WO2012103016A2 - Patchs transdermiques à libération prolongée associant un bêta-agoniste et un anticholinergique et leurs procédés d'utilisation - Google Patents

Patchs transdermiques à libération prolongée associant un bêta-agoniste et un anticholinergique et leurs procédés d'utilisation Download PDF

Info

Publication number
WO2012103016A2
WO2012103016A2 PCT/US2012/022233 US2012022233W WO2012103016A2 WO 2012103016 A2 WO2012103016 A2 WO 2012103016A2 US 2012022233 W US2012022233 W US 2012022233W WO 2012103016 A2 WO2012103016 A2 WO 2012103016A2
Authority
WO
WIPO (PCT)
Prior art keywords
patch according
patch
acid
anticholinergic
beta agonist
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.)
Ceased
Application number
PCT/US2012/022233
Other languages
English (en)
Other versions
WO2012103016A3 (fr
Inventor
Larry J. Caldwell
Sadanobu Shirai
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.)
CSI GmbH
Original Assignee
CSI GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by CSI GmbH filed Critical CSI GmbH
Priority to EP12739786.7A priority Critical patent/EP2667861A4/fr
Publication of WO2012103016A2 publication Critical patent/WO2012103016A2/fr
Publication of WO2012103016A3 publication Critical patent/WO2012103016A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system

