WO2015011730A1 - Formulation comprising a hypolipidemic agent - Google Patents

Formulation comprising a hypolipidemic agent Download PDF

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Publication number
WO2015011730A1
WO2015011730A1 PCT/IN2014/000489 IN2014000489W WO2015011730A1 WO 2015011730 A1 WO2015011730 A1 WO 2015011730A1 IN 2014000489 W IN2014000489 W IN 2014000489W WO 2015011730 A1 WO2015011730 A1 WO 2015011730A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
sodium
formula
formulation
calcium
Prior art date
Application number
PCT/IN2014/000489
Other languages
English (en)
French (fr)
Inventor
Jitendre D. PATEL
Prakash DAVADRA
Snehal Patel
Shafiq Sheikh
Original Assignee
Cadila Healthcare Limited
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
Priority to NZ714558A priority Critical patent/NZ714558A/en
Priority to CN201480041453.7A priority patent/CN105407873A/zh
Priority to SG11201509798PA priority patent/SG11201509798PA/en
Priority to AU2014294548A priority patent/AU2014294548B2/en
Priority to US14/899,912 priority patent/US9610277B2/en
Priority to MX2015016971A priority patent/MX374628B/es
Priority to CA2917923A priority patent/CA2917923A1/en
Priority to BR112015031878A priority patent/BR112015031878A2/pt
Priority to KR1020157036380A priority patent/KR101786843B1/ko
Priority to EA201690072A priority patent/EA201690072A1/ru
Priority to HK16107193.2A priority patent/HK1219222A1/zh
Priority to EP14787059.6A priority patent/EP3024446A1/en
Application filed by Cadila Healthcare Limited filed Critical Cadila Healthcare Limited
Priority to MA38865A priority patent/MA38865A1/fr
Priority to JP2016522969A priority patent/JP2016523895A/ja
Publication of WO2015011730A1 publication Critical patent/WO2015011730A1/en
Priority to AP2015008876A priority patent/AP2015008876A0/xx
Priority to ZA2015/08682A priority patent/ZA201508682B/en
Priority to PH12015502802A priority patent/PH12015502802A1/en
Priority to US15/475,812 priority patent/US10098868B2/en

Links

Classifications

    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • A61K9/2009—Inorganic compounds
    • 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
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61P3/06—Antihyperlipidemics

