WO2011054033A1 - Thérapies d'association utilisant une lumière non ablative et des agents topiques - Google Patents
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- WO2011054033A1 WO2011054033A1 PCT/AU2010/001455 AU2010001455W WO2011054033A1 WO 2011054033 A1 WO2011054033 A1 WO 2011054033A1 AU 2010001455 W AU2010001455 W AU 2010001455W WO 2011054033 A1 WO2011054033 A1 WO 2011054033A1
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- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N2005/065—Light sources therefor
- A61N2005/0651—Diodes
- A61N2005/0652—Arrays of diodes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
- A61N2005/0659—Radiation therapy using light characterised by the wavelength of light used infrared
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
- A61N2005/0661—Radiation therapy using light characterised by the wavelength of light used ultraviolet
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
- A61N2005/0662—Visible light
Definitions
- the present invention in preferred forms, relates to methods for improving skin and treating skin conditions involving combination therapies employing non- ablative, non-coherent and/or coherent light therapy and topical agents. More specifically the present invention relates to synergistic combination treatments employing non-ablative, non-coherent light and/or coherent light therapy and a topical agent.
- LEDs, lasers and other sources of light have been used for the purpose of skin rejuvenation and other skin based therapies.
- a light emitting diode is a small semiconductor that emits non-coherent light when a current is passed through it. Different wavelengths of LED or lasers can be used to target various skin conditions as each wavelength penetrates a different depth to cause a different effect within the skin.
- Topical agents such as cosmeceuticals that include biologically active ingredients are being increasingly used for dermatological applications.
- the present invention provides a method for improving skin comprising a treatment regime including the sequential steps of:
- the present invention also provides a method for treating a skin condition comprising a treatment regime including the sequential steps of:
- the present invention also provides a method for increasing the amount of a product of a skin cell produced over the course of skin phototherapy treatment with non-ablative, non-coherent and/or coherent light including the step of treating the skin, between phototherapy treatments, with an agent that modulates the product of the skin cell.
- the present invention also provides a method of maintaining elevated levels of a product of a skin cell over the course of skin phototherapy treatment with non- ablative, non-coherent and/or coherent light including the step of treating the skin, between phototherapy treatments, with an agent that modulates the product of the skin cell.
- the present invention also provides a method for improving the results of skin phototherapy with non-ablative, non-coherent and/or coherent light, the method comprising the step of treating the skin with an agent that modulates a product of the skin cell, after said phototherapy.
- the present invention still further provides a method for improving skin comprising a treatment regime including the sequential steps of: (i) pretreating the skin to prepare it for light treatment and/or the application of a topical agent post light treatment;
- the present invention also provides a method for improving skin comprising a treatment regime including the sequential steps of:
- the present invention still further provides a method for improving skin comprising a treatment regime including the sequential steps of:
- the present invention also provides a method for improving skin comprising a treatment regime including the sequential steps of:
- the present invention also provides a kit comprising: (i) a means for applying non-ablative, non-coherent and/or coherent light; and (ii) a topical agent for application to the skin to modulate a product of the skin cells therein.
- Figure 1 is before and after photographs illustrating a test subject's result after 8 weeks following the combination LED and topical treatment regime showing reduction in fine lines and wrinkles and improvement in skin smoothness, firmness, overall appearance of skin.
- Figure 2 is before and after photographs illustrating a test subject's result after 8 weeks following the combination LED and topical treatment regime showing reduction of crows feet;
- Figure 3 is before and after photographs illustrating a test subject's result after 8 weeks following the combination LED and topical treatment regime showing reduction of photodamaged skin.
- a treatment regime including the sequential steps of:
- the present invention seeks to improve the patient outcomes from the use of non-ablative, non-coherent and/or coherent light therapies by combining them with topical agents. Whilst not wishing to be bound to any particular mode of effect, it is believed that application of agents to skin cells in accordance with the present invention maintains, establishes or otherwise causes desirable levels of proteins to be produced by the skin cells that are associated with skin improvement. More particularly, there is evidence herein that the use of topical agents in combination with light therapy results in improved protein levels in the skin that are associated with skin improvement.
- improving skin means to increase or enhance a positive characteristic of skin and/or to decrease or negate a negative characteristic of skin.
- coherent light means coherent light that can be used safely to treat subjects and thus generally has a wavelength and dosage that ensures a safe and effective penetration of tissue without ablating the epidermis.
