WO1996001799A1

WO1996001799A1 - Oligohydroxydicarboxylic acid derivatives

Info

Publication number: WO1996001799A1
Application number: PCT/EP1995/002563
Authority: WO
Inventors: Hinrich Möller; Rolf Wachter; Peter Busch
Original assignee: Henkel Kommanditgesellschaft Auf Aktien
Priority date: 1994-07-12
Filing date: 1995-07-03
Publication date: 1996-01-25
Also published as: DE4424533A1

Abstract

New oligohydroxycarboxylic acid derivatives having the formula (I) are described. In formula (I), R1 stands for a linear or branched alkyl and/or alkenyl residue with 6 to 30 carbon atoms, R2 stands for a linear or branched alkyl and/or alkenyl residue with 1 to 30 carbon atoms, X?1 and X2¿ are the same or different and stand for oxygen or a NR4 group, in which R4 stands for oxygen or a linear or branched alkyl residue with 1 to 30 carbon atoms, R3 stands for hydrogen or a hydroxyl group and n equals 1 to 5, provided that when n equals 1, R3 be a hydroxyl group. These substances are suitable as synthetic barrier lipids for skin care products.

Description

Oligohydroxydicarboxylic acid derivatives

Field of Invention

The invention relates to oligohydroxydicarboxylic acid derivatives which are obtainable by reacting oligohydroxydicarboxylic acids or their esters with fatty alcohols and / or fatty amines, a process for the preparation of the oligohydroxycarboxylic acid derivatives, skin care products containing the oligohydroxydicarboxylic acid derivatives and the use of the oligohydroxy-derived carboxylic acid derivatives.

State of the art

A balanced water balance in the individual skin layers plays an important role for the elasticity and appearance of the skin. The amount of bound water is greatest in the Dennis and in the boundary layer of the epidermis near the basement membrane. The skin elasticity is decisively shaped by the collagen fibrils in the Dennis, the specific conformation of the collagen being achieved by the incorporation of water molecules. Destruction of the lipid barrier in the stratum corneum (SC), for example by surfactants, leads to an increase in the transepidermal water loss, as a result of which the aqueous environment of the cells is disturbed. Because that in deeper Water bound to the skin layers can only be supplied via the body fluid via vessels, but not from the outside, it becomes clear that maintaining the barrier function of the stratum corneum is essential for the overall condition of the skin. [see. SE Friberg et al., CR 23rd CED Congress, Barcelona, 1992, p.29].

Ceramides are lipophilic amides of long-chain fatty acids, which are generally derived from sphingosine or phytosphingosine. This class of endogenous fatty substances has gained considerable importance since they have been recognized in the intercellular space between the corneocytes as key components for the structure of the lipid bilayer, ie the permeability barrier, in the stratum corneum of human skin. Ceramides have molecular weights of significantly less than 1000, so that the external location in a cosmetic formulation makes it possible to reach the site of action. The external application of ceramides leads to the restoration of the lipid barrier, as a result of which the described disorders of the skin function can be counteracted. [see. R.D. Petersen, Cosm. Toil. 107, 45 (1992)].

So far, the use of ceramides has been limited due to their lack of availability. There have therefore already been attempts to synthesize ceramide-analogous structures, so-called "synthetic barrier lipids (SBL)" or "pseudoceramides" and to use them for skin care, [cf. G. Imokawa et al., J. Soc. Cosmet. Che. 40, 273 (1989)].

For example, the European patent application EP-A 0 277 641 and EP-A 0 227 994 (Kao) Ceramidanaloge the following structure are proposed: OH CH2CH2OH

1 I R-0-CH2-CH-CH2-N-COR '.

Structures of the following formula, which are related to ceramides, are known from the European patent applications EP-A 0 482 860 and EP-A 0 495 624 (Unilever):

OR * R *

I I

RO-CH2-CH-CH2-N-CO- (CH2) b (CHOR *) _a R '.

For the protection of skin and hair, sugar derivatives of the following composition are also proposed in European patent application EP-A 0 455 429 (Unilever):

Rb IR ^a -O- (CH ₂ ) _z CO-N-CH ₂ - [Z]

Here, R ^a stands for hydrogen or an unsaturated fatty acyl radical, z for numbers from 7 to 49, R- ° for a hydroxyalkyl and Z for a sugar or phosphate radical.