Definitions

  • the present invention relates to stable pharmaceutical compositions of a suitable hypolipidemic agent.
  • the present invention discloses novel formulations of the compound of formula (I), or pharmaceutically acceptable salts of compounds of formula (I). More particularly the present invention relates to the stable pharmaceutical composition of compounds of formula (I) comprising compounds of formula (I) or its pharmaceutically acceptable salts, wherein the pH of the formulation is maintained above 7.
  • the compounds of formula (I) are new synthetic compounds having hypolipidemic activity.
  • the compounds of formula (I) are used primarily for triglyceride lowering, with concomitant beneficial effect on glucose lowering and cholesterol lowering.
  • R' is selected from hydroxy, hydroxyalkyl, acyl, alkoxy, alkylthio, thioalkyl, aryloxy, arylthio and M + represents suitable metal cations such as Na + , K + , Ca +2 , Mg +2 and the like.
  • R is selected from alkylthio or thioalkyl groups; most preferably R represents -SCH 3 .
  • the Mg +2 salt is preferred.
  • the compounds of formula (I) are generally insoluble in water, but freely soluble in dimethyl sulfoxide, dichloromethane & slightly soluble in methanol and IPA.
  • the compounds of formula (I) are susceptible to oxidation, alkaline & acid hydrolysis and stress degradation during synthesis, purification and storage of the drug substance or when formulated as a dosage form.
  • Sulfoxide and sulfone derivatives are the potential oxidized product.
  • one of the impurity (sulfoxide) which was being generated in API increases from 0.17% to 0.76% over a period of 6 months.
  • suitable alkalinizer(s) which maintains the pH of the formulation above 7
  • the increase in the level of said impurity is restricted (from 0.13% to 0.26% over six months with no further increase with time). Therefore stabilization of compositions containing compounds of formula (I) can be made by maintaining the microenvironmental pH of composition above 7 by using suitable alkalinizers.
  • Use of a suitable antioxidant(s) and chelating agent(s) further stabilizes the formulation.
  • the present invention describes a stable pharmaceutical composition of compounds of formula (I) or their derivatives, wherein the microenvironmental pH of the composition is maintained above 7.
  • Figure 1 Percentage of sulfoxide impurity level (0.3 RRT) at different pH after 24 hours.
  • Figure 1 shows the percentage impurity level of sulfoxide. When the pH was modulated by addition of alkalinizer(s) then sulfoxide impurity level in API is restricted.
  • the present invention describes a stable pharmaceutical composition of compounds of formula (I) or their derivatives,
  • 'R' is selected from hydroxy, hydro yalkyl, acyl, alkoxy, alkylthio, thioalkyl, aryloxy, arylthio and M + represents suitable metal cations such as Na + , K + , Ca +2 , Mg +2 and the like and wherein the pH of the composition is maintained above 7.
  • the compound of formula (I) represents Saroglitazar Magnesium of formula (la) having the chemical name Benzenepropanoic acid, a - ethoxy-4-[2-[2-methyl-5-[4-(methylthio) phenyl]-lH - pyrrol-l-yl] ethoxy] magnesium salt and having the following structure
  • the present invention further describes a stable pharmaceutical composition of compounds of formula (I) or their derivatives, preferably a compound of formula (la), comprising one or more pharmaceutical excipients, alkalinizers, antioxidants and chelating agents, wherein the pH of the composition is maintained above 7.
  • the pharmaceutical composition of compound of formula (I) or their derivatives of the present invention essentially comprises of
  • Suitable stabilizers may be selected from the classes of antioxidants or chelating agents.
  • the other pharmaceutical excepients according to the present invention can be selected from suitable diluents, fillers, disintegrants, binder, lubricants, glidants, wetting agents, solvents and the like as is known in the art.
  • Antioxidants used according to the present invention include, but are not limited to citric acid, alpha tocopherol, sodium sulphite, sodium metabisulphite, butylated hydroxy anisole (BHA), BHT (2,6-di-tert-butyl-4-methylphenol), monothioglycerol, Vitamin C (ascorbic acid), and propyl gallate and combinations thereof and other similar material known to those of the ordinary skilled in the art.
  • Chelating agent used according to the present invention include, but are not limited to Disodium EDTA, citric acid and or its salts, maleic acid, chlorambutol, chlorhexidine or its salts, chlorocresol, combinations thereof and other similar material known to those of ordinary skill in the art.
  • Alkalinizers or suitable pH modifying agents which maintain the pH of the formulation above 7 used according to the present invention include, but are not limited to attapulgite, bentonite, calcium carbonate, calcium phosphate, calcium sulphate, mono ethanolamine, tri ethanolamine, potassium bicarbonate, potassium citrate, potassium hydroxide, sodium benzoate, sodium hydroxide, sodium sulfite, sodium bicarbonate, sodium carbonate, Disodium Hydrogen phosphate, mono basic potassium phosphate, Dicalcium phosphate, meglumine, light or heavy magnesium oxide and other similar excipients and their suitable combinations and other materials known to those of ordinary skill in the art.
  • binder is intended to mean substances used to cause adhesion of powder particles in tablet granulations.
  • Such compounds include, by way of example and without limitation, acacia alginic acid, tragacanth, carboxymethylcellulose sodium, poly (vinylpyrrolidone), compressible sugar (e.g., NuTab), ethyl cellulose, gelatin, liquid glucose, methyl cellulose, povidone and pregelatinized starch, combinations thereof and other similar materials known to those of ordinary skill in the art.
  • binders include starch, poly(ethylene glycol), guar gum, polysaccharide, bentonites, sugars, invert sugars, poloxamers (PLURONIC F68, PLURONIC F127), collagen, albumin, celluloses in nonaqueous solvents, and the like or their suitable combinations.