- Coherent light includes low energy radiation including visible light wavelengths, near-IR, mid-1 R, and far-IR wavelengths. Visible red wavelengths (shorter than 800 nm) do not penetrate as far, and are therefore more applicable to superficial tissue and treatment points. Photons emitted at shorter wavelengths do, however, have greater energy/mass which is measured in electron-volts (eV).
- skin cell is any cell type found in the epidermis, dermis or hypodermis of skin and includes fibroblasts, fibrocytes, melanocytes, adipocytes, keratinocytes, macrophages, Langerhans cells and Merkel cells.
- modulate and variants such as “modulating” and “modulation” when used herein in respect of skin cells includes (i) direct and indirect activation of the skin cells to increase or decrease their activity (ii) direct and indirect activation of the skin cells to increase or decrease the levels of a product of the skin cells (iii) direct and indirect increase or decrease of the number of the skin cells.
- any of the above (i)-(iii) modulating effects of the skin cells can occur for a period of 24 hrs, 48 hrs, 72 hrs, or 1 wk after exposure of the skin with non-coherent and/or coherent light has concluded.
- the topical agent is used daily.
- the wavelength and energy dose of the non-ablative, non-coherent or coherent light and the dose of the topical agent may be varied and is preferably adapted to allow for the light and the topical agent to act synergistically.
- the wavelength and light dosage and the agent dosage are adapted to allow for an overall net increase in the level or amount of one or more skin cell products relative to that which may be produced using either of the respective monotherapies, that is using only light or a topical agent.
- the amount of the topical agent is from about 0.1 % to about 0.2%, about 0.1 % to about 0.4%, about 0.4% to about 1 .6%, or about 0.2% to about 2.0%.
- the treatment regime may be repeated at least 2, 3, 5, 10, 50 or 100 times.
- the time between repeats of the treatment regime may be at least 12, 16, 20, 24, 48, or 72 hours or 1 wk.
- the wavelength of the non-ablative, non-coherent or coherent light may be varied to provide for particular treatment outcomes.
- the light has a wavelength selected from the group of wavelengths comprising: 364 nm-1400 nm, 364 nm, 400 nm, 404 nm, 420 nm, 430 nm, 434 nm, 445 nm, 454 nm, 475 nm 560 nm, 633 nm, 663 nm, 675 nm, 750 nm, 810 nm, 830 nm, 840 nm, 860 nm, 890 nm, 904 nm , 950 nm, 980 nm, 1015 nm, 1060 nm, 1260 nm, 1400 nm, 400-440 nm, 620-695 nm, 700-890 nm and any of the preceding wavelengths and/or wavelength ranges +/- 20 nm
- the non-ablative, non-coherent or coherent light may be derived from any source of light that is capable of producing light that is therapeutically useful.
- the non-ablative non-coherent is derived from at least one LED and even more preferably from an LED array.
- each LED in the array has a luminous intensity of about 3000 millicandelas.
- the LED is capable of emitting light of at least two discrete wavelengths.
- non-ablative non-coherent light examples include organic LEDs, light emitting polymers, sulfur lamps, flash lamps, xenon arc lamps, metal halide lamps, broad band intense pulsed light sources, filamentous light sources and lasers filtered to produce a non-ablative, non-coherent light.
- coherent light When coherent light is applied it is preferably light from a low energy laser diode such as a red light laser diode, preferably a visible red light laser diode such as one with a wavelength shorter than 800 nm.
- a low energy laser diode such as a red light laser diode, preferably a visible red light laser diode such as one with a wavelength shorter than 800 nm.
- the laser diode of the present invention may also be capable of emitting light of at least two discrete wavelengths.
- the non-ablative, non-coherent or coherent light may be applied continuously or pulsed.
- the light When the light is pulsed it may have a duration length of about 0.1 milliseconds to about 1 000 milliseconds.
- the pulsed light may have a frequency of about 3Hz and an on time of 200-300ms such as 250ms and an off time of 1 00-200ms such as 1 50ms.
- the light may have a frequency of 92Hz and an on time of 5-6ms such as 5.5ms and an off time of 5-6ms such as 5.5ms.
- the emitted light energy of non-ablative, non-coherent or coherent light applied to the skin may be varied and is preferably no more than about 0.05, 0.1 , 0.5, 1 , 5, 1 0, 50, 1 00, 1 26 or 200 J/cm 2 .
- the emitted light energy is no greater than about 1 0 J/cm 2 and more preferably is no greater than about 2.5 J/cm 2 .
- the intensity of light may be about 1 , 3, 4.74 mW/cm 2 or about 1 to 12 mW/cm 2 .