Definitions

  • Chronic obstructive pulmonary disease is characterized by a chronic inflammatory process and irreversible airflow obstruction with a decline in the lung function FEV1 (i.e., forced expiratory volume in 1 second).
  • the disease may be divided into two subgroups, namely chronic bronchitis and emphysema.
  • Chronic bronchitis is characterized by mucus hypersecretion from the conducting airways, inflammation and eventual scarring of the bronchi (airway tubes).
  • Emphysema is characterized by destructive changes and enlargement of the alveoli (air sacs) within the lungs.
  • Many persons with COPD have a component of both of these conditions. COPD patients have difficulty breathing because they develop smaller, inflamed air passageways and have partially destroyed alveoli.
  • the presenting symptoms for COPD are typically breathlessness
  • Chronic bronchitis can also be diagnosed by asking the patient whether they have a "productive cough," i.e. one that yields sputum.
  • COPD patients are traditionally treated with bronchodilators and/or anticholinergics and evaluated by spirometry for the presence of airflow obstruction and reversibility. If airflow obstruction is present and reversibility less than 15%, particularly in a smoker, then they are often diagnosed as having COPD.
  • COPD is characterized by an increase in the activation and/or number of alveolar macrophages, CD 8 + T-cells and neutrophils.
  • the neutrophil is believed to play a central role in the pathophysiology of COPD.
  • Neutrophil activation results in the release of a number of inflammatory mediators and proteinases, most importantly neutrophil elastase which contributes to the progressive fibrosis, airway stenosis and destruction of the lung parenchyma, leading to an accelerated decline in airway function.
  • Neutrophil elastase also induces mucus secretion and thus may contribute to the characteristic mucus hypersecretion that characterizes COPD.
  • Transdermal patches of embodiments of the invention have an adhesive matrix which includes both a beta agonist, e.g., tulobuterol, and an anticholinergic, e.g., scopolamine, where the matrix is configured to be storage-stable and provide for extended release of the beta agonist and anticholinergic.
  • a beta agonist e.g., tulobuterol
  • an anticholinergic e.g., scopolamine
  • aspects of the invention further include methods of using the transdermal patches, e.g., in the treatment of pulmonary conditions, such as chronic obstructive pulmonary disease (COPD).
  • COPD chronic obstructive pulmonary disease
  • Fig. 1 provides a cross-sectional view of a transdermal patch preparation according to the invention.
  • Transdermal patches have an adhesive matrix which includes both a beta agonist, e.g., tulobuterol, and an anticholinergic, e.g., scopolamine, where the matrix is configured to be storage-stable and provide for extended release of the beta agonist and anticholinergic.
  • a beta agonist e.g., tulobuterol
  • an anticholinergic e.g., scopolamine
  • aspects of the invention further include methods of using the transdermal patches, e.g., in the treatment of pulmonary conditions, such as chronic obstructive pulmonary disease (COPD).
  • COPD chronic obstructive pulmonary disease
  • aspects of the invention include extended-release transdermal patches, where the transdermal patches are configured to
  • transdermal ⁇ deliver i.e., deliver across the skin into the bloodstream
  • a therapeutic amount of both a beta agonist e.g., tulobuterol
  • an anticholinergic e.g., scopolamine
  • the therapeutic amount that is delivered by the patches may vary depending on the particular condition being treated.
  • the transdermal patches are configured to provide a plasma level of a beta agonist, e.g., tulobuterol, which ranges from 0.5 ng/ml to 5 ng/ml, such as 1 ng/ml to 3 ng/ml.
  • the transdermal patches are configured to provide a plasma level of an anticholinergic, e.g., scopolamine, which ranges from 0.1 ng/ml to 1 .0 ng/ml, such as 0.2 ng/ml to 0.4 ng/ml. While the extended period of time over which the therapeutic amount is provided may vary, in some instances the extended period of time is 6 hours or longer, such as 1 2 hours or longer, including 24 hours or longer.
  • an anticholinergic e.g., scopolamine
  • Transdermal patches of certain embodiments include an adhesive layer and a backing layer.
  • the adhesive layer includes an amount of both a beta-agonist and an anticholinergic agent as active agents in an adhesive matrix that is formulated to provide extended release of the active agents, e.g., as described above.
  • FIG. 1 provides a schematic of a transdermal patch according to certain embodiments of the invention. As can be seen in FIG. 1 , the depicted transdermal patch 10 contains an adhesive base 12 present on a surface of a backing 14 (i.e., support).
  • Adhesive layers of interest include an amount of both a beta agonist and an anticholinergic present in an adhesive matrix, where the adhesive layer is a homogenous mixture of the active agents in the matrix material.
  • the amount of the active agents present in the adhesive matrix may vary. In some instances, the total amount of active agent (i.e., the combined amount of both the beta agonist and the anticholinergic together) ranges from 0.5 to 10, such as 1 to 5 and including 1 to 3 % by weight.
  • the weight ratio of the beta agonist to the anticholinergic in the adhesive layer may also vary, ranging in some instances from 15 to 1 , such as 1 0 to 1 and including 3 to 1 . In some instances, the amount of beta agonist in the adhesive layer ranges from 0.01 to 5, such as 0.1 to 4 and including from 0.2 to 2 % by weight.
