WO2008003529A1 - Use of tropolone derivatives as antioxidants in cosmetic and/or topical pharmaceutical compositions - Google Patents
Use of tropolone derivatives as antioxidants in cosmetic and/or topical pharmaceutical compositions Download PDFInfo
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- WO2008003529A1 WO2008003529A1 PCT/EP2007/053347 EP2007053347W WO2008003529A1 WO 2008003529 A1 WO2008003529 A1 WO 2008003529A1 EP 2007053347 W EP2007053347 W EP 2007053347W WO 2008003529 A1 WO2008003529 A1 WO 2008003529A1
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- cosmetic
- tropolone
- derivatives
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- antioxidants
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- 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
- A61K8/35—Ketones, e.g. benzophenone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0208—Tissues; Wipes; Patches
-
- 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
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/52—Stabilizers
- A61K2800/522—Antioxidants; Radical scavengers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning 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
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
Definitions
- This invention relates to the use of one or more tropolone derivatives of general formula (I)
- H a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms
- OH OR 6 , wherein R 6 is a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms
- COOH COOR 7 , wherein R 7 is a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms; NO 2 ; NH 2 ; F; Cl; Br or I as antioxidants in cosmetic and/or topical pharmaceutical compositions.
- Oxidative damage of biological systems is caused by many different intrinsic and extrinsic factors. Antioxidants are considered to play a pivotal role in preventing or alleviating many human diseases as well as slowing down aging processes by reducing the oxidative damage to cellular components caused by reactive oxygen species. Although there are several enzyme systems within the body that scavenge free radicals, under certain conditions it is advantageous to support the bodies own defense system by supplying to it additional antioxidants.
- antioxidants comprising in a cosmetic and/or topical pharmaceutical composition to the skin and/or hair, to scavenge free radicals and prevent the skin and/or hair from oxidative damage and aging caused by any common extrinsic and/or intrinsic generators of reactive oxygen.
- antioxidants may have an impact on chemical compounds that get easily oxidised (oxidative labile chemical compounds) and therefore antioxidants can considerably increase the shelf-life these compounds in cosmetic and/or topical pharmaceutical compositions.
- antioxidants like butylated hydroxytoluene (BHT)
- BHT butylated hydroxytoluene
- nature also provides very different structural types of antioxidants like carotenoids, antho- cyanins, flavonoids, catechins or oligomeric procyanidins possessing strong antioxidant properties.
- Plant-derived products which are well known to the consumer comprising high concentrations of phenolic antioxidants like catechins or oligomeric proanthocya- nidine derivatives (OPCs) are tea leaf extract and grape seed extract, respectively.
- OPCs oligomeric proanthocya- nidine derivatives
- the aim of the present invention is to provide one or more alternative antioxidants, which can be used in cosmetic and/or topical pharmaceutical composi- tions.
- the invention is related to the use of one or more tropolone derivatives of general formula (I)
- H a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms
- OH a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms
- OR 6 wherein R 6 is a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms
- COOH COOR 7
- R 7 is a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms
- antioxidants in cosmetic and/or topical pharmaceutical compositions.
- topical pharmaceutical compositions means a pharmaceutical composition which has to be applied topically to skin and/or hair.
- Preferred topical pharmaceutical compositions are dermatological compositions which have to be applied topically to skin and/or hair.
- cosmetic compositions are applied also topically to skin and/or hair.
- the invention is based on the surprising finding that the tropolone derivatives of general formula (I) have a high activity on scavenging free radicals and are therefore antioxidative active agents and can be used in cosmetic and/or topical pharmaceutical compositions as the or one of the antioxidants.
- tropolone derivatives of the general formula (II) are toxicologically acceptable, readily tolerated by the skin, stable in the conventional cosmetic and/or topical pharmaceutical formulations, largely and preferably completely odourless and inexpensive to prepare.
- tropolone derivatives of general formula (I) can be of natural or of synthetic origin.
- a preferred natural tropolone derivative of general formula (I) is the tro- polone of formula (II) (CAS-Nr.: 533-75-5; 2,4,6-Cycloheptatriene-1one, 2- hydroxy):
- the authors describe with respect to the antioxidative activity that the oxidation of methyl linoleate is only weakly inhibited by the addition of the tropolone of formula (II) in comparison to the addition of the same concentration of comparative compounds, i.e. alpha-tocopherol, 2,6-di-tert-butyl-4-methyl-phenol, and (+)- catechin.
