Classifications

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  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
  • A61K8/11—Encapsulated compositions
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  • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
  • A61K31/05—Phenols
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  • A61K31/12—Ketones
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  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
  • A61K31/19—Carboxylic acids, e.g. valproic acid
  • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
  • A61K31/203—Retinoic acids ; Salts thereof
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  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
  • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
  • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
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  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
  • A61K31/402—1-aryl substituted, e.g. piretanide
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  • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
  • A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• • 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
  • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
  • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
  • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• • 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
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  • 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
  • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• • A—HUMAN NECESSITIES
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  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
  • A61K8/37—Esters of carboxylic acids
• • A—HUMAN NECESSITIES
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  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
  • A61K8/37—Esters of carboxylic acids
  • A61K8/375—Esters of carboxylic acids the alcohol moiety containing more than one hydroxy group
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/55—Phosphorus compounds
  • A61K8/553—Phospholipids, e.g. lecithin
• • A—HUMAN NECESSITIES
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  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/67—Vitamins
  • A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
  • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
  • A61K8/86—Polyethers
• • 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
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  • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
• • A—HUMAN NECESSITIES
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• • A—HUMAN NECESSITIES
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  • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
• • A—HUMAN NECESSITIES
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  • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
  • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
  • A61K9/5005—Wall or coating material
  • A61K9/5015—Organic compounds, e.g. fats, sugars
• • A—HUMAN NECESSITIES
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  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
• • A—HUMAN NECESSITIES
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  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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• • A—HUMAN NECESSITIES
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• • A—HUMAN NECESSITIES
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  • A61P17/00—Drugs for dermatological disorders
  • A61P17/12—Keratolytics, e.g. wart or anti-corn preparations
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2121/00—Preparations for use in therapy
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
  • A61K2800/41—Particular ingredients further characterized by their size
  • A61K2800/412—Microsized, i.e. having sizes between 0.1 and 100 microns

Definitions

• the present invention relates to lipid microcapsules having an oily internal phase and a non-polymeric envelope obtained from a lipophilic microcapsule having an internal oily phase and a non-polymeric envelope obtained from less a lipid compound selected from amphiphilic lipids.
• the invention relates to lipid microcapsules comprising at least one lipophilic active principle, said active ingredient being present in lubilized form in the oily heart of the microcapsules.
• the invention also relates to the primary emulsion composed of oily heart microcapsules dispersed in an aqueous phase and to the composition comprising, within an acceptable vehicle, the primary emulsion.
• the invention also relates to a process for preparing the primary emulsion and the composition comprising the lipid microcapsules. Finally, the invention relates to a pharmaceutical composition for its use in the treatment of dermatological conditions.
• the problem that the present invention proposes to solve here is therefore to design a physically and chemically stable composition capable of facilitating the formulation of the active ingredient while improving its protection as well as its stability within the composition in which it is present. is incorporated.
• the Applicant has surprisingly discovered that the use of particular lipid microcapsules for modifying the structure of the interface between the solubilizing medium of the active and the external phase had an impact on the attained content of active so lubilized and on its stability within a composition.
• the active ingredient is lubilized in the oily heart of lipid microcapsules.
• Microencapsulation is defined as the set of technologies that make it possible to obtain the preparation of individualized microparticles, consisting of a coating material containing an active material.
• microcapsules implies entities whose diameter is between 1 and 1000 ⁇ .
• nanocapsules is reserved for capsules whose size is less than one micron.
• the encapsulated material may be in the form of fine particles of split liquid, a liquid, or a gaseous compound.
• the microcapsule makes it possible to preserve the encapsulated substance in the form of a finely divided state, and to release it in the desired conditions.
• Microparticles obtained by microencapsulation can be presented under two different types of morphology:
• Microspheres which are particles consisting of a continuous macromolecular or lipidic network forming a matrix in which the active material is finely dispersed.
• the latter may be in the form of fine solid particles or droplets of solutions.
• Microcapsules which are reservoir particles consisting of a core of liquid or solid active material, surrounded by a continuous solid envelope of encapsulating material.
• the nature of the dispersing medium can also serve as a basis for a classification: it can be liquid (interfacial polycondensation, coacervation), gaseous (spray drying, fluidized bed coating), or in the supercritical state (phase separation)
• the family to which the compound used to obtain the capsule belongs can also make it possible to classify the encapsulation modes: preformed polymers (coacervation), lipids (spray-freezing), or monomers (interfacial polycondensation, polymerization in dispersed medium)
• microcapsules are generally obtained by physicochemical or chemical methods. These methods require the use of preformed coating agents such as polymers or monomers which in situ via a specific polymerization mechanism allow formation of the coating material.
• the microcapsules and processes making it possible to obtain them have the advantage over the prior art of not containing a polymer, or of an organic solvent, and not to I had temperature cycles.
• any solvent considered unstable, ie having a boiling point strictly below 100 ° C.
• any solvent having a boiling point greater than or equal to 100 ° C. will be considered non-vo latile according to the invention.
• the active substances are initially maintained and protected in the microcapsule core for a defined period of time, and in a second time are either progressively released through the membrane according to a certain speed of release, are liberated massively at one time. In this case, the release is triggered by a method providing specific release.
• the problem which the present invention proposes to solve here is therefore to design a physically and chemically stable composition capable of containing at least one lipophilic active principle for the treatment of dermatological pathologies, said active ingredient being in solubilized form.
• the composition according to the invention has the objective of improving the formulation of the active ingredient while ensuring stability and ease of use and cosmetology acceptable for application to all areas of the body that can be affected by pathology.
• physical stability is meant a composition whose physical properties such as organoleptic characteristics, microcapsule size, pH and viscosity are stable over time and under different temperature conditions, 4 ° C, temperature ambient, 40 ° C.
• chemical stability is meant a composition capable of containing a chemically stable active ingredient over time and regardless of the temperature condition: 4 ° C, room temperature, 40 ° C.