  • Beta agonists of interest include, but are not limited to: amines, such as secondary amines, e.g., 2-hydroxy-phenyl-ethyl amines, e.g., salmeterol, formoterol, albuterol, bambuterol, procaterol, and tulobuterol.
  • the beta agonist is generally present as a free base, although a pharmaceutically acceptable salt may also be employed.
  • the total amount of beta agonist in the adhesive matrix may vary, and in some instances ranges from 1 to 5 w/w %, such as from 1 to 3 w/w %.
  • Anticholinergics of interest include, but are not limited to, amines, e.g., tertiary amines.
  • the nitrogen of the tertiary amine may be part of a ring, e.g., glycopyrrolate, or acyclic, e.g., isopropamide, orphenadrine, benzalkonium chloride, etc.
  • the tertiary amine includes a tropane group, i.e., a bridged nitrogenous bicyclic group such as is found in a tropane alkaloid, or an N-alkylated version thereof.
  • the tropane group may be substituted with an arylalkanoyloxy substituent such as a phenylalkanoyloxy or a thienylacetyloxy substituent.
  • the thienylacetyloxy substituent is a hydroxidi-2-thienylacetyloxy group.
  • the phenylalkanoyloxy substituent is a 2-hydroxy-phenylacetate or a 3- hydroxy-2-phenylpropanoyloxy group.
  • Tropane containing tertiary amines of interest include Scopolamine, Atropine, Hyoscyamine, and Tiotropium.
  • the anticholinergic of interest may be an individual isomer of any of the above or a pharmaceutically acceptable salt or hydrate of any of the above, or a combination of two or more of the above.
  • the anticholinergic may be present as a free base or pharmaceutically acceptable salt.
  • a given topical patch may include a single anticholinergic or two or more different anticholinergics in combination.
  • the total amount of the one or more anticholinergics in the adhesive matrix may vary, and in some instances ranges from 0.1 to 5 w/w %, such as from 0.2 to 2 w/w %.
  • the adhesive layer comprises an adhesive matrix.
  • the adhesive matrix is configured to provide for the desired extended release of the active agents.
  • the various components of the matrix are chosen and present in amounts that provide for the desired extended release of the active agents.
  • the adhesive matrices include the following components: a rubber; an adhesive resin; and a higher fatty acid. Each of these components is now described in great detail below.
  • any convenient rubber may be employed in the adhesive matrix, including both natural and synthetic rubbers.
  • Suitable synthetic rubber-type adhesives include, but are not limited to, styrene-isoprene-styrene block copolymer, polyisobutylene, isoprene rubber, styrene-butadiene-styrene block copolymer, styrene-butadiene rubber, and silicon rubber.
  • the adhesive will, in some instances, comprise one type of synthetic rubber. In other embodiments, the adhesives will include two or more types of synthetic rubber.
  • the total amount of the one or more rubbers in the adhesive matrix may vary, and in some instances ranges from 5 to 35 w/w %, such as from 10 to 30 w/w %, including from 15 to 25 w/w %.
  • the matrix further includes an adhesive resin.
  • Any convenient adhesive resin may be employed.
  • Adhesive resins of interest include, but are not limited to: petroleum resins, polyterpene resins, polyolefin resins, rosin-type resins, resin-ester-type resins, saturated alicyclic hydrocarbon resins, oil-soluble phenol type resins, etc.
  • the adhesive will in some instances comprise one type of adhesive resin. In other embodiments, the adhesive will include two or more types of adhesive resins.
  • the total amount of the one or more adhesive resins in the adhesive matrix may vary, and in some instances ranges from 20 to 70 w/w %, such as from 30 to 60 w/w %, including from 40 to 55 w/w %.
  • the matrix further includes a higher fatty acid.
  • Higher fatty acids of interest include C11-22 fatty acids, such as C14-18 fatty acids.
  • Specific higher fatty acids of interest include, but are not limited to: linolic acid, linolenic acid, oleic acid, stearic acid, palmitic acid, lauric acid, myristic acid, isostearic acid, ricinolic acid, etc.
  • the adhesive will, in some instances, comprise one type of higher fatty acid. In other embodiments, the adhesive will include two or more types of higher fatty acids.
  • the total amount of the one or more higher fatty acids in the adhesive matrix may vary, and in some instances ranges from 0.1 to 3 w/w %, such as from 0.2 to 2 w/w %, including from 0.3 to 1 w/w %.
  • the matrix further includes a plasticizer.
  • plasticizers of interest include, but are not limited to: oils, liquid paraffins, polybutenes, etc.
  • the adhesive will, in some instances, comprise one type of plasticizer. In other embodiments, the adhesive will include two or more types of plasticizers. The total amount of the one or more plasticizers in the adhesive matrix may vary, and in some instances ranges from 5 to 60 w/w %, such as from 10 to 50 w/w %, including from 15 to 30 w/w %.
  • the matrix further includes an antioxidant component.
  • an antioxidant component Any convenient anti-oxidant may be employed. Antioxidants of interest include, but are not limited to: ascorbic acid, tocopherol acetate, natural vitamin E,
  • the adhesive will, in some instances, comprise one type of antioxidant. In other embodiments, the adhesive will include two or more types of antioxidants. The total amount of the one or more antioxidants in the adhesive matrix may vary, and in some instances ranges from 0.25 to 5 w/w %, such as from 0.5 to 4 w/w %, including from 0.5 to 3 w/w %.