  • binders which may be included may be, for example, poly(propylene glycol), polyoxyethylene-polypropylene copolymer, polyethylene ester, polyethylene sorbitan ester, poly(ethylene oxide), microcrystalline cellulose, poly( vinylpyrrolidone), combinations thereof and other such materials known to those of ordinary skill in the art.
  • the term "diluent” or “filler” is intended to mean inert substances used as fillers to create the desired bulk, flow properties, and compression characteristics in the preparation of tablets and capsules.
  • Such compounds include, by way of example and without limitation, dibasic calcium phosphate, kaolin, sucrose, mannitol, microcrystalline cellulose, powdered cellulose, precipitated calcium carbonate, sorbitol, starch, combinations thereof and other such materials known to those of ordinary skill in the art.
  • the term "glidant” is intended to mean agents used in tablet and capsule formulations to improve flow-properties during tablet compression and to produce an anti-caking effect.
  • Such compounds include, by way of example and without limitation, colloidal silica, calcium silicate, magnesium silicate, silicon hydrogel, cornstarch, talc, combinations thereof and other such materials known to those of ordinary skill in the art.
  • the term “lubricant” is intended to mean substances used in tablet formulations to reduce friction during tablet compression. Such compounds include, by way of example and without limitation, calcium stearate, magnesium stearate, mineral oil, stearic acid, zinc stearate, suitable combinations thereof and other such materials known to those of ordinary skill in the art.
  • disintegrant is intended to mean a compound used in solid dosage forms to promote the disruption of the solid mass into smaller particles which are more readily dispersed or dissolved.
  • exemplary disintegrants include, by way of example and without limitation, starches such as corn starch, potato starch, pre- gelatinized and modified starched thereof, sweeteners, clays, such as bentonite, microcrystalline cellulose (e.g. AvicelTM.), carsium (e.g. Amberlite.TM.), alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pectin, tragacanth, combinations thereof and other such materials known to those of ordinary skill in the art.
  • starches such as corn starch, potato starch, pre- gelatinized and modified starched thereof, sweeteners, clays, such as bentonite, microcrystalline cellulose (e.g. AvicelTM.), carsium (e.g. Amberlite.TM.), alginates, sodium starch glycolate, gum
  • wetting agent is intended to mean a compound used to aid in attaining intimate contact between solid particles and liquids.
  • exemplary wetting agents include, by way of example and without limitation, poloxamers, gelatin, casein, Glycerol mono-oleate, lecithin (phosphatides), gum acacia, cholesterol, tragacanth, stearic acid, benzalkonium chloride, calcium stearate, glycerol monostearate, cetostearyl alcohol, sodium lauryl sulphate, sodium dodecyl sulfate, salts of bile acids (taurocholate, glycocholate, cholate, deoxycholate, etc.), cetomacrogol emulsifying wax, sorbitan esters, polyoxyethylene alkyl ethers (e.g., macrogol ethers such as cetomacrogol 1000), polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, (e.
  • the stable pharmaceutical composition according to the present invention may be in the form of a tablet or a caplet or a capsule or a powder or a suspension in a liquid or an aerosol formulation or solutions, preferably in the form of a tablet or capsule.
  • the stable pharmaceutical composition may be made by direct compression, wet granulation or dry granulation methods by techniques known to persons skilled in the art.
  • the drug in the wet granulation process, the drug is mixed with one or more pharmaceutical excepients and granulated with suitable binding solution to form wet granules, the wet granules are dried and optionally sieved.
  • the dried granules are mixed with one or more suitable excepients from those described elsewhere and then compressed into tablets or filled into capsules.
  • direct compression process the drug is mixed with all the pharmaceutical excepients required and then is either compressed into tablets or filled in capsules.
  • the drug is mixed with one or more pharmaceutical excepients and compressed into slugs and these slugs are passed through required sieve.
  • the sieved granules are mixed with one or more suitable excepients from those described elsewhere and then compressed into tablets or filled into capsules.
  • One or more solvents used in the formulation are selected from acetone, chloroform, dichloromethane, ethyl alcohol, ethyl acetate, methyl alcohol, isopropyl alcohol and combinations thereof and other such materials known to those of ordinary skill in the art.
  • About 1 % w/v aqueous dispersion of tablets was used for pH measurement. pH degradation can be seen with API when kept in different standard pH buffers. Percentage individual impurity at 0.3 RRT (Sulphoxide impurity) decreases as the solution of pH increases above pH 7 as shown in Fig 1.
  • Colloidal silicon is weighed and passed along with the dried granules through # 30.
  • the colloidal silicon is mixed with the granules in the conta blender and to the dried mass Talc and Magnesium stereate is added and mixed.
  • Table 1 shows that moisture absorption of API increases when exposed to 40°C/75%RH condition. Therefore the inventors of the present invention have tried to develop a stable formulation of API such that the API is protected and cannot absorb moisture.
  • alkalinizers were added and table 4 shows such alkalizer containing formulations. These formulations were also tested for their stability by loading them in stability chambers as per techniques and protocols known in the art as shown in Table 5.
  • Table 5 Three months stability data of the formulations of Table 4

