WO2011152832A1 - Procédés d'utilisation de compositions à base de nitroalcène dans des applications dermatologiques pour prévenir ou traiter le vieillissement de la peau - Google Patents
Procédés d'utilisation de compositions à base de nitroalcène dans des applications dermatologiques pour prévenir ou traiter le vieillissement de la peau Download PDFInfo
- Publication number
- WO2011152832A1 WO2011152832A1 PCT/US2010/037419 US2010037419W WO2011152832A1 WO 2011152832 A1 WO2011152832 A1 WO 2011152832A1 US 2010037419 W US2010037419 W US 2010037419W WO 2011152832 A1 WO2011152832 A1 WO 2011152832A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- acid
- skin
- nitroalkene
- nitro
- ascorbyl
- Prior art date
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Classifications
-
- 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
-
- 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
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
-
- 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
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K8/86—Polyethers
Definitions
- the present invention relates to topical nitroalkene compositions to improve skin conditions.
- the nitroalkene compositions may be used to prevent skin damage, and to treat skin damage, particularly skin inflammation.
- Methods of use include treatment of rosacea, eczema, psoriasis, xerosis, dermatitis, seborrhea, thermal and radiation burns (including sunburn), acne, alopecia, skin aging, scars, and skin inflammation.
- eicosanoids e.g. prostaglandins, leukotrines, and hyroxyeicosatetraenoic acid (HETE) are produced, which cause erythma, edema, and free radical production.
- HETE hyroxyeicosatetraenoic acid
- Free fatty acids and esterified fatty acids are important components of lipoproteins and membranes. They react with nitric oxide ( ⁇ ) and nitric oxide derived species (NOx) to produce a variety of oxidized and nitrated products.
- the oxidation of polyunsaturated fatty acids plays an important role in biological systems and some of the metabolic products from polyunsaturated fatty acid oxidation are important biological mediators.
- the nitrated lipids produced act as signaling mediators leading to secondary changes in protein function via electrophilic based modifications.
- Nitric oxide and its metabolites also induce cyclic guanosine monophosphate (cGMP)-independent actions in host defense mechanisms and cell signaling.
- cGMP cyclic guanosine monophosphate
- the reaction of NOx with eicosanoids and their impact on biosynthetic enzymes are significant elements in the modulation of inflammatory response. Reactions of ⁇ and ⁇ .
- metabolites can influence catalytic reactions in eicosanoid synthesis and modulated gene expression of related enzymes.
- the transcription factor NFkB mediates inducible nitric oxide synthase expression in LPS-activated macrophages.
- ⁇ can serve to down-regulate initial lipoid-mediated signaling events.
- Nitrated fatty acids particularly, nitroalkene derivatives of fatty acids, have been detected in vivo in the blood and urine of healthy humans. (Baker et al., J. Biol. Chem., 2005 280:42464-42475).
- ⁇ is an endogenously generated, lipophilic signaling molecule that maintains vascular homeostasis via stimulation of soluble guanylate cyclase.
- ⁇ potently modulates oxygen radical reactions, inflammatory cell function, post-translational protein
- ⁇ -derived species can mediate the oxidation and nitration of biomolecules such as unsaturated fatty acids.
- Acute inflammation is often characterized generation of excited oxygen species, e.g. superoxide anion, which damages the lipid-rich membranes and activate the chemical mediators of the proinflammation and inflammation cascades.
- excited oxygen species e.g. superoxide anion
- These oxygenated species tend to concentrate in hydrophobic regions.
- ⁇ and NOx undergo a rich spectrum of reactions with oxygen species, transition metals, thiols, lipids, and a variety of organic radicals. These multifaceted reactions yield reactive species that transduce ⁇ signaling and modulate tissue inflammatory responses.
- Nitric oxide reacts with superoxide (0 2 ) to yield peroxynitrite (ONOO ) and its conjugate acid, peroxynitritrous acid (ONOOH), the latter of which undergoes homolytic scission to nitrogen dioxide (N0 2 ) and hydroxyl radical (OH).
- ONOO can react with C0 2 , to form nitrosoperoxycarbonate (ONOOCO2 " ), which breaks down to NO 2 and carbonate (CO3 " ) radicals via homolysis, or rearrangement to NO3 " and C0 2 .
- Heme oxygenase 1 plays a central role in vascular inflammatory signaling and mediates a protective response to inflammatory stresses such as atherosclerosis, acute renal failure, vascular restenosis, transplant rejection, and sepsis. Heme oxygenase 1 catalyzes the degradation of heme to biliverdin, iron, and CO, the last of which has been shown to display diverse, adaptive biological properties, including antiinflammatory, anti-apoptotic, and vasodilatory actions.
- HO- 1 gene expression is up-regulated, with induction typically occurring
- Neutrophil myeloperoxidase and heme proteins such as myoglobin and cytochrome c catalyze H 2 0 2 -dependent oxidation of nitrite (N0 2 " ) to N0 2 , resulting in biomolecule oxidation and nitration that is influenced by the spatial distribution of catalytic heme proteins.
