NZ751885A - Sustained-release formulations of colchicine and methods of using same - Google Patents

Sustained-release formulations of colchicine and methods of using same Download PDF

Info

Publication number
NZ751885A
NZ751885A NZ751885A NZ75188514A NZ751885A NZ 751885 A NZ751885 A NZ 751885A NZ 751885 A NZ751885 A NZ 751885A NZ 75188514 A NZ75188514 A NZ 75188514A NZ 751885 A NZ751885 A NZ 751885A
Authority
NZ
New Zealand
Prior art keywords
formulation
colchicine
granules
amount
disease
Prior art date
Application number
NZ751885A
Other versions
NZ751885B2 (en
Inventor
Susanne Riel
Original Assignee
Murray And Poole Enterprises Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Murray And Poole Enterprises Ltd filed Critical Murray And Poole Enterprises Ltd
Priority claimed from NZ713151A external-priority patent/NZ713151B2/en
Publication of NZ751885A publication Critical patent/NZ751885A/en
Publication of NZ751885B2 publication Critical patent/NZ751885B2/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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • 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
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • 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
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Inorganic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pain & Pain Management (AREA)
  • Biophysics (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Rheumatology (AREA)
  • Cardiology (AREA)
  • Biochemistry (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Ophthalmology & Optometry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Pharmaceutical compositions of colchicine for once-a-day oral administration are provided. The formulations comprise a sustained-release component and an optional immediate-release component, the compositions of which can be selectively adjusted, respectively, to release the active ingredient along a pre-determined or desired release profile. The formulation comprises a release-retarding agent comprising HMPC and lactose monohydrate. Methods of treating or preventing cardiovascular disease and/or inflammatory disease in mammalian subjects comprising the administration of the novel formulations disclosed herein is also provided.

Description

(93%) and statins (95%) were randomly assigned colchicine 0.5 mg/day or no colchicine and followed for a median of 3 years (Nidorf et al., JACC, 2013, 61 (4), 404-410). This study showed that colchicine 0.5 mg/day administered in addition to statins and other standard secondary prevention therapies appeared effective for the prevention of cardiovascular events in patients with stable coronary disease.
For the treatment of gout, the recommended dose of colchcine (COLCRYS®) is 1.8 mg/day in one or multiple doses in one hour. For adults with gout, treatment is initiated with a dose of 1.2 mg at the first sign of symptoms followed by 0.6 mg one hour later. (Physician's Desk Reference, 68th ed., (2014)).
COLCRYS® is an immediate release formulation. Adverse effects associated with the administration of COLCRYS® include, but are not limited to, nausea, vomiting, abdominal pain, diarrhea, hair loss, weakness, nerve irritation, severe anemia, low white blood counts, and low platelets (Physician's Desk Reference, 68th ed., (2014)).
The instant invention addresses these and other needs by providing a modified formulation of colchicine characterized by a sustained release of an active ingredient. This invention additionally provides an effective, once-daily dosage form of colchicine or salts thereof, which may improve patient compliance and also may reduce some of the side effects of colchicine compared to the current or higher daily doses of immediate release colchicine formulations.
BRIEF SUMMARY OF THE INVENTION [0013a] In a first aspect there is provided a sustained release formulation of colchicine, comprising: (a) granules comprising colchicine or a pharmaceutically acceptable salt thereof in an amount of not more than 0.6 mg, and a binder comprising hydroxypropyl methylcellulose (HPMC) 6 mPa•s in an amount of 1% to 30% (w/w) of the formulation; (b) a release retarding agent admixed with, or blended with, the granules in an amount of between 25% and 30% w/w of the formulation, wherein the retarding agent comprises a combination of equal parts hydroxypropyl methylcellulose (HPMC) with a viscosity grade of 4000 mPa*s and lactose monohydrate; and (c) at least one additional pharmaceutically acceptable excipient admixed with or blended with the granules, wherein the at least one additional pharmaceutically acceptable excipient is starch, gelatin, polyvinylpyrrolidone (PVP), polyvinyl AH26(25551143_1):RTK alcohol, microcrystalline cellulose, hydroxypropyl cellulose (HPC) or a mixture thereof, wherein the sustained release formulation is in a form of a tablet, and wherein the formulation is homogeneous. [0013b] In a second aspect there is provided use of a therapeutically effective amount of a sustained release formulation of colchicine according to the first aspect in the preparation of a medicament for the treatment and/or prevention of a cardiovascular event in a subject, wherein the cardiovascular event is acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke. [0013c] In a third aspect there is provided use of a therapeutically effective amount of a sustained release formulation of colchicine according to the first aspect in the preparation of a medicament for the treatment and/or prevention of an inflammatory disease in a subject, wherein the inflammatory disease is gout, familial Mediterranean fever, Behcet´s disease, Age- related macular degeneration, or Alzheimer´s disease. [0013d] In a fourth aspect there is provided use of a therapeutically effective amount of a sustained release formulation of colchicine according to the first aspect in the preparation of a medicament for the treatment and/or prevention of an atherosclerotic vascular disease in a subject. [0013e] In a fifth aspect there is provided use of a therapeutically effective amount of a sustained release formulation of colchicine according to the first aspect in the preparation of a medicament for the treatment and/or prevention of atherosclerotic vascular disease in a subject, wherein the formulation comprises: (a) granules comprising not more than 0.6 mg of colchicine or a pharmaceutically acceptable salt thereof; (b) a release retarding agent admixed with the colchicine granules in an amount of 25% to 30% w/w of the formulation, and wherein the release retarding agent comprises equal parts hydroxypropyl methylcellulose (HPMC) with a viscosity grade of 4000 mPa•s and lactose monohydrate; and (c) at least one pharmaceutically acceptable excipient admixed with the granules.
According to aspects of the invention illustrated herein, there is provided a sustained release formulation of colchicine as an active ingredient, the formulation comprising colchicine or a pharmaceutically acceptable salt thereof; a retarding agent; and at least one pharmaceutically acceptable excipient.
AH26(25551143_1):RTK According to aspects of the invention illustrated herein, there is provided a method for treating and/or preventing a cardiovascular disease in a subject, comprising administering to the subject a therapeutically effective amount of a sustained release formulation of colchicine.
According to aspects of the invention illustrated herein, there is provided a method for treating and/or preventing an inflammatory disease in a subject, comprising administering AH26(25551143_1):RTK WE

