the sum of components A to E is 100%. In formulation examples 10-13, the sum of components A to C is 100%.

(recipe embodiment 8)

a.

agar 2.0% Xanthan gum 0.2% caffeine 0.1% purify water 50.0%

b.

Glycerin 7.0% PEG-1500 8.0% Methylparaben 0.1% L-Carnitine 2-Hexyldecanoate Hydrochloride 0.8%

purify water Surplus

The ingredients of A and B were mixed together, respectively, and A and B were heated at 90°C and 50°C, respectively, to obtain dispersions. Subsequently, A was cooled to 50 °C. With A stirring, B was added to A and the mixture was gelled by cooling under stirring to not more than 30°C. When the gel became solid enough, it was broken into microgels using a dispersing device, followed by degassing to produce a homogeneous (translucent) gel.

(recipe example 9)

a.

carboxy vinyl polymer 0.35% purify water 50.0%

b.

sodium hydroxide 0.1% purify water 10.0%

c.

1% sodium hyaluronate aqueous solution 6.0% purified water Surplus

d.

Polyoxyethylene polyoxypropylene myristyl ether 0.3% ethanol 5.0% Methylparaben 0.1% L-Carnitine 2-Hexyldecanoate Hydrochloride 0.3%

E.

Perfluoropolyether 0.2%

Separately mix together ingredients A, B, C and D. A and B were allowed to form a solution at room temperature, and C and D were heated at 50°C and 40°C, respectively, to obtain a solution. Subsequently, with stirring A, B is added to A and the mixture is gelled. Thereafter, C, D and E were added to the gel and mixed together by stirring, followed by degassing to produce a homogeneous (translucent) gel.

(recipe example 10)

a.

carboxy vinyl polymer 0.5% purify water 40.0%

b.

Potassium hydroxide 0.1% purify water 10.0%

c.

Dipropylene glycol 10.0% Methylparaben 0.1% Dipotassium Glycyrrhizinate 0.05% Hydrolyzed Collagen 0.05% L-Carnitine 2-Methyl Palmitate Hydrochloride 0.5% purify water Surplus

Mix together ingredients A, B and C separately. A and B were allowed to form a solution at room temperature, and C was heated at 50°C to obtain a solution. Subsequently, with stirring A, B is added to A and the mixture is gelled. Thereafter, C was added to the gel and mixed together by stirring, followed by degassing to produce a homogeneous (translucent) gel.

(recipe example 11)

a.

Glycerin 10.0% 1,3-Butanediol 6.0% Polydimethylsiloxane 2.0% PEG-60 hydrogenated castor oil 0.6% Laureth-2 (laureth-2) 0.1%

Laureth-21 (laureth-21) 0.1% Methylparaben 0.26% Propylparaben 0.1% Ethyl p-Hydroxymethylbenzoate 0.1% Phenoxyethanol 0.1% Tocopheryl Acetate 0.1% Chitosan Succinamide 0.01% Yeast extract 0.1% ethanol 0.01% Spices 0.01% L-Carnitine 2-Hexyldecanoate Hydrochloride 0.3%

b.

carboxy vinyl polymer 0.5% Urea 0.02% Glucosamine hydrochloride 0.01% Disodium edetate 0.01% purify water 50.0%

c.

Arginine 0.63% purify water Surplus

Mix together ingredients A, B and C separately. A was heated at 60°C to obtain a solution, and B and C were allowed to form a solution at room temperature. Subsequently, with stirring A, B is added to A and the mixture is gelled. Thereafter, C was added to the gel and mixed together by stirring, followed by cooling to room temperature to produce a homogeneous (translucent) gel.

(recipe example 12)

a.

Glycerin 50.0% L-Carnitine 2-Hexyldecanoate Hydrochloride 0.5% Tourmaline 5.0% olive oil 1.0% PEG-12 28.0% PEG-75 7.5% Polyglyceryl Laurate 1.0% ethanol 0.49% (Acrylic acid/(C10-30) alkyl acrylate) copolymer 0.11% Methylparaben 0.11% Propylparaben 0.02% Ginkgo Biloba Extract 0.02% tea extract 0.02% Horse Chestnut Extract 0.02% Brown Algae Extract 0.02%

b.

carboxy vinyl polymer 0.07% purify water 3.0%

c.

sodium hydroxide 0.01% purify water Surplus

Mix together ingredients A, B and C separately. A was heated at 60°C to obtain a solution, and B and C were allowed to form a solution at room temperature. Subsequently, with stirring A, B is added to A and the mixture is gelled. Thereafter, C was added to the gel and mixed together by stirring, followed by cooling to room temperature to produce a homogeneous (translucent) gel.

