[go: up one dir, main page]

US20170181991A1 - Method for the treatment of acne using pharmaceutical compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid - Google Patents

Method for the treatment of acne using pharmaceutical compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid Download PDF

Info

Publication number
US20170181991A1
US20170181991A1 US15/456,933 US201715456933A US2017181991A1 US 20170181991 A1 US20170181991 A1 US 20170181991A1 US 201715456933 A US201715456933 A US 201715456933A US 2017181991 A1 US2017181991 A1 US 2017181991A1
Authority
US
United States
Prior art keywords
acne
adapalene
treatment
company
adamantyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US15/456,933
Inventor
Michael Graeber
Janusz Czernielewski
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Galderma Research and Development SNC
Original Assignee
Galderma Research and Development SNC
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27806678&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20170181991(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from FR0203070A external-priority patent/FR2837101B1/en
Application filed by Galderma Research and Development SNC filed Critical Galderma Research and Development SNC
Priority to US15/456,933 priority Critical patent/US20170181991A1/en
Assigned to GALDERMA RESEARCH & DEVELOPMENT reassignment GALDERMA RESEARCH & DEVELOPMENT ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: GRAEBER, MICHAEL, CZERNIELEWSKI, JANUSZ
Publication of US20170181991A1 publication Critical patent/US20170181991A1/en
Abandoned legal-status Critical Current

Links

Images

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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/07—Retinol compounds, e.g. vitamin A
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • 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
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • 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
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/362—Polycarboxylic acids
    • 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
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • 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
    • A61K9/08—Solutions
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • A61P17/06—Antipsoriatics
    • 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
    • A61P17/10—Anti-acne agents
    • 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
    • A61P17/12—Keratolytics, e.g. wart or anti-corn preparations
    • 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
    • A61P17/18—Antioxidants, e.g. antiradicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning 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
    • A61Q19/007—Preparations for dry 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
    • A61Q19/008—Preparations for oily skin
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6903—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/56—Ring systems containing bridged rings
    • C07C2603/58—Ring systems containing bridged rings containing three rings
    • C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
    • C07C2603/74—Adamantanes

Definitions

  • the present invention relates to novel pharmaceutical compositions comprising about 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid, the chemical structure of which is as follows:
  • compositions for the treatment of dermatological ailments, disorders, conditions or afflictions having an inflammatory or proliferative component.
  • 6-[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic acid (hereinafter referred to as adapalene) is a retinoid derived from naphthoic acid, having anti-inflammatory properties. This molecule has been the subject of development for the topical treatment of common acne and dermatoses sensitive to retinoids.
  • Adapalene is described in EP-0199636, and a process for synthesizing same is described in EP-0358574, both assigned to the assignee hereof.
  • the assignee hereof markets adapalene formulated at a weight concentration of 0.1% in the form of an alcoholic lotion, an aqueous gel and a cream. These compositions are suited for the treatment of acne.
  • Novel pharmaceutical compositions have now been developed containing adapalene at a weight concentration on the order of or about 0.3%, formulated into pharmaceutically acceptable media therefor, suited for the treatment (regime or regimen) of dermatological ailments, conditions or afflictions having an inflammatory or proliferative component.
  • the compositions according to the invention exhibit good tolerance, comparable to those of the known compositions with a lower concentration of active principle.
  • FIGS. 1-3 are graphs illustrating the effectiveness of the dermatological compositions of the present invention versus comparative compositions and controls.
  • the present invention features pharmaceutical compositions comprising about 0.3% by weight of adapalene (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid) relative to the total weight of the composition, or salts thereof, preferably in the form of aqueous gels.
  • adapalene 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid
  • Such compositions are suited for the treatment (regime or regimen) of dermatological ailments, disorders or conditions having an inflammatory or proliferative component.
  • adapalene salts is intended to mean the salts formed with a pharmaceutically acceptable base, in particular organic bases such as sodium hydroxide, potassium hydroxide and aqueous ammonia, or organic bases such as lysine, arginine or N-methylglucamine.
  • adapalene salts is also intended to mean the salts formed with a pharmaceutically acceptable base, in particular in organic bases such as sodium hydroxide, potassium hydroxide and aqueous ammonia, or organic bases such as lysine, arginine or N-methylglucamine.
  • adapalene salts is also intended to mean the salts formed with fatty amines such as dioctylamine and stearylamine.
  • compositions according to the invention are preferably applied topically.
  • compositions according to the invention are more particularly suited for treatment of the skin and the mucous membranes, and may be in the form of ointments, creams, milks, pomades, powders, impregnated pads, solutions, gels, sprays, lotions or suspensions. They may also be in the form of suspensions of microspheres or nanospheres or of lipid or polymeric vesicles, or of polymeric patches and hydrogels for controlled release. These compositions for topical application may be in anhydrous form, in aqueous form or in the form of an emulsion.
  • the pharmaceutical compositions according to the invention are in the form of a gel, preferably aqueous, a cream, a lotion or a solution.
  • this invention also features pharmaceutical compositions comprising about 0.3% by weight of adapalene (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid) relative to the total weight of the composition, or salt thereof, formulated as creams.
  • adapalene 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid
  • compositions comprising about 0.3% by weight of adapalene (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid) relative to the total weight of the composition, or salt thereof, formulated as lotions.
  • adapalene 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid
  • the lotions according to the invention do not comprise any alcohol, but may comprise at least one glycol; consequently, they are not alcoholic, but preferably glycolic.
  • compositions comprising about 0.3% by weight of adapalene (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid) relative to the total weight of the composition, or salt thereof, formulated as solutions or spray solutions.
  • adapalene 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid
  • solution is intended a liquid composition at ambient temperature (20-30°) and comprising a single phase.
  • Such compositions are preferably alcoholic or may comprise at least one glycol or lipophilic component.
  • the pharmaceutical composition may be an aqueous gel comprising at least one ingredient selected from among:
  • the pharmaceutical composition may be a cream comprising at least one ingredient selected from among:
  • the common oils are representative such as paraffin oil, Vaseline (or petroleum jelly), almond oil, perhydrosqualene, apricot oil, wheat germs oil, sweet almond oil, calophyllum oil, palm oil, castor oil, avocado oil, jojoba oil, olive oil or cerales germs oil; fatty acids esters or fatty alcohols esters such as dodecyl octyl octanoates, alcohols or polyalcohols decanoates or ricinoleates; fatty acids triglycerides; glycerides; hydrogenated polyisobutene, solid at 25° C. hydrogenated oils; lanolines; solid at 25° C.
  • fatty esters adipate diisopropyl (tradename Crodamol DA by Croda company), PPG 15 stearyl ether (tradename Arlamol E by UNIQEMA company), octyl dodecanol (tradename Eutanol G by COGNIS company), Caprilic/capric triglycerides (tradename Miglyol 812N by SPCI company), C12-C15 alkyl benzoate (tradename Tegosoft TN by Degussa company).
  • tensioactive agents or as emulsifying agents several components are representative selected from among PEG-20 methyl glucose sequistearate (tradename GLUCAMATE SSE 20 by Amerchol company) or Methyl glucose sesquistearate (tradename GLUCATE SS by Amerchol company), unsaturated or saturated fatty acids esters, oleic acid or isostearic acid such as polyglycerin and isostearic acid esters (tradename LAMEFORM TGI by SIDOBRE-SINNOVA HENKEL company), sorbitan isostearate (tradename ARLACEL 987 by UNIQEMA company), sorbitan sesquioleate (tradename ARLACEL 83 by UNIQEMA company), sorbitan laurate (tradename SPAN 20 by UNIQEMA company), glycol and isostearic acid esters such as PEG-6 isostearate (tradename OLEPAL ISOSTEARIQUE by GATTEFOSSE company), sorbitol and oleic acid esters
  • the pharmaceutical composition may be a lotion comprising at least one ingredient selected from among:
  • the pharmaceutical composition may be a solution or a spray solution comprising alcohol and at least one ingredient selected from among:
  • the composition has of following formula:
  • compositions according to the invention may also comprise inert additives or combinations thereof, such as:
  • preservatives such as para-hydroxybenzoic acid esters
  • antioxidants such as ⁇ -tocopherol, butylhydroxyanisole or butylhydroxytoluene, superoxide dismutase, ubiquinol or certain metal chelating agents.
  • compositions according to the invention are suited for the treatment of dermatological ailments, conditions and afflictions having an inflammatory or proliferative component, selected from the group consisting of:
  • compositions according to the invention are particularly suitable for the treatment of acne, such as common acne, and in particular for the treatment of common acne of moderate to moderately severe intensity.
  • compositions comprising 0.3% of adapalene will now be given, it being understood that same are intended only as illustrative and in nowise limitative. Also given are results showing the therapeutic effects of the compositions according to the invention and the good tolerance to same by the treated patients.
  • the adapalene of the present example was obtained from the company Sylachim.
  • Tests were carried out on a population consisting of patients suffering from acne. In this population, three groups were differentiated; the first received a daily topical application of the 0.3% adapalene gel, the second a daily topical application of the 0.1% adapalene gel in the same vehicle, and the third is a control group which receives a daily topical application of the gel corresponding to the composition of the first two gels but containing no active agent.
  • FIGS. 1 to 3 provide the results obtained in terms of regression of the number of lesions according to their nature.
  • the 0.3% adapalene gel acts more rapidly than the 0.1% adapalene gel; specifically, from the fourth week of treatment, a difference is noted between the effectiveness of the 0.1% adapalene gel and the 0.3% adapalene gel;
  • the 0.3% adapalene gel produces a clearly greater therapeutic effect after 8 weeks of treatment.
  • Blood samples are taken on the days 1, 2, 4, 6, 8 and 10. During day 10, and following the final application, samples are taken at 1, 2, 6, 8, 10, 12, 16 and 24 hours.
  • the plasma concentration of total adapalene (free and conjugated) in these samples is determined using the following protocol:
  • This method makes it possible to detect a minimum concentration of 0.15 ng/ml and permits quantification of the adapalene for a minimum concentration of 0.25 ng/ml.
  • the plasma concentrations of adapalene measured after 10 days of treatment are very low and confirm the safety of daily use of the 0.3% adapalene gel.
  • a pharmaceutical composition containing 0.3% of adapalene exhibits a benefit/risk ratio which makes it particularly suitable for the treatment of dermatological maladies having an inflammatory or proliferative component, and in particular, common acne.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Emergency Medicine (AREA)
  • Birds (AREA)
  • Inorganic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Cosmetics (AREA)

