Patent Application
20130302389
The present invention relates to novel cosmetic compositions containing a combination of at least two osmolytes, and to its use as an active cosmetic agent, referred to hereinbelow as an “active agent”, in cosmetic compositions, especially moisturizing and/or antiaging compositions.
Kosmotropic molecules are organic compounds that are specifically accumulated by the cell in response to a hyperosmotic stress such as dehydration, and which are then rapidly released therefrom (Kwon and Handler, Current Opin. Cell. Biol.; 1995; 7: 465-471 and Häussinger 1996; Biochem. J 313: 697-710).
These compounds, which are also known under the generic term “osmolytes”, perturb the cell very little even at high concentrations and, furthermore, do not interfere with the functions of the proteins of said cells (Burg et al., Annu. Rev. Physiol. 1997; 59: 437-455).
WO 91/914 435 discloses a method for treating osmotic disorders, comprising the administration of an effective amount of osmolytes or precursors.
WO 03/005 979 discloses the use, in a cosmetic composition, of at least one osmolyte for treating or preventing impairments of cutaneous homeostasis, especially for caring for, treating or preventing dry skin or sensitive skin.
None of these publications discloses the synergistic combination of osmolytes that is the subject of the present invention, or reveals the noteworthy cosmetic properties demonstrated for said combination, especially in the field of moisturization and/or protection and/or antiaging.
The present invention thus relates to a cosmetic composition which comprises at least one cosmetic active agent comprising a combination of at least two osmolytes, and also to a novel use of a combination of at least two osmolytes as active agent in a cosmetic composition.
Said combination makes it possible especially to restore, maintain or reinforce the moisturization of the skin and/or to protect it against different types of stress and/or to prevent or retard the appearance of the signs of aging of the skin, or to attenuate the effects thereof, or alternatively to promote cell or tissue longevity.
The present invention also relates to a cosmetic care method for moisturizing the skin or for producing an anti-stress or antiaging protective effect, comprising such a combination of at least two osmolytes as active agent in a cosmetic composition.
The main aim of the present invention is to provide a novel cosmetic active agent, referred to hereinbelow as an “active agent”, in a cosmetic composition especially having a moisturizing and/or protecting and/or antiaging effect.
A main aim of the present invention is also to provide a novel active agent of a cosmetic composition that has a good capacity for restoring, maintaining or reinforcing the moisturization of the skin and/or for protecting it against different types of stress and/or for preventing or retarding the appearance of the signs of aging of the skin, or for attenuating the effects thereof, or alternatively for promoting cell or tissue longevity.
A main aim of the present invention is also to provide a cosmetic care method for moisturizing the skin or for producing an anti-stress protective effect or an antiaging effect by means of the abovementioned novel active agent.
A main aim of the present invention is also to provide a novel cosmetic active agent that is compatible with repeated application to the skin without any significant side effects, especially any skin irritation.
An aim of the invention is also to solve the technical problem via a solution that is particularly simple, relatively inexpensive and usable at the industrial scale.
A first subject of the present invention is a cosmetic composition which comprises at least one cosmetic active agent comprising a combination of at least two osmolytes chosen from the group comprising taurine or a derivative thereof, inositol, betaine and trehalose.
Among the taurine derivatives, mention is made of hypotaurine.
According to the invention, inositol is also referred to as myoinositol.
Betaine is, itself, known without discrimination as trimethylglycine.
The trehalose is preferably in the form of D-trehalose.
Among the combinations comprising at least two osmolytes, a combination comprising taurine, or a derivative thereof, and inositol is preferred.
According to one preferred embodiment, said combination comprises three osmolytes chosen from the group comprising taurine or a derivative thereof, inositol, betaine and trehalose.
Among these combinations, a preferred combination is formed from taurine or a derivative thereof, inositol and betaine.
According to another preferred embodiment, said combination comprises four osmolytes chosen from the group comprising taurine or a derivative thereof, inositol, betaine and trehalose.
Among these combinations, a preferred combination is formed from taurine, inositol, D-trehalose and betaine.
These combinations make it possible to stimulate, in an unexpected manner for a person skilled in the art, the synergistic expression of the chaperone protein HSPA1A in epidermal cells.
According to a first variant, the weight ratio of each osmolyte in the abovementioned combination relative to the weight of the osmolyte of the combination that is present in smallest amount is between 1 and 10, preferably between 1 and 5 and even more preferably between 1 and 2.
According to yet another embodiment variant of the invention, the weight ratio of each osmolyte of the combination comprising taurine or a derivative thereof, inositol, betaine and trehalose is between 1/1/1/1 and 1/2/2/2. The combination of osmolytes according to the invention proved to be synergistic and to afford unexpected effects, and may consequently be used as an active agent in a cosmetic composition also comprising at least one cosmetically acceptable excipient.
The cosmetic composition thus comprises an effective amount of said combination of osmolytes to obtain the desired cosmetic effect.
The composition thus preferentially comprises from 0.001% to 10% by weight and preferably from 0.01% to 2% by weight of the combination according to the invention.
According to yet another embodiment of the invention, the abovementioned composition is characterized in that the abovementioned combination of osmolytes is encapsulated in lipid vesicles such as unilamellar or multilamellar liposomes.
According to one preferred embodiment, the lipid vesicles are based on amphiphilic lipids containing phosphatidylcholine, and especially based on lecithins.
According to another preferred variant of the invention, the abovementioned composition is which comprises D-xylose in addition to the abovementioned combination.
The cosmetic compositions according to the invention may comprise one or more other cosmetic active agents.
The cosmetic properties demonstrated for the combination of osmolytes according to the invention may be improved in the presence of cosmetic active agents that have similar and/or complementary cosmetic effects.
Besides a combination of osmolytes as defined previously, the cosmetic composition according to the invention may thus comprise one or more other plant extracts or molecules with moisturizing properties, such as glycols, in particular glycerol, or natural polyols, natural or synthetic ceramides, hyaluronic acid or fragments thereof of smaller molecular weight, or alternatively all or some of the molecular constituents of natural moisturizing factor (NMF), for instance lactate, citrate, urea, a PCA (pyrrolidonecarboxylic acid) salt, Na+, K+, Ca2+or Mg2+ ions, serine, citrulline, alanine and threonine, or alternatively lipid constituents such as cholesterols and cholesteryl sulfate, and fatty acids, including omega-3, omega-6 and omega-9.
Among the other cosmetic agents that may also advantageously be used in the composition according to the invention, mention may be made more particularly of:
Moreover, besides the combination of osmolytes according to the invention, the cosmetic composition comprises at least one cosmetically acceptable excipient, defined as a substance lacking a cosmetic effect per se, but which is useful for incorporating the active agent into the cosmetic composition or for formulating said composition.
This excipient may be chosen more particularly from pigments, colorants, polymers, surfactants, rheological agents, fragrances, electrolytes, pH modifiers, antioxidants and preserving agents, and mixtures thereof
The cosmetic composition according to the invention may be, for example, a serum, a lotion, an emulsion, for example a cream, or alternatively a hydrogel, preferably a mask, or may be in the form of a stick or a patch, or alternatively a hygiene product for the scalp such as a shampoo or a hair conditioner, or alternatively a makeup product, in particular a composition intended to be applied to the nails, for example a nail varnish.
According to one variant of the invention, the abovementioned combination of osmolytes is encapsulated in lipid vesicles, for instance unilamellar or multilamellar liposomes.
The cosmetic composition comprising the lipid vesicles is itself preferably formulated in the form of an aqueous gel or of an emulsion of oil-in-water (O/W) type, in order to facilitate the diffusion of said active agents, i.e. the combination of osmolytes optionally combined with the abovementioned molecules or extracts, across the stratum corneum.
