ES2695931T3 - Composiciones y métodos para estimular el crecimiento del pelo - Google Patents
Composiciones y métodos para estimular el crecimiento del pelo Download PDFInfo
- Publication number
- ES2695931T3 ES2695931T3 ES10776512T ES10776512T ES2695931T3 ES 2695931 T3 ES2695931 T3 ES 2695931T3 ES 10776512 T ES10776512 T ES 10776512T ES 10776512 T ES10776512 T ES 10776512T ES 2695931 T3 ES2695931 T3 ES 2695931T3
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- ES
- Spain
- Prior art keywords
- composition
- hair
- weight
- alopecia
- bimatoprost
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Abstract
Una composición adecuada para hacer crecer el pelo mediante aplicación tópica, comprendiendo la composición bimatoprost y uno o más potenciadores de la penetración, en donde la composición comprende monooleato de glicerol como un potenciador de la penetración.
Description
DESCRIPCION
Composiciones y metodos para estimular el crecimiento del pelo
Campo de la invencion
La presente invencion se refiere a composiciones para estimular el crecimiento del pelo. Las composiciones pueden utilizarse para tratar trastornos que implican la perdida del pelo.
Antecedentes de la invencion
Los dermatologos reconocen muchos tipos diferentes de perdida de pelo, siendo el mas comun la “ alopecia” o “ calvicie” , en donde las personas (principalmente los hombres) comienzan a perder el pelo del cuero cabelludo en las sienes y en la coronilla. Sin embargo, la perdida del pelo puede deberse a muchos otros trastornos.
La perdida del pelo esta acompanada frecuentemente de un cambio en el ciclo de crecimiento del pelo. Todo el pelo de los mairnferos pasa por un ciclo de vida que incluye la fase anagena, la fase catagena y la fase telogena. La fase anagena es el periodo de crecimiento activo del pelo. En el cuero cabelludo, esta fase dura de 3 a 5 anos. La fase catagena es una fase de transicion corta de 1-2 semanas entre la fase anagena y la fase telogena. La fase telogena final se considera una “ fase de reposo” donde cesa todo el crecimiento. Esta fase es tambien relativamente corta, que dura aproximadamente 3-4 meses antes de que el pelo se caiga y otro pelo nuevo comience a crecer. Con la presentacion de la calvicie, una parte cada vez mayor del pelo esta en la fase telogena con un numero en consecuencia menor en fase anagena de crecimiento activo.
Ademas, existen diferentes tipos de pelo, incluido los vellos terminales, vello corporal y vello terminal modificado. Los vellos terminales son pelos gruesos, pigmentados y largos, en los que el bulbo del folfculo piloso esta profundamente asentado en la dermis. Por otra parte, el vello corporal esta constituido por pelos finos, delgados, no pigmentados y cortos, en los que el bulbo piloso esta situado superficialmente en la dermis. El vello terminal modificado se ve en las pestanas y en las cejas. A medida que avanza la alopecia, se produce una transicion en donde los pelos pasan de ser de tipo terminal a tipo vello. Por tanto, la alopecia (calvicie) tambien incluye una deficiencia de vello terminal.
Un tratamiento no medicamentoso para la alopecia es el trasplante de pelo. Los tapones de piel que contienen pelo se trasplantan desde areas del cuero cabelludo en donde crece el pelo a areas de calvicie. Este enfoque puede ser razonablemente exitoso; sin embargo, es caro, consume mucho tiempo y es doloroso. Otros enfoques relacionados no medicamentosos para tratar la alopecia incluyen radiacion ultravioleta, masaje, tratamiento psiquiatrico y terapia con ejercicio. Ninguno de estos metodos, sin embargo, han sido generalmente aceptados como eficaces. Incluso cosas tales como la cirugfa de revascularizacion o la acupuntura han demostrado una eficacia que, si la tienen, es reducida.
La solicitud US 2008/0070988 A1 describe una composicion para el crecimiento del pelo que comprende bimatoprost y alcohol absoluto, y describe composiciones que comprenden bimatoprost y propilenglicol.
Sumario de la invencion
Un aspecto de la presente invencion es una composicion adecuada para hacer crecer el pelo mediante aplicacion topica, comprendiendo la composicion bimatoprost y uno o mas potenciadores de la penetracion, en donde la composicion comprende monooleato de glicerol como un potenciador de la penetracion.
