WO1998026763A1 - Excipient pour liberer de l'apomorphine dans la cavite buccale - Google Patents

Excipient pour liberer de l'apomorphine dans la cavite buccale Download PDF

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Publication number
WO1998026763A1
WO1998026763A1 PCT/EP1997/006529 EP9706529W WO9826763A1 WO 1998026763 A1 WO1998026763 A1 WO 1998026763A1 EP 9706529 W EP9706529 W EP 9706529W WO 9826763 A1 WO9826763 A1 WO 9826763A1
Authority
WO
WIPO (PCT)
Prior art keywords
apomorphine
pharmaceutical preparation
preparation according
active ingredient
active substance
Prior art date
Application number
PCT/EP1997/006529
Other languages
German (de)
English (en)
Inventor
Karsten Cremer
Original Assignee
Lts Lohmann Therapie-Systeme 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 Lts Lohmann Therapie-Systeme Gmbh filed Critical Lts Lohmann Therapie-Systeme Gmbh
Priority to JP52593498A priority Critical patent/JP2001506612A/ja
Priority to EP97952795A priority patent/EP0959875A1/fr
Priority to CA002274893A priority patent/CA2274893A1/fr
Priority to AU56547/98A priority patent/AU746373B2/en
Publication of WO1998026763A1 publication Critical patent/WO1998026763A1/fr
Priority to NO992944A priority patent/NO992944D0/no

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
    • A61K9/20—Pills, tablets, discs, rods
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs

Definitions

  • the present invention relates to a medicament preparation for the application of active substances in the area of the oral cavity or the oral mucosa. It relates in particular to a preparation that is flat and designed as a film, paper or wafer-like dosage form.
  • DE-OS 27 46 414 which describes a film-like band of active substance, binder and other auxiliaries, in which, due to homogeneous thickness and density, there is a direct connection between a unit length of the band and the dose of active substance contained therein, can be regarded as fundamental for this dosage form .
  • the advantages of continuous dosing were also recognized by other applicants and described in special individual variants.
  • DE-PS 36 30 603 claims a flat carrier material e.g. in the form of a release paper with a coating containing the active substance, the latter being subtracted from the carrier material in doses after being divided up into dose units.
  • a flat, film-like or paper-like active ingredient carrier enables a faster onset of action than the application of conventional dosage forms, such as tablets.
  • Tablets are usually designed for drug release after swallowing in the gastrointestinal tract. Ordinary, rapidly disintegrating tablets release their active ingredient in the stomach. The disintegration of the dosage form is a prerequisite for the release of the active ingredient.
  • the disintegration of a tablet in the fluids of the gastrointestinal tract is often a multi-stage process. If the tablet has a coating, it must first disintegrate and expose the compact.
  • the latter are suitable for introducing active substances into the organism more quickly than with tablets, and can advantageously be used when a quick onset of action is necessary or particularly desirable, for example when administering analgesics, antiallergics, antitussives, antiemetics, active substances against Angina, migraines, hypotension, etc.
  • the object of the present invention is therefore to create a medicinal preparation based on and with the general advantages of flat, film-like or paper-like active substance carriers, which, however, in addition, through the combination with a special active substance, also have additional economic and / or therapeutic advantages over medicament preparations thereof Active ingredient based on conventional dosage forms such as tablets.
  • a medicinal preparation is provided on the basis of a flat, film, paper or wafer-like active ingredient carrier which contains apomorphine or one of its therapeutically suitable salts as the active ingredient.
  • a pharmaceutical preparation according to claim 1 is, as will be explained in the following, a conventional oral dosage form for the administration of apomorphine far superior both from an economic as well as from a therapeutic point of view and is particularly suitable for the therapy of Parkinson's disease.
  • apomorphine a potent dopamine agonist
  • apomorphine must be injected subcutaneously for this purpose, since it is hardly bioavailable after oral administration, i.e. it only appears to a very small extent in the bloodstream of a few percent of the dose taken.
  • the reason for the lack of bioavailability probably lies in the extensive breakdown of the substance during the first passage through the liver after gastrointestinal absorption ("first pass effect").
  • One way to circumvent the first-pass effect in the case of oral administration is to induce the active ingredient to be absorbed on the oral mucosa.
  • Active substance that enters the blood here does not first have to pass through the portal vein system and thus in concentrated form through the liver metabolizing the active substance in order to get into the central body circulation.
  • a prerequisite for buccal or sublingual application is the sufficient permeability of the oral mucosa for the active substance, taking into account the necessary dose. The permeability in turn depends to a large extent on the physicochemical properties of the active ingredient.
  • buccal or sublingual administration of apomorphine appears to be very desirable for the patients because of the injections to be avoided.
  • apomorphine with the aid of a pharmaceutical preparation according to claim 1 is completely different.
  • This dosage form can be brought into direct contact with the oral mucosa during application. Due to the flat design, about half of the already large surface of the dosage form is immediately on the mucosa immediately after application.
  • the released apomorphine therefore finds two particularly favorable factors for entry into the body, namely a short diffusion distance and a large diffusion area. This reduces the amount of apomorphine that is swallowed, which would not be particularly problematic with other active ingredients. In the case of apomorphine, however, the swallowing of active ingredient should be avoided or reduced as far as possible, since swallowed apomorphine remains ineffective for the reasons set out above.
  • test person showed the superiority of an apomorphine-containing film over an apomorphine-containing tablet.
  • An improved contact of the pharmaceutical preparation according to the invention with the oral mucosa can be brought about by the selection of the auxiliary substances.
  • pharmaceutically customary, orally administrable auxiliaries have mucosal properties.
  • mucoadhesive substances are polyacrylic acid, carboxylmethyl cellulose, tragacanth, alginic acid, gelatin, hydroxymethyl cellulose, methyl cellulose and gum arabic.
  • various non-mucoadhesive substances are known to also form mucoadhesive properties in certain mixing ratios.
  • An example of such a mixture is glycerol monooleate / water in the ratio 84:16 (Engström et al., Pharm. Tech. Eur. 7 [1995], No. 2, pages 14-17).
  • a two- or multi-layer structure of the dosage form of the medicinal preparation according to the invention is to be preferred, only one layer, which should come into contact with the mucous membrane when the preparation is applied, to be provided with mucoadhesive properties. This prevents the preparation from sticking together different parts of the mucous membrane, which would lead to considerable discomfort during use.
  • the amount of active ingredient or the proportion of the administered active ingredient dose which is absorbed in the preparation according to the invention depends not only on the contact area and the perme bailiness of the mucous membrane, but also on the contact time.
  • auxiliaries can be, for example, film-forming polymers with low water solubility, such as ethyl cellulose, cellulose acetate, highly hydrolyzed polyvinyl alcohol and many others.
  • apomorphine usually leads to undesirable side effects. First of all there are nausea, vomiting and a drop in blood pressure. These side effects can be seen as serious and therapy-limiting. However, it is known that the simultaneous administration of antiemetic dopamine antagonists such as metoclopramide, but especially domperidone, can prevent or alleviate the occurrence of these side effects without losing the anti-Parkinson effect of apomorphine.
  • antiemetic dopamine antagonists such as metoclopramide, but especially domperidone
  • a further preferred embodiment of the present invention therefore contains apomorphine in combination with a dopamine antagonist in a combination as active ingredients.
  • Production examples of the pharmaceutical preparation according to the invention are given below:
  • H 2 0 Place H 2 0 in a heatable, evacuable batch vessel and disperse Ti0 2 in it.

