WO2010102183A1 - Procédés d'amélioration de l'activité peroxyde - Google Patents

Procédés d'amélioration de l'activité peroxyde Download PDF

Info

Publication number
WO2010102183A1
WO2010102183A1 PCT/US2010/026327 US2010026327W WO2010102183A1 WO 2010102183 A1 WO2010102183 A1 WO 2010102183A1 US 2010026327 W US2010026327 W US 2010026327W WO 2010102183 A1 WO2010102183 A1 WO 2010102183A1
Authority
WO
WIPO (PCT)
Prior art keywords
skin
energy
peroxide
light
chromophore
Prior art date
Application number
PCT/US2010/026327
Other languages
English (en)
Inventor
Jose E. Ramirez
Joseph R. Faryniarz
Original Assignee
Jr Chem, Llc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Jr Chem, Llc filed Critical Jr Chem, Llc
Priority to EP10708471A priority Critical patent/EP2403533A1/fr
Priority to CA2754840A priority patent/CA2754840A1/fr
Publication of WO2010102183A1 publication Critical patent/WO2010102183A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/327—Peroxy compounds, e.g. hydroperoxides, peroxides, peroxyacids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/38—Percompounds, e.g. peracids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/81—Preparation or application process involves irradiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q15/00—Anti-perspirants or body deodorants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/004—Aftersun preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/008—Preparations for oily skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations

Definitions

  • This disclosure relates to the preparation of compositions containing organic peroxide in solution and methods of enhancing the activity of the peroxide by application of energy.
  • Peroxide activity can be enhanced by chemical and photodecomposition, enhancing micro spectrum and also for whitening of skin and nails.
  • benzoyl peroxide (BPO) is the peroxide used.
  • BPO benzoyl peroxide
  • the interaction of the energy with the peroxide can intensify the action of solubilized peroxide for the treatment of acne, including cystic acne.
  • BPO action against cystic sebaceous glands can be enhanced by photo dynamic excitation of the molecule in accordance with the present disclosure.
  • BPO solubilized in an appropriate vehicle will penetrate the follicle.
  • electromagnetic energy of the appropriate wavelength excites BPO to a higher energy electronic state, the solubilized BPO molecule will act as a stronger oxidizing agent increasing the availability of the peroxide degradation products in the cystic nodule.
  • selective photothermolysis of the sebaceous glands followed by solubilized BPO treatment are performed in a treatment regimen in accordance with the present disclosure.
  • a chromophore is used in connection with the energy treatment.
  • an amine initiator is used in conjunction with the peroxide composition and the application of energy to the area of skin to be treated.
  • Solubilized BPO has a better, faster follicular kill which is enhanced into the sebaceous glands, especially for cystic and nodular acne, the most extreme forms of acne.
  • Methods in accordance with the present disclosure include applying an organic peroxide solution to the skin of a user, and then exposing the peroxide-treated skin with an energy source.
  • the Organic Peroxide Compositions include applying an organic peroxide solution to the skin of a user, and then exposing the peroxide-treated skin with an energy source.
  • Organic peroxide refers generally to any organic molecule containing the peroxide functional group ROOR'.
  • Suitable non-limiting examples of organic peroxides for use in accordance with the present disclosure include any in the following classes: diacyl, dialkyl, hydroperoxides, ketone peroxides, peroxyesters, peroxyketals, peroxydicarbonates, and combinations thereof.
  • Additional non-limiting examples of organic peroxides include acetone peroxide, benzoyl peroxide, cumene hydroperoxide, methyl ethyl ketone peroxide, pinane peroxide, diethyl ether peroxide.
  • the organic peroxide is benzoyl peroxide.
  • the amount of organic peroxide employed in the composition will depend on a number of factors including, but not limited to the nature of the organic peroxide, the concentration of the organic peroxide, the nature of any solvents present and the nature of the ultimate product to be formulated using the composition. Typically however, the organic peroxide will be present in an amount of about 1 to 70 percent by weight of the total composition. In particularly useful embodiments, the organic peroxide will be present in an amount of about 2 to 35 percent by weight of the total composition.
  • Benzoyl peroxide is normally commercially available as either pure (98% active) crystals or in a wet crystalline state containing 70 to 80% active benzoyl peroxide in 20- 30% water.
  • Such benzoyl peroxide products are commercially available from The Norac Company Inc., Azusa, CA under the BENOX ® tradenames or from EIf Atochem North America, Inc., Philadelphia, PA under the LUCIDOL ® tradenames. Any of these or other forms of benzoyl peroxide can be mixed with the disclosed solvents to form compositions in accordance with this disclosure.
  • the benzoyl peroxide is present in an amount of about 2 to about 35 weight percent of total composition.
  • the benzoyl peroxide is present in an amount of about 2 to about 15 weight percent of the total composition.
  • Solvents useful for preparing solutions in accordance with the present disclosure include any solvent capable solubilizing the organic peroxide. Non-limiting examples of such solvents include short chain alkyl esters, ethers, aldehydes, ketones or alcohols of benzoic acid, benzyl alcohol, salicylic acid, phenol or phthalic acid. As used herein "short chain” refers to a molecule having two to six carbon atoms (C 2 -C 6 ).
  • compositions in accordance with the present disclosure include one or more of the following classes of solvent: alkyl esters of benzoic acid, alkyl esters of benzyl alcohol, alkyl esters of salicylic acid, alkyl esters of phenol, alkyl esters of phthalic acid, alkyl ethers of benzyl alcohol, alkyl esters of phthalic acid, alkyl ethers of benzyl alcohol, alkyl ethers of phenol.
  • suitable solvents include benzoyl benzoate, benzoyl alcohol, diethyl phthalate, benzoic acid 2-phenyl ethyl ester, methyl salicylate, ethyl salicylate, propyl salicylate, butyl salicylate, ethyl benzoate, methyl benzoate, propyl benzoate, butyl benzoate, dimethyl phthalate, diethyl phthalate, benzyl ethyl ether, benzyl methyl ether, phenetole, phenyl acetone, phenyl ethyl alcohol, phenoxyethanol, phenyl acetaldehyde, ethyl phenyl acetate, phenyl methyl ketone, phenyl acetate, benzyl acetate, benzyl aceto acetate, benzyl formate, benzaldehyde, benzyl alcohol,
  • the amount of solvent mixed with the organic peroxide will vary depending on a number of factors, including, for example, the ultimate form of the product and the particular solvent employed. Generally, the solvent will be present in an amount of about 1 to about 70 weight percent of the total organic peroxide/solvent mixture. In embodiments, the solvent will be present in an amount of about 10 to about 50 weight percent of the total composition. In embodiments, the solvent will be present in an amount of about 20 to about 40 weight percent of the total composition. In embodiments, solvent is present in amounts effective for dissolving organic peroxide.
  • compositions in accordance with the present disclosure may contain one or more secondary solvents.
  • Suitable secondary solvents include, for example, ethanol, acetone, dimethyl isosorbide, and glycol ethers of Ci to C ⁇ alcohols with no greater than 2 moles of ethylene oxide.
  • Suitable glycol ethers include glycol ethers of phenol with no greater than 2 moles of ethylene oxide, glycol ethers of methanol with no greater than 2 moles of ethylene oxide, glycol ethers of ethanol with no greater than 2 moles of ethylene oxide and glycol ethers of propanol with no greater than 2 moles of ethylene oxide.
  • Non-limiting examples of such co-solvents include phenoxy ethanol, ethoxy diglycol and propylene glycol methyl ether.
  • the amount of secondary solvent mixed with the organic peroxide/solvent mixture will vary depending on a number of factors, including, for example, the ultimate form of the product and the particular solvent and/or secondary solvent employed. Generally, the secondary solvent will be present in an amount of about 1 to about 40 weight percent of the total composition. In embodiments, the secondary solvent will be present in an amount of about 5 to about 30 weight percent of the total composition. In embodiments, the secondary solvent will be present in an amount of about 10 to about 20 weight percent of the total composition.
  • benzoyl peroxide in pharmaceutical industry is based on several chemical properties. Benzoyl peroxide is considered a mild antimicrobial compound that will control P. Acnes bacteria. Benzoyl peroxide free radicals can attack the cell walls of the bacteria thus destroying the bacteria. Secondly, the decomposition of the benzoyl peroxide will result in forming benzoic acid, benzene, phenyl benzoate and biphenyls, all of which can be toxic to cells. Lastly, it has even been proposed that because anaerobic P. Acnes cannot live in the presence of oxygen, oxygen available from the benzoyl peroxide may also kill the bacteria. The exact mechanism for the antimicrobial properties for benzoyl peroxide is however unknown. What is known is that chemical reactions take place on an individual molecular level. Molecules in solution will react much more readily than in solid crystal form.
  • the decomposition of the organic peroxide (although believed to be desired in order to achieve effectiveness) must be controlled in order to allow use of solutions while providing sufficient storage life.
  • Decomposition of organic peroxides can occur via a variety of mechanisms, such as the following three mechanisms: 1.
  • the thermolysis decomposition of diacyl peroxide (benzoyl peroxide is given below): Il0- -» 2R- + 2 CO 2
  • Induced decomposition is represented by the following equation where a free radical attacks a peroxide to generate and ester and a different free radical, but no carbon dioxide.
  • R-C-OO-C-R - R-O-C-O-C-R ⁇ > R-OH + CO 2 + R-C-OH
  • Organic peroxides will have different stability depending on a variety of factors including, but not limited to solvent type, solvent polarity, impurities, peroxide concentration and the occurrence of radical-induced decomposition.
  • Peroxides decompose in more polar or polarizable solvents.
  • Solvents such as benzoates have greater solution stability, which may be attributed to the delocalized electrons of the benzene ring.
  • compositions in accordance with this disclosure include at least one antioxidant in combination with one or more organic peroxides.
  • the antioxidant may be any of the type materials that are soluble in the solvent carrier for the desired organic peroxide, and/or soluble or dispersible in the organic peroxide itself.
  • Suitable non- limiting examples of antioxidants for oil soluble systems include, but are not limited to, butylated hydroxyl toluene (BHT) 1 butylated hydroxyanisole (BHA), vitamin E acetate, ascorbyl palmitate, tetrahydrocurcuminoids, t-butyl hydroquinone, meta and para cresols, phenolics and the like, and combinations of these antioxidants.
  • antioxidants can be used in making the present compositions and/or formulations.