(recipe example 13)

a.

Decamethylcyclopentasiloxane 20.0% Potassium ascorbate 3.0% L-Carnitine 2-Butyl Caprylate Hydrochloride 0.3%

b.

squalane 50.0% Light liquid paraffin Surplus Dextrin Palmitate 8.0%

c.

octyl p-methoxycinnamate 1.0% Phenoxyethanol 0.5% Alpha-tocopherol 0.1%

Weigh the components of A, B and C separately. The ingredients of A were kneaded at room temperature with a ball mill. The ingredients of B are heated to obtain a homogeneous solution. The components of C were allowed to form a solution at room temperature. Subsequently, C was added to B with stirring B. The mixture was homogenized and cooled to room temperature with stirring. After this time, A was added and the mixture was stirred well to produce a homogeneous (translucent) gel.

[Example 8]

Preparation of essence (serum)

Serums were prepared according to recipe examples 14-16. In formulation example 14, the sum of components A to D is 100%. In formulation example 15, the sum of components A and B is 100%. In formulation example 16, the sum of components A to C is 100%.

(recipe example 14)

a.

Xanthan gum 0.4% Hydroxyethyl cellulose 0.1% carboxy vinyl polymer 0.1% 1,3-Butanediol 5.0% L-Carnitine 2-Hexyldecanoate Hydrochloride 0.3% purify water 50.0%

b.

Potassium hydroxide (1% aqueous solution) 2.5% purified water 10.0%

c.

caffeine 1.0% purify water Surplus

d.

Methylparaben 0.1% ethanol 3.0%

Separately mix together ingredients A, B, C and D. A, B and D were allowed to form a solution at room temperature, and C was heated at 50°C to obtain a solution. Subsequently, with stirring A, add B to A to form a viscous liquid. Thereafter, C and D were added thereto and mixed together by stirring to produce a homogeneous liquid (essence).

(Formulation Example 15)

a.

1,3-Butanediol 10.0% Glycerin 5.0% Sodium hyaluronate 0.2%

Xanthan gum 0.2% Dipotassium Glycyrrhizinate 0.02% L-Carnitine 2-Methyl Palmitate Hydrochloride 0.3% purify water Surplus

b.

ethanol 3.0% Hydrogenated Lecithin 0.5% Glyceryl tricaprylate 0.3%  Diphenylpolydimethylsiloxane 0.2% Methylparaben 0.22% Phenoxyethanol 0.08% PEG-50 hydrogenated castor oil 0.1% PEG-60 hydrogenated castor oil 0.1% Alpha-tocopherol 0.01% Polyglyceryl-10 Myristate 0.05%

The ingredients of A and B were mixed together separately, and A and B were heated at 50° C. to obtain a solution. Subsequently, while stirring A, B is mixed with A under stirring, and the mixture is cooled under stirring to produce a homogeneous liquid (essence).

(Recipe Example 16)

a.

Xanthan gum 0.4% Hydroxyethyl cellulose 0.4% 1,3-Butanediol 3.0% Glycerin 3.0% Methylparaben 0.1% purify water Surplus

b.

L-Carnitine 2-Butyl Caprylate Hydrochloride 0.3% 1,2-Hexanediol 4.0% purify water 50.0%

c.

Magnesium Ascorbyl-2-Phosphate 1.5% Sodium Ascorbyl-2-Phosphate 1.5% Sodium citrate 0.5% Tetrasodium EDTA 0.1% purified water 9.4%

Mix together ingredients A, B and C separately. A and C were allowed to form a solution at room temperature and B was heated at 50°C to obtain a solution. Subsequently, with stirring A, add B to A to form a viscous liquid. Thereafter, C is mixed under stirring to produce a homogeneous liquid (essence).

