FR3015292A1 - COMPOSITION BASED ON OMEGA 6 AMIDE BOURRACHE - Google Patents

Abstract

The invention relates to a cosmetic and / or dermatological composition for the treatment of itchy skin and inflamed through various biochemical pathways. It includes as active ingredient omega 6 borage amide which stimulates the formation of natural molecules involved in the resolution of cutaneous inflammation and inhibit the production of certain pro-inflammatory molecules secreted by the body during surgery. a cutaneous aggression.

Description

The technical field of the present invention is that of compositions intended for treating itchy and / or inflamed skin. Pruritus is a functional sign and is defined as "a sensation that causes the need to scratch". It can be localized or generalized. Pruritus becomes pathological when it induces scratching lesions. There are many pruritus stimuli, external stimuli (physical or chemical) but also very often endogenous stimuli (histamine, proteases, prostaglandins, neuropeptides). All pruritus stimuli are not known. In the skin, pruritus is recorded by non-myelinated nociceptive C endings (free endings). Typically, itching causes "the need to scratch" and then a painful irritation caused by scratching and subsequent inflammatory phenomena. We can then fall into chronic pruritus. Most current antipruriginous or anti-inflammatory dermatological compositions include antihistaminic molecules (fexofenadine, mizolastine, isothipendyl) for ingesting or topical application, but also local anesthetics, antiseptics or even corticosteroids (hydrocortisone). Nevertheless, some of these compounds may be aggressive to the skin (especially corticosteroids) and / or have undesirable side effects. One of the recently used routes for treating pruritus involves action on cannabinoid receptors using specific molecules included in pharmaceutical compositions (EP2130820). In this latter document, it is disclosed that CB1 and CB2 cannabinoid receptor agonist compounds have antipruritic effect in orally administered compositions, and that compounds having antagonist activity of these receptors effectively block the antipruritic effect of the agonist compounds. However, most of the antipruritic or effective anti-inflammation compounds are incorporated in often complex compositions, including those comprising an antiseptic, a local anesthetic, several antipruriginous, a corticoid, etc. These compositions frequently exhibit some toxicity to human skin and / or undesirable side effects. Therefore, we are still actively seeking compounds that are significantly effective against cutaneous inflammatory phenomena and well tolerated by the body. The present invention proposes to meet this need with cosmetic and / or dermatological compositions comprising, as active principle, omega 6 borage amide. The authors of the present invention have discovered in a totally fortuitous and surprising manner that a composition comprising, as an active principle, omega 6 borage amide makes it possible to participate in the resolution (arrest) of the cutaneous inflammatory reaction by promoting the secretion of anti-inflammatory molecules and by inhibiting the secretion of pro-inflammatory molecules, without any undesirable side effects. The subject of the invention is therefore a cosmetic and / or dermatological composition, characterized in that it comprises, as active ingredient, omega 6 borage amide in a mass proportion of greater than or equal to 0.001%, the other ingredients consisting of by products which are eligible in the cosmetic and / or dermatological fields, for its use in stimulating the secretion by the body of molecules involved in the resolution of cutaneous inflammation such as lipoxins, resolvinins and marines, and inhibition of the secretion of pro-inflammatory molecules such as lipid mediators PGE2, 5-HETE, 18-HETE and LTB4. According to another characteristic of the invention, the composition is characterized in that the omega 6 borage amide is in a mass proportion of between 0.001% and 10%.

According to yet another characteristic of the invention, the composition is characterized in that it comprises 0.002% by weight of omega 6 borage amide. According to another characteristic of the invention, the composition is characterized in that it comprises 0.01% by mass of omega 6 borage amide. According to yet another characteristic of the invention, the composition is characterized in that it comprises 0.1% by weight of omega 6 borage amide. According to another characteristic of the invention, the composition is characterized in that it comprises 1% by weight of omega 6 borage amide. According to yet another characteristic of the invention, the composition is characterized in that it comprises 5% by mass of omega 6 borage amide. According to another characteristic of the invention, the composition is characterized in that it further comprises, as active principle, a mineral water comprising - between 40 mg / l and 600 mg / l of calcium, and / or salts and / or derivatives thereof, - between 12.5 mg / L and 125 mg / L magnesium, and / or salts and / or derivatives thereof, - between 0.455 mg / L and 45, 5 mg / L of potassium, and / or of salts and / or derivatives thereof, between 23.6 mg / L and 2360 mg / L of sodium, and / or of salts and / or derivatives of it, in a mass proportion of between 1% and 99%. According to yet another characteristic of the invention, the composition is characterized in that it comprises Uriage Thermal Water. According to another characteristic of the invention, the composition is used to treat cutaneous inflammation. According to yet another characteristic of the invention, the composition is used to treat pruritus. A first advantage of the invention is a significant action against cutaneous inflammatory reactions by a completely natural biochemical pathway.