  • the amount of antioxidant employed in the composition will depend on a number of factors including, but not limited to the nature of the organic peroxide, the concentration of the organic peroxide, the nature of any solvents present and the nature of the ultimate product to be formulated using the composition.
  • the antioxidant is present in an amount of about 0.1 to 30 percent by weight of the total composition.
  • the antioxidant is present in an amount of about 0.1 percent to 10 percent by weight of the total composition.
  • the amount of peroxide mixed with the antioxidant will vary depending on a number of factors, including, for example, the activity of the peroxide, the ultimate form of the product and the particular disclosed solvent employed.
  • benzoyl peroxide will be present in an amount of about 1 to about 70 weight percent of the benzoyl peroxide/antioxidant mixture.
  • reducing agent antioxidants in solutions with oxidizer organic peroxides can be used to decrease the effects of thermal decomposition.
  • Antioxidants are normally used as sacrificial materials that are more easily oxidized over the material that is to be protected. For some unknown reason, the quenching of the free radicals formed, prevents the further decomposition of the organic peroxide.
  • the generation of carbon dioxide gas is possible by thermolysis or heterolytic decomposition.
  • the heterolytic decomposition reaction does not involve generation of a free radical so it is not evident that use of an antioxidant will affect this reaction outcome.
  • the free radical is a direct consequence of the peroxide splitting at the oxygen bonds.
  • the antioxidant might prevent the intermediate free radical from further splitting and giving off CO2, but does not give an indication that the organic peroxide would be kept from splitting in the first place.
  • an antioxidant in accordance with the present disclosure can be used to improve the stability of organic peroxides in any type of composition, such as for example, emulsions or suspensions, in embodiments, the antioxidants are used to stabilize organic peroxides in solutions of the organic peroxide.
  • the reduced decomposition of the organic peroxide provided by the present compositions improves the shelf life of products formulated using the compositions, a result which would not normally be obtained.
  • stable or “stability” refers to the ability of a material or composition to remain unchanged in the presence of heat, moisture or air. With respect to shelf life the terms further can refer to compositions that, when in a closed container, remain within the tolerances and limits set forth in US Pharmacopoeia and/or the US FDA guidelines or monographs for compositions containing organic peroxides.
  • the ratio of organic peroxide to antioxidant is about 10:1 by weight of the composition, as well as about 2.5:1 by weight of the composition.
  • suitable compositions include a stable mixture of organic peroxide and antioxidant, wherein the weight ratio of organic peroxide to antioxidant is about 2.5:1 to about 10:1.
  • the composition is a solution having less than 2% antioxidant, and no more than about 10% organic peroxide.
  • suitable embodiments such as solutions have an amount of about 5 to 10% antioxidant, and no more than about 20% organic peroxide.
  • the compositions may have a ratio of organic peroxide to antioxidant between about 10:1 by weight of the composition.
  • compositions have a ratio of organic peroxide to antioxidant between about 2.5:1 by weight of the composition.
  • suitable solutions include a stable mixture of organic peroxide and antioxidant, wherein the weight ratio of organic peroxide to antioxidant is about 2.5:1 to about 10:1.
  • the organic peroxide is dissolved into a solvent to the limits of solubility. The additional ingredients and the antioxidants can then be added to the composition to formulate the final desired product.
  • thickeners and/or rheology modifiers such as fumed silica may be added to the organic peroxide solutions of the present disclosure to increase the viscosity of the compositions and/or gel the compositions.
  • the thickener and/or rheology modifiers may be present in an amount of about 0.1 to about 10 weight percent of the total composition. Any thickener or rheology modifier can be used so long as it does not react with the organic peroxides.
  • products containing organic peroxide compositions in accordance with the present disclosure can be in the form of solutions, emulsions (including microemulsions), suspensions, creams, fluid cream, oils, lotions, gels, powders, sticks, or other typical solid or liquid compositions used for treatment of undesirable skin conditions.
  • compositions may contain, in addition to the organic peroxide solutions in accordance with this disclosure, other ingredients typically used in such products, such as other active cosmetic substances such as retinol, retinol derivatives, allantoin, tocopherol, tocopherol derivatives, niacinamide, phytosterols, isoflavones, panthenol, panthenol derivatives, bisabolol, famesol, and combinations thereof, other active drug substances such as corticosteroid, metronidazole, sulfacetamide, sulfur, and combinations thereof, antioxidants, antimicrobials, coloring agents, detergents, dyestuffs, emulsifiers, emulsifying wax, emollients, fillers, fragrances, gelling agents, hydration agents, moisturizers, odor absorbers, natural or synthetic oils, penetration agents, powders, preservatives, solvents, surfactants, thickeners, viscosity-controlling agents, water, distilled water, waxe
  • compositions may also contain, in addition to the organic peroxide and/or organic peroxide compositions in accordance with this disclosure, one or more: fatty alcohols, fatty acids, organic bases, inorganic bases, wax esters, steroid alcohols, triglyceride esters, phospholipids, polyhydric alcohol esters, fatty alcohol ethers, hydrophilic lanolin derivatives, hydrophilic beeswax derivatives, cocoa butter waxes, silicon oils, pH balancers, cellulose derivatives, hydrocarbon oils, or mixtures and combinations thereof.
  • fatty alcohols fatty acids, organic bases, inorganic bases, wax esters, steroid alcohols, triglyceride esters, phospholipids, polyhydric alcohol esters, fatty alcohol ethers, hydrophilic lanolin derivatives, hydrophilic beeswax derivatives, cocoa butter waxes, silicon oils, pH balancers, cellulose derivatives, hydrocarbon oils, or mixtures and combinations thereof.
  • product forms can be formulated to contain humectant in amounts from about 1 % to about 15% by weight of the total composition.
  • humectant in amounts from about 1 % to about 15% by weight of the total composition.
  • glycerine can be added to the composition in amounts from about 1% to about 15% by weight of the total composition.
  • glycerine can be added to the composition in amounts from about 1 % to about 5% by weight of the total composition.
  • product forms can be formulated to contain solvent in an amount of about 1 % to about 45% by weight of the total composition.
  • solvent such as propylene glycol
  • propylene glycol, polyethylene glycol, ethoxy diglycol can be added to the composition in an amount of about 15% to about 30% by weight of the total composition.
  • product forms can be formulated to contain water in an amount of about 40% to about 99% by weight of the total composition.
  • distilled water can be added to the composition in an amount of about 40% to about 99% by weight of the total composition.
  • distilled water can be added to the composition in an amount of about 65% to about 80% by weight of the total composition.
  • organic peroxide compositions in accordance with the present disclosure are useful in the formation of oil-in-water emulsion product forms.
  • the compositions may include an aqueous phase.
  • Conventional emulsion formulation typically requires mixing the aqueous phase ingredients and the dispersant with heating until a uniform solution or dispersion is obtained (optionally in several stages), mixing the organic phase ingredients with heating until a uniform solution or dispersion is obtained (also optionally in several stages), then adding the aqueous phase to the organic phase with agitation (e.g. stirring or other shearing or heating technique) to form an oil-in-water emulsion of the two phases.
  • agitation e.g. stirring or other shearing or heating technique
  • heating steps are problematic in that heat decomposes organic peroxides such as benzoyl peroxide.
  • the present compositions are capable of a low temperature blending and shearing techniques that do not require an intensive heating step. Accordingly, such blending can occur at room temperature.
  • the aqueous phase constituting the dispersion medium may include any suitable surfactant, humectant, suspending agent, and/or buffer systems, and combinations thereof suitable for combining with organic peroxide compositions in accordance with the present disclosure.
  • Non-limiting examples of suitable surfactants include natural compounds, such as phospholipids and cholates, or nonnatural compounds such as: polysorbates, which are fatty acid esters of polyethoxylated sorbitol; polyethylene glycol esters of fatty acids from sources such as castor oil; polyethoxylated fatty acid, e.g.
  • stearic acid octylphenolpoly(ethyleneglycolether); polyethoxylated isooctylphenol/formaldehyde polymer; poloxamers, e.g., poly(oxyethylene)poly(oxypropylene) block copolymers; polyoxyethylene fatty alcohol ethers; polyoxyethylene nonylphenyl ethers; polyoxyethylene isooctyl phenyl ethers; SDS, and combinations thereof.
  • non-limiting examples of suitable mixtures of surfactant molecules are acceptable.
  • Surfactants should be suitable for cosmetic or pharmaceutical administration and compatible with the benzoyl peroxide to be delivered.
  • Non-limiting examples of surfactants include phospholipids such as phosphatidylcholines (lecithins), including soy or egg lecithin.
  • Other suitable phospholipids include phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, phosphatidic acid, cardiolipin, and phosphatidylethanolamine. The phospholipids may be isolated from natural sources or prepared by synthesis.