Claims (16)

CLAIM :
1. A sustained release formulation of colchicine, comprising: (a) granules comprising colchicine or a pharmaceutically acceptable salt thereof in an amount of not more than 0.6 mg, and a binder comprising hydroxypropyl methylcellulose (HPMC) 6 mPa•s in an amount of 1% to 30% (w/w) of the formulation; (b) a release retarding agent admixed with, or blended with, the granules in an amount of between 25% and 30% w/w of the formulation, wherein the retarding agent comprises a combination of equal parts hydroxypropyl methylcellulose (HPMC) with a viscosity grade of 4000 mPa*s and lactose monohydrate; and (c) at least one additional pharmaceutically acceptable excipient admixed with or blended with the granules, wherein the at least one additional pharmaceutically acceptable excipient is starch, gelatin, polyvinylpyrrolidone (PVP), polyvinyl alcohol, microcrystalline cellulose, hydroxypropyl cellulose (HPC) or a mixture thereof, wherein the sustained release formulation is in a form of a tablet, and wherein the formulation is homogeneous.
2. The formulation of claim 1, wherein less than about 70% of the colchicine is released in vitro within 2 hours at 37 °C.
3. The formulation of claims 1 or 2, wherein the formulation releases at least about 20% of the colchicine in vitro within the first 30 minutes.
4. The formulation of any one of claims 1 to 3, wherein the granules in part (a) further comprise a first filling agent comprising lactose monohydrate in an amount of 10% to 80 % (w/w) of the formulation.
5. The formulation of any one of claims 1 to 4, further comprising a second filling agent admixed or blended with the granules comprising lactose monohydrate in an amount of 10% to 30% (w/w) of the formulation.
6. The formulation of any one of claims 1 to 5, wherein the formulation comprises no immediate release component or layer. AH26(25551143_1):RTK
7. The formulation of any one of claims 1 to 6, wherein the formulation is formulated for once daily administration.
8. The formulation of any one of claims 1 to 7, wherein the compression strength of the tablet is between 30N and 130N.
9. The formulation of any one of claims 1 to 8, wherein the formulation further comprises a statin.
10. The formulation of claim 9, wherein the statin is admixed with the formulation.
11. The formulation of claim 9 or claim 10, wherein the statin is one or more of atorvastatin, rosuvastatin, simvastatin, and pravastatin, or a salt thereof.
12. Use of a therapeutically effective amount of a sustained release formulation of colchicine according to any one of claims 1 to 11 in the preparation of a medicament for the treatment and/or prevention of a cardiovascular event in a subject, wherein the cardiovascular event is acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke.
13. Use of a therapeutically effective amount of a sustained release formulation of colchicine according to any one of claims 1 to 11 in the preparation of a medicament for the treatment and/or prevention of an inflammatory disease in a subject, wherein the inflammatory disease is gout, familial Mediterranean fever, Behcet´s disease, Age-related macular degeneration, or Alzheimer´s disease.
14. Use of a therapeutically effective amount of a sustained release formulation of colchicine according to any one of claims 1 to 11 in the preparation of a medicament for the treatment and/or prevention of an atherosclerotic vascular disease in a subject.
15. Use of a therapeutically effective amount of a sustained release formulation of colchicine according to any one of claims 1 to 11 in the preparation of a medicament for the treatment and/or prevention of atherosclerotic vascular disease in a subject, wherein the formulation comprises: (a) granules comprising not more than 0.6 mg of colchicine or a pharmaceutically acceptable salt thereof; AH26(25551143_1):RTK (b) a release retarding agent admixed with the colchicine granules in an amount of 25% to 30% w/w of the formulation, and wherein the release retarding agent comprises equal parts hydroxypropyl methylcellulose (HPMC) with a viscosity grade of 4000 mPa•s and lactose monohydrate; and (c) at least one pharmaceutically acceptable excipient admixed with the granules.
16. The use of claim 14 or claim 15, wherein the atherosclerotic vascular disease is a coronary disease. Murray and Poole Enterprises Limited By the Attorneys for the Applicant SPRUSON & FERGUSON Per: AH26(25551143_1):RTK
NZ751885A 2013-04-16 2014-04-16 Sustained-release formulations of colchicine and methods of using same NZ751885B2 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201361812514P 2013-04-16 2013-04-16
US61/812,514 2013-04-16
EPEP13194505.7 2013-11-26
EP13194505 2013-11-26
NZ713151A NZ713151B2 (en) 2013-04-16 2014-04-16 Sustained-release formulations of colchicine and methods of using same

