EP0973496A1

EP0973496A1 - USE OF LOW MOLECULAR OLIGOMER ESTERS OF $g(a)-HYDROXY ACIDS AND/OR AROMATIC OF o-HYDROXY ACIDS IN COSMETIC FORMULATIONS

Info

Publication number: EP0973496A1
Application number: EP98921437A
Authority: EP
Inventors: Berthold Nies; Wolfgang Ritter
Original assignee: Merck Patent GmbH
Current assignee: Merck Patent GmbH
Priority date: 1997-04-10
Filing date: 1998-04-07
Publication date: 2000-01-26
Also published as: JP2001521508A; DE19714765A1; HUP0001693A2; CN1251034A; AU7429598A; PL335423A1; KR20000076112A; WO1998044903A1; CA2283517A1

Abstract

The invention relates to the use of low molecular oligomer esters of alpha -hydroxy acids and/or aromatic o-hydroxy acids in cosmetic formulations, wherein the corresponding alpha -hydroxy acid and/or aromatic o-hydroxy acid is controllably released by hydrolysis during use.

Description

Use of low molecular weight, oligomeric esters of α-hydroxy acids and / or aromatic o-hydroxy acids in cosmetic formulations

The invention relates to the use of low molecular weight, oligomeric

Esters of α-hydroxy acids and / or aromatic o-hydroxy acids in cosmetic formulations.

In recent years, the effects of α-hydroxy acids, abbreviated "AHA", have been increasingly investigated in modern cosmetology and used as an anti-aging substance. In German, these acids are often referred to as fruit acids, a name that indicates their natural occurrence. The most important fruit acids include, for example, glycolic acid (from sugar cane), lactic acid (from sour milk), citric acid (from citrus fruits), tartaric acid (from wine), malic acid (from apples) or pyruvic acid (from papaya fruits). But also the aromatic o-hydroxy acids, e.g. salicylic acid have the same effects.

The clinical and therapeutic effects of this AHA were first investigated in the 1980s and since then, dermatologists have used them in concentrations of more than 12% to treat extremely dry skin and chronic eczema. It has now been found that these acids have further effects on the skin. The skin became smoother, softer, impurities disappeared and the skin looked healthier during this treatment. The AHA probably work to the extent that they soften the glue-like substance that holds the outer layers of the epidermis together. This accelerates the normal exfoliation of the dead skin cells and smoothes fine wrinkles on the surface.

Salicylic acid, which has also long been used to treat acne, psoriasis, warts or dandruff, is of great importance as a keratolytic and keratoplastic substance in cosmetics, since its use causes a mild peeling of the skin.

A large number of cosmetic products are now flooding the market which contain such AHA or aromatic o-hydroxy acids and which are positioned as an anti-wrinkle cream or anti-aging product or as a product for regenerating the skin.

Another theory of the mode of action of the α-hydroxy acids and aromatic o-hydroxy acids in addition to the skin peeling already described, however, consists in the view that the AHA only irritate the skin, which leads to a slight swelling of the skin and thus leads to smoothing. If this effect is really behind the anti-aging results, the use of these free acids and their advantages must be difficult to question, especially with regard to the long-term effect.

The incorporation of the free acid into the cosmetic carrier has further disadvantages. On the one hand, the relatively low pH value can lead to considerable intolerance reactions; secondly, the readily water-soluble acids are washed out again shortly after application. Products that contain derivatives of these AHAs, which initially do not bring about a sharp drop in pH and from which the AHA would be released slowly over a longer period of time, would be desirable.

It was an object of the present invention to bring the AHA customary in cosmetics into a form which is insoluble in water, primarily does not lead to a massive drop in pH and from which the effective AHA is released over a long period of time.

It has now been found that α-hydroxy acids and / or aromatic o-hydroxy acids can be esterified to form water-insoluble, oligomeric products which can then hydrolyze in the presence of water and release the monomeric AHA.

The invention therefore relates to the use of low molecular weight, oligomeric esters of α-hydroxy acids and / or aromatic o-hydroxy acids in cosmetic formulations, the corresponding α-hydroxy acid and / or aromatic o-hydroxy acid being released in a controlled manner by hydrolysis during use.

Such polymers or oligomers are known in principle. For example, it is known that high polymeric esters of selected lower hydroxy acids, possess and in particular of lactic acid, high body vertäglichkeit be used in the surgical technique for example, as tolerated by the body and körperresorbierbares thread material degraded in the course of weeks or months and flushed out of the ^'body becomes. Oligomeric esters, in particular of lactic acid and / or of glycolic acid, which have an average degree of oligomation of up to 100, are known from DE 36 20 685. There the use of these esters as resorbable carriers and / or film formers in agents for covering human or animal skin is described.