- the authors conclude that the wood preservation cannot be explained by an antioxidative effect of the tropolone.
- tropolone of formula (II) possesses much weaker radical scavenging activity, namely 14%, compared to alpha- Tocopherol, namely 90%, or (+)-Catechin, namely 80%, in the DPPH antioxidant assay (2,2-JDip_henyl-1-pjcryl]iydrazyl) method).
- tropolone derivatives of general formula (I), preferably the tropolone of formula (II), in cosmetic and/or topical pharmaceutical compositions oxidative labile chemical compounds can be protected of oxidative degradation and/or deterioration thereof caused by any common extrinsic and/or intrinsic generators of reactive oxygen species.
- tropolone derivatives of general formula (I), preferably the tropolone of formula (II), in cosmetic and/or topical pharmaceutical compositions skin and/or hair can be prevented from oxidative damage and aging caused by any common extrinsic and/or intrinsic generators of reactive oxygen species.
- the tropolone derivatives of formula (I) are used in cosmetic and/or topical pharmaceutical compositions in the form of a soap, synthetic detergent, liquid washing, shower and bath preparation, emulsion (as a solution, dispersion, suspension; cream, lotion or milk depending on the production process and ingredients as a VWO, O/W or multiple emulsion W/O/W, PIT emulsion, emulsion foam, micro-emulsion, nano-emulsion, Pickering emulsion), as an ointment, paste, gel (including hydrogel, hydrodispersion gel, oleogel), oil, toner, balsam, serum, powder, eau de toilette, toilette, eau de cologne, perfume, wax, as a stick, roll-on, (pump) spray, aerosol (foaming, non-foaming or post-foaming), as a foot care product (including keratolytics, deodorants), as a shaving foam or aftershave (balm
- shampoo including 2-in-1 shampoo, conditioner, hair tonic, hair water, hair rinse, hair cream, pomade, perm and setting lotion, hair smoothing product (de- tangling product, relaxer), hair strengthener, styling aid (e.g. gel or wax); blonding product, hair dye (e.g. temporary hair dyes, colour rinses, semi-permanent and permanent hair dyes), as nail care products such as e.g. nail polish and nail polish remover, as deodorants and/or antiperspirants; mouthwash, makeup, makeup remover, decorative cosmetics (e.g. powder, eyeshadows, kohl pencil, lipstick).
- hair dye e.g. temporary hair dyes, colour rinses, semi-permanent and permanent hair dyes
- nail care products such as e.g. nail polish and nail polish remover, as deodorants and/or antiperspirants
- mouthwash makeup, makeup remover
- decorative cosmetics e.g. powder, eyeshadows, kohl pencil, lipstick.
- the tropolone of formula (II) is used in a cosmetic and/or topical pharmaceutical composition as described hereinbefore.
- the topical pharmaceutical composition is preferably a dermatological composition which has to be applied topically.
- a preferred embodiment relates to cosmetic and/or topical pharmaceutical emulsions, because in emulsions a high antioxidative efficacy was observed, preferably of the water-in-oil (VWO) type or of the oil-in-water (O/W) type or a multiple emulsion, for example of the water-in-oil-in-water (W/O/W) type, a PIT emulsion, an emulsion foam, a micro-emulsion, a nano-emulsion or a Pickering emulsion, more preferred are emulsions of the (W/O), (O/W) or (W/O/W) type and most preferred are emulsions of the (O/W) and (W/O/W) type, because in these emulsions the highest antioxidative efficacy was observed.
- the tropolone of formula (II) is used in a cosmetic and/or topical pharmaceutical emulsion as described hereinbefore.
- a preferred embodiment also relates to a use of a cosmetic and/or topical pharmaceutical composition of the present invention comprising one or more antioxi- dative active tropolone derivatives of general formula (I) and one or more further antioxidant.
- the or one of the tropolone derivatives of formula (I) is preferably the tropolone of formula (II).
- the further antioxidants have a different structure com- pared to the tropolone derivatives of general formula (I) and can be selected of all suitable or common antioxidants for cosmetic and/or topical pharmaceutical applications.
- the antioxidants are advantageously selected from the group consisting of amino acids (e.g. glycine, histidine, tyrosine, tryptophane) and derivatives thereof, imidazoles (e.g.
