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WO2012010854A1 - Composition pharmaceutique - Google Patents

Composition pharmaceutique Download PDF

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Publication number
WO2012010854A1
WO2012010854A1 PCT/GB2011/001114 GB2011001114W WO2012010854A1 WO 2012010854 A1 WO2012010854 A1 WO 2012010854A1 GB 2011001114 W GB2011001114 W GB 2011001114W WO 2012010854 A1 WO2012010854 A1 WO 2012010854A1
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WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
composition according
carmoterol
fluticasone
mometasone
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/GB2011/001114
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English (en)
Inventor
Geena Malhotra
Shrinivas Madhukar Purandare
Amar Lulla
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Cipla Ltd
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Cipla Ltd
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Filing date
Publication date
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Publication of WO2012010854A1 publication Critical patent/WO2012010854A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • 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
    • A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
    • 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
    • A61K31/4704—2-Quinolinones, e.g. carbostyril
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • 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
    • A61K9/0012—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
    • A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
    • 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
    • A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
    • 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

  • the present invention relates to pharmaceutical compositions for inhalation. There is also provided a process for preparing the compositions and use thereof in the treatment and / or prevention of respiratory, inflammatory or obstructive airway disease.
  • Asthma and chronic obstructive pulmonary disease are the very common conditions which affect many people. Airflow obstruction is the main characteristic feature in each of these airway diseases and the medications utilized in the treatment are also often similar. Asthma is a chronic inflammatory disorder of the airways associated with airway hyper responsiveness, which leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. These episodes are associated with variable airflow obstruction within the lung which is often reversible, either spontaneously or with treatment. Chronic obstructive pulmonary disease (COPD) is a severe respiratory condition that is increasingly prevalent worldwide. In India, the estimated prevalence is about 12.36 million.
  • COPD chronic obstructive pulmonary disease
  • bronchodilators such as beta 2 -agonists, anticholinergics and steroids. More specifically asthma, COPD and other related disorders have been known to be treated with beta 2 -agonist as they provide a bronchodilator effect, resulting in relief from the symptoms of breathlessness. Beta 2 -agonists can be short acting for immediate relief, or long acting for long term prevention of asthma symptoms.
  • Long acting p 2 -agonists improve lung function, reduce symptoms and protect against exercise-induced dyspnea in patients with asthma and COPD.
  • Long acting p 2 -agonists induce bronchodilation by causing prolonged relaxation of airway smooth muscle.
  • long acting p 2 -agonists (LABAs) exert other effects such as inhibition of airway smooth-muscle cell proliferation and inflammatory mediator release, as well as non smooth-muscle effects, such as stimulation of mucociliary transport, cytoprotection of the respiratory mucosa and attenuation of neutrophil recruitment and activation.
  • use of a long acting p 2 -agonist reduces the frequency of drug administration.
  • LAAs long acting beta 2 -agonists
  • beta 2 -agonists provide a symptomatic relief in bronchoconstriction
  • another component of asthma which is inflammation
  • requires separate treatment such as steroid.
  • Most of the inhaled corticosteroids need to be administered in multiple dosage regimens.
  • Inhaled corticosteroids are the mainstay of asthma management and are used in almost all patients with persistent asthma. Many patients with persistent asthma can be controlled with the use of regular inhaled corticosteroids (ICS) therapy. Corticosteroids are known to exhibit inhibitory effect on inflammatory cells as well as inflammatory mediators involved in the pathogenesis of respiratory disorders. However, a considerable proportion of patients treated with inhaled corticosteroids (ICS) have been found to remain symptomatic, despite the use of low to moderate doses of inhaled corticosteroids (ICS). Also, use of these corticosteroids, especially in children, has been limited due to their potential side effects. In children and teenagers, these medicines can prohibit or slow down growth and may affect the function of adrenal glands. Another possible problem in children is that these corticosteroids may cause infections such as chickenpox and measles.
  • corticosteroids cause suppression of the Hypothalamic-Pituitary-Adrenal (HP A) axis, produces adverse effects on the bone growth in children and on the bone density in the elderly, ocular complications (cataract formation and glaucoma) and skin atrophy.
  • HP A Hypothalamic-Pituitary-Adrenal
  • corticosteroids may seem to increase the risk of high blood pressure and bone diseases. Bone associated diseases by using corticosteroids are especially more likely to occur in elderly females.
  • ICS chronic obstructive pulmonary disease
  • COPD chronic obstructive pulmonary disease
  • corticosteroids include beclomethasone, budesonide, fluticasone, mometasone, ciclesonide and triamcinolone.
  • Anticholinergic agents also act as bronchodilators and are potential alternatives to beta agonists.
  • anticholinergics can also be administered along with beta2-agonists (LABAs) for the management of asthma.
  • Anticholinergics act by competing with acetylcholine for the receptor sites at vagus nerve or nerve-muscle junctions. This prevents the transmission of reflexes that are induced by asthma stimuli.
  • anticholinergics provides an advantage in elderly patients as the responsiveness of ⁇ 2- agonists declines with old age. Further it would be advantageous to use in patients who are intolerant to the use of beta2-agonists. Further, anticholinergics can also be used in patients suffering from nocturnal asthma, chronic asthma with concurrent fixed way obstruction, intrinsic asthma and also in patients with asthma of longer duration.
  • combination therapy of a bronchodilator with an inhaled corticosteroid improves pulmonary efficiency, reduces inflammatory response and provides symptomatic relief as compared to higher doses of inhaled corticosteroid alone in patients affected by respiratory disorders such as asthma, the selection of a specific bronchodilator and inhaled corticosteroid plays a very important role in formulation of fixed dose combinations.
  • LAA long-acting beta agonist
  • ICS inhaled corticosteroid
  • COPD chronic obstructive pulmonary disease
  • LAA long-acting beta agonist
  • ICS inhaled corticosteroid
  • US20050059643 discloses a composition of a steroid and a betamimetic such as carmoterol.