En una realizacion, el bimatoprost esta contenido en la composicion a una concentracion de aproximadamente 0,001 -1,5 % en peso, de 0,01 - 1,0 % en peso, 0,02 - 1,0 % en peso, 0,03 a aproximadamente 1,0 % en peso, 0,03 - 0,9 % en peso, 0,04 - 0,8 % en peso, 0,05 - 0,7 % en peso, 0,06 % - 0,6 % en peso, 0,07 % - 0,5 % en peso, 0,08 - 0,4 % en peso, 0,09 - 0,3 % en peso, 0,1 % en peso, 0,2 % en peso, 0,3 % en peso, 0,4 % en peso, 0,5 % en peso, 0,6 % en peso, 0,7% en peso, 0,8% en peso, 0,9% en peso o 1,0% en peso. Los siguientes excipientes tambien pueden incluirse: Carbomero a una concentracion de aproximadamente 0,05 - 1,0% en peso; base a una concentracion de aproximadamente 0,01 a aproximadamente 2,0% en peso; etanol a una concentracion de aproximadamente 10 a aproximadamente 90 % en peso; glicerina a una concentracion de aproximadamente 1,0 a aproximadamente 20 % en peso; eter monoetilico de dietilenglicol a una concentracion de aproximadamente 1,0 a aproximadamente 50% en peso; polisorbato 20 a una concentracion de aproximadamente 0,1 a aproximadamente 5,0 % en peso; polisorbato 40 a una concentracion de aproximadamente 0,1 a aproximadamente 5,0 % en peso; polisorbato 60 a una concentracion de aproximadamente 0,1 a aproximadamente 5,0 % en peso; polisorbato 80 a una concentracion de aproximadamente 0,1 a aproximadamente 5,0% en peso; PPG-5 ceteth-20 a una concentracion de aproximadamente 0,1 a aproximadamente 5,0 % en peso; acido oleico a una concentracion de aproximadamente 0,1 a aproximadamente 5,0 % en peso; isostearato de isoestearilo a una concentracion de aproximadamente 0,1 a aproximadamente 10 % en peso; miristato de isopropilo a una concentracion de aproximadamente 0,1 a aproximadamente 10 % en peso; dimetileter de dipropilenglicol a una concentracion de aproximadamente 1 a aproximadamente 50 % en peso; dietilenglicol a una concentracion de aproximadamente 1 a aproximadamente 50 % en peso; dipropilenglicol a una concentracion de aproximadamente 1 a aproximadamente 50 % en peso; capnlico/caprico a una concentracion de aproximadamente 0,1
a aproximadamente 10 % en peso; alcohol bendlico a una concentracion de aproximadamente 0,1 a aproximadamente 2,0 % en peso; silicona a una concentracion de aproximadamente 0,1 a aproximadamente 10 % en peso; y/o agua a una concentracion de aproximadamente 0 a aproximadamente 90 % en peso.
La composicion puede fabricarse utilizando un procedimiento general en el cual los componentes no acuosos (p. ej., bimatoprost, etanol, glicoles) se combinan en un vaso de precipitados y se agitan utilizando un mezclador colgante de tipo propulsor hasta que la solucion queda transparente, se anade agua a la mezcla no acuosa seguido de la adicion de un agente espesante polimerico, y tras la dispersion del agente espesante, se anade una base para neutralizar el polfmero y espesar la solucion para obtener un gel otra composicion deseada.
Otro aspecto de la invencion es una composicion como se ha definido anteriormente para utilizar en un metodo terapeutico de tratamiento de un trastorno de perdida de pelo en un mairnfero mediante la administracion topica de la composicion.
Otro aspecto adicional de la invencion es un metodo no terapeutico para estimular el crecimiento del pelo en un marnffero, comprendiendo el metodo la aplicacion topica de una composicion como se ha definido anteriormente.
Descripcion detallada
El bimatoprost es un compuesto moderadamente soluble previsto para la administracion topica a la piel para estimular el crecimiento del pelo. El crecimiento del pelo incluye, aunque no de forma limitativa, estimular la conversion del vello de tipo corporal de modo que crezca como vello terminal, asf como aumentar la velocidad de crecimiento del vello terminal. La composicion de la invencion comprende bimatoprost y uno o mas potenciadores de la penetracion que incluyen monooleato de glicerol. Los potenciadores de la penetracion facilitan la penetracion y/o mantenimiento del componente activo en el lugar de accion en la piel. Las formulaciones descritas en la presente memoria pueden ser autoconservadas o contener un agente antimicrobiano tal como alcohol bendlico.
