FR2905601A1 - Use of oleic derivatives as a method and composition promoting dermal penetration of active agents present in cosmetic, pharmaceutical or dermatological compositions - Google Patents

Abstract

Use of oleic derivatives as a method and composition promoting dermal penetration of active agents present in cosmetic, pharmaceutical or dermatological compositions, is claimed. An independent claim is included for a cosmetic, pharmaceutical or dermatological composition for topical use, comprising the oleic derivatives optionally in combination with other factors promoting the dermal penetration, in a medium, as an agent promoting the dermal penetration.

Description

The present invention relates to the use of derivatives

  oleic acid as a method and composition promoting cutaneous penetration of the active ingredients contained in cosmetic, pharmaceutical or dermatological compositions. By oleic derivatives, the applicant understands the synthetic or natural molecules having at least in their molecular structure a hydrocarbon chain called oleic. More specifically, these are lipid or amphiphilic molecules chosen from fatty acids, alcohols and esters, alkyl polyglucosides, sucrose esters and mono-, di- or triglycerides, virgin vegetable oils, treated or refined, composed of at least one oleic chain, that is to say a linear hydrocarbon chain of eighteen carbon atoms having a cis double bond in the 9-position, used in cosmetic, pharmaceutical or dermatological compositions such as factor promoting skin penetration of active ingredients. The skin is a structurally complex and relatively thick membrane. It consists of three layers the epidermis, the dermis and the hypodermis. The epidermis is a stratified and keratinized squamous epithelium whose outer layer is the stratum corneum. The dermis, underlying the epidermis, comprises elastin and collagen fibers, cellular elements such as fibroblasts bathed in a fundamental substance composed of glycosaminoglycans (chondroitin sulfate, dermatan sulfate, heparins and hyaluronic acid), glycoproteins and water. The hypodermis, the innermost structure, consists essentially of adipose tissue and fibrous septa. These three structures contain appendages 2905601 2 cutaneous hair follicles with their sebaceous glands, eccrine and apocrine sweat glands. The penetration of the active ingredients through the layers of human skin has many advantages: it is a comfortable, practical and non-invasive way of administering an active that is cosmetic, pharmaceutical or dermatological. Candidate molecules for penetration of intact skin must first penetrate the stratum corneum. Then they must cross the epidermis, the basement membrane, then the dermis. For pharmaceutical active ingredients, only allowed to penetrate deeper, they will also have to cross the walls of the capillaries before reaching the blood vessels and the general circulation.

  To be absorbed, the active molecules must overcome resistance to penetration of different skin tissues. The passage of such substances within the skin is a very complex phenomenon. However, it is the corneum statum that represents the first barrier that stands before the biological or chemical assets contained in cosmetic, pharmaceutical or dermatological compositions. The stratum corneum is a thin and dense layer composed of strongly keratinized cells, about 10 to 15 microns thick. The lipid structure of this layer is extremely dense and compact. This high degree of compactness creates a barrier impervious to the penetration of active molecules.

  In order to improve the permeability of the skin, it is common to introduce into the compositions for topical use, factors promoting skin penetration. The method usually used by the formulators of these preparations is to use short-chain glycols, in particular propylene glycol, butylene glycol, hexylene glycol, dipropylene glycol, methylpropane diol, and glycols ethers. such as ethoxydiglycol or alcohols such as ethanol.

However, the use of these ingredients has the disadvantage of causing irritation, sometimes severe, especially on sensitive skin. There remains therefore the need to use another method 10 as effective as the prior art, but not having this disadvantage. A first object of the present invention therefore relates to the use of oleic derivatives as a method promoting the cutaneous penetration of the active ingredients contained in cosmetic, pharmaceutical or dermatological compositions. The term "oleic derivatives" means the lipid or amphiphilic molecules chosen from fatty acids, alcohols and esters, alkyl polyglucosides, sucrose esters and mono-, di- or tri-glycerides and virgin vegetable oils. treated or refined, composed of at least one oleic chain, that is to say a linear hydrocarbon chain of eighteen carbon atoms having a cis double bond in position 9. More particularly, it is mono glyceryl , di- or trioleate, alone or in combination with other factors promoting skin penetration, used in topical cosmetic or pharmaceutical compositions. More particularly, it is the use of glyceryl trioleate as a method for promoting skin penetration of the active ingredients contained in cosmetic, pharmaceutical or dermatological compositions.

It also relates to a cosmetic or pharmaceutical composition for topical use, characterized in that it comprises, as a factor promoting skin penetration, one or more oleic derivatives as defined in the present invention, mixed or not with other factors promoting skin penetration in a physiologically acceptable medium.

