WO2019162800A1 - Composition pharmaceutique comprenant de la remogliflozine et un agent antidiabétique - Google Patents

Composition pharmaceutique comprenant de la remogliflozine et un agent antidiabétique Download PDF

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Publication number
WO2019162800A1
WO2019162800A1 PCT/IB2019/051116 IB2019051116W WO2019162800A1 WO 2019162800 A1 WO2019162800 A1 WO 2019162800A1 IB 2019051116 W IB2019051116 W IB 2019051116W WO 2019162800 A1 WO2019162800 A1 WO 2019162800A1
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WIPO (PCT)
Prior art keywords
pharmaceutically acceptable
pharmaceutical composition
remogliflozin
acceptable salt
weight
Prior art date
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PCT/IB2019/051116
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English (en)
Inventor
Ulhas Dhuppad
Nitin Deshmukh
Krishna SADAPHAL
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Glenmark Pharmaceuticals Limited
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Publication date
Application filed by Glenmark Pharmaceuticals Limited filed Critical Glenmark Pharmaceuticals Limited
Priority to MX2020008546A priority Critical patent/MX2020008546A/es
Priority to BR112020017056-9A priority patent/BR112020017056A2/pt
Priority to RU2019144196A priority patent/RU2019144196A/ru
Priority to CN201980005075.XA priority patent/CN111246917A/zh
Priority to KR1020207006000A priority patent/KR20200035437A/ko
Publication of WO2019162800A1 publication Critical patent/WO2019162800A1/fr
Priority to PH12020500228A priority patent/PH12020500228A1/en

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    • 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
    • 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
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
    • 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
    • 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
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • 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
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the invention relates to a pharmaceutical composition comprising remogliflozin or pharmaceutically acceptable salt or ester thereof, and metformin or pharmaceutically acceptable salt thereof.
  • a pharmaceutical composition comprising remogliflozin or pharmaceutically acceptable salt or ester thereof, and metformin or pharmaceutically acceptable salt thereof.
  • an immediate release pharmaceutical composition comprising: (a) remogliflozin or pharmaceutically acceptable salt or ester thereof, (b) metformin or pharmaceutically acceptable salt thereof, and (c) a pharmaceutically acceptable excipient.
  • Diabetes is a metabolic syndrome characterized by hyperglycemia, which results from an absolute deficiency in insulin secretion (type 1 diabetes) or from resistance to insulin action combined with an inadequate compensatory increase in insulin secretion (type 2 diabetes).
  • Type 1 diabetes is also called insulin-dependent diabetes.
  • type 2 diabetes accounting for 95% of diabetes cases in adults.
  • the chronic hyperglycemia in type 2 diabetes can cause major health complications, particularly in the smallest blood vessels in the body that nourish the kidneys, nerves, and eyes.
  • the chronic hyperglycemia of diabetes is also associated with long term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels.
  • SGLT2 is a member of the sodium glucose cotransporter family which are sodium-dependent glucose transport proteins. SGLT2 is the major cotransporter involved in glucose reabsorption in the kidney. SGLT2 inhibitors lead to a reduction in blood glucose levels. Therefore, SGLT2 inhibitors have potential use in the treatment of type 2 diabetes.
  • Remogliflozin etabonate is the pro-drug of remogliflozin.
  • Remogliflozin etabonate also known as 5-methyl-4- [4-( 1 -methylethoxy)benzyl] - 1 -( 1 -methylethyl)- 1 H-pyrazol-3-yl-6-0- (ethoxycarbonyl)-P -D-glucopyranoside has the following formula
  • US Patent 7,084,123 discloses Remogliflozin etabonate and its salts.
  • Remogliflozin etabonate has the potential to be used as monotherapy for the treatment of type 2 diabetes mellitus.
  • the other antihyperglycemic agent may be an oral antihyperglycemic agent including biguanides, sulfonylureas, thiazolidinediones, and alpha-glucosidase inhibitors.
  • biguanide such as metformin or other known biguanides improves hyperglycemia primarily through suppression of hepatic glucose production.
  • monotherapy has been used as the initial treatment in diabetic patients. If monotherapy fails it may be supplemented with other drugs.
  • a second drug e.g., biguanides, sulfonylureas, thiazolidinediones, and alpha-glucosidase inhibitors
  • a second drug e.g., biguanides, sulfonylureas, thiazolidinediones, and alpha-glucosidase inhibitors
  • biguanides, sulfonylureas, thiazolidinediones, and alpha-glucosidase inhibitors to the concurrent treatment can provide a balance of stimulated release of insulin while ameliorating insulin resistance.
  • This can provide an optimal level of glycemic control that is unattainable using monotherapy.
  • requiring a patient to take multiple medications for the prophylaxis or treatment of diseases can result in patient inconvenience and lead to non-compliance of the prescribed dosage regimen.
  • the ease of using single composition for multiple medications as opposed to separate administration of the individual medications has long been recognized in the practice of medicine.
  • PCT publication WO2012/006398 A2 relates to a biphasic composition comprising remogliflozin etabonate delayed release portions dispersed in remogliflozin immediate release portions.
  • PCT publication W02009/022010A1 relates to a pharmaceutical composition comprising combination of SGLT2 inhibitor and DPP-IV inhibitor.