  • the adhesive layer of a transdermal patch will in some embodiments include, in addition to the above-discussed components, one or more additional
  • Additional components of interest include, but are not limited to, a transdermal absorption enhancer, a preservative (e.g., paraben), a stabilizing agent, a filling agent that contains a hydrophilic polymer; cross-linking agents; etc.
  • the transdermal patch does not include any of these additional components.
  • an aspect of the subject transdermal patches is that they are storage stable.
  • storage-stable is meant that the compositions may be stored for extended periods of time without significant degradation and/or significant reduction in activity of the beta agonist and anticholinergic active agents.
  • the subject compositions are stable for 3 years or longer, etc., when maintained at 25°C.
  • the above storage stability values are determining using the protocol described in United States Published Application Publication No. US 2009-0297590, modified to evaluate the presence of the beta agonist and anticholinergic free base (the disclosure of the storage stability assay reported in this publication is specifically incorporated by reference).
  • the adhesive layers are self-adhesive, i.e., inherently adhesive, and thus may be fixed in a position over the skin, i.e., removably bonded to and/or about a given skin surface, without the use of additional adhesives or other means to hold the transdermal patch in place over the formulation.
  • the adhesive compositions are adhesive, when applied to human skin they remain stably positioned at the site of application. As such, application of force is required to remove the adhesive compositions from the site of application. While application of force is required for removal, the adhesive compositions are not so adhesive such that removal of the compositions irritates or wounds the skin site to which the compositions were applied.
  • a subject transdermal patch may be held in a fixed position on a skin surface using a separate adhesive such as an adhesive backing or the like or a combination of inherent adhesiveness and an additional separate adhesion means may be employed.
  • the shape of the patch may vary, where shapes of interest include, but are not limited to: square, rectangle, oval, circle, etc.
  • the size of the patch may also vary, where in certain embodiments the size ranges from about 1 to 20 cm 2 , such as 1 to 1 5 cm 2 , such as 1 to 10 cm 2 .
  • the transdermal patch which includes an adhesive layer, e.g., as described above, also includes a backing (i.e., support), where the adhesive layer is present on a surface of the backing.
  • the backing may be made of a flexible material which is capable of fitting in the movement of human body.
  • Flexible materials of interest include, but are not limited to: various non-woven fabrics, woven fabrics, spandex, flannel, or laminates of these materials with polyethylene film, polyethylene glycol terephthalate film, polyvinyl chloride film, ethylene-vinyl acetate copolymer film, polyurethane film, and the like.
  • Suitable backing layer materials include, but are not limited to, polyethylene terephthalate, polyethylene, polypropylene, vinyl acetate-vinyl chloride copolymer, polyurethane, acetylcellulose, ethylcellulose, soft polyvinyl chloride, polyvinylidene chloride, polytetrafluoroethylene, polyamide, paper, a single film of metal foil such as aluminum foil or a laminated film of foil, woven or unwoven fabric made from the aforementioned materials, and combined materials with the aforementioned films.
  • transdermal patches may also include a release film (shown as element 16 in FIG. 1 ) on the surface of the adhesive layer that is opposite the backing.
  • the release film may provide for protection of the adhesive layer from the environment.
  • the release film may be any convenient material, where release films include polyesters, such as PET
  • transdermal patches are present in a sealed package.
  • the sealed package may be fabricated from a packaging material that includes a hydrophilic layer to prevent the passage of oxygen, and a hydrophobic layer to prevent passage of moisture and other polar materials.
  • Barrier materials of interest also include metallic layers, e.g., aluminum, where in certain embodiments, the barrier layer is an aluminum layer. This barrier layer has a thickness sufficient to provide for the barrier function, where the thickness may range in some instances from 5 to 15, such as 6 to 10 ⁇ .
  • the package is a laminate of the barrier layer in combination with one or more additional layers, e.g., polymeric layers, paper layers, etc.
  • An aluminum containing package that may be used with the subject patch preparations is sold by Dainippon Printing Co., Ltd. (Kyoto, Japan). EXTENDED- RELEASE TRANSDERMAL PATCH FABRICATION
  • Transdermal patches of the invention may be fabricated using any combination of
  • components of the adhesive layer e.g., matrix components such as the rubber, adhesive resin, higher fatty acid, plasticizer and anti-oxidant are combined with the active agents using any convenient combination protocol to produce a solution; and then the solution is pasted onto backing and dried.
  • the adhesive base is pasted in a hot melt method, the adhesive polymer components may be first dissolved; then other components (e.g., active agents etc.,) may be added and pasted onto the backing.
  • the opposing surface of the adhesive layer may then be conveniently covered with a release liner.