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  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Psychology (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une préparation médicamenteuse à forme galénique plate, de type film, papier ou hostie, servant à administrer et à libérer des principes actifs dans la cavité buccale, qui se caractérise par une teneur en apomorphine ou en un de ses sels appropriés sur le plan thérapeutique.
PCT/EP1997/006529 1996-12-16 1997-11-21 Excipient pour liberer de l'apomorphine dans la cavite buccale WO1998026763A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
JP52593498A JP2001506612A (ja) 1996-12-16 1997-11-21 アポモルヒネを口腔に放出するための活性物質担体
EP97952795A EP0959875A1 (fr) 1996-12-16 1997-11-21 Excipient pour liberer de l'apomorphine dans la cavite buccale
CA002274893A CA2274893A1 (fr) 1996-12-16 1997-11-21 Excipient pour liberer de l'apomorphine dans la cavite buccale
AU56547/98A AU746373B2 (en) 1996-12-16 1997-11-21 Active substance carrier for releasing apomorphine into the buccal cavity
NO992944A NO992944D0 (no) 1996-12-16 1999-06-16 Virkestoffbµrer for avgivelse av apomorfin i munnhulen

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19652268A DE19652268C2 (de) 1996-12-16 1996-12-16 Arzneizubereitung für die Freisetzung von Apomorphin in der Mundhöhle
DE19652268.4 1996-12-16

Publications (1)

Publication Number Publication Date
WO1998026763A1 true WO1998026763A1 (fr) 1998-06-25

Family

ID=7814859

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1997/006529 WO1998026763A1 (fr) 1996-12-16 1997-11-21 Excipient pour liberer de l'apomorphine dans la cavite buccale

Country Status (8)

Country Link
EP (1) EP0959875A1 (fr)
JP (1) JP2001506612A (fr)
KR (1) KR20000057627A (fr)
AU (1) AU746373B2 (fr)
CA (1) CA2274893A1 (fr)
DE (1) DE19652268C2 (fr)
NO (1) NO992944D0 (fr)
WO (1) WO1998026763A1 (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6291471B1 (en) 1998-12-17 2001-09-18 Abb Holdings, Inc. Use of apomorphine for the treatment of organic erectile dysfunction in males
US6596298B2 (en) 1998-09-25 2003-07-22 Warner-Lambert Company Fast dissolving orally comsumable films
US7067116B1 (en) 2000-03-23 2006-06-27 Warner-Lambert Company Llc Fast dissolving orally consumable solid film containing a taste masking agent and pharmaceutically active agent at weight ratio of 1:3 to 3:1
US7314716B2 (en) 1999-11-19 2008-01-01 Mount Sinai School Of Medicine Gustducin γ subunit materials and methods
USRE40594E1 (en) 1998-12-23 2008-12-02 Mount Sinai School Of Medicine Of New York University Inhibitors of the bitter taste response
WO2010144817A1 (fr) 2009-06-12 2010-12-16 Adagio Pharmaceuticals Ltd. Apomorphine sublinguale
US7910132B2 (en) 1998-09-24 2011-03-22 Orexo Ab Pharmaceutical composition for the treatment of acute disorders
WO2012083269A1 (fr) 2010-12-16 2012-06-21 Cynapsus Therapeutics, Inc. Films sublinguaux
US8481059B2 (en) 2001-05-01 2013-07-09 A.V. Topchiev Institute Of Petrochemical Synthesis, Russian Academy Of Sciences Hydrogel compositions
US8481071B2 (en) 2001-05-01 2013-07-09 Corium International, Inc. Hydrogel compositions with an erodible backing member
US8541021B2 (en) 2001-05-01 2013-09-24 A.V. Topchiev Institute Of Petrochemical Synthesis Hydrogel compositions demonstrating phase separation on contact with aqueous media
US8617647B2 (en) 2001-05-01 2013-12-31 A.V. Topchiev Institutes of Petrochemical Synthesis, Russian Academy of Sciences Water-absorbent adhesive compositions and associated methods of manufacture and use
US8658201B2 (en) * 2004-01-30 2014-02-25 Corium International, Inc. Rapidly dissolving film for delivery of an active agent
US8784879B2 (en) 2009-01-14 2014-07-22 Corium International, Inc. Transdermal administration of tamsulosin
US8840918B2 (en) 2001-05-01 2014-09-23 A. V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences Hydrogel compositions for tooth whitening
USRE45666E1 (en) 2000-07-07 2015-09-08 A.V. Topchiev Institute Of Petrochemical Synthesis Preparation of hydrophilic pressure sensitive adhesives having optimized adhesive properties
US10449146B2 (en) 2015-04-21 2019-10-22 Sunovion Pharmaceuticals Inc. Methods of treating parkinson's disease by administration of apomorphine to an oral mucosa

