US3873680A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Mercaptan and thioketal complexes of technetium 99M for diagnostic scanning
Assignee: 3M Co
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Filing: 1972-08-30
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Granted: 1975-03-25
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Expires: 1992-08-30
Abstract
Abstract Chemical complexes containing a radioactive technetium isotope are liver specific when the complexing agent is a lipophilic mercaptan or thioketal. To permit excretion of the complex from the liver into the bile, the lipophilic mercaptan contains a polar group which moderates this lipophilic property. The complexes can be made by reducing pertechnetate ion and reacting the reduced technetium species with the mercaptan or thioketal. The complexes are normally used in a biologically sterile substantially isotonic aqueous medium.
Inventors
- 👤 Richard A Jackson
- 👤 Theodore F Bolles
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 18:24
CPC Classifications
C; C07; C07C; C07C323/00; A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K2123/00
Claims Analysis
Total Claims: 16
Claim 1
Independent Claim
249 words
A PROCESS FOR MAKING A REACTION PRODUCT WHICH CAN BE LIVER SPECIFIC IN VIO COMPRISING THE STEPS OF: A. REDUCING A SOLUTION COMPRISING AT LEAST 0.01 BUT LESS THAN 500 MILLICURES PER MILLILITER OF 99M-PERTECHNETATE ION UNTIL MORE THAN 50 MOLE % OF SAID 99M-PERTECHNETTATE ION HAS BEEN REDUCED TO A 99M-TECHNETIUM SPIECES HAVING AN OXIDATION STAGE GREATER THAN ZERO BUT LESS THAN +7 B. REACTING SAID 99M-TECHNETIUM SPECIES WITH AN EXCESS, REGARDLESS OF THE STOICHIOMETRY OF THE RESULTING PRODUCT OF A SULFUR-CONTAINING COMPOUND SELECTED FROM THE GROUP CONSISTING OF: A. A LIPOPHILIC COMPOUND OF THE FORMULA HS - CR1R2 -NX WHEREIN R1 AND R2 ARE THE SAME OR DIFFERENT IN EACH REPEATING UNIT AND ARE SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, LOWER ALKYL, AND -SH, N IS AN INTEGER RANGING FROM 1 TO ABOUT 6, AND X IS A MAMMALIAN BLOOD-SOLUBILIZING POLAR GROUP WHICH ONLY PARTIALLY DETRACTS FROM THE LIVER SPECIFIC AND LIPOPHILIC PROPERTIES OF THE SAID RESULTING REACTION PRODUCT; B. A LIPOPHILIC COMPOUND OF THE FORMULA HS - A - X WHERE A IS A CYCLOALIPHATIC OR HETROCYCLIC ALIPHATIC RING AND X IS AS DEFINED PREVIOUSLY; C. A LIPOPHILIC THIOENOL OR THIOKETAL SUBSTITUTED ON THE THIOKETAL- OR THIOENOL-CARBON WITH A WATER SOLUBILIZING GROUP AND, ON THE CARBON TO THE THIOKETAL- OR THIOENOL CARBON WITH A LIPOPHILIC GROUP; AND D. A CARBOCYCLIC OR HETEROCYCLIC AROMATIC CARBOXYLIC, SULFONIC, OR PHOSPHONIC ACID BEARING A MERCAPTO GROUP SUBSTITUTED MORE REMOTELY THAN ORTHO TO THE CARBOXYLIC, SULFONIC OR PHOSPHONIC ACID GROUP.
Claim 2
Dependent Claim
249 words
A PROCESS FOR MAKING A REACTION PRODUCT WHICH CAN BE LIVER SPECIFIC IN VIO COMPRISING THE STEPS OF: A. REDUCING A SOLUTION COMPRISING AT LEAST 0.01 BUT LESS THAN 500 MILLICURES PER MILLILITER OF 99M-PERTECHNETATE ION UNTIL MORE THAN 50 MOLE % OF SAID 99M-PERTECHNETTATE ION HAS BEEN REDUCED TO A 99M-TECHNETIUM SPIECES HAVING AN OXIDATION STAGE GREATER THAN ZERO BUT LESS THAN +7 B. REACTING SAID 99M-TECHNETIUM SPECIES WITH AN EXCESS, REGARDLESS OF THE STOICHIOMETRY OF THE RESULTING PRODUCT OF A SULFUR-CONTAINING COMPOUND SELECTED FROM THE GROUP CONSISTING OF: A. A LIPOPHILIC COMPOUND OF THE FORMULA HS - CR1R2 -NX WHEREIN R1 AND R2 ARE THE SAME OR DIFFERENT IN EACH REPEATING UNIT AND ARE SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, LOWER ALKYL, AND -SH, N IS AN INTEGER RANGING FROM 1 TO ABOUT 6, AND X IS A MAMMALIAN BLOOD-SOLUBILIZING POLAR GROUP WHICH ONLY PARTIALLY DETRACTS FROM THE LIVER SPECIFIC AND LIPOPHILIC PROPERTIES OF THE SAID RESULTING REACTION PRODUCT; B. A LIPOPHILIC COMPOUND OF THE FORMULA HS - A - X WHERE A IS A CYCLOALIPHATIC OR HETROCYCLIC ALIPHATIC RING AND X IS AS DEFINED PREVIOUSLY; C. A LIPOPHILIC THIOENOL OR THIOKETAL SUBSTITUTED ON THE THIOKETAL- OR THIOENOL-CARBON WITH A WATER SOLUBILIZING GROUP AND, ON THE CARBON TO THE THIOKETAL- OR THIOENOL CARBON WITH A LIPOPHILIC GROUP; AND D. A CARBOCYCLIC OR HETEROCYCLIC AROMATIC CARBOXYLIC, SULFONIC, OR PHOSPHONIC ACID BEARING A MERCAPTO GROUP SUBSTITUTED MORE REMOTELY THAN ORTHO TO THE CARBOXYLIC, SULFONIC OR PHOSPHONIC ACID GROUP.