  • EP 1787639 discloses an aerosol solution of a beta-agonist of the phenylalkylamino class and a steroid.
  • EP 1452179 discloses a combination preparation of carmoterol and a corticosteroid.
  • EP 1834643 discloses a combined preparation of carmoterol and an active ingredient for simultaneous, sequential or separate use in the treatment of inflammatory or obstructive airway disease.
  • EP 1603565 discloses a composition of carmoterol and budesonide with a weight ratio from 1:1000 to 1 :50.
  • US2009088408 discloses pharmaceutical compositions of anticholinergics, corticosteroids and betamimetics and their use in the treatment of respiratory diseases.
  • US2005042174 discloses a combination of doses of a beta2-agonist, an anticholinergic agent and an anti-inflammatory steroid.
  • WO2006105401 discloses anticholinergic in combination with a corticosteroid, and a long acting beta agonist, for simultaneous or sequential administration in the prevention or treatment of a respiratory, inflammatory or obstructive airway disease.
  • a combination of a long-acting beta 2 agonist (LABA) and an inhaled corticosteroid (ICS) is critical since both drugs should be capable of being administered once daily.
  • a treatment method where a long-acting beta 2 agonist (LABA) is required to be administered once daily and an inhaled corticosteroid (ICS) is required to be administered twice daily or vice versa will not be useful since the purpose of once a day treatment is defeated.
  • none of the above prior art specifically discloses the combination of carmoterol with fluticasone furcate or carmoterol with ciclesonide or carmoterol with mometasone furoate or carmoterol with fluticasone furoate and tiotropium.
  • the object of the present invention is to provide a pharmaceutical composition comprising one or more bronchodilators and one or more inhaled corticosteroids (ICS) for administration in the prevention or treatment of respiratory, inflammatory or obstructive airway disease.
  • Another object of the present invention is to provide such a pharmaceutical composition for once daily administration for the prevention or treatment of respiratory, inflammatory or obstructive airway disease.
  • Yet another object of the present invention is to provide a process for preparing the pharmaceutical composition comprising one or more bronchodilators and one or more inhaled corticosteroids (ICS) for administration in the prevention or treatment of respiratory, inflammatory or obstructive airway disease.
  • ICS inhaled corticosteroids
  • a further object of the present invention is to provide a method for prophylaxis or treatment of asthma, COPD or a related respiratory disorder which comprises administering a pharmaceutical composition comprising one or more bronchodilators and one or more inhaled corticosteroids (ICS).
  • ICS corticosteroids
  • a pharmaceutical composition comprising one or more bronchodilators and one or more inhaled corticosteroids (ICS).
  • ICS inhaled corticosteroids
  • the composition further comprises one or more anticholinergics.
  • a process for preparing pharmaceutical composition comprising carmoterol and fluticasone, especially an ester of fluticasone, in particular fluticasone furoate.
  • a pharmaceutical composition comprising carmoterol and ciclesonide.
  • a pharmaceutical composition comprising carmoterol and mometasone.
  • a pharmaceutical composition comprising carmoterol, tiotropium and fluticasone, especially an ester of fluticasone, in particular fluticasone furoate .
  • a method for prophylaxis or treatment of asthma, COPD or a related respiratory disorder which comprises administering a pharmaceutical compositions described above.
  • a eighth aspect of the present invention there is provided the use of the pharmaceutical compositions described above in treating disorders or conditions that respond to, or are prevented, ameliorated or eliminated by, the administration of a long-acting beta agonist (LABA) and inhaled corticosteroid (ICS).
  • LAA long-acting beta agonist
  • ICS inhaled corticosteroid
  • the bronchodilator includes one or more long acting beta agonists (LABA).
  • the bronchodilator further includes one or more anticholinergics.
  • It is a particular feature of the invention to provide a pharmaceutical composition comprising carmoterol in combination with one or more corticosteroids, wherein the corticosteroid is selected from fluticasone, mometasone and ciclesonide, along with one or more optional pharmaceutically acceptable excipients.
  • composition with an anti- cholinergic, which is preferably tiotropium.
  • compositions according to the invention include:
  • a corticosteroid comprising fluticasone in combination with a beta2-agonist comprising carmoterol.
  • a corticosteroid consisting of fluticasone in combination with a beta2-agonist consisting of carmoterol.
  • a corticosteroid comprising fluticasone in combination with a beta2-agonist comprising carmoterol and an anti-cholinergic comprising tiotropium.
  • corticosteroid consisting of fluticasone in combination with a beta2-agonist consisting of carmoterol and an anti-cholinergic consisting of tiotropium.
  • a corticosteroid comprising ciclesonide in combination with a beta2-agonist comprising carmoterol.
  • a corticosteroid comprising mometasone in combination with a beta2-agonist comprising carmoterol.
  • the fluticasone may be provided as the ester of fluticasone, in particular the furoate or the valerate or propionate.
  • the invention also encompasses methods of preparing the pharmaceutical compositions according to the invention and their use in respiratory, inflammatory or obstructive airway diseases.
  • the present invention thus provides a novel combination for inhalation comprising carmoterol in combination with fluticasone furoate for the prevention or treatment of respiratory, inflammatory or obstructive airway disease while simultaneously reducing the frequency of dosage administration.
  • the term “carmoterol” is used in a broad sense to include not only “carmoterol” per se but also any pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs, and pharmaceutically acceptable prodrugs thereof.
  • the carmoterol may be carmoterol hydrochloride.
  • Carmoterol chemically known as 8-hydroxy-5 - (l-hydroxy-2-(N-(2-(4-methoxy:phenyl) -1- methyl:ethyl) amino)ethyl)-2 (lH)-quinolinone hydrochloride salt is a long acting beta 2 - agonist characterized by having a rapid onset of action, similar to that of salbutamol and formoterol, prolonged duration of action up to 30 hours, and also having a high selectivity towards the beta 2 adrenoreceptor. Further more carmoterol is more potent than other long acting P2-agonists such as formoterol, and salmeterol.
