WO2004110422A1 - Extended-release tablets of metformin - Google Patents
Extended-release tablets of metformin Download PDFInfo
- Publication number
- WO2004110422A1 WO2004110422A1 PCT/IB2004/050901 IB2004050901W WO2004110422A1 WO 2004110422 A1 WO2004110422 A1 WO 2004110422A1 IB 2004050901 W IB2004050901 W IB 2004050901W WO 2004110422 A1 WO2004110422 A1 WO 2004110422A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- extended
- release
- metformin
- cellulose
- tablets
- Prior art date
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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
- A61K9/2004—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
- 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
- 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
- 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
Definitions
- the present invention relates to extended-release unit dosage formulations of metformin or its pharmaceutically acceptable salt thereof and the process for their preparation.
- Extended-release pharmaceutical dosage forms have received much attention in recent years and are highly desirable for providing a constant level of pharmaceutical agent to a patient.
- the nature of the delivery system is dictated by the properties and dose of the drug, desired release profile and physiological factors. For example, it is challenging to develop an extended-release system for a high dose, water-soluble drug with a narrow absorption window limited to either stomach and/or the upper intestine.
- Extended-release dosage forms not only increase patient compliance due to reduction in frequency of dosing, but they also reduce the severity and frequency of side-effects, as they maintain substantially constant blood levels and avoid fluctuations associated with the conventional immediate release formulations.
- Metformin has been widely prescribed for lowering blood glucose in patients with non-insulin dependent diabetes mellitus (NIDDM).
- NIDDM non-insulin dependent diabetes mellitus
- metformin requires twice (bid) or three times-a-day (tid) dosing.
- bid twice or three times-a-day (tid) dosing.
- tid times-a-day
- Adverse events associated with metformin use are often gastrointestinal, e.g. anorexia, nausea, vomiting and occasionally diarrhea, etc. These adverse effects may be partially avoided by reducing the initial and/or maintenance dose or using an extended-release dosage form.
- Metformin has intrinsically poor permeability in the lower portion of the gastrointestinal tract, leading to absorption from the upper part of the tract. It has very high solubility in water (>300mg/ml at 25 0 C). These parameters can lead to difficulty in providing a sustained release of the drug from a formulation and the concomitant problems associated with controlling the initial burst from such a formulation.
- the rate of dissolution of such high solubility drugs may be reduced by embedding the drug in a polymeric matrix or surrounding it with a polymeric barrier membrane through which the drug must diffuse to be released for absorption.
- Metformin hydrochloride is commercially available under the brand name
- Glucophage® (conventional) and Glucophage XR (extended-release tablets), currently marketed by Bristol Myers Squibb.
- Glucophage conventional tablets contain 500 mg, 850 mg and 1000 mg of metformin hydrochloride.
- Glucophage XR tablets (500 mg metformin hydrochloride; extended-release) comprise a dual hydrophilic matrix system which is described in U.S. Patent 6,475,521, which relates to a method for preparing a biphasic controlled release delivery system adapted for delivery of metformin. It describes a two phase system which includes an inner solid particulate phase containing the drug and an extended-release material and an outer solid continuous phase containing extended-release material. On coming in contact with the release medium, the drug released from the particles of the inner phase, migrates through the outer solid continuous phase and is then released into the upper gastrointestinal tract.
- each tablet containing 500mg of the active ingredient is about 1000 mg, as substantial amounts of polymers are required for controlling the rate of drug release.
- a scale-up formulation containing lOOOmg drug, when made according to this invention would weigh at least 2 g. This would be un- acceptably large for human consumption, and two tablets of 500mg strength each would be required for administering the daily adult dose of lOOOmg metformin.
- Metformin is a highly water soluble drug having poor flow and compressibility characteristics, hence, cannot be compressed in its pure form. Moreover, it is a high dose drug and therefore the tendency for capping is particularly high during the production of tablets. This capping results not only in loss of yield but also impairment of the quality. The high drag content does not allow much variation in the amount of excipients.
- U.S. Patent No. 5,955,106 discloses a process comprising granulating metformin and a hydrocolloid-forming retarding agent with an aqueous solvent to form a granulated product and drying the granulated product.
- the hydrocolloid-forming agents on coming in contact with aqueous medium, swell and form a gel matrix which erodes to release the drug.
- Extended-release compositions of metformin have also been formulated using other techniques.
- U.S. Patent No. 6,340,475 describes oral dosage forms in which the drugs are incorporated into polymeric matrices comprised of hydrophilic polymers that swell upon uptake of water to a size that is large enough to promote retention of the dosage form in the stomach. The swollen polymeric matrix remains intact long enough for substantially all of the drug to be released before dissolution of the matrix occurs.
