EP1465603A1 - Verfahren zur herstellung hohler mikroporöser partikel, insbesondere zur inhalation - Google Patents

Verfahren zur herstellung hohler mikroporöser partikel, insbesondere zur inhalation

Info

Publication number
EP1465603A1
EP1465603A1 EP03709880A EP03709880A EP1465603A1 EP 1465603 A1 EP1465603 A1 EP 1465603A1 EP 03709880 A EP03709880 A EP 03709880A EP 03709880 A EP03709880 A EP 03709880A EP 1465603 A1 EP1465603 A1 EP 1465603A1
Authority
EP
European Patent Office
Prior art keywords
poly
blowing agent
cellulose
particles
composition
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.)
Withdrawn
Application number
EP03709880A
Other languages
English (en)
French (fr)
Inventor
El Hassane Larhrib
Joseph Chukwuemeka Okpala
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.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of EP1465603A1 publication Critical patent/EP1465603A1/de
Withdrawn legal-status Critical Current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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1682—Processes
    • A61K9/1688—Processes resulting in pure drug agglomerate optionally containing up to 5% of excipient
    • 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
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
    • 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

  • TITLE Process for manufacturing hollow micro-porous particles, in particular intended to be inhaled.
  • the present invention relates to a method of manufacturing hollow microporous particles, in particular intended to be inhaled, as well as said hollow microporous particles obtained by the implementation of the method.
  • the present invention is in no way limited to such an application, and on the contrary may find its application in all the fields in which it is advantageous to put using such hollow microporous particles, whatever the routes of administration or their use.
  • the invention further relates to an inhalation device comprising the hollow microporous particles obtained by the implementation of the method.
  • powders containing particles to be inhaled by a patient have been known for a number of years. These powders consisting of said particles contain different substances such as active principles, intended to treat different types of diseases, and among these respiratory diseases.
  • the inhalation of the particles must allow the deposition of said particles at the level of the bronchi and / or the lungs.
  • these particles were too dense and were deposited before the adequate deposition zone, and for example in the mouth or in the throat or even in the inhalation device, or light particles were used, making it possible to reach the area to be treated this time, but not without posing flow difficulties inherent to their structural characteristics and to the cohesion forces between particles.
  • hollow microporous particles have been proposed.
  • These known hollow microporous particles are generally manufactured from a mixture of active principles and an agent allowing brutal cooling, said mixture being sprayed in the form of droplets on a cold intermediate. The frozen droplets are then lyophilized and dried, allowing the solvent to be removed and thus creating the microporous particles.
  • the object of the present invention is to propose a method for manufacturing hollow microporous particles, in particular intended to be inhaled or any other application, which overcomes the aforementioned drawbacks, and makes it possible to manufacture hollow microporous particles having a very low density and a specific surface. high.
  • Another object of the present invention is to provide a process for the manufacture of hollow microporous particles, in particular intended for inhalation or any other simplified application which allows good control of the physical characteristics of said hollow microporous particles, and which is economical to use. work as well as a transposition easy industrial.
  • Another object of the present invention is to provide a medicament, intended to be administered by inhalation, in particular for the treatment of respiratory diseases, as well as a corresponding inhalation device, which are particularly suitable and effective.
  • a medicament intended to be administered by inhalation, in particular for the treatment of respiratory diseases, as well as a corresponding inhalation device, which are particularly suitable and effective.
  • suitable particles made up of 100% of active product.
  • the process for manufacturing hollow microporous particles is characterized in that:
  • composition in a given form, comprising at least one active principle and at least one blowing agent,
  • the hollow microporous particles obtained according to the invention have particles ranging in size from 0.1 ⁇ m to 2000 ⁇ m and with a powder density of between 0.4 g / cm 3 and 0.0001 g / cm 3 .
  • micro-particles are used for obtaining a medicament, intended to be administered by inhalation, in particular for the treatment of respiratory diseases.
  • a medicament intended to be administered by inhalation, in particular for the treatment of respiratory diseases.
  • it can be administered by any traditional route.
  • FIG. 1 is a view of a first type of 100% active product, in an initial micronized form, used in the process of the present invention
