CA2530460A1 - Method of treating acute coronary syndromes - Google Patents
Method of treating acute coronary syndromes Download PDFInfo
- Publication number
- CA2530460A1 CA2530460A1 CA002530460A CA2530460A CA2530460A1 CA 2530460 A1 CA2530460 A1 CA 2530460A1 CA 002530460 A CA002530460 A CA 002530460A CA 2530460 A CA2530460 A CA 2530460A CA 2530460 A1 CA2530460 A1 CA 2530460A1
- Authority
- CA
- Canada
- Prior art keywords
- therapeutic agent
- group
- formulation
- encapsulated
- bisphosphonate
- 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.)
- Granted
Links
- 208000004476 Acute Coronary Syndrome Diseases 0.000 title claims abstract 8
- 238000000034 method Methods 0.000 title abstract 3
- 239000003814 drug Substances 0.000 claims abstract 25
- 229940124597 therapeutic agent Drugs 0.000 claims abstract 25
- 239000000203 mixture Substances 0.000 claims abstract 16
- 238000009472 formulation Methods 0.000 claims abstract 15
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 9
- 210000001539 phagocyte Anatomy 0.000 claims abstract 6
- 206010000891 acute myocardial infarction Diseases 0.000 claims abstract 5
- 230000007423 decrease Effects 0.000 claims abstract 4
- 206010002388 Angina unstable Diseases 0.000 claims abstract 3
- 208000007814 Unstable Angina Diseases 0.000 claims abstract 3
- 230000000694 effects Effects 0.000 claims abstract 3
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims abstract 3
- 210000002540 macrophage Anatomy 0.000 claims abstract 3
- 210000001616 monocyte Anatomy 0.000 claims abstract 3
- 229940122361 Bisphosphonate Drugs 0.000 claims 8
- 150000004663 bisphosphonates Chemical group 0.000 claims 8
- 125000005843 halogen group Chemical group 0.000 claims 4
- 125000001072 heteroaryl group Chemical group 0.000 claims 4
- 230000003834 intracellular effect Effects 0.000 claims 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 4
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 claims 3
- DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 claims 3
- DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 claims 3
- 229940062527 alendronate Drugs 0.000 claims 3
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 claims 3
- 229960002286 clodronic acid Drugs 0.000 claims 3
- 239000000084 colloidal system Substances 0.000 claims 3
- 229940009626 etidronate Drugs 0.000 claims 3
- 239000002502 liposome Substances 0.000 claims 3
- 239000011859 microparticle Substances 0.000 claims 3
- 239000004005 microsphere Substances 0.000 claims 3
- 239000002105 nanoparticle Substances 0.000 claims 3
- 239000002077 nanosphere Substances 0.000 claims 3
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 claims 3
- 229940046231 pamidronate Drugs 0.000 claims 3
- 229920000642 polymer Polymers 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- 229940019375 tiludronate Drugs 0.000 claims 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 2
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 2
- 125000003282 alkyl amino group Chemical group 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- -1 chlorosubstituted phenyl Chemical group 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 claims 2
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 2
- 150000002431 hydrogen Chemical group 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 239000002245 particle Substances 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 2
- 239000000126 substance Substances 0.000 claims 2
- 150000003512 tertiary amines Chemical class 0.000 claims 2
- 239000000824 cytostatic agent Substances 0.000 claims 1
- 230000001085 cytostatic effect Effects 0.000 claims 1
- 231100000433 cytotoxic Toxicity 0.000 claims 1
- 230000001472 cytotoxic effect Effects 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 239000003053 toxin Substances 0.000 claims 1
- 231100000765 toxin Toxicity 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 abstract 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
- A61K31/66—Phosphorus compounds
- A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61K31/663—Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
-
- 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)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to methods and compositions designed for the treatment or management of acute coronary syndromes, particularly, unstable angina and acute myocardial infarction. The methods of the invention comprise the administration of an effective amount of a formulation containing one or more therapeutic agents which specifically decreases or inhibits the activity of phagocytic cells and/or eliminates or diminishes the amount of phagocytic cells including, but not limited to, macrophages and monocytes. The formulations are specifically targeted to phagocytic cells. The invention also provides pharmaceutical compositions of formulations containing one or more therapeutic agents of the invention for administration to subjects currently suffering from or having recently suffered an acture coronary syndrome such as unstable angina and acute myocardial infarction.
Claims (28)
1. Use of an effective amount of a formulation that decreases phagocytic cell activity for treating an acute coronary syndrome, said formulation comprising a therapeutic agent which is encapsulated, embedded, or in a particle that is 0.05-1.0 microns in size.
2. Use of an effective amount of a formulation that decreases the phagocytic cell numbers for treating an acute coronary syndrome, said formulation comprising a therapeutic agent which is encapsulated, embedded, or in a particle that is 0.05-1.0 microns in size.
