Granted Patent
B2
US 12,357,696 · App. 17/511,220 · Granted Jul 15, 2025
Preserved etherified cyclodextrin derivatives containing liquid aqueous pharmaceutical composition
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Abstract
A preserved liquid aqueous pharmaceutical composition includes one or more etherified cyclodextrin derivatives, at least one water-soluble preservative, and at least one pharmaceutically active compound which is poorly water-soluble, very poorly water-soluble or water-insoluble. The liquid aqueous pharmaceutical composition provides an acceptable solubility of the pharmaceutically active compound, such as pimobendan, in aqueous solution whereby the water-soluble preservatives retain their effectiveness in the presence of the etherified cyclodextrin derivatives allowing the use in an oral administration form.
Claims (26)
1. A preserved liquid aqueous pharmaceutical composition comprising:
pimobendan, or pharmaceutically acceptable salts thereof;
at least one etherified cyclodextrin derivative comprising hydroxypropyl-ß-cyclodextrin (HPβCD);
at least one water-soluble antimicrobial preservative comprising sorbic acid in an amount of 0.20 g/100 mL to 0.40 g/100 mL;
at least one water-soluble antioxidant comprising ascorbic acid in an amount of 0.3 g/100 mL to 1.0 g/100 mL; and
hydroxypropyl methylcellulose (hypromellose);
wherein a pH of the composition is from 2.5 to 5, and the composition is free of paraben and sodium edetate.
2. The composition of claim 1 , wherein the pH of the composition is from 3 to 5.
3. The composition of claim 1 , wherein the pH of the composition is from 3.4 to 5.
4. The composition of claim 1 , wherein the pH of the composition is from 3.4 to 4.
5. The composition of claim 1 , wherein the pH of the composition is from 3.1 to 5 and the ratio of sorbic acid to ascorbic acid is from 0.1 to 1.5.
6. The composition of claim 1 , wherein the composition further comprises:
0.1 g/100 mL to 0.25 g/100 mL pimobendan or pharmaceutically acceptable salts thereof;
20 g/100 mL to 35 g/100 mL of hydroxypropyl-ß-cyclodextrin (HPβCD); and
0.05 g/100 mL to 0.30 g/100 mL of hydroxypropyl methylcellulose (hypromellose).
7. The composition of claim 1 , wherein the at least one water-soluble antimicrobial preservative further comprises at least one component selected from the group consisting of sodium sorbate, potassium sorbate, calcium sorbate, sodium benzoate, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, sodium metabisulfite, sodium acetate, and combinations thereof.
8. The composition of claim 1 , wherein the at least one water-soluble antioxidant further comprises at least one component selected from the group consisting of citric acid (anhydrous and/or monohydrate) or a pharmaceutically acceptable salt thereof, erythorbic acid, fumaric acid, malic acid, monothioglycerol, phosphoric acid, sodium metabisulfite, potassium metabisulfite, propionic acid, sodium bisulfite, sodium sulfite, resveratrol, butylhydroxyanisol, a gallate derivative, and combinations thereof.
9. The composition of claim 1 , wherein the at least one water-soluble antioxidant further comprises sodium metabisulfite, potassium metabisulfite and/or resveratrol.
10. The composition of claim 1 , wherein the at least one water-soluble antioxidant further comprises at least one component selected from the group consisting of sodium ascorbate, sodium citrate, propylgallate, and a combination thereof.
11. The composition of claim 1 , wherein the hydroxypropyl methylcellulose (hypromellose) has a molar mass of 5,000 to 500,000 g/mol.
12. The composition of claim 1 , wherein the at least one etherified cyclodextrin derivative further comprises at least one further etherified cyclodextrin derivative selected from the group consisting of hydroxyethyl-β-cyclodextrin, dihydroxypropyl-β-cyclodextrin, sulphobutyl ether-β-cyclodextrin, and combinations thereof.
13. The composition of claim 1 , wherein the composition is for oral administration.
14. The composition of claim 1 , wherein the composition is for parenteral administration.
15. A kit of parts comprising:
the preserved liquid aqueous pharmaceutical composition of claim 1 ; and
a package leaflet including the information that the pharmaceutical composition is to be used for the prevention of heart failure and/or hypertrophic cardiomyopathy, in a subject in need of such prevention or treatment.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 27, 2021
From: AVEN, MICHAEL; LUKAS, TIM
To: BOEHRINGER INGELHEIM VETMEDICA GMBH
Reel/Frame 058592/0110 →
Priority Claims (1)
EP 13177268
· Jul 19, 2013
· regional
Continuity (3)
References Cited (400)
US 3574859A
· Kosti
· 1971
[cited by applicant]
US 3822349A
· Kosti
· 1974
[cited by applicant]
US 3832460A
· Kosti
· 1974
[cited by applicant]
US 3839522A
· Kosti
· 1974
[cited by applicant]
US 3950333A
· Durant et al.
· 1976
[cited by applicant]
US 4128658A
· Price et al.
· 1978
[cited by applicant]
US 4256743A
· Goldhaber
· 1981
[cited by applicant]
US 4283400A
· von Bittera et al.
· 1981
[cited by applicant]
US 4283408A
· Hirata et al.
· 1981
[cited by applicant]
US 4293557A
· Shibata et al.
· 1981
[cited by applicant]
US 4361563A
· Austel et al.
· 1982
[cited by applicant]
US 4375547A
· Pioch
· 1983
[cited by applicant]
US 4386099A
· Cereda et al.
· 1983
[cited by applicant]
US 4427648A
· Brickl et al.
· 1984
[cited by applicant]
US 4569837A
· Suzuki et al.
· 1986
[cited by applicant]
US 4585790A
· Padfield et al.
· 1986
[cited by applicant]
US 4596705A
· Schepky et al.
· 1986
[cited by applicant]
US 4654342A
· Slater
· 1987
[cited by applicant]
US 4704284A
· Beatty et al.
· 1987
[cited by applicant]
US 4732915A
· Ayer et al.
· 1988
[cited by applicant]
US 4851226A
· Julian et al.
· 1989
[cited by applicant]
US 4865851A
· James et al.
· 1989
[cited by applicant]
US 4868182A
· Dage
· 1989
[cited by applicant]
US 4906628A
· Coates
· 1990
[cited by applicant]
US 4933182A
· Higashi et al.
· 1990
[cited by applicant]
US 4954501A
· Herter et al.
· 1990
[cited by applicant]
US 4973469A
· Mulligan et al.
· 1990
[cited by applicant]
US 5024998A
· Bodor
· 1991
[cited by applicant]
US 5151420A
· Backstrom et al.
· 1992
[cited by applicant]
US 5188836A
· Muhammad et al.
· 1993
[cited by applicant]
US 5364646A
· Gruber et al.
· 1994
[cited by applicant]
US 5472954A
· Loftsson
· 1995
[cited by applicant]
US 5569657A
· Nore et al.
