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ANEXO I.
PARTE B
FORMATO FNSOC-001
NOTIFICACIÓN SANITARIA OBLIGATORIA (NSO), SOLICITUD DE RENOVACIÓN,

RECONOCIMIENTO E INFORMACIÓN DE MODIFICACIONES
X Notificación Sanitaria Obligatoria (NSO)

□ Solicitud de Renovación del código de identificación de la NSO
□ Solicitud de Reconocimiento del código de identificación de la NSO
□ Información de Modificaciones
I. DATOS DEL TITULAR DE LA NSO

Artículo 7 y 9, numeral 1, literales a), b) y g) de la Decisión 833 de 2018
Nombre o razón social: MARÍA ODILA LEÓN ARAQUE
Número de identificación de contribuyente: 51611427
Domicilio o dirección legal: Ciudad / Distrito / Provincia / Departamento:
CALLE 30 SUR 50 A 75 PISO 4 BOGOTÁ D.C. / CUNDINAMARCA
País: COLOMBIA Teléfono: (304)642-5239
E-mail: edisonserji@gmail.com
Nombre del: Representante Legal X Apoderado □
MARIA ODILA LEON ARAQUE
Teléfono/Celular: E-mail: edisonserji@gmail.com
Nombre del: Responsable Técnico (Químico Farmacéutico)
EDILMA VARGAS SALCEDO
Teléfono: -------- Celular: 3108036442
E-mail: dtecnicadulcemaria@gmail.com
II. DATOS DEL FABRICANTE O FABRICANTES
Artículo 9, numeral 1, literal b) de la Decisión 833 de 2018
(Para notificación, solicitud de renovación y reconocimiento)
Nombre o razón social: COSMÉTICOS DULCE MARÍA S.A.S
Número de autorización sanitaria de funcionamiento o capacidad de producción o permiso de
funcionamiento (cuando corresponda): DC 5456
Domicilio o dirección: CRA29A#28-16SUR Ciudad / Distrito / Provincia / Departamento:
BOGOTÁ D.C. / CUNDINAMARCA
País: COLOMBIA Teléfono: 302 2219827
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E-mail: edisonserji@gmail.com
III. DATOS DE OTROS OPERADORES (CUANDO SEA EL CASO)
□ MAQUILADOR (Fabricante por encargo)
□ ENVASADOR (cuando corresponda) □ ACONDICIONADOR (cuando

corresponda)
Artículo 2 y 9, numeral 1, literal c) de la Decisión 833 de 2018

(Para notificación, solicitud de renovación y reconocimiento)
Nombre o razón social:
Domicilio o dirección: Ciudad / Distrito / Provincia / Departamento:
País: Teléfono:
No. de identificación del contribuyente: E-mail:
IV. DATOS GENERALES DEL PRODUCTO

Artículo 9, numeral 1, literales d) y f), Artículo 12 de la Decisión 833 de 2018
Nombre del producto: CREMA TERMOACTIVA
Denominación genérica: CREMA TERMOACTIVA
Presentación comercial: ENVASE POLICARBONATO, PET, PVC, PEAD,

PEBD, CAJA PLEGADIZA Y CAJA NO PLEGADIZA, HOJALATA
5,8,10,12,15,18,20,25,30,50,60,70,75,80,90,100,110,120,200, 250, 300, 330, 350, 400, 450
500 g o mL
Forma Cosmética: Emulsión Grupo cosmético: (Tonos o variedades):
VERDE OSCURO, VERDE CLARO,
AMARILLO, NARANJA,ROJO OSCURO,
ROJO CLARO, AZUL OSCURO, AZUL
CLARO, MORADO, LILA, FUCSIA,ROSADO,
BLANCO, MAGENTA
Marca(s): NATURKEN, SIN AGÜERO LEON, ANDRINAS NATURKEN, INGAICO
NATURKEN, CHUCHUGUAZA NATURKEN
Código de identificación de la NSO
(Incluir en caso de solicitud de renovación,
reconocimiento e información de
Número de Expediente
modificaciones)
Vigencia del Código de identificación de la

(Incluir en caso de solicitud de NSO
reconocimiento) País que emitió el Código de identificación de
la NSO
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VI. DOCUMENTACIÓN QUE SE ANEXA
A ser presentada por el titular de la NSO

Documentación para notificación
1. Documento que acredite la representación legal o la condición de apoderado según la
normativa nacional vigente (literal a)
2. Solicitud totalmente diligenciada y firmada por los responsables.
3. Declaración del fabricante, en caso de maquila (cuarto párrafo del artículo 9), el cual debe
contener al menos el nombre del producto, y la razón social del Titular de la NSO y del
maquilador
4. Descripción del producto (literales i y j)

4.1 Fórmula cualitativa (básica y secundaria), en nomenclatura INCI.
4.2 Fórmula cuantitativa, en nomenclatura INCI, de las sustancias de uso restringido,
cuando corresponda
4.3 Fórmula cuantitativa, en nomenclatura INCI, de los ingredientes de la composición
básica que ejerzan la acción (función) cosmética
4.4 Denominación química y tamaño de partícula de la sustancia nanomaterial, cuando
corresponda
5. Especificaciones organolépticas y fisicoquímicas del producto terminado (literal k).
6. Especificaciones microbiológicas cuando corresponda, de acuerdo a la naturaleza del
producto terminado y a la normativa andina vigente (literal l)
7. Estudios técnicos, experimentales, científicos, entre otros, que justifiquen las bondades,
proclamas y efectos de carácter cosmético atribuibles al producto terminado, cuya no
veracidad pueda representar problemas para la salud (literal m).
8. Etiqueta o rotulado, o Proyecto de arte de la etiqueta o rotulado (literal n),
indique el que adjunta:
8.1. Etiqueta o rotulado con el que se comercializará el produto; o
8.2. Proyecto de arte de la etiqueta o rotulado;
9. Instrucciones de uso del producto, cuando corresponda (literal o).
10. Material del envase primario y secundario cuando corresponda (literal p)

11. Descripción del sistema de codificación de lotes de producción por cada fabricante. (literal
q)
12. Comprobante de pago por derecho de trámite.
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VII. DECLARACIÓN JURADA
VII.1 DE LA INFORMACIÓN TÉCNICA DEL PRODUCTO
Yo, EDILMA VARGAS SALCEDO, identificado con cédula de ciudadanía número 1.052.388.953 de
Duitama-Boyacá, actuando en mi condición de químico farmacéutico titulado y con registro
profesional No.1.052.388.953 del Colegio Nacional de Químicos Farmacéuticos de Colombia
declaro que el producto cosmético descrito fue fabricado cumpliendo con las Buenas Prácticas de
Manufactura (BPM) y no perjudica la salud humana, siempre que se apliquen las condiciones
normales o razonablemente previsibles de uso.
FIRMA DEL RESPONSABLE TÉCNICO (QUÍMICO FARMACÉUTICO)

Nombre completo: EDILMA VARGAS SALCEDO
Número de Registro o Colegiatura Profesional: 1.052.388.953 del Colegio Nacional de
Químicos Farmacéuticos de Colombia
VII.2 DEL TITULAR DE LA NSO
Yo, MARIA ODILA LEON ARAQUE, identificado con cédula de ciudadanía 51.611.427 de Bogotá
D.C. actuando en condición de Representante legal o Apoderado, declaro bajo la gravedad de
juramento, que el presente documento y la información suministrada adjunta son auténticos y
veraces, y cumplen con todos los requisitos establecidos por la Decisión 833 de la Comisión de la
Comunidad Andina y la normativa comunitaria que la complemente. Asimismo, declaro el cumpliendo
de las Buenas Prácticas de Manufactura (BPM) y que la comercialización será posterior a la
presentación del presente documento, cumpliendo estrictamente con las especificaciones de calidad
definidas para el producto.
FIRMA DEL REPRESENTANTE LEGAL O APODERADO

Nombre completo: MARIA ODILA LEON ARAQUE
Número de identificación: CC 51.611.427 de Bogotá D.C.
Lugar y fecha: 16 de junio de 2023.
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FICHA TECNICA
1. NOMBRE DEL PRODUCTO

CREMA TERMOACTIVA
2. MARCA
APLICA PARA TODAS LAS MARCAS .VARIEDADES SEGÚN COLOR
3. FABRICANTE
COSMETICOS DULCE MARÍA S.A.S
4. TITULAR
MARIA ODILA LEON ARAQUE
5. MODALIDAD DE NOTIFICACIÓN SANITARIA

FABRICAR Y VENDER
6. PRESENTACIÓN COMERCIAL Y TIPO DE ENVASE
Presentación comercial: ENVASE POLICARBONATO, PET, PVC, PEAD, PEBD, CAJA

PLEGADIZA Y CAJA NO PLEGADIZA, HOJALATA
5,8,10,12,15,18,20,25,30,50,60,70,75,80,90,100,110,120,200, 250, 300, 330, 350, 400, 450 500
g o mL
7. FORMULA CUALI-CUANTITATIVA
INGREDIENTE FUNCIÓN PORCENTAJE

WATER SOLVENTE
TITANIUM DIOXIDE OPACIFICANTE 1%
PARAFFIN EMOLIENTE
PETROLATUM EMOLIENTE
MENTHOL REFRESCANTE 1.2%
METHYL SALICILATE ACONDICIONADOR DE PIEL
PHENOXYETHANOL PRESERVANTE 0.3%
ALOE BARBADENSIS ACONDICIONADOR DE LA PIEL
EXTRACT
UNCARIA TOMENTOSA ACONDICIONADOR DE LA PIEL
EXTRACT
CALENDULA OFFICINALIS ACONDICIONADOR DE LA PIEL
EXTRACT
CAMELLIA SINENSIS LEAF ACONDICIONADOR DE LA PIEL
EXTRACT
ARNICA MONTANA FLOWER ACONDICIONADOR DE LA PIEL
EXTRACT
PRUNUS AMYGDALUS ACONDICIONADOR DE LA PIEL
DULCIS OIL
SULFUR ACONDICIONADOR DE LA PIEL
CHAMOMILLA RECUTITA
EXTRACT ACONDICIONADOR DE LA PIEL
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AVENA SATIVA KERNEL ACONDICIONADOR DE LA PIEL

EXTRACT
MELALEUCA ALTERNIFOLIA ACONDICIONADOR DE LA PIEL
LEAF EXTRACT
TARAXACUM OFFICINALE ACONDICIONADOR DE LA PIEL
EXTRACT
EXTRACTO DE ÁLBUM DE ACONDICIONADOR DE LA PIEL
SANTALUM
EUCALYPTUS GLOBULUS ACONDICIONADOR DE LA PIEL
LEAF EXTRACT
CURCUMA LONGA ROOT AGENTE DE
EXTRACT ENMASCARAMIENTO
CAMPHOR AGENTE DE
ENMASCARAMIENTO
CI 19140 (AMARILLO) COLORANTE
CI 42090(AZUL) COLORANTE
CI 16255 (ROJO) COLORANTE
CI 77220 (BLANCO) COLORANTE
8. ESPECIFICACIONES DEL PRODUCTO TERMINADO
ORGANOLEPTICAS
Color Conforme al estándar de control de calidad según variedad
Olor Conforme al estándar de control de calidad según variedad
Aspecto Aspecto uniforme, libre de partículas extrañas
FISICOQUIMICAS
pH 5,0-7,5 Potenciómetro
Densidad 0,85-1,05 g/mL Picnómetro
MICROBIOLÓGICAS
Recuento de macroorganismos Límite máximo 5x10 3 UFC/g o mL
mesófilos aerobios totales
Pseudomonas aureginosa Ausencia 1g o mL
Sthaphylococcus aureus Ausencia 1g o mL
Escherichia Coli Ausencia 1g o mL
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9. VARIEDADADES
VARIEDAD INCI
VERDE CLARO CI 19140+CI 42090
VERDE OSCURO CI 19140+CI 42090
AMARILLO CI 19140
NARANJA CI 16255+CI 19140
ROJO CLARO CI 16255
ROJO OSCURO CI 16255
AZUL OSCURO CI 42090
MORADO CI 42090+CI 16255
LILA CI 42090+CI 16255+CI 77220
FUCSIA CI 16255+CI 42090+CI 19140
ROSADO CI 16255+CI 77220
BLANCO CI 77220
MAGENTA CI 16255+CI 42090
10. JUSTIFICACIÓN DE BONDADES DEL PRODUCTO
La crema termoactiva es un producto que centra su actividad cosmética en el mentol una

sustancia natural de origen vegetal con amplias y poderosas propiedades brindando una
sensación de frescura y bienestar para su piel
11. CODIFICACIÓN DEL LOTE
El número de lote se codifica de la siguiente manera
LOTE: C16AAXXXNNND
C: COSMÉTICOS
16: CODIGO INTERNO DE PRODUCTO
AA: ÚLTIMOS DOS DÍGITOS DEL AÑO
XXX: CONSECUTIVO ORDEN DE PRODUCCIÓN
NNN: LISTADO INTERNO DE FRAGANCIAS
D: LETRA CORRESPONDE CON EL COLOR DE LA VARIEDAD
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CONTRATO DE PRESTACIÓN DE SERVICIOS DE MAQUILA
ENTRE LOS SUCRITOS A SABER, EDISON MANUEL SERNA JIMENÉZ ,MAYOR DE EDAD, DOMICILIADO
EN LA CIUDAD DE BOGOTÁ, IDENTIFICADO CON LA CÉDULA DE CIUDADANÍA 1.038..416.078 DE
MARINILLA-ANTIOQUIA, ACTUANDO EN CALIDAD DE REPRESENTANTE LEGAL DE COSMÉTICOS
DULCE MARA S.A.S, SOCIEDAD COMERCIAL, DOMICILIADA EN LA CRA29A#28-16 SUR DE LA CIUDAD
DE BOGOTÁ D.C. , IDENTIFICADA CON NIT 901090145, QUIEN PARA EFECTOS DEL PRESENTE
CONTRATO SE DENOMINA EL CONTRATISTA Y POR OTRA PARTE MARÍA ODILA LEON ARAQUE
MAYOR DE EDAD, DOMICILIADO EN LA CIUDAD DE BOGOTÁ D.C, IDENTIFICADO CON LA CÉDULA DE
CIUDADANÍA 51.611.427 DE BOGOTÁ D.C , DOMICILIADA EN LA CARRERA 30 SUR 50A-75 PISO 4
DE LA CIUDAD DE BOGOTA D.C , QUIEN PARA EFECTOS DEL PRESENTE CONTRATO SE DENOMINA EL
CONTRATANTE, HEMOS DECIDIDO CELEBRAR EL PRESENTE CONTRATO DE PRESTACIÓN DE
SERVICIOS DE MAQUILA DE PRODUCTOS COSMÉTICOS, EL CUAL SE REGIRÁ POR LAS LEYES
APLICABLES A ESTE TIPO DE CONTRATOS Y POR LAS CLAUSULAS CONSAGRADAS EN EL PRESENTE
CONTRATO.
CLAUSULA PRIMERA. OBJETO CONTRACTUAL. EL PRESENTE CONTRATO TIENE COMO OBJETO LA

PRESTACIÓN DE SERVICIOS DE MAQUILA DE PRODUCTOS XXXXXXX, ANÁLISIS FISICOQUÍMICOS,
ANÁLISIS MICROBIOLÓGICOS DE PRODUCTO TERMINADO, MATERIAS PRIMAS, MATERIALES DE
ENVASE DE LOS PRODUCTOS CONTENIDOS EN EL ANEXO 1, EL CUAL HACE PARTE INTEGRAL DEL
PRESENTE CONTRATO, LOS CUALES SE ENCUENTRAN DEBIDAMENTE REGISTRADOS ANTE EL INVIMA
Ó ANTE LA AUTORIDAD SANITARIA COMPETENTE SEGÚN SEA EL CASO.
EN TODO CASO PARA LOS EFECTOS ESPECÍFICOS DE ESTE CONTRATO LAS PARTES INCLUYEN LA
REALIZACIÓN DE LAS ACTIVIDADES Y PROCESOS QUE SE PRESENTAN EN EL SIGUIENTE CUADRO, EN
DONDE SE SEÑALAN LAS QUE QUEDAN INCLUIDAS Y LAS EXCLUIDAS DEL CONTRATO Y SE
DETERMINA SU RESPECTIVA RESPONSABILIDAD.
ETAPA DEL PROCESO RESPONSABLE OBSERVACIONES

