EP1725296A1

EP1725296A1 - Retinoid-containing preparations

Info

Publication number: EP1725296A1
Application number: EP05700914A
Authority: EP
Inventors: Arne Ptock; Axel Jentzsch
Original assignee: BASF SE
Current assignee: BASF SE
Priority date: 2004-01-22
Filing date: 2005-01-14
Publication date: 2006-11-29
Also published as: WO2005070373A1; US20070202060A1; CA2552359A1; CN1909877A; JP2007518757A; BRPI0506935A; DE102004003478A1

Abstract

The invention relates to preparations containing a) at least one type of retinoid, b) at least one type of water-soluble antioxidant, c) at least one type of oil-soluble antioxidant and d) at least 0.01 to 10 % by weight of UV filter. Said invention is characterised in that the inventive preparations contain at least 1 part by weight of one or several water-soluble antioxidants and 0.1 to 100 parts by weight of one or several oil-soluble antioxidants per part by weight of retinoid, the content of one or several water-soluble antioxidants ranging from 0.05 to 0.8 % by weight with respect to the total quantity of the preparations.

Description

Preparations containing retinoids

description

The present invention relates to retinoid-containing preparations, their production and use in cosmetics and pharmacy.

Retinoids are among the most active ingredients that are used in cosmetics and dermatology. They have a regulating effect on normal cell growth and influence it _. Differentiation of epithelial cells. For example, retinoic acids are used to treat acne and retinol in anti-wrinkle creams.

However, the use of the retinoids is severely restricted, which is due among other things to the high instability of the compounds. For this reason, strict precautionary measures must be observed when manufacturing retinoid-containing preparations. For example, the production must take place completely under protective gas and the finished product must be packaged so that it is opaque to light and oxygen.

These requirements require sophisticated technological equipment from the manufacturer and are therefore associated with high manufacturing costs.

A number of methods for stabilizing retinoids have been described. For example, EP-A-1 055 720 discloses the stabilization of oxygen-sensitive compounds by using thio compounds or glycoproteins in the absence of oxygen.

According to WO 93/00085 and EP-A-0 440 398, both water- and fat-soluble antioxidants are used together with chelating agents to stabilize retinoids.

However, the methods described do not always lead to adequate stabilization in the sense of the invention. Rather, both water-soluble antioxidants, in particular ascorbic acid, and fat-soluble antioxidants, in particular tocopherol, have a destabilizing effect in connection with retinoids in certain concentration ranges.

In addition, under certain circumstances, the use of certain combinations of antioxidants together with retinoids can lead to undesirable side effects, for example yellowish discoloration of the preparations. that make the use of these systems in cosmetics or in the food sector unusable.

It was therefore an object of the present invention to provide retinoid-containing preparations which do not have the disadvantages mentioned above with regard to stability and discoloration and which are simple to prepare.

This object has been achieved by preparations containing

a. at least one retinoid,

b. at least one water-soluble antioxidant,

c. at least one oil soluble antioxidant and

d. 0.01 to 10% by weight of at least one UV filter,

characterized in that at least 1 part by weight of one or more water-soluble antioxidants and 0.1 to 100 parts by weight of one or more oil-soluble antioxidants are present in the preparations per part by weight of retinoid, the content of one or more water-soluble antioxidants in the range from 0.05 to 0.8% by weight, based on the total amount of the preparations.

The preparations according to the invention are cosmetic and dermatological or pharmaceutical preparations. Cosmetic preparations, in particular skin care preparations, are preferred.

An advantageous embodiment of the preparations according to the invention contains 1 to 100 parts by weight per part by weight of retinoid, preferably 1 to 20 parts by weight, particularly preferably 1 to ^'6 parts by weight, most preferably 3 to 5 parts by weight of one or more water-soluble antioxidants and 1 to 20 parts by weight, preferably 1 to 15 parts by weight, particularly preferably 1 to 10 parts by weight, very particularly preferably 3 to 5 parts by weight of one or more oil-soluble antioxidants.

In the context of the present invention, retinoids mean vitamin A alcohol (retinol) and its derivatives such as vitamin A aldehyde (retinal), vitamin A acid (retinoic acid) and vitamin A esters such as retinyl acetate and retinyl palmitate. The term retinoic acid encompasses both all-trans retinoic acid and 13-cis retinoic acid. The terms retinol and retinal preferably include those all-trans connections. All-trans retinol is used as the preferred retinoid for the preparations according to the invention.

The water-soluble antioxidants include Ascorbic acid, sodium sulfite, sodium metabisulfite, sodium bisulfite, sodium thiosulfite, sodium formaldehyde sulfoxylate, isoascorbic acid, thioglycerin, thiosorbitol, thiourea, thioglycolic acid, cysteine hydrochloride, 1, 4-diazobicyclo- (2,2,2) or mixtures thereof meant .

Preferred water-soluble antioxidants are ascorbic acid (L-ascorbic acid) and isoascorbic acid (D-ascorbic acid), particularly preferably L-ascorbic acid.

The L-ascorbic acid used with particular preference can be the free acid but also its salts. Examples of salts of L-ascorbic acid are alkali or alkaline earth metal salts of L-ascorbic acid such as sodium L-ascorbate, potassium L-ascorbate or calcium L-ascorbate, but also salts of L-ascorbic acid with an organic amine compound such as choline ascorbate or L-carnitine ascorbate. Free L-ascorbic acid or sodium L-ascorbate is very particularly preferably used. The same applies to the use of D-ascorbic acid.