· 1996
[cited by applicant]
US 5571533A
· Santus et al.
· 1996
[cited by applicant]
US 6407079B1
· Muller et al.
· 2002
[cited by applicant]
US 6476078B2
· Jerussi et al.
· 2002
[cited by applicant]
US 6669955B2
· Chungi et al.
· 2003
[cited by applicant]
US 6713487B2
· Yu et al.
· 2004
[cited by applicant]
US 7262165B2
· Lindenblatt et al.
· 2007
[cited by applicant]
US 8183230B2
· Adami et al.
· 2012
[cited by applicant]
US 8409612B1
· Criere et al.
· 2013
[cited by applicant]
US 8846679B2
· Folger et al.
· 2014
[cited by applicant]
US 8980894B2
· Daemmgen et al.
· 2015
[cited by applicant]
US 9107952B2
· Folger et al.
· 2015
[cited by applicant]
US 20030059471A1
· Compton et al.
· 2003
[cited by applicant]
US 20030190343A1
· Thombre et al.
· 2003
[cited by applicant]
US 20040037869A1
· Cleverly et al.
· 2004
[cited by applicant]
US 20040081691A1
· Debregeas et al.
· 2004
[cited by applicant]
US 20040152664A1
· Chang et al.
· 2004
[cited by applicant]
US 20040157887A1
· Whittle et al.
· 2004
[cited by applicant]
US 20040214797A1
· Lyons et al.
· 2004
[cited by applicant]
US 20050095293A1
· Brauns et al.
· 2005
[cited by applicant]
US 20070112010A1
· Kleeman et al.
· 2007
[cited by applicant]
US 20090220611A1
· Dargelas et al.
· 2009
[cited by applicant]
US 20100166857A1
· Yan et al.
· 2010
[cited by applicant]
US 20100183718A1
· Ovaert et al.
· 2010
[cited by applicant]
US 20100273807A1
· Kleeman et al.
· 2010
[cited by applicant]
US 20110189283A1
· Derrieu et al.
· 2011
[cited by applicant]
US 20120308662A1
· Konishi et al.
· 2012
[cited by applicant]
US 20130115301A1
· Bele et al.
· 2013
[cited by applicant]
US 20140363510A1
· Folger et al.
· 2014
[cited by applicant]
US 20170368062A1
· Folger et al.
· 2017
[cited by applicant]
AU 2012101682A4
· 2013
[cited by applicant]
CA 950833A1
· 1974
[cited by applicant]
CA 1102240A
· 1981
[cited by applicant]
CA 1222697A1
· 1987
[cited by applicant]
CA 1238277A
· 1988
[cited by applicant]
CA 2034569A1
· 1991
[cited by applicant]
CA 1336498C
· 1995
[cited by applicant]
CA 2858941A1
· 2013
[cited by applicant]
CN 1258220A
· 2000
[cited by applicant]
CN 1662250A
· 2005
[cited by applicant]
CN 1702243A
· 2005
[cited by applicant]
CN 101090735A
· 2007
[cited by applicant]
CN 101316595A
· 2008
[cited by applicant]
CN 101534864A
· 2009
[cited by applicant]
CN 103655502A
· 2014
[cited by applicant]
CN 112618505A
· 2021
[cited by applicant]
DE 3728244A1
· 1989
[cited by applicant]
DE 4001623A1
· 1991
[cited by applicant]
EP 0008391A1
· 1980
[cited by applicant]
EP 0241179A1
· 1987
[cited by applicant]
EP 0256566A1
· 1988
[cited by applicant]
EP 0268146A1
· 1988
[cited by applicant]
EP 0306846A2
· 1989
[cited by applicant]
EP 0330052A2
· 1989
[cited by applicant]
EP 0335545A2
· 1989
[cited by applicant]
EP 0349657A1
· 1990
[cited by applicant]
EP 439030A2
· 1991
[cited by applicant]
EP 1123703A1
· 2001
[cited by applicant]
EP 1247456A2
· 2002
[cited by applicant]
EP 1260215A1
· 2002
[cited by applicant]
EP 1579862A1
· 2005
[cited by applicant]
EP 1903039A1
· 2008
[cited by applicant]
EP 1920785A1
· 2008
[cited by applicant]
EP 2338493A1
· 2011
[cited by applicant]
EP 3034071A1
· 2016
[cited by applicant]
FR 2350105A1
· 1997
[cited by applicant]
GB 1045031A
· 1966
[cited by applicant]
GB 2228004A
· 1990
[cited by applicant]
JP 61500788A
· 1986
[cited by applicant]
JP H029825A
· 1990
[cited by applicant]
JP H03157314A
· 1991
[cited by applicant]
JP H0489428A
· 1992
[cited by applicant]
JP H0570612A
· 1993
[cited by applicant]
JP H11228302A
· 1999
[cited by applicant]
JP 2001276597A
· 2001
[cited by applicant]
JP 2002523475A
· 2002
[cited by applicant]
JP 2005521691A
· 2005
[cited by applicant]
JP 2005526738A
· 2005
[cited by applicant]
JP 2005281283A
· 2005
[cited by applicant]
JP 2006507285A
· 2006
[cited by applicant]
JP 2006523687A
· 2006
[cited by applicant]
JP 2007191419A
· 2007
[cited by applicant]
JP 2007536228A
· 2007
[cited by applicant]
JP 2008504308A
· 2008
[cited by applicant]
JP 2008534681A
· 2008
[cited by applicant]
JP 2009114148A
· 2009
[cited by applicant]
JP 2009531451A
· 2009
[cited by applicant]
JP 2009535378A
· 2009
[cited by applicant]
JP 2010508372A
· 2010
[cited by applicant]
JP 2011503044A
· 2011
[cited by applicant]
JP 2011516441A
· 2011
[cited by applicant]
JP 2011157390A
· 2011
[cited by applicant]
JP 2012533595A
· 2012
[cited by applicant]
JP 2013006798A
· 2013
[cited by applicant]
JP 2013503113A
· 2013
[cited by applicant]
JP 2013524900A
· 2013
[cited by applicant]
KR 20090084925A
· 2009
[cited by applicant]
WO 1985002767A1
· 1985
[cited by applicant]
WO 1989004178A1
· 1989
[cited by applicant]
WO 1995031963A1
· 1995
[cited by applicant]
WO 1998055148A1
· 1998
[cited by applicant]
WO 0012137A1
· 2000
[cited by applicant]
WO 2000012137A1
· 2000
[cited by applicant]
WO 2000012138A2
· 2000
[cited by applicant]
WO 2000069414A2
· 2000
[cited by applicant]
WO 2001035925A1
· 2001
[cited by applicant]
WO 2001064190A1
· 2001
[cited by applicant]
WO 2001097861A2
· 2001
[cited by applicant]
WO 0245693A1
· 2002
[cited by applicant]
WO 2002049646A1
· 2002
[cited by applicant]
WO 2003012030A2
· 2003
[cited by applicant]
WO 03072141A1
· 2003
[cited by applicant]
WO 2003072141A1
· 2003
[cited by applicant]
WO 2003074032A1
· 2003
[cited by applicant]
WO 2003075895A1
