Claims for Patent: 6,056,941

Summary for Patent: 6,056,941

Title:	Kit for the preparation of technetium TC 99m teboroxime myocardial perfusion agent
Abstract:	A kit containing a solution of boronic acid adducts of technetium-99 m dioxime complexes; and hydroxypropyl gamma cyclodextrin to maintain the solution free of particulate matter originating from the formulation.
Inventor(s):	Schramm; Ernest (North Brunswick, NJ), Newborn; Margaret (Hamilton, NJ), Zodda; Julius P. (Mercerville, NJ), Katona; Thomas (Mercerville, NJ), Monteferrante; Jo Anna (Flemington, NJ)
Assignee:	Bracco Research USA (Princeton, NJ)
Application Number:	09/363,132
Patent Claims:	1. In an improved kit for myocardial diagnosis of a patient with suspected coronary artery diseases using rest and stress techniques, said kit having (a) a first container containing lyophilized ingredients; and (b) a second container containing technetium TC-99 m; wherein said first container contains 5 to 15 mg sodium chloride, or sodium bromide; 1 to 3 mg of boronic acid derivative, or compounds which can react in situ to form a boronic acid derivative, having the formula ##STR5## or a pharmaceutically acceptable salt thereof, wherein R.sub.3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aloxy, carboxyalkyl, carboxyalkenyl, hydroxyalkyl, hydroxalkenyl, alkoxyalkyl, aloxy-alkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl, or R.sub.4 R.sub.5 N-alkyl and R.sub.4 and R.sub.5 are each independently hydrogen, alkyl, or arylalkyl, or R.sub.4 and R.sub.5 when taken together with nitrogen atom to which they are attached form a 5 or 6-membered nitrogen containing heterocycle, and R.sub.7 is hydrogen, alkyl or aryl; 1 to 3 mg of a dioxime having the formula ##STR6## or a pharmaceutically acceptable salt thereof, wherein R.sub.1 and R.sub.2 are each independently hydrogen, halogen, alkyl, aryl, amino or a 5 or 6-membered nitrogen or oxygen containing heterocycle, or together R.sub.2 and R.sub.3 are --(CH.sub.2 R.sub.9)-- wherein n is 3, 4, 5, or 6 and R.sub.8 and R.sub.9 are each independently hydrogen or alkyl; 0.03 to 0.06 mg stannous chloride; 1 to 3 mg pentetic acid; and 8 to 10 mg citric acid; and said second container contains 1 to 3 ml of technetium Tc-99 m in physiological saline containing 10 to 100 mCi; wherein the improvement comprises: 30 to 50 mg hydroxypropyl gamma cyclodextrin added to said first container. 2. The kit for myocardial diagnosis of a patient according to claim 1, wherein said dioxime is selected from the group consisting of: dimethyl glyoxime, 1,2-cyclohexanedione dioxime, 1,2-ethanedione dioxime, .alpha.-furyldioxime, 1, 2-cyclopentanedione dioxime and 3-methyl-1, 2-cyclopentanedione dioxime. 3. The kit for myocardial diagnosis of a patient according to claim 1, wherein said boronic acid derivative is selected from the group consisting of: B-alkyl, B-alkoxy, B-benzyl and B-cycloalkyl. 4. The kit for myocardial diagnosis of a patient according to claim 1 wherein when said technetium Tc-99 m is added to the first container forms a complex with the content thereof, said complex selected from the group consisting of: .sup.99m Tc (chlorine) (dimethyl glyoxime).sub.3 methoxy boron; .sup.99m Tc (chlorine) (dimethyl glyoxime).sub.3 hydroxy boron; .sup.99m Tc (chlorine) (dimethyl glyoxime).sub.3 ethoxy boron; .sup.99m Tc (chlorine) (dimethyl glyoxime).sub.3 propyloxy boron; .sup.99m Tc (chlorine) (dimethyl glyoxime).sub.3 hexyloxy boron; .sup.99m Tc (chlorine) (dimethyl glyoxime).sub.3 1-methylpropyl boron; .sup.99m Tc (bromine) (dimethyl glyoxime).sub.3 butyl boron; .sup.99m Tc (iodine) (dimethyl glyoxime).sub.3 butyl boron; .sup.99m Tc (fluorine) (dimethyl glyoxime).sub.3 butyl boron; .sup.99m Tc (chlorine) (dimethyl glyoxime).sub.3 3-(4-morpholinyl)propyl boron; .sup.99m Tc (chlorine) (dimethyl glyoxime).sub.3 2-phenylethyl boron; .sup.99m Tc (chlorine) (1,2-cyclohexanedione dioxime).sub.3 methyl boron; and .sup.99m Tc (chlorine) (dimethyl glyoxime).sub.3 4-formylphenyl boron. 5. In an improved kit for myocardial diagnosis of a patient with suspected coronary artery diseases using rest and stress techniques said kit; having a) a first container containing lyophilized ingredients containing 1 to 3 mg cyclohexanedione dioxime; 1 to 3 mg methyl boronic acid; 8 to 10 mg citric acid; 5 to 10 mg sodium chloride; and 0.030 to 0.060 mg stannous chloride (SnCl.sub.2); and b) a second container containing 1 to 3 ml technetium Tc-99 m in physiological saline; wherein the improvement comprises: 30 to 50 mg hydroxypropyl gamma cyclodextrin added to said first container.