It relates more particularly to a cosmetic or pharmaceutical composition for topical use, comprising between 0.01 to 99.9% by weight relative to the total weight of the composition, of one or more oleic derivatives defined in the present invention, alone or in combination with other factors promoting skin penetration. It has surprisingly and unexpectedly been found that these oleic derivatives according to the invention promote the cutaneous penetration of the active ingredients of the cosmetic or pharmaceutical compositions which contain them, without affecting their physicochemical properties. In that they promote dermal penetration of the active ingredients, these oleic derivatives according to the present invention can therefore be employed in cosmetic or pharmaceutical compositions as penetration factors alone or in combination with others. Surprisingly and unexpectedly, the use of the oleic derivatives as defined in this invention in cosmetic or pharmaceutical compositions makes it possible to potentiate the effects of the other penetration factors and to enhance their action.

In compositions for the treatment of wrinkled skin containing anti-wrinkle active ingredients, when glyceryl trioleate is added to the formula, there is an improvement of about 27% efficiency in the depth and length of wrinkles. (measured by profilometry). The compositions thus have improved anti-wrinkle activity due to the presence of an oleic derivative. Similarly, in the compositions for the treatment of dry skin, when oleic alcohol is added to the formula, there is an improvement of about 18%, measured by corneometry of the cutaneous hydration rate. The compositions thus have an improved moisturizing activity due to the presence of an oleic derivative.

The invention also relates to cosmetic compositions for the treatment of wrinkled skin and to cosmetic compositions intended for the treatment of dry skin comprising these oleic derivatives according to the invention.

It relates more particularly to cosmetic compositions for the treatment of wrinkled and / or dry skin comprising from 0.01 to 99% by weight relative to the total weight of the oleic derivative composition as defined in this invention. Advantageously, the safety of the topical products thus manufactured is greatly improved over those containing the penetration factors of the prior art. Indeed, one of the major disadvantages of these products is their poor skin tolerance. It is found that the products made according to the subject of this invention are also effective without being irritating to the cutaneous mucous membranes. Compositions comprising the oleic derivatives according to the invention comprise a cosmetically or pharmaceutically acceptable medium, that is to say compatible with the skin, the mucous membranes, the hair and the scalp. They may be in any of the galenic forms suitable for topical application, especially in the form of aqueous, hydroalcoholic, organic or oily solution; suspension or dispersion in solvents or fatty substances, of lotion or serum type; as a vesicular dispersion; in the form of W / O, O / W or multiple emulsion such as cream or milk; in the form of an ointment, a gel, a solid stick, anhydrous pasty or solid products, foam, especially aerosol, or spray. The physiologically acceptable medium in which the oleic derivatives according to the invention can be employed, as well as its constituents, their quantity, the galenic form of the composition and its method of preparation, may be chosen by those skilled in the art on the basis of of his general knowledge according to the type of composition sought.

In particular, the composition may comprise any fatty substance usually used in the intended field of application. Mention may in particular be made of silicone fatty substances such as oils, gums and silicone waxes, as well as non-silicone fatty substances such as oils and waxes of vegetable, mineral, animal and / or synthetic origin. The oils may optionally be volatile or non-volatile. Mention may also be made of hydrocarbons, esters and synthetic ethers, fatty alcohols and fatty acids. The composition may also comprise an aqueous medium, an aqueous-alcoholic medium containing an alcohol such as ethanol or isopropanol, or an organic medium comprising usual organic solvents such as alcohols containing a carbon chain composed of 1 to 6 carbon atoms. carbons, especially ethanol and isopropanol, ketones.

The composition may comprise at least one conventional emulsifier chosen from amphoteric, anionic, cationic or nonionic emulsifiers, used alone or in admixture.

