WO2012103015A2 - Patchs transdermiques à libération prolongée associant un bêta-agoniste et un stéroïde et leurs procédés d'utilisation - Google Patents

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

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Publication number
WO2012103015A2
WO2012103015A2 PCT/US2012/022232 US2012022232W WO2012103015A2 WO 2012103015 A2 WO2012103015 A2 WO 2012103015A2 US 2012022232 W US2012022232 W US 2012022232W WO 2012103015 A2 WO2012103015 A2 WO 2012103015A2
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WO
WIPO (PCT)
Prior art keywords
patch according
patch
acid
beta agonist
adhesive
Prior art date
Application number
PCT/US2012/022232
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English (en)
Other versions
WO2012103015A3 (fr
Inventor
Larry J. Caldwell
Sadanobu Shirai
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
Publication of WO2012103015A2 publication Critical patent/WO2012103015A2/fr
Publication of WO2012103015A3 publication Critical patent/WO2012103015A3/fr

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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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • 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
    • A61P11/06—Antiasthmatics

Definitions

  • Asthma is a chronic inflammatory disease that affects millions in the U.S. alone. Symptoms of asthma include recurrent episodes of wheezing,
  • Airway inflammation associated with asthma can be detected through observation of a number of physiological changes, such as, denudation of airway epithelium, collagen deposition beneath basement membrane, edema, mast cell activation, inflammatory cell infiltration, including neutrophils, eosinophils, and lymphocytes.
  • asthma patients often experience airway hyper-responsiveness, airflow limitation, respiratory symptoms, and disease chronicity.
  • Airflow limitations include acute bronchoconstriction, airway edema, mucous plug formation, and airway remodeling, features which often lead to bronchial obstruction.
  • subbasement membrane fibrosis may occur, leading to persistent abnormalities in lung function.
  • Asthma is a complex disorder which arises at different stages in development and can be classified based on the degree of symptoms of acute, subacute or chronic.
  • An acute inflammatory response is associated with an early recruitment of cells into the airway.
  • the subacute inflammatory response involves the recruitment of cells as well as the activation of resident cells causing a more persistent pattern of inflammation.
  • Chronic inflammatory response is characterized by a persistent level of cell damage and an ongoing repair process, which may result in permanent abnormalities in the airway.
  • Medications for the treatment of asthma are generally separated into two categories, quick-relief medications and long-term control medications.
  • Asthma patients take the long-term control medications on a daily basis to achieve and maintain control of persistent asthma.
  • Long-term control medications include antiinflammatory agents such as corticosteroids, chromolyn sodium and medacromil; long-acting bronchodilators, such as long-acting 2 -agonists and methylxanthines; and leukotriene modifiers.
  • the quick-relief medications include short-acting ⁇ 2 - agonists, anti-cholinergics, and systemic corticosteroids.
  • Transdermal patches of embodiments of the invention have an adhesive matrix which includes both a beta agonist, e.g., tulobuterol, and steroid, e.g.,
  • dexamethasone where the matrix is configured to be storage-stable and provide for extended release of the beta agonist and steroid.
  • aspects of the invention further include methods of using the transdermal patches, e.g., in the treatment of pulmonary conditions, such as asthma.
  • Fig. 1 provides a cross-sectional view of a transdermal patch preparation according to the invention.
  • Transdermal patches of embodiments of the invention have an adhesive matrix which includes both a beta agonist, e.g., tulobuterol, and steroid, e.g.,
  • dexamethasone where the matrix is configured to be storage-stable and provide for extended release of the beta agonist and steroid.
  • aspects of the invention further include methods of using the transdermal patches, e.g., in the treatment of pulmonary conditions, such as asthma.
  • 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
  • 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 antiinflammatory steroid, e.g., dexamethasone, 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 12 hours or longer, including 24 hours or longer.
  • an antiinflammatory steroid e.g., dexamethasone
  • 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 anti-inflammatory steroidal 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 1 0 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 anti-inflammatory steroid 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.
  • the total amount of active agent i.e., the combined amount of both the beta agonist and the anti-inflammatory steroid together
  • the weight ratio of the beta agonist to the antiinflammatory steroid in the adhesive layer may also vary, ranging in some instances from 15 to 1 , such as 10 to 1 and including 3 to 1 .
  • 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 %.
  • an anti-inflammatory steroid is present in the topical formulation.
  • the anti-inflammatory steroid comprises a steroid framework with a carbonyl at the C-3 position.
  • the anti-inflammatory is a steroid comprising one or more fluorine substituents.
  • the antiinflammatory is a steroid comprising at the C-17 position a 2-hydroxyacetyl group, a protected 2-hydroxyacetyl group, or a derivative of a 2-hydroxyacetyl group.
  • the anti-inflammatory has the structure of formula (I)
  • a and ⁇ represent optional double bonds
  • R7 is selected from H, halo, and alkyl
  • R9 is selected from H and halo;
  • R1 1 is selected from H and OH when ⁇ is absent, and is an oxygen atom when ⁇ is present;
  • R13 is selected from alkyl and acyl
  • R16 is selected form H and alkyl
  • R17 is selected from H, OH, and alkylcarbonyloxy, provided that R1 6 and
  • R17 may be taken together to form a 5- or 6-memebered ring containing one or more heteroatoms and one or more substituents;
  • R is selected from halo, hydroxyl, and protected hydroxyl.
  • anti-inflammatory compounds suitable for the patches of the invention include steroids such as alclometasone, aldosterone, amcinonide, beclomethasone dipropionate, betamethasone, budesonide, ciclesonide, clobetasol, clocortolone, Cortisol, cortisone, corticosterone, desonide, desoximetasone, 1 1 - desoxycorticosterone, 1 1 -desoxycortisol, dexamethasone, diflorasone,
  • fludrocortisone flunisolide, fluticasone, fluocinolone, fluocinonide, fluorometholone, flurandrenolide, halcinonide, medrysone, 6a-methylprednisolone, mometasone, paramethasone, prednisolone, prednisone, tetrahydrocortisol, triamcinolone.
  • the anti-inflammatory steroid 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. In some instances, the anti-inflammatory may be present as a pharmaceutically acceptable salt.
  • a given topical patch may include a single anti-inflammatory or two or more different anti-inflammatory steroids in combination. The total amount of the one or more anti-inflammatory steroids 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. Rubber
  • 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 Cn-22 fatty acids, such as C 1 . 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 anti-inflammatory 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 anti-inflammatory (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 convenient protocol.
  • 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 anti-inflammatory 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 anti-inflammatory 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 to 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 anti-inflammatory, e.g., dexamethasone, 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 30%, e.g., less than about 25%, less than about 20%, or less than about 15%, 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 anti-inflammatory steroidal agent to a subject.
  • pulmonary conditions such asthma. Treating an individual diagnosed with asthma includes, in some instances, at least reducing severity of symptoms arising from acute, subacute and/or chronic asmtha conditions. Treating includes, in some instances, at least reducing the frequency of symptom occurrence.
  • 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 %)
  • Weight of adhesive 100 g/m 2 .
  • Backing PET 10 ⁇ .
  • Liner PET 75 ⁇ (Release coating on one side) .
  • tulobuterol, dexamethasone 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.