[Example 9]

Preparation of cream

Creams are prepared according to formulation examples 17-19, wherein the sum of components A and B is 100%.

(Formulation Example 17)

a.

Hydrogenated Rapeseed Alcohol 4.2% Isononyl isononanoate 6.0% squalane 9.6% Octyldodecyl myristate 4.8% Polyglyceryl monostearate 2.0% Glyceryl Stearate 1.0% Propylparaben 0.05% Xanthan gum 0.1%

Alpha-tocopherol 0.5%

b.

1,3-Butanediol 4.8% Glycerin 4.8% L-Carnitine 2-Hexyldecanoate Hydrochloride 0.8% Sodium Ascorbyl-2-Phosphate-6-Palmitate 1.0% Methylparaben 0.1% purify water Surplus

The ingredients of A and B were mixed together separately, and A and B were heated at 85° C. to obtain a solution. Subsequently, with stirring A, B is added to A to create an emulsion. The emulsion was cooled with stirring. When the temperature is about 40°C, the agitation is stopped and the emulsion is degassed to produce a cream.

(Formulation Example 18)

A cream was prepared according to Formulation Example 17, except that L-carnitine 2-hexyldecanoate hydrochloride was replaced by L-carnitine 2-methylpalmitate hydrochloride.

(Formulation Example 19)

A cream was prepared according to Formulation Example 17, except that L-carnitine 2-hexylcaprate hydrochloride was replaced by L-carnitine 2-butylcaprylate hydrochloride.

[Example 10]

Preparation of sheet cosmetic mask (cosmetic pack)

Sheet beauty masks were prepared according to formulation examples 20-23, wherein the sum of components A and B was 100%.

(Formulation Example 20)

a.

Glycerin 30.0% Magnesium Aluminum Hydroxide 1.0%

b.

Diisopropanolamine 1.0% Sodium polyacrylate 2.0% Acrylic acid/sodium acrylate copolymer (50/50 molar ratio) 2.0% L-Carnitine 2-Hexyldecanoate Hydrochloride 0.3% Magnesium Ascorbyl-2-Phosphate 3.0% purify water Surplus

(Formulation Example 21)

a.

1,3-Butanediol 30.0% Aluminum hydroxide gel/sodium hydrogen acid co-precipitate 0.05%

b.

Sodium acrylate/acrylic acid copolymer (70/30 molar ratio) 1.0% Polyacrylic acid 1.0% N-vinylacetamide/sodium acrylate copolymer (9/1 weight ratio) 3.0% Aluminum Lactate 0.05% 10% ammonia solution 0.01% L-Carnitine 2-Hexyldecanoate Hydrochloride 2.0% Magnesium Ascorbyl-2-Phosphate 0.01% purify water Surplus

In the recipe examples above, the ingredients of A and B were mixed together separately. A was allowed to form a dispersion at room temperature and B was heated at 50°C to obtain a solution. Subsequently, B was cooled to room temperature with stirring, and A was gradually added to B with kneading. The resulting sol was applied to a polypropylene liner with a knife coater with a gap of 0.5 mm. Thereafter, a non-woven fabric was attached to the sol and placed in an aluminum laminated bag, which was then heat-sealed. After aging for 3 days, a sheet-shaped beauty mask was obtained.

(Formulation Example 22)

A sheet-shaped beauty mask was prepared according to Formulation Example 20, except that L-carnitine 2-hexyldecanoate hydrochloride was replaced by L-carnitine 2-methylpalmitate hydrochloride.

(Formulation Example 23)

A sheet-shaped beauty mask was prepared according to Formulation Example 20 except that L-carnitine 2-butyl caprylate hydrochloride was used instead of L-carnitine 2-hexyl caprate hydrochloride.

[Example 11]

Preparation of mask (pack)

Masks (peel-off masks) were prepared according to formulation examples 24-26, wherein the sum of components A and B was 100%.

(Formulation Example 24)

a.

polyvinyl alcohol 13.0% carrageenan 0.5% purify water Surplus

b.