El compuesto activo es ciclopentano N-etil heptanamida-5-cis-2- (3a-hidroxi-5-fenil-1-trans-pentenil)-3,5-dihidroxi, [1a,2p,3a,5a], tambien conocido como bimatoprost y comercializado con el nombre de LUMIGAN® por Allergan, Inc., California, EE. UU. Este compuesto tiene la siguiente estructura:
La smtesis del compuesto anterior se ha descrito en la solicitud US-5.607.978.
El experto en la tecnica puede determinar cantidades eficaces de bimatoprost, pero variaran dependiendo de la frecuencia de aplicacion y el resultado deseado. La cantidad estara generalmente en el intervalo de aproximadamente 1 x 10-7 a aproximadamente 50% en peso de la composicion, en una realizacion de aproximadamente 0,001 a aproximadamente 50 % en peso de la composicion y en otra realizacion de aproximadamente 0,1 a aproximadamente 30% en peso de la composicion. Tambien se incluyen los intervalos de aproximadamente 10-50% en peso, aproximadamente 20-50 % en peso y aproximadamente 30-40 % en peso, y una cantidad de aproximadamente 35 %.
Las formulaciones farmaceuticas descritas en la presente memoria incluyen uno o mas potenciadores de la penetracion. La frase “ potenciadores de la penetracion” incluye cualquier agente que facilite la transferencia de componentes activos a su sitio de accion o los mantenga en su sitio de accion. Ejemplos no limitativos de clases de promotores de la penetracion apropiados incluyen alcoholes, glicoles, acidos grasos, eteres, esteres, agentes oclusivos y agentes tensioactivos. A continuacion se proporcionan ejemplos representativos de estas clases.
Los alcoholes incluyen, de forma no limitativa, etanol, propanol, N-propanol, isopropanol, alcohol butflico, octanol, alcohol bendlico y alcohol acetflico, en una realizacion, como se describe en la solicitud US-5.789.244. Los alcoholes grasos incluyen, por ejemplo, alcohol esteanlico y alcohol oleflico.
Los glicoles incluyen, de forma no limitativa, glicerina, propilenglicol, polietilenglicol y otros glicoles de bajo peso molecular tales como glicerol y tioglicerol.
Los acidos grasos, esteres y eteres incluyen, ademas del monooleato de glicerol, acido oleico, acido palmitoleico, acidos monocarboxflicos y dicarboxflicos C4-C20 de cadena lineal, acido octanoico y acido decanoico, laurato de metilo, oleato de etilo, monolaurato de polietileno, monolaurato de propilenglicol, dilaurato de propilenglicerol, monolaurato de glicerol, ndecanoato de isopropilo, miristato de octildodecilo, eter monoetilico de dietilenglicol, eter monometflico de dietilenglicol y compuestos en donde un alcanodiol o alcanotriol C2-C4 esta sustituido con uno o dos sustituyentes de tipo eter graso.
Los agentes oclusivos incluyen, de forma no limitativa, siliconas, aceites minerales y grasas, acidos de cadena larga, grasas duras y blandas animales, grasas duras y blandas vegetales, polfmeros insolubles en agua, parafina, aceite de parafina, parafina lfquida, petrolato, petrolato lfquido, petrolato blanco, petrolato amarillo, cera microcristalina y ceresina.
Los agentes tensioactivos incluyen, de forma no limitativa, polisorbato 20, 40, 60 y 80, TWEEN® (20, 40, 60, 80), POLOXAMER® (231, 182, 184), dodecilsulfato sodico (SDS), lecitina, lisolecitina, nonilfenoxipolioxietileno, lisofosfatidilcolina, polietilenglicol 400, eteres de polioxietileno, tensioactivos de poliglicol eter, DMSO, laurato de sodio, laurilsulfato de sodio, bromuro de cetiltrimetilamonio y cloruro de benzalconio.
Los potenciadores de la penetracion adicionales seran conocidos por los expertos en la tecnica de suministro topico de farmacos y/o se describen en los textos y la literatura pertinentes.