Oil-soluble antioxidants include butylated hydroxytoluene (BHT), ascorbyl palmitate, butylated hydroxyanisole, α-tocopherol, phenyl-naphthylamine or mixtures thereof.

The preferred oil-soluble antioxidant is α-tocopherol, which can be either (R, R, R) - or (all-rac) -α-tocopherol.

In the context of the present invention, UV filter means UV-A, UV-B and / or broadband filters.

Advantageous broadband filters, UV-A or UV-B filter substances are, for example, representatives of the following classes of compounds: Bis-resorcinyltriazine derivatives with the following structure:

where R ¹ , R ² and R ³ are selected independently of one another from the group of branched and unbranched alkyl groups with 1 to 10 carbon atoms or represent a single hydrogen atom. This is particularly preferably 2,4-bis- [[4- (2-ethylhexyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) -1,3,5-triazine (INCI: Aniso triazine), which is available under the trade name Tinosorb ^® S from CIBA-Chemicals GmbH.

Also other UV filter substances, which the structural motif

are advantageous UV filter substances for the purposes of the present invention, for example the s-triazine derivatives described in European patent application EP 570 838 A1, the chemical structure of which is given by the generic formula

is reproduced, a branched or unbranched Ci-Ciβ-alkyl radical, a C ₅ -C -cycloalkyl radical, optionally substituted with one or more C ₁ -C ₄ alkyl groups,

X represents an oxygen atom or an NH group,

Ri is a branched or unbranched C ₁ -C ₈ alkyl radical, a C ₅ -C ₂ cycloalkyl radical, optionally substituted with one or more C ₁ -C ₄ alkyl groups, or a hydrogen atom, an alkali metal atom, an ammonium group or a group of the formula

means in which

A represents a branched or unbranched Ci-Ciβ-alkyl radical, a C ₅ -C -cycloalkyl or aryl radical, optionally substituted with one or more C ₁ -C ₄ alkyl groups,

R _{3 represents} a hydrogen atom or a methyl group,

n represents a number from 1 to 10,

R _{2 represents} a branched or unbranched Ci-Cis-alkyl radical, a C ₅ -Ci ₂ cycloalkyl radical, optionally substituted with one or more C ₁ -C ₄ alkyl groups, when X represents the NH group, and a branched or unbranched C-Cis-alkyl radical, a C ₅ -C ₂ cycloalkyl radical, optionally substituted with one or more C ₁ -C ₄ alkyl groups, or a hydrogen atom, an alkali metal atom, an ammonium group or a group of the formula

means in which represents a branched or unbranched C ₁ -C ₈ alkyl radical, a C ₅ -C ₂ cycloalkyl or aryl radical, optionally substituted with one or more C ₁ -C ₄ alkyl groups,

R _{3 represents} a hydrogen atom or a methyl group,

n represents a number from 1 to 10 when X represents an oxygen atom.

A particularly preferred UV filter substance in the sense of the present invention is also an asymmetrically substituted s-triazine, the chemical structure of which is represented by the formula

is reproduced, which is also referred to below as dioctylbutyl amidotriazon (INCI: Diethylhexylbutamidotriazone) and is available under the trade name UVASORB ^® HEB from Sigma 3V.

For the purposes of the present invention, a symmetrically substituted s-triazine which is 4, ', 4''- (1, 3, 5-triazine-2, 4, 6-triyltriimino) -tris-benzoic acid tris ( 2-ethylhexyl ester), synonymous: 2,4,6-tris [anilino- (p-carbo-2'-ethyl-1'-hexyloxy)] -1,3,5-triazine (INCI: ethylhexyl Triazone), which is sold by BASF Aktiengesellschaft under the trade name UVINUL ^® T 150.

European published patent application 775 698 also describes bis-resorcinyltriazine derivatives which are to be used with preference, the chemical structure of which is given by the generic formula

is reproduced, wherein R 1 and R _{2 represent,} inter alia, C ₃ -C ₈ -alkyl or C ₂ -C ₈ -alkenyl and Ai an aromatic radical.

Also advantageous in the sense of the present invention are the 2,4-bis- [[4- (3-sulfonato) -2-hydroxypropyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) - 1,3,5-triazine sodium salt, the 2,4-bis- {[4- (3- (2-propyloxy) -2-hydroxypropyloxy) -2-hydroxy] phenyl} -6- (4th -methoxyphenyl) -1,3,5-triazine, the 2,4-bis- {[4- (2-ethylhexyloxy) -2-hydroxy] phenyl} -6- [4- (2-methoxyethyl-carboxyl ) -phenylamino] -1, 3, 5-triazine, the 2,4-bis- {[4- (3- (2-propyloxy) -2-hydroxypropyloxy) -2-hydroxy] phenyl } -6- [4- (2-ethyl-carboxyl) phenylamino] -1, 3, 5-triazine, the 2,4-bis- {[4- (2-ethyl-hexyloxy) -2-hy - droxy] -phenyl} -6- (l-methyl-pyrrol-2-yl) -1,3,5-triazine, the 2,4-bis- {[4-tris (trimethylsiloxysilylpropyloxy) -2-hydroxy ] -phenyl} -6- (4-methoxyphenyl) -1,3,5-triazine, the 2,4-bis- {[4- (2 "-methylpropenyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) -1,3,5- triazine and the 2,4-bis- {[4- (1 ', 1', 1 ', 3', 5 ', 5', 5 '- Heptarethyl-siloxy-2 "-methyl-pr opyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) -1, 3, 5-triazine. Advantageous sulfonated, water-soluble UV filters in the sense of the present invention are:

Phenylene-1, 4-bis (2-benzimidazyl) -3, 3 '-5, 5' -tetrasulfonic acid, which is characterized by the following structure:

As well as their salts, especially the corresponding sodium, potassium or triethanolammonium salts, in particular the phenylene-1,4-bis (2-benzimidazyl) -3, 3 '-5, 5'-tetrasulfonic acid bis-sodium salt

with the INCI name bisimidazylate (CAS no .: 180898-37-7), wweellcchheess bbeeiissppiieellsswweeiissee uunntteerr ddeerr HHaandnddeell.sbebung Neo Heliopan AP is available from Haarmann & Reimer.

Another sulfonated UV filter which is advantageous in the sense of the present invention are the salts of 2-phenylbenzimidazole-5-sulfonic acid, such as its sodium, potassium or triethanolammonium salt, and the sulfonic acid itself

with the INCI name phenylbenzimidazole sulfonic acid (CAS.- no. 27503-81-7), which is available from Merck or under Neo Heliopan Hydro from Haarmann & ^® Reimer example, under the trade name Eusolex 232. Another advantageous sulfonated UV filter is the 3,3 - (1,4-phenylenedimethylene) bis (7,7-dimethyl-2-oxo-bicyclo- [2.2.1] hept-1-ylmethane sulfonic acid, like her Sodium, potassium or their triethanolammonium salt, as well as the sulfonic acid itself:

with the INCI name Terephtalidene Dicampher Sulfonic Acid (CAS. No .: 90457-82-2), which is available, for example, under the trade name Mexoryl SX from Chimex.

Further advantageous water-soluble UV-B and / or broadband filter substances are e.g. B.:

Sulfonic acid derivatives of 3-benzylidene camphor, e.g. 4- (2-oxo-3-bornylidene methyl) benzenesulfonic acid, 2-methyl-5- (2-oxo-3-bornylidene methyl) sulfonic acid and their salts.

The UV-B and / or broadband filters can be oil-soluble or water-soluble. Advantageous oil-soluble UV-B and / or broadband filter substances include:

3-benzylidene camphor derivatives, preferably 3- (4-methylbenzylidene) camphor, 3-benzylidene camphor;

4-aminobenzoic acid derivatives, preferably 4- (dimethylamino) benzoic acid (2-ethylhexyl) ester, 4- (dimethylamino) benzoic acid amyl ester, 4-bis (polyethoxy) amino-benzoic acid polyethoxyethyl ester (under the trade name Uvinul® P25 available from BASF);

Derivatives of benzophenone, preferably 2-hydroxy-4-methoxybenzophenone (under the trade name Uvinul ^® M40 from the Fa. BASF available) 2-hydroxy-4-methoxy-4 '-methylbenzophenon, 2,2'-dihydroxydiphenyl droxy- 4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (under the trade name Uvinul MS40 from the Available from BASF), 2, 2 ', 4, 4 ^λ- tetrahydroxybenzophenone (available under the trade name Uvinul D 50 from BASF);

as well as UV filters bound to polymers.

Particularly advantageous UV filter substances which are liquid at room temperature for the purposes of the present invention are homomenthyl salicylate, 2-ethylhexyl-2-cyano-3, 3-diphenyl acrylate, 2-ethylhexyl-2-hydroxybenzoate and esters of cinnamic acid, preferably 4-methoxycinnamic acid (2-ethylhexyl) ester and isopentyl 4-methoxycinnamate.

Ho omenthyl salicylate (INCI: Homosalate) is characterized by the following structure:

2-Ethylhexyl-2-cyano-3,3-diphenylacrylate (INCI: Octocrylene) is available from BASF under the name Uvinul N 539T and is characterized by the following structure:

2-Ethylhexyl-2-hydroxybenzoate (2-ethylhexyl salicylate, octyl salicylicate, INCI: ethylhexyl salicylate) is available, for example, from Haarmann & Reimer under the trade name Neo Heliopan ^® OS and is characterized by the following structure:

4-methoxycinnamic acid (2-ethylhexyl) ester (2-ethylhexyl-4-methoxycinamate, INCI: ethylhexyl methoxycinnamate) is available, for example, from BASF under the trade name Uvinul ^® MC 80 and is characterized by the following structure:

Hscσ "^^

4-methoxycinnamic acid isopenyl ester (isopentyl-4-methoxycinnamate, INCI: isoamyl p-methoxycinnamate) is available, for example, from Haarmann & Reimer under the trade name Neo Heliopan E 1000 and is characterized by the following structure:

A further advantageous UV filter substance which is liquid at room temperature in the sense of the present invention (3- (4- (2,2-bis-ethoxycarbonylvinyl) phenoxy) propenyl) methylsiloxane / dimethylsiloxane copolymer, which is described, for example, by Hoffmann-La Röche is available under the trade name Parsol SLX.

