WO2012107602A1 - Form of administration of phospholipids for the formation on the skin of laminar phospholipid layers - Google Patents

Form of administration of phospholipids for the formation on the skin of laminar phospholipid layers Download PDF

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Publication number
WO2012107602A1
WO2012107602A1 PCT/ES2011/000371 ES2011000371W WO2012107602A1 WO 2012107602 A1 WO2012107602 A1 WO 2012107602A1 ES 2011000371 W ES2011000371 W ES 2011000371W WO 2012107602 A1 WO2012107602 A1 WO 2012107602A1
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WO
WIPO (PCT)
Prior art keywords
administration
skin
surfactant
phospholipids
component
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PCT/ES2011/000371
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Spanish (es)
French (fr)
Inventor
Oscar Domenech
Carmejo SCIRÉ
Rafael BERNARD
Manuel Ramos
Jordi HERNÁNDEZ-BORRELL
Martha Leticia VÁZQUEZ GONZALEZ
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Labiana Life Sciences, S.A.U.
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Publication date
Priority claimed from ES201100011A external-priority patent/ES2385706B1/en
Priority claimed from ES201101329A external-priority patent/ES2414554B1/en
Application filed by Labiana Life Sciences, S.A.U. filed Critical Labiana Life Sciences, S.A.U.
Publication of WO2012107602A1 publication Critical patent/WO2012107602A1/en

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    • 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
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14—Liposomes; Vesicles
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • 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
    • A61K9/127—Liposomes
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings

Definitions

  • the present invention relates to a form of administration so that the liposomal structures of phospholipids in aqueous suspension are applied to the skin in the form of lamellar structures of phospholipids.
  • the present invention is applicable in the pharmaceutical and cosmetic sectors.
  • Phospholipids are those lipids that contain phosphoric acid. Lipids are understood as a set of organic molecules, generally of biological origin, whose main characteristic is to be hydrophobic. Fats are lipids, but they are not the only type of them.
  • the main constituents of the membranes in epithelial cells consist of phospholipids that adopt a bilayer structure where the lipid (hydrophobic) areas of each layer are facing inside and the polar (hydrophilic) zones of each layer form the corresponding outer surfaces of said bilayer.
  • the lipids that make up the intercellular substance also contain a high percentage of phospholipids.
  • phospholipids of any external composition containing them Due to their chemical affinity, phospholipids of any external composition containing them have exceptional compatibility with epithelial cells.
  • liposomes During the formation of liposomes in aqueous medium, the lipophilic tails of the phospholipids come into contact with each other forming a double layer membrane that is lipophilic in its interior and hydrophilic both in the outer surface and in the inner hollow.
  • the inside of the liposome contains a portion of the aqueous medium in which it was generated.
  • liposomes are mainly used as transporters of various substances between the exterior and interior of the cell. These substances are usually medications or cosmetics. In their functioning, liposomes act as if they were a wrapper of aqueous compositions. This wrapper crosses the cell membrane after which they release their contents inside the cell.
  • liposomes administered in aqueous suspension generally consist of liposomes of different sizes encapsulated within each other: a small liposome enclosed in a larger one and these two, in turn, encapsulated within an even larger one, and so on.
  • the result is usually a multicapsular liposome formed by up to 12 liposomes of different sizes, with 5 to 7 being encapsulated.
  • the size of these multicapsular liposomes varies between 20 and 300 nanometers.
  • the applicant of the present invention is unaware of the existence of a background that satisfactorily solves the problem presented.