- These and other products are capable of concerted oxidation, nitrosation and nitration of target molecules.
- the body contains an endogenous antioxidant defense system made up of antioxidants such as vitamins C and E, glutathione, and enzymes, e.g., superoxide dismutase.
- the present invention is directed at the selection, formulation, and use of compounds which act with a protective response to prevent and attenuate inflammation to provide a therapeutic effect in their control of the pathological inflammation processes, and are also important in providing useful biochemical tools for mechanistic investigation of the enzymes involved.
- Lipid nitration provides a means by which the proinflammatory aspects of reactive oxygen and nitrogen species and eicosanoids are down- regulated.
- the present invention is directed at the topical use of nitroalkene compositions, including particularly, nitrolinoleic acid, nitrooleic acid, nitrated species of arachidonic acid and nitrated cholesteryl lineolate, as lipid signaling mediators to reduce inflammation and inflammation mediated skin conditions.
- topical methods of use of nitroalkenes to prevent or treat rosacea, eczema, psoriasis, xerosis, dermatitis, seborrhea, acne, alopecia, other types of skin inflammation, skin aging, and scarring are disclosed.
- the amount of nitroalkene necessary to treat skin or prevent skin damage is not fixed per se and is necessarily dependent upon the amount and identity of any adjunct ingredients in the preparation. In some typical
- the composition comprises about 0.025% to about 70% by weight nitroalkene in a dermatologically acceptable polymer polyether and/or phosphatidycholine carrier.
- a dermatologically acceptable polymer polyether and/or phosphatidycholine carrier optionally, at least one or a mixture of lipoic acid, fatty acid ester of ascorbic acid may be added to the composition.
- the method for preventing and/or treating skin damage comprises applying a composition containing about 0.025% to about 70% by weight of nitroalkene in a dermatologically acceptable carrier.
- a dermatologically acceptable carrier for preventing and/or treating skin damage.
- at least one or a mixture of lipoic acid or fatty acid ester of ascorbic acid may be added to the composition.
- Nitrated fatty acids serve as mediators of physiological and pathophysiological cell signaling processes. Functional consequences of these signaling mechanisms have been shown in inhibition of platelet and neutrophil functions, activation of the transcription factor Nrf2 which upregulates gene expressions of cytoprotective phase 2 protienases such as heme oxygenase-1 (HO-1 ), inhibition of LPS-induced cytokine release in moncytes, increased insulin sensitivity and glucose uptake in adipocytes, and relaxation of preconstricted rat aortic segments.
- Nrf2 cytoprotective phase 2 protienases
- HO-1 heme oxygenase-1
- nitro fatty acids undergo reversible and exchangeable electrophilic reactions with nucleophilic targets and are metabolized predominantly via saturation of the double bond and beta- oxidation reactions that terminate at the site of acyl-chain nitration (Rudolph et al., J. Biol Chem, 2009 284:1461-73).
- Reversible nitroalkylation reactions with glutathione (GSH) and the Cys and His residues of proteins demonstrate the electrophilic nature of the ⁇ -carbon adjacent to the nitro-bonded carbon.
- Nitrated fatty acids have been reported as potential endogenous ligands for PPARy because of their ability to react with cellular nucleophiles to postranslationally modify protein structure, function, and localization (Baker et al., Free Radic Biol Med, 2009 46:989-1003).
- Nitro-oleic acid has been reported to inhibit xanthine oxidoreductase (XOR) activity, which generates proinflammatory oxidants and secondary nitrating species, with an IC50 of 0.6 ⁇ (Kelley et al., J Biol Chem, 2008 283:36176-84).
- Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibition by nitro-oleic and -linoleic acid displayed an IC50 of 3 ⁇ , indicating a pathway for redox regulation of enzyme function, cell signaling and protein trafficking (Batthyany et al., J Biol Chem, 2006 281 :20450-63).
- Nrf2 nuclear factor-erythroid 2-related factor 2
- cytoprotective phase 2 enzymes i.e. heme oxygenase 1 (HO-1 ), superoxide dismutase, catalase, glutathione peroxidases, the peroxy redoxines, NADPH, and quinone oxyreductases.
- LNO2 also inhibits fMLP and PMA-mediated active of human neutrophils and blocks NF-kB activity, inhibits Keapl , resulting in activation of Nrf2 which induces expression of cytoprotective molecules.
- LNO2 and OANO2 have been shown to exert cell signaling action via ligation and activation of PPARy.
- PPARy activation can effect modulation of metabolic and cellular differentiation genes and regulation of inflammatory responses.
- PPARy is expressed in monocytes, macrophages, smooth muscle cells, and endothelium and plays a central role in regulating the genes related to lipid trafficking, cell proliferation and inflammatory signaling.
- the removal of LNO2-GSH adducts by MRP1 shows that electrophilic reactivity likely plays a role in inhibiting LNO2 dependent PPARy transcription.