1,3-Butanediol 3.0% Methylparaben 0.1% ethanol 8.0% L-Carnitine 2-Hexyldecanoate Hydrochloride 1.0%

Mix A and B ingredients together separately. A was swollen by heating at 50°C and B was allowed to form a solution at room temperature. Then, with stirring A, gradually add B to A and mix together. The mixture was cooled with stirring. When the temperature is about 30°C, stop stirring and leave the mixture to create a peel-off mask.

(Formulation Example 25)

A peel-off mask was prepared according to Formulation Example 24, except that L-carnitine 2-hexyldecanoate hydrochloride was replaced by L-carnitine 2-methylpalmitate hydrochloride.

(Formulation Example 26)

A peel-off mask was prepared according to Formulation Example 24 except that L-carnitine 2-butyl caprylate hydrochloride was substituted for L-carnitine 2-hexyl caprate hydrochloride.

[Example 12]

Preparation of body wash

Body washes were prepared according to formulation examples 27 and 28, wherein the sum of the ingredients was 100%.

(Formulation Example 27)

Polyoxyethylene sorbitan tetraoleate 14.0% polyoxyethylene oleyl ether 3.0% Sorbitan Sesquioleate 3.0% squalane 10.0% jojoba oil 20.0% avocado oil 5.0% Propylparaben 0.1% L-Carnitine 2-Hexyldecanoate Hydrochloride 1.0% Liquid paraffin Surplus

(Formulation Example 28)

sodium bicarbonate 35.5% citric acid 37.1% polyethylene glycol 2.1% Magnesium Oxide 1.1% Alpha-tocopherol 1.2% Sodium Ascorbyl-2-Phosphate 1.5%  Ascorbic acid-2-glucoside 1.5% L-Carnitine 2-Methyl Palmitate Hydrochloride 0.5%

In the formulation examples above, the body wash was produced by stirring the ingredients until homogeneous at room temperature.

[Example 13]

Preparation of facial cleanser

Facial cleansers were prepared according to Formulation Examples 29-31. In formulation examples 29 and 30, the sum of components A to C is 100%. In Formulation Example 31, the sum of components A and B is 100%.

(Formulation Example 29)

a.

myristic acid 15.0% Palmitic acid 5.0% stearic acid 3.0% beeswax 3.0% PEG-6000 2.0% ethylene glycol distearate 2.0% Coconut fatty acid diethanolamide 3.0% concentrated glycerin 15.0% L-Carnitine 2-Hexyldecanoate Hydrochloride 0.5%

b.

Potassium hydroxide 5.5% purify water 14.5%

c.

Sodium N-lauroyl sarcosinate 10.0% purify water Surplus

Mix together ingredients A, B and C separately. A and B were heated at 80°C to obtain a solution, and C was allowed to form a solution at room temperature. Subsequently, with A being stirred, B was gradually added to A, after which C was added. The mixture was cooled with stirring. When the temperature was about 30°C, the stirring was stopped and the solution was left to stand. As a result, a facial cleanser is obtained.

(Formulation Example 30)

A facial cleanser was prepared according to Formulation Example 29, except that L-carnitine 2-hexyldecanoate hydrochloride was replaced by L-carnitine 2-methylpalmitate hydrochloride.

(Formulation Example 31)

a.

Lauric acid 2.0% myristic acid 17.0% Palmitic acid 4.0% stearic acid 4.0% Potassium Coco Fatty Acid 8.0% Coconut fatty acid diethanolamide 3.0% Sodium N-Cocoyl Methyl Taurate 10.0% concentrated glycerin 10.0% 1,3-Butanediol 10.0% L-Carnitine 2-Butyl Caprylate Hydrochloride 1.0%

b.

Potassium hydroxide 5.5% Tetrasodium edetate 0.2% purify water Surplus

Mix A and B ingredients together separately. A was heated at 80°C to obtain a solution and B was allowed to form a solution at room temperature. Subsequently, B was gradually added to A with stirring A. The mixture was cooled with stirring. When the temperature was about 30°C, the stirring was stopped and the solution was left to stand. As a result, a facial cleanser is obtained.

[Example 14]

Shampoo preparation

Shampoos are prepared according to Formulation Examples 32-34, wherein the sum of the ingredients is 100%.