  • the present object of the invention relates to a form of phospholipid administration for the formation on the skin of laminar phospholipid layers that avoids the inconveniences that the treatment of the skin with multicapsular liposomes of unequal and uncontrolled contents can cause in the subject .
  • This form of administration consists in the application of two components whose suitable combination destroys liposomes on the skin, transforming them into lamellar layers of natural phospholipids found in the same cell membranes.
  • the aqueous compositions initially transported by the liposomes become in situ vehicles in the laminar phospholipid layers, which thus ensure a uniform distribution and absorption of the drug or cosmetic throughout the treated epithelial area.
  • One of the components comprises a surfactant, and the other component consists of an aqueous phospholipid suspension. containing the compound to be transported.
  • the phospholipids in the second component form the usual liposomes with the usual occlusions and multiencapsulations.
  • the method of administration comprises a sequential application in which the first component with the surfactant is first applied to the skin, forming a deposit on the skin, and then the second component with the aqueous liposome suspension.
  • Liposomes upon contact with the deposit on the skin of the first component, break down and phospholipids adopt the layered bilayer structure of biological membranes.
  • the advantages of this new structure are that the cytoplasms do not assimilate inconvenient amounts of phospholipids and that the diffusion rate, inside the cell, of the substances initially occluded in the liposomes becomes fully controllable.
  • the surfactant is a low molecular weight liquid alcohol.
  • the first component surfactant comprises an aqueous solution of at least one non-ionic surfactant, said non-ionic surfactants being taken from among the alkyl polyglucosides, or from among the ethoxylated fatty alcohols, or from among the esters of sorbitan or polyethylene glycol sorbitan.
  • Sorbitan is the mixture of chemical compounds that results from the dehydration of sorbitol; This mixture may vary, but usually consists of 1,4-anhydrosorbitol, 1,5-anhydrosorbitol and 1,4,3,6-dianhydrosorbitol.
  • esters of sorbitan or polyethylene glycol sorbitan may be one or more esters from the monostearate, the triestearate, the monooleate, or the monolaurate.
  • the main technical advantage obtained by this invention is a significant improvement in the absorption of the vehicular active ingredient when the lipophilic character of said active to vehicular principle reaches a certain notoriety, as in the case of the analgesic known as ibuprofen.
  • Topical application of these two components can be done several times a day, for several days in a row, without any damage to the epithelial tissues.
  • Both the aqueous solution of the non-ionic surfactant, and the liposomal suspension with product to be transported can be applied to the skin in several ways, for example by nebulization or by a carrier support, such as a wipe.
  • a first preferred embodiment comprises that: 5 grams of phosphatidylcholine and 2 grams of ciprofloxacin are placed in a container with 100 milliliters of water. The suspension is stirred at temperatures not exceeding 45 degrees Celsius until the liposomal suspension is satisfactory.
  • a layer of ethanol is nebulized on the skin to be treated as a first component until a thin layer of this alcohol is formed.
  • a part of the liposomal suspension prepared according to the previous paragraph is nebulized on this ethanol layer, as a second component.
  • Ciprofloxacin is transported according to a perfectly uniform surface density.
  • a second preferred embodiment comprises soaking a wipe with a solution containing 0.4 grams of polyoxyethylene sorbitan triestearate, which is the non-ionic surfactant, per 100 milliliters of water. With this wipe rub the area of skin to be treated.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Dispersion Chemistry (AREA)
  • Dermatology (AREA)
  • Birds (AREA)
  • Medicinal Preparation (AREA)
  • Cosmetics (AREA)