Las realizaciones descritas en la presente memoria tambien pueden incluir agentes de aumento de la viscosidad. Los agentes apropiados incluyen, de forma no limitativa, metilcelulosa, alcohol polivimlico, polivinilpirrolidona, acido hialuronico y sulfato de condroitina.
Determinadas realizaciones descritas en la presente memoria pueden incluir conservantes, incluidos, de forma no limitativa, alcohol bendlico, cloruro de benzalconio, clorhexidina, clorobutanol, acidos metilparahidroxibenzoico, propilparahidroxibenzoico o butilparahidroxibenzoico, sales fenilmercuricas, incluidos, de forma no limitativa, nitrato, cloruro, acetato, y borato, y betama.
Pueden incluirse diversos aditivos diferentes en las composiciones de la presente invencion ademas de los arriba identificados. Estos incluyen, aunque no de forma limitativa, agentes antioxidantes, astringentes, perfumes, emolientes, pigmentos, colorantes, humectantes, propelentes, y agentes de filtro solar, asf como otras clases de materiales cuya presencia puede ser deseable desde el punto de vista cosmetico, terapeutico u otro. Las composiciones y formulaciones tambien pueden tomarse junto con minoxidil y propecia.
Las composiciones tambien pueden formularse como formulaciones “ de liberacion lenta” de modo que la actividad de los componentes activos se mantiene durante un penodo de tiempo mas largo entre tratamientos.
Si bien las realizaciones particulares descritas en la presente memoria pueden incluir cada uno de los componentes descritos anteriormente, puede requerirse que otras realizaciones particulares esten “ practicamente exentas” de uno o mas de estos componentes en diversas combinaciones. “ Sustancialmente exento” , en la presente memoria, significa que el componente no se anade a una formulacion y no puede estar presente en cualquier cantidad superior a aproximadamente 1 % en peso.
Aunque no limitan el alcance de la exclusion expresa del parrafo anterior, las realizaciones particulares descritas en la presente memoria pueden estar sustancialmente exentas de uno o mas de bimatoprost, carbomero, NaOH (s), t Ea , etanol, glicerina, dietilenglicol, eter monoetflico, propilenglicol, polisorbato 20, polisorbato 40, polisorbato 60, polisorbato 80, PPG-5 ceteth-20, acido oleico, isoestearato de isoestearilo, miristato de isopropilo, dimetileter de dipropilenglicol, dietilenglicol, dipropilenglicol, trigliceridos, capnlico/caprico, alcohol bendlico, silicona y agua.
Todos los componentes de las formulaciones descritas en la presente memoria se incluiran en cantidades dermatologicamente aceptables. Como se utiliza en la presente memoria, “ dermatologicamente aceptable” significa que las composiciones o componentes de las mismas son adecuadas para estar en contacto con la piel humana sin una toxicidad, incompatibilidad, inestabilidad, reaccion alergica, y similares indebidas. Como se utiliza en la presente memoria, cuando se aplica a agentes activos y excipientes, el termino “ aproximadamente” se refiere a variaciones en concentraciones que se consideran bioequivalentes.
Las realizaciones descritas en la presente memoria son de aplicacion en especies de mairnferos, incluidos tanto los humanos como los animales. En los humanos, los compuestos de las realizaciones descritas en la presente memoria pueden aplicarse, de forma no limitativa, al cuero cabelludo, rostro, barba, cabeza, area pubica, labio superior, cejas y parpados. Las composiciones de las presentes invenciones pueden utilizarse para tratar diversos trastornos de perdida del pelo incluidos, aunque no de forma limitativa, alopecia areata, efluvio telogenico, efluvio anagenico, alopecia cicatricial y alopecia de cicatriz; anomalfas del tallo piloso tales como trichorrexis nudosa, smdrome anagenico suelto, tricotilomama y alopecia de traccion; trastornos infecciosos del pelo, tales como tinea capitis, dermatitis seborreica, y foliculitis del cuero cabelludo; trastornos geneticos tales como la alopecia androgenetica y pacientes que experimentan perdida de pelo debido a quimioterapia, desequilibrio hormonal (p. ej., trastornos del tiroides, tales como hipotiroidismo e hipertiroidismo, embarazo, parto, interrupcion de pfldoras anticonceptivas o cambios en el ciclo menstrual), infeccion fungica del cuero cabelludo, tal como empeine, medicamentos que ocasionan perdida de pelo, tales como anticoagulantes, medicamentos para la gota, depresion, presion arterial alta y determinados medicamentos para el corazon. Las formulaciones de la presente invencion pueden utilizarse para tratar la perdida del pelo relacionada con otras enfermedades, tales como la diabetes, el lupus, y nutricion deficiente, estres mental y ffsico, tal como el debido a
cirugfa, enfermedad y fiebre elevada. La perdida del pelo puede deberse a factores ambientales y sustancias qmmicas utilizadas en el tratamiento del pelo (coloracion, tenido y decoloracion).