  • Non-limiting examples of suitable suspending agents include the following constituents: polyacrylamide, C 13-14 isoparaffin & laureth 7; C13-14 isoparaffin, mineral oil, polyacrylate, polyacrylamide and ethoxylated sorbitan ester; acrylamide/sodium acryloyldimethyl taurate copolymer, isohexadecane and ethoxylated sorbitan ester; and combinations thereof.
  • any cosmetically or pharmaceutically acceptable suspending agent suitable for combining with benzoyl peroxide may be used.
  • humectants include glycerin, however any material capable of obtaining moisture may be added provided it is stable with organic peroxide.
  • the products formulated with the present solutions can be packaged in any type of container within the purview of those skilled in the art, including, but not limited to bottles, tubes, pump type, roll-ons, daubers, wipes, and the like.
  • the organic peroxide compositions in accordance with the present disclosure can be topically applied to skin in need of improvement in order to reduce or eliminate undesirable skin conditions.
  • the word "treat,” “treating” or “treatment” refers to using the compositions of the present disclosure prophylactically to prevent outbreaks of undesirable skin condition such as Acne Vulgaris, or therapeutically to ameliorate an existing undesirable skin condition.
  • a number of different treatments are now possible, which reduce and/or eliminate skin conditions such as Acne Vulgaris.
  • skin condition refers to any detectable skin manifestations caused by one or more pathogens or microbes. Such manifestations can be compounded due to a number of factors such as, for example, chronological aging, environmental damage, and/or other diseased or dysfunctional state. Non-limiting examples of such manifestations include the development of skin lines, crevices, bumps, comedones, craters, scaliness, flakiness and/or other forms of skin unevenness, roughness, or mottled appearance. It is understood, that the listed skin conditions are non-limiting and that only a portion of the skin conditions suitable for treatment in accordance with the present disclosure are listed herein.
  • compositions for use in accordance with the present disclosure contain organic peroxide in an effective amount to improve undesirable skin conditions.
  • effective amount refers to an amount of a compound or composition having organic peroxide constituents in accordance with the present disclosure that is sufficient to induce a particular positive benefit to skin having a skin condition.
  • the positive benefit can be health-related, or it may be more cosmetic in nature, or it may be a combination of the two.
  • the positive benefit is achieved by contacting skin with a combination of solvated organic peroxide, and/or one or more antibiotic constituents, to improve a skin condition such as Acne Vulgaris.
  • the particular organic peroxide concentration in the compositions generally depends on the purpose for which the composition is to be applied. For example, the dosage and frequency of application can vary depending upon the type and severity of the skin condition.
  • Suitable energy sources include, but are not limited to LEDs, ultrasound, laser or light energy, microwave energy and radio frequency energy. Exemplary of known light sources are fluorescent lights, flashlamps, filamentous lights, etc.
  • any light source capable of emitting electromagnetic radiation at a medically useful wavelength, as described herein, directly, or by means of optical filtration, is within the scope of suitable light sources according to the present disclosure.
  • any source capable of emitting light having a wavelength from about 300 nm to about 1400 nm, or producing electromagnetic radiation which is filtered or otherwise altered to exposure the skin, a topical composition, or other component of the present treatment regime to a wavelength of light in the aforementioned range is "medically useful".
  • the peroxide treated skin may be exposed to one or more wavelengths of LED, laser or non-laser light such as filtered filamentous sources or fluorescent sources or single or multiple frequencies of ultrasound.
  • a variety of parameters may be used (including pulse duration, energy, single or multiple pulses, the interval between pulses, the total number of pulses, etc.) to deliver sufficient cumulative energy to interact with the chromophore or tissue complex.
  • Ultrasound may also be used to preheat the target structures or the entire skin.
  • the light source may be diffused through a device such as a holographic diffuser.
  • the light source may be comprised of an array of individual emitters such as the three-panel array of LEDs.
  • smaller arrays or individual LEDs such as in commercially available hand held devices may be used. Since LED sources are considered "insignificant risk devices," no medical supervision is required and these devices may be used by the patient for at-home treatment or as part of an ongoing skin-care system after receiving treatment by a physician.
  • lasers such as yellow, green and blue wavelength lasers which produce laser light suitable of being absorbed by an exogenous chromophore
  • lasers include Argon ion lasers, Copper-vapor lasers, alexandrite lasers, ruby lasers, semiconductor diode lasers, frequency-doubled Nd:YAG lasers, and other dye lasers pumped by a Nitrogen laser or Argon-ion laser and the like.
  • the lasers and other light sources within the scope of the present disclosure may be pulsed but may also operate in a continuous-wave (cw) mode with a scanner to automatically scan the treatment area and provide temporal modulation of the laser intensity on the treatment site.
  • cw continuous-wave
  • Some examples of possible operating parameters for the energy delivery device may include the wavelength of the electromagnetic radiation, the duration of pulses (pulse duration) of the electromagnetic radiation, the number of pulses, the duration between pulses (also referred to as repetition rate or interpulse interval), the energy intensity of the radiation as measured at the living tissue (typically measured in Joules per centimeter squared, watts per centimeter squared, etc.).
  • the pH of the cell, tissue or skin, the skin temperature, and time from application to treatment with a light source are additional parameters to be considered. Intervals between treatments can be as long as hours, days, weeks, months, etc., and the total number of treatments is determined by the response of the individual patient.
  • Each target cell or subcellular component, or molecular bond therein tends to have at least one unique and characteristic "action spectrum" at which it exhibits certain electromagnetic or light absorption peaks or maxima.
  • Different cell lines (of the same cell-for example fibroblasts from 3 different patients) may exhibit some differences in their absorption spectra and thus using narrow band multichromatic light (rather than monochromatic light) can also be useful in producing a desired clinical effect.
  • narrow band multichromatic light rather than monochromatic light
  • the wavelength should roughly correlate with absorption maxima for the target cell or subcellular component or tissue, or exogenous chromophore. In some cases it may be desirable to target more than one maxima-either simultaneously or sequentially on the same or different treatment dates. The presence of multiple maxima action spectra is common for a given cell or subcellular component or exogenous chromophore and different wavelength maxima irradiation may produce different results. If the wavelength band is overly broad, then the desired photomodulation effects may be altered from those intended. Consequently, use of broad band non-coherent intense light sources or multiple narrowband emitters may be used in accordance with the present disclosure.
  • the laser diodes are also multi-chromatic with narrow wavelength bands around a dominant band, i.e., they are narrowband multi-chromatic devices-devices which emit electromagnetic in a narrow band of radiation either symetrically or asymetrically around a dominant wavelength.
  • any device that emits electromagnetic radiation in a bandwidth of +/- about 1000 nanometers around a dominant wavelength can be considered to be a narrowband, multichromatic emitter.
  • LEDS while not monochromatic, emit in such a narrow band as to be considered narrowband multichromatic emitters.
  • the narrow band allows photons of slightly different wavelengths to be emitted. This can potentially be beneficial for creating certain desirable multi photon interactions.
  • most commercial lasers emit light at a single wavelength of light and are considered monochromatic. The use of lasers has relied upon the coherent, i.e., monochromatic, nature of their electromagnetic emissions.
  • Wavelength may also determine tissue penetration depth, ensuring that the desired target cell, tissue or organ is reached.
  • Tissue penetration depth for intact skin may be different than the tissue penetration depth for ulcerated or burned skin and may also be different for skin that has been abraded or enzymatically peeled or that has had at least a portion of the stratum corneum removed by any method. Any interfering chromophore that also absorbs at this same wavelength (e.g. dark ethnic skin, plastic Petrie dishes for tissue or cell culture, etc.) should also be penetrated.
  • light having a dominant wavelength emission in the range of about 400 nm to about 420 nm has such a short wavelength that not all sebaceous glands or acne cysts can be effectively treated due to the limited depth of penetration of the radiation, whereas light having a wavelength of about 600 nm to about 660 nm can more easily penetrate to a greater depth, if treatment of the lower dermal layers or even deeper is desirable. Accordingly, the selection of the dominant wavelength of the radiation emitter is also dependent on the depth of treatment desired.
  • useful wavelengths are between about 700 nm and about 1200 nm, in embodiments between about 750 nm and about 850 nm and in other embodiments between about 800 nm and about 820 nm.