  • fluticasone is used in a broad sense to include not only “fluticasone” per se but also any pharmaceutically acceptable salts, pharmaceutically available esters, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs, and pharmaceutically acceptable prodrugs thereof.
  • fluticasone furoate is used in a broad sense to include not only “fluticasone furoate” per se but also any pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs, and pharmaceutically acceptable prodrugs thereof.
  • Fluticasone is currently commercially available as a furoate salt and a propionate salt.
  • Fluticasone furoate is a corticosteroid which substantially overcomes the potential side effects that are generally produced by the use of conventional corticosteroids.
  • fluticasone furoate exhibits a 1.7 times higher binding affinity for the human glucocorticoid receptor as compared to that of fluticasone propionate and also provides prolonged protection up to 26 hours against airway hyperresponsiveness as compared to fluticasone propionate.
  • Fluticasone furoate has a longer duration of action with an elimination half life of 15.1 hrs.
  • Fluticasone furoate is a synthetic fluorinated corticosteroid that has been developed as an intranasal treatment for patients with symptoms of rhinitis and has an enhanced affinity towards the glucocorticoid receptor.
  • Fluticasone furoate and carmoterol mainly act on two different components of asthma exhibiting a complimentary action. Chronic inflammation which is commonly associated with asthma is managed by fluticasone furoate while other aspects of asthma, such as abnormalities in bronchial smooth muscle are improved, by carmoterol.
  • fluticasone furoate has greater potency than other clinically used corticosteroids for the glucocorticoid receptor and against the proinflammatory transcription factors nuclear factor KB (NF-KB), activation protein- 1 , and tumor necrosis factor- induced interleukin-8 cytokine production.
  • NF-KB nuclear factor KB
  • activation protein- 1 activation protein- 1
  • tumor necrosis factor- induced interleukin-8 cytokine production NF-KB
  • fluticasone furoate has a longer duration of action with an elimination half life of 15.1 hrs.
  • Carmoterol has a longer duration of action up to 30 hrs.
  • the combination of fluticasone furoate with carmoterol provides a novel combination which has the convenience of once daily administration for patients of asthma and COPD.
  • carmoterol is administered once daily and fluticasone propionate is administered twice daily it may be possible to use half dose of carmoterol along with Fluticasone propionate.
  • Another embodiment of the present invention provides a novel combination for inhalation comprising carmoterol in combination with fluticasone propionate, wherein the combination is administered twice daily.
  • Yet another embodiment of the present invention provides a novel combination for inhalation comprising carmoterol in combination with an ester of fluticasone, wherein the combination is administered once daily.
  • fluticasone furoate exhibits a synergistic activity, in which fluticasone furoate helps in increasing the activity of carmoterol; at the same time carmoterol helps in improving the efficacy of fluticasone furoate.
  • carmoterol may be present in the in the amount of about 0.5mcg to lOmcg.
  • an ester of fluticasone may be present in the in the amount of about 0.5 meg to 800mcg.
  • the pharmaceutical composition may comprise carmoterol and fluticasone furoate with one or more pharmaceutically acceptable excipients.
  • the present invention thus provides a novel combination for inhalation comprising carmoterol in combination with ciclesonide for the prevention or treatment of respiratory, inflammatory or obstructive airway disease while simultaneously reducing the frequency of dosage administration.
  • ciclesonide are used in a broad sense to include not only “ciclesonide” per se but also any pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs, and pharmaceutically acceptable prodrugs thereof.
  • Ciclesonide a non halogenated corticosteroid is a prodrug which is hydrolysed enzymatically by esterases to form its active metabolite desisobutyryl ciclesonide in the lung. Further ciclesonide has negligible systemic effects and therefore exhibits a better safety profile.
  • Ciclesonide and carmoterol mainly act on two different components of asthma exhibiting a complimentary action. Chronic inflammation which is commonly associated with asthma is managed by ciclesonide while other aspects of asthma, such as abnormalities in bronchial smooth muscle are improved, by carmoterol.
  • Ciclesonide exhibits a longer duration of action due to its lipophilic nature and lipid conjugation property.
  • Carmoterol has a longer duration of action up to 30 hrs.
  • the combination of ciclesonide with carmoterol provides a novel combination which has the convenience of once daily administration for patients of asthma and COPD.
  • combination of ciclesonide and carmoterol exhibits a synergistic activity, in which ciclesonide helps in increasing the activity of carmoterol; at the same time carmoterol helps in improving the efficacy of ciclesonide.
  • carmoterol may be present in the in the amount of about 10 05mcg to lOmcg.
  • ciclesonide may be present in the in the amount of about 20mcg to 800mcg.
  • the pharmaceutical composition may comprise carmoterol and ciclesonide with one or more pharmaceutically acceptable excipients.
  • the present invention thus provides a novel combination for inhalation comprising carmoterol in combination with mometasone for the prevention or treatment of respiratory, 25 inflammatory or obstructive airway disease while simultaneously reducing the frequency of dosage administration.
  • the term “mometasone” is used in a broad sense to include not only “mometasone” per se but also any pharmaceutically acceptable salts, pharmaceutically 0 acceptable esters, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs, and pharmaceutically acceptable prodrugs thereof.
  • the mometasone may be mometasone furoate.
  • Mometasone is a potent synthetic corticosteroid which exhibits a greater binding affinity towards the corticosteroid receptor. Mometasone and carmoterol mainly act on two different components of asthma exhibiting a complimentary action.
  • mometasone chronic inflammation which is commonly associated with asthma is managed by mometasone, while, other aspects of asthma, such as abnormalities in bronchial smooth muscle are improved, by carmoterol.
  • carmoterol the combination of mometasone with carmoterol provides a novel combination which has the convenience of once daily administration for patients of asthma and COPD.