• ambient temperature is meant a temperature of between 15 and 25 ° C.
• the lipophilic active principle is in a solubilized form in a stable composition.
• lipophilic active agents often have difficulty in solubilization and stability, thus limiting the incorporation of these into the vehicles conventionally used, and making it difficult to obtain a stable composition.
• composition according to the invention is therefore capable of containing, within the microcapsules, at least one active ingredient known to those skilled in the art for presenting problems of solubilization and stability.
• active agents that can be used according to the invention may be in a nonlimiting manner:
• active substances that are difficult to grow and stable in highly aqueous media, such as plant extracts, and in particular Indigo Naturalis.
• Other active agents that can be used preferentially according to the invention are also the prostaglandin analogues.
• prostaglandin analogs non-limiting mention may be made of travoprost, latanoprost and tafluprost. Preferably, travoprost is used.
• the active agents exhibiting a pH-dependent degradation of the composition such as corticosteroids, and in particular clobetasol and its esters, betamethasone and its esters, aclomethasome and its esters, which destabilize at pH> 5.
• clobetasol propionate is used.
• Oxidation-sensitive assets such as phenolic derivatives.
• phenol derivative mention may be made, without limitation, of hydroquinone, rucino l or lucino l, resorcino l, 4-hydroxyaniso l, hydroquinone monoethyl ether and hydroquinone monobenzylether.
• hydroquinone and rucinol are used.
• lipid microcapsules a vesicular system of micrometric size that is to say greater than one micrometer consisting of a non-polymeric lipid envelope surrounding a liquid or semi-liquid oily heart at room temperature.
• oily heart, or internal lipid phase is meant the internal phase of lipid microcapsules of micrometric size containing a lipophilic solvent immiscible with water.
• the present invention therefore relates to the formulation of lipid microcapsules of micrometric size that can improve the formulation and stability of the lipophilic active principles, in the treatment of cutaneous pathologies
• the oily heart of the lipid microcapsules of micrometric size of the present invention is lipophilic allowing the solubilization of hydrophobic active ingredients in greater quantity.
• the present invention is a system for implementing lipid microcapsules of micrometric size without the use of organic solvents vo latil often used for the formation of the envelope, thus limiting the risks of toxicity and intolerance and in particular irritation .
• the composition comprises lipid microcapsules of micrometric size and not lipid microspheres.
• lipid microspheres are matrix particles, i.e. the whole of the mass is solid at room temperature.
• the lipid microcapsules of micrometric size according to the invention are particles whose core is composed of one or more fats liquid (s) or semi-liquid (s) at room temperature and is likely to contain the active ingredient in the form of lubilized, and whose envelope is lipidic and nonpolymeric in nature. Indeed, lipid microcapsules of micrometric size according to the invention do not require any polymer and therefore no in situ polymerization.
• compositions comprising at least one lipophilic active principle, in lubilized form in lipid microcapsules of micrometric size in a hydrophilic environment, do not require the use of polymer or solvent. organic vo latil, guarantee the stability of the active ingredient by encapsulating said active ingredient in microcapsules.
• the compositions according to the invention can also promote the cutaneous penetration of the active agent, which is useful in the treatment of cutaneous affections.
• the present invention therefore has for first obj and a lipid microcapsule of micrometric size containing an oily internal phase, a non-polymeric envelope obtained from at least one lipid compound selected from amphiphilic lipids.
• the lipid microcapsule of micrometric size according to the invention contains at least one lipophilic active ingredient solubilized in the oily internal phase.
• lipid microcapsules of micrometric size preferably consist of:
• a non-polymeric envelope obtained from at least one lipid compound obtained from at least one lipid compound
• At least one lipophilic active principle solubilized in said oily heart at least one lipophilic active principle solubilized in said oily heart.
• the invention relates in particular to lipid microcapsules of micrometric size made without organic solvents vo latil.
• the present invention also relates to a primary emulsion composed of lipid microcapsules of micrometric size dispersed in an aqueous phase.
• primary emulsion is thus meant the lipid system composed of lipid microcapsules of micron size with a solid or semi-solid interface dispersed in a continuous aqueous phase, said microcapsules containing an oily heart capable of containing the lipophilic active principle in solubilized form. an envelope obtained from a lipid compound forming the semi-solid or solid interface between the oily internal phase and the continuous aqueous phase.
• This primary emulsion is therefore an oil-in-water type emulsion.
• Said primary oil-in-water emulsion according to the invention may be incorporated into a pharmaceutically acceptable vehicle, such as a gel, a solution or an emulsion such as a cream or a lotion.
• the present invention therefore also relates to a composition comprising the primary emulsion according to the invention.
• the present invention therefore also relates to a composition, in particular a pharmaceutical and / or a cosmetic composition, said composition comprising, within a pharmaceutically or cosmetically acceptable vehicle, the primary emulsion according to the invention.
• the present invention therefore relates to a pharmaceutical composition, said composition comprising, within a pharmaceutically acceptable vehicle, the primary emulsion composed of lipid microcapsules of micrometric size preferably consisting of:
• At least one oily heart in which the lipophilic active principle is solubilized is solubilized
• At least one lipophilic active principle at least one lipophilic active principle.
• said lipid microcapsules of micrometric size being dispersed in an aqueous phase.
• composition according to the invention is therefore meant the primary emulsion, incorporated in a pharmaceutically acceptable vehicle, such as an excipient or a mixture of excipients which can form a composition in the form of a gel, a solution or an emulsion such as a cream or a lotion that can be sprayable or not.
• a pharmaceutically acceptable vehicle such as an excipient or a mixture of excipients which can form a composition in the form of a gel, a solution or an emulsion such as a cream or a lotion that can be sprayable or not.
• compositions according to the invention have the advantage of being chemically and physically stable.
• Lipid microcapsules of micrometric size means lipid microsystems whose size is preferably between 1 ⁇ and ⁇ ⁇ ⁇ .