Abstract

Dermatological disorders having an inflammatory or proliferative component, notably common acne, are treated with topically applicable pharmaceutical compositions containing about 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid (adapalene) or salt thereof, formulated into pharmaceutically acceptable media therefor, advantageously formulated into topically applicable gels, preferably aqueous gels, creams, lotions or solutions.

Description

    CROSS-REFERENCE TO EARLIER APPLICATIONS
  • This application is a continuation of U.S. application Ser. No. 14/524,602, filed Oct. 27, 2014, now allowed, which is a continuation of U.S. application Ser. No. 12/957,882, filed Dec. 1, 2010, now U.S. Pat. No. 8,921,423, which is a continuation of U.S. application Ser. No. 12/772,861 filed May 3, 2010, now U.S. Pat. No. 7,868,044, which is a division of U.S. application Ser. No. 11/494,693, filed Jul. 28, 2006, now U.S. Pat. No. 7,737,181, which is a continuation-in-part of U.S. application Ser. No. 10/937,612, filed Sep. 10, 2004, now U.S. Pat. No. 7,579,377, which is a continuation of PCT/EP03/03246 filed Mar. 12, 2003 and designating the United States (published in English on Sep. 18, 2003 as WO 03/075908 A1), claiming benefit of U.S. Provisional Application No. 60/370,223, filed Apr. 8, 2002, and also claiming foreign priority under 35 U.S.C. §119 of Application No. 02/03070 filed in France on Mar. 12, 2002, each of the above applications being hereby expressly incorporated by reference in its entirety and each being assigned to the assignee hereof.
    • BACKGROUND OF THE INVENTION
  • Technical Field of the Invention
  • The present invention relates to novel pharmaceutical compositions comprising about 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid, the chemical structure of which is as follows:
  • Figure US20170181991A1-20170629-C00001
  • in particular dermatological compositions, for the treatment of dermatological ailments, disorders, conditions or afflictions having an inflammatory or proliferative component.
  • Description of Background and/or Related and/or Prior Art
  • 6-[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic acid (hereinafter referred to as adapalene) is a retinoid derived from naphthoic acid, having anti-inflammatory properties. This molecule has been the subject of development for the topical treatment of common acne and dermatoses sensitive to retinoids.
  • Adapalene is described in EP-0199636, and a process for synthesizing same is described in EP-0358574, both assigned to the assignee hereof.
  • The assignee hereof markets adapalene formulated at a weight concentration of 0.1% in the form of an alcoholic lotion, an aqueous gel and a cream. These compositions are suited for the treatment of acne.
    • SUMMARY OF THE INVENTION
  • Novel pharmaceutical compositions have now been developed containing adapalene at a weight concentration on the order of or about 0.3%, formulated into pharmaceutically acceptable media therefor, suited for the treatment (regime or regimen) of dermatological ailments, conditions or afflictions having an inflammatory or proliferative component. Specifically, it has now surprisingly been shown that, in addition to exhibiting better therapeutic efficacy compared to known compositions, the compositions according to the invention exhibit good tolerance, comparable to those of the known compositions with a lower concentration of active principle.
  • The results regarding tolerance observed in trials relating to photo-damaged skin (indication “photodamage”), obtained on individuals on average 65 years old, could not be exploited in the context of the present invention. Specifically, as regards use of adapalene on young individuals (in particular regarding acne with populations of teenagers or young adults), the skin exhibits very different physiopathological characteristics (presence of many lesions, in particular inflammatory lesions, modifying skin permeability, hypercornification of the follicular channel, immuno response, bacterial colonization of the skin (P. acnes), sebaceous hyperplasia with hyperseborrhea).
    • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIGS. 1-3 are graphs illustrating the effectiveness of the dermatological compositions of the present invention versus comparative compositions and controls.
    •  DETAILED DESCRIPTION OF BEST MODE AND SPECIFIC/PREFERRED EMBODIMENTS OF THE INVENTION
  • Thus, the present invention features pharmaceutical compositions comprising about 0.3% by weight of adapalene (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid) relative to the total weight of the composition, or salts thereof, preferably in the form of aqueous gels. Such compositions are suited for the treatment (regime or regimen) of dermatological ailments, disorders or conditions having an inflammatory or proliferative component.
  • The term “adapalene salts” is intended to mean the salts formed with a pharmaceutically acceptable base, in particular organic bases such as sodium hydroxide, potassium hydroxide and aqueous ammonia, or organic bases such as lysine, arginine or N-methylglucamine.
  • The term “adapalene salts” is also intended to mean the salts formed with a pharmaceutically acceptable base, in particular in organic bases such as sodium hydroxide, potassium hydroxide and aqueous ammonia, or organic bases such as lysine, arginine or N-methylglucamine.
  • The term “adapalene salts” is also intended to mean the salts formed with fatty amines such as dioctylamine and stearylamine.
  • The pharmaceutical compositions according to the invention are preferably applied topically.
  • Topically, the pharmaceutical compositions according to the invention are more particularly suited for treatment of the skin and the mucous membranes, and may be in the form of ointments, creams, milks, pomades, powders, impregnated pads, solutions, gels, sprays, lotions or suspensions. They may also be in the form of suspensions of microspheres or nanospheres or of lipid or polymeric vesicles, or of polymeric patches and hydrogels for controlled release. These compositions for topical application may be in anhydrous form, in aqueous form or in the form of an emulsion.
  • In a preferred embodiment of the invention, the pharmaceutical compositions according to the invention are in the form of a gel, preferably aqueous, a cream, a lotion or a solution.
  • Accordingly, this invention also features pharmaceutical compositions comprising about 0.3% by weight of adapalene (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid) relative to the total weight of the composition, or salt thereof, formulated as creams.
  • This invention also features pharmaceutical compositions comprising about 0.3% by weight of adapalene (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid) relative to the total weight of the composition, or salt thereof, formulated as lotions.
  • By “lotion” is intended a fluid emulsion of water-in-oil or oil-in-water type. Preferably, the lotions according to the invention do not comprise any alcohol, but may comprise at least one glycol; consequently, they are not alcoholic, but preferably glycolic.
  • Another embodiment of the invention features pharmaceutical compositions comprising about 0.3% by weight of adapalene (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid) relative to the total weight of the composition, or salt thereof, formulated as solutions or spray solutions.
  • By “solution” is intended a liquid composition at ambient temperature (20-30°) and comprising a single phase. Such compositions are preferably alcoholic or may comprise at least one glycol or lipophilic component.
  • In particular, the pharmaceutical composition may be an aqueous gel comprising at least one ingredient selected from among:
      • Carbomers, for example Carbopol 980 NF marketed by NOVEON;
      • polymeric emulsifying agents such as PEMULEN (crosspolymers acrylates/C10-30 alkyl acrylates, for example, PEMULEN TR1, PEMULEN TR2, CARBOPOL 1342, CARBOPOL 1382, Carbopol 981 or carbopol Ultrez marketed by the company NOVEON);
      • polysaccharidic biopolymers such as xanthan gum (for example, Keltrol T and Xantural 180 marketed by the company Kelco);
      • gums such as caroub gum, guar gum;
      • alginates;