- the amount of time the light is applied can also be varied but is preferably about 2-4 minutes such as 3 minutes.
- the present invention may be used to treat skin conditions.
- the present invention also provides a method for treating a skin condition comprising a treatment regime including the sequential steps of:
- the skin condition may be related to inappropriate amounts, activities or products of one or more types of skin cell.
- the skin condition is selected from the group comprising: acne, rosacea, wrinkles, scars, inflammation, reduction of pain, tissue and wound healing, photo damage, bacterial or fungal or viral infection, blemishes, lesions, rosacea, psoriasis, eczema, hyperpigmentation and cellulite.
- the present invention may also be used to increase the levels of a skin cell and/or product of a skin cell over the course of a skin phototherapy regime.
- the present invention also provides a method for increasing the amount of a skin cell and/or a product of a skin cell produced over the course of skin phototherapy treatment with non-ablative, non-coherent and/or coherent light including the step of treating the skin, between phototherapy treatments, with a topical agent.
- the present invention may also be used to maintain levels of a skin cell product over the course of a skin phototherapy regime.
- the present invention also provides a method of maintaining elevated levels of a product of a skin cell over the course of skin phototherapy treatment with non-ablative, non-coherent and/or coherent light including the step of treating the skin, between phototherapy treatments, with an agent that modulates the product of the skin cell.
- the present invention may also be used to improve the results of skin phototherapy.
- the present invention also provides a method for improving the results of skin phototherapy with non-ablative, non-coherent and/or coherent light, the method comprising the step of treating the skin with an agent that modulates a product of the skin cell, after said phototherapy.
- the improved result is selected from the group comprising: prolonging at least one treatment outcome; enhancing at least one treatment outcome; expediting at least one treatment outcome; improved overall skin appearance; improved skin smoothness; increased skin softness; increased skin firmness; reduction of wrinkles; reduction of fine lines; and reduction of photodamage.
- kits comprising: (i) a means for applying non- ablative, non-coherent and/or coherent light to the skin to modulate skin cells therein; and (ii) a topical agent for application to the skin to modulate a product of the skin cells therein.
- the means for applying non-ablative, non-coherent or coherent light includes at least one LED or a laser diode and even more preferably an LED or a laser diode array.
- the means includes an LED array, it preferably includes LEDs with a luminous intensity of about 3000 millicandelas.
- the kit includes an LED device capable of emitting light of at least two discrete wavelengths.
- the methods of the present invention may further comprise pretreatment of the skin to facilitate the later method steps.
- Pretreatments can be varied and include exfoliation, microdermabrasion, skin peels and other treatments that remove the stratum corneum or otherwise improve the permeability of the skin such as ultrasound, sonophoresis, treatment with steam or other sources of heat and the use of topical agents that otherwise prepare the skin to receive the light treatment and or the topical agent.
- Preferred agents for use pretreatment include those that alter the refractive index of the skin or target tissue, so that the light may more efficiently penetrate into the skin and the absorption spectrum of the skin or target tissue is closer to the emission spectrum of the non-ablative, non-coherent or coherent light.
- Such agents include one or more agents selected from the group comprising: a vitamin such as Vitamin C, Vitamin E, Vitamin D, Vitamin A, Vitamin K or Vitamin F, retin A, retinol, retinoid derivative, adapalene, hydroquinone, Kojic acid, a growth factor, Echinacea, an antibiotic, an antifungal, an antiviral, a bleaching agent, an alpha hydroxyl acid, beta hydroxy acid, salicylic acid, antioxidant triad compound, a seaweed derivative, a salt water derivative, algae, an antioxidant a phytoanthocyanin, a phytonutrient, plankton, a botanical product, a herbaceous product, a hormone, an enzyme, a mineral, a genetically engineered substance, a cofactor, a catalyst, an antiaging substance, insulin, trace elements, minerals, minoxidil, melanin, a MMP inhibitor, proline, hydroxyproline, an anaesthetic, chlorophyll, bacteriochlorophyll,
- the present invention also provides a method for improving skin comprising a treatment regime including the sequential steps of:
- Fibroblasts synthesize extracellular matrix products, including the structural proteins collagen, elastin; specialized proteins including fibrillin, fibronectin, and laminin; proteoglycans and glycosoaminoglycans (e.g., hyaluronate, dermatin sulphate).
