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WO2016016353A1 - Stearate emulsions - Google Patents

Stearate emulsions Download PDF

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Publication number
WO2016016353A1
WO2016016353A1 PCT/EP2015/067459 EP2015067459W WO2016016353A1 WO 2016016353 A1 WO2016016353 A1 WO 2016016353A1 EP 2015067459 W EP2015067459 W EP 2015067459W WO 2016016353 A1 WO2016016353 A1 WO 2016016353A1
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WO
WIPO (PCT)
Prior art keywords
composition according
trometamol
composition
emulsion
salt
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2015/067459
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French (fr)
Inventor
Jean- François CORDOLIANI
Valérie MUGUET
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pierre Fabre Medicament SA
Original Assignee
Pierre Fabre Medicament SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pierre Fabre Medicament SA filed Critical Pierre Fabre Medicament SA
Publication of WO2016016353A1 publication Critical patent/WO2016016353A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/01—Hydrocarbons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids

Definitions

  • the subject of the present invention is a composition for topical use in the form of an oil-in-water or water-in-oil emulsion comprising a combination of glycerol, petrolatum, and liquid paraffin and as a component of the trometamol-emulsifying system.
  • the skin is composed of three layers of tissue, it forms a barrier of protection of the body against the external environment but also provides other vital functions. From a chemical point of view, the skin contains on average 70% water, 27.5% protein, 2% fat and 0.5% mineral salts and trace elements.
  • the epidermis which corresponds to the most superficial layer, is an epithelial semi-permeable coating tissue. It is composed of several types of cells, mainly keratinocytes with more than 90%, melanocytes, Langherans and Merkel cells. The epidermis divides itself into five layers:
  • the basal layer the deepest of the epidermis. It ensures the continuous regeneration of the skin by cell division, the cells produced migrate gradually to the upper layers undergoing various mutations. Between these basal cells melanocytes are intercalated;
  • the spiny layer or mucous body of Malpighi with 3 to 10 layers of keratinocytes, which gradually flatten towards the surface;
  • the granular layer (stratum granulosum), where the keratinization of keratinocytes that evolve into corneocytes begins;
  • the clear layer (stratum lucidum), which corresponds to a transition phase between the granular layer and the stratum corneum;
  • the corneous layer (stratum corneum) composed of corneocytes, results of differentiation of keratinocytes that migrate progressively from the basal layer, and epidermal lipids. Its lower part is a real protective barrier against exogenous attacks (pollution, sun, cold, irritating substances or allergens) and the loss of endogenous water;
  • the dermis is a connective tissue that supports the epidermis, protects the vascular network and nerve fibers. The dermis is divided into two layers:
  • the papillary dermis (superficial dermis), intermediate layer, rich in nerve endings and in permanent symbiosis with the epidermis from which it is separated by the dermal-epidermal junction;
  • the reticular dermis deep and medium dermis
  • a dense connective tissue composed of a network of elastic fibers.
  • the dermis has different types of cells, mostly fibroblasts, histiocytes and mast cells.
  • hypodermis is an adipose tissue lying under the dermis. It is crossed by the vessels and the nerves arriving in the dermis. He plays several roles:
  • Cutaneous hydration is based on two phenomena: the supply of water through the trans-epidermal flow brought from the bloodstream and the retention of epidermal water which involves the cutaneous barrier function.
  • the barrier to water loss is not absolute.
  • the normal flow of water exchange between the outer and inner environment through the stratum corneum is called TEWL (transepidermal water loss) and is a part of the water insensitive loss.
  • the cutaneous barrier function is impaired in the majority of pathologies of skin with an inflammatory component, which are the most widespread in the population (psoriasis, atopy, ictyosis, xerosis or dry skin ). It is also present in a large number of physiological states in response to weather (skin aging) or environmental aggressions (exposure to UVs, humidity levels, pollution, exposure to irritating substances, burns, etc.). ).
  • atopic dermatitis or atopic eczema is a common dermatological disease, affecting 10 to 15% of infants in France, increasing in recent decades.
  • Atopic dermatitis is a chronic inflammatory skin disease that evolves by localized episodes, interspersed with periods of remission during which the inflammatory state is still present, although subclinical, and is manifested essentially by permanent xerosis and pruritus.
  • the breakdown of the barrier function associated with xerosis increases exposure to external aggression and therefore the frequency and severity of inflammatory attacks.
  • compositions for topical use according to the invention are intended to be applied to dry to very dry, sensitive, more or less damaged or irritated skin. Their spreading properties as well as their organoleptic characteristics are therefore particularly important, as well as a maintenance of these properties of spreading over time. The spreadability is approximated by consistency measurements, conducted using a texture analyzer.
  • the desired consistency should allow a good spread of the product on the skin. It must be high enough to manufacture (T0) to ensure a consistent consistency value throughout the life of the product (expiry).
  • a suitable consistency value is about 30 g, a value below which the emulsion becomes too fluid to exhibit acceptable grip and film-forming power (see procedure described in Example 1).
  • the consistency of an emulsion measured by a texture analysis corresponds to the maximum force encountered by the measuring probe during the penetration into the emulsion sample.
  • WO2009 / 138517 and WO2009 / 138515 describe an emulsion comprising, as active ingredient, a combination of glycerol, petrolatum, and liquid paraffin and, as an excipient, trolamine.
  • the inventors have been particularly interested in this type of emulsion and have made it quite surprising that replacement within an emulsion with Stearates of trolamine with trometamol improved both the consistency of the emulsion from its manufacture but also the stability over time of this consistency.
  • the stabilizing emulsifier system of a stearate emulsion is formed in situ during the emulsification phase by the action of a base (trolamine / trometamol) on an acid such as stearic acid.
  • trometamol stearate the surfactant
  • a first subject of the invention relates to a composition for topical use in the form of an oil-in-water or water-in-oil emulsion comprising a combination of glycerol, petrolatum and liquid paraffin and as a component of the trometamol-emulsifying system and / or a of its salts.
  • composition of the invention is a pharmaceutical composition or a cosmetic composition.
  • the combination of glycerol, petrolatum, liquid paraffin is present in the composition according to the invention as active ingredient, or even as sole active ingredient.
  • the combination of glycerol, petrolatum, liquid paraffin is present in a proportion of between 10 and 50%, and preferably between 20 and 30% by weight relative to the total weight of the composition.
  • concentration of glycerol is between 5 and 30%, preferably between 10 and 20% and particularly preferably is about 15% by weight relative to the total weight of the composition.
  • the petrolatum concentration is between 3 and 20%, preferably between 5 and 10% and particularly preferably is about 8% by weight relative to the total weight of the composition.
  • the liquid paraffin concentration is between 0.5 and 5%, preferably between 1 and 3% and particularly preferably is about 2% by weight relative to the total weight of the composition.
  • the water is between 30 and 80% by weight relative to the total weight of the composition.
  • the composition according to the invention comprises about 15% glycerol, about 8% petrolatum, about 2% liquid paraffin by weight relative to the total weight of the composition.
  • composition according to the invention is considered an emollient.
  • An emollient according to the invention is a composition whose properties are to soften and relax the tissues of the body, in this case the skin.
  • the dermatological composition according to the invention can be prepared in the form of a single water-in-oil (W / O) or oil-in-water (O / W) emulsion, a multiple emulsion, for example a water-in-oil emulsion. in water (W / O / W) or an oil-in-water-in-oil emulsion (W / W / W).
  • Emulsions are intimate mixtures of two liquid substances. They are always two liquids which in normal situation are immiscible but which go through specific operations (agitation, mixtures, additions of emulsifiers) to obtain a macroscopically homogeneous but microscopically heterogeneous appearance.
  • the emulsions consist of a fatty phase and an aqueous phase. The emulsification of these two phases also requires the presence of an appropriate emulsifying system whose components are included in the fatty phase and / or the aqueous phase.
  • Another subject of the invention relates to a method for preparing a composition according to the invention comprising the emulsion of a fatty phase and of an aqueous phase, said phases comprising trometamol and an acid, preferably stearic acid, to form the corresponding salt of trometamol, preferably trometamol stearate.
  • trometamol is a component of the emulsifying system which also comprises an acid.
  • Trometamol and this acid will form in situ during emulsification a trometamol salt.
  • this acid is stearic acid and the salt formed is trometamol stearate.
  • the concentration of trometamol is between 0.05 and 5%, preferably between 0.1 and 1%, preferably between 0.1 and 0.5%, particularly preferably between 0.2% and 0.4% and in another equally preferred manner is about 0.3% by weight based on the total weight of the composition.
  • the acid concentration is between 0.5 and 30%, preferably 4% by weight relative to the total weight of the composition.
  • the composition according to the invention comprises approximately 15% of glycerol, approximately 8% of petrolatum, approximately 2% of liquid paraffin and approximately 0.3% of trometamol by weight relative to the total weight of the composition.
  • the composition according to the invention comprises about 15% of glycerol, about 8% of petrolatum, about 2% of liquid paraffin, about 0.3% of trometamol, about 4% of acid, preferably stearic acid, by weight relative to the total weight of the composition.
  • Another subject of the invention relates to a process for the preparation of a composition according to the invention, comprising the emulsion of a fatty phase and of an aqueous phase, one of these phases comprising a salt of trometamol, of preferably trometamol stearate.
  • a salt of trometamol is a component of the emulsifier system added directly to one of the fatty and aqueous phases to participate in the formation of the emulsion.
  • the trometamol stearate concentration is between 0.05 and 5%, preferably between 0.1 and 1%, preferably between 0.1 and 0.5%, particularly preferably is between 0.2% and 0.4% and in another equally preferred manner is about 0.3% by weight based on the total weight of the composition.
  • the composition according to the invention comprises approximately 15% of glycerol, approximately 8% of petrolatum, approximately 2% of liquid paraffin and approximately 0.3% of trometamol stearate by weight relative to the total weight of the composition.
