US4451450A
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Cationic compounds useful for making radiodiagnostic agents
Assignee: Bristol Myers Squibb Pharma Co
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Filing: 1981-10-15
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Granted: 1984-05-29
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Expires: 2001-10-15
Abstract
Abstract A normally solid, hydrophilic compound capable of binding with Tc-99m to form a cationic complex is provided. The compound has a formula selected from: ##STR1## wherein: R, R', R", R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently selected from hydrogen; or substituted or unsubstituted alkyl, alkylene, aryl, alkylaryl, arylalkyl, monocycloalkyl, polycycloalkyl, heterocyclic and carbocyclic groups; and R plus R i in formula (A) may be taken together to form a cyclic compound; A, A', A", A 1 , A 2 , A 3 , A 4 , A 5 and A 6 are independently neutral functional elements, each having a free electron pair available for accepting a proton to provide a charged ligand and having the capability of complexing with Tc-99m to form a cationic complex; Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 are each independently selected from hydrogen; or substituted or unsubstituted alkyl, alkylene, aryl, alkylaryl, arylalkyl, monocycloalkyl, polycycloalkyl, heterocyclic and carbocyclin groups; Z is an anion; i is an integer from 0 to 6; j, j' and j" are each independently 0 or 1; k 1 , k 2 , k 3 , k 4 , k 5 and k 6 are each independently 0 or 1; n, n' and n" are each independently the integer 1 or 2; n 1 , n 2 , n 3 , n 4 , n 5 , n 6 , are independently 0 or 1; and n 7 and n 8 are each an integer from 1 to 6; and n 9 and n 10 are each an integer from 1 to 3. These compounds are capable of reducing technetium to form stable cationic complexes. Radiolabelled such complexes are useful in connection with radiodiagnostic test of myocardial and/or hepatobiliary tissues.
Inventors
- 👤 Vinayakam Subramanyam
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 10:32
CPC Classifications
A; A61; A61Q; A61Q5/00; A61K; A61K51/00; A61K51/02; A61K51/04; C; C07; C07F; C07F9/00; C07F9/02; C07F9/28; C07F9/50; C07F9/5045; C07F9/54; C07F9/5449; A61K2123/00
Claims Analysis
Total Claims: 37
Claim 1
Independent Claim
280 words
A normally solid, hydrophilic compound capable of binding with Tc-99m to form a cationic complex and having a formula selected from: ##STR7## wherein: R, R', R", R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently selected from hydrogen; or substituted or unsubstituted alkyl, alkylene, aryl, alkylaryl, arylalkyl, monocycloalkyl, polycycloalkyl, heterocyclic and carbocyclic group; and R plus R i in formula (A) may be taken together to form a cyclic compound; A, A', A", A 1 , A 2 , A 3 , A 4 , A 5 and A 6 are independently neutral functional elements, each having a free electron pair available for accepting a proton to provide a charged ligand and having the capability of complexing with Tc-99m to form a cationic complex; Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 are each independently selected from hydrogen; or substituted or unsubstituted alkyl, alkylene, aryl, alkylaryl, arylalkyl, monocycloalkyl, polycycloalkyl, heterocyclic and carbocyclic groups; Z is an anion; i is an integer from 0 to 6; j, j' and j" are each independently 0 or 1; k 1 , k 2 , k 3 , k 4 , k 5 and k 6 are each independently 0 or 1; n, n' and n" are each independently the integer 1 or 2; n 1 , n 2 , n 3 , n 4 , n 5 , n 6 , are independently 0 or 1; n 7 and n 8 are each an integer from 1 to 6; and n 9 and n 10 are each an integer from 1 to 3.
Claim 2
Dependent Claim
280 words
A normally solid, hydrophilic compound capable of binding with Tc-99m to form a cationic complex and having a formula selected from: ##STR7## wherein: R, R', R", R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently selected from hydrogen; or substituted or unsubstituted alkyl, alkylene, aryl, alkylaryl, arylalkyl, monocycloalkyl, polycycloalkyl, heterocyclic and carbocyclic group; and R plus R i in formula (A) may be taken together to form a cyclic compound; A, A', A", A 1 , A 2 , A 3 , A 4 , A 5 and A 6 are independently neutral functional elements, each having a free electron pair available for accepting a proton to provide a charged ligand and having the capability of complexing with Tc-99m to form a cationic complex; Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 are each independently selected from hydrogen; or substituted or unsubstituted alkyl, alkylene, aryl, alkylaryl, arylalkyl, monocycloalkyl, polycycloalkyl, heterocyclic and carbocyclic groups; Z is an anion; i is an integer from 0 to 6; j, j' and j" are each independently 0 or 1; k 1 , k 2 , k 3 , k 4 , k 5 and k 6 are each independently 0 or 1; n, n' and n" are each independently the integer 1 or 2; n 1 , n 2 , n 3 , n 4 , n 5 , n 6 , are independently 0 or 1; n 7 and n 8 are each an integer from 1 to 6; and n 9 and n 10 are each an integer from 1 to 3.
Claim 3
Dependent Claim
18 words
An essentially aqueous solution of a cationic complex formed by complexing said compound of claim 1 with technetium.
Claim 4
Dependent Claim
31 words
An essentially aqueous solution of a cationic complex formed by complexing said compound of claim 1 with technetium in the presence of a halide or other suitable complex formation assisting anion.
Claim 5
Dependent Claim
9 words
An aqueous solution comprising the compound of claim 1.
Claim 6
Dependent Claim
36 words
The compound of claim 1 having the formula: R(AH.sub.j R'.sub.n').sub.n.sup.+n.n"Z wherein R is ethyl or phenyl, A is phosporous or arsenic, and R' is a lower alkyl group having from 1 to about 6 carbon atoms.