- HO-1 plays a central role in vascular inflammatory signaling reactions and mediates a protective response.
- LNO2 was shown to induce pulmonary epithelial HO-1 mRNA expression and adaptive responses to inflammation via both
- nitroalkenes in topical applications for improvement of skin conditions has not been described in the literature.
- the present invention comprises topical nitroalkene treatments which improve skin condition by disrupting the cascade of reactions that cause inflammation.
- Nitroalkenes consist of the general formula NO2-A-B, in which A is a saturated hydrocarbon chain and B is (CH2) admit(COOH) m in which n is 0 to 2 and m is 0 to 2; and the derivatives thereof having further one or more substitution selected from the group consisting of hydroxyl, hydroperoxy, epoxy and perxoy.
- A is a hydrocarbon chain of 17 atoms and B is CH2(COOH).
- the preferred compounds are nitro-linoleic acid, nitro-oleic acid, nitrated arachidonic acid, or nitrated cholesteryl lineolate. Of these, nitro-linoleic acid, and nitro-oleic acid are preferred.
- Additional nitroalkene compounds that may be used in accordance with the invention include the compounds disclosed in Ferrante, U.S. Patent No. 6,924,309; and Freeman, U.S. Patent Publication No. US
- the most preferred compounds are those in which a N02 group is located adjacent a double bond in the carbon chain, such as in the compounds illustrated in Table 1 below.
- nitro compounds have been compared to fatty acids, which have a variety of biological activities including anti-inflammatory properties, since the nitro group is chemically similar to COOH groups of essential fatty acids with regard to size, charge and shape.
- the nitro compounds are a group of relatively stable compounds and are resistant to ⁇ - oxidation by preventing CoA thiosester production, which is the first step in ⁇ - oxidation of fatty acids. Because of this, they are not readily incorporated into lipids and are more likely to be present in a free form.
- Polyunsaturated nitro compounds have the ability to penetrate cells and tissues suggesting their use to prevent oxidative damage including anti-aging agents.
- IFN- ⁇ interferon-gamma
- nitroalkenes of the present invention may be possible through any of the routes disclosed in U.S. Patent No. 6,924,309, and in Trostchansky and Rubbo supra.
- Lipid nitration in vivo may also arise through one or more of several different pathways, namely: 1 ) nitrogen dioxide radical reacts with unsaturated lipids and lipid radicals leading to isomerized, oxidized and/or nitro- allylic, nitroalkane, dinitro, or nitro-hydroxy lipid derivatives; 2) peroxynitrite and peroxynitrous acid homolyze yielding nitrogen dioxide radical and hydroxyl radical which mediate oxidation, nitrosation, and nitration reactions; 3) addition of nitronium ion by electrophilic substitution at the double bond; 4) reaction of a carbon-centered radical with nitrogen dioxide radical both coming from a caged radical rearrangement of unstable alkyl peroxynitrite intermediates; and 5) nitroaldol addition by combining known precursors yielding a nitro-alcohol product i.e. activation of hydroxyl group followed by dehydration reaction via catalytic base.
- 1 nitrogen dioxide radical reacts with unsaturated lipids
- topical compositions containing nitroalkene are needed to achieve the intended benefits including prevention and treatment of inflammatory skin conditions, aging and scarring.
- effective amount is meant an amount of active ingredient(s) sufficient to turn on the Nrf2 transcription factor and inhibit NF-kB and/or upregulate expression of other protective ligands, thereby inhibiting the products of the arachidonic acid cascade which leads to the activation of transcription factors that direct the cell nucleus in producing proinflammatory cytokines.
- the topical compositions are based on a carrier in which the nitroalkene is soluble per se or is effectively solublized (e.g. as an emulsion or microemulsion).
- the carrier is dermatologically acceptable in the sense of not bringing about any adverse effect on the skin areas to which it is applied.
- the carrier preferably is appropriately selected for topical application, and forms a film or layer on the skin to which it is applied so as to localize the application.
- the nitroalkene is applied in admixture with the dermatologically acceptable carrier or vehicle (e.g. as a lotion, cream, gel, ointment, soap, stick, or the like) to as to facilitate topical application and provide therapeutic effects.
- Non-polar and hydrophobic carriers are required for the compositions of the invention.
- Aqueous solvents and other polar solvents should be avoided because nitroalkenes are unstable in such solvents.
- Carriers may include polyethylene glycol, including PEG-1000, PEG-200, PEG-400; PEG-600; Labrasol® (a lipid-based self-emulsifying excipient mainly composed of PEG esters and glycerides with medium acyl chains); glycerin; polypropylene glycol; Stabileze® 06 (a PVM/MA Decadiene Crosspolymer); hydrogenated
- a phosphatidycholine based carrier is another possible embodiment.
- Phosphatidylcholine commonly called lecithin, is a mixture of diglycerides of stearic, palmitic, and oleic acids, linked to the choline ester of phosphoric acid. It can be isolated from eggs, soybeans, and other biological materials, chemically synthesized, or obtained commercially from many sources.
