US4337240A
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Denatured albumin complexes for radioscintigraphic imaging and evaluation of reticuloendothelial systems
Assignee: Bristol Myers Squibb Pharma Co
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Filing: 1979-03-07
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Granted: 1982-06-29
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Expires: 1999-03-07
Abstract
Abstract Small sized material (less than 0.2 mu m, preferably less than 0.1 mu m) comprising a complex of (1) denatured albumin, particularly human serum albumin and (2) a metal reducing agent, particularly a stannous reducing agent, preferably formed in the presence of a stabilizing ligand, which complex, when labelled with technetium-99m provides an excellent agent for imaging or otherwise evaluating reticuloendothelial systems (RES) and/or components thereof, particularly the bone marrow, liver and/or lymphatic system; methods of making and using the same; a complex (physical or chemical) of technetium-99m with such materials and methods of using such latter complex.
Inventors
- 👤 Eugene L. Saklad
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 12:37
CPC Classifications
A; A61; A61K; A61K51/00; A61K51/12; A61K51/1217; A61K51/02; A61K51/04; A61K51/08; A61K51/081; A61K51/1241; A61K51/1255; A61K2123/00
Claims Analysis
Total Claims: 67
Claim 1
Independent Claim
36 words
A composition for labelling with 99m Tc for radioactive imaging comprising complexes of denatured albumin and a reducing metal, at least a major portion of which having a particle size of less than about 0.2 μm.
Claim 2
Dependent Claim
36 words
A composition for labelling with 99m Tc for radioactive imaging comprising complexes of denatured albumin and a reducing metal, at least a major portion of which having a particle size of less than about 0.2 μm.
Claim 3
Dependent Claim
18 words
A composition according to claim 1, said composition also comprising an additional stabilizing ligand for said reducing metal.
Claim 4
Dependent Claim
26 words
A composition according to claim 2, said ligand being selected from the group consisting of a phosphonate, a phosphate, an aminocarboxylate, a polyhydroxycarboxylate and a polycarboxylate.
Claim 5
Dependent Claim
14 words
A composition according to claim 3, said reducing metal comprising a stannous reducing metal.
Claim 6
Dependent Claim
22 words
A composition according to claim 2, at least 90% of said complexes being not greater than about 0.1 μm in particle size.
Claim 7
Dependent Claim
21 words
A composition according to claim 5, at least 90% of said complexes being about 0.004 to 0.1 μm in particle size.
Claim 8
Dependent Claim
21 words
A composition according to claim 5, at least 85% of said complexes being about 0.01 to 0.08 μm in particle size.
Claim 9
Dependent Claim
20 words
A composition according to claim 7, said reducing metal comprising a stannous reducing metal and said ligand being a diphosphonate.
Claim 10
Dependent Claim
11 words
A composition according to claim 2, said ligand being a diphosphonate.
Claim 11
Dependent Claim
21 words
A composition according to claim 2, said albumin being human serum albumin and said reducing metal being a stannous reducing metal.
Claim 12
Dependent Claim
13 words
A composition according to claim 10 stabilized with undenatured albumin and a buffer.
Claim 13
Dependent Claim
11 words
A composition according to claim 11 further comprising a non-ionic surfactant.
Claim 14
Dependent Claim
16 words
A composition according to claim 10, said composition being in the form of a freeze-dried solid.
Claim 15
Dependent Claim
37 words
A composition according to claim 10, said albumin having been denatured by application of heat at a pH differing from the apparent isoelectric point of said albumin in said composition by about 1.5 to 4 pH units.
Claim 16
Dependent Claim
26 words
A composition according to claim 14, the pH at denaturation differing from the apparent isoelectric point of said albumin by about 2 to 3.5 pH units.
Claim 17
Dependent Claim
15 words
A composition according to claim 14, said albumin having been denatured at about 80°-100° C.
Claim 18
Dependent Claim
23 words
A composition according to claim 10, said albumin having been denatured by application of heat at a pH of about 6.5 to 11.
Claim 19
Dependent Claim
27 words
A composition according to claim 17, said albumin having been denatured at a pH of about 7.5 to 9.5, and at a temperature of about 80°-100° C.
