CA2283517A1 - Use of low molecular oligomer esters of .alpha.-hydroxy acids and/or aromatic of o-hydroxy acids in cosmetic formulations - Google Patents
Use of low molecular oligomer esters of .alpha.-hydroxy acids and/or aromatic of o-hydroxy acids in cosmetic formulations Download PDFInfo
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- CA2283517A1 CA2283517A1 CA002283517A CA2283517A CA2283517A1 CA 2283517 A1 CA2283517 A1 CA 2283517A1 CA 002283517 A CA002283517 A CA 002283517A CA 2283517 A CA2283517 A CA 2283517A CA 2283517 A1 CA2283517 A1 CA 2283517A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
- A61K8/375—Esters of carboxylic acids the alcohol moiety containing more than one hydroxy group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/10—Washing or bathing preparations
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
- A61K2800/28—Rubbing or scrubbing compositions; Peeling or abrasive compositions; Containing exfoliants
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
~I~,E, PIN IN THIS AMENDED
~FXT TRANSLATION
Use of low molecular weight, oligomeric esters of a-hydroxy acids and/or aromatic o-hydroxy acids in cosmetic formulations The invention relates to the use of low molecular weight, oligomeric esters of a-hydroxy acids and/or aromatic o-hydroxy acids in cosmetic formulations.
In recent years a-hydroxy acids called "AHAs~~
for short, have been investigated for their activity to an increased extent in modern cosmetology and have been used as an anti-ageing substance. These acids are often also referred to as fruit acids, a name which indicates . their natural origin. Examples of the most important fruit acids are glycolic acids (from sugar cane), . lactic acid (from sour milk), citric acid (from citrus fruits), tartaric acid (from wine), malic acid (from apples) and also pyruvic acid (from papaya fruits).
However, aromatic o-hydroxy acids, such as, for example, salicylic acid, also have the same effects.
The clinical and therapeutic activity of these AHAs was first investigated during the 1980s and since this time they have been used by dermatologists in concentrations of more than 12~ for the treatment of extremely dry skin and chronic eczema. In this connection, it has now been shown that these acids have other effects on the skin. During treatment the skin became smoother, softer, impurities disappeared and the skin looked more healthy.
The AHAs in fact work by softening the glutinous substance which holds the outer layers of the epidermis together. This accelerates normal desquama-tion of the dead skin cells and fine surface lines are smoothed in the process.
Salicylic acid too, which has likewise been used for a long time for the treatment of acne, psoriasis, warts or dandruff is of great importance as a keratolytically and keratoplastically acting aI0 98/44903 - 2 - PCT/EP98/02013 substance in cosmetics since its use effects mild peeling of the skin.
The market is now being flooded by a large number of cosmetic products which comprise such AHAs and also aromatic o-hydroxy acids and are positioned as antiwrinkle cream or antiageing product or as product for regenerating the skin.
Another theory for the mode of action of the a-hydroxy acids and aromatic o-hydroxy acids, in addition to the skin peeling already described, consists, however, in the view that the AHAs merely irritate the skin, which leads to a slight swelling of the skin and thus to smoothing. Should this effect actually lie behind the antiageing results, then the use of these free acids and their advantages must be called into serious question, particularly with regard to the long-term effect.
Incorporation of the free acid into the cosmetic carrier has further disadvantages. Firstly, the relatively low pH can lead to considerable incompatibility reactions, secondly the readily water-soluble acids are washed out again shortly after application.
Products which comprise derivatives of these AHAs which initially do not bring about a great drop in pH and from which the AHAs would be released slowly over a relatively long period would be desirable.
The object of the present invention was then to bring the AHAs customary in cosmetics into a form which is insoluble in water and primarily does not lead to a massive drop in the pH and from which the effective AHAs are released over a relatively long period.
It has now been found that a-hydroxy acids and/or aromatic o-hydroxy acids can be esterified to be water-insoluble, oligomeric products which can then hydrolyse in the presence' of water and release the monomeric AHAs.
The invention thus provides the use of low _, _ __ _ . __ . _ _ _ ~'r _...r~C.r'..~.a~Gi VY'L''l~ill., Wy~~Gllt~il~. e:7l.C~...J 'u~ ~~l"1 r~L'.._ C.3.L4J
i :iiay G
' ~ WO 98/44903 - 3 - PCT/EP98/02013 and/or aromatic o-hydroxy acids in cosmetic formula-tions, the corresponding a-hydroxy acid and/or aromatic o-hydroxy acid being controllably released by hydrolysis during use.
In principle, such polymers and oligomers are known. For example, it is known that highly polymeric esters of selected lower hydroxy acids, and in particular of lactic acid, are well tolerated by the body and are used in operative techniques, for example, as body-compatible and body-absorbable thread material, which is degraded over a period of weeks or months and flushed out of the body.
Oligomeric esters, in particular of lactic acid and/or of glycolic acid which have an average degree of oligomerization of up to 100 are disclosed in DE 36 20 685. The latter describes the use in these esters as absorbable carriers and/or film formers in compositions for covering human or animal skin.
