EP0914128A1 - Formulation and method for treating congestive heart failure - Google Patents
Formulation and method for treating congestive heart failureInfo
- Publication number
- EP0914128A1 EP0914128A1 EP97928011A EP97928011A EP0914128A1 EP 0914128 A1 EP0914128 A1 EP 0914128A1 EP 97928011 A EP97928011 A EP 97928011A EP 97928011 A EP97928011 A EP 97928011A EP 0914128 A1 EP0914128 A1 EP 0914128A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- formulation
- moxonidine
- dosage form
- pharmaceutically acceptable
- acceptable salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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- GOLXNESZZPUPJE-UHFFFAOYSA-N spiromesifen Chemical compound CC1=CC(C)=CC(C)=C1C(C(O1)=O)=C(OC(=O)CC(C)(C)C)C11CCCC1 GOLXNESZZPUPJE-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- GMFOMTHMMJGZDI-UHFFFAOYSA-N sulfo hydrogen sulfate;sulfuric acid Chemical compound OS(O)(=O)=O.OS(=O)(=O)OS(O)(=O)=O GMFOMTHMMJGZDI-UHFFFAOYSA-N 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000008700 sympathetic activation Effects 0.000 description 1
- 206010042772 syncope Diseases 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 229940100640 transdermal system Drugs 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 206010047302 ventricular tachycardia Diseases 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 229920003176 water-insoluble polymer Polymers 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229940071104 xylenesulfonate Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
Definitions
- Plasma half life (t 1/2 ) is between 2 and 3 hours.
- the presently claimed invention provides a method of treating congestive heart failure comprising
- the fifth intermediate, N-(1-acetylimidazolin-2- ylidene)-4,6-dichloro-5-pyrimidinamine, is then prepared by combining phosphorous oxychloride, N-acetylimidazolin-2-one and 5-amino-4,6-dichloro-2-methylpyrimidine, and heating to boiling during from 2 to 4 hours, and then cooling, with stirring to room temperature.
- nonimmediate (sustained) release pharmaceutical formulation comprising one or more pharmaceutically acceptable carriers, diluents or excipients and the compound or a
- Nonimmediate release dosage forms release of the drug from its dosage form is the rate limiting step in the release-absorption-elimination kinetic scheme. This is distinguished from the immediate release dosage forms where absorption of drug across a biological membrane is a rate limiting step.
- Nonimmediate release delivery systems have been divided into four categories: (1) delayed release; (2) sustained release; (3) site-specific release; and (4) receptor release.
- Sustained release delivery systems include both controlled release and prolonged release.
- sustained release systems include any drug delivery system that achieves slow release of drug over an extended period of time. When the system maintains relatively constant drug levels in the blood or target tissue it is considered a controlled release system. Where the system extends the duration of action over that afforded by a conventional delivery system, it is considered a prolonged release system.
- Site-specific and receptor release systems refer to targeting of a drug directly to a desired biological location.
- a target is a particular organ or tissue.
- the target is the particular receptor for a drug within a particular organ or tissue.
- microencapsulation of drug particles and press-coating of whole tablets or particles.
- particles coated by microencapsulation form a system where the drug is contained in the coating film as well as in the core of the microcapsule.
- Drug release typically includes a combination of dissolution and diffusion with dissolution being the process that controls the release rate.
- Common material used as the membrane barrier coat, alone or in combination, are hardened gelatine, methyl and
- tristearate Preparation of these matrix systems are by methods well known to those skilled in the art. These methods of preparation generally comprise mixing the drug with the matrix material and compressing the mixture into tablets. With wax matrixes, the drug is generally dispersed in molten wax, which is then congealed, granulated and compressed into cores. As with other nonimmediate systems, it is common for a portion of the drug to be available immediately as a priming dose and the remainder to be released in a sustained fashion. This is generally
- the hydrophilic substance which operates as the coating material, is selected from a wide variety of natural and synthetic polymers including shellacs, waxes, starches, cellulose acetate, phthalate or butyrate,
- Coated particles can, of course, be directly compressed into tablets or placed into capsules.