- urocanic acid and derivatives thereof, peptides such as D,L-carnosine, D-carnosine, L-carnosine and derivatives thereof (e.g. anserine), carotenoids, carotenes (e.g. ⁇ -carotene, ⁇ -carotene, lycopene) and derivatives thereof, chlorogenic acid and derivatives thereof, lipoic acid and derivatives thereof (e.g. dihydrolipoic acid), aurothioglucose, propyl thiouracil and other thiols (e.g.
- thioredoxin glutathione, cysteine, cystine, cystamine and glyco- syl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, ⁇ - linoleyl, cholesteryl and glyceryl esters thereof) and the salts thereof, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and sulfoximine compounds (e.g.
- buthionine sulfoximines homocysteine sulfoximine, buthionine sulfones, penta-, hexa-, heptathionine sulfoximine
- metal chelators like ⁇ -hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin, ⁇ -hydroxy acids (e.g. citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and derivatives thereof, unsaturated fatty acids and derivatives thereof (e.g.
- ⁇ -linolenic acid linoleic acid, oleic acid
- folic acid and derivatives thereof ubiquinone and ubiqui- nol and derivatives thereof
- vitamin C and derivatives e.g. ascorbyl palmitate, Mg ascorbyl phosphate, ascorbyl acetate, ascorbyl glycosides such as e.g.
- 6-O-acyl- 2-O- ⁇ -D-glucopyranosyl-L-ascorbic acid 6-O-acyl-2-O- ⁇ -D-glucopyranosyl-L- ascorbic acid, 2-O- ⁇ -D-glucopyranosyl-L-ascorbic acid or 2-O- ⁇ -D- glucopyranosyl-L-ascorbic acid), tocopherols and derivatives thereof (e.g.
- vitamin E acetate
- vitamin A and derivatives thereof vitamin A palmitate
- coniferyl benzoate retinoic acid and derivatives thereof
- ⁇ -glucosyl rutin quercetin and derivatives thereof
- rosemarinic acid carnosol
- carnosolic acid carnosolic acid
- resveratrol caffeic acid and derivatives thereof
- sinapic acid and derivatives thereof ferulic acid and derivatives thereof
- curcuminoids butyl hydroxytoluene, butyl hydroxyanisole, nordihydroguaiacic resin acid, nordi- hydroguaiaretic acid, trihydroxybutyrophenone
- uric acid and derivatives thereof mannose and derivatives thereof
- superoxide dismutase zinc and derivatives thereof
- ZnO, ZnSO 4 selenium and derivatives thereof (e.g. selenium methionine), stilbenes and derivatives thereof (e.g. stilbene oxide, trans-stilbene oxide), anthranilic acid amides and derivatives thereof along with derivatives (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of these cited active ingredients or extracts or fractions of plants having an antioxidant effect, such as e.g.
- the concentration of tropolone derivatives of general formula (I), preferably the tropolone of formula (II), in cosmetic and/or topical pharmaceutical compositions can range typically from 1 ppm to 10000 ppm and preferably from 10 ppm to 5000 ppm, based on the total weight of the cosmetic and/or topical pharmaceuti- cal composition.
- Cosmetic and/or topical pharmaceutical compositions optionally contain further components, e.g. solvents, emulsifiers, glycerides, fats, pigments, UV-filters, preservatives and other ingredients.
- further components e.g. solvents, emulsifiers, glycerides, fats, pigments, UV-filters, preservatives and other ingredients.
- Example 1 The invention is explained in more detail in the following examples, whereby the present invention is not limited to the disclosed examples.
- Example 1
- tropolone derivatives of the general formula (I) and specifically tropolone of formula (II) CARN: 533-75-5; 2,4,6-Cycloheptatriene-1- on, 2-hydroxy
- the antioxidant capacity of tropolone derivatives of the general formula (I) and specifically tropolone of formula (II) was evaluated with the ABTS assay, a cell free in vitro test.
- the assay principle bases on the chemical reduction being accompanied by discoloration of the green coloured cationic radical 2,2'-Azinobis(3- ethylbenzothiazoline 6-sulfonic acid) (ABTS + ) by antioxidants.
- the grade of discoloration can be measured photometrically at 734 nm.
- Tropolone derivatives of general formula (I) and plant extracts comprising tropolone derivatives of general formula (I) as well as standard antioxidants like alpha-Tocopherol and Trolox, a water soluble alpha-Tocopherol analog were tested on 96-well microtiter plates at 5 concentrations. Each concentration was tested in double in two independent experiments. Mean IC 5 O values and mean deviation values for the tropolone of formula (II) as well as for the comparative examples are depicted in table 1.