Despite these attempts, the success that can be achieved with these substances has so far been unsatisfactory; in particular, the performance of natural ceramides is not achieved. Furthermore, the synthesis sequences are technically complex and therefore expensive, which further relativizes the importance of the substances.

The object of the present invention is to develop new high-performance ceramide-analog structures which are distinguished by the simplest possible synthesis. Another task is to create new connections with one another Manufacture structure that comes very close to ceramides or pseudoceramides on the basis of non-animal raw materials.

Description of the invention

The invention relates to oligohydroxycarboxylic acid derivatives of the formula I.

0 R ³ O v 1 o

R ¹ -X ¹ -C- (CH) _n -CX ² -R ² (I)

wherein

R ¹ for a linear or branched alkyl and / or alkenyl radical with 6 to 30 carbon atoms and R ² for a linear or branched alkyl and / or alkenyl radical with 1 to 30 carbon atoms, X ¹ and X ² identical or different are and are oxygen or an R ^* * group, in which R "* is hydrogen or a linear or branched alkyl radical having 1 to 30 carbon atoms, R ^{3 is} hydrogen or a hydroxyl group and n is a number from 1 to 5, with the Provided that when n is 1, R ^{3 is} a hydroxy group.

Oligohydroxydicarboxylic acid derivatives of the formula I are particularly preferred, in which R ¹ and R ^{2 are} identical or different and for a linear or branched alkyl and / or alkenyl radical having 12 to 22 carbon atoms, X ¹ and X ² for oxygen, R ³ for a hydroxyl group and n stand for a number of 4.

Herstel1 experienced

The invention further relates to a process for the preparation of oligohydroxydicarboxylic acid derivatives of the formula I.

0 R ³ O

1 | II

_R l_χl_C- (CH) _n -CX ² -R ² (I)

wherein

R for a linear or branched alkyl and / or alkenyl radical with 6 to 30 carbon atoms and R ² for a linear or branched alkyl and / or alkenyl radical with 1 to 30 carbon atoms, X ^x and X ^{2 are the} same or different and for oxygen or an NR ^ group, in which R ^* * is hydrogen or a linear or branched alkyl radical having 1 to 30 carbon atoms, R ^{3 is} hydrogen or a hydroxyl group and n is a number from 1 to 5, with the proviso that that when n is 1, R ^{3 is} a hydroxy group, which is characterized in that

Oligohydroxydicarboxylic acids of the formula II,

OR ³ O fl | II HO-C- (CH) _n -C-OH (II)

wherein R ³ and n have the meaning given above, or a reactive derivative thereof, in a manner known per se with compounds of the formula III and / or IV

H-∑iR ¹ (III)

HX ² -R ² (IV) in which R ¹ , R ² , X ¹ and X ^{2 have} the meanings given above.

Outgoing connections

Suitable oligohydroxydicarboxylic acids which come under general formula II are those having 3 to 7 carbon atoms and 1 to 5 hydroxyl groups. Typical examples are tartronic acid, malic acid, D - (-) - tartaric acid, L - (+) - tartaric acid, DL-tartaric acid, glucaric acid, mucic acid, mannosugaric acid, arabinosugaric acid or heptaglucaric acid.

To prepare the compounds of general formula I according to the invention, the dicarboxylic acids themselves or their reactive derivatives are used. Lactones and C1-C4-alkyl esters are particularly suitable as reactive carboxylic acid derivatives. For the preparation of the corresponding dicarboxamides, ie when X ¹ and / or X ^{2 represent} an NR ^ group, it is particularly advantageous to convert the oligohydroxydi carboxylic acids into the corresponding C 4 -C 4 alkyl esters. These esters can be obtained in a manner known per se by esterifying the acids in the C 1 -C 4 alcohols in the presence of a catalyst.