Advantageous dibenzoylmethane derivatives for the purposes of the present invention are, in particular 4- (tert-butyl) -4'-methoxydibenzoylmethane (CAS No. 70356-09-1), which is available from BASF under the Uvinul BMBM brand and from Merck under the trade name Eusolex ^® 9020 is characterized by the following structure:

A further advantageous dibenzoylmethane derivative is 4-isopropyl-dibenzoylmethane (CAS No. 63250-25-9). which is sold by Merck under the name Eusolex ^® 8020. The Eusolex 8020 is characterized by the following structure:

Benzotriazoles are characterized by the following structural formula:

wherein

R 1 and R ² independently of one another are linear or branched, saturated or unsaturated, substituted (for example substituted with a phenyl radical) or unsubstituted alkyl radicals having 1 to 18 carbon atoms and / or polymer radicals which themselves do not absorb UV rays (such as silicone radicals, Acrylate radicals and the like), and R _{3 is selected} from the group H or alkyl radical with 1 to 18 carbon atoms.

An advantageous benzotriazole for the purposes of the present invention is 2,2'-methylene-bis- (6- (2H-benzotriazol-2-yl) -4- (1,1,3,3-tetramethylbutyl) phenol) Broadband filter, which by the chemical structural formula

and is available under the trade name Tinosorb ^® M from CIBA-Chemicals GmbH.

An advantageous benzotriazole for the purposes of the present invention is also 2- (2H-benzotriazol-2-yl) -4-methyl-6- [2-methyl-3- [1,3,3, 3-tetramethyl-l- [( trimethylsilyl) oxy] disiloxanyl] -propyl] -phenol (CAS no .: 155633-54-8) with the INCI name Dormetrizole Trisiloxane, which is sold by Chimex under the Mexoryl XL brand and by following chemical structural formula

is marked.

Further advantageous benzotriazoles in the sense of the present invention are [2, 4 ^λ- dihydroxy-3- (2H-benzotriazol-2-yl) -5- (1,1,3, 3-tetramethylbutyl) -2 '-n-octoxy- 5 ^x -benzoyl] diphenylmethane, 2,2 'methylene-bis- [6- (2H-benzotriazol-2-yl) -4- (methyl) phenol], 2,2 ^λ -methylene-bis- [6- (2H -benzotriazol-2-yl) -4- (1,1,3, 3-tetramethylbutyl) phenol], 2- (2 '-hydroxy-5' -octylphenyl) -benzotriazole, 2- (2'-hydroxy-3 ' , 5 '-di-t-amylphenyl) benzotriazole and 2- (2'-hydroxy-5' methylphenyl) benzotriazole. Another UV filter which is advantageous in the sense of the present invention is the diphenylbutadiene compound of the following formula described in EP-A-0 916 335.

Another UV-A filter which is advantageous in the sense of the present invention is the diethyl 2- (4-ethoxyanilinomethylene) propanedicarboxylate of the following formula described in EP-A-0 895 776. l ethyl

An amino-substituted hydroxybenzophenone of the following formula is also advantageous in the sense of the present invention:

which is sold by BASF Aktiengesellschaft as UV-A filter under the product name UVINUL A Plus.

Cosmetic and dermatological preparations according to the invention also advantageously, although not necessarily, contain inorganic pigments based on metal oxides and / or other metal compounds which are sparingly soluble or insoluble in water, in particular the oxides of titanium (Ti0 ₂ ), zinc (ZnO), iron (eg Fe203) , Zirconium (Zr0), silicon (Si0 ₂ ), manganese (eg MnO), aluminum (Al0 ₃ ), cerium (eg Ce0 ₃ ), mixed oxides of the corresponding metals and mixtures of such oxides. This pig- elements are X-ray amorphous or non-X-ray amorphous. Pigments based on TiO 2 are particularly preferred.

X-ray amorphous oxide pigments are metal oxides or semi-metal oxides, which show no or no recognizable crystal structure in X-ray diffraction experiments. Such pigments are often obtainable by flame reaction, for example by reacting a metal or semimetal halide with hydrogen and air (or pure oxygen) in a flame.

10 In cosmetic, dermatological or pharmaceutical formulations, X-ray amorphous oxide pigments are used as thickening and thixotropic agents, flow aids, for stabilizing emulsions and dispersions and as carriers (e.g. for

15 increase in volume of finely divided powders or powders).

Known and often used in cosmetic or dermatological galenics are the X-ray amorphous oxide pigments, the silicon oxides of the type Aerosil ^® (CAS No. 7631-86-9. Aerosile ^® , obtained).

20 borrowed from DEGUSSA, are characterized by a small particle size (for example between 5 and 40 nm), the particles being spherical particles of very uniform dimensions. Aerosile ^® are macroscopically recognizable as loose, white powders. For the purposes of the present invention, X-ray amorphous

25 phe silicon dioxide pigments are particularly advantageous, and especially preferred among these are those of the Aerosil type.

Advantageous Aerosil ^® grades are, for example Aerosil® 0x50, Aerosil ^® 130, Aerosil ^® 150, Aerosil ^® 200, Aerosil ^® 300, Aerosil ^® 30 380 Aerosil ^® MOX 80 Aerosil ^® MOX 170 Aerosil ^® COK 84, Aerosil ^® R 202, Aerosil ^® R 805, Aerosil ^® R 812, Aerosil ^® R 972, Aerosil ^® R 974, Aerosil ^® R976.