- the present invention also provides a method for improving skin comprising a treatment regime including the sequential steps of:
- the wavelength and energy dose of the non-ablative, non-coherent or coherent light and the dose of the topical agent dosage may be varied and is preferably adapted to allow for the light and the topical agent to act synergistically.
- the fibroblasts are modulated by the light to increase their production of at least one fibroblast cell and/or a fibroblast cell product comprising an extracellular matrix product, such as collagen and/or elastin.
- an extracellular matrix product such as collagen and/or elastin.
- the topical agent modulates collagen and/or elastin levels. This can be achieved by directly or indirectly activating fibroblasts to increase their production. This can also be achieved by the topical agent stimulating the activity of fibroblast to produce skin protein products comprising collagen and/or elastin; or by directly or indirectly suppressing an agent that suppresses fibroblast activity and/or degrades collagen and/or elastin.
- the topical agent modulates collagen or elastin levels by suppressing an agent that degrades collagen or elastin
- the topical agent is preferably an agent that inhibits production of metalloproteinases.
- topical agents include: (i) agents that upregulate TIMPs (tissue inhibitors of metalloproteinases) (ii) vitamin A and its retinoid derivatives that inhibit nuclear transcription factor AP-1 (iii) inhibitors of VEGF or anti-angiogenic agents that reduce the formation of leaky microvasculature (iv) anti-inflammatory inhibitors that inhibit transcription factor N F-KB and pre-inflammatory cytokine genes including IL- 1 B, TNF-a, IL-6, IL-8 and adhesion molecules.
- the topical agent is retinol or a function equivalent of retinol.
- the "functional equivalents of retinol” include retinoids and other agents related to retinol that are capable of inhibiting degradation of collagen and/or otherwise enhancing or maintaining the levels of collagen in the skin.
- the retinoid is a first generation retinoid.
- the retinoid is selected from the group comprising: retinal, tretinoin (retinoic acid), isotretinoin, alitretinoin, or corresponding salts thereof.
- the topical agent modulates collagen or elastin levels by suppressing reactive oxygen species (ROS) and/or free radicals
- the topical agent is preferably selected from the group comprising indocyanine green, methylene blue, rose Bengal, vitamin C, vitamin E, vitamin K, hydroquinone, ascorbate, Kojic acid, and other antioxidants.
- the improved skin is reflected by an improvement in one or more of: overall skin appearance, skin smoothness, wrinkles, fine lines, skin softness and skin firmness.
- the non-coherent and/or coherent light modulating effects of fibroblasts can occur for a period of 24 hrs, 48 hrs, 72 hrs, or 1 wk after exposure of the skin with non-coherent and/or coherent light has concluded.
- the topical agent that acts synergistically with the applied light modulates a product of the fibroblasts and can be applied pre-, during, or post-light treatment.
- the agent is applied daily, and the light treatments occur with at least 24 hours between treatments in wk 1 ; at least 48 hrs between treatments in wks 2-6; and a weekly maintenance treatment thereafter.
- Melanocytes are responsible for the production of melanin and the present invention also provides a method for improving skin comprising a treatment regime including the sequential steps of:
- the wavelength and energy dose of the non-ablative, non-coherent or coherent light and the dose of the topical agent may be varied and is preferably adapted to allow for the light and the topical agent to act synergistically.
- the melanocytes may be modulated by the light to increase their production of melanin to address hypopigmentation including hypopigmentation associated with disorders such as albinism, idiopathic guttate hypomelanosis, leprosy, leucism, phenylketonuria, pityriasis alba, vitiligo, Angelman syndrome or tinea versicolor.
- melanocytes can be modulated by the light to decrease their production of melanin to address hyperpigmentation including hyperpigmentation associated with disorders such as Addison's disease and other diseases where hormones that stimulate melanin synthesis, such as melanocyte-stimulating hormone (MSH) are elevated, Cushing's disease or other diseases associated with excessive adrenocorticotropic hormone (ACTH) production, Acanthosis nigricans, Melasma, Linea nigra, Peutz-Jeghers syndrome, side effects from the use of salicylic acid, bleomycin and/or cisplatin, smoker's melanosis, Celiac disease, Cronkite-Canada syndrome, Porphyria, Tinea fungal infections such as ringworm and Haemochromatosis - a common but debilitating genetic disorder characterized by the chronic accumulation of iron in the body.
- MSH melanocyte-stimulating hormone
- ACTH adrenocorticotropic hormone
- the topical agent can act to decrease melanin levels by directly or indirectly suppressing melanocytes to decrease their production of melanin; or by directly or indirectly activating an agent that suppresses melanocyte activity and/or degrades melanin.