• 50% of the lipid microcapsules have at least an average size of between 1 and 80 ⁇ and preferably between 1 and 50 ⁇ .
• the microcapsules according to the invention have an average size of between 1 and 20 ⁇ .
• the lipid microcapsules of micrometric size are present in the composition according to the invention in an amount of between 0.1 and 30% by weight relative to the total weight of the composition, preferably between 0.5 and 20%, and more particularly between 1 and 10%.
• microcapsules each consist of a liquid or semi-liquid core at room temperature, and an envelope obtained from at least one lipid compound.
• the lipid microcapsules consist of a liquid or semi-liquid heart at room temperature containing at least one lipophilic active ingredient solubilized within the oily heart.
• the present invention relates to lipid microcapsules of micrometric size containing exclusively phosphatidylcho lines without any other additional lipophilic or hydrophilic co-surfactant.
• the envelope encapsulating the oily liquid or semiliquid heart at room temperature is preferably composed of a rigid material at room temperature, non-polymeric and whose transition temperature or melting is high.
• the transition or melting temperature must be greater than 35 ° C, preferably greater than 40 ° C and ideally greater than 45 ° C.
• the envelope consists of at least one lipid compound of amphiphilic type.
• the envelope consists of a single lipid compound, advantageously chosen from amphiphilic lipids.
• the lipid compound is selected from the family of phospholipids, and more specifically, phosphatidylcho lines or lecithins. Phosphatidylcho lines or lecithins show good compatibility with the skin with a very low irritating potential.
• lecithins there may be mentioned in particular soy or egg lecithins, natural or synthetic or derived.
• the first type of lecithin is phosphatidylcholine (PC).
• lecithin including phosphatidylglycerol, phosphatidylinositol, sphingomyelin and phosphatidylethanolamine.
• lecithins having a transition temperature greater than 35 ° C. mention may be made more particularly of dipalmitoylphosphatidylcholine (DPPC), phosphatidylcholine distearoyl (DSPC), phosphatidylcholine dibehenyl (DBPC), palmitoylstearoyl phosphatidylcholine (PSPC). palmitoyl-behenyl phosphatidylcholine (PSPC), stearoyl-behenyl phosphatidylcholine (SBPC), as well as all saturated lecithins with long chains of fatty acids and their derivatives.
• DPPC dipalmitoylphosphatidylcholine
• DSPC phosphatidylcholine distearoyl
• DBPC phosphatidylcholine dibehenyl
• PSPC palmitoylstearoyl phosphatidylcholine
• SBPC stearoyl-behenyl phosphat
• the lecithins especially used in the present invention are soluble at room temperature, which favors the formation of a semi-solid interface around the liquid or semi-liquid core. This formulation allows the encapsulation of the active ingredient solubilized in the oily heart.
• the lipid microcapsules of micrometric size according to the invention more particularly contain a semi-solid or solid interface between the internal phase and the aqueous continuous phase, thanks to the use as a single lipid compound of a preferably hydrogenated lecithin.
• the hydrogenated lecithin used according to the invention has a high percentage of saturated phosphatidylcholine. By high percentage is meant an amount greater than 85% hydrogenated phosphatidylcho line (or saturated) relative to the total weight of lecithin.
• lecithin preferentially used according to the invention, mention may be made of certain hydrogenated lecithins with a content of hydrogenated phosphatidylcho line greater than 85%, such as, for example, Lipoid® grade P 100-3, Phospholipon® grade 90H sold by Lipoid, Epikuron® grade 200 SH marketed by Cargill, or Emulmetik® 950 sold by Lucas Meyer.
• the lecithin used as the sole lipid compound is Phospholipon® 90H for which the content of hydrogenated phosphatidylcho line is greater than 90%>, whose transition temperature is about 54 ° C.
• the lipid compound surrounding the liquid or semiliquid heart as defined above is present in an amount of between 0.01 and 10% by weight, preferably between 0.05 and 5% by weight, and more preferably between 0.1 and 1. % by weight relative to the total weight of the composition.
• the lipid compound, especially hydrogenated lecithin, according to the invention alone allows the encapsulation of the active agent, which avoids the contact of this active agent with the aqueous phase, and thus ensures chemical stability.
• the lipid microcapsule, and in particular the envelope is free of any co-surfactant, in particular lipophilic or hydrophilic co-surfactant.
• Lipid microcapsules of micrometric size are in particular free of organic solvent vo latil.
• lipid microcapsules of micrometric size are free of polymer.
• active in the sense of the present invention a compound having a pharmaceutical activity and / or a cosmetic activity.
• lipophilic means a compound which is soluble in a liquid or semi-liquid fatty substance at ambient temperature or in a range of temperatures between 25 and 90 ° C.
• a lipophilic substance is liposo luble.
• the lipophilic active principle is chosen from plant extracts, prostaglandin analogs, corticosteroids and phenol derivatives.
• the active ingredient is chosen from plant extracts, in particular Indigo Naturalis.
• the active principle is chosen from prostaglandin analogues, in particular travoprost, latanoprost and tafluprost and more preferably travoprost.
• the active ingredient is chosen from corticosteroids, in particular clobetasol propionate.
• the active ingredient is chosen from phenol derivatives, preferably hydroquinone, rucino l or lucino l, resorcino l, 4-hydroxyaniso l, hydroquinone monoethyl ether and hydroquinone monobenzylether. . More preferably, according to this embodiment, the active ingredient is selected from hydroquinone and rucinol.
• the active ingredient is chosen from indigo naturalis, travoprost, clobetasol propionate, hydroquinone and rucinol.
• the lipophilic active ingredient has a cosmetic activity and can be chosen in particular from moisturizing active agents and sunscreens.
• the lipophilic active principle present in the microcapsules according to the present invention is different from an irritating active ingredient.
• composition according to the invention comprises between 0.001 and 10% of at least one lipophilic active ingredient by weight relative to the total weight of the composition, preferably from 0.005 to 5% of an active ingredient by weight relative to the total weight of the composition.