En animales criados por sus pieles, p. ej., el vison, las formulaciones pueden aplicarse en toda la superficie del cuerpo para mejorar el conjunto de la piel por razones comerciales. El proceso puede utilizarse tambien para fines cosmeticos en animales, p. ej., aplicado a la piel de perros y gatos que tienen zonas de calvicie debidas a la sarna u otras enfermedades que causan un determinado grado de alopecia.
Las composiciones y metodos de la presente invencion pueden aplicarse a los pacientes que padecen de perdida de pelo o en pacientes sanos simplemente para aumentar el crecimiento del pelo en cualquier parte del cuerpo.
Las composiciones descritas en la presente memoria se formulan para la administracion topica. El termino “ administracion topica” , como se utiliza en la presente memoria, incluye la aplicacion de una formulacion como se describe en la presente memoria al pelo o piel exterior. La aplicacion generalmente tendra lugar en o cerca del area de crecimiento de pelo deseado.
Por tanto, los tipos apropiados de formulacion o composicion incluyen, de forma no limitativa, soluciones, geles, unguentos, espumas, pelfculas, linimentos, cremas, champus, lociones, pastas, gelatinas, pulverizaciones y aerosoles. Tales tipos de formulacion pueden aplicarse en tiras, parches, aplicadores o mediante el uso de apositos impregnados en funcion de la situacion y parte del cuerpo a tratar.
De forma tfpica, las formulaciones descritas en la presente memoria se aplicaran repetidas veces durante un penodo de tiempo constante a la parte del cuerpo a tratar. En realizaciones particulares, las formulaciones descritas en la presente memoria pueden incluir una o mas aplicaciones diarias, una o mas aplicaciones semanales, una o mas aplicaciones mensuales o una o mas aplicaciones anuales durante el tratamiento de al menos un dfa, al menos una semana, al menos un mes, al menos un ano o hasta que el tratamiento haya alcanzado o alcanzado y mantenido un resultado deseado.
Las formulaciones descritas en la presente memoria se administraran en cantidades seguras y eficaces. Como se utiliza en la presente memoria, “ cantidades seguras y eficaces” incluyen una cantidad suficiente para que la composicion proporcione el efecto de estimulacion del crecimiento del pelo deseado con una relacion de ventaja/riesgo razonable presente con cualquier tratamiento medico. Dentro del alcance del juicio medico razonable, la cantidad de componentes activos utilizados puede variar en funcion de la afeccion concreta tratada, la gravedad de la afeccion, la duracion del tratamiento, el componente activo espedfico empleado, su concentracion, el vehfculo espedfico utilizado, la salud general del paciente, la tolerancia del paciente a diversos efectos de la administracion, otros farmacos que se administran al paciente, y factores similares dentro del conocimiento y experiencia espedficos del paciente o el medico que lo atienda.
Para la administracion diaria, una dosis apropiada puede incluir, de forma no limitativa, de aproximadamente 0,1 ng a aproximadamente 100 mg, de aproximadamente 1 ng a aproximadamente 10 mg por dfa o en otra realizacion de aproximadamente 10 ng a aproximadamente 1 mg por dfa.
Ejemplos no limitativos de algunos componentes con sus intervalos de concentracion apropiados y funcion se proporcionan a continuacion en la tabla 1.
Tabla 1: Componentes ilustrativos con funcion e intervalos de concentracion
Ejemplos de referencia
Ejemplo I.