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  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Dermatology (AREA)
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  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des patchs transdermiques à libération prolongée associant un bêta-agoniste et un stéroïde. Les patchs transdermiques des modes de réalisation de l'invention présentent une matrice adhésive qui contient à la fois un bêta-agoniste, par exemple du tulobutérol, et un stéroïde, par exemple de la dexaméthasone, ladite matrice étant conçue pour être stable au stockage et assurer une libération prolongée du bêta-agoniste et du stéroïde. D'autres aspects de l'invention concernent des procédés d'utilisation desdits patchs transdermiques, par exemple pour le traitement d'affections pulmonaires, telles que l'asthme.
PCT/US2012/022232 2011-01-27 2012-01-23 Patchs transdermiques à libération prolongée associant un bêta-agoniste et un stéroïde et leurs procédés d'utilisation WO2012103015A2 (fr)

Applications Claiming Priority (2)

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US201161436900P 2011-01-27 2011-01-27
US61/436,900 2011-01-27

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WO2012103015A2 true WO2012103015A2 (fr) 2012-08-02
WO2012103015A3 WO2012103015A3 (fr) 2012-09-20

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CN110433146A (zh) * 2018-05-03 2019-11-12 中国医学科学院药物研究所 一种妥洛特罗晶体贮库型透皮贴剂及其制备方法

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CN110433146B (zh) * 2018-05-03 2022-03-15 中国医学科学院药物研究所 一种妥洛特罗晶体贮库型透皮贴剂及其制备方法

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