Claims for Patent: 5,093,105

Summary for Patent: 5,093,105

Title:	Radiopharmaceutical bacteriostats
Abstract:	Benzalkonium chloride and benzethonium chloride are each useful in radiopharmaceutical preparations as bacteriostatic agents which are compatible with anti-oxidants.
Inventor(s):	Flanagan; Richard J. (St. Lazare, CA), Tartaglia; Daniel (Anjou, CA)
Assignee:	Merck Frosst Canada, Inc. (Quebec, CA)
Application Number:	07/682,170
Patent Claims:	1. A radiopharmaceutical composition comprising: (a) a .sup.99m Tc-based radiopharmaceutical; (b) a water-soluble pertechnetate reducing agent; (c) a radical-scavenging antioxidant; and (d) a bacteriostat selected from: (i) benzalkonium chloride, and (ii) benzethonium chloride. 2. The radiopharmaceutical composition of claim 1 wherein the bacteriostat is benzethonium chloride. 3. The radiopharmaceutical composition of claim 1 wherein the radical-scavenging antioxidant is selected from the group consisting of: para-aminobenzoic acid; gentisic acid; and ascorbic acid. 4. A method of administering a radiopharmaceutical agent to a subject, which comprises administering an effective amount of the radiopharmaceutical composition of claim 1 by intravenous, oral, or nebular administration. 5. The radiopharmaceutical composition of claim 1 wherein the bacteriostat is benzalkonium chloride. 6. The radiopharmaceutical composition of claim 5 wherein the water-soluble pertechnetate reducing agent is stannous chloride. 7. The radiopharmaceutical composition of claim 6 wherein the radical-scavenging antioxidant is para-aminobenzoic acid. 8. The radiopharmaceutical composition of claim 7 wherein the .sup.99m Tc-based radiopharmaceutical is .sup.99m Tc-methylene-disphosphonic acid or a pharmaceutically acceptable salt thereof. 9. The radiopharmaceutical composition according to claim 1, wherein (d) is present in a concentration from about 0.00001% to about 0.01% (w/v). 10. The radiopharmaceutical composition according to claim 9, wherein (d) is present in a concentration from about 0.00005% to about 0.001% (w/v). 11. The radiopharmaceutical composition according to claim 10, wherein (d) is present in a concentration from about 0.0001% to about 0.0005% (w/v). 12. The radiopharmaceutical compostion of claim 1 wherein the .sup.99m Tc-based radiopharmaceutical is selected from the group consisting of: .sup.99m Tc-methylene-disphosphonic acid; .sup.99m Tc-hydroxymethylene-diphosphonic acid; .sup.99m Tc-ethane-1-hydroxy-1,1-diphosphonic acid; .sup.99m Tc-1-hydroxypropane-1,1-diphosphonic acid; .sup.99m Tc-2,3-dicarboxypropane-1,1-diphosphonic acid; .sup.99m Tc-pyrophosphate; .sup.99m Tc-trimetaphosphate; .sup.99m Tc-diethylenetriaminepentaacetic acid; .sup.99m Tc-2,3-dimercaptosuccinic acid; .sup.99m Tc-glycero-glucoheptanoic acid; [N-[N-[N-(mercaptoacetyl)glycyl]glycyl]glycinato(5-)-N,N',N",S]-oxo-[.sup.9 9m Tc]technetate(V); .sup.99m Tc-macroaggregated albumin; .sup.99m Tc-albumin colloid; .sup.99m Tc-aggregated human albumin; .sup.99m Tc-recombinant human albumin/human serum albumin in microspherical form; .sup.99m Tc-imminodiphosphonic acid; .sup.99m Tc-[(acac).sub.2 en]; .sup.99m Tc-hydrophosphonic acid; .sup.99m Tc-monoclonal antibody to fibrin; .sup.99m Tc-monoclonal antibody to myosin; .sup.99m Tc-tissue plasminogen activator; hexakis(1-isocyano-2-methoxy-2-methylpropane)-[.sup.99m Tc]technetium(I); bis[(1,2-cyclohexanedionedioximato)-(1-)-O]-[(1,2-cyclohexanedionedioximato )-(2-)-O]-methylborato-(2-)-N,N',N",N'",N"",N'""-chloro[.sup.99m Tc]technetium (III); ]bis(2,3-butanedione-dioximato)(1-)-O]-[(2,3-butanedione-dioximato)(2-)-O]- (2-methylpropyl)borato-(2)-N,N',N",N'",N"",N'""-chloro[.sup.99m Tc]technetium; .sup.99m Tc-ethyl cystinate dimer; .sup.99m Tc-3,3'-[(2,2-dimethyltrimethylene)diimino]di-2-butanone-dioxime; bis[N-[2-[(3-bromo-2,4,6-trimethylphenyl)amino]-2-oxoethyl]-N-(carboxymethy l)-glycyl]-[.sup.99m Tc]technetium; bis[N-[2-[[2,6-bis(1-methylethyl)phenyl]-amino]2-oxoethyl]-N-(carboxymethyl )-glycyl][.sup.99m Tc]technetium; bis[-N-(carboxymethyl)-N-[2-[2,6-dimethylphenyl)-amino]-2-oxoethyl]-glycyl] -[.sup.99m Tc]technetium; and .sup.99m Tc-polyisohexylcyanoacrylate nanoparticles; or a pharmaceutically acceptable salt thereof. 