Patent Application
20160361245
This invention relates to biology and medicine and in particular to cosmetology, and may be used for manufacturing a composition for protecting the skin from damage caused by free radicals and/or active forms of oxygen.
Mitochondrially targeted antioxidants (MTA) are one of the most promising classes of anti-age products for use in various products including cosmetic products. However, various MTAs, including those in the SkQ class, in multi-component liquid mixtures are not greatly stable over long periods of storage (over 30 days). The prior art refers to a number of versions of stable compositions of MTA (see for example application WO2012167236), but the number of compositions discovered in technical terms is extremely limited for application as a finished cosmetic product. Therefore, the creation of a finished cosmetic product containing a MTA, and particularly SkQ-class compounds, with sufficient storage stability is an unresolved technical task.
Definitions
1. Mitochondrial antioxidant—compound with general formula 1:
Where A is an antioxidant with general formula 2:
Where Y where m is an integer from 1 to 3; Y refers to single or various substitutes that constitute a lower alkyl or lower alkoxy, including the methyl or methoxy groups;
and/or its restored form
L is a linker group, that is:
a) a straight or branched hydrocarbon chain, not necessarily replaced with one or more substitutes, and where necessary containing one or more double or triple bonds; or
b) a natural isoprenoid chain;
n is an integer from 1 to 20;
B is a Skulachev ion Sk:
Sk+Z−
where Sk is a lipophilic cation; Z is a pharmacologically acceptable anion
2. Stable composition for cosmetic use is a composition within which the formula 1 compound retains sufficient stability over at least 30 days when stored at a temperature of +5° C.
3. Emollients are substances from various chemical groups, hydrophilic and lipophilic, capable of softening the skin.
4. Multifunctional components are components of a cosmetic product that fulfil more than one function.
Names and Description of Some Components of Finished Cosmetic Products and Their Manufacturers:
(manufacturers shown in square brackets)
Application of the invention is not limited to use of the specific components shown (trade names) or specifically these manufacturers. The composition of components is significant, and the manufacturer and trade product may be different. Manufacturers and trade names are shown as proof of possibility of applying the invention and as an indication for qualified specialists of what ingredients (regardless of their trade names and manufacturers) were used in the present invention.
Biocol LG (Ceratonia Siliqua Gum, Pectin, Algin) [Manufacturer: Biogenico Worldwide].
Biocol AX (Pectin, Xanthan Gum) [Biogenico Worldwide].
Makimousse12 (Sodium Polyacrylate Starch) [Daito Kasei].
Methocel 40-202 (Hydroxypropyl Methylcellulose) [DOW].
Nexbase 2006 FG (Hydrogenated Polydecene) [Neste Oil Oyj].
Silsoft 034 (Caprylyl Methicone) [Momentive Performance Materials].
Sensolene (Ethyl hexyl Olivate) [B@TCompany].
Lexfeel 7 (Neopentyl Glycol Diheptanoate) [Inolex].
Biolin/P (Inulin, Alpha-glucan Oligosaccharide) [Goya Ingredients].
Drieline1s (Sorbitol, Yeast Extract) [LucasMeyer cosmetics].
Peptiskin (Arginine/lysine Polypeptide) [Solabia Group].
Gatuline In-Tense (Caprylic/Capric Triglyceride, Spilanthes Acmella Flower Extract) [Gattefosse].
Vegetensor (Pisum Sativum Extract, Sclerotium Gum) [Alban Muller International].
Argireline (Aqua, Acetyl Hexapeptide-8) [Lipotec Group].
Ecoffea (Aqua, Glycerine, Coffea Arabica (Coffee) Seedcake Extract) [Chemyunion Quimica LTDA].
Dermocea (Aqua, Sucrose, Meristotheca Dakarensis Extract, Jania Rubens Extract) [Gelyma].
RonaCare Cyclopeptide-5 (Aqua, Alcohol, Lecithin, Ectoin, Cyclotetrapeptide-24 Aminocyclohexane Carboxylate) [Merck KGaA].
RonaCare Luremin (Dihydroxymethylchromone, Sorbitol) [Merck KGaA].
RonaFlair MTU (Bismuth Oxychloride) [Merck KGaA].
Colorona Oriental Beige (Mica, C177891 (TiO2), C177491 (FeO)) [Merck KGaA].
Colorona Red Gold (Mica, Titanium Dioxide, Iron Oxide) [Merck KGaA].
Microcare IT (Methylchloroisothiazolinone, Methylisothiazolinone) [Thor Sp].
Dipotassium Glycyrrhizate [Selco].
Ethyl Ascorbic Acid [Selco].
Allantoin [DSM]
D-Panthenol [DSM]
Sodium Ascorbyl Phosphate. [BASF]
Propylene Glycol. [INEOS].