Preparaciones de composiciones de gel bimatoprost para el crecimiento del pelo del cuero cabelludo
El alcohol etflico se pesa en un frasco de medio adecuado equipado para mezclar y se anade a continuacion bimatoprost al alcohol etilico y se agita a velocidad moderada hasta que se disuelve el bimatoprost. A un tanque de mezclado aparte, se anade agua para inyeccion, glicerina, eter monoetflico de dietilenglicol, y propilenglicol y se mezcla hasta dispersar los disolventes. La solucion de alcohol etilico/bimatoprost se anade a continuacion a la mezcla de agua y se mezcla hasta que los componentes se mezclan homogeneamente (aproximadamente 5 minutos de mezclado). A la mezcla se anade el espesante de carbomero y se mezcla hasta que este bien dispersado. Una vez dispersado se anade una base para espesar la solucion formando un gel. Las formulaciones representativas elaboradas segun el metodo anterior se muestran a continuacion en la tabla 2.
Tabla 2: Formulaciones de gel bimatoprost topico para el crecimiento del pelo del cuero cabelludo
Ejemplo II.
Tratamiento in vivo
Se inicia un estudio para evaluar sistematicamente el aspecto del pelo en el cuero cabelludo y las cejas administrado con formulaciones de gel bimatoprost de la tabla 2. En el estudio participan 10 sujetos, 5 varones, 5 mujeres, de edad media 70 anos (en el intervalo de 50-94 anos). Cada sujeto se trata diariamente mediante la aplicacion topica de bimatoprost con la formulacion de bimatoprost de 0,3 % en peso de la tabla 2.
El estudio se limita a individuos a los que se ha administrado bimatoprost durante mas de 3 meses. La duracion media de exposicion a la formulacion de gel bimatoprost al 0,3 % en peso antes de evaluar el parametro del crecimiento del cabello o las cejas entre el control y el ojo de estudio es de 129 dfas (intervalo de 90-254 dfas). Las observaciones se realizan con un gran aumento con un biomicroscopio de lampara de hendidura. La documentacion de las diferencias entre el control y las zonas de tratamiento se realiza utilizando una camara especialmente adaptada para utilizar con un biomicroscopio de lampara de hendidura.
Los resultados de las observaciones seran los siguientes:
Longitud del pelo y las cejas: Se observa de forma homogenea un aumento de la longitud del pelo en ambos grupos. La diferencia en longitud vana de aproximadamente 10 % hasta 30 %.
Numero de pelos: Se observa una mayor cantidad de pelos en el cuero cabelludo y las cejas de cada paciente. La diferencia en el numero de pelos vana de aproximadamente 5 % hasta 30 %. Ya sea estadfsticamente significativo o no, el bimatoprost con un promotor de la penetracion proporcionara resultados mejores y/o mas rapidos que el bimatoprost sin un promotor de la penetracion.
Las observaciones anteriores estableceran que el 0,03 % en peso de la composicion de bimatoprost penetra en la piel y hace crecer el pelo.
Claims (6)
1. Una composicion adecuada para hacer crecer el pelo mediante aplicacion topica, comprendiendo la composicion bimatoprost y uno o mas potenciadores de la penetracion, en donde la composicion comprende monooleato de glicerol como un potenciador de la penetracion.
2. Una composicion segun la reivindicacion 1, que esta en la forma de una solucion, un gel, un unguento, una espuma, una pelfcula, un linimento, una crema, un champu, una locion, una pasta, una gelatina, un pulverizador o un aerosol.
3. Una composicion segun la reivindicacion 1 o la reivindicacion 2 para utilizar en un metodo terapeutico de tratamiento de un trastorno de perdida de pelo en un mairnfero mediante administracion topica de la composicion.
4. Una composicion para utilizar segun la reivindicacion 3, en donde el metodo comprende aplicar la composicion al menos una vez al dfa al cuero cabelludo.
5. Una composicion para utilizar segun la reivindicacion 3 o la reivindicacion 4, en donde el trastorno de perdida de pelo se selecciona de alopecia areata, efluvio telogenico, efluvio anagenico, alopecia cicatrizal, alopecia de cicatriz, una anormalidad del tallo piloso tal como trichorrexis nudosa, smdrome anagenico suelto, tricotilomama y alopecia de traccion, un trastorno infeccioso del pelo tal como tinea capitis, dermatitis seborreica y foliculitis del cuero cabelludo, y alopecia androgenetica.
6. Un metodo no terapeutico para estimular el crecimiento del pelo en un marnffero, comprendiendo el metodo la aplicacion topica de una composicion como se define en la reivindicacion 1 o la reivindicacion 2.
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