- tropolone derivatives of general formula (I) possess a very high antioxidant capacity showing better or comparable results to several well known products like Trolox or alpha- Tocopherol. Therefore, tropolone derivatives of the general formula (I) including the tropolone of formula (II) itself are highly suitable new products either to protect biological systems from damage caused by free radicals of different type and origin or to extend the shelf life of products comprising highly unstable, easily oxidising molecules.
- Table 1 IC 50 values for the tropolone of formula (II) (CARN: 533-75-5; 2,4,6- Cycloheptatriene-1-on, 2-hydroxy), alpha-Tocopherol (CAS-Nr. 59-02-9; 2,5,7,8- tetramethyl-2-(4,8,12-trimethyltridecyl)chroman-6-ol) and Trolox (2H-1- Benzopyran-2-carboxylic acid, 3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-; 6- hydroxy ⁇ . ⁇ j. ⁇ -tetramethylchroman ⁇ -carboxylic acid)measured with the ABTS method:
- Example 2 Cosmetic and/or topical pharmaceutical compositions comprising one or more tropolone derivatives of general formula (I)
- Cosmetic and/or topical pharmaceutical compositions in particular topical admin- isterable compositions thereof, disclosed herein comprising antioxidative active natural extracts with standardized content of tropolone derivatives of general formula (I) or highly pure synthetic tropolone derivatives of the general formula (I) and specifically the tropolone of formula (II) itself to protect skin and scalp from damage caused by reactive oxygen species may further contain other components like solvents, emulsifiers, glycerides, fats, pigments, UV-filters, preservatives and other ingredients that can be added to a topical administerable formulations.
- Such cosmetic and/or topical pharmaceutical compositions are illustrated by the following examples.
- Example F4 Skin whitening cream
- Example F5 Moisturising eye gel with anti-oxidants
- Example F6 Base for anti-oxidant wet wipes
- Example F7 Silicone emulsion
Abstract
The present invention relates to the use of one or more tropolone derivatives of general formula (I) wherein the substituents R1, R2, R3, R4, R5 independently of one another have the following meaning: H; a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms; OH; OR6, wherein R6 is a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms; COOH; COOR7, wherein R7 is a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms; NO2; NH2; F; CI; Br; or I; as antioxidants in cosmetic and/or topical pharmaceutical compositions.
Description
Use of Tropolone Derivatives as Antioxidants in Cosmetic and/or Topical Pharmaceutical Compositions
This invention relates to the use of one or more tropolone derivatives of general formula (I)
wherein the substituents R1, R2, R3, R4 and R5 independently of one another have the following meaning:
H; a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms; OH; OR6, wherein R6 is a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms; COOH; COOR7, wherein R7 is a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms; NO2; NH2; F; Cl; Br or I
as antioxidants in cosmetic and/or topical pharmaceutical compositions.
Oxidative damage of biological systems is caused by many different intrinsic and extrinsic factors. Antioxidants are considered to play a pivotal role in preventing or alleviating many human diseases as well as slowing down aging processes by reducing the oxidative damage to cellular components caused by reactive oxygen species. Although there are several enzyme systems within the body that scavenge free radicals, under certain conditions it is advantageous to support the bodies own defense system by supplying to it additional antioxidants.
In the cosmetic and/or topical pharmaceutical field it is therefore advantageous to apply antioxidants comprising in a cosmetic and/or topical pharmaceutical composition to the skin and/or hair, to scavenge free radicals and prevent the skin and/or hair from oxidative damage and aging caused by any common extrinsic and/or intrinsic generators of reactive oxygen.
Besides, antioxidants may have an impact on chemical compounds that get easily oxidised (oxidative labile chemical compounds) and therefore antioxidants can considerably increase the shelf-life these compounds in cosmetic and/or topical pharmaceutical compositions.
For the above mentioned reasons natural and synthetic antioxidants find wide use in many different cosmetic and/or topical pharmaceutical products.
In the cosmetic and topical pharmaceutical field referred to a large number of antioxidative active compounds are indeed already employed, but alternatives nevertheless continue to be sought. In this context, however, in the search for alternative agents having an antioxidative activity, it is to be noted that the substances used in the cosmetics and/or topical pharmaceutical field must be
Toxicologically acceptable,
Readily tolerated by the skin,
Stable (in particular in the conventional cosmetic and/or topical pharma- ceutical formulations),
Largely and preferably completely odourless and
Inexpensive to prepare (i.e. employing standard processes and/or starting from standard precursors).