  • the fatty phase of the composition according to the invention comprises liquid paraffin and petrolatum. It can furthermore comprise:
  • Spreading agents such as squalane, isohexadecane, medium chain triglycerides, vegetable oils (such as soybean oil, olive oil or almond oil), silicone (such as dimethicone or polydimethylclosiloxane), esters (such as isopropyl myristate, isopropyl palmitate, dipropylene glycol dipelargonate, propylene glycol dicapate dicaprate, decyl oleate or ethyl oleate), alcohols (such as octyldodecanol), acids (such as oleic acid or undecylenic acid);
  • vegetable oils such as soybean oil, olive oil or almond oil
  • silicone such as dimethicone or polydimethylclosiloxane
  • esters such as isopropyl myristate, isopropyl palmitate, dipropylene glycol dipelargonate, propylene glycol dicapate dicaprate, decyl ole
  • Viscosity agents such as esters (such as glycerol monostearate, glycerol distearate, cetostearyl isononanoate, glycerol dibehenate or cetyl palmitate), solid paraffins, vegetable waxes (such as wax) carnauba), waxes of mineral origin (such as ozokerite) or waxes of animal origin (such as beeswax), fatty alcohols (such as cetyl alcohol), fatty acids (such as stearic acid);
  • the aqueous phase of the emulsion according to the invention comprises glycerol and may further comprise:
  • water-fixing agents such as propylene glycol, polyethylene glycols or macrogols such as macrogol 400, or macrogol 600, sorbitol
  • alcohols such as ethanol or isopropyl alcohol
  • triacetin triacetin
  • Suitable pH adjusting agents such as citric acid and / or its salts, lactic acid, phosphoric acid and / or its salts alone or in combination, sodium hydroxide, amines such as than triethanolamine or trometamol
  • Viscosifying agents such as vegetable gums, such as locust bean gum, guar gum or gum arabic
  • polymers derived from cellulose such as
  • Hydroxyethylcellulose hydroxypropylcellulose, methylcellulose or hydroxypropylmethylcellulose
  • polysaccharides obtained by bioconversion such as xanthan gum or sclerotium gum rolfssii
  • natural or modified starches such as xanthan gum or sclerotium gum rolfssii
  • pectins such as pectins, algae derivatives
  • electrolytes such as sodium chloride, magnesium sulfate heptahydrate.
  • the emulsifier system based on trometamol according to the invention may further comprise:
  • anionic surfactants such as stearates sodium stearate, sodium oleate, sodium cetostearyl sulfate, potassium cetyl phosphate
  • Nonionic surfactants such as polyoxyethylenated or non-polyethoxylated sorbitan esters (such as sorbitan stearate, polyoxyethylene sorbitan stearate, sorbitan laurate, polyoxyethylenated sorbitan laurate, sorbitan palmitate, polyoxyethylenated sorbitan palmitate, sorbitan oleate or polyoxyethylenesorbitan oleate), macrogol esters (such as polyethylene glycol 100 stearate, macrogol glycerol monostearate or macrogol glycerol cocoate), sucroesters (such as sucrose stearate or sucrose monopalmitate) ), ethers (such as steareth 20, steareth2, ceteareth 20, macrogol lauryl ether, macrogol stearyl ether or stearoyl macrogol glycerides), poloxamers, silicone derivatives (such as diethicone copolyo
  • the emulsion of the invention comprises, besides trometamol or one of its salts, at least one other emulsifier based on stearic acid.
  • stearic emulsifier means any amphiphilic molecule comprising one to several stearic chains (ether or ester).
  • stearoyl macrogol glyceride or sorbitan stearate may be mentioned.
  • composition according to the invention is intended for cutaneous application.
  • the dermatological composition according to the invention further comprises one or more dermatologically compatible excipients.
  • the term "dermatologically compatible” is intended to mean that which is useful in the preparation of a dermatological composition which is generally safe, non-toxic and neither biologically nor otherwise undesirable and which is acceptable for dermatological use in humans.
  • the dermatologically compatible excipients may be any excipient among those known to those skilled in the art in order to obtain a composition for topical application in the form of a cream, a lotion, an emulsion or a microemulsion. .
  • composition according to the invention may further contain additives and formulation aids, such as emulsifiers, thickeners, gelling agents, water binders, spreading agents, stabilizers, dyes, perfumes and the like. conservatives.
  • additives and formulation aids such as emulsifiers, thickeners, gelling agents, water binders, spreading agents, stabilizers, dyes, perfumes and the like. conservatives.
  • the composition according to the invention has between 0.5 and 30% of stearic acid, preferably between 1 and 5%, particularly preferably about 4% by weight relative to the total weight of the composition.
  • the composition according to the invention has between 0 and 2% of PEG-40-stearate, preferably about 0.5% by weight relative to the total weight of the composition.
  • Suitable thickeners include glycerol monostearate, PEG 600.
  • the composition according to the invention has about 5% thickeners by weight relative to the total weight of the composition.
  • the composition according to the invention has between 2 and 10% of glycerol monostearate, preferably about 5% by weight relative to the total weight of the composition.
  • the composition according to the invention has between 2 and 10% of PEG 600, preferably about 5% by weight relative to the total weight of the composition.
  • Suitable preservatives include propyl parahydroxybenzoate, chlorocresol.
  • the composition according to the present invention about 0.1% of preservatives by weight relative to the total weight of the composition.
  • the composition according to the invention has between 0.05 and 1% of propyl parahydroxybenzoate, preferably about 0.1% by weight relative to the total weight of the composition.
  • the composition according to the invention has about 2% spreading agents by weight relative to the total weight of the composition.
  • the composition according to the invention has between 0.2 and 2% dimethicone, preferably about 0.5% by weight relative to the total weight of the composition.
  • the composition according to the invention has between 1 and 3% of polydimethylcyclosiloxane, preferably about 2.5% by weight relative to the total weight of the composition.
  • the composition according to the invention has about 8% water fixers by weight relative to the total weight of the composition.
  • the composition according to the invention has between 2 and 10% of polyethylene glycol, preferably about 5% by weight relative to the total weight of the composition.
  • the water used for the aqueous phase of the emulsion may be distilled water or thermal water having dermato-cosmetic properties.
  • composition according to the invention comprises, by weight relative to the weight of the composition:
  • the present invention also relates to the composition according to the invention as a medicament, in particular in infants or the elderly.
  • composition according to the invention is useful for any indication and any population for which an emollient can be used.
  • the present invention also relates to the use of the composition according to the invention as an emollient.
  • composition according to the present invention is particularly suitable for pediatrics and especially for infants.
  • composition according to the present invention is also particularly suitable for the elderly, especially for senile xerosis or astheatotic.
  • the subject of the present invention is also the cosmetic use of the composition according to the invention, in particular in infants or the elderly, preferably for preventing dryness conditions.
  • composition according to the present invention is particularly suitable for preventing and / or treating iatrogenic xeroses and other side effects of treatments requiring the application of an emollient.
  • the present invention also relates to the composition according to the invention for its use in the prevention and / or treatment of iatrogenic xeroses and other side effects of treatments requiring the application of an emollient.
  • the present invention also relates to the use of the composition according to the invention for the preparation of a medicament for preventing and / or treating xeroses iatrogenic and other side effects of treatments requiring the application of an emollient.
  • composition according to the present invention is particularly suitable for preventing and / or treating xeroses that have appeared as side effects or cutaneous symptoms of pathologies such as renal insufficiency, diabetic ...
  • the subject of the present invention is also the composition according to the invention for its use in the prevention and / or the treatment of xeroses that appear as side effects or cutaneous symptoms of pathologies such as renal insufficiency, diabetic ...
  • the present invention also relates to the use of the composition according to the invention for the preparation of a medicament for preventing and / or treating xeroses that have appeared as side effects or cutaneous symptoms of pathologies such as renal insufficiency, diabetic ...
  • the present invention also relates to the composition according to the invention for its use in the prevention and / or treatment of dry skin conditions associated with certain dermatoses such as atopic dermatitis, ichthyotic conditions, psoriasis.
  • the subject of the present invention is also the use of a composition according to the invention for the preparation of a medicament intended to prevent and / or treat the conditions of cutaneous dryness associated with certain dermatoses such as atopic dermatitis, ichthyotic states, psoriasis.
  • the present invention also relates to the composition according to the invention for its use to reduce the frequency and / or reduce the intensity of eczematous outbreaks observed in patients with atopic dermatitis.
  • the present invention also relates to the use of a composition according to the invention for the preparation of a medicament for reducing the frequency and / or reducing the intensity of eczematous flares observed in patients with atopic dermatitis.
  • the present invention also relates to the composition according to the invention for its use in the prevention and / or treatment of superficial burns.
  • the present invention also relates to the use of a composition according to the invention for the preparation of a medicament for preventing and / or treating superficial burns.
  • the spreadability is approximated by consistency measurements, conducted using a texture analyzer.
  • the maximum force encountered by the probe during the penetration into the sample is the consistency.
  • the following reference emulsion is prepared: glycerol 15%, petrolatum 8%, liquid paraffin 2%, trolamine 0.5%, (0.5% w / w trolamine, ie 3.35 mmol per 100 g of emulsion ).
  • test emulsions consist of the reference emulsion in which the trolamine was replaced by disodium phosphate, sodium hydroxide, trometamol or arginine.
  • Ph diS disodium phosphate
  • TRIS trometamol
  • mol molecular
  • Conc concentration
  • Equival molar equivalent
  • Emulsion A 15% glycerol, 8% petrolatum, 2% liquid paraffin, 0.5% triethanolamine (0.5% w / w of triethanolamine, ie 3.35 mmol).
  • Emulsion B 15% glycerol, 8% petrolatum, 2% liquid paraffin, 0.3% trometamol, (0.3% w / w trometamol, ie 2.48 mmol).
  • the trometamol concentration was set so as to have a pH equivalent to the reference emulsion (emulsion A).
  • the consistency values of the emulsion A are lower than the values found for the emulsion B in the manufacture (T0) and also in the time (45 days and 12 months). It should be noted that this improvement is obtained at a lower molar concentration of trometamol.
  • the inventors clearly show that the choice of trometamol as a base involved in the formation of the emulsifying system has an undeniable advantage over the consistency of the emulsion during manufacture and over time.