  • 810 nm is a particularly useful wavelength since melanin, the primary human skin pigment, does not absorb strongly at that wavelength.
  • commonly used topical acne treatments such as Retin-A® (all-trans-retinoic acid), typically absorb light at about 351 nm. Thus, acne patients may undergo the treatment methods described here while continuing with other topical acne treatments.
  • the energy density corresponds to the amount of energy delivered during irradiation and is also referred to as energy intensity and light intensity.
  • the optimal 'dose' is affected by pulse duration and wavelength.
  • the delivered fluence of pulsed laser light is between about 1 J/cm2 and about 50 J/cm2, preferably between about 5 J/cm2 and about 40 J/cm2 and more preferably about 10 J/cm2.
  • the exposure time for the irradiation varies with the desired effect and the target cell, subcellular component, exogenous chromophore tissue or organ, (e.g. 0.5 microseconds to 10 min may be effective for human fibroblasts, though greater or lesser may also be used successfully).
  • the laser light has a pulse duration less than the thermal relaxation time of the volume of tissue being irradiated. Specific pulse durations include between 0.1 milliseconds and about 500 milliseconds, in embodiments between about 1 millisecond and about 200 milliseconds.
  • the energy requirements are different if pulsed mode is used compared to continuous (CW) modes.
  • the pulsed mode is preferred for certain treatment regimen and the CW mode for others.
  • the irradiated spot size is sufficient to include the manifestation of the unwanted skin condition of interest as a whole or portions thereof.
  • the spot size is sufficient to include not only the acne, but also an area of normal tissue adjacent to or surrounding the acne to be treated which may include sebaceous glands which have not yet developed into visible acne, e.g. preferentially the entire holocrine gland and surrounding tissue including other sebaceous glands are treated.
  • the area of visibly normal tissue adjacent to or surrounding the acne to be treated is referred to herein as the "margin” or "margin of tissue.”
  • the laser light has a spot size sufficient to irradiate only the margin or portions thereof, or part of the margin and part of the acne.
  • Spot sizes in accordance with the present disclosure include those between about 1 mm to about 20 mm, in embodiments about 5 mm to about 15 mm.
  • the spot size may be smaller, e.g. about 500 /vm to about 1 mm for use in infants, or larger, e.g. about 20 mm to about 30 mm for use in adults having larger sebaceous glands.
  • the spot size may be reduced during use by adjustment of the optical fiber aperture, e.g. the spot size can be increased or decreased during use.
  • laser light is produced by a tunable pulsed dye laser system or diode laser system and is characterized as having a wavelength corresponding to that which is absorbed by the selected chromophore.
  • the laser light also has a wavelength that is substantially transmitted by the outer layers of the skin, i.e., the first 1 to 2 millimeters of skin. "Substantially transmitted” is used herein to indicate that not less than 60% of the laser light is transmitted through the first 2 millimeters of skin, or alternatively, not less than 60% of the laser light reaches target sebaceous glands.
  • suitable pulsed dye laser systems useful in the present disclosure include a power source, a flashlamp capable of emitting multiple pulses of light, a dye reservoir containing a dye suitable for stimulated emission of light, and an optical resonator having an output coupler.
  • the power source, flashlamp, dye reservoir and optical resonator are operatively connected so as to generate multiple pulses of laser light having a defined wavelength and pulse duration.
  • An optical fiber is optically coupled to the optical resonator in a manner to allow the multiple pulses of laser light to travel from the optical resonator through the optical fiber to the tissue area to be irradiated with a defined pulse fluence.
  • a handpiece delivery system incorporating the terminal end of the optical fiber is used to effectively direct the laser light source to the target area.
  • light is produced by a tunable dye system that emits light continuously. That is, light is emitted continuously from the source.
  • the light has a wavelength that is substantially transmitted by the outer layers of skin.
  • Suitable light system have a light source, such as an arc lamp, a dye reservoir for selecting the wavelength of light emitted from the system, a monochromator, and one or more shutters to prevent passage of the light.
  • the shutter can be opened and closed using a pre-selected delay time to provide for pulsing of the light. For example, the shutter can be opened for about 1 millisecond and then closed for about 1 second to provide for a pulse duration of about 1 millisecond with a delay time of about 1 second.
  • An optical fiber is optically coupled to the light system in a manner to allow the multiple pulses of light to travel from the optical resonator through the optical fiber to the tissue area to be irradiated with a defined pulse fluence.
  • a handpiece delivery system incorporating the terminal end of the optical fiber is used to effectively direct the light source to the target area.
  • photomodulation refers to the treatment of living tissue with light along, heat emitted by a light source, or light-activated chemical compositions, or any combination thereof. Falling within the scope of photomodulatory treatments are photothermal treatment, photoactivation, photoinhibition, and photochemical treatment of living tissue and, in particular, sebaceous structures within human skin.
  • electromagnetic emitters suitable for use in accordance with the present disclosure can fall into three categories: those which emit light in the visible spectrum and are useful for photoactivation and photoinhibition photomodulatory process; those that emit light in the ultraviolet spectrum and are also useful for photoactivation and photoinhibition photomodulatory process; and those that emit light in the infrared region and permit photomodulation treatment to be carried out through photothermal means, e.g., heat activation of the exogenous chromorphore, living ceils or tissue, or both.
  • photothermal means e.g., heat activation of the exogenous chromorphore, living ceils or tissue, or both.
  • a chromophore is applied to the area of skin to be treated to enhance the effectiveness of the energy application.
  • Chromophores useful in the present methods strongly absorb light at a selected wavelength or portion of the spectrum.
  • the chromophore penetrates into the sebaceous glands (in embodiments in less than 2 hours, in other embodiments less than 1 hour), has adequate shelf-life (at least a few weeks), and has a yield value (i.e. sag resistance) to facilitate ease of application.
  • Chromophores known to have hazardous thermal decomposition products at temperatures up to 200 0 C should be avoided.
  • chromophores are used that strongly absorb light energy at a wavelength or portion of the spectrum that is not strongly absorbed by natural skin pigments such as melanin, which absorbs at between about 500 nm to 600 nm.
  • the chromophore may be included in the peroxide composition or may be applied as a separate composition.
  • the chromophore may be incorporated into the target tissue by a variety of mechanisms. These mechanisms include, but are not limited to: 1 ) physical incorporation into the gland or target tissue cells while leaving the chemical structure essentially unaffected, or 2) undergoing a chemical reaction resulting in a new chromophore-tissue complex which then becomes a target for energy absorption.
  • Application of the chromophore may be a single or multi- step process and may involve the use of cofactors, catalysts, enzymes, or multiple agents which interact to ultimately become or create an active agent or agent-tissue complex.
  • the selective introduction of a chromophore to sebaceous glands is accomplished by topically applying a selected chromophore to the skin under conditions that permit the chromophore to selectively localize to the sebaceous glands.
  • the selective introduction of a chromophore to sebaceous glands is most readily accomplished using lipophilic chromophores, or alternatively, by preparing less lipophilic chromophores in a carrier that renders them more lipophilic.
  • a chromophore is considered "selectively introduced" to sebaceous glands according to the invention if greater than or equal to about 90% of the chromophore remaining associated with the skin after removal of excess chromophore preparation from the skin surface is observed in sebaceous glands.
  • Chromophore may include, without limitation, the following compositions and derivatives and analogs thereof: hair dyes, vegetable dyes, food coloring, fabric dyes, tissue stains, shoe or leather dyes, other plant products (such as flavonols, chlorophyll, copper chlorophyllin, bacteria chlorophylls, carotenoids, enzymes, monoclonal antibodies, any immunological agent, genetically engineered agent, benign infectious agents, whether naturally occurring or genetically engineered (e.g.
  • chromophores suitable for use in accordance with the present invention.
  • the chromophore chosen will have certain absorption characteristics that augment the penetration of the radiation to the tissue targeted for treatment, e.g., sebaceous oil gland, acne-scarred tissue, etc.
  • Exogenous chromophores are substances which absorb light or electromagnetic radiation in at least one narrow band of wavelengths and assist with the treatment method and system of the present methods by applying them to an area of the skin to be treated. Selection of the exogenous chromophore is determined by the absorption spectra of the chromophores and is dependent on the wavelength of the narrowband multichromatic emitter used for treatment. In accordance with a certain embodiments, the chromophore will aid in treatment by enabling at least the dominant or central wavelength of the narrowband, multichromatic radiation to penetrate at least the stratum corneum layer of the skin and permitting the photomodulation or photothermal injury or destruction of living tissue, sebaceous oil gland, duct, or supporting tissue in and below the stratum corneum. In some instances, the photomodulated tissue can be below all of the epithelial layers of the skin.