A second advantage of the invention is the prevention of skin inflammations by the stimulation of anti-inflammatory molecules even in the absence of cutaneous aggression. A third advantage of the invention is to prevent the appearance of pruritus or to participate in its resolution. A final advantage of the invention is its total safety for the human body. By omega 6 borage amide means the particular amides of borage oil referred to by the INCI name Borage seed oil aminopropanediol amides, of plant origin and obtained by enzymatic biotechnology. Borage oil is increasingly used in cosmetology, in particular because of its high omega-6 content. Nevertheless, very few inventions still involve borage oil amides. Like borage oil, omega 6 borage amide has no toxicity to the skin. The authors of the present invention have surprisingly discovered that the local application of borage omega 6 amide makes it possible to participate in the resolution (arrest) of the cutaneous inflammatory reaction by promoting the formation of lipoxins, resolvers and marines, and by inhibiting the formation of secreted pro-inflammatory molecules in case of skin aggression. The anti or pro-inflammatory molecules respectively stimulated or inhibited by the present invention are lipid mediators naturally secreted by the body. Thus, a cosmetic and / or dermatological composition comprising omega 6 borage amide allows the treatment of itchy and / or inflamed skin through a completely natural biochemical mechanism. It is obvious that its local application is within cosmetic and / or dermatological compositions whose other ingredients are acceptable compounds in these fields.

It is quite possible to combine omega 6 borage amide included in the composition according to the invention with other active ingredients effective in the treatment of inflamed skin, irritated and / or itchy. For example, omega 6 borage amide may be combined with certain mineral waters rich in trace elements and mineral salts, such as Uriage Thermal Water (whose INCI EU name is "Uriage Thermal Spring Water") or Avene Thermal Water. By mineral waters rich in trace elements and mineral salts is meant mineral waters having significantly high and defined proportions of calcium, magnesium, magnesium and sodium, and / or salts and / or derivatives thereof, and a ratio of mass Ca / Mg between 1 and 10. According to its mineral salts content, mineral water, as active ingredient in combination with omega 6 borage amide, may be present in an antipruritic cosmetic and / or dermatological composition and / or anti-inflammatory in a proportion ranging from 1 to 99%. Such mineral water makes it possible to treat the pruritus and the afferent affections by biochemical routes different from that of the borage omega 6 amide according to the invention, that is to say by decreasing the release of TSLP and / or by regulating TRPV1 receptor and CB1 and CB2 cannabinoid receptors. Thus, it is possible to combat pruritus and / or treat inflamed skin through a wide range of simultaneous biochemical processes. Finally, as omega 6 borage amide according to the invention, the mineral waters rich in trace elements and mineral salts has no toxicity to humans.

The authors of the present invention evaluated the effect of omega 6 borage amide on the synthesis of molecules involved in the resolution of inflammation and pro-inflammatory molecules.

Study protocol: Primary culture keratinocytes (NHEK) are prepared. After one week, the NHEKs are deposited in inserts, then the omega 6 borage amide at 0.0005% mass concentrations and 0.005% is added to the NHEKs. After one day of stimulation with the active ingredient, the inflammatory stimulation (PMA / A23187) and / or PUFA (polyunsaturated fatty acids) DHA / EPA are added according to a predefined plate plan. PUFA (DHA / EPA) is the lipid substrate used to form lipid mediators. Among the anti-inflammatory mediators, there are in particular lipoxins (including LXA4 and LXB4), resolvins (including RvD2), and marines (including 7- (R) MarR1). Among the inflammatory mediators, there are in particular LTB4, 5-HETE, PGE2 and 18-HEPE. 1h after culture supernatants were taken for analysis of lipid mediators. Table of results Induction value (in%) relative to the control (CTRL) of each condition Test medium / CTRL without omega 6 amide borage Omega 6 amide Borage Anti-inflammatory lipid mediators Proinflammatory lipid mediators (% by mass) LXA4 LXB4 RvD2 7- (R) Mar R1 PGE2 5- HETE 18- HEPE LTB4 Clean effect (omega 6 amide borage alone) 0.005 10 183 1 202 26 005 7 678 -56 # 0 0 0.0005 0 e 0 0 5 # 0 0 PUFA (lipid substrate) 0.005 2 191 1 636 33 708 8 183 -63 -97 -19 0 0.0005 # e 0 0 -14 44 -15 # PMA / A23 (inflammatory stimulation) 0.005 9 088 4 389 26 190 9 377 -65 -87 # -99 0.0005 0 e 0 0 172 4 -17 PUFA + PMA / A23 0.005 11 701 3 397 24 251 6 067 -80 -96 -42 -98 0.0005 0 -70 0 0 58 - 29 0 -16 # Control and test below the limit of quantification so inductive induction.