- the quantity of the nitroalkene active ingredient in the carrier may be varied or adjusted widely depending upon the particular application, the potency of the particular compound, and the desired concentration. Generally, the quantity of nitroalkene active ingredient will range between 0.025% to 70% by weight of the topical composition. Generally, lower concentrations of nitroalkene active ingredients in a carrier are suitable, depending upon the application regimen and the active and adjunct ingredients employed.
- the topical composition of the invention can contain additional ingredients commonly found in skin care compositions and cosmetics, such as, for example, tinting agents, emollients, skin conditioning agents, emulsifying agents, humectants, preservatives, antioxidants, perfumes, chelating agents, etc., provided that they are physically and chemically compatible with other components of the composition.
- additional ingredients commonly found in skin care compositions and cosmetics, such as, for example, tinting agents, emollients, skin conditioning agents, emulsifying agents, humectants, preservatives, antioxidants, perfumes, chelating agents, etc.
- a nitroalkene topical composition desirably includes a substantial antioxidant and preservative system.
- the antioxidant system is OxynexTM AP, OynexTM LM, or OxynexTM K.
- the preferred embodiments uses fatty acids of Vitamin C, specifically ascorbyj palmitate, as a significant component of the antioxidant system.
- Antioxidants are typically present in an amount ranging from about 0.025% to about 5.00% by weight of the composition, include, but are not limited to, butylated hydroxy toluene (BHT); vitamin C and/or vitamin C derivatives, such as fatty acid esters of ascorbic acid, particularly asocorbyl palmitate;
- antioxidants are those that provide additional benefits to the skin such as ascorbyl palmitate.
- Preservatives are typically present in an amount ranging from about 0.5% to about 2.0% by weight percent, based on the total composition.
- Emollients typically present in amounts ranging from about 0.01% to 5% of the total composition include, but are not limited to, fatty esters, fatty alcohols, mineral oils, polyether siloxane copolymers, and mixtures thereof.
- Humectants may be present in amounts ranging from about 0.1% to about 5% by weight of the total composition. Non-polar humectants are preferred.
- Emulsifiers typically present in amounts from about 1 % to about 10% by weight of the composition, include, but are not limited to, stearic acid, cetyl alcohol, stearyl alcohol, steareth 2, steareth 20, acrylates/C 10-30 alkyl acrylate cross- polymers, and mixtures thereof.
- Chelating agents typically present in amounts ranging from about 0.01% to about 2% by weight, include, but are not limited to, ethylenediamine tetraacetic acid (EDTA) and derivatives and salts thereof, dihydroxyethyl glycine, tartaric acid, and mixtures thereof.
- EDTA ethylenediamine tetraacetic acid
- Some embodiments of this invention contain at least one other adjunct ingredient in addition to nitroalkene(s).
- Fat-soluble fatty acid esters of ascorbic acid (vitamin C) are employed as an adjunct ingredient as well as an antioxidant in some embodiments.
- the more oxidation-resistant saturated fatty acid esters of ascorbic acid are preferred, including, but not limited to, ascorbyl laurate, ascorbyl myristate, ascorbyl palmitate, ascorbyl stearate, and ascorbyl behenate.
- Ascorbyl palmitate is used in one prefrerred embodiment.
- Other possible adjunct ingredients include, but are not limited to one or more of: amino acids, lipoic acid; or tocotrienols and tocotrienol derivatives and vitamin E compositions enriched with tocotrienols or tocotrienol derivatives
- a nitroalkene topical composition formulation is as follows.
- a nitroalkene topical composition formulation is as follows.
- a nitroalkene topical composition formulation is as follows.
- Two nitroalkene emulsion topical composition formulations are as follows.
- the topical composition is topically applied to the skin areas, such as that of the face, at predetermined intervals with gradual improvement in the skin areas expected with each successive application.
- Topical compositions containing nitroalkene according to the present invention can be topically applied to and absorbed by the skin tissue.
- Nitroalkenes activate Nrf2, PPARv, modify NF-kB gene expression or inhibit IFN- Y and TNF and human neutrophils and macrophage degranulation as well as cytokine release, thus preventing the cascade of reactions that lead to inflammation and degranulation.
- nitroalkenes react with cellular nucleophiles to postranslationally modify protein structure thus affecting XOR, GAPDH or any of the aforementioned inflammatory regulating compounds.
- nitro compounds of the present invention work in a similar manner to the polyunsaturated nitro compounds of Ferrante.
- nitroalkenes of the invention may enhance Nrf2 nuclear translocation, activate PPARy, or modify the NF-kB subunit 65 that encodes proinflammatory cytokines.
- ⁇ is also observed in aqueous environments. The release is independent of the presence of thiol adjuvants such as cysteines.
- the capacity to release ⁇ is has been related to the vasorelaxing properties of nitroalkenes observed in rat aortic ring, specifically AAN0 2 and AA(OH)N0 2 .