13. The radiopharmaceutical composition of claim 12 wherein the .sup.99m Tc-based radiopharmaceutical is selected from: .sup.99m Tc-methylene-disphosphonic acid; .sup.99m Tc-hydroxymethylene-diphosphonic acid; .sup.99m Tc-ethane-1-hydroxy-1,1-diphosphonic acid; .sup.99m Tc-1-hydroxypropane-1,1-diphosphonic acid; .sup.99m Tc-2,3-dicarboxypropane-1,1-diphosphonic acid; .sup.99m Tc-pyrophosphate; and .sup.99m Tc-trimetaphosphate; or a pharmaceutically acceptable salt thereof. 14. A method for bone scintigraphy in a subject, which comprises administering an effective amount of the radiopharmaceutical composition of claim 13 by intravenous administration. 15. The radiopharmaceutical composition of claim 12 wherein the .sup.99m Tc-based radiopharmaceutical is selected from: .sup.99m Tc-diethylenetriaminepentaacetic acid; .sup.99m Tc-2,3-dimercaptosuccinic acid; .sup.99m Tc-glycero-glucoheptanoic acid; and [N-[N-[N-(mercaptoacetyl)glycyl]glycyl]glycinato(5-)-N,N',N",S]-oxo-[.sup.9 9m Tc]technetate(V); or a pharmaceutically acceptable salt thereof. 16. A method for radioimaging of the kidney in a subject, which comprises administering an effective amount of the radiopharmaceutical composition of claim 15 by intravenous administration. 17. The radiopharmaceutical composition of claim 12 wherein the .sup.99m Tc-based radiopharmaceutical is selected from: .sup.99m Tc-macroaggregated albumin; .sup.99m Tc-albumin colloid; .sup.99m Tc-aggregated human albumin; and .sup.99m Tc-recombinant human albumin/human serum albumin in microspherical form. 18. A method for radioimaging of the lung in a subject, which comprises administering an effective amount of the radiopharmaceutical composition of claim 17 by intravenous or nebular administration. 19. The radiopharmaceutical composition of claim 12 wherein the .sup.99m Tc-based radiopharmaceutical is selected from: .sup.99m Tc-imminodiphosphonic acid; .sup.99m Tc-[(acac).sub.2 en]; .sup.99m Tc-hydrophosphonic acid; .sup.99m Tc-monoclonal antibody to fibrin; .sup.99m Tc-monoclonal antibody to myosin; .sup.99m Tc-tissue plasminogen activator; hexakis(1-isocyano-2-methoxy-2-methylpropane)-[.sup.99m Tc]technetium(I); bis[(1,2-cyclohexanedionedioximato)-(1-)-O]-[(1,2-cyclohexanedionedioximato )-(2-)-O]-methylborato-(2-)-N,N',N",N'",N"",N'""-chloro[.sup.99m Tc]technetium (III); and .sup.99m Tc-glycero-glucoheptanoic acid; or a pharmaceutically acceptable salt thereof. 20. A method for radioimaging of blood pool and myocardial infarct in a subject, which comprises administering an effective amount of the radiopharmaceutical composition of claim 19 by intravenous administration. 21. The radiopharmaceutical composition of claim 12 wherein the .sup.99m Tc-based radiopharmaceutical is selected from: .sup.99m Tc-diethylenetriaminepentaacetic acid; [bis(2,3-butanedione-dioximato)(1-)-O]-[(2,3-butanedione-dioximato)(2-)-O]- (2-methylpropyl)borato-(2-)-N,N',N",N'",N"",N'""-chloro[.sup.99m Tc]technetium; .sup.99m Tc-ethyl cystinate dimer; and .sup.99m Tc-3,3'-[(2,2-dimethyltrimethylene)diimino]di-2-butanone-dioxime; or a pharmaceutically acceptable salt thereof. 22. A method for brain/cerebral perfusion radioimaging in a subject, which comprises administering an effective amount of the radiopharmaceutical composition of claim 21 by intravenous administration. 23. The radiopharmaceutical composition of claim 12 wherein the .sup.99m Tc-based radiopharmaceutical is selected from: bis[N-[2-[(3-bromo-2,4,6-trimethylphenyl)amino]-2-oxoethyl]-N-(carboxymethy l)-glycyl]-[.sup.99m Tc]technetium; bis[N-[2-[[2,6-bis(1-methylethyl)phenyl[amino]-2-oxoethyl]-N-(carboxymethyl )-glycyl]-[.sup.99m Tc]technetium; bis[-N-(carboxymethyl)-N-[2-[2,6-dimethylphenyl)-amino]-2-oxoethyl]-glycyl] -[.sup.99m Tc]technetium; and .sup.99m Tc-polyisohexylcyanoacrylate nanoparticles; or a pharmaceutically acceptable salt thereof. 24. A method for radioimaging of the liver, gall bladder, and/or spleen in a subject, which comprises administering an effective amount of the radiopharmaceutical composition of claim 23 by intravenous administration.

Details for Patent 5,093,105

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Grifols Therapeutics Llc	ALBUKED, PLASBUMIN-20, PLASBUMIN-25, PLASBUMIN-5	albumin (human)	For Injection	101138	10/21/1942		2040-01-28
Baxalta Us Inc.	BUMINATE, FLEXBUMIN	albumin (human)	Injection	101452	03/03/1954		2040-01-28
Csl Behring Ag	ALBURX	albumin (human)	Injection	102366	07/23/1976		2040-01-28