According to the invention, the non-X-ray amorphous inorganic pigments are advantageously in hydrophobic form, i.e. they are treated on the surface to be water-repellent. This surface treatment can consist in that the pigments are provided with a thin hydrophobic layer by methods known per se.

40 Such a process consists, for example, in that the hydrophobic surface layer after a reaction in accordance with n Ti0 ₂ + m (R0) 3Si-R '→ n Ti0 ₂ (surface)

45 is generated, n and m are stoichiometric parameters to be used at will, R and R 'are the desired organic radicals. For example, hydrophobized pigments shown in analogy to DE-OS 33 14 742 are advantageous.

Organic surface coatings in the sense of the present invention can consist of vegetable or animal aluminum stearate, vegetable or animal stearic acid, lauric acid, dimethylpolysiloxane (also: dimethicone), methylpolysiloxane (methicone), simethicone (a mixture of dimethylpolysiloxane with an average chain length of 200 up to 350 dimethylsiloxane units and silica gel), octyltrimethoxysilane or alginic acid. These organic surface coatings can occur alone, in combination and / or in combination with inorganic coating materials.

Zinc oxide particles and predispersions of zinc oxide particles suitable according to the invention are available under the following trade names from the listed companies:

Suitable titanium dioxide particles and predispersions of titanium dioxide particles are available under the following trade names from the companies listed:

Advantageous Ti0 ₂ pigments are available, for example, under the trade name Uvinul ^® Ti0, advantageous Ti0 / Fe0 ₃ mixed oxides under the trade name Uvinul ® Ti0 ₂ A from BASF. The total amount of at least one UV filter used in the finished cosmetic or dermatological preparations is advantageously in the range from 0.01 to 10% by weight, preferably in the range from 0.5 to 8% by weight, particularly preferably in the range from 1 to 7% by weight, based on the total weight of the preparations.

The UV filters present in the preparations according to the invention can be used both for stabilizing retinol (product protection) and for protecting human skin from UV radiation (skin protection).

For use as a product protection, the necessary amount of ^'UV filters to be used and is significantly reduced in these cases advantageously in the range of 0.01 to 0.5

% By weight, preferably in the range from 0.05 to 0.1% by weight, based on the total weight of the preparations.

The UV filters which are preferred for use in the preparations according to the invention are the following Uvinul ^® brands from BASF: Uvinul ^® A Plus, Uvinul ^® D 50, Uvinul ^® M 40, Uvinul ^® MS 40 and Uvinul ^® P 25, Uvinul ^® MC 80, Uvinul ^® N 539, Uvinul ^® T150 and the inorganic pigments Ti0 ₂ and ZnO.

Especially for use as product protection, the following UV filters are: Uvinul A Plus ^®, Uvinul ^® D 50, Uvinul ^® M 40, Uvinul ^® MS 40 and Uvinul ^® P 25th

The preparations according to the invention generally contain 0.015 to 0.2% by weight, preferably 0.02 to 0.15% by weight, particularly preferably 0.03 to 0.15% by weight, very particularly preferably 0.04 up to 0.12% by weight of one or more retinoids, in particular all-trans-retinol, 0.05 to 0.8% by weight, preferably 0.08 to 0.7% by weight, particularly preferably 0.12 up to 0.6% by weight, very particularly preferably 0.16 to 0.5% by weight of one or more water-soluble antioxidants, in particular L-ascorbic acid and 0.0005 to 2% by weight, preferably 0.01 to 1 , 8% by weight, particularly preferably 0.1 to 1.5% by weight, very particularly preferably 0.15 to 1.2% by weight of one or more oil-soluble antioxidants, in particular α-tocopherol.

The preparations according to the invention are distinguished, inter alia, by the fact that the use of protective gas can be dispensed with in their manufacture, filling and storage, while at the same time ensuring adequate stability. Sufficient stability in the sense of the invention is understood to mean that at least 90% of the retinoid is found in the preparation after 12 weeks of storage at 40 ° C. Furthermore, there are no undesirable color changes when the preparations according to the invention are stored.

It is advantageous if the preparations according to the invention are kept in oxygen-impermeable packaging.

The oxygen-impermeable packaging can be all commercially available packaging suitable for this purpose, e.g. Glass containers or aluminum packaging.

Another advantage of the preparations according to the invention is that these products no longer have to be stored in the absence of light.

In comparison to the previously known retinoid-containing cosmetic preparations, it is now possible when using the preparations according to the invention in skin care to correct the increased sensitivity of the skin to sunlight, which is often triggered by the retinoid.

The cosmetic as well as the dermatological or pharmaceutical preparations are generally based on a carrier which contains at least one oil phase. However, preparations based on water alone are also possible. Accordingly, oils, creams, pastes, foams, preparations in stick form or fat-free gels or preferably emulsions are suitable.

O / W emulsions, W / O emulsions, microemulsions or multiple emulsions such as O / W / O emulsions or W / O / W emulsions with one or more of the retinoids according to the invention in dispersed form are suitable as emulsions Question, the emulsions being obtainable, for example, by phase inversion technology in accordance with DE-A-197 26 121.