However, the use of such oligomers in cosmetic preparations for the purpose of releasing the free hydroxy

10 acids described.

The oligomers according to the invention are notable for an average degree of oligomerization of the chosen acid of up to about 30 and preferably up to about 10.

In principle, polyester oligomers from hydroxycarboxylic acids can be obtained directly by polycondensation of the hydroxycarboxylic acids or

20 hydroxycarboxylic acid mixtures are produced, however, it is useful to adjust the degree of oligomerization in a known manner

Way to add co-reactants to regulate the degree of oligomerization, here primarily mono- or polyhydric alcohols or

“_ Organic acids can be considered. The two esters forming groups of the monomers or the oligomers, i.e. the hydroxyl group on the one hand and the carboxyl group on the other hand are generally suitable as reactive sites for this.

30

In particular, alcohols are preferred in preferred embodiments

'Up to 4, in particular with up to 3 hydroxyl groups into consideration, where monohydric alcohols can be of particular importance on the one hand, and dihydric and in particular trihydric alcohols on the other

³⁵ key position. In the latter case it is in particular the glycerin, which leads to extraordinarily varied products when reacted with the AHA oligomers. Examples of other suitable alcohols are: ethylene glycol, propylene glycol, 1, 3-butylene glycol, trimethyloipropane, low molecular weight polyethylene glycols, polypropylene glycol, 1, 5-pentanediol or higher alcohols.

In the field of the use of carboxylic acids, physiologically compatible carboxylic acids, in particular monocarboxylic acids, can be of interest, but also polyfunctional carboxylic acids, for example di- or tricarboxylic acids.

The oligomeric hydroxycarboxylic acids or their derivatives are prepared in a manner known per se. Of course, in all cases, i.e. Not only the free reactive components of the type mentioned, but also those derivatives which form the desired polyester oligomers in a manner known per se under the conditions of esterification or transesterification are used both in the case of the α-hydroxcarboxylic acids and in the case of the co-reactants . The esters of hydroxy acids are therefore suitable, for example, and the easily manageable dimerization products, e.g. lactic acid and / or glycolic acid, i.e. use the lactide and / or the glycolide.

The polycondensation reaction is usually carried out by heating the starting materials to a temperature above the melting point, preferably in the presence of a catalyst, in particular an esterification catalyst, under anhydrous conditions in an inert gas atmosphere. The amount and type of catalyst used determine the process temperature and the duration of the Implementation. Since the conversion of the reactions is normally almost 100%, the composition of the end products can be controlled well by adding the reactants. Such polycondensation reactions are well known to those skilled in the art. A detailed list of the most diverse reaction conditions is therefore not necessary at this point.

The invention also relates to low molecular weight oligomers

10 holding α-hydroxy acids and / or aromatic o-hydroxy acids, produced by reacting the monomeric α-hydroxy acids and / or aromatic o-hydroxy acids or their reactive derivatives with mono- or polyhydric alcohols or organic acids, for use in cosmetics Formulations, the corresponding α-hydroxy acid and / or aromatic o-hydroxy acid being released in a controlled manner by hydrolysis from these oligomers during use.

The α-hydroxy acids and o-hydroxy acids used are preferably the compounds listed below: glycolic acid and lactic acid, both of which occur in the metabolism of the living organism and can be processed or excreted by the body, whereby

25 the lactic acid is used in the form of its racemate or in the form of its optical antipodes or as any mixtures of the optical antipodes; Hydroxylbutyric acid, hydroxyvaleriaric acid, citric acid, tartaric acid, malic acid, trimethylene carbonate, ε-caprolactone, salicylic acid, m-hydroxybenzoic acid, p-hydroxybenzoic acid, gallic acid, or the like

Grape acid, benzilic acid, mandelic acid or pyruvic acid.

35 Glycolic acid and / or lactic acid or their dimerization products are very particularly preferably used.

So-called homooligomers are used in important embodiments of this invention. This means that only a single α-hydroxy acid or one of its reactive derivatives or only a single o-hydroxy acid or one of its reactive derivatives, e.g. only lactic acid or only salicylic acid can be used to prepare the oligomeric esters.

In a further preferred embodiment of this invention, so-called heterooligomers are used. This means that two or more different α-hydroxy acids and / or aromatic o-hydroxy acids are used in the polycondensation reaction to produce the oligomeric products. Mixtures of α-hydroxy acids and e.g. Salicylic acid can be used as monomers.