However, the use of such oligomers in cosmetic preparations for the purpose of releasing free hydroxy acids is not described anywhere.
The oligomers according to the invention are characterized by an average degree of oligomerization of the chosen acid up to about 30 and preferably up to about 10.
Polyester oligomers from hydroxycarboxylic acids can in principle be prepared directly by poly-condensation of the hydroxycarboxylic acids or hydroxy-carboxylic acid mixtures, but it is useful for the specific setting of the degree of oligomerization to add, in a known manner, coreactants for the regulation of the degree of oligomerization, where mono- or polyhydric alcohols or organic acids may primarily be suitable here. The two ester-forming groups of the monomers or of the oligomers, i.e. the hydroxyl group on the one hand and the carboxyl group on the other hand, in fact generally suggest themselves as reactive sites.
- , In particular, in preferred embodiments alcohols having up to 4 , in particular having up to 3 , hydroxyl groups are suitable, it being possible here for monohydric alcohols on the one hand to have particular importance, and on the other hand di- and, in particular trihydric alcohols can adopt a key position. In the last-mentioned case, the alcohol is in particular glycerol, which leads to extremely varied products by reaction with the AHA oligomers. Examples of other suitable alcohols are: ethylene glycol, propylene glycol, 1,3-butylene glycol, trimethylol-propane, low molecular weight polyethylene glycols, polypropylene glycol, 1,5-pentanediol or alternatively more highly hydric alcohols.
In the field of the co-use of carboxylic acids, on the one hand physiologically tolerable carboxylic acids, in this case in particular monocarboxylic acids, may 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 . a . both in the case of the a-hydroxycarboxylic acids and in the case of the co-reactants - not only the respective free reactive components of the type mentioned, but also those derivatives may be employed which form the desired polyester oligomers in a manner known per se under the conditions of the esterification or transesterifica-tion. The esters of the hydroxy acids, for example, are thus suitable, furthermore also the easy-to-handle dimerization products, for example, of lactic acid and/or glycolic acid, i.e. the lactide and/or the glycolide, can be used.
The polycondensation reaction is in this case customarily carried out by heating the starting materials to a temperature above the melting point, preferably in the presence of a catalyst, in particular of an esterification catalyst, under anhydrous con ditions in an inert-gas atmosphere. The amount and type of the catalyst used determine the process temperature and the duration of the reaction. Since the conversion of the reactions is normally almost 100, the composition of the final products can be easily controlled by the addition of the reactants.
Polycondensation reactions of this type are well known to the person skilled in the art. A detailed listing of a very wide variety of reaction conditions is therefore not necessary here.
The invention also provides low molecular weight oligomers comprising a-hydroxy acids and/or aromatic o-hydroxy acids, prepared by reaction of the monomeric a-hydroxy acids and/or aromatic o-hydroxy acids or reactive derivatives thereof with mono- or ' 15 polyhydric alcohols or organic acids, for use in cosmetic formulations, the corresponding a-hydroxy acid and/or aromatic o-hydroxy acid being controllably released from these oligomers by hydrolysis during use.
The a-hydroxy acids and o-hydroxy acids used are preferably the compounds listed in the following:
glycolic acid and lactic acid, which both occur in the metabolism of the living organism and are processed and excreted by the body, lactic acid being used here in the form of its racemate or alternatively in the form of its optical antipodes or as any desired mixtures of the optical antipodes; a-hydroxybutyric acid, a-hydroxyvaleric acid, citric acid, tartaric acid, malic acid, trimethylene carbonate, s-caprolactone, salicylic acid, m-hydroxybenzoic acid, p-hydroxybenzoic acid, gallic acid, racemic acid, benzilic acid, mandelic acid or alternatively pyruvic acid.
Very particular preference is given in this case to glycolic acid and/or lactic acid or dimeriza-tion products thereof.
In important embodiments of this invention, homooligomers are used. This means that only a single a-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, are used to prepare the oligomeric esters.
In a further, preferred embodiment of this invention, heterooligomers are used. This means that in the polycondensation reaction for the preparation of the oligomeric products two or more different a-hydroxy acids and/or aromatic o-hydroxy acids are used. It is, therefore, also possible to use mixtures of a-hydroxy acids and, for example, salicylic acid 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; glycerol and lactide; glycerol, glycolic acid and hydroxybutyric acid; ethylene glycol and hydroxyvaleric acid; glycerol and ethyl lactate;
glycerol, trimethylene carbonate and glycolic acid;
ethylene glycol and lactide; ethylene glycol, glycolic acid and ethyl lactate; glycerol, glycolic acid and E-caprolactone.
In this connection, the product of glycerol, lactide and glycolide looks, for example, as follows:
H2C-O- [ -CO-CH ( CH3 ) -O-CO-CH2-0- ] k-HC-O- [ -CO-CH ( CH3 ) -O-CO-CHZ-O- J 1-HZC-0- [ -CO-CH ( CH3 ) -O-CO-CH2-0- ] nr--where the sum k+1+m is preferably less than or equal to 12, particularly preferably less than or equal to 6 (based on lactide).
The listing of the preceding compounds is only a small selection of particularly preferred products and should in no case have limiting character.