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10252726B4 (de) * 2002-11-13 2008-05-08 Lts Lohmann Therapie-Systeme Ag Mehrschichtiges transmucosales therapeutisches System
US20060035008A1 (en) * 2002-11-14 2006-02-16 Givaudan Sa Edible film containing food acid
KR100945741B1 (ko) * 2003-01-16 2010-03-05 부광약품 주식회사 염산아포모르핀을 함유하는 구강스프레이 제제
US20050281757A1 (en) * 2004-06-17 2005-12-22 Sayed Ibrahim Oral care film
US10806703B2 (en) * 2012-01-20 2020-10-20 Lts Lohmann Therapie-System Ag Transmucosal administration system for a pharmaceutical drug
WO2015070156A1 (fr) * 2013-11-11 2015-05-14 Impax Laboratories, Inc. Formulations à désintégration rapide et leurs méthodes d'utilisation

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US3972995A (en) * 1975-04-14 1976-08-03 American Home Products Corporation Dosage form
WO1995028930A1 (fr) * 1994-04-22 1995-11-02 Pentech Pharmaceuticals, Inc. Formes galeniques et procede de traitement du dysfonctionnement de l'erection masculine

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DE2746414A1 (de) * 1977-10-15 1979-04-26 Gerlach Eduard Chem Fab Mittel zum dosieren von stoffen und verfahren zu seiner herstellung
FR2732896B1 (fr) * 1995-04-11 1997-06-13 Prographarm Lab Forme pharmaceutique transdermique pour l'administration percutanee de l'apomorphine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3972995A (en) * 1975-04-14 1976-08-03 American Home Products Corporation Dosage form
WO1995028930A1 (fr) * 1994-04-22 1995-11-02 Pentech Pharmaceuticals, Inc. Formes galeniques et procede de traitement du dysfonctionnement de l'erection masculine