      • modified celluloses such as hydroxyethylcellulose, methylcellulose, hydroxypropylcellulose (for example Natrosol HHX 250 marketed by the company Aqualon), hydroxypropylmethylcellulose and carboxymethylcellulose;
      • starch derived products such as Structure XL marketed by the company National Starch;
      • a mix of polysorbate 80 and isohexadecane and acrylamide/sodium acryloyldimethyltaurate (such as Simulgel 600); and
      • humectants or pro-penetrant agents such as propylene glycol or equivalent, for example, glycerin and sorbitol, for example, alkylene and polyalkylene glycols (C1 to CE) such as ethylene glycol, polyethylene glycol (2 to 20 monomers), propylene glycol, dipropylene glycol, butylene glycol, pentylene glycol, hexylene glycol. These latter could be oxyethylened or not (2 to 50 QE). Glycol ethers are also representative such as ethoxydiglycol, diethylene glycol monoethylether (tradename transcutol HP by GATTEFOSSE company), dipelargonate propylene glycol, propylene glycol laurate (tradename Lauroglycol by GATTEFOSSE company), Propylene glycol dicaprate dicaprylate (tradename Estol 1526 by UNIQEMA company); and
      • the pro-penetrants such as fatty esters family, fatty acids or fatty alcohols or alcohols, for example, ethanol, dimethyl isosorbide (tradename Arlasolve DMI by UNIQEMA company), pyrrolidone methyl (tradename Pharmasolve by ISP company), oleic acid (tradename Oleine V2 by Stearinerie Dubois company), PEG-8 capric/caprylic glycerides (tradename LAERASOL by GATTEFOSSE company) and oleic alcohol (tradename HD EUTANOL V PH by COGNIS company).
  • In particular, the pharmaceutical composition may be a cream comprising at least one ingredient selected from among:
      • mineral oils such as perhydrosqualene;
      • silicone oils such as cyclomethicone;
      • siliconed oily components such as siliconed fatty components;
      • non-siliconed fatty components such as vegetable, mineral, animal or synthetic oils;
      • tensioactive agents or emulsifying agents, preferably such as PEG-20 methyl glucose sequistearate or Methyl glucose sesquistearate.
  • Among the non-siliconed oily components, the common oils are representative such as paraffin oil, Vaseline (or petroleum jelly), almond oil, perhydrosqualene, apricot oil, wheat germs oil, sweet almond oil, calophyllum oil, palm oil, castor oil, avocado oil, jojoba oil, olive oil or cerales germs oil; fatty acids esters or fatty alcohols esters such as dodecyl octyl octanoates, alcohols or polyalcohols decanoates or ricinoleates; fatty acids triglycerides; glycerides; hydrogenated polyisobutene, solid at 25° C. hydrogenated oils; lanolines; solid at 25° C. fatty esters; adipate diisopropyl (tradename Crodamol DA by Croda company), PPG 15 stearyl ether (tradename Arlamol E by UNIQEMA company), octyl dodecanol (tradename Eutanol G by COGNIS company), Caprilic/capric triglycerides (tradename Miglyol 812N by SPCI company), C12-C15 alkyl benzoate (tradename Tegosoft TN by Degussa company).
  • As tensioactive agents or as emulsifying agents, several components are representative selected from among PEG-20 methyl glucose sequistearate (tradename GLUCAMATE SSE 20 by Amerchol company) or Methyl glucose sesquistearate (tradename GLUCATE SS by Amerchol company), unsaturated or saturated fatty acids esters, oleic acid or isostearic acid such as polyglycerin and isostearic acid esters (tradename LAMEFORM TGI by SIDOBRE-SINNOVA HENKEL company), sorbitan isostearate (tradename ARLACEL 987 by UNIQEMA company), sorbitan sesquioleate (tradename ARLACEL 83 by UNIQEMA company), sorbitan laurate (tradename SPAN 20 by UNIQEMA company), glycol and isostearic acid esters such as PEG-6 isostearate (tradename OLEPAL ISOSTEARIQUE by GATTEFOSSE company), sorbitol and oleic acid esters such as polysorbates (tradename TWEEN by UNIQEMA company), fatty alcohols ethers such as oleic acid and particularly glycol and oleic acid esters such as oleths (tradename BRIJ by UNIQEMA company), oxyethylenated sorbitan monostearate, fatty alcohols such as stearylic alcohol or cetylic alcohol and particularly selected from among macrogol 21 stearylether (tradename BRIJ 721 by UNIQEMA company), macrogol 2 stearylether (tradename BRIJ 72P by UNIQEMA company), glyceryl/PEG 100 stearate (tradename Arlacel 165FL by UNIQEMA company), ceteareth 20 (tradename Eumulgin B2 by COGNIS company), PEG-6 and PEG 32 palmitostearate (tradename TEFOSE 1500 by GATTEFOSSE company).
  • In particular, the pharmaceutical composition may be a lotion comprising at least one ingredient selected from among:
      • humectant agent or pro-penetrant agent such as propylene glycol (or equivalent such as glycerin and sorbitol), polyethylene glycol, PEG400;
      • mineral oils such as perhydrosqualene as previously described;
      • lipophilic components such as Caprilic/capric triglycerides as previously described;
      • emulsifying agents such as described, for example, PEG-20 methyl glucose sequistearate and methyl glucose sequistearate.
  • Also in particular, the pharmaceutical composition may be a solution or a spray solution comprising alcohol and at least one ingredient selected from among:
      • humectant agent or pro-penetrant agent as described previously and preferably such as propylene glycol, polyethylene glycol, or PEG400;
      • a lipophilic component, such as siliconed or non-siliconed fatty components or Caprilic/capric triglycerides.
  • Preferably in the form of gel, the composition has of following formula:
  •
    Adapalene 3 mg
    Carbomer 940 (Carbopol 980 NF) 11 mg
    Disodium edetate 1 mg
    Methyl paraben
    2 mg
    Poloxamer 124 2 mg
    Propylene glycol
    40 mg
    Sodium hydroxide: amount required to obtain
    a pH 5.0 +/− 0.3
    Purified water q.s. 1 g
  • The pharmaceutical compositions according to the invention may also comprise inert additives or combinations thereof, such as:
  • wetting agents;
  • flavor enhancers;
  • preservatives such as para-hydroxybenzoic acid esters;
  • stabilizers;
  • moisture regulators;
  • pH regulators;
  • osmotic pressure modifiers;
  • emulsifiers; UV-A and UV-B screening agents; and
  • antioxidants, such as α-tocopherol, butylhydroxyanisole or butylhydroxytoluene, superoxide dismutase, ubiquinol or certain metal chelating agents.
  • Of course, those skilled in the art will take care to select the optional compound(s) to be added to these compositions in such a way that the advantageous properties intrinsically associated with the present invention are not, or are not substantially, adversely affected by the envisaged addition.
  • The pharmaceutical compositions according to the invention are suited for the treatment of dermatological ailments, conditions and afflictions having an inflammatory or proliferative component, selected from the group consisting of:
      • common acne, comedones, polymorphous acne, nodulocystic acne, acne conglobata, secondary acne such as solar, drug-related or occupational acne;
      • widespread and/or severe forms of psoriasis, ichtyoses and ichtyosiform states;
      • Darier's disease;
      • actinic keratoses;
      • palmo plantar keratoderma and keratosis pilaris;
      • leucoplasias and leucoplasiform states, lichen planus;
      • any benign or malignant, severe and extensive dermatological preparations.
  • The compositions according to the invention are particularly suitable for the treatment of acne, such as common acne, and in particular for the treatment of common acne of moderate to moderately severe intensity.
  • Various formulations of compositions comprising 0.3% of adapalene will now be given, it being understood that same are intended only as illustrative and in nowise limitative. Also given are results showing the therapeutic effects of the compositions according to the invention and the good tolerance to same by the treated patients.
  • In said examples to follow, all parts and percentages are given by weight, unless otherwise indicated.
    • Example 1—Formulation for Topical Administration
  • In this example, various specific topical formulations comprising 0.3% of adapalene are illustrated.
  • The adapalene of the present example was obtained from the company Sylachim.
  • (a) Cream:
  •
    Adapalene 3 mg
    Carbomer 934 (BF Goodrich Carbopol 974) 4.5 mg
    Disodium edetate
    1 mg
    PEG
    20 methyl glucose sesquistearate 35 mg
    Methyl glucose sesquistearate 35 mg
    Glycerol
    30 mg
    Methyl paraben
