Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1992-06-23
1994-12-20
Cintins, Marianne M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514564, 514565, 514561, 514567, 514419, A61K 31195
Patent
active
053746511
ABSTRACT:
Methods and compositions for treating and inhibiting hypotension are provided. A therapeutic regimen useful in the present invention includes an arginine-free parenteral formulation administered concurrently with or followed by an arginine analog. The combination therapy provides an augmentation of the anti-hypotensive effect found by the present inventors with arginine analogs, such as N.sup..omega. -methyl-L-arginine, N.sup..omega. -amino-L-arginine or N.sup..omega. -nitro-L-arginine. These arginine analogs, otherwise described as nitric oxide synthase inhibitors, provide for a decrease in nitric oxide concentrations, and are demonstrated to elicit an increase in blood pressure in vivo, particularly in animals with cytokine and/or endotoxin induced hypotension. The parenteral formulation of the therapeutic regimen and methods of the invention are arginine-free and provide a decrease in plasma arginine levels. Reduced plasma and tissue levels of arginine in the animal function to augment the hypertensive action of arginine analogs to be administered concurrently or subsequent to administration of the parenteral formulation. This method provides a regiment for treating and/or inhibiting hypotension attendant a variety of conditions, including chemotherapeutic agent therapy (i.e., IFN, TNF), septic shock, trauma, exposure to endotoxins or cytokines, or other condition in which hypotension is attendant. The arginine-free formulations may also include ornithine, citrulline, or both.
REFERENCES:
patent: 4100160 (1978-07-01), Walser et al.
patent: 4282217 (1981-08-01), Baglioni et al.
patent: 4426378 (1984-01-01), Holaday
patent: 4734438 (1988-03-01), Macri
patent: 4859452 (1989-08-01), Ajani et al.
patent: 4988724 (1991-01-01), Ajani et al.
patent: 5006559 (1991-04-01), Askanazi et al.
patent: 5028627 (1991-07-01), Kilbourn et al.
patent: 5036052 (1991-07-01), Ozeki et al.
patent: 5059712 (1991-10-01), Griffith
patent: 5132453 (1992-07-01), Griffith
patent: 5158883 (1992-10-01), Griffith
patent: 5196195 (1993-03-01), Griffith
patent: 5216025 (1993-06-01), Gross et al.
patent: 5286739 (1994-02-01), Kilbourn et al.
patent: 5296466 (1994-03-01), Kilbourn et al.
PCT/US92/08227 International Preliminary Examination Report mailed Dec. 3, 1993.
Martin et al., "Selective Blockade of Endothelium-Dependent and Glyceryl Trinitrate-Induced Relaxation by Hemoglobin and by Methylene Blue in the Rabbit Aorta," The Journal of Pharmacology and Experimental Therapeutics, 232(3):708-716, 1985, published in USA.
Buga et al., "Endothelium-Derived Nitric Oxide Relaxes Nonvascular Smooth Muscle," European Journal of Pharmacology, 161:61-72, 1989, published in Europe.
Torti et al., "A Macrophage Factor Inhibits Adipocyte Gene Expression: An in Vitro Model of Cachexia," Scinece, 229:867-871, 1985, published in USA.
Old, Lloyd J., "Tumor Necrosis Factor (TNF)," 230:630-632, 1985, published in USA.
Yoshida and Kasama, "Biotransformation of Nitric Oxide," Environmental Health Perspectives, 73:201-206, 1987, published in USA.
Reif and Simmons, "Nitric Oxide Mediates Iron Release from Ferritin," Archives of Biochemistry and Biophysics, 283(2):537-541, 1990, published in USA.
Kruszyna et al., "Nitrite Conversion to Nitric Oxide in Red Cells and Its Stabilization as a Nitrosylated Valency Hybrid of Hemoblobin," The Journal of Pharmacology and Experimental Therapeutics, 241(1):307-313, 1987, published in USA.
Kosaka et al., "The Interaction Between Nitrogen Oxides and Hemoglobin and Endothelium-Derived Relaxing Factor," Free Radical Biology and Medicine, 7:653-658, 1989, published in USA.
Chevion et al., "Iron-Nitrosyl Bond Configuration in Nitrosyl-Hemoproteins: A Comparative EPR Study of Hemoglobin A and Hemoglobin Kansas," Israel Journal of Chemistry, 15:311-317, 1976, published in Israel.
Collier and Vallance, "Second Messenger Role for NO Widens to Nervous and Immune Systems," Trends in Pharmacological Sciences Including Toxicological Sciences, Elseview Science Publishers, Ltd., front page and pp. 428-431, 1989, published in United Kingdom.
Ignarro et al., "Endothelium-Derived Relaxing Factor Produced and Released from Artery and Vein is Nitric Oxide," Proc. Natl. Acad. Sci. USA, 84:9265-9269, 1987, published in USA.
Murray et al., "Stailization and Partial Characterization of Endothelium-Derived Relaxing Factor from Cultured Bovine Aortic Endothelial Cells," Biochemical and Biophysical Research Communications, 141(2):689-696, 1986, published in USA.