· 2003
[cited by applicant]
WO 2003097067A1
· 2003
[cited by applicant]
WO 2003099194A2
· 2003
[cited by applicant]
WO 2004000317A1
· 2003
[cited by applicant]
WO 2004000344A1
· 2003
[cited by applicant]
WO 2004016252A1
· 2004
[cited by applicant]
WO 2004033444A1
· 2004
[cited by applicant]
WO 2004037201A2
· 2004
[cited by applicant]
WO 2004050657A2
· 2004
[cited by applicant]
WO 2004058726A2
· 2004
[cited by applicant]
WO 2004060353A1
· 2004
[cited by applicant]
WO 2004089418A1
· 2004
[cited by applicant]
WO 2005035505A2
· 2005
[cited by applicant]
WO 2005084647A1
· 2005
[cited by applicant]
WO 2005092343A1
· 2005
[cited by applicant]
WO 2005107756A1
· 2005
[cited by applicant]
WO 2005117911A2
· 2005
[cited by applicant]
WO 2006000229A2
· 2006
[cited by applicant]
WO 2006022562A1
· 2006
[cited by applicant]
WO 2006060122A2
· 2006
[cited by applicant]
WO 2006060127A2
· 2006
[cited by applicant]
WO 2007036671A2
· 2007
[cited by applicant]
WO 2007038796A1
· 2007
[cited by applicant]
WO 2007054514A2
· 2007
[cited by applicant]
WO 2007092026A1
· 2007
[cited by applicant]
WO 2007112274A2
· 2007
[cited by applicant]
WO 2007128749A1
· 2007
[cited by applicant]
WO 2008055871A1
· 2008
[cited by applicant]
WO 2009060226A1
· 2009
[cited by applicant]
WO 2009121585A1
· 2009
[cited by applicant]
WO 2010010257
· 2010
[cited by applicant]
WO 2010055119A1
· 2010
[cited by applicant]
WO WO2010055119A2
· 2010
[cited by examiner]
WO 2010060874A1
· 2010
[cited by applicant]
WO 2011009818A1
· 2011
[cited by applicant]
WO 2011042463A2
· 2011
[cited by applicant]
WO 2011076738A1
· 2011
[cited by applicant]
WO 2011131259A1
· 2011
[cited by applicant]
WO 2013024023A1
· 2013
[cited by applicant]
WO 2013135852A1
· 2013
[cited by applicant]
WO 2013164473A1
· 2013
[cited by applicant]
WO 2013170317A1
· 2013
[cited by applicant]
WO 2014136035A1
· 2014
[cited by applicant]
WO 2015082389A1
· 2015
[cited by applicant]
WO 2017103054A1
· 2017
[cited by applicant]
WO 2017174571A1
· 2017
[cited by applicant]
WO 2021081366A1
· 2021
[cited by applicant]
Castro et al., “Interactions Between Additives: Its Effect on Sorbate Stability and Z. bailii Minimum Inhibitory Concentration in Model Aqueous Systems Resembling Salad Dressings,” Food Sci Tech Int 2002;8(1):33-39. (Ye…
[cited by examiner]
Casado et al., “Stability of sorbic and ascorbic acids in packed green table olives during long-term storage as affected by different packing conditions, and its influence on quality parameters,” Food Chemistry, vol. 12…
[cited by examiner]
Liewen et al., “Growth and Inhibition of Microorganisms in the Presence of Sorbic Acid: A Review,” Journal of Food Protection, vol. 48, No. 4, pp. 364-375 (1985). (Year: 1985).
[cited by examiner]
Fahelelbom et al., Analysis of preservatives in pharmaceutical products, Pharmaceuticals Reviews Year: 2007 vol. 5 Issue 1. (Year : 2007).
[cited by examiner]
Redenti, E. et al., “Drug/Cyclodextrin/Hydroxy Acid Multicomponent Systems Properties and Pharmaceutical Applications”, Journal of Pharmaceutical Sciences, vol. 89, No. 1, Jan. 2000, pp. 1-8.
[cited by applicant]
Lezcano, M. et al., “Complexation of Several Benzimidazole-Type Fungicides with α- and β-Cyclodextrins”, Journal Jf Agricultural and Food Chemistry, vol. 50, No. 1, 2002, pp. 108-112.
[cited by applicant]
Rowe R.C. et al., Handbook of Pharmaceutical Excipients, Pharmaceutical Press, 6th Edition, USA, 2009, pp. 61-62, 441-442, 596-597, 672-673.
[cited by applicant]
Pharmacy edited by Ning Lin, First Edition, Jan. 2008, p. 283, Hubei Science and Technology Press, Wuhan, Hubei, China.
[cited by applicant]
Food Biochemistry edited by Li Peiqing, First Edition, Jul. 2006, p. 258, Light Industry Press, Beijing, China.
[cited by applicant]
Food Aditives edited by YChi Yujie, First Edition, Apr. 2013, pp. 34-35, China Light Industry Press, Beijing, China.
[cited by applicant]
Machine English translation of JP H03-157314 A.
[cited by applicant]
Rackley, Charles E., “Diseases of the Heart and Pericardium”., The Merck Manual, Chapter 25, 16th Edition, 1992, pp. 446-459.
[cited by applicant]
Remme et al., “Hemodynamic Effects of Intravenous Pimobendan in Patients with Left Ventricular Dysfunction”. Journal of Cardiovascular Pharmacology, vol. 15, Supp. 2, 1989, pp. S41-S44.
[cited by applicant]
Remme et al., “Hemodynamic, Neurohumoral, and Myocardial Energetic Effects of Pimobendan, a Novel Calcium-Sensitizing Compound, in Patients with Mild to Moderate Heart Failure”. Journal of Cardiovascular Pharmacology, v…
[cited by applicant]
Rinsyo to Kenkyu, “A case of diastolic hypertrophic cardiomyopathy in which sinus bradycardia and associated cardiac failure were improved as a result of cilostazol administration.” The Japanese Journal of Clinical and …
[cited by applicant]
Rodriguez, Damon B., “Treatment of Feline Hypertrophic Cardiomyopathy*”. Compendium, vol. 24, No. 6, Jun. 2002, pp. 470-476.
[cited by applicant]
Roland et al., “The Use of Pimobendan in Feline Heart Failure Secondary to Spontaneous Heart Disease”. The 18th Annual ECVIM Congress, Abstract, Belgium, Sep. 2008, 1 page.
[cited by applicant]
Rudnic et al., “Oral Solid Dosage Forms”. Remington: The Science and Practice of Pharmacy, 20th Edition, Lippincott Williams & Wilkins, Baltimore, Maryland, Chapter 45, 2000, pp. 858-870.