Besides synthetic antioxidants like butylated hydroxytoluene (BHT), nature also provides very different structural types of antioxidants like carotenoids, antho- cyanins, flavonoids, catechins or oligomeric procyanidins possessing strong antioxidant properties.
Plant-derived products which are well known to the consumer comprising high concentrations of phenolic antioxidants like catechins or oligomeric proanthocya- nidine derivatives (OPCs) are tea leaf extract and grape seed extract, respectively. The antioxidant efficacy of such compounds was proven in numerous in vitro and in vivo studies by many different research groups.
The aim of the present invention is to provide one or more alternative antioxidants, which can be used in cosmetic and/or topical pharmaceutical composi- tions.
The invention is related to the use of one or more tropolone derivatives of general formula (I)
wherein the substituents R1, R2, R3, R4, R5 independently of one another have the following meaning:
H; a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms; OH; OR6, wherein R6 is a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms; COOH; COOR7, wherein R7 is a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms; NO2; NH2; F; Cl; Br; or I
as antioxidants in cosmetic and/or topical pharmaceutical compositions.
In the sense of this invention topical pharmaceutical compositions means a pharmaceutical composition which has to be applied topically to skin and/or hair. Preferred topical pharmaceutical compositions are dermatological compositions which have to be applied topically to skin and/or hair.
In the sense of this invention cosmetic compositions are applied also topically to skin and/or hair.
The invention is based on the surprising finding that the tropolone derivatives of general formula (I) have a high activity on scavenging free radicals and are therefore antioxidative active agents and can be used in cosmetic and/or topical pharmaceutical compositions as the or one of the antioxidants.
Besides, tropolone derivatives of the general formula (II) are toxicologically acceptable, readily tolerated by the skin, stable in the conventional cosmetic and/or
topical pharmaceutical formulations, largely and preferably completely odourless and inexpensive to prepare.
The tropolone derivatives of general formula (I) can be of natural or of synthetic origin. A preferred natural tropolone derivative of general formula (I) is the tro- polone of formula (II) (CAS-Nr.: 533-75-5; 2,4,6-Cycloheptatriene-1one, 2- hydroxy):
P. N. Diouf et al. (Applied and Environmental Microbiology 68 (9), p.4377-4382, 2002) relates to wood preservatives as alternatives to traditional methods of wood preservation and the tropolone of formula (II) as wood preservative. It is known that Gloeophyllum trabeum as a fungus uses an extracellular Fenton system (Fe2+H2Oa) to generate hydroxyl radicals, powerful oxidants to degrade wood. It is further known that biochelators, like catechols, not only sequester metals, but are also known to possess reductive capabilities to reduce transition metal species. The authors of the referred article have therefore studied whether the tropolone of formula (II) produced its effects on wood preservation by acting as a chelator, an antioxidant, a scavenger of chemical radicals or some combination of these effects.
The authors describe with respect to the antioxidative activity that the oxidation of methyl linoleate is only weakly inhibited by the addition of the tropolone of formula (II) in comparison to the addition of the same concentration of comparative compounds, i.e. alpha-tocopherol, 2,6-di-tert-butyl-4-methyl-phenol, and (+)-
catechin. The authors conclude that the wood preservation cannot be explained by an antioxidative effect of the tropolone.
Besides the authors also describe that the tropolone of formula (II) possesses much weaker radical scavenging activity, namely 14%, compared to alpha- Tocopherol, namely 90%, or (+)-Catechin, namely 80%, in the DPPH antioxidant assay (2,2-JDip_henyl-1-pjcryl]iydrazyl) method).
Surprisingly, our new research studies, as described in Example 1 , show in contrast to the investigations performed by Diouf et al., that tropolone derivatives of formula (I), in particular the tropolone of formula (II), possess excellent radical scavenging activity which is comparable or better to commonly known antioxidants like Trolox (θ-hydroxy^.δ.y.δ-tetramethylchroman^-carboxylic acid) and alpha-Tocopherol (vitamin E). Therefore tropolone derivatives of general formula (I) and the tropolone of formula (II) possess a potent antioxidative activity and can be used as the or one of the antioxidants in cosmetic and/or topical pharma- ceutical compositions.
By using tropolone derivatives of general formula (I), preferably the tropolone of formula (II), in cosmetic and/or topical pharmaceutical compositions oxidative labile chemical compounds can be protected of oxidative degradation and/or deterioration thereof caused by any common extrinsic and/or intrinsic generators of reactive oxygen species.