- the stability of nitro-fatty acids is better in hydrophobic environments.
- the release of ⁇ from LNO2 is inhibited when inserted in phosphatidylcholine/ cholesterol liposomes and it is considered stable in hydrophobic environments.
- Methods and compositions of the present invention are expected to be particularly useful for treating skin tissue suffering from or damaged by inflammatory conditions.
- the methods and compositions are expected to be useful in prevention and treatment of the following conditions: rosacea, eczema, psoriasis, xerosis, dermatitis (both contact dermatitis and atopic dermatitis), seborrhea, thermal and radiation burns (including sunburn), acne, alopecia, aging-induced skin tissue degeneration, scars, and other types of skin inflammation.
- Skin aging bears some similarities to chronic inflammatory conditions. Cell aging is due in part to free radical damage, which takes place mostly within the cell membrane.
- the cell membrane is most susceptible to attack by free radicals because of its dense molecular structure largely comprising lipids and lipoproteins, which are easily oxidized by reactive oxygen species.
- reactive oxygen species such as singlet oxygen, the superoxide anion, and hydroxyl radicals, as well as other free radicals, are generated in normal metabolism, as well as through ultraviolet sun exposure, other forms of radiation, other environmental factors such as pollution or exposure to chemicals in the home or workplace, and the like, active in the arachidonic acid cascade.
- nitroalkene compounds according to the invention will be effective to protect collagen and elastin from degradation by matrix metallopritenases. After treatment for a period of time, it is expected that elasticity and a supple feeling will return to the skin, fine lines and wrinkles will be reduced, and skin coloring will even out.
- the present invention thus includes use of nitroalkene compositions to prevent and treats skin aging, as well as both preventing and treating skin damage.
- compositions of the present invention are in encouraging wound healing without scarring, and also, in remodeling scarred skin to a smoother, unscarred appearance.
- Scars result from wound healing, which occurs in three separate phases: inflammation, formation of granulation tissue, and matrix formation.
- inflammation occurs in three separate phases: inflammation, formation of granulation tissue, and matrix formation.
- matrix formation occurs in three separate phases: inflammation, formation of granulation tissue, and matrix formation.
- damage to endothelial cells, complement, and platelets at the wound site release chemotactic factors that result in the infusion of neutrophils, lymphocytes and macrophages, which aids in the removal of infection and foreign debris.
- the granulation phase begins with an influx of fibroblasts and endothelial cells to the wound.
- Other key cells in this phase are
- Macrophages induce the beginning of granulation by releasing platelet-derived growth factor (PDGF), tumor necrosis growth factor (TGF)- , and an epidermal growth factor-like substance.
- PDGF platelet-derived growth factor
- TGF tumor necrosis growth factor
- EGF epidermal growth factor
- PDGF platelet-derived growth factor
- TGF-a tumor necrosis growth factor
- TGF- ⁇ epidermal growth factor-like substance
- EGF epidermal growth factor
- keratinocytes cells migrate in sheaths over a provisional matrix consisting primarily of fibrin, fibronectin, type V collagen, and tenascin, and produce their own fibronectin receptors. Once re-epithelilization has occurred, keratinocytes resume their normal differentiated form, and matrix formation begins.
- Matrix formation consists primarily of the construction of dermal matrix, which is regulated by fibroblasts. Chemotaxis of fibroblasts results in the production of abundant quantities of hyaluronate, fibronectin, and types I and III collagen. These components comprise the bulk of the provisional extracellular matrix in the early part of this wound repair phase.
- Hyaluronic acid (HA) creates an open-weave pattern in the collagen/fibronectin scaffold, facilitating fibroblast movement. HA production falls after about the fifth day of wound healing, and levels of chron- roitin sulfate in dermatan sulfate increase. Fibronectin deposits in the collagen, and wound contraction begins. Biochemically during the contraction stage, hyaluronidase and proteinase are present, type I collagen synthesis is stimulat- ed, and increased levels of chronroitin sulfate, dermatin sulfate and
- proteoglycans are observed; together these restructure the matrix.
- the final scar shows collagen fibers mostly parallel to the epidermis.
- Hypertrophic and keloid-type scars result in extension of scar tissue so that a bulky lesion results.
- a keloid is an exuberant scar that proliferates beyond the original wound.
- keloids only occur in humans, often causing burning, stinging and itching sensations as well as cosmetic embarrassment. The etiology of unsightly keloid formation is not known.
- fibronectin formation continues for years, while fibronectin formation in normal scars disappears within a few days after wound closure. Keloid scars exhibit a high rate of collagen synthesis in comparison to normal scars, and a low proportion of cross-linked collagen.
- Hypertrophic scars sometimes are difficult to distinguish from keloid scars histologically and biochemically, but unlike keloids, hypertropic scars remain confined to the injury site and often mature and flatten out over time. Both types secrete larger amounts of collagen than normal scars, but typically the hypertrophic type exhibits declining collagen synthesis after about six months. However, hypertrophic scars contain nearly twice as much glycosaminoglycan as normal scars, and this and enhanced synthetic and enzymatic activity result in significant alterations in the matrix which affects the mechanical properties of the scars, including decreased extensibility that makes them feel firm.