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Abstract

The present invention concerns a pharmaceutical and/or cosmetic composition for topical use in the form of an oil-in-water or water-in-oil emulsion comprising, as an emulsifying system component, trometamol and/or one of the salts of same.

Description

EMULSIONS AUX STEARATES  EMULSIONS TO STEARATES

La présente invention a pour objet une composition à usage topique sous forme d'une émulsion huile dans eau ou eau dans huile comprenant une association de glycérol, vaseline, et paraffine liquide et à titre de composant du système émulsionnant le trometamol . The subject of the present invention is a composition for topical use in the form of an oil-in-water or water-in-oil emulsion comprising a combination of glycerol, petrolatum, and liquid paraffin and as a component of the trometamol-emulsifying system.

La peau est composée de trois couches de tissus, elle forme une barrière de protection de l'organisme contre le milieu extérieur mais assure également d'autres fonctions vitales. D'un point de vue chimique la peau comprend en moyenne 70% d'eau, 27,5% de protéines, 2% de matières grasses et 0,5% de sels minéraux et oligo-éléments. L'épiderme qui correspond à la couche la plus superficielle, est un tissu épithélial de revêtement semi-perméable. Il est composé de plusieurs types de cellules, majoritairement des kératinocytes à plus de 90%, des mélanocytes, des cellules de Langherans et de Merkel. L'épiderme se divise lui-même en cinq couches : The skin is composed of three layers of tissue, it forms a barrier of protection of the body against the external environment but also provides other vital functions. From a chemical point of view, the skin contains on average 70% water, 27.5% protein, 2% fat and 0.5% mineral salts and trace elements. The epidermis, which corresponds to the most superficial layer, is an epithelial semi-permeable coating tissue. It is composed of several types of cells, mainly keratinocytes with more than 90%, melanocytes, Langherans and Merkel cells. The epidermis divides itself into five layers:

La couche basale, la plus profonde de l'épiderme. Elle assure la régénération continue de la peau par division cellulaire, les cellules produites migrent progressivement vers les couches supérieures en subissant diverses mutations. Entre ces cellules basales s'intercalent les mélanocytes ;  The basal layer, the deepest of the epidermis. It ensures the continuous regeneration of the skin by cell division, the cells produced migrate gradually to the upper layers undergoing various mutations. Between these basal cells melanocytes are intercalated;

La couche épineuse ou corps muqueux de Malpighi, comportant 3 à 10 assises de kératinocytes qui s'aplatissent peu à peu vers la surface ;  The spiny layer or mucous body of Malpighi, with 3 to 10 layers of keratinocytes, which gradually flatten towards the surface;

La couche granuleuse (stratum granulosum) , où commence la kératinisation des kératinocytes qui évoluent en cornéocytes ;  The granular layer (stratum granulosum), where the keratinization of keratinocytes that evolve into corneocytes begins;

La couche claire (stratum lucidum) , qui correspond à une phase de transition entre la couche granuleuse et la couche cornée ; La couche cornée (stratum corneum) composée de cornéocytes, résultats de la différenciation des kératinocytes qui migrent progressivement depuis la couche basale, et de lipides épidermiques . Sa partie inférieure constitue une véritable barrière de protection face aux agressions exogènes (pollution, soleil, froid, substances irritantes ou allergènes) et à la perte d'eau endogène ; Le derme est un tissu conjonctif qui soutient l'épiderme, protège le réseau vasculaire et les fibres nerveuses. Le derme se divise en deux couches : The clear layer (stratum lucidum), which corresponds to a transition phase between the granular layer and the stratum corneum; The corneous layer (stratum corneum) composed of corneocytes, results of differentiation of keratinocytes that migrate progressively from the basal layer, and epidermal lipids. Its lower part is a real protective barrier against exogenous attacks (pollution, sun, cold, irritating substances or allergens) and the loss of endogenous water; The dermis is a connective tissue that supports the epidermis, protects the vascular network and nerve fibers. The dermis is divided into two layers:

le derme papillaire (derme superficiel), couche intermédiaire, riche en terminaisons nerveuses et en symbiose permanente avec l'épiderme dont il est séparé par la jonction dermo-épidermique ;  the papillary dermis (superficial dermis), intermediate layer, rich in nerve endings and in permanent symbiosis with the epidermis from which it is separated by the dermal-epidermal junction;

le derme réticulaire (derme profond et moyen) , un tissu conjonctif dense composé d'un réseau de fibres élastiques .  the reticular dermis (deep and medium dermis), a dense connective tissue composed of a network of elastic fibers.

Le derme comporte différents types de cellules, majoritairement des fibroblastes, des histiocytes et mastocytes.  The dermis has different types of cells, mostly fibroblasts, histiocytes and mast cells.

Enfin, l'hypoderme est un tissu adipeux se trouvant sous le derme. Il est traversé par les vaisseaux et les nerfs arrivant dans le derme. Il joue plusieurs rôles :  Finally, the hypodermis is an adipose tissue lying under the dermis. It is crossed by the vessels and the nerves arriving in the dermis. He plays several roles:

- protecteur, il sert d'amortisseur entre le derme et les os, d'isolant thermique,  - protective, it serves as damper between the dermis and bones, thermal insulation,

- morphologique, il modèle la silhouette en fonction de l'âge, du sexe, de l'état nutritionnel de l'individu,  - morphological, it shapes the silhouette according to the age, the sex, the nutritional state of the individual,

- et énergétique, il est le lieu du stockage des graisses. La présence d'un gradient d'eau qui passe de 70% dans les couches visibles de l'épiderme à 30% dans les couches inférieures de la couche cornée et à 15% au niveau des couches de cellules les plus externes de l'épiderme suggère qu'une partie de l'eau est retenue dès la jonction entre couche granuleuse et couche cornée. Une des fonctions de l'eau dans la couche cornée est de permettre les réactions d'hydrolyse enzymatique nécessaires à l'élasticité de la peau et à une desquamation normale. Si la quantité d'eau présente dans la couche cornée descend en dessous d'un seuil critique, les réactions enzymatiques sont perturbées, conduisant à l'adhésion des cornéocytes et à l'accumulation des cellules à la surface de la peau. Cela crée un épaississement du stratum corneum et une sécheresse, des démangeaisons ; la peau pèle et s'écaille. L'hydratation cutanée repose sur deux phénomènes : l'apport d'eau par le flux trans-épidermique apporté depuis la circulation sanguine et la rétention d'eau épidermique qui met en jeu la fonction barrière cutanée. Cependant, la barrière vis- à-vis des pertes hydriques n'est pas absolue. Le flux normal d'échange d'eau entre le milieu externe et interne à travers la couche cornée est appelé TEWL (transepidermal water loss) et constitue une part de la perte insensible en eau. - and energy, it is the place of fat storage. The presence of a water gradient that goes from 70% in the visible layers of the epidermis to 30% in the lower layers of the stratum corneum and 15% in the outermost layers of cells of the epidermis suggests that some of the water is retained from the junction between layer granular and stratum corneum. One of the functions of the water in the stratum corneum is to allow the enzymatic hydrolysis reactions necessary for the elasticity of the skin and for normal desquamation. If the amount of water present in the stratum corneum falls below a critical threshold, the enzymatic reactions are disrupted, leading to the adhesion of corneocytes and the accumulation of cells on the surface of the skin. This creates a thickening of the stratum corneum and a dryness, itching; the skin peels and flakes. Cutaneous hydration is based on two phenomena: the supply of water through the trans-epidermal flow brought from the bloodstream and the retention of epidermal water which involves the cutaneous barrier function. However, the barrier to water loss is not absolute. The normal flow of water exchange between the outer and inner environment through the stratum corneum is called TEWL (transepidermal water loss) and is a part of the water insensitive loss.

La fonction barrière cutanée est altérée dans la majorité des pathologies de la peau à composante inflammatoire, qui sont les plus répandues dans la population (psoriasis, atopie, ictyoses, xérose ou sécheresse cutanée...) . Elle l'est également dans un grand nombre d'états physiologiques en réponse au temps (vieillissement cutané) ou aux agressions de l'environnement (exposition aux UVs, taux d'humidité, pollution, exposition à des substances irritantes, brûlures...) .  The cutaneous barrier function is impaired in the majority of pathologies of skin with an inflammatory component, which are the most widespread in the population (psoriasis, atopy, ictyosis, xerosis or dry skin ...). It is also present in a large number of physiological states in response to weather (skin aging) or environmental aggressions (exposure to UVs, humidity levels, pollution, exposure to irritating substances, burns, etc.). ).