  • One convenient protocol for fabrication of a transdermal patch includes preparing an adhesive paste through the uniform mixing of the aforementioned ingredients and then coating the paste onto the support, followed by cutting of the resultant product to the specified size to obtain the desired transdermal patch preparation.
  • the resultant transdermal patch preparation is then heat-sealed, one sheet to a package, using a suitable packaging material, to obtain the sealed transdermal patch.
  • the present invention provides methods of delivering a beta agonist and an anticholinergic to an individual in need thereof. Aspects of the methods include contacting a topical surface of an individual with a transdermal patch, e.g., as described above.
  • the topical surface is generally a skin surface, such that embodiments of the invention include contacting a skin surface of an individual with a transdermal patch in a manner sufficient to deliver a therapeutic amount of the beta agonist and anticholinergic to the individual for an extended period of time.
  • the transdermal patch is applied to any convenient skin surface.
  • Skin surfaces of interest include, but are not limited to: arms, leg, torso (e.g., stomach or back), head, neck, etc.
  • the surface area that is covered by the transdermal patch following application is generally sufficient to provide for the desired amount of active agent administration, and in certain embodiments ranges froml cm 2 to 20 cm 2 , such as from 1 cm 2 to 10 cm 2 .
  • the applied patch is maintained at the target site for a period of time sufficient for delivery the desired amount of active agents.
  • the period of time is 6 hours or longer, such as 12 hours or longer, including 24 hours or longer.
  • practice of the methods results in extended release of the active agents from the transdermal patch.
  • practice of the methods results in a plasma level of a beta agonist, e.g., tulobuterol, which ranges from 0.5 ng/ml to 5 ng/ml, such as 1 ng/ml to 3 ng/ml.
  • practice of the methods provides a plasma level of an anticholinergic, e.g., scopolamine, which ranges from 0.1 ng/ml to 1 .0 ng/ml, such as 0.2 ng/ml to 0.4 ng/ml.
  • the extended period of time over which the therapeutic amount is provided may vary, in some instances the extended period of time is 6 hours or longer, such as 12 hours or longer, including 24 hours or longer.
  • a transdermal patch when applied to a skin surface of an individual, will provide a relatively constant plasma level of the active agents over the extended period of time.
  • a "relatively constant" level is a level that varies by no more than about 60%, e.g., less than about 40%, less than about 30%, or less than about 20%, over a given period of time.
  • a transdermal patch is generally applied a single time over a given time period.
  • the dosing schedule may be daily, such that an old patch is replaced with a new patch every 24 hours.
  • the patch may be designed for multi-day use, such as three days.
  • Transdermal patches of the invention find use in the treatment of any condition in which it is desired to deliver a beta agonist and an anticholinergic agent to a subject.
  • pulmonary conditions such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, etc.
  • COPD chronic obstructive pulmonary disease
  • Treating an individual diagnosed with COPD encompasses a method of inhibiting the progression of COPD in an individual diagnosed with COPD.
  • inhibiting the progression of COPD is intended to mean that the progressive histological and morphometric changes associated with the clinical sequelae of COPD, including inflammation, alveolar remodeling, and lung cell death, are attenuated.
  • kits where the subject kits at least include one or more transdermal patches (e.g., as described above), as well as instructional material for using the same, e.g., in the methods of the invention.
  • the kits include two or more transdermal patches as described above.
  • a transdermal delivery patch in a kit may be present in a package, as described supra.
  • the transdermal patches of the kits may be present in individual pouches or analogous containers, to preserve the composition of the patches until use.
  • the subject kits also may include instructions for how to use the patches, where the instructions typically include information about where to apply the patch, dosing schedules etc.
  • the instructions may be recorded on a suitable recording medium.
  • the instructions may be printed on a substrate, such as paper or plastic, etc.
  • the instructions may be present in the kits as a package insert, in the labeling of the container of the kit or components thereof (i.e.
  • the instructions are present as an electronic storage data file present on a suitable computer readable storage medium, e.g. CD-ROM, diskette, etc.
  • Adhesive Component (w/w %)
  • Backing PET 10 ⁇ .
  • Liner PET 75 ⁇ (Release coating on one side) .
  • tulobuterol, scopolamine and oleic acid are dissolved in a suitable amount of toluene (Solution A).
  • Styrene-isoprene-styrene block copolymer, saturated alicyclic hydrocarbon resin, polybutene, liquid paraffin and dibutylhydroxytoluene are mixed with a suitable amount of toluene until being homogenous (Mixture B).
  • the solution A and the mixture B are stirred until being homogenous, and the mixture is spread on the release coated surface of the polyethyleneterephthalate (PET) liner in the amount of 100 g/m 2 and dried.
  • PET polyethyleneterephthalate
  • the PET backing is laminated on the adhesive side of the liner and the product is cut in a suitable size to be packed in a sealed package.