The oligohydroxydicarboxylic acids or their reactive derivatives are reacted in a manner known per se with compounds of the formulas III and / or IV, it being possible for the compounds of the formulas III and IV to be identical or different. The amount of compounds III and IV is usually selected so that in the end product with the formula I at least one of R ¹ or R ^{2 is} a carbon radical having more than 6, preferably more than 12, carbon atoms. Usually will the oligohydroxydicarboxylic acids or their reactive derivatives and the compounds of the formulas III and / or IV are used in a molar ratio of 1: 0.9 to 1: 2.2.

Either alcohols, ie when X ¹ and X ^{2 are} oxygen, or amines, ie when X ¹ and X ^{2 are} a group NR ^* *, can be used as compounds with the formulas III and IV.

Alcohols with the formula R — OH and R ² OH are in particular those in which R 1 and R ^{2 are} linear or branched alkyl and / or alkenyl radical having 12 to 22 carbon atoms. Typical examples of suitable alcohols are 1-, 2-hexadecanol, 1-octadecanol, 9-octadecen-l-ol, 1-tetradecanol, 1-dodecanol, 1-isononol, 1-isotridecanol, 1-octanol , 2-octanol, hexanol, 1-eicosanol, 1-heneicosanol, 1-docosanol, 1-nonanol, 1-isononanol, 1-isotridecanol, 1-iso-octadecanol, particularly suitable. Other suitable alcohols are, for example, the native fatty alcohols based on plants, such as lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, behen alcohol, oleyl alcohol, elaidyl alcohol, ricinol alcohol, linoleyl alcohol, linolenyl alcohol and their technical mixtures, such as coconut oil alcohol, palm fat and palm alcohol or also natural alcohol.

Particularly suitable amines with the compounds HNR ¹ R ⁴ and HNR ² R ⁴ are alkylamines, in which R ^{2 is} a linear or branched alkyl and / or alkenyl radical having 12 to 22 carbon atoms and R ^{4 is} hydrogen or a linear one or branched alkyl radical having 1 to 22 carbon atoms, so-called fatty amines. Examples include fatty amines, especially primary fatty alkylamines, such as hexadecylamine, octadecylamine, dodecylamine, decylamine or octylamine, but also dialkylamines, such as dioctadecylamine, dihexadecylamine, and Guerbetamines, such as. As methyloctadecylamine can be called. As a technical Fatty amines, in particular those based on plants, such as coconut amine, palm kernel amine or oleyl amine, and the Guerbet amines are suitable.

The condensation reaction is preferably carried out at temperatures in the range from 20 to 95 ° C. in the presence of a suitable catalyst, the reaction times typically being up to 24 hours. Both basic catalysts such as NaOH, KOH, CH3θNa, C2HsONa and acidic catalysts such as H2SO4, p-toluenesulfonic acid, methanesulfonic acid, phosphoric acid or amidosulfonic acid are used for the transesterification of the lower alkyl esters with fatty alcohols. Examples of suitable solvents are gasoline fractions, 1,2-dimethoxyethane, acetone, butanone, tert-butyl methyl ether or tetrahydrofuran.

In the case of aminolysis of the lower alkyl esters with fatty amines, it is possible to work without a catalyst or with basic catalysts such as CHßONa or C2H5θ a.

Skin care i11e1

The invention further relates to skin care compositions containing oligohydroxydicarboxylic acid derivatives of the formula I.