Claim 7
Dependent Claim
12 words
The compound of claim 5 wherein Z is bisulfate, biphosphate, or tetrafluoroborate.
Claim 8
Dependent Claim
21 words
The compound of claim 1 wherein Z is derived from sulfuric acid, phosphoric acid, perchloric acid, nitric acid or boric acid.
Claim 9
Dependent Claim
23 words
The compound of claim 1 wherein A is selected from the group consisting of P, As, N, O, S, Sb, Se and Te.
Claim 10
Dependent Claim
35 words
The compound of claim 1 having the formula: ##STR8## wherein A is P or As; and each R is independently H, a lower alkyl group having from 1 to about 6 carbon atoms, or phenyl.
Claim 11
Dependent Claim
14 words
The compound of claim 9 wherein Z is bisulfate, biphosphate, nitrate, tetrafluoroborate or perchlorate.
Claim 12
Dependent Claim
18 words
An essentially aqueous solution of a cationic complex formed by complexing the compound of claim 9 with technetium.
Claim 13
Dependent Claim
31 words
An essentially aqueous solution of a cationic complex formed by complexing the compound of claim 9 with technetium in the presence of a halide or other suitable complex formation assisting anion.
Claim 14
Dependent Claim
9 words
The compound of claim 9 wherein A is phosphorus.
Claim 15
Dependent Claim
15 words
The compound of claim 9 wherein A is phosphorous and R is methyl or ethyl.
Claim 16
Dependent Claim
9 words
The compound of claim 9 having the formula: ##STR9##
Claim 17
Dependent Claim
34 words
The compound of claim 1 having the formula: ##STR10## wherein A is P or As; and each R is independently H, or a lower alkyl group having from 1 to about 6 carbon atoms.
Claim 18
Dependent Claim
14 words
The compound of claim 16 wherein Z is bisulfate, biphosphate, nitrate, tetrafluoroborate or perchlorate.
Claim 19
Dependent Claim
21 words
An essentially aqueous solution of a cationic complex formed by complexing the compound of claim 15 or claim 16 with technetium.
Claim 20
Dependent Claim
34 words
An essentially aqueous solution of a cationic complex formed by complexing the compound of claim 15 or claim 16 with technetium in the presence of a halide or other suitable complex formation assisting anion.
Claim 21
Dependent Claim
9 words
The compound of claim 16 wherein A is phosphorous.
Claim 22
Dependent Claim
15 words
The compound of claim 16 wherein A is phosphorus and R is methyl or ethyl.
Claim 23
Dependent Claim
9 words
The compound of claim 16 having the formula: ##STR11##
Claim 24
Dependent Claim
33 words
A kit for preparing a radiopharmaceutical preparation comprising a sealed, sterilized vial containing the compound of claim 1, 5, 6, 7, 8, 9, 10, 13, 14, 15, 16, 17, 20, 21, or 22.
Claim 25
Dependent Claim
19 words
The kit of claim 23 wherein said vial further contains a halide or other suitable complex formation assisting anion.
Claim 26
Dependent Claim
50 words
A method for making a cationic complex comprising Tc-99m for radioscintigraphic imaging, said method comprising admixing the compound of claim 1 with an essentially aqueous solution containing Tc-99m in the presence of a halide or other suitable complex formation assisting anion and heating the admixture to form a stable complex.
Claim 27
Dependent Claim
15 words
The method of claim 25 carried out under aseptic conditions and in a closed system.
Claim 28
Dependent Claim
24 words
The method of claim 26 wherein said compound is contained in a sterile, sealed vial and said solution is aseptically added to said vial.
Claim 29
Dependent Claim
36 words
The method of claim 25 wherein said compound is a solid, water-soluble salt of bis-1,2-(dimethylphosphino)ethane or o-phenylenebis(dimethylarsine), the halide is bromide or chloride, and the 99m Tc-containing solution comprises a physiological saline solution of 99m Tc-pertechnetate.
Claim 30
Dependent Claim
14 words
The method of claim 25 wherein said solution is substantially free of organic solvents.
Claim 31
Dependent Claim
14 words
The method of claim 25 wherein said solution further comprises ethanol or propylene glycol.
Claim 32
Dependent Claim
19 words
The method of claim 25 wherein said heating step is carried out at a temperature greater than 80° C.
Claim 33
Dependent Claim
19 words
The method of claim 25 wherein said heating step is carried out at a temperature greater than 100° C.
Claim 34
Dependent Claim
40 words
A method for visualizing the heart or the hepatobiliary system of a mammal by radioscintigraphy, and method comprising injecting into the mammal the cationic complex formed by the method of claim 25, and scanning the mammal using radioscintigraphic imaging apparatus.
Claim 35
Dependent Claim
26 words
The method of claim 25 wherein the pH is maintained in the range of from about 1.0 to about 3.0 during the admixing and heating steps.
Claim 36
Dependent Claim
24 words
The method of claim 25 wherein the pH is maintained in the range of from about 1.0 to about 3.0 during the heating step.
Claim 37
Dependent Claim
39 words
The method of claim 34 or claim 35 further comprising the step of adjusting the pH into the range of about 4.0 to about 9.0, injecting said complex into a mammal, and scanning the mammal using radioscintigraphic imaging apparatus.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-05-29 | 1987-11-28 | 1988-05-29 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-05-29 | 1991-11-28 | 1992-05-29 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-05-29 | 1995-11-28 | 1996-05-29 | $7700.00 | Window Closed / Lapsed |