• the lipophilic active principle is thus solubilized in the core of the lipid microcapsules of micrometric size according to the invention.
• Said core, or oily internal phase comprises at least one liquid or semi-liquid fatty substance at ambient temperature.
• the composition of the internal phase is therefore essential for the stability of the active ingredient.
• the oily internal phase must of course be likely to be compatible with the asset to be solubilized and solubilizing the asset.
• solubilizing phase of the active is meant a phase in which the active ingredient is stable and has a solubility allowing its use at the active concentration in the final composition.
• stability of the active principle in the oily phase is meant in the sense of the invention that the active ingredient is chemically stable over time and regardless of the temperature condition: 4 ° C, room temperature, 40 ° C.
• the stability of the active ingredient in the oily phase is evaluated in particular by liquid chromatography coupled to a UV detector (HPLC-UV).
• liquid or semi-liquid fatty substance at ambient temperature means an oily solvent.
• oily solvent any material immiscible with water at room temperature.
• the oily solvent may be a vegetable, mineral, animal or synthetic oil.
• vegetable oils mention may be made, without limitation, of olive oil, almond oil, palm oil, soya oil, sesame oil, canola oil, cottonseed oil, corn oil, safflower oil, castor oil or sunflower oil.
• mineral oils mention may be made, without limitation, of paraffin oils of different viscosities, for example those sold by Exxon Mobil, Marcol 152®, Marcol 82® and Primol 352®.
• oils of animal origin non-limiting mention may be made of lanolin, squalene, cod liver oil and squalane sold by Laserson under the trade name Cosbiol®.
• synthetic oils non-limiting mention may be made of triglycerides, fatty acid esters, fatty alcohols, polyethylene glycol ethers, the corresponding fatty alcohols and esters, polyethylene glycol ethers, amides or the like. glycols.
• the oily solvent constituting the oily internal phase does not comprise fatty acids which are not esterified or polyethoxylated.
• the oily solvent may be a mineral oil, a triglyceride, a fatty acid ester, a carboxylic acid ester, a fatty alcohol, a volatile or non-volatile silicone, or a polyethylene glycol ether.
• mineral oils there may be mentioned, without limitation, paraffin oil.
• oils containing triglycerides include without limitation, the octanoic acid triglycerides or triglycerides of caprylic / capric acids such as those sold by Stéarineries Dubois or those sold under the name Miglyol ® 810, 812 , and 818 by the company Sasol.
• fatty acid esters mention may be made, without limitation, of diisopropyl adipate, such as the commercial product Crodamol® DA sold by Croda or Schercemol DIA Ester® sold by Lubrizol, or cetearyl isononanoate sold under the name Cetiol SN® by BASF.
• diisopropyl adipate such as the commercial product Crodamol® DA sold by Croda or Schercemol DIA Ester® sold by Lubrizol, or cetearyl isononanoate sold under the name Cetiol SN® by BASF.
• alkyl benzoate C 12-15
• Crodamol® AB sold by Croda
• propylene glycol caprylate sold under the name Capryol. 90® by the company Gattefossé.
• fatty alcohols non-limiting mention may be made of octyl dodecanol or octyl dodecanol octanoate.
• ethers of polyethylene glycols mention may be made, without limitation, of the PPG-15 stearyl ether sold under the name Arlamol PS11E-LQ by the company Croda.
• volatile and non-volatile silicones mention may be made of dimethicones and cyclomethicones, such as those sold by Dow Corning under the trade name Q7-9120 silicone fluid® and ST-Cyclomethicone 5-NF®.
• the solvents used in the oily internal phase are alkyl benzoate (C 12-15 ), propylene glycol caprylate or caprylic / capric acid triglycerides.
• the preferred oily internal solvent phase of the active ingredient is diisopropyl adipate or PPG-15-stearyl ether.
• the oily solvent may be a vegetable oil, a triglyceride, a fatty acid ester, fatty alcohols, or polyethylene glycol ethers.
• the oily solvent constituting the oily internal phase does not comprise fatty acids which are not esterified or polyethoxylated.
• oily solvent (s) adapted according to the lipophilic active agent capable of being solubilized.
• the preferred oily solvents for solubilizing Indigo Naturalis are olive oil or triglycerides of caprylic / capric acids.
• the preferred oily solvent for solubilizing Travoprost is PPG-15 stearyl ether.
• the preferred oily solvents for solubilizing Clobetasol propionate are Apricot kerneil oil PEG-6 esters, PPG-15 stearyl ether or caprylic / capric acid triglycerides.
• the preferred oily solvents for solubilizing hydroquinone are diisopropyl adipate, PPG-15 stearyl ether.
• the preferred oily solvents for solubilizing rucino are diisopropyl adipate, PPG-stearyl ether or caprylic / capric acid triglycerides.
• the lipid microcapsules contain:
• an oily internal phase comprising at least one liquid or semi-liquid fatty substance at ambient temperature chosen from a vegetable oil, a triglyceride, a fatty acid ester, fatty alcohols, or polyethylene glycol ethers,
• a non-polymeric envelope obtained from at least one lipid compound obtained from at least one lipid compound
• At least one active ingredient chosen from indigo naturalis, travoprost, clobetasol propionate, hydroquinone and rucino l; said active ingredient being solubilized in the oily internal phase.
• oily internal phase may also contain one or more non-oily co-solvents or other nonvolatile organic co-solvents.
• the internal phase does not require any solvents / cosolvent of alcoholic type to solubilize the active ingredient.
• the blends of solvents selected according to the invention are sufficient to obtain the required solubility and stability of the active ingredient within the microcapsules without resorting to any alcoholic solvent.
• the internal phase may also include one or more liquid or semi-liquid fatty substances at room temperature unsolubilizing asset.
• non-solubilising fatty substance of the active ingredient is meant a compound for which the active ingredient does not exhibit a solubility allowing its use at the active concentration in the final composition.
