WO2020044344A1 - Compositions comprenant de l'ozénoxacine - Google Patents

Compositions comprenant de l'ozénoxacine Download PDF

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Publication number
WO2020044344A1
WO2020044344A1 PCT/IL2019/050967 IL2019050967W WO2020044344A1 WO 2020044344 A1 WO2020044344 A1 WO 2020044344A1 IL 2019050967 W IL2019050967 W IL 2019050967W WO 2020044344 A1 WO2020044344 A1 WO 2020044344A1
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Prior art keywords
composition according
composition
ozenoxacin
derivative
salt
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PCT/IL2019/050967
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English (en)
Inventor
Ofer Toledano
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Sol-Gel Technologies Ltd
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Publication of WO2020044344A1 publication Critical patent/WO2020044344A1/fr

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    • 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
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/203—Retinoic acids ; Salts thereof
    • A—HUMAN NECESSITIES
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    • A61K31/327—Peroxy compounds, e.g. hydroperoxides, peroxides, peroxyacids
    • A—HUMAN NECESSITIES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
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    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
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    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
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    • 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
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    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
    • A—HUMAN NECESSITIES
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    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
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    • A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
    • A—HUMAN NECESSITIES
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    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
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    • A61K9/12—Aerosols; Foams
    • A61K9/122—Foams; Dry foams
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    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/501—Inorganic compounds
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    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
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    • A61P17/10—Anti-acne agents

Definitions

  • compositions comprising ozenoxacin or any derivatives or salts thereof alone or with other agents for use in the treatment of dermatological diseases and conditions.
  • Antibacterial agents and retinoids are known to be effective in the treatment of skin disorders such as acne vulgaris. Antibacterial agents act by destroying P. acnes, the bacteria that causes acne condition. Retinoids allow the keratin plugs of microcomedones to be expelled, thus fewer lesions are able to rupture and cause papules, pustules and nodules of acne vulgaris. Most of the treatments developed thus far for the treatment of acne have a common disadvantage of severe adverse events during treatment such as erythema, irritation, burning, stinging, scaling and itching.
  • the inventors of the present application have found that a combination of an antibacterial agent and a retinoid provides both the comedogenesis and the bacteriostatic effect in acne treatment.
  • Ozenoxacin is a highly tolerable known antibacterial agent which in combination with a retinoid can provide safe and efficacious drug product for treatment of acne vulgaris.
  • this invention is directed to a composition
  • a composition comprising as active ingredients (i) ozenoxacin or any derivative or salt thereof, and at least one of (ii) a retinoid; (iii) a peroxide, or combinations thereof.
  • this invention provides a composition comprising (i) ozenoxacin or any derivative or salt thereof, and (ii) a retinoid.
  • this invention provides a composition comprising (i) ozenoxacin or any derivative or salt thereof, and (iii) a peroxide.
  • the composition of this invention is for use in the treatment of a dermatological disease, disorder or symptom thereof.
  • this invention provides a method of treating a dermatological disease or disorder comprising topically applying a composition of this invention to an affected area of a subject in need thereof.
  • the dermatological disease, disorder or symptom is selected from acne, rosacea, infection, inflammation, pruritis, psoriasis, seborrhea, impetigo, herpes, contact and atopic dermatitis and any combination thereof.
  • this invention provides a method of treating rosacea comprising topically applying a composition comprising ozenoxacin or any derivative or salt thereof to an affected area of a subject in need thereof.
  • the invention provides a composition comprising as active ingredients (i) ozenoxacin or any derivative or salt thereof, and at least one of (ii) a retinoid; (iii) a peroxide, or combinations thereof.
  • the salts of basic groups include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, tartaric acid, formic acid, citric acid, trichloroacetic acid trifluoroacetic acid, methanesulfonic acid, benzenesulfonie acid, p-toluenesulfonie acid, mesitylenesulfonic acid and naphthalenesulfonic acid, and the like.
