ES2618802T3 - Composición de rejuvenecimiento cutáneo fotoactivada oxidativa que comprende ácido hialurónico, glucosamina o alantoína - Google Patents
Composición de rejuvenecimiento cutáneo fotoactivada oxidativa que comprende ácido hialurónico, glucosamina o alantoína Download PDFInfo
- Publication number
- ES2618802T3 ES2618802T3 ES09824320.7T ES09824320T ES2618802T3 ES 2618802 T3 ES2618802 T3 ES 2618802T3 ES 09824320 T ES09824320 T ES 09824320T ES 2618802 T3 ES2618802 T3 ES 2618802T3
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- ES
- Spain
- Prior art keywords
- allantoin
- glucosamine
- skin rejuvenation
- hyaluronic acid
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000000203 mixture Substances 0.000 title abstract description 19
- 230000003716 rejuvenation Effects 0.000 title abstract description 8
- 230000001590 oxidative effect Effects 0.000 title abstract description 5
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 title abstract 4
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 title abstract 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 title abstract 2
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 title abstract 2
- 229960000458 allantoin Drugs 0.000 title abstract 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 title abstract 2
- 229960002442 glucosamine Drugs 0.000 title abstract 2
- 229920002674 hyaluronan Polymers 0.000 title abstract 2
- 229960003160 hyaluronic acid Drugs 0.000 title abstract 2
- 239000007800 oxidant agent Substances 0.000 abstract description 4
- 230000003213 activating effect Effects 0.000 abstract description 2
- 230000035876 healing Effects 0.000 abstract description 2
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 abstract 1
- 125000002081 peroxide group Chemical group 0.000 abstract 1
- 208000027418 Wounds and injury Diseases 0.000 description 7
- 238000000034 method Methods 0.000 description 6
- 238000009472 formulation Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
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- 239000004677 Nylon Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000002978 peroxides Chemical group 0.000 description 1
- 230000002186 photoactivation Effects 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 230000017363 positive regulation of growth Effects 0.000 description 1
- ZBWBYBYOJRDPDE-UHFFFAOYSA-K potassium titanium(4+) phosphate Chemical compound P(=O)([O-])([O-])[O-].[Ti+4].[K+] ZBWBYBYOJRDPDE-UHFFFAOYSA-K 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000010282 redox signaling Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000009221 stress response pathway Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
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Abstract
Una composición de rejuvenecimiento cutáneo que comprende: al menos un oxidante, en el que el oxidante es un peróxido; un fotoactivador capaz de activar al oxidante, en el que el fotoactivador comprende eosina Y; y al menos un factor de cicatrización elegido de ácido hialurónico, glucosamina y alantoína; junto con un vehículo farmacéuticamente aceptable.
Description
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La inclusión de compuestos fotosensibles adecuados y la activación con una fuente de luz de una longitud de onda adecuada, conduce a la aceleración del proceso de descomposición de la fuente de peróxido (el oxidante) y las otras reacciones que tienen lugar, por medio de un fenómeno fotodinámico. Los colorantes incluidos se iluminan mediante fotones de una cierta longitud de onda y se excitan hasta un estado de energía superior. Cuando los electrones excitados del fotoactivador vuelven a un estado de energía inferior, emiten fotones con un nivel de energía inferior, por lo que se provoca la emisión de luz de una longitud de onda más larga (desplazamiento de Stokes). En el medio adecuado, mucha de esta transferencia de energía se transfiere al oxígeno o al peróxido de hidrógeno reactivo y provoca la formación de radicales de oxígeno, tales como el oxígeno singlete.
Se cree que el oxígeno singlete y otras especies reactivas de oxígeno generadas mediante la activación de la composición funcionan de una manera hormética. Es decir, se provoca un efecto beneficioso para la salud mediante la exposición baja a estímulos normalmente tóxicos (p.ej. oxígeno reactivo), estimulando y modulando las rutas de respuesta al estrés en las células de los tejidos seleccionados como objetivo. La respuesta endógena a los radicales libres generados de manera exógena (especies de oxígeno reactivo) se modula con una capacidad de defensa incrementada contra los radicales libres exógenos, e induce la aceleración de la cicatrización y los procesos regenerativos. Además, la activación de la composición producirá además un efecto antibacteriano. La sensibilidad extrema de las bacterias a la exposición a radicales libres hace de la composición de la presente invención una composición bactericida de facto.
El posible mecanismo de acción debería ser un fenómeno de señalización redox fortalecido que dé como resultado un proceso de transducción de señales acentuado en el que las células conviertan un tipo de señal en otro; los "segundos mensajeros" activados inducen una "cascada de señales" que comienza con un estímulo relativamente pequeño que genera una gran respuesta por medio de una amplificación monitorizada biológicamente de tales señales. Estos mecanismos complejos actúan posiblemente implicando fenómenos angiogénicos por medio de la activación de factores de crecimiento.
Este método se podría describir como una forma de terapia fotodinámica. Sin embargo, a diferencia de otras técnicas fotodinámicas, en las que los fotoactivadores se incorporan en la estructura del tejido, en el presente método, el material fotoactivo está en contacto simple con el tejido y actúa cuando se activa mediante la luz, como un "dispositivo fotodinámico" que interacciona químicamente con el tejido. Además, la luz actínica penetra en el tejido, y la luz que es emitida por el fotoactivador (luz de una longitud de onda más larga) también es absorbida por el tejido.