(Formulation Example 32)

POE(2) sodium lauryl ether sulfate 30.0% POE(2) ammonium lauryl ether sulfate 20.0% Betaine Lauryl Dimethyl Glycine 6.0% O-[2-Hydroxy-3-(trimethylammonio)propyl]hydroxyethylcellulose chloride 0.25% Coconut fatty acid diethanolamide 4.0% ethylene glycol distearate 2.0% 1,3-Butanediol 3.0% Disodium edetate 0.2% L-Carnitine 2-Hexyldecanoate Hydrochloride 1.0% purify water Surplus

The ingredients were mixed together and heated at 80°C followed by stirring to obtain an emulsion. The emulsion was cooled with stirring. When the temperature is about 30°C, the stirring is stopped and the emulsion is left. As a result, shampoo is obtained.

(Formulation Example 33)

A shampoo was prepared according to Formulation Example 32 except that L-carnitine 2-hexyldecanoate hydrochloride was replaced by L-carnitine 2-methylpalmitate hydrochloride.

(Formulation Example 34)

A shampoo was prepared according to Formulation Example 32 except that L-carnitine 2-hexylcaprate hydrochloride was replaced by L-carnitine 2-butylcaprylate hydrochloride.

[Example 15]

Preparation of hair tonic

A hair tonic is prepared according to formulation examples 35-37, wherein the sum of the ingredients is 100%.

(Formulation Example 35)

Salicylic acid 0.3% Menthol 0.2% ethanol 60.0%

Glycerin 5.0% L-Carnitine 2-Hexyldecanoate Hydrochloride 1.0% purify water Surplus

The ingredients were mixed together and allowed to give a solution at room temperature. As a result, hair tonic is obtained.

(Formulation Example 36)

A hair tonic was prepared according to Formulation Example 35, except that L-carnitine 2-hexyldecanoate hydrochloride was replaced by L-carnitine 2-methylpalmitate hydrochloride.

(Formulation Example 37)

A hair tonic was prepared according to Formulation Example 35, except that L-carnitine 2-butyl caprylate hydrochloride was substituted for L-carnitine 2-hexyl caprate hydrochloride.

Claims (19)

1. preparation for external application to skin, it comprises by the carnitine derivative of formula (1) expression and/or by the salt of the carnitine derivative of formula (2) expression:

R wherein ¹And R ²One of be the linear alkyl of 6 carbon atoms, and another is the linear alkyl of 8 carbon atoms;

R wherein ¹And R ²Suc as formula defined in (1), X ^-Be that cationic moiety with said carnitine derivative keeps electroneutral inorganic or organic anion, and Y ⁺Be that anionicsite with said carnitine derivative keeps electroneutral inorganic or organic cation.

2. preparation for external application to skin, it comprises by the carnitine derivative of formula (1) expression and/or by the salt of the carnitine derivative of formula (2) expression:

R wherein ¹And R ²One of be the linear alkyl of 4 carbon atoms, and another is the linear alkyl of 6 carbon atoms;

R wherein ¹And R ²Suc as formula defined in (1), X ^-Be that cationic moiety with said carnitine derivative keeps electroneutral inorganic or organic anion, and Y ⁺Be that anionicsite with said carnitine derivative keeps electroneutral inorganic or organic cation.

3. preparation for external application to skin, it comprises by the carnitine derivative of formula (1) expression and/or by the salt of the carnitine derivative of formula (2) expression:

R wherein ¹And R ²One of be methyl, and another is the linear alkyl of 14 carbon atoms;

R wherein ¹And R ²Suc as formula defined in (1), X ^-Be that cationic moiety with said carnitine derivative keeps electroneutral inorganic or organic anion, and Y ⁺Be that anionicsite with said carnitine derivative keeps electroneutral inorganic or organic cation.

4. each preparation for external application to skin among the claim 1-3, the X in its Chinese style (2) ^-Be to be selected from following anion: anion, ascorbic acid root anion and the Ascorbic acid 2-phosphate anion of the carnitine derivative of hydroxide ion, nitrate ion, sulfate ion, carbanion, bicarbonate ion, halide ion, formate ion, acetate ion, citrate ion, tartrate anion ion, oxalate denominationby, fumarate ion, the saturated or undersaturated fatty acid anion that can have 3-20 carbon atom of side chain, formula (1).