  • a rapid onset of action of the combination due to carmoterol may increase in patient's confidence in the treatment and subsequently improve compliance to therapy.
  • carmoterol exhibits a synergistic activity, in which mometasone helps in increasing the activity of carmoterol; at the same time carmoterol helps in improving the efficacy of mometasone.
  • carmoterol may be present in the amount of about lmcg to 4mcg.
  • mometasone may be present in the amount of about 50mcg to 800mcg.
  • the pharmaceutical composition may comprise carmoterol and mometasone with one or more pharmaceutically acceptable excipients.
  • ICS inhaled corticosteroid
  • fluticasone furoate, carmoterol and tiotropium is effective for treating inflammatory and/or obstructive diseases of the respiratory tract, particularly asthma or chronic obstructive pulmonary disease (COPD).
  • COPD chronic obstructive pulmonary disease
  • the combination of fluticasone furoate, carmoterol and tiotropium provides a rapid onset of action and improved control of obstructive or inflammatory airway diseases, or reduction in the exacerbations of the diseases.
  • Another advantage of the combination is that it facilitates the treatment of an obstructive and inflammatory airway disease with a single medicament.
  • this combination therapy provides for administration by the use of a single inhaler for patients who currently have to make use of multiple inhalers. This is because Fluticasone Furoate can be administered once daily along with Tiotropium as compared to Fluticasone Propionate which is to be administered twice daily. This is particularly important in case of elderly patients who may get confused between the inhalers and who also suffer from several other medical conditions such as heart disease, arthritis etc. and are receiving multiple other medications.
  • the present invention provides a pharmaceutical composition comprising fluticasone furoate, carmoterol and tiotropium for once daily administration.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising fluticasone propionate, carmoterol and tiotropium, preferably for twice daily administration.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising an ester of fluticasone, carmoterol and tiotropium, preferably for once daily administration.
  • the anticholinergic used according to the present invention is preferably tiotropium, especially tiotropium bromide, and particularly tiotropium bromide monohydrate.
  • Tiotropium bromide is an anticholinergic bronchodilator that antagonises muscarinic Ml, M2 and M3 receptors. Tiotropium, is chemically described as (la, 2 ⁇ , 4 ⁇ , 5a, 7B)-7-[(Hydroxydi- 2-thienylacetyl) oxy]-9, 9-dimethyl-3-oxa-9-azoniatricyclo [3.3.1.0 2 ' 4 ] nonane bromide monohydrate. Tiotropium has a longer duration of action of up to 32 hours. Also tiotropium exhibits an improvement in dyspnea and ceases the need for rescue therapy. Tiotropium in combination with pulmonary rehabilitation (PR) associated with an increased exercise endurance time produces clinically meaningful improvements in dyspnea and health status as compared to pulmonary rehabilitation (PR alone in COPD patients.
  • PR pulmonary rehabilitation
  • tiotropium is more potent than ipratropium in the treatment of patients with COPD in terms of the effect of lung function, dyspnea, exacerbation rates and health status.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising fluticasone furoate, tiotropium and carmoterol.
  • an ester of fluticasone may be present in the in the amount of about 0.5 meg to 800mcg.
  • tiotropium (particularly tiotropium bromide) may be present in the in the amount of about 2.25mcg to 30mcg.
  • carmoterol particularly carmoterol hydrochloride
  • carmoterol hydrochloride may be present in the in the amount of about 0.5mcg to lOmcg.
  • the pharmaceutical composition may comprise carmoterol and fluticasone furoate, indacaterol and tiotropium with one or more pharmaceutically acceptable excipients.
  • the pharmaceutical compositions of the present invention may be administered by any suitable methods used for delivery of the drugs to the respiratory tract.
  • the composition of the present invention may thus be administered as metered dose inhalers (MDI), dry powder inhalers (DPI), nebuliser, nasal spray, nasal drops, insufflation powders.
  • MDI metered dose inhalers
  • DPI dry powder inhalers
  • nebuliser nasal spray, nasal drops, insufflation powders.
  • the various dosage forms according to the present invention may comprise one or more pharmaceutically acceptable carriers/excipients suitable for formulating the same.
  • the metered dose inhalers may comprise one or more pharmaceutically acceptable excipients such as but not limited to HFC/HFA propellants, co- solvents, bulking agents, non volatile component, buffers/pH adjusting agents, surface active agents, preservatives, complexing agents, or combinations thereof.
  • pharmaceutically acceptable excipients such as but not limited to HFC/HFA propellants, co- solvents, bulking agents, non volatile component, buffers/pH adjusting agents, surface active agents, preservatives, complexing agents, or combinations thereof.
  • Propellants are those which, when mixed with the cosolvent(s), form a homogeneous propellant system in which a therapeutically effective amount of the medicament can be dissolved.
  • the HFC/HFA propellant must be toxicologically safe and must have a vapor pressure which is suitable to enable the medicament to be administered via a pressurized MDI.
  • the HFC/HFA propellants may comprise, one or more of 1,1,1,2-tetrafluoroethane (HFA-134(a)) and 1,1 ,1,2,3,3,3,-heptafluoropropane (HFA-227), difluoromethane (HFC-32), 1,1,1-trifluoroethane HFC-I43(a)), 1,1,2,2-tetrafluoroethane HFC- 134), and 1,1-difluoroethane HFC- 152(a)) and such other propellants which may be known to the person skilled in the art.
  • Co-solvent is any solvent which is miscible in the formulation in the amount desired and which, when added, provides a formulation in which the medicament can be dissolved.
  • the function of the cosolvent is to increase the solubility of the medicament and the excipients in the formulation.
  • the co-solvent may comprise one or more of, C 2- C 6 aliphatic alcohols, such as but not limited, to ethyl alcohol and isopropyl alcohol; glycols such as but not limited to propylene glycol, polyethylene glycols, polypropylene glycols, glycol ethers, and block copolymers of oxyethylene and oxypropylene; and other substances, such as.
