CA2360727A1

CA2360727A1 - Antioxidant skin care products

Info

Publication number: CA2360727A1
Application number: CA002360727A
Authority: CA
Inventors: Angela Muller; Marianne Waldmann-Laue; Christina Hammes; Stefanie Ortanderl; Elke Blumenkamp; Gabriele Munk
Original assignee: Henkel AG and Co KGaA
Current assignee: Individual
Priority date: 1999-01-30
Filing date: 2000-01-21
Publication date: 2000-08-03
Also published as: DE19903716A1; CN1345225A; EP1146853B1; DE50001610D1; JP2002535348A; AU3276200A; EP1146853A2; WO2000044344A2; ATE235885T1; WO2000044344A3

Abstract

The invention relates to an antioxidant combination from tocopherol and/or tocopherol ester, a gallic acid ester and a tea plant extract. The inventive combination is characterized by a much more potent antioxidant effect as compared to the individual components. The antioxidant combination is excellent for use in the production of skin care products which prevent oxidative damages to the skin or which improve the appearance of aged skin.< /SDOAB>

Description

"Antioxidant skin care products"
The invention relates to cosmetic preparations with a synergistic antioxidant combination which are used as skin care products.
Being the external organ with the largest surface area, the skin is exposed to environmental influences to a particularly high degree. Since the skin serves primarily to protect the body, it has numerous natural protective barriers and regeneration processes.
However, increasing stresses from noxae and UV in recent times are leading to excessive stressing of the skin and interfering with the natural regeneration capacity in a sensitive manner. For example, excessive stressing by high-energy UV rays leads both to acute damage, such as, for example, sunburn, and also to chronic changes, such as, for example, premature skin aging in the form of structural changes to the connective tissue. As a consequence of excessive W
stress, various reactive oxygen species form in the skin which have a triggering or intensifying effect on numerous undesired oxidative processes. In order to control "oxidative stress", the skin contains various substances with an antioxidative action, e.g.
superoxide dismutase, tocopherols and ascorbic acid.
These antioxidants prevent free oxygen radicals from attacking the lipid membranes of the living cells (lipid peroxidation) or even from leading to irreversible damage of the genetic material.
More recent research has shown that the external application of antioxidants may also reduce oxidative stress. The endeavors of the cosmetics industry have promoted the development of body care products which, as a preventative measure, comprise highly effective and in particular physiologically safe antioxidants.
More recently, multicomponent systems with a synergistic activity in particular have been used, with extracts from natural substances being employed to an increasing extent.
The person skilled in the art is familiar with a large number of plant extracts comprising active antioxidative substances (H. Eggensperger, Pflanzliche Wirkstoffe fur Kosmetika [Plant active ingredients for cosmetics], Melcher Verlag GmbH, Munich, 1995, p. 402 ff.). A process for obtaining a natural antioxidant mixture from green tea is taught in US 4673530. A skin care product based on a-tocopheryl retinoate is described in JP 8099821. The synergistic or cooperative antioxidative effect of a mixture of procyanidines and vitamin E has been described by M. Caribi et al.
[International Journal of Cosmetic Science 20, 203-215, (1998) ] .
The antioxidants or antioxidant mixtures currently in use cannot, however, satisfy the requirements entirely.
Extracts of natural substances with synergistic antioxidants frequently lead to an unwanted discoloration of the cosmetics and can therefore only be used to a limited extent.
It was therefore an object to develop an antioxidant combination which develops a high synergistic effect ("booster effect") and is compatible with the components of the skin care product. For the purposes of the invention, synergistic effect is understood as meaning a cooperative effect of the antioxidants, i.e.
that the antioxidant effect for the combination of the individual components is not additive, but is increased many times over. The antioxidative effect or the "antioxidative potential" has been detected using a chemiluminescence method in analogy with DD 249 618 A3.
Surprisingly, we have now found an antioxidant combination with a high synergistic effect which is compatible with the physiological carriers and other ingredients of a skin care product and is odorless and colorless. Preparations which comprise this combination of antioxidants not only have excellent care properties, but can also prevent skin aging by oxidative processes and/or improve the appearance of aged skin.
The invention therefore provides a cosmetic preparation, characterized in that the antioxidant present is a combination of (a) at least one tocopherol and/or tocopherol ester, (b) at least one gallic acid ester and (c) a tea plant extract in a carrier suitable for topical application to the skin.
The antioxidant mixture comprises tocopherols and/or tocopherol esters as obligatory component (a). The antioxidants or oxidation inhibitors used are organic compounds from various classes of compound which partially or completely inhibit changes caused by the effect of oxygen or by other oxidative processes.
Because of their physiological safety and their ready accessibility, tocopherols and esters thereof are used widely as antioxidants in cosmetics and in foods.
Tocopherols, pale yellowish to reddish liquids, are 3,4-dihydro-2H-1-benzopyran-6-ols, i.e. chroman-6-ols, which are substituted in the 2-position by a 4,8,12-trimethyltridecyl radical. They occur in many plant oils, in particular in seed oils of soybean, wheat, corn, rice, cotton, lucerne and nuts, but also in fruits and vegetables. Tocopherols which are suitable for the purposes of the invention are natural or synthetically accessible tocopherols in enantiomerically pure form or as a mixture of the stereoisomers, including a-, ~-, y-, 8- and E-tocopherols. A preferred variant of the preparation according to the invention is characterized in that component (a) present is a natural or synthetic a-tocopherol in an amount of from 0.005 - 2.0% by weight of the total composition. An amount of from 0.1 - 1.0%
by weight is particularly suitable.
A particularly preferred tocopherol-containing component is a product known under the tradename Controx~ KS. Alternatively to or in combination with the tocopherols it is also possible to use esters of the tocopherols. Suitable esters for the purposes of the invention are, inter alia, C1-CZZ alkyl or aryl esters, but also tocopheryl succinate, tocopheryl poly(oxyethylene)succinate, tocopheryl nicotinate and tocopheryl retinoate.
A further preferred variant of the preparations according to the invention is characterized in that, in addition to a-tocopherol, a-tocopheryl acetate is additionally present in the preparation in an amount of from 0.005 - 5.0% by weight, an amount of from 0.1 -2.0% by weight being particularly preferred. The combination of the two components has proven to be relevant particularly with regard to the color neutrality of the cosmetic preparation. The quantitative ratio of tocopherol to a-tocopheryl acetate is usually 1:(2-10), a ratio of 1:(2-5) being particularly preferred.
The preparations according to the invention also comprise at least one gallic acid ester as obligatory component (b). Gallic acid esters have been known for a long time for their antioxidative properties. The esters suitable for the purposes of the invention include the esters of gallic acid (3,4,5-trihydroxybenzoic acid) with aliphatic C1-C22-alcohols.
The most important representatives used in cosmetics, pharmaceuticals and foods include methyl gallate, ethyl gallate, propyl gallate, octyl gallate, nonyl gallate, dodecyl gallate, cetyl gallate and stearyl gallate. A