It may also comprise the usual adjuvants in the field under consideration, such as hydrophilic or lipophilic thickeners or gelling agents, hydrophilic or lipophilic additives, especially cosmetic active agents, preservatives, antioxidants, perfumes, fillers, pigments, W filters, odor absorbers, dyes, moisturizers (glycerol), vitamins, essential fatty acids, liposoluble polymers including hydrocarbon, opacifiers, stabilizers, sequestering agents, conditioners, propellants. Of course, those skilled in the art will take care to choose this or these optional additional adjuvants and / or their quantity in such a way that the advantageous properties of the composition according to the invention are not, or not substantially, impaired by the addition envisaged. . The oleic derivatives according to the invention make it possible to promote the penetration of the active ingredients; they therefore find a very particular application in compositions which may be: in the form of a dermatological or cosmetic care product of the skin of the face, of the body including the scalp, lips, such as a base lip care, a fixing base to be applied to a conventional lipstick, a sunscreen or artificial tanning composition; a deodorant product; a care composition (day, night, anti-wrinkle, moisturizing, etc.) for the face, a mattifying composition for the face, a gel or a cream 2905601 8 for cleaning or removing make-up, a protective body lotion or of care, a purifying milk, - in the form of a deodorizing composition, an aftershave gel or lotion, a depilatory cream, 5 - in the form of a pharmaceutical composition, - in the form of a composition for hair care, and in particular a shampoo, a setting lotion, a treatment lotion, a cream or a styling gel, a dyeing composition (in particular oxidation), optionally in the form of a coloring shampoo or a restructuring lotion; for hair, a permanent composition, a lotion or an anti-hair loss gel, a pest control shampoo, an anti-dandruff lotion or shampoo, an anti-seborrhoeic treating shampoo, in the form of a composition for oral use, by exe mple a toothpaste. Evaluation tests intended to show the effect induced by these oleic derivatives on the cutaneous penetration of various cosmetic and pharmaceutical active agents were carried out according to a method inspired by the study by Wigman, H et al., (1999) Skin Pharmacopoeia. Apple. Skin Physiol. 12, 46-53.5.

Two formulas of similar composition are compared by this method: in the first formula, the fatty phase is partly composed of an oleic derivative, whereas in the second formula, the oleic derivative is replaced by a non-oleic functional ingredient, the percentage of the active ingredient is identical. The effect on skin penetration was estimated on the forearm of volunteers: the formulas to be compared are applied at a level of 2 mg.cm-1. The application surface 2905601 9 is a rectangle of 4cm by 5cm (20 cm2 are thus treated) whose length is positioned in the axis of the arm. After one hour, a series of 15 samples per 5 adhesive strips is performed on the forearms treated. The active ratio of each self-adhesive strip is analyzed by infrared spectroscopy. Test 1: comparison Glyceryl trioleate against caprylic / capric glycerol In this first test, the comparison relates to two emollients: formula I contains 6% of a triglyceride composed of oleic hydrocarbon chains, Glyceryl trioleate, whereas formula II contains 6% Caprylic / Capric Glyceryl.

Composition of Formulas I and II: Formula I Water Glycerin Ethoxylated Stearic Acid 21 Moles Ethoxylated Stearic Acid 2 Moles Cyclopentasiloxane Hydrogenated Polyisobutene Dimethicone Active Glyceryl Trioleate Cetearyl Alcohol Polyacrylamide C13-14 Isoparaffin 35 Preservative qs 100% 5% 3% 2% 5 % 5% 4% 6% 0.5% 0.5% 0.48% 0.24% 0.5% 2905601 10 Disodium Edta 0.2% Lauryl alcohol ethoxylated 7 moles 0.06% 5 Formula II: Water qs 100% Glycerin 5% Ethoxylated Stearic Acid 21 moles 3% Ethoxylated Stearic Acid 2 moles 2% Cyclopentasiloxane 5% Hydrogenated Polyisobutene 5% Dimethicone 4% Caprylic / Caprique Triglycerides 6% Active 0.5% 15 Cetearyl Alcohol 0.5% Polyacrylamide 0 , 48% C13-14 Isoparaffin 0.24% Preservative 0.5% Disodium Edta 0.2% 20 Lauryl alcohol ethoxylated 7 moles 0.06% 25 It is found that the amounts of active ingredients, whether they are the cosmetic layers or pharmaceutical products contained in deep epidermis (test strips layers 10 to 15) are from 69% to 85% higher for the forearm treated with formula I, which contains Glyceryl trioleate. Alcohol 2nd test: comparison Oleic alcohol versus cetostearyl 30 In this second test, the comparison relates to two alcohol consistency factors: the formula III contains 1% oleic, oleic derivative, while the formula IV contains 1% of d cetostearyl alcohol.