Cited By (64)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8454996B2 (en) 1998-09-24 2013-06-04 Orexo Ab Pharmaceutical composition for the treatment of acute disorders
US8512747B2 (en) 1998-09-24 2013-08-20 Orexo Ab Pharmaceutical composition for the treatment of acute disorders
US7910132B2 (en) 1998-09-24 2011-03-22 Orexo Ab Pharmaceutical composition for the treatment of acute disorders
EP1676557A2 (fr) 1998-09-25 2006-07-05 Warner-Lambert Company LLC Films comestibles à dissolution rapide
US7025983B2 (en) 1998-09-25 2006-04-11 Warner-Lambert Company Llc Fast dissolving orally consumable films
US7491406B2 (en) 1998-09-25 2009-02-17 Mcneil-Ppc, Inc. Fast dissolving orally consumable films
US6923981B2 (en) 1998-09-25 2005-08-02 Warner-Lambert Company Fast dissolving orally consumable films
US6596298B2 (en) 1998-09-25 2003-07-22 Warner-Lambert Company Fast dissolving orally comsumable films
US6291471B1 (en) 1998-12-17 2001-09-18 Abb Holdings, Inc. Use of apomorphine for the treatment of organic erectile dysfunction in males
USRE40594E1 (en) 1998-12-23 2008-12-02 Mount Sinai School Of Medicine Of New York University Inhibitors of the bitter taste response
US7314716B2 (en) 1999-11-19 2008-01-01 Mount Sinai School Of Medicine Gustducin γ subunit materials and methods
US7067116B1 (en) 2000-03-23 2006-06-27 Warner-Lambert Company Llc Fast dissolving orally consumable solid film containing a taste masking agent and pharmaceutically active agent at weight ratio of 1:3 to 3:1
EP1674078A2 (fr) 2000-03-23 2006-06-28 Warner-Lambert Company LLC Films consommables par voie orale à dissolution rapide contenant une résine d'échange ionique comme agent de masquage du goût
US7648712B2 (en) 2000-03-23 2010-01-19 Mcneil-Ppc, Inc. Fast dissolving orally consumable films containing a taste masking agent
USRE45666E1 (en) 2000-07-07 2015-09-08 A.V. Topchiev Institute Of Petrochemical Synthesis Preparation of hydrophilic pressure sensitive adhesives having optimized adhesive properties
US9687428B2 (en) 2001-05-01 2017-06-27 A. V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences Hydrogel compositions for tooth whitening
US9532935B2 (en) 2001-05-01 2017-01-03 A. V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences Hydrogel compositions for tooth whitening
US10179096B2 (en) 2001-05-01 2019-01-15 Corium International, Inc. Hydrogel compositions for tooth whitening
US8481059B2 (en) 2001-05-01 2013-07-09 A.V. Topchiev Institute Of Petrochemical Synthesis, Russian Academy Of Sciences Hydrogel compositions
US8481071B2 (en) 2001-05-01 2013-07-09 Corium International, Inc. Hydrogel compositions with an erodible backing member
US9127140B2 (en) 2001-05-01 2015-09-08 A. V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences Water-absorbent adhesive compositions and associated methods of manufacture and use
US8541021B2 (en) 2001-05-01 2013-09-24 A.V. Topchiev Institute Of Petrochemical Synthesis Hydrogel compositions demonstrating phase separation on contact with aqueous media
US8617647B2 (en) 2001-05-01 2013-12-31 A.V. Topchiev Institutes of Petrochemical Synthesis, Russian Academy of Sciences Water-absorbent adhesive compositions and associated methods of manufacture and use
US10869947B2 (en) 2001-05-01 2020-12-22 Corium, Inc. Hydrogel compositions
US8741331B2 (en) 2001-05-01 2014-06-03 A. V. Topchiev Institute of Petrochemicals Synthesis, Russian Academy of Sciences Hydrogel compositions with an erodible backing member
US9259504B2 (en) 2001-05-01 2016-02-16 A. V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences Non-electrically conductive hydrogel composition
US8840918B2 (en) 2001-05-01 2014-09-23 A. V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences Hydrogel compositions for tooth whitening
US10835454B2 (en) 2001-05-01 2020-11-17 Corium, Inc. Hydrogel compositions with an erodible backing member
US9089481B2 (en) 2001-05-01 2015-07-28 A. V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences Hydrogel compositions demonstrating phase separation on contact with aqueous media