[cited by applicant]
Saavedra et al., “Reverse Remodeling and Enhanced Adrenergic Reserve From Passive External Support in Experimental Dilated Heart Failure”. Journal of the American College of Cariology, vol. 39, No. 12, 2002, pp. 2069-10…
[cited by applicant]
Sabbah et al., “Effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of left ventricular dysfuntion and dilation in dogs with reduced ejection fraction”. Circulation, vol. 89, 1994…
[cited by applicant]
Sabbah, Hani N., “The Cardiac Support Device and the Myosplint: Treating Heart Failure by Targeting Left Ventricular Size and Shape”. The Annals of Thoracic Surgery, vol. 75, 2003, pp. S13-S19.
[cited by applicant]
Shiga et al., “b-Blocker Therapy Combined with Low-Dose Pimobendan in Patients with Idiopathic Dilated Cardiomyopathy and Chronic Obstructive Pulmonary Disease: Report on Two Cases”. Cardiovascular Drugs and Therapy, vo…
[cited by applicant]
Sisson et al., “Myocardial Diseases of Dogs”. Textbook of Canine and Feline Cardiology: Principles and Clinical Practice, Second Edition, Chapter 27, Saunders, 1999, pp. 581-619.
[cited by applicant]
Sisson, David, “Lecture Notes: Cardiology”, The District of Columbia Academy of Veterinary Medicine, May 2001, pp. 1-18.
[cited by applicant]
Summerfield et al., “Efficacy of Pimobendan in the Prevention of Congestive Heart Failure or Sudden Death in Doberman Pinschers with Preclinical Dilated Cardiomyopathy (The PROTECT Study)”. Journal of Veterinary Interna…
[cited by applicant]
Takeda et al., “Normalization of Left Ventricular Parameters Following Combined Pimobendan and Carvedilol Treatment in a Case of Unclassified Cardiomyopathy with Longstanding Refractory Status”. Internal Medicine, vol. …
[cited by applicant]
The American Heritage Dictionary, homogeneous, Last Accessed Feb. 10, 2011, 1 page, http://www.xreferplus.com/entry/hmdictenglang/homogeneous.
[cited by applicant]
Tomanek et al., “Growth of the Coronary Vasculature in Hypertrophy: Mechanisms and Model Dependence”. Cellular and Molecular Biology Research, vol. 40, No. 2, 1994, pp. 129-136.
[cited by applicant]
Van Meel et al., “Pimobendan Increases Survival of Cardiomyopathie Hamsters”. Journal of Cardiovascular Pharmacology, vol. 13, 1989, pp. 508-509.
[cited by applicant]
Villar et al., “Ibuprofen, Aspirin and Acetaminophen Toxicosis and Treatment in Dogs and Cats”. Veterinary and Human Toxicology, vol. 40, No. 3, Jun. 1998, pp. 156-162.
[cited by applicant]
Wikipedia, the Free Encyclopedia, “Milrinone”. [Accessed at: http://en.wikipedia.org/wiki/Milrinone on Mar. 10, 2014].
[cited by applicant]
Wikipedia, the Free Encyclopedia, “Pimobendan”. [Accessed at: http://en.wikipedia.org/wiki/Pimobenan on Mar. 10, 2014].
[cited by applicant]
Woolley et al., “Effects of Treatment Type on Vertebral Heart Size in Dogs With Myxomatous Mitral Valve Disease”. The Journal of Applied Research in Veterinary Medicine, vol. 5, No. 1, 2007, pp .43-48.
[cited by applicant]
Brewster et al., “Cyclodextrins as pharmaceutical solubilizers”. Advanced Drug Delivery Reviews, vol. 59, No. 7, 2007, pp .645-666.
[cited by applicant]
Vidal et al., “Making sense of antisense”. European Journal of Cancer, vol. 41, 2005, pp. 2812-2818.
[cited by applicant]
Pirollo et al., “Targeted Delivery of Small Interfering RNA: Approaching Effective Cancer Therapies”. Cancer Research, vol. 68, No. 5, Mar. 2008, pp. 1247-1250.
[cited by applicant]
Phillips et al., “The challenge of gene therapy and DNA delivery”. Journal of Pharmacy and Pharmacology, vol. 53, 2001, pp. 1169-1174.
[cited by applicant]
Ettinger et al., “Therapeutic Considerations in Medicine and Disease”. Textbook of Veterinary Internal Medicine, Diseases of the Dog and Cat, Sixth Edition, vol. I, 2004, pp. 530-531.
[cited by applicant]
Pagel et al., “Comparison of the effects of levosimendn, pimobendan, and milrinone on canine left ventricular-arterial coupling and mechanical efficiency”. Basic Respiratory Cardiology, vol. 91, 1996, pp. 296-307.
[cited by applicant]
Kitzen et al., “Pimobendan”. Cardiovascular Drug Reviews, vol. 6, No. 4, 1989, pp. 265-291.
[cited by applicant]
Stuber et al., “The Pharmaceutical and Biological Availability of Commercial Preparations of Furosemide”. Arzneimittel-Forschung, vol. 32, No. 6, 1982, pp. 693-697.
[cited by applicant]
“905 Uniformity of Dosage Units”. 2011 The United States Pharmacopeial Convention, Stage 6 Harmonization, Dec. 1, 2011, pp. 1-3.
[cited by applicant]
“Cardiovascular system”. MIMS, IVS Annual, Chapter 5, 2003, p. 104.
[cited by applicant]
“Citric Acid”. The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, 13th Edition, Merck Research Laboratories Division of Merck & Co., Inc., Whitehouse Station, NJ, Index 2350, 2001, pp. 405-406.
[cited by applicant]
“Guidance for Industry, Container Closure Systems for Packaging Human Drugs and Biologics: Chemistry, Manufacturing, and Controils Documentation”. U.S. Department of Health and Human Services Food and Drug Administratio…
[cited by applicant]
“Pharmaceutical Necessities”. Remington's Pharmaceutical Sciences, 18th Edition, Mack Publishing Company, Easton, Pennsylvania, Chapter 66, 1990, pp. 1288-1300.
[cited by applicant]
“Pimobendan”. The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, 13th Edition, Merck Research Laboratories Division of Merck & Co., Inc., Whitehouse Station, NJ, Index 7515, 2001, p. 1332.
[cited by applicant]
Abstract in English for CN1702243A, 2005.
[cited by applicant]
Abstract in English for DE3728244, 1989.
[cited by applicant]
Abstract in English for EP0306846, 1989.
[cited by applicant]
Abstract in English for EP0330052, 1989.
[cited by applicant]
Abstract in English for JP2005281283, 2005.
[cited by applicant]
Abstract in English of JPH0570612, 1993.
[cited by applicant]
Abstract in English of JPH11228302, 1999.
[cited by applicant]
Ahmed et al., “Pharmaceutical challenges in veterinary product development”. Advanced Drug Delivery Reviews, vol. 54, 2002, pp. 871-882.