  • the salts of acidic groups include, for example, salts with alkali metals such as sodium and potassium; salts with alkaline earth metals such as calcium and magnesium; ammonium salts; and salts with nitrogen-containing organic bases such as trimethylamine, triefhylamine, tributylamine, pyridine, N.N-di methyianili ne, N-methylpiperidine, N ⁇ methylmorpholme, diethyl amine, dicyclohexyl amine, procain, dibenzylamme, N-benzyl-b- phenethyl amine, 1-ephenamine and N,N'-dibenzylethyienediamine, and the like.
  • alkali metals such as sodium and potassium
  • salts with alkaline earth metals such as calcium and magnesium
  • ammonium salts and salts with nitrogen-containing organic bases
  • nitrogen-containing organic bases such as trimethylamine, triefhylamine, tributyl
  • retinoid it should be understood to encompass any compound of a class of vitamers of vitamin A.
  • the retinoid is selected from tretinoin, isotretinoin, alitretinoin, etretinate, acitretin, tazarotene, adapalene, bexarotene or any combinations thereof.
  • peroxide it should be understood to encompass a compound containing an oxygen single bond including, but not limited to the group consisting of benzoyl peroxide, carbamide peroxide or hydrogen peroxide or any combinations thereof.
  • composition of the invention comprises two active ingredients being (i) ozenoxacin or any derivative or salt thereof, and (ii) a retinoid.
  • a composition of the invention comprises two active ingredients being (i) ozenoxacin or any derivative or salt thereof, and (iii) a peroxide.
  • said ozenoxacin or any derivative or salt thereof is in a solid particulate form (i.e. the ozenoxacin or any derivative or salt thereof is present in the composition in a non-dissolved form or substantially non-dissolved form). In other embodiments, said ozenoxacin or any derivative or salt thereof is dissolved in water.
  • said retinoid is in a solid particulate form (i.e. said retinoid is present in the composition in a non-dissolved form or substantially non-dissolved form).
  • said peroxide is in a solid particulate form (i.e. said peroxide is present in the composition in a non-dissolved form or substantially non-dissolved form).
  • At least one of said active ingredients is coated. In other embodiments at least one of said active ingredient is coated with a metal oxide layer.
  • a metal oxide layer or“ coated with a metal oxide layer’” used herein interchangeably should be understood to refer to the substantial or partial cover of the active ingredient by a metal oxide solid layer wherein said active ingredient is embedded, dispersed, entrapped, or encased, e.g. as a solid dispersion or molecular dispersion in said metal oxide layer.
  • said metal oxide is selected from silica, titania, alumina, zirconia, ZnO, and mixtures thereof.
  • said metal oxide is silica.
  • coated form of the active ingredient is meant that the active ingredient is embedded, dispersed, entrapped, or encased, e.g. as a solid dispersion or molecular dispersion in a polymeric carrier which may be an organic or inorganic carrier and which may serve as a matrix for dispersing the active ingredient or as encapsulated material coating said active ingredient (i.e. the active ingredient is present in a core or is a core material encapsulated by a shell composed of a polymeric material which may be an organic or inorganic polymer).
  • a composition of the invention comprises as active ingredients (i) ozenoxacin or any derivative or salt thereof, and (ii) a retinoid; wherein at least one of the active ingredients is coated with a metal oxide layer.
  • a composition of the invention comprises as active ingredients (i) ozenoxacin or any derivative or salt thereof, and (iii) a peroxide; wherein at least one of the active ingredients is coated with a metal oxide layer.
  • At least one of said active ingredients is encapsulated within a microcapsule.
  • microcapsule refers to a spherical microparticle consisting of a polymeric shell serving as a wall -forming material and encapsulated active agent located within the core of the microcapsule and partially also found in the shell matrix, but not on the outer surface of the shell. Microcapsules are distinct from microspheres, which consist of spherical homogeneous granules of the active substance dispersed in a polymer and are, in strict sense, spherically empty particles.
  • At least one active ingredient is encapsulated within a microcapsule.
  • the term "encapsulated within a microcapsule” should be understood to refer to a microcapsule that is formed around the active ingredient of a composition of the invention wherein said active ingredient is embedded, dispersed, entrapped, or encased, e.g. as a solid dispersion or molecular dispersion in said microcapsule.
  • said microcapsules are prepared by deposition of metal oxide on the surface of a solid particulate matter of the active ingredient. In other embodiments said microcapsules are prepared by oil-in- water in situ polymerization encapsulation processes.