Par exemple, la dermatite atopique ou eczéma atopique est une maladie dermatologique fréquente, touchant 10 à 15% des nourrissons en France, en augmentation au cours des dernières décennies. La dermatite atopique est une maladie cutanée inflammatoire chronique qui évolue par poussées localisées, entrecoupées de périodes de rémission durant lesquelles l'état inflammatoire est toujours présent, bien que subclinique, et se manifeste essentiellement par une xérose permanente et un prurit. La rupture de la fonction barrière associée à la xérose accroît l'exposition aux agressions externes et par conséquent la fréquence et la sévérité des poussées inflammatoires. For example, atopic dermatitis or atopic eczema is a common dermatological disease, affecting 10 to 15% of infants in France, increasing in recent decades. Atopic dermatitis is a chronic inflammatory skin disease that evolves by localized episodes, interspersed with periods of remission during which the inflammatory state is still present, although subclinical, and is manifested essentially by permanent xerosis and pruritus. The breakdown of the barrier function associated with xerosis increases exposure to external aggression and therefore the frequency and severity of inflammatory attacks.

Il existe un besoin en une nouvelle composition émolliente pour la prévention et/ou le traitement des états de sécheresse cutanée de certaines dermatoses associés à une altération de la fonction barrière.  There is a need for a novel emollient composition for the prevention and / or treatment of cutaneous dry states of certain dermatoses associated with an alteration of the barrier function.

Les compositions à usage topique selon l'invention sont destinées à être appliquées sur des peaux sèches à très sèches, sensibles, plus ou moins lésées ou irritées. Leurs propriétés d'étalement ainsi que leurs caractéristiques organoleptiques sont donc particulièrement importantes, de même qu'un maintien de ces propriétés d'étalement dans le temps. L'aptitude à l'étalement est approchée par des mesures de consistance, conduites à l'aide d'un analyseur de texture. The compositions for topical use according to the invention are intended to be applied to dry to very dry, sensitive, more or less damaged or irritated skin. Their spreading properties as well as their organoleptic characteristics are therefore particularly important, as well as a maintenance of these properties of spreading over time. The spreadability is approximated by consistency measurements, conducted using a texture analyzer.

La consistance recherchée doit permettre un bon étalement du produit sur la peau. Elle doit être suffisamment élevée à la fabrication (T0) pour assurer une valeur de consistance convenable toute la durée de vie du produit (péremption) . Une valeur convenable de consistance est d'environ 30 g, valeur en dessous de laquelle l'émulsion devient trop fluide pour présenter une préhension et un pouvoir filmogène acceptables (voir mode opératoire décrit dans l'exemple 1) .  The desired consistency should allow a good spread of the product on the skin. It must be high enough to manufacture (T0) to ensure a consistent consistency value throughout the life of the product (expiry). A suitable consistency value is about 30 g, a value below which the emulsion becomes too fluid to exhibit acceptable grip and film-forming power (see procedure described in Example 1).

Selon l'invention, la consistance d'une émulsion mesurée par une analyse de texture correspond à la force maximale rencontrée par la sonde de mesure lors de la pénétration dans l'échantillon d'émulsion.  According to the invention, the consistency of an emulsion measured by a texture analysis corresponds to the maximum force encountered by the measuring probe during the penetration into the emulsion sample.

Les demandes WO2009/138517 et WO2009/138515 décrivent une émulsion comprenant, à titre de principe actif, une association de glycérol, vaseline, et paraffine liquide et, à titre d'excipient, la trolamine.  Applications WO2009 / 138517 and WO2009 / 138515 describe an emulsion comprising, as active ingredient, a combination of glycerol, petrolatum, and liquid paraffin and, as an excipient, trolamine.

Les inventeurs se sont particulièrement intéressés à ce type d'émulsions et ont mis en évidence de façon toute à fait surprenante que le remplacement au sein d'une émulsion aux stéarates de la trolamine par le trometamol améliorait à la fois la consistance de l'émulsion dès sa fabrication mais aussi la stabilité dans le temps de cette consistance. The inventors have been particularly interested in this type of emulsion and have made it quite surprising that replacement within an emulsion with Stearates of trolamine with trometamol improved both the consistency of the emulsion from its manufacture but also the stability over time of this consistency.

Pour rappel le système émulsionnant stabilisateur d'une émulsion aux stéarates se forme in situ au cours de la phase d' émulsification par action d'une base (trolamine / trometamol) sur un acide comme l'acide stéarique.  As a reminder, the stabilizing emulsifier system of a stearate emulsion is formed in situ during the emulsification phase by the action of a base (trolamine / trometamol) on an acid such as stearic acid.

Les inventeurs ont montré que le choix judicieux du trometamol comme base permet la formation du tensioactif, « le stéarate de trometamol » qui augmente de façon surprenante la valeur de la consistance de l'émulsion à la fabrication et toute la durée de vie du produit (jusqu'à la péremption) .  The inventors have shown that the judicious choice of trometamol as a base allows the formation of the surfactant, "trometamol stearate", which surprisingly increases the value of the consistency of the emulsion during manufacture and the entire life of the product ( until the expiry).

Un premier objet de l'invention concerne une composition à usage topique sous forme d'une émulsion huile dans eau ou eau dans huile comprenant une association de glycérol, vaseline et paraffine liquide et à titre de composant du système émulsionnant le trometamol et/ou un de ses sels.  A first subject of the invention relates to a composition for topical use in the form of an oil-in-water or water-in-oil emulsion comprising a combination of glycerol, petrolatum and liquid paraffin and as a component of the trometamol-emulsifying system and / or a of its salts.

La composition de l'invention est une composition pharmaceutique ou une composition cosmétique.  The composition of the invention is a pharmaceutical composition or a cosmetic composition.

Selon un mode de réalisation, l'association de glycérol, vaseline, paraffine liquide est présente dans la composition selon l'invention à titre de principe actif, voire à titre de seul principe actif.  According to one embodiment, the combination of glycerol, petrolatum, liquid paraffin is present in the composition according to the invention as active ingredient, or even as sole active ingredient.

Dans la composition selon l'invention, l'association de glycérol, vaseline, paraffine liquide est présente selon une proportion comprise entre 10 et 50%, et préférentiellement entre 20 et 30% en poids par rapport au poids total de la composition. La concentration en glycérol est comprise entre 5 et 30%, préférentiellement entre 10 et 20% et de manière particulièrement préférée est d'environ 15% en poids par rapport au poids total de la composition. La concentration en vaseline est comprise entre 3 et 20%, préférentiellement entre 5 et 10% et de manière particulièrement préférée est d'environ 8% en poids par rapport au poids total de la composition. La concentration en paraffine liquide est comprise entre 0,5 et 5%, préférentiellement entre 1 et 3% et de manière particulièrement préférée est d'environ 2% en poids par rapport au poids total de la composition. In the composition according to the invention, the combination of glycerol, petrolatum, liquid paraffin is present in a proportion of between 10 and 50%, and preferably between 20 and 30% by weight relative to the total weight of the composition. The concentration of glycerol is between 5 and 30%, preferably between 10 and 20% and particularly preferably is about 15% by weight relative to the total weight of the composition. The petrolatum concentration is between 3 and 20%, preferably between 5 and 10% and particularly preferably is about 8% by weight relative to the total weight of the composition. The liquid paraffin concentration is between 0.5 and 5%, preferably between 1 and 3% and particularly preferably is about 2% by weight relative to the total weight of the composition.

Dans la phase aqueuse, l'eau est comprise entre 30 et 80% en poids par rapport au poids total de la composition.  In the aqueous phase, the water is between 30 and 80% by weight relative to the total weight of the composition.

Avantageusement la composition selon l'invention comprend environ 15% de glycérol, environ 8% de vaseline, environ 2% de paraffine liquide en poids par rapport au poids total de la composition.  Advantageously, the composition according to the invention comprises about 15% glycerol, about 8% petrolatum, about 2% liquid paraffin by weight relative to the total weight of the composition.

La composition selon l'invention est considérée comme un émollient .  The composition according to the invention is considered an emollient.

Un émollient selon l'invention est une composition ayant pour propriétés d'assouplir et de détendre les tissus de l'organisme, en l'occurrence la peau.  An emollient according to the invention is a composition whose properties are to soften and relax the tissues of the body, in this case the skin.

La composition dermatologique selon l'invention peut être préparée sous la forme d'une émulsion simple eau dans huile (E/H) ou huile dans eau (H/E) , d'une émulsion multiple comme par exemple, une émulsion eau dans huile dans eau (E/H/E) ou une émulsion huile dans eau dans huile (H/E/H) . The dermatological composition according to the invention can be prepared in the form of a single water-in-oil (W / O) or oil-in-water (O / W) emulsion, a multiple emulsion, for example a water-in-oil emulsion. in water (W / O / W) or an oil-in-water-in-oil emulsion (W / W / W).

Les émulsions sont des mélanges intimes de deux substances liquides. Ce sont toujours deux liquides qui en situation normale sont non miscibles mais qui vont par des opérations spécifiques (agitation, mélanges, ajouts d' émulsionnants ) réussir à avoir un aspect macroscopiquement homogène mais microscopiquement hétérogène. Les émulsions se composent d'une phase grasse et d'une phase aqueuse. L' émulsification de ces deux phases nécessite en outre la présence d'un système émulsionnant approprié dont les composantes sont comprises dans la phase grasse et/ou la phase aqueuse.  Emulsions are intimate mixtures of two liquid substances. They are always two liquids which in normal situation are immiscible but which go through specific operations (agitation, mixtures, additions of emulsifiers) to obtain a macroscopically homogeneous but microscopically heterogeneous appearance. The emulsions consist of a fatty phase and an aqueous phase. The emulsification of these two phases also requires the presence of an appropriate emulsifying system whose components are included in the fatty phase and / or the aqueous phase.