    2 mg
    Cyclomethicone 130 mg
    Perhydrosqualene
    60 mg
    Phenoxyethanol 5 mg
    Propyl paraben
    1 mg
    Sodium hydroxide quantity required for pH 6.5 +/− 0.3
    Purified water q.s. 1 g
  • (b) Alcoholic solution:
  •
    Adapalene 3 mg
    PEG 400 700 mg
    Ethanol q.s. 1 g
  • (c) Lotion: (% w/w)
    Adapalene 0.30
    Methyl paraben 0.15
    Simulgel 600 PHA 1.00
    Steareth 21 3.00
    Glyceryl and PEG 100 stearate 3.00
    Disodium edetate 0.10
    Propyl paraben 0.05
    Perhydrosqualene 5.00
    Cetearyl isononanoate 5.00
    Sodium Hydroxide 10% m/m q.s. pH 5.5 ± 0.5
    Purified water q.s. 100
  • (d) Lotion: (% w/w)
    Disodium EDTA 0.1
    Methyl paraben 0.2
    Glycerine 7.0
    Carbopol 981 NF 0.15
    Propyl paraben 0.1
    Ceteareth 20 3.0
    Stearyl alcohol 2.0
    Caprilic/capric triglycerides 7
    Glyceryl and PEG 100 stearate 3.0
    Cyclomethicone 5 6
    Poloxamer 124 0.2
    Propylene glycol 4.0
    Adapalene 0.3
    Simulgel 600 PHA 1.0
    Solution aq. De NaOH 10% 0.4
    Purified water q.s. 100
  • (e) Lotion: (% w/w)
    EDTA disodium 0.1
    Methyl paraben 0.2
    Carbopol 980 NF 0.15
    Carbapol 981 NF 0.3
    Glycerine 3.0
    Phenoxyethanol 1.0
    Propyl paraben 0.2
    Methyl glucose sesquistearate 1.0
    PEG 20 methyl glucose sesquistearate 5.0
    Caprilic/capric triglycerides 6.0
    Dimethicone 20 cst 1.0
    Poloxamer 124 0.2
    Propylene glycol 4
    Adapalene 0.3
    Sodium hydroxide 10% (w/w) 0.8
    Purified water q.s. 100
  • (f) Aqueous Gel:
  •
    Adapalene 3 mg
    Carbomer 940 (Carbapol 980) 11 mg
    Disodium edetate 1 mg
    Methyl paraben
    2 mg
    Poloxamer 124 2 mg
    Propylene glycol
    40 mg
    Sodium hydroxide: amount required to obtain
    a pH 5.0 +/− 0.3
    Purified water q.s. 1 g
  • (g) Aqueous Gel:
  •
    Adapalene 3 mg
    Xanthan gum 8 mg
    Hydroxypropylethyl cellulose
    10 mg
    Disodium edetate 1 mg
    Methyl paraben
    2 mg
    Phenoxyethanol
    10 mg
    Poloxamer 124 2 mg
    Propylene glycol
    40 mg
    Purified water q.s. 1 g
  • (h) Cream Gel:
  •
    Adapalene 3 mg
    Simulgel 600 PHA 20 mg
    Cetearyl isononanoate 100 mg
    Disodium edetate 1 mg
    Methyl paraben
    2 mg
    Poloxamer 124 2 mg
    Propylene glycol
    40 mg
    Purified water q.s. 1 g
  • (i) Cream gel:
  •
    Adapalene 3 mg
    Pemulen TR1 5 mg
    Mineral oil 120 mg
    Disodium edetate
    1 mg
    Methyl paraben
    2 mg
    Propyl paraben
    1 mg
    Poloxamer 124 2 mg
    Propylene glycol
    40 mg
    Sodium hydroxide: amount required to obtain
    a pH 5.0 +/− 0.3
    Purified water q.s. 1 g
  • (j) Spray solution: (% w/w)
    Adapalene 0.3
    Caprilic/capric triglycerides 50
    N-methyl pyrrolidone 3
    Ethanol q.s. 100
    • Example 2—Effectiveness of 0.3% Adapalene Gel and Comparison with 0.1% Adapalene Gel
  • Tests were carried out on a population consisting of patients suffering from acne. In this population, three groups were differentiated; the first received a daily topical application of the 0.3% adapalene gel, the second a daily topical application of the 0.1% adapalene gel in the same vehicle, and the third is a control group which receives a daily topical application of the gel corresponding to the composition of the first two gels but containing no active agent.
  • FIGS. 1 to 3 provide the results obtained in terms of regression of the number of lesions according to their nature.
  • These observations lead to the following conclusions:
  • the 0.3% adapalene gel acts more rapidly than the 0.1% adapalene gel; specifically, from the fourth week of treatment, a difference is noted between the effectiveness of the 0.1% adapalene gel and the 0.3% adapalene gel;
  • the 0.3% adapalene gel produces a clearly greater therapeutic effect after 8 weeks of treatment.
    • Example 3—Tolerance Regarding the 0.3% Adapalene Gel
  • 1. Measurement of the Plasma Concentration of Adapalene:
  • Eight individuals suffering from common acne of medium to moderately severe intensity are treated for 10 days with 2 g of 0.3% adapalene gel applied daily over 1000 cm2 of skin to be treated (face, chest and back).
  • Blood samples are taken on the days 1, 2, 4, 6, 8 and 10. During day 10, and following the final application, samples are taken at 1, 2, 6, 8, 10, 12, 16 and 24 hours.
  • The plasma concentration of total adapalene (free and conjugated) in these samples is determined using the following protocol:
  • enzymatic hydrolysis with a mixture of β-glucurodinase and arylsulfatase;
  • liquid-liquid extraction;
  • passage through HPLC (high performance liquid chromatography); and
  • then fluorometric detection.
  • This method makes it possible to detect a minimum concentration of 0.15 ng/ml and permits quantification of the adapalene for a minimum concentration of 0.25 ng/ml.
    • CONCLUSION
  • The plasma concentrations of adapalene measured after 10 days of treatment are very low and confirm the safety of daily use of the 0.3% adapalene gel.
  • 2 a) Clinical Observation of the Side Effects Caused by Topical Administration of the 0.3% Adapalene Gel:
  • Two types of observation could be made:
  • firstly, monitoring of the patients treated within the framework of point 1 of the present example 3 made it possible to note that tolerance to the 0.3% adapalene gel was good for all patients. They all showed signs of dryness of the skin and of desquamation with a maximum on the seventh day of treatment, these symptoms then decrease up to the end of the treatment.
  • 2 b) Furthermore, Reference May Also be Made to the Tests Described in Example 2 Above:
  • In parallel to the measurements of effectiveness, the experimenters recorded the possible side effects caused, firstly, by topical application of the 0.3% adapalene gel and those caused, secondly, by application of the 0.1% adapalene gel; finally, the same observations were made on a control population to which a gel without active principle was administered.
  • These observations are reported in the table below.
  • Local undesirable 0.3% adapalene 0.1% adapalene Vehicle gel
    effects gel (N = 70) gel (N = 70) (N = 74)
    Skin and secondary 31 (44.3%) 28 (40.0%) 5 (6.8%)
    structures (nails, hair)
    Dry skin 16 (22.9%) 13 (18.6%) 2 (2.7%)
    Erythema 8 (11.4%) 3 (4.3%) 0 (0.0%)
    Skin discomfort 8 (11.4%) 7 (10.0%) 0 (0.0%)
    Desquamation 6 (8.6%) 5 (7.1%) 0 (0.0%)
    Dermatitis 3 (4.3%) 1 (1.4%) 0 (0.0%)
    Pruritus 3 (4.3%) 1 1.4%) 1 (1.4%)
    Irritant dermatitis 2 (2.9%) 7 (10.0%) 0 (0.0%)
    Local allergic reactions 1 (1.4%) 0 (0.0%) 0 (0.0%)
    Pediculosis 1 (1.4%) 0 (0.0%) 0 (0.0%)
    Contact dermatitis 1 (1.4%) 0 (0.0%) 0 (0.0%)
    Insolation 1 (1.4%) 3 (4.3%) 1 (1.4%)
    Burning sensation 1 (1.4%) 0 (0.0%) 0 (0.0%)
    Urticaria 1 1.4%) 0 (0.0%) 0 (0.0%)
    Infection 1 (1.4%) 0 (0.0%) 0 (0.0%)
    Excoriation 0 (0.0%) 0 (0.0%) 1 (1.4%)
    Eczema 0 (0.0%) 0 (0.0%) 1 (1.4%)
    Oedema 0 (0.0%) 1. (1.4%) 0 (0.0%)
  • From this table, it is noted that the occurrence of undesirable side effects is statistically the same for the two gels with the different concentrations of active agent. The intensity of the undesirable side effects is average, which leads to the conclusion that the two gels are well-tolerated by the patients.
  • On the basis of these observations, it may be concluded that patients suffering from common acne can be treated with 0.3% adapalene gel, such an exposure to adapalene being described as weak or very weak under clinical conditions.
  • It therefore ensues from these various studies that a pharmaceutical composition containing 0.3% of adapalene exhibits a benefit/risk ratio which makes it particularly suitable for the treatment of dermatological maladies having an inflammatory or proliferative component, and in particular, common acne.
  • Each patent, patent application, publication and literature article/report cited or indicated herein is hereby expressly incorporated by reference.
  • While the invention has been described in terms of various specific and preferred embodiments, the skilled artisan will appreciate that various modifications, substitutions, omissions, and changes may be made without departing from the spirit thereof. Accordingly, it is intended that the scope of the present invention be limited solely by the scope of the following claims, including equivalents thereof.