Landscapes

  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Emergency Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pulmonology (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne des patchs transdermiques à libération prolongée associant un bêta-agoniste et un anticholinergique. Ces patchs transdermiques présentent une matrice adhésive qui contient à la fois un bêta-agoniste, par exemple du tulobutérol, et un anticholinergique, par exemple de la scopolamine, ladite matrice étant conçue pour être stable au stockage et assurer une libération prolongée du bêta-agoniste et de l'anticholinergique. D'autres aspects de l'invention concernent des procédés d'utilisation desdits patchs transdermiques, par exemple pour le traitement d'affections pulmonaires, telles que la broncho-pneumopathie chronique obstructive (BPCO).
PCT/US2012/022233 2011-01-26 2012-01-23 Patchs transdermiques à libération prolongée associant un bêta-agoniste et un anticholinergique et leurs procédés d'utilisation Ceased WO2012103016A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP12739786.7A EP2667861A4 (fr) 2011-01-26 2012-01-23 Patchs transdermiques à libération prolongée associant un bêta-agoniste et un anticholinergique et leurs procédés d'utilisation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161436489P 2011-01-26 2011-01-26
US61/436,489 2011-01-26

Publications (2)

Publication Number Publication Date
WO2012103016A2 true WO2012103016A2 (fr) 2012-08-02
WO2012103016A3 WO2012103016A3 (fr) 2012-09-20

Family

ID=46581346

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2012/022233 Ceased WO2012103016A2 (fr) 2011-01-26 2012-01-23 Patchs transdermiques à libération prolongée associant un bêta-agoniste et un anticholinergique et leurs procédés d'utilisation

Country Status (2)

Country Link
EP (1) EP2667861A4 (fr)
WO (1) WO2012103016A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019110306A1 (fr) * 2017-11-21 2019-06-13 Lts Lohmann Therapie-Systeme Ag Système thérapeutique transdermique à base de matrices plastifiant-polymère adhésives