US9084723B2 (en) 2001-05-01 2015-07-21 A. V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences Hydrogel compositions with an erodible backing member
US9144552B2 (en) 2004-01-30 2015-09-29 A.V. Topchiev Institute Of Petrochemical Synthesis, Russian Academy Of Sciences Rapidly dissolving film for delivery of an active agent
US8658201B2 (en) * 2004-01-30 2014-02-25 Corium International, Inc. Rapidly dissolving film for delivery of an active agent
US9610253B2 (en) 2009-01-14 2017-04-04 Corium International, Inc. Transdermal administration of tamsulosin
US8784879B2 (en) 2009-01-14 2014-07-22 Corium International, Inc. Transdermal administration of tamsulosin
US10238612B2 (en) 2009-01-14 2019-03-26 Corium International, Inc. Transdermal administration of tamsulosin
CN102480958B (zh) * 2009-06-12 2015-08-19 Cynapsus疗法有限公司 舌下阿扑吗啡
EP2442650A4 (fr) * 2009-06-12 2012-11-14 Adagio Pharmaceuticals Inc Apomorphine sublinguale
EP2442650B1 (fr) 2009-06-12 2015-08-26 Cynapsus Therapeutics Inc. Apomorphine sublinguale
WO2010144817A1 (fr) 2009-06-12 2010-12-16 Adagio Pharmaceuticals Ltd. Apomorphine sublinguale
US9326981B2 (en) 2009-06-12 2016-05-03 Cynapsus Therapeutics, Inc. Sublingual apomorphine
AU2019200308B2 (en) * 2009-06-12 2020-11-26 Sunovion Pharmaceuticals Inc. Sublingual apomorphine
EP2442650A1 (fr) * 2009-06-12 2012-04-25 Adagio Pharmaceuticals Inc. Apomorphine sublinguale
AU2010259971B2 (en) * 2009-06-12 2016-10-27 Sunovion Pharmaceuticals Inc. Sublingual apomorphine
US9044475B2 (en) 2009-06-12 2015-06-02 Cynapsus Therapeutics, Inc. Sublingual apomorphine
AU2010259971C1 (en) * 2009-06-12 2017-02-16 Sunovion Pharmaceuticals Inc. Sublingual apomorphine
US10420763B2 (en) 2009-06-12 2019-09-24 Sunovion Pharmaceuticals Inc. Sublingual apomorphine
US9669021B2 (en) 2009-06-12 2017-06-06 Sunovion Pharmaceuticals Inc. Sublingual apomorphine
US9669018B2 (en) 2009-06-12 2017-06-06 Sunovion Pharmaceuticals Inc. Sublingual apomorphine
US9669020B2 (en) 2009-06-12 2017-06-06 Sunovion Pharmaceuticals Inc. Sublingual apomorphine
US9669019B2 (en) 2009-06-12 2017-06-06 Sunovion Pharmaceuticals Inc. Sublingual apomorphine
EP2952191A1 (fr) * 2009-06-12 2015-12-09 Cynapsus Therapeutics Inc. Apomorphine sublinguale
AU2017200329B2 (en) * 2009-06-12 2018-11-08 Sunovion Pharmaceuticals Inc. Sublingual apomorphine
CN102480958A (zh) * 2009-06-12 2012-05-30 Adagio制药有限公司 舌下阿扑吗啡
EP3434270A1 (fr) * 2009-06-12 2019-01-30 Sunovion Pharmaceuticals Inc. Apomorphine sublinguale
WO2012083269A1 (fr) 2010-12-16 2012-06-21 Cynapsus Therapeutics, Inc. Films sublinguaux
US10285953B2 (en) 2010-12-16 2019-05-14 Sunovion Pharmaceuticals Inc. Sublingual films
US8846074B2 (en) 2010-12-16 2014-09-30 Cynapsus Therapeutics, Inc. Sublingual films
EP3735988A1 (fr) * 2010-12-16 2020-11-11 Sunovion Pharmaceuticals Inc. Films sublingues
US9427412B2 (en) 2010-12-16 2016-08-30 Cynapsus Therapeutics, Inc. Sublingual films
EP2651357A4 (fr) * 2010-12-16 2016-07-20 Cynapsus Therapeutics Inc Films sublinguaux
US9283219B2 (en) 2010-12-16 2016-03-15 Cynapsus Therapeutics, Inc. Sublingual films
US11419769B2 (en) 2010-12-16 2022-08-23 Sunovion Pharmaceuticals Inc. Sublingual films
US10449146B2 (en) 2015-04-21 2019-10-22 Sunovion Pharmaceuticals Inc. Methods of treating parkinson's disease by administration of apomorphine to an oral mucosa
US10959943B2 (en) 2015-04-21 2021-03-30 Sunovion Pharmaceuticals Inc. Methods of treating Parkinson's disease by administration of apomorphine to an oral mucosa

Also Published As

Publication number Publication date
NO992944L (no) 1999-06-16
CA2274893A1 (fr) 1998-06-25
KR20000057627A (ko) 2000-09-25
NO992944D0 (no) 1999-06-16
AU5654798A (en) 1998-07-15
DE19652268A1 (de) 1998-06-18
JP2001506612A (ja) 2001-05-22
AU746373B2 (en) 2002-04-18
DE19652268C2 (de) 2000-06-29
EP0959875A1 (fr) 1999-12-01

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