Claims (1)

What is claimed is:
1. A method for treating common acne, comedones, polymorphous acne, nodulocystic acne, acne conglobata, or secondary acne afflicting the skin of an individual in need of such treatment, comprising topically administering to said individual a topically applicable pharmaceutical aqueous gel composition consisting essentially of an anti-acne effective amount of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid (adapalene) of 0.3% by weight thereof, formulated into a topically applicable, pharmaceutically acceptable aqueous gel medium therefor, wherein said aqueous gel medium comprises at least one ingredient selected from the group consisting of carbomers, polymeric emulsifying agents, polysaccharidic biopolymers, gums, alginates, modified celluloses, starch derived products, a mix of polysorbate 80 and isohexadecane and acrylamide/sodium acryloyldimethyltaurate, and mixtures thereof.
US15/456,933 2002-03-12 2017-03-13 Method for the treatment of acne using pharmaceutical compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid Abandoned US20170181991A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US15/456,933 US20170181991A1 (en) 2002-03-12 2017-03-13 Method for the treatment of acne using pharmaceutical compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid

Applications Claiming Priority (10)

Application Number Priority Date Filing Date Title
FR0203070A FR2837101B1 (en) 2002-03-12 2002-03-12 USE OF 6- [1-ADAMANTYL) -4-METHOXYPHENYL] -2- NAPHTHOIC ACID FOR THE TREATMENT OF DERMATOLOGICAL DISORDERS
FR0203070 2002-03-12
US37022302P 2002-04-08 2002-04-08
PCT/EP2003/003246 WO2003075908A1 (en) 2002-03-12 2003-03-12 Use of adapalene for the treatment of dermatological disorders
US10/937,612 US7579377B2 (en) 2002-03-12 2004-09-10 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US11/494,693 US7737181B2 (en) 2002-03-12 2006-07-28 Pharmaceutical compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US12/772,861 US7868044B2 (en) 2002-03-12 2010-05-03 Method for the treatment of acne using compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid
US12/957,882 US8921423B2 (en) 2002-03-12 2010-12-01 Method for the treatment of acne using compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid
US14/524,602 US9622994B2 (en) 2002-03-12 2014-10-27 Method for the treatment of acne using pharmaceutical compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid
US15/456,933 US20170181991A1 (en) 2002-03-12 2017-03-13 Method for the treatment of acne using pharmaceutical compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US14/524,602 Continuation US9622994B2 (en) 2002-03-12 2014-10-27 Method for the treatment of acne using pharmaceutical compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid

Publications (1)

Publication Number Publication Date
US20170181991A1 true US20170181991A1 (en) 2017-06-29

Family

ID=27806678

Family Applications (17)

Application Number Title Priority Date Filing Date
US10/937,612 Active 2026-09-10 US7579377B2 (en) 2002-03-12 2004-09-10 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US11/494,693 Expired - Fee Related US7737181B2 (en) 2002-03-12 2006-07-28 Pharmaceutical compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US12/103,182 Expired - Fee Related US7838558B2 (en) 2002-03-12 2008-04-15 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US12/437,008 Expired - Fee Related US7834060B2 (en) 2002-03-12 2009-05-07 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphtoic acid for the treatment of dermatological disorders
US12/772,861 Expired - Fee Related US7868044B2 (en) 2002-03-12 2010-05-03 Method for the treatment of acne using compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid
US12/902,931 Abandoned US20110027367A1 (en) 2002-03-12 2010-10-12 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US12/902,972 Expired - Lifetime US8703820B2 (en) 2002-03-12 2010-10-12 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US12/957,882 Active 2026-02-08 US8921423B2 (en) 2002-03-12 2010-12-01 Method for the treatment of acne using compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid
US13/024,681 Expired - Lifetime US8729127B2 (en) 2002-03-12 2011-02-10 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US13/475,827 Expired - Lifetime US8653140B2 (en) 2002-03-12 2012-05-18 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US14/222,185 Expired - Fee Related US9381179B2 (en) 2002-03-12 2014-03-21 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US14/263,758 Expired - Fee Related US9387187B2 (en) 2002-03-12 2014-04-28 Administration of 6[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US14/524,602 Expired - Fee Related US9622994B2 (en) 2002-03-12 2014-10-27 Method for the treatment of acne using pharmaceutical compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid
US15/175,188 Expired - Lifetime US9872842B2 (en) 2002-03-12 2016-06-07 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US15/184,262 Expired - Lifetime US9901556B2 (en) 2002-03-12 2016-06-16 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US15/456,933 Abandoned US20170181991A1 (en) 2002-03-12 2017-03-13 Method for the treatment of acne using pharmaceutical compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid
US15/846,663 Abandoned US20180104203A1 (en) 2002-03-12 2017-12-19 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders

Family Applications Before (15)

Application Number Title Priority Date Filing Date
US10/937,612 Active 2026-09-10 US7579377B2 (en) 2002-03-12 2004-09-10 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US11/494,693 Expired - Fee Related US7737181B2 (en) 2002-03-12 2006-07-28 Pharmaceutical compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US12/103,182 Expired - Fee Related US7838558B2 (en) 2002-03-12 2008-04-15 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US12/437,008 Expired - Fee Related US7834060B2 (en) 2002-03-12 2009-05-07 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphtoic acid for the treatment of dermatological disorders
US12/772,861 Expired - Fee Related US7868044B2 (en) 2002-03-12 2010-05-03 Method for the treatment of acne using compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid
US12/902,931 Abandoned US20110027367A1 (en) 2002-03-12 2010-10-12 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US12/902,972 Expired - Lifetime US8703820B2 (en) 2002-03-12 2010-10-12 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US12/957,882 Active 2026-02-08 US8921423B2 (en) 2002-03-12 2010-12-01 Method for the treatment of acne using compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid
US13/024,681 Expired - Lifetime US8729127B2 (en) 2002-03-12 2011-02-10 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US13/475,827 Expired - Lifetime US8653140B2 (en) 2002-03-12 2012-05-18 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US14/222,185 Expired - Fee Related US9381179B2 (en) 2002-03-12 2014-03-21 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US14/263,758 Expired - Fee Related US9387187B2 (en) 2002-03-12 2014-04-28 Administration of 6[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US14/524,602 Expired - Fee Related US9622994B2 (en) 2002-03-12 2014-10-27 Method for the treatment of acne using pharmaceutical compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid
US15/175,188 Expired - Lifetime US9872842B2 (en) 2002-03-12 2016-06-07 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders
US15/184,262 Expired - Lifetime US9901556B2 (en) 2002-03-12 2016-06-16 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders

Family Applications After (1)

Application Number Title Priority Date Filing Date
US15/846,663 Abandoned US20180104203A1 (en) 2002-03-12 2017-12-19 Administration of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid for the treatment of dermatological disorders

Country Status (18)

Country Link
US (17) US7579377B2 (en)
EP (2) EP1532974B1 (en)
JP (2) JP2005526063A (en)
CN (1) CN1642538B (en)
AT (2) ATE432072T1 (en)
AU (2) AU2003216898B2 (en)
BR (1) BRPI0307550B8 (en)
CA (1) CA2478237C (en)
CY (2) CY1108868T1 (en)
DE (2) DE60327745D1 (en)
DK (2) DK1485080T3 (en)
ES (2) ES2319778T3 (en)
MX (1) MXPA04008684A (en)
PL (1) PL216763B1 (en)
PT (2) PT1485080E (en)
RU (2) RU2332208C2 (en)
SI (2) SI1532974T1 (en)
WO (1) WO2003075908A1 (en)