The heterooligomers generally have advantageous properties since they show lower tendency towards crystallization and the onset of clouding associated therewith. In addition, they can be more rapidly degraded on account of higher water absorption and hydrolysis rate.
On the other hand, this more rapid hydrolysis rate is responsible for the fact that the corresponding oligomer products are very sensitive to hydrolysis and are unstable in customary hydrous cosmetic preparations. It is therefore necessary to formulate them without water. One advantageous way of solving this problem is the separate formulation of anhydrous AHA oligomers optionally with suitable auxiliaries and a second hydrous component which comprises the auxiliaries customary for cosmetic preparations. The two components are only mixed directly prior to application of the finished cosmetic preparation. This can, preferably, be carried out using mixing systems which are known per se from (medical) technology, such as, for example, systems for mixing bone cements, reactive adhesives or moulding materials. An example which can be mentioned is the double chamber syringe with attached static mixer which is known to a person skilled in the art. In the case of these mixing systems it is also possible to simply adjust and vary the mixing ratio of oligomer phase to aqueous phase. Thus, for example, mixing ratios of from 1:10 to 1:1 are possible. Also suitable are, for example, mixing systems from MIXPAC Systems AG.
The invention thus also provides a cosmetic preparation consisting of a ready-to-use set of two or more separate components, of which one component comprises an anhydrous formulation of oligomer products according to at least one of Claims 1 to 7, optionally with other auxiliaries, and as one other component comprises a water-containing cosmetic formulation, optionally with other auxiliaries and additives customary in such cosmetic preparations.
The advantage of using the described oligomeric products is then that there is primarily no great reduction in pH, which could irritate the skin.
However, during hydrolytic attack of the, oligomeric ' PTO 98/44903 - 8 - pCT/EP98/02013 structure in situ the monomeric AHAs and the aromatic o-hydroxy acids are gradually released, and can then trigger their known advantageous effects on the skin.
In addition, it is of course possible for a relatively large amount of these oligomers, which serve as donor for the free acids, to be incorporated, meaning that the effect is considerably better compared with the use of free AHAs.
The components for formulating corresponding cosmetic preparations can be chosen from the large number of known and proven substances. The oligomer esters of a-hydroxy acids and/or aromatic o-hydroxy acids can be readily mixed with customary skincare components and auxiliaries, recourse advantageously ' 15 being had to an anhydrous preparation.
In the case of the separate formulation, on the one hand an anhydrous formulation of the oligomers possibly with suitable auxiliaries or additives is prepared and on the other hand a cosmetic preparation consisting of the customary skincare components. For example, in the preparation of an O/W cream, the oligomers can be present in the oily phase, the aqueous phase is formulated separately. Or, it is also possible to prepare an oligomer mixture without any additives as one phase, the remaining components customary for a skincare preparation then being present in the second aqueous phase. The two separate phases are then only mixed in each case prior to application.
A number of customary components and additives may be listed below:
Fatty alcohols, fatty acid esters, in particular triglycerides of fatty acids, fatty acids, lanolin, natural or synthetic oils or waxes, emulsifiers such as, for example, Tegacid special, Teginacids, Tego Care (all from Th. Goldschmidt, Essen), Cremophors (BASF, Ludwigshafen), Emulgins (Henkel, Diisseldorf), Hostacerin DGS or alternatively Hostaphat (Hoechst), optionally perfume oils, lower ' WO 98/44903 - 9 - PCT/EP98/02013 alcohols, glycols or polyols and also thickeners such as, for example, silica.
The cosmetic preparations according to the invention may comprise the oligomer products in amounts of from about 5 up to nearly 100, use of the pure oligomer substance also being possible. The preferred content of oligomer esters in the finished product is from 5~ to 50~.
It is assumed that a person skilled in the art can utilize the above description in the widest sense without further detail. Preferred embodiments are thus merely to be perceived as a descriptive disclosure which is in no way limiting.
The complete disclosure of all applications, " 15 patents and publications listed above and below are incorporated into this application by reference.
The examples below serve to illustrate the present invention.
~FXT TRANSLATION
Use of low molecular weight, oligomeric esters of a-hydroxy acids and/or aromatic o-hydroxy acids in cosmetic formulations The invention relates to the use of low molecular weight, oligomeric esters of a-hydroxy acids and/or aromatic o-hydroxy acids in cosmetic formulations.
In recent years a-hydroxy acids called "AHAs~~
for short, have been investigated for their activity to an increased extent in modern cosmetology and have been used as an anti-ageing substance. These acids are often also referred to as fruit acids, a name which indicates . their natural origin. Examples of the most important fruit acids are glycolic acids (from sugar cane), . lactic acid (from sour milk), citric acid (from citrus fruits), tartaric acid (from wine), malic acid (from apples) and also pyruvic acid (from papaya fruits).
However, aromatic o-hydroxy acids, such as, for example, salicylic acid, also have the same effects.
The clinical and therapeutic activity of these AHAs was first investigated during the 1980s and since this time they have been used by dermatologists in concentrations of more than 12~ for the treatment of extremely dry skin and chronic eczema. In this connection, it has now been shown that these acids have other effects on the skin. During treatment the skin became smoother, softer, impurities disappeared and the skin looked more healthy.