Claim 20
Dependent Claim
49 words
A composition according to claim 1, said albumin being human serum albumin, said reducing metal being a stannous reducing metal, said composition being stabilized with undenatured human serum albumin and a buffer, said complexes being denatured at a pH of about 7.5 to 9.5, and said composition being freeze-dried.
Claim 21
Dependent Claim
33 words
A radioactive imaging agent comprising 99m Tc-labelled complexes of denatured albumin and a reducing metal, at least a major portion of said complexes having a particle size of less than about 0.2 μm.
Claim 22
Dependent Claim
33 words
A radioactive imaging agent comprising 99m Tc-labelled complexes of denatured albumin and a reducing metal, at least a major portion of said complexes having a particle size of less than about 0.2 μm.
Claim 23
Dependent Claim
15 words
An agent according to claim 20 further comprising a stabilizing ligand for said reducing metal.
Claim 24
Dependent Claim
36 words
An agent according to claim 21 said albumin being human serum albumin, said reducing metal comprising a stannous reducing metal, and said ligand being selected from the group consisting of phosphonates, phosphates, aminocarboxylates, polyhydroxycarboxylates and polycarboxylates.
Claim 25
Dependent Claim
11 words
An agent according to claim 21, said ligand being a diphosphonate.
Claim 26
Dependent Claim
11 words
An agent according to claim 23, said ligand being hydroxyethylene diphosphonate.
Claim 27
Dependent Claim
11 words
An agent according to claim 23, said ligand being methylene diphosphonate.
Claim 28
Dependent Claim
21 words
An agent according to claim 21, at least 90% of said microaggregates having a particle size not greater than 0.2 μm.
Claim 29
Dependent Claim
23 words
An agent according to claim 26, at least about 85% of said complexes having a particle size of about 0.01 to 0.08 μm.
Claim 30
Dependent Claim
14 words
An agent according to claim 21, further comprising undenatured albumin, a buffer and surfactant.
Claim 31
Dependent Claim
37 words
An agent according to claim 20, said albumin being human serum albumin, said reducing metal being a stannous, reducing metal, at least 90% of said complexes having a particle size of between about 0.01 and 0.08 μm.
Claim 32
Dependent Claim
41 words
An agent according to claim 20, stabilized with undenatured human serum albumin and a buffer, said complexes being denatured at a pH differing from the apparent isoelectric point of the albumin in the composition by about 1.5 to 4 pH units.
Claim 33
Dependent Claim
16 words
An agent according to claim 30, said pH at denaturation being between about 7.5 and 9.5.
Claim 34
Dependent Claim
16 words
An agent according to claim 30, said pH at denaturation being between about 1.0 and 4.5
Claim 35
Independent Claim
50 words
A method for making an agent for labelling with 99m Tc for radioactive imaging, said method comprising denaturing albumin in the presence of a reducing metal to form reducing metal/denatured albumin complexes, at least the major part of said complexes having a particle size of less than about 0.2 μm.
Claim 36
Independent Claim
50 words
A method for making an agent for labelling with 99m Tc for radioactive imaging, said method comprising denaturing albumin in the presence of a reducing metal to form reducing metal/denatured albumin complexes, at least the major part of said complexes having a particle size of less than about 0.2 μm.
Claim 37
Dependent Claim
22 words
A method according to claim 33, said denaturation being carried out in the presence of a stabilizing ligand for said reducing metal.
Claim 38
Dependent Claim
39 words
A method according to claim 34, said albumin being human serum albumin, said reducing metal being Sn ++ and said ligand being selected from the group consisting of a phosphonate, a phosphate, an aminocarboxylate, a polyhydroxycarboxylate and a polycarboxylate.
Claim 39
Dependent Claim
29 words
A method according to claim 35, said denaturation being carried out at a pH at which at least about 85% have a particle size between 0.01 and 0.08 μm.
Claim 40
Dependent Claim
31 words
A method according to claim 34, said denaturation being carried out at a pH at which at least 90% of the complexes have a particle size not greater than 0.2 μm.
Claim 41
Dependent Claim
34 words
A method according to claim 37, said denaturation being carried out at a pH which differs from the apparent isoelectric point of the albumin in the composition by about 1.5 to 4 pH units.
Claim 42
Dependent Claim
26 words
A method according to claim 38, said denaturation being carried out at a pH on the alkaline side of the apparent isoelectric point of said albumin.
Claim 43
Dependent Claim
23 words
A method according to claim 38, said denaturation being carried out on the acid side of the apparent isoelectric point of said albumin.
Claim 44
Dependent Claim
11 words
A method according to claim 34, said ligand being a diphosphonate.
Claim 45
Dependent Claim
11 words
A method according to claim 41, said ligand being hydroxyethylene diphosphonate.
Claim 46
Dependent Claim
11 words
A method according to claim 41, said ligand being methylene diphosphonate.
Claim 47
Dependent Claim
68 words
A method according to claim 43, said denaturation being carried out by heating at a pH of between about 7.5 and 9.5, at which at least 90% of the complexes have a particle size not greater than 0.2 μm and at least 85% have a particle size between about 0.01 and 0.08 μm, said reducing metal being a stannous reducing metal, and said albumin being human serum albumin.
Claim 48
Dependent Claim
21 words
A method according to claim 33, said denaturation being carried out by heating albumin and said reducing metal by microwave heating.
Claim 49
Dependent Claim
21 words
A method according to claim 33, said denaturation being carried out by heating albumin and said reducing metal by induction heating.
Claim 50
Independent Claim
57 words
A method of evaluating at least one element of the reticuloendothelial system of a primate, comprising injecting into the primate a composition comprising 99m Tc labelled reducing metal/denatured albumin complexes at least a major portion of which have a particle size of less than about 0.2 μm, to concentrate said 99m Tc-labelled complexes in the reticuloendothelial system.
Claim 51
Independent Claim
57 words
A method of evaluating at least one element of the reticuloendothelial system of a primate, comprising injecting into the primate a composition comprising 99m Tc labelled reducing metal/denatured albumin complexes at least a major portion of which have a particle size of less than about 0.2 μm, to concentrate said 99m Tc-labelled complexes in the reticuloendothelial system.
Claim 52
Dependent Claim
17 words
A method according to claim 47, said composition further comprising a stabilizing ligand for said reducing metal.
Claim 53
Dependent Claim
20 words
A method according to claim 48, said reducing metal being a stannous reducing metal and said ligand being a diphosphonate.
Claim 54
Dependent Claim
38 words
A method according to claim 47, at least 90% of said complexes having a particle size not greater than 0.1 μm and at least a majority of said complexes having a particle size between 0.01 and 0.08 μm.
Claim 55
Independent Claim
33 words
A method of imaging bone marrow in a primate, comprising injecting into the primate a composition comprising 99m Tc-labelled reducing agent/denatured albumin complexes to concentrate said 99m Tc-labelled complexes in the bone marrow.
Claim 56
Independent Claim
33 words
A method of imaging bone marrow in a primate, comprising injecting into the primate a composition comprising 99m Tc-labelled reducing agent/denatured albumin complexes to concentrate said 99m Tc-labelled complexes in the bone marrow.
Claim 57
Dependent Claim
36 words
The method of claim 51, wherein at least 90% of the labelled reducing agent/denatured albumin complexes have a particle size below about 0.2 μm, and the composition further comprises a stabilizing ligand for said reducing agent.
Claim 58
Dependent Claim
45 words
The method of claim 52, wherein the reducing agent is stannous, the denatured albumin is denatured human serum albumin, the stabilizing ligand is a diphosphonate, and at least 85% of the reducing agent/denatured albumin has a particle size of between about 0.01 and 0.08 μm.
Claim 59
Independent Claim
43 words
A method of imaging at least one component of the lymphatic system in a mammal, comprising injecting into the mammal a composition comprising 99m Tc-labelled reducing agent/denatured albumin complexes to concentrate said 99m Tc-labelled complexes in the aforementioned components of the lymphatic system.
Claim 60
Independent Claim
43 words
A method of imaging at least one component of the lymphatic system in a mammal, comprising injecting into the mammal a composition comprising 99m Tc-labelled reducing agent/denatured albumin complexes to concentrate said 99m Tc-labelled complexes in the aforementioned components of the lymphatic system.
Claim 61
Dependent Claim
36 words
The method of claim 54, wherein at least 90% of the labelled reducing agent/denatured albumin complexes have a particle size below about 0.2 μm, and the composition further comprises a stabilizing ligand for said reducing metal.
Claim 62
Dependent Claim
45 words
The method of claim 55, wherein the