WO2004101043A1 - Nouveau traitement - Google Patents

Nouveau traitement Download PDF

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Publication number
WO2004101043A1
WO2004101043A1 PCT/SE2004/000749 SE2004000749W WO2004101043A1 WO 2004101043 A1 WO2004101043 A1 WO 2004101043A1 SE 2004000749 W SE2004000749 W SE 2004000749W WO 2004101043 A1 WO2004101043 A1 WO 2004101043A1
Authority
WO
WIPO (PCT)
Prior art keywords
drug
lung
inhalation
inhaler
aerosol
Prior art date
Application number
PCT/SE2004/000749
Other languages
English (en)
Inventor
Lars Asking
Eva Bondesson
Eva Trofast
Original Assignee
Astrazeneca Ab
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 Astrazeneca Ab filed Critical Astrazeneca Ab
Publication of WO2004101043A1 publication Critical patent/WO2004101043A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/0003—Accessories therefor, e.g. sensors, vibrators, negative pressure
    • A61M2016/003—Accessories therefor, e.g. sensors, vibrators, negative pressure with a flowmeter
    • A61M2016/0033—Accessories therefor, e.g. sensors, vibrators, negative pressure with a flowmeter electrical
    • A61M2016/0039—Accessories therefor, e.g. sensors, vibrators, negative pressure with a flowmeter electrical in the inspiratory circuit