  • Suitable surfactants may be employed in the aerosol solution formulation meant for administration through metered dose inhalers of the present invention which may serve to stabilize the solution formulation and improve the performance of valve systems of the metered dose inhaler.
  • the surfactant may comprise one or more ionic and/or non-ionic surfactant, but not limited to, salts of stearic acids such as magnesium stearate or esters such, as ascorbyl palmitate, isopropyl myristate and tocopherol esters oleic acid, sorbitan trioleate, lecithin, isopropylmyristate, tyloxapol, polyvinylpyrrolidone, polysorbates such as polysorbate 80, Polysorbate 20, Polysorbate 40, vitamin E-TPGS, and macrogol hydroxystearates such as macrogol- 15-hydroxystearate, acetylated monoglycerides like Myvacet 9-45 and Myvacet 9-08, Polyoxyethylene ethers, ethyloleate, glyceryl trioleate, glyceryl monolaurate, glyceryl monooleate, glyceryl monosterate, glyceryl mon
  • the surfactants may also be selected from the vast class known in the art like oils such as, but not limited to, corn oil, olive oil, cottonseed oil and sunflower seed oil, mineral oils like liquid paraffin, oleic acid and also phospholipids such as lecithin, or sorbitan fatty acid esters like sorbitan trioleate or Tween 20, Tween 60, Tween 80, PEG - 25 Glyceryl trioleate, PVP, citric acid, PFDA (per fluoro-n-decanoic acid).
  • oils such as, but not limited to, corn oil, olive oil, cottonseed oil and sunflower seed oil, mineral oils like liquid paraffin, oleic acid and also phospholipids such as lecithin, or sorbitan fatty acid esters like sorbitan trioleate or Tween 20, Tween 60, Tween 80, PEG - 25 Glyceryl trioleate, PVP, citric acid, PFDA (per fluoro-n-decano
  • Non- volatile component is all the suspended or dissolved constituents that would be left after evaporation of the solvent.
  • the non-volatile component may comprise one or more of monosaccharides such as, but not limited to, glucose, arabinose; disaccharides such as but not limited to lactose, maltose; oligosaccharides and polysaccharides such as, but not limited to, dextrans; polyalcohol such, as but not limited to, glycerol, sorbitol, mannitol, xylitol; salts such as but not limited to potassium chloride, magnesium chloride, magnesium sulphate, sodium chloride, sodium citrate, sodium phosphate, sodium hydrogen phosphate, sodium hydrogen carbonate, potassium citrate, potassium phosphate, potassium hydrogen phosphate, potassium hydrogen carbonate, calcium carbonate and calcium chloride.
  • Suitable bulking agents may be employed in metered dose inhalation formulation of the present invention.
  • the bulking agent may comprise one or more of saccharides, including monosaccharides, disaccharides, polysaccharides and sugar alcohols such as arabinose, glucose, fructose, ribose, mannose, sucrose, terhalose, lactose, maltose, starches, dextran or mannitol.
  • saccharides including monosaccharides, disaccharides, polysaccharides and sugar alcohols such as arabinose, glucose, fructose, ribose, mannose, sucrose, terhalose, lactose, maltose, starches, dextran or mannitol.
  • Suitable buffers or pH adjusting agents may be employed in the metered dose inhalation formulation of the present invention.
  • the buffer or the pH adjusting agent may comprise one or more of organic or inorganic acids such as, but not limited to, citric acid, ascorbic acid, hydrochloric acid, sulfuric acid, nitric acid, or phosphoric acid.
  • Suitable preservatives may be employed in the aerosol solution formulation of the present invention to protect the formulation from contamination with pathogenic bacteria.
  • the preservative may comprise one or more of benzalkonium chloride, benzoic acid, benzoates such as sodium benzoate and such other preservatives which may be known to the person skilled in the art.
  • Suitable complexing agents may be employed in the aerosol solution formulation of the present invention which is capable of forming complex bonds.
  • the complexing agent may comprise one or more of, but not limited to, sodium EDTA or disodium EDTA.
  • the pharmaceutical composition of the present invention may be administered by a dry powder inhaler (DPI).
  • DPI dry powder inhaler
  • the pharmaceutically acceptable excipients suitable for dry powder inhalation according to the present invention may be selected from suitable carriers which may comprise one or more of, but not limited to, sugars such as glucose, saccharose, lactose and fructose, starches or starch derivatives, oligosaccharides such as dextrins, cyclodextrins and their derivatives, polyvinylpyrrolidone, alginic acid, tylose, silicic acid, cellulose, cellulose derivatives (for example cellulose ether), sugar alcohols such as mannitol or sorbitol, calcium carbonate, calcium phosphate, etc.
  • suitable carriers may comprise one or more of, but not limited to, sugars such as glucose, saccharose, lactose and fructose, starches or starch derivatives, oligosaccharides such as dextrin
  • lactose lactitol
  • dextrates dextrose
  • maltodextrin saccharides including monosaccharides, disaccharides, polysaccharides; sugar alcohols such as arabinose, ribose, mannose, sucrose, trehalose, maltose, dextran.
  • the pharmaceutical composition of the present invention may be administered by nebulization.
  • Nebulisation therapy has an advantage over other inhalation therapy, since it is easy to use and does not require co-ordination or much effort .It also works much more rapidly than medicines taken by mouth.
  • the composition according to the present invention may comprise suitable excipients such as tonicity agents, pH regulators, chelating agents, tonicity adjusting agents, surfactants, buffer agents in a suitable vehicle.
  • suitable excipients such as tonicity agents, pH regulators, chelating agents, tonicity adjusting agents, surfactants, buffer agents in a suitable vehicle.
  • Isotonicity-adjusting agents may comprise one or more of, but not limited to, sodium chloride, potassium chloride, zinc chloride, calcium chloride and mixtures thereof.
