WO2013131967A1 - Pharmaceutical compositions comprising metformin and a dpp -4 inhibitor or a sglt-2 inhibitor - Google Patents

Pharmaceutical compositions comprising metformin and a dpp -4 inhibitor or a sglt-2 inhibitor Download PDF

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Publication number
WO2013131967A1
WO2013131967A1 PCT/EP2013/054524 EP2013054524W WO2013131967A1 WO 2013131967 A1 WO2013131967 A1 WO 2013131967A1 EP 2013054524 W EP2013054524 W EP 2013054524W WO 2013131967 A1 WO2013131967 A1 WO 2013131967A1
Authority
WO
WIPO (PCT)
Prior art keywords
coating
pharmaceutical composition
film
linagliptin
composition according
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/EP2013/054524
Other languages
English (en)
French (fr)
Inventor
Masanori Ito
Kenji Egusa
Kyle KLEINBECK
Roman Messerschmid
Peter Schneider
Venkata VOLETI
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.)
Boehringer Ingelheim International GmbH
Original Assignee
Boehringer Ingelheim International GmbH
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=47827222&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2013131967(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority to EA201400986A priority Critical patent/EA201400986A1/ru
Priority to JP2014560356A priority patent/JP2015509519A/ja
Priority to IN6501DEN2014 priority patent/IN2014DN06501A/en
Priority to SG11201405509UA priority patent/SG11201405509UA/en
Priority to AU2013229538A priority patent/AU2013229538A1/en
Priority to HK15105677.2A priority patent/HK1204953A1/xx
Priority to EP13707649.3A priority patent/EP2822544A1/en
Priority to CA2866421A priority patent/CA2866421A1/en
Priority to MX2014010560A priority patent/MX2014010560A/es
Application filed by Boehringer Ingelheim International GmbH filed Critical Boehringer Ingelheim International GmbH
Priority to CN201380019305.0A priority patent/CN104220049A/zh
Priority to KR1020147024974A priority patent/KR20140131950A/ko
Publication of WO2013131967A1 publication Critical patent/WO2013131967A1/en
Priority to PH12014501984A priority patent/PH12014501984A1/en
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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers

Definitions

  • the present invention relates to a pharmaceutical composition, particularly a solid preparation (e.g. an oral solid dosage form, such as e.g. a tablet), comprising or consisting essentially of
  • DPP-4 inhibitor preferably linagliptin
  • the polyethylene oxide is SENTRYTM POLYOXTM WSR 303.
  • the plasticizer may be one or more of polyethylene glycol (PEG, such as e.g. Macrogol 400, 3000, 4000, 6000 and/or 8000), propylene glycol, diethyl phthalate, tributyl sebacate and/or triacetin, or mixtures thereof (e.g. a mixture of polyethylene glycol and triacetin).
  • PEG polyethylene glycol
  • the plasticizer may be one or more of polyethylene glycol (PEG, such as e.g. Macrogol 400, 3000, 4000, 6000 and/or 8000), propylene glycol, diethyl phthalate, tributyl sebacate and/or triacetin, or mixtures thereof (e.g. a mixture of polyethylene glycol and triacetin).
  • - linagliptin such as e.g. from 0.5 mg to 10 mg (e.g. 2.5 mg or 5 mg),
  • Table 1 Example (prototypical) formulations for API-coating of linagliptin on top of metformin XR cores
  • methylcellulose 19.5 19.5 19.5 19.5 e.g. 3 cP
  • hydroxypropylmethylcellulose and polyethylene glycol may be employed as a further film coating system in the preparation of the API coating.
  • an immediate release coating comprising
  • Polyethylene glycol e.g. PEG 8000, e.g. 2.70% w/w
  • the parts hydroxypropyl methylcellulose (e.g. 3 cP) and polyethylene glycol (e.g. PEG 8000) may be employed together (such as e.g. as a film coating system) or separately in the preparation of the API coating.
  • talc e.g. 5-20 % w/w, preferably 8-16 % w/w, such as 12.5 or 10.7 % w/w
  • an extended release core comprising
  • metformin particularly metformin hydrochloride
  • polyethylene oxide e.g. high molecular weight, e.g. about 7,000,000, such as WSR-303, e.g. 23-35 % w/w
  • WSR-303 e.g. 23-35 % w/w
  • L-arginine e.g. the weight ratio L-arginine:linagliptin may be 1 :1 to 5:1 , preferably 2:1 to 4:1 , especially 4:1 ; such as e.g. 4-40 % w/w, preferably 10-30 % w/w, such as 14 or 24 % w/w), hydroxypropyl methylcellulose (e.g. hydroxypropyl methylcellulose of 3 cP, e.g. 40-70 % w/w, preferably 40-65 % w/w, such as 53.2 or 45.2 % w/w), polyethylene glycol of molecular weight of about 8000 (e.g. 0-5 % w/w, preferably 2-4 % w/w, such as 2.8 or 2.4 % w/w),
  • hydroxypropyl methylcellulose e.g. hydroxypropyl methylcellulose of 3 cP, e.g. 40-70 % w/w, preferably 40
  • the API (linagliptin or Compound “A") and - preferably in case of linagliptin - the stabilizer L- arginine are dissolved or suspended in water and added to the aqueous solution of HPMC,
  • the API (linagliptin or Compound “A”) is dissolved or suspended in water and added to the aqueous solution of HPMC, PEG or PG, optional L-arginine and optional talc to provide the API coating suspension.
  • the film-coating operation is carried out in a conventional film coater.
  • the film coating suspension and/or API (linagliptin or Compound “A") coating suspension/solution are coated at (optionally seal and/or barrier coated) metformin XR cores via coating process.
  • plasticizers e.g. selected from polyethylene glycol (such as e.g.
  • IGF paired fasting blood glucose
  • a subject with "normal fasting glucose” has a fasting glucose concentration smaller than 100 mg/dl, i.e. smaller than 5.6 mmol/l.
  • insulin resistance the response of a patient with insulin resistance to therapy, insulin sensitivity and hyperinsulinemia may be quantified by assessing the "homeostasis model assessment to insulin resistance (HOMA-IR)" score, a reliable indicator of insulin resistance (Katsuki A, et al. Diabetes Care 2001 ; 24: 362-5). Further reference is made to methods for the determination of the HOMA-index for insulin sensitivity (Matthews et al., Diabetologia 1985, 28: 412-19), of the ratio of intact proinsulin to insulin (Forst et al., Diabetes 2003, 52(Suppl.1): A459) and to an euglycemic clamp study.
  • HOMA-IR homeostasis model assessment to insulin resistance
  • NODAT new onset diabetes after transplantation
  • PTMS post- transplant metabolic syndrome
  • IDF International Diabetes Federation
  • PTMS post- transplant metabolic syndrome
  • NODAT and/or PTMS are associated with an increased risk of micro- and macrovascular disease and events, graft rejection, infection, and death.
  • a number of predictors have been identified as potential risk factors related to NODAT and/or PTMS including a higher age at transplant, male gender, the pre-transplant body mass index, pre- transplant diabetes, and immunosuppression.
  • Purified water is charged into a stainless steel mixing vessel equipped with a suitable mixer. While mixing at a speed that ensures vortex formation, each component polyethylene glycol (PEG 6000), L-arginine, linagliptin, talc and the Film Forming System (HPMC 2910-3 and PEG 8000) is added. The coating suspension is mixed for at least 20 minutes or until the last component added is homogenized. An appropriate quantity of barrier-coated tablet cores are charged to the coating pan of the perforated coating system equipped with a peristaltic pump and two spray nozzles. After the cores are preheated, pan rotation and spraying of the coating suspension begin. A fixed amount of the active coating suspension, which incorporates approximately 10% excess to account for losses during spraying, is applied.
  • PEG 6000 polyethylene glycol
  • L-arginine L-arginine
  • linagliptin linagliptin
  • talc the Film Forming System
  • HPMC 2910-3 and PEG 8000 Film Forming System
  • compositions can be obtained.
  • Titanium dioxide (e.g. 32.43% w/w)

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Molecular Biology (AREA)
  • Physiology (AREA)
  • Nutrition Science (AREA)
  • Obesity (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Emergency Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/EP2013/054524 2012-03-07 2013-03-06 Pharmaceutical compositions comprising metformin and a dpp -4 inhibitor or a sglt-2 inhibitor Ceased WO2013131967A1 (en)

Priority Applications (12)

Application Number Priority Date Filing Date Title
KR1020147024974A KR20140131950A (ko) 2012-03-07 2013-03-06 메트포르민 및 ｄｄｐ―４ 억제제 또는 ｓｇｌｔ―２ 억제제를 포함하는 약제학적 조성물
EP13707649.3A EP2822544A1 (en) 2012-03-07 2013-03-06 Pharmaceutical compositions comprising metformin and a dpp -4 inhibitor or a sglt-2 inhibitor
IN6501DEN2014 IN2014DN06501A (https=) 2012-03-07 2013-03-06
SG11201405509UA SG11201405509UA (en) 2012-03-07 2013-03-06 Pharmaceutical compositions comprising metformin and a dpp -4 inhibitor or a sglt-2 inhibitor
AU2013229538A AU2013229538A1 (en) 2012-03-07 2013-03-06 Pharmaceutical compositions comprising metformin and a DPP-4 inhibitor or a SGLT-2 inhibitor
HK15105677.2A HK1204953A1 (en) 2012-03-07 2013-03-06 Pharmaceutical compositions comprising metformin and a dpp -4 inhibitor or a sglt-2 inhibitor
CA2866421A CA2866421A1 (en) 2012-03-07 2013-03-06 Pharmaceutical compositions comprising metformin and a dpp -4 inhibitor or a sglt-2 inhibitor
EA201400986A EA201400986A1 (ru) 2012-03-07 2013-03-06 Фармацевтические композиции, содержащие метформин и ингибитор dpp-4 или ингибитор sglt-2
MX2014010560A MX2014010560A (es) 2012-03-07 2013-03-06 Composiciones farmaceuticas que comprenden metformina y un inhibidor de dpp-4 o un inhibidor de sglt-2.
JP2014560356A JP2015509519A (ja) 2012-03-07 2013-03-06 メトホルミン及びｄｐｐ−４阻害薬又はｓｇｌｔ−２阻害薬を含む医薬組成物
CN201380019305.0A CN104220049A (zh) 2012-03-07 2013-03-06 包含二甲双胍和dpp-4抑制剂或sglt-2抑制剂的药物组合物
PH12014501984A PH12014501984A1 (en) 2012-03-07 2014-09-05 Pharmaceutical compositions comprising metformin and a dpp-4 inhibitor or a sglt-2 inhibitor

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261607771P 2012-03-07 2012-03-07
US61/607,771 2012-03-07

Publications (1)

Publication Number Publication Date
WO2013131967A1 true WO2013131967A1 (en) 2013-09-12

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ID=47827222

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Application Number Title Priority Date Filing Date
PCT/EP2013/054524 Ceased WO2013131967A1 (en) 2012-03-07 2013-03-06 Pharmaceutical compositions comprising metformin and a dpp -4 inhibitor or a sglt-2 inhibitor

Country Status (17)

Country Link
US (3) US9555001B2 (https=)
EP (1) EP2822544A1 (https=)
JP (1) JP2015509519A (https=)
KR (1) KR20140131950A (https=)
CN (1) CN104220049A (https=)
AR (1) AR090269A1 (https=)
AU (1) AU2013229538A1 (https=)
CA (1) CA2866421A1 (https=)
CL (1) CL2014002325A1 (https=)
EA (1) EA201400986A1 (https=)
HK (1) HK1204953A1 (https=)
IN (1) IN2014DN06501A (https=)
MX (1) MX2014010560A (https=)
PH (1) PH12014501984A1 (https=)
SG (1) SG11201405509UA (https=)
TW (1) TW201400144A (https=)
WO (1) WO2013131967A1 (https=)

Cited By (35)

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WO2014056942A1 (en) 2012-10-09 2014-04-17 Boehringer Ingelheim International Gmbh Use of selectively moisture-adjusted tabletting material in the production of mechanically stable tablets which contain at least one hydrate-forming active substance and/or adjuvant relevant to the mechanical stability of the tablets, particularly arginine-containing tablets
WO2014080384A1 (en) * 2012-11-26 2014-05-30 Ranbaxy Laboratories Limited Pharmaceutical composition of linagliptin
US9192617B2 (en) 2012-03-20 2015-11-24 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof
WO2015107536A3 (en) * 2013-12-09 2015-11-26 Intas Pharmaceuticals Limited Fixed dose combination comprising linagliptin and metformin hci
WO2016059219A1 (en) * 2014-10-17 2016-04-21 Boehringer Ingelheim International Gmbh Pharmaceutical composition and uses thereof
US9415016B2 (en) 2008-04-03 2016-08-16 Boehringer Ingelheim International Gmbh DPP-IV inhibitor combined with a further antidiabetic agent, tablets comprising such formulations, their use and process for their preparation
US9457029B2 (en) 2009-11-27 2016-10-04 Boehringer Ingelheim International Gmbh Treatment of genotyped diabetic patients with DPP-IV inhibitors such as linagliptin
US9486526B2 (en) 2008-08-06 2016-11-08 Boehringer Ingelheim International Gmbh Treatment for diabetes in patients inappropriate for metformin therapy
US9493462B2 (en) 2006-05-04 2016-11-15 Boehringer Ingelheim International Gmbh Polymorphs
US9499546B2 (en) 2004-11-05 2016-11-22 Boehringer Ingelheim International Gmbh Process for the preparation of chiral 8-(3-aminopiperidin-1-yl)-xanthines
US9526728B2 (en) 2014-02-28 2016-12-27 Boehringer Ingelheim International Gmbh Medical use of a DPP-4 inhibitor
US9526730B2 (en) 2012-05-14 2016-12-27 Boehringer Ingelheim International Gmbh Use of a DPP-4 inhibitor in podocytes related disorders and/or nephrotic syndrome
US9556175B2 (en) 2002-08-21 2017-01-31 Boehringer Ingelheim International Gmbh 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and thier use as pharmaceutical compositions
US9555001B2 (en) 2012-03-07 2017-01-31 Boehringer Ingelheim International Gmbh Pharmaceutical composition and uses thereof
US9603851B2 (en) 2010-05-05 2017-03-28 Boehringer Ingelheim International Gmbh Combination therapy
WO2017093419A1 (en) * 2015-12-04 2017-06-08 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof
US9713618B2 (en) 2012-05-24 2017-07-25 Boehringer Ingelheim International Gmbh Method for modifying food intake and regulating food preference with a DPP-4 inhibitor
WO2017211979A1 (en) 2016-06-10 2017-12-14 Boehringer Ingelheim International Gmbh Combinations of linagliptin and metformin
US9873714B2 (en) 2009-09-30 2018-01-23 Boehringer Ingelheim International Gmbh Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivatives
US9949998B2 (en) 2013-04-05 2018-04-24 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof
US9949997B2 (en) 2013-04-05 2018-04-24 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof
WO2018087132A1 (en) 2016-11-10 2018-05-17 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof
US20180185291A1 (en) 2011-03-07 2018-07-05 Boehringer Ingelheim International Gmbh Pharmaceutical compositions
US10080754B2 (en) 2006-05-04 2018-09-25 Boehringer Ingelheim International Gmbh Uses of DPP IV inhibitors
US10406172B2 (en) 2009-02-13 2019-09-10 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof
US10610489B2 (en) 2009-10-02 2020-04-07 Boehringer Ingelheim International Gmbh Pharmaceutical composition, pharmaceutical dosage form, process for their preparation, methods for treating and uses thereof
US11033552B2 (en) 2006-05-04 2021-06-15 Boehringer Ingelheim International Gmbh DPP IV inhibitor formulations
US11666590B2 (en) 2013-04-18 2023-06-06 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof
US11813275B2 (en) 2013-04-05 2023-11-14 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof
US11911387B2 (en) 2010-11-15 2024-02-27 Boehringer Ingelheim International Gmbh Vasoprotective and cardioprotective antidiabetic therapy
US11911388B2 (en) 2008-10-16 2024-02-27 Boehringer Ingelheim International Gmbh Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral or non-oral antidiabetic drug
EP4403168A1 (en) 2023-01-18 2024-07-24 Adamed Pharma S.A. Fixed-dose combination composition of metformin and empagliflozin
US12312352B2 (en) 2012-05-14 2025-05-27 Boehringer Ingelheim International Gmbh Use of a DPP-4 inhibitor in SIRS and/or sepsis
US12433906B2 (en) 2013-04-05 2025-10-07 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof
US12527810B2 (en) 2009-02-13 2026-01-20 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof

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US7772191B2 (en) 2005-05-10 2010-08-10 Boehringer Ingelheim International Gmbh Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivatives and intermediates therein
UY32030A (es) 2008-08-06 2010-03-26 Boehringer Ingelheim Int "tratamiento para diabetes en pacientes inapropiados para terapia con metformina"
JP2012512848A (ja) 2008-12-23 2012-06-07 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 有機化合物の塩の形態
TW201036975A (en) 2009-01-07 2010-10-16 Boehringer Ingelheim Int Treatment for diabetes in patients with inadequate glycemic control despite metformin therapy
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AR090269A1 (es) 2014-10-29
IN2014DN06501A (https=) 2015-06-12
AU2013229538A1 (en) 2014-08-21
US20130236543A1 (en) 2013-09-12
KR20140131950A (ko) 2014-11-14
HK1204953A1 (en) 2015-12-11
CN104220049A (zh) 2014-12-17
SG11201405509UA (en) 2014-10-30
CL2014002325A1 (es) 2014-12-12
JP2015509519A (ja) 2015-03-30
TW201400144A (zh) 2014-01-01
US20220287980A1 (en) 2022-09-15
CA2866421A1 (en) 2013-09-12
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