Hydrolite-5 (Pentylene Glycol) [Symrise].
Sensiva SC 50 (Ethyl hexyl glycerine) [Schulke@Mayr].
The present invention provides a composition and manufacturing process for finished multi-component cosmetic products containing MTAs. Overall, the key aspect of the invention is stable cosmetic composition containing mitochondrial antioxidant, and at least one additional component from the following list: gel-forming component, emollient, multi-functional component with antimicrobial activity, additional component—active cosmetic ingredient.
Examples (not limited to scope of claims under the present invention) are the following compositions:
10 mcM
10 mcM
Other examples of compositions are compositions according to the table shown above, in which Biocol LG is replaced with Biocol AX. The experiment conducted showed that SkQ retrains its stability with such replacement.
Other examples of compositions are compositions containing 0.1-1,000 mcM of SkQ1 and Biocol of any type without emollients.
Another aspect of this invention is the method of manufacturing compositions containing a mitochondrial antioxidant. The said method includes the following procedures: addition to water of gel-forming agent (at temperature suitable for the gel-forming agent specifically chosen), mixing (for certain gel-forming agents after swelling, for certain gel-forming agents after the required pH value is reached), introduction of remaining active ingredients, in which case the oil-soluble active ingredients should preferably be introduced together with the hydrophobic emollients, and the mitochondrial antioxidant is introduced last.
The experimental samples shown below illustrate possible ways of applying the invention and do not in any measure limit the scope of claims for this invention.
All experiments concerning stability of the cosmetic components tested are conducted under a single plan. The composition was prepared by adding gel-forming agent to water at the corresponding temperature and pH. Depending on the type of gel-forming agent with mixing or withholding necessary to swell the component and/or achieve the specific pH values. Then, after mixing, the remaining components (oil-soluble active ingredients, together with hydrophobic emollients) and the mitochondrial antioxidant are added.
The mixture was then kept in darkness at different temperatures, and the mitochondrial antioxidant content levels were determined using the LCMS/MS method on a Waters TQD chromatographic mass spectrometer.
The quantitative analysis was conducted using the UPLC-MS/MS method with SkQ-d15 of a known concentration as the internal standard and 3-chlorperbenzoic acid as the oxidising agent. The analysis was conducted in accordance with the method shown in the PCS for Visomytin eye drops.
1 analytical sample was prepared from each sample (extraction of 1 ml of methanol 12 hours, thermoshaker (27° C. 1400 rpm), centrifuging, preparation of analytical samples with dilution 5 times).
Each standard sample was injected 6 times before every nine injections of analytical samples. S/Sstd for standard samples were averaged at 45 injections.
The basic composition (BC1) used in this experiment was a composition with the following ingredients:
Biocol LG—2.9%
Propylene glycol—3%
Pentylene glycol—5%
Ethyl hexyl glycerine—0.3%
SkQ1—2 mcM
The following versions of compositions were examined:
0-point: Samples of cosmetics after manufacture and weighing were stored at −78 . . . -80° C. in dark plastic bottles 2 ml in volume until the analysis was conducted.
Time points: Samples of cosmetics after manufacture and weighing were stored for a set number of months at 37° C. in dark plastic bottles 2 ml in volume then stored at −78 . . . -80° C. until the analysis was conducted.
Test preparation: Heating at room temperature (30 min), extraction with methanol (1 ml, vortex, thermoshaker 1.5 hours 1,200 rpm), centrifuging (15 min 13,400 rpm)
Numerical Material:
On the basis of the kinetic curves and initial losses, the time taken to reach 20% losses, and residual SkQ1 content after 1 year of storage, were calculated. The values obtained were extrapolated to real conditions of storage at room temperature (25 C) and in refrigeration temperature (4 C). The values calculated are shown in the table.
Conclusion: Compositions 1 and 6 provide greater SkQ1 stability levels.
The basic composition (BC2) used in this experiment was a composition with the following ingredients:
Biocol LG—2.9%
Propylene glycol—3%
Pentylene glycol—5%
Ethyl hexyl glycerine—0.3%
SkQ1—3 mcM
The experiment also used an additional mixture of components (DSK) with the following ingredients:
Caprylyl methicone (Silsoft 034) 0.5%
Hydrogenated polydecene (Nexbase) 0.5%
The following versions of compositions were examined:
Coffea Arabica (Coffee) Seedcake Extract
Meristotheca Dakarensis Extract (and) Jania
Rubens Extract (Dermocea) 2%.
Brief Description:
Experiment start date: 27.07.2012
0-point: Samples of cosmetics after manufacture and weighing were stored at −78 . . . -80° C. in dark plastic bottles 2 ml in volume until the analysis was conducted.
3.5 months, 60° C.: Samples of cosmetics after manufacture and weighing were stored for 3.5 months at 60° C. in dark plastic bottles 2 ml in volume, then stored at −78 . . . -80° C. until the analysis was conducted.
Test preparation: Heating at room temperature (30 min), extraction with methanol (1 ml, vortex, thermoshaker 1 hour 1,200 rpm), centrifuging (15 min 13,400 rpm)
Numerical Data
Discussion of results: Accelerated storage of cosmetic compositions at 60° C. is not a sufficiently reliable way of studying the stability of mitochondrial antioxidants within a cosmetic product. However, with a specified level of reliability, the speed constant assessment values obtained can be used to extrapolate to real conditions of storage. The results of this extrapolation are shown in the table:
Therefore, for samples 5.2, 5.4 and 5.11, we unexpectedly obtained results indicating that these compositions possibly retain more than 50% of the active substance over a year of storage at room temperature.
The basic composition (BC3) used in this experiment was a composition with the following ingredients:
Methocel 40-202 (hydroxypropyl methyl cellulose) 2%
Propylene glycol 3%
Pentylene glycol 5%
Ethyl hexyl glycerine 0.3%
SkQ1 1.5 mcM
The basic composition (BC4) used in this experiment was a composition with the following ingredients:
Methocel 2%
Caprylyl methicone (Silsoft 034) 0.5%
Hydrogenated polydecene (Nexbase) 0.5%
Propylene glycol 3%
Pentylene glycol 5%
Ethyl hexyl glycerine 0.3%
SkQ1 1.5 mcM
Basic composition BC5, with the following ingredients, was also used:
Biocol LG—2.9%
Propylene glycol 3%
Pentylene glycol 5%
Ethyl hexyl glycerine 0.3%
SkQ1 1.5 mcM
Basic composition BC6, with the following ingredients, was also used:
Biocol LG—2.9%
Propylene glycol 3%
Pentylene glycol 5%
Ethyl hexyl glycerine 0.3%
SkQ1 1.5 mcM
Caprylyl methicone (Silsoft 034) 0.5%
Hydrogenated polydecene (Nexbase) 0.5%
The following versions of compositions were examined:
Brief Description:
Experiment Start Date: 01.03.2013
0-points: Samples of cosmetics after manufacture and weighing were stored at −78 . . . -80° C. in dark plastic bottles 2 ml in volume until the analysis was conducted.
Time points: Samples of cosmetics after manufacture and weighing were stored for 3.5 months at 42° C. or 60° C. in dark plastic bottles 2 ml in volume, then stored at −78 . . . -80° C. until the analysis was conducted.
Test preparation: Heating at room temperature (30 min), extraction with methanol (1 ml, vortex, thermoshaker), centrifuging (15 min 13,400 rpm)
Conclusion: At 60° C. more than 35% SkQ1 remained in compositions 2, 4, 5, 7, 11, 16, 17 and 21; for storage without heating (over 70% retained)—compositions 3, 11, 14, 15, 17 and 21, but in this case the highest substance content (over 0.5 mcg/g) at the initial point was observed in compositions 5, 9, 10, 12-19 and 22.
The following versions of compositions were examined:
Numerical Data
In brief:
Brief Description:
The quantitative analysis was conducted using the UPLC-MS/MS method with PDTF-d15 of a known concentration as the internal standard and 3-chlorperbenzoic acid as the oxidising agent. The analysis was conducted in accordance with the method shown in the PCS for Visomytin eye drops.
1 analytical sample was prepared from each sample (extraction of 1 ml of methanol 12 hours, thermoshaker (27° C. 1400 rpm), centrifuging, preparation of analytical samples with dilution 5 times)
In this experiment, with accelerated storage (at temperature +60° C.), the following composition (symbol Cos44) was used:
Here follow the introductory data for this experiment.
Results of Analysis
In brief:
Conclusion: Extrapolation of the data obtained for real storage temperatures of cosmetic products indicates that 50% of substance is lost over 50-100 days of storage at 25 C or 200-400 days of storage at 4 C.
Brief Description:
The quantitative analysis was conducted using the UPLC-MS/MS method with SkQ1-d15 of a known concentration as the internal standard and 3-chlorperbenzoic acid as the oxidising agent. The analysis was conducted in accordance with the method shown in the PCS for Visomytin eye drops.
From each sample of solution, a drop was produced for 1 analytical sample.
S/Sstd for standard samples was averaged for 24 injections (no ejections). Average value of S/Sstd for standard samples, equal to 2.162+/−0.124, used for calculating SkQl concentration in solutions studied.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/IB2015/001030 | 2/25/2015 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 61944205 | Feb 2014 | US |
