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WO2009080693A2 - Compositions pharmaceutiques - Google Patents

Compositions pharmaceutiques Download PDF

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Publication number
WO2009080693A2
WO2009080693A2 PCT/EP2008/067856 EP2008067856W WO2009080693A2 WO 2009080693 A2 WO2009080693 A2 WO 2009080693A2 EP 2008067856 W EP2008067856 W EP 2008067856W WO 2009080693 A2 WO2009080693 A2 WO 2009080693A2
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutically acceptable
acceptable salt
beta blocker
compound
stereoisomers
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/EP2008/067856
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English (en)
Other versions
WO2009080693A3 (fr
Inventor
Dieter H. Meier
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.)
NTG Nordic Transport Group AS
Original Assignee
Neurosearch AS
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 Neurosearch AS filed Critical Neurosearch AS
Publication of WO2009080693A2 publication Critical patent/WO2009080693A2/fr
Publication of WO2009080693A3 publication Critical patent/WO2009080693A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents

Definitions

  • This invention relates to novel pharmaceutical compositions comprising a therapeutically effective combination of a compound of Formula I and a beta blocker.
  • the pharmaceutical compositions for use according to the invention are contemplated particularly useful for combating obesity or an obesity associated disease.
  • a combination of a compound of Formula I and a beta blocker constitute a particularly useful combination for use in therapy associated with obesity or an obesity associated disease.
  • the invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I, any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof and a beta blocker or a pharmaceutically acceptable salt thereof, together with one or more adjuvants, excipients, carriers and/or diluents.
  • the invention relates to the use of a combination of a compound of Formula I, any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof and a beta blocker or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment, prevention or alleviation of obesity or an obesity associated disease of a mammal, including a human.
  • the invention provides a kit of parts comprising at least two separate unit dosage forms (A) and (B), wherein (A) comprises a compound of Formula I, any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof; and (B) comprises a beta blocker or a pharmaceutically acceptable salt thereof; and optionally (C) instructions for the simultaneous, sequential or separate administration of the compound of (A) and the beta blocker of (B) to a patient in need thereof.
  • the invention provides a method of treatment, prevention or alleviation of obesity or an obesity associated disease of a living animal body, including a human, which method comprises the step of administering to such a living animal body in need thereof, a therapeutically effective amount of a compound of Formula I, any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof; and a beta blocker or a pharmaceutically acceptable salt thereof.
  • the invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a therapeutically effective amount of (i) a compound of Formula I
  • R a represents hydrogen or alkyl
  • R b represents a dihalophenyl group; any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof; and (ii) a beta blocker; or a pharmaceutically acceptable salt thereof; together with one or more adjuvants, excipients, carriers and/or diluents.
  • the compounds of Formula I for use according to the invention are monoamine neurotransmitter re-uptake inhibitors, and are described in WO 97/30997 (NeuroSearch A/S).
  • the compounds may be prepared by conventional methods for chemical synthesis, e.g. those described in WO 97/30997 and WO 2005/073228.
  • R a represents hydrogen or methyl. In a special embodiment, R a represents hydrogen. In a further embodiment, R a represents methyl.
  • R b represents dichlorophenyl. In a special embodiment, R b represents 3,4-dichlorophenyl.
  • the compound of Formula I is tesofensine [(-/R,2R,3S,5S)-3-(3,4-dichlorophenyl)-2-(ethoxymethyl)-8-methyl- 8-azabicyclo[3.2.1]octane]; or
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof. In a further special embodiment, the compound of Formula I is the citrate salt of tesofensine.
  • halo represents fluoro, chloro, bromo or iodo.
  • an alkyl group means a straight chain or branched chain of one to six carbon atoms, including but not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, and hexyl; methyl, ethyl, propyl and isopropyl are preferred groups.
  • the present invention involves the use of a class of drugs known as beta blocking compounds or simply beta blockers.
  • the beta blocker for use according to the invention is any conventional beta blocker known in the art.
  • the beta blocking drug is selected from the following groups of compounds, which groups of compounds are known in the art and may be commercially available under different brand names, or may be obtained as described in the literature:
  • the beta blocker for use according to the invention is a non-selective beta blocker.
  • non-selective beta blockers examples include alprenolol, amosulalol, bucindolol, carteolol, levobunolol, mepindolol, metipranolol, nadolol, oxprenolol, penbutolol, pindolol, propranolol, sotalol and timolol.
  • the beta blocker is selected from the group consisting of alprenolol, amosulalol, bucindolol, carteolol, levobunolol, mepindolol, metipranolol, nadolol, oxprenolol, penbutolol, pindolol, propranolol, sotalol, timolol and pharmaceutically acceptable salts thereof.
  • the beta blocker for use according to the invention is a beta 1 -selective beta blocker.
  • beta 1 -selective beta blockers examples include acebutolol, atenolol, betaxolol, bisoprolol, esmolol, landiolol, metoprolol and nebivolol.
  • the beta blocker is selected from the group consisting of acebutolol, atenolol, betaxolol, bisoprolol, esmolol, landiolol, metoprolol, nebivolol and pharmaceutically acceptable salts thereof.
  • the beta blocker for use according to the invention is a mixed alpha and beta blocker.
  • mixed alpha and beta blockers examples include carvedilol, celiprolol and labetalol.
  • the beta blocker is selected from the group consisting of carvedilol, celiprolol, labetalol and pharmaceutically acceptable salts thereof.
  • Beta 2-selective beta blockers are selected from the group consisting of carvedilol, celiprolol, labetalol and pharmaceutically acceptable salts thereof.
  • the beta blocker for use according to the invention is a beta 2-selective beta blocker.
  • beta 2-selective beta blocker is butaxamine.
  • the beta blocker is selected from the group consisting of butaxamine and pharmaceutically acceptable salts thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is selected from the group consisting of: alprenolol, amosulalol, bucindolol, carteolol, levobunolol, mepindolol, metipranolol, nadolol, oxprenolol, penbutolol, pindolol, propranolol, sotalol, timolol, acebutolol, atenolol, betaxolol, bisoprolol, esmolol, landiolol, metoprolol, nebivolol, carvedilol, celiprolol, labetalol, butaxamine, and pharmaceutically acceptable salts thereof.
  • the beta blocker is selected from the group consisting of: alprenolol, amosulalol,
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is alprenolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is amosulalol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is bucindolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is carteolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is levobunolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is mepindolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is metipranolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is nadolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is oxprenolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is penbutolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is pindolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is propranolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is sotalol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is timolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is acebutolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is atenolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is betaxolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is bisoprolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is esmolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is landiolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is metoprolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is nebivolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is carvedilol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is celiprolol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is labetalol or a pharmaceutically acceptable salt thereof.
  • the compound of Formula I is tesofensine or a pharmaceutically acceptable salt thereof and the beta blocker is butaxamine or a pharmaceutically acceptable salt thereof.
  • the active compounds for use according to the invention may be provided in any form suitable for the intended administration. Suitable forms include pharmaceutically (i.e. physiologically) acceptable salts, and pre- or prodrug forms of the compound of the invention.
  • Examples of pharmaceutically acceptable addition salts include, without limitation, the non-toxic inorganic and organic acid addition salts such as the hydrochloride, the hydrobromide, the nitrate, the perchlorate, the phosphate, the sulphate, the formate, the acetate, the aconate, the ascorbate, the benzene- sulphonate, the benzoate, the cinnamate, the citrate, the embonate, the enantate, the fumarate, the glutamate, the glycolate, the lactate, the maleate, the malonate, the mandelate, the methanesulphonate, the naphthalene-2-sulphonate, the phthalate, the salicylate, the sorbate, the stearate, the succinate, the tartrate, the toluene-p-sulphonate, and the like.
  • the non-toxic inorganic and organic acid addition salts such as the hydrochloride, the hydrobromide,
  • Such salts may be formed by procedures well known and described in the art.
  • Examples of pharmaceutically acceptable cationic salts of a chemical compound of the invention include, without limitation, the sodium, the potassium, the calcium, the magnesium, the zinc, the aluminium, the lithium, the choline, the lysinium, and the ammonium salt, and the like, of a chemical compound of the invention containing an anionic group.
  • Such cationic salts may be formed by procedures well known and described in the art.
  • onium salts of N-containing compounds are also contemplated as pharmaceutically acceptable salts.
  • Preferred “onium salts” include the alkyl-onium salts, the cycloalkyl-onium salts, and the cycloalkylalkyl-onium salts.
  • pre- or prodrug forms of the chemical compound for use according to the invention include examples of suitable prodrugs of the substances for use according to the invention include compounds modified at one or more reactive or derivatizable groups of the parent compound. Of particular interest are compounds modified at a carboxyl group, a hydroxyl group, or an amino group. Examples of suitable derivatives are esters or amides.
  • the chemical compounds for use according to the invention may be provided in dissoluble or indissoluble forms together with a pharmaceutically acceptable solvent such as water, ethanol, and the like.
  • Dissoluble forms may also include hydrated forms such as the monohydrate, the dihydrate, the hemihydrate, the trihydrate, the tetrahydrate, and the like. In general, the dissoluble forms are considered equivalent to indissoluble forms for the purposes of this invention.
  • compositions for use according to the invention are contemplated particularly useful for combating obesity or an obesity associated disease.
  • obesity or an obesity associated disease is a disorder or condition selected from the group consisting of obesity, over-eating disorders, bulimia nervosa, binge eating disorder (BED), compulsive over-eating, impaired appetite regulation, metabolic syndrome, type 2 diabetes, dyslipidemia, atherosclerosis.
  • BED binge eating disorder
  • compositions for use according to the invention are also contemplated useful for obesity management, obtaining weight loss, weight maintenance, and weight maintenance used in conjunction with a reduced-calorie diet.
  • Pharmaceutical Compositions are also contemplated useful for obesity management, obtaining weight loss, weight maintenance, and weight maintenance used in conjunction with a reduced-calorie diet.
  • the compounds for use according to the invention may be administered in the form of the raw compound, it is preferred to introduce the active ingredients, optionally in the form of physiologically acceptable salts, in a pharmaceutical composition together with one or more adjuvants, excipients, carriers, buffers, diluents, and/or other customary pharmaceutical auxiliaries.
  • the invention provides pharmaceutical compositions comprising the active compounds or pharmaceutically acceptable salts or derivatives thereof, together with one or more pharmaceutically acceptable carriers therefore, and, optionally, other therapeutic and/or prophylactic ingredients, know and used in the art.
  • the carher(s) must be "acceptable” in the sense of being compatible with the other ingredients of the formulation and not harmful to the recipient thereof.
  • the pharmaceutical composition of the invention may be administered by any convenient route, which suits the desired therapy.
  • Preferred routes of administration include oral administration, in particular in tablet, in capsule, in drage, in powder, or in liquid form, and parenteral administration, in particular cutaneous, subcutaneous, intramuscular, or intravenous injection.
  • the pharmaceutical composition of the invention can be manufactured by the skilled person by use of standard methods and conventional techniques appropriate to the desired formulation. When desired, compositions adapted to give sustained release of the active ingredient may be employed.
  • each of the active ingredients depends on the nature and severity of the disease being treated, the exact mode of administration, form of administration and is within the discretion of the physician, and may be varied by titration of the dosage to the particular circumstances of this invention to produce the desired therapeutic effect.
  • the below dosages for the compound of Formula I and the beta blocker are considered suitable.
  • the dosage of the compound of Formula I is determined as the API (Active Pharmaceutical Ingredient), i.e. calculated as the free base.
  • the daily dosage of the compound of Formula I may be administered in one or several doses, such as two, per day. In one embodiment, the daily dosage is administered in one dose.
  • the daily dosage of the beta blocker is presently contemplated to be in the range of about 0.1-500 mg of active ingredient depending on the actual compound. More specific dosage intervals may be in the range of about 0.1 -2 mg, about 1-10 mg, about 10-50 mg, about 25-100 mg, about 50-200 mg and about 100-500 mg daily.
  • the daily dosage of the beta blocker may be administered in one or several doses, such as two, per day. In one embodiment, the daily dosage is administered in one dose.
  • kit of parts comprising at least two separate unit dosage forms (A) and (B): (A) a compound of Formula I
  • R a represents hydrogen or alkyl
  • R b represents a dihalophenyl group; any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof;
  • the compound of Formula I for use according to the invention and the beta blocker for use according to the invention may preferably be provided in a form that is suitable for administration in conjunction with the other. This is intended to include instances where one or the other of two formulations may be administered (optionally repeatedly) prior to, after, and/or at the same time as administration with the other component.
  • the compound of Formula I for use according to the invention and the beta blocker for use according to the invention may be administered in a combined form, or separately or separately and sequentially, wherein the sequential administration is close in time or remote in time.
  • This may in particular include that two formulations are administered (optionally repeatedly) sufficiently closely in time for there to be a beneficial effect for the patient, that is greater over the course of the treatment of the relevant condition than if either of the two formulations are administered (optionally repeatedly) alone, in the absence of the other formulation, over the same course of treatment. Determination of whether a combination provides a greater beneficial effect in respect of, and over the course of treatment of, a particular condition, will depend upon the condition to be treated or prevented, but may be achieved routinely by the person skilled in the art.
  • administered simultaneously and “administered at the same time as” include that individual doses of the compound of Formula I and the beta blocker are administered within 48 hours, e.g. 24 hours, of each other.
  • Bringing the two components into association with each other includes that components (A) and (B) may be provided as separate formulations (i.e. independently of one another), which are subsequently brought together for use in conjunction with each other in combination therapy; or packaged and presented together as separate components of a "combination pack" for use in conjunction with each other in combination therapy.
  • the invention provides methods of treatment, prevention or alleviation of obesity or an obesity associated disease of a living animal body, including a human, which method comprises the step of administering to such a living animal body in need thereof, a therapeutically effective amount of a combination of a compound of Formula I, any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof and a beta blocker or a pharmaceutically acceptable salt thereof.
  • the dose regimen When administered in combination with further compounds known in the art for treatment of the diseases, the dose regimen may be reduced.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention porte sur de nouvelles compositions pharmaceutiques comprenant une combinaison thérapeutiquement efficace d'un composé représenté par la formule I et d'un bêta-bloquant. Les compositions pharmaceutiques destinées à être utilisées selon l'invention sont considérées comme étant particulièrement utiles pour combattre l'obésité ou une maladie associée à l'obésité.
PCT/EP2008/067856 2007-12-20 2008-12-18 Compositions pharmaceutiques Ceased WO2009080693A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DKPA200701834 2007-12-20
DKPA200701834 2007-12-20
US1606707P 2007-12-21 2007-12-21
US61/016,067 2007-12-21

Publications (2)

Publication Number Publication Date
WO2009080693A2 true WO2009080693A2 (fr) 2009-07-02
WO2009080693A3 WO2009080693A3 (fr) 2009-08-27

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PCT/EP2008/067856 Ceased WO2009080693A2 (fr) 2007-12-20 2008-12-18 Compositions pharmaceutiques

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013120935A1 (fr) 2012-02-16 2013-08-22 Neurosearch A/S Compositions pharmaceutiques pour traitement combiné
WO2016138908A1 (fr) * 2015-03-03 2016-09-09 Saniona A/S Formulation à base de combinaison de tésofensine et de bêta-bloquant

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2005205880B2 (en) * 2004-01-22 2010-06-10 Neurosearch A/S Compounds for the sustained reduction of body weight

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EA029543B1 (ru) * 2012-02-16 2018-04-30 Саниона А/С Способ лечения, профилактики или уменьшения сердечно-сосудистых побочных эффектов тезофенсина
CN104244935A (zh) * 2012-02-16 2014-12-24 神经研究公司 用于联合治疗的药物组合物
JP2015508765A (ja) * 2012-02-16 2015-03-23 ニューロサーチ・エー／エスＮｅｕｒｏｓｅａｒｃｈ Ａ／Ｓ 併用療法のための医薬組成物
US9211271B2 (en) 2012-02-16 2015-12-15 Saniona A/S Pharmaceutical compositions for combination therapy
US9387184B2 (en) 2012-02-16 2016-07-12 Saniona A/S Pharmaceutical compositions for combination therapy
WO2013120935A1 (fr) 2012-02-16 2013-08-22 Neurosearch A/S Compositions pharmaceutiques pour traitement combiné
CN108853071A (zh) * 2012-02-16 2018-11-23 萨尼奥纳有限责任公司 用于联合治疗的药物组合物
AU2013220424B2 (en) * 2012-02-16 2017-03-23 Saniona A/S Pharmaceutical compositions for combination therapy
CN108434129A (zh) * 2012-02-16 2018-08-24 萨尼奥纳有限责任公司 用于联合治疗的药物组合物
US20180185304A1 (en) * 2012-02-16 2018-07-05 Saniona A/S Pharmaceutical compositions for combination therapy
WO2016138908A1 (fr) * 2015-03-03 2016-09-09 Saniona A/S Formulation à base de combinaison de tésofensine et de bêta-bloquant
JP2018507875A (ja) * 2015-03-03 2018-03-22 サニオナ・エー／エス テソフェンシンとベータブロッカーの合剤
KR20170134393A (ko) * 2015-03-03 2017-12-06 사니오나 에이/에스 테소펜신, 베타 차단제 복합 제형
US9579288B2 (en) 2015-03-03 2017-02-28 Saniona A/S Tesofensine and beta blocker combination formulations
US10231951B2 (en) 2015-03-03 2019-03-19 Saniona A/S Tesofensine, beta blocker combination formulation
EA033298B1 (ru) * 2015-03-03 2019-09-30 Саниона А/С Комбинированная лекарственная форма тезофензина и метопролола
KR101999463B1 (ko) * 2015-03-03 2019-10-01 사니오나 에이/에스 테소펜신, 베타 차단제 복합 제형
US10537551B2 (en) 2015-03-03 2020-01-21 Saniona A/S Tesofensine and beta blocker combination formulations
US20200129478A1 (en) * 2015-03-03 2020-04-30 Saniona A/S Tesofensine and beta blocker combination formulations
US10828278B2 (en) 2015-03-03 2020-11-10 Saniona A/S Tesofensine and beta blocker combination formulations
US11426383B2 (en) 2015-03-03 2022-08-30 Saniona A/S Tesofensine and beta blocker combination formulations
US12016840B2 (en) 2015-03-03 2024-06-25 Saniona A/S Tesofensine and beta blocker combination formulations

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