- Atrophic scars are characterized by a thinning and diminished elasticity of the skin due to a loss of normal skin architecture.
- An example of an atrophic scar is striae distensae, also known as stretch marks. Striae commonly occur in postpartum women after childbirth and also during times of larger-than- average weight gain and also in association with steroids. Atrophic scars are sometimes also observed after trauma, infection and disease, and may show loss of surface markings and smoothness or dry, fine wrinkles over time.
- nitric oxide synthetase activity is aberrant in keloid scars when compared to normal tissue (Lim, T.C., et al., Plastic and Reconst. Surgery, 1996, 98: 911- 912). Hypertrophic and keloid scars also show inflammatory activity that is not seen in mature scars.
- the nitroalkene compositions and methods of the present invention are expected to be effective to reduce scarring during the process of wound healing and to remodel previously damaged or scarred skin. After treatment for a period of time, decreased inflammation, irritation, and erythema of the skin should occur, with a flattening of the scars and evening out of skin coloring.
- Acne is the most common pustular condition of the. skin, disfiguring afflicted persons with inflammatory and noninflammatory lesions (including pustules, papules and comedones) during the active phase, and with atrophic scars afterwards. It occurs most commonly in teenagers, but is not confined to adolescents. A significant number of persons continue to seek advice on treatment for acne after the teenage years (Collier et al., J. Am. Acad. Dermatology, 2008 58:56-59). Although acne is generally considered to be self- limiting, its social effects can be substantial, and it may have its most severe effects on the psyche (Am. J. Clinical Dermatology, 2008 9(5):279-284). In about 60% of teenagers, disease severity and embarrassment are sufficient for them to self-medicate with proprietary preparations and/or seek medical advice.
- Acne is a multifactorial disease affecting the pilosebaceous units of the skin.
- Each unit consists of a large, m ' ultilobed sebaceous gland, a rudimentary hair and a wide follicular canal lined with stratefied squamous epithelium. They are found over most of the body surface but are largest and most numerous on the face, chest, and upper back. Normally, desquamated follicular cells are carried to the surface by the flow of sebum. Under the abnormal circumstances of acne vulgaris, an abnormal desquamination process provokes increased sloughing of the epithelium, which becomes more cohesive because of defective keratinization.
- This process causes blockage of the follicular orifice with accumulation of dead cells. Androgen stimulates the undifferentiated hormonally responsive cells making up the outer layer of the sebaceous gland lobule to divide and differentiate. Sebum production favors proliferation of the anaerobe Propionibacterium acnes, which is a normal commensal to the pilosebaceous unit, which can elicit hypersensitivity responses in acne.
- the aims of treating acne are to minimize the number and severity of lesions, prevent scarring, limit disease duration, and reduce the social and psychological stress that affects many patients, particularly teenagers.
- Conventional treatment is directed at correcting the three major factors that seem to cause acne: (1 ) androgenic stimulation of the sebaceous glands and increased sebum production; (2) abnormal keratinization and impaction in the pilosebaceous canal causing obstruction to sebum flow; and (3) proliferation of P. acnes.
- topical agents that remove comedones are particularly effective because they normalize desquamination within the follicular orifice, which allows the sebum to flow freely onto the surface of the skin; adalpalene, tretinoin, and tazarotene have been shown to have efficacy in treating mild to moderate acne, but all three have reported to have skin-irritating side effects including erythema, pruritis, burning/stinging, and scaling/flaking (Physicians' Desk Reference®, 56th ed. 2002, p. 2523, hereinafter referred to as "PDR").
- PDR Physical Desk Reference®
- nitroalkene compositions and methods of the present invention are expected to be effective to prevent and to treat acne. After treatment for a period of time, decreased inflammation, irritation and erythema of the skin. This should result in an elimination of acne and repair microscarring of the dermis from prior acne lesions.
- Psoriasis is another inflammatory skin disease that occurs when faulty signals in the immune system cause keratinocyte skin cells to regenerate too quickly, on the order of every three to four days instead of the usual 30-day cycle. Extra skin cells build up on the skin's surface, forming red, flaky, scaly lesions that can itch, crack, bleed and be extremely painful. Psoriasis generally involves the joints, limbs and scalp but it can appear anywhere on the body, covering some people from head to toe. More than 5 million Americans have been diagnosed with psoriasis and/or psoriatic arthritis, a degenerative disease of the joints and connective tissues associated with psoriasis.
- Psoriasis typically first strikes people between the ages of 15 and 35, but can affect anyone at any age, including children.
- Psoriasis is characterized by erythematous eruptions, often in papules or plaques, and usually having a white, silvery scale.
