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Method for enhancing the safety of metal-ligand chelates as magnetic resonance imaging agents by addition of calcium ions

Assignee: Mallinckrodt Inc
•
Filing: 1989-06-22
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Granted: 1992-01-21
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Expires: 2009-06-22
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Abstract

Abstract Paramagnetic chelates, as for example, Gadolinium diethylenetriaminepentaacetic acid (DTPA), manganese, ethylenediaminetetraacetic acid (EDTA), and others used as magnetic resonance imaging contrast agents are more toxic acutely when injected in high concentration or at rapid rates. The use of effective amounts of calcium in the form of, calcium chloride, calcium gluconate, or balanced salt solutions substantially reduces this toxicity without the need to add additional ligand.

Inventors

  • 👤 Donald R. VanDeripe

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-30 16:18
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/06; Y; Y10; Y10S; Y10S424/00; Y10S424/90; Y10S436/00; Y10S436/806; Y10T; Y10T436/00; Y10T436/24

Claims Analysis

Total Claims: 17
Claim 1
Independent Claim 113 words
In a method for enhancing safety in the in vivo use of methal-ligand chelate complexes as magnetic resonance imaging agents comprising administering to a mammal a diagnostically effective amount of a metal-ligand complex, the improvement comprising: adding calcium ions to a charge-balanced metal-ligand complex formed from the anion of a complexing acid and a central ion of an element with an atomic number of 21 to 29, 42, 44, or 57-70, said calcium ions being added in substantially less than stoichiometric amounts to the metal-ligand complex, said calcium ions being provided from a member of the group consisting of inorganic calcium salts, organic calcium salts and mixtures thereof without excess ligand being added.
Claim 2
Dependent Claim 113 words
In a method for enhancing safety in the in vivo use of methal-ligand chelate complexes as magnetic resonance imaging agents comprising administering to a mammal a diagnostically effective amount of a metal-ligand complex, the improvement comprising: adding calcium ions to a charge-balanced metal-ligand complex formed from the anion of a complexing acid and a central ion of an element with an atomic number of 21 to 29, 42, 44, or 57-70, said calcium ions being added in substantially less than stoichiometric amounts to the metal-ligand complex, said calcium ions being provided from a member of the group consisting of inorganic calcium salts, organic calcium salts and mixtures thereof without excess ligand being added.
Claim 3
Dependent Claim 18 words
The methods of claims 1 wherein the metal-ligand chelate complex is used in the form of a salt.
Claim 4
Dependent Claim 15 words
The methods of claims 1 wherein the metal-ligand chelate complex is used in non-ionic form.
Claim 5
Independent Claim 29 words
The method of claims 1, wherein the calcium ions are provided at levels of from about 1 to about 25% of the stoichiometric amount required by the metal-ligand complex.
Claim 6
Dependent Claim 23 words
The method of claim 4 wherein the calcium ions are provided at levels of about 3 to about 15% of the stoichiometric amount.
Claim 7
Dependent Claim 17 words
The method of claim 1 wherein the calcium ions are provided in the form of calcium chloride.
Claim 8
Dependent Claim 29 words
The method of claim 1 wherein the calcium ions are provided at levels of from about 1 to about 15% of the stoichiometric amount required by the metal-ligand complex.
Claim 9
Dependent Claim 29 words
The method of claim 2 wherein the calcium ions are provided at levels of from about 1 to about 25% of the stoichiometric amount required by the metal-ligand complex.
Claim 10
Dependent Claim 29 words
The method of claim 3 wherein the calcium ions are provided at levels of from about 1 to about 25% of the stoichiometric amount required by the metal-ligand complex.
Claim 11
Dependent Claim 23 words
The method of claim 7 wherein the calcium ions are provided at levels of about 3 to about 15% of the stoichiometric amount.
Claim 12
Dependent Claim 23 words
The method of claim 8 wherein the calcium ions are provided at levels of about 3 to about 15% of the stoichiometric amount.
Claim 13
Dependent Claim 23 words
The method of claim 9 wherein the calcium ions are provided at levels of about 3 to about 15% of the stoichiometric amount.
Claim 14
Dependent Claim 126 words
In a method for enhancing safety in the in vivo use of methal-ligand chelate complexes as magnetic resonance imaging agents comprising administering to a mammal a diagnostically effective amount of a metal-ligand complex, the improvement comprising: adding calcium ions to a charge-balanced metal-ligand complex formed from the anion of a complexing acid and a central ion of an element with an atomic number of 21 to 29, 42, 44, or 57-70, said calcium ions being added in substantially less than stoichiometric amounts to the metal-ligand complex, said calcium ions being provided from a member of the group consisting of inorganic calcium salts, organic calcium salts and mixtures thereof and being added in addition to any calcium present as the salt of an excess of said ligand.
Claim 15
Dependent Claim 126 words
In a method for enhancing safety in the in vivo use of methal-ligand chelate complexes as magnetic resonance imaging agents comprising administering to a mammal a diagnostically effective amount of a metal-ligand complex, the improvement comprising: adding calcium ions to a charge-balanced metal-ligand complex formed from the anion of a complexing acid and a central ion of an element with an atomic number of 21 to 29, 42, 44, or 57-70, said calcium ions being added in substantially less than stoichiometric amounts to the metal-ligand complex, said calcium ions being provided from a member of the group consisting of inorganic calcium salts, organic calcium salts and mixtures thereof and being added in addition to any calcium present as the salt of an excess of said ligand.
Claim 16
Dependent Claim 17 words
The method of claim 13 wherein the metal-ligand complex is used in the form of a salt.
Claim 17
Dependent Claim 14 words
The method of claim 13 wherein the metal-ligand complex is used in non-ionic form.

References Cited (Backward Citations)

GB736432A Cited
US4647447A Cited
US4478816A Cited
US4822594A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1995-01-20 1995-07-22 1996-01-21 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1999-01-20 1999-07-22 2000-01-21 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2003-01-20 2003-07-22 2004-01-21 $7700.00 Window Closed / Lapsed

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