Families Citing this family (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7820186B2 (en) 2001-12-21 2010-10-26 Galderma Research & Development Gel composition for once-daily treatment of common acne comprising a combination of benzoyl peroxide and adapalene and/or adapalene salt
DK1485080T3 (en) 2002-03-12 2009-08-31 Galderma Res & Dev Use of adapalene for the treatment of dermatological diseases
US20060128808A1 (en) * 2004-10-20 2006-06-15 Galderma Research & Development, S.N.C. Method of using adapalene in acne maintenance therapy
US20080161273A1 (en) * 2004-10-20 2008-07-03 Galderma Research & Development Method of Using Adapalene in Acne Maintenance Therapy
KR20070091613A (en) * 2004-11-08 2007-09-11 그렌마크 파머수티칼스 엘티디. Topical pharmaceutical compositions containing anti-acne compounds and antibiotic compounds
FR2879459B1 (en) * 2004-12-22 2007-02-16 Galderma Res & Dev COMPOSITION COMPRISING ADAPALENE SOLUBILIZED WITH CYCLODEXTRINS
MX2007007976A (en) * 2005-01-26 2007-08-22 Galderma Res & Dev ADAPALENO FOR LONG-TERM TREATMENT OF ACNE VULGARIS.
ITRM20050248A1 (en) * 2005-05-20 2006-11-21 Sigma Tau Ind Farmaceuti USE OF ACID ADAMANTYL METOXIDIDENYL PROPENOIC FOR THE TREATMENT OF SKIN PATHOLOGIES.
CA2612497C (en) * 2005-06-17 2015-10-06 Medichem, S.A. Process for the preparation of adapalene and related compounds
MX2008003422A (en) * 2005-09-16 2008-03-27 Galderma Res & Dev COMPOSITIONS THAT INCLUDE AT LEAST A NAFTOIC ACID DERIVATIVE AND AT LEAST A POLYURETHANE POLYMER TYPE COMPOSITE OR DERIVATIVES, PREPARATION PROCESSES AND COMPOSITIONS THAT INCLUDE AT LEAST A NAFTOIC ACID DERIVATIVE AND AT LEAST
FR2890861B1 (en) 2005-09-16 2010-05-28 Galderma Res & Dev COMPOSITIONS COMPRISING AT LEAST ONE NAPHTHOTIC ACID DERIVATIVE AND AT LEAST ONE POLYURETHANE POLYMER TYPE COMPOUND OR DERIVATIVES THEREOF, PROCESS FOR PREPARING THE SAME, AND USE THEREOF
FR2894821B1 (en) * 2005-12-15 2008-02-29 Galderma Res & Dev COMPOSITIONS COMPRISING AT LEAST ONE RETINOID COMPOUND AND AT LEAST ONE ANTI-IRRITANT COMPOUND AND USES THEREOF
CN1989956B (en) * 2005-12-29 2010-09-01 北京德众万全医药科技有限公司 Adapalene gel composition and its preparation
FR2901701B1 (en) * 2006-05-31 2010-10-29 Galderma Res & Dev COMPOSITIONS COMPRISING AT LEAST ONE NAPHTHOIC ACID DERIVATIVE AND AT LEAST ONE FILMOGENIC AGENT, PROCESSES FOR THEIR PREPARATION, AND USES THEREOF
WO2008062135A1 (en) * 2006-11-20 2008-05-29 Galderma Research & Development Use of adapalene for modulating the expression of il-1ra
FR2909000B1 (en) * 2006-11-28 2009-02-06 Galderma Res & Dev S N C Snc COMPOSITIONS COMPRISING BENZOYL PEROXIDE, AT LEAST ONE NAPHTHOIC ACID DERIVATIVE AND AT LEAST ONE POLYURETHANE POLYMER COMPOUND OR DERIVATIVES THEREOF, AND USES THEREOF.
AU2007334119B2 (en) 2006-12-15 2011-04-21 Colgate-Palmolive Company Liquid detergent composition
FR2910321B1 (en) 2006-12-21 2009-07-10 Galderma Res & Dev S N C Snc CREAM GEL COMPRISING AT LEAST ONE RETINOID AND BENZOLE PEROXIDE
FR2910320B1 (en) 2006-12-21 2009-02-13 Galderma Res & Dev S N C Snc EMULSION COMPRISING AT LEAST ONE RETINOID AND BENZOLE PEROXIDE
JP5670008B2 (en) * 2007-01-31 2015-02-18 大正製薬株式会社 Adapalene-containing external preparation composition
JP5338030B2 (en) * 2007-01-31 2013-11-13 大正製薬株式会社 Adapalene-containing external preparation composition
JP5125122B2 (en) * 2007-01-31 2013-01-23 大正製薬株式会社 Adapalene-containing external preparation composition
US20100130603A1 (en) 2007-03-09 2010-05-27 Kyoto University Medicament for prophylactic and therapeutic treatment of dermatosis resulting from excessively advanced keratinization
EP2065032A1 (en) * 2007-11-27 2009-06-03 Galderma Research & Development A method for producing adapalene gels
US20110117182A1 (en) * 2009-07-30 2011-05-19 Allergan, Inc. Combination of dapsone with other anti-acne agents
US20130203850A1 (en) * 2010-04-29 2013-08-08 Galderma Research & Development Method for treating scars with adapalene 0.3%
US10758630B2 (en) 2010-08-13 2020-09-01 The Johns Hopkins University Topical compositions and methods of detection and treatment
DE102010063825A1 (en) * 2010-12-22 2012-06-28 Beiersdorf Ag Cosmetic or dermatological preparation comprises a thickener based on polyacrylate, a thickener based on polyacrylamide and a UV-filter substance e.g. octocrylene, homosalate or titania
FR2969492B1 (en) * 2010-12-23 2013-07-05 Galderma Res & Dev DERMATOLOGICAL FOAMS OBTAINED FROM GEL OR SUSPENSION CONTAINING ADAPALENE
US20140037694A1 (en) * 2011-02-25 2014-02-06 Hisamitsu Pharmaceutical Co., Inc. Adjuvant for transdermal or transmucosal administration and pharmaceutical preparation containing same
US10137823B2 (en) 2011-06-29 2018-11-27 SMR Patents S.à.r.l. Exterior rearview device with illumination functions
US10787177B2 (en) 2011-06-29 2020-09-29 SMR Patents S.à.r.l. Exterior rearview device with illumination functions and autonomous vehicles using same
US9206381B2 (en) 2011-09-21 2015-12-08 Ecolab Usa Inc. Reduced misting alkaline cleaners using elongational viscosity modifiers
FR2991175B1 (en) * 2012-06-01 2014-12-19 Galderma Res & Dev TOPICAL PHARMACEUTICAL COMPOSITIONS OF O / W EMULSION TYPE CONTAINING RETINOID
RU2538680C2 (en) * 2013-03-12 2015-01-10 Открытое акционерное общество "Химико-фармацевтический комбинат "АКРИХИН" (ОАО "АКРИХИН") Pharmaceutical composition for treating atopic dermatitis and method for preparing it
JP5980171B2 (en) * 2013-06-05 2016-08-31 大正製薬株式会社 Adapalene-containing external preparation composition
ES2836132T3 (en) 2013-08-08 2021-06-24 Novan Inc Topical compositions and methods of using them
JP2015081244A (en) * 2013-10-23 2015-04-27 第一三共ヘルスケア株式会社 Acne treating pharmaceutical composition
EP3064218B1 (en) 2013-10-31 2019-06-19 Hisamitsu Pharmaceutical Co., Inc. Adjuvant composition
US9637708B2 (en) 2014-02-14 2017-05-02 Ecolab Usa Inc. Reduced misting and clinging chlorine-based hard surface cleaner
US10322082B2 (en) 2014-07-11 2019-06-18 Novan, Inc. Topical antiviral compositions and methods of using the same
KR20170035916A (en) * 2014-07-25 2017-03-31 갈데르마 리써어치 앤드 디벨로프먼트 Combination of adapalene and benzoyl peroxide for the treatment of severe acne
JP6753312B2 (en) * 2014-12-26 2020-09-09 ニプロ株式会社 Topical skin preparation for medical use
EP3464541B1 (en) 2016-05-23 2020-04-29 Ecolab USA Inc. Reduced misting alkaline and neutral cleaning, sanitizing, and disinfecting compositions via the use of high molecular weight water-in-oil emulsion polymers
US10370626B2 (en) 2016-05-23 2019-08-06 Ecolab Usa Inc. Reduced misting acidic cleaning, sanitizing, and disinfecting compositions via the use of high molecular weight water-in-oil emulsion polymers
EP3589125A1 (en) 2017-03-01 2020-01-08 Ecolab USA, Inc. Reduced inhalation hazard sanitizers and disinfectants via high molecular weight polymers
US12350341B2 (en) 2017-03-02 2025-07-08 Duke University Methods for the treatment of cancer and benign lesions by ablation
US9987239B1 (en) 2017-03-14 2018-06-05 Rey Ventures, LLC Pharmaceutical retinoid preparation for topical use
US20200345671A1 (en) * 2017-10-24 2020-11-05 Glenmark Pharmaceuticals Limited Topical pharmaceutical composition of adapalene and minocycline
JPWO2019240290A1 (en) * 2018-06-16 2021-06-24 ロート製薬株式会社 Topical composition
US20200222358A1 (en) 2019-01-15 2020-07-16 Derma Research Group Inc. Topical dermatologic acne treatment cream composition and method of manufacture
BR112022000446A2 (en) 2019-07-12 2022-03-03 Ecolab Usa Inc Sprayable cleaning composition, system for applying sprayable cleaning composition with reduced mist production, and method of cleaning a hard surface using a sprayable cleaning composition with reduced mist production
CN119837892A (en) 2019-08-01 2025-04-18 博世健康爱尔兰有限公司 Topical compositions