Customary cosmetic auxiliaries which can be considered as additives to the cosmetic or pharmaceutical preparations are, for example, co-emulsifiers, fats and waxes, stabilizers, thickeners, biogenic active ingredients, film formers, fragrances, colorants, pearlescent agents, preservatives, pigments, electrolytes (e.g. magnesium sulfate) and pH regulators. Known W / O and also O / W emulsifiers such as polyglycerol esters, sorbitan esters or partially esterified glycerides are preferably suitable as co-emulsifiers. Typical examples of fats are glycerides; beeswax, paraffin wax or micro waxes may be mentioned in combination with hydrophilic waxes. Metal salts of fatty acids such as magnesium, aluminum and / or zinc stearate can be used as stabilizers. Suitable thickeners are, for example, crosslinked polyacrylic acids and their derivatives, polysaccharides, in particular xanthan gum, guar guar, agar agar, alginates and tyloses, carboxymethyl cellulose and hydroxyethyl cellulose, furthermore fatty alcohols, monoglycerides and fatty acids, polycrystals latex, polyvinyl alcohol and polyvinyl pyrrolidone. Biogenic active substances are understood to mean, for example, plant extracts, protein hydrolysates and vitamin complexes. Common film formers are, for example, hydrocolloids such as chitosan, microcrystalline chitosan or quaternized chitosan, polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymers, polymers of the acrylic acid series, quaternary cellulose derivatives and similar compounds. Suitable preservatives are, for example, formaldehyde solution, p-hydroxybenzoate or sorbic acid. Suitable pearlizing agents are, for example, glycol distearic acid esters such as ethylene glycol distearate, but also fatty acids and fatty acid remonoglycol esters. As dyes, the substances suitable and approved for cosmetic purposes can be used, as compiled, for example, in the publication "Cosmetic Dyes" by the Dye Cooperation of the German Research Foundation, published by Verlag Chemie, Weinheim, 1984. These dyes are usually used in a concentration of 0.001 to 0.1% by weight, based on the mixture as a whole.

The use of other antioxidants is beneficial in many cases. Thus, in addition to the antioxidants according to the invention mentioned at the outset, all antioxidants suitable or customary for cosmetic and / or dermatological applications can be used.

The antioxidants are advantageously selected from the group consisting of amino acids (eg glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (eg urocanic acid) and their derivatives, peptides such as D, L-carnosine, D-carnosine , L-carnosine and its derivatives (eg anserine), carotenoids, carotenes (eg ß-carotene, lycopene) and their derivatives, chlorogenic acid and its derivatives, lipoic acid and its derivatives (eg dihydroliponic acid), aurothioglucose, propylthiouracil and others Thiols (e.g. thiorodoxin, glutathione, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl, and lauryl, palmitoyl, oleyl, γ-linoleyl -, Cholesteryl and Glyceryl esters) and their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and their derivatives (esters, Ethers, peptides, lipids, nucleotides, nucleosides and salts) and sulfoximine compounds (e.g. buthioninsulfoximines, homocysteine sulfoximines, buthioninsulfones, penta-, hexa-, heptathioninsulfoxi in) in very low tolerable dosages (e.g. pmol to μmol / kg), furthermore (Metal) chelators (e.g. α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (e.g. citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, biliburin, biliverdin, EDTA and their derivatives, unsaturated fatty acids and their derivatives (eg γ-linolenic acid, linoleic acid, oleic acid), folic acid and its derivatives as well as coniferyl benzoate of benzoin, rutinic acid and its derivatives, α-glycosyl rutin, ferulic acid, furfurylidene glucitol, carnosine, nordihydroguaj resin acid, nordihydroguydroxybenzoic acid, trihydric acid Derivatives, mannose and their derivatives, zinc and its derivatives (eg ZnO, ZnS0 ₄ ), selenium and its derivatives (eg Selenomethionine), stilbenes and their derivatives (e.g. stilbene oxide, trans-stilbene oxide):

The total amount of the aforementioned antioxidants (one or more compounds) in the preparations is preferably

0.075 to 30% by weight, particularly preferably 0.1 to 20% by weight, in particular 0.55 to 10% by weight, based on the total weight of the preparation.

Typical oil components in cosmetics are, for example, paraffin oil, glyceryl stearate, isopropyl myristate, diisopropyl adipate, 2-ethylhexanoic acid cetyl stearyl ester, hydrogenated polyisobutene, petrolatum, caprylic acid / capric acid triglycerides, microcrystalline wax, lanolin and stearic acid.

Manufacturing process:

There are numerous options for producing a cosmetic preparation. Thus come the hot / hot process, the hot / cold process or the cold / cold process, as described, for example, in "Cosmetics - Development, Production and Application of Cosmetics", ed. Wilfried Umbach, Thieme Verlag, 1995, Page 511 are described for use. These processes can be used to produce oil-in-water (0 / W-), water-in-oil (W / 0-), but also multiple emulsions as well as cream gels and gels. The active ingredients are preferably incorporated after the formulation has cooled to below 40 ° C., in particularly sensitive cases preferably after cooling to room temperature. For the investigations on which this invention is based, a 0 / W emulsion was produced in a hot / hot process and the active ingredients then incorporated into the finished formulation at room temperature.