  • the US patent 8,951,976 relates to a method of treatment for NAFL, NASH, hypernutritive fatty liver, alcoholic fatty liver disease, diabetic fatty liver and acute fatty liver using remogliflozin etabonate.
  • PCT publication WO2010/092125 A 1 relates to a composition comprising (a) an SGLT2 inhibitor, and (b) a DPPIV inhibitor, and (c) a third anti-diabetic agent.
  • PCT publication has still exists a need for stable immediate release formulation of remogliflozin or pharmaceutically acceptable salt or ester thereof in combination with biguanide such as metformin used for treatment of type 2 diabetes mellitus.
  • an immediate release pharmaceutical composition comprising: (a) remogliflozin or pharmaceutically acceptable salt or ester thereof, (b) metformin or pharmaceutically acceptable salt thereof, and (c) a pharmaceutically acceptable excipient.
  • the remogliflozin or pharmaceutically acceptable salt or ester thereof is remogliflozin etabonate.
  • the excipients are one or more of a diluent, a disintegrant, a binder, a glidant, a lubricant, a preservative, a buffering agent, a chelating agent, a polymer, an opacifier, a colorant, a gelling agent or viscosity modifying agent, an antioxidant, a solvent, a co-solvent, and combinations thereof.
  • the remogliflozin or pharmaceutically acceptable salt or ester thereof, and metformin or pharmaceutically acceptable salt thereof present in a weight ratio of about 1 : 1 to about 1: 15.
  • the remogliflozin or pharmaceutically acceptable salt or ester thereof and the disintegrant is present in weight ratio of about 1:0.1 to about 1: 10.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin or pharmaceutically acceptable salt or ester thereof, (b) metformin or pharmaceutically acceptable salt thereof, and (c) a pharmaceutically acceptable excipient, and (B) an extra-granular portion comprising a pharmaceutically acceptable excipient.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, and (c) a pharmaceutically acceptable excipient selected from the group consisting of a diluent, a disintegrant, a glidant, a binder, a lubricant, a preservative, a buffering agent, a chelating agent, a polymer, an opacifier, a colorant, a gelling agent or viscosity modifying agent, an antioxidant, a solvent, a co-solvent, and combinations thereof, and (B) an extra-granular portion comprising a pharmaceutically acceptable excipient selected from the group consisting of a diluent, a disintegrant, a glidant, a lubricant, a preservative, a buffering agent, a chelating agent, a polymer
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) a diluent, (d) a disintegrant, and (e) a binder, and (B) an extra- granular portion comprising a disintegrant and a lubricant.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) microcrystalline cellulose, (d) crosscarmellose sodium, and (e) polyvinylpyrrolidone, and (B) an extra-granular portion comprising a crosscarmellose sodium and magnesium stearate.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) about lOmg to about lOOOmg of remogliflozin etabonate, (b) about lOmg to l500mg of metformin hydrochloride, (c) about 5-30% w/w by weight of microcrystalline cellulose, (d) about 1-30% w/w by weight of crosscarmellose sodium, and (e) about 0.1-10% w/w by weight of polyvinylpyrrolidone, and (B) an extra-granular portion comprising about 1-30% w/w by weight of crosscarmellose sodium and about 0.1-5% w/w by weight of magnesium stearate.
  • a bilayer tablet dosage form comprising: (A) a first layer comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, and (c) a pharmaceutically acceptable excipient, and (B) a second layer comprising a pharmaceutically acceptable excipient, and wherein the remogliflozin etabonate, and metformin hydrochloride present in a weight ratio of about 1: 1 to about 1 : 15.
  • a bilayer tablet dosage form comprising: (A) a first layer comprising: (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) a diluent, (d) a disintegrant, and (e) a binder, and (B) a second layer comprising a disintegrant and a lubricant.
  • a bilayer tablet dosage form comprising: (A) a first layer comprising: (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) microcrystalline cellulose, (d) crosscarmellose sodium, and (e) polyvinylpyrrolidone, and (B) a second layer comprising crosscarmellose sodium and magnesium stearate.
  • a process of preparing an immediate release pharmaceutical composition comprising: (a) remogliflozin or pharmaceutically acceptable salt or ester thereof, (b) metformin or pharmaceutically acceptable salt thereof, and (c) a pharmaceutically acceptable excipient, and wherein the said process comprises steps of: (i) sifting and mixing the remogliflozin or pharmaceutically acceptable salt or ester thereof, metformin or pharmaceutically acceptable salt thereof and the pharmaceutically acceptable excipients to obtain a granule, (ii) mixing said granules of step (i) with the pharmaceutically acceptable excipients and compressing to obtain a tablet dosage form, and (iii) coating the said the tablet dosage form.
  • a process of preparing an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin or pharmaceutically acceptable salt or ester thereof, (b) metformin or pharmaceutically acceptable salt thereof, and (c) a pharmaceutically acceptable excipient, and (B) an extra-granular portion comprising a pharmaceutically acceptable excipient, and wherein said process comprises steps of: (i) sifting and mixing the remogliflozin or pharmaceutically acceptable salt or ester thereof, metformin or pharmaceutically acceptable salt thereof and the pharmaceutically acceptable excipients to obtain a granule, (ii) mixing said granules of step (i) with the pharmaceutically acceptable excipients and compressing to obtain a tablet dosage form, and (iii) coating the said the tablet dosage form.