  • said microcapsule further comprises a phase changing material (PCM) in the core.
  • PCM phase changing material
  • the preparation of microcapsules under this embodiment can be found in WO 2011/080741 which is herein incorporated by reference.
  • phase changing material PCM is meant to encompass any substance capable of changing its state of matter (phase), or at least its viscosity, in accordance with the temperature it is exposed to.
  • PCMs typically have a high heat of fusion which enables them to melt and solidify at certain temperatures, and are capable of storing and releasing large amounts of energy. Heat is absorbed or released when the PCM material changes from solid to liquid and vice versa.
  • a phase changing material is an organic material, and is characterized by the fact that at room temperature said PCM has a viscosity of between about 300cP to l,000,000cP (when measured under various conditions).
  • the viscosity of said PCM at room temperature may be 300cP, 350cP, 400cP, 450cP, 500cP, 550cP, 600cP, 650cP, 700cP, 750cP, 800cP, 900cP, lOOOcP, 2000cP, 3000cP, 4000cP, 5000cP, 6000cP, 7000cP, 8000cP, 9000cP, l0,000cP, 20,000cP, 30,000cP, 40,000 cP, 50,000cP, 60,000 cP, 70,000cP, 80,000cP, 90,000cP, l00,000cP, 200,000cP, 300,000cP, 400,000cP, 500,000cP, 600,000cP, 700,000cP, 800,000cP, 900,000cP or l,000,000cP (when measured under various conditions).
  • Cio-Cioo alkane Cio- Cioo alkene (having at least one double bond)
  • Cio-Cioo alkyne having at least one
  • phase changing material is at least one natural or synthetic paraffin.
  • said at least one phase changing material is a Cio-Cioo aliphatic alcohol (in other embodiments Cio, C20, C30, C40, C50, C60, C70, Cso, C90 to C100 aliphatic alcohol).
  • said at least one phase changing material is a Cio-Cioo aliphatic fatty acid (in other embodiments Cio, C20, C30, C40, C50, C60, C70, Cso, C90 to C100 aliphatic fatty acid).
  • said PCMs are liquified (or at least become substantially or partially liquified, pliable or semi-solid) at a temperature range of between about 35 °C to about 60°C, more preferably in a temperature range of between about 35°C to about 45°C.
  • phase changing materials include, but are not limited to: Carnauba wax (m.p. 82-86°C), Beeswax pure (m.p. 6l-65°C), Beeswax white pure, (m.p. 6l-65°C), Beeswax bleached technical (m.p. 6l-65°C), Montan wax bleached (m.p. 80-86°C), Montan wax bleached, partially saponified (m.p. 99-l05°C), Montanic acid (m.p. 8 l-87°C), Hydrocarbon wax synthetic (m.p. 106-1 l4°C), Microcrystalline wax (m.p. 89-95°C), Microcrystalline wax (m.p.
  • the coated form of the active ingredient may be in form of a polymeric microsponge where the active ingredient is adsorbed or entrapped in said microsponge as described for example in US Pat. No. 4,690,825; US Pat. No. 5,145,675, US Pat. No. 5,879,716 and US Pat. No. 5,955,109, incorporated herein by reference in their entirety.
  • a microparticle of the invention may also be prepared by a process as disclosed in co-owned PCT application, publication number WO 2007/015243, the content of which is incorporated herein by reference in its entirety.
  • an encapsulated microcapsule of the invention may also be prepared by a process as disclosed in US Pat. No. 6,932,984, US pat. No. 9,682,031 and PCT application, publication number WO 2007/023495 which are incorporated herein by reference in their entirety.
  • an encapsulated microcapsule of the invention may also be prepared by a Sol-Gel process, thus isolating the active ingredient from the environments.
  • the microcapsules are formed using a sol-gel process as disclosed in the following documents (herein incorporated by reference): US patent Nos. 6,303,149, 6,238,650, 6,468,509, 6,436,375, US2005037087, US2002064541, and International publication Nos.