~

preferred variant of the preparations according to the invention is characterized in that the gallic acid ester present is propyl gallate in an amount of from 0.005 - 2.0~ by weight of the total composition. A
product known under the tradename Danox 200 is particularly suitable.
The third obligatory component (c) of the antioxidant mixture is a tea plant extract (Camellia sinensis, Theaceae). For this purpose, use is usually made of leaves, leaf-buds and the soft stalks of the tea plant, which are available commercially as "tea". However, for the purposes of the invention, other parts of the plant could be used (seeds, fruits, flowers, stems, bark, roots). A distinction is made between green unfermented tea and black fermented tea. The ingredients of tea include numerous polyphenol compounds which are responsible for its typical aroma. As well as catechol tannins and pyrogallol tannins and flavonoids, caffeine, purine compounds, proteins, oligosaccharides, starch, pectin, inositol, cellulose, lignin, oxalic acid, fruit acids and trace elements are present. In the volatile constituents of tea, between 300-400 substances have been found, of which, however, only two have been identified. In addition, the composition of the tea leaves varies considerably depending on cultivation area and position and variety. The fermentation process considerably reduces the tannin content of the leaves. The known antioxidative effect of tea is attributed to the tannins present therein, in particular to epicatechin, gallocatechin, epigallocatechin, epigallocatechin gallate and epicatechin gallate.
The tea extracts can be obtained by extraction or distillation. Suitable for the extraction are the solvents customarily used for this purpose (alcohols, ketones and ethers), the use of water or water/alcohol ~