- TNF- ⁇ 3 ⁇ 4 tumor necrosis factor «(TNF- ⁇ 3 ⁇ 4) as a particularly relevant cytokine regulating this complex inflammatory cascade. Its key role is underlined by the therapeutic efficacy of compounds that interfere with TNF- ⁇ * functions.
- neutrophils another leukocyte population abundantly present in psoriatic infiltrates, are recruited by the neutrophil-attracting chemokine interleukin-8 (CXCL8).
- CXCL8 neutrophil-attracting chemokine interleukin-8
- nitroalkene compositions and methods of the present invention are expected to be effective to prevent and to treat psoriasis.
- the present invention thus prevents skin aging and treats skin aging, as well as both preventing and treating skin damage including
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Abstract
L'invention porte sur des compositions topiques qui comportent une quantité efficace d'un nitroalcène et d'un support, lesdites compositions étant utilisées pour prévenir ou traiter le vieillissement de la peau.
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PCT/US2010/037419 WO2011152832A1 (fr) | 2010-06-04 | 2010-06-04 | Procédés d'utilisation de compositions à base de nitroalcène dans des applications dermatologiques pour prévenir ou traiter le vieillissement de la peau |
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US8563609B2 (en) | 2010-05-13 | 2013-10-22 | Nitromega Corp. | Nitro fatty acids - neuroprotection and/or inhibition of cognitive decline |
Citations (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4775530A (en) | 1987-01-06 | 1988-10-04 | Perricone Nicholas V | Method for treatment and prevention of pseudofolliculitis barbae |
US5376361A (en) | 1993-01-13 | 1994-12-27 | Perricone; Nicholas V. | Method and compositions for topical application to the skin for prevention and/or treatment of radiation-induced skin damage |
US5409693A (en) | 1989-10-12 | 1995-04-25 | Perricone; Nicholas V. | Method for treating and preventing sunburn and sunburn damage to the skin |
US5545398A (en) | 1993-01-13 | 1996-08-13 | Perricone; Nicholos V. | Method and compositions for topical application to the skin of tocotrienol for prevention and/or treatment of skin damage |
US5574063A (en) | 1989-10-12 | 1996-11-12 | Perricone; Nicholas V. | Method and compositions for topical application of ascorbic acid fatty acid esters for treatment and/or prevention of skin damage |
US5643586A (en) | 1995-04-27 | 1997-07-01 | Perricone; Nicholas V. | Topical compositions and methods for treatment of skin damage and aging using catecholamines and related compounds |
US5709868A (en) | 1995-09-20 | 1998-01-20 | Perricone; Nicholas V. | Lipoic acid in topical compositions |
US5879690A (en) | 1995-09-07 | 1999-03-09 | Perricone; Nicholas V. | Topical administration of catecholamines and related compounds to subcutaneous muscle tissue using percutaneous penetration enhancers |
US5965618A (en) | 1997-11-17 | 1999-10-12 | Perricone; Nicholas V. | Treatment of scar tissue using lipoic acid |
US6051244A (en) | 1993-01-27 | 2000-04-18 | Perricone; Nicholas V. | Fructose diphosphate topical compositions |
US6162419A (en) | 1996-11-26 | 2000-12-19 | Nicholas V. Perricone | Stabilized ascorbyl compositions |
US6191121B1 (en) | 2000-04-06 | 2001-02-20 | Nicholas V. Perricone | Treatment of skin damage using polyenylphosphatidylcholine |
US6924309B2 (en) | 1999-09-17 | 2005-08-02 | Children, Youth And Women's Health Service Incorporated | Anti-inflammatory nitro and thia-fatty acids |
US7182956B2 (en) | 2002-05-31 | 2007-02-27 | Nicholas V. Perricone | Stable topical drug delivery compositions |
US20070232579A1 (en) | 2004-04-28 | 2007-10-04 | Uab Research Foundation, The | Nitrated Lipids and Methods of Making and Using Thereof |
US20100286257A1 (en) * | 2009-05-08 | 2010-11-11 | Perricone Nicholas V | Methods Of Use Of Nitroalkane Compositions In Dermatologic Applications To Prevent or Treat Skin Aging |
WO2010129763A1 (fr) * | 2009-05-08 | 2010-11-11 | Perricone Nicholas V | Compositions à base de nitroalcène |
WO2010129777A1 (fr) * | 2009-05-08 | 2010-11-11 | Perricone Nicholas V | Procédés d'utilisation de compositions à base de nitroalcène dans des applications dermatologiques |
-
2010
- 2010-06-04 WO PCT/US2010/037419 patent/WO2011152832A1/fr active Application Filing