  • WO 00/09652, WO00/72806, WO 01/80823, WO 03/03497, WO 03/039510, WO00/71084, W005/009604, and WO04/81222 disclose sol-gel microcapsules and methods for their preparation;
  • EP 0 934 773 and U.S. Pat. No. 6,337,089 teach microcapsules containing core material and a capsule wall made of organopolysiloxane, and their production;
  • EP0941 761 and U.S. Pat. No. 6,251,313 also teach the preparation of microcapsules having shell walls of organopolysiloxane; U.S. Pat. No.
  • 4,931 ,362 describes a method of forming microcapsules or micromatrix bodies having an interior water- immiscible liquid phase containing an active, water-immiscible ingredient.
  • Microcapsules prepared by a sol-gel process are also disclosed in GB2416524, US6,855,335, W003/066209; which are all incorporated herein by reference in their entirety.
  • microcapsules are formed by the encapsulation process disclosed in the following publications (herein incorporated by reference): US 7,629,394, US 9,205,395, US 2015/0328615, US 2014/0186630.
  • Controlled release microcapsules IN01958CH2007, IN02080CH2007, US 4,235,872, US4670250, EP 0248531, US 4,970,031, US 5,238,714, W01993/21764, US 5,575,987, WO 1994/20075, US 2004/137031 , US 2006/003014, US 2010/180464. which are all incorporated herein by reference in their entirety.
  • the encapsulated benzoyl peroxide (E-BPO) is prepared as described in US patent publication 2010-0016443, and the encapsulated All Trans Retinoic Acid (E-ATRA) is prepared as described in US patent publication US 2012/0202695.
  • a composition of the invention comprises as active ingredients (i) ozenoxacin or any derivative or salt thereof, and (ii) a retinoid; wherein at least one of the active ingredients is encapsulated within a microcapsule.
  • a composition of the invention comprises as active ingredients (i) ozenoxacin or any derivative or salt thereof, and (iii) a peroxide; wherein at least one of the active ingredients is encapsulated within a microcapsule.
  • said ozenoxacin or any derivative or salt thereof comprises at least
  • the ozenoxacin or any derivative or salt thereof comprises between about 0.2% w/w to about 5%w/w of the composition. In another embodiment, the ozenoxacin or any derivative or salt thereof comprises between about 0.2% w/w to about l%w/w of the composition. In another embodiment, the ozenoxacin or any derivative or salt thereof comprises between about 0.2% w/w to about 2%w/w of the composition. In another embodiment, the ozenoxacin or any derivative or salt thereof comprises between about 0.2% w/w to about 3%w/w of the composition.
  • the ozenoxacin or any derivative or salt thereof comprises between about 0.2% w/w to about 4%w/w of the composition. In another embodiment, the ozenoxacin or any derivative or salt thereof comprises between about 1 % w/w to about 5% w/w of the composition.
  • said retinoid comprises at least 0.01 %w/w of the composition. In other embodiments, said retinoid comprises between about 0.01 %w/w to about l%w/w of the composition. In other embodiments, said retinoid comprises between about 0.01 %w/w to about 0.05%w/w of the composition. In other embodiments, said retinoid comprises between about
  • the retinoid is selected from tretinoin, isotretinoin, alitretinoin, etretinate, acitretin, tazarotene, adapalene, bexarotene or any combinations thereof.
  • said peroxide comprises at least l%w/w of the composition. In further embodiments, said peroxide comprises between about l%w/w to about l5%w/w of the composition. In further embodiments, said peroxide comprises between about l%w/w to about 5%w/w of the composition. In further embodiments, said peroxide comprises between about 5%w/w to about l0%w/w of the composition. In further embodiments, said peroxide comprises between about 3%w/w to about l0%w/w of the composition. In some embodiments, the peroxide is selected from benzoyl peroxide, carbamide peroxide or hydrogen peroxide or any combinations thereof.
  • the composition of this invention is stable for a period between 2 weeks to about 2 years at room temperature. In some embodiment, the composition of this invention is stable for a period between 2 weeks to about 2 years at ambient conditions.