Abstract

This form of administration comprises applying, to the skin, a first component that comprises at least one surfactant and then applying a second component consisting in an aqueous suspension of liposomes containing a drug or cosmetic to be conveyed into the epithelial cells.

Description

DESCRIPCIÓN  DESCRIPTION
FORMA DE ADMINISTRACIÓN DE FOSFOLÍPIDOS PARA LA FORMACIÓN SOBRE LA PIEL DE CAPAS LAMINARES DE FOSFOLÍPIDOS. FORM OF ADMINISTRATION OF PHOSPHOLIPIDS FOR TRAINING ON THE SKIN OF LAMINARY LAYERS OF PHOSPHOLIPIDS.
Objeto de la invención Object of the invention
La presente invención se refiere a una forma de administración para que las estructuras liposomales de fosfolípidos en suspensión acuosa sean aplicadas a la piel en forma de estructuras laminares de fosfolípidos.  The present invention relates to a form of administration so that the liposomal structures of phospholipids in aqueous suspension are applied to the skin in the form of lamellar structures of phospholipids.
Campo de aplicación de la invención. Field of application of the invention.
La presente invención es aplicable en los sectores de la farmacia y la cosmética.  The present invention is applicable in the pharmaceutical and cosmetic sectors.
Antecedentes de la invención. Background of the invention.
Los fosfolípidos son aquellos lípidos que contienen ácido fosfórico. Se entiende por lípidos a un conjunto de moléculas orgánicas, generalmente de origen biológico, que tienen por característica principal ser hidrófobas. Las grasas son lípidos, pero no son el único tipo de ellos.  Phospholipids are those lipids that contain phosphoric acid. Lipids are understood as a set of organic molecules, generally of biological origin, whose main characteristic is to be hydrophobic. Fats are lipids, but they are not the only type of them.
Los principales constituyentes de las membranas en las células epiteliales consisten en fosfolípidos que adoptan una estructura en bicapa en donde las zonas lipídicas (hidrófugas) de cada capa están enfrentadas en el interior y las zonas polares (hidrófilas) de cada capa forman las correspondientes superficies extemas de dicha bicapa.  The main constituents of the membranes in epithelial cells consist of phospholipids that adopt a bilayer structure where the lipid (hydrophobic) areas of each layer are facing inside and the polar (hydrophilic) zones of each layer form the corresponding outer surfaces of said bilayer.
Además, los lípidos que componen la sustancia intercelular también contienen un alto porcentaje de fosfolípidos.  In addition, the lipids that make up the intercellular substance also contain a high percentage of phospholipids.
Por su afinidad química, los fosfolípidos de cualquier composición externa que los contenga disponen de una compatibilidad excepcional con las células epiteliales.  Due to their chemical affinity, phospholipids of any external composition containing them have exceptional compatibility with epithelial cells.
Pero la estructura de los fosfolípidos en suspensión acuosa no es laminar. Cuando están en suspensión acuosa forman la estructura esférica hueca conocida como liposoma. But the structure of phospholipids in aqueous suspension does not It is laminar. When they are in aqueous suspension they form the hollow spherical structure known as liposome.
Durante la formación de los liposomas en medio acuoso las colas lipófilas de los fosfolípidos entran en contacto entre ellas formando una membrana de doble capa que es lipófila en su interior e hidrófila tanto en la superficie externa como en la del hueco interior. El interior del liposoma contiene una porción del medio acuoso en el que se generó. Actualmente los liposomas se utilizan principalmente como transportadores de diversas sustancias entre el exterior y el interior de la célula. Estas sustancias son generalmente medicamentos o cosméticos. En su funcionamiento, los liposomas actúan como si fueran un envoltorio de composiciones acuosas. Este envoltorio atraviesa la membrana celular tras lo que liberan su contenido en el interior de la célula.  During the formation of liposomes in aqueous medium, the lipophilic tails of the phospholipids come into contact with each other forming a double layer membrane that is lipophilic in its interior and hydrophilic both in the outer surface and in the inner hollow. The inside of the liposome contains a portion of the aqueous medium in which it was generated. Currently, liposomes are mainly used as transporters of various substances between the exterior and interior of the cell. These substances are usually medications or cosmetics. In their functioning, liposomes act as if they were a wrapper of aqueous compositions. This wrapper crosses the cell membrane after which they release their contents inside the cell.