The AHAs in fact work by softening the glutinous substance which holds the outer layers of the epidermis together. This accelerates normal desquama-tion of the dead skin cells and fine surface lines are smoothed in the process.
Salicylic acid too, which has likewise been used for a long time for the treatment of acne, psoriasis, warts or dandruff is of great importance as a keratolytically and keratoplastically acting aI0 98/44903 - 2 - PCT/EP98/02013 substance in cosmetics since its use effects mild peeling of the skin.
The market is now being flooded by a large number of cosmetic products which comprise such AHAs and also aromatic o-hydroxy acids and are positioned as antiwrinkle cream or antiageing product or as product for regenerating the skin.
Another theory for the mode of action of the a-hydroxy acids and aromatic o-hydroxy acids, in addition to the skin peeling already described, consists, however, in the view that the AHAs merely irritate the skin, which leads to a slight swelling of the skin and thus to smoothing. Should this effect actually lie behind the antiageing results, then the use of these free acids and their advantages must be called into serious question, particularly with regard to the long-term effect.
Incorporation of the free acid into the cosmetic carrier has further disadvantages. Firstly, the relatively low pH can lead to considerable incompatibility reactions, secondly the readily water-soluble acids are washed out again shortly after application.
Products which comprise derivatives of these AHAs which initially do not bring about a great drop in pH and from which the AHAs would be released slowly over a relatively long period would be desirable.
The object of the present invention was then to bring the AHAs customary in cosmetics into a form which is insoluble in water and primarily does not lead to a massive drop in the pH and from which the effective AHAs are released over a relatively long period.
It has now been found that a-hydroxy acids and/or aromatic o-hydroxy acids can be esterified to be water-insoluble, oligomeric products which can then hydrolyse in the presence' of water and release the monomeric AHAs.
The invention thus provides the use of low _, _ __ _ . __ . _ _ _ ~'r _...r~C.r'..~.a~Gi VY'L''l~ill., Wy~~Gllt~il~. e:7l.C~...J 'u~ ~~l"1 r~L'.._ C.3.L4J
i :iiay G
' ~ WO 98/44903 - 3 - PCT/EP98/02013 and/or aromatic o-hydroxy acids in cosmetic formula-tions, the corresponding a-hydroxy acid and/or aromatic o-hydroxy acid being controllably released by hydrolysis during use.
In principle, such polymers and oligomers are known. For example, it is known that highly polymeric esters of selected lower hydroxy acids, and in particular of lactic acid, are well tolerated by the body and are used in operative techniques, for example, as body-compatible and body-absorbable thread material, which is degraded over a period of weeks or months and flushed out of the body.
Oligomeric esters, in particular of lactic acid and/or of glycolic acid which have an average degree of oligomerization of up to 100 are disclosed in DE 36 20 685. The latter describes the use in these esters as absorbable carriers and/or film formers in compositions for covering human or animal skin.
However, the use of such oligomers in cosmetic preparations for the purpose of releasing free hydroxy acids is not described anywhere.
The oligomers according to the invention are characterized by an average degree of oligomerization of the chosen acid up to about 30 and preferably up to about 10.
Polyester oligomers from hydroxycarboxylic acids can in principle be prepared directly by poly-condensation of the hydroxycarboxylic acids or hydroxy-carboxylic acid mixtures, but it is useful for the specific setting of the degree of oligomerization to add, in a known manner, coreactants for the regulation of the degree of oligomerization, where mono- or polyhydric alcohols or organic acids may primarily be suitable here. The two ester-forming groups of the monomers or of the oligomers, i.e. the hydroxyl group on the one hand and the carboxyl group on the other hand, in fact generally suggest themselves as reactive sites.
- , In particular, in preferred embodiments alcohols having up to 4 , in particular having up to 3 , hydroxyl groups are suitable, it being possible here for monohydric alcohols on the one hand to have particular importance, and on the other hand di- and, in particular trihydric alcohols can adopt a key position. In the last-mentioned case, the alcohol is in particular glycerol, which leads to extremely varied products by reaction with the AHA oligomers. Examples of other suitable alcohols are: ethylene glycol, propylene glycol, 1,3-butylene glycol, trimethylol-propane, low molecular weight polyethylene glycols, polypropylene glycol, 1,5-pentanediol or alternatively more highly hydric alcohols.
In the field of the co-use of carboxylic acids, on the one hand physiologically tolerable carboxylic acids, in this case in particular monocarboxylic acids, may 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 . a . both in the case of the a-hydroxycarboxylic acids and in the case of the co-reactants - not only the respective free reactive components of the type mentioned, but also those derivatives may be employed which form the desired polyester oligomers in a manner known per se under the conditions of the esterification or transesterifica-tion. The esters of the hydroxy acids, for example, are thus suitable, furthermore also the easy-to-handle dimerization products, for example, of lactic acid and/or glycolic acid, i.e. the lactide and/or the glycolide, can be used.