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Biophysics (AREA)
  • Inorganic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
PCT/IN2014/000489 2013-07-25 2014-07-24 Formulation comprising a hypolipidemic agent WO2015011730A1 (en)

Priority Applications (18)

Application Number Priority Date Filing Date Title
CN201480041453.7A CN105407873A (zh) 2013-07-25 2014-07-24 包含降血脂剂的制剂
SG11201509798PA SG11201509798PA (en) 2013-07-25 2014-07-24 Formulation comprising a hypolipidemic agent
AU2014294548A AU2014294548B2 (en) 2013-07-25 2014-07-24 Formulation comprising a hypolipidemic agent
US14/899,912 US9610277B2 (en) 2013-07-25 2014-07-24 Formula comprising a hypolipidemic agent
MX2015016971A MX374628B (es) 2013-07-25 2014-07-24 Formulacion que comprende un agente hipolipidemico.
CA2917923A CA2917923A1 (en) 2013-07-25 2014-07-24 Formulation comprising a hypolipidemic agent
BR112015031878A BR112015031878A2 (pt) 2013-07-25 2014-07-24 composição farmacêutica
EA201690072A EA201690072A1 (ru) 2013-07-25 2014-07-24 Состав, содержащий гиполипидемическое средство
KR1020157036380A KR101786843B1 (ko) 2013-07-25 2014-07-24 지질 저하제를 포함하는 제제
NZ714558A NZ714558A (en) 2013-07-25 2014-07-24 Formulation comprising a hypolipidemic agent
EP14787059.6A EP3024446A1 (en) 2013-07-25 2014-07-24 Formulation comprising a hypolipidemic agent
HK16107193.2A HK1219222A1 (zh) 2013-07-25 2014-07-24 包含降血脂药的制剂
MA38865A MA38865A1 (fr) 2013-07-25 2014-07-24 Formulation comprenant un agent hypolipidémiant
JP2016522969A JP2016523895A (ja) 2013-07-25 2014-07-24 脂質低下剤を含む製剤
AP2015008876A AP2015008876A0 (en) 2013-07-25 2015-07-24 Formulation comprising a hypolipidemic agent
ZA2015/08682A ZA201508682B (en) 2013-07-25 2015-11-25 Formulation comprising a hypolipidemic agent
PH12015502802A PH12015502802A1 (en) 2013-07-25 2015-12-17 Formulation comprising a hypolipidemic agent
US15/475,812 US10098868B2 (en) 2013-07-25 2017-03-31 Formula comprising a hypolipidemic agent

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN2470/MUM/2013 2013-07-25
IN2470MU2013 IN2013MU02470A (en, 2012) 2013-07-25 2013-07-25

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US14/899,912 A-371-Of-International US9610277B2 (en) 2013-07-25 2014-07-24 Formula comprising a hypolipidemic agent
US15/475,812 Continuation US10098868B2 (en) 2013-07-25 2017-03-31 Formula comprising a hypolipidemic agent

Publications (1)

Publication Number Publication Date
WO2015011730A1 true WO2015011730A1 (en) 2015-01-29

Family

ID=51787141

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2014/000489 WO2015011730A1 (en) 2013-07-25 2014-07-24 Formulation comprising a hypolipidemic agent

Country Status (21)