- the topical agent When the topical agent decreases melanin levels it may act via modulating tyrosinase transcription and glycosylation.
- these agents are tretinoin, glucosamine, retinol, N-acetyl glucosamine and retinaldehyde. It may also act via tyrosinase inhibition e.g. Hydroquinone, 4-hydroxy-anisole, arbutin aloesin, azelaic acid and kojic acid; tyrosinase degradation e.g. ellagic acid, resveratrol and oxyresveratrol; inhibition of melanosome transfer e.g. linoleic acid; anti-inflammatory e.g.
- niacinamide soybean/milk extracts
- ROS scavengers e.g. indocyanine green, methylene blue, rose Bengal, vitamin C, vitamin E, vitamin K, hydroquinone, ascorbate, Kojic acid, and other antioxidants
- topical steroids glycyrrhetinic acid
- increased epidermal turnover e.g. Vitamin C, vitamin E, thioctic acid, retinoids, lactic acid, glycolic acid, salicylic acid and liquirtin.
- Other topical agents include, alpha hydroxy acids, topical glucocorticoids, and licorice extract.
- topical agent increases melanin levels it may act via modulating albeit in reverse, one or more of the above agents.
- the topical agent is retinol or a function equivalent of retinol.
- the topical agent may also be a combination of hydroquinone and retinol or a function equivalent of retinol.
- the "functional equivalents of retinol” include retinoids and other agents related to retinol that are capable of decreasing melanin levels in the skin.
- the retinoid is a first generation retinoid.
- the retinoid is selected from the group comprising: retinal, tretinoin (retinoic acid), isotretinoin, alitretinoin, or corresponding salts thereof.
- the improved skin is reflected by an improvement in overall skin pigmentation.
- the topical agent that modulates a product of the melanocytes can be applied at least once a day.
- Other treatment regimes for the post light treatment use of topicals are described elsewhere in this specification.
- Adipocytes also known as lipocytes or fat cells, are the cells that primarily compose adipose tissue and the present invention also provides a method for improving skin comprising a treatment regime including the sequential steps of:
- the wavelength and energy dose of the non-ablative, non-coherent or coherent light and the dose of the topical agent may be varied and is preferably adapted to allow for the light and the topical agent to act synergistically.
- the adipocytes may be modulated by the light to decrease their stored fat to improve one or more skin conditions associated with excess fat stored in adipocytes such as cellulite.
- the topical agent can act to decrease fat levels by directly or indirectly causing breakdown of fat stores within adipocytes. This may be achieved through activation of the lipolytic pathway and/or proteins that are able to hydrolyze triglycerols to fatty acids, such as lipoprotein and/or lipases.
- the topical agent is able to enhance adipocyte lipolysis at the post beta or alpha2 adrenoceptor level.
- suitable topical agents are Bupleurem falcatum extract, methylxanthine caffeine, Coenzyme A and phosphatidylcholine and analogs thereof.
- topical agents are able to enhance adipocyte lipolysis and/or decrease cellulite by suppressing reactive oxygen species (ROS) and/or free radicals.
- ROS reactive oxygen species
- suitable topical agents are indocyanine green, methylene blue, rose Bengal, vitamin C, vitamin E, vitamin K, hydroquinone, ascorbate, Kojic acid, and other antioxidants.
- the topical agent that modulates a product of the adipocytes can be applied at least once a day.
- Other treatment regimes for the post light treatment use of topicals are described elsewhere in this specification.
- Example 1 In Vitro Treatment of Human Skin Cells with LED and Retinoic Acid
- Neonatal human dermal fibroblasts (HDFn cells) (Invitrogen C-004-5C) were handled as recommended in the Invitrogen manual (http://products.invitrogen.com/ivgn/product/C0045C).
- the HDFn cells were propagated in three 75 cm 2 flasks containing Invitrogen Medium 106 with a low serum growth supplement (LSGS) grown to 80% confluence, trypsinised, aliquoted and re-frozen under liquid nitrogen in medium with 10% dimethyl sulfoxide (DMSO).
- LSGS low serum growth supplement
- DMSO dimethyl sulfoxide
- the LED device was mounted inside a plastic housing with an aperture of exactly the size of a well of a six well plate, and fitted with opaque polystyrene (same material as plates) to diffuse light from the LEDs. Cells attached to the plate could thus be exposed through the plastic bottom of the plate, one well at a time, whilst minimising exposure of other wells.