  • the composition of this invention is stable for at least 3 months when the composition is stored at room temperature. In other embodiments the composition of this invention is stable for a period of between about 3 months to about 2 years when it is stored at room temperature. [048] In some embodiments, the composition of this invention comprising ozenoxacin or any derivative or salt thereof, and a peroxide, is stable for at least one year under refrigeration conditions.
  • composition of this invention comprising ozenoxacin or any derivative or salt thereof, a peroxide and a retinoid, is stable for at least one year under refrigeration conditions.
  • tablette refers to the ability of the composition to maintain said at least one active ingredient within said composition, with a maximal degradation of between about 0 to 5% of said active agent, for a set period of time under conditions of temperature and RH.
  • room temperature refers herein to a temperature between 20-25°C.
  • the present invention also relates to pharmaceutical compositions comprising the defined active ingredients in admixture with pharmaceutically acceptable auxiliaries, and optionally other therapeutic agents.
  • the auxiliaries must be“acceptable” in the sense of being compatible with the other ingredients of the composition and not deleterious to the recipients thereof.
  • compositions include those suitable for topical (including transdermal, buccal and sublingual, vaginal, anal) administration or administration via an implant or dermatological or topical patch.
  • the compositions may be prepared by any method well known in the art of pharmacy. Such methods include the step of bringing in association compounds used in the invention or combinations thereof with any auxiliary agent.
  • the auxiliary agent(s), also named accessory ingredient(s) include those conventional in the art, such as carriers, fillers, binders, diluents, disintegrants, lubricants, colorants, flavouring agents, anti-oxidants, and wetting agents.
  • the invention further includes a pharmaceutical composition, as hereinbefore described, in combination with packaging material, including instructions for the use of the composition for a use as hereinbefore described.
  • compositions or formulations suitable for transdermal administration e.g. gels, patches or sprays can be contemplated.
  • Compositions or formulations suitable for pulmonary administration e.g. by nasal inhalation include fine dusts or mists which may be generated by means of metered dose pressurized aerosols, nebulisers or insufflators.
  • the exact dose and regimen of administration of the composition will necessarily be dependent upon the therapeutic or nutritional effect to be achieved and may vary with the particular formula, the route of administration, and the age and condition of the individual subject to whom the composition is to be administered.
  • a composition of the invention is formulated to a dermatological composition.
  • Topical therapies can be delivered in various vehicles, which include powders, liquids, combinations of liquid and oil.
  • the vehicle influences a therapy’s effectiveness and may itself cause adverse effects (e.g., contact or irritant dermatitis).
  • aqueous and alcohol-based preparations are drying because the liquid evaporates and are used in acute inflammatory conditions. Powders are also drying.
  • Oil-based preparations are moisturizing and are preferred for chronic inflammation. Vehicle selection is guided by location of application, cosmetic effects, and convenience.
  • Inert powders may be mixed with active agents to deliver therapy. They are prescribed for lesions in moist or intertriginous areas.
  • Liquid vehicles include baths and soaks, foams, solutions, lotions and gels. Baths and soaks are used when therapy must be applied to large areas, such as with extensive contact dermatitis or atopic dermatitis.
  • Foams are alcohol- or emollient-based aerosolized preparations. They tend to be rapidly absorbed and may be favored in hair-bearing areas of the body. Solutions are ingredients dissolved in a solvent, usually ethyl alcohol, propylene glycol, polyethylene glycol, or water.
  • Lotions are water-based emulsions. They are easily applied to hairy skin. Lotions cool and dry acute inflammatory and exudative lesions, such as contact dermatitis, tinea pedis, and tinea cruris. Gels are ingredients suspended in a solvent thickened with polymers. Gels are often more effective for controlled release of topical agents. They are often used in acne, rosacea, and psoriasis of the scalp. Combinations include creams, ointments. Combination vehicles usually contain oil and water but may also contain propylene or polyethylene glycol.
  • Creams are semi-solid emulsions of oil and water. They are used for moisturizing and cooling and when exudation is present. They vanish when rubbed into skin. Ointments are oil based with little if any water. Ointments are optimal lubricants and increase drug penetration because of their occlusive nature; a given concentration of drug is typically more potent in an ointment. They are used for lichenified lesions and lesions with thick crusts or heaped- up scales, including psoriasis and lichen simplex chronicus. Ointments are less irritating than creams for erosions or ulcers. They are usually best applied after bathing or dampening the skin with water. Dressings protect open lesions, facilitate healing, increase drug absorption, and protect the patient’s clothing.