  • - Figure 2 shows an example of hollow microporous particles, in accordance with l invention, made from said 100% micronized active product illustrated in FIG. 1, according to a first operating mode
  • FIG. 3 represents a second example of hollow microporous particles, in accordance with the invention, obtained from said 100% micronized active product illustrated in FIG. 1, according to a second operating mode,
  • FIG. 4 shows a third example of hollow microporous particles, according to the invention, obtained from the micronized active product illustrated in Figure 1, combined with an excipient, according to said first operating mode
  • - Figure 5 shows a view another 100% active product, in an initial micronized form, implemented according to the process of the present invention
  • FIG. 6 shows a view of the hollow microporous particles obtained from said other active product shown in Figure 4, combined with an excipient.
  • the present invention relates to a method for manufacturing hollow microporous particles as illustrated in FIGS. 2, 3, 4 or 6, in particular intended to be inhaled, in which a composition is provided in a given form, as illustrated in FIGS. 1 or 5, comprising at least one active principle and at least one blowing agent.
  • said composition is projected in particular by atomization, in the form of droplets of given dimensional characteristics.
  • This atomization can be carried out by any means known to those skilled in the art, and in particular using pneumatic, ultrasonic, pressurized means, nozzles, rotary atomizers, blowing means, high rotation, spray devices, gauge needles or hair dryer.
  • the atomization distance modifies the final structure of the hollow microporous particle obtained.
  • the atomization was carried out approximately 70 cm from the intermediate cooling element, described below in more detail, while for FIG. 3, the atomization distance is only 10 cm. .
  • the atomizing gas is advantageously chosen from the group consisting in particular of carbon dioxide, nitrogen, argon, oxygen, air and a mixture of the latter.
  • gases can also be envisaged, and in particular inert gases.
  • said composition comprises at least one active principle and at least one blowing agent.
  • Said at least active principle is intended, for example, for therapeutic, prophylactic or even diagnostic use. There are obviously a very large number of active ingredients which can be used by inhalation.
  • active ingredients are more suitable for this type of use and among these, without limitation, the active ingredients chosen from the group consisting of proteins, lipids, nucleic acids, short chain peptides, corticosteroids, drugs anti-inflammatories, analgesics, neoplastic agents, cough suppressants, bronchodilators, diuretics, anti-colinergics, hormones, anginal preparations, antiallergics, anti-infections, antihistamines, anti-tuberculosis agents, therapeutic proteins and peptides.
  • the active ingredients chosen from the group consisting of proteins, lipids, nucleic acids, short chain peptides, corticosteroids, drugs anti-inflammatories, analgesics, neoplastic agents, cough suppressants, bronchodilators, diuretics, anti-colinergics, hormones, anginal preparations, antiallergics, anti-infections, antihistamines, anti-tuberculosis agents, therapeutic
  • the following compounds may also be used as active principle in anti-inflammatory drugs: beclomethasone, betamethasone, fluticasone, flunisolide, budesonide, dexamethasone, tipredane, acetonide triamcinolone.
  • bronchodilators mention may be made of the compounds ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol, reproterol, rimiterol, salbutamol, salmeterol, formoterol, terbutaline, isoetharine, tulobuterol 4-amino-3,5-dichloro- ⁇ [[[6- [2-
  • amiloride Among the diuretics, it is possible in particular to use amiloride.
  • anticholinergics mention may be made of the following components: ipratropium, ipatropium bromide, atropine, oxitropium or oxitropium bromide.
  • cortisone Among the hormones, mention may in particular be made of cortisone, hydrocortisone or prednisolone.
  • xanthines mention may in particular be made of aminophylline, choline theophyllinate, lysine theophyllinate or theophylline.
  • analgesics mention may be made in particular of the following compounds: codeines, dihydromorphine, ergotamine, fentanyl or morphine.
  • anginal preparations mention may be made of diltiazem.
  • anti-allergic agents mention may be made of cromoglycate, etotifen or nedocromyl.
  • anti-infectives mention may be made of the following compounds: cephalosporin, penicilin, streptomycin, sulphonamides, tetracyclines or pentamidines.
  • antihistamines mention may in particular be made of methapyrilene.
  • antineoplastic agents mention may be made of bleomycin, carboplatin, methotrexate, adriamycin, amphotericin B.
  • anti-tuberculosis agents mention may in particular be made of isoniazid or ethanbutol.
  • therapeutic proteins and peptides mention may be made of insulin, glucagon, prostaglandin, leukotrienes as well as their activators and inhibitors including prostacyclin (epoprostanol) and prostaglandins E. and E 2 .
  • any other type of agent can be used, to be delivered in particular by inhalation, for a prophylactic, therapeutic or diagnostic purpose.
  • said active ingredients may be used in the form of salts such as metal alkaly, addition salt of acid or ether such as lower alkyl ether or solvate such as hydrates so as to optimize the activity and / or the stability of said active ingredients.