[cited by applicant]
Asanoi et al., “Disparate Inotropic and Lusitropic Responses to Pimobendan in Conscious Dogs with Tachycardia-Induced Heart Failure”. Journal of Cardiovascular Pharmacology, vol. 23, No. 2, 1994, pp. 268-274.
[cited by applicant]
Atkins et al., “Guidelines for the Diagnosis and Treatment of Canine Chronic Valvular Heart Disease”. Journal of Veterinary Internal Medicine, vol. 23, No.; 6, 2009, pp. 1-9.
[cited by applicant]
Banker et al., “Uniformity of Dosage Units”. Modern Pharmaceutics, Fourth Edition, Revised and Expanded, Marcel Dekker, Inc., New York, NY, 2006, p. 498.
[cited by applicant]
Bassani et al., “Enhanced Water-Solubility of Albendazole by Hydroxy-Propyl-β-Cyclodextrin Complexation”. Journal of Inclusion Phenomena and Molecular Recognition in Chemistry, vol. 25, No. 1-3, Mar. 1996, pp. 149-152.
[cited by applicant]
Bastien et al., “Chronic AT receptor blockade and angiotensin-converting enzyme (ACE) inhibition in (CHF 146) cardiomyopathie hamsters: effects on cardiac hypertrophy and survival”. Cardiovascular Research, vol. 43, 199…
[cited by applicant]
Baur et al., “Cardiac remodelling and myocardial contractility in patients with congestive heart failure treated with furosemide and enalapril”. Basic Research in Cardiology, vol. 86, Supp. 1, 1991, pp. 157-163.
[cited by applicant]
Beers, et al., Merck Manual of Diagnosis and Therapy, 17th Edition, Chapter 203, Section 16, Merck Research Laboratories, Whitehouse Station, NJ, USA, 1999, pp. 1688-1692.
[cited by applicant]
Berny et al., “Review: Animal Poisoning in Europe. Part 2: Companion Animals”. The Veterinary Journal, vol. 193, 2010, pp. 255-259.
[cited by applicant]
Boehringer Ingelheim Vetmedica GmbH, 1st International Canine Valvular Disease Symposium, Paris, Oct. 30-31, 2004, pp. 1-45.
[cited by applicant]
Boehringer Ingelheim Vetmedica, Inc. “Freedom of Information Summary: Original New Animal Drug Application”. NADA 141-273, Vetmedin, Pimobendan Chewable Tablets, Apr. 30, 2007, pp. 1-46.
[cited by applicant]
Borgarelli et al., “Canine Idiopathic Dilated Cardiomyopathy. Part II: Pathophysiology and therapy”. The Veterinary Journal, vol. 162, 2001, pp. 182-195.
[cited by applicant]
Bozzone, Scott, “Solid Oral Dosage Forms Powder Blending” and “Solid Oral Dosage Forms, Blend Uniformity: Principles and Examples”. Pfizer, IKEV Meeting, May 31, 2001, pp. 1-66.
[cited by applicant]
Buchanan et al. “Vertebral scale system to measure canine heart size in radiographs”. Journal of the American Veterinary Medical Association, vol. 206, No. 2, Jan. 1995, pp. 194-199.
[cited by applicant]
Burlage et al., “Other Pharmaceutical Adjuncts”., Physical and Technical Pharmacy, The Blakiston Division: The McGraw-Hill Book Company, Inc., New York, 1963, pp. 653-662.
[cited by applicant]
Calvert et al., “Congestive cardiomyopathy in Doberman Pinscher dogs”. Journal of the American Veterinary Medical Association, vol. 181, 1982, pp. 598-602.
[cited by applicant]
Calvert et al., “Signalment, Survival, and Prognostic Factors in Doberman Pinschers With End-Stage Cardiomyopathy”. Journal of Veterinary Internal Medicine, vol. 11, No. 6, 1997, pp. 323-326.
[cited by applicant]
Cambridge Dictionary, homogeneous, Last Accessed Feb. 10, 2011, 1 page, http://dictionary.cambridge.org/dictionary/british/homogeneous.
[cited by applicant]
Chambers 21st Century Dictionary, homogeneous, Last Accessed Feb. 10, 2011, 1 page, http://www.xreferplus.com/entry/chambdict/homogeneous.
[cited by applicant]
Chetboul, et al., “Comparitive Adverse Cardiac Effects of Pimobendan and Benazepril Monotherapy in Dogs with Mild Degenerative Mitral Valve Disease: A Prospective, Controlled, Blinded, and Randomized Study”. Journal of …
[cited by applicant]
Choy et al., “Scaling of myocardial mass to flow and morphometry of coronary arteries”. Journal of Applied Physiology, vol. 104, 2008, pp. 1281-1286.
[cited by applicant]
Cohn et al., “Cardiac Remodeling-Concepts and Clinical Implications: A Consensus Paper From an International Forum on Cardiac Remodeling”. Journal of the American College of Cardiology, vol. 35, No. 3, 2000, pp. 569-582.
[cited by applicant]
Collins English Dictionary, homogeneous, Last Accessed Feb. 10, 2011, 1 page, http://xreferplus.com/entry/hcengdict/homogeneous.
[cited by applicant]
Conlon, P.D., “Nonsteroidal Drugs Used in the Treatment of Inflammation”. Veterinary Clinics of North America: Small Animal Practice, vol. 18, No. 6, Nov. 1988, pp. 1115-1131.
[cited by applicant]
Cowley et al., “Treatment of severe heart failure: quantity or quality of life? A trial of enoximone”. , British Heart Journal, vol. 72, 1994, pp. 226-230.
[cited by applicant]
Côté et al., “Congestive Heart Failure”. Feline Cardiology, Ch. 19, Wiley-Blackwell, ISBN 978-0-8138-1242-7, 2011, p. 259.
[cited by applicant]
Deneke et al., “Medikamentöse Therapie der Herzinsuffizienz”. Herzschr Elektrophys, vol. 15, Suppl. 1, 2004, pp. 1/74-1/80.
[cited by applicant]
Dictionary of Veterinary Drugs and Animal Health Products Marketed in France, 12th Edition, 2003, 3 pages.
[cited by applicant]
El-Hagrasy et al., “A Process Analytical Technology Approach to Near-Infrared Process Control of Pharmaceutical Power Blending: Part II: Qualitative Near-Infrared Models for Prediction of Blend Homogeneity”. Journal of …
[cited by applicant]
El-Hagrasy et al., “Near-Infrared Spectroscopy and Imaging for the Monitoring of Powder Blend Homogeneity”. Journal of Pharmaceutical Sciences, vol. 90, No. 9, Sep. 2001, pp. 1298-1307.
[cited by applicant]
Elliott, P., “Diagnosis and management of dilated cardiomyopathy”. Heart, vol. 83, 2000, pp. 106-112.
[cited by applicant]
Endoh, Masao, “New Aspects of the Treatment of Myocardial Failure from a Pharmacological Standpoint”. Journal of Clinical and Experimental Medicine, vol. 187, No. 10, 1998, pp. 827-831.