The polycondensation reaction is in this case customarily carried out by heating the starting materials to a temperature above the melting point, preferably in the presence of a catalyst, in particular of an esterification catalyst, under anhydrous con ditions in an inert-gas atmosphere. The amount and type of the catalyst used determine the process temperature and the duration of the reaction. Since the conversion of the reactions is normally almost 100, the composition of the final products can be easily controlled by the addition of the reactants.
Polycondensation reactions of this type are well known to the person skilled in the art. A detailed listing of a very wide variety of reaction conditions is therefore not necessary here.
The invention also provides low molecular weight oligomers comprising a-hydroxy acids and/or aromatic o-hydroxy acids, prepared by reaction of the monomeric a-hydroxy acids and/or aromatic o-hydroxy acids or reactive derivatives thereof with mono- or ' 15 polyhydric alcohols or organic acids, for use in cosmetic formulations, the corresponding a-hydroxy acid and/or aromatic o-hydroxy acid being controllably released from these oligomers by hydrolysis during use.
The a-hydroxy acids and o-hydroxy acids used are preferably the compounds listed in the following:
glycolic acid and lactic acid, which both occur in the metabolism of the living organism and are processed and excreted by the body, lactic acid being used here in the form of its racemate or alternatively in the form of its optical antipodes or as any desired mixtures of the optical antipodes; a-hydroxybutyric acid, a-hydroxyvaleric acid, citric acid, tartaric acid, malic acid, trimethylene carbonate, s-caprolactone, salicylic acid, m-hydroxybenzoic acid, p-hydroxybenzoic acid, gallic acid, racemic acid, benzilic acid, mandelic acid or alternatively pyruvic acid.
Very particular preference is given in this case to glycolic acid and/or lactic acid or dimeriza-tion products thereof.
In important embodiments of this invention, homooligomers are used. This means that only a single a-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, are used to prepare the oligomeric esters.
In a further, preferred embodiment of this invention, heterooligomers are used. This means that in the polycondensation reaction for the preparation of the oligomeric products two or more different a-hydroxy acids and/or aromatic o-hydroxy acids are used. It is, therefore, also possible to use mixtures of a-hydroxy acids and, for example, salicylic acid 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; glycerol and lactide; glycerol, glycolic acid and hydroxybutyric acid; ethylene glycol and hydroxyvaleric acid; glycerol and ethyl lactate;
glycerol, trimethylene carbonate and glycolic acid;
ethylene glycol and lactide; ethylene glycol, glycolic acid and ethyl lactate; glycerol, glycolic acid and E-caprolactone.
In this connection, the product of glycerol, lactide and glycolide looks, for example, as follows:
H2C-O- [ -CO-CH ( CH3 ) -O-CO-CH2-0- ] k-HC-O- [ -CO-CH ( CH3 ) -O-CO-CHZ-O- J 1-HZC-0- [ -CO-CH ( CH3 ) -O-CO-CH2-0- ] nr--where the sum k+1+m is preferably less than or equal to 12, particularly preferably less than or equal to 6 (based on lactide).
The listing of the preceding compounds is only a small selection of particularly preferred products and should in no case have limiting character.
The heterooligomers generally have advantageous properties since they show lower tendency towards crystallization and the onset of clouding associated therewith. In addition, they can be more rapidly degraded on account of higher water absorption and hydrolysis rate.
On the other hand, this more rapid hydrolysis rate is responsible for the fact that the corresponding oligomer products are very sensitive to hydrolysis and are unstable in customary hydrous cosmetic preparations. It is therefore necessary to formulate them without water. One advantageous way of solving this problem is the separate formulation of anhydrous AHA oligomers optionally with suitable auxiliaries and a second hydrous component which comprises the auxiliaries customary for cosmetic preparations. The two components are only mixed directly prior to application of the finished cosmetic preparation. This can, preferably, be carried out using mixing systems which are known per se from (medical) technology, such as, for example, systems for mixing bone cements, reactive adhesives or moulding materials. An example which can be mentioned is the double chamber syringe with attached static mixer which is known to a person skilled in the art. In the case of these mixing systems it is also possible to simply adjust and vary the mixing ratio of oligomer phase to aqueous phase. Thus, for example, mixing ratios of from 1:10 to 1:1 are possible. Also suitable are, for example, mixing systems from MIXPAC Systems AG.
The invention thus also provides a cosmetic preparation consisting of a ready-to-use set of two or more separate components, of which one component comprises an anhydrous formulation of oligomer products according to at least one of Claims 1 to 7, optionally with other auxiliaries, and as one other component comprises a water-containing cosmetic formulation, optionally with other auxiliaries and additives customary in such cosmetic preparations.
The advantage of using the described oligomeric products is then that there is primarily no great reduction in pH, which could irritate the skin.
However, during hydrolytic attack of the, oligomeric ' PTO 98/44903 - 8 - pCT/EP98/02013 structure in situ the monomeric AHAs and the aromatic o-hydroxy acids are gradually released, and can then trigger their known advantageous effects on the skin.
In addition, it is of course possible for a relatively large amount of these oligomers, which serve as donor for the free acids, to be incorporated, meaning that the effect is considerably better compared with the use of free AHAs.