- Liposomes generally, are phospholipids that when dispersed with aqueous media swell, hydrate and form
- a geometric mean for time to maximum plasma concentration should be from about 2.5 hours to about 5.0 hours, preferably 2.5 - 4.0 hours, with a geometric mean plasma elimination half- life of from about 6.0 hours to about 16.0 hours, preferably 7.0 - 15.0 hours.
- t max time to maximum plasma concentration
- the dosage size was progressively larger from the first to the sixth group. For each group the starting dose was smallest, with a maximum of two subsequent dose progression steps at 1-week intervals.
- Moxonidine and placebo tablets were provided to the hospital pharmacy and dispensed to patients in a number sufficient for each visit interval. Tablets of 0.1 mg of moxonidine and tablets of placebo were identical in appearance and combined in the proper proportions to assure desired dosages (including twice daily dosing if required), ease of compliance, and maintenance of the blind.
- dose in this protocol refers to the combination of study drug tablets taken on a single day. The current commercial formulations were used with lactose content adjusted to accommodate the presence or absence of active ingredient as described above.
- Moxonidine at 0.1 mg produced a maximum reduction in mean PNE 2 hours after dosing at Visit 3. Two hours after dosing, PNE was reduced by over 30% relative to placebo.
- the batch analysis tests showed a high sensitivity of the formula to variations of the mixing time. Increased mixing times tend to lead to an uneven lubricant distribution which caused insufficient tablet hardness.
- Example 1 Because of the delayed therapeutic effect with Example 1 (data not included), it was decided to combine a sustained release formulation with an initial dose. As data
- Example 2 The tablets were coated for humidity protection.
- Example 2 The tablets were coated for humidity protection.
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US65946396A | 1996-06-06 | 1996-06-06 | |
US659463 | 1996-06-06 | ||
PCT/US1997/009914 WO1997046241A1 (en) | 1996-06-06 | 1997-06-05 | Formulation and method for treating congestive heart failure |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0914128A1 true EP0914128A1 (en) | 1999-05-12 |
Family
ID=24645503
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP97928011A Withdrawn EP0914128A1 (en) | 1996-06-06 | 1997-06-05 | Formulation and method for treating congestive heart failure |
Country Status (17)
Country | Link |
---|---|
EP (1) | EP0914128A1 (ko) |
JP (1) | JP2000511906A (ko) |
KR (1) | KR20000016406A (ko) |
CN (1) | CN1226166A (ko) |
AU (1) | AU3233197A (ko) |
BR (1) | BR9709546A (ko) |
CA (1) | CA2256720A1 (ko) |
CZ (1) | CZ397698A3 (ko) |
EA (1) | EA199900006A1 (ko) |
HU (1) | HUP0003885A2 (ko) |
IL (1) | IL126966A0 (ko) |
NO (1) | NO985695L (ko) |
PL (1) | PL330637A1 (ko) |
TR (1) | TR199802496T2 (ko) |
WO (1) | WO1997046241A1 (ko) |
YU (1) | YU55998A (ko) |
ZA (1) | ZA974978B (ko) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19815411A1 (de) * | 1998-04-06 | 1999-10-07 | Solvay Pharm Gmbh | Thermogenese stimulierend wirksame Arzneimittel |