A percentage of positive induction corresponds to a stimulation of the secretion of the mediator relative to the control (CTRL) carried out under the same conditions without omega 6 borage amide. For example, the effect of the omega 6 borage amide at 0.005% for the LXA4 mediator corresponds to a 183% increase in the secretion of LXA4 compared to the control without omega 6 borage amide. Similarly, the effect of omega 6 borage amide with 0.0005% PUFA for the lipid mediator PGE2 corresponds to a 5% increase in the secretion of PGE2 compared to control with PUFA but without omega 6 borage amide. A percentage of negative induction corresponds to an inhibition of the secretion of the mediator (it can not be less than -100).

The percentage of induction is interpreted as follows: greater than 200: strong stimulation; between 100 and 200: net stimulation; - between 50 and 100: moderate stimulation; - between -35 and 50: neutral (no significant influence on secretion); - between -35 and -50: moderate inhibition; - between -50 and -70: net inhibition; - less than -70: strong inhibition.

The secretion of the anti-inflammatory mediators LXA4, LXB4, RvD2 and 7- (R) MarR1 is strongly stimulated to 0.005% by mass of omega 6 borage amide, irrespective of the medium (alone, with PUFA, with PMA / A23 or with PUFA and PMA / A23). On the other hand, the secretion of several pro-inflammatory mediators is significantly inhibited, in particular in the AGPI + PMA / A23 condition. These results are all the more surprising as they do not appear at 0.0005% by weight of omega 6 borage amide. Indeed, in this proportion, omega 6 borage amide has only a neutral effect or slightly favors pro-inflammatory mechanisms, with a clear inhibition of LXB4 in the case of PUFA + PMA / A23, a net stimulation of PGE2. in the case of AGPI + PMA / A23, and moderate stimulation of 5-HETE with the PUFA case.

Conclusion It is found that at a concentration of 0.005%, omega 6 borage amide significantly stimulates the secretion of resolving lipid mediators, lipoxins and marines (respectively generically referred to as Rv, LX and Mar), natural molecules particularly involved in the resolution. skin inflammation. In addition, omega 6 borage amide significantly inhibits the secretion of pro-inflammatory molecules naturally produced by the body during cutaneous aggression (inflammatory stimulation). Examples of compositions comprising omega 6 amide borage amides (INCI name EU: "Borage seed oil aminopropanediol amides") according to the invention: Example 1: Anti-itching milk - O / W Emulsion INCI Name EU% (mass) Aqua qss Uriage Thermal Spring Water 35 Borage seed oil aminopropanediol amides 0.002 Butyrospermum parkll (shea butter) 5 Cetearyl isononanoate 5 Isodecyl neopentanoate 4 Butylene glycol 3 Glycerin 3 Hydrogenated polydecene 2,5 Dimethicone 2 Squalane 2 Steareth-2 2 Steareth-21 2 Cetyl alcohol 1 Pentaerythrityl distearate 1 Polyacrylate-13 0.6 Brassica campestris sterols 0.5 Chlorphenesin 0.3 Piroctone olamine 0.3 Polyisobutene 0.27 Sodium dextran sulfate 0.2 Citric acid 0.1 o-cymen-5-ol 0.1 Tocopheryl acetate 0.1 Xanthan gum 0.1 Raspberry seed oil / palm oil aminopropanediol esters 0.05 Polysorbate 20 0.045 Sorbitan isostearate 0.04 Asiaticoside 0.02 Phytosphingosine 0.02 Example 2: Cleaning oil INCI name EU% (mass) Aqua qsp Uriage Thermal Spring Water 5 Borage ed oil aminopropanediol amides 0.01 Glycerin 19 Hydrogenated starch hydrolysate 15.4 PEG-7 glyceryl cocoate 2 Sodium cocoyl glutamate 1.8 Sodium laureth sulfate 1.8 Sodium laureth-8 sulfate 1.62 Ceteareth-60 myristyl glycol 1 Polysorbate 20 0 , 97 Coco-glucoside 0.66 Glyceryl oleate 0.66 Sodium chloride 0.646 Citric acid 0.54 Magnesium laureth sulfate 0.45 Sodium oleth sulfate 0.45 Polyquaternum-10 0.364 Magnesium laureth-8 sulfate 0.36 PEG-75 shea butter glycerides 0.25 Magnesium oleth sulfate 0.09 Sodium acetate 0.006 Example 3: Hand cream INCI name EU% (mass) Aqua qsp Uriage Thermal Spring Water 15 Borage seed oil aminopropane diol amides 0.1 Glycerin 3 Phenoxyethanol 0.5 Chlorphenesin 0.2 Acrylates / C10-30 alkyl acrylate crosspolymer 0.17 Glyceryl stearate PEG-100 stearate 3 Cetyl alcohol 2 Cetearyl isononoate 4 Squalane 4 Hydrogenated polydecene 8 Dimethicone 1 Tromethamine 0.19 Example 4: Face cream INCI name EU% (mass) Aqua qsp Uriage Thermal Spring Water 60 Borage Seed Oil amides aminopropanediol 1 Fragrance 0.2 Citric acid 0.028 Phenoxyethanol 0.7 Chlorphenesin 0.3 Glycerin 7 Xanthan gum 0.3 Glyceryl stearate PEG-100 stearate 1,2 Cetearyl isononanoate 5 Propylheptyl caprylate 3 Pentaerythriltyl distearate 2 Cetyl alcohol 0.7 Cetearyl alcohol 2 Glyceryl stearate 1.8 Butyrospermum parkll (shea butter) Tocopheryl acetate 0.5 Dimethicone 1 Cetearyl alcohol cetearyl glucoside 2 o-cymen-5-ol 0.1 Butylene glycol 3 Example 5: Body milk INCI name EU% (mass) Aqua qsp Borage seed oil aminopropanediol amides 5 Butyrospermum parkll (shea butter) 5 Cetearyl isononanoate 5 Isodecyl neopentanoate 4 Butylene glycol 3 Glycerin 3 Hydrogenated polydecene 2,5 Dimethicone 2 Squalane 2 Steareth-2 2 Steareth-21 2 Cetyl alcohol 1 Pentaerythrityl distearate 1 Polyacrylate- 13 & polysorbate 20 0.645 Xanthan gum & sorbitan isostearate 0.14 Chlorphenesin & piroctone olamine 0.6 Polyisobutene 0.27 Tocopheryl acetate 0.1 Citric acid 0.105 o-cymen-5-ol 0.1 Butylene glycol 3 Ex Embodiments of the above illustrated compositions are not limiting and may extend especially to all milks, creams, lotions, and gels, etc. The compositions described above are prepared according to the rules of the art, and in the same way the methods of preparation creams, gels or lotions according to the invention are known do not have to be detailed further. The actives in the compositions are used at the same concentrations as in previous in vitro studies. Their activity will be equivalent because most pruriginous skin has an impaired skin barrier and penetration is facilitated. The actives can thus be easily in contact with the underlying cell layers consisting of living epidermal cells. It goes without saying that these examples are not limiting and one skilled in the art can incorporate other active and excipients specific cosetological and / or dermatological domains. 20 here and