- an extended-release pharmaceutical composition of metformin which maintains therapeutic blood level concentrations of the medicament in a patient for sufficiently long time, can be formulated as a monolithic matrix, which slowly releases the active agent over a prolonged period of time.
- extended-release metformin tablets are fonnulated as a monolithic matrix comprising metformin, rate-controlling polymers and other pharmaceutically acceptable excipients.
- the extended-release metformin tablets are provided which can incorporate a high dose of metformin and are of acceptable size, making it convenient for oral administration.
- the extended-release metformin tablet comprises a monolithic system that delivers highly soluble metformin at a relatively constant rate over extended periods of time, and is easy to manufacture.
- extended-release metformin tablets which comprise 5-25% w/w of rate controlling polymers.
- rate controlling polymers lesser amounts of rate controlling polymers than known for previous formulations ensures that the total weight of the dosage form is low and a single dosage unit is sufficient to provide the therapeutic dosage of the drug.
- extended-release tablets provide benefits with respect to better patient convenience and patient compliance.
- an extended-release metformin tablets of 850 mg strength comprising metformin, 5-25% w/w of rate-controlling polymers and other pharmaceutically acceptable excipients.
- an extended-release metformin tablets of 1000 mg strength comprising metformin, 5-25% w/w of rate-controlling polymers and other pharmaceutically acceptable excipients.
- a process for preparing extended-release tablets of metformin or non-toxic acid addition salts thereof which comprises blending of the ingredients followed by roller compaction or slugging. The compacts are suitably sized and compressed to form tablets.
- a process for preparing extended-release metformin tablets of 850 mg strength by roller compaction is provided.
- a process for preparing extended-release metformin tablets of 1000 mg strength by roller compaction is provided.
- Roller compaction generally involves a screening procedure that can lead to a narrower particle size distribution with fewer particles at either extreme of the size range. Roller compaction provides several other advantages, for example, uniform blends are produced with uniform particle size range, flow properties are improved, aids in dust control, increases bulk density and controls particle hardness.
- [30] a. from about 500 mg to about 1000 mg metformin,
- a process for preparing extended-release metformin tablets comprises:
- step (b) c. milling or crushing the compacted / slugged material of step (b) into granules
- metformin may be moisture conditioned before blending with rate controlling polymers and other excipients to further improve the flow properties.
- metformin may be blended with the rate controlling polymers and/or other excipients and then moisture-conditioned.
- a process for preparing extended-release metformin tablets comprises:
- step (b) d. milling or crushing the compacted / slugged material of step (b) into granules
- Another process for preparing extended-release metformin tablets comprises:
- step (b) d. milling or crushing the compacted / slugged material of step (b) into granules
- [50] e. lubricating and compressing the granules to form tablets.
- a process for preparing metformin extended- release tablets wherein the tablets have better strength, aesthetic appeal, desired profile and yield and are capable of incorporating very high doses of the drug, without making them unacceptably large to swallow.
- the extended-release tablets may further include one or more of sulfonylureas, insulin, glitazones, alpha-glucosidase inhibitors, meglitinides, fibrates, statins, squalene synthesis inhibitors and angiotensin-converting enzyme inhibitors.
- sulfonylureas insulin, glitazones, alpha-glucosidase inhibitors, meglitinides, fibrates, statins, squalene synthesis inhibitors and angiotensin-converting enzyme inhibitors.
- the term 'monolithic matrix' as described herein refers to a drug-containing matrix, formed by dispersing or dissolving the drug homogeneously in a suitable polymer.
- a monolithic matrix can be prepared by the direct compression, wet and dry granulation methods. The diffusion of a drag through a matrix is the designed to be rate-limiting step in case of such dosage forms. The rate of release from such matrices typically follows a square root of time dependency. In monolithic preparations made of hy- drophilic polymers, the drug release is governed by the swelling rate of the polymer matrix.
- Metformin can be used in the form of acid addition salts of inorganic or organic acids. These acids are exemplified by, but are not limited to, acids such as hydrochloric acid, formic acid, acetic acid, malic acid, tartaric acid or fumaric acid.
- Metformin can constitute up to 1000 mg per tablet.
- Rate-controlling polymers may be selected from cellulose derivatives, starch or its derivatives, alginates, acrylic and methacrylic acid derivatives, polyethylene oxides, gums, carbohydrate based polymers and similar materials.