The components for formulating corresponding cosmetic preparations can be chosen from the large number of known and proven substances. The oligomer esters of a-hydroxy acids and/or aromatic o-hydroxy acids can be readily mixed with customary skincare components and auxiliaries, recourse advantageously ' 15 being had to an anhydrous preparation.
In the case of the separate formulation, on the one hand an anhydrous formulation of the oligomers possibly with suitable auxiliaries or additives is prepared and on the other hand a cosmetic preparation consisting of the customary skincare components. For example, in the preparation of an O/W cream, the oligomers can be present in the oily phase, the aqueous phase is formulated separately. Or, it is also possible to prepare an oligomer mixture without any additives as one phase, the remaining components customary for a skincare preparation then being present in the second aqueous phase. The two separate phases are then only mixed in each case prior to application.
A number of customary components and additives may be listed below:
Fatty alcohols, fatty acid esters, in particular triglycerides of fatty acids, fatty acids, lanolin, natural or synthetic oils or waxes, emulsifiers such as, for example, Tegacid special, Teginacids, Tego Care (all from Th. Goldschmidt, Essen), Cremophors (BASF, Ludwigshafen), Emulgins (Henkel, Diisseldorf), Hostacerin DGS or alternatively Hostaphat (Hoechst), optionally perfume oils, lower ' WO 98/44903 - 9 - PCT/EP98/02013 alcohols, glycols or polyols and also thickeners such as, for example, silica.
The cosmetic preparations according to the invention may comprise the oligomer products in amounts of from about 5 up to nearly 100, use of the pure oligomer substance also being possible. The preferred content of oligomer esters in the finished product is from 5~ to 50~.
It is assumed that a person skilled in the art can utilize the above description in the widest sense without further detail. Preferred embodiments are thus merely to be perceived as a descriptive disclosure which is in no way limiting.
The complete disclosure of all applications, " 15 patents and publications listed above and below are incorporated into this application by reference.
The examples below serve to illustrate the present invention.
2 0 Exaa~le 1 4 Mol of L-lactide and 1 mol of glycerol were melted under nitrogen and with stirring in a customary bench apparatus and then heated to 190°C over the course of 1 hour. The reaction was left to proceed at 25 188 - 192°C for 5 h, and the glycero-oligo-lactide product was drawn off whilst hot. 0.5~ of o-phosphoric acid (based on the amount of lactide) had been added as catalyst.
3 0 Exaa~le 2 1 Mol of glycerol, 2 mol of L-lactide and 1 mol of glycolide were heated to 195°C over the course of one hour under nitrogen and with stirring in a customary bench apparatus. The mixture was then left to 35 react for 5 hours, and the glycero-oligo-lactide coglycolide (1:2:1) was drawn off whilst hot. The catalyst added was o-phosphoric acid, in an amount of 0.5~ based on the total amount of lactide and glycolide. The residual content of glycerol was _< 2~.
' WO 98/44903 - 10 - PCT/EP98/02013 Exaa~le 3 1 Mol of glycerol and 3 mol of glycolide were reacted as in Example 2 to give a glycero-oligo-glycolide. The catalyst added here was an Sn(II) chloride solution in ether (7 ml of a solution of 2.5 g of SnCl2 in 1000 ml of ether).
Exa~le 4 1 Mol of ethylene glycol and 1.5 mol of DL-lactic acid were heated up to from 150° to 200°C
over the course of 6 hours under nitrogen and with stirring in a customary bench apparatus. The system was then cooled to 150°C and carefully evacuated, and conversion was completed at 200°C and 10 torr. After 30 minutes, the product was drawn off at about 150°C
whilst hot.
Example A
Preparation of a skincare cream Phase I:
At 60°C, ethylene glycol oligolactide of the com-position 1:1.5 (preparation as in Example 4) and glycerol oligolactide of the composition 1:5 (prepara-tion as in Example 1) in the ratio 40:60 are mixed homogeneously. The mixture is transferred at this temperature to a 10 ml chamber of a 1:1 double-chamber syringe. After cooling, this mixture has a honey-like consistency.
i ' ~ WO 98/44903 - 11 - PCT/EP98/02013 Phase II:
The aqueous phase comprises:
3.0~ of 1,2-propanediol (Art. No. 107478) (1~
1.2~ of preservative 0.25 of methyl-4-hydroxybenzoate, sodium salt (Art. No. 106756) (1) 2.0~ of TWEFN 80 (emulsifier) (1) Polyacrylic acid, sodium salt is added to match the viscosity of phase II to that of phase I at room temperature. Phase II is then introduced into the second chamber of the double-chamber syringe. The ' 10 double-chamber syringe is closed in the normal manner.
Source of supply:
(1) Merck KGaA, Darmstadt
' WO 98/44903 - 10 - PCT/EP98/02013 Exaa~le 3 1 Mol of glycerol and 3 mol of glycolide were reacted as in Example 2 to give a glycero-oligo-glycolide. The catalyst added here was an Sn(II) chloride solution in ether (7 ml of a solution of 2.5 g of SnCl2 in 1000 ml of ether).