Country Link
US (2) US9610277B2 (en, 2012)
EP (1) EP3024446A1 (en, 2012)
JP (1) JP2016523895A (en, 2012)
KR (1) KR101786843B1 (en, 2012)
CN (1) CN105407873A (en, 2012)
AP (1) AP2015008876A0 (en, 2012)
AR (1) AR097067A1 (en, 2012)
AU (1) AU2014294548B2 (en, 2012)
BR (1) BR112015031878A2 (en, 2012)
CA (1) CA2917923A1 (en, 2012)
EA (1) EA201690072A1 (en, 2012)
HK (1) HK1219222A1 (en, 2012)
IN (1) IN2013MU02470A (en, 2012)
MA (1) MA38865A1 (en, 2012)
MX (1) MX374628B (en, 2012)
NZ (1) NZ714558A (en, 2012)
PH (1) PH12015502802A1 (en, 2012)
SG (1) SG11201509798PA (en, 2012)
TW (1) TW201545773A (en, 2012)
WO (1) WO2015011730A1 (en, 2012)
ZA (1) ZA201508682B (en, 2012)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9656954B2 (en) 2013-07-05 2017-05-23 Cadila Healthcare Limited Synergistic compositions
US9783495B2 (en) 2011-01-31 2017-10-10 Cadila Healthcare Limited Treatment for lipodystrophy
US9814697B2 (en) 2013-04-22 2017-11-14 Cadila Healthcare Limited Composition for nonalcoholic fatty liver disease (NAFLD)
US10098868B2 (en) 2013-07-25 2018-10-16 Cadila Healthcare Limited Formula comprising a hypolipidemic agent
US10112898B2 (en) 2013-09-06 2018-10-30 Cadila Healthcare Limited Process for the preparation of saroglitazar pharmaceutical salts
US10385017B2 (en) 2015-10-14 2019-08-20 Cadila Healthcare Limited Pyrrole compound, compositions and process for preparation thereof
US10435363B2 (en) 2013-05-30 2019-10-08 Cadila Healthcare Limited Process for preparation of pyrroles having hypolipidemic hypocholesteremic activities
WO2020165782A1 (en) * 2019-02-13 2020-08-20 Cadila Healthcare Limited Treatment for polycystic ovarian syndrome (pcos)
WO2020183379A1 (en) * 2019-03-11 2020-09-17 Cadila Healthcare Limited Novel salts, crystalline forms and premix of hypolipidemic agent
US11433050B2 (en) 2016-12-09 2022-09-06 Cadila Healthcare Ltd. Treatment for primary biliary cholangitis

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE602006020785D1 (de) 2006-05-23 2011-04-28 Intel Corp Millimeterwellen-kommunikationssystem für den innenraum
KR101913830B1 (ko) * 2016-12-05 2018-10-31 주식회사 코쿤디자인 기능성 led 어셈블리를 이용한 디스플레이 장치

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012104869A1 (en) * 2011-01-31 2012-08-09 Cadila Healthcare Limited Treatment for lipodystrophy
WO2014174524A1 (en) * 2013-04-22 2014-10-30 Cadila Healthcare Limited A novel composition for nonalcoholic fatty liver disease (nafld)