WO2000044355A1 (en) * | 1999-01-29 | 2000-08-03 | Eli Lilly And Company | Moxonidine salts |
DE10003771A1 (de) | 1999-02-01 | 2000-08-03 | Solvay Pharm Gmbh | Arzneimittel zur Behandlung nach Herzinfarkt |
DE602006018139D1 (de) * | 2006-08-31 | 2010-12-23 | Chemagis Ltd | Verwendung der Monoxidinssalze zur Reinigung von Monoxidin |
KR100812287B1 (ko) * | 2007-01-03 | 2008-03-13 | 주식회사 챠콜코리아 | 내면에 반사층을 갖는 신호등 갓 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4323570A (en) * | 1978-11-15 | 1982-04-06 | Beiersdorf Aktiengesellschaft | Substituted aminopyrimidines |
DE3617158C2 (de) * | 1986-05-22 | 1994-10-06 | Lohmann Therapie Syst Lts | Transdermales Arzneimittel |
DE3729299A1 (de) * | 1987-09-02 | 1989-03-23 | Beiersdorf Ag | Transdermales therapeutisches system |
DE3904795C2 (de) * | 1989-02-17 | 2000-10-12 | Lilly Pharma Produktion Gmbh & | Pharmazeutisches Präparat und dessen Verwendung |
DE4325491A1 (de) * | 1993-07-29 | 1995-02-02 | Boehringer Ingelheim Kg | Verwendung von zentral wirksamen alpha-2-Agonisten zur Hemmung des Postaggressionsstoffwechsels |
DE4423177A1 (de) * | 1994-07-01 | 1996-01-04 | Kali Chemie Pharma Gmbh | Antihyperglykämisch wirksame Arzneimittel |
CA2182851A1 (en) * | 1995-08-15 | 1997-02-16 | August Masaru Watanabe | Method for treating substance abuse withdrawal |
-
1997
- 1997-06-05 TR TR1998/02496T patent/TR199802496T2/xx unknown
- 1997-06-05 BR BR9709546A patent/BR9709546A/pt not_active Application Discontinuation
- 1997-06-05 WO PCT/US1997/009914 patent/WO1997046241A1/en not_active Application Discontinuation
- 1997-06-05 PL PL97330637A patent/PL330637A1/xx unknown
- 1997-06-05 AU AU32331/97A patent/AU3233197A/en not_active Abandoned
- 1997-06-05 CZ CZ983976A patent/CZ397698A3/cs unknown
- 1997-06-05 JP JP10500901A patent/JP2000511906A/ja active Pending
- 1997-06-05 HU HU0003885A patent/HUP0003885A2/hu unknown
- 1997-06-05 ZA ZA974978A patent/ZA974978B/xx unknown
- 1997-06-05 EP EP97928011A patent/EP0914128A1/en not_active Withdrawn
- 1997-06-05 CN CN97196854A patent/CN1226166A/zh active Pending
- 1997-06-05 KR KR1019980709980A patent/KR20000016406A/ko not_active Application Discontinuation
- 1997-06-05 IL IL12696697A patent/IL126966A0/xx unknown
- 1997-06-05 CA CA002256720A patent/CA2256720A1/en not_active Abandoned
-
1998
- 1998-12-04 NO NO985695A patent/NO985695L/no not_active Application Discontinuation
- 1998-12-04 YU YU55998A patent/YU55998A/sr unknown
-
1999
- 1999-01-06 EA EA199900006A patent/EA199900006A1/ru unknown
Non-Patent Citations (1)
Title |
---|
See references of WO9746241A1 * |
Also Published As
Publication number | Publication date |
---|---|
HUP0003885A2 (hu) | 2001-04-28 |
KR20000016406A (ko) | 2000-03-25 |
BR9709546A (pt) | 1999-08-10 |
AU3233197A (en) | 1998-01-05 |
EA199900006A1 (ru) | 1999-06-24 |
IL126966A0 (en) | 1999-09-22 |
ZA974978B (en) | 1998-12-07 |
TR199802496T2 (xx) | 1999-02-22 |
WO1997046241A1 (en) | 1997-12-11 |
CZ397698A3 (cs) | 1999-05-12 |
NO985695L (no) | 1999-02-04 |
JP2000511906A (ja) | 2000-09-12 |
NO985695D0 (no) | 1998-12-04 |
YU55998A (en) | 1999-11-22 |
PL330637A1 (en) | 1999-05-24 |
CN1226166A (zh) | 1999-08-18 |
CA2256720A1 (en) | 1997-12-11 |
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