Marletta, Michael A., "Nitric Oxide: Biosynthesis and Biological Significance," name of publication unknown, Elseview Science Publishers, Ltd., pp. 448-493, 1989, published in United Kingdom.
Sakuma, I. et al., (1988) "Identification of Arginine as a Precursor of Endothelium-Derived Relaxing Factor," Proc. Natl. Acad. Sci. USA, 85:8664-8667, published in U.S.A.
Abstract entitled "Nitric Oxide Damages DNA in Bacteria," Chem. and Engineering News, Nov. 18, 1991, published in U.S.A.
Wink et al., (1991) "DNA Deaminating Ability and Genotoxicity of Nitric Oxide and its Progenitors," Scinece, 254:1001-1003, published in U.S.A.
Kilbourn et al., (1984) "Activated Macrophages Secrets a Soluble Factor that Inhibits Mitochondrial Respiration of Tumor Cells," J. Immunology, 133:2577-2581, published in U.S.A.
Kilbourn et al., (1990) "Reversal of Endotoxin-Mediated Shock by N.sup.G -Methyl-L-Arginine, an Inhibitor of Nitric Oxide Synthesis," Biochem. and Biophys. Res. Commun., 172:1132-1138, published in U.S.A.
Kilbourn, R. G., et al., (1990) "N.sup.G -Methyl-L-Arginine Inhibits Tumor Necrosis Factor-Induced Hypotension: Implications for the Involvement of Nitric Oxide," Proc. Natl. Acad. Sci. USA, 87:3629-3632, published in U.S.A.
Schmidt et al., (1992) "Insulin Secretion from Pancreatic B Cells Caused by L-Arginine-Derived Nitrogen Oxides," Scinece, 255:721-723, published in U.S.A.
Turan, A. et al., (1975) "Removal of the Nitro Group from Nitroarginine and Nitroarginine Peptides," Acta Chimica Academiae Scientiarum Hungaricae, Tomas, 85:327-332, published in Europe.
Iyengar, R. et al., (1987) "Macrophage Synthesis of Nitrite, Nitrate, and N-Nitrosamines: Precursors and Role of the Respiratory Burst," Proc. Natl. Acad. Sci. USA, 84:6369-6373, published in U.S.A.
Stuehr et al., (1987) "Induction of Nitrite/Nitrate Synthesis in Murine Macrophages by BCG Infection, Lymphokines, or Interferon-.gamma..sup.1 " J. Immunology, 139:518-525, published in U.S.A.
Marletta et al., (1988) "Macrophage Oxidation of L-Arginine to Nitrite and Nitrate: Nitric Oxide Is an Intermediate," Biochemistry, 27:8706-8711, published in U.S.A.
Palmer, R. M. J. et al., (1988) "Vascular Endothelial Cells Synthesize Nitric Oxide from L-Arginine," Nature, 333:664-666, published in the United Kingdom.
Palmer, R. M. J. et al., (1988) "L-Arginine is the Physiological Precursor for the Formation of Nitric Oxide in Endothelium-Dependent Relaxation," Biochem. Biophys. Res. Commun., 153:1251-1256, published in U.S.A.
Schmidt et al., (1988) "Arginine is a Physiological Precursor of Endothelium-Derived Nitric Oxide," European J. Pharmacology, 154:213-216, published in Europe.
Aisaka et al., (1989) "N.sup.G -Methylarginine, An Inhibitor of Endothelium-Derived Nitric Oxide Synthesis, Is a Potent Pressor Agent in the Guinea Pig: Does Nitric Oxide Regulate Blood Pressure in Vivo?" Biochem. Biophys. Res. Commun., 160:881-886, published in U.S.A.
Rees, D. D. et al., (1989) "Role of Endothelium-Derived Nitric Oxide in the Regulation of Blood Pressure," Proc. Natl. Acad. Sci. USA, 86:3375-3378, published in U.S.A.
Stuehr, D. J., et al., (1989) "Activated Murine Macrophages Secrete a Metabolite of Arginine with the Bioactivity of Endothelium-Derived Relaxing Factor and the Chemical Reactivity of Nitric Oxide," J. Exp. Med., 169:1011-1020, published in U.S.A.
Stuehr, D. J. et al., (1989) "Synthesis of Nitrogen Oxides from L-Arginine by Macrophage Cytosol: Requirement for Inducible and Constitutive Components," Biochem. Biophys. Res. Commun., 161:420-426, published in U.S.A.
Piguet et al., (1989) "Tumor Necrosis Factor/Cachect
Griffith Owen W.
Gross Steven S.
Kilbourn Robert G.
Board of Regents , The University of Texas System
Cintins Marianne M.
Criapres T. J.
LandOfFree
Methods and compositions for the treatment of hypotension with a does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods and compositions for the treatment of hypotension with a, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods and compositions for the treatment of hypotension with a will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2386426