By using tropolone derivatives of general formula (I), preferably the tropolone of formula (II), in cosmetic and/or topical pharmaceutical compositions skin and/or hair can be prevented from oxidative damage and aging caused by any common extrinsic and/or intrinsic generators of reactive oxygen species.
Preferably the tropolone derivatives of formula (I) are used in cosmetic and/or topical pharmaceutical compositions in the form of a soap, synthetic detergent, liquid washing, shower and bath preparation, emulsion (as a solution, dispersion,
suspension; cream, lotion or milk depending on the production process and ingredients as a VWO, O/W or multiple emulsion W/O/W, PIT emulsion, emulsion foam, micro-emulsion, nano-emulsion, Pickering emulsion), as an ointment, paste, gel (including hydrogel, hydrodispersion gel, oleogel), oil, toner, balsam, serum, powder, eau de toilette, toilette, eau de cologne, perfume, wax, as a stick, roll-on, (pump) spray, aerosol (foaming, non-foaming or post-foaming), as a foot care product (including keratolytics, deodorants), as a shaving foam or aftershave (balm, lotion) as a depilatory product, hair care product such as e.g. shampoo (including 2-in-1 shampoo), conditioner, hair tonic, hair water, hair rinse, hair cream, pomade, perm and setting lotion, hair smoothing product (de- tangling product, relaxer), hair strengthener, styling aid (e.g. gel or wax); blonding product, hair dye (e.g. temporary hair dyes, colour rinses, semi-permanent and permanent hair dyes), as nail care products such as e.g. nail polish and nail polish remover, as deodorants and/or antiperspirants; mouthwash, makeup, makeup remover, decorative cosmetics (e.g. powder, eyeshadows, kohl pencil, lipstick).
Preferably the tropolone of formula (II) is used in a cosmetic and/or topical pharmaceutical composition as described hereinbefore. The topical pharmaceutical composition is preferably a dermatological composition which has to be applied topically.
A preferred embodiment relates to cosmetic and/or topical pharmaceutical emulsions, because in emulsions a high antioxidative efficacy was observed, preferably of the water-in-oil (VWO) type or of the oil-in-water (O/W) type or a multiple emulsion, for example of the water-in-oil-in-water (W/O/W) type, a PIT emulsion, an emulsion foam, a micro-emulsion, a nano-emulsion or a Pickering emulsion, more preferred are emulsions of the (W/O), (O/W) or (W/O/W) type and most preferred are emulsions of the (O/W) and (W/O/W) type, because in these emulsions the highest antioxidative efficacy was observed.
Preferably the tropolone of formula (II) is used in a cosmetic and/or topical pharmaceutical emulsion as described hereinbefore. The topical pharmaceutical emulsion is preferably a dermatological emulsion which has to be applied topically.
A preferred embodiment also relates to a use of a cosmetic and/or topical pharmaceutical composition of the present invention comprising one or more antioxi- dative active tropolone derivatives of general formula (I) and one or more further antioxidant. The or one of the tropolone derivatives of formula (I) is preferably the tropolone of formula (II). The further antioxidants have a different structure com- pared to the tropolone derivatives of general formula (I) and can be selected of all suitable or common antioxidants for cosmetic and/or topical pharmaceutical applications. The antioxidants are advantageously selected from the group consisting of amino acids (e.g. glycine, histidine, tyrosine, tryptophane) and derivatives thereof, imidazoles (e.g. urocanic acid) and derivatives thereof, peptides such as D,L-carnosine, D-carnosine, L-carnosine and derivatives thereof (e.g. anserine), carotenoids, carotenes (e.g. α-carotene, β-carotene, lycopene) and derivatives thereof, chlorogenic acid and derivatives thereof, lipoic acid and derivatives thereof (e.g. dihydrolipoic acid), aurothioglucose, propyl thiouracil and other thiols (e.g. thioredoxin, glutathione, cysteine, cystine, cystamine and glyco- syl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, γ- linoleyl, cholesteryl and glyceryl esters thereof) and the salts thereof, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and sulfoximine compounds (e.g. buthionine sulfoximines, homocysteine sulfoximine, buthionine sulfones, penta-, hexa-, heptathionine sulfoximine) in very small compatible doses, also (metal) chelators like 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, bilirubin, biliverdin, EDTA, EGTA and derivatives thereof, unsaturated fatty acids and derivatives thereof (e.g. γ-linolenic acid, linoleic acid, oleic acid), folic acid and derivatives thereof, ubiquinone and ubiqui- nol and derivatives thereof, vitamin C and derivatives (e.g. ascorbyl palmitate, Mg