In the particular case in which the cosmetic composition comprising lipid vesicles is an oil-in-water emulsion, said vesicles are more particularly stabilized in the aqueous phase of the emulsion by adding to said aqueous phase a polysaccharide, more particularly by adding sodium alginate.
The cosmetic compositions according to the invention have a particularly desired effect for restoring, maintaining or reinforcing the skin moisturizing effect.
The cosmetic compositions according to the invention also have a particularly desired effect for protecting the skin against different types of stress.
Finally, the compositions have an effect on preventing or slowing down the appearance of the signs of aging of the skin.
A subject of the invention is also the use of a combination of at least two osmolytes chosen from the group comprising taurine or a derivative thereof, inositol, betaine and trehalose as an active agent in a cosmetic composition as defined previously, for restoring, maintaining or reinforcing the moisturization of the skin and/or for protecting the skin against different types of stress and/or for preventing or retarding the appearance of the signs of aging of the skin, or for attenuating the effects thereof, or alternatively for promoting cell or tissue longevity, said combination being used alone or combined with other cosmetically active agents as defined previously or as resulting from the description that follows, including the examples.
A subject of the invention is also a cosmetic care method comprising applying to at least one body zone in need thereof of an efficient amount of a composition comprising a cosmetic agent as previously defined or is defined later on. According to a particular feature said method is for moisturizing the skin, and/or for protecting it against any type of stress, and/or alternatively for producing an antiaging effect, which comprises the application to the part of the facial or bodily skin concerned of an effective amount of a combination of at least two osmolytes in a cosmetic composition as defined previously or as resulting from the description that follows, including the examples, which form an integral part of the invention.
Other aims, characteristics and advantages of the invention will emerge clearly in the light of the examples and especially of the examples of cosmetic compositions using said combination, which data are given simply as illustrations and shall not therefore in any way limit the scope of the invention.
The examples form an integral part of the invention for any characteristic that appears to be novel relative to any prior art.
In the examples, all the percentages are given on a weight basis, the temperature is in degrees Celsius, and the pressure is atmospheric pressure, unless otherwise indicated.
Materials and Methods
Cell type: normal human keratinocytes (NHK) as an immersed monolayer, strongly post-confluent and at the third subculture.
Culture medium: low-calcium K-SFM (Invitrogen) supplemented with Epidermal Growth Factor (EGF Sigma) at 2.5 ng/ml, pituitary extract (EP Invitrogen) 2.5 μg/ml and gentamicin (Sigma) 25 μg/ml. For the treatments with the various compounds, this medium is replaced with K-SFM medium not supplemented with EGF and EP.
Treatment time: 24 hours with the various kosmotropes, and other molecules or extracts, and combinations thereof.
Test compounds: the taurine, D-trehalose, inositol and betaine (Sigma) are dissolved in the culture medium and tested at concentrations of 166 and 500 μg/ml, or, when this was not possible for reasons of solubility or cytotoxicity, at substantially lower concentrations.
The combination of these four compounds in proportions of 1/1/1/1 by weight is tested at the same concentrations.
Assays of the mRNA of HMSPA1A by RT-QPCR: at the end of the incubation period, the culture supernatants are removed and the cells, rinsed with PBS (Invitrogen), are covered with a solution of Tri-reagent (Sigma) and then frozen immediately at −80° C.
Extraction of the total RNA is performed according to the protocol of the Tri-reagent supplier (Sigma) and removal of the traces of DNA is performed with the DNA-free kit (Ambion). The reverse transcription reaction is performed using Oligo(dT) primers and the enzyme superscript II (Gibco).