  • said active principle is chosen from the group of anti-inflammatories or bronchodilators. More particularly, the preferred active ingredients are beclometasone dipropionate and salbutamol sulfate.
  • retinoids such as all-cis retinoic acid, 13-trans retinoic acid and others, vitamins A as well as betacarotene derivatives, vitamins D, E, K, water-insoluble precursors and their derivatives.
  • Said at least one blowing agent is formed from a liquid or gas whose volume after cooling below the solidification point is greater than that occupied in the liquid or gaseous state. It is also preferable to use as blowing agent solvents having in addition to an expansion coefficient, significant volatile properties.
  • blowing agent in fact, during projection, it is advantageous for the blowing agent to be volatile so as to evaporate from the surface of the droplets during said projection.
  • chlorofluorocarbons such as perfluorocarbons, such as perfluoro-octylbromides, freon, exotic solvents such as hexafluoro-isopropanol, hexafluorides, hexafluorocyclobutanes, fluorocarbon refrigerants such as dichlorodifluoromethane, perfluoropropane, CF4, C2F6, C3F8, C4F8, C2F4,
  • inhalational anesthetics such as halothane, enflurane, isoflurane, methoxyflurane, sevoflurane, hydrofluoroalkane, such as HFA-134a, HFA-227, ketones, such as acetones, alcohols such as ethanol, tertiary butyl alcohols methanol and other organic solvents such as as dichloromethanes, chloroforms, acetonitrile, dioxane, dimethyl sulfoxide, ethyl acetate, methyl acetate, tetrahydrofuran (THF).
  • Volatile salts such as ammonium bicarbonate, ammonium acetate, ammonium chlorhyde, ammonium benzoate.
  • the blowing agents used have a low and pharmaceutically accessible toxicity.
  • acetone will be used as blowing agent.
  • a corticosteroid may be chosen, such as bechlometasone dipropionate (BDP), as illustrated in FIGS. 2, 3 and 4 in the presence, where appropriate, of cellulose acetate phthalate (CAP). ) as shown in Figure 4.
  • BDP bechlometasone dipropionate
  • CAP cellulose acetate phthalate
  • blowing agents gases and among these the group of gases chosen from gases dissolved in particular carbon dioxide, nitrogen, in agents producing gas such as carbonate, bicarbonate, carboxylic acid and their derivatives or in agents producing nitrogen. It is also possible to use said blowing agents in liquid or gaseous form in combination.
  • a composition in a given form, consisting of microparticles including a residual blowing agent.
  • the process for manufacturing hollow microporous particles consists, after having sprayed said composition in particular, of cooling it below the solidification point of said at least one blowing agent so as to increase the volume of the given shape and creating ruptures at the level of the surface and / or all of said given shape making it possible to obtain the structure of the hollow microporous particle.
  • the composition was sprayed onto a cold intermediate having a temperature below said solidification point of said at least one blowing agent.
  • the cooling is carried out in particular by freezing by means of a gas, advantageously chosen from the group consisting of liquid hydrogen, liquid nitrogen, liquid argon and, liquid oxygen.
  • V F represents the initial volume and V F the final volume of the blowing agent.
  • liquefied nitrogen gases with other blowing agents and in particular dichloromethane, the expansion coefficient of which is approximately 20% and the solidification point is at - 95.1 ° C, methanol, the expansion coefficient of which is close to 36 % and the solidification point is - 97.5 ° C or the carbonated carbonated water whose expansion coefficient is close to 33% and the solidification point 0 ° C.
  • the blowing agent has a coefficient minimum expansion.
  • water cannot be considered as an agent for expansion, the coefficient of expansion of water close to 2% being in fact relatively low and insufficient.
  • the very low temperature obtained by freezing weakens the resistance of the structure of said active ingredient, making it more brittle, the surface and / or all of the latter then being subject to ruptures taking into account the force caused, from inside to outside of the particle, or vice versa, by the expansion of said blowing agent.
  • the composition can comprise, for example, an acetone-water mixture at 80/20 per unit volume.
  • composition at least one additional excipient.
  • Said additional excipient may in particular be intended to make it possible to act on the density, to delay, control or target the action of said at least one active principle, it may for example be a polymer compound.
  • the active ingredient can be combined in various ways with said at least one blowing agent and optionally said at least one additional excipient. It will thus be possible to dissolve, emulsify or suspend the active principle, alone or in combination, in said at least one blowing agent, and if necessary with said at least one additional excipient.
  • the composition comprises a short-acting beta 2 agonist compound associated with an anti-muscarenic agent such as salbutamol associated with ipatropium bromide; or pheneterol combined with ipatropium bromide.
  • an anti-muscarenic agent such as salbutamol associated with ipatropium bromide; or pheneterol combined with ipatropium bromide.
  • Another preferred composition may include a short acting beta 2 agonist compound associated with a corticosteroid such as salbutamol and bechlometasone.