[cited by applicant]
Erhardt, L., “An Emerging Role for Calcium Sensitisation in the Treatment of Heart Failure”. Expert Opinion on Investigational Drugs, vol. 14, No. 6, 2005, pp. 659-670.
[cited by applicant]
Ettinger et al., “Effects of enalapril maleate on survival of dogs with naturally acquired heart failure”. Journal of the American Veterinary Medical Association, vol. 213, No. 11, 1998, pp .1573-1577.
[cited by applicant]
Fitton et al., “Pimobendan. A Review of its Pharmacology and Therapeutic Potential in Congestive Heart Failure”. Drugs and Aging, vol. 4, No. 5, 1994, pp .417-441.
[cited by applicant]
Fox et al., “Prosepective Double-Blinded, Multicenter Evaluation of Chronic Therapies for Feline Diastolic Heart Failure: Interim Analysis”. ACVIM Abstracts, Abstract 78, 2003, pp. 398-399.
[cited by applicant]
Fox, Philip R., “Hypertrophic Cardiomyopathy. Clinical and Pathologic Correlates”. Journal of Veterinary Cardiology, vol. 5, No. 2, Nov. 2003, pp. 39-45.
[cited by applicant]
Thiel et al., “Content uniformity of microdose tablets (dosage 1 μg-10 mg) produced by fluid bed granulation of interactive mixtures”. Journal of Pharmacy and Pharmacology, vol. 38, 1986, pp. 335-343.
[cited by applicant]
Petit et al., “VETMEDIN® 1.25 mg, VETMEDIN® 5 mg, Chewable tablets, Inodilator (pimobendan) tablet for dogs”. Dictionary of Veterinary Drugs and Animal Health Products Marketed in France, 16th Edition, Les Editions du P…
[cited by applicant]
“Vetmedin®—1,25 mg appetizing tablets for dogs Veterinary use”. Summary of Product Characteristics, SCS Boehringer Ingelheim Comm. V, Mar. 25, 2009, pp. 1-4.
[cited by applicant]
“Rimadyl F 50 mg”. Summary of Product Characteristics, Zoetis France, May 15, 2013, pp. 1-4.
[cited by applicant]
Hemati et al., “Fluidized bed coating and granulation: influence of process-related variables and physicochemical properties on the growth kinetics”. Powder Technology, vol. 13, 2002, pp. 18-34.
[cited by applicant]
Abstract in English for JPH0489428, 1992.
[cited by applicant]
Ash et al., “Receptor Mediating Some Actions of Histamine”. British Journal of Pharmacology and Chemotherapy, vol. 27, No. 2, Aug. 1996, pp. 427-439.
[cited by applicant]
Black et al., “Definition and Antagonism of Histamine H2-receptors”. Nature, vol. 236, Apr. 1972, pp. 385-390.
[cited by applicant]
Dews et al., “The Antihistamine Substance 2786 R.P.” British Journal of Pharmacology, vol. 1, 1946, pp. 278-286.
[cited by applicant]
Loew, Earl R., “Gastric Secretion in Dogs Treated with Histamine Antagonist, Thymoxyethyldiethylamine”. Experimental Biology and Medicine, vol. 48, No. 1, Oct. 1941, pp. 65-68.
[cited by applicant]
Lantz et al., “Stability of nizatidine in extemporaneous oral liquid preparations”. American Journal of Hospital Pharmacy, vol. 47, No. 12, Dec. 1990, pp. 2716-2719.
[cited by applicant]
Nakamoto et al., “The role of ascorbic acid deficiency in human gingivitis—a new hypothesis”. Journal of Theoretical Biology, vol. 108, No. 2, May 1984, pp. 163-171.
[cited by applicant]
Pernsteiner et al., “Effect of Topical Application of Phenylephrine Hydrochloride on Hyperplastic Gingivitis”. Journal of Periodontology, vol. 48, No. 8, Aug. 1977, pp. 473-477.
[cited by applicant]
Trendelenburg, U. “The Action of Histamine and 5-Hydroxytryptamine On Isolated Mammalian Atria”. The Journal of Pharmacology and Experimental Therapeutics, vol. 130, No. 4, Dec. 1960, pp. 450-460.
[cited by applicant]
Beaufrere et al., “Therapeutic Review: Pimobendan.” Journal of Exotic Pet Medicine, vol. 18, No. 4, Oct. 2009, pp. 311-313.
[cited by applicant]
Boswood et al., “Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and cardiomegaly! the EPIC Study—A Randomized Clinical Trial.” Journal of Veterinary Internal Medicine, vol. 30, 2016, pp. 1…
[cited by applicant]
Boswood et al., “Evaluation of pimobendan in dogs with cardiomegaly caused by preclinical mitral valve disease.” The Veterinary Record, vol. 168, No. 8, Feb. 2011, p. 222.
[cited by applicant]
Bourezg et al., “Redispersible lipid nanoparticles of Spironolactone obtained by three drying methods.” Colloids and Surfaces A: Physicochemical and Engineering Aspects, vol. 413, 2012, pp. 191-199.
[cited by applicant]
El-Badry et al., “Physicochemical Characterization and Dissolution Properties of Meloxicam-Gelucire 50/13 Binary Systems.” Scientia Pharmaceutica, vol. 79, 2011, pp. 375-386.
[cited by applicant]
Fasinu et al., “Diverse approaches for the enhancement of oral drug bioavailability.” Biopharmaceutics & Drug Disposition, vol. 32, 2011, pp. 185-209.
[cited by applicant]
Fox et al., “Bradykinin-evoked sensitization of airway sensory nerves: A mechanism for ACE-inhibitor cough.” Nature Medicine, vol. 2, No. 7, Jul. 1996, pp. 814-817.
[cited by applicant]
Kanno et al., “Effects of Pimobendan for Mitral Valve Regurgitation in Dogs.” Journal of Veterinary Medical Science, vol. 69, No. 4, Apr. 2007, pp. 373-377.
[cited by applicant]
Lindenberg et al., “Classification of orally administered drugs on the World Health Organization Model list of Essential Medicines according to the biopharmaceutics classification system.” European Journal of Pharmaceut…
[cited by applicant]
Nainar et al., “Biopharmaceutical Classification System in In-vitro/In-vivo Correlation: Concept and Development Strategies in Drug Delivery.” Tropical Journal of Pharmaceutical Research, vol. 11, No. 2, Apr. 2012, pp. …
[cited by applicant]
Ouellet et al., “Effect of Pimobendan on Echocardiographic Values in Dogs with Asymptomatic Mitral Valve Disease.” Journal of Veterinary Internal Medicine, vol. 23, 2009, pp. 258-263.
[cited by applicant]
Upadhyay et al., “Formulation of Fast-Release Gastroretentive Solid Dispersion of Glibenclamide with Gelucire 50/13.” Tropical Journal of Pharmaceutical Research, vol. 11, No. 3, Jun. 2012, pp .361-369.
[cited by applicant]
Vromans et al., “Densification properties and compactibility of mixtures of pharmaceutical excipients with and without magnesium stearate.” International Journal of Pharmaceutics, vol. 46, 1988, pp. 183-192.
[cited by applicant]
Liu et al., “Pharmacology Preparation Technology.” Chemical Industry Press, 2006, pp. 113-114.
[cited by applicant]
Sun et al., “Pimobendan.” Chemical Industry Press, 2002, pp. 29-30.
[cited by applicant]
Goineau et al., “Cardiomyopathie Syrian Hamster as a Model of Congestive Heart Failure”. Current Protocols in Pharmacology, Supp. 42, Unit 5.50, John Wiley & Sons, Inc., Sep. 2008, 12 pages.
[cited by applicant]
Wasaki et al., “Pimobendan Inhibits the Production of Proinflammatory Cytokines and Gene Expression of Inducible Nitric Oxide Synthase in a Murine Model of Viral Myocarditis”. Journal of the American College of Cardiolo…
[cited by applicant]
Rekis, Toms, et al. “A maze of solid solutions of pimobendan enantiomers: an extraordinary case of polymorph and solvate diversity.” Crystal Growth & Design 18.1 (2018): 264-273.
[cited by applicant]
English Abstract JP2008534681A.
[cited by applicant]
English Abstract CN103655502.
[cited by applicant]
Atkins et al., “Pharmacologic management of myxomatous mitral valve disease in dogs.” Journal of Veterinary Cardiology, vol. 14, 2012, pp. 165-184.
[cited by applicant]
Fraker et al., “Reversal of phosphate induced decreases in force by the benzimidazole pyridazinone, UD-CG 212 CL, in myofilaments from human ventricle.” Molecular and Cellular Biochemistry, vol. 176, 1997, pp. 83-88.
[cited by applicant]
International Search Report and Written Opinion for PCT/EP2005/002133 mailed May 31, 2005.
[cited by applicant]
International Search Report and Written Opinion for PCT/EP2005/002957 mailed on Jun. 30, 2005.
[cited by applicant]
International Search Report and Written Opinion for PCT/EP2006/068231 mailed Jun. 25, 2007.
[cited by applicant]
International Search Report and Written Opinion for PCT/EP2007/061879 mailed on Mar. 18, 2008.
[cited by applicant]
International Search Report and Written Opinion for PCT/EP2009/065618 mailed Dec. 28, 2009.
[cited by applicant]
International Search Report and Written Opinion for PCT/EP2013/055310 mailed on Jun. 5, 2013.
[cited by applicant]
International Search Report and Written Opinion for PCT/EP2017/057970 mailed on Jun. 12, 2017.
[cited by applicant]
Vasconcelos et al., “Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs.” Drug Discovery Today, vol. 12, Nos. 23/24, Dec. 2007, pp. 1068-1075.
[cited by applicant]
“Summary of Product Characteristics: Vetmedin Chew 1.25 mg chewable tablets for dogs.” Boehringer Ingelheim Vetmedica GmbH, Feb. 23, 2016, pp. 1-6. [Accessed at: http://bijsluiters.fagg-afmps.be/DownloadLeafletServlet?i…
[cited by applicant]
Chiang, Chung-Seung, “Management of Congestive Heart Disease.” Medical Session, vol. 7, No. 8, Oct. 2002, pp. 4-9.
[cited by applicant]
Proceedings of the 1st International Canine Valvular Disease Symposium, ICVS, Paris, Oct. 2004, Boehringer-Ingelheim Animal Health, pp. 1-45.
[cited by applicant]
Dictionnaire Medicament Veterinaire et des produits Sante Animal commercialises en France, 2003, entry for Vetmedin.
[cited by applicant]
Anses, Resume des characteristiques du produit de Rimadyl, published Feb. 18, 2015 (2015).
[cited by applicant]
Hagemeijer, Frans, Hetty J. Brand, and Willy Roth. “Cardiovascular effects and plasma level profile of pimobendan (UD-CG 115 BS) and its metabolite UD-CG 212 in patients with congestive heart failure after single and re…
[cited by applicant]
VHS Score Pamphlet, Boehringer-Ingelheim Animal Health, 2006.
[cited by applicant]
Health and human Services, Guidance for Industry, May 1999, Food and Drug Administration, pp. 1-56.
[cited by applicant]
English Abstract JP2009114148A.
[cited by applicant]
English Abstract JP2001276597A.
[cited by applicant]
Fuentes, et al., “A Double-Blind, Randomized, Placebo-Controlled Study of Pimobendan in Dogs with Dilated Cardiomyopathy,” Journal of Veterinary Internal Medicine, vol. 16, 2002, pp. 255-261.
[cited by applicant]
Fujino et al., “Differential Effects of d- and l-Pimobendan on Cardia Myofilament Calcium Sensitivity
[cited by applicant]
Goineau et al., “Cardiomyopathic Syrian Hamster as a Model of Congestive Heart Failure”. Current Protocols in Pharmacology, Supp. 42, Unit 5.50, John Wiley & Sons, Inc., Sep. 2008, 12 pages.
[cited by applicant]
Groban, Leanne, “Diastolic Dysfunction in the Older Heart”. Journal of Cardiothoracic and Vascular Anesthesia, vol. 19, No. 2, Apr. 2005, pp .228-236.
[cited by applicant]
Gwathmey et al., “Abnormal Intracellular Calcium Handling in Myocardium From Patients With End-Stage Heart Failure”. Circulation Research, vol. 61, No. 1, 1987, pp. 70-76.
[cited by applicant]
Hasenfuss et al., “Influence of the calcium-sensitizer UDCG-115 on hemodynamics and myocardial energetics in patients with idiopathic dilated cardiomyopathy. Comparison with nitroprusside”. Basic Research Cardiology, vo…
[cited by applicant]
Hauf et al., “Acute and Long-Term Hemodynamic Effects of Pimobendan (UD-CG 115 BS) in Comparison with Captopril”. Journal of Cardiovascular Pharmacology, vol. 15, Supp. 2, 1989, pp. S49-S56.
[cited by applicant]
Häggstrom et al., “Effect of Pimobendan or Benazepril Hydrochloride on Survival Times in Dogs with Congestive Heart Failure Caused by Naturally Occurring Myxomatous Mitral Valve Disease: The QUEST Study”. Journal of Vet…
[cited by applicant]
Häggstrom et al., “Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Myxomatous Mitral Valve Disease Rexceiving Pimobendan or Benazepril: The QUES…
[cited by applicant]
Häggström et al., “Effects of long-term treatment with enalapril or hydralazine on the renin-angiotension-aldosterone system and fluid balance in dogs with naturally acquired mitral valve regurgitation”. American Journa…
[cited by applicant]
Häggström et al., “New insights into degenerative mitral valve disease in dogs”. Veterinary Clinics Small Animal Practice, vol. 34, 2004, pp. 1209-1226.