Se puede usar cualquier fuente de luz actínica. Puede ser adecuado cualquier tipo de lámpara halógena, LED o lámpara de arco voltaico, o láser. La característica principal de las fuentes adecuadas de luz actínica será que emiten luz de una longitud de onda (o longitudes de onda) adecuadas para activar el o los fotoactivadores presentes en la composición. En una realización, se usa un láser de argón. En otra realización, se usa un láser de titanil fosfato de potasio (KTP) (p.ej. un láser GreenLight™). En otra realización, un dispositivo de fotocurado LED es la fuente de luz actínica. En otra realización, la fuente de luz actínica es una fuente de luz visible que tiene una longitud de onda entre 400 y 600 nm. Además, la fuente de luz actínica debería tener una densidad de potencia adecuada. La densidad de potencia adecuada para las fuentes de luz sin colimación (LED, lámparas halógenas o de arco voltaico) están en el intervalo de alrededor de 900 mW/cm2 a alrededor de 2000 mW/cm2. La densidad de potencia adecuada para las fuentes de luz láser están en el intervalo de alrededor de 0,5 mW/cm2 a alrededor de 0,8 mW/cm2.
La duración de la exposición a la luz actínica dependerá de la superficie del área tratada, y del tipo de lesión, traumatismo o herida que se va a tratar. La fotoactivación de la composición puede tener lugar en segundos o incluso en fracciones de segundo, pero un periodo prolongado de exposición es beneficioso para aprovechar el efecto sinérgico de la luz absorbida, reflejada y reemitida en la composición de la presente invención y su interacción con el tejido a tratar. En una realización, el tiempo de exposición a la luz actínica del tejido, piel o herida en la que se ha aplicado la composición de rejuvenecimiento cutáneo es un periodo de entre 60 segundos y 5 minutos. En otra realización, el tiempo de exposición a la luz actínica del tejido, piel o herida en la que se ha aplicado la composición de rejuvenecimiento cutáneo es un periodo de entre 60 segundos y 5 minutos por cm2 del área a tratar, de forma que el tiempo total de exposición de 10 cm2 sería de entre 10 minutos y 50 minutos. En otra realización, la fuente de luz actínica está en continuo movimiento sobre el área tratada durante el tiempo adecuado de exposición. En otra realización, se llevan a cabo múltiples aplicaciones de la composición de rejuvenecimiento cutáneo y de la luz actínica. En ciertas realizaciones, el tejido, piel o herida se expone a la luz actínica al menos dos, tres, cuatro, cinco
o seis veces. En ciertas realizaciones, se da una aplicación nueva de la composición de rejuvenecimiento cutáneo antes de la exposición a la luz actínica.
Ejemplos
EJEMPLO I
Se preparó una composición de rejuvenecimiento cutáneo ejemplar, fuera del alcance de las presentes reivindicaciones, mezclando los siguientes componentes:
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los bordes de la herida. Durante una hora, se colocó una barrera impermeable (p.ej. una lámina de silicona) entre el colgajo y su sitio donante para eliminar la posibilidad de apoyo del lecho de la herida. Después se retiró la lámina, el colgajo volvió a su posición original y los bordes del colgajo se cerraron quirúrgicamente mediante el uso de sutura de nailon 4/0 de una manera discontinua. Inmediatamente tras el cierre del colgajo, se revistió el pedículo del colgajo
5 con 13,5 g de formulación de gel (0,5 g/cm2) y se irradiaron. Los controles no recibieron tratamiento. Se tuvo cuidado de distribuir uniformemente la pomada a lo largo de todo el colgajo. La formulación de gel se preparó el mismo día del experimento. Para el grupo de Gel + Luz, los animales se trataron con la formulación de gel y el colgajo se irradió durante 3 minutos con una lámpara LED.
Con respecto a la Fig. 3, los resultados muestran un grosor dérmico incrementado y la formación de colágeno nuevo
10 en la piel tratada con la composición de la presente invención frente a la piel sin tratar. Este resultado apoya el papel de la composición de la presente invención en la estimulación de mejores resultados en el proceso de rejuvenecimiento cutáneo.
Las realizaciones y ejemplos presentados en la presente memoria son ilustrativos de la naturaleza general de la materia reivindicada, y no son limitantes. Los expertos en la técnica entenderán cómo se pueden modificar 15 fácilmente estas realizaciones y/o adaptarlas para las diversas aplicaciones y de diversas maneras sin apartarse del alcance de la materia reivindicada. Se debe entender que las reivindicaciones del presente documento incluyen sin limitación todas las realizaciones alternativas de la materia del presente documento. Las frases, palabras y términos empleados en la presente memoria son ilustrativos, y no son limitantes. Se apreciará que cualquier aspecto de las diferentes realizaciones descritas en la presente memoria se puede combinar en una diversidad de posibles
20 realizaciones alternativas, todas las cuales se entiende que forman parte de la materia reivindicada.
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Claims (1)
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ES16199672T Active ES2743314T3 (es) | 2008-11-07 | 2009-11-06 | Composición de rejuvenecimiento cutáneo fotoactivada oxidativa |
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