ascorbyl phosphate, ascorbyl acetate, ascorbyl glycosides such as e.g. 6-O-acyl- 2-O-α-D-glucopyranosyl-L-ascorbic acid, 6-O-acyl-2-O-β-D-glucopyranosyl-L- ascorbic acid, 2-O-α-D-glucopyranosyl-L-ascorbic acid or 2-O-β-D- glucopyranosyl-L-ascorbic acid), tocopherols and derivatives thereof (e.g. vitamin E acetate), vitamin A and derivatives thereof (vitamin A palmitate) as well as coniferyl benzoate, retinoic acid and derivatives thereof, α-glucosyl rutin, quercetin and derivatives thereof, rosemarinic acid, carnosol, carnosolic acid, resveratrol, caffeic acid and derivatives thereof, sinapic acid and derivatives thereof, ferulic acid and derivatives thereof, furfurylidene glucitol, curcuminoids, butyl hydroxytoluene, butyl hydroxyanisole, nordihydroguaiacic resin acid, nordi- hydroguaiaretic acid, trihydroxybutyrophenone, uric acid and derivatives thereof, mannose and derivatives thereof, superoxide dismutase, zinc and derivatives thereof (e.g. ZnO, ZnSO4) selenium and derivatives thereof (e.g. selenium methionine), stilbenes and derivatives thereof (e.g. stilbene oxide, trans-stilbene oxide), anthranilic acid amides and derivatives thereof along with derivatives (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of these cited active ingredients or extracts or fractions of plants having an antioxidant effect, such as e.g. green tea, rooibos, honeybush, grape, rosemary, sage, melissa, thyme, lavender, olive, oats, cocoa, ginkgo, ginseng, liquorice, honey- suckle, sophora, pueraria, pinus, citrus, Phyllanthus emblica or St. John's wort.
The concentration of tropolone derivatives of general formula (I), preferably the tropolone of formula (II), in cosmetic and/or topical pharmaceutical compositions can range typically from 1 ppm to 10000 ppm and preferably from 10 ppm to 5000 ppm, based on the total weight of the cosmetic and/or topical pharmaceuti- cal composition.
Cosmetic and/or topical pharmaceutical compositions optionally contain further components, e.g. solvents, emulsifiers, glycerides, fats, pigments, UV-filters, preservatives and other ingredients.
The invention is explained in more detail in the following examples, whereby the present invention is not limited to the disclosed examples.
Example 1
ABTS Assay - Measurement of the Antioxidant Capacity of Tropolone
The antioxidant capacity of tropolone derivatives of the general formula (I) and specifically tropolone of formula (II) (CARN: 533-75-5; 2,4,6-Cycloheptatriene-1- on, 2-hydroxy) disclosed here was evaluated with the ABTS assay, a cell free in vitro test. The assay principle bases on the chemical reduction being accompanied by discoloration of the green coloured cationic radical 2,2'-Azinobis(3- ethylbenzothiazoline 6-sulfonic acid) (ABTS+) by antioxidants. The grade of discoloration can be measured photometrically at 734 nm. Tropolone derivatives of general formula (I) and plant extracts comprising tropolone derivatives of general formula (I) as well as standard antioxidants like alpha-Tocopherol and Trolox, a water soluble alpha-Tocopherol analog were tested on 96-well microtiter plates at 5 concentrations. Each concentration was tested in double in two independent experiments. Mean IC5O values and mean deviation values for the tropolone of formula (II) as well as for the comparative examples are depicted in table 1.
The ABTS study for the tropolone of formula (II) exemplifies that tropolone derivatives of general formula (I) possess a very high antioxidant capacity showing better or comparable results to several well known products like Trolox or alpha- Tocopherol. Therefore, tropolone derivatives of the general formula (I) including the tropolone of formula (II) itself are highly suitable new products either to protect biological systems from damage caused by free radicals of different type and origin or to extend the shelf life of products comprising highly unstable, easily oxidising molecules.