  • Other isotonicity-adjusting agents may also include, but are not limited to, mannitol, glycerol, and dextrose and mixtures thereof.
  • the pH may be adjusted by the addition of pharmacologically acceptable acids.
  • Pharmacologically acceptable inorganic acids or organic acids may be used for this purpose. Examples of preferred inorganic acids which may be used include one or more of, but not limited to, hydrochloric acid, hydrobromic acid, nitric acid, sulphuric acid and phosphoric acid or combinations thereof.
  • Examples of particularly suitable organic acids which may be used include one or more of, but not limited to, ascorbic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, fumaric acid, acetic acid, formic acid and propionic acid or combinations thereof.
  • Examples of preferred bases which may be used include one or more of, but not limited to, aqueous ammonia solution, ammonium carbonate, sodium borate, sodium carbonate, and sodium hydroxide or combinations thereof.
  • Complexing/chelating agents according to the present invention may comprise one or more of, but not limited to, editic acid (EDTA) or one of the known salts thereof, e.g. sodium EDTA or disodium EDTA dihydrate (sodium edetate) or combinations thereof.
  • EDTA editic acid
  • salts thereof e.g. sodium EDTA or disodium EDTA dihydrate (sodium edetate) or combinations thereof.
  • surfactant may comprise one or more, but not limited to Polysorbates such as uch as polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, polysorbate 65, polysorbate 85, sorbitan fatty acid esters such as Span 20, Span 40, Span 60 Span 80, Span 120; sodium lauryl sulfate; polyethoxylated castor oil; polyethoxylated hydrogenated castor oil, sodium dodecyl sulfate (sodium lauryl sulfate), Lauryl dimethyl amine oxide, Docusate sodium, Cetyl trimethyl ammonium bromide (CTAB) Polyethoxylated alcohols, Polyoxyethylene sorbitan, Octoxynol, N, N- dimethyldodecylamine-N-oxide, Hexadecyltrimethylammonium bromide, Polyoxyl 10 la
  • Carboxylates Sulphonates, Petroleum sulphonates, alkylbenzenesulphonates, Naphthalenesulphonates, Olefin sulphonates, Alkyl sulphates, Sulphates, Sulphated natural oils & fats, Sulphated esters, Sulphated alkanolamides, Alkylphenols, ethoxylated & sulphated, Ethoxylated aliphatic alcohol, polyoxyethylene surfactants, carboxylic esters Polyethylene glycol esters, Anhydrosorbitol ester & it's ethoxylated derivatives, Glycol esters of fatty acids, Carboxylic amides, Monoalkanolamine condensates, Polyoxyethylene fatty acid amides, Quaternary ammonium salts, Amines with amide linkages, Polyoxyethylene alkyl & alicyclic amines, ⁇ , ⁇ , ⁇ , ⁇ tetrakis substituted ethylenediamines 2- al
  • the buffer agents may comprise one or more of organic or inorganic acids such as but not limited to citric acid/sodium hydrogensulphate borate buffer, phosphates (sodium hydrogen orthophosphate, disodium hydrogenphosphate), trometamol, acetate buffer, citrate buffer, sodium citrate dehydrate, citric acid monohydrate, sodium dihydrogen phosphate dehydrate, anhydrous disodium hydrogen phosphate or equivalent conventional buffers.
  • organic or inorganic acids such as but not limited to citric acid/sodium hydrogensulphate borate buffer, phosphates (sodium hydrogen orthophosphate, disodium hydrogenphosphate), trometamol, acetate buffer, citrate buffer, sodium citrate dehydrate, citric acid monohydrate, sodium dihydrogen phosphate dehydrate, anhydrous disodium hydrogen phosphate or equivalent conventional buffers.
  • Anti-microbial preservative agent may be added for multi-dose packages.
  • compositions according to the present invention may be provided in suitable containers with suitable means enabling the application of the contained formulation to the respiratory tract.
  • the powder for inhalation intended for administration through DPI may either be encapsulated in capsules of gelatin or HPMC or in blisters or alternatively, the dry powder may be contained as a reservoir either in a single dose or multi-dose dry powder inhalation device.
  • the powder for inhalation intended to be used for DPI may be suspended in a suitable liquid vehicle and packed in an aerosol container along with suitable propellants or mixtures thereof.
  • the powder for inhalation intended to be used for DPI may also be dispersed in a suitable gas stream to form an aerosol composition.
  • the MDI composition according to the present invention may be packed in plain aluminium cans or SS (stainless steel) cans.
  • Some aerosol drugs tend to adhere to the inner surfaces, i.e., walls of the cans and valves, of the MDI. This can lead to the patient getting significantly less than the prescribed amount of the active agent upon each activation of the MDI.
  • Coating the inner surface of the container with a suitable polymer can reduce this adhesion problem.
  • Suitable coatings include fluorocarbon copolymers such as FEP-PES (fluorinated ethylene propylene and polyethersulphone) and PFA-PES (perfluoroalkoxyalkane and polyethersulphone), epoxy and ethylene.
  • the inner surfaces of the cans may be anodized, plasma treated or plasma coated.
  • the said pharmaceutical composition may further comprise one or more active(s) selected from anticholinergics, antihistamines, antiallergics or leukotriene antagonist or their pharmaceutically acceptable salts, solvates, tautomers, derivatives, enantiomers, isomers, hydrates, prodrugs or polymorphs thereof.
  • active(s) selected from anticholinergics, antihistamines, antiallergics or leukotriene antagonist or their pharmaceutically acceptable salts, solvates, tautomers, derivatives, enantiomers, isomers, hydrates, prodrugs or polymorphs thereof.
  • the present invention also provides a process to manufacture the compositions according to the present invention.
  • the present invention provides a process of preparing a metered dose inhalation compositions which process comprises admixing of a pharmaceutically acceptable carrier or excipient with the actives and the propellant and providing the compositions in precrimped cans.
  • the present invention provides a process of preparing a dry powder inhalation compositions which process comprises admixing of a pharmaceutically acceptable carrier or excipient with the actives and providing the compositions to be administered through a dry powder inhaler.
  • the present invention also provides a process of preparing an inhalation solution/suspension which process comprises dissolving/dispersing the drugs, optionally chelating agents, osmotic agents and any other suitable ingredients in the vehicle and adjusting the pH using a suitable pH adjusting agent.
  • the present invention also provides a method for the treatment in a mammal, such as a human, for treating chronic obstructive pulmonary disease and asthma, which method comprises administration of a therapeutically effective amount of pharmaceutical compositions according to the present invention.
  • the method of treatment may be characterized in that the pharmaceutical compositions according to the present invention are administered once a day in therapeutically effective amounts.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising one or more bronchodilators (such as a long-acting beta agonist (LABA)) and an inhaled corticosteroid (ICS) for use in treating disorders or conditions that respond to, or are prevented, ameliorated or eliminated by, the administration of one or more bronchodilators (such as a long-acting beta agonist (LABA)) and inhaled corticosteroid (ICS).
  • bronchodilators such as a long-acting beta agonist (LABA)
  • ICS inhaled corticosteroid
  • step 2 The suspension obtained in step 1 was transferred to the mixing vessel where remaining quantity of HFA was added.
  • step 2 The suspension obtained in step 1 was transferred to the mixing vessel where remaining quantity of HFA was added.
  • Step 2 The solution obtained in Step 1 was transferred to a mixing vessel.
  • step 3 The suspension obtained in step 3 was transferred to the mixing vessel where remaining quantity of HFA was added.
  • Example 4 Sr. No. Ingredients Qty / Spray
  • step (2) The mixture obtained in step (1) was blended.
  • step (2) The mixture obtained in step (1) was blended.
  • step 2 The suspension obtained in step 1 was transferred to the mixing vessel where remaining quantity of HFA was added.
  • step 2 The suspension obtained in step 1 was transferred to the mixing vessel where remaining quantity of HFA was added.
  • Step 2 The solution obtained in Step 1 was transferred to a mixing vessel.
  • step 3 The suspension obtained in step 3 was transferred to the mixing vessel where remaining quantity of HFA was added.
  • step (2) The mixture obtained in step (1) was blended.
  • step 2 The suspension obtained in step 1 was transferred to the mixing vessel where remaining quantity of HFA was added.
  • step 2 The suspension obtained in step 1 was transferred to the mixing vessel where remaining quantity of HFA was added.
  • Step 2 The solution obtained in Step 1 was transferred to a mixing vessel.
  • step 3 The suspension obtained in step 3 was transferred to the mixing vessel where remaining quantity of HFA was added.
  • Example 21 Sr. No. Ingredients Qty / Spray
  • step (2) The mixture obtained in step (1) was blended.
  • step (2) The mixture obtained in step (1) was blended.
  • step (2) The mixture obtained in step (1) was blended.
  • step 1 Fluticasone furoate, Carmoterol and Tiotropium bromide were sifted with a part quantity of lactose. 2) The cosift of step 1 was then sifted with the remaining quantity of lactose and blended.
  • step 2 was then filled in capsules.
  • step 2 The cosift of step 1 was then sifted with the remaining quantity of lactose and blended. 3) The blend of step 2 was then filled in capsules.
  • step 2 The cosift of step 1 was then sifted with the remaining quantity of lactose and blended. 3) The blend of step 2 was then filled in capsules.
  • step 2 The suspension obtained in step 1 was transferred to the mixing vessel where remaining quantity of HFA was added.
  • step 2 The suspension obtained in step 1 was transferred to the mixing vessel where remaining quantity of HFA was added. 3) The resulting suspension was mixed, recirculated and filled in into pre-crimped aluminum cans.
  • PVP was dissolved in PEG and part quantity of HFA134A or HFA227.
  • Step 2 The solution obtained in Step 1 was transferred to a mixing vessel.
  • step 3 The suspension obtained in step 3 was transferred to the mixing vessel where remaining quantity of HFA was added.
  • step (2) The solution obtained in step (2) was transferred to the main mixing vessel where it was mixed with entire quantity of HFA134a.
  • step (2) Fluticasone furoate, Carmoterol and Tiotropium were dissolved in the solution obtained in step (1). 3) The solution obtained in step (2) was transferred to the main mixing vessel where it was mixed with entire quantity of HFA 134a.
  • Lecithin was dissolved in ethanol.
  • step (3) The slurry obtained in step (2) was added to the main bulk obtained in step (1).
  • Weight was made up with WFI and filled in 2.0ml in LDPE form fill seal ampoules.
  • step (3) The slurry obtained in step (2) was added to the main bulk obtained in step (1).
  • step (3) The slurry obtained in step (2) was added to the main bulk obtained in step (1).
  • Weight was made up with WFI and filled in 2.0ml in LDPE form fill seal ampoules.
  • step (3) The slurry obtained in step (2) was added to the main bulk obtained in step (1).
  • Weight was made up with WFI and filled in 2.0ml in LDPE form fill seal ampoules.
  • step (2) Carmoterol, Ciclesonide, Polysorbate 80 and WFI were colleted in a pressure vessel and subjected to sterilization by autoclave to obtain slurry. 3) The slurry obtained in step (2) was added to the main bulk obtained in step (1).
  • Weight was made up with WFI and filled in 2.0ml in LDPE form fill seal ampoules.
  • step (3) The slurry obtained in step (2) was added to the main bulk obtained in step (1).
  • Weight was made up with WFI and filled in 2.0ml in LDPE form fill seal ampoules.
  • step (3) The slurry obtained in step (2) was added to the main bulk obtained in step (1).
  • Weight was made up with WFI and filled in 2.0ml in LDPE form fill seal ampoules.