• the solvent will be present in an amount of between 50 and 99.997% by weight relative to the total weight of the internal phase; preferably in an amount of between 70 and 99.997% by weight relative to the total weight of the internal phase, preferably between 95 and 99.997%).
• the optional fatty substance or cosolvent is present in an amount of between 0 and 50% by weight relative to the total weight of the internal phase; preferably in an amount of between 0.1 and 25% by weight relative to the total weight of the internal phase, preferably between 0.5 and 10% by weight.
• the internal phase may also comprise one or more compounds such as, for example, antioxidants or preservatives.
• the oily internal phase of the microcapsules is present in an amount of between 0.1 and 50% by weight relative to the total weight of the primary emulsion, preferably in an amount of between 0.5 and 35%. by weight relative to the total weight of the primary emulsion.
• the ratio between the internal oily phase and the amount of hydrogenated lecithin is between 5 to 10 to 1.
• this ratio in the emulsion is between 6 to 8 for 1 and preferably 7 to 1.
• the ratio between the water and the internal oily phase is between 1.25 to 5 to 1.
• this ratio between the water and the internal oily phase is between 2 to 4 for 1 and preferentially 2 to 3 to 1.
• the microcapsules are dispersed in an aqueous phase.
• the continuous aqueous phase comprises water.
• This water can be demineralised water, floral water, or natural thermal or mineral water,
• the water may be present in a content of between 55 and 95% by weight relative to the total weight of the composition, preferably between 60 and 95% by weight.
• composition in particular a pharmaceutical or a cosmetic composition, said composition comprising the primary emulsion containing the lipid microcapsules of micrometric size defined above in the text of the present invention in a pharmaceutically or cosmetically acceptable vehicle, such as a gel, solution or emulsion such as a cream or lotion.
• a pharmaceutically or cosmetically acceptable vehicle such as a gel, solution or emulsion such as a cream or lotion.
• the primary emulsion is dispersed in an aqueous phase which comprises at least one gelling agent.
• This gelling agent may be a cellulose derivative chosen from semi-synthetic cellulosic gelling agents.
• the gelling agent may also be chosen from natural gums, in particular xanthan gum (known for example under the name Satiaxane and sold by Cargill), starch and its derivatives, polyacrylic acid polymers which have been crosslinked as carbomers such as Carbopol 980, Carbopol Ultrez 10 and among their alkylated derivatives such as copolymers of acrylates / C 10-30 alkyl acrylates such as Carbopol ETD2020, Pemulen TR I, Pemulen TR2, carboxyvinyl polymers, polyvinyl pyrrolidones and their derivatives, polyvinyl alcohols.
• natural gums in particular xanthan gum (known for example under the name Satiaxane and sold by Cargill), starch and its derivatives, polyacrylic acid polymers which have been crosslinked as carbomers such as Carbopol 980, Carbopol Ultrez 10 and among their alkylated derivatives such as copolymers of acrylates / C
• the gelling agent may also be chosen from emulsifying polymers such as S epigel 305 consisting of a polyacrylamide / isoparaffin C 13 -C 14 / laureth-7 mixture, or Simulgel® 600PHA or Sepineo® P600, namely the sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80. These two products being marketed by the company Seppic.
• the primary emulsion is dispersed in a vehicle composed of an aqueous phase.
• aqueous phase which constitutes the pharmaceutically acceptable vehicle is meant any aqueous phase as defined above in the present invention.
• the pharmaceutically or cosmetically acceptable vehicle is a cream or a lotion
• the primary emulsion is dispersed in a vehicle composed of an aqueous phase and a fatty phase comprising or not at least one surfactant or emulsifier.
• the composition according to the invention therefore comprises a fatty phase.
• This fatty phase may comprise, for example, vegetable, mineral, animal or synthetic oils, silicone oils, and mixtures thereof.
• the emulsion is in the form of an oil-in-water (O / W) emulsion.
• This emulsion may not comprise or comprise at least one emulsifying agent.
• the cream or the lotion according to the invention also comprises an aqueous phase.
• aqueous phase which constitutes the pharmaceutically or cosmetically acceptable vehicle, alone or within an emulsion, is meant any aqueous phase as defined previously in the present invention.
• composition according to the invention may also contain, within the primary emulsion or the pharmaceutically acceptable vehicle, one or more additives or combinations of additives, such as:
• UV-A and UV-B filters are UV-A and UV-B filters
• ingredients of the pharmaceutically or cosmetically acceptable vehicle and in particular, the aqueous phases, the fatty phases, the emulsifiers and the optional compound (s) to be added to these compositions, in such a way that the advantageous properties intrinsically attached to the present invention are not or substantially unaffected by the choice of ingredients.
• composition according to the invention thus comprises, in a pharmaceutically or cosmetically acceptable vehicle, by weight relative to the total weight of the composition, compound microcapsules:
• a non-polymeric envelope obtained from 0.0 to 10% of lipid compound selected from amphiphilic lipids
• composition according to the invention thus preferably comprises, in a pharmaceutically or cosmetically acceptable vehicle, by weight relative to the total weight of the composition, microcapsules composed of:
• lipid compound selected from amphiphilic lipids, preferably hydrogenated lecithin;
• liquid or semi-liquid fatty substance at room temperature preferably fatty acid esters or polyethylene glycol ethers
• the composition comprises, in a pharmaceutically acceptable vehicle, by weight relative to the total weight of the composition:
• the vehicle is pharmaceutically acceptable.
• the pharmaceutical composition that can be used according to the invention is intended for the treatment of the skin and can be administered topically, parenterally or orally.
• the pharmaceutical composition may be in liquid or pasty form, and more particularly in the form of capsules, dragees, or syrups.
• composition may be in the form of suspensions for infusion or for injection.
• the composition is in a form suitable for topical administration.
• Topical administration we mean an application on the skin, the mucous membranes, the hair or the scalp.