Un autre objet de l'invention concerne un procédé de préparation d'une composition selon l'invention comprenant l'émulsion d'une phase grasse et d'une phase aqueuse, lesdites phases comprenant du trometamol et un acide, de préférence l'acide stéarique, pour former le sel correspondant de trometamol, de préférence le stéarate de trometamol. Another subject of the invention relates to a method for preparing a composition according to the invention comprising the emulsion of a fatty phase and of an aqueous phase, said phases comprising trometamol and an acid, preferably stearic acid, to form the corresponding salt of trometamol, preferably trometamol stearate.

En effet, selon un premier mode de réalisation, le trometamol est une composante du système émulsionnant qui comprend également un acide. Le trometamol et cet acide vont former in situ au cours de 1 ' émulsification un sel de trometamol. Avantageusement, cet acide est l'acide stéarique et le sel formé est le stéarate de trometamol. Selon ce mode de réalisation, la concentration en trometamol est comprise entre 0,05 et 5%, d'une manière préférée entre 0,1 et 1%, préférentiellement entre 0,1 et 0,5%, de manière particulièrement préférée est entre 0,2% et 0,4% et d'une autre manière tout aussi préférée est d'environ 0,3% en poids par rapport au poids total de la composition. Selon ce mode de réalisation, la concentration en acide est comprise entre 0,5 et 30%, d'une manière préférée est de 4% en poids par rapport au poids total de la composition. Avantageusement, selon ce mode de réalisation, la composition selon l'invention comprend environ 15% de glycérol, environ 8% de vaseline, environ 2% de paraffine liquide et environ 0,3% de trometamol en poids par rapport au poids total de la composition. Avantageusement encore, selon ce mode de réalisation, la composition selon l'invention comprend environ 15% de glycérol, environ 8% de vaseline, environ 2% de paraffine liquide, environ 0,3% de trometamol, environ 4% d'acide, de préférence d'acide stéarique, en poids par rapport au poids total de la composition.  Indeed, according to a first embodiment, trometamol is a component of the emulsifying system which also comprises an acid. Trometamol and this acid will form in situ during emulsification a trometamol salt. Advantageously, this acid is stearic acid and the salt formed is trometamol stearate. According to this embodiment, the concentration of trometamol is between 0.05 and 5%, preferably between 0.1 and 1%, preferably between 0.1 and 0.5%, particularly preferably between 0.2% and 0.4% and in another equally preferred manner is about 0.3% by weight based on the total weight of the composition. According to this embodiment, the acid concentration is between 0.5 and 30%, preferably 4% by weight relative to the total weight of the composition. Advantageously, according to this embodiment, the composition according to the invention comprises approximately 15% of glycerol, approximately 8% of petrolatum, approximately 2% of liquid paraffin and approximately 0.3% of trometamol by weight relative to the total weight of the composition. Advantageously, according to this embodiment, the composition according to the invention comprises about 15% of glycerol, about 8% of petrolatum, about 2% of liquid paraffin, about 0.3% of trometamol, about 4% of acid, preferably stearic acid, by weight relative to the total weight of the composition.

Un autre objet de l'invention concerne un procédé de préparation d'une composition selon l'invention, comprenant l'émulsion d'une phase grasse et d'une phase aqueuse, l'une de ces phases comprenant un sel de trometamol, de préférence le stéarate de trometamol . Another subject of the invention relates to a process for the preparation of a composition according to the invention, comprising the emulsion of a fatty phase and of an aqueous phase, one of these phases comprising a salt of trometamol, of preferably trometamol stearate.

En effet, selon un second mode de réalisation, un sel de trometamol est une composante du système émulsionnant ajouté directement à l'une des phases grasse et aqueuse pour participer à la formation de l'émulsion. Selon ce mode de réalisation, la concentration en stéarate de trometamol est comprise entre 0,05 et 5%, d'une manière préférée entre 0,1 et 1%, préférentiellement entre 0,1 et 0,5%, de manière particulièrement préférée est entre 0,2% et 0,4% et d'une autre manière tout aussi préférée est d'environ 0,3% en poids par rapport au poids total de la composition. Avantageusement, selon ce mode de réalisation, la composition selon l'invention comprend environ 15% de glycérol, environ 8% de vaseline, environ 2% de paraffine liquide et environ 0,3% de stéarate de trometamol en poids par rapport au poids total de la composition . According to a second embodiment, a salt of trometamol is a component of the emulsifier system added directly to one of the fatty and aqueous phases to participate in the formation of the emulsion. According to this embodiment, the trometamol stearate concentration is between 0.05 and 5%, preferably between 0.1 and 1%, preferably between 0.1 and 0.5%, particularly preferably is between 0.2% and 0.4% and in another equally preferred manner is about 0.3% by weight based on the total weight of the composition. Advantageously, according to this embodiment, the composition according to the invention comprises approximately 15% of glycerol, approximately 8% of petrolatum, approximately 2% of liquid paraffin and approximately 0.3% of trometamol stearate by weight relative to the total weight of the composition.

La phase grasse de la composition selon l'invention comprend de la paraffine liquide et de la vaseline. Elle peut comporter en outre : The fatty phase of the composition according to the invention comprises liquid paraffin and petrolatum. It can furthermore comprise:

• des agents d'étalement tels que le squalane, 1 ' isohexadecane, les triglycérides à chaînes moyennes, les huiles végétales (comme l'huile de soja, l'huile d'olive ou l'huile d'amande), les huiles de silicone (telles que la diméthicone ou le polydimethylclosiloxane ) , des esters (comme le myristate d' isopropyle, le palmitate d' isopropyle, le dipropylène glycol dipélargonate, le propylèneglycoldicaprylate dicaprate, l'oléate de décyle ou l'oléate d'éthyle), des alcools (comme 1 ' octyldodecanol ) , des acides (comme l'acide oléique ou l'acide undécylénique ) ;  Spreading agents such as squalane, isohexadecane, medium chain triglycerides, vegetable oils (such as soybean oil, olive oil or almond oil), silicone (such as dimethicone or polydimethylclosiloxane), esters (such as isopropyl myristate, isopropyl palmitate, dipropylene glycol dipelargonate, propylene glycol dicapate dicaprate, decyl oleate or ethyl oleate), alcohols (such as octyldodecanol), acids (such as oleic acid or undecylenic acid);

· des agents de viscosité tels que des esters (comme le monostéarate de glycérol, le distéarate de glycérol, le cetostearyl isononanoate, le dibéhénate de glycérol ou le palmitate de cétyle) , les paraffines solides, les cires d'origine végétale (comme la cire de carnauba) , les cires d'origine minérale (comme l'ozokerite) ou les cires d'origine animale (comme la cire d' abeille ) , les alcools gras (comme l'alcool cétylique) , les acides gras (comme l'acide stéarique) ; · Viscosity agents such as esters (such as glycerol monostearate, glycerol distearate, cetostearyl isononanoate, glycerol dibehenate or cetyl palmitate), solid paraffins, vegetable waxes (such as wax) carnauba), waxes of mineral origin (such as ozokerite) or waxes of animal origin (such as beeswax), fatty alcohols (such as cetyl alcohol), fatty acids (such as stearic acid);

La phase aqueuse de l'émulsion selon l'invention comprend le glycérol et peut comporter en outre: The aqueous phase of the emulsion according to the invention comprises glycerol and may further comprise:

• d'autres agents fixateurs d'eau (tels que le propylèneglycol , les polyethylèneglycols ou macrogols comme le macrogol 400, ou le macrogol 600, le sorbitol), les alcools (comme l'éthanol ou l'alcool isopropylique) , la triacétine ;  Other water-fixing agents (such as propylene glycol, polyethylene glycols or macrogols such as macrogol 400, or macrogol 600, sorbitol), alcohols (such as ethanol or isopropyl alcohol), triacetin;

• des agents d'ajustement du pH appropriés (tels que l'acide citrique et/ou ses sels, l'acide lactique, l'acide phosphorique et/ou ses sels seuls ou en combinaison, l'hydroxyde de sodium, des aminés telles que la triethanolamine ou le trometamol)  Suitable pH adjusting agents (such as citric acid and / or its salts, lactic acid, phosphoric acid and / or its salts alone or in combination, sodium hydroxide, amines such as than triethanolamine or trometamol)

• des agents viscosants (tels que les gommes végétales, comme la gomme de caroube, la gomme guar ou la gomme arabique) , les polymères dérivés de la cellulose (comme Viscosifying agents (such as vegetable gums, such as locust bean gum, guar gum or gum arabic), polymers derived from cellulose (such as

1 ' hydroxyethylcellulose, 1 ' hydroxypropylcellulose, la methylcellulose ou 1 ' hydroxypropylmethylcellulose ) , les polysaccharides obtenus par bioconversion (comme la gomme xanthane ou la gomme de sclerotium rolfssii), les amidons naturels ou modifiés, les pectines, les dérivés d'alguesHydroxyethylcellulose, hydroxypropylcellulose, methylcellulose or hydroxypropylmethylcellulose), polysaccharides obtained by bioconversion (such as xanthan gum or sclerotium gum rolfssii), natural or modified starches, pectins, algae derivatives

(comme les carraghénates ou les alginates), les silices, les argiles, les polymères synthétiques comme les polymères carboxyvinyliques ou les polymères acryliques ; (such as carrageenates or alginates), silicas, clays, synthetic polymers such as carboxyvinyl polymers or acrylic polymers;

• des électrolytes (tels que le chlorure de sodium, le sulfate de magnésium heptahydraté) .  • electrolytes (such as sodium chloride, magnesium sulfate heptahydrate).

