US4842845A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Radioactive metal chelates for dipyridoxyl phosphate
Assignee: Amersham Health Salutar Inc
•
Filing: 1987-05-08
•
Granted: 1989-06-27
•
Expires: 2007-05-08
Abstract
Abstract Radioactive metal ion chelates of N,N'-bis-(pyridoxal-5-phosphate)-alkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal-5-phosphate)-1,2-cycloalkylenediamine-N,N'-diacetic acids, and N,N'-bis-(pyridoxal-5-phosphate)-1,2-arylenediamine-N,N'-diacetic acids, the corresponding monophosphate compounds and monoacetic acid compounds, and their salts and esters form stable, highly soluble chelates with paramagnetic metal ions, and are highly effective agents for radiopharmaceutical imaging. Preferred contrast agents are radioactive metal ion such as technetium-99m and indium-111 ion chelates of N,N'-bis-(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-cyclohexylene-diamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-arylenediamine-N,N'-diacetic acid, and the soluble calcium salts thereof.
Inventors
- 👤 Scott M. Rocklage
- 👤 Steven C. Quay
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 06:18
CPC Classifications
C; C07; C07F; C07F13/00; C07F13/005; A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K51/0474; A61K51/0478; C07F9/00; C07F9/02; C07F9/547; C07F9/553; C07F9/576; C07F9/58; A61K2123/00
Claims Analysis
Total Claims: 45
Claim 1
Independent Claim
154 words
A radioactive metal ion chelate of the chelating compound of the formula: ##STR9## wherein said compound is chelated with a radioactive metal iron, wherein R is hydrogen or ##STR10## R 1 is hydrogen or ##STR11## and one of R and R 1 is other than hydrogen; R 3 is alkylene having from 1 to 8 carbons, 1,2-cycloalkylene having from 5 to 8 carbons, or 1,2-arylene having from 6 to 10 carbons, or R 4 is hydrogen, hydroxymethyl, alkyl having from 1 to 6 carbons or ##STR12## R 5 and R 6 are each, individually, hydroxy, alkoxy having from 1 to 18 carbons, hydroxy-substituted alkoxy having from 1 to 18 carbons, amino or alkylamido having from 1 to 18 carbons; the phosphate group mono and diesters of the compounds thereof with monohydric and polyhydric alcohols having from 1 to 18 carbons, or alkylamino alcohols, each having from 1 to 18 carbons, and the salts thereof.
Claim 2
Dependent Claim
154 words
A radioactive metal ion chelate of the chelating compound of the formula: ##STR9## wherein said compound is chelated with a radioactive metal iron, wherein R is hydrogen or ##STR10## R 1 is hydrogen or ##STR11## and one of R and R 1 is other than hydrogen; R 3 is alkylene having from 1 to 8 carbons, 1,2-cycloalkylene having from 5 to 8 carbons, or 1,2-arylene having from 6 to 10 carbons, or R 4 is hydrogen, hydroxymethyl, alkyl having from 1 to 6 carbons or ##STR12## R 5 and R 6 are each, individually, hydroxy, alkoxy having from 1 to 18 carbons, hydroxy-substituted alkoxy having from 1 to 18 carbons, amino or alkylamido having from 1 to 18 carbons; the phosphate group mono and diesters of the compounds thereof with monohydric and polyhydric alcohols having from 1 to 18 carbons, or alkylamino alcohols, each having from 1 to 18 carbons, and the salts thereof.
Claim 3
Dependent Claim
23 words
A radioactive metal ion chelate of a chelating compound of claim 1 wherein R 3 is alkylene having from 2 to 6 carbons.
Claim 4
Dependent Claim
21 words
A radioactive metal ion chelate of the chelating compound of claim 1 wherein R is ##STR13## and R 1 is ##STR14##
Claim 5
Dependent Claim
38 words
A radioactive metal ion chelate of the chelating compound of claim 3 wherein R 5 and R 6 are each, individually, hydroxy, alkoxy having from 1 to 8 carbons, amino or alkylamido having from 1 to 8 carbons.
Claim 6
Dependent Claim
24 words
A radioactive metal ion chelate of the chelating compound of claim 4 wherein R 5 and R 6 are hydroxy or a salt thereof.
Claim 7
Dependent Claim
24 words
As a radioactive metal ion chelate of a chelating compound of claim 5, a radioactive metal chelate of N,N'-bis-(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid or a salt thereof.