Family Cites Families (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4231938A (en) 1979-06-15 1980-11-04 Merck & Co., Inc. Hypocholesteremic fermentation products and process of preparation
US4444784A (en) 1980-08-05 1984-04-24 Merck & Co., Inc. Antihypercholesterolemic compounds
MX7065E (es) 1980-06-06 1987-04-10 Sankyo Co Un procedimiento microbiologico para preparar derivados de ml-236b
US5354772A (en) 1982-11-22 1994-10-11 Sandoz Pharm. Corp. Indole analogs of mevalonolactone and derivatives thereof
US5030447A (en) * 1988-03-31 1991-07-09 E. R. Squibb & Sons, Inc. Pharmaceutical compositions having good stability
FI94339C (fi) 1989-07-21 1995-08-25 Warner Lambert Co Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi
US5089514A (en) 1990-06-14 1992-02-18 Pfizer Inc. 3-coxazolyl [phenyl, chromanyl or benzofuranyl]-2-hydroxypropionic acid derivatives and analogs as hypoglycemic agents
SK695A3 (en) 1992-07-03 1995-07-11 Smithkline Beecham Plc Heterocyclic compounds method of their production and using
GB9225386D0 (en) 1992-12-04 1993-01-27 Smithkline Beecham Plc Novel compounds
US5387613A (en) 1993-07-23 1995-02-07 Ribogene, Inc. Treatment of tachyarrhythmias of supraventricular origin
GB9326171D0 (en) 1993-12-22 1994-02-23 Smithkline Beecham Plc Novel compounds
WO1996004261A1 (en) 1994-07-29 1996-02-15 Smithkline Beecham Plc Benzoxazoles and pryridine derivatives useful in the treatment of the type ii diabetes
PT826688E (pt) 1995-04-28 2002-02-28 Daiichi Seiyaku Co Composto pentaciclico
GB9600464D0 (en) 1996-01-09 1996-03-13 Smithkline Beecham Plc Novel method
GB9606805D0 (en) 1996-03-30 1996-06-05 Glaxo Wellcome Inc Medicaments
CN1280574A (zh) 1997-10-27 2001-01-17 雷迪研究基金会 新的杂环化合物及其在医药中的应用、它们的制备方法和含有它们的药物组合物
WO1999019313A1 (en) 1997-10-27 1999-04-22 Dr. Reddy's Research Foundation Novel tricyclic compounds and their use in medicine; process for their preparation and pharmaceutical compositions containing them
EP1073643B1 (en) 1998-04-23 2004-12-29 Dr. Reddy's Laboratories Ltd. New heterocyclic compounds and their use in medicine, process for their preparation and pharmaceutical compositions containing them
JP2002507543A (ja) 1998-05-27 2002-03-12 ドクター・レディーズ・リサーチ・ファウンデーション 二環系化合物、その製造方法およびそれらを含有する薬学的組成物
JP2002527503A (ja) 1998-10-21 2002-08-27 ノボ ノルディスク アクティーゼルスカブ 新規化合物類、それらの調製及び使用
EP1123292A1 (en) 1998-10-21 2001-08-16 Novo Nordisk A/S New compounds, their preparation and use
WO2000023451A1 (en) 1998-10-21 2000-04-27 Novo Nordisk A/S New compounds, their preparation and use
CO5150173A1 (es) 1998-12-10 2002-04-29 Novartis Ag Compuestos n-(glicilo sustituido)-2-cianopirrolidinas inhibidores de peptidasa de dipeptidilo-iv (dpp-iv) los cuales son efectivos en el tratamiento de condiciones mediadas por la inhibicion de dpp-iv
ES2449194T3 (es) 2000-01-19 2014-03-18 Cadila Healthcare Limited Compuestos que tienen actividades hipolipidémica e hipocolesterolémica, procedimiento para su preparación y composiciones farmacéuticas que los contienen
US6395767B2 (en) 2000-03-10 2002-05-28 Bristol-Myers Squibb Company Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method
WO2002024625A2 (en) 2000-09-22 2002-03-28 Dr. Reddy's Research Foundation Process for the preparation of 3-aryl-2-hydroxy propanoic acid derivatives
UA74912C2 (en) 2001-07-06 2006-02-15 Merck & Co Inc Beta-aminotetrahydroimidazo-(1,2-a)-pyrazines and tetratriazolo-(4,3-a)-pyrazines as inhibitors of dipeptylpeptidase for the treatment or prevention of diabetes
US6987123B2 (en) 2001-07-26 2006-01-17 Cadila Healthcare Limited Heterocyclic compounds, their preparation, pharmaceutical compositions containing them and their use in medicine
US7407955B2 (en) 2002-08-21 2008-08-05 Boehringer Ingelheim Pharma Gmbh & Co., Kg 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
JP4745616B2 (ja) * 2003-02-26 2011-08-10 武田薬品工業株式会社 安定化されたイミダゾール誘導体含有医薬組成物、イミダゾール誘導体の安定化方法
US20070051626A1 (en) 2003-09-26 2007-03-08 Chiho Itou Cataphoresis apparatus cataphoresis method, and detection method for organism-related material using the apparatus and the method
MXPA06010571A (es) 2004-03-15 2007-02-16 Takeda Pharmaceutical Inhibidores de dipeptidil peptidasa.
CN101389333A (zh) * 2006-02-22 2009-03-18 卫材R&D管理有限公司 稳定化药物组合物
WO2007122635A2 (en) 2006-04-26 2007-11-01 Astron Research Limited Controlled release formulation comprising anti-epileptic drugs
JP5424571B2 (ja) * 2007-04-12 2014-02-26 協和発酵キリン株式会社 トピラマート含有固形製剤
EP2641596B1 (en) 2009-11-26 2018-05-02 Genfit Use of 1,3-diphenylprop-2-en-1-one derivatives for treating liver disorders
US8501816B2 (en) * 2010-10-12 2013-08-06 Cerecor, Inc. Antitussive compositions comprising memantine
MX2015016403A (es) 2013-05-30 2016-04-11 Cadila Healthcare Ltd Proceso para la preparacion de pirroles que tienen actividad hipolipidemica e hipocolesterolemica.
TW201636015A (zh) 2013-07-05 2016-10-16 卡地拉保健有限公司 協同性組成物
IN2013MU02470A (en, 2012) 2013-07-25 2015-06-26 Cadila Healthcare Ltd
WO2015029066A1 (en) 2013-08-29 2015-03-05 Cadila Healthcare Limited Polymorphic form of pyrrole derivative and intermediate thereof
WO2015033357A2 (en) 2013-09-06 2015-03-12 Cadila Healthcare Limited An improved process for the preparation of pyrrole derivatives