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4436741A (en) * 1975-12-08 1984-03-13 Alza Corporation Method for administering scopolamine transdermally
DE4002281A1 (de) * 1990-01-26 1991-08-01 Lohmann Therapie Syst Lts Transdermales therapeutisches system mit dem wirkstoff tulobuterol
JP3930984B2 (ja) * 1997-12-12 2007-06-13 日東電工株式会社 経皮吸収型製剤
BRPI0405662A (pt) * 2003-06-20 2005-07-19 Teikoku Seiyaku Kk Emplastros contendo turobuterol
WO2005046600A2 (fr) * 2003-11-07 2005-05-26 Nexmed Holdings, Inc. Systeme d'application de tulobuterol transdermique, procede et composition correspondants
TWI239252B (en) * 2003-12-31 2005-09-11 Ind Tech Res Inst A patch and the manufacturing method of the same
DE102004059674B4 (de) * 2004-12-10 2010-05-06 Acino Ag Transdermales System zur Abgabe von Scopolamin

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of EP2667861A4 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019110306A1 (fr) * 2017-11-21 2019-06-13 Lts Lohmann Therapie-Systeme Ag Système thérapeutique transdermique à base de matrices plastifiant-polymère adhésives
CN111372575A (zh) * 2017-11-21 2020-07-03 Lts勒曼治疗系统股份公司 基于粘合性增塑剂聚合物基质的tts
US11304912B2 (en) 2017-11-21 2022-04-19 Lts Lohmann Therapie-Systeme Ag Transdermal therapeutic system on the basis of adhesive plasticizer-polymer matrices
CN111372575B (zh) * 2017-11-21 2023-12-01 Lts勒曼治疗系统股份公司 基于粘合性增塑剂聚合物基质的tts

Also Published As

Publication number Publication date
EP2667861A4 (fr) 2014-07-16
EP2667861A2 (fr) 2013-12-04
WO2012103016A3 (fr) 2012-09-20

Similar Documents

Publication Publication Date Title
AU2005244214B2 (en) Topical methadone compositions and methods for using the same
US6277401B1 (en) Drug delivery device
KR101725832B1 (ko) 경피 흡수형 제제
US8609134B2 (en) Methods of transdermally administering an indole serotonin receptor agonist and transdermal compositions for use in the same
AU684838B2 (en) Transdermal therapeutic system with acetylsalicylic acid as active substance
KR20110118525A (ko) 경피 흡수 제제
WO2007099966A1 (fr) Preparation pour absorption transdermique
KR101766495B1 (ko) 펜타닐 함유 외용 첩부제
JP2019516671A (ja) 二重ディスク経皮システム
EP0301589B1 (fr) Système pour l'administration transdermique du procatèrol
JP4809062B2 (ja) カバー材及びカバー材付き貼付剤
KR101770675B1 (ko) 도네페질-함유 경피흡수제제 및 그의 제조방법
JP5883459B2 (ja) ガランタミンまたはその塩を含む経皮送達システム
WO2012103016A2 (fr) Patchs transdermiques à libération prolongée associant un bêta-agoniste et un anticholinergique et leurs procédés d'utilisation
EP2514424A1 (fr) Préparation endermique contenant du piroxicam
CN108289859A (zh) 用于透皮给药的系统和方法
CN110913912A (zh) 不可再贴的贴剂
WO2012103015A2 (fr) Patchs transdermiques à libération prolongée associant un bêta-agoniste et un stéroïde et leurs procédés d'utilisation
JP2004224701A (ja) 外用貼付剤
TW202114649A (zh) 一種經皮吸收的含醯胺類局部麻醉藥的醫藥組成物及其製備方法
KR101558454B1 (ko) 셀레질린 또는 그의 약학적으로 허용가능한 염을 함유하는 경피흡수제제
CN118178357A (zh) 妥洛特罗透皮贴剂及其制备方法
JP2007045779A (ja) 外用貼付剤

Legal Events

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

Ref document number: 12739786

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase in:

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2012739786

Country of ref document: EP