WO1995019366A1

WO1995019366A1 - Pseudo-ceramides

Info

Publication number: WO1995019366A1
Application number: PCT/EP1995/000064
Authority: WO
Inventors: Manfred Weuthen; Petra Riegels; Rolf Wachter
Original assignee: Henkel Kommanditgesellschaft Auf Aktien
Priority date: 1994-01-17
Filing date: 1995-01-09
Publication date: 1995-07-20
Also published as: DE4401102A1

Abstract

The proposal is for novel pseudo-ceramides of formula (I) obtained by the esterification or transesterification of hydroxyalkyl oligoglycosides of formula (I): R1-O-[G]¿p? in which R?1¿ is a hydroxyalkyl radical with 2 to 18 carbon atoms, G is a saccharose radical with 5 or 6 carbon atoms and p is a number from 1 to 10, in the presence of acid or basic catalysts with fatty acid or fatty acid esters of formula (II): R2CO-OR3 in which R2CO is linear or branched acyl radical with 6 to 22 carbon atoms and 0 and/or 1, 2 or 3 double bonds and R3 is hydrogen or an alkyl radical with 1 to 4 carbon atoms. The substances are suitable as synthetic barrier lipids for the production of skin-care agents.

Description

Pseudoceramides

Field of the Invention

The invention relates to pseudoceramides obtainable by esterification or transesterification of hydroxyalkyl oligoglycosides with fatty acids or fatty acid esters in the presence of alkaline catalysts, a process for the preparation of the pseudoceramides, skin care products containing the pseudoceramides and the use of the pseudoceramides for the preparation of Skin care products.

State of the art

A balanced water balance in the individual skin layers plays an important role for the elasticity and the appearance of the skin. The content of bound water is greatest in the dermis and in the boundary layer of the epidermis near the basement membrane. The skin elasticity is decisively shaped by the collagen fibrils in the dermis, 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 transepidermal water loss, which disturbs the aqueous environment of the cells. Since the water bound in the deeper layers of the skin can only be supplied through 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 [cf. SEFriberg 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 site of 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, which can cause the described disorders of the skin function to be counteracted [cf. R.D. Petersen, Cosm. oil. 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.Chem. 1989, 4O, 273]. For example, the European patent application EP-A 0 277 641 and EP-A 0 227 994 (Kao) ceramide analogues of the following structure are proposed:

OH CH2CH2OH

I I R-O-CH2-CH-CH2-N-COR '.

Ceramide-related structures of the following formula are known from the European patent applications EP-AI 0 482 860 and EP-AI 0 495 624 (Unilever):

OR # R *

I I

RO-CH2-CH-CH2-NH-CH2-N-CO- (CH ₂ ) (CHOR *) _a R '.

For the protection of skin and hair, sugar derivatives of the following composition are also proposed in European patent application EP-A2 0 455 429 (Unilever):

Rb

I.

R ^a -0- (CH ₂ ) _z C0-N-CH ₂ - [Z]

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

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

The object of the invention was therefore to develop new high-performance ceramide-analog structures which are distinguished by the simplest possible synthesis. Another task was to produce the new pseudoceramides based on non-animal raw materials.

Description of the invention

The invention relates to pseudoceramides, obtainable by reacting hydroxyalkyl oligoglycosides of the formula (I)

Rl-0- [G] _p (I)

in which R ^{1 stands} for a hydroxyalkyl radical with 2 to 18 carbon atoms, G for a sugar radical with 5 or 6 carbon atoms and p for numbers from 1 to 10, in the presence of acidic or basic catalysts with fatty acids or fatty acid - reesters of formula (II),

R ² CO-OR ³ (II)

in which R ^ CO represents a linear or branched acyl radical having 6 to 22 carbon atoms and 0 and / or 1, 2 or 3 double bonds and R ^{3 represents} hydrogen or an alkyl radical having 1 to 4 carbon atoms, esterified or transesterified. Surprisingly, it was found that the pseudoceramides to be used in accordance with the invention strengthen the natural barrier function of the skin, strengthen the skin and protect it from drying out. The substances are modeled on the natural skin lipids, are dermatologically and ecotoxicologically harmless and can be incorporated homogeneously into the oil phase of cosmetic products. They are colored white or ivory-like, odor-free, hydrolysis-resistant in the range of the skin pH value and color-stable against atmospheric oxygen. The invention includes the knowledge that the pseudoceramides can be produced on the basis of vegetable fatty alcohols and sugar, ie without the use of undesirable animal raw materials.

From an application point of view, pseudoceramides are particularly preferred, obtainable by transesterification of hydroxyalkyl oligoglycosides of the formula (1) _/ in which R * stands for a 1-hydroxydecyl residue, G for a glucose residue and p for numbers from 1 to 3, with fatty acid esters of Formula (II) in which R ^ CO represents an acyl radical having 12 to 18 carbon atoms and R ^{3 represents} a methyl radical.

The invention further relates to a process for the preparation of pseudoceramides, in which H droxyalkyl oligoglycosides of the formula (I) _#

in which R ^{1 represents} a hydroxyalkyl radical having 2 to 18 carbon atoms, G represents a sugar radical having 5 or 6 carbon atoms and p represents numbers from 1 to 10, in the presence of acidic rer or basic catalysts with fatty acids or fatty acid esters of the formula (II),

R ² CO-OR ³ (II)

in which R ² C0 represents a linear or branched acyl radical having 6 to 22 carbon atoms and 0 and / or 1, 2 or 3 double bonds and R ^{3 represents} hydrogen or an alkyl radical having 1 to 4 carbon atoms, esterified or transesterified.

Hydroxyalkyloligoσlvkoside

Hydroxyalkyl oligoglycosides are known substances which can be obtained by the relevant processes for the preparation of alkyl oligoglycosides. Representative of the extensive literature, reference is made here to the publications EP-Al-0 301 298 and WO 90/3977.

The hydroxyalkyl oligoglycosides can be derived from aldoses or ketoses with 5 or 6 carbon atoms, preferably glucose. The preferred hydroxyalkyl oligoglycosides are thus hydroxyalkyl oligoglucosides.

The index number p in the general formula (I) indicates the degree of oligogenization (DP degree), ie the distribution of mono- and oligoglycosides, and stands for a number between 1 and 10. While p in a given compound is always an integer must and can assume the values p = 1 to 6 here, the value p for a certain hydroxyalkyl oligoglycoside is an analytically determined arithmetic parameter that usually is a fractional number. Hydroxyalkyl oligoglycosides with an average degree of oligomerization p of 1.1 to 3.0 are preferably used. From the point of view of application technology, preference is given to those hydroxyalkyl oligoglycosides whose degree of oligomerization is less than 1.7 and in particular between 1.2 and 1.4.

The hydroxyalkyl radical can be derived from dihydroxy compounds having 2 to 18, preferably 2 to 10, carbon atoms, especially won alpha, omega-diols. Typical examples are ethylene glycol, propylene glycol, 1,2-butanediol, 1,4-butanediol and in particular 1,10-decanediol.

Accordingly, a total of those hydroxyalkyl oligoglycosides of the formula (I) are used in which R ^{1 is} a 1-hydroxydecyl radical, G is a glucose radical and p is a number from 1 to 3.

Fatty acids or fatty acid esters

In addition to the preferably primary hydroxyl group in the alkyl chain, the hydroxyalkyl oligoglycosides have further primary and secondary OH functions in the glycoside residue, which are in principle accessible to esterification or transesterification. Analytical investigations by the applicant show that the primary hydroxyl groups in the glycoside residue react first, followed by the OH function in the alkyl chain; The secondary hydroxyl groups in the sugar body are the most difficult to esterify / transesterify. Fatty acids with 6 to 22 carbon atoms are suitable for the esterification or transesterification. Typical examples are caproic acid, caprylic acid, 2-ethylhexanoic acid, capric acid, lauric acid, isotridecanoic acid, myristic acid, palmitic acid, palmoleic acid, stearic acid, isosteric acid, oleic acid, elaidic acid, petroselinic acid, linoleic acid, linolenic acid, elaleostearic acid, gadic acid and arachic acid, arachic acid as well as their technical mixtures, which occur, for example, in the pressure splitting of natural fats and oils, in the reduction of aldehydes from Roelen's oxosynthesis or in the dimerization of unsaturated fatty acids.