• the composition may be in liquid or pasty form, and more particularly in the form of creams, milks, ointments, soaked swabs, syndets, wipes, gels, sprays, foams, lotions, sticks, shampoos, or washing bases.
• the subject of the invention is also a process for the preparation of the compositions according to the invention.
• the object of the invention is the process for the preparation of compositions comprising at least one lipophilic active agent.
• the process according to the invention does not involve phase inversion phenomena characterized by a Phase Inversion Temperature (TIP) (used in particular in Patents FR 2 805 761 and FR 2 840 53 1), and therefore does not require a cycle (s) of rise and fall in temperature.
• TIP Phase Inversion Temperature
• the process according to the invention does not use a high pressure homogenizer (HHP) and therefore does not require a prehomogenization step.
• HHP high pressure homogenizer
• the process according to the invention therefore has the advantage of not having successive heating and cooling cycles, of not using organic solvents, polymer, of not requiring a gelling step. of the emulsion and no prehomogenization step.
• the process as presented according to the invention and proposed for the production of lipid microcapsules of micrometric size uses equipment allowing emulsification at high shear rate.
• rotor / stator type mixers such as Polytron (Kinematica) or Magic Lab (Ika).
• sonication can be used with eg a Branson type probe.
• the process consists of producing a primary emulsifier, which is then diluted in a pharmaceutically acceptable vehicle.
• This primary emulsion makes it possible to vary the amount of introduction of the lipid compound, preferably hydrogenated lecithin, which can be introduced completely into the oily phase (100% oily phase) or into the aqueous phase (100%). % aqueous phase) or introduced in different ratios such as a 50/50 ratio in the oily phase and in the aqueous phase.
• the lipid compound preferably hydrogenated lecithin
• the production of the primary emulsion comprises 3 steps:
• the preparation of the aqueous phase and the oily phase are dependent on the choice of the dispersion mode of the lipid compound, preferably hydrogenated lecithin:
• the hydrogenated lecithin used is dispersed throughout the heated aqueous phase at about 75 ° C., using a rotor / stator type mixer.
• high shear such as Ultra Turrax (Ika), Polytron (Kinematica) or Magic Lab (Ika), with stirring between 5,000 to 10,000 rpm, for a defined time that will not exceed 30 minutes.
• a preservative and an antioxidant can be added at this stage.
• the active ingredient in a suitable container and using a magnetic bar, is solubilized in the internal oily phase heated to about 75.degree. C., comprising, inter alia, soiling oil. active ingredient.
• a preservative and an antioxidant can be added to this phase after solubilization of the active ingredient.
• all of the aqueous phase is heated to 75 ° C. A preservative and an antioxidant can be added at this stage.
• the active ingredient if present, is solubilized in the internal oily phase heated to about 75 ° C., comprising, inter alia, the oil which solubilizes the active ingredient.
• a preservative and an antioxidant may be added at this stage after lubilization of the active ingredient.
• the lipid compound, preferably the hydrogenated lecithin used is dispersed in this oily phase still at about 75 ° C, using a high shear rotor / stator type mixer such as an Ultra Turrax (Ika) , or a Polytron (Kinematica) with stirring between 5,000 to 10,000 rpm, for a defined time that will not exceed 30 minutes.
• a high shear rotor / stator type mixer such as an Ultra Turrax (Ika) , or a Polytron (Kinematica) with stirring between 5,000 to 10,000 rpm, for a defined time that will not exceed 30 minutes.
• all of the aqueous phase is heated to 75 ° C.
• About half of the lipid compound, preferably hydrogenated lecithin, is dispersed in this aqueous phase. always heated to about 75 ° C, using a high shear rotor / stator mixer such as Ultra Turrax (Ika), Polytron (Kinematica), or the Magic Lab (Ika) with stirring included between 5,000 and 10,000 rpm, for a defined time that will not exceed 30 minutes.
• a preservative and an antioxidant can be added at this stage.
• the active ingredient in a suitable container and using a magnetic bar, is solubilized in the internal oily phase heated to about 75 ° C., comprising, inter alia, the oil which solubilizes the active ingredient.
• the other part of the lipid compound preferably hydrogenated lecithin, is dispersed in this oily phase still heated to about 75 ° C., using a high shear rotor / stator mixer such as an Ultra Turrax (Ika) or a Polytron (Kinematica), with stirring between 5,000 to 10,000 rpm, for a defined time that will not exceed 30 minutes.
• a preservative and an antioxidant may be added at this stage after lubilization of the active ingredient.
• the aqueous and oily phases are mixed by incorporation of the oily phase into the aqueous phase.
• the operating mode is dependent on the type of device used. Three types of apparatus are preferentially used to effect the mixing of the two phases resulting in the primary emulsion according to the invention: the method with Polytron, the method with Magic Lab, the method with sonication probe. According to the different types of agitators, the emulsion is produced as described: ⁇ Process with Polytron under temperature regulation at
• the primary emulsion obtained above is then introduced into a pharmaceutically acceptable vehicle previously made, solution, cream, lotion and gel.
• a pharmaceutically acceptable vehicle previously made, solution, cream, lotion and gel.
• the gelling step is carried out instantaneously at the end of the production of the primary emulsion:
• Stirring can be generated by using a light deflocculator attached to an IKA or Rayneri type stirring motor.
• a gentle stirring corresponds to a speed which makes it possible to obtain a homogeneous gel after 20 min without generating excessive aeration of the formulation, for example at a speed around 200 rpm.
• a quantity of primary emulsion can be removed and then diluted in one part of water. This mixture is then thickened by the addition of a gelling agent.
• compositions according to the invention comprises the following steps:
• step (e) stirring mixture of the oily and aqueous phases obtained at the end of step (d);
• the lipid compound is introduced either 100% into the oily phase or 100% into the aqueous phase depending on the nature of the oily core chosen to solubilize the lipophilic active ingredient in the microcapsule.
• the hydrogenated lecithin is introduced either at 100%) in the oily phase, or at 100% in the aqueous phase depending on the nature of the oily core chosen to solubilize the lipophilic active ingredient in the microcapsule.