  • Another preferred composition may comprise a long-acting beta 2 agonist compound associated with a corticosteroid such as salmeterol and fluticasone or formeterol and budesonide.
  • Hydophilic it is necessary to understand a material which is very soluble in water and / or capable of swelling and forming a gel.
  • these are active principles and / or excipients which may have a sensitivity in an aqueous medium greater than 5 mg / ml, or even greater than 50 mg / ml, and even greater than 100 mg / ml or more.
  • excipients can be envisaged and in particular without limitation the excipient may be a non-biodegradable, biodegradable or bioerodible polymer, that is to say that the polymer degrades chemically or enzymatically in vivo into small molecules which are not toxic.
  • the polymers suitable for the applications mentioned can be synthetic, natural and can include in particular cyclodextrins and derivatives thereof, sodium casemate, L - ⁇ - phosphatidylcholine dipalmitoyl (DPPC), albumin human serum, cellulose acetate phthalatate, phospholipids, hydroxypropyl methylcellulose phthalate, ethyl cellulose, methyl hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethy cellulose, carboxy methyl cellulose, methyl cellulose, cellulose acetate butyrade, poloxamer, poly ( lactic acid), poly (lactic glycolic acid), poly (lactide), poly (glycolide), poly (lactide coglycolide), poly (p-dioxyanone), poly (caprolactone), polycarbonate, polyamide, polyanhydride, poly (alkylene alkylate) , polyamino acid, polyhydroxyalkanoates, polypropy
  • the selected polymer is biocompatible and degrades or erodes in vivo to form small, non-toxic molecules. More preferably, the polymer is biocompatible and pharmaceutically acceptable to be delivered to the respiratory tract. Finally, the polymer can in addition to being pharmaceutically acceptable include therapeutic properties.
  • a particularly suitable polymer may in particular include cellulose acetate phthalate (CAP) or hydroxypropyl cellulose acetate phthalate, polymer drugs or genetically engineered polymers.
  • the process for manufacturing hollow microporous particles consists, if necessary, in addition of removing all or part of said at least one blowing agent. This evacuation takes place in particular by evaporation through the pores produced during the rupture of the surface of said given form of increased volume. As shown in FIGS. 2, 3, 4 or 6, hollow microporous particles are thus obtained, comprising only a residual or even zero amount of blowing agent.
  • the manufacturing process may further comprise an additional step in which said hollow microporous particles obtained are dried.
  • the drying step can be carried out using all the techniques known to those skilled in the art in the field of drying and in particular can be carried out using a conventional oven, vacuum oven, dryer in a fluidized bed or means of blowing.
  • Said drying step comprises, according to an advantageous embodiment of the invention, a step of evaporation of said at least one blowing agent, making it possible to evaporate the blowing agent residues not removed during step d evaporation through the pores of the structure and during the previous step.
  • the drying step can also comprise a step of lyophilization of said hollow microporous particles.
  • the hollow microporous particles obtained are of a diameter between 0.1 ⁇ m and 2,000 ⁇ m, and advantageously between 0.1 ⁇ m and 100 ⁇ m, the density of the corresponding particles being less than 0.5 g / cm 3 and up to 0.0001 g / cm 3 .
  • said hollow microporous particles can be used in the manufacture of a medicament, in particular for the treatment of respiratory diseases.
  • hollow microporous particles obtained by implementing the method as mentioned above will be administered using an inhalation device comprising said hollow microporous particles.
  • an inhalation device comprising said hollow microporous particles.
  • the hollow microporous particles can be used alone as such, but also in the presence of diluents. They can be used as is, broken or crushed as well.
  • the diluents are used to improve the dispersion of the powder in the inhalation device and / or to improve the flow of the powder and its handling.
  • diluents mention may in particular be made of monosaccharides, such as arobinose, xylitol and dextrose and monohydrates, or di-saccharides, such as lactose, moltose and sucrose, or polysaccharides, such as strachs, dextrins or dextrons.
  • diluent lactose monohydrate the amount of which to be added to the microporous particles of the present invention will be adjusted by a person skilled in the art, such as for example so that the final amount of the composition is 0 , 1 to 90% w / w.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Pulmonology (AREA)
  • Otolaryngology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
EP03709880A 2002-01-15 2003-01-14 Verfahren zur herstellung hohler mikroporöser partikel, insbesondere zur inhalation Withdrawn EP1465603A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR0200427A FR2834636B1 (fr) 2002-01-15 2002-01-15 Procede de fabrication de particules micro-poreuses creuses, notamment destinees a etre inhalees
FR0200427 2002-01-15
PCT/FR2003/000102 WO2003059324A1 (fr) 2002-01-15 2003-01-14 Procede de fabrication de particules micro-poreuses creuses, notamment destinees a etre inhalees