The compositions according to the invention can contain the oligohydroxydicarboxylic acid derivatives in amounts of 1 to 50, preferably 1 to 30, in particular 2 to 10% by weight, based on the composition, both as "water-in-oil" and "oil-in-water" emulsions are present; further conventional auxiliaries and additives can be present in amounts of 5 to 95, preferably 10 to 80,% by weight. Furthermore, the formulations can contain water in an amount of up to 99% by weight, preferably 5 to 80% by weight. Suitable carrier oils include, for example: mineral oils, vegetable oils, silicone oils, fatty acid esters, dialkyl ethers, fatty alcohols and Guerbet alcohols. Examples of emulsifiers that can be used are: sorbitan esters, monoglycerides, polysorbates, polyethylene glycol mono / difatty acid esters, highly ethoxylated fatty acid esters and high molecular weight silicone compounds, such as dimethylpolysiloxanes with an average molecular weight of 10,000 to 50,000. Other additives can be: preservatives such as p-hydroxybenzoic acid ester; Antioxidants, such as butylated hydroxytoluene, tocopherol: humectants, such as glycerol, sorbiol. 2-pyrrolidine-5-carboxylate, dibutyl phthalate, gelatin, polyglycols with an average molecular weight of 200 to 600; Buffers such as lactic acid / TEA or lactic acid / NaOH; mild surfactants, such as, for example, alkyl oligoglucosides, fatty alcohol ether sulfates, fatty acid isethionates, taurides and sarcosinates, ether carboxylic acids, sulfosuccinates, protein hydrolyzates or fatty acid condensates, sulfotriglycerides, short-chain glucamids; Phospholipids, waxes such as beeswax, ozocerite wax, paraffin wax; Plant extracts, for example from aloe vera; Thickeners; Dyes and perfumes, and sunscreens, such as, for example, ultrafine titanium dioxide or organic substances, such as p-aminobenzoic acid and its esters, ethylhexyl-p-meth-oxycinnamate, 2-ethoxyethyl-p-methoxycinnamate, butyl methoxydibenzoylmethane and mixtures thereof .

In a preferred embodiment of the invention, the oligohydroxydicarboxylic acid derivatives can be mixed with conventional ceramides, pseudoceramides, cholesterol, cholesterol fatty acid esters, fatty acids, triglycerides, cerebrosides, phospholipids and similar substances, liposomes being formed. In a further preferred embodiment of the invention, the oligohydroxydicarboxylic acid derivatives can be mixed with accelerators, in particular with essential oils, such as eucalyptol, menthol and the like.

In a third preferred embodiment, the oligohydroxydicarboxylic acid derivatives can finally also be dissolved in squalene or squalane and optionally formulated with the other ingredients mentioned together with volatile or non-volatile silicone compounds as anhydrous or almost anhydrous single-phase systems. Further examples of constituents and typical compositions can be found, for example, in WO 90/01323 (Bernstein) and SE Friberg, J. Soc. Coε et. Chem. 41, 155 (1990).

Industrial applicability

The oligohydroxydicarboxylic acid derivatives to be used as "synthetic barrier lipids" in the sense of the invention strengthen the natural barrier function of the skin against external stimuli. They improve the firmness, suppleness and elasticity of the skin, increase the moisture content and protect the skin from drying out; at the same time, the finest wrinkles are smoothed out.

Another object of the invention therefore relates to the use of oligohydroxydicarboxylic acid derivatives of the formula I as "synthetic barrier lipids" for the production of skin care products in which they are used in amounts of 1 to 50, preferably 1 to 30, in particular 2 to 10 % By weight, based on the composition, may be present. However, special formulations which form liquid-crystalline, lamellar structures are also particularly advantageous for maintaining the barrier function of the skin. These formulations can be based on the composition of the horny layer lipids as main components 5% by weight to 50% by weight of a compound with the formula I, 25% by weight to 75% by weight of saturated and unsaturated fatty acids, their alkali metal salts or mixtures of the Fatty acids and their salts, 10% by weight to 50% by weight of cholesterol, phytosterols and / or cholesteryl sulfate, 5% by weight to 30% by weight of triglycerides (triolein) and wax esters, and 2% by weight. -% to 20 wt .-% phospholides such as lecithins or kephalins contain. Typical examples of such formulations are skin creams, soft creams, nutritional creams, sunscreen creams, night creams, skin oils, skin care lotions and body aerosols.

The following examples are intended to explain the subject matter of the invention in more detail without restricting it. Examples

1) Mucic acid di-CiB / 22-alkyls

A mixture of 64.5 g (0.2 mol) of mucic acid dibutyl ester, 119.4 g (0.4 mol) of the equimolar mixture of octadecanol and docosanol and 0.5 g of p-toluenesulfonic acid was at 90 ° C. under pressure for 12 hours of 50 mbar, heated, butanol formed was distilled off at the same time. The reaction mixture was dissolved in acetone, stirred with 0.3 g of sodium carbonate and filtered. The filtrate was evaporated and dried. 146 g (95% of theory) of a beige-colored product which had a melting point of 59-88 ° C. were obtained.