CONTRATISTA CONTRATANTE
COMPRA DE MATERIAS PRIMAS X
COMPRA DE MATERIAL DE X
ENVASE
COMPRA DE MATERIAL DE X
EMPAQUE
INSPECCIÓN Y APROBACIÓN DE X SI LO REALIZA EL
MATERIAS PRIMAS CONTRATANTE SE
SOLICITARÁ EL REGISTRO
CORRESPONDIENTE DE
ESTADO DE CALIDAD
APROBADO Ó
COMUNICADO POR
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CORREO ELECTRÓNICO
AUTORIZANDO LA
FABRICACIÓN.
MATERIAL DE ENVASE CONTRATANTE SE
CORRESPONDIENTE DE
ESTADO DE CALIDAD
APROBADO Ó
COMUNICADO POR
CORREO ELECTRÓNICO
AUTORIZANDO LA
FABRICACIÓN.
MATERIAL DE EMPAQUE CONTRATANTE SE
CORRESPONDIENTE DE
ESTADO DE CALIDAD
APROBADO Ó
COMUNICADO POR
CORREO ELECTRÓNICO
AUTORIZANDO LA
FABRICACIÓN.
MANUFACTURA DE GRANEL X
ANÁLISIS DE PRODUCTO EN X
PROCESO
ENVASE DE PRODUCTO X
ACONDICIONAMIENTO DE X
PRODUCTO
ANÁLISIS ORGANOLÉPTICO Y X
FISICOQUÍMICO DE PRODUCTO
TERMINADO
ANÁLISIS MICROBIOLÓGICO DE X
PRODUCTO TERMINADO
LIBERACIÓN DE PRODUCTO X
TERMINADO
ALMACENAMIENTO DE X
MUESTRAS DE RETENCIÓN
CUSTODIA DEL REGISTRO DE X EL ORIGINAL LO GUARDA
LOTE EL CONTRATISTA Y LA
COPIA EL CONTRATANTE.
SE GUARDARÁ POR UN
AÑO Ó POR EL TIEMPO DE
VIDA ÚTIL DEL
PRODUCTO.
ESTUDIOS DE ESTABILIDAD X
NATURAL
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PARÁGRAFO PRIMERO. LOS SERVICIOS DEL PROCESO DE MANUFACTURA Y DE ANÁLISIS DE

PRODUCTO CON LOS QUE NO CUENTE EL CONTRATISTA DIRECTAMENTE, SERÁN REALIZADOS A
TRAVÉS DEL CONTRATISTA POR UN TERCERO PREVIA APROBACIÓN DEL CONTRATANTE.
PARAGRAFO SEGUNDO. LAS PARTES PODRÁN DE MUTUO ACUERDO EFECTUAR ADICIONES Ó

EXCLUSIONES DE LOS PRODUCTOS DEL ANEXO 1, LAS CUALES QUEDARÁN REGIDAS POR LAS
DISPOSICIONES DE ESTE CONTRATO MEDIANTE DOCUMENT SUSCRITO POR AMBAS PARTES
CONTRATANTES Y FIRMADO POR LAS MISMAS Y HARÁ PARTE INTEGRAL DE ESTE CONTRATO.
CLAUSULA SEGUNDA. PRECIO Y FORMA DE PAGO. LOS PRECIOS SE DETERMINAN DE ACUERDO A LA

ESTRUCTURA QUE ESTABLECE LA PRESENTE CLAUSULA, EN DONDE EL CONTRATANTE CANCELARÁ
EL 50% DEL VALOR TOTAL DE CADA ORDEN DE COMPRA, A TITULO DE ANTICIPO AL INICIO DE LA
PRODUCCIÓN Y EL 50% RESTANTE A LA ENTREGA DEL PRODUCTO.
PARÁGRAFO PRIMERO. LOS PRECIOS ACORDADOS POR SERVICIO DE FABRICACIÓN ENTRE LAS
PARTES SERÁN DEFINIDOS EN DOLARES, LOS CUALESESTÁN SUJETOS A NEGOCIACIÓN, SI LAS
MATERIAS PRIMAS Y LOS MATERIALES Y MATERIAS PRIMAS PRESENTAN INCREMENTOSQUE SEAN
REPRESENTATIVOS Y AFECTEN EL COSTO DEL PRODUCTO DE MANERA CONSIDERABLE.
ADICIONALMENTE LAS PARTES ACUERDAN QUE LOS PRECIOS DE LOS PRODUCTOS DEL ANEXO 1 Y
LAS MODIFICACIONES POSTERIORES TENDRÁN UN INCREMENTO A PARTIR DEL 01 DE ENERO DE
CADA ANUALIDAD, CON BASE EN EL IPC AUTORIZADO POR EL GOBIERNO.
PARÁGRAFO TERCERO. EN CASO DE CAMBIOS O MODIFICACIONES EN CUANTO A LAS

OBLIGACIONES, COMO EL SUMINISTRO DE MATERIA PRIMA, MATERIAL DE ENVASE Y EMPAQUE,
ANÁLISIS Ó NUEVOS SERVICIOS, SE DEBE INDICAR ESTA MODIFICACIÓN EN UN DOCUMENTO
SUSCRITO POR LAS PARTES A TITULO DE OTRO SI.
CLÁUSULA TERCERA. OBLIGACIONES DEL CONTRATISTA.
A. PROPORCIONAR LAS MATERIAS PRIMAS Y/O LOS MATERIALES SEGÚ LAS ESPECIFICACIONES
DEL CONTRATANTE PARA CADA ENTREGA DE PRODUCTO.
B. DESPLEGAR TODOS SUS CONOCIMIENTOS Y CAPACIDAD TÉCNICA A FIN DE CUMPLIR CON
LAS ESPECIFICACIONES DE CALIDAD ÓPTIMAS ACORDADAS POR EL CONTRATANTES Y LAS
DERIVADAS DE LA INFORMACIÓN TÉCNICA QUE SE DESARROLLE O SE SUMINISTRE ENTRE
LAS PARTES EN CUALQUIERA DE LAS ETAPAS DE MANUFACTURA Ó ANÁLISIS.
C. ASUMIR LA CUSTODIA Y CUIDADO DE LOS MATERIALES Y MATERIAS PRIMAS ENTREGADOS
POR EL CONTRATANTE, DESDE SU LLEGADA A LAS INSTALACIONES DEL CONTRATISTA,
HASTA LA ENTREGA DEL PRODUCTO TERMINADO. EL CONTRATANTE TENDRÁ 5 DÍAS
DESPÚÉS DE LA COMUNICACIÓN DE ENTREGA DELPRODUCTO PARA RECOGERLO EN LAS
INTALACIONESDEL CONTRATISTA.
D. GARANTIZAR LAS BUENAS PRÁCTICAS DE MANUFACTURA EN EL PROCESO DE FABRICACIÓN.
E. NOTIFICAR POR ESCRITO AL CONTRATANTE LOS RESULTADOS DE LOS ANÁLISIS DE INSUMOS
Y MATERIALES SUMINISTRADOS DE ACUERDO AL CUADRO DE RESPONSABILIDADES DEL
PRESENTE CONTRATO Ó LA MODIFICACIÓN QUE POR PRODUCTO SE DETERMINE.
F. CUMPLIR CON TODAS LAS NORMAS DE SEGURIDAD INDUSTRIAL TENDIENTES A
GARANTIZAR UNA PRODUCCIÓN QUE CONTEMPLE EL MÍNIMO DE RIESGOS TANTO EN EL
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FACTOR HUMANO COMO EN LOS ELEMENTOS (EQUIPOS, INSTALACIONES, HERRAMIENTAS,

ETC.).
G. SOLICITAR LOS DOCUMENTOS COMPLETOS NECESARIOS AL CONTRATANTE PARA LLEVAR A
CABO LA LABOR DE MANUFACTURA DEL PRDUCTO REQUERIDO.
H. ENTREGAR EL PRODUCTO ACORDADO EN LA FECHA ACORDAD ENTRE LAS PARTES, EN EL
CASO DE QUE NO FUESE ENTREGADO EN ESTE PLAZO, EL CONTRATISTA MEDIANTE
COMUNICACIÓN ESCRITA REPORTARÁ LAS CAUSAS DEL RETRASO AL CONTRATANTE, LAS
CUALES DEBEN ESTAR ENMARCADAS DENTRO DE LAS EXCLUSIONES DE RESPONSABILIDAD
POR FUERZA MAYOR Y CASO FORTUITO.
I. MARCAR EL NUMERO DE LOTE A TODAS LAS UNIDADES ENVASADAS, DE FORMA LEGIBLE E
INDELEBLE, SEGÚN LO DISPUESTO POR EL CONTRATANTE.
J. EMITIR CON EL PRODUCTO TERMINADO UNA COPIA DEL REGISTRO DE LOTE CON TODA LA
DOCUMENTACIÓN GENERADA DURANTE EL PROCESO DE FABRICACIÓN Y DE CONTROL DE
CALIDAD DE ACUERDO A LA RESPONSABILIDAD ACORDADA.
K. CONSERVAR EN LAS INSTALACIONES DEL CONTRATISTA LAS MUESTRAS DE RETENCIÓN DE
LOS LOTES, NECESARIAS PARA LA REALIZACIÓN DE ANÁLISIS DE SEGUIMIENTO EN CASO DE
SER NECESARIAS. DICHAS MUESTRAS SE TENDRÁN OR UN TIEMPO DE UN (1) AÑO DESPUÉS
DE LA FECHA DE FABRICACIÓN Ó POR EL TIEMPO DE VIDA ÚTIL DEL PRODUCTO SI ESTE
FUERA MAYOR.
L. EL CONTRATISTA RECIBIRÁ VISITAS, INSPECCIONES Y AUDITORIAS DEL CONTRATANTE
PREVIO AVISO POR LO MENOS CON 24 HORAS DE ANTELACIÓN.
M. EL CONTRATISTAPERMITIRÁ QUE EL CONTRATANTE PUEDE ESTAR PRESENTE EN LOS
PROCESOS DE MANUFACTURA DE SUS PRODUCTOS PREVIO AVISO Y SOLO EN CALIDAC DE
OBSERVADOR. PARA ELLO DEBERÁ PRESENTAR LOS DOCUMENTOS QUE LE SOLICITE EL
CONTRATISTA.
CLÁUSULA CUARTA. OBLIGACIONES DEL CONTRATANTE.
A. REALIZAR LOS ENVÍOS DE ÓRDENES DE COMPRA Y PRODUCCIÓN AL CONTRATISTA, CON UN

TIEMPO NO INFERIOR A VEINTE (20) DÍAS, CON EL FIN DE REALIZAR LA PROGRAMACIÓN DE
MANUFACTURA.
B. SUMINISTRAR EN LA ORDEN DE SERVICIOS, LAS ESPECIFICACIONES REQUERIDAS POR EL
CONTRATANTE, PRESENTACIÓN Y CANTIDA DE UNIDADES A ENVASAR.
C. TRANSPORTAR LOS MATERIALES Y MATERIAS PRIMAS DE FABRICACIÓN DESDE SUS
BODEGAS Ó PROVEEDORES HASTA LAS INTALACIONES DEL CONTRATISTA, ASUMINEDO LOS
RIESGOS DE QUIEN POR SU CUENTA LO TRANSPORTE.
D. TRASPORTAR EL PRODUCTO TERMINADO DESDE LAS INSTALACIONES DEL CONTRATISTA EN
UN TERMINO NO SUPERIOR A 5 DÍAS, UNA VEZ INFORMADO DE LA ENTREGA DEL
PRODUCTO POR PARTE DEL CONTRATISTA.
E. INFORMAR PREVIAMENTE AL CONTRATISTA DE LAS MODIFICACIONES QUE SOBRE LA
NOTIFICACIÓN INICIAL SE HAYAN HECHO ANTE EL INVIMA Ó LA AUTORIDAD NACIONAL
COMPETENTE.
F. INFORMAR AL CONTATISTA DE LOS CAMBIOS DE FABRICANTE QUE SE LLEVEN A CABO DE
LAS MATARIAS PRIMAS SUMINISTRADAS PARA FABRICACIÓN.
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G. ENTREGAR LAS FICHAS SE SEGURIDAD DE LAS MATERIAS PRIMAS AL CONTRATISTA.

H. ENTREGAR MATERIAS PRIMAS Y MATERIAES PARA LA FABRICACIÓN DE CADA PRODUCTO
CON LOS RESPECTIVOS CERTIFICADOS DE ANÁLISIS DEL LOTE ENVIADO.
I. SOLICITAR LAS RESPECTIVAS FABRICACIONES TANTO EN PROCESO COMO EN MATERIAS
PRIMAS, MATERIALES Y ETIQUETAS DE AJUSTADO A LA NORMATIVA VIGENTE Y LO
ACEPTADO POR EL INVIMA O LA AUTORIDAD NACIONAL COMPETENTE.
J. LAS MARCAS CONTENIDAS EN LA NOTIFICACIÓN SON DE PROPIEDAD EXCLUSIVA DEL
CONTRATANTE Y EN EL RECAE LA RESPONSABILIDAD DE USO Y NOTIFICACIÓN A LAS
AUTORIDADES PERTINENTES EN LA MATERIA.
CLÁUSULA QUINTA. PERDIDAS EN EL PROCESO Ó MERMAS. EL CONTARTISTA TENDRÁ UN

MÁXIMO DE PERDIDAS EN PROCESO POR CUENTA DE LA DINÁMICA PROPIA DE LOS PROCESOS
PRODUCTIVOS Y DE LOS DESPERDICIOS DE MATRIAL QUE QUEDA EN LOS EQUIPOS DE
MANUFACTURA. DE TAL FORMA LAS MERMAS PROPIAS DEL PROCESO DE LÍQUIDOS NO
VISCOSOS SERÁ MÁXIMO DE 2%, LAS DE LÍQUIDOS VISCOSOS MÁXIMO DE 3,5% Y LAS DE CREMA
MÁXIMO DE 5%.
CLÁUSULA SEXTA. RESPONSABILIDAD CIVIL. LAS PARTES DEJAN EXPRESA CONSTANCIA QUE EL
PRESENTE ACUERDO DE VOLUNTADES GENERA RELACIÓN CONTRACTUAL CIVIL
EXCLUSIVAMENTE ENTRE EL CONTRATANTE Y EL CONTRATISTA, EN LOS TÉRMINOS Y
CONDICIONES DEL MISMO, SIENDO CADA UNA DE LAS PARTES RESPONSABLE DEL
CUMPLIMIENTO Y EJECUCIÓN DE LAS OBLIGACIONES EN EL ESTIPULADAS.
LAS RELACIONES QUE MANTENGA EL CONTRATANTE Ó EL FABRICANTE CON TERCEROS, A PESAR

DE QUE TENGAN RELACIÓN DIRECTA CON LA EJECUCIÓN DEL PRESENTE CONTRATO, SERÁN
ASUMIDAS POR CADA UNA DE LAS PARTES DIRECTAMENTE
LAS PARTES DECLARAN QUE LA RESPONSABILIDAD DEL CONTRATISTA POR LOS SERVICIOS QUE
PRESTA SE LIMITA UNICA Y EXCLUSIVAMENTE RESPECTO DE SUS RELACIONES CONTRACTUALES
CON EL CONTRATANTE. EN ESTAS CIRCUNSTANCIAS EL CONTRATISTA DESLINDA TODA Y
CULAQUIER RESPONSABILIDAD RESPECTO DEL MAL USO Ó DESTINO QUE EL CONTRATANTE DE
A LOS SERVICIOS Y/O PRODUCTOS RESULTANTES DE LOS SERVICIOS QUE PRESTA.
CLAUSULA SÉPTIMA. FUERZA MAYOR. CUALQUIER CIRCUNSTANCIA, EVENTO Ó IMPREVISO DEL

CUAL NO ES POSIBLE RESISTIRSE AÚN EJERCIENDO UNA DILIGENTE ADMINISTRACIÓN
COMPROBADA, Y QUE COMO TALES AFECTEN Ó DIFICULTEN SUSTANCIALMENTE EL
CUMPLIMIENTO DEL CONTRATO, LIBERAN A LA PARTE AFECTADA DEL CUMPLIMIENTO DE SUS
OBLIGACIONES CONTRACTUALES, MIENTRAS DURE LA INTERRUPCIÓN, Y EN LA MEDIDA DE SUS
EFECTOS.
CLÁUSULA OCTAVA. TERMINACIÓN DEL SERVICIO.
A. POR VENCIMIENTO DEL TÉRMINO DE DURACIÓN PACTADO.