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
LU85849A1 (en) * 1985-04-11 1986-11-05 Cird BENZONAPHTHALENIC DERIVATIVES, THEIR PREPARATION PROCESS AND THEIR APPLICATION IN THE PHARMACEUTICAL AND COSMETIC FIELDS
ES2084753T3 (en) 1990-11-26 1996-05-16 Bayer Ag NICLOSAMIDE IN TOPICAL LOTION.
JP2697999B2 (en) * 1992-06-29 1998-01-19 株式会社 フィルインターナショナル Cosmetics
US5306486A (en) * 1993-03-01 1994-04-26 Elizabeth Arden Co., Division Of Conopco, Inc. Cosmetic sunscreen composition containing green tea and a sunscreen
FR2710854B1 (en) 1993-10-08 1995-12-01 Oreal Oil-in-water emulsion usable for obtaining a cream.
US6133326A (en) * 1994-08-31 2000-10-17 Pfizer Inc Compositions and methods for decreasing sebum production
FR2730930B1 (en) 1995-02-27 1997-04-04 Oreal USE OF NO-SYNTHASE INHIBITORS TO REDUCE THE IRRITANT SKIN EFFECT OF PRODUCTS USED IN THE COSMETIC OR PHARMACEUTICAL FIELD
US6413536B1 (en) * 1995-06-07 2002-07-02 Southern Biosystems, Inc. High viscosity liquid controlled delivery system and medical or surgical device
US5665364A (en) * 1995-07-24 1997-09-09 The Procter & Gamble Company Compositions for topical delivery of active ingredients
FR2753626B1 (en) * 1996-09-20 1998-11-06 Centre International De Rech Dermatologiques Galderma Cird Galderma NOVEL TOPICAL COMPOSITIONS IN THE FORM OF A FLUID O / W EMULSION WITH A HIGH PRO-PENETRATING GLYCOL CONTENT
JPH10114648A (en) * 1996-10-11 1998-05-06 Kao Corp External composition for skin
WO1998051273A1 (en) * 1997-05-12 1998-11-19 Sage Pharmaceuticals, Inc. Topical spray for burn treatment and anti-infection
US6267985B1 (en) * 1999-06-30 2001-07-31 Lipocine Inc. Clear oil-containing pharmaceutical compositions
JP2001097847A (en) * 1999-09-29 2001-04-10 Pola Chem Ind Inc Production of gel composition
CN1379667A (en) * 1999-10-19 2002-11-13 宝洁公司 Compositions and methods of use for preventing and treating cold and flu-like symptoms
US6967023B1 (en) * 2000-01-10 2005-11-22 Foamix, Ltd. Pharmaceutical and cosmetic carrier or composition for topical application
US6383505B1 (en) 2000-11-09 2002-05-07 Steris Inc Fast-acting antimicrobial lotion with enhanced efficacy
BRPI0101486B1 (en) 2001-04-17 2017-09-19 Cristália Produtos Químicos Farmacêuticos Ltda. PHARMACEUTICAL COMPOSITION FOR TOPIC USE CONTAINING HEPARIN FOR TREATMENT OF SKIN OR MUCOSAL INJURIES CAUSED BY BURNS
DK1485080T3 (en) 2002-03-12 2009-08-31 Galderma Res & Dev Use of adapalene for the treatment of dermatological diseases
MX2007007976A (en) 2005-01-26 2007-08-22 Galderma Res & Dev ADAPALENO FOR LONG-TERM TREATMENT OF ACNE VULGARIS.
JP4962858B2 (en) 2007-06-21 2012-06-27 スズキ株式会社 instrument panel

Also Published As

Publication number Publication date
US20050059740A1 (en) 2005-03-17
US20140249232A1 (en) 2014-09-04
WO2003075908A1 (en) 2003-09-18
PT1532974E (en) 2009-02-23
JP2011032287A (en) 2011-02-17
US20180104203A1 (en) 2018-04-19
RU2004130308A (en) 2005-04-10
US7579377B2 (en) 2009-08-25
ES2327508T3 (en) 2009-10-30
US7834060B2 (en) 2010-11-16
CY1109307T1 (en) 2014-07-02
BR0307550B1 (en) 2018-01-09
CY1108868T1 (en) 2014-07-02
US9381179B2 (en) 2016-07-05
BRPI0307550B8 (en) 2021-05-25
CA2478237A1 (en) 2003-09-18
US20150045440A1 (en) 2015-02-12
US20120231062A1 (en) 2012-09-13
US9387187B2 (en) 2016-07-12
US20170049732A1 (en) 2017-02-23
AU2003216898B2 (en) 2008-04-24
RU2008118056A (en) 2009-11-10
US7868044B2 (en) 2011-01-11
US20100273882A1 (en) 2010-10-28
EP1532974B1 (en) 2008-12-17
US20070043119A1 (en) 2007-02-22
PL216763B1 (en) 2014-05-30
CN1642538A (en) 2005-07-20
US7737181B2 (en) 2010-06-15
US20160361282A1 (en) 2016-12-15
SI1485080T1 (en) 2009-10-31
US20080293817A1 (en) 2008-11-27
US9872842B2 (en) 2018-01-23
JP5722598B2 (en) 2015-05-20
EP1532974A3 (en) 2005-12-14
ATE417610T1 (en) 2009-01-15
US8703820B2 (en) 2014-04-22
CA2478237C (en) 2009-05-12
AU2008203279A1 (en) 2008-08-14
US20110027204A1 (en) 2011-02-03
PT1485080E (en) 2009-07-31
RU2332208C2 (en) 2008-08-27
EP1485080B1 (en) 2009-05-27
US20110027367A1 (en) 2011-02-03
AU2008203279B2 (en) 2011-06-30
ATE432072T1 (en) 2009-06-15
RU2377981C1 (en) 2010-01-10
PL372317A1 (en) 2005-07-11
DE60325379D1 (en) 2009-01-29
BR0307550A (en) 2005-01-04
US8653140B2 (en) 2014-02-18
US8729127B2 (en) 2014-05-20
DK1532974T3 (en) 2009-05-11
SI1532974T1 (en) 2009-04-30
HK1073996A1 (en) 2005-10-28
US20090281188A1 (en) 2009-11-12
MXPA04008684A (en) 2004-12-06
US9901556B2 (en) 2018-02-27
EP1485080A1 (en) 2004-12-15
AU2003216898A1 (en) 2003-09-22
US20110130461A1 (en) 2011-06-02
US20110070176A1 (en) 2011-03-24
DK1485080T3 (en) 2009-08-31
DE60327745D1 (en) 2009-07-09
US20140308223A1 (en) 2014-10-16
EP1532974A2 (en) 2005-05-25
US8921423B2 (en) 2014-12-30
US9622994B2 (en) 2017-04-18
ES2319778T3 (en) 2009-05-12
JP2005526063A (en) 2005-09-02
CN1642538B (en) 2010-05-26
US7838558B2 (en) 2010-11-23

Similar Documents

Publication Publication Date Title
US9622994B2 (en) Method for the treatment of acne using pharmaceutical compositions comprising 0.3% by weight of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid
US20160287614A1 (en) Stable Pharmaceutical Formulation(s) of Tetracycline Antibiotic
HK1073996B (en) Use of adapalene for the treatment of dermatological disorders

Legal Events

Date Code Title Description
AS Assignment

Owner name: GALDERMA RESEARCH & DEVELOPMENT, FRANCE

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:GRAEBER, MICHAEL;CZERNIELEWSKI, JANUSZ;SIGNING DATES FROM 20060902 TO 20060918;REEL/FRAME:041557/0602

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION