Patents by Inventor Luis Sobral
Luis Sobral has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 11434194Abstract: The present invention relates to an amorphous form of vilanterol trifenatate, processes for its preparation and its use in pharmaceutical formulations for the treatment of respiratory diseases, particularly for the treatment of asthma and chronic obstructive pulmonary disease. In particular, the invention relates to an amorphous form of vilanterol trifenatate, characterized by the X-ray powder diffraction (XRPD) pattern, obtained using copper K-alpha1 radiation.Type: GrantFiled: July 9, 2018Date of Patent: September 6, 2022Assignee: Hovione Scientia LimitedInventors: Nuno Torres Lourenço, Luis Sobral, Joana Fernandes
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Patent number: 11427584Abstract: The present invention discloses processes comprising a) reacting ethyl isonipecotate with 1-bromo-2-chloroethane in the presence of an organic base in a solvent to form ethyl 1-(2-chloroethyl)piperidine-4-carboxylate (II) or a salt thereof. Process step a) may be included in a process for preparing umeclidinium bromide that comprises further process steps: b) reacting ethyl 1-(2-chloroethyl)piperidine-4-carboxylate (II) or a salt thereof with lithium diisopropylamide in a solvent to form ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (III); c) reacting ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (III) with phenyl lithium in a solvent to form 1-azabicyclo[2.2.2]oct-4-yl(diphenyl)methanol (IV); and d) reacting 1-azabicyclo[2.2.2]oct-4-yl(diphenyl)methanol (IV) with ((2-bromoethoxy)methyl) benzene in a solvent to form 4-[hydroxyl(diphenyl)methyl]-1-[2-(phenylmethyl)oxy]ethyl]-1-azoniabicyclo[2.2.2]octane bromide (I), umeclidinium bromide. A process comprising d) reacting 1-azabicyclo[2.2.Type: GrantFiled: July 13, 2020Date of Patent: August 30, 2022Assignee: Hovione Scientia LimitedInventors: Nuno Torres Lourenço, Luis Sobral, Rafael Antunes, Maria Santos, Margarida Espadinha
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Patent number: 11414374Abstract: The present invention relates to new crystalline forms of vilanterol trifenatate, processes for their preparation, and their use in a pharmaceutical composition for the treatment of respiratory diseases, particularly for the treatment of asthma and chronic obstructive pulmonary disease. In particular, the present invention relates to a crystalline form of vilanterol trifenatate characterised in that the form has an XRPD pattern as defined herein having characteristic diffraction angles (2-theta or 20 (°)) falling within or at each end of one or more of the following ranges: (a) 3 to 5°, such as 3.8 to 4.4°; and/or (b) 7 to 9.9°, such as 7 to 8.5°; and/or (c) 12 to 13.3°, such as 12 to 13.3?; and/or (d) 16.4 to 17.3°, such as 16.4 to 17.3?; and/or (e) 26.8 to 28.3°, such as 26.8 to 28.3°.Type: GrantFiled: July 9, 2018Date of Patent: August 16, 2022Assignee: Hovione Scientia LimitedInventors: Nuno Torres Lourenço, Luis Sobral, Joana Fernandes
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Publication number: 20200347060Abstract: The present invention discloses processes comprising a) reacting ethyl isonipecotate with 1-bromo-2-chloroethane in the presence of an organic base in a solvent to form ethyl 1-(2-chloroethyl)piperidine-4-carboxylate (II) or a salt thereof. Process step a) may be included in a process for preparing umeclidinium bromide that comprises further process steps: b) reacting ethyl 1-(2-chloroethyl)piperidine-4-carboxylate (II) or a salt thereof with lithium diisopropylamide in a solvent to form ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (III); c) reacting ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (III) with phenyl lithium in a solvent to form 1-azabicyclo[2.2.2]oct-4-yl(diphenyl)methanol (IV); and d) reacting 1-azabicyclo[2.2.2]oct-4-yl(diphenyl)methanol (IV) with ((2-bromoethoxy)methyl) benzene in a solvent to form 4-[hydroxyl(diphenyl)methyl]-1-[2-(phenylmethyl)oxy]ethyl]-1-azoniabicyclo[2.2.2]octane bromide (I), umeclidinium bromide. A process comprising d) reacting 1-azabicyclo[2.2.Type: ApplicationFiled: July 13, 2020Publication date: November 5, 2020Inventors: Nuno Torres LOURENÇO, Luis SOBRAL, Rafael ANTUNES, Maria SANTOS, Margarida ESPADINHA
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Patent number: 10759801Abstract: The present invention discloses processes comprising a) reacting ethyl isonipecotate with 1-bromo-2-chloroethane in the presence of an organic base in a solvent to form ethyl 1-(2-chloroethyl)piperidine-4-carboxylate (II) or a salt thereof. Process step a) may be included in a process for preparing umeclidinium bromide that comprises further process steps: b) reacting ethyl 1-(2-chloroethyl)piperidine-4-carboxylate (II) or a salt thereof with lithium diisopropylamide in a solvent to form ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (III); c) reacting ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (III) with phenyl lithium in a solvent to form 1-azabicyclo[2.2.2]oct-4-yl(diphenyl)methanol (IV); and d) reacting 1-azabicyclo[2.2.2]oct-4-yl(diphenyl)methanol (IV) with ((2-bromoethoxy)methyl) benzene in a solvent to form 4-[hydroxyl(diphenyl)methyl]-1-[2-(phenylmethyl)oxy]ethyl]-1-azoniabicyclo[2.2.2]octane bromide (I), umeclidinium bromide. A process comprising d) reacting 1-azabicyclo[2.2.Type: GrantFiled: November 10, 2017Date of Patent: September 1, 2020Assignee: Hovione Scientia LimitedInventors: Nuno Torres Lourenço, Luis Sobral, Rafael Antunes, Maria Santos, Margarida Espadinha
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Publication number: 20200165190Abstract: The present invention relates to an amorphous form of vilanterol trifenatate, processes for its preparation and its use in pharmaceutical formulations for the treatment of respiratory diseases, particularly for the treatment of asthma and chronic obstructive pulmonary disease. In particular, the invention relates to an amorphous form of vilanterol trifenatate, characterized by the X-ray powder diffraction (XRPD) pattern, obtained using copper K-alpha1 radiation, depicted in FIG. 1.Type: ApplicationFiled: July 9, 2018Publication date: May 28, 2020Inventors: Nuno Torres LOURENÇO, Luis SOBRAL, Joana FERNANDES
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Publication number: 20200148626Abstract: The present invention relates to new crystalline forms of vilanterol trifenatate, processes for their preparation, and their use in a pharmaceutical composition for the treatment of respiratory diseases, particularly for the treatment of asthma and chronic obstructive pulmonary disease. In particular, the present invention relates to a crystalline form of vilanterol trifenatate characterised in that the form has an XRPD pattern as defined herein having characteristic diffraction angles (2-theta or 20(°)) falling within or at each end of one or more of the following ranges: (a) 3 to 5°, such as 3.8 to 4.4°; and/or (b) 7 to 9.9°, such as 7 to 8.5°; and/or (c) 12 to 13.3°, such as 12 to 13.3?; and/or (d) 16.4 to 17.3°, such as 16.4 to 17.3?; and/or (e) 26.8 to 28.3°, such as 26.8 to 28.3°.Type: ApplicationFiled: July 9, 2018Publication date: May 14, 2020Inventors: Nuno Torres LOURENÇO, Luis SOBRAL, Joana FERNANDES
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Patent number: 10543298Abstract: A tetracycline salt comprising a tetracycline and an organic acid wherein the organic acid is oxalic acid or maleic acid is provided. The tetracycline is preferably doxycycline, minocycline, sancycline, lymecycline, tetracycline or demeclocycline, and preferred salts include oxycycline maleate, minocycline oxalate, tetracycline oxalate, demeclocycline maleate, demeclocycline oxalate, sancycline maleate, lymecycline maleate, or lymecycline oxalate. A pharmaceutical formulation comprising a tetracycline salt according to the invention is also provided, as is a medical device having coated thereon a salt or pharmaceutical formulation according to the invention. A salt of the invention, or a formulation of the invention are also provided for use as medicaments, particularly for use in the treatment or prevention of an inflammation and/or an infection.Type: GrantFiled: November 24, 2016Date of Patent: January 28, 2020Assignee: Hovione Scientia LimitedInventors: Luis Sobral, Livia Santana De Arruda, Margarida Figueiredo, Rafael Antunes, Ana Paula Filipe
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Publication number: 20190263814Abstract: The present invention discloses processes comprising a) reacting ethyl isonipecotate with 1-bromo-2-chloroethane in the presence of an organic base in a solvent to form ethyl 1-(2-chloroethyl)piperidine-4-carboxylate (II) or a salt thereof. Process step a) may be included in a process for preparing umeclidinium bromide that comprises further process steps: b) reacting ethyl 1-(2-chloroethyl)piperidine-4-carboxylate (II) or a salt thereof with lithium diisopropylamide in a solvent to form ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (III); c) reacting ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (III) with phenyl lithium in a solvent to form 1-azabicyclo[2.2.2]oct-4-yl(diphenyl)methanol (IV); and d) reacting 1-azabicyclo[2.2.2]oct-4-yl(diphenyl)methanol (IV) with ((2-bromoethoxy)methyl) benzene in a solvent to form 4-[hydroxyl(diphenyl)methyl]-1-[2-(phenylmethyl)oxy]ethyl]-1-azoniabicyclo[2.2.2]octane bromide (I), umeclidinium bromide. A process comprising d) reacting 1-azabicyclo[2.2.Type: ApplicationFiled: November 10, 2017Publication date: August 29, 2019Inventors: Nuno Torres LOURENÇO, Luis SOBRAL, Rafael ANTUNES, Maria SANTOS, Margarida ESPADINHA
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Patent number: 10328027Abstract: A new scalable process to control the particle size and the particle size distribution, comprising 5 steps: (i) suspension preparation in a mixture of solvents in which the API and/or excipient is partially soluble in one of the solvents; (ii) particle size reduction of the suspension; (iii) aging; (iv) stopping the aging by solvent removal; and (v) optionally, a step of isolating the processed ingredients in the form of powder.Type: GrantFiled: January 27, 2015Date of Patent: June 25, 2019Assignee: Hovione International Ltd.Inventors: Eunice Costa, Marcio Temtem, Luis Sobral, Constanca Cacela, Peter Villax
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Publication number: 20180344903Abstract: A tetracycline salt comprising a tetracycline and an organic acid wherein the organic acid is oxalic acid or maleic acid is provided. The tetracycline is preferably doxycycline, minocycline, sancycline, lymecycline, tetracycline or demeclocycline, and preferred salts include oxycycline maleate, minocycline oxalate, tetracycline oxalate, demeclocycline maleate, demeclocycline oxalate, sancycline maleate, lymecycline maleate, or lymecycline oxalate. A pharmaceutical formulation comprising a tetracycline salt according to the invention is also provided, as is a medical device having coated thereon a salt or pharmaceutical formulation according to the invention. A salt of the invention, or a formulation of the invention are also provided for use as medicaments, particularly for use in the treatment or prevention of an inflammation and/or an infection.Type: ApplicationFiled: November 24, 2016Publication date: December 6, 2018Applicant: Hovione Scientia LimitedInventors: Luis SOBRAL, Livia SANTANA DE ARRUDA, Margarida FIGUEIREDO, Rafael ANTUNES, Ana Paula FILIPE
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Patent number: 9670246Abstract: A process for preparing compounds of formula [II] by esterification of the C-17 hydroxyl group of 6?,9?-difluoro-11?,17?-dihydroxy-16?-methyl-3-oxoandrosta-1,4-diene-17?-carbothioic acid, the compound of formula [I] comprises treating compound [I] with a slight excess of an acyl chloride of general formula R—COCl, where R represents —CH2CH3, —CH2CH2CH3 or —CH(CH3)2, in an inert solvent, in the presence of a tertiary amine. Preferably the process is carried out using pyridine in the presence of acetone at a temperature of from 5° C. to ?20° C.Type: GrantFiled: December 2, 2004Date of Patent: June 6, 2017Assignee: Hovione Inter Ltd.Inventors: Luis Sobral, Dionisio Martin, William Heggie, Emilia Leitäo
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Publication number: 20160346206Abstract: A new scalable process to control the particle size and the particle size distribution, comprising5 steps: (i) suspension preparation in a mixture of solvents in which the API and/or excipient is partially soluble in one of the solvents; (ii) particle size reduction of the suspension; (iii) aging; (iv) stopping the aging by solvent removal; and (v) optionally, a step of isolating the processed ingredients in the form of powder.Type: ApplicationFiled: January 27, 2015Publication date: December 1, 2016Inventors: Eunice Costa, Marcio Temtem, Luis Sobral, Constanca Cacela, Peter Villax
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Patent number: 9090607Abstract: The present invention relates to a novel process for the preparation of tiotropium bromide there is provided a process for preparing tiotropium bromide comprising (i) reacting scopine oxalate with diethylamine in an inert solvent to form scopine; (ii) reacting scopine and methyl di-(2-dithienyl)glycolate (MDTG) in the presence of an inorganic base, and in an inert solvent to form N-demethyltiotropium; (iii) reacting N-demethyltiotropium with bromomethane in an inert solvent to form tiotropium bromide; (iv) crystallizing tiotropium bromide in a mixture of methanol and acetone, and optionally thereafter, (v) micronizing the tiotropium bromide so formed.Type: GrantFiled: February 8, 2013Date of Patent: July 28, 2015Assignee: Hovione International LimitedInventors: Luis Sobral, Marcio Temtem, Rafael Antunes, Bruna Nunes