B. POR INCUMPLIEMINTO DE LAS CLÁUSULAS Y OBLIGACIONES CONSIGNADAS EN EL
PRESENTE CONTRATO.
13
C. POR DECISIÓN DE ALGUNA DE LAS PARTES QUE DEBE SER FUNDAMENTADA MEDIANTE
COMUNICACIÓN ESCRITA Y PRESENTADA CON NO MENOS DE 60 DÍAS CALENDARIO.
D. POR MUTUO ACUERDO.
E. POR QUIEBRA, CONCORDATO Y/O LIQUIDACIÓN DE CUALQUIERA DE LAS PARTES.
PARÁGRAFO PRIMERO. UNA VEZ TERMINADO EL CONTRATO EL CONTRATISTA DEVOLVERÁ AL

CONTRATANTE TODOS LOS MATERIALES DE ENVASE Y EMPAQUE, MATERIAS PRIMAS Y PRODUCTO
TERMINADO Y TODA INFORMACIÓN QUE RESPECTO DEL CONTRAATANTE Y SUS PRODUCTOS HAYA
SIDO ENTREGADA AL CONTRATISTA, EN EL TÉRMINO DE LOS 15 DÍAS CALENDARIO SIGUIENTES A LA
TERMINACIÓN DEL CONTRATO.
CLÁUSULA NOVENA. CONFIDENCIALIDAD. TODA INFORMACIÓN TÉCNICA RECIBIDA POR LAS

PARTES, YA SEA POR ESCRITO, VERBAL, EN GRÁFICOS O POR CUALQUIER OTRO MEDIO, SERÁ
CONSIDERADA COMO CONFIDENCIAL Y POR LO TANTO NO SERÁ DIVULGADA POR EL CONTRATISTA
NI POR EL CONTRATANTE A TERCEROS SIN PREVIA AUTORIZACIÓN POR ESCRITO DE QUIEN ENTREGA
LA INFORMACIÓN. DE IGUAL FORMA NI EL CONTRATISTA NI EL CONTRATANTE UTILIZARÁN PARA
SU BENEFICIO NI EL DE TERCEROS LA INFORMACIÓN QUE RECIBA DE ESTA RELACIÓN
CONTRACTUAL. EN TODO CASO LAS PARTES SE REGIRÁN PARA ESTE EFECTO EN LO ESTIPULADO EN
EL ACUERDO D CONFIDENCIALIDAD SUSCRITO PREVIAMENTE ENTRE LAS PARTES Y QUE HACE PARTE
INTEGRAL DE ESTE ACUERDO CONTRACTUAL.
CLÁUSULA DECIMA. NO CONFORMIDAD DEL SERVICIO. EL CONTRATANTE TENDRÁ DIEZ (10) DÍAS
HÁBILES PARA PRESENTAR QUEJA POR NO CONFORMIDAD DEL SERVICIO RECIBIDO. UNA VEZ
CUMPLIDO ESTE PLAZO SE RECIBIRÁN OBSERVACIONES DEL SERVICIO Y SE PROCEDERÁ A REALIZAR
LAS DEBIDAS INVESTIGACIONES Y GENERAR LA RESPUESTA RESPECTIVA AL CONTRATANTE.
CLÁUSULA DÉCIMA PRIMERA. MÉRITO EJECUTIVO. LAS PARTES RECONOCEN Y ACEPTAN QUE EL
PRESENTA CONTRATO DE SERVICIOS, CON LA ACEPTACIÓN DEL MISMO POR PARTE DEL
CONTRATANTE, PRESTA MÉRITO EJECUTIVO PARA LA EXGENCIA JUDICIAL DEL CUMPLIMIENTO DE
TODAS O ALGUNAS DE LAS OBLIGACIONES QUE DE ESTE DOCUMENTO SE DERIVEN.
CLÁUSULA DÉCIMO SEGUNDA. DURACIÓN. EL PRESENTE CONTRATO TENDRÁ UNA DURACIÓN DE

12 MESES CONTADOS A PARTIR DE LA FECHA DE SU FIRMA Y SE RENOVARÁ AUTOMÁTICAMENTE
POR EL MISMO PERÍODO DE COMÚN ACUERDO ENTRE LAS PARTES.
CLÁUSULA DECIMO TERCERA. CESIÓN. ESTABLECEN LAS PARTES DE MUTUO ACUERDO QUE ESTÁ
PROHIBIDO A CUALQUIERA DE ELLAS CEDER A CUALQUIER TITULO EL PRESENTE CONTRATOSIN EL
PREVIO CONSENTIMIENTO POR ESCRITO DE LA OTRA PARTE. SI ALGUNA DE ELLAS CONTRAVIENE
ESTA ESTIPULACIÓN, LA CESIÓN NO TENDRÁ EFECTOS JURÍDICOS EN RELACIÓN CON LA OTRA Y SERÁ
TOMADO COMO UN INCUMPLIMIENTO DEL CONTRATO.
CLÁUSULA DÉCIMO CUARTA. COMPROMISORIA. CUALQUIER CONTROVERSIA RELACIONADA CON Ó

DERIVADA DE ESTE CONTRATO Y SU EJECUCIÓN O LIQUIDACIÓN, QUE NO PUEDA SER RESULETA DE
MUTUO ACUERDO ENTRE LAS PARTES, LAS MISMAS DECIDEN SOMETERLAS A UN TRIBUNAL DE
ARBITRAMENTO QUE SE REGIRÁ DE ACUERDO A LAS DISPOSICIONES CONTENIDAS EN LA LEY 1563
DE 2012 Y LAS DISPOSICIONES LEGALES VIGENTES, Y SE SOMETERÁ A LAS SIGUIENTES REGLAS:
14
LOS ARBITROS SERÁN SELECCIONADOS POR SORTEO DE LALISTA DE ÁRBITROS DE LA CÁMARA DE

COMERCIO DE BOGOTÁ.
A. EL TRIBUNAL DECIDIRÁ EN DERECHO.

B. EL TRIBUNAL DE ARBITRAJE ESTÁ INTEGRADO POR UN ÁRBITRO.
C. LA ORGANIZACIÓN INTERNAA DEL TRIBUNAL SE SUJETARÁ A LAS REGLAS PREVISTAS PARA EL
EFECTO POR EL CENTRO DE CONCILIACIÓN Y ARBITRAJE DE LA CÁMARA DE COMERCIO DE
BOGOTÁ.
CLÁUSULA DÉCIMO QUINTA. DECLARACIONES.

A. QUE SON LEGALMENTE CAPACES DE CONTRATAR Y QUE HAN RECIBIDO AUTORIZACIÓN
SUFICIENTE DE SUS RESPECTIVOS ÓRGANOS ESTATUTARIOS.
B. QUE HAN TENIDO LA OPORTUNIDAD DE DISCUTIR Y NEGOCIAR TODAS Y CADA UNA DE LAS
CLÁUSULAS DEL PRESENTE CONTRATO, LAS CUALES ENTIENDEN Y LAS ENCUENTRAN
LEGALMENTE CORRECTAS.
C. QUE ESTE DOCUMENTO CONTIENE TODO EL CONTRATO DE SERVICIO DE MAQUILA E INTEGRA
EN EL TODOS LOS PROCESOS PERTINENTES A LA ELABORACIÓN Y ANÁLISIS DE UN PRODUCTO
XXXXXXXX, QUE REEMPLAZA Y PREVALECE SOBRE CUALQUIER OTRO CONTRATO VERBAL Ó
ESCRITO QUE LAS PARTES HAYA PODIDO CELEBRAR CON ANTERIORIDAD.
D. QUE LA NULIDAD DE CUALQUIERA DE LAS CLÁUSULAS NO AFECTA LA VALIDEZ DE LAS
RESTANTES SIEMPRE Y CUANDO EL CONTRATO PUEDA SUBSISTIR LEGALMENTE SIN LA
CLÁUSULA ANULADA.
E. AMBAS PARTES ENTIENDEN Y ACEPTAN EL HECHO DE QUE EL CONTRATISTA ES UNA COMPAÑÍA
DE INTACHABLE REPUTACIÓNY DE QUE, ASI MISMO EL CONTRATANTE ES UNA SOCIEDAD
LEGALMENTE CONSTITUIDA EN COLOMBIA Y ES UNA COMPAÑÍA DE INTACHABLE REPUTACIÓN.
POR LO TANTO, AMBAS PARTES ACEPTAN QUE EL CONTRATO PODRÁ SER TERMINADO
UNILATERALMENTE EN CUALQUIER MOMENTO COMO ACTO DE PRESERVACIÓN DEL BUEN
NOMBRE Y LA REPUTACIÓN, SIN NECESIDAD DE PREVIO AVISO NI INDEMNIZACIÓN ALGUNA, EN
EL EVENTO DE QUE ALGUNA DE LAS PARTES, ALGUNO DE SUS ACCIONISTAS, GERENTES Ó
DIRECTIVOS, RESULTE FORMALMENTE INCLUIDO EN LA ORDEN EJECUTIVA NÚMERO 12.978
“SPECIALLY DESIGNED NARCOTICS TRAFFICKERS SDNT” CONOCIDA COMO “LA LISTA CLINTON”,
O SEA ACUSADO FORMALMENTE ANTE UN JUEZ DE CUALQUIER PAÍS POR NARCOTRÁFICO,
LAVADO DE ACTIVOS,TERRORISMO Ó TRÁFICO DE ARMAS, EN LOS TÉRMINOS INDICADOS POR
EL ACTA PATRIOTA ( PATRIOT ACT), Y EN LAS DEMÁS LEYES NORTEAMERICANAS Y
COLOMBIANAS APLICABLES. ASÍ MISMO EL CONTRATO PUEDE SEER TERMINADO
UNILATERALMENTE POR UNA DE LAS PARTES EN CUALQUIER MOMENTO, SIN NECESIDAD DE
INDEMNIZACIÓN ALGUNA, EN EL CASO DE COMPROBARSE QUE LA OTRA A USADO MANO DE
OBRA INFANTIL EN UNA FORMA VIOLATORIA DEL CONVENIO 138 DE LA OIT (CHILD AND FORCED
LABOR), SUS MODIFICACIONES Y ADICIONES.
DADO EN LA CIUDAD DE BOGOTÁ D.C. A LOS 26 DÍAS DEL MES DE ABRIL DE AÑO 2023 EN DOS
ORIGINALES DEL MISMO TENOR
15
EDISON MANUEL SERNA JIMENEZ MARIA ODILA LEON ARAQUE
CC 1.038.416.078 DE MARINILLA-ANTIOQUIA C.C 51.611.427 DE BOGOTÁ D.C
REPRESENTANTE LEGAL
COSMÉTICOS DULCE MARÍA S.A.S
COMPAÑÍA CONTRATISTA CONTRATANTE
ANEXO 1. PRODUCTOS CUBIERTOS POR EL CONTRATO DE SERVICIO DE MAQUILA.
CREMA TERMOACTIVA

16
CAMARA DE COMERCIO DE BOGOTA
SEDE VIRTUAL
CÓDIGO VERIFICACIÓN: B23038778E1C13

25 DE ABRIL DE 2023 HORA 15:57:19
AB23038778 PÁGINA: 1 DE 2
* * * * * * * * * * * * * * * * * * * * * *
**********************************************************************
ESTE CERTIFICADO FUE GENERADO ELECTRÓNICAMENTE Y CUENTA CON UN CÓDIGO
DE VERIFICACIÓN QUE LE PERMITE SER VALIDADO ILIMITADAMENTE DURANTE
60 DÍAS, INGRESANDO A WWW.CCB.ORG.CO
**********************************************************************
RECUERDE QUE ESTE CERTIFICADO LO PUEDE ADQUIRIR DESDE SU CASA U
OFICINA DE FORMA FÁCIL, RÁPIDA Y SEGURA EN WWW.CCB.ORG.CO
**********************************************************************
PARA SU SEGURIDAD DEBE VERIFICAR LA VALIDEZ Y AUTENTICIDAD DE ESTE
CERTIFICADO SIN COSTO ALGUNO DE FORMA FÁCIL, RÁPIDA Y SEGURA EN
WWW.CCB.ORG.CO/CERTIFICADOSELECTRONICOS
**********************************************************************
QUE, LOS DATOS DEL EMPRESARIO Y/O EL ESTABLECIMIENTO DE COMERCIO HAN
SIDO PUESTOS A DISPOSICIÓN DE LA POLICÍA NACIONAL A TRAVÉS DE LA
CONSULTA A LA BASE DE DATOS DEL RUES
**********************************************************************
CERTIFICADO DE EXISTENCIA Y REPRESENTACION LEGAL O INSCRIPCION DE
DOCUMENTOS.
LA CAMARA DE COMERCIO DE BOGOTA, CON FUNDAMENTO EN LAS MATRICULAS E
INSCRIPCIONES DEL REGISTRO MERCANTIL
======================================================================
|ADVERTENCIA: ESTA SOCIEDAD NO HA CUMPLIDO CON LA OBLIGACION LEGAL DE|
|RENOVAR SU MATRICULA MERCANTIL. POR TAL RAZON LOS DATOS CORRESPONDEN|
| A LA ULTIMA INFORMACION SUMINISTRADA POR EL COMERCIANTE EN EL |
| FORMULARIO DE MATRICULA Y/O RENOVACION DEL AÑO : 2020 |
======================================================================
CERTIFICA:
NOMBRE : COSMETICOS DULCE MARIA S.A.S.
N.I.T. : 901090145 2
DOMICILIO : BOGOTÁ D.C.
CERTIFICA:
MATRICULA NO: 02815898 DEL 12 DE MAYO DE 2017
CERTIFICA:
RENOVACION DE LA MATRICULA :25 DE JUNIO DE 2020
ULTIMO AÑO RENOVADO : 2020
ACTIVO TOTAL : 200,000,000
CERTIFICA:
DIRECCION DE NOTIFICACION JUDICIAL : CRA 29 A # 28-16 SUR PISO 2
MUNICIPIO : BOGOTÁ D.C.
EMAIL DE NOTIFICACION JUDICIAL : COSMETICOSDULCEMARIAS.A.S@GMAIL.COM
DIRECCION COMERCIAL : CRA 29 A # 28-16 SUR PISO 2
EMAIL COMERCIAL : COSMETICOSDULCEMARIAS.A.S@GMAIL.COM
CERTIFICA:

17
CONSTITUCION: QUE POR DOCUMENTO PRIVADO NO. SIN NUM DE ACCIONISTA
UNICO DEL 3 DE MAYO DE 2017, INSCRITA EL 12 DE MAYO DE 2017 BAJO EL
NUMERO 02223860 DEL LIBRO IX, SE CONSTITUYO LA SOCIEDAD COMERCIAL
DENOMINADA COSMETICOS DULCE MARIA S.A.S..
CERTIFICA:
VIGENCIA: QUE EL TERMINO DE DURACION DE LA SOCIEDAD ES INDEFINIDO
CERTIFICA:
OBJETO SOCIAL: LOS OBJETIVOS DE ESTA SOCIEDAD SON LOS SIGUIENTES:
ELABORACIÓN Y DISTRIBUCIÓN DE PRODUCTOS COSMÉTICOS, COSMETOLOGÍA Y
PERFUMERÍA. NUESTRA MISIÓN: BRINDAR A NUESTROS CLIENTES SATISFACCIÓN
EN RELACIÓN CON NUESTROS PRODUCTOS COSMÉTICOS DE EXCELENTE CALIDAD.
CERTIFICA:
ACTIVIDAD PRINCIPAL:
4645 (COMERCIO AL POR MAYOR DE PRODUCTOS FARMACÉUTICOS, MEDICINALES,
COSMÉTICOS Y DE TOCADOR)
CERTIFICA:
CAPITAL:
** CAPITAL AUTORIZADO **
VALOR : $12,000,000.00
NO. DE ACCIONES : 1,200.00
VALOR NOMINAL : $10,000.00
** CAPITAL SUSCRITO **
VALOR : $12,000,000.00
** CAPITAL PAGADO **
VALOR : $12,000,000.00
CERTIFICA:
REPRESENTACIÓN LEGAL: LA ADMINISTRACIÓN Y REPRESENTACIÓN LEGAL DE LA
SOCIEDAD ESTÁ EN CABEZA DEL REPRESENTANTE LEGAL, QUIEN TENDRÁ UN
SUPLENTE QUE PODRÁ REEMPLAZARLO EN SUS FALTAS ABSOLUTAS, TEMPORALES O
ACCIDENTALES. LA REPRESENTACIÓN LEGAL PUEDE SER EJERCIDA POR PERSONAS
NATURALES O JURÍDICAS, LA ASAMBLEA GENERAL DE ACCIONISTAS, DESIGNARÁ A
LOS REPRESENTANTES LEGALES POR EL PERÍODO QUE LIBREMENTE DETERMINE O
EN FORMA INDEFINIDA, SI ASÍ LO DISPONE, Y SIN PERJUICIO DE QUE LOS
NOMBRAMIENTOS SEAN REVOCADOS LIBREMENTE EN CUALQUIER TIEMPO.
CERTIFICA:
** NOMBRAMIENTOS **
QUE POR DOCUMENTO PRIVADO NO. SIN NUM DE ACCIONISTA UNICO DEL 3 DE
MAYO DE 2017, INSCRITA EL 12 DE MAYO DE 2017 BAJO EL NUMERO 02223860
DEL LIBRO IX, FUE (RON) NOMBRADO (S):
NOMBRE IDENTIFICACION
REPRESENTANTE LEGAL
SERNA JIMENEZ EDISON MANUEL C.C. 000001038416078
CERTIFICA:
FACULTADES DEL REPRESENTANTE LEGAL: LOS REPRESENTANTES LEGALES PUEDEN
CELEBRAR O EJECUTAR TODOS LOS ACTOS Y CONTRATOS COMPRENDIDOS EN EL
OBJETO SOCIAL O QUE SE RELACIONEN DIRECTAMENTE CON LA EXISTENCIA Y
FUNCIONAMIENTO DE LA SOCIEDAD.
CERTIFICA:
DE CONFORMIDAD CON LO ESTABLECIDO EN EL CÓDIGO DE PROCEDIMIENTO
ADMINISTRATIVO Y DE LO CONTENCIOSO ADMINISTRATIVO Y DE LA LEY 962 DE

18
CAMARA DE COMERCIO DE BOGOTA
SEDE VIRTUAL
CÓDIGO VERIFICACIÓN: B23038778E1C13

25 DE ABRIL DE 2023 HORA 15:57:19
AB23038778 PÁGINA: 2 DE 2
* * * * * * * * * * * * * * * * * * * * * *
2005, LOS ACTOS ADMINISTRATIVOS DE REGISTRO AQUÍ CERTIFICADOS QUEDAN
EN FIRME DIEZ (10) DÍAS HÁBILES DESPUÉS DE LA FECHA DE LA
CORRESPONDIENTE ANOTACIÓN, SIEMPRE QUE NO SEAN OBJETO DE RECURSO. LOS
SÁBADOS NO SON TENIDOS EN CUENTA COMO DÍAS HÁBILES PARA LA CÁMARA DE
COMERCIO DE BOGOTÁ.
* * * EL PRESENTE CERTIFICADO NO CONSTITUYE PERMISO DE * * *
* * * FUNCIONAMIENTO EN NINGUN CASO * * *
INFORMACION COMPLEMENTARIA
LOS SIGUIENTES DATOS SOBRE PLANEACION DISTRITAL SON INFORMATIVOS
FECHA DE ENVIO DE INFORMACION A PLANEACION DISTRITAL : 11 DE AGOSTO DE
2020
SEÑOR EMPRESARIO, SI SU EMPRESA TIENE ACTIVOS INFERIORES A 30.000
SMLMV Y UNA PLANTA DE PERSONAL DE MENOS DE 200 TRABAJADORES, USTED
TIENE DERECHO A RECIBIR UN DESCUENTO EN EL PAGO DE LOS PARAFISCALES DE
75% EN EL PRIMER AÑO DE CONSTITUCION DE SU EMPRESA, DE 50% EN EL
SEGUNDO AÑO Y DE 25% EN EL TERCER AÑO. LEY 590 DE 2000 Y DECRETO 525
DE 2009.
RECUERDE INGRESAR A WWW.SUPERSOCIEDADES.GOV.CO PARA VERIFICAR SI SU
EMPRESA ESTA OBLIGADA A REMITIR ESTADOS FINANCIEROS. EVITE SANCIONES.
TAMAÑO EMPRESA
DE CONFORMIDAD CON LO PREVISTO EN EL ARTÍCULO 2.2.1.13.2.1 DEL DECRETO
1074 DE 2015 Y LA RESOLUCIÓN 2225 DE 2019 DEL DANE EL TAMAÑO DE LA
EMPRESA ES MICROEMPRESA
LO ANTERIOR DE ACUERDO A LA INFORMACIÓN REPORTADA POR EL MATRICULADO O
INSCRITO EN EL FORMULARIO RUES:
INGRESOS POR ACTIVIDAD ORDINARIA $0
ACTIVIDAD ECONÓMICA POR LA QUE PERCIBIÓ MAYORES INGRESOS EN EL PERÍODO
- CIIU : 4645
**********************************************************************
** ESTE CERTIFICADO REFLEJA LA SITUACION JURIDICA DE LA **
** SOCIEDAD HASTA LA FECHA Y HORA DE SU EXPEDICION. **
**********************************************************************
EL SECRETARIO DE LA CAMARA DE COMERCIO,
VALOR : $ 7,200

19
**********************************************************************
PARA VERIFICAR QUE EL CONTENIDO DE ESTE CERTIFICADO CORRESPONDA CON LA
INFORMACIÓN QUE REPOSA EN LOS REGISTROS PÚBLICOS DE LA CÁMARA DE
COMERCIO DE BOGOTÁ, EL CÓDIGO DE VERIFICACIÓN PUEDE SER VALIDADO POR
SU DESTINATARIO SOLO UNA VEZ, INGRESANDO A WWW.CCB.ORG.CO
**********************************************************************
ESTE CERTIFICADO FUE GENERADO ELECTRÓNICAMENTE CON FIRMA DIGITAL Y
CUENTA CON PLENA VALIDEZ JURÍDICA CONFORME A LA LEY 527 DE 1999.
**********************************************************************
FIRMA MECÁNICA DE CONFORMIDAD CON EL DECRETO 2150 DE 1995 Y LA
AUTORIZACIÓN IMPARTIDA POR LA SUPERINTENDENCIA DE INDUSTRIA Y
COMERCIO, MEDIANTE EL OFICIO DEL 18 DE NOVIEMBRE DE 1996.
20
ffiffi &trnaru CAMARA DE COMERCIO DE BOGOTA
ffiffi d* §omercio
de §ogotá
SEDE KENNEDY
cóoreo DE vERrrrcacró¡l :8230616028cC45

2I DE ABRIL DE 2023 HORA 09: 01 : 30
s8230 61602 pÁcrNe: 1 DE 2

*********** ********
**********************************************************************
ESTE cERTrFrcADo FUE GENERADo pr,ncrRóUTcAMENTE y cUENTA coN uN cónrco
DE VERITTCACTÓU QUE LE PERMITE SER VALIDADo ILIMITADAMENTE DURANTE
60 oÍAS, TNGRESANDo A rdltvv. ccB. oRG. co
**********************************************************************
RECUERDE QUE ESTE CERTIFICADO LO PUEDE ADQUIRIR DESDE SU CASA U
oFrcrNA DE FoRMA rÁcrr,, nÁetDA y sEGURA EN trülvw.ccB.oRG.co
**********************************************************************
PARA SU SEGUR]DAD DEBE VERIEICAR LA VAL]DEZ Y AUTENTICIDAD DE ESTE
cERTrErcADo srN cosro ALGUNo DE FoRMA ¡,Ácrr,, RÁprDA y sEGURA EN
V/W!{. CCB . ORG . CO/CERT I FI CADOSELECTRONICOS
**********************************************************************
QUE, LOS DATOS DEL EMPRESARIO Y/O EL ESTABLEC]M]ENTO DE COMERCIO HAN
srDo PUESToS A Drsposrcrór,t os LA pol,rcÍa NecroNAL a rRavÉs DE LA
CONSULTA A LA BASE DE DATOS DEL RUES
**********************************************************************
CERT]F]CADO DE MATR]CULA DE PERSONA NATURAL

LA CAMARA DE COMERCIO DE BOGOTA, CON FUNDAMENTO EN LAS MATR]CULAS E
]NSCRIPC]ONES DEL REGISTRO MERCANTIL
CERT T F] CA:
NOMBRE : MARIA ODILA LEON ARAQUE
C. C. : 51 . 617 .421
N. I. T. : 57677421 9
CERTI EICA:
MATRICULA NO : 01981142 DEL 13 DE ABRIL DE 2010
CERT ] EI CA:
DTRECCTON DE NorrErcACroN JUDTCTAL : GALLE 30 suR 50 A 75 prso 4
EMAIL NOTIFICACION JUD]CIAL : MARYLEONO2GGMA]L.COM
DIRECCION COMERCIAL : CALLE 30 SUR 50 A 75 prSO 4
EMAIL COMERCIAL : MARYLEONO2GGMAIL. COM
**********************************************************************
CERTI EICA:
RENOVACION DE LA MATRICULA :15 DE MARZO DE 2023
uLTrMo año Rpr.¡ovADo: 2023
ACTIVO TOTAL REPORTADO: 91, 500, 000
CERT ] E] CA:
ACT]VIDAD ECONOMICA : 4113 COMERC]O AL POR MENOR DE PRoDUCToS
FARMACÉUT]COS Y MEDICINAI,ES, CoSMÉTICoS Y ARTÍCULoS I]E ToCADoR EN
C()nstan?a
ESTABLECIM]ENTOS ESPECIAL]ZADOS. HOMOLOGADO(S) VNNSTÓN 4 AC.
, delPila¡¿ ,/ CERT I E] CA:
*fuaikE{"
Irujíl lo PROP]ETARIO DE LOS S]GUIENTES ESTABLEC]MIENTOS DE COMERCIO
NOMBRE : NATURKEN
21
DIRECCION COMERCIAL : CARRERA 44 # 3A -34 PISO 3
MUNICIP]O : BOGOTÁ D.C.
MATRICULA NO : 019871 44 DE 13 DE ABRIL DE 2010
RENOVACION DE LA MATRICULA : EL 15 DE MARZO DE 2023
ULTIMO AÑO RENOVADO : 2023
**********************************************************************
CERT I EI CA:
LA INEORMAC]ON ANTER]OR HA S]DO TOMADA DIRECTAMENTE DEL FORMULARIO DE
MATRICULA DILIGENC]ADO POR EL COMERCIANTE.
DE CONEORM]DAD CON LO ESTABLEC]DO EN EL CODIGO DE PROCEDIMIENTO

ADMINISTRAT]VO Y DE LO CONTENCIOSO Y DE LA LEY 962 DE 2005, LOS ACTOS
ADMIN]STRATIVOS DE REG]STRO AQUI CERTIFICADOS QUEDAN EN FIRME DIEZ
(10) DIAS HAB]LES DESPUES DE LA EECHA DE ]NSCR]PC]ON, STEMPRE QUE NO
SEAN OBJETO DE RECURSOS.
EL PRESENTE CERTIF]CADO NO CONSTITUYE PERMISO DE

FUNCIONAM]ENTO EN NINGUN CASO
sEñoR EMPRESARTO, Sr SU EMPRESA TrENE ACTIVOS TNFERTORES A 30.000

SMLMV Y UNA PLANTA DE PERSONAL DE MENOS DE 2OO TRABAJADORES, USTED
TIENE DERECHO A RECIBIR UN DESCUENTO EN EL PAGO DE LOS PARAFISCALES DE
15% EN EL PR]MER AÑO DE CONSTITUCION DE SU EMPRESA, DE 50% EN EL
SEGUNDO AÑO Y DE 25% EN EL TERCER AÑO. LEY 590 DE 2OOO Y DECRETO 525
DE 2009.
TAMAÑO EMPRESA
DE CONEORMIDAD CON LO PREVISTO EN EL ARTÍCUIO 2.2.7.73.2.\ DEL DECRETO

701 4 DE 2075 Y LA RESOLUCIÓN 2225 DE 2079 DEL DANE EL TAMAÑO DE LA
EMPRESA ES MICROEMPRESA
LO ANTER]OR DE ACUERDO A LA ]NEORMACIÓN REPORTADA POR EL MATRICULADO O
]NSCRITO EN EL EORMULARIO RUES:
]NGRESOS POR ACT]VIDAD ORDINARIA $O
ACTIVIDAD ECONÓUTCE PON LA QUE PERCIBIÓ MAYORES INGRESOS EN EL PERÍODO

- CIIU : 4113
**********************************************************************
** ESTE CERTIFICADO REFLEJA LA SITUAC]ON JURID]CA DE LA **
** PERSONA NATURAL HASTA LA FECHA Y HORA DE SU EXPEDICION. **
**********************************************************************
EL SECRETARIO DE LA CAMARA DE COMERCIO,

VALOR : $ 3,600
**********************************************************************
PARA VERIFICAR QUE EL CONTENIDO DE ESTE CERT]EICADO CORRESPONDA CON LA
INF9RMACIÓN QUE REPoSA EN LOS REGISTROS PÚBL]COS DE LA CÁMARA DE
COMERCIO DE BOGOTÁ, EL CÓDIGO DE VER]FICACIÓN PUEDE SER VALIDADO POR
su DESTINATARIO SOLO UNA VEZ, INGRESANDO A hl!{W. CCB. ORG. CO
**********************************************************************
ESTE CERTIE]CADO EUE GENERADO ELECTRÓNICAMENTE CON FIRMA D]GITAL Y
*******************************************************r(**************
22
PROYECTO DE ETIQUETAS
CREMA TERMOACTIVA
APLICA PARA TODAS LAS MARCAS

VARIEDADES SEGÚN COLOR
La crema termoactiva es un producto que centra su actividad cosmética en el mentol una sustancia
natural de origen vegetal con amplias y poderosas propiedades brindando una sensación de frescura
y bienestar para su piel
MODO DE USO
Aplique generosamente producto en las manos, extiéndalo y use en la zona deseada.
PRECAUCIONES
Producto cosmético para uso externo. No aplicar sobre piel irritada o herida. Evitar el
contacto con los ojos y mantener fuera del alcance de los niños. Mantener en su envase
original en lugar fresco y seco a menos de 25°C. Si nota cualquier irritación en la piel,
suspenda su uso inmediatamente.
INGREDIENTES
WATER, PARAFFIN, PETROLATUM,MENTHOL, CAMPHOR, METHYL

SALICILATE,TITANIUM DIOXIDE,PHENOXYETHANOL,ALOE BARBADENSIS
EXTRACT,UNCARIA TOMENTOSA EXTRACT,CALENDULA OFFICINALIS
EXTRACT,CAMELLIA SINENSIS LEAF EXTRACT,ARNICA MONTANA FLOWER
EXTRACT, PRUNUS AMYGDALUS DULCIS OIL,SULFUR ,CHAMOMILLA RECUTITA
EXTRACT,AVENA SATIVA KERNEL EXTRACT,MELALEUCA ALTERNIFOLIA LEAF
EXTRACT,TARAXACUM OFFICINALE EXTRACT,EXTRACTO DE ÁLBUM DE
SANTALUM, EUCALYPTUS GLOBULUS LEAF EXTRACT,CI19140 (AMARILLO) ,CI
42090(AZUL), CI 16255 (ROJO),CI 77220 (BLANCO)
FABRICADO POR: COSMÉTICOS DULCE MARÍA S.A.S
FABRICADO PARA: MARIA ODILA LEON ARAQUE
NSOC ………………………. CONTENIDO NETO……………g
LOTE: C16AAXXXNNND
C: COSMÉTICOS
16: CODIGO INTERNO DE PRODUCTO
AA: ÚLTIMOS DOS DÍGITOS DEL AÑO
XXX: CONSECUTIVO ORDEN DE PRODUCCIÓN
NNN: LISTADO INTERNO DE FRAGANCIAS
D: LETRA CORRESPONDE CON EL COLOR DE LA VARIEDAD
8/6/23, 10:59 Bienvenido al Sistema de Trámites en Línea INVIMA
23

Pago Electrónico de Tarifas - Datos de la Transacción
Puede usar la transacción para radicar tramite
RECUERDE:
Una vez finalizado el pago, FAVOR imprimir el comprobante del soporte en la Opción Pago Electrónico
Tarifas (Revisar Pagos), RECUERDE estará habilitado DENTRO DEL MES DE PAGO de acuerdo a las
Políticas de Seguridad de ACH Colombia.
Nit Comercio: 830.000.167-2
Razon Social: Instituto Nacional de Vigilancia de Medicamentos y Alimentos – INVIMA

Usuario Tramites en Linea: cossmeticosdulcemaria
Numero de transacción/CUS: 2127142281

Valor Transacción: 3.062.995,00
Fecha: 2023/06/08
Entidad Bancaria: BANCOLOMBIA
Nro. Referencia de Pago: 20230608105646200
Tarifa: 1027
Cantidad: 1
Valor Base Tarifa: 3.062.995,00
Estado: TRANSACCION APROBADA
Identificacion Consignante: 901090145
Descripción del Pago: Pago Tarifa
2127142281
Imprimir Regresar a Tramites en Linea

Revise el estado de su cuenta bancaria para confirmar si el debito por el valor de la transacción fue aplicado por su entidad financiera.
Si desea puede comunicarse con la entidad para verificar su pago al siguiente correo electronico: invimast@invima.gov.co
https://sivicos.invima.gov.co/pse/proceso/regreso.jsp 1/1
24
USOO6503517 B1
(12) United States Patent (10) Patent No.: US 6,503,517 B1

Mohammadi et al. (45) Date of Patent: Jan. 7, 2003
(54) COSMETIC COMPOSITIONS WITH 5,833.973 A 11/1998 Dobkowski et al. ..... 424/18.08
MENTHOL 5,833,998 A * 11/1998 Biedermann et al. ....... 424/401
5,853,741 A 12/1998 Znaiden et al. ............. 424/401
(75) Inventors: Fatemeh Mohammadi, Hebron, CT 5,854,336 A 12/1998 Divone, Sr. et al. ........ 524/588
(US); Anthony Vargas, Monroe, CT 6,183,766 B1 6/2001 Sine et al. .................. 424/405
(US) OTHER PUBLICATIONS
(73) Assignee: Conopco, Inc., New York, NY (US)
John A. Wenninger and G.N. McEwen, Jr., Ph.D., J.D.,
(*) Notice: Subject to any disclaimer, the term of this International Cosmetic Ingredient Dictionary and Hand
patent is extended or adjusted under 35 book, 1997, THer Cosmetic, Toiletry, and Fragnance Asso
U.S.C. 154(b) by 0 days. ciation, Seventh Edition, vol. 1, pp. 810-811.*
(21) Appl. No.: 09/544,027 * cited by examiner
(22) Filed: Apr. 6, 2000
Primary Examiner Michael G. Hartley
Related U.S. Application Data Assistant Examiner-Konata M. George
(60) Provisional application No. 60/178,992, filed on Jan. 28, (74) Attorney, Agent, or Firm Milton L. Honig
2000. (57) ABSTRACT
(51) Int. Cl. .................................................. A61K 7700
(52) U.S. Cl. ........................................ 424/401; 424/747 Acosmetic composition is provided which includes menthol
(58) Field of Search .................................. 424/401, 474 Suspended in a carrier System of a crosslinked non
emulsifying siloxane elastomer and a volatile Siloxane. The
(56) References Cited carrier System prevents crystallization and granulation of
menthol from the cosmetic compositions.
U.S. PATENT DOCUMENTS
5,753,210 A * 5/1998 McEleney et al. ............ 424/59 4 Claims, No Drawings
25
US 6,503,517 B1
1 2
COSMETIC COMPOSITIONS WITH average number molecular weight in excess of 2,000, pref
MENTHOL erably in excess of 1,000,000 and optimally will range from
10,000 to 20 million. The term “non-emulsifying defines a
This application claims priority from Provisional Appli Siloxane from which polyoxyalkylene units are absent.
cation Serial No. 60/178,992 filed Jan. 28, 2000. Advantageously the elastomers are formed from a divinyl
compound, particularly a polymer with at least two free
BACKGROUND OF THE INVENTION Vinyl groups, reacting with Si-H linkages of a polysiloxane
1. Field of the Invention backbone Such as a molecularly Spherical MO resin. Elas
tomer compositions are commercially available from the
The invention concerts cosmetic compositions formulated General Electric Company under product designation Gen
with menthol and its derivatives.
eral Electric Silicone 839 with CTFA name of Cyclomethi
2. The Related Art cone and Vinyl Dimethicone/Methicone Cross Polymer,
Somatic Sensation enables our bodies to feel, ache and delivered as 5-7.5% elastomer in a cyclomethicone carrier,
react to temperature changes. The reactions occur when skin and under the designation Polysilicone-11. A related elas
Sensory receptors throughout the body are Stimulated by 15 tomer composition under the CTFA name of Crosslinked
mechanical, physical or chemical contact. Different recep Stearyl Methyl Dimethyl Siloxane Copolymer is available as
tors are responsible for different Stimuli; these are catego Gransil SR-CYC (25-35% elastomer in cyclomethicone)
rized as pain, preSSure or temperature changes. Special from Grant Industries, Inc., Elmwood Park, N.J. The com
pathways exist for face Sensations. The trigeminal nerve is mercial products from General Electric and Grant Industries
located on the right side of the face. It extends beyond the may be further processed by Subjecting them to a high
ear, underneath and branches out towards the cheek area. pressure (approximately 5,000 psi) treatment in a Sonolator
Properly formulated cosmetic compositions can Stimulate with recycling in 10 to 60 passes. Sonolation achieves a
the receptors to produce very positive pleasant effects. resultant fluid with elastomer average particle size ranging
One of the oldest Stimulants is 1-menthol; it imparts a from 0.2 to 10 micron, preferably 0.5 to 5 micron. Viscosity
cooling Sensation to the Skin. Menthol and related terpenes 25 is best when ranging between 300 and 20,000 cps at 25 C.
do not really cool through the effect of latent cold. Actually as measured by a Brookfield LV Viscometer (size 4 bar. 60
they heighten the perception of cold in the nerve endings in rpm. 15 Sec.).
the skin, so that the Surface of skin "feels cold'. Amounts of the elastomer may range from about 0.1 to
A problem with menthol is dissolving or uniformly dis about 30%, preferably from about 1 to about 15%, optimally
persing the compound in a cosmetic delivery System. After from about 3 to about 10% by weight.
Storage, in many Systems menthol has a tendency to crys A Second element of the present invention is that of a
tallize. Severe crystallization leads to granulation effects volatile polyorganosiloxane. The term “volatile” refers to
being perceived by a consumer. Granulation is particularly those materials having a measurable pressure at ambient
evident in anhydrous Systems. 35
conditions. Volatile poly organosiloxanes useful herein may
Accordingly, it is an object of the present invention to be cyclic or linear. Preferred cyclic Silicones include poly
provide a cosmetic composition formulated with menthol dimethylsiloxanes containing from about 3 to about 9 silicon
which avoids crystallization and the aesthetically displeas atoms, preferably containing from about 4 to about 5 Silicon
ing effects of granulation. atoms, generally known as cyclomethicones. Preferred lin
Another object of the present invention is to provide a 40
ear Silicone oils include the polydimethylsiloxane contain
cosmetic composition incorporating menthol which ing from about 3 to about 9 silicone atoms. The linear
enhances pleasant skin Sensations while minimizing any Volatile Silicones generally have Viscosities of less then
negative properties of menthol. about 5 centistokes at 25 C., while the cyclic materials have
viscosities of less than about 10 centistokes, the preferable
These and other objects of the present invention will range being from 0.1 to 8 centistokes. Examples of volatile
become more readily apparent from consideration of the 45
Silicone oils useful in the present invention include: Dow
following Summary and detailed description. Corning 224, Dow Corning 245, Dow Corning 344, Dow
SUMMARY OF THE INVENTION Corning 345 and Dow Corning 200 (manufactured by the
Dow Corning Corporation); Silicone 7207 and Silicone
A cosmetic composition is provided which includes: 7158 (manufactured by the Union Carbide Corporation); and
50
(i) from about 0.1 to about 30% of a crosslinked non SF1202 (manufactured by General Electric).
emulsifying Siloxane elastomer; Amounts of the Volatile poly organosiloxane will range
(ii) from about 1 to about 80% of a volatile polyorga from about 1 to about 80%, preferably from about 20 to
nosiloxane, and about 70%, optimally from about 30 to about 65% by
(iii) from about 0.0001 to about 5% of menthol. 55
weight.
DETAILED DESCRIPTION OF THE
Menthol is another essential element of the present inven
INVENTION
tion. The material may be in dextro, levo or racemic form
although the levo form is preferred. Amounts may range
Now it has been found that menthol can be suspended from about 0.0001 to about 5%, preferably from about 0.01
without fear of crystallization in a vehicle delivery system of 60 to about 2%, more preferably from about 0.1 to about 1%,
a crosslinked non-emulsifying siloxane elastomer and a optimally from about 0.2 to about 0.5% by weight of the
Volatile polyorganosiloxane. Moreover, the effectiveness of cosmetic composition.
menthol in providing a cooling Sensation to the Skin is Cosmetic compositions of the present invention are par
enhanced when delivered in the elastomer and volatile ticularly preferred when in the anhydrous form (less than
poly organosiloxane vehicle. 65 about 5% water, preferably less than about 1% water). Yet
Crosslinked non-emulsifying Siloxane elastomers are a oil and water emulsions may also be Suitable for the present
first essential element of this invention. They will have an invention. Whether anhydrous or emulsion type, composi
26
US 6,503,517 B1
3 4
tions of the present invention may further include a variety Company under the Neodol trademark. Copolymers of poly
of pharmaceutically acceptable carriers and skin actives. oxypropylenepolyoxyethylene sold by the BASF Corpora
Amounts of the carrier may range from about 1 to about tion under the Pluronic trademark are Sometimes also useful.
95%, preferably from about 5 to about 70%, optimally from Alkyl polyglycosides available from the Henkel Corporation
about 10 to about 40% by weight. Among the carriers are may also be utilized for purposes of this invention.
emollients, water, inorganic powders, foaming agents, Sur Anionic type Surfactants include fatty acid Soaps, Sodium
factants and combinations thereof.
lauryl Sulphate, Sodium lauryl ether Sulphate, alkylbenzene
Emollients are Substances Selected from polyols, esters Sulphonate, mono- and di-alkyl acid phosphates,
and hydrocarbons. Polyols suitable for the invention may
include propylene glycol, dipropylene glycol, polypropylene Sarcosinates, taurates and Sodium fatty acyl isethionate.
glycol, polyethylene glycol, Sorbitol, hydroxypropyl Amphoteric Surfactants include Such materials as dialky
Sorbitol, heXylene glycol, 1,3-butylene glycol, 1,2,6- lamine oxide and various types of betaines (Such as coca
hexanetriol, glycerin, ethoxylated glycerin, propoxylated midopropyl betaine).
glycerin, Xylitol and mixtures thereof. Among the Skin actives may be included Vitamin C and
Esters useful as emollients include: 15 its derivatives, alpha- and beta-hydroxycarboxylic acids,
(1) Alkyl esters of fatty acids having 10 to 20 carbon retinoids, Sunscreens, botanical extracts and Sunless tanners.
atoms. Methyl, isopropyl, and butyl esters of fatty acids Vitamin C covers ascorbic acid, magnesium ascorbate,
are useful herein. Examples include hexyl laurate, ascorbyl tetra fatty esterS Such as the tetraiSopalmitate and
isohexyl laurate, isohexyl palmitate, isopropyl Similar derivatives. Suitable alpha-hydroxycarboxylic acids
palmitate, decyl oleate, isodecyl oleate, hexadecyl include glycolic, lactic, malic and hydroxycaprylic acids.
Stearate, decyl Stearate, isopropyl isoStearate, diisopro Salicylic acid is representative of the beta
pyl adipate, diisohexyl adipate, dihexyldecyl adipate, hydroxycarboxylic acids. By the term “acids” is meant to
diisopropyl Sebacate, lauryl lactate, myristyl lactate, include Salts Such as alkali metal and ammonium Salts
and cetyl lactate. Particularly preferred are C-Cls
alcohol benzoate esters. 25 thereof. Examples of retinoids include retinol, retinoic acid,
(2) Alkenyl esters of fatty acids having 10 to 20 carbon retinyl palmitate, retinyl linoleate and retinyl acetate.
atoms. Examples thereof include oleyl myristate, oleyl Botanical extracts include aloe, chamomile, borage, green
Stearate and oleyl oleate. tea, Sage, yarrow, genistein, tulsi, kamala, rosemary, henna,
(3) Ether-esters such as fatty acid esters of ethoxylated lavender, Sandalwood, eucalyptus and combinations thereof.
fatty alcohols. Sunless tanners are particularly represented by dihydroxy
(4) Polyhydric alcohol esters. Ethylene glycol mono and acetone and Sugars (e.g. Xylitol). Sunscreens are those
di-fatty acid esters, diethylene glycol mono- and materials having at least one chromophoric group absorbing
di-fatty acid esters, polyethylene glycol (200-6000) within the ultraviolet range somewhere from 290 to 400 nm.
mono- and di-fatty acid esters, polyglycerol poly-fatty 35
Particularly useful Sunscreens are benzophenone-3, octyl
esters, ethoxylated glyceryl monoStearate, 1,3-butylene dimethyl PABA, butyl methoxy dibenzoylmethane, octyl
glycol monoStearate, 1,3-butylene glycol distearate, methoxycinnamate and Octocrylene.
polyoxyethylene polyol fatty acid ester, Sorbitan fatty Amounts of the skin actives will depend upon the par
acid esters, and polyoxyethylene Sorbitan fatty acid ticular Substance. Generally they may range from about
esters are Satisfactory polyhydric alcohol esters. 40 0.0001 to about 30%, preferably from about 0.01 to about
(5) Wax esterS Such as beeswax, Spermaceti, myristyl 20%, more preferably from about 0.1 to about 10%, opti
myristate, Stearyl Stearate. mally from about 0.5 to about 5% by weight of the cosmetic
(6) Sterol esters, of which cholesterol fatty acid esters are composition.
examples thereof. Minor adjunct ingredients may also be included in cos
Illustrative hydrocarbons are mineral oil, 45 metic compositions of this invention. These ingredients may
polyalphaolefins, petrolatum, isoparaffin, polybutenes and be selected from preservatives, fragrances, anti-foam agents,
mixtures thereof. opacifiers, colorants and mixtures thereof, each in their
Inorganic powders are useful carriers. Examples include effective amounts to accomplish their respective functions.
clays (Such as Montmorillonite, Hectorite, Laponite and The compositions of the present invention may be applied
Bentonite), talc, mica, Silica, alumina, Zeolites, Sodium 50 to a variety of cosmetics. Most particularly they are Suitable
Sulfate, Sodium bicarbonate, Sodium carbonate, calcium for skin creams and lotions. However, the compositions will
Sulfate and mixtures thereof. have applicability to hair care products Such as Shampoos,
AeroSol propellants may also be used as carriers. Propel conditioners, Styling gels and hair sprays, Shaving products
lants are normally based on volatile hydrocarbons Such as (shaving foam, aftershave lotion); underarm products
propane, butane, isobutane, pentane, isopropane and mix 55
(antiperspirants and deodorants); personal wash products
tures thereof. Phillips Petroleum Company is a source of (toilet bars and body wash liquids); perfume and cologne;
Such propellants under trademarks including A31, A32, A51 and lip care products (lipstick and lip balm), all of which are
and A70. Halocarbons including fluorocarbons and dimethyl merely illustrative.
ether are further widely employed propellants.
Surfactants may constitute at least a portion of the carrier 60 Except in the operating and comparative examples, or
for compositions according to the present invention. These where otherwise explicitly indicated, all numbers in this
may be Selected from nonionic, anionic, cationic or ampho description indicating amounts of material ought to be
teric emulsifying agents. They may range in amount any understood as modified by the word “about'.
where from about 0.1 to about 20% by weight. Illustrative The following examples will more fully illustrate the
nonionic Surfactants are alkoxylated compounds based on 65 embodiments of this invention. All parts, percentages and
Co-C fatty alcohols and acids and Sorbitan. These mate proportions referred to herein and in the appended claims are
rials are available, for instance, from the Shell Chemical by weight unless otherwise illustrated.
27
US 6,503,517 B1
S 6
EXAMPLE 1. EXAMPLE 3
A typical Sunscreen formulation according to the present

invention is reported in Table III.
A typical Vitamin C skin cream formulation is reported in 5
Table I. TABLE III
TABLE I INGREDIENT WEIGHT 9%
Phase A
COMPONENT WEIGHT 2% 1O
Deionized Water balance
Cyclomethicone 36.0 Disodium EDTA O.10
Crosslinked Silicone Elastomer 24.0 Glycerin 1.50
Sodium Chloride 3.OO
In Cyclomethicone (25% Active) Butylene Glycol 2.50
Propylene Glycol 20.5 15 Phase B
Polyethylene Glycol 200 10.5
Dimethyl Isosorbide 2.O Octymethoxycinnamate 7.50
Ascorbic Acid 5.0 Octyl Salicylate S.OO
Phenonip O60
Menthol 1.2 Vitamin E Acetate OSO
Cetyl Dimethicone Copolyol O.8 Retinyl Linoleate O.O1
Aluminum Stearate S.OO
Dow Corning 5225C 1O.OO
(Cyclomethicone/Dimethicone Copolyol)
Cetyl Dimethicone 1.OO
DC 345 (Cyclomethicone) 2.OO
25 Crosslinked Silicone Elastomer in 3O.OO
EXAMPLE 2 Cyclomethicone (25% Active)
ABIL-EM 97 (R) 1.OO
Menthol 1.OO
Fragrance O.15
A foaming skin cosmetic formulation is illustrated in

Table II. The formulation is intended for delivery via a
EXAMPLE 4
non-aerosol mechanical pump.
TABLE II A lipstick formulation according to the present invention
35 is reported in Table IV.
COMPONENT WEIGHT 2%
PHASE A TABLE IV
Carbopol 1382 (R) 5.0 INGREDIENT WEIGHT 2%
(2% Active) 40
PHASEA
Disodium EDTA O1
Butylene Glycol 1.7
Glycerin 1.9 Castor Oil 16.33
Allantoin O.2 Ozokerite 3.10
Colorant O.12 Carnauba 1.OO
Water Bal. Candelillate 4.2O
45 Beeswax 3.36
PHASEB
Lanolin Ultra S.OO
Primrose Oil 1.O Softisan 649 (E) 4.OO
Elefac-205 (R) 3.0 (Triglyceride Wax)
Borage Oil 1.O Butylated Hydroxytoluene O.18
Tridecylsalicylate 2.O Hydroxylated Lanolin OSO
Alpha-Bisabolol O1 50 Mango Butter 2.OO
Glyceryl Stearate 1.O Tridecyl Salicylate OSO
Cetyl Alcohol 1.5 Rice Bran Oil 3.OO
Vitamin E Acetate 0.5 Parsol. MCX (E) 7.OO
Preservatives 0.4 Benzophenone 3 4.OO
Amphisol A (R) 2.O Tocopherol 1.50
PHASE C 55 Sunflower Monoglycerides 3.50
Lecithin 1.OO
Water 18 Phase B
Triethanolamine 1.O
Panthenol O.2 Oryzanol O.25
PHASE D Rice Starch 3.OO
Phase C
60
Cyclomethicone 2.O
Silicone Elastomer 25.0 Red #6 240
(7.5% Elastomer Solids in Titanium Dioxide
Cyclomethicone) Blue #1
Menthol 1.O Yellow Iron Oxide 1.63
Fragrance O.2 PHASE D
65
Timica Silkwhite 4.40
28
US 6,503,517 B1
8
TABLE IV-continued TABLE VI
INGREDIENT WEIGHT 2% INGREDIENT WEIGHT 2%
PHASE E PHASEA
Water Balance Babassuu. Oil 37.40

Trehalose 1.OO Pentaerythrityl Tetraisostearate 25.OO
Green Tea 1.OO Lanolin Wax 4.OO
Ginko Biloba OSO Beeswax 7.OO
Aloe Vera Powder O.10 1O Petrolatum S.OO
Neosorb (E) 2.OO Glyceryl Behenate 3.OO
(Sorbitol) Microcrystalline Wax 4.OO
PHASEF Propyl Paraben O.10
PHASEB
Crosslinked Silicone Elastomer in 13.71
Cyclomethicone (25% Active) 15 Cyclomethicone 1.OO
Menthol Vitamin E Acetate OSO
Amethole Crosslinked Silicone Elastomer in 1O.OO
PHASE G Cyclomethicone (7.5% Solid Elastomer)
Dimethicone Copolyol 1.OO
Fragrance/Flavor O.70 Menthol 2.OO
EXAMPLE 7
EXAMPLE 5
A depilatory formulation according to the present inven
25 tion is described in Table VII.
An after Sun lotion according to the present invention is
reported in Table V. TABLE VII
INGREDIENT WEIGHT 2%
TABLE V
PHASEA
Deionized Water 53.90
PHASEA Xanthan Gum (2% Solution) 1O.OO
Disodium EDTA O.10
Deionized Water 29.13 Butylene Glycol 1.OO
Aloe Powder OSO 35 Urea 4.OO
Carbopol 1382 (R) (2% Active) 1O.OO Allantoin O.2O
Butylene Glycol 4.21 PHASEB
Glycerin O.2O
Allantoin OSO Decyl Oleate 3.OO
Trehalose OSO Bean Tree Oil 2.OO
PHASEB Ceteareth-12 2.OO
40
Cetearyl Alcohol 2.OO
Squalane S.OO Phenonip (R) O.45
Cetyl Alcohol 1.OO PHASE C
Beeswax 6.8O
Petrolatum Jelly 4.OO Crosslinked Silicone Elastomer in
Lanolin 2.OO Cyclomethicone (7.5% Solid Elastomer)
BR 76 2.25 45 Cyclomethicone 1.OO
Glyceryl Stearate 1.75 Menthol 1.OO
Cetyl Phosphate O.25 Fragrance O.30
Polydecene 8.OO
Phenonip (R) O.58
PHASE C
50 EXAMPLE 8
Vitamin E Acetate OSO
Cyclomethicone 1.OO
An aeroSol Shaving foam according to the present inven
tion is described in Table VIII.
Retinyl Linoleate O.10
Menthol 2.OO
Crosslinked Silicone Elastomer in 1O.OO 55 TABLE VIII
Cyclomethicone (7.5% Solid Elastomer)
DL-Panthanol O.2O INGREDIENT WEIGHT 2%
Triethanolamine O.70
Deionized Water 6.33 PHASEA
Botanical Extract 1.OO
Deionized Water 71.25
60
Sorbitol (70%) S.OO
Sodium Hydroxide (10% Solution) 2.OO
PHASEB
EXAMPLE 16 Myristic Acid 3.OO
Bean Tree Oil 1.OO
65 Stearic Acid 4.OO
A lip balm formulation according to the present invention Penonip (R) O.45
is illustrated in Table VI.
29
US 6,503,517 B1
9
TABLE VIII-continued TABLE X-continued
INGREDIENT WEIGHT 2% INGREDIENT WEIGHT 2%
PHASE C Cyclomethicone (7.5% Solid Elastomer)
Dimethicone Copolyol 1.OO Menthol 1.OO
Crosslinked Silicone Elastomer in 1O.OO PHASE C
Cyclomethicone (7.5% Solid Elastomer)
Cyclomethicone 1.OO Deionized Water 66.8O
Menthol 1.OO 1O Disodium EDTA O.10
Fragrance O.30 Butylene Glycol 1.OO
Allantoin O.2O
Methyl Paraben O.30
EXAMPLE 9
15
An after Shave lotion according to the present invention is
reported in Table IX.
EXAMPLE 11
TABLE IX
PHASEA An antiperSpirant gel formulation according to the present
Deionized Water 38.23 invention is reported in Table XI.
Carbopol 1382 (R) (2% Solution) S.OO
Xanthan Gum (2% Solution) 1O.OO 25 TABLE XI
Disodium EDTA O.10
Butylene Glycol 1.OO INGREDIENT WEIGHT 2%
Allantoin O.2O
PHASEB PHASEA
Isostearyl Isostearate 3.OO Cyclomethicone S.OO

Bean Tree Oil 2.OO Crosslinked Silicone Elastomer in 1O.OO
Benzophenone-3 2.OO Cyclomethicone (7.5% Solid Elastomer)
Stearyl Alcohol 1.20 Menthol 1.OO
Steareth-2 2.62 Dimethicone 200 Fluid (5Ocst) S.OO
Steareth-21 0.87 Stearyl Heptonoate 1.OO
Phenonip (R) O.45 35 PHASEB
PHASE C
Bean Tree Oil 1.OO
Crosslinked Silicone Elastomer in 1O.OO PPG Butyl Ether 15.OO
Cyclomethicone (7.5% Solid Elastomer) Aluminum Zirconium 44.70
Cyclomethicone 1.OO Tetrachlorohydrox Glycinate
Menthol 1.OO
40 Hydroxylated Milk Glyceride 2.OO
Fragrance 3.OO Fragrance O.30
PHASE D
Sodium Hydroxide (10% Solution) OSO

PHASE E
Deionized Water 1.83 45

Ethyl Alcohol 16.OO EXAMPLE 12
EXAMPLE 10
50
An anhydrous mask was formulated to evaluate the Sta
A facial foundation according to the present invention is bility enhancing effect of the croSS-linked non-emulsifying
described in Table X.
Siloxane and elastomers of the present invention with respect
to menthol. Table XII lists a test and a control mask
TABLE X
55
composition. Formulation A combines menthol with the
INGREDIENT WEIGHT 2% Siloxane elastomer while Formulation B is a control con
PHASEA
taining none of the elastomer. These formulations were
subjected to a freeze/thaw cycle of 0° C. and 25 C. in
Dimethicone and Dimethicone Copolyol 7.OO alternate 24 hour periods for a total of six days. The
Bean Tree Oil
Vitamin E Acetate
3.OO
O.05 60 formulations were then evaluated for menthol crystallization
Propyl Paraben O.10 using a DermaVision Micrograph System. The System con
PHASEB sisted of a Sony Color Video Camera (Model DXC9000)
Cyclomethicone 1.OO
coupled to a Zeiss Microscope (Model SV11) operating with
Silicone Powder 1.50 a polarizing attachment (Fostec Inc) to a light Source.
Pigment 1.50 65 Camera and microscope were connected to a Video camera
Crosslinked Silicone Elastomer in 15.OO interfaced with a computer KS200 Software (Carl Zeiss
Inc.). Micrographs of Formulation A revealed no crystalli
30
US 6,503,517 B1
11 12
zation of menthol while the micrograph of control Formu What is claimed is:
lation B possessed considerable amounts of crystallized 1. A cosmetic composition comprising:
menthol. Storage stability was evidently enhanced by the
presence of the cross-linked siloxane elastomer. (i) from about 0.1 to about 30% of a crosslinked non
emulsifying Siloxane elastomer;
TABLE XII (ii) from about 1 to about 80% of a volatile polyorga
nosiloxane, and
FORMULATION A FORMUALTION B
INGREDIENTS (WEIGHT 9%) (WEIGHT 9%) (iii) from about 0.0001 to about 5% of menthol in levo
form, the menthol being Suspended without crystalli
PHASE A 1O
Zation in the Siloxane elastomer and providing an
Versagel M750 (R)* SO.O SO.O enhanced cooling Sensation to skin when delivered in
Behenyl Behenate S.OO S.OO the Siloxane elastomer.
Silicone Powder
Salicylic Acid
2.OO
1.OO
2.OO
1.OO
2. The composition according to claim 1 wherein the
PHASE B 15 crosslinked non-emulsifying Siloxane elastomer is formed
from a divinyl monomer reacting with the Si-H linkages of
Crosslinked Silicone 3O.OO a siloxane backbone.
Elastomer in Cyclomethicone 3. The composition according to claim 1 wherein the
(7.5% Solid Elastomer) Volatile Siloxane is cyclomethicone.
Cyclomethicone 3O.OO
Menthol 1.OO 1.OO 4. A cosmetic composition comprising:
Tridecyl Salicylate 1O.OO 1O.OO
(i) from about 0.1 to about 30% of a crosslinked non
* Mineral Oil with Hydrogenated Ethylene/Propylene/Styrene Copolymer emutsifying Siloxane elastomer;
(ii) from about 1 to about 80% of a volatile polyorga
The foregoing description and examples illustrate nosiloxane, and
Selected embodiments of the present invention. In light 25
(iii) from about 0.0001 to about 5% of menthol in the levo
thereof variations and modifications will be Suggested to one form.
skilled in the art, all of which are within the spirit and
purview of this invention.
31
INFLUENCE OF STORAGE TEMPERATURE ON COOLING

INTENSITY OF TOPICAL EMULSIONS CONTAINING
ENCAPSULATED MENTHOL
VIVIAN ZAGUE1,3, DEBORAH DE OLIVEIRA NISHIKAWA1, DIEGO DE

ALMEIDA SILVA1, ANDRÉ ROLIM BABY1, JORGE HERMAN BEHRENS2,
TELMA MARY KANEKO1 and MARIA VALÉRIA ROBLES VELASCO1
1
Departament of Pharmacy
2
Departament of Food and Experimental Nutrition
School of Pharmaceutical Sciences, University of Sao Paulo
580 Professor Lineu Prestes Av.
Butanta, Sao Paulo, SP, Brazil, 05508-900
Accepted for Publication December 20, 2006
ABSTRACT
The cooling intensity of topical emulsions added with encapsulated or

free menthol was evaluated by a screened and trained panel recruited based on
the American Society for Testing and Materials method. A sensory panel
composed of 10 trained judges performed the evaluation of samples stored at
22 ⫾ 2C for 24 h and, after 28 days of storage, at 37.0 ⫾ 0.5C. The obtained
data were analyzed by analysis of variance and Tukey’s test. The results
showed an increase of cooling intensity as a function of encapsulated menthol
concentration. The opposite was observed in samples added with free menthol,
which may have caused sensory fatigue. Storage at 37 ⫾ 0.5C for 28 days
had no impact on the cooling intensity of emulsions containing encapsulated
menthol, demonstrating high stability and suggesting its application in cooling
skin care products. In contrast, emulsions added with free menthol showed a
drastic decrease of cooling intensity at 37 ⫾ 0.5C.
PRATICAL APPLICATIONS
This article deals with sensory assessment of the cooling intensity of

topical emulsions added with encapsulated menthol under accelerated storage
conditions. In all, the work is a major contribution to (1) investigating the
3
Corresponding author. TEL: 55-11-3091-2217; FAX: 55-11-3815-4418; EMAIL: vizague@
hotmail.com
Journal of Sensory Studies 23 (2008) 26–34. All Rights Reserved.

26 © 2008, The Author(s)
Journal compilation © 2008, Blackwell Publishing
32
INFLUENCE OF TEMPERATURE ON COOLING OF EMULSIONS 27
feasibility of sensory analysis for evaluating the sensory properties of topical

products during storage; (2) verifying the cooling intensity of topical emul-
sions containing encapsulated menthol; and (3) evaluating the effect of encap-
sulation of menthol on its stability during accelerated storage conditions.
INTRODUCTION
Cooling sensation is desired by consumers of skin care products designed

to clean, hydrate, rejuvenate and refresh skin after exposure to sun. In order to
develop this attribute, formulators have used menthol, which when applied
topically, causes a feeling of coolness as a result of the stimulation of cold
receptors by inhibition of calcium currents of neuronal membranes (Eccles
1994; Galeotti et al. 2002).
Menthol, a cyclic terpene alcohol found in high concentrations in oils of
peppermint and corn mint, occurs widely in nature and is endowed with the
peculiar property to be a fragrance, flavor and cooling agent. For this reason,
menthol has been widely used in over-the-counter medications, cosmetics and
food for over a century. However, its high volatility is an important issue in
its application and in the shelf life of cooling skin care products, as evapora-
tion reduces the initial cooling intensity (Liu et al. 2000; Buschmann and
Schollmeyer 2002; Layre et al. 2002; Soottitantawat et al. 2005). In this sense,
the encapsulation of menthol in carrier matrices seems to be useful in preventing
and solving the problem already mentioned as well as degradative reactions
and solubility enhancement in water to avoid the use of organic solvents such
as ethanol. In addition, controlled release of menthol from the carrier matrices
could also be a useful application (Buschmann and Schollmeyer 2002;
Soottitantawat et al. 2005). These advantages could increase the stability of
menthol and extend the cooling sensation it produces, even after long periods.
The skin sensory performance of topical products is an important factor
for potential sales of any cosmetic product. Sensory characteristics are as
important to consumers as efficacy and safety claims, and motivation to pur-
chase and use the product is influenced by its sensory properties (Close 1994).
Meanwhile, the storage conditions during the whole shelf life of a product can
modify the initial intensity of skin sensory attributes. Although significant
advances have been made in the understanding of how different storage con-
ditions influence the physical, chemical and microbiological properties of skin
care products, little attention has been given to the sensory characteristics of
such products. As a consequence, interest in techniques for evaluating sensory
attributes in a reliable manner has been growing in scientific research on
cosmetics. In this context, descriptive sensory analysis has been considered the
most appropriate method to measure the intensity and quality of sensations
33
28 V. ZAGUE ET AL.
evoked during and after product application and can be used to assess the
stability of sensory attributes during the shelf life of a product (Civille and Dus
1991; Lawless and Heymann 1999; Wortel and Wiechers 2000; Murray et al.
2001; Irigoyen et al. 2005).
Thus, this work aimed to evaluate the cooling intensity of topical emul-
sions containing different concentrations of encapsulated and free menthol
and to verify the influence of storage temperatures on the intensity of this
attribute by a screened and trained panel recruited based on the American
Society for Testing and Materials (ASTM) method.
MATERIALS AND METHODS
Samples
Non-ionic oil-in-water emulsions containing magnesium aluminum sili-
cate (RT Vanderbilt, Norwalk, CT), xanthan gum (Rhodia, Cranbury, NJ),
bi-distilled glycerin USP (Labsynth, Diadema, Brazil), propylene glycol
(Labsynth, Diadema, Brazil), C12-C15 alkyl benzoate (Eigenmann &
Veronelli, Milan, Italy), phenoxyethanol and caprylyl glycol (ISP, Wayne, NJ)
and distilled water were used and to which the following were added: (1) 1.0,
3.0 and 5.0% w/w of encapsulated menthol (Chemyunion, Sao Paulo, Brazil);
and (2) 0.1, 0.5 and 1.0% w/w of menthol as conventional raw material (free
form) (Pharmaspecial, Sao Paulo, Brazil). It is important to emphasize that
preliminary tests were carried out to identify the lowest concentration of both
menthol forms capable of providing perceptible cooling, and the concentra-
tions were adjusted to provide about equal sensory impact.
Samples were packed in identical white polyethylene flasks codified with
three aleatory digits, which were randomly changed in training and at each
evaluation, and assessed after 24 h of storage at room temperature (22 ⫾ 2C)
and after a period equal to 28 days of storage at 37.0 ⫾ 0.5C (Brasil 2004).
Subjects and Methods

Sensory analysis was developed according to ASTM (1997) method E
1490 by selecting and training judges in order to form a panel able to quantify
the cooling intensity of the emulsions.
Selecting Subjects. The subjects were recruited based on questionnaires

and on inclusion criteria suggested by ASTM (1997) method E 1490. In the
questionnaires, the subjects’ ability to use rating scales and their capacity to
interpret and verbalize sensations using descriptive words were assessed.
According to the inclusion criteria, individuals demonstrating readiness and
34
interest to participate in the test, without health problems, with 75% or more
correct answers in reporting sensations and with 80% or more success in scale
exercises, were qualified to be included in the panel. Thus, 14 women, whose
ages ranged from 19 to 30 years, were selected to participate in training for
descriptive sensory analysis.
Training. After selection, subjects were exposed to a range of reference

materials in order to understand and produce their own definition of the
attribute “cooling intensity.” This process was facilitated by a panel leader,
who was not part of the judging. The substances used in this phase were
mineral oil (Labsynth, Diadema, Brazil) and cyclopentasiloxane (Dow
Corning, Midland, MI) to represent none or minimum cooling effect, and
ethylic and isopropyl alcohols (Labsynth, Diadema, Brazil) to represent high
cooling effect. Candidates were asked to rate the cooling intensity of three
samples chosen specifically to represent the range for the attribute tested, and
then they defined the reference materials and the descriptive evaluation ballot.
The reference materials selected were cyclopentasiloxane and isopropyl
alcohol, representing minimum (low) and maximum (high) cooling intensity,
respectively. A non-structured scale anchored on both ends with the terms for
minimum and maximum intensity was used.
In order to ensure panel performance, the subjects evaluated three differ-
ent samples containing only encapsulated menthol using the descriptive evalu-
ation ballot. The assessment was performed in triplicate. Two-way analysis of
variance (ANOVA - samples ¥ subjects interaction) was carried out to assess
discrimination, reproducibility and samples ¥ subjects interactions. Signifi-
cant levels (p) of Fsample and Freplicate values were computed for each judge, and
individuals were selected as judges based on their discriminative capacity
(pFsample < 0.30) ability to reproduce results (pFreplicate > 0.05) and individual
consensus with the sensory panel. After 15 rubs, two subjects did not perceive
a significant difference between at least two samples, while two individuals did
not reproduce their results. Moreover, the values attributed to samples by these
subjects were different from that of the panel as a whole. Therefore, these
subjects were eliminated and only 10 subjects were selected as judges for the
sensory panel.
Sensory Analysis. The sensory analysis protocol proceeded in con-

trolled temperature conditions with preconditioning of samples and judges.
Three circles, each 40 mm in diameter, were marked in the forearm
of judges. Before product application, the test areas were cleansed. Samples
were presented in monadic form following an experimental design based on
Williams’ Latin squares: each sample was dispensed once in each position by
each judge (Périnel and Pagès 2004). The evaluations were accomplished in
35
30 V. ZAGUE ET AL.
individual booths, being requested between samples that excess of previous

one was removed with absorbent paper.
Each judge evaluated the samples using a 9-cm non-structured scale with
terms for minimum and maximum intensity anchored on the ends. One gram
of each sample was dispensed, and the judges were instructed to scoop the
product out of the weight boat with a specified finger (index, medium or ring
finger) and place it on the center of the circle. Immediately after the sample
was dispensed, judges spread the product in the circle with constant circular
movements (one stroke per second). After 3 and 15 rubs, the judges evaluated
cooling intensity by tracing a vertical mark on the scale (ASTM 1997).
Data analysis was carried out by using a three-way ANOVA with repeated
measures in a statistical mixed model. Menthol concentrations, number of rubs
and storage duration were considered as fixed effects and the judges as random
effects. This analysis was carried out for data related to each type of menthol.
RESULTS AND DISCUSSION
The cooling average values attributed to samples containing encapsulated

menthol stored at 22 ⫾ 2C and at 37.0 ⫾ 0.5C, after 3 and 15 rubs, are
presented in Fig. 1, while data obtained from samples containing free menthol
are presented in Fig. 2
9 a
Rating cooling intensity
a
8 b b
7 b b
c
6 c c
d
scale
5 d d
4 7.8 7.7
3 6.5 6.3 6.3 5.9
4.8 4.1 5.3 4.7
2 3.5 3.1
1
0
1.0 3.0 5.0
Samples (% w/w of encapsulated menthol)
3 rubs: 22 ± 2 ºC 15 rubs: 22 ± 2 ºC 3 rubs: 37.0 ± 0.5 ºC 15 rubs: 37.0 ± 0.5 ºC
FIG. 1. COOLING AVERAGE VALUES ATTRIBUTED TO SAMPLES CONTAINING 1.0, 3.0

AND 5.0% (W/W) OF ENCAPSULATED MENTHOL STORED FOR 24 H AT 22 ⫾ 2C AND
28 DAYS AT 37.0 ⫾ 0.5C, AFTER 3 AND 15 RUBS
The same letters on top of the averages indicate that the difference among them was not statistically
significant (P > 0.05).
36
a
a
Rating cooling intensity
9 a b
8 b
b
7
6 c c
5 c
scale
d c 8.6
4 8.2 7.3 d
6.3 5.9 6.8
3
2 3.7 4.1
3.2
1 2.6 2.9 2.1
0
0.1 0.5 1.0
Samples (% w/w of free menthol)
3 rubs: 22 ± 2 ºC 15 rubs: 22 ± 2 ºC 3 rubs: 37.0 ± 0.5 ºC 15 rubs: 37.0 ± 0.5 ºC
FIG. 2. COOLING AVERAGE VALUES ATTRIBUTED TO SAMPLES CONTAINING 0.1, 0.5

AND 1.0% (W/W) OF FREE MENTHOL STORED FOR 24 H AT 22 ⫾ 2C AND 28 DAYS
AT 37.0 ⫾ 0.5C, AFTER 3 AND 15 RUBS
The same letters on top of the averages indicate that the difference among them was not statistically
significant (P > 0.05).
In Fig. 1, the results indicate a statistically significant difference

(Frub = 71.76, P < 0.05) in perceptible cooling intensity after 3 and 15 rubs
among different encapsulated menthol concentrations in both storage tempera-
tures. Judges attributed higher cooling values to samples added with higher
encapsulated-menthol concentration (Fconcentration = 66.59, P < 0.05). These
results suggest that encapsulated menthol promoted no sensory fatigue in the
studied concentrations. Thus, encapsulated menthol allowed discriminated
cooling perception even in the highest concentration (5.0% w/w) as demon-
strated in Fig. 1. The opposite was true for samples containing free menthol, as
judges noticed no statistically significant difference (P > 0.05) among samples
containing 0.5 and 1.0% w/w in both temperatures, suggesting the occurrence
of sensory fatigue caused by menthol in its conventional form (Fig. 2). The
perceived temperature effect is not caused by the evaporation of menthol or by
vasodilatation, but is due to its specific action on sensory nerve endings.
Menthol exerts effects on cold receptors by interfering with the movement of
calcium across the cell membrane (Eccles 1994). Cool sensation caused by
application of menthol to the skin is apparent when low or threshold concen-
trations are used, but menthol has both irritant and local anesthetic actions
when used in higher concentrations (1.0–5.0%) (Eccles 1994). Therefore, the
encapsulation could promote a gradual liberation of menthol that could pos-
sibly stimulate the sensory nerve endings little by little without causing fatigue
in higher concentrations.
37
32 V. ZAGUE ET AL.
The sensory impact of menthol when applied to skin depends on the

concentration of menthol. There is some information on the dose–response
characteristics of menthol which report that low concentrations give a cool
sensation whereas high concentrations of 1–5% cause irritation and local
anesthesia. However, it is often difficult to compare studies when different
aqueous and organic vehicles are used for the application of menthol, as the
solvent influences the biological activity of the menthol.
Yosipovitch et al. (1996) found that menthol had a subjective cooling
effect lasting up to 70 min in 12 out of 18 subjects, and alcohol produced an
immediate cold sensation lasting up to 5 min in 4 out of 18 subjects. Moreover,
the transepidermal water loss at the site treated with menthol was significantly
higher than the transepidermal water loss at the alcohol-treated and control
sites, suggesting that menthol has a stronger skin irritating effect, or at least
alters the water permeability of the stratum corneum. Green (1992) carried out
psychophysical measurements on the sensory effects of menthol applied topi-
cally to the human forearm under controlled thermal conditions. Menthol as a
5.0% solution in ethanol heightened the perception of skin cooling and attenu-
ated the perception of moderate skin warming. Menthol was also shown to
have pungent or irritant properties, which were enhanced by the cooling of
the skin.
The volatility of menthol propitiates its evaporation at room temperature
in a short period of time. According to Liu et al. (2000), the encapsulation of
this substance could provide higher stability, delaying its evaporation and
prolonging its cooling effect. This interpretation is supported by the results
obtained in this study and presented in Fig. 1. After 3 and 15 rubs, submitting
samples added with encapsulated menthol at 37 ⫾ 0.5C for 28 days did not
alter cooling perception in a significant manner (Ftime = 1.27, P > 0.05) when
compared with the initial condition. Thus, data indicate the stability of encap-
sulated menthol and its convenient use in topical formulations in order to
maintain cooling effect over the whole shelf life of the product. In contrast,
samples containing free menthol presented a drastic decrease of their initial
cooling intensity after 28 days at 37 ⫾ 0.5C (Ftime = 1,488.42, P < 0.05) as
shown in Fig. 2. The temperature sensitivity of free menthol could be an
explanation for these results.
Finally, we noted that cooling values attributed to samples containing 3
and 5% w/w encapsulated menthol, stored at 22 ⫾ 2C and 37 ⫾ 0.5C, after 15
rubs, were significantly smaller (P < 0.05) than those reported after three rubs
(Fig. 1). It was surprising because an increase in cooling intensity should have
happened after a longer rubbing time (15 rubs), as encapsulated menthol
consists of a modified liberation system. A possible explanation for this could
be the generation of warmth during rubbing movements (friction), which may
have masked the true cooling intensity.
38
The results reported here clearly show the feasibility of sensory analysis
for determining the cooling intensity of different forms and concentrations of
menthol and for evaluating the preservation of this attribute in different storage
temperatures. Further studies will focus on time–intensity descriptive analysis
to examine the effect of time on the perception of the cooling intensity of
encapsulated menthol.
CONCLUSIONS
In conclusion, this study was useful for assessing the impact of storage
temperature on the cooling intensity of topical emulsions added with encap-
sulated menthol when compared with menthol in its conventional form. The
results showed that the concentration of encapsulated menthol had a signifi-
cant (P < 0.05) influence on cooling intensity: the higher the concentration, the
higher cooling intensity perceived. The opposite was observed in samples
added with free menthol, which probably caused sensory fatigue. Moreover,
storage at 37 ⫾ 0.5C for 28 days had no statistically significant (P > 0.05)
impact on the cooling intensity of emulsions containing encapsulated menthol,
demonstrating its high stability and suggesting its application in cooling skin
care products. On the other hand, emulsions added with free menthol showed
a drastic decrease of cooling intensity after 28 days at 37 ⫾ 0.5C.
ACKNOWLEDGMENTS
The authors are grateful to CAPES (Brazil) and National Council for
Scientific and Technological Development (CNPq).
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40
Menthol: A refreshing look at this

ancient compound
Tejesh Patel, MD,a Yozo Ishiuji, MD,a and Gil Yosipovitch, MDa,b
Winston-Salem, North Carolina
Menthol is a naturally occurring cyclic terpene alcohol of plant origin, which has been used since antiquity
for medicinal purposes. Its use in dermatology is ubiquitous, where it is frequently part of topical
antipruritic, antiseptic, analgesic, and cooling formulations. Despite its widespread use, it was only recently
that the mechanism by which menthol elicits the same cool sensation as low temperature was elucidated
upon, with the discovery of the TRPM8 receptor. Although almost 5 years have passed since the discovery
of this receptor, many dermatologists are still unaware of menthol’s underlying target. The purpose of this
review is to highlight the recent advances in the mechanism of action of menthol and to provide an
overview of its dermatologic applications. ( J Am Acad Dermatol 2007;57:873-8.)
M enthol (C10H20O; molecular weight, 156) is menthol’s use since antiquity, the mechanism by
a naturally occurring cyclic terpene alco- which it is able to impart a cooling sensation when
hol of plant origin, which gives plants of applied topically to the skin or mucous membrane
the Mentha species their distinctive smell and flavor. remained a mystery until recently. Although almost 5
It was first isolated as a crystalline principle in 1771 years have passed since the discovery of a common
by the Dutch botanist Gambius. However, Shimoyama receptor for menthol and low temperature, many
asserted that the peppermint plant, the main source of dermatologists are still unaware of menthol’s under-
menthol, has been cultivated for medicinal purposes lying target. The purpose of this review is to highlight
in Japan for more than 2000 years.1 the recent advances in the mechanism of action of
In the present day, menthol consumption is stag- menthol and to provide an overview of its dermato-
gering, and exceeds 7000 tons annually, with a raw logic applications.
product value approaching $300 million.2 Its use is
multifold and includes oral hygiene products, con-
fectionary, pharmaceuticals, cosmetics, pesticides, MECHANISM OF ACTION
and as a flavoring agent, to name but a few.2,3 With Over the past 5 years, understanding of the
regards to its medicinal purposes, menthol is currently mechanism by which menthol elicits the same cool
available in both prescribed and over-the-counter sensation as low temperature has advanced a great
(OTC) medications for a host of conditions, includ- deal. The ability of menthol to produce such a sen-
ing gastrointestinal disorders, common cold and sation was attributed to stimulation of thermorecep-
respiratory conditions, and musculoskeletal pain.3 tors by Goldscheider as early as 1886.4,5 However,
In addition, its use in dermatology is ubiquitous, the major breakthrough regarding a common site of
where it is frequently part of topical antipruritic, an- action for both menthol and cold came in 2002
tiseptic, analgesic, and cooling formulations. Despite through two independent studies employing differ-
ent approaches. McKemy et al6 and Peier et al7
cloned and characterized a menthol receptor using a
cDNA expression library and by searching genomic
From the Departments of Dermatologya and Neurobiology & DNA databases, respectively. Both methods, how-
Anatomy and Regenerative Medicine,b Wake Forest University ever, resulted in the identification of the 1104 amino
School of Medicine.
Funding sources: None. acid cation channel, TRPM8 (formerly CMR1 or Trp-
Conflicts of interest: None declared. p8). This cloned channel could be activated by both
Reprint requests: Gil Yosipovitch, MD, Department of Dermatol- menthol and thermal stimuli in the cool to cold range
ogy, Wake Forest University Medical Center, Medical Center (8-288C), proving that menthol elicits a sensation
Blvd, Winston-Salem, NC 27157. E-mail: gyosipov@wfubmc.edu.
of cool by serving as an agonist of a thermally sensi-
Published online May 11, 2007.
0190-9622/$32.00
tive receptor.6 This finding was reminiscent of the
ª 2007 by the American Academy of Dermatology, Inc. cloning of the vanilloid receptor (TRPV1), an excit-
doi:10.1016/j.jaad.2007.04.008 atory ion channel, activated by either temperatures
873
41
874 Patel, Ishiuji, and Yosipovitch J AM ACAD DERMATOL
NOVEMBER 2007
Table I. The characteristics of the current thermosensitive TRP channels9