[cited by applicant]
Iwasaki et al., “Pimobendan Inhibits the Production of Proinflammatory Cytokines and Gene Expression of Inducible Nitric Oxide Synthase in a Murine Model of Viral Myocarditis”. Journal of the American College of Cardiol…
[cited by applicant]
Jain et al., “Effects of Milrinone on Left Ventricular Remodeling After Acute Myocardial Infarction”. Circulation, vol. 84, No. 2, Aug. 1991, pp. 798-804.
[cited by applicant]
Kashem et al., “CardioClasp: A New Passive Device to Reshape Cardiac Enlargement”. ASAIO Journal, vol. 48, No. 3, 2002, pp. 253-259.
[cited by applicant]
Kato et al., “Clinical Evaluation of Pimobendan (UD-CG115BS) for Chronic Heart Failure—A Multicentre Placebo-Controlled Double Blind Study”. Journal of Clinical Therapeutics & Medicines, vol. 8, No. 6, 1992, pp. 1311-13…
[cited by applicant]
Kato, Kazuzo, “Clinical Efficacy and Safety of Pimobendan in Treatment of Heart Failure-Experience in Japan”. Cardiology, vol. 88, Supp. 2, 1997, pp. 28-36.
[cited by applicant]
Katz et al., “A multicenter, randomized, double-blind, placebo-controlled trial of pimobendan, a new cardiotonic and vasodilator agent, in patients with severe congestive heart failure”. American Heart Journal, vol. 123…
[cited by applicant]
Kittleson et al., “The Acute Hemodynamic Effects of Milrinone in Dogs With Severe Idiopathic Myocardial Failure”. Journal of Veterinary Medicine, vol. 1, 1987, pp. 121-127.
[cited by applicant]
Koob et al., “Acute Effects of Furosemide on Blood Electrolytes and Hemodynamics in Dogs”. Angiology, 1978, pp. 463-472.
[cited by applicant]
Kubo et al., “Beneficial Effects of Pimobendan on Exercise Tolerance and Quality of Life in Patients with Heart Failure. Results of a Multicenter Trial”. Circulation, vol. 85, No. 3, Mar. 1992, pp. 942-949.
[cited by applicant]
Kvart et al., “Efficacy of Enalapril for Prevention of Congestive Heart Failure in Dogs with Myxomatous Valve Disease and Asymptomatic Mitral Regurgitation”. Journal of Veterinary Internal Medicine, vol. 16, 2002, pp. 8…
[cited by applicant]
Lachman et al., “The Theory and Practice of Industrial Pharmacy”., 3rd Edition, Lea & Febiger, Philadelphia, 1986, pp. 58-60.
[cited by applicant]
Lai et al., “Real Time and Noninvasive Monitoring of Dry Powder Blend Homogeneity”. AlChE Journal, vol. 47, No. 11, Nov. 2001, pp. 2618-2622.
[cited by applicant]
Lamb et al., “Assessment of the value of the vertebral heart scale in the radiographic diagnosis of cardia disease in dogs”. Veterinary Record, vol. 146, 2000, pp. 687-690.
[cited by applicant]
Lewis et al., “Near-Infrared Chemical Imaging for Product and Process Understanding”. in Process Analytical Technology, Second Edition, John Wiley & Sons, Ltd., United Kingdom, 2010, pp. 272-276.
[cited by applicant]
Lewis, Alan B., “Clinical Profile and Outcome of Restrictive Cardiomyopathy in Children”. American Heart Journal, vol. 123, No. 6, 1992, pp. 1589-1593.
[cited by applicant]
Lip et al., “ABC of heart failure: Aetiology”. British Medical Journal, vol. 320, Jan. 2000, pp. 104-107.
[cited by applicant]
Liu et al., “Cardiovascular Pathology: The Role of Cardiovascular Pathology in Practice”. Textbook of Canine and Feline Cardiology: Principles and Clinical Practice, Second Edition, Chapter 36, Saunders, 1999, pp. 817-8…
[cited by applicant]
Loftsson et al., “Pharmaceutical Applications of Cyclodextrins. 1. Drug Solubilization and Stabilization”. Journal of Pharmaceutical Sciences, vol. 85, No. 10, Oct. 1996, pp. 1017-1025.
[cited by applicant]
Lombard et al., “Clinical Efficacy of Pimobendan Versus Benazepril for the Treatment of Acquired Atrioventricular Valvular Disease in Dogs”. Journal of the American Animal Hospital Association, vol. 42, No. 4, Jul./Aug.…
[cited by applicant]
Lombard, Christophe W., “Therapy of Congestive Heart Failure in Dogs with Pimobendan”. Proceedings of the 18th Annual Veterinary Medical Forum, American College of Veterinary Internatl Medicine, Seattle, WA, 2000, pp. 1…
[cited by applicant]
Lord et al., “Radiology: Role of Radiology in Diagnosis and Management of Thoracic Disease”. Textbook of Canine and Feline Cardiology: Principles and Clinical Practice, Second Edition, Chapter 7, Saunders, 1999, pp. 111…
[cited by applicant]
Luis-Fuentes, Virginia, “The effect of pimobendan in English Cocker Spaniels and Doberman dogs with heart failure and idiopathic dilated cardiomyopathy (DCM)”. Ingelheimer Dialog, Boehringer Inglehim Vetmedica GmbH, Jun…
[cited by applicant]
Lyon et al., “Near-Infrared Spectral Imaging for Quality Assurance of Pharmaceutical Products: Analysis of Tablets to Assess Powder Blend Homogeneity”. AAPS PharmSciTech, vol. 3, No. 3, Art. 17, Sep. 2002, pp. 1-15.
[cited by applicant]
Malik et al., “Permethrin Spot-On Intoxication of Cats: Literature review and survey of veterinary practitioners in Australia”. Journal of Feline Medicine and Surgery, vol. 12, 2010, pp. 5-14.
[cited by applicant]
Mamoru et al., “Effects of Long-term, Very-low-dose Pimobendan for Patients with Diastolic Heart Failure”. Journal of Cardial Failure, vol. 12, No. 8, Oct. 2006, p. S171.
[cited by applicant]
Matsumori et al., “Pharmacology letters: Accelerated Communication: Pimobendan inhibits the activation of transcription factor Nf-κb A mechanism which explains its inhibition of cytokine production and inducible nitric …
[cited by applicant]
Mccrohon et al., “Differentiation of Heart Failure Related to Dilated Cardiomyopathy and Coronary Artery Disease Using Gadolinium-Enhanced Cardiovascular Magnetic Resonance”. Circulation, vol. 108, Jul. 2003, pp. 54-59.…
[cited by applicant]
Medline, homogeneous, Merriam-Webster, Last Accessed Feb. 10, 2011, 1 page, http://www.merriam-webster.com/medlineplus/homogeneous.
[cited by applicant]