Compositions and methods for preventing cardiac arrhythmia

• US 8,980,296 B2
• Filed: 02/17/2010
• Issued: 03/17/2015
• Est. Priority Date: 02/18/2009
• Status: Active Grant

• Current Assignee: Elutia Med LLC
• Original Assignee: Cormatrix Cardiovascular, Inc.
• Inventors: Matheny, Robert G., Lewis, Beecher C.
• Primary Examiner(s): Buckley, Audrea
• Application Number:
  US12/707,427
• Publication Number:
  US 20100233235A1
• Time in Patent Office: 1,854 Days
• US Class Current: 424/423
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/166 having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/22 of acyclic acids, e.g. pravastatin
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/4166 having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4402 only substituted in position 2, e.g. pheniramine, bisacodyl
• CPC Class Codes: A61K 31/4418 having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/22 : Urine; Urinary tract, e.g. kidney or bladder; Intraglomerular mesangial cells; Renal mesenchymal cells; Adrenal gland
• CPC Class Codes: A61K 35/34 : Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes vascular smooth muscle A61K35/44
• CPC Class Codes: A61K 35/36 : Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells islets of Langerhans A61K35/39
• CPC Class Codes: A61K 35/38 : Stomach; Intestine; Goblet cells; Oral mucosa; Saliva
• CPC Class Codes: A61K 35/407 : Liver; Hepatocytes
• CPC Class Codes: A61K 35/50 : Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
• CPC Class Codes: A61K 38/1825 : Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 38/1841 : Transforming growth factor [TGF]
• CPC Class Codes: A61K 38/202 : IL-3
• CPC Class Codes: A61K 38/2026 : IL-4
• CPC Class Codes: A61K 38/2066 : IL-10
• CPC Class Codes: A61K 38/2086 : IL-13 to IL-16
• CPC Class Codes: A61K 38/2093 : Leukaemia inhibitory factor [LIF]
• CPC Class Codes: A61K 38/217 : IFN-gamma
• CPC Class Codes: A61K 38/48 : acting on peptide bonds (3.4)
• CPC Class Codes: A61K 45/06 : Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0012 : Galenical forms characterised by the site of application
• CPC Class Codes: A61L 27/3633 : Extracellular matrix [ECM]
• CPC Class Codes: A61L 27/3834 : Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/54 : Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Disclosed herein are compositions and methods for treating or preventing cardiac arrhythmia in a subject.

Claims

1. A method of treating post-operative atrial fibrillation in a subject, comprising:

providing an extracellular matrix (ECM) composition comprising acellular ECM and a statin, said statin being linked to said ECM, wherein, when said ECM composition is administered to damaged cardiovascular tissue, said ECM composition modulates inflammation of said damaged cardiovascular tissue and induces myofibroblast proliferation and angiogenesis; and

delivering a therapeutically effective amount of said ECM composition directly to post-operative damaged myocardium tissue of said subject, wherein, said ECM composition modulates inflammation of said damaged myocardium tissue and induces myofibroblast proliferation and angiogenesis and, thereby, bioremodeling and regeneration of new myocardium tissue, whereby said ECM composition modulates electrical activity of said subject'"'"'s heart.

2. The method of claim 1, wherein said acellular extracellular matrix comprises mammalian extracellular matrix selected from the group consisting of small intestinal submucosa, urinary bladder submucosa, stomach submucosa, and liver basement membrane.

3. The method of claim 1, wherein the mammalian extracellular matrix is selected from the group of tissues consisting of dermis, fascia, pericardium, parenchymal tissue, and myocardial extracellular matrix.

4. The method of claim 1, wherein said acellular extracellular matrix comprises a collagen scaffold from a mammalian tissue source.

5. The method of claim 1, wherein the mammalian extracellular matrix is injectable.

6. The method of claim 1, wherein the mammalian extracellular matrix is in fluidized form.

7. The method of claim 1, wherein the mammalian extracellular matrix is emulsified.

8. The method of claim 1, wherein the mammalian extracellular matrix is a powder or an aerosol.

9. The method of claim 1, wherein the mammalian extracellular matrix is sprayed on the cardiac tissue.

10. The method of claim 1, wherein the composition is administered to the epicardial or endocardial surfaces of the heart.

11. The method of claim 1, wherein said subject presents with a myocardial infarction.

12. The method of claim 1, wherein said statin is selected from the group consisting of lovastatin, simvastatin, atorvastatin, fluvastatin, pravastatin, rosuvastatin, cerivastatin and pitavastatin.