Claim 8
Dependent Claim
17 words
A radioactive metal ion chelate of a chelating compound of claim 1 wherein R 3 is cyclohexyl.
Claim 9
Dependent Claim
24 words
As a radioactive metal ion chelate of a chelating compound of claim 7, a radioactive metal chelate of N,N'-bis-(pyridoxal-5-phosphate)-trans-1,2-cyclohexyl-diamine-N,N'-diacetic acid or a salt thereof.
Claim 10
Dependent Claim
38 words
A radioactive metal ion chelate of claim 1, 2, 3, 4, 5, 6, 7, or 8 with a metal ion having a gamma emission between 20 and 600 KeV and a half-life between one hour and one year.
Claim 11
Dependent Claim
64 words
A radioactive metal ion chelate of claim 9 wherein the metal ion is selected from the group consisting of ions of 99m Tc, 99 Tc, 95 Tc, 51 Cr, 57 Co, 67 Ga, 68 Ga, 111 In, 113m In, 197 Hg, 75 Se, 201 Tl, 203 Pb, 85 Sr, 87m Sr, 135m Sm, 153 Sm, 171 Er, 169 Yb, 62 Zn, and 186 Re.
Claim 12
Dependent Claim
9 words
A calcium salt of a chelate of claim 9.
Claim 13
Dependent Claim
20 words
A calcium salt of claim 11 wherein the molar ratio of calcium to chelating compound is from 0.05 to 1.0.
Claim 14
Dependent Claim
20 words
A calcium salt of claim 12 wherein the molar ratio of calcium to chelating compound is from 0.1 to 0.5.
Claim 15
Dependent Claim
24 words
A radioactive metal ion chelate of a compound of claim 1, 2, 3, 4, 5, 6, 7, or 8 with a technetium-99m metal ion.
Claim 16
Dependent Claim
16 words
As a chelate of claim 14, a technetium-99m chelate of N,N'-bis-(pyridoxal-5-phosphate)-trans-1,2-cyclohexyldiamine-N,N,-diacetic acid or a salt thereof.
Claim 17
Dependent Claim
16 words
As a chelate of claim 14, a technetium-99m chelate of N,N'-bis-(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid or a salt thereof.
Claim 18
Dependent Claim
9 words
A calcium salt of the chelate of claim 15.
Claim 19
Dependent Claim
20 words
A calcium salt of claim 16 wherein the molar ratio of calcium to chelating compound is from 0.05 to 1.0.
Claim 20
Dependent Claim
20 words
A calcium salt of claim 17 wherein the molar ratio of calcium to chelating compound is from 0.1 to 0.5.
Claim 21
Dependent Claim
37 words
A radioactive metal ion imaging composition consisting essentially of a chelate of a radioactive metal ion chelate of a compound of claim 1, 2, 3, 4, 5, 6, 7 or 8 and a pharmaceutically acceptable, compatible excipient.
Claim 22
Dependent Claim
43 words
A radioactive metal ion imaging composition of claim 20 consisting essential of a chelate of a radioactive metal ion having a gamma emission between 20 and 600 KeV and a half-life between one hour and one year and a pharmaceutical acceptable, compatible excipient.
Claim 23
Dependent Claim
65 words
A radioactive metal ion imaging composition of claim 21 wherein the metal ion is selected from the group consisting of ions of 99m Tc, 99 Tc, 95 Tc, 51 Cr, 57 Co, 67 Ga, 68 Ga, 111 In, 113m In, 197 Hg, 75 Se, 201 Tl, 203 Pb, 85 Sr, 87m Sr, 135m Sm, 153 Sm, 171 Er, 169 Yb, 62 Zn, and 186 Re.
Claim 24
Dependent Claim
17 words
A radioactive metal ion imaging composition of claim 22 wherein the metal ion is a technetium-99m ion.
Claim 25
Dependent Claim
16 words
A radioactive metal ion imaging composition of claim 21 containing a calcium salt of the chelate.
Claim 26
Dependent Claim
30 words
A radioactive metal ion imaging composition of claim 24 containing a calcium salt of the chelate wherein the molar ratio of calcium to chelating compound is from 0.05 to 1.0.
Claim 27
Dependent Claim
27 words
A radioactive metal ion imaging composition of claim 25 containing a calcium salt wherein the molar ratio of calcium to chelating compound is from 0.1 to 0.5.