Composition of Formulas III and IV: Formula III: Water qs 100% Glycerin 5% Ethoxylated Stearic Acid 21 Moles 3% Ethoxylated Stearic Acid 2 Moles 2% Cyclopentasiloxane 5% Polyisobutene Hydrogenated 5% Dimethicone 4% Caprylic / Caprique Triglycerides 6% Active 0.5% Oleic alcohol 1% Polyacrylamide 0.48 C13-14 Isoparaffin 0.24% Preservative 0.5% Disodium Edta 0.2% Lauryl alcohol ethoxylated 7 moles 0.06% Formula IV: Water Glycerin Stearic acid ethoxylated 21 moles Ethoxylated stearic acid 2 moles Cyclopentasiloxane Hydrogenated polyisobutene Caprylic / Capric dimethicone Triglycerides Active Cetearyl alcohol Polyacrylamide C13-14 Isoparaffin qs 100% 5% 0 3% 0 2% 0 5% 0 5% 0 4% 0 6 % a 0.5% 0, 5% 0.48% 0.24% 2905601 12 Preservative 0.5% Disodium Edta 0.2% Lauryl alcohol ethoxylated 7 moles 0.06% 5 In this case also, it is found that the quantities of cosmetic or pharmaceutical active ingredients contained in the deep layers of the epidermis (test strips 10 to 15) are 45% to 71% higher for the formula III forearm compared to the formula IV results. The present invention is illustrated in more detail in the following examples, without these being limiting. EXAMPLE 1 Anti-Aging Care Cream Water 20 Mineral Oil Propylene Glycol Stearic Acid Caryaryl Ethylhexanoate Oleic Alcohol 25 Glyceryl Stearate Beeswax Sorbitan Sesquioleate Triethanolamine Stearyl Heptanoate Ascorbyl Methylsilanol Pectinate Stearyl Caprylate Fragrance Preservatives Acrylic Polymer 35 Tocopheryl Acetate 100% 15, 000000 3,956250 3,000,800 1,820000 1,700,000 1,500,000 1,000000 1,000000 0.880000 0.680000 0.500000 0.320000 0.300000 qs 0.200000 0.200000 2905601 13 Retinyl Palmitate 0, EXAMPLE 2 Moisturizing Care Cream Water Glyceryl trioleate Peg-6 Stearate Octyldodecanol Glyceryl Stearate Ethoxylated Cetyl Alcohol 20 m. Preservatives Ethoxylated stearic alcohol 20 m. Caprylyl / Capryl Glucoside Ethoxylated cetyl alcohol 12 m. Tri ethanol amine Fragrance Glycerine Polymer carboxyvinyl Sodium Hydroxide Sodium Hyaluronate qs 100% 5,000000 3,630000 2,500,000 2,385,000 1,100,000 qs 0,385,000 0,300,000 0,300,000 0,200,000 qs 8,000000 0,200000 0 EXAMPLE 3 Cream for the treatment of oily skin 30 Water Glyceryl Trioleate Lauroyl Lysine Glycerine Oleic alcohol Sucrose Distearate Sucrose Stearate Panthenol Cyclomethicone Arachidyl Glucoside qs 100% 12.000000 2.000000 1.500000 1.100000 1, 040000 0.560000 0.375000 0.355000 0.300000 2905601 14 Perfume qs Tocopheryl acetate 0.200000 Acrylic polymer grafted alkyl 0.150000 Sodium Hydroxide 0.050000 5 Pyridoxine Hcl 0.010000 Zinc Gluconate 0.010000 10 Preservatives qs 15 20 25 30 35

Claims (7)

  1. Use of oleic derivatives as a method and composition promoting cutaneous penetration of the active ingredients contained in cosmetic, pharmaceutical or dermatological compositions.   2. Method defined according to claim 1 characterized in that the oleic derivatives are synthetic or natural lipid or amphiphilic molecules having at least in their molecular structure a hydrocarbon chain called oleic.   3. Method defined according to claims 1 and 2 characterized in that the oleic derivatives are preferably selected from acids, alcohols and fatty esters, alkyl polyglucosides, sucro-esters and mono-, di- or triglycerides virgin vegetable oils, treated or refined, composed of at least one oleic chain, that is to say a linear hydrocarbon chain of eighteen carbon atoms having a cis double bond in position 9.   4. Method defined according to claims 1, 2 and 3 characterized in that the oleic derivatives are preferably selected by glyceryl mono, di- or trioleate.   5. The method defined in claims 1, 2, 3 and 4 characterized in that the oleic derivative is glyceryl trioleate.   6. Cosmetic, dermatological or pharmaceutical composition for topical use, characterized in that it comprises, as a factor promoting skin penetration, one or more oleic derivatives as defined in Claims 1 to 5, whether or not mixed with other factors promoting skin penetration in a physiologically acceptable medium. 5   Cosmetic, dermatological or pharmaceutical composition for topical use as defined in claim 6, characterized in that it comprises between 0.01% and 99.9% by weight relative to the total weight of the composition, one or more derivatives. oleic compounds as defined in claims 1 to 5, in combination with other factors promoting skin penetration. 15 20 25 30 35