mixtures being preferred for the purposes of the invention. The tannin content increases with extraction time. In this case, high molecular weight or polymeric catechol tannins and pyrogallol tannins, which impart the characteristic dark coloration to the extracts, are also chiefly dissolved. Tea extracts which have been obtained by distillation are, by contrast, virtually colorless and are suitable particularly for the preparation of colorless and storage-stable cosmetics.
The active ingredient content in the distillates is generally very much lower than in the extracts.
A preferred embodiment of the preparation is characterized in that the tea plant extract present in the preparation is the steam distillate of leaves of green, unfermented Camellia Sinensis tea in an amount of from 1.0 - 20.0% by weight. Particular preference is given to amounts of from 1.0 - 5.0% by weight. These steam distillates are colorless and, in addition to the volatile essential oils, comprise theaflavin, the active ingredient content usually being between 0.01 -0.5% by weight. The antioxidative potential, at 0.00014 vitamin E units, is in the very low range (Table 1).
Only in combination with oc-tocopheryl acetate, tocopherol and propyl gallate is an unexpectedly high intensification of the antioxidative effect, i.e. a synergism, observed. Such mixtures are therefore particularly suitable as antioxidant combinations for skin care products.
The antioxidant combination is present in the physiologically compatible carriers customary for cosmetic formulations. As well as water and physiologically suitable solvents, it is possible for the customary care constituents, oils, waxes, fats, refatting substances, thickeners, emulsifiers, substances suitable as sunscreen filters and ~

fragrances, inter alia, to be present. Depending on requirements, the composition can be formulated as an aqueous or alcoholic solution, as a gel, oil, W/O
emulsion or O/W emulsion or as an aerosol. For suitable formulation bases, reference may be made at this point to the formulations customary in cosmetics (K. Schrader, Grundlagen and Rezepturen der Kosmetika [Bases and formulations of cosmetics], 2nd edition, Huthig Buch Verlag, Heidelberg 1989, page 424-437, 442 451, 456-465).
The invention likewise provides for the use of the preparation according to the invention for the caring treatment of the skin. The antioxidant combination can prevent the consequences of oxidative stress and favorably influence regeneration processes in the skin.
The preparation of the emulsions described below is carried out in accordance with processes generally customary in cosmetics.

TnlO 00/44344 - 8 - PCT/EP00/00451 Measurement of the antioxidative potential (AOP) The antioxidative potential (AOP) characterizes the "free-radical-scavenging" properties of a substance or a mixture of substances.
A detailed description of the method and apparatus is given in DD 249 618 A3. The method is based on the photochemiluminescence of luminol (3-aminophthalic hydrazide), induced by oxygen free radicals, in the absence and in the presence of certain free-radical scavengers (antioxidants). The photochemiluminescence in the absence of antioxidants serves as a blank value.
In the presence of free-radical scavengers, a decrease in the chemiluminescence of the luminol is observed. To calibrate the system, a defined amount of vitamin E is added and the chemiluminescence is determined in the presence of this free-radical scavenger. This value serves as a reference and is referred to as 1 vitamin E
unit. The luminescence decrease caused by the test substance is compared with the decrease in luminescence for vitamin E and expressed in vitamin E units. Thus, the antioxidative potential of numerous substances and mixtures of substances can be determined in relation to vitamin E.
Carrying out the AOP measurements 1. Design principle of the measurement system The apparatus consists principally of 2 components, a free-radical generator and a detector system.
Using a UV radiation source, superoxide free radical anions or singlet oxygen are generated in the aqueous medium by reducing or exciting oxygen molecules. The resulting free radicals react with luminol, the chemiluminescence of which is ascertained quantitatively by means of the detector system.
2. Required chemicals - luminol, HPLC grade (Baker) - methanol, HPLC grade (Baker) - ethanol, HPLC grade (Baker) - Na2C03 - Na2EDTA~ 2H20 - NaOH
- a-tocopherol (Merck) 3. Required apparatus Photochem, FAT, Berlin Software: Poplab 2.0 Vibrof ix Customary laboratory material:
Syringe filters, 0.2 Vim, Millipore 4. Carrying out the experiment 4.1 Stock solutions (A) ACL buffer stock solution (ACL - Antioxidative Capacity of Lipid soluble substances To prepare the ACL buffer (pH = 11), 10.6 g of NazC03 (M = 106.0 g/mol) and 0.0372 g of Na2EDTA~2H20 (M = 372.24 g/mol) were weighed in and made up to 1 liter using Milli-Q water. The buffer solution was filtered over a 0.45 ~.m syringe filter.
(B) Methanolic ACL buffer 950 ml of methanol (HPLC grade) were added to 50 ml of the ACL buffer stock solution (A), and the mixture was stirred until a clear solution resulted.