Pero en la práctica, los liposomas administrados en suspensión acuosa constan generalmente de liposomas de distintos tamaños encapsulados unos dentro de otros: un liposoma pequeño encerrado en otro mayor y estos dos, a su vez, encapsulados dentro de otro todavía mayor, y así sucesivamente. El resultado suele ser un liposoma multicapsular formado por hasta 12 liposomas de diferentes tamaños, siendo lo habitual tener de 5 a 7 encapsulados. El tamaño de estos liposomas multicapsulares varía entre 20 y 300 nanómetros. El resultado práctico cuando se pretende utilizar los liposomas para la administración tópica de un medicamento o de un cosmético es la falta de uniformidad en la absorción por la piel, pues allí donde se absorba un liposoma multicapsular la cantidad de la sustancia vehiculada podría ser considerablemente mayor que allí en donde se absorba un liposoma que no encapsule a otros.  But in practice, liposomes administered in aqueous suspension generally consist of liposomes of different sizes encapsulated within each other: a small liposome enclosed in a larger one and these two, in turn, encapsulated within an even larger one, and so on. The result is usually a multicapsular liposome formed by up to 12 liposomes of different sizes, with 5 to 7 being encapsulated. The size of these multicapsular liposomes varies between 20 and 300 nanometers. The practical result when it is intended to use liposomes for the topical administration of a drug or a cosmetic is the lack of uniformity in skin absorption, since where a multicapsular liposome is absorbed the amount of the vehicle substance could be considerably higher that there where a liposome is absorbed that does not encapsulate others.
La incorporación de los liposomas multicapsulares al citoplasma celular puede resultar en un inconveniente ya que, según sea la heterogeneidad en las encapsulaciones, se llegan a producir efectos negativos por exceso de la cantidad de disolución acuosa original vehiculada por el liposoma multicapsular que ha penetrado en la célula, efectos que pueden resultar por ejemplo en reacciones alérgicas. The incorporation of multicapsular liposomes into the cell cytoplasm can result in an inconvenience since, depending on the heterogeneity in the encapsulations, negative effects occur due to excess of the amount of original aqueous solution carried by the multicapsular liposome that has penetrated the cell, effects that they can result for example in allergic reactions.
En la familia de patentes a la que pertenece el documento de patente española ES2089226T3 se describe la utilización de agentes detergentes iónicos fuertemente bipolares, en concreto sales alcalinas de sulfonatos de alquilo, sales de amonio cuaternario, óxidos de aminas terciarias, o derivados de ácidos fosfóricos, en combinación de liposomas, para su uso en productos de limpieza corporal, en concreto geles de ducha y champúes. No obstante, el uso tópico continuado de agentes fuertemente polarizados acaba provocando alteraciones e irritaciones en las zonas de la piel que se expone repetidamente a ellos, por lo que no es recomendable usar estos productos en humanos con frecuencia superior a la de una vez al día durante tres días seguidos.  In the family of patents to which Spanish patent document ES2089226T3 belongs, the use of strongly bipolar ionic detergent agents is described, in particular alkaline salts of alkyl sulfonates, quaternary ammonium salts, tertiary amine oxides, or phosphoric acid derivatives , in combination of liposomes, for use in body cleansers, specifically shower gels and shampoos. However, the continued topical use of strongly polarized agents ends up causing alterations and irritations in the areas of the skin that is repeatedly exposed to them, so it is not advisable to use these products in humans with a frequency higher than once a day. for three days straight.
El solicitante de la presente invención desconoce la existencia de antecedentes que resuelvan de forma satisfactoria la problemática expuesta.  The applicant of the present invention is unaware of the existence of a background that satisfactorily solves the problem presented.
Descripción de la invención Description of the invention
El presente objeto de invención se refiere a una forma de administración de fosfolípidos para la formación sobre la piel de capas laminares de fosfolípidos que evita los inconvenientes que el tratamiento de la piel con liposomas multicapsulares de contenidos desiguales e incontrolados puede llegar a causar en el sujeto. Esta forma de administración consiste en la aplicación de dos componentes cuya adecuada combinación destruye sobre la piel los liposomas, transformándolos en capas laminares de fosfolípidos del tipo natural que se encuentra en las mismas membranas celulares. Las composiciones acuosas vehiculadas inicialmente por los liposomas pasan a estar vehiculadas ¡n situ por las capas fosfolipídicas laminares, las que aseguran así una distribución y absorción uniforme del medicamento o cosmético por toda la zona epitelial tratada.  The present object of the invention relates to a form of phospholipid administration for the formation on the skin of laminar phospholipid layers that avoids the inconveniences that the treatment of the skin with multicapsular liposomes of unequal and uncontrolled contents can cause in the subject . This form of administration consists in the application of two components whose suitable combination destroys liposomes on the skin, transforming them into lamellar layers of natural phospholipids found in the same cell membranes. The aqueous compositions initially transported by the liposomes become in situ vehicles in the laminar phospholipid layers, which thus ensure a uniform distribution and absorption of the drug or cosmetic throughout the treated epithelial area.