Claims (11)

REVENDICATIONS1. Cosmetic and / or dermatological composition, characterized in that it comprises as active ingredient omega 6 borage amide in a mass proportion greater than or equal to 0.001%, the other ingredients being constituted by products that are eligible in the cosmetic and or dermatological, for its use in stimulating the secretion by the body of molecules involved in the resolution of cutaneous inflammation such as lipoxins, resolvins and marines, and the inhibition of the secretion of pro-inflammatory molecules such as as the lipid mediators PGE2, 5-HETE, 18-HETE and LTB4. 2. Composition according to claim 1, characterized in that the omega 6 borage amide is in a mass proportion of between 0.001% and 10%. 3. Composition according to one of the preceding claims, characterized in that it comprises 0.002% by weight of omega 6 borage amide. 4. Composition according to one of the preceding claims, characterized in that it comprises 0.01% by mass of omega 6 borage amide. 5. Composition according to one of the preceding claims, characterized in that it comprises 0.1% by weight of omega 6 borage amide. 25 6. Composition according to one of the preceding claims, characterized in that it comprises 1% by weight of omega 6 borage amide. 7. Composition according to one of the preceding claims, characterized in that it comprises 5% by weight of omega 6 borage amide. 8. Composition according to one of the preceding claims, characterized in that it further comprises as an active ingredient a mineral water comprising: - between 40 mg / L and 600 mg / L of calcium, and / or salts 35 and / or derivatives thereof, - between 12.5 mg / L and 125 mg / L magnesium, and / or salts and / or derivatives thereof, - between 0.455 mg / L and 45, 5 mg / L of potassium, and / or salts and / or derivatives thereof, - between 23.6 mg / L and 2360 mg / L of sodium, and / or salts and / or derivatives thereof in a mass proportion of between 1% and 99%. 9. Composition according to claim 4, characterized in that it comprises Uriage Thermal Water. 10. Composition according to one of the preceding claims, for its use in the treatment of cutaneous inflammation. 11. Composition according to one of the preceding claims, for its use in the treatment of pruritus.