The PCR (Polymerase Chain Reaction) reactions are performed using a Light Cycler (Roche Molecular Systems, Inc.) and according to the procedures recommended by the supplier. The pairs of primers used in this study allow amplification of the following fragments:
Homo sapiens heat shock protein HSP70 protein 1A (abbreviation HSPA1A; Gene bank NM 02045; fragment size 213 bp) and liver glyceraldehyde 3-phosphate dehydrogenase 1A (abbreviation G3PDH; Gene bank NM 02046; fragment size 269 bp) serving as the reference gene (caretaker gene) for determining the relative expression of the target HSPA1A.
The reaction medium (10 μl) is formed from the primers for the two target mRNAs (HSPA1A and G3PDH), 2.5 μl of tenfold-diluted cDNA, reaction mixture (Roche) containing the enzyme Taq DNA polymerase, SYBR Green I fluorochrome (which becomes incorporated into the double-stranded DNA during the elongation step), and MgCl2.
The incorporation of fluorescence into the amplified DNA is measured continuously in the course of the PCR cycles. For the same used marker, the later a sample leaves (high number of cycles), the lower the initial number of copies of mRNA.
Normal human keratinocyte cultures are treated for 24 hours with noncytotoxic doses (166 and 500 μg/ml) of each of the four osmolytes separately: taurine, D-trehalose, inositol and betaine. The transcriptional expression of HMSPA1A is measured by RT-PCR.
The control (untreated cells) is normalized to correspond to 100% expression.
Results
Strong heterogeneity of response is demonstrated for these osmolytes. A moderate but significant stimulation of expression of HSPA1A of 171% and 139%, respectively, is observed with taurine, and of 142% and 181%, respectively, with D-trehalose.
On the other hand, no significant stimulation can be demonstrated with inositol (90% and 101%, respectively) or betaine (52% and 85%, respectively).
Unexpectedly, treatment of the keratinocytes with a mixture corresponding to a 1/1 combination by weight of taurine and inositol is identified as an activator of HSPA1A expression: +476% at 166 μg/ml.
This is likewise the case for a combination of taurine, inositol and betaine in a 1/1/1 weight ratio, which stimulates the expression of HSPA1A by +455% at 166 μg/ml.
This is also similarly the case for the combination of four osmolytes formed from taurine, D-trehalose, inositol and betaine in a 1/1/1/1 weight ratio, which stimulates the expression of HSPA1A very significantly more than that of each of the kosmotropic compounds taken individually (stimulation of 404% and 400% for respective doses of 166 and 500 μg/ml of the mixture).
Hypotaurine also significantly stimulates the expression of HSPA1A (+379% at 166 μg/ml), more efficiently than taurine.
These results demonstrate a synergistic effect of these combinations for stimulating the expression of HSPA1A, and the value of using these combinations as active agent in cosmetic compositions for moisturizing the skin, promoting tissue longevity, preventing or treating cell aging and improving the resistance of skin cells to stress.
The cosmetic composition below is a moisturizing lotion (percentages expressed on a weight basis relative to the weight of the composition):
This composition is a lotion applied daily to facial skin to obtain the desired moisturizing effect.
The percentages are indicated on a weight basis relative to the weight of the final composition.
This composition is an oil-in-water emulsion including the synergistic combination of four osmolytes mentioned above and D-xylose.
The cream is applied daily to facial skin to obtain the desired moisturizing effect.
The percentages are indicated on a weight basis relative to the weight of the final composition.
This composition is an oil-in-water emulsion whose formulation is suited to dry skin. It thus includes among the excipients shea butter and jojoba esters whose nutrient, emollient and substantive properties make them particularly suitable for use in compositions intended for dry skin.
This composition is applied daily to facial skin to obtain the desired moisturization.
| Number | Date | Country | Kind |
|---|---|---|---|
| 0859083 | Dec 2008 | FR | national |
This application is a continuation of U.S. application Ser. No. 12/644,067, filed Dec. 22, 2009, which claims the benefit of French Patent Application No. 0859083, filed Dec. 24, 2008, the entireties of which are incorporated herein.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 12644067 | Dec 2009 | US |
| Child | 13943873 | US |