  • topical compositions include a quantity of naturally occurring chromophores such as chlorophyll, chlorophyllin, polyporphyin, bacteriochlorophyll, protopolyporphyin, etc. As those skilled in the art will appreciate, these compositions are characterized by a metal-ligand bond. In contrast, synthetic chromophores (e.g., methylene blue, indocyanin green ("ICG”) and the like) generally do not include a metal- ligand bond, nor do they exhibit the same general physical structure as naturally occurring chromophores.
  • ICG indocyanin green
  • chromophores While not a limiting factor, a common aspect of the most useful natural chromophores is found in their chemical structure.
  • Naturally occurring chromophores have a metal-ligand bonding site.
  • chromophores For chlorophyll a, a magnesium atom is present at the metal-ligand bonding site.
  • Chlorophyll a exhibits absorption maxima at 409 nm, 429 nm, 498 nm, 531 nm, 577 nm, 613 nm, and 660 nm.
  • Chlorophyll b exhibits absorption maxima at 427 nm, 453 nm, 545 nm, 565 nm, 593 nm, and 642 nm.
  • chlorophyll can be used as topically applied chromophores to assist the absorption of certain wavelengths of light delivered through the skin or soft tissue for various treatments.
  • treatment can be even more effective or can be carried out with reduced light intensities or can produce multiple beneficial effects, such as treating acne bacteria and reducing or eliminating acne scarring.
  • the chromophore may be a compound having a metal ligand bond that dissociates the metal ion under acidic conditions.
  • Topical skin care formulations may be used for altering the pH or acidity of the skin.
  • indocyanine green is used as the chromophore and is dissolved in a carrier system that retains its very high absorption around ⁇ OOnm. If water is used as a solvent, the highest possible ICG concentration may be dissolved in water and retains its very high absorption around ⁇ OOnm. If ICG-carrying water droplets are embedded in a lipophilic carrier, delivery into the sebaceous glands will be improved. ICG is particularly useful since it does not penetrate in the epidermis, does not stain the stratum corneum or the epidermis or dermis and is easy to clean from the surface of the skin after application. It should of course be understood that more than one chromophore may be used in the present methods.
  • exogenous light activated chromophores may be used alone or in combination with exogenous chromophores.
  • two or more exogenous light activated chromophores may be used.
  • the two chromophores may then be activated by an energy source simultaneously or very closely in time.
  • Two different light sources or wavelengths may be used serially or simultaneous to have different effects such as treating active acne lesions and also acne scarring; treating acne rosacea lesions and also rosacea blood vessels ortelangectasia; or using photothermal means for active acne and non-thermal photomodulation for treating acne scarring or skin wrinkles.
  • Two entirely different laser, LED, or light beams may be delivered substantially simultaneously through the same optics at different parameters.
  • one beam may be delivered primarily to release or to activate, and a second beam primarily to treat.
  • Additive effects may be achieved by using two beams at the same time, such as the use of blue light with a wavelength of approximately 400 nm and red light with a wavelength of approximately 600 nm.
  • a process for acne reduction may be optimal at 1064 nm for safety and for treating all skin colors, using lasers or LEDS as the low-level light source at a wavelength chosen according to the absorption spectrum of the topical composition used.
  • Suitable topical compositions are those comprising naturally occurring chlorophyll-containing compounds, carotenoid-containing compounds, derivatives thereof, and mixtures thereof, as well as derivatives, analogs, and genetically engineered forms of such agents.
  • a hand-held device containing the low-level light source may be used to photomodulate or photothermally activate, or both, the living tissue or peroxide in the topical composition, or both, and either simultaneous or synchronized sequentially in time to deliver another wavelength that may be optimal to in view of the absorption characteristics of the patient's fibroblast spectrum or the spectrum of the topical composition.
  • a natural chromophore may be targeted for photoactivation or photoinhibition, each falling under the general term photomodulation for directly treating the naturally occurring porphyrin compounds in acne bacteria, in addition to targeting exogenous chromophores like carotenoids, chlorophyll and its derivatives including copper chlorophyllin and other dyes such as indocyanine green dye, methylene blue dye, and similar compositions known to those skilled in the art.
  • Chromophore may be delivered in pure form, in solution, in suspension, in emulsions, in liposomes, in synthetic or natural microspheres, microsponges or other known microencapsulation vehicles, alone or in combination. This list of the forms of the chromophore is illustrative and not exhaustive. Those skilled in the art will recognize that there are a wide variety of forms for the delivery of topical compositions suitable for use in accordance with this disclosure.
  • the chromophore is delivered by a mask or a patch that the patient can apply at home, with the chromophore penetrating into the sebaceous glands overnight in preparation for application of energy the next day.
  • chromophore useful in the present methods are lipophilic, i.e., substantially soluble in a fat or lipid.
  • the lipophilic nature of the chromophore facilitates the selective introduction of the chromophore to the sebaceous gland.
  • Lipophilic chromophores include, for example, organic tissue stains and beta-carotene. Lipophilic chromophores may be dissolved in an acceptable oil (for example at a final concentration from about 0.001% to about 20% (w/v)) and then applied directly to the area of skin one wishes to treat. In other embodiments, the pores of the skin may be opened using heat, steam and the like to facilitate entry of the chromophores into the sebaceous glands.
  • non-lipophilic chromophores e.g., indocyanine green, methylene blue, Rhodamine B, cresyl violet and the like
  • a lipophilic carrier preparation e.g., indocyanine green, methylene blue, Rhodamine B, cresyl violet and the like
  • the chromophores are intended for contact with a living being, the chromophore should be safe to apply to human skin.
  • the chromophore should not be toxic or carcinogenic in the amounts to be applied.
  • microencapsulation processes may be used to deliver the chromorphore. If the diameter of the micro encapsulations is about five microns, then there may be relatively site specific preferential delivery into the sebaceous oil glands or skin surface stratum corneum cells. If the diameter of the microencapsulations is in the range of about one micron, then the chromorphore may be delivered with a more random distribution between the hair ducts and the oil glands. If the diameter of the microencapsulations is larger, on the order of about 20 microns or greater, then delivery will tend to be restricted primarily to the skin surface.
  • the micro encapsulations may be synthetic or natural. If ultrasound is used to enhance penetration, then the diameters and ultrasound treatment parameters may need to be adjusted according to the applicable principles which allow the estimation of the optimal ultrasound parameters for driving small particles into the skin, skin appendages or skin orifices.
  • Microencapsulation may be used to improve delivery of known chromophores such as chlorophyll, carotenoids, methylene blue, indocyanine green and particles of carbon or graphite. Using smaller particles and putting the smaller particles into more uniform diameter microencapsulations, may achieve more site specific or uniform targeting.
  • An illustrative formulation includes indocyanine green or other dyes or agents to form a lipid complex which is fat-loving (lipophilic).
  • chromophores and dyes such as indocyanine green dye may be refined and enhanced by selecting a carrier or encapsulation having a diameter that increases the probability of preferential delivery to a desired space, and/or that enables interaction with ultrasound to thereby increase the probability of preferential delivery, and/or that selectively attaches to the sebaceous gland, duct, supporting tissues, oil itself or bacteria, yeasts, or other organisms residing within these tissues.
  • lndocyanine green dye is presently in medical use, appears to be relatively benign, may be activated by red visible lasers, or other source of monochromatic or multichromatic light, (in the 800 nm range) may penetrate deeply enough to reach the oil glands, is used for leg vein and hair removal, and is relatively safe, cheap, and reliable. Methylene blue may also been used according to the present methods.
  • pressure may be used to impel chromophore particles into the skin, either in the spaces between the stratum corneum, into the hair ducts and hair follicles, the sebaceous oil glands, or other structures.
  • Air pressure or other gases or liquids may be used to enhance delivery or increase the quantity of delivered chromophore.
  • ultrasound may also physically drive chromophore particles down for the treatment of unwanted hair or acne which may ⁇ 1 ) enhance penetration of a chromophore into the hair shaft itself, or into surrounding cells; (2) drive chromophore particles into spaces between the stratum corneum to enhance the effects of a skin peel process (which physically removes a portion of the outer layers of the skin surface); or (3) physically removing the hair by methods such as waxing or pulling and then injecting the chromophore into the sebaceous gland or duct.