  • Nonocclusive dressings include gauze dressings. They maximally allow air to reach the wound, which is often preferred in healing, and allow the lesion to dry.
  • Nonocclusive dressings wetted with solution, usually saline, are used to help cleanse and debride thickened or crusted lesions. The dressings are applied wet and removed after the solution has evaporated (wet-to-dry dressings); materials from the skin then adhere to the dressing.
  • Occlusive dressings increase the absorption and effectiveness of topical therapy. Most common are transparent films such as polyethylene (plastic household wrap) or flexible, transparent, semi-permeable dressings. Hydrocolloid dressings can be applied with a gauze cover in patients with cutaneous ulceration.
  • Zinc oxide gelatin (Unna paste boot) is an effective occlusive dressing for patients with stasis dermatitis and ulcers.
  • Plastic tape impregnated with flurandrenolide, a corticosteroid, can be used for isolated or recalcitrant lesions.
  • Occlusive dressings applied over topical corticosteroids to increase absorption are sometimes used to treat psoriasis, atopic dermatitis, skin lesions resulting from systemic lupus erythematosus, and chronic hand dermatitis, among other conditions.
  • Other occlusive dressings are used to protect and help heal open wounds, such as burns.
  • said dermatological composition is selected from a gel, cream, foam, lotion, ointment, paste, patch, liniment, paint, aerosol, suppository and any combination thereof.
  • the invention provides a composition as defined herein above for use in the treatment of a dermatological disease, disorder or symptom thereof.
  • the treatment comprises once daily or twice daily topical administration of the composition of the present invention to a subject in need thereof.
  • the treatment is for a period of time of up to 12 weeks.
  • co-administration of the active agents/ingredients exhibits an additive and/or synergistic effect during or following the treatment.
  • co-administration of the active ingredients may be made either by administration of a single combination composition, or alternatively by separate administration of a first composition comprising (i) ozenoxacin or any derivative or salt thereof, and (ii) one or both of a peroxide and a retinoid.
  • this invention provides a dual chamber dispenser, having a first chamber charged with a first composition comprising ozenoxacin or any derivative or salt thereof, and a second chamber charged with a second composition comprising at least one of (ii) a retinoid; (iii) a peroxide, or combinations thereof, wherein the two compositions are mixed before applying on the skin of a patient in need thereof, thus administering a combination product.
  • at least one active ingredient is coated/encapsulated.
  • this invention provides a dual chamber dispenser, having a first chamber charged with a first composition comprising ozenoxacin or any derivative or salt thereof, and a second chamber charged with a second composition comprising at a retinoid, wherein the two compositions are mixed before applying on the skin of a patient in need thereof, thus administering a combination product.
  • at least one active ingredient is coated/encapsulated.
  • this invention provides a dual chamber dispenser, having a first chamber charged with a first composition comprising ozenoxacin or any derivative or salt thereof, and a second chamber charged with a second composition comprising at a peroxide, wherein the two compositions are mixed before applying on the skin of a patient in need thereof, thus administering a combination product.
  • at least one active ingredient is coated/encapsulated.
  • this invention provides a dual chamber dispenser, having a first chamber charged with a first composition comprising ozenoxacin or any derivative or salt thereof, and a second chamber charged with In some embodiments, this invention provides a dual chamber dispenser, having a first chamber charged with a first composition comprising ozenoxacin or any derivative or salt thereof, and a second chamber charged with a second composition comprising at a retinoid and a peroxide, wherein optionally at least one or both of the retinoid and peroxide is coated/encapsulated, wherein the two compositions are mixed before applying on the skin of a patient in need thereof, thus administering a combination product.
  • treatment means the management and care of a patient for the purpose of combating a disease, disorder or condition.
  • the term is intended to include the delaying of the progression of the disease, disorder or condition, the alleviation or relief of symptoms and complications, and/or the cure or elimination of the disease, disorder or condition.