2) Mucic acid didodecyl ester a) A mixture of 53.3 g (0.2 mol) of diethyl mucic acid and 74.5 g (0.4 mol) of dodecanol was reacted as in Example 1. An almost colorless resin-like product was obtained which had a melting point of 92-115 ° C.

b) A mixture of 64.5 g (0.2 mol) of mucic acid butyl ester and 74.5 g (0.4 mol) of dodecanol was prepared in the presence of 1,2-dimethoxyethane in analogy to the example in analogy to patent specification WO / PCT 93/02039 obtained from sulfuric acid. An almost colorless waxy product was obtained which had a melting point of 115-126 ° C.

3) Mucic acid di-Ci6 / 18 alkyl ester

A mixture of 64.5 g (0.2 mol) of mucic acid dibutyl ester, 102.6 g (0.4 mol) of the equimolar mixture of hexadecanol and octadecanol was prepared analogously to Example 2b. A colorless waxy product with a melting point of 100-112 ° C. was obtained.

Claims

claims

1. Oligohydroxycarboxylic acid derivatives of the formula I.

OR ³ O

»I 'R ¹ -X --— C- (CH) _n -CX ² -R ² (I)

wherein

R - * - for a linear or branched alkyl and / or the alkenyl radical with 6 to 30 carbon atoms, and R ² for a linear or branched alkyl and / or alkenyl radical with 1 to 30 carbon atoms, X ¹ and X ^{2 are the} same or are different and are oxygen or an NR ⁴ group, in which R ^{4 is} hydrogen or a linear or branched alkyl radical having 1 to 30 carbon atoms, R ^{3 is} hydrogen or a hydroxyl group and n is a number from 1 to 5, with the proviso that when n is 1, R ^{3 is} a hydroxy group.

2. Oligohydroxydicarboxylic acid derivatives according to claim 1, da¬ characterized in that in the formula IR ¹ and R ^{2 is} an alkyl and / or alkenyl radical having 12 to 18 carbon atoms, X ** - and X ² oxygen, R ^{3 is} a hydroxy group and n 4 mean.

3. Process for the preparation of oligohydroxydicarboxylic acid derivatives with the formula I.

OR ³ O

■ I *

Rl-χl_C- (CH) _n -CX ² -R ² (I)

in the R ¹ and R ^{2 are the} same or different and are the same or different for a linear or branched alkyl and / or alkenyl radical having 6 to 30 carbon atoms, X ¹ and X ^{2 are the} same and are different for oxygen or an NR ⁴ group, wherein R ^{4 is} hydrogen or linear or branched alkyl radical having 1 to 30 carbon atoms, and n is a number from 0 to 4, characterized in that

Oligohydroxydicarboxylic acids of the formula II,

OR ³ OHI u HO-C- (CH) _n -C-OH (II)

wherein R ³ and n have the meaning given above, or a reactive derivative thereof, known per se

Way with compounds of formula III and / or IV

H-Xi-R ¹ (III)

HX ² -R ² (IV)

wherein R ¹ , R ² , X ¹ and X ^{2 have} the meanings given above, are implemented.

4. The method according to claim 3, characterized in that d ate a lower alkyl ester is used as the reactive derivative of oligohydroxydicarboxylic acid with the formula II.

5. The method according to any one of claims 3 or 4, characterized ge indicates that as the oligohydroxydicarboxylic acid with the formula II tartronic acid, malic acid, D - (-) - tartaric acid, L - (+) - tartaric acid, DL-tartaric acid, glucaric acid, Mucic acid, Mannosugaric acid, arabinosugaric acid or heptaglucaric acid.

6. The method according to any one of claims 3 to 5, characterized ge indicates that one uses as compounds with the formula III or IV fatty alcohols R --- OH and / or R ² 0H, wherein R ¹ and R ² in claim 3 have given meanings.

7. Skin care agent containing oligohydroxydicarboxylic acid derivatives according to claim 1.

8. Use of oligohydroxydicarboxylic acid derivatives according to claim 1 as a component of "synthetic barrier lipids" for the production of skin care products.