• the preferred apparatus is the Magic Lab.
• the preferred mode of dispersion of the lipid compound, and more preferably hydrogenated lecithin is 100% in the fatty phase, in the case of using oily solvents of the triglyceride and ester type. acids such as diisopropyl adipate,
• the preferred mode of dispersion of the lipid compound, and more preferably of hydrogenated lecithin is 100% in the aqueous phase, particularly in the case of the use of oily solvents of the polyethylene ether type.
• glycols such as, for example, PPG-15-stearyl ether.
• the process for preparing a composition according to the invention comprises the following steps:
• the process for preparing a composition according to the invention comprises the following steps:
• the composition according to the invention comprises, within a pharmaceutically or cosmetically acceptable vehicle, lipid microcapsules of micrometric size dispersed in an aqueous phase, said lipid microcapsules of micrometric size containing an internal oily phase in which at least one lipophilic active ingredient is solubilized, and a non-polymeric envelope obtained from at least one lipid compound selected from amphiphilic lipids.
• composition according to the invention is usable as a medicament.
• the subject of the invention is also the composition as defined above for its use for treating dermatological conditions, in particular human affections, as defined below:
• dermatological disorders related to a keratinization disorder relating to differentiation and cell proliferation in particular to treat vulgar, comedonal, polymorphic, rosacea acne, nodulocystic acne, conglobata, senile acnes, secondary acnes such as acne soothing, medicated or professional;
• disorders of keratinization including ichthyosis, ichthyosiform states, lamellar ichthyosis, Darrier's disease, palmoplantar keratoderma, leukoplakia, pityriasis rubra pilaire and leucoplasiform states, cutaneous or mucosal lichen (oral) ;
• dermatological disorders such as immune dermatoses such as lupus erythematosus, oily immune diseases and collagen diseases, such as scleroderma;
• disorders of pigmentation such as hyperpigmentation, melasma, hypopigmentation or vitiligo
• cancerous or precancerous, cutaneous or mucosal states such as actinic keratoses, Bowen's disease, in-situ carcinomas, keratoacanthoma and skin cancers such as basal cell carcinoma (BCC), spinal cell carcinoma (SCC) and cutaneous tek lymphoma than T-cell lymphoma.
• the invention relates to the composition for use in the treatment of acne, ichthyos, ichthyosiform states, palmoplantar hyperkeratosis or psoriasis.
• the invention relates to the composition according to the invention for its use as a medicament in the treatment of dermatological conditions, especially human, as previously defined.
• the invention relates to the use of the composition according to the invention for the treatment of dermatological conditions, in particular human affections, as previously defined.
• composition is used for the treatment of acne, ichthyos, ichthyosiform states, palmoplantar hyperkeratosis or psoriasis.
• composition according to the invention may be a cosmetic composition.
• the cosmetic composition is used for the protection and / or skin care of the skin.
• the cosmetic composition is used for the treatment, and in particular for moisturizing the skin.
• the cosmetic composition is used to protect the skin from the effects of ultraviolet radiation.
• the cosmetic composition is used to prevent or delay the signs of skin aging due to ultraviolet radiation.
• compositions comprising a lipophilic acid
• Example 1 Primary Emulsions Containing Lipid Microcapsules Placebos Before Dilution in a Composition
• lipid microcapsules were made with an oily heart containing an oil or a mixture of oils.
• compositions of the primary emulsions E 1 to E 5 are therefore as follows:
• EXAMPLE 2 Examples of compositions in the form of a gel according to the invention made from the placebo primary emulsions of compositions E1 to E5 of Example 1 In order to produce the compositions in the form of G1 to G16 gel according to the invention, different amounts of primary emulsions prepared according to Example 1 were removed and diluted in a gel base.
• the primary emulsion placebo is added in the formulation.
• the gels G1, G6, G9 to G12 were obtained from the primary emulsion E1
• the gels G4, G7, G13 to G16 were obtained from the primary emulsion E4
• the G5 and G8 gels were obtained from the primary emulsion E5.
• compositions in gel form obtained according to the invention are therefore the following:
• compositions (% m / m)
• compositions in the form of C 1 to C 3 cream according to the invention a quantity of primary emulsion prepared according to Example 1 was taken and incorporated at a given moment during the process of producing a cream.
• the primary emulsions E 1, E 4 and E 5 lead respectively to the creams C 1, C 2 and C 3 described in the table below.
• compositions in the form of cream obtained according to the invention are therefore the following:
• compositions (% m / m)
• EXAMPLE 4 Characterization of the gel compositions of Example 2 Gl, G4 and G5 according to the invention, prepared from the E1, E4 and E5 placebo primary emulsions which were obtained according to two different modes of introduction of the hydrogenated lecithin.
• the measurement of the viscosity is carried out using a Brookfield RVDVII + type apparatus. The measurements are carried out after 1 min, in the original packaging.
• Example 1 E5 of Example 1 were carried out according to two distinct modes of introduction of hydrogenated lecithin, namely 100% of the hydrogenated lecithin in the aqueous phase and 100% of the hydrogenated lecithin in the fatty phase.
• the equipment used to produce the primary emulsions is the Magic Lab.
• the dispersion mode of the hydrogenated lecithin may generate different characteristics.
• FIGS. 1 and 2 represent the images obtained under the microscope (objective 40 and x252 magnification) of the microcapsules in the No. 1 and No. 2 gels respectively, which were made from the primary emulsion E4 containing PPG-stearyl ether as an oil.
• microcapsules of Figure 1 are regular in size and shape.
• those of FIG. 2 are more irregular both in size and in shape.
• the mode of dispersion of hydrogenated lecithin can impact on the physical appearance of the microcapsules.
• FIGS. 3 and 4 show the microscope images (objective 40 and x252 magnification) of the microcapsules in gels No. 1 and No. 2, respectively, which were made from the primary emulsion E5 containing triglycerides of acids capric / caprylic as oil.