Uno de los componentes comprende un agente tensioactivo, y el otro componente consiste en una suspensión acuosa de fosfolípidos conteniendo el compuesto a ser vehiculado. Los fosfolípidos en el segundo componente forman los habituales liposomas con las habituales oclusiones y multiencapsulaciones. One of the components comprises a surfactant, and the other component consists of an aqueous phospholipid suspension. containing the compound to be transported. The phospholipids in the second component form the usual liposomes with the usual occlusions and multiencapsulations.
De acuerdo con la invención, la forma de administración comprende una aplicación secuencial en la que primero se aplica sobre la piel el primer componente con el agente tensioactivo, formando un depósito sobre la piel, y a continuación el segundo componente con la suspensión acuosa de liposomas. Los liposomas, al tomar contacto con el depósito sobre la piel del primer componente, se deshacen y los fosfolípidos adoptan la estructura bicapa laminar de las membranas biológicas. Las ventajas de esta nueva estructura consisten en que los citoplasmas no asimilan cantidades inconvenientes de fosfolípidos y que la velocidad de difusión, al interior de la célula, de las sustancias inicialmente ocluidas en los liposomas se hace totalmente controlable.  According to the invention, the method of administration comprises a sequential application in which the first component with the surfactant is first applied to the skin, forming a deposit on the skin, and then the second component with the aqueous liposome suspension. Liposomes, upon contact with the deposit on the skin of the first component, break down and phospholipids adopt the layered bilayer structure of biological membranes. The advantages of this new structure are that the cytoplasms do not assimilate inconvenient amounts of phospholipids and that the diffusion rate, inside the cell, of the substances initially occluded in the liposomes becomes fully controllable.
En una primera realización el agente tensioactivo es un alcohol líquido de bajo peso molecular.  In a first embodiment the surfactant is a low molecular weight liquid alcohol.
En una segunda realización el agente tensioactivo del primer componente, comprende una disolución acuosa de al menos un agente tensioactivo no iónico, siendo dichos agentes tensioactivos no iónicos tomados de entre los alquilpoliglucósidos, o de entre los alcoholes grasos etoxilados, o de entre los ésteres de sorbitano o de polietilenglicolsorbitano.  In a second embodiment the first component surfactant comprises an aqueous solution of at least one non-ionic surfactant, said non-ionic surfactants being taken from among the alkyl polyglucosides, or from among the ethoxylated fatty alcohols, or from among the esters of sorbitan or polyethylene glycol sorbitan.
El sorbitano es la mezcla de compuestos químicos que resulta de la deshidratación del sorbitol; esta mezcla puede variar, pero usualmente consta de 1 ,4-anhidrosorbitol, 1 ,5-anhidrosorbitol y 1 ,4,3,6-dianhidrosorbitol.  Sorbitan is the mixture of chemical compounds that results from the dehydration of sorbitol; This mixture may vary, but usually consists of 1,4-anhydrosorbitol, 1,5-anhydrosorbitol and 1,4,3,6-dianhydrosorbitol.
Los ésteres de sorbitano o de polietilenglicolsorbitano pueden ser uno o varios ésteres de entre el monoestearato, el triestearato, el monooleato, o el monolaurato.  The esters of sorbitan or polyethylene glycol sorbitan may be one or more esters from the monostearate, the triestearate, the monooleate, or the monolaurate.
La principal ventaja técnica obtenida por esta invención, es una significativa mejora en la absorción del principio activo vehiculado cuando el carácter lipófilo de dicho principio activo a vehicular alcanza una cierta notoriedad, como en el caso del analgésico conocido como ibuprofeno. La aplicación tópica de estos dos componentes puede hacerse varias veces al día, durante varios días seguidos, sin que se observe daño alguno en los tejidos epiteliales. The main technical advantage obtained by this invention is a significant improvement in the absorption of the vehicular active ingredient when the lipophilic character of said active to vehicular principle reaches a certain notoriety, as in the case of the analgesic known as ibuprofen. Topical application of these two components can be done several times a day, for several days in a row, without any damage to the epithelial tissues.