Definitions

  • the present invention relates to regional lung deposition of a drug delivered from an inhaler by actuating the dose later in the inhalation cycle than is normally done.
  • Drug biodistribution is often secondary to drug action.
  • the deposition of drugs into the airways by inhalation are dependent on effective deposition at the intended site of action - for local or systemic effect.
  • targeting of specific areas of the lung will become more desirable.
  • the relationship between therapeutic effects of inhaled locally acting drugs and their regional distribution within the airways is not well established in man due to the inherent difficulties in delivering aerosol to either central or peripheral structures of the lung.
  • aerosol will always have to pass through the tracheobronchial airways in order to reach the alveoli, it may become subject to deposition not only in peripheral, but also in central lung.
  • bronchodilator aerosol particle size The influence of bronchodilator aerosol particle size on the effect of lung function has been studied in patients with mild asthma (P. Zanen et al. The optimal particle size for ⁇ - adrenergic aerosols in mild asthmatics, Int J Pharm 1994; 107: 211-217; P. Zanen et al The optimal particle size for parasympathicolytic aerosols in mild asthmatics, Int J Pharm 1995; 114: 111-115). Aerosols with monodisperse particle size distributions were generated using a spinning top generator to mass median aerodynamic diameters of 1.5, 2.8, and 5 ⁇ m.
  • Bennett et al J. Aerosol Med., 15(2), 179 (2002) point out the need for more basic mechanistic studies to determine the optimal delivery conditions for targeting parallel regions of the lung.
  • RU 2 089 226 relates to a method to administering medical agents into upper respiratory tracts and trachea in form of an aerosol.
  • the drug is delivered after 75-95 % of the inhaled volume and ends when 90-100 % has passed.
  • RU 2 141 349 relates to a method including supply of aerosol after inhalation of 70-95 % of inhalation volume and discontinued after inhalation of 80-100 % of inhalation volume by treatment with low-frequency magnetic field of pathologic focus in the respiratory tracts.
  • the invention therefore provides a method of administering a drug by inhalation which comprises administering the drug from an inhaler by triggering release of the dose at 50% or greater of the inhaled volume.
  • the method of the invention is used to administer drug to the lower respiratory tract.
  • the dose is released at about 70% of the inhaled volume.
  • inhaled volume is meant the volume of the total inhalation made by the patient during the inhalation of the drug from the inhaler. For example, if the total breath inhalation is 3 litres, the drug will be released following inhalation of at least 1.5 litres, that is at least half way through the inhalation.
  • the invention provides an inhaler suitable for administering the drug by triggering release of the dose at 50% or greater of the inhaled volume.
  • the method of delivery according to the invention is suitable for dispensing medicament to the lung, particularly for the treatment of asthma, chronic obstructive pulmonary disease (COPD), interstitial lung diseases like idiopathic pulmonary fibrosis and pulmonary fibrosis, cystic fibrosis and alveolitis.
  • Appropriate medicaments may thus be selected from, for example, anti-inflammatories e.g. beclomethasone (e.g. as dipropionate), fluticasone (e.g. as propionate), flunisolide, budesonide, ciclesonide, rofleponide, mometasone (e.g. as furoate) or the like, bronchodilators like formoterol (e.g.
  • salmeterol e.g. as xinafoate
  • salbutamol e.g. as terbutaline or the like
  • anticholinergic agents like ipratropium, tiotropium or oxitropium salts (e.g.
  • PDE-IV inhibitors as bromides or the like, PDE-IV inhibitors, antihistamines, cyclooxygenas inhibitors, leukotriene synthesis inhibitors, leukotriene antagonists, phospholipase-A2 inhibitors, antiarrhytmic medicaments, hormones, antihypertensive medicaments, antiparasitic and anticancer medicaments, sedatives and analgetic medicaments, antibiotics, antirheumatic medicaments, antifungal and antihypotension medicaments, antiviral medicaments, therapeutic peptides or proteins like insulin or glucagon.
  • the medicaments may be administered in the form of pharmacologically acceptable esters, acetals, salts, solvates, such as hydrates, or solvates of such esters or salts, if any. Both racemic mixtures as well as one or more optical isomers of the above compounds are within the scope of the invention. Medicaments could also be delivered in combinations e.g. formoterol and budesonide.
  • the method of the invention is especially useful for treating respiratory diseases.
  • the method of the invention is used to teat asthma and COPD.
  • glucocorticosteroids such as: budesonide, fluticasone (e.g. as propionate ester), mometasone (e.g. as furoate ester), beclomethasone (e.g. as 17- propionate or 17,21-dipropionate esters), ciclesonide, triamcinolone (e.g. as acetonide), flunisolide, zoticasone, flumoxonide, rofleponide, butixocort (e.g.
  • Long-acting ⁇ 2 agonists include: salmeterol, formoterol, bambuterol, TA 2005 (chemically identified as 2(lH)-Quinolone, 8-hydroxy-5- [ 1 -hydroxy-2- [ [2-(4-methoxy-phenyl)- 1 -methylethyl] amino] ethyl] -monohydrochloride, [R-(R*,R*)] also identified by Chemical Abstract Service Registry Number 137888-11-0 and disclosed in U.S. Patent No 4.579.854, formanilide derivatives (III) e.g.
  • the preferred pharmacologically active long-acting ⁇ 2 -agonist is salmeterol xinafoate, formanilide derivatives (III), benzenesulfonamide derivatives (IV) and formoterol (e.g. as fumarate dihydrate) and even more preferred is formoterol fumarate dihydrate.
  • the preferred combinations include fluticasone propionate/salmeterol xinafoate, ciclesonide/formoterol fumarate dihydrate, mometasone furoate/formoterol fumarate dihydrate, fluticasone propionate/formoterol fumarate dihydrate, and budesonide/formoterol fumarate dihydrate.
  • steroids from WO 2002/88167 /formanilide derivatives from WO 2002/76933 steroids from WO 2002/88167/benzenesulfonamide derivatives from WO 2002/88167, steroids from DE 4129535/formoterol fumarate dihydrate, zoticasone/benzenesulfonamide derivatives from WO 2002/88167 and zoticasone/formanilide derivative.
  • the most preferred combination is budesonide/formoterol fumarate dihydrate.
  • a fit-for-purpose aerosol delivery system was developed on the basis of a prototype version of a dry-powder inhaler.
  • the inhaler delivers ordered mixtures of smaller drug particles and larger carrier particles of lactose in pre-metered bolus doses.
  • the delivery system consists of a dedicated Teflon holder that, during inhalation, directs the air to pass by or through the inhaler.
  • the holder is connected in series with a computerized pneumotachograph activating bolus delivery at a set percentage of the total volume of air inhaled through the inhaler at a preceding reference inhalation.
  • the pneumotachygraph, Vitalograph 2120 (Vitalograph Ltd, UK) provides real-time measurements of air flow during inhalations.
  • the primary objective of the clinical study was to compare the regional distribution of 99m Tc-labelled lactose within the airways of healthy subjects after inhalation via the dry- powder inhaler actuated either in the beginning of inhalation (corresponding to 20% of total inhaled volume) or at near end of inhalation (corresponding to 70% of total inhaled volume).
  • the secondary objective was to compare total lung deposition between treatments.
  • the study was of an open, randomised and two-way crossover design carried out at one centre. Twelve (12) healthy subjects were enrolled at the Clinical Pharmacology Unit, AstraZeneca R&D Lund. After enrolment, subjects received two single doses of inhaled radioaerosol administered at least 2 days apart.
  • drugs e.g. cardiovascular drugs, hormones like insulin to reach the peripheral part of the lung.
  • Other drugs that can be administered using the methods of the invention include drugs for CNS application, such as migraine, anti-cancer drugs, and antibiotics.
  • the way of administering the drug by inhalation could be by a dry powder inhaler (DPI), a pressurized metered dose inhaler (pMDI), a small volume nebulizer or a conventional nebulizer.
  • DPI dry powder inhaler
  • pMDI pressurized metered dose inhaler
  • small volume nebulizer or a conventional nebulizer.
  • the mass medium aerodynamic diameter of the particles should be 1-7 ⁇ m, preferably between 2 and 5 ⁇ m.
  • the release of the drug should occur when at least 50 %, preferably at least 70 % of the tidal volume has been inhaled.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Preparation (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne le dépôt local dans les poumons d'un médicament administré au moyen d'un inhalateur par apport tardif de la dose dans le cycle d'inhalation.
PCT/SE2004/000749 2003-05-15 2004-05-14 Nouveau traitement WO2004101043A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE0301426A SE0301426D0 (sv) 2003-05-15 2003-05-15 Novel treatment
SE0301426-3 2003-05-15