- the samples labelled with the iTRAQ labels are shown in Table 2.
- analysis was carried out using LC-MS/MS using a gas-phase fractionation approach. In this method, the sample is analysed multiple times, focussing on different mass ranges in order to increase the sensitivity and peptide coverage in each mass range. Identification and quantitation of proteins was achieved concurrently through bioinformatic processing of the concatenated dataset using an in-house Mascot protein identification server.
- Relative protein quantitation was achieved by comparing the reporter ion intensities between peptides derived from each sample, and calculating a weighted average of the peptide ratios. Ratios greater than 1 indicate higher abundance of a protein for the sample in the numerator. Ratios smaller than 1 indicate higher abundance of that protein for the sample in the denominator. Only peptides with an identification score greater than 15 were allowed. To contribute to quantitation peptides were required to have a score of at least 25. At least two peptides were required for quantitation of a protein.
- Sample 1 Sample 2 (1 /2)
- Sample 1 Sample 8 (1 /8)
- Sample 3 Sample 1 (3/1 )
- Sample 4 Sample 1 (4/1 )
- Sample 5 Sample 1 (5/1 )
- Sample 6 Sample 1 (6/1 )
- Sample 7 Sample 3 (7/3).
- the first three ratios theoretically, should be approximately unity since they share the same key parameters (no LED light, no retinoic acid). In addition to the raw comparisons, it was decided to also recalculate the ratios based on an average of the three control values. Both the original ratios and the recalculated values are reported.
- the absolute amounts of protein extracted from the cells were small (1 .5 ⁇ 9/ ⁇ on average). In total, 42 proteins were identified (Table 3). These were divided in three tiers according to the strength of the quantitative information. Proteins where the 1 /2, 1 /8 or 2/8 ratios were inside the [0.75-1 .33] interval were ranked in the highest tier (16 proteins in total). Proteins with one or more of these ratios outside the [0.75-1 .33] interval were ranked in the second tier (14 proteins in total). Proteins without or with partial quantitative information were placed in the lowest tier (12 proteins in total).
- Protein name Mascot Accession score number beta actin variant [Homo sapiensl 1015 gi
- AHNAK nucleoprotein isoform 1 [Homo sapiens] 81 gi
- calreticulin precursor [Homo sapiens] 61 gi
- FK506 binding protein 1 A 12kDa [Homo sapiens] 48 gi
- Table 3 shows the list of identified proteins.
- Detailed identification and quantitation data for the Tier 1 and Tier 2 proteins associated with structure e.g. actin
- energy regulation e.g. glyceraldehyde-3-phosphate dehydrogenase
- protection e.g. heat shock proteins
- beta actin variant [Homo sapiens
- annexin A2 isoform 2 [Homo sapiensl
- AHNAK nucleoprotein isoform 1 [Homo sapiens]
- tubulin 5-beta [Homo sapiens]
- lactate dehydrogenase A isoform 1 [Homo sapiens]
- Table 4 shows that upregulation of beta actin, annexin A2, glyceraldehyde-3- phosphate dehydrogenase, peptidylprolyl isomerase A, calreticulin, calmodulin, tubulin 5-beta, and phosphoglycerate kinase is due to the combination of LED and retinoic acid.
- these proteins are downregulated using 10 ⁇ g/mL retinoic acid (as control) or with increasing energy dose exposure of 3, 7.5 and 15 minutes. The levels of these proteins (except for calmodulin) are successively decreased until LED and retinoic acid at 15 minute exposure dramatically reverses this reduced protein level trend.
- the fibroblast protein profiling data shows that an increasing light dose is inhibitory in producing reduced levels of key structural and energy related skin proteins. It is proposed herein that with increasing light doses that other inhibitory molecules (such as, MMPs) are competitively produced that explains the downregulation in the levels of these structure and energy related skin proteins.
- MMPs inhibitory molecules
- the results obtained with low energy LED-retinoic acid indicates that this combination is capable of reversing the action of inhibitory molecules towards positively affecting gene and protein expression of key structural and energy related skin proteins.
- Example 2 In Vivo Skin Rejuvenation using combination treatment of light and a topical
- LED device delivers red light at 660nm (+/-20nm) at pre-set time intervals and is capable of continuous and pulsed modes:
- Dermal cleanser including aqua, sodium laureth sulfate, sodium lauroyl sarcosinate, coco-betaine, PEG-150 pentaerythrityl tetrastearate, glucono- deltalactone, hydroxyethylcellulose, glycol stearate phenoxyethanol and ethylhexylglycerin, salicylic acid, fragrance, polysorbate 20, citric acid, Syzygium luehmanii and Acronychia acidula and Davidsonia pruriens and Glycerin Malus domestica fruit cell culture and lecithin and glycerine and 2-phenoxyethanol and xanthan gum.