Claim 3
Dependent Claim
29 words
A process according to claim 1 wherein said sulfur-containing compound is itself used to chemically reduce the 99m pertechnetate compound, thereby combining said reducing step and said reacting step.
Claim 4
Dependent Claim
68 words
A process according to claim 1 wherein said sulfur-containing compound is selected from the group consisting of A. HS - CR3R4 -n X wherein R3 and R4 are the same or different and are selected from the group consisting of hydrogen and methyl, n is an integer ranging from 1 to 5, and X is selected from the group consisting of -OH;-NR22, where R2 is hydrogen or methyl;
Claim 5
Dependent Claim
33 words
A process according to claim 3 wherein said sulfur-containing compound is selected from the group consisting of N-acetyl-penicillamine, 2-mercaptoethanol, 3-mercaptopropanol, 4-mercaptobutanol 4-mercapto-2-methyl-2-butanol, 2-mercaptoethylamine, 6,8-dihydrothioctic acid, alpha-thio-2-furan pyruvic acid, p-mercaptobenzoic acid, and mixtures thereof.
Claim 6
Dependent Claim
39 words
A process according to claim 1 wherein said reducing step is carried through the use of a reducing agent selected from the group consisting of a tin (II) salt, an iron (II) salt, a Cu(I)/Cu(II) couple, and combinations thereof.
Claim 7
Dependent Claim
11 words
A process according to claim 2 wherein said process is acid-catalyzed.
Claim 8
Dependent Claim
46 words
A process according to claim 1 wherein said 99m-pertechnetate ion is derived from the dissociation of a salt of the formula M x(TcO4 )x wherein M x is a pharmaceutically acceptable cation having a valence of x, and x is a positive integer less than 4.
Claim 9
Dependent Claim
33 words
A process according to claim 1 wherein 0.1 - 10 ml. of an aqueous solution of the reaction product obtained from step (b) is injected into the blood stream of a living mammal.
Claim 10
Dependent Claim
74 words
A process according to claim 1 wherein X is selected such that the natural logarithm of the partition coefficient of the resulting reaction product, expressed as the natural logarithm of the ratio of the activity in water to the activity in n-octyl alcohol, has the following values: less than 2 at a pH of 5 to 6 less than 5 at a pH of 7, and less than 9 at a pH of 8.
Claim 11
Dependent Claim
32 words
A process according to claim 9 wherein said natural logarithm of said ratio is at least -2 at a pH of 6 and is less than 8 at a pH of 8.
Claim 12
Dependent Claim
36 words
A process according to claim 8 wherein said excess of sulfur-containing compound does not exceed 25% of the LD 50 in rodents and in at least one other species and wherein said solution is substantially isotonic.
Claim 13
Dependent Claim
76 words
A liver specific 99mTc/6,8-dihydrothioctic acid complex, said complex being characterized by the following Rf values determined by thin layer chromatography on a 100 micron-thick, unactivated, neutral pH silica gel chromatogram sheet, wherein the silica gel of said chromatogram sheet is bound together with polyvinyl alcohol: Rf 0, when said chromatogram is developed with anhydrous acetone; Rf 0.66, when said chromatogram developed with a solvent system consisting of ethanol:water:concentrated ammonium hydroxide in the volume/volume/volume ratio of 95:17:16.
Claim 14
Dependent Claim
76 words
A liver specific 99mTc/6,8-dihydrothioctic acid complex, said complex being characterized by the following Rf values determined by thin layer chromatography on a 100 micron-thick, unactivated, neutral pH silica gel chromatogram sheet, wherein the silica gel of said chromatogram sheet is bound together with polyvinyl alcohol: Rf 0, when said chromatogram is developed with anhydrous acetone; Rf 0.66, when said chromatogram developed with a solvent system consisting of ethanol:water:concentrated ammonium hydroxide in the volume/volume/volume ratio of 95:17:16.
Claim 15
Dependent Claim
64 words
A liver specific 99mTc/4-mercaptobutanol complex, said complex being characterized by the following Rf values determined by thin layer chromatography on a 100 micron-thick, unactivated, neutral pH silica gel chromatogram sheet, wherein the silica gel of said chromatoGram sheet is bound together with polyvinyl alcohol: Rf 0, when said chromatogram is developed with anhydrous acetone; Rf 0.69, when said chromatogram is developed with anhydrous methanol.
Claim 16
Dependent Claim
64 words
A liver specific 99mTc/4-mercaptobutanol complex, said complex being characterized by the following Rf values determined by thin layer chromatography on a 100 micron-thick, unactivated, neutral pH silica gel chromatogram sheet, wherein the silica gel of said chromatoGram sheet is bound together with polyvinyl alcohol: Rf 0, when said chromatogram is developed with anhydrous acetone; Rf 0.69, when said chromatogram is developed with anhydrous methanol.
References Cited (Backward Citations)
US3749913A
Cited
US3725295A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1978-03-24 | 1978-09-23 | 1979-03-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1982-03-24 | 1982-09-23 | 1983-03-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1986-03-24 | 1986-09-23 | 1987-03-25 | $7700.00 | Window Closed / Lapsed |