  • step (3) The slurry obtained in step (2) was added to the main bulk obtained in step (1).
  • Weight was made up with WFI and filled in 2.0ml in LDPE form fill seal ampoules.

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Abstract

L'invention concerne une composition pharmaceutique comprenant du carmotérol en combinaison avec un corticostéroïde choisi parmi la fluticasone, le ciclésonide ou la mométasone, et éventuellement un ou plusieurs excipients pharmaceutiquement acceptables.
PCT/GB2011/001114 2010-07-23 2011-07-25 Composition pharmaceutique Ceased WO2012010854A1 (fr)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
IN2105/MUM/2010 2010-07-23
IN2105MU2010 2010-07-23
IN2219MU2010 2010-08-04
IN2219/MUM/2010 2010-08-04
IN2346/MUM/2010 2010-08-20
IN2346MU2010 2010-08-20
IN69/MUM/2011 2011-01-10
IN69MU2011 2011-01-10

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012093252A1 (fr) * 2011-01-06 2012-07-12 Cipla Limited Composition pharmaceutique
RU2678992C2 (ru) * 2012-04-11 2019-02-05 Сипла Лимитед Фармацевтическая композиция, содержащая арформотерол и флутиказона фуроат
WO2019142214A1 (fr) * 2018-01-19 2019-07-25 Cipla Limited Composition pharmaceutique comprenant du tiotropium destinée à être inhalée

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1452179A1 (fr) 2003-02-27 2004-09-01 CHIESI FARMACEUTICI S.p.A. Nouveau combination d'un puissant agoniste beta 2 de longue duree et un corticosteroid
US20050042174A1 (en) 2003-06-19 2005-02-24 Microdrug Ag Combined doses
US20050059643A1 (en) 2003-08-05 2005-03-17 Boehringer Ingelheim International Gmbh Medicaments for inhalation comprising a steroid and a betamimetic
WO2006105401A2 (fr) 2005-03-30 2006-10-05 Schering Corporation Medicaments et procedes de combinaison d'un anticholinergique, un corticosteroide, et un agoniste beta a action prolongee
EP1787639A2 (fr) 2000-05-22 2007-05-23 CHIESI FARMACEUTICI S.p.A. Formulations de solutions pharmaceutiques stables pour inhalateurs à dosage mesuré pressurisés
EP1944018A1 (fr) * 2007-01-10 2008-07-16 CHIESI FARMACEUTICI S.p.A. Particules micronisées comprenant des principes actifs agissant même à faible dose pour préparations en poudre pour inhalation
WO2008102128A2 (fr) * 2007-02-19 2008-08-28 Cipla Limited Combinaisons pharmaceutiques
US20090088408A1 (en) 2001-06-23 2009-04-02 Meade Christopher J M Pharmaceutical compositions on anticholinergics, corticosteroids and betamimetics
WO2010097188A1 (fr) * 2009-02-25 2010-09-02 Chiesi Farmaceutici S.P.A. Particules pour inhalation comprenant un sel de carmotérol et un corticostéroïde
WO2011048412A1 (fr) * 2009-10-21 2011-04-28 Prosonix Limited Procédé d'amélioration de la cristallinité

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1787639A2 (fr) 2000-05-22 2007-05-23 CHIESI FARMACEUTICI S.p.A. Formulations de solutions pharmaceutiques stables pour inhalateurs à dosage mesuré pressurisés
US20090088408A1 (en) 2001-06-23 2009-04-02 Meade Christopher J M Pharmaceutical compositions on anticholinergics, corticosteroids and betamimetics
EP1452179A1 (fr) 2003-02-27 2004-09-01 CHIESI FARMACEUTICI S.p.A. Nouveau combination d'un puissant agoniste beta 2 de longue duree et un corticosteroid
EP1603565A1 (fr) 2003-02-27 2005-12-14 CHIESI FARMACEUTICI S.p.A. Medicament comportant un agoniste beta 2 de longue duree et tres puissant en combinaison avec d'autres ingredients actifs
EP1834643A2 (fr) 2003-02-27 2007-09-19 CHIESI FARMACEUTICI S.p.A. Nouveau médicament comportant un agoniste BETA2 de très longue durée combiné à d'autres ingrédients actifs
US20050042174A1 (en) 2003-06-19 2005-02-24 Microdrug Ag Combined doses
US20050059643A1 (en) 2003-08-05 2005-03-17 Boehringer Ingelheim International Gmbh Medicaments for inhalation comprising a steroid and a betamimetic
WO2006105401A2 (fr) 2005-03-30 2006-10-05 Schering Corporation Medicaments et procedes de combinaison d'un anticholinergique, un corticosteroide, et un agoniste beta a action prolongee
EP1944018A1 (fr) * 2007-01-10 2008-07-16 CHIESI FARMACEUTICI S.p.A. Particules micronisées comprenant des principes actifs agissant même à faible dose pour préparations en poudre pour inhalation
WO2008102128A2 (fr) * 2007-02-19 2008-08-28 Cipla Limited Combinaisons pharmaceutiques
WO2010097188A1 (fr) * 2009-02-25 2010-09-02 Chiesi Farmaceutici S.P.A. Particules pour inhalation comprenant un sel de carmotérol et un corticostéroïde
WO2011048412A1 (fr) * 2009-10-21 2011-04-28 Prosonix Limited Procédé d'amélioration de la cristallinité

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012093252A1 (fr) * 2011-01-06 2012-07-12 Cipla Limited Composition pharmaceutique
RU2678992C2 (ru) * 2012-04-11 2019-02-05 Сипла Лимитед Фармацевтическая композиция, содержащая арформотерол и флутиказона фуроат
WO2019142214A1 (fr) * 2018-01-19 2019-07-25 Cipla Limited Composition pharmaceutique comprenant du tiotropium destinée à être inhalée

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