- Activator Stimulates light receptors located in the mitochondria of skin cells and contains aqua, glycerin, polyacrylamide (and), C13-14 isoparaffin (and), laureth-7, polysorbate 20, panthenol, cyclopentasiloxane dimethicone, Terminalia ferdinandiana extract (and) Davidsonia pruriens extract (and) alcohol, phenoxyethanol (and) ethylhexylglycerin, Malus domestica fruit cell culture, tocopherol, retinol and disodium edetate.
- Treatment frequency minimum of 3 treatments with at least 24 hours between treatments.
- Topical A Morning and Night and prior to LED therapy treatment Topical B: Apply prior to LED therapy treatment LED Treatment:
- Topical C Apply every 4 hours if exposed to direct sunlight
- Topical D apply every night
- Weeks 2-6 Treatment frequency twice per week with at least 48 hours between treatments.
- Topical A Morning and night and prior to LED therapy treatment
- Topical B Apply prior to LED therapy treatment
- Topical A Morning and Night and prior to LED therapy treatment
- Topical B Apply prior to LED therapy treatment
- LED (i) apply to entire area to be treated (in pulsed mode) for 3 minutes in 15 constant mode
- Topical C Apply every 4 hours if exposed to direct sunlight
- Exclusion criteria comprised those with a history of an inflammatory skin condition, history of photosensitivity reactions, or those who were currently prescribed medication were excluded. Also excluded were those who had used a light skin treatment within 6 months preceding this study, including use of chemical peels/glycolic acid and retinoid treatments within 6 months of the study. Inclusion criteria were those subjects who presented wrinkles or crows feet in the periorbital region, wrinkles or fines lines in the nasolabial region, and those presenting photodamage Glogau grade 11-111 (moderate to advanced photaging).
- Subjects were assessed before and after treatment by a physician involving evaluation of digital photographs, Fitzpatrick skin scale type, Glogau photodamage classification, and tactile grading.
- the physician graded the assessment in accordance with the following: score 1 (100% improvement), score 2 (70% improvement), score 3 (50% improvement), score 4 (25% improvement), score 5 (no response), score 6 (skin condition worsened).
- score 1 (100% improvement)
- score 2 (70% improvement)
- score 3 (50% improvement)
- score 4 (25% improvement
- score 5 no response
- score 6 skin condition worsened
- the subjects completed a self assessment whether the treatment had provided "excellent”, “moderate”, “poor”, or “no effect”.
- the physician graded these responses as > 75% for "excellent”, 50% for "moderate”, ⁇ 20% “poor”, or 0% for "no effect”.
- Group 1 Five subjects received LED treatment and a "sham" topical treatment containing sodium chloride;
- Group 2 Five subjects received a "sham” light treatment (white light, with intensity ⁇ 0.01 watts/cm 2 ) and a “sham” topical treatment containing sodium chloride.
- the physician evaluation results obtained indicates that using the combination LED-topical (actives) treatment regime has significant benefit in reducing wrinkles and improving skin softness and elasticity in comparison to the skin results obtained from the two control groups.
- the self-assessment by these subjects also compared favorably with the physician assessment results with an average 70% indicating reduction of wrinkles and improvement in skin softness and elasticity, which corresponds to 8 subjects indicating "excellent” results and two subjects indicating "moderate” results.
- two subjects were clinically evaluated as having a score 2 (70%) improvement in "crows feet” and two subjects had a score 2 (70%) improvement in photodamaged skin.
- the skin improvement results in reduction of wrinkles, crows feet, photodamaged for one typical subject is shown in Figures 1 , 2, and 3.