Claim 28
Dependent Claim
22 words
A radioactive metal ion imaging composition of claim 21 wherein the compound is N,N'-bis-(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)-trans-1,2-cyclohexyl diamine-N,N'-diacetic acid, or a salt thereof.
Claim 29
Dependent Claim
13 words
A radioactive metal ion imaging composition of claim 27 containing a calcium salt.
Claim 30
Dependent Claim
27 words
A radioactive metal ion imaging composition of claim 28 containing a calcium salt, wherein the molar ratio of calcium to chelating compound is from 0.05 to 1.0.
Claim 31
Dependent Claim
27 words
A radioactive metal ion imaging composition of claim 29 containing a calcium salt, wherein the molar ratio of calcium to chelating compound is from 0.1 to 0.5.
Claim 32
Dependent Claim
26 words
A radioactive metal ion imaging composition of claim 21 wherein the concentration of chelate salt in the medium is from 0.01 to 10 mCi per ml.
Claim 33
Dependent Claim
26 words
A radioactive metal ion imaging composition of claim 31 wherein the concentration of chelate salt in the medium is from 2 to 5 mCi per ml.
Claim 34
Dependent Claim
37 words
An improvement in the method of performing radiopharmaceutical imaging with a patient comprising administering to the patient, an effective amount of a radioactive metal ion chelate of claim 1, 2, 3, 4, 5, 6, 7 or 8.
Claim 35
Dependent Claim
38 words
An improvement in the method of performing radiopharmaceutical imaging of a patient of claim 33 wherein the radioactive metal ion has a gamma emission between 20 and 600 KeV and a half-life between one hour and one year.
Claim 36
Dependent Claim
71 words
An improvement in the method for performing radiopharmaceutical imaging of a patient of claim 34 wherein the metal ion is selected from the group consisting of ions of 99m Tc, 99 Tc, 95 Tc, 51 Cr, 57 Co, 67 Ga, 68 Ga, 111 In, 113 mIn, 197 Hg, 75 Se, 201 Tl, 203 Pb, 85 Sr, 87m mSr, 135m Sm, 153 Sm, 171 Er, 169 Yb, 62 Zn, and 186 Re.
Claim 37
Dependent Claim
20 words
An improvement in the method for performing radiopharmaceutical imaging of claim 34 wherein the metal ion is a technetium-99m ion.
Claim 38
Dependent Claim
24 words
An improvement in the method for performing radiopharmaceutical imaging of claim 34 wherein the compound is N,N'-bis-(pyroxidal-5-phosphate)ethylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxyl-5-phosphate)-trans-1,2-cyclohexyldiamine-N,N'-diacetic acid, or a salt thereof.
Claim 39
Dependent Claim
22 words
An improvement in the method for performing radiopharmaceutical imaging of claim 34 wherein the chelate of the compound is a calcium salt.
Claim 40
Dependent Claim
25 words
An improvement in the method for performing radiopharmaceutical imaging of claim 38 wherein the molar ratio of calcium to chelate is from 0.05 to 1.0.
Claim 41
Dependent Claim
25 words
An improvement in the method for performing radiopharmaceutical imaging of claim 39 wherein the molar ratio of calcium to chelate is from 0.1 to 0.5.
Claim 42
Dependent Claim
30 words
An improvement in the method for performing radiopharmaceutical imaging of claim 34 wherein the metal ion is technetium-99m and the compound is N,N'-bis-(phyidoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid, N,N'-bis-(phridoxyl-5-phosphate)-trans-1,2-cyclohexyldiamine-N,N'-diacetic acid, or a salt thereof.
Claim 43
Dependent Claim
33 words
An improvement in the method for performing radiopharmaceutical imaging of claim 41 wherein the salt is a calcium salt with a molar ratio of calcium to chelating compound of from 0.05 to 1.0.
Claim 44
Dependent Claim
28 words
An improvement in the method of performing radiopharmaceutical imaging of claim 33 wherein from 0.001 to 1 mCi of chelate is administered per kg of patient body weight.
Claim 45
Dependent Claim
28 words
An improvement in the method of performing radiopharmaceutical imaging of claim 43 wherein from 0.002 to 0.1 mCi of chelate is administered per kg of patient body weight.
References Cited (Backward Citations)
US3981980A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-06-26 | 1992-12-26 | 1993-06-27 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-06-26 | 1996-12-26 | 1997-06-27 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-06-26 | 2000-12-26 | 2001-06-27 | $7700.00 | Window Closed / Lapsed |