Patent Citations (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4775530A (en) | 1987-01-06 | 1988-10-04 | Perricone Nicholas V | Method for treatment and prevention of pseudofolliculitis barbae |
US5409693A (en) | 1989-10-12 | 1995-04-25 | Perricone; Nicholas V. | Method for treating and preventing sunburn and sunburn damage to the skin |
US5574063A (en) | 1989-10-12 | 1996-11-12 | Perricone; Nicholas V. | Method and compositions for topical application of ascorbic acid fatty acid esters for treatment and/or prevention of skin damage |
US5376361A (en) | 1993-01-13 | 1994-12-27 | Perricone; Nicholas V. | Method and compositions for topical application to the skin for prevention and/or treatment of radiation-induced skin damage |
US5545398A (en) | 1993-01-13 | 1996-08-13 | Perricone; Nicholos V. | Method and compositions for topical application to the skin of tocotrienol for prevention and/or treatment of skin damage |
US6051244A (en) | 1993-01-27 | 2000-04-18 | Perricone; Nicholas V. | Fructose diphosphate topical compositions |
US5643586A (en) | 1995-04-27 | 1997-07-01 | Perricone; Nicholas V. | Topical compositions and methods for treatment of skin damage and aging using catecholamines and related compounds |
US5879690A (en) | 1995-09-07 | 1999-03-09 | Perricone; Nicholas V. | Topical administration of catecholamines and related compounds to subcutaneous muscle tissue using percutaneous penetration enhancers |
US5709868A (en) | 1995-09-20 | 1998-01-20 | Perricone; Nicholas V. | Lipoic acid in topical compositions |
US6162419A (en) | 1996-11-26 | 2000-12-19 | Nicholas V. Perricone | Stabilized ascorbyl compositions |
US5965618A (en) | 1997-11-17 | 1999-10-12 | Perricone; Nicholas V. | Treatment of scar tissue using lipoic acid |
US6924309B2 (en) | 1999-09-17 | 2005-08-02 | Children, Youth And Women's Health Service Incorporated | Anti-inflammatory nitro and thia-fatty acids |
US6191121B1 (en) | 2000-04-06 | 2001-02-20 | Nicholas V. Perricone | Treatment of skin damage using polyenylphosphatidylcholine |
US7182956B2 (en) | 2002-05-31 | 2007-02-27 | Nicholas V. Perricone | Stable topical drug delivery compositions |
US20070232579A1 (en) | 2004-04-28 | 2007-10-04 | Uab Research Foundation, The | Nitrated Lipids and Methods of Making and Using Thereof |
US20100286257A1 (en) * | 2009-05-08 | 2010-11-11 | Perricone Nicholas V | Methods Of Use Of Nitroalkane Compositions In Dermatologic Applications To Prevent or Treat Skin Aging |
WO2010129763A1 (fr) * | 2009-05-08 | 2010-11-11 | Perricone Nicholas V | Compositions à base de nitroalcène |
WO2010129777A1 (fr) * | 2009-05-08 | 2010-11-11 | Perricone Nicholas V | Procédés d'utilisation de compositions à base de nitroalcène dans des applications dermatologiques |
Non-Patent Citations (17)
Title |
---|
AM. J. CLINICAL DERMATOLOGY, vol. 9, no. 5, 2008, pages 279 - 284 |
BAKER ET AL., FREE RADIC BIOL MED, vol. 46, 2009, pages 989 - 1003 |
BAKER ET AL., FREE RADICAL BIOLOGY & MEDICINE, vol. 46, 2009, pages 989 - 1003 |
BAKER ET AL., J. BIOL. CHEM., vol. 280, 2005, pages 42464 - 42475 |
BATTHYANY ET AL., J BIOL CHEM, vol. 281, 2006, pages 20450 - 63 |
COLLIER ET AL., J. AM. ACAD. DERMATOLOGY, vol. 58, 2008, pages 56 - 59 |
FREE RADICAL BIOLOGY & · MEDICINE, vol. 44, 2008, pages 1887 - 96 |
ILES ET AL., FREE RADICAL BIOLOGY & MEDICINE, vol. 46, 2009, pages 866 - 75 |
KELLEY ET AL., J BIOL CHEM, vol. 283, 2008, pages 36176 - 84 |
LIM, T.C. ET AL., PLASTIC AND RECONST. SURGERY, vol. 98, 1996, pages 911 - 912 |
LIMA ET AL., FREE RADIC. BIOL. MED., vol. 39, 2005, pages 532 - 39 |
PLAST. RECONST. SURGERY, vol. 122, 2008, pages 1068 - 78 |
PROC. NATL. ACAD. SCI. U.S.A., vol. 101, 2004, pages 11577 - 82 |
RUDOLPH ET AL., J. BIOL CHEM, vol. 284, 2009, pages 1461 - 73 |
SCHOPFER ET AL., J. BIOL. CHEM., vol. 280, 2005, pages 19289 - 97 |
TROSTCHANSKY; RUBBO, FREE RADICAL BIOLOGY & MEDICINE, vol. 44, 2008, pages 1887 - 96 |
VILLACORTA ET AL., AM J PHYSIOL HEART CIRC PHYSIOL, vol. 293, 2007, pages H770 - 6 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8563609B2 (en) | 2010-05-13 | 2013-10-22 | Nitromega Corp. | Nitro fatty acids - neuroprotection and/or inhibition of cognitive decline |
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