Exa~le 4 1 Mol of ethylene glycol and 1.5 mol of DL-lactic acid were heated up to from 150° to 200°C
over the course of 6 hours under nitrogen and with stirring in a customary bench apparatus. The system was then cooled to 150°C and carefully evacuated, and conversion was completed at 200°C and 10 torr. After 30 minutes, the product was drawn off at about 150°C
whilst hot.
Example A
Preparation of a skincare cream Phase I:
At 60°C, ethylene glycol oligolactide of the com-position 1:1.5 (preparation as in Example 4) and glycerol oligolactide of the composition 1:5 (prepara-tion as in Example 1) in the ratio 40:60 are mixed homogeneously. The mixture is transferred at this temperature to a 10 ml chamber of a 1:1 double-chamber syringe. After cooling, this mixture has a honey-like consistency.
i ' ~ WO 98/44903 - 11 - PCT/EP98/02013 Phase II:
The aqueous phase comprises:
3.0~ of 1,2-propanediol (Art. No. 107478) (1~
1.2~ of preservative 0.25 of methyl-4-hydroxybenzoate, sodium salt (Art. No. 106756) (1) 2.0~ of TWEFN 80 (emulsifier) (1) Polyacrylic acid, sodium salt is added to match the viscosity of phase II to that of phase I at room temperature. Phase II is then introduced into the second chamber of the double-chamber syringe. The ' 10 double-chamber syringe is closed in the normal manner.
Source of supply:
(1) Merck KGaA, Darmstadt
Claims (8)
1. Use of low molecular weight, oligomeric esters of .alpha.-hydroxy acids and/or aromatic o-hydroxy acids in cosmetic formulations, the corresponding .alpha.-hydroxy acid and/or aromatic o-hydroxy acid being controllably released by hydrolysis during use.
2. Use according to Claim 1, characterized in that the low molecular weight oligomers are obtained by reaction of the monomeric .alpha.-hydroxy acids and/or aromatic o-hydroxy acids or also reactive derivatives thereof with mono- or polyhydric alcohols or organic acids.
3. Use according to Claim 1 or 2, characterized in that homooligomers are used which are prepared using just one monomeric .alpha.-hydroxy acid or aromatic o-hydroxy acid.
4. Use according to Claim 1 or 2, characterized in that heterooligomers are used which are prepared using two or more different monomeric .alpha.-hydroxy acids and/or aromatic o-hydroxy acids.
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 having an average degree of oligomerization up to about 30, preferably up to about 10, are used.
7. Low molecular weight oligomers comprising .alpha.-hydroxy acids and/or aromatic o-hydroxy acids, prepared by reaction of monomeric .alpha.-hydroxy acids and/or aromatic o-hydroxy acids or reactive derivatives thereof with mono- or polyhydric alcohols or organic acids, for use in cosmetic formulations, the corresponding .alpha.-hydroxy acid and/or aromatic o-hydroxy acid being controllably released from these oligomers by hydrolysis during use.
8. Cosmetic preparation consisting of a ready-to-use set of two or more separate components, of which one component comprises an anhydrous formulation of oligomer products according to at least one of Claims 1 to 7, optionally with other auxiliaries, and as one other component comprises a water-containing cosmetic formulation, optionally with other auxiliaries and additives customary in such cosmetic preparations.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19714765A DE19714765A1 (en) | 1997-04-10 | 1997-04-10 | Use of low molecular weight, oligomeric esters of alpha-hydroxy acids and / or aromatic o-hydroxy acids in cosmetic formulations |
| DE19714765.8 | 1997-04-10 | ||
| PCT/EP1998/002013 WO1998044903A1 (en) | 1997-04-10 | 1998-04-07 | USE OF LOW MOLECULAR OLIGOMER ESTERS OF α-HYDROXY ACIDS AND/OR AROMATIC OF o-HYDROXY ACIDS IN COSMETIC FORMULATIONS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2283517A1 true CA2283517A1 (en) | 1998-10-15 |
Family
ID=7825977
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002283517A Abandoned CA2283517A1 (en) | 1997-04-10 | 1998-04-07 | Use of low molecular oligomer esters of .alpha.-hydroxy acids and/or aromatic of o-hydroxy acids in cosmetic formulations |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP0973496A1 (en) |
| JP (1) | JP2001521508A (en) |
| KR (1) | KR20000076112A (en) |
| CN (1) | CN1251034A (en) |
| AU (1) | AU7429598A (en) |
| CA (1) | CA2283517A1 (en) |
| DE (1) | DE19714765A1 (en) |
| HU (1) | HUP0001693A2 (en) |
| PL (1) | PL335423A1 (en) |
| WO (1) | WO1998044903A1 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8642528B2 (en) * | 2006-07-06 | 2014-02-04 | Stepan Company | Alkyl lactyllactates and processes of making the same |