The recipe used:

Ingredient INCI

Phase A 2.00 Cremophor A 6 Ceteareth-6, Stearyl Alcohol 2.00 Cremophor A 25 Ceteareth-25 3.00 Jo obaöl Simmondsia Chinensis (Jojoba) Seed Oil 3.00 Cetylstearyl Alcohol Cetearyl Alcohol 10.00 Paraffin oil, viscous Mineral Oil 5.00 Vaseline Petrolatum 4.00 Miglyol 812 Caprylic / Cap - glyceride 0.10 BHT BHT

Phase B 5.00 1, 2-propylene glycol Propylene Glycol USP 0.10 Edeta BD Disodium EDTA 20.00 Carbopol 934, carbomer 1% in water. 0.30 Chemag 2000 ad 100 Water dem. Aqua dem.

Phase C 0.80 sodium hydroxide, sodium hydroxide 10% in water.

Phase D 0.50 Vitamin E acetate Tocopheryl Acetate 0.20 Phenoxyethano1 Phenoxyethano1 q.s. perfume oil

production:

Phases A and B were heated separately to approx. 80 ° C. Phase B was then stirred into phase A and homogenized. Phase C was neutralized and post-homogenized. The cream was cooled to about 40 ° C. with stirring, phase D was stirred in and homogenized again.

The water-soluble and oil-soluble antioxidants and the UV filters were then incorporated into the finished emulsion after the cream had cooled to room temperature. First D, L-alpha-tocopherol and the UV filter were added, then the Ascorbic acid or sodium ascorbate and then retinol (Retinol 15D®, BASF; 15% solution of retinol in a medium-chain triglyceride) are incorporated with stirring.

The cream was then filled both in aluminum tubes with an internal protective lacquer and in translucent glass vessels.

According to the manufacturing process described above, creams with different amounts of retinol, (all-rac) -α-tocopherol and L-ascorbic acid and at least one UV filter were prepared and stored for 12 weeks at 40 ° C. for stability studies.

The subject matter of the invention is explained in more detail using the following example formulations.

example 1

Skin lotion (O / W emulsion)

Weight -%

Ceteareth-6 and stearyl alcohol 2,, 50

Ceteareth-25 2, 50

Hydrogenated cocoglyceride 1, 50

PEG-40 Dodecyl Glycol Copolymer 3,, 00 Dimethicone 3,, 00

Phenethyl Dimethicone 2, 00

Cyc1omethicone X, 00

Cetearyl octanoate 5, 00

Avocado oil 1, 00 Almond oil 2, 00

Wheat germ oil 0.80

Panthenol USP 1, .00

Phytantriol 0, 20

Vitamin E acetate 0.30 propylene glycol 5.00

Perfume q-, s.

Preservatives q. s.

Sodium ascorbate o.20

Retinol 15D® ^' , 20

Tocopherol o. 10

Diethylamino-hydroxybenzoyl-hexylbenzoate (Uvinul® A Plus) 0.06

Water ad 100 Example 2

Hand cream (w / o emulsion)

Wt .-%

Cetearyl alcohol 1.00

Glyceryl stear t 1.50

Stearyl alcohol 1.50

Cetyl palmitate 2.00 vitamin E acetate 0.50

Dimethicone 8.00

Ceteareth-6 and stearyl alcohol 3.00

Octyl methoxycinnamate 5.00

Propylene glycol 8.00 panthenol 1.00

Evening primrose oil 3.00

PEG-7 hydrogenated castor oil 6.00

Glyceryl oleate 1.00

Phenethyl Dimethicone 3.00 beeswax 1.50

Locust bean gum 0.80

Silk powder 0.80

Preservative q.s.

Perfume q.s. Borax 0.10

Sodium ascorbate 0.30

Tocopherol 0.60

Retinol 15D ^® 0.66

Benzophenone-2 (Uvinul ^® D 50) ad 100 water 0.05

Example 3

Sun protection lotion (W / O emulsion)

Wt .-%

PEG-7 hydrogenated castor oil 6.00

PEG-40 hydrogenated castor oil 0.50

Isopropyl palmitate 7.00 PEG-45 / dodecyl glycol copolymer 2.00

Jojoba oil 3.00

Magnesium stearate 0.60

Octyl methoxycinnamate 5.00

C 12-15 alkyl benzoate 5.00 titanium dioxide 4.00

Propylene glycol 5.00

EDTA 0.20 Preservative qs

Retinol 15D ^® 0.33

Water ad 100

N trium ascorbyl phosphate 1.00

Vitamin E acetate 0.50

Sodium ascorbate 0.20

Tocopherol 1.00

Perfume q.s.