Le système émulsionnant à base de trométamol selon l'invention peut comporter en outre: The emulsifier system based on trometamol according to the invention may further comprise:

des tensioactifs anioniques (tels que les stéarates comme le stéarate de sodium, l'oléate de sodium, le sodium cetostéaryl sulfate, le potassium cetyl phosphate) ; anionic surfactants (such as stearates sodium stearate, sodium oleate, sodium cetostearyl sulfate, potassium cetyl phosphate);

• des tensioactifs non ioniques tels que les esters de sorbitan polyoxyéthylénés ou non (comme le stéarate de sorbitan, le stéarate de sorbitan polyoxyéthyléné, le laurate de sorbitan, le laurate de sorbitan polyoxyéthyléné, le palmitate de sorbitan, le palmitate de sorbitan polyoxyéthyléné, l'oléate de sorbitan ou l'oléate de sorbitan polyoxyéthyléné) , des esters de macrogol (comme le polyéthylène glycol 100 stéarate, le macrogol 20 glycérol monostéarate ou le macrogol glycérol cocoate) , les sucroesters (comme le stéarate de sucrose ou le monopalmitate de sucrose) , des éthers (comme le steareth 20, le steareth2, le ceteareth 20, le macrogol lauryl éther, le macrogol stearyl éther ou le stearoyl macrogol glycerides) , les poloxamers, les dérivés de silicone (comme les diéthicone copolyols ou le cetyldimethicone copolyol), les phospholipides . Nonionic surfactants such as polyoxyethylenated or non-polyethoxylated sorbitan esters (such as sorbitan stearate, polyoxyethylene sorbitan stearate, sorbitan laurate, polyoxyethylenated sorbitan laurate, sorbitan palmitate, polyoxyethylenated sorbitan palmitate, sorbitan oleate or polyoxyethylenesorbitan oleate), macrogol esters (such as polyethylene glycol 100 stearate, macrogol glycerol monostearate or macrogol glycerol cocoate), sucroesters (such as sucrose stearate or sucrose monopalmitate) ), ethers (such as steareth 20, steareth2, ceteareth 20, macrogol lauryl ether, macrogol stearyl ether or stearoyl macrogol glycerides), poloxamers, silicone derivatives (such as diethicone copolyols or cetyldimethicone copolyol) , phospholipids.

Préférentiellement, l'émulsion de l'invention comprend, outre le trometamol ou un de ses sels, au moins un autre émulsionnant sur base stéarique. On entend par « émulsionnant sur base stéarique » toute molécule amphiphile comprenant une à plusieurs chaînes stéariques (éther ou ester) . On peut citer par exemple le stearoyl macrogol glyceride ou le stéarate de sorbitan.  Preferably, the emulsion of the invention comprises, besides trometamol or one of its salts, at least one other emulsifier based on stearic acid. The term "stearic emulsifier" means any amphiphilic molecule comprising one to several stearic chains (ether or ester). For example, stearoyl macrogol glyceride or sorbitan stearate may be mentioned.

La composition selon l'invention est destinée à une application cutanée. The composition according to the invention is intended for cutaneous application.

La composition dermatologique selon l'invention comprend en outre, un ou plusieurs excipients usuels dermatologiquement compatibles .  The dermatological composition according to the invention further comprises one or more dermatologically compatible excipients.

Dans la présente invention, on entend désigner par « dermatologiquement compatible » ce qui est utile dans la préparation d'une composition dermatologique qui est généralement sûr, non toxique et ni biologiquement ni autrement non souhaitable et qui est acceptable pour une utilisation dermatologique chez l'homme. Les excipients dermatologiquement compatibles peuvent être tout excipient parmi ceux connus de l'homme de l'art en vue d'obtenir une composition pour l'application topique sous forme de crème, d'une lotion, d'une émulsion, d'une microémulsion . In the present invention, the term "dermatologically compatible" is intended to mean that which is useful in the preparation of a dermatological composition which is generally safe, non-toxic and neither biologically nor otherwise undesirable and which is acceptable for dermatological use in humans. The dermatologically compatible excipients may be any excipient among those known to those skilled in the art in order to obtain a composition for topical application in the form of a cream, a lotion, an emulsion or a microemulsion. .

La composition selon l'invention peut en outre contenir des additifs et aides à la formulation, tels que des émulsionnants, des épaississants, des gélifiants, des fixateurs d'eau, des agents d'étalement, des stabilisants, des colorants, des parfums et des conservateurs.  The composition according to the invention may further contain additives and formulation aids, such as emulsifiers, thickeners, gelling agents, water binders, spreading agents, stabilizers, dyes, perfumes and the like. conservatives.

Avantageusement, la composition selon l'invention présente entre 0,5 et 30% d'acide stéarique, de préférence entre 1 et 5%, de manière particulièrement préférée environ 4% en poids par rapport au poids total de la composition.  Advantageously, the composition according to the invention has between 0.5 and 30% of stearic acid, preferably between 1 and 5%, particularly preferably about 4% by weight relative to the total weight of the composition.

Avantageusement, la composition selon l'invention présente entre 0 et 2% de PEG-40-stéarate, de préférence environ 0,5% en poids par rapport au poids total de la composition.  Advantageously, the composition according to the invention has between 0 and 2% of PEG-40-stearate, preferably about 0.5% by weight relative to the total weight of the composition.

Des épaississants appropriés comprennent le monostéarate de glycérol, le PEG 600.  Suitable thickeners include glycerol monostearate, PEG 600.

De préférence, la composition selon l'invention présente environ 5% d'épaississants en poids par rapport au poids total de la composition.  Preferably, the composition according to the invention has about 5% thickeners by weight relative to the total weight of the composition.

Avantageusement, la composition selon l'invention présente entre 2 et 10% de monostéarate de glycérol, de préférence environ 5% en poids par rapport au poids total de la composition .  Advantageously, the composition according to the invention has between 2 and 10% of glycerol monostearate, preferably about 5% by weight relative to the total weight of the composition.

Avantageusement, la composition selon l'invention présente entre 2 et 10% de PEG 600, de préférence environ 5% en poids par rapport au poids total de la composition.  Advantageously, the composition according to the invention has between 2 and 10% of PEG 600, preferably about 5% by weight relative to the total weight of the composition.

Des conservateurs appropriés comprennent le parahydroxybenzoate de propyle, le chlorocrésol .  Suitable preservatives include propyl parahydroxybenzoate, chlorocresol.

De préférence, la composition selon l'invention présente environ 0,1% de conservateurs en poids par rapport au poids total de la composition. Preferably, the composition according to the present invention about 0.1% of preservatives by weight relative to the total weight of the composition.

Avantageusement, la composition selon l'invention présente entre 0,05 et 1% de parahydroxybenzoate de propyle, de préférence environ 0,1% en poids par rapport au poids total de la composition.  Advantageously, the composition according to the invention has between 0.05 and 1% of propyl parahydroxybenzoate, preferably about 0.1% by weight relative to the total weight of the composition.

De préférence, la composition selon l'invention présente environ 2% d'agents d'étalement en poids par rapport au poids total de la composition.  Preferably, the composition according to the invention has about 2% spreading agents by weight relative to the total weight of the composition.

Avantageusement, la composition selon l'invention présente entre 0,2 et 2% de diméthicone, de préférence environ 0,5% en poids par rapport au poids total de la composition.  Advantageously, the composition according to the invention has between 0.2 and 2% dimethicone, preferably about 0.5% by weight relative to the total weight of the composition.

Avantageusement, la composition selon l'invention présente entre 1 et 3% de polydiméthylcyclosiloxane, de préférence environ 2,5% en poids par rapport au poids total de la composition .  Advantageously, the composition according to the invention has between 1 and 3% of polydimethylcyclosiloxane, preferably about 2.5% by weight relative to the total weight of the composition.

De préférence, la composition selon l'invention présente environ 8% de fixateurs d'eau en poids par rapport au poids total de la composition.  Preferably, the composition according to the invention has about 8% water fixers by weight relative to the total weight of the composition.

Avantageusement, la composition selon l'invention présente entre 2 et 10% de polyéthylène glycol, de préférence environ 5% en poids par rapport au poids total de la composition.  Advantageously, the composition according to the invention has between 2 and 10% of polyethylene glycol, preferably about 5% by weight relative to the total weight of the composition.

L'eau utilisée pour la phase aqueuse de l'émulsion peut être une eau distillée ou une eau thermale ayant des propriétés dermato-cosmétique .  The water used for the aqueous phase of the emulsion may be distilled water or thermal water having dermato-cosmetic properties.

Avantageusement, la composition selon l'invention comprend en poids par rapport au poids de la composition:  Advantageously, the composition according to the invention comprises, by weight relative to the weight of the composition:

environ 15 % de glycérol,  about 15% glycerol,

environ 8% de vaseline,  about 8% petrolatum,

- environ 2% de paraffine liquide, et à titre d'excipients : environ 0,3% de trometamol  - about 2% liquid paraffin, and as excipients: about 0.3% trometamol

environ 1 à 5% d'acide stéarique,  about 1 to 5% stearic acid,

environ 2 à 10% de monostéarate de glycérol,  about 2 to 10% of glycerol monostearate,

environ 1 à 3% de polydiméthylcyclosiloxane, environ 0,2 à 2% de diméthicone, about 1 to 3% of polydimethylcyclosiloxane, about 0.2 to 2% of dimethicone,

environ 2 à 10% de polyéthylène glycol 600,  about 2 to 10% polyethylene glycol 600,

environ 0,05 à 1% de parahydroxybenzoate de propyle jusqu'à 100% en eau.  about 0.05 to 1% propyl parahydroxybenzoate up to 100% water.