| US8956644B2 (en) | 2006-11-03 | 2015-02-17 | Durect Corporation | Transdermal delivery systems |
| US9174923B2 (en) | 2006-07-06 | 2015-11-03 | Stepan Company | Alkyl lactyllactate solvent compositions |
| US11083796B2 (en) | 2005-07-26 | 2021-08-10 | Durect Corporation | Peroxide removal from drug delivery vehicle |
| US11400019B2 (en) | 2020-01-13 | 2022-08-02 | Durect Corporation | Sustained release drug delivery systems with reduced impurities and related methods |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7833543B2 (en) | 1995-06-07 | 2010-11-16 | Durect Corporation | High viscosity liquid controlled delivery system and medical or surgical device |
| US6413536B1 (en) * | 1995-06-07 | 2002-07-02 | Southern Biosystems, Inc. | High viscosity liquid controlled delivery system and medical or surgical device |
| US20040001889A1 (en) | 2002-06-25 | 2004-01-01 | Guohua Chen | Short duration depot formulations |
| CA2507522C (en) | 2002-12-13 | 2015-02-24 | Durect Corporation | Oral drug delivery system |
| LT2767292T (en) | 2004-09-17 | 2016-12-12 | Durect Corporation | Sustained Local Anesthetic Composition Containing SAIB |
| CN105411870B (en) * | 2006-07-06 | 2018-12-25 | 斯蒂潘公司 | Alkyl lactyllactate and preparation method thereof |
| CA2706658A1 (en) | 2007-12-06 | 2009-06-18 | Durect Corporation | Methods useful for the treatment of pain, arthritic conditions or inflammation associated with a chronic condition |
| US20100260844A1 (en) | 2008-11-03 | 2010-10-14 | Scicinski Jan J | Oral pharmaceutical dosage forms |
| JP5219093B2 (en) * | 2009-11-14 | 2013-06-26 | 公益財団法人北九州産業学術推進機構 | Lactic acid oligomer and molded article thereof |
| CN105120659A (en) | 2013-03-15 | 2015-12-02 | 度瑞公司 | Compositions with a rheological modifier to reduce dissolution variability |
| JP2015093854A (en) * | 2013-11-12 | 2015-05-18 | 株式会社クレハ | Aqueous composition and method for inhibiting hydrolysis |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3620685A1 (en) * | 1986-06-20 | 1987-12-23 | Henkel Kgaa | NEW AGENTS FOR COVERING INJURED AND / OR INJURED AREAS OF HUMAN OR ANIMAL SKIN |
| US5091171B2 (en) * | 1986-12-23 | 1997-07-15 | Tristrata Inc | Amphoteric compositions and polymeric forms of alpha hydroxyacids and their therapeutic use |
| DE19520237A1 (en) * | 1995-06-02 | 1996-12-05 | Beiersdorf Ag | Cosmetic or dermatological preparations containing oligomers or polymers of alpha-hydroxycarboxylic acids |
-
1997
- 1997-04-10 DE DE19714765A patent/DE19714765A1/en not_active Withdrawn
-
1998
- 1998-04-07 CN CN98803176A patent/CN1251034A/en active Pending
- 1998-04-07 AU AU74295/98A patent/AU7429598A/en not_active Abandoned
- 1998-04-07 CA CA002283517A patent/CA2283517A1/en not_active Abandoned
- 1998-04-07 PL PL98335423A patent/PL335423A1/en unknown
- 1998-04-07 HU HU0001693A patent/HUP0001693A2/en unknown
- 1998-04-07 EP EP98921437A patent/EP0973496A1/en not_active Withdrawn
- 1998-04-07 KR KR1019997008200A patent/KR20000076112A/en not_active Application Discontinuation
- 1998-04-07 JP JP54238398A patent/JP2001521508A/en active Pending
- 1998-04-07 WO PCT/EP1998/002013 patent/WO1998044903A1/en not_active Application Discontinuation
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11083796B2 (en) | 2005-07-26 | 2021-08-10 | Durect Corporation | Peroxide removal from drug delivery vehicle |
| US8642528B2 (en) * | 2006-07-06 | 2014-02-04 | Stepan Company | Alkyl lactyllactates and processes of making the same |
| US9133092B2 (en) | 2006-07-06 | 2015-09-15 | Stepan Company | Alkyl lactyllactates and processes of making the same |
| US9174923B2 (en) | 2006-07-06 | 2015-11-03 | Stepan Company | Alkyl lactyllactate solvent compositions |
| US8956644B2 (en) | 2006-11-03 | 2015-02-17 | Durect Corporation | Transdermal delivery systems |
| US11400019B2 (en) | 2020-01-13 | 2022-08-02 | Durect Corporation | Sustained release drug delivery systems with reduced impurities and related methods |
| US11771624B2 (en) | 2020-01-13 | 2023-10-03 | Durect Corporation | Sustained release drug delivery systems with reduced impurities and related methods |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2001521508A (en) | 2001-11-06 |
| DE19714765A1 (en) | 1998-10-15 |
| EP0973496A1 (en) | 2000-01-26 |
| CN1251034A (en) | 2000-04-19 |
| AU7429598A (en) | 1998-10-30 |
| WO1998044903A1 (en) | 1998-10-15 |
| HUP0001693A2 (en) | 2000-09-28 |
| KR20000076112A (en) | 2000-12-26 |
| PL335423A1 (en) | 2000-04-25 |
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