Table 1 : IC50 values for the tropolone of formula (II) (CARN: 533-75-5; 2,4,6- Cycloheptatriene-1-on, 2-hydroxy), alpha-Tocopherol (CAS-Nr. 59-02-9; 2,5,7,8- tetramethyl-2-(4,8,12-trimethyltridecyl)chroman-6-ol) and Trolox (2H-1- Benzopyran-2-carboxylic acid, 3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-; 6- hydroxy^.δj.δ-tetramethylchroman^-carboxylic acid)measured with the ABTS method:
Example 2: Cosmetic and/or topical pharmaceutical compositions comprising one or more tropolone derivatives of general formula (I)
Cosmetic and/or topical pharmaceutical compositions, in particular topical admin- isterable compositions thereof, disclosed herein comprising antioxidative active natural extracts with standardized content of tropolone derivatives of general formula (I) or highly pure synthetic tropolone derivatives of the general formula (I) and specifically the tropolone of formula (II) itself to protect skin and scalp from damage caused by reactive oxygen species may further contain other components like solvents, emulsifiers, glycerides, fats, pigments, UV-filters, preservatives and other ingredients that can be added to a topical administerable formulations. Such cosmetic and/or topical pharmaceutical compositions are illustrated by the following examples.
Example F1: Anti-aging lotion
Example F2: Triple anti-oxidant cream
Example F5: Moisturising eye gel with anti-oxidants
Example F6: Base for anti-oxidant wet wipes
Raw Material % weight
Phase 1
Water 88.89 Butylene Glycol 8.00 Citric Acid 10% 0.10
Phase 2
PEG-40 Hydrogenated Castor Oil, Trideceth-9, Propylene Glycol, 2.00 Water Fragrance 0.10
Phase 3
Tropolone of formula (II) 0.01
Phase 4
Phenoxyethanol 0.90
Example F7: Silicone emulsion
Example F8: Anti-oxidant spray
Example F9: Anti-oxidant shower gel
Example F10: Hair protectant
Claims
1. Use of one or more tropolone derivatives of general formula (I)
wherein the substituents R1, R2, R3, R4, R5 independently of one another have the following meaning:
H; a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms; OH; OR6, wherein R6 is a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms; COOH; COOR7, wherein R7 is a linear or branched, saturated or unsaturated, aliphatic carbon chain with up to 30 C-atoms; NO2; NH2; F; Cl; Br; or I;
as antioxidants in cosmetic and/or topical pharmaceutical compositions.
2. Use according to claimi , wherein the or one of the tropolone derivatives is the tropolone of formula (II):
(H)
3. Use according to one of claims 1 or 2, wherein the concentration of the or one of the tropolone derivatives of general formula (I) or the tropolone of formula (II) in cosmetic and/or topical pharmaceutical compositions is from 1 ppm to 10000 ppm, preferably from 10 ppm to 5000 ppm, based on the total weight of the cosmetic and/or topical pharmaceutical composition.
4. Use according to one of the preceding claims, wherein the cosmetic and/or topical pharmaceutical composition is an emulsion.
5. Use according to one of the preceding claims, wherein the compositions further comprise one or more further antioxidants.
6. Use according to one of the preceding claims to protect oxidative degradation and/or deterioration of oxidative labile ingredients in cosmetic and/or topical pharmaceutical compositions caused by any common extrinsic and/or intrinsic generators of reactive oxygen species.
7. Use according to one of the preceding claims to prevent skin and/or hair from oxidative damage and aging caused by any common extrinsic and/or intrinsic generators of reactive oxygen species.
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US9889080B2 (en) | 2015-05-07 | 2018-02-13 | Celeb LLC | Color depositing shampoo |
US10245221B2 (en) | 2015-05-07 | 2019-04-02 | Celeb LLC | Stabilized color depositing shampoo |
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011042423A2 (en) | 2009-10-06 | 2011-04-14 | Basf Se | Stabilization of household, body-care and food products by using benzotropolone containing plant extracts and/or related benzotropolone derivatives |
WO2011042423A3 (en) * | 2009-10-06 | 2014-02-20 | Basf Se | Use of benzotropolone derivatives as photostabilizer and antioxidant for stabilization of body-care and household products. |
US8784853B2 (en) | 2009-10-06 | 2014-07-22 | Basf Se | Stabilization of household, body-care and food products by using benzotropolone containing plant extracts and/or related benzotropolone derivatives |
US9663442B2 (en) | 2009-10-06 | 2017-05-30 | Basf Se | Stabilization of household, body-care and food products by using benzotropolone containing plant extracts and/or related benzotropolone derivatives |
US9889080B2 (en) | 2015-05-07 | 2018-02-13 | Celeb LLC | Color depositing shampoo |
US10245221B2 (en) | 2015-05-07 | 2019-04-02 | Celeb LLC | Stabilized color depositing shampoo |
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