La présente invention a également pour objet la composition selon l'invention en tant que médicament, en particulier chez les nourrissons ou les personnes âgées.  The present invention also relates to the composition according to the invention as a medicament, in particular in infants or the elderly.

La composition selon l'invention est utile à toute indication et à toute population pour laquelle un émollient peut être utilisé.  The composition according to the invention is useful for any indication and any population for which an emollient can be used.

La présente invention a également pour objet l'utilisation de la composition selon l'invention en tant qu' émollient .  The present invention also relates to the use of the composition according to the invention as an emollient.

La composition selon la présente invention est particulièrement adaptée à la pédiatrie et notamment chez les nourrissons.  The composition according to the present invention is particularly suitable for pediatrics and especially for infants.

La composition selon la présente invention est également particulièrement adaptée aux personnes âgées, notamment pour la xérose sénile ou asthéatotique .  The composition according to the present invention is also particularly suitable for the elderly, especially for senile xerosis or astheatotic.

La présente invention a également pour objet l'utilisation cosmétique de la composition selon l'invention, en particulier chez les nourrissons ou les personnes âgées, de préférence pour prévenir les états de sécheresse cutanée.  The subject of the present invention is also the cosmetic use of the composition according to the invention, in particular in infants or the elderly, preferably for preventing dryness conditions.

La composition selon la présente invention est particulièrement adaptée pour prévenir et/ou traiter les xéroses iatrogènes et autres effets secondaires de traitements nécessitant l'application d'un émollient.  The composition according to the present invention is particularly suitable for preventing and / or treating iatrogenic xeroses and other side effects of treatments requiring the application of an emollient.

La présente invention a également pour objet la composition selon l'invention pour son utilisation dans la prévention et/ou le traitement des xéroses iatrogènes et autres effets secondaires de traitements nécessitant l'application d'un émollient .  The present invention also relates to the composition according to the invention for its use in the prevention and / or treatment of iatrogenic xeroses and other side effects of treatments requiring the application of an emollient.

La présente invention a également pour objet l'utilisation de la composition selon l'invention pour la préparation d'un médicament destiné à prévenir et/ou traiter les xéroses iatrogènes et autres effets secondaires de traitements nécessitant l'application d'un émollient. The present invention also relates to the use of the composition according to the invention for the preparation of a medicament for preventing and / or treating xeroses iatrogenic and other side effects of treatments requiring the application of an emollient.

La composition selon la présente invention est particulièrement adaptée pour prévenir et/ou traiter les xéroses apparues comme effets secondaires ou symptômes cutanés de pathologies telles que l'insuffisance rénale, diabétique ... The composition according to the present invention is particularly suitable for preventing and / or treating xeroses that have appeared as side effects or cutaneous symptoms of pathologies such as renal insufficiency, diabetic ...

La présente invention a également pour objet la composition selon l'invention pour son utilisation dans la prévention et/ou le traitement des xéroses apparues comme effets secondaires ou symptômes cutanés de pathologies telles que l'insuffisance rénale, diabétique ...  The subject of the present invention is also the composition according to the invention for its use in the prevention and / or the treatment of xeroses that appear as side effects or cutaneous symptoms of pathologies such as renal insufficiency, diabetic ...

La présente invention a également pour objet l'utilisation de la composition selon l'invention pour la préparation d'un médicament destiné à prévenir et/ou traiter les xéroses apparues comme effets secondaires ou symptômes cutanés de pathologies telles que l'insuffisance rénale, diabétique ...  The present invention also relates to the use of the composition according to the invention for the preparation of a medicament for preventing and / or treating xeroses that have appeared as side effects or cutaneous symptoms of pathologies such as renal insufficiency, diabetic ...

La présente invention a également pour objet la composition selon l'invention pour son utilisation dans la prévention et/ou le traitement des états de sécheresse cutanée associés à certaines dermatoses telles que dermatite atopique, états ichtyosiques , psoriasis. The present invention also relates to the composition according to the invention for its use in the prevention and / or treatment of dry skin conditions associated with certain dermatoses such as atopic dermatitis, ichthyotic conditions, psoriasis.

La présente invention a également pour objet l'utilisation d'une composition selon l'invention pour la préparation d'un médicament destiné à prévenir et/ou le traiter les états de sécheresse cutanée associés à certaines dermatoses telles que dermatite atopique, états ichtyosiques, psoriasis. La présente invention a également pour objet la composition selon l'invention pour son utilisation pour diminuer la fréquence et/ou réduire l'intensité des poussées eczémateuses observées chez les patients atteints de dermatite atopique. La présente invention a également pour objet l'utilisation d'une composition selon l'invention pour la préparation d'un médicament destiné à diminuer la fréquence et/ou réduire l'intensité des poussées eczémateuses observées chez les patients atteints de dermatite atopique. The subject of the present invention is also the use of a composition according to the invention for the preparation of a medicament intended to prevent and / or treat the conditions of cutaneous dryness associated with certain dermatoses such as atopic dermatitis, ichthyotic states, psoriasis. The present invention also relates to the composition according to the invention for its use to reduce the frequency and / or reduce the intensity of eczematous outbreaks observed in patients with atopic dermatitis. The present invention also relates to the use of a composition according to the invention for the preparation of a medicament for reducing the frequency and / or reducing the intensity of eczematous flares observed in patients with atopic dermatitis.

La présente invention a également pour objet la composition selon l'invention pour son utilisation dans la prévention et/ou le traitement les brûlures superficielles.  The present invention also relates to the composition according to the invention for its use in the prevention and / or treatment of superficial burns.

La présente invention a également pour objet l'utilisation d'une composition selon l'invention pour la préparation d'un médicament destiné à prévenir et/ou traiter les brûlures superficielles . The present invention also relates to the use of a composition according to the invention for the preparation of a medicament for preventing and / or treating superficial burns.

Les exemples suivants illustrent l'invention sans en limiter la portée. The following examples illustrate the invention without limiting its scope.

1/ Influence des bases utilisées pour la formation du système tensioactif sur la consistance des émulsions 1 / Influence of the bases used for the formation of the surfactant system on the consistency of the emulsions

L'aptitude à l'étalement est approchée par des mesures de consistance, conduites à l'aide d'un analyseur de texture. La force maximale rencontrée par la sonde lors de la pénétration dans l'échantillon représente la consistance.  The spreadability is approximated by consistency measurements, conducted using a texture analyzer. The maximum force encountered by the probe during the penetration into the sample is the consistency.

Le mode opératoire utilisé pour caractériser les échantillons d'émulsion est le suivant : The procedure used to characterize the emulsion samples is as follows:

Relever la valeur de la force maximale à la pénétration avec un texturomètre (type, TATX2) muni d'une sonde mobile cylindrique (Vitesse de mesure : 8 mm/s, Déplacement : 20 mm) .  Record the value of the maximum penetration force with a texturometer (type, TATX2) with a cylindrical moving probe (Measuring speed: 8 mm / s, Displacement: 20 mm).

De façon à évaluer l'influence de la base utilisée lors de la fabrication de l'émulsion sur sa consistance, différents essais ont été menés à l'échelle du laboratoire. In order to evaluate the influence of the base used during the manufacture of the emulsion on its consistency, various tests were conducted at the laboratory scale.

L'émulsion de référence suivante est préparée : glycérol 15%, vaseline 8%, paraffine liquide 2%, trolamine 0,5%, (0,5% m/m de trolamine, soit 3,35 mmol pour 100 g d'émulsion) .  The following reference emulsion is prepared: glycerol 15%, petrolatum 8%, liquid paraffin 2%, trolamine 0.5%, (0.5% w / w trolamine, ie 3.35 mmol per 100 g of emulsion ).

Les émulsions tests consistent en l'émulsion de référence dans laquelle la trolamine a été remplacée par du phosphate disodique, de la soude, du trometamol ou de l'arginine.  The test emulsions consist of the reference emulsion in which the trolamine was replaced by disodium phosphate, sodium hydroxide, trometamol or arginine.

Résultats Results

L'étude a été réalisée à une température ambiante (soit environ 25°C) . The study was performed at room temperature (about 25 ° C).

Les essais sont résumés dans le tableau ci-dessous, en présentant les différentes bases utilisées, ainsi que les valeurs de consistance mesurées à T0 (date de fabrication des essais) . The tests are summarized in the table below, showing the different bases used, as well as the consistency values measured at T0 (date of manufacture of tests).

Figure imgf000018_0001
Figure imgf000018_0001

Ph diS : phosphate disodique ; TRIS : trometamol ; mol : moléculaire ; Conc : concentration ; Equival : équivalent molaire .  Ph diS: disodium phosphate; TRIS: trometamol; mol: molecular; Conc: concentration; Equival: molar equivalent.

Pour des concentrations équimolaires en bases avec la référence (quantité de base égale à la quantité de trolamine) , les valeurs de consistance mesurées pour les différents essais sont toutes inférieures à celles trouvées pour l'émulsion référence, à l'exception de l'essai 5 réalisé avec le trometamol. De plus, il a été observé que pour une concentration de base divisée par 2 par rapport à celle de la référence (quantité de base égale à la quantité de trolamine divisée par 2), l'essai 4 (trometamol) présente une consistance supérieure à l'essai de référence. On peut noter qu'une consistance semblable est obtenue à l'essai 8 avec une concentration double en trometamol . 2/ Mesure et comparaison de la consistance de deux émulsions pendant 12 mois For equimolar concentrations in bases with the reference (basic amount equal to the amount of trolamine), the consistency values measured for the different tests are all lower than those found for the reference emulsion, with the exception of the test. 5 made with trometamol. In addition, it has been observed that for a base concentration divided by 2 relative to that of the reference (amount of base equal to the amount of trolamine divided by 2), the test 4 (trometamol) has a consistency greater than the reference test. It can be noted that a similar consistency is obtained in test 8 with a double concentration of trometamol. 2 / Measurement and comparison of the consistency of two emulsions for 12 months

Le mode opératoire est le même que pour l'exemple 1.  The procedure is the same as for example 1.