In addition to the fatty acids mentioned, their esters with lower alcohols having 1 to 4 carbon atoms, preferably their methyl esters, are also suitable as starting materials. Particular preference is given to the use of fatty acid esters of the formula (II) in which R ^ CO represents an acyl radical having 12 to 18 carbon atoms and R ^{3 represents} a methyl radical, such as, for example, methyl Ci2-Cιg coconut °

fatty acid methyl ester.

The hydroxyalkyl oligoglycosides and the fatty acids or fatty acid esters can usually be used in a molar ratio of 1: 1 to 1:10, preferably 1: 2 to 1: 5. The use of fatty acid methyl esters as transesterification components is preferred, inter alia, since the degree of ester substitution and thus also the hydrophilicity of the pseudoceramides can be adjusted in a simple manner by removing the methanol released during the transesterification from the reaction equilibrium. Catalysts

The esterification or transesterification takes place in the presence of acidic or basic catalysts. Suitable acidic catalysts are preferably carboxylic acids. If sulfonic acids are used as catalysts, transacetalizations and polymerization reactions can occur. A transesterification is therefore preferably carried out in the presence of basic catalysts, which are preferably selected from the group formed by alkali and / or alkaline earth metal oxides, hydroxides, carbonates, bicarbonates and / or C 1 -C 4 -alcoholates . Typical examples are sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, magnesium oxide and sodium methoxide. The basic catalysts can usually be used in amounts of 1 to 10, preferably 2 to 5% by weight, based on the starting materials.

Esterification or transesterification

The esterification or transesterification can be carried out in a manner known per se at temperatures in the range from 100 to 180 ° C. When fatty acid methyl esters are used, it is advisable to continuously remove the methanol released from the reaction equilibrium and, after the reaction has ended, to neutralize basic catalyst, for example lactic acid or phosphoric acid, by adding an acid. Excess fatty acid or unreacted fatty acid methyl ester can then be distilled off in vacuo. Skin care products

The invention further relates to skin care compositions containing pseudoceramides of the formula (I).

The agents according to the invention can contain the pseudoceramides in amounts of 1 to 30, preferably 2 to 10% by weight, based on the agents, and both as "water-in-oil" and "oil-in" Water "emulsions are present; It can also contain other customary auxiliaries and additives 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.

Examples of suitable carrier oils for this purpose are: mineral oils, vegetable oils, silicone oils, fatty acid esters, dialkyl ethers, fatty alcohols and Guerbet alcohols. Examples of emulsifiers which can be used are: alkyl and hydroxyalkyl oligoglycosides, 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, for example, p-hydroxybenzoic acid ester; Antioxidants, such as butylated hydroxytoluene, tocopherol; Humectants, such as glycerol, sorbitol, 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 fatty alcohol ether sulfates, fatty acid isethionates, taurides and sarcosinates, ether carboxylic acids, ren, sulfosuccinates, protein hydrolyzates or fatty acid condensates, sulfotriglycerides, short-chain glucamides; Phospholipids, waxes such as beeswax, ozokerite wax, paraffin wax; Plant extracts, for example from aloe vera; Thickener; 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-methoxycinnamic acid ester, 2-ethoxyethyl-p-methoxycinnamic acid ester, butyl methoxydibenzoylmethane and mixtures thereof.

In a preferred embodiment of the invention, the pseudoceramides can be mixed with conventional ceramides, further pseudo-ceramides, cholesterol, cholesterol fatty acid esters, fatty acids, triglycerides, cerebrosides, phospholipids and similar substances, whereby liposomes can be formed.

In a further preferred embodiment of the invention, the pseudoceramides can be mixed with active substance accelerators, in particular with essential oils, such as, for example, eucalyptol, menthol and the like.