  • Topical dermatologic treatments include cleansing agents, absorbent dressings (eg, hydrocolloid patches or powder) and super-absorbent powders, anti-infective agents, anti- inflammatory agents, astringents (drying agents that precipitate protein and shrink and contract the skin), emollients (skin hydrators and softeners), keratolytics (agents that soften, loosen, and facilitate exfoliation of the squamous cells of the epidermis).
  • absorbent dressings eg, hydrocolloid patches or powder
  • super-absorbent powders e.g, anti-infective agents, anti- inflammatory agents, astringents (drying agents that precipitate protein and shrink and contract the skin), emollients (skin hydrators and softeners), keratolytics (agents that soften, loosen, and facilitate exfoliation of the squamous cells of the epidermis).
  • said dermatological disease, disorder or symptom is selected from acne, rosacea, infection, inflammation, pruritis, psoriasis, seborrhea, impetigo, herpes, contact and atopic dermatitis and any combination thereof.
  • said dermatological disease, disorder or symptom is acne.
  • the invention provides a method of treating a dermatological disease or disorder comprising topically applying a composition as defined herein above.
  • the composition of the present invention is applied once daily or twice daily.
  • the composition of the present invention is applied once daily or twice daily for a period of time of up to 12 weeks.
  • the invention further provides a composition comprising ozenoxacin or any derivative or salt thereof, for use in the treatment of rosacea and any symptom thereof.
  • said composition further comprising benzoyl peroxide optionally in an encapsulated form.
  • the invention provides a method of treating rosacea and any symptom thereof comprising topically applying a composition comprising ozenoxacin or any derivative or salt thereof to an affected area of a subject in need thereof.
  • Example 1 Cream formulation of ozenoxacin and tretinoin.
  • Example 2 Gel formulation of ozenoxacin and adapalene.

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Abstract

La présente invention concerne des compositions comprenant de l'ozénoxacine ou n'importe quels dérivés ou sels de celle-ci seuls ou avec d'autre agents, en vue d'une utilisation dans le traitement de maladies et d'affections dermatologiques.
PCT/IL2019/050967 2018-08-29 2019-08-28 Compositions comprenant de l'ozénoxacine WO2020044344A1 (fr)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100099704A1 (en) * 2005-08-01 2010-04-22 Tsuyoshi Hirota Lotion Preparation Containing Pyridonecarboxylic Acid Derivative
US20120269874A1 (en) * 2007-02-01 2012-10-25 Sol-Gel Technologies Ltd. Compositions for topical application comprising a peroxide and retinoid

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100099704A1 (en) * 2005-08-01 2010-04-22 Tsuyoshi Hirota Lotion Preparation Containing Pyridonecarboxylic Acid Derivative
US20120269874A1 (en) * 2007-02-01 2012-10-25 Sol-Gel Technologies Ltd. Compositions for topical application comprising a peroxide and retinoid

Non-Patent Citations (4)

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Title
FENERAN ASHELY N . ET AL.: "Retinoid plus antimicrobial combination treatments for acne", CLINICAL, COSMETIC AND INVESTIGATIONAL DERMATOLOGY, vol. 4, 30 June 2011 (2011-06-30), pages 79 - 92, XP055696914 *
KEATING GILLIAN M: "Adapalene 0.1%/benzoyl peroxide 2.5% gel: a review of its use in the treatment of acne vulgaris in patients aged >= 12 years", AMERICAN JOURNAL OF CLINICAL DERMATOLOGY, vol. 12, no. 6, 1 December 2011 (2011-12-01), pages 407 - 420, XP008163489, DOI: 10.2165/11208170-000000000-00000 *
NAKAJIMA A ET AL.: "Antimicrobial activities of ozenoxacin against isolates of propionibacteria and staphylococci from Japanese patients with acne vulgaris", JOURNAL OF MEDICAL MICROBIOLOGY, vol. 65, no. 8, 1 August 2016 (2016-08-01), pages 745 - 750, XP055696909 *
RATHI SANJAY K.: "Acne vulgaris treatment: the current scenario", INDIAN JOURNAL OF DERMATOLOGY, vol. 56, no. 1, 28 February 2012 (2012-02-28), pages 7 - 13 *

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