3. The use of claim 1 or 2, wherein said acute coronary syndrome is unstable angina.
4. The use of claim 1 or 2, wherein said acute coronary syndrome is impending or actual plaque rupture.
5. The use of claim 1 or 2, wherein said acute coronary syndrome is acute myocardial infarction.
6. The use of claim 1 or 2, wherein said therapeutic agent is a bisphosphonate.
7. The use of claim 6, wherein said bisphosphonate comprises a compound having formula (I):
wherein R1 is H, OH or halogen group; and R2 is halogen; linear or branched C1-C10 alkyl or C2-C10 alkenyl, optionally substituted by heteroaryl or heterocyclyl C1-C10 alkylamino or C3-C8 cycloalkylamino, where the amino may be a primary, secondary or tertiary amine; -NHY where Y is hydrogen, C3-C8 cycloalkyl, aryl or heteroaryl; or -SZ, where Z is chlorosubstituted phenyl or pyridinyl.
wherein R1 is H, OH or halogen group; and R2 is halogen; linear or branched C1-C10 alkyl or C2-C10 alkenyl, optionally substituted by heteroaryl or heterocyclyl C1-C10 alkylamino or C3-C8 cycloalkylamino, where the amino may be a primary, secondary or tertiary amine; -NHY where Y is hydrogen, C3-C8 cycloalkyl, aryl or heteroaryl; or -SZ, where Z is chlorosubstituted phenyl or pyridinyl.
8. The use of claim 6, wherein said bisphosphonate is selected from the group consisting of clodronate, etidronate, tiludronate, pamidronate, alendronate and risenthonate.
9. The use according to claim 1 or 2, wherein said therapeutic agent is encapsulated in a liposome.
10. The use of claim 1 or 2, wherein said therapeutic agent is embedded in a carrier selected from the group consisting of microparticles, nanoparticles, microspheres, and nanospheres.
11. The use of claim 1 or 2, wherein said therapeutic agent is formulated as a particulate selected from the group consisting of aggregates, flocculates, colloids, polymer chains, insoluble salts and insoluble complexes.
12. The use of claim 1 or 2, wherein more than one therapeutic agent is contained in the formulation.
13. The use of an effective amount of a formulation that decreases phagocytic cell activity or numbers for treating acute myocardial infarction, said formulation comprising a therapeutic agent which is encapsulated, embedded, or in a particulate that is 0.05-1.0 microns in size.
14. The use of claim 13, wherein said therapeutic agent is a bisphosphonate.
15. The use of claim 14, wherein said bisphosphonate comprises a compound having formula (I):
wherein R1 is H, OH or halogen group; and R2 is halogen; linear or branched C1-C10 alkyl or C2-C10 alkenyl, optionally substituted by heteroaryl or heterocyclyl C1-C10 alkylamino or C3-C5 cycloalkylamino, where the amino may be a primary, secondary or tertiary amine; -NHY where Y is hydrogen, C3-C8 cycloalkyl, aryl or heteroaryl; or -SZ, where Z is chlorosubstituted phenyl or pyridinyl.
wherein R1 is H, OH or halogen group; and R2 is halogen; linear or branched C1-C10 alkyl or C2-C10 alkenyl, optionally substituted by heteroaryl or heterocyclyl C1-C10 alkylamino or C3-C5 cycloalkylamino, where the amino may be a primary, secondary or tertiary amine; -NHY where Y is hydrogen, C3-C8 cycloalkyl, aryl or heteroaryl; or -SZ, where Z is chlorosubstituted phenyl or pyridinyl.
16. The use of claim 14, wherein said bisphosphonate is selected from the group consisting of clodronate, etidronate, tiludronate, pamidronate, alendronate and risendronate.
17. The use according to claim 13, wherein said therapeutic agent is encapsulated in a liposome.
18. The use of claim 13, wherein said therapeutic agent is embedded in a carrier selected from the group consisting of microparticles, nanoparticles, microspheres, and nanospheres.
19. The use of claim 13, wherein said therapeutic agent is formulated as a particulate selected from the group consisting of aggregates, flocculates, colloids, polymer chains, insoluble salts and insoluble complexes.
20. The use of claim 13, wherein more than one therapeutic agent is contained in the formulation.
21. A pharmaceutical composition for the treatment of patients with an acute coronary syndrome, comprising a formulation selected from the group consisting of an encapsulated therapeutic agent, an embedded therapeutic agent and a particulate therapeutic agent that is 0.05-1.0 microns in size, together with a pharmaceutically acceptable carrier, wherein the formulation inhibits blood monocytes or tissue macrophages.
22. A pharmaceutical composition for the treatment of patients with an acute myocardial infarction, comprising a formulation selected from the group consisting of an encapsulated therapeutic agent, an embedded therapeutic agent and a particulate therapeutic agent that is 0.05-1.0 microns in size, together with a pharmaceutically acceptable carrier;
wherein the formulation inhibits blood monocytes or tissue macrophages.
wherein the formulation inhibits blood monocytes or tissue macrophages.