• the dispersion mode of hydrogenated lecithin does not affect the physical appearance of the microcapsules.
• a mode of dispersion of hydrogenated lecithin may be preferred for each type of oil.
• the preferred mode of dispersion of hydrogenated lecithin is 100% in the fatty phase.
• the preferred mode of dispersion of hydrogenated lecithin is 100% in the aqueous phase.
• the measurement of the viscosity is carried out using a Brookfield RVDVII + type apparatus. The measurements are carried out after 1 min, in the original packaging.
• oil used PPG-stearyl ether
• oil used PPG-stearyl ether
• FIGS. 5 and 6 show the images obtained under the microscope (objective 40 and x225 magnification) of the microcapsules in No. 1 and No. 2 gels which were made from the primary emulsion E4 containing PPG-stearyl ether. as an oil after 6 months of storage at a temperature of 40 ° C.
• the microcapsules are more regular and more uniform in size (FIG. 5).
• FIGS. 7 and 8 show the images obtained under the microscope of the microcapsules in No. 1 and No. 2 gels which were made from the primary emulsion E5 containing capric / caprylic acid triglycerides after 6 months of storage at a temperature of 40 ° C.
• microcapsules are generally uniform and uniform in size, after 6 months of stability at 40 ° C. (FIGS. 7 and 8).
• the equipment that was used to make the primary emulsion is the Magic Lab.
• the preferred dispersion mode for hydrogenated lecithin with diisopropyl adipate is 100% in the fat phase.
• Gels No. 1, No. 2 and No. 3 have the same formulation as the G1, G9 and G11 gels described in Example 2.
• thickening agent sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80
• oil used diisopropyl adipate
• Gel No. 2 Thickening agent used: Carbomer Obtained from the primary emulsion El (oil used diisopropyl adipate)
• thickening agent Acrylates / C 10-30 Alkyl Acrylate Crosspoly
• the equipment that has been used for producing the primary emulsions is the Magic Lab
• the primary emulsions E2 and E3 were made by introducing 100% of the hydrogenated lecithin into the fatty phase in order to obtain the corresponding gels.
• Example 8 The stability of the gels of Example 8, obtained from the primary emulsions E2 and E3, was studied for a period of one month.
• EXAMPLE 10 Primary Emulsions Containing the Lipid Microcapsules Containing a Lipophilic Active Element Before Dilution in a Composition Using the methods cited above and according to the dispersion method of hydrogenated lecithin as defined above in the present description, lipid microcapsules were produced and contain in the oily heart a lipophilic active solubilized in an oil.
• the lipophilic active agents used in primary emulsions are indigo naturalis, travoprost, clobetasol propionate, hydroxyquinone and rucino l.
• compositions of the primary emulsions ⁇ ⁇ to ⁇ ⁇ 1 are therefore the following:
• compositions in gel form according to the invention a quantity of primary emulsion prepared according to Example 1b was taken and added to the formulation.
• 71.71 grams of the primary emulsion are added with stirring to 26.29 grams of water. This mixture is then thickened by the addition of a gelling agent at 2%, with moderate stirring.
• Stirring can be generated by the use of a deflocculator light attached to an IKA or Rayneri type stirring motor.
• Moderate stirring corresponds to a speed which makes it possible to obtain a homogeneous gel after 20 minutes without generating excessive aeration of the formulation, for example a speed of between 400-600 rpm.
• compositions in gel form according to the invention a quantity of primary emulsion prepared according to Example 1b was taken and added to the formulation.
• 71.71 grams of the primary emulsion E'3 are added with stirring to 26.29 grams of water. This mixture is then thickened by the addition of a gelling agent at 2%, with moderate stirring.
• Stirring can be generated by the use of a deflocculator light attached to an IKA or Rayneri type stirring motor.
• Moderate stirring corresponds to a speed which makes it possible to obtain a homogeneous gel after 20 min without generating excessive aeration of the formulation, for example a speed of between 400-600 rpm.
• the gel G'3 was obtained from the primary emulsion E'3.
• EXAMPLE 13 Examples of Gel and Cream-type Compositions According to the Invention Made from the Primary Emulsions E'4 to E'6 of Example 10 Containing Clobetasol Proprionate
• 71.71 grams of the primary emulsion E'6 is added with stirring to 26.29 grams of water having a pH equal to 5. This mixture is then thickened by the addition of a gelling agent to
• Stirring can be generated by the use of a deflocculator light attached to an IKA or Rayneri type stirring motor.
• a moderate stirring corresponds to a speed which makes it possible to obtain a homogeneous gel after 20 minutes without generating too much aeration of the formulation, for example a speed between
• the G'4 and G'5 gels were respectively obtained from the primary emulsion E'5 and E'6.
• a quantity of primary emulsion prepared according to the example was taken and added to the formulation.
• Clobetasol propionate contained in the presence of 10%> solvent oil within the capsules, 35.855 grams of the primary emulsion E'4 are added in the formulation.
• 35.855 grams of the primary emulsion are added with stirring to 57.145 grams of water having a pH equal to 5. This mixture is then thickened by the addition of a 4% gelling agent, with moderate stirring.
• 71.71 grams of the primary emulsion are added with stirring to 26.29 grams of water put having a pH equal to 5. This mixture is then thickened by the addition of a gelling agent to 2%, with moderate stirring.
• Stirring can be generated by the use of a deflocculator light attached to an IKA or Rayneri type stirring motor.
• Moderate stirring corresponds to a speed which makes it possible to obtain a homogeneous gel after 20 minutes without generating excessive aeration of the formulation, for example a speed of between 400-600 rpm.
• Stirring can be generated by the use of a deflocculator light attached to an IKA or Rayneri type stirring motor.
• Moderate stirring corresponds to a speed which makes it possible to obtain a homogeneous gel after 20 minutes without generating excessive aeration of the formulation, for example a speed of between 400-600 rpm.

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