Publications (2)

Publication Number Publication Date
NZ751885A true NZ751885A (en) 2021-01-29
NZ751885B2 NZ751885B2 (en) 2021-04-30

Family

ID=

Also Published As

Publication number Publication date
HUE054663T2 (en) 2021-09-28
HRP20210963T1 (en) 2021-09-17
IL242001B (en) 2021-07-29
LT2986280T (en) 2021-06-25
JP2020125335A (en) 2020-08-20
DK2986280T3 (en) 2021-06-14
JP6697539B2 (en) 2020-05-20
JP6887043B2 (en) 2021-06-16
ES2870718T3 (en) 2021-10-27
NZ713151A (en) 2021-01-29
JP2019065032A (en) 2019-04-25

Similar Documents

Publication Publication Date Title
RU2404750C2 (en) Composition containing base or coat for moderated release and antagonist of nmda receptor, method for introduction of such nmda antagonist to individual
WO2005065069A3 (en) Pharmaceutical methods, dosing regimes and dosage forms for the treatment of alzheimer's disease
JP2010525050A5 (en)
CA2563058C (en) Supportive treatment of liver disease
RU2010123027A (en) PHARMACEUTICAL COMPOSITIONS OF DUAL ACTION ON THE BASIS OF NADMOLECULAR STRUCTURES OF ANTAGONISTS / ANGIOTENZINE (ARB) RECEPTOR BLOCK AND NEUTRAL ENDEPEPTIDASE (NEP) INHIBITOR (NEP)
JP6068765B2 (en) Pharmaceutical combination preparation
CA2642851A1 (en) Low flush niacin formulation
CA3097053A1 (en) Edaravone pharmaceutical composition
JP2017533211A5 (en)
JP2010065060A (en) Composite treatment for heart failure treatment
RU2013105513A (en) Derivatives of 1-aminoalkylcyclohexane for the treatment of inflammatory skin diseases
RU2011113733A (en) Derivatives of 1-amino-alkylcyclohexane for the treatment of cognitive impairment in noise in the ears
NZ751885A (en) Sustained-release formulations of colchicine and methods of using same
NZ751885B2 (en) Sustained-release formulations of colchicine and methods of using same
AU2012276476B2 (en) Pharmaceutical composition for treating premature ejaculation and method for treating premature ejaculation
KR20120120519A (en) Combination preparations comprising niacin and hmg-coa reductase inhibitor and the preparation method thereof
JPH05201861A (en) Reinforcement of anti-tussis effect of dexthorphan
JP2016514125A (en) Compound preparation containing valsartan and rosuvastatin calcium and method for producing the same
NZ713151B2 (en) Sustained-release formulations of colchicine and methods of using same
US20230028539A1 (en) Pharmaceutical composition, complementary kit and application thereof
JP2015515971A5 (en)
JP2000229853A (en) Menstruation pain-improving composition
BRPI0617184A2 (en) delayed-release pralnacasan formulation
KR20170141524A (en) Controlled-release tablet containing bepotastine
WO2023091107A1 (en) Preparation of new drug formulations capable of exhibiting an anti-viral effect and investigation of their effect against covid-19

Legal Events

Date Code Title Description
PSEA Patent sealed
RENW Renewal (renewal fees accepted)

Free format text: PATENT RENEWED FOR 1 YEAR UNTIL 16 APR 2023 BY CPA GLOBAL

Effective date: 20220401

RENW Renewal (renewal fees accepted)

Free format text: PATENT RENEWED FOR 1 YEAR UNTIL 16 APR 2024 BY CPA GLOBAL

Effective date: 20230331

RENW Renewal (renewal fees accepted)

Free format text: PATENT RENEWED FOR 1 YEAR UNTIL 16 APR 2025 BY DENNEMEYER AND CO. SARL

Effective date: 20240408