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Publication number: 20150018556Abstract: The present invention relates to a novel process for the preparation of tiotropium bromide there is provided a process for preparing tiotropium bromide comprising (i) reacting scopine oxalate with diethylamine in an inert solvent to form scopine; (ii) reacting scopine and methyl di-(2-dithienyl)glycolate (MDTG) in the presence of an inorganic base, and in an inert solvent to form N-demethyltiotropium; (iii) reacting N-demethyltiotropium with bromomethane in an inert solvent to form tiotropium bromide; (iv) crystallizing tiotropium bromide in a mixture of methanol and acetone, and optionally thereafter, (v) micronizing the tiotropium bromide so formed.Type: ApplicationFiled: February 8, 2013Publication date: January 15, 2015Applicant: Hovione International LimitedInventors: Luis Sobral, Marcio Temtem, Rafael Antunes, Bruna Nunes
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Publication number: 20130131378Abstract: This invention relates to a new process for preparing 4-nitro-oxy-methyl-benzoic acid, comprising the following steps: a) reaction of 4-chloromethyl-benzoic acid with silver nitrate and in the presence of an acid as a catalyst in acetonitrile at reflux temperature, followed by cooling and adding of a polar aprotic solvent; b) separation of the silver salts by filtration, followed by washout with a polar aprotic solvent; c) precipitation of the 4-nitro-oxy-methyl-benzoic acid with water from the filtrate obtained in step b); and d) drying of the 4-nitro-oxy-methyl-benzoic acid.Type: ApplicationFiled: November 15, 2010Publication date: May 23, 2013Applicants: NICOX S.A., FERRER INTERNACIONAL, S.AInventors: Luis Anglada, Albert Palomer, Luis Sobral
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Patent number: 8445471Abstract: A process for obtaining 21-disodium phosphate pregnane derivative compounds of formula (I), wherein X?R?H or X?F and R=?-CH3 or X?F and R=?-CH3: comprises spray drying a solution comprising compound of formula (I).Type: GrantFiled: May 16, 2008Date of Patent: May 21, 2013Assignee: Hovione Inter LimitedInventors: Luis Sobral, Filipe Gaspar, William Heggie, Emilia Leitao, Jose Rafael Antunes
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Publication number: 20100240916Abstract: A process for obtaining 21-disodium phosphate pregnane derivative compounds of formula (I), wherein X?R?H or X?F and R=?-CH3 or X?F and R=?-CH3 comprises spray drying a solution comprising compound of formula (I).Type: ApplicationFiled: May 16, 2008Publication date: September 23, 2010Applicant: HOVIONE INTER LIMITEDInventors: Luis Sobral, Filipe Gaspar, William Heggie, Emilia Leitao, Jose Rafael Antunes
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Publication number: 20070287846Abstract: A process for preparing compounds of formula [II] by esterification of the C-17 hydroxyl group of 6?,9?-difluoro-11?,17?-dihydroxy-16?-methyl-3-oxoandrosta-1,4-diene-17?-carbothioic acid, the compound of formula [I] comprises treating compound [I] with a slight excess of an acyl chloride of general formula R—COCl, where R represents —CH2CH3, —CH2CH2CH3 or —CH(CH3)2, in an inert solvent, in the presence of a tertiary amine. Preferably the process is carried out using pyridine in the presence of acetone at a temperature of from 5° C. to ?20° C.Type: ApplicationFiled: December 2, 2004Publication date: December 13, 2007Inventors: Luis Sobral, Dionisio Martin, William Heggie, Emilia Leitao
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Patent number: 6204368Abstract: A process for the purification of roxithromycin, an antibiotic for therapeutic purposes, in which the purification is carried out by the dissolution or suspension of the product in methanol followed by cooling. Purification may also be obtained by addition of a non-solvent and/or by concentration of the mixture, thus obtaining a purified product.Type: GrantFiled: August 11, 1999Date of Patent: March 20, 2001Assignee: Hovione Inter Ltd.Inventors: William Heggie, Alexandre Carvalho, Luis Sobral