Temperature TRPV1 TRPV2 TRPV3 TRPV4 TRPM8 TRPA1
range (8C) [43 [52 [34-39 25-34 8-28 \17
Agonists d Capsaicin d Camphor d Menthol d Icilin
d Extracellular protons d Extracts from d Icilin d Musturd oil
d Lipoxygenase products oregano d Eucalyptol d Wasabi
d Amide derivatives of and cloves d Garlic
arachidonic acid d Acrolein
(eg anandomide d Cinnamaldehyde
and NADA)
d Resiniferatoxin
Expression in Yes No Yes Yes No No

keratinocytes
exceeding 438C or capsaicin (the main pungent demonstrated a central role for the lipid second
ingredient in ‘‘hot’’ chilies), both of which evoked a messenger, phosphatidylinositol 4,5-bisphosphate
psychophysical sensation of warmth.8,9 (PI(4,5)P2), in both the activation and desensitization
TRPM8 is a member of the transient receptor of TRPM8.
potential (TRP) family of excitatory ion channels.
Recent advances in thermosensation have identified MENTHOL AND THE OLFACTORY SYSTEM
six temperature sensitive TRPs that perceive thermal Inhalation of menthol elicits a distinctive cooling
input depending on the type or combination of TRPs sensation which is mediated through the stimulation
stimulated.5 These thermo-TRPs display a wide spec- of trigeminal nerve, which belongs to the sensory
trum of temperature sensitivities, ranging from nox- system of the olfactory epithelium. Menthol also has
ious heat to noxious cold, and include TRPV1-4, a characteristic minty aroma, which has been attrib-
TRPM8, and TRPA1.10 Although studies have shown uted to stimulation of olfactory nerves.3 The pleasant
that these six TRPs are expressed in small diameter aroma associated with menthol may be particularly
primary sensory neurons, there is controversy beneficial in cosmetic and topical facial formula-
whether they coexist at this location.7,11-13 In addi- tions, because it increases patient acceptability.
tion, there is evidence that TRPV1, TRPMV3, and Behrendt et al23 recently suggested that TRPM8,
TRPV4 are expressed in keratinocytes, indicating that which is expressed in the trigeminus, could be an
keratinocytes are capable of detecting temperature important ‘‘chemosensory trigeminal nerve recep-
via receptors similar to those in temperature-sensing tor.’’23 Interestingly, Cometto-Muniz and Cain24
neurons.9,14-16 Epidermal expression of TRPM8 has showed that anosmics could detect menthol via
yet to be demonstrated, but this receptor is present pungency, implying that the integrity of the olfactory
in prostate epithelia,17 suggesting that it may, under system is not essential for menthol detection.24 Of
certain circumstances, be expressed in nonneuronal note, Murphy25 reported that the ability to detect the
epithelial cells9 (Table I). intensity and pleasantness associated with menthol
Menthol, icilin, and cool temperatures have all declines with age.
been shown to activate TRPM8.6,7,18 Stimulation of
TRPM8 leads to an increase in intracellular Ca21 THE PSYCHOPHYSICS OF TOPICAL
through voltage-dependent gating of the channel, MENTHOL
resulting in depolarization and generation of an Psychophysical studies have shown that menthol
action potential.19,20 In addition, Macpherson et al21 evokes a cool sensation to the skin or mucous mem-
recently showed that menthol could also stimulate brane, but only at low concentrations.26-29 Yosipo-
heat-activated TRPV3, but at concentrations well vitch et al29 showed that menthol had no effect on
above that needed to activate TRPM8.21 Furthermore, cold detection or cold pain threshold; however,
the authors of the same study went on to demonstrate recent studies have shown that menthol decreases
that menthol inhibits TRPA1, a thermo-TRP activated cold pain thresholds and enhances pain responses
by noxious cold and pungent/burning compounds.21 to suprathreshold noxious cold stimuli.30-32 With
The original study by Peier et al7 also showed that regards to heat stimuli, it has been shown that
repeated exposure to menthol could desensitize menthol has no effect on warmth detection or heat
TRPM8. Interestingly, Rohacs et al22 recently pain thresholds, although there is again some
42
J AM ACAD DERMATOL Patel, Ishiuji, and Yosipovitch 875
VOLUME 57, NUMBER 5
contradiction.27,30-32 In addition, recent studies have between 1.25% and 16%, it stimulates sensory recep-
reported significant mechanical pinprick hyperalge- tors and thus acts as a counter-irritant.41
sia with menthol, while others have not.30-32 Dis- Menthol at high concentrations (30% and above)
crepancies between these psychophysical studies can induce cold pain. Wasner et al42 showed that
may be explained by differences with regards to topical application of menthol induces cold pain by
menthol concentration, duration of application, and activation and sensitization of cold-sensitive C noci-
methods used to assess sensation. ceptors and activation of cold-specific A-delta fibers.
In a recent study, Hatem et al30 proposed that the
hyperalgesic effects of menthol may not only result
ANTIPRURITIC ACTIONS OF TOPICAL
from C nociceptor sensitization, but also depend on
MENTHOL
the balance between the activation of A-delta and C
Although menthol has been used to relive pruritus
nociceptor fibers.30 This study also highlighted indi-
for many years, there is surprisingly little literature
vidual variability in response to menthol. Menthol
assessing its efficacy. Bromm et al33 showed cooling
evoked no cold allodynia or hyperalgesia in one-
the skin by 28C to 48C resulted in a reduction in the
third of the study population. The authors of this
intensity of histamine-induced itch. More impor-
study postulated that a subpopulation exists in which
tantly, application of 1% menthol yielded a similar
the menthol-sensitive receptor is either underex-
reduction of pruritus.33 In contrast, Yosipovitch et al29
pressed on C nocicpetor fibres or overexpressed in
showed that 10% menthol had no effect on histamine-
A-delta fibers.30 Green and Schoen43 provided further
induced itch duration or magnitude. Of note, Riser
evidence that TRPM8 plays a role in cold nociception
et al34 have described a menthol-containing itch re-
and showed that dynamic contact may modify per-
lief product, formulated in a sprayable, moisturizing
ception of nonpainful cold.43
microemulsion, which is safe, tolerable, and fast-
Similar to capsaicin, menthol may also cause
acting. The optimal concentration of menthol for the
analgesia by desensitizing nociceptive C fibres. Cliff
relief of pruritus has not been established; however,
and Green26 demonstrated that 0.3% menthol pro-
we frequently use concentrations of 1% in our own
duced irritation that declined in intensity over re-
practice to relieve this distressing symptom.
peated exposure. The authors went on to show that
The mechanism by which menthol alleviates
this decline was caused by desensitization rather
pruritus is unknown. Bromm et al33 suggested the
than adaptation. In addition to self-desensitization,
activation of A-delta fibres by menthol centrally in-
Green and McAuliffe28 showed that menthol can
hibits itch. An imbalance of the endogenous opioi-
transiently desensitize capsaicin-sensitive fibers, but
dergic system has received recent attention in terms
persistent nociceptive stimuli in the form of capsaicin
of the pathophysiology of pruritus.35 Different opi-
overrides this effect.
oid receptors have contrasting effects upon pruritus.
The exact underlying mechanism by which men-
Both -opioid receptor agonists and k-opioid recep-
thol produces analgesia is unresolved. Macpherson
tor antagonists can induce itch, while -receptor
et al21 postulated that menthol’s analgesic proper-
antagonists and k-receptor agonists can reduce it.
ties can be explained via its activation of TRPM8
Menthol has been shown to selectively activate
and/or inhibition of TRPA1. The latter of these two
k-opioid receptors,36 and thus we postulate that this
TRPs is activated by a variety of noxious stimuli,
mechanism may also possibly explain the antipruritic
including cold temperatures, pungent natural com-
properties of this compound. Furthermore, there is a
pounds, and environmental irritants.44 In addition,
subset of patients who suffer from chronic pruritic
Galeotti et al36 demonstrated that oral menthol
conditions, such as atopic dermatitis, uremic pruri-
produced a dose-dependent increase in murine
tus, and psoriasis, who report a reduction in itch
pain thresholds, and that this analgesic effect was
associated with cold showers.37-40 It is thus possible
mediated through a selective activation of k-opioid
that the cooling sensation menthol imparts to the
receptors. Furthermore, menthol has been shown to
skin serves as a possible mechanism to reduce itch
increase cutaneous blood flow at the site of appli-
perception in these patients.
cation.32 Such a vasodilatation would result in an
increase in skin temperature, and it is therefore
ACTIONS OF TOPICAL MENTHOL ON PAIN possible that menthol mediates at least part of its
In the present day, menthol can be found in a analgesic effect in a similar fashion to superficial
variety of topical pain relief medications because of heat therapy.5 Despite the use of heat to relieve
its counter-irritant and local anesthetic properties. musculoskeletal pain since ancient times, the mech-
In concentrations of 1% or less, menthol depresses anisms responsible for this therapeutic effect remain
cutaneous sensory receptors, while at concentrations controversial.45
43
NOVEMBER 2007
LOCAL ANAESTHETIC ACTIVITY OF but detectable human plasma levels of menthol

TOPICAL MENTHOL following application of dermal patches.
Galeotti et al46 demonstrated that menthol has a More importantly, menthol has been shown to act
strong dose-dependent local anesthetic action as- as a penetration enhancer, demonstrating that it not
sessed in vivo in the rabbit conjunctival reflex test only permeates the epidermis, but also acts to in-
and in vitro in a rat phrenic nerve hemidiaphragm crease the accessibility of other drug molecules.56,57
preparation. Interestingly, both of the enantiomers This effect may be explained by menthol’s ability to
of menthol were equiactive in terms of local anes- disrupt the lipid bilayer of the stratum corneum as
thetic activity. In a more recent study, Haeseler et al47 well as forming pools within it.58,59 In addition, polar
concluded that menthol blocks voltage-gated neu- groupecontaining terpenes, such as menthol, have
ronal and skeletal muscle sodium channels in a been suggested to provide particular enhancement
concentration-dependent manner in resting and for hydrophilic permeants.54 The ability of menthol
inactivated states. Furthermore, the authors sug- to act as a penetration enhancer, along with its other
gested that this effect provided a molecular basis beneficial properties, makes it an ideal vehicle to be
for the antinociceptive and local anesthetic proper- used in topical combination therapies. Although the
ties of this compound. US Food and Drug Administration (FDA) discour-
ages the use of such combination therapies, the
prospect of combining menthol with topical steroids
ANTIBACTERIAL AND ANTIFUNGAL
in the treatment of atopic dermatitis and other
PROPERTIES OF MENTHOL
pruritic conditions, for example, is particularly ap-
Menthol not only has an effect on sensory param-
pealing. Menthol is already used in combination with
eters, but also has antibacterial and antifungal activ-
camphor and pramoxine for the treatment of itch.
ity.48 Such properties are exploited in diverse
products, including dental root canal sealers, anti-
septics, food preservatives, and feed supplements.49 SAFETY AND TOXICITY
Both peppermint oil and menthol have been shown Menthol is considered a safe and effective topical
to be active against a variety of microorganisms, OTC product according to the FDA. Concentrations
including both gram-positive and -negative bacteria, of menthol up to 16% have been approved by the
as well as fungi.48-50 In addition, both have recently FDA for OTC external use, and their safety profile
been shown to display synergy with oxytetracy- has been well established. Based on the large post-
cline.50 The toxic effects on membrane structure marketing data, the FDA panel concluded that men-
and function have generally been used to explain the thol in these concentrations have an excellent safety
antimicrobial activity of peppermint oil and menthol, profile. Customer complaints of 1 per 310,000 were
although the exact mechanism of action is not fully reported by one major manufacturer, while a second
understood.49 Trombetta et al49 recently speculated manufacturer reported 1 per 950,000. No complaints
that the antimicrobial effect of menthol may result, at of a serious nature have been filed with the FDA.41
least partially, from a perturbation of the lipid frac- Menthol in concentrations of 40% (but not 30%)
tion of microorganism plasma membrane, resulting resulted in skin erythema and spontaneous burn-
in alterations of membrane permeability and in leak- ing.30,31 In addition, menthol has been associated
age of intracellular materials. Furthermore, Schelz with allergic contact dermatitis60,61 and systemic
et al50 demonstrated that peppermint oil and men- allergic reactions.62
thol displayed antiplasmid activity.
CONCLUSION
MENTHOL AS A VEHICLE Menthol has been used since antiquity for medic-
In topical and transdermal formulations, the se- inal purposes, but it is only the relatively recent
lection of an appropriate vehicle is highly important, discovery of TRPM8 that has identified its underlying
because it can influence both drug release and receptor. This thermosensitive cation channel finally
percutaneous absorption.51 Menthol has long been provides the answer to how menthol can elicit the
used as a vehicle because it is derived from natural same cool sensation as low temperatures. Menthol
sources, has a pleasant aroma (increasing patient is widely used in dermatologic practice, where it is
acceptability), and is effective at low concentrations frequently part of topical antipruritic, analgesic,
(in the range 0.5-5%).52 Topical and transdermal antiseptic, and cooling formulations. It has an excel-
menthol formulations have been shown to facilitate lent safety as well as toxicity profile, and is currently
drug permeation in both animal and human used as a vehicle in a host of topical and transdermal
models.51,53,54 Of note, Martin et al55 reported low formulations. The future potential dermatologic uses
44
J AM ACAD DERMATOL Patel, Ishiuji, and Yosipovitch 877
VOLUME 57, NUMBER 5
of this ancient compound is exciting, particularly in 20. Reid G. ThermoTRP channels and cold sensing: what are they
the setting of topical combination therapies. really up to? Pflugers Arch 2005;451:250-63.
21. Macpherson LJ, Hwang SW, Miyamoto T, Dubin AE, Patapou-
tian A, Story GM. More than cool: promiscuous relationships
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NOTIFICACIÓN SANITARIA OBLIGATORIA (NSO), SOLICITUD DE RENOVACIÓN,

X Notificación Sanitaria Obligatoria (NSO)

I. DATOS DEL TITULAR DE LA NSO

III. DATOS DE OTROS OPERADORES (CUANDO SEA EL CASO)

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10. Material del envase primario y secundario cuando corresponda (literal p)

VII. DECLARACIÓN JURADA

VII.1 DE LA INFORMACIÓN TÉCNICA DEL PRODUCTO

FIRMA DEL RESPONSABLE TÉCNICO (QUÍMICO FARMACÉUTICO)

VII.2 DEL TITULAR DE LA NSO

FIRMA DEL REPRESENTANTE LEGAL O APODERADO

1. NOMBRE DEL PRODUCTO

5. MODALIDAD DE NOTIFICACIÓN SANITARIA

6. PRESENTACIÓN COMERCIAL Y TIPO DE ENVASE

Presentación comercial: ENVASE POLICARBONATO, PET, PVC, PEAD, PEBD, CAJA

INGREDIENTE FUNCIÓN PORCENTAJE

AVENA SATIVA KERNEL ACONDICIONADOR DE LA PIEL

8. ESPECIFICACIONES DEL PRODUCTO TERMINADO

10. JUSTIFICACIÓN DE BONDADES DEL PRODUCTO

La crema termoactiva es un producto que centra su actividad cosmética en el mentol una

11. CODIFICACIÓN DEL LOTE

El número de lote se codifica de la siguiente manera

CONTRATO DE PRESTACIÓN DE SERVICIOS DE MAQUILA

CLAUSULA PRIMERA. OBJETO CONTRACTUAL. EL PRESENTE CONTRATO TIENE COMO OBJETO LA

ETAPA DEL PROCESO RESPONSABLE OBSERVACIONES

PARÁGRAFO PRIMERO. LOS SERVICIOS DEL PROCESO DE MANUFACTURA Y DE ANÁLISIS DE

PARAGRAFO SEGUNDO. LAS PARTES PODRÁN DE MUTUO ACUERDO EFECTUAR ADICIONES Ó

CLAUSULA SEGUNDA. PRECIO Y FORMA DE PAGO. LOS PRECIOS SE DETERMINAN DE ACUERDO A LA

PARÁGRAFO TERCERO. EN CASO DE CAMBIOS O MODIFICACIONES EN CUANTO A LAS

CLÁUSULA TERCERA. OBLIGACIONES DEL CONTRATISTA.

FACTOR HUMANO COMO EN LOS ELEMENTOS (EQUIPOS, INSTALACIONES, HERRAMIENTAS,

CLÁUSULA CUARTA. OBLIGACIONES DEL CONTRATANTE.

A. REALIZAR LOS ENVÍOS DE ÓRDENES DE COMPRA Y PRODUCCIÓN AL CONTRATISTA, CON UN

G. ENTREGAR LAS FICHAS SE SEGURIDAD DE LAS MATERIAS PRIMAS AL CONTRATISTA.

CLÁUSULA QUINTA. PERDIDAS EN EL PROCESO Ó MERMAS. EL CONTARTISTA TENDRÁ UN

LAS RELACIONES QUE MANTENGA EL CONTRATANTE Ó EL FABRICANTE CON TERCEROS, A PESAR

CLAUSULA SÉPTIMA. FUERZA MAYOR. CUALQUIER CIRCUNSTANCIA, EVENTO Ó IMPREVISO DEL

CLÁUSULA OCTAVA. TERMINACIÓN DEL SERVICIO.

A. POR VENCIMIENTO DEL TÉRMINO DE DURACIÓN PACTADO.

PARÁGRAFO PRIMERO. UNA VEZ TERMINADO EL CONTRATO EL CONTRATISTA DEVOLVERÁ AL

CLÁUSULA NOVENA. CONFIDENCIALIDAD. TODA INFORMACIÓN TÉCNICA RECIBIDA POR LAS

CLÁUSULA DÉCIMO SEGUNDA. DURACIÓN. EL PRESENTE CONTRATO TENDRÁ UNA DURACIÓN DE

CLÁUSULA DÉCIMO CUARTA. COMPROMISORIA. CUALQUIER CONTROVERSIA RELACIONADA CON Ó

LOS ARBITROS SERÁN SELECCIONADOS POR SORTEO DE LALISTA DE ÁRBITROS DE LA CÁMARA DE

A. EL TRIBUNAL DECIDIRÁ EN DERECHO.

CLÁUSULA DÉCIMO QUINTA. DECLARACIONES.

EDISON MANUEL SERNA JIMENEZ MARIA ODILA LEON ARAQUE