Résultats de la consistance : Results of the consistency:

L'étude de vieillissement dans le temps a été réalisée à une température de 25 °C et à un taux d'humidité relative de 40' The study of aging over time was carried out at a temperature of 25 ° C and at a relative humidity of 40 '

Figure imgf000019_0001
Figure imgf000019_0001

Emulsion A: glycérol 15%, vaseline 8%, paraffine liquide 2%, triethanolamine 0,5%, (0,5% m/m de triethanolamine, soit 3,35 mmo1 ) . Emulsion A: 15% glycerol, 8% petrolatum, 2% liquid paraffin, 0.5% triethanolamine (0.5% w / w of triethanolamine, ie 3.35 mmol).

Emulsion B : glycérol 15%, vaseline 8%, paraffine liquide 2%, trometamol 0,3%, (0,3% m/m de trometamol, soit 2,48 mmol) .  Emulsion B: 15% glycerol, 8% petrolatum, 2% liquid paraffin, 0.3% trometamol, (0.3% w / w trometamol, ie 2.48 mmol).

La concentration en trometamol a été fixée de façon à présenter un pH équivalent à l'émulsion de référence (émulsion A) . The trometamol concentration was set so as to have a pH equivalent to the reference emulsion (emulsion A).

Les valeurs de consistance de l'émulsion A sont inférieures aux valeurs trouvées pour l'émulsion B à la fabrication (T0) et également dans le temps (45 jours et 12 mois) . Il est à noter que cette amélioration est obtenue à une concentration molaire inférieure en trometamol . The consistency values of the emulsion A are lower than the values found for the emulsion B in the manufacture (T0) and also in the time (45 days and 12 months). It should be noted that this improvement is obtained at a lower molar concentration of trometamol.

Les inventeurs montrent clairement que le choix du trometamol comme base impliquée dans la formation du système émulsionnant présente un avantage indéniable sur la consistance de l'émulsion à la fabrication et dans le temps. The inventors clearly show that the choice of trometamol as a base involved in the formation of the emulsifying system has an undeniable advantage over the consistency of the emulsion during manufacture and over time.

Claims

Revendications claims Composition à usage topique sous forme d'une émulsion huile dans eau ou eau dans huile comprenant une association de glycérol, vaseline et paraffine liquide et à titre de composant du système émulsionnant le trometamol et/ou un de ses sels. A composition for topical use in the form of an oil-in-water or water-in-oil emulsion comprising a combination of glycerol, petrolatum and liquid paraffin and as a component of the system emulsifying trometamol and / or a salt thereof. Composition selon la revendication 1, dans laquelle ladite association de glycérol, vaseline et paraffine liquide est présente en tant que principe actif. The composition of claim 1, wherein said combination of glycerol, petrolatum and liquid paraffin is present as an active ingredient. Composition selon la revendication 1 ou 2 , caractérisée en ce que ledit sel de trometamol est le stéarate de trometamol . Composition according to claim 1 or 2, characterized in that said trometamol salt is trometamol stearate. 4. Composition selon l'une quelconque des revendications 1 à 3, comprenant une association de glycérol, vaseline et paraffine liquide et à titre de composants du système émulsionnant le trometamol et un acide, de préférence l'acide stéarique. 5. Composition selon l'une quelconque des revendications 1 à4. Composition according to any one of claims 1 to 3, comprising a combination of glycerol, petrolatum and liquid paraffin and as components of the system emulsifying trometamol and an acid, preferably stearic acid. 5. Composition according to any one of claims 1 to 4 dans laquelle la concentration de trometamol est de 0,05 à 5% en poids par rapport au poids total de la composition . 4 in which the concentration of trometamol is 0.05 to 5% by weight relative to the total weight of the composition. Composition selon la revendication 5 dans laquelle la concentration de trometamol est de 0,3% en poids par rapport au poids total de la composition. Procédé de préparation d'une composition selon l'une quelconque des revendications précédentes comprenant l'émulsion d'une phase grasse et d'une phase aqueuse, lesdites phases comprenant du trometamol et un acide pour former le sel correspondant de trometamol . Composition according to Claim 5, in which the concentration of trometamol is 0.3% by weight relative to the total weight of the composition. A process for preparing a composition according to any one of the preceding claims comprising emulsifying a fatty phase and an aqueous phase, said phases comprising trometamol and an acid to form the corresponding salt of trometamol. 8. Procédé selon la revendication 7, l'acide étant l'acide stéarique et le sel formé le stéarate de trometamol . 8. Process according to claim 7, the acid being stearic acid and the salt formed trometamol stearate. 9. Procédé de préparation d'une composition selon l'une quelconque des revendications 1 à 6, comprenant l'émulsion d'une phase grasse et d'une phase aqueuse, l'une de ces phases comprenant un sel de trometamol. 9. Process for the preparation of a composition according to any one of claims 1 to 6, comprising the emulsion of a fatty phase and an aqueous phase, one of these phases comprising a trometamol salt. 10. Procédé selon la revendication 9, ledit sel étant le stéarate de trometamol . 11. Composition selon l'une quelconque des revendications10. The method of claim 9, said salt being trometamol stearate. 11. Composition according to any one of the claims 1 à 6, pour son utilisation en tant que médicament. 1-6, for use as a medicine. 12. Composition selon l'une quelconque des revendications12. Composition according to any one of the claims 1 à 6, pour son utilisation dans la prévention et/ou le traitement des xéroses iatrogènes et autres effets secondaires de traitements nécessitant l'application d'un émollient . 1 to 6 for its use in the prevention and / or treatment of iatrogenic xeroses and other side effects of treatments requiring the application of an emollient. Composition selon l'une quelconque des revendications 1 à 6, pour son utilisation dans la prévention et/ou le traitement des xéroses apparues comme effets secondaires ou symptômes cutanés de pathologies telles que l'insuffisance rénale ou diabétique. Composition according to any one of Claims 1 to 6, for its use in the prevention and / or the treatment of xeroses that appear as side effects or cutaneous symptoms of pathologies such as renal or diabetic insufficiency. 14. Composition selon l'une quelconque des revendications 1 à 6, pour son utilisation dans la prévention et/ou le traitement des états de sécheresse cutanée associés à certaines dermatoses telles que dermatite atopique, états ichtyosiques , psoriasis. 14. Composition according to any one of claims 1 to 6, for its use in the prevention and / or treatment of dry skin conditions associated with certain dermatoses such as atopic dermatitis, ichthyotic conditions, psoriasis. 15. Composition selon l'une quelconque des revendications 1 à 6, pour son utilisation pour diminuer la fréquence et/ou réduire l'intensité des poussées eczémateuses observées chez les patients atteints de dermatite atopique . 15. A composition according to any one of claims 1 to 6, for its use to reduce the frequency and / or reduce the intensity of eczematous outbreaks observed in patients with atopic dermatitis. 16. Composition selon l'une quelconque des revendications16. Composition according to any one of the claims 1 à 6, pour son utilisation dans la prévention et/ou le traitement des brûlures superficielles. 1 to 6 for its use in the prevention and / or treatment of superficial burns. 17. Utilisation cosmétique d'une composition selon l'une quelconque des revendications 1 à 6, en particulier chez les nourrissons ou les personnes âgées. 17. Cosmetic use of a composition according to any one of claims 1 to 6, in particular in infants or the elderly. 18. Utilisation cosmétique selon la revendication 17 pour prévenir les états de sécheresse cutanée. 18. The cosmetic use according to claim 17 for preventing dry skin conditions.
PCT/EP2015/067459 2014-07-30 2015-07-30 Stearate emulsions Ceased WO2016016353A1 (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990014093A1 (en) * 1989-05-22 1990-11-29 Iowa State University Research Foundation, Inc. Water-soluble vitamin a preparations for application to the skin
WO1998055113A1 (en) * 1997-06-04 1998-12-10 Laboratorios Menarini S.A. Semisolid pharmaceutical formulation containing dexketoprofen trometamol
US7368122B1 (en) * 2002-03-08 2008-05-06 Dow Pharmaceutical Sciences Skin cream
WO2009138515A1 (en) * 2008-05-16 2009-11-19 Pierre Fabre Dermo-Cosmetique Emollient composition for the preventive treatment of atopic dermatitis
WO2009138517A1 (en) * 2008-05-16 2009-11-19 Pierre Fabre Dermo-Cosmetique Emollient composition

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990014093A1 (en) * 1989-05-22 1990-11-29 Iowa State University Research Foundation, Inc. Water-soluble vitamin a preparations for application to the skin
WO1998055113A1 (en) * 1997-06-04 1998-12-10 Laboratorios Menarini S.A. Semisolid pharmaceutical formulation containing dexketoprofen trometamol
US7368122B1 (en) * 2002-03-08 2008-05-06 Dow Pharmaceutical Sciences Skin cream
WO2009138515A1 (en) * 2008-05-16 2009-11-19 Pierre Fabre Dermo-Cosmetique Emollient composition for the preventive treatment of atopic dermatitis
WO2009138517A1 (en) * 2008-05-16 2009-11-19 Pierre Fabre Dermo-Cosmetique Emollient composition

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