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012104869A1 (en) * 2011-01-31 2012-08-09 Cadila Healthcare Limited Treatment for lipodystrophy
WO2014174524A1 (en) * 2013-04-22 2014-10-30 Cadila Healthcare Limited A novel composition for nonalcoholic fatty liver disease (nafld)

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SONALI S. BHARATE ET AL: "Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients: a comprehensive review", JOURNAL OF EXCIPIENTS AND FOOD CHEMICALS, 30 December 2010 (2010-12-30), pages 3 - 26, XP055131570, Retrieved from the Internet <URL:http://ojs.abo.fi/index.php/jefc/article/view/26> *

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10017470B2 (en) 2011-01-31 2018-07-10 Cadila Healthcare Limited Treatment for lipodystrophy
US9783495B2 (en) 2011-01-31 2017-10-10 Cadila Healthcare Limited Treatment for lipodystrophy
US9814697B2 (en) 2013-04-22 2017-11-14 Cadila Healthcare Limited Composition for nonalcoholic fatty liver disease (NAFLD)
US10435363B2 (en) 2013-05-30 2019-10-08 Cadila Healthcare Limited Process for preparation of pyrroles having hypolipidemic hypocholesteremic activities
US9957230B2 (en) 2013-07-05 2018-05-01 Cadila Healthcare Limited Synergistic compositions
US10315993B2 (en) 2013-07-05 2019-06-11 Cadila Healthcare Limited Synergistic compositions
US9656954B2 (en) 2013-07-05 2017-05-23 Cadila Healthcare Limited Synergistic compositions
US10098868B2 (en) 2013-07-25 2018-10-16 Cadila Healthcare Limited Formula comprising a hypolipidemic agent
US10112898B2 (en) 2013-09-06 2018-10-30 Cadila Healthcare Limited Process for the preparation of saroglitazar pharmaceutical salts
US10385017B2 (en) 2015-10-14 2019-08-20 Cadila Healthcare Limited Pyrrole compound, compositions and process for preparation thereof
US11433050B2 (en) 2016-12-09 2022-09-06 Cadila Healthcare Ltd. Treatment for primary biliary cholangitis
US11872209B2 (en) 2016-12-09 2024-01-16 Zydus Lifesciences Limited Treatment for primary biliary cholangitis
US12178799B2 (en) 2016-12-09 2024-12-31 Zydus Lifesciences Limited Treatment for primary biliary cholangitis
WO2020165782A1 (en) * 2019-02-13 2020-08-20 Cadila Healthcare Limited Treatment for polycystic ovarian syndrome (pcos)
WO2020183379A1 (en) * 2019-03-11 2020-09-17 Cadila Healthcare Limited Novel salts, crystalline forms and premix of hypolipidemic agent

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US20170266158A1 (en) 2017-09-21
KR20160013150A (ko) 2016-02-03
TW201545773A (zh) 2015-12-16
US20160136131A1 (en) 2016-05-19
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AR097067A1 (es) 2016-02-17
MX374628B (es) 2025-03-06
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US9610277B2 (en) 2017-04-04
EP3024446A1 (en) 2016-06-01
MA38865A1 (fr) 2017-12-29
AU2014294548B2 (en) 2017-08-10
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CN105407873A (zh) 2016-03-16
IN2013MU02470A (en, 2012) 2015-06-26
AP2015008876A0 (en) 2015-11-30
US10098868B2 (en) 2018-10-16
ZA201508682B (en) 2017-03-29
HK1219222A1 (zh) 2017-03-31
NZ714558A (en) 2017-02-24

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