In a third preferred embodiment, the pseudoceramides can finally also be dissolved in squalene or squalane and, if appropriate, 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). Industrial applicability

The pseudoceramides 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 pseudoceramides of the formula (I) as "synthetic barrier lipids" for the production of skin care products, in which they are present in amounts of 1 to 30, preferably 2 to 10% by weight. based on the funds - may be included. Typical examples are skin creams, soft creams, nutritional creams, sunscreen creams, night creams, skin oils, 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

Example 1:

Preparation of 1,10-decanediol glucoside dilaurate. 168.2 g (0.5 mol) of 1,10-decanediol glucoside and 1071.5 g (5.0 mol) of methyl laurate were placed in a 2-1 three-necked flask equipped with a stirrer, internal thermometer and distillation head, at 110 ° C heated and mixed with 12.5 g - corresponding to 1 wt .-% based on the starting materials - potassium carbonate. The reaction mixture was heated to 136 ° C., 15.9 g of methanol distilling off over the course of 2 h. The mixture was then cooled to 115 ° C. and concentrated by adding 14.9 g. Phosphoric acid adjusted to a pH of 6.4. After the excess methyl laurate (140 ° C., 20 mbar) had been removed by distillation, 355 g of the 1, 10-decanediol glucoside dilaurate were obtained as an ivory-colored solid; the residual unreacted glucoside content was 5% by weight.

Example 2:

Production of 1,10-decanediol glucoside monoearate. Analogously to Example 1, 168.2 g (0.5 mol) of 1, 10-decanediol glucoside, 1492 g (5.0 mol) of methyl stearate and 16.6 g of potassium carbonate were reacted. After removal of the excess methyl stearate by distillation, 400 g of the 1,10-decanediol-glucoside monostearate were obtained as a slightly yellow-colored solid; the residual unreacted glucoside content was 11% by weight.

Claims

claims

1. pseudoceramides, obtainable by reacting hydroxyalkyl oligoglycosides of the formula (I),

Rl-0- [G] _p (I)

in which R ^{1 is} a hydroxyalkyl radical having 2 to 18 carbon atoms, G is a sugar radical having 5 or 6 carbon atoms and p is a number from 1 to 10, in the presence of acidic or basic catalysts with fatty acids or fatty acid esters of the formula (II) ,

R ² CO-OR ³ (II)

2. Pseudoceramides according to claim 1, obtainable by transesterification of hydroxyalkyl oligoglycosides of the formula (I) in which R 1 is a 1-hydroxydecyl radical, G is a glucose radical and p is a number from 1 to 3, with fatty acid reesters Formula (II) in which R ² C0 represents an acyl radical having 12 to 18 carbon atoms and R ^{3 represents} a methyl radical.

3. Process for the preparation of pseudoceramides, characterized in that hydroxyalkyl oligoglycosides of the formula (I),

R! -0- [G] p (I)

R ² CO-OR ³ (II)

in which R CO represents a linear or branched acyl radical having 6 to 22 carbon atoms and 0 and / or 1, 2 or 3 double bonds and R ^{3 represents} hydrogen or an alkyl radical having 1 to 4 carbon atoms, esterified or transesterified.

4. The method according to claim 3, characterized in that one uses hydroxyalkyl oligoglycosides of the formula (I) in which R ^{1 is} a 1-hydroxydecyl radical, G is a glucose radical and p is a number from 1 to 3.

5. The method according to claims 3 and 4, characterized gekenn¬ characterized in that one uses fatty acid esters of formula (II) in which R ² C0 is an acyl radical having 12 to 18 carbon atoms and R ^{3 is} a methyl radical.

6. The method according to claims 3 to 5, characterized gekenn¬ characterized in that the hydroxyalkyl oligoglycosides and the fatty acids or fatty acid esters are used in a molar ratio of 1: 1 to 1:10.

7. The method according to claims 3 to 6, characterized gekenn¬ characterized in that alkali and / or alkaline earth metal oxides, hydroxides, carbonates, bicarbonates and / or C ^ -C ^ alcoholates are used as basic catalysts.

8. The method according to claims 3 to 7, characterized gekenn¬ characterized in that the basic catalysts in amounts of 1 to 10 wt .-% - based on the starting materials - used.

9. The method according to claims 3 to 8, characterized gekenn¬ characterized in that the esterification or transesterification is carried out at temperatures in the range of 100 to 180 ° C.

10. Skin care agent containing pseudoceramides according to claim 1.

11. Use of pseudoceramides according to claim 1 as "synthetic barrier lipids" for the production of skin care products.