Example 4

Multiple emulsion (W / O / W emulsion)

% By weight paraffin oil 7, 50

Cetearyl octanoate 2, 50

Aluminum stearate 0, 25

Magnesium stearate 0.25

Microcrystalline wax H 0.50 Cetearyl alcohol 1.00

Lanolin alcohol 1, 50

Wool wax alcohol ointment 1, 50

PEG-7 hydrogenated castor oil o., 75

PEG-45 / Dodecyl Glyokol Copolymer 2,, 00 ceteareth-6 and stearyl alcohol 2,, 00

Ceteareth-25 2, 00

Trilauret-4 phosphate 1, 00

Hydroxyethyl cellulose 0, 20

Propylene glycol 7.50 magnesium sulfate 0.25

Sodium ascorbate 0.30

Tocopherol 0.01

Retinol 15D ^® 0, 40

Diethylamine ino-hydroxybenzoyl hexylbenzoate (Uvinul ^® A Plus) 0, 06

Water ad 100

Example 5

microemulsion

Wt .-%

Ceteareth-25 ^'13 .00 PEG-7 glyceryl cocoate 20.00 octyldodecanol 5.00

Preservative qs. Sodium ascorbate 0.10 Tocopherol 0.10

Retinol 15D ^® 0.66

Benzophenone-3 (Uvinul I ^ ® M 40) 0.07

Water ad 100

Example 6

Liposome gel (hydrophilic gel)

% By weight

PEG-40 hydrogenated castor oil 1.00

Bisabolol rac. 0.10

Propylene glycol 8.00

Panthenol 0.50 water, Vitamim E-acetate,

Polysorbate 80 and Caprylic / Capric

Triglycerides and lecithin 3, 00

Preservative q-, s.

Perfume q-, s. Carbomer 0.50

Sodium ascorbate o.15

Tocopherol o.15

Triethanolamine 70

Retinol 15D ^® o, 33 diethylamino-hydroxybenzoyl-hexylbenzoate (Uvinul ^® A Plus) o.06

Water ad 100

Example 7

Make-up (decorative cosmetics)

Wt .-%

Ceteareth-6 and stearyl alcohol 9.00 Dimethicone 5.00

Cetearyl octanoate 8.00

Macadamia nut oil 5.00

Propylene glycol 5.00

Retinol 15D ^® 0.66 water ad 100

Sicovit Weiss E 171 8.00

Sicomet Braun 70 13E 3717 2.00

Sodium ascorbate 0.20

Tocopherol 0.50 perfume q.s.

Benzophenone-3 (Uvinul M ^® 40) 5.00 Example 8

Fluid make-up (decorative cosmetics)

Wt% ceteareth-6 and stearyl alcohol 7.00 ceteareth-25 5.00

Dimethicone 5.00

Cetearyl octanoate 8.00 Macadamia nut oil 5.00

Propylene glycol 5.00

Retinol 15D ^® 0.33

Water ad 100

Sicovit Weiss E 171 8.00 Sicomet Braun 70 13E 3717 1.00

Sodium ascorbate 0.10

Tocopherol 0.01

Perfume q. s.

Benzophenone-3 (Uvinul M ^® 40) 5.00

Example 9

Sun protection lotion (O / W emulsion)

weight

Ceteareth-6 and stearyl alcohol 2.30

Ceteareth-25 1.00

Cetyl steary alcohol 4.80

Cetyl stearyl octanoate 10.0 glyceryl monostearate 3.00

Vaseline 3.00

Panthenol USP 1.00

Disodium EDTA 0.20

Imidazolidinyl urea 0.30 propylene glycol 5.00

Sodium ascorbyl-2-monophosphate 0.20

Vitamin E acetate 1.00

Bisabolol 0.10

Retinol 0.05 tocopherol 0.20

Sodium ascorbate 0.20

Diethylamino hydroxybenzoyl hexylbenzoate ^'(Uvinul A Plus ^®) 2.00 p-methoxycinnamate (Uvinul MC ^® 80) 3.00

Water ad 100

Claims

claims

1. Preparations containing a. at least one retinoid, b. at least one water-soluble antioxidant, c. at least one oil-soluble antioxidant and d. 0.01 to 10% by weight of at least one UV filter, characterized in that at least 1 part by weight of one or more water-soluble antioxidants and 0.1 to 100 parts by weight of one or more oil-soluble antioxidants are present in the preparations per part by weight of retinoid, where the content of one or more water-soluble antioxidants is in the range from 0.05 to 0.8% by weight, based on the total amount of the preparations.

2. Preparations according to claim 1, characterized in that it is cosmetic or pharmaceutical preparations.

3. Preparations according to one of claims 1 or 2, containing 1 to 6 parts by weight of one or more water-soluble antioxidants and 1 to 10 parts by weight of one or more oil-soluble antioxidants per part by weight of retinoid.

4. Preparations according to one of claims 1 to 3, containing 3 to 5 parts by weight of one or more water-soluble antioxidants and 3 to 5 parts by weight of one or more oil-soluble antioxidants per part by weight of retinoid.

5. Preparations according to one of claims 1 to 4, containing as water-soluble antioxidant L-ascorbic acid or salts of L-ascorbic acid.

6. Preparations according to one of claims 1 to 5, containing α-tocopherol as an oil-soluble antioxidant.

7. Preparations according to one of claims 1 to 6, characterized in that the retinoid is all-trans retinol.

8. Preparations according to claim 7, containing 0.015 to 0.2 wt .-% all-trans-retinol.

9. Preparations according to one of claims 1 to 8, characterized 5 indicates that the UV filters are UV-A, UV-B and / or broadband filters.

10. Preparations according to one of claims 1 to 9 in the form of an O / W, W / O or multiple emulsion.

10 11. Preparations according to one of claims 1 to 10, characterized in that they are stored in oxygen-impermeable packaging without the addition of protective gas.

15 12. Preparations according to one of claims 1 to 11, characterized in that it is skin care preparations.

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