Tanto la disolución acuosa del agente tensioactivo no iónico, como la suspensión liposomal con producto a vehicular se puede aplicar sobre la piel de varias maneras, por ejemplo mediante nebulización o bien mediante un soporte portador, como por ejemplo una toallita.  Both the aqueous solution of the non-ionic surfactant, and the liposomal suspension with product to be transported can be applied to the skin in several ways, for example by nebulization or by a carrier support, such as a wipe.
Realización preferente de la invención Preferred Embodiment of the Invention
Una primera realización preferente comprende que: en un recipiente con 100 mililitros de agua se colocan 5 gramos de fosfatidilcolina y 2 gramos de ciprofloxacino. La suspensión se agita a temperaturas no superiores a 45 grados centígrados hasta que la suspensión liposomal es satisfactoria.  A first preferred embodiment comprises that: 5 grams of phosphatidylcholine and 2 grams of ciprofloxacin are placed in a container with 100 milliliters of water. The suspension is stirred at temperatures not exceeding 45 degrees Celsius until the liposomal suspension is satisfactory.
Sobre la piel a tratar se nebuliza como primer componente una capa de etanol hasta formar una delgada capa de este alcohol. Sobre esta capa de etanol se nebuliza una parte de la suspensión liposomal preparada según el párrafo anterior, a modo de segundo componente.  A layer of ethanol is nebulized on the skin to be treated as a first component until a thin layer of this alcohol is formed. A part of the liposomal suspension prepared according to the previous paragraph is nebulized on this ethanol layer, as a second component.
Mediante microscopía de fuerza atómica, que es la única que puede trabajar a alta resolución en condiciones de temperatura y pH adecuados para los lípidos sin pasar previamente por una fase de secado, se constata que sobre la piel los liposomas han desaparecido y que la fosfatidilcolina ha adoptado una estructura de capas laminares. El ciprofloxacino es vehiculado según una densidad superficial perfectamente uniforme.  By means of atomic force microscopy, which is the only one that can work at high resolution under suitable temperature and pH conditions for lipids without previously passing through a drying phase, it is verified that on the skin the liposomes have disappeared and that phosphatidylcholine has Adopted a layered structure. Ciprofloxacin is transported according to a perfectly uniform surface density.
Una segunda realización preferente comprende que se empape una toallita con una disolución que contiene 0,4 gramos del triestearato de polioxietilensorbitano, que es el agente tensioactivo no iónico, por cada 100 mililitros de agua. Con esta toallita se frota la zona de la piel a tratar.  A second preferred embodiment comprises soaking a wipe with a solution containing 0.4 grams of polyoxyethylene sorbitan triestearate, which is the non-ionic surfactant, per 100 milliliters of water. With this wipe rub the area of skin to be treated.
Sobre la zona de la piel que ha recibido el agente tensioactivo no iónico se nebuliza una suspensión acuosa de 5 gramos de ibuprofeno y 5 gramos de fosfatidilcolina, preparada, agitando hasta satisfacción, a temperaturas no superiores a 45 grados centígrados. An aqueous suspension of 5 grams of ibuprofen and 5 grams is sprayed on the area of the skin that has received the non-ionic surfactant grams of phosphatidylcholine, prepared, stirring to satisfaction, at temperatures not exceeding 45 degrees Celsius.
Mediante microscopía de fuerza atómica, se constata que sobre la piel los liposomas han desaparecido y que la fosfatidilcolina ha adoptado una estructura de capas laminares. El ibuprofeno es vehiculado en una densidad superficial perfectamente uniforme.  By means of atomic force microscopy, it is verified that on the skin the liposomes have disappeared and that the phosphatidylcholine has adopted a layered structure. Ibuprofen is transported in a perfectly uniform surface density.
Una vez descrita suficientemente la naturaleza de la invención, así como unos ejemplos de realización preferente, se hace constar a los efectos oportunos que los materiales de los elementos descritos podrán ser modificados, siempre y cuando ello no suponga una alteración de las características esenciales de la invención que se reivindican a continuación.  Once the nature of the invention has been sufficiently described, as well as some examples of preferred embodiment, it is stated for the appropriate purposes that the materials of the described elements may be modified, provided that this does not imply an alteration of the essential characteristics of the invention claimed below.