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Abstract
La présente invention concerne un procédé pour améliorer la peau et/ou traiter des affections de la peau comprenant un régime de traitement d'association comprenant les étapes séquentielles de : (i) application de lumière non ablative, non cohérente et/ou cohérente sur la peau pour moduler des cellules cutanées dans celle-ci; et (ii) application d'un agent topique sur la peau pour moduler un produit desdites cellules cutanées.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2009905419A AU2009905419A0 (en) | 2009-11-06 | Combination Therapies Employing Non-ablative, Non-coherent Light and Topical Agents | |
AU2009905419 | 2009-11-06 |
Publications (1)
Publication Number | Publication Date |
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WO2011054033A1 true WO2011054033A1 (fr) | 2011-05-12 |
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ID=43969469
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/AU2010/001455 WO2011054033A1 (fr) | 2009-11-06 | 2010-11-03 | Thérapies d'association utilisant une lumière non ablative et des agents topiques |
Country Status (1)
Country | Link |
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WO (1) | WO2011054033A1 (fr) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013186108A2 (fr) * | 2012-06-15 | 2013-12-19 | L'oreal | Procédé de matification des peaux grasses |
WO2014141188A1 (fr) * | 2013-03-14 | 2014-09-18 | Medos International Sarl | Coadministration de la lumière et d'un agent thérapeutique pour stimuler des mitochondries dysfonctionnelles affectées par un trouble neurologique |
CN112752566A (zh) * | 2018-07-27 | 2021-05-04 | 强生消费者公司 | 显示出类视黄醇活性的植物提取物和细菌提取物 |
Citations (7)
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US6106514A (en) * | 1996-08-12 | 2000-08-22 | O'donnell, Jr.; Francis E. | Laser method for subsurface cutaneous treatment |
WO2003059144A2 (fr) * | 2002-01-14 | 2003-07-24 | Parsons Diana J | Procede et procedure permettant de laisser la peau souple, avec de petits pores et un aspect jeune |
US20050021012A1 (en) * | 2001-12-12 | 2005-01-27 | Bernstein Eric F | Laser treatment for reducing wrinkles |
US20050197681A1 (en) * | 2004-02-06 | 2005-09-08 | Lumiphase Inc. | Method and device for the treatment of mammalian tissues |
US20080015554A1 (en) * | 2004-07-16 | 2008-01-17 | Cole Curtis A | Treatment of skin with light and a benefit agent to mitigate acne |
US20090192438A1 (en) * | 2008-01-25 | 2009-07-30 | Jones Dennis R | Use of Iontophoresis or Electrotherapy and Ultrasound to Deliver Melanin for Skin Rejuvenation |
US20090246270A1 (en) * | 2008-01-31 | 2009-10-01 | Jones Dennis R | Use of Iontophoresis or Electrotherapy and Ultrasound to Deliver Agents for Skin Rejuvenation. |
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2010
- 2010-11-03 WO PCT/AU2010/001455 patent/WO2011054033A1/fr active Application Filing
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6106514A (en) * | 1996-08-12 | 2000-08-22 | O'donnell, Jr.; Francis E. | Laser method for subsurface cutaneous treatment |
US20050021012A1 (en) * | 2001-12-12 | 2005-01-27 | Bernstein Eric F | Laser treatment for reducing wrinkles |
WO2003059144A2 (fr) * | 2002-01-14 | 2003-07-24 | Parsons Diana J | Procede et procedure permettant de laisser la peau souple, avec de petits pores et un aspect jeune |
US20050197681A1 (en) * | 2004-02-06 | 2005-09-08 | Lumiphase Inc. | Method and device for the treatment of mammalian tissues |
US20080015554A1 (en) * | 2004-07-16 | 2008-01-17 | Cole Curtis A | Treatment of skin with light and a benefit agent to mitigate acne |
US20090192438A1 (en) * | 2008-01-25 | 2009-07-30 | Jones Dennis R | Use of Iontophoresis or Electrotherapy and Ultrasound to Deliver Melanin for Skin Rejuvenation |
US20090246270A1 (en) * | 2008-01-31 | 2009-10-01 | Jones Dennis R | Use of Iontophoresis or Electrotherapy and Ultrasound to Deliver Agents for Skin Rejuvenation. |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013186108A2 (fr) * | 2012-06-15 | 2013-12-19 | L'oreal | Procédé de matification des peaux grasses |
FR2991871A1 (fr) * | 2012-06-15 | 2013-12-20 | Oreal | Procede pour matifier la peau grasse |
WO2013186108A3 (fr) * | 2012-06-15 | 2014-05-30 | L'oreal | Procédé de matification des peaux grasses |
WO2014141188A1 (fr) * | 2013-03-14 | 2014-09-18 | Medos International Sarl | Coadministration de la lumière et d'un agent thérapeutique pour stimuler des mitochondries dysfonctionnelles affectées par un trouble neurologique |
CN112752566A (zh) * | 2018-07-27 | 2021-05-04 | 强生消费者公司 | 显示出类视黄醇活性的植物提取物和细菌提取物 |
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