5. each preparation for external application to skin among the claim 1-3, the Y in its Chinese style (2) ⁺It is to be selected from following cation: the cation of the carnitine derivative of hydrion, sodium ion, potassium ion, calcium ion, magnesium ion, zinc ion, ammonium ion and formula (1).

6. each described preparation for external application to skin among the claim 1-3, wherein said by formula (1) expression carnitine derivative and/or account for the 0.01-20 quality % of said preparation for external application to skin by the salt of the carnitine derivative of formula (2) expression.

7. the described preparation for external application to skin of claim 5, wherein said by formula (1) expression carnitine derivative and/or account for the 0.01-20 quality % of said preparation for external application to skin by the salt of the carnitine derivative of formula (2) expression.

8. the carnitine derivative of representing by formula (7):

9. by the salt of the carnitine derivative of formula (8) expression:

X wherein ^-Be that cationic moiety with said carnitine derivative keeps electroneutral inorganic or organic anion, and Y ⁺Be that anionicsite with said carnitine derivative keeps electroneutral inorganic or organic cation.

10. the salt of the carnitine derivative of claim 9, the X in its Chinese style (8) ^-Be to be selected from following anion: anion, ascorbic acid root anion and the Ascorbic acid 2-phosphate anion of the carnitine derivative of hydroxide ion, nitrate ion, sulfate ion, carbanion, bicarbonate ion, halide ion, formate ion, acetate ion, citrate ion, tartrate anion ion, oxalate denominationby, fumarate ion, the saturated or undersaturated fatty acid anion that can have 3-20 carbon atom of side chain, claim 8.

11. the salt of the carnitine derivative of claim 9 or 10, the Y in its Chinese style (8) ⁺It is to be selected from following cation: the cation of the carnitine derivative of hydrion, sodium ion, potassium ion, calcium ion, magnesium ion, zinc ion, ammonium ion and claim 8.

12. carnitine derivative by formula (9) expression:

13. salt by the carnitine derivative of formula (10) expression:

X wherein ^-Be that cationic moiety with said carnitine derivative keeps electroneutral inorganic or organic anion, and Y ⁺Be that anionicsite with said carnitine derivative keeps electroneutral inorganic or organic cation.

14. the salt of the carnitine derivative of claim 13, the X in its Chinese style (10) ^-It is to be selected from following anion: hydroxide ion; Nitrate ion; Sulfate ion; Carbanion; Bicarbonate ion; Halide ion; Formate ion; Acetate ion; Citrate ion; The tartrate anion ion; Oxalate denominationby; Fumarate ion; Saturated or the undersaturated fatty acid anion that can have 3-20 carbon atom of side chain; The anion of the carnitine derivative of claim 12; Ascorbic acid root anion and Ascorbic acid 2-phosphate anion.

15. the salt of the carnitine derivative of claim 13 or 14, the Y in its Chinese style (10) ⁺It is to be selected from following cation: the cation of the carnitine derivative of hydrion, sodium ion, potassium ion, calcium ion, magnesium ion, zinc ion, ammonium ion and claim 12.

16. carnitine derivative by formula (11) expression:

17. salt by the carnitine derivative of formula (12) expression:

X wherein ^-Be that cationic moiety with said carnitine derivative keeps electroneutral inorganic or organic anion, and Y ⁺Be that anionicsite with said carnitine derivative keeps electroneutral inorganic or organic cation.

18. the salt of the carnitine derivative of claim 17, the X in its Chinese style (12) ^-It is to be selected from following anion: hydroxide ion; Nitrate ion; Sulfate ion; Carbanion; Bicarbonate ion; Halide ion; Formate ion; Acetate ion; Citrate ion; The tartrate anion ion; Oxalate denominationby; Fumarate ion; Saturated or the undersaturated fatty acid anion that can have 3-20 carbon atom of side chain; The anion of the carnitine derivative of claim 16; Ascorbic acid root anion and Ascorbic acid 2-phosphate anion.

19. the salt of the carnitine derivative of claim 17 or 18, the Y in its Chinese style (12) ⁺It is to be selected from following cation: the cation of the carnitine derivative of hydrion, sodium ion, potassium ion, calcium ion, magnesium ion, zinc ion, ammonium ion and claim 16.

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