23. The pharmaceutical composition of claim 21 or 22, wherein the therapeutic agent is selected from the group consisting of an intra-cellular inhibitor, an intra-cellular deactivator, an intra-cellular arrestor, an intra-cellular toxin, a cytostatic substance, and a cytotoxic substance.
24. The pharmaceutical composition of claim 21 or 22, wherein the therapeutic agent is a bisphosphonate.
25. The pharmaceutical composition of claim 21 or 22, wherein the therapeutic agent is encapsulated in a liposome.
26. The pharmaceutical composition of claim 21 or 22, wherein the therapeutic agent is encapsulated in a carrier selected from the group consisting of microparticles, nanoparticles, microspheres, and nanospheres.
27. The pharmaceutical composition of claim 21 or 22, wherein the particulates are selected from the group consisting of aggregates, flocculates, colloids, polymer chains, insoluble salts and insoluble complexes.
28. The pharmaceutical composition according to claim 24, wherein said bisphosphonate is selected from the group consisting of clodronate, etidronate, tiludronate, pamidronate, alendronate, and risendronate.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/607,623 | 2003-06-27 | ||
| US10/607,623 US10517883B2 (en) | 2003-06-27 | 2003-06-27 | Method of treating acute myocardial infarction |
| US10/871,488 US9498488B2 (en) | 2003-06-27 | 2004-06-18 | Method of treating acute coronary syndromes |
| US10/871,488 | 2004-06-18 | ||
| PCT/US2004/020487 WO2005002545A1 (en) | 2003-06-27 | 2004-06-24 | Method of treating acute coronary syndromes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2530460A1 true CA2530460A1 (en) | 2005-01-13 |
| CA2530460C CA2530460C (en) | 2012-08-14 |
Family
ID=33568009
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2530460A Expired - Fee Related CA2530460C (en) | 2003-06-27 | 2004-06-24 | Method of treating acute coronary syndromes |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JP4621202B2 (en) |
| AU (1) | AU2004253527B2 (en) |
| CA (1) | CA2530460C (en) |
| WO (1) | WO2005002545A1 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060051407A1 (en) * | 2003-06-27 | 2006-03-09 | Yoram Richter | Method of treating ischemia-reperfusion injury |
| US10517883B2 (en) | 2003-06-27 | 2019-12-31 | Zuli Holdings Ltd. | Method of treating acute myocardial infarction |
| EP2316441A1 (en) * | 2005-02-17 | 2011-05-04 | Hadasit Medical Research Services And Development | Bisphosphonates for treating endometriosis |
| EP1888034A2 (en) * | 2005-05-26 | 2008-02-20 | Yissum Research Development Company, of The Hebrew University of Jerusalem | Compositions and methods using same for delivering agents into a target organ protected by a blood barrier |
| CN102639137A (en) | 2009-09-01 | 2012-08-15 | 杜克大学 | Bisphosphonate compositions and methods for treating heart failure |
| WO2013074587A1 (en) | 2011-11-16 | 2013-05-23 | Duke University | Bishophonate compositions and methods for treating and/or reducing cardiac dysfunction |
| US9993427B2 (en) | 2013-03-14 | 2018-06-12 | Biorest Ltd. | Liposome formulation and manufacture |
| CN106456775A (en) * | 2014-05-16 | 2017-02-22 | 生物休眠有限公司 | Use of bisphosphonates as hiv/aids adjunctive treatment |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6139871A (en) * | 1995-07-26 | 2000-10-31 | The University Of British Columbia | Liposome compositions and methods for the treatment of atherosclerosis |
| AU7525296A (en) * | 1995-11-01 | 1997-05-22 | Chiron Corporation | Treatment of a cardiovascular indication by delivery of therapeutics to the pericardial space |
| DE19637890A1 (en) * | 1996-09-17 | 1998-03-19 | Max Planck Gesellschaft | Liposomal medicament containing bi:phosphonic acid salt, |
| IL125336A0 (en) * | 1998-07-14 | 1999-03-12 | Yissum Res Dev Co | Compositions for inhibition and treatment of restinosis |
| EP1390077B1 (en) | 2001-05-02 | 2014-07-16 | Purdue Research Foundation | Treatment and diagnosis of macrophage mediated disease |
-
2004
- 2004-06-24 WO PCT/US2004/020487 patent/WO2005002545A1/en active Application Filing
- 2004-06-24 CA CA2530460A patent/CA2530460C/en not_active Expired - Fee Related
- 2004-06-24 AU AU2004253527A patent/AU2004253527B2/en not_active Ceased
- 2004-06-24 JP JP2006517683A patent/JP4621202B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU2004253527B2 (en) | 2010-04-08 |
| WO2005002545A8 (en) | 2006-02-16 |
| CA2530460C (en) | 2012-08-14 |
| JP4621202B2 (en) | 2011-01-26 |
| JP2007524632A (en) | 2007-08-30 |
| WO2005002545A1 (en) | 2005-01-13 |
| AU2004253527A1 (en) | 2005-01-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20200831 |