Particularly preferred oligomers are synthesized, for example, from the following monomers: glycerol, lactide and glycolide; Ethylene glycol, lactic acid and glycolic acid; Propylene glycol, lactide and glycolide; Glycerin and lactide; Glycerin, glycolic acid and hydroxylbutyric acid; Ethylene glycol and hydroxyvaleric acid; Glycerin and lactic acid ethyl ester; Glycerin, trimethylene carbonate and glycolic acid; Ethylene glycol and lactide; Ethylene glycol, glycolic acid and lactic acid ethyl ester; Glycerin, glycolic acid and ε-caprolactone.

The product of glycerin, lactide and glycolide looks like this, for example: H ₂ C - O - [- CO - CH (CH ₃ ) - O - CO - CH ₂ - O -] k-

I.

HC - O - [- CO - CH (CH ₃ ) - O - CO - CH ₂ - O -] l-

I.

H ₂ C - O - [- CO - CH (CH ₃ ) - O - CO - CH ₂ - O -] m—

wherein the sum k + l + m is preferably less than or equal to 12, particularly preferably less than or equal to 6 (based on lactide).

10

The list of previous connections is only a small one

Selection of particularly preferred products, it should by no means be limiting. 15

The heterooligomers generally have advantageous properties because, for example, they have a lower tendency to crystallize and the associated clouding. Furthermore, they can be broken down more quickly through a higher water absorption and hydrolysis rate.

On the other hand, this faster hydrolysis rate is responsible for the fact that the corresponding oligomer products are very sensitive to hydrolysis and in the usual water-containing cosmetic products

Preparations are not stable. It is therefore necessary to formulate them anhydrous. An advantageous way of solving this problem is the separate formulation of anhydrous AHA oligomers, optionally with suitable auxiliaries and a second water-containing one

OU component containing conventional auxiliaries for cosmetic preparations. Both components are only mixed directly before use for the finished cosmetic preparation. This can preferably be done with known mixing systems from (medicine) technology, 35 such as systems for mixing bone cements, reactive adhesives or impression materials. The double-chamber syringe known to the person skilled in the art with a static mixer attached can be mentioned as an example. With these mixing systems, the mixing ratio of oligomer phase to aqueous phase can also be easily adjusted and varied. Mixing ratios of 1:10 to 1: 1 are possible, for example. Mixing systems from MIXPAC Systems AG are also suitable, for example.

The invention therefore also relates to a cosmetic preparation consisting of a ready-to-use set of two or more separate components, one component of which is a water-free formulation of oligomer products according to at least one of the

Claims 1 to 7, optionally with further auxiliaries, and as another component a water-containing cosmetic formulation, optionally with further auxiliaries and additives customary in such cosmetic preparations.

The advantage of using the described oligomeric products is that there is primarily no sharp drop in pH which could irritate the skin. However, in the event of the hydrolytic attack on the oligomeric structure in situ, the monomeric AHA or the aromatic o-hydroxy acids are gradually released, and these can then trigger their known advantageous effects on the skin. Further, this can, of course, a larger amount of serving as a depot for the free acids oligomers are incorporated, ^'so that the effect is considerably improved compared to use of the free AHA. The components for the formulation of the corresponding cosmetic preparations can be selected from the large number of known and proven substances. The oligomeric esters of the α-hydroxy acids and / or aromatic o-hydroxy acids can be mixed well with the customary skin-care components and auxiliaries, advantageously using a water-free preparation.

In the separate formulation, on the one hand an anhydrous formulation of the oligomers is possibly prepared with suitable auxiliaries or additives and, on the other hand, a cosmetic preparation consisting of the usual skin-care components. For example, when producing an O / W cream, the oligomers can be contained in the oily phase, and the aqueous phase is formulated separately. Or it is also possible to prepare an oligomer mixture without any additives as one phase, the second aqueous phase then contains the remaining components which are customary for a skin-care preparation. The two separate phases are then only mixed before each application.

A number of common components and additives are listed below:

Fatty alcohols, fatty acid esters, especially triglycerides of fatty acids, fatty acids, lanolin, natural or synthetic oils or waxes, emulsifiers such as Tegacid special, Teginacide, Tego Care (all Th. Goldschmidt, Essen), Cremophore (BASF, Ludwigshafen), Emulgine ^" (Henkel , Düsseldorf), Hostace n DGS or Hostaphat (Hoechst), optionally perfume oils, low alcohols, glycols or polyols or also thickeners, such as silica. The cosmetic preparations according to the invention can contain the oligomeric products in amounts of approximately 5 to almost 100%, the use of the pure oligomer substance also being possible. The preferred content of oligomeric esters in the finished product is 5% to 50%.

Without further elaboration, it is assumed that a person skilled in the art can use the above description to the greatest extent. The preferred embodiments are therefore only to be understood as a descriptive disclosure, and in no way as a limitation in any way.