  • One embodiment uses the transdermal application of chlorophyll to the sebaceous oil gland and surrounding tissue.
  • the chlorophyll is then exposed to a source of electromagnetic radiation such as from a laser, an LED, a flash-lamp, or other source filtered to provide a dominant wavelength of from about 400 to about 450 nm.
  • a source of electromagnetic radiation such as from a laser, an LED, a flash-lamp, or other source filtered to provide a dominant wavelength of from about 400 to about 450 nm.
  • Other suitable wavelengths include from about 360 nm to about 440 nm and, in embodiments, from about 380 nm to about 420 nm.
  • Pulse durations may be selected with sufficient power density to allow the target tissue to be appropriately inhibited to reduce acne bacteria content and to reduce or destroy gland activity through photomodulation and photothermal means.
  • red light may also be effective in accordance with the present disclosure.
  • a light wavelength for treatment in the range of about 300 nm to about 1400 nm based on the absorption spectrum of the chromophore or other light-activated topical composition.
  • the primary absorption peak is at around 400 nm. This would indicate that for this chromophore, the most suitable wavelength for photomodulator and/or photothermal treatment would be at around 400 nm.
  • Another absorption peak occurs at around 620 nm, thus in an instance where a light source with a dominant wavelength of around 400 nm was not available, a light source with a dominant wavelength of around 620 nm could be used.
  • the absorption spectra of a carotenoid exhibits a broad absorption band from 400 nm to 520 nm, allowing the use of more wavelengths including those of green light (500 nm to 520 nm).
  • Absorption spectra of various synthetic and naturally occurring chromophores are known to those skilled in the art.
  • One acne treatment process uses a solution of graphite in a carrier solution and a Q-switched 1064 nm ND:YAG laser.
  • the solution may be applied to the skin which is then treated with the laser using known parameters.
  • a high repetition rate is used and the laser handpiece is moved slowly enough that pulses are "stacked" in one spot for several pulses before the handpiece is moved to an adjacent spot.
  • pulses are "stacked" in one spot for several pulses before the handpiece is moved to an adjacent spot.
  • a faster repetition rate also tends to help build the heat up faster, and to higher levels.
  • the dyes and similar agents may actually remain absorbing for a brief time until they reach a critical temperature at which time they are destroyed or become non absorbers, thus acting as a sort of heat sink for a brief time, allowing more heat to accumulate than with carbon solutions and short pulsed Q-Switched lasers.
  • Safety remains at about the same level, since dye related damage tends to be confined to target tissues. There is no appreciable change in patient treatment time. In other embodiments a longer pulsed laser in the 750 nanometer to 1000 nanometer range is used and appropriate parameters to achieve the desired tissue damage goal.
  • Another embodiment uses a tissue dye which attaches to, or is incorporated into, a target cell and surrounding tissues.
  • the target tissue may be illuminated with a multi- wavelength non-laser light source using appropriate parameters to achieve the desired tissue damage goal.
  • Another embodiment uses a light source which is well-absorbed by the melanin naturally present in skin and undyed darker hairs. Natural or synthetic melanin or derivatives thereof will be well-absorbed by the same wavelength of light (or alternatively two or more wavelengths, one for melanin and one or more for the dye).
  • This melanin agent is delivered into the sebaceous gland, duct, or supporting tissue, resulting in an enhanced or greater injury to the target tissue (or permitting lower treatment energy parameters, resulting in safer treatment than if the sebaceous gland, duct, or supporting tissue were treated without the melanin dye). This tends to benefit people having darker skin or tanned skin, by allowing lower treatment energy.
  • a diode laser or LED or non-laser light source could produce a continuous or pseudo-continuous beam of light energy using pulse durations as long as seconds at a wavelength which is absorbed by the light-activated chromophore, native porphyrin containing acne bacteria porphyrin compound, or native sebaceous gland, duct, or supporting tissue pigment and also by the melanin or dye used.
  • a pulse duration on the order of between about one and thirty seconds is suitable.
  • Another embodiment uses an agent which facilitates cavitation shock waves or a thermal effect or both. This preferentially damages (or stimulates) the target tissues while minimizing damage (or other adverse effects) on surrounding non-target tissues. This may be used with very short pulsed lasers or light sources or with ultrasound alone.
  • a process in accordance with the present invention may be used to provide short or long-term control, improvement, reduction or elimination of acne or other related skin diseases.
  • a chromophore may be physically or chemically or immunologically incorporated into cells of the sebaceous (oil) glands, ducts, or supporting tissue, or into the naturally occurring acne bacteria, porphyrin compounds, naturally occurring light activated chromophores, yeast or similar organisms which feed on the oil in the oil glands (or sweat glands) or exists in the oil or oil glands as otherwise relatively benign inhabitants.
  • Some acne bacteria may not inhabit all sebaceous structures and other strains may not produce native porphyrins to target with light.
  • acne bacteria may be located deeper than 400 nm to 420 nm light can adequately penetrate, thus treatment with light alone may be only partially effective in clinical treatment. Improvement in skin disorders may be a direct or indirect result of the application of the agents in this process, as may reduced oiliness of the skin, reduced size or diminished appearance of pores, etc.
  • the present methods are also useful for treating enlarged pores, oily skin, and other disorders where there is no active acne- related disorder.
  • folliculitis which involve the pilosebaceous (hair/oil gland) unit may also be treated using the present methods.
  • the present methods may also be used to reduce perspiration, sweating, or hyperhidrosis from eccrine (sweat) glands or apocrine glands.
  • the present methods may be used to treat other skin disorders such as, for example, viral warts, psoriasis, precancerous solar keratosis or skin lesions, hyperh id ros is/excessive sweating, aging, wrinkled or sun damaged skin, and skin ulcers (diabetic, pressure, venous stasis).
  • an amine initiator is applied to the skin before application of the energy.
  • the amine initiator may be included in the peroxide composition, applied in a composition containing a chromophore, or may be applied as a separate composition.
  • the amine initiator is a tertiary amine.
  • Tertiary amines potentiate radical formation by BPO.
  • a possible mechanism involves reaction of the amine and BPO by a SN2 mechanism.
  • the intermediate thus formed thermally decomposes to benzoyloxy radicals and an amine radical cation.
  • the benzoyloxy radicals may further decompose into phenyl radicals. All of these radicals can react with biological molecules causing some biological effect.
  • tertiary amines include Alfuzosin, Alimemazine, Analgesic drug (Reference 97), Atropine, alpha,alpha-bis [3-(N-benzyl-N-methyl- carbamoyl)-piperidino]-p-xylene dihydrobromide, Bupivacaine, cis-trans-Cavinton, Cloperastine, Cyamemeazine, Cyclopentolate, 2-(4,5-dihydro-1H-imidazol-2-yl)-2- propyl-1 ,2,3,4-tetrahydropyrrolo]3,2,1-hi[-indole, 1-decyl-3-(N,N-diethylcarbamoyl) piperidine hydrobromide, Diltiazem, Dimethindene, Diperodone, Disopyramide, Disopyamide, semipreparative, Dixyrazine, Doxazosin, Drop
  • tertiary amines are known to those skilled in the art.
  • the listed amines are all drugs, but the methods of the present disclosure are not limited to just drugs, rather, any tertiary amine may be used.
  • an antibiotic contain tertiary amines is used as the amine initiator. Suitable antibiotics include, but are not limited to ERY, doxycycline (Monodox ® ), minocycline (Vectrin ® ), levofloxacin (Levaquin ® ), and trovofloxacin (Trovan ® ). It should, of course, be understood that combinations of amine initators can also be employed. In embodiments, ERY-BP, Levaquin®-BP, and Vectrin®-BP combinations exhibit faster kinetics for radical formation than BPO alone. Treatment Regimens
  • Treatments in accordance with the present disclosure contact skin ⁇ in embodiments, skin suffering from an acne related condition) with a stable mixture of organic peroxide (such as Benzoyl peroxide), and optionally an antioxidant.
  • a stable mixture of organic peroxide such as Benzoyl peroxide
  • an antioxidant such as Benzoyl peroxide
  • the skin that has been treated with the peroxide is then exposed to energy that will cause decomposition of the peroxide, thereby enhancing efficacy of the peroxide.
  • a chromophore and/or an amine may be applied to the treated skin prior to application of the energy to help absorption of the energy.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Emergency Medicine (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Birds (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Cosmetics (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne le traitement de la peau par application d'une composition comprenant un peroxyde organique à une zone de la peau puis par exposition de la zone de peau à une source d'énergie.
PCT/US2010/026327 2009-03-06 2010-03-05 Procédés d'amélioration de l'activité peroxyde WO2010102183A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP10708471A EP2403533A1 (fr) 2009-03-06 2010-03-05 Procédés d'amélioration de l'activité peroxyde
CA2754840A CA2754840A1 (fr) 2009-03-06 2010-03-05 Procedes d'amelioration de l'activite peroxyde