Publications (1)

Publication Number Publication Date
WO2004101043A1 true WO2004101043A1 (fr) 2004-11-25

Family

ID=20291317

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE2004/000749 WO2004101043A1 (fr) 2003-05-15 2004-05-14 Nouveau traitement

Country Status (2)

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SE (1) SE0301426D0 (fr)
WO (1) WO2004101043A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1906960A1 (fr) * 2005-07-11 2008-04-09 AstraZeneca AB Nouvelle combinaison 1
GB2461752B (en) * 2008-07-14 2013-04-17 Neo Inhalation Products Ltd Metered dose inhaler

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2089226C1 (ru) * 1993-03-10 1997-09-10 Сунцов Виктор Владимирович Способ лечения воспалительных заболеваний верхних дыхательных путей и трахеи и устройство для его осуществления
RU2141349C1 (ru) * 1995-07-20 1999-11-20 Сунцов Виктор Владимирович Способ лечения заболеваний дыхательных путей и устройство для его осуществления
US6357442B1 (en) * 1995-06-08 2002-03-19 Innovative Devices, Llc Inhalation actuated device for use with metered dose inhalers (MDIS)
WO2003000329A2 (fr) * 2001-06-20 2003-01-03 Inhale Therapeutic Systems, Inc. Regulateur de debit pour dispositif d'administration de medicament en aerosol et procedes associes

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2089226C1 (ru) * 1993-03-10 1997-09-10 Сунцов Виктор Владимирович Способ лечения воспалительных заболеваний верхних дыхательных путей и трахеи и устройство для его осуществления
US6357442B1 (en) * 1995-06-08 2002-03-19 Innovative Devices, Llc Inhalation actuated device for use with metered dose inhalers (MDIS)
RU2141349C1 (ru) * 1995-07-20 1999-11-20 Сунцов Виктор Владимирович Способ лечения заболеваний дыхательных путей и устройство для его осуществления
WO2003000329A2 (fr) * 2001-06-20 2003-01-03 Inhale Therapeutic Systems, Inc. Regulateur de debit pour dispositif d'administration de medicament en aerosol et procedes associes

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1906960A1 (fr) * 2005-07-11 2008-04-09 AstraZeneca AB Nouvelle combinaison 1
EP1906960A4 (fr) * 2005-07-11 2010-03-10 Astrazeneca Ab Nouvelle combinaison 1
GB2461752B (en) * 2008-07-14 2013-04-17 Neo Inhalation Products Ltd Metered dose inhaler

Also Published As

Publication number Publication date
SE0301426D0 (sv) 2003-05-15

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