Publications (1)

Publication Number Publication Date
EP1465603A1 true EP1465603A1 (de) 2004-10-13

Family

ID=8871289

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03709880A Withdrawn EP1465603A1 (de) 2002-01-15 2003-01-14 Verfahren zur herstellung hohler mikroporöser partikel, insbesondere zur inhalation

Country Status (5)

Country Link
US (1) US20050214226A1 (de)
EP (1) EP1465603A1 (de)
AU (1) AU2003214315A1 (de)
FR (1) FR2834636B1 (de)
WO (1) WO2003059324A1 (de)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0228826D0 (en) * 2002-12-11 2003-01-15 Okpala Joseph Hair technology in creating particles with improved delivery capabilities
US6931888B2 (en) * 2003-02-07 2005-08-23 Ferro Corporation Lyophilization method and apparatus for producing particles
GB0709115D0 (en) * 2007-05-11 2007-06-20 Katholieke Universltelt Leuven Membrane comprising hollow particles
WO2016067252A1 (en) 2014-10-31 2016-05-06 Glaxosmithkline Intellectual Property Development Limited Powder formulation

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5019400A (en) * 1989-05-01 1991-05-28 Enzytech, Inc. Very low temperature casting of controlled release microspheres
JPH0739339B2 (ja) * 1989-05-01 1995-05-01 アルカーメス コントロールド セラピューティクス，インコーポレイテッド 生物活性を有する分子の小粒子の製造方法
US5798091A (en) * 1993-07-30 1998-08-25 Alliance Pharmaceutical Corp. Stabilized gas emulsion containing phospholipid for ultrasound contrast enhancement
US6309623B1 (en) * 1997-09-29 2001-10-30 Inhale Therapeutic Systems, Inc. Stabilized preparations for use in metered dose inhalers
ES2261195T3 (es) * 1999-04-05 2006-11-16 Mannkind Corporation Metodo de formacion de particulas finas.

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO03059324A1 *

Also Published As

Publication number Publication date
FR2834636B1 (fr) 2006-02-24
FR2834636A1 (fr) 2003-07-18
AU2003214315A1 (en) 2003-07-30
US20050214226A1 (en) 2005-09-29
WO2003059324A1 (fr) 2003-07-24

Similar Documents

Publication Publication Date Title
JP3210012B2 (ja) 医薬品
KR101926060B1 (ko) 활성제의 호흡기 전달용 조성물, 및 연관된 방법 및 시스템
CN1177582C (zh) 含HFA227和HFA134a的药物气雾剂组合物
CN1155367C (zh) 微粒吸入制剂
CN1138532C (zh) 药用气溶胶组合物
FR2843882A1 (fr) Formulation pharmaceutique de propionate de fluticasone
RU2565438C2 (ru) Фармацевтическая аэрозольная композиция
US6306368B1 (en) Aerosol formulation containing a particulate medicament
EP1465603A1 (de) Verfahren zur herstellung hohler mikroporöser partikel, insbesondere zur inhalation
EP2167042B1 (de) Pharmazeutische aerosol-zusammensetzungen mit fluticason

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20040715

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PT SE SI SK TR

AX Request for extension of the european patent

Extension state: AL LT LV MK RO

17Q First examination report despatched

Effective date: 20060822

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20100803