The full disclosure of all applications, patents, and publications listed above and below are incorporated by reference into this application.

The following examples are intended to illustrate the present invention.

example 1

4 moles of L-lactide and 1 mole of glycerol were melted in a conventional laboratory apparatus with nitrogen and stirring and then within

Heated to 190 ° C for 1 hour. The reaction was allowed to run at 188-192 ° C for 5 hours and the glycero-oligo-lactide product was hot filled. 0.5% o-phosphoric acid (based on the amount of lactide) had been added as catalyst. Example 2

In a conventional laboratory apparatus, 1 mol of glycerol, 2 mol of L-lactide and 1 mol of glycolide were heated to 195 ° C. in the course of one hour with nitrogen and stirring. The mixture was then allowed to react for 5 hours and the glycero-oligo-lactide-co-glycolide (1: 2: 1) was filled hot. As a catalyst, o-phosphoric acid was added, namely 0.5%, based on the sum of the amount of lactide and glycolide. The residual glycerol content is <2%.

10

Example 3

Analogously to Example 2, 1 mole of glycerol and 3 moles of glycolide were converted to a glycero-oligo-glycolide. A * Sn-Il-

Chloride solution in ether added (7 ml of a solution of 2.5 g of SnCl ₂ in 100 ml of ether).

20 Example 4

In a conventional laboratory apparatus, 1 mol of ethylene glycol and 1.5 mol of DL-lactic acid were rapidly heated to 150 ° C. under nitrogen and with stirring and then from 150 ° to 200 ° C. in the course of 6 hours. Then allowed to cool to 150 ° C, carefully evacuated and completed the conversion at 200 ° C and 10 torr. After 30 minutes the product was filled hot at approx. 150 ° C.

30

35 Example A

Production of a skin care cream

Phase I:

At 60 ° C., ethylene glycol oligolactide of the composition 1: 1.5 (preparation analogous to Example 4) and glycerol oligolactide of the composition 1: 5 (preparation analogous to Example 1) are mixed homogeneously in a ratio of 40:60. The mixture is filled into a 10 ml chamber of a 1: 1 double chamber syringe at this temperature. After cooling, this mixture has a honey-like consistency.

Phase II:

The aqueous phase contains:

3.0% propanediol-1, 2 (item no.107478) (1)

1.2% preservative (1) 0.25% methyl 4-hydroxybenzoate sodium salt

(Art.no.106756) (1)

2.0% TWEEN 80 (emulsifier) (1)

The viscosity of phase II is adjusted to that of phase I at room temperature by adding polyacrylic acid sodium salt. Phase II is then filled into the second chamber of the double-chamber syringe. The double-chamber syringe is closed as usual.

Source of supply:

(1) Merck KGaA, Darmstadt

Claims

claims

1. Use of low molecular weight, oligomeric esters of α-hydroxy acids and / or aromatic o-hydroxy acids in cosmetic formulations, the corresponding α-hydroxy acid and / or aromatic o-hydroxy acid being released in a controlled manner by hydrolysis during use.

2. Use according to claim 1, characterized in that the low molecular weight oligomers are obtained by reacting the monomeric α-hydroxy acids and / or aromatic o-hydroxy acids or their reactive derivatives with mono- or polyhydric alcohols or organic acids.

3. Use according to claim 1 or 2, characterized in that homooligomers, in the preparation of which a monomeric α-hydroxy acid or aromatic o-hydroxy acid is used alone.

4. Use according to claim 1 or 2, characterized in that 5 one uses heterooligomers, in the production of which several different monomeric α-hydroxy acids and / or aromatic o-hydroxy acids are used.

5. Use according to one of claims 1 to 4, characterized in that preferably oligomeric reaction products of lactic acid, glycolic acid and / or o-salicylic acid or their reactive derivatives are reacted with mono- or polyhydric alcohols or organic acids.

6. Use according to one of claims 1 to 5, characterized in that oligomers with an average degree of oligomerization up to about 30, preferably up to about 10 are used.

7. Low molecular weight oligomers containing α-hydroxy acids and / or aromatic o-hydroxy acids, produced by reacting the monomeric α-hydroxy acids and / or aromatic o-hydroxy acids or their reactive derivatives with mono- or polyhydric alcohols or organic acids, for use in cosmetic formulations , the corresponding α-hydroxy acid and / or aromatic o-hydroxy acid being released in a controlled manner by hydrolysis from these oligomers.

8. Cosmetic preparation consisting of a ready-to-use set of two or more separate components, one component of which is a water-free formulation of oligomer products according to at least one of claims 1 to 7, optionally with further auxiliaries, and as another component a water-containing cosmetic formulation, optionally with other auxiliary and customary in such cosmetic preparations

Additives.