(C) Luminol solution A 1 mM luminol solution in 0.1 M sodium hydroxide solution was used for the detection. The solution has to be stored protected from light and in chilled conditions.
4.2 Measurement solutions (D) Solution for determining the blank value 2.0 ml of the prepared clear methanolic ACL buffer were pipetted into a sealable Autosampler vial (4 ml). To this were added about 100 ~1 of the luminol solution and as much anhydrous non-denatured ethanol to make the sum of the volumes of ethanol and luminol solution 0.5 ml. The solution was homogenized on the Vibrofix for a few seconds and measured immediately on the Photochem (cf. 4.4).
(E) Sample solution The analytically accurately weighed amount (about 0.5 g) of the sample to be analyzed was made up to the mark in a 10 ml volumetric flask with methanol. The solution was treated for 10 minutes with ultrasound and then filtered.
(F) Measurement solution 2.0 ml of methanolic ACL buffer (cf. B) were pipetted into a sealable 4 ml Autosampler vial. To this were added the same volume of luminol solution which had been used for the blank value determination, as well as a defined amount of the filtered sample solution (E) and as much anhydrous non-denatured ethanol to make the sum of the volumes of luminol solution, sample solution and ethanol 0.5 ml. The solution was homogenized on the Vibrofix for a few seconds and measured immediately on the Photochem.

4.3 Calibration Calibration was carried out with a vitamin E standard.
An analytically accurately weighed amount of d,l-a-tocopherol (80 ~ 5 mg) was made up to the mark in a 50 ml volumetric flask with methanol. This solution was diluted with ethanol such that the content was 12 mg/l.
For the calibration, solutions (each 2.5 ml) were prepared with, in each case, 30, 50 and 100 ~1 of vitamin E standard solution. In addition, in each case, 2 ml of methanolic ACL buffer solution was combined with the same volume of luminol solution which had been used for the blank value determination, and in each case 30, 50 and 100 ~l of vitamin E standard solution and enough anhydrous non-denatured ethanol were added to make the sum of the volumes of luminol solution, vitamin E standard solution and ethanol 0.5 ml. The measurement was carried out as described under 4.4.
4.4 Chemoluminescence measurement After the instrument had been switched on and after each pause, the chemiluminescence of the blank value solution (cf. D) was determined. When the measured values remained stable, the actual measurement could be started. The measurement time was 180 seconds per sample. The blank value (integral below the curve) was taken into consideration automatically by the software for the subsequent measurements.
The system was then calibrated to vitamin E standards (cf. 4.3), i.e. the chemiluminescence of the three vitamin E standards was determined. The chemi-luminescence of the measurement solutions (F) of the samples to be investigated was then determined. The inhibition of the chemiluminescence was given by the integral of the blank value minus the integral of the measurement solution normalized to the integral of the blank value.
5. Calculation of the analytical result The curves determined for the measurement solutions were compared with the calibration curves for vitamin E. The inhibition of chemiluminescence specific for a substance sample was expressed in vitamin E equivalents per g of sample (mg of vit. E/g of sample) and referred to as the an tioxidative potential (AOP) .
Test results Numerous combinations of antioxidants (pure substances and plant extracts) were investigated with regard to their antioxidative potential, in particular with regard to synergistic effects. Synergism is used to describe the behavior where the antioxidative potential of a mixture does not arise by adding the AOP of the individual components, but is increased many times over. Synergistic effects have been established for the following active ingredient combinations (a + b + c):
a) tocopherol and/or tocopherol esters b) gallic acid esters c) steam distillate of green tea By way of example, Table 1 summarizes the results of the active ingredient combination (5) which is present in the formulation examples according to the invention and has a particularly marked synergism, i.e. a "booster effect".

Table 1 Substances AOP (vitamin E units) (1) Vitamin E acetate 1.0 (2) Controx KS 1.6 (3) Green tea, distillate 0.00014 (4) Danox 200 6.8 (5) Mixture of (1)+(2)+(3)+(4) 97.0 Evaluation:
While the distillate of green tea has a very low antioxidative effect and the vitamin E-containing Controx KS and vitamin E acetate have a comparable antioxidative effect, propyl gallate (DanoX 200) on its own has a significantly higher AOP (6.8 vitamin E
units). However, only the active ingredient combination of vitamin E acetate, Controx KS, the distillate of green tea and DanoX 200 produces a booster effect and leads to a multiplication of the AOP value (AOP - 97 vitamin E units).
Formulation examples according to the invention All of the amounts given below are % by weight of the commercially available substances or mixtures of substances, based on the total amount of the composition.
Example 1 (according to the invention):
The formulation comprises the antioxidant mixture according to the invention:

' CA 02360727 2001-07-27 Substance Amount in ~ by weight Montanov 68 5.00 Myritol~ 318 5.50 Lanette~ 22 4.25 Cutina~ MD-V 1.25 Cetiol~ V 2.00 Baysilon M 350 0.50 Vitamin E acetate 0.50 ControX KS 0.25 Generol~ 122 NElOD 0.50 W-B filter 3.00 UV-A filter 2.00 Preservative 0.20 Polyacrylate 0.40 Talc 0.80 Green tea, distillate 3.00 Perfume 0.40 Glycerol 4.50 DanoX 200 0.05 NaOH, 10% strength 0.46 Water, demineralized ad 100 Example 2 (according to the invention):
The formulation comprises the antioxidant mixture according to the invention:
Substance Amount in $ by weight Lipoid S75-3 1.5 Stenol~ 1618 2.0 Cetiol~ SB 45 1.0 Cegesoft~ C24 6.0 Prisorine~ IPIS 5.0 Controx KS 0.25 Tocopherol acetate 0.5 LTV-A filter 1.0 W-B filter 4.0 Preservative 0.4 Polyacrylate 0.50 Methocel~ E4M (prem.) 0.1 Green tea, distillate 3.0 Danox 200 0.05 Perfume 0 . 2 1,2-Propylene glycol 5.0 Glycerol 5.0 NaOH (10% strength) 1.25 Water, dist. ad 100 Annex List of trademarks and comanercial names for the raw materials used 1) Montanov 68:
INCI: Cetearyl alcohol, Cetearyl glucoside Manufacturer: Seppic (Interorgana) 2 ) Myritol~ 318 INCI: Caprylic/Capric triglyceride Manufacturer: Henkel KGaA
3) Lanette~ 22 INCI: Behenyl alcohol Manufacturer: Henkel (Sidobre-Sinnova) 4) Cutina~ MD-V
INCI: Stearyl stearate Manufacturer: Henkel KGaA
5) Cetiolo V
INCI: Decyl oleate Manufacturer: Henkel KGaA
6) Baysilori M 350 INCI: Dimethicone Manufacturer: Bayer AG
7) Vitamin E acetate INCI: Tocopheryl acetate Manufacturer: BASF

8) Controx KS
INCI: Tocopherol, hydrogenated palm glycerides citrate Tocopherol content: about 56% by weight Manufacturer: Henkel (Griinau) 9) Generol~ 122 NElOD
INCI: PEG-10 Soya sterol Manufacturer: Griinau (Henkel KGaA) 10) Herbasol~ distillate green tea special Henkel, without alcohol INCI: Aqua, camellia sinensis extract, benzoic acid, polysorbate-20 Steam distillate: with 0.75% by weight of benzoic acid, about 2% by weight of polysorbate 20 100 kg of distillate comprise the volatile constituents of 100 kg of green tea Active ingredient content: about 0.01 - 0.5% by weight Manufacturer: Cosmetochem AG, Steinhausen, Switzerland 11) Danox 200 INCI: Propyl gallate Manufacturer: IFSC (Rahn) 12 ) Lipoid~ S75-3 INCI: Hydrogenated lecithin Manufacturer: Lipoid GmbH

13) Stenolo 1618 INCI: Cetearyl alcohol Manufacturer: Henkel KGaA

14 ) Cetiol~ SB 45 INCI: Shea butter Butyrospermum Parkii Manufacturer: Henkel KGaA

15) Cegesoft~ C24 INCI: Octyl palmitate Manufacturer: Henkel (Griinau) 16) Prisorine~ IPIS 2021 INCI: Isopropyl isostearate Manufacturer: Unichema 17) Methocel~ E4M premium INCI: Hydroxypropyl methylcellulose Manufacturer: Dow Chemical (Colorcon Ltd.)

Claims

claims

1. A cosmetic preparation, characterized in that the antioxidant present is a combination of (a) at least one tocopherol and/or tocopherol ester (b) at least one gallic acid ester and (c) a tea plant extract in a carrier suitable for topical application to the skin.

2. The preparation as claimed in claim 1, characterized in that component (a) present is a natural or synthetic .alpha.-tocopherol in an amount of from 0.005 - 2.0% by weight.

3. The preparation as claimed in claim 2, characterized in that .alpha.-tocopheryl acetate is additionally present in an amount of from 0.005 -5.0% by weight.

4. The preparation as claimed in any of claims 1 to 3, characterized in that the gallic acid ester present is propyl gallate in an amount of from 0.005 - 2.0% by weight.

5. The preparation as claimed in any of claims 1 to 4, characterized in that the tea plant extract present in the preparation is the steam distillate of leaves of green, unfermented Camellia Sinensis tea in an amount of from 1.0 - 20.0% by weight.

6. The use of a preparation as claimed in any of claims 1 to 5 for the caring treatment of the skin.