  • Figure 1A & 2A shows antihyperglycemic effect measured as AUCo-i20 min in remogliflozin etabonate treated, metformin hydrochloride treated, combination of remogliflozin etabonate and metformin hydrochloride treated in comparison with control (untreated) groups.
  • an immediate release pharmaceutical composition comprising: (a) remogliflozin or pharmaceutically acceptable salt or ester thereof, (b) metformin or pharmaceutically acceptable salt thereof, and (c) a pharmaceutically acceptable excipient.
  • an immediate release pharmaceutical composition comprising: (a) remogliflozin or pharmaceutically acceptable salt or ester thereof, (b) metformin or pharmaceutically acceptable salt thereof, and wherein the remogliflozin or pharmaceutically acceptable salt or ester thereof, and metformin or pharmaceutically acceptable salt thereof present in a weight ratio of about 1 : 1 to about 1: 15.
  • a stable immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin or pharmaceutically acceptable salt or ester thereof, (b) metformin or pharmaceutically acceptable salt thereof, and (c) a pharmaceutically acceptable excipient, and (B) an extra-granular portion comprising a pharmaceutically acceptable excipient.
  • the invention composition comprising the combination of remogliflozin or pharmaceutically acceptable salt or ester thereof, and metformin or pharmaceutically acceptable salt thereof shows synergy in terms of reducing the hyperglycemia when compared with standalone treatments.
  • an excipient includes a single excipient as well as two or more different excipients, and the like.
  • the term "about” is used synonymously with the term “approximately.”
  • the use of the term “about” with regard to a certain therapeutically effective pharmaceutical dose indicates that values slightly outside the cited values, e.g., plus or minus 0.1% to 10%, which are also effective and safe.
  • remogliflozin refers to remogliflozin, its salts, hydroxylated forms, hydrates, solvates, polymorphic forms, analogs, derivatives, esters, complex, cocrystals, cogeners and prodrugs thereof.
  • remogliflozin refers to remogliflozin etabonate.
  • an effective amount or "therapeutically effective amount” denotes an amount of an active ingredient that, when administered to a subject for treating metabolic disorders, produces an intended therapeutic benefit in a subject.
  • active ingredient (used interchangeably with“active” or“active substance” or“drug”) as used herein includes remogliflozin etabonate and metformin hydrochloride.
  • treating or“treatment” as used herein also covers the prophylaxis, mitigation, prevention, amelioration, or suppression of a disorder modulated by remogliflozin etabonate and metformin in a mammal.
  • patient includes mammals like human and other animals.
  • the patient is a human.
  • pharmaceutically acceptable excipients any of the components of a pharmaceutical composition other than the actives and which are approved by regulatory authorities or are generally regarded as safe for human or animal use.
  • composition includes administration of one or more active pharmaceutical ingredients either in a single dosage form or in separate dosage forms; in fixed dose combination or administered separately as adjuvant therapy.
  • the invention composition comprises remogliflozin or pharmaceutically acceptable salt or ester thereof as remogliflozin etabonate.
  • the remogliflozin etabonate is present in an amount of about lOmg to about lOOOmg.
  • the remogliflozin etabonate is present in an amount of 20mg, or about 30mg, or about 40mg, or about 50mg, or about 60mg, or about 70mg, or about 80mg, or about 90mg, or about lOOmg, about l50mg, or about 200mg, or about 250mg, or about 300mg, or about 400mg, or about 500mg, or about 600mg, or about 700mg, or about 800mg, or about 900mg.
  • the invention composition comprises about 50mg, or about lOOmg or about 250mg of remogliflozin etabonate.
  • the remogliflozin or pharmaceutically acceptable salt or ester thereof is administered orally as once a day or twice a day or thrice a day. Preferred dosing is twice a day.
  • the invention composition comprises the metformin or pharmaceutically acceptable salt thereof as metformin hydrochloride.
  • the metformin hydrochloride is present in an amount of about lOmg to l500mg.
  • the metformin hydrochloride is present in about lOOmg, or about 200mg, or about 300mg, or about 400mg, or about 500mg, or about 600mg, or about 700mg, or about 800mg, or about 900mg, or about lOOOmg, or about 1 lOOmg, or about l200mg, or about l300mg, or about l400mg.
  • the invention composition comprises about 500mg, or 800mg, or lOOOmg of metformin hydrochloride.
  • the pharmaceutical composition comprising remogliflozin etabonate and metformin hydrochloride exhibit a synergistic effect in reducing the hyperglycemia and glycated hemoglobin as compared to alone remogliflozin etabonate or alone metformin hydrochloride.
  • the pharmaceutical composition comprising remogliflozin or pharmaceutically acceptable salt or ester thereof, and metformin or pharmaceutically acceptable salt thereof are present in a weight ratio of about 1: 1 to about 1: 15.
  • the remogliflozin or pharmaceutically acceptable salt or ester thereof, and metformin or pharmaceutically acceptable salt thereof present in a weight ratio of about 1 :2, or about 1:4, or about 1:5, or about 1: 10.
  • the pharmaceutical composition can be present in the form of a tablet, capsule, tablets in capsule, bilayer tablet, soft gelatin capsule, pill, oral suspension or solution.
  • the compositions of the invention can be prepared by using known formulation methods such as direct compaction, wet granulation, dry granulation, hot melt granulation, granulation using spheronization etc.
  • the pharmaceutical composition of this invention comprises a pharmaceutically acceptable excipient.
  • the excipients are one or more of a diluent, a disintegrant, a binder, a glidant, a lubricant, a preservative, a buffering agent, a chelating agent, a polymer, an opacifier, a colorant, a gelling agent or viscosity modifying agent, an antioxidant, a solvent, a co-solvent, or combinations thereof.
  • the diluent is selected from the group consisting of microcrystalline cellulose, silicified microcrystalline cellulose, micro fine cellulose, lactose, starch, pregelatinized starch, mannitol, sorbitol, dextrates, dextrin, maltodextrin, dextrose, calcium carbonate, calcium sulfate, dibasic calcium phosphate dihydrate, tribasic calcium phosphate, magnesium carbonate, magnesium oxide, sugars such as dextrose, mannitol, sorbitol, sucrose and combinations thereof.
  • the diluent is present in a concentration of about 5-30% w/w by weight of composition.
  • the diluent is present in a concentration of about 8-25% w/w, or about 12-20% w/w, or about 14- 18% w/w by weight of composition.
  • the disintegrant is selected from the group consisting of crosscarmellose sodium, starch, potato starch, corn starch, crospovidone, sodium starch glycolate, microcrystalline cellulose, low substituted hydroxypropyl cellulose and combination thereof.
  • the disintegrant is present in a concentration of about 1-30% w/w by weight of composition.
  • the disintegrant is present in a concentration of about 1.5-25% w/w, or about 1.5-20% w/w, or about 1.5-15% w/w, or about 1.5-10% w/w, or about 1.5-5% w/w by weight of composition.
  • the glidant is selected from the group consisting of stearic acid, magnesium stearate, talc, colloidal silicon dioxide, and sodium stearyl fumarate and combination thereof.
  • the glidant is present in a concentration of about 0.1-5% w/w by weight of composition.
  • the glidant is present in a concentration of about 0.2-4% w/w, or about 0.5-3.5% w/w, or about 0.7-3% w/w, or about 0.9-2% w/w by weight of composition.
  • the binder is selected from the group consisting of starches, pregelatinize starches, gelatin, polyvinylpyrrolidone, povidone, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols and combination thereof.
  • the binder is present in a concentration of about 0.1-10% w/w by weight of composition.
  • the binder is present in a concentration of about 0.5-8% w/w, or about 1-6% w/w, or about 1.2-4% w/w, or about 1.5-3% w/w, or about 2-3% w/w by weight of composition.
  • the preservative is selected from the group consisting of phenoxyethanol, parabens such as methyl paraben and propyl paraben and their sodium salts, propylene glycols, sorbates, urea derivatives such as diazolindinyl urea, and mixtures thereof.
  • the preservative is present in a concentration of about 0.1-30% w/w by weight of composition.
  • the preservative is present in a concentration of about 0.1-30% w/w, or about 0.5-25% w/w, or about 1-20% w/w, or about 2-15% w/w, or about 3-10% w/w by weight of composition.
  • the buffering agent is selected from the group consisting of sodium hydroxide, potassium hydroxide, ammonium hydroxide and mixtures thereof.
  • the chelating agent is selected from the group consisting of ethylene diamine tetraacetic acid (“EDTA”), and disodium edetate and EDTA derivatives.
  • the polymer is selected from the group consisting of gum arabic, sodium based lignosulfonate, methyl methacrylate, methacrylate copolymers, isobutyl methacrylate, ethylene glycol dimethacrylate and combination thereof.
  • the solvent is selected from the group consisting of water; tetrahydrofuran; alcohols, such as methanol, ethanol, isopropyl alcohol and higher alcohols; alkanes such as pentane, hexane and heptane; ketones, such as acetone and methyl ethyl ketone; chlorinated hydrocarbons, such as chloroform, carbon tetrachloride, methylene chloride and ethylene dichloride acetates, such as ethyl acetate and combination thereof.
  • the diluent is microcrystalline cellulose.
  • the disintegrant is crosscarmellose sodium.
  • the glidant is magnesium stearate.
  • the binder is polyvinylpyrrolidone.
  • compositions wherein the remogliflozin or pharmaceutically acceptable salt or ester thereof and the disintegrant is present in weight ratio of about 1 :0.1 to about 1: 10.
  • a composition wherein the remogliflozin or pharmaceutically acceptable salt or ester thereof and the disintegrant is present in weight ratio of about 1:0.08, or about 1:0.2, or about 1:0.3.
  • the disintegrant is crosscarmellose sodium.
  • an immediate release pharmaceutical composition comprising: (A) an intra- granular portion comprising (a) remogliflozin or pharmaceutically acceptable salt or ester thereof, (b) metformin or pharmaceutically acceptable salt thereof, and (c) a pharmaceutically acceptable excipient, and (B) an extra-granular portion comprising a pharmaceutically acceptable excipient.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, and (c) a pharmaceutically acceptable excipient, and (B) an extra-granular portion comprising a pharmaceutically acceptable excipient.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, and (c) a pharmaceutically acceptable excipient selected from the group consisting of a diluent, a disintegrant, a glidant, a binder, a lubricant, a preservative, a buffering agent, a chelating agent, a polymer, an opacifier, a colorant, a gelling agent or viscosity modifying agent, an antioxidant, a solvent, a co-solvent, and combinations thereof, and (B) an extra-granular portion comprising a pharmaceutically acceptable excipient selected from the group consisting of a diluent, a disintegrant, a glidant, a lubricant, a preservative, a buffering agent, a chelating agent, a polymer, an o
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, and (c) a pharmaceutically acceptable excipient, and (B) an extra-granular portion comprising a pharmaceutically acceptable excipient, and wherein the remogliflozin etabonate is present in an amount of about lOmg to about lOOOmg or about lOOmg or 250mg and the metformin hydrochloride is present in an amount of about lOmg to l500mg or about 500mg or 800mg or lOOOmg.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, and (c) a pharmaceutically acceptable excipient, and (B) an extra-granular portion comprising a pharmaceutically acceptable excipient, and wherein the remogliflozin etabonate, and metformin hydrochloride present in a weight ratio of about 1: 1 to about 1 : 15 or in a weight ratio of about 1 :2, or about 1 :4, or about 1:5, or about 1: 10.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, and (c) a pharmaceutically acceptable excipient selected from the group consisting of a diluent, a disintegrant, a glidant, a binder, a lubricant, a preservative, a buffering agent, a chelating agent, a polymer, an opacifier, a colorant, a gelling agent or viscosity modifying agent, an antioxidant, a solvent, a co-solvent, and combinations thereof, and (B) an extra-granular portion comprising a pharmaceutically acceptable excipient selected from the group consisting of a diluent, a disintegrant, a glidant, a lubricant, a preservative, a buffering agent, a chelating agent, a polymer, an
  • the disintegrant is crosscarmellose sodium.
  • the remogliflozin etabonate and the crosscarmellose sodium is present in weight ratio of about 1:0.1 to about 1: 10 or the remogliflozin etabonate and the crosscarmellose sodium is present in weight ratio of about 1:0.08, or about 1:0.2, or about 1:0.3.
  • the disintegrant is present in either intra-granular portion or extra-granular portion or both.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) a diluent, (d) a disintegrant, and (e) a binder, and (B) an extra-granular portion comprising a disintegrant and a lubricant.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) microcrystalline cellulose, (d) crosscarmellose sodium, and (e) polyvinylpyrrolidone, and (B) an extra-granular portion comprising a crosscarmellose sodium and magnesium stearate.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) about lOmg to about lOOOmg of remogliflozin etabonate, (b) about lOmg to l500mg of metformin hydrochloride, (c) about 5-30% w/w by weight of microcrystalline cellulose, (d) about 1-30% w/w by weight of crosscarmellose sodium, and (e) about 0.1-10% w/w by weight of polyvinylpyrrolidone, and (B) an extra- granular portion comprising about 1-30% w/w by weight of crosscarmellose sodium and about 0.1-5% w/w by weight of magnesium stearate.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) about lOOmg or 250mg of remogliflozin etabonate, (b) about 500mg or 800mg or lOOOmg of metformin hydrochloride, (c) about 5-30% w/w by weight of microcrystalline cellulose, (d) about 1-30% w/w by weight of crosscarmellose sodium, and (e) about 0.1-10% w/w by weight of polyvinylpyrrolidone, and (B) an extra- granular portion comprising about 1-30% w/w by weight of crosscarmellose sodium and about 0.1-5% w/w by weight of magnesium stearate.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) about 5-30% w/w by weight of microcrystalline cellulose, (d) about 1-30% w/w by weight of crosscarmellose sodium, and (e) about 0.1-10% w/w by weight of polyvinylpyrrolidone, and (B) an extra-granular portion comprising about 1-30% w/w by weight of crosscarmellose sodium and about 0.1-5% w/w by weight of magnesium stearate, wherein the remogliflozin etabonate, and metformin hydrochloride present in a weight ratio of about 1: 1 to about 1: 15.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) about 5-30% w/w by weight of microcrystalline cellulose, (d) about 1-30% w/w by weight of crosscarmellose sodium, and (e) about 0.1-10% w/w by weight of polyvinylpyrrolidone, and (B) an extra-granular portion comprising about 1-30% w/w by weight of crosscarmellose sodium and about 0.1-5% w/w by weight of magnesium stearate, wherein the remogliflozin etabonate, and metformin hydrochloride present in a weight ratio of about 1:2, or about 1:4, or about 1:5, or about 1: 10.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) a diluent, (d) a disintegrant, and (e) a binder, and (B) an extra-granular portion comprising a disintegrant and a lubricant, wherein the remogliflozin etabonate and the disintegrant is present in weight ratio of about 1 :0.1 to about 1 : 10 in the intra-granular portion or extra-granular portion.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) microcrystalline cellulose, (d) crosscarmellose sodium, and (e) polyvinylpyrrolidone, and (B) an extra-granular portion comprising a crosscarmellose sodium and magnesium stearate, wherein the remogliflozin etabonate and the crosscarmellose sodium is present in weight ratio of about 1:0.1 to about 1: 10 in the intra-granular portion.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) microcrystalline cellulose, (d) crosscarmellose sodium, and (e) polyvinylpyrrolidone, and (B) an extra-granular portion comprising a crosscarmellose sodium and magnesium stearate, wherein the remogliflozin etabonate and the crosscarmellose sodium is present in weight ratio of about 1:0.1 to about 1: 10 in the intra or extra-granular portion.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) about lOmg to about lOOOmg of remogliflozin etabonate, (b) about lOmg to l500mg of metformin hydrochloride, (c) about 5-30% w/w by weight of microcrystalline cellulose, (d) about 1-30% w/w by weight of crosscarmellose sodium, and (e) about 0.1-10% w/w by weight of polyvinylpyrrolidone, and (B) an extra- granular portion comprising about 1-30% w/w by weight of crosscarmellose sodium and about 0.1-5% w/w by weight of magnesium stearate, wherein the remogliflozin etabonate and the crosscarmellose sodium is present in weight ratio of about 1 :0.1 to about 1 : 10 in the intra-granular portion.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) about lOOmg or 250mg of remogliflozin etabonate, (b) about 500mg or 800mg or lOOOmg of metformin hydrochloride, (c) about 5-30% w/w by weight of microcrystalline cellulose, (d) about 1-30% w/w by weight of crosscarmellose sodium, and (e) about 0.1-10% w/w by weight of polyvinylpyrrolidone, and (B) an extra- granular portion comprising about 1-30% w/w by weight of crosscarmellose sodium and about 0.1-5% w/w by weight of magnesium stearate, wherein the remogliflozin etabonate and the crosscarmellose sodium is present in weight ratio of about 1 :0.1 to about 1 : 10 in the intra-granular portion.
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) about 5-30% w/w by weight of microcrystalline cellulose, (d) about 1-30% w/w by weight of crosscarmellose sodium, and (e) about 0.1-10% w/w by weight of polyvinylpyrrolidone, and (B) an extra-granular portion comprising about 1-30% w/w by weight of crosscarmellose sodium and about 0.1-5% w/w by weight of magnesium stearate, wherein the remogliflozin etabonate, and metformin hydrochloride present in a weight ratio of about 1: 1 to about 1: 15, and wherein the remogliflozin etabonate and the crosscarmellose sodium is present in weight ratio of about 1:0.1 to about 1 : 10 in the intra-granular portion
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) about 5-30% w/w by weight of microcrystalline cellulose, (d) about 1-30% w/w by weight of crosscarmellose sodium, and (e) about 0.1-10% w/w by weight of polyvinylpyrrolidone, and (B) an extra-granular portion comprising about 1-30% w/w by weight of crosscarmellose sodium and about 0.1-5% w/w by weight of magnesium stearate, wherein the remogliflozin etabonate, and metformin hydrochloride present in a weight ratio of about 1: 1 to about 1: 15, and wherein the remogliflozin etabonate and the crosscarmellose sodium is present in weight ratio of about 1:0.1 to about 1 : 10 in the extra- granular
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) about 5-30% w/w by weight of microcrystalline cellulose, (d) about 1-30% w/w by weight of crosscarmellose sodium, and (e) about 0.1-10% w/w by weight of polyvinylpyrrolidone, and (B) an extra-granular portion comprising about 1-30% w/w by weight of crosscarmellose sodium and about 0.1-5% w/w by weight of magnesium stearate, wherein the remogliflozin etabonate, and metformin hydrochloride present in a weight ratio of about 1:2, or about 1 :4, or about 1:5, or about 1: 10, and wherein the remogliflozin etabonate and the crosscarmellose sodium is present in weight ratio of about 1:0.1 to about 1
  • an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) about 5-30% w/w by weight of microcrystalline cellulose, (d) about 1-30% w/w by weight of crosscarmellose sodium, and (e) about 0.1-10% w/w by weight of polyvinylpyrrolidone, and (B) an extra-granular portion comprising about 1-30% w/w by weight of crosscarmellose sodium and about 0.1-5% w/w by weight of magnesium stearate, wherein the remogliflozin etabonate, and metformin hydrochloride present in a weight ratio of about 1:2, or about 1 :4, or about 1:5, or about 1: 10, and wherein the remogliflozin etabonate and the crosscarmellose sodium is present in weight ratio of about 1:0.1 to about 1
  • a bilayer tablet dosage form comprising: (A) a first layer comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, and (c) a pharmaceutically acceptable excipient, and (B) a second layer comprising a pharmaceutically acceptable excipiens, and wherein the remogliflozin etabonate, and metformin hydrochloride present in a weight ratio of about 1: 1 to about 1: 15, or the remogliflozin etabonate, and metformin hydrochloride present in a weight ratio of about 1 :2 or about 1:4 or about 1 :5 or about 1: 10.
  • a bilayer tablet dosage form comprising: (A) a first layer comprising: (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) a diluent, (d) a disintegrant, and (e) a binder, and (B) a second layer comprising a disintegrant and a lubricant.
  • a bilayer tablet dosage form comprising: (A) a first layer comprising: (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) microcrystalline cellulose, (d) crosscarmellose sodium, and (e) polyvinylpyrrolidone, and (B) a second layer comprising crosscarmellose sodium and magnesium stearate.
  • a bilayer tablet dosage form comprising: (A) a first layer comprising: (a) about lOmg to about lOOOmg of remogliflozin etabonate, (b) about lOmg to l500mg of metformin hydrochloride, (c) about 5-30% w/w by weight of microcrystalline cellulose, (d) about 1-30% w/w by weight of crosscarmellose sodium, and (e) about 0.1-10% w/w by weight of polyvinylpyrrolidone, and (B) a second layer comprising about 1-30% w/w by weight of crosscarmellose sodium and about 0.1-5% w/w by weight of magnesium stearate.
  • a bilayer tablet dosage form comprising: (A) a first layer comprising: (a) about lOOmg or 250mg of remogliflozin etabonate, (b) about 500mg or 800mg or lOOOmg of metformin hydrochloride, (c) about 5-30% w/w by weight of microcrystalline cellulose, (d) about 1-30% w/w by weight of crosscarmellose sodium, and (e) about 0.1-10% w/w by weight of polyvinylpyrrolidone, and (B) a second layer comprising about 1-30% w/w by weight of crosscarmellose sodium and about 0.1-5% w/w by weight of magnesium stearate.
  • a bilayer tablet dosage form comprising: (A) a first layer comprising: (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) about 5-30% w/w by weight of microcrystalline cellulose, (d) about 1-30% w/w by weight of crosscarmellose sodium, and (e) about 0.1-10% w/w by weight of polyvinylpyrrolidone, and (B) a second layer comprising about 1-30% w/w by weight of crosscarmellose sodium and about 0.1-5% w/w by weight of magnesium stearate, wherein the remogliflozin etabonate, and metformin hydrochloride present in a weight ratio of about 1 : 1 to about 1 : 15.
  • a bilayer tablet dosage form comprising: (A) a first layer comprising: (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) about 5-30% w/w by weight of microcrystalline cellulose, (d) about 1-30% w/w by weight of crosscarmellose sodium, and (e) about 0.1-10% w/w by weight of polyvinylpyrrolidone, and (B) a second layer comprising: about 1-30% w/w by weight of crosscarmellose sodium and about 0.1-5% w/w by weight of magnesium stearate, wherein the remogliflozin etabonate, and metformin hydrochloride present in a weight ratio of about 1:2, or about 1:4, or about 1:5, or about 1: 10.
  • a bilayer tablet dosage form comprising: (A) a first layer comprising: (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) a diluent, (d) a disintegrant, and (e) a binder, and (B) a second layer comprising a disintegrant and a lubricant, and wherein the remogliflozin etabonate and the disintegrant is present in weight ratio of about 1 :0.1 to about 1: 10 in the intra-granular portion or extra-granular portion.
  • a bilayer tablet dosage form comprising: (A) a first layer comprising: (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) microcrystalline cellulose, (d) crosscarmellose sodium, and (e) polyvinylpyrrolidone, and (B) a second layer comprising crosscarmellose sodium and magnesium stearate, and wherein the remogliflozin etabonate and the crosscarmellose sodium is present in weight ratio of about 1 :0.1 to about 1 : 10 in the intra-granular portion or extra-granular portion.
  • a process of preparing an immediate release pharmaceutical composition comprising: (a) remogliflozin or pharmaceutically acceptable salt or ester thereof, (b) metformin or pharmaceutically acceptable salt thereof, and (c) a pharmaceutically acceptable excipient, and wherein the said process comprises steps of: (i) sifting and mixing the remogliflozin or pharmaceutically acceptable salt or ester thereof, metformin or pharmaceutically acceptable salt thereof and the pharmaceutically acceptable excipients to obtain a granules, (ii) mixing said granule of step (i) with the pharmaceutically acceptable excipients and compressing to obtain a tablet dosage form, and (iii) coating the said a tablet dosage form.
  • a process of preparing an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin or pharmaceutically acceptable salt or ester thereof, (b) metformin or pharmaceutically acceptable salt thereof, and (c) a pharmaceutically acceptable excipient, and (B) an extra-granular portion comprising a pharmaceutically acceptable excipiens, and wherein said process comprises steps of: (i) sifting and mixing the remogliflozin or pharmaceutically acceptable salt or ester thereof, metformin or pharmaceutically acceptable salt thereof and the pharmaceutically acceptable excipients to obtain a granule, (ii) mixing said granules of step (i) with the pharmaceutically acceptable excipients and compressing to obtain a tablet dosage form, and (iii) coating the said the tablet dosage form.
  • a process of preparing an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) a diluent, (d) a disintegrant, and (e) a binder, and (B) an extra-granular portion comprising a disintegrant and a lubricant, and wherein said process comprises steps of: (i) sifting and mixing the remogliflozin etabonate, metformin hydrochloride, the diluent, the disintegrant and the binder to obtain a granule, (ii) mixing said granules of step (i) with the extra-granular portion comprising the disintegrant and the lubricant and compressing to obtain a tablet dosage form, and (iii) coating the said the tablet dosage form.
  • a process of preparing an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) microcrystalline cellulose, (d) crosscarmellose sodium, and (e) polyvinylpyrrolidone, and (B) an extra-granular portion comprising a crosscarmellose sodium and magnesium stearate, and wherein said process comprises steps of: (i) sifting and mixing the remogliflozin etabonate, metformin hydrochloride, microcrystalline cellulose, crosscarmellose sodium, polyvinylpyrrolidone to obtain a granule, (ii) mixing said granules of step (i) with the extra-granular portion comprising crosscarmellose sodium and magnesium stearate and compressing to obtain a tablet dosage form, and (iii) coating the said the tablet dosage form.
  • a process of preparing an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) microcrystalline cellulose, (d) crosscarmellose sodium, and (e) polyvinylpyrrolidone, and (B) an extra-granular portion comprising a crosscarmellose sodium and magnesium stearate, and wherein said process comprises steps of: (i) sifting and mixing the remogliflozin etabonate, metformin hydrochloride, microcrystalline cellulose, crosscarmellose sodium, polyvinylpyrrolidone to obtain a granule, (ii) mixing said granules of step (i) with the extra-granular portion comprising crosscarmellose sodium and magnesium stearate and compressing to obtain a tablet dosage form, and (iii) coating the said the tablet dosage form, and wherein the re
  • a method of treating diabetes using an immediate release pharmaceutical composition comprising: (A) an intra-granular portion comprising (a) remogliflozin etabonate, (b) metformin hydrochloride, (c) a diluent, (d) a disintegrant, and (e) a binder, and (B) an extra-granular portion comprising a disintegrant and a lubricant.
  • Step 1 dry mix was granulated with step 2 solution to get wet mass.
  • Coating solution was prepared by dispersing Opadry in water, this dispersion was used to coat the above tablets.
  • Example 3 One month stability data of the formulations prepared as per example 1.
  • the animals were given a single oral administration of either Vehicle (lOml/kg) or remogliflozin alone or metformin alone or a combination of remogliflozin and metformin (See figures).
  • Remogliflozin etabonate 1 mg/kg decreased blood glucose AUC by 15%
  • Metformin hydrochloride 30mg/kg decreased blood glucose AUC by 2%
  • the combination of remogliflozin etabonate and metformin hydrochloride decreased blood glucose AUC by 23%
  • Remogliflozin etabonate 1 mg/kg decreased blood glucose AUC by 15%
  • Metformin hydrochloride lOOmg/kg decreased blood glucose AUC by 53%
  • the combination of remogliflozin etabonate and metformin hydrochloride decreased blood glucose AUC by 67%.

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Abstract

L'invention concerne une composition pharmaceutique comprenant de la remogliflozine ou un sel ou un ester pharmaceutiquement acceptable de celle-ci, et de la metformine ou un sel pharmaceutiquement acceptable de celle-ci. En particulier, l'invention concerne une composition pharmaceutique à libération immédiate comprenant : (a) de la remogliflozine ou un sel ou ester pharmaceutiquement acceptable de celle-ci, (b) de la metformine ou un sel pharmaceutiquement acceptable de celle-ci, et (c) un excipient pharmaceutiquement acceptable.
PCT/IB2019/051116 2018-02-21 2019-02-12 Composition pharmaceutique comprenant de la remogliflozine et un agent antidiabétique WO2019162800A1 (fr)

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MX2020008546A MX2020008546A (es) 2018-02-21 2019-02-12 Composicion farmaceutica que comprende remogliflozina y un agente antidiabetico.
BR112020017056-9A BR112020017056A2 (pt) 2018-02-21 2019-02-12 Composição farmacêutica compreendendo remogliflozina e um agente antidiabético
RU2019144196A RU2019144196A (ru) 2018-02-21 2019-02-12 Фармацевтическая композиция, содержащая ремоглифлозин и противодиабетическое средство
CN201980005075.XA CN111246917A (zh) 2018-02-21 2019-02-12 包含瑞格列净和抗糖尿病药物的药物组合物
KR1020207006000A KR20200035437A (ko) 2018-02-21 2019-02-12 레모글리플로진 및 당뇨병 치료제를 포함하는 약제학적 조성물
PH12020500228A PH12020500228A1 (en) 2018-02-21 2020-01-30 Pharmacutical composition comprising remogliflozin and antidiabetic agent

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WO2022263935A1 (fr) * 2021-06-14 2022-12-22 Glenmark Pharmaceutical Limited Composition pharmaceutique comprenant de l'étabonate de remogliflozine, du chlorhydrate de metformine et de la vildagliptine

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CN111588713B (zh) * 2020-06-22 2021-03-09 广州市力鑫药业有限公司 一种治疗糖尿病的药物组合物及其制备方法

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WO2010045656A2 (fr) * 2008-10-17 2010-04-22 Nectid, Inc. Nouvelles formes posologiques d'inhibiteur sglt2
WO2011060290A2 (fr) * 2009-11-13 2011-05-19 Bristol-Myer Squibb Company Formulations pour comprimés à libération immédiate

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CN104586834A (zh) * 2014-12-12 2015-05-06 周连才 一种艾帕列净和二甲双胍的药物组合物及其制备方法
CN110753540A (zh) * 2017-06-08 2020-02-04 格兰马克药品有限公司 瑞格列净的口服药物制剂

Patent Citations (2)

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WO2010045656A2 (fr) * 2008-10-17 2010-04-22 Nectid, Inc. Nouvelles formes posologiques d'inhibiteur sglt2
WO2011060290A2 (fr) * 2009-11-13 2011-05-19 Bristol-Myer Squibb Company Formulations pour comprimés à libération immédiate

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022263935A1 (fr) * 2021-06-14 2022-12-22 Glenmark Pharmaceutical Limited Composition pharmaceutique comprenant de l'étabonate de remogliflozine, du chlorhydrate de metformine et de la vildagliptine

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