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US15806609P 2009-03-06 2009-03-06
US61/158,066 2009-03-06

Publications (1)

Publication Number Publication Date
WO2010102183A1 true WO2010102183A1 (fr) 2010-09-10

Family

ID=42104160

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2010/026327 WO2010102183A1 (fr) 2009-03-06 2010-03-05 Procédés d'amélioration de l'activité peroxyde

Country Status (3)

Country Link
EP (1) EP2403533A1 (fr)
CA (1) CA2754840A1 (fr)
WO (1) WO2010102183A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006099187A2 (fr) * 2005-03-10 2006-09-21 Jr Chem, Llc Compositions de peroxyde de benzoyle et methodes d'utilisation
US20070244195A1 (en) * 2004-05-18 2007-10-18 Burkhart Craig N Treatment methods with peroxides and tertiary amines

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070244195A1 (en) * 2004-05-18 2007-10-18 Burkhart Craig N Treatment methods with peroxides and tertiary amines
WO2006099187A2 (fr) * 2005-03-10 2006-09-21 Jr Chem, Llc Compositions de peroxyde de benzoyle et methodes d'utilisation

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ASTNER S ET AL: "Clinical evaluation of a 1,450-nm diode laser as adjunctive treatment for refractory facial acne vulgaris", DERMATOLOGIC SURGERY 200808 GB LNKD- DOI:10.1111/J.1524-4725.2008.34206.X, vol. 34, no. 8, August 2008 (2008-08-01), pages 1054 - 1061, XP002582140, ISSN: 1076-0512 *
CHANG S -E ET AL: "Treatment of facial acne papules and pustules in Korean patients using an intense pulsed light device equipped with a 530- to 750-nm filter", DERMATOLOGIC SURGERY 200706 GB LNKD- DOI:10.1111/J.1524-4725.2007.33142.X, vol. 33, no. 6, June 2007 (2007-06-01), pages 676 - 679, XP002579429 *
IBBOTSON S H ET AL: "The effects of radicals compared with UVB as initiating species for the induction of chronic cutaneous photodamage", JOURNAL OF INVESTIGATIVE DERMATOLOGY 1999 US LNKD- DOI:10.1046/J.1523-1747.1999.00591.X, vol. 112, no. 6, 1999, pages 933 - 938, XP002579431, ISSN: 0022-202X *
RELYVELD ET AL: "Benzoyl peroxide/clindamycin/UVA is more effective than fluticasone/UVA in progressive macular hypomelanosis: A randomized study", JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, C.V. MOSBY, ST. LOUIS, MO, US LNKD- DOI:10.1016/J.JAAD.2006.03.020, vol. 55, no. 5, 1 November 2006 (2006-11-01), pages 836 - 843, XP005702552, ISSN: 0190-9622 *

Also Published As

Publication number Publication date
EP2403533A1 (fr) 2012-01-11
CA2754840A1 (fr) 2010-09-10

Similar Documents

Publication Publication Date Title
US6183773B1 (en) Targeting of sebaceous follicles as a treatment of sebaceous gland disorders
US9474707B1 (en) Optical treatment methods
US6676655B2 (en) Low intensity light therapy for the manipulation of fibroblast, and fibroblast-derived mammalian cells and collagen
US9814906B2 (en) Method and apparatus for skin treatment
JP4907057B2 (ja) 脱毛用発色団の局所的塗布
US5647866A (en) Method of hair depilation
US6086580A (en) Laser treatment/ablation of skin tissue
US9227082B2 (en) Method and apparatus for acne treatment using low intensity light therapy
AU2002343438A1 (en) Topical application of chromophores for hair removal
EP2968889A1 (fr) Méthodes de délivrance de nanocoquilles à des glandes sébacées
EP2403533A1 (fr) Procédés d'amélioration de l'activité peroxyde
IL160505A (en) A device for treating acne
Simao et al. Combining superficial chemical peels
Kalil et al. Intense Pulsed Light and Drug Delivery
Tanzi et al. Complications of ablative and nonablative lasers and light sources
Al-Amoudi The effect of a long pulsed dye laser on photodamaged skin and facial telangiectasia

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 10708471

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2754840

Country of ref document: CA

REEP Request for entry into the european phase

Ref document number: 2010708471

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2010708471

Country of ref document: EP