Claims

REIVINDICACIONES
1.- Forma de administración de fosfolípidos para la formación sobre la piel de capas laminares de fosfolípidos caracterizada porque comprende la aplicación sobre la piel de un primer componente consistente en un agente tensioactivo y a continuación la aplicación de un segundo componente consistente en una suspensión acuosa de liposomas conteniendo un medicamento o un cosmético a ser vehiculado al interior de las células epiteliales. 1.- Form of administration of phospholipids for the formation on the skin of layered phospholipid layers characterized in that it comprises the application on the skin of a first component consisting of a surfactant and then the application of a second component consisting of an aqueous suspension of Liposomes containing a medication or a cosmetic to be transported inside the epithelial cells.
2.- Forma de administración, según la reivindicación 1 , caracterizada porque el agente tensioactivo del primer componente es un alcohol líquido de bajo peso molecular. 2. Administration form according to claim 1, characterized in that the first component surfactant is a low molecular weight liquid alcohol.
3. - Forma de administración, según la reivindicación 1 , caracterizada porque el agente tensioactivo del primer componente es una disolución acuosa de al menos un agente tensioactivo no iónico. 3. - Method of administration, according to claim 1, characterized in that the first component surfactant is an aqueous solution of at least one non-ionic surfactant.
4. - Forma de administración según la reivindicación 3, caracterizada porque el agente tensioactivo no iónico está tomado de entre los alquilpoliglucósidos, o de entre los alcoholes grasos etoxilados, o de entre los ésteres de sorbitano o de polietilenglicolsorbitano. 4. - Method of administration according to claim 3, characterized in that the non-ionic surfactant is taken from among the alkyl polyglycosides, or from among the ethoxylated fatty alcohols, or from among the esters of sorbitan or polyethylene glycol sorbitan.
5. - Forma de administración según la reivindicación 4, caracterizada porque los ésteres de sorbitano o de polietilenglicolsorbitano pueden ser uno o varios ésteres de entre el monoestearato, el triestearato, el monooleato, o el monolaurato. 5. - Method of administration according to claim 4, characterized in that the sorbitan or polyethylene glycol sorbitan esters can be one or more esters from the monostearate, the triestearate, the monooleate, or the monolaurate.
6. - Forma de administración, según cualquiera de las reivindicaciones 3 a 5 caracterizada porque tanto la disolución acuosa del componente tensioactivo, como la suspensión liposomal con producto a vehicular se aplican sobre la piel mediante nebulización o bien mediante un soporte portador. 6. - Method of administration, according to any of claims 3 to 5, characterized in that both the aqueous solution of the surfactant component and the liposomal suspension with product to be applied are applied to the skin by nebulization or by a carrier support.
PCT/ES2011/000371 2010-12-30 2011-12-23 Form of administration of phospholipids for the formation on the skin of laminar phospholipid layers WO2012107602A1 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
ESP201100011 2010-12-30
ES201100011A ES2385706B1 (en) 2010-12-30 2010-12-30 FORM OF ADMINISTRATION OF PHOSPHOLIPIDS FOR TRAINING ON THE SKIN OF LAMINARY LAYERS OF PHOSPHOLIPIDS.
ESP201101329 2011-12-19
ES201101329A ES2414554B1 (en) 2011-12-19 2011-12-19 FORM OF ADMINISTRATION OF PHOSPHOLIPIDS FOR TRAINING ON THE SKIN OF LAMINARY LAYERS OF PHOSPHOLIPIDS, IMPROVED

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991004731A1 (en) * 1989-09-21 1991-04-18 Micro Vesicular Systems, Inc. Liposomal cleaner
US5164320A (en) * 1990-03-05 1992-11-17 Becton, Dickinson And Company Method for lysing hard liposomes using polyethyleneglycol mono-n-alkyl ethers
EP0524788A1 (en) * 1991-07-23 1993-01-27 Wako Pure Chemical Industries Ltd Process for lysing liposome membrane
US5366895A (en) * 1990-03-05 1994-11-22 Becton, Dickinson And Company Method for lysing liposomes using polyethyleneglycol monononylphenyl ethers
US6183451B1 (en) * 1991-05-30 2001-02-06 Thomas L. Mehl, Sr. Method of delivery of skin treatment agents using freeze-dried liposomes

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991004731A1 (en) * 1989-09-21 1991-04-18 Micro Vesicular Systems, Inc. Liposomal cleaner
US5164320A (en) * 1990-03-05 1992-11-17 Becton, Dickinson And Company Method for lysing hard liposomes using polyethyleneglycol mono-n-alkyl ethers
US5366895A (en) * 1990-03-05 1994-11-22 Becton, Dickinson And Company Method for lysing liposomes using polyethyleneglycol monononylphenyl ethers
US6183451B1 (en) * 1991-05-30 2001-02-06 Thomas L. Mehl, Sr. Method of delivery of skin treatment agents using freeze-dried liposomes
EP0524788A1 (en) * 1991-07-23 1993-01-27 Wako Pure Chemical Industries Ltd Process for lysing liposome membrane

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