- Cellulose derivatives may be selected from ethyl cellulose, methyl cellulose, hy- droxypropyl cellulose, hydroxyethyl cellulose, hydroxymethylcellulose, hy- droxypropyl methyl cellulose and sodium carboxy methyl cellulose of different degrees of substitution and molecular weights or similar materials. These polymers may be used alone or in combination.
- the acrylic acid polymers may be carboxy vinyl polymers such as those available under the brand name Carbopol® (B .F. Goodrich, USA).
- Carbohydrate based polymers may be selected from xanthan gum, tragacanth gum, gum karaya, guar gum, acacia, gellan gum, locust bean gum and the like. Rate-controlling polymers constitute 5-25% w/w of the formulation.
- the pharmaceutically acceptable excipients may be selected from diluents, binders, lubricants, glidants and flavouring agents which are physically and chemically compatible with metformin and which would help in optimizing tablet hardness, friability, drug dissolution and the production process.
- Diluents may be selected from any such pharmaceutically acceptable excipients, which give bulk to the composition and improve compressibility. These may be selected from starch and starch derivatives, dicalcium phosphate, calcium sulphate, sorbitol, microcrystalline cellulose, lactose, glucose, mannitol, alginates, alkali earth metal salts, clay, polyethylene glycols or similar materials.
- Binders may be selected from starch, mannitol, polyvinyl pyrrolidone, car- boxymethyl cellulose, hydroxy alkyl celluloses, dextrin, carbohydrate gums, alginates, polyacrylic acid, polyvinylalcohol and similar materials or mixtures thereof.
- Lubricants may be selected from talc, magnesium stearate, other alkali earth metal stearates like zinc, calcium stearate etc; sodium lauryl sulphate, hydrogenated vegetable oil, sodium benzoate, sodium stearyl fumarate, glyceryl monostearate, polyethylene glycol and similar materials.
- Glidants may be selected from colloidal silicon dioxide, talc and similar materials.
- the blend is compacted by roller compaction. Alternatively, this blend could be compressed to make slugs.
- One of the embodiments includes compaction or slugging of metformin either alone or after blending with rate controlling polymers and/or with excipients.
- antidiabetic agents include antidiabetic agents selected from the group consisting of sulfonylureas (e.g., glyburide, glipizide, glimepiride and gliclazide), a-glucosidase inhibitors (e.g., acarbose and miglitol); and glitazones (e.g., rosiglitazone and pioglitazone), as well as combinations of two or more of the foregoing antidiabetic agents.
- sulfonylureas e.g., glyburide, glipizide, glimepiride and gliclazide
- a-glucosidase inhibitors e.g., acarbose and miglitol
- glitazones e.g., rosiglitazone and pioglitazone
- Metformin hydrochloride and microcrystalline cellulose were mixed in a blender and sprayed with required quantity of purified water.
- step 2 was mixed with sodium carboxymethylcellulose, hydroxypropyl methyl cellulose, magnesium stearate and a part of colloidal silicon dioxide.
- step 3 The mass of step 3 was sifted and then compacted using a roller compactor.
- Table 1 Release profile of tablets of Example 1 and 2 in pH 6.8 phosphate buffer/900 ml/USP Apparatus 11/50 rpm.
- Tablet 2 Release profiles of tablets of Example 3 and 4 in pH 6.8 phosphate buffer/ 900 ml/USP Apparatus 11/50 rpm.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
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- Endocrinology (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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- Obesity (AREA)
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Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP04736789A EP1646374A1 (en) | 2003-06-16 | 2004-06-14 | Extended-release tablets of metformin |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN805DE2003 | 2003-06-16 | ||
IN805/DEL/2003 | 2003-06-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2004110422A1 true WO2004110422A1 (en) | 2004-12-23 |
Family
ID=33548811
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IB2004/050901 WO2004110422A1 (en) | 2003-06-16 | 2004-06-14 | Extended-release tablets of metformin |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP1646374A1 (zh) |
CN (1) | CN1805738A (zh) |
WO (1) | WO2004110422A1 (zh) |
Cited By (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1755568A1 (en) * | 2004-04-01 | 2007-02-28 | Hanmi Pharm. Co., Ltd. | Controlled release formulation for oral administration of metformin |
WO2007041053A3 (en) * | 2005-09-29 | 2008-03-13 | Novartis Ag | Formulation comprising metformin and vildagli ptin |
WO2008113000A1 (en) * | 2007-03-15 | 2008-09-18 | Nectid, Inc. | Anti-diabetic combinations comprising a slow release biguanide composition and an immediate release dipeptidyl peptidase iv inhibitor composition |
US7674479B2 (en) | 2006-07-25 | 2010-03-09 | Intelgenx Corp. | Sustained-release bupropion and bupropion/mecamylamine tablets |
WO2011060255A1 (en) * | 2009-11-13 | 2011-05-19 | Bristol-Myers Squibb Company | Reduced mass metformin formulations |
US8192761B2 (en) * | 2005-04-26 | 2012-06-05 | Dainippon Sumitomo Pharma Co., Ltd. | Granular preparation containing biguanide compound |
US8551524B2 (en) | 2008-03-14 | 2013-10-08 | Iycus, Llc | Anti-diabetic combinations |
EP2661266A2 (en) * | 2011-01-07 | 2013-11-13 | Elcelyx Therapeutics, Inc. | Chemosensory receptor ligand-based therapies |
US8703191B2 (en) | 2006-07-25 | 2014-04-22 | Intelgenx Corp. | Controlled-release pharmaceutical tablets |
EP2737897A3 (en) * | 2005-12-09 | 2014-10-01 | Metaproteomics, LLC | Anti-inflammatory botanical products for the treatment of metabolic syndrome and diabetes |
US9211263B2 (en) | 2012-01-06 | 2015-12-15 | Elcelyx Therapeutics, Inc. | Compositions and methods of treating metabolic disorders |
WO2016042567A1 (en) * | 2014-09-16 | 2016-03-24 | Suresh Pareek | Extended release formulation of metformin |
US9480663B2 (en) | 2011-01-07 | 2016-11-01 | Elcelyx Therapeutics, Inc. | Biguanide compositions and methods of treating metabolic disorders |
US9481642B2 (en) | 2011-01-07 | 2016-11-01 | Elcelyx Therapeutics, Inc. | Biguanide compositions and methods of treating metabolic disorders |
US9572784B2 (en) | 2011-01-07 | 2017-02-21 | Elcelyx Therapeutics, Inc. | Compositions comprising statins, biguanides and further agents for reducing cardiometabolic risk |
US9616028B2 (en) | 2009-11-13 | 2017-04-11 | Astrazeneca Ab | Bilayer tablet formulations |
US9717682B2 (en) | 2009-12-08 | 2017-08-01 | Intelgenx Corporation | Solid oral film dosage forms and methods for making same |
US10154972B2 (en) | 2011-01-07 | 2018-12-18 | Elcelyx Therapeutics, Inc. | Biguanide compositions and methods of treating metabolic disorders |
US10166246B2 (en) | 2014-05-27 | 2019-01-01 | City Of Hope | TGR5 agonist complexes for treating diabetes and cancer |
WO2019121685A1 (en) * | 2017-12-18 | 2019-06-27 | Bayer Aktiengesellschaft | Fixed dose combination tablet formulation of acarbose and metformin and process for producing the same |
US10610528B2 (en) | 2009-12-08 | 2020-04-07 | Intelgenx Corp. | Solid oral film dosage forms and methods for making same |
US10668031B2 (en) | 2011-01-07 | 2020-06-02 | Anji Pharma (Us) Llc | Biguanide compositions and methods of treating metabolic disorders |
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US11759441B2 (en) | 2011-01-07 | 2023-09-19 | Anji Pharmaceuticals Inc. | Biguanide compositions and methods of treating metabolic disorders |
US11974971B2 (en) | 2011-01-07 | 2024-05-07 | Anji Pharmaceuticals Inc. | Compositions and methods for treating metabolic disorders |
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US6117451A (en) * | 1998-08-25 | 2000-09-12 | Pharmalogix, Inc. | Direct compression metformin hydrochloride tablets |
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WO2003026637A2 (en) * | 2001-09-28 | 2003-04-03 | Sun Pharmaceutical Industries Limited | Dosage form for treatment of diabetes mellitus |
WO2003028704A1 (en) * | 2001-09-28 | 2003-04-10 | Ranbaxy Laboratories Limited | Extended release pharmaceutical composition containing metformin |
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2004
- 2004-06-14 EP EP04736789A patent/EP1646374A1/en not_active Withdrawn
- 2004-06-14 CN CNA2004800167682A patent/CN1805738A/zh active Pending
- 2004-06-14 WO PCT/IB2004/050901 patent/WO2004110422A1/en not_active Application Discontinuation
Patent Citations (7)
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Cited By (51)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1755568A1 (en) * | 2004-04-01 | 2007-02-28 | Hanmi Pharm. Co., Ltd. | Controlled release formulation for oral administration of metformin |
EP1755568A4 (en) * | 2004-04-01 | 2010-03-03 | Hanmi Pharm Ind Co Ltd | FORMULATION WITH CONTROLLED RELEASE FOR ORAL ADMINISTRATION OF METFORMIN |
US8192761B2 (en) * | 2005-04-26 | 2012-06-05 | Dainippon Sumitomo Pharma Co., Ltd. | Granular preparation containing biguanide compound |
RU2483716C2 (ru) * | 2005-09-29 | 2013-06-10 | Новартис Аг | Новый состав |
WO2007041053A3 (en) * | 2005-09-29 | 2008-03-13 | Novartis Ag | Formulation comprising metformin and vildagli ptin |
NO20200301A1 (no) * | 2005-09-29 | 2008-06-27 | Novartis Ag | Ny formulering |
NO344875B1 (no) * | 2005-09-29 | 2020-06-08 | Novartis Ag | Fremgangsmåte for fremstilling av en farmasøytisk tablett |
RU2483716C9 (ru) * | 2005-09-29 | 2021-08-10 | Новартис Аг | Новый состав |
NO346101B1 (no) * | 2005-09-29 | 2022-02-14 | Novartis Ag | Farmasøytisk tablett eller direkte sammenpresset tablett |
EP2737897A3 (en) * | 2005-12-09 | 2014-10-01 | Metaproteomics, LLC | Anti-inflammatory botanical products for the treatment of metabolic syndrome and diabetes |
US8703191B2 (en) | 2006-07-25 | 2014-04-22 | Intelgenx Corp. | Controlled-release pharmaceutical tablets |
US7674479B2 (en) | 2006-07-25 | 2010-03-09 | Intelgenx Corp. | Sustained-release bupropion and bupropion/mecamylamine tablets |
WO2008113000A1 (en) * | 2007-03-15 | 2008-09-18 | Nectid, Inc. | Anti-diabetic combinations comprising a slow release biguanide composition and an immediate release dipeptidyl peptidase iv inhibitor composition |
US8551524B2 (en) | 2008-03-14 | 2013-10-08 | Iycus, Llc | Anti-diabetic combinations |
JP2013510872A (ja) * | 2009-11-13 | 2013-03-28 | ブリストル−マイヤーズ スクイブ カンパニー | 低質量のメトホルミン製剤 |
CN102711738A (zh) * | 2009-11-13 | 2012-10-03 | 百时美施贵宝公司 | 质量得以减小的二甲双胍制剂 |
WO2011060255A1 (en) * | 2009-11-13 | 2011-05-19 | Bristol-Myers Squibb Company | Reduced mass metformin formulations |
US9616028B2 (en) | 2009-11-13 | 2017-04-11 | Astrazeneca Ab | Bilayer tablet formulations |
AU2010319438B2 (en) * | 2009-11-13 | 2015-05-21 | Astrazeneca Uk Limited | Reduced mass metformin formulations |
RU2712757C2 (ru) * | 2009-11-13 | 2020-01-31 | Астразенека Аб | Композиция двухслойной таблетки |
US9717682B2 (en) | 2009-12-08 | 2017-08-01 | Intelgenx Corporation | Solid oral film dosage forms and methods for making same |
US10610528B2 (en) | 2009-12-08 | 2020-04-07 | Intelgenx Corp. | Solid oral film dosage forms and methods for making same |
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US9463170B2 (en) | 2011-01-07 | 2016-10-11 | Elcelyx Therapeutics, Inc. | Chemosensory receptor ligand-based therapies |
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US10201511B2 (en) | 2011-01-07 | 2019-02-12 | Elcelyx Therapeutics, Inc. | Compositions and methods for treating metabolic disorders |
US11759441B2 (en) | 2011-01-07 | 2023-09-19 | Anji Pharmaceuticals Inc. | Biguanide compositions and methods of treating metabolic disorders |
US9962344B2 (en) | 2011-01-07 | 2018-05-08 | Elcelyx Therapeutics, Inc. | Chemosensory receptor ligand-based therapies |
US10028923B2 (en) | 2011-01-07 | 2018-07-24 | Elcelyx Therapeutics, Inc. | Biguanide compositions and methods of treating metabolic disorders |
EP3763419A1 (en) * | 2011-01-07 | 2021-01-13 | Anji Pharma (US) LLC | Chemosensory receptor ligand-based therapies |
US9050292B2 (en) | 2011-01-07 | 2015-06-09 | Elcelyx Therapeutics, Inc. | Chemosensory receptor ligand-based therapies |
US9572784B2 (en) | 2011-01-07 | 2017-02-21 | Elcelyx Therapeutics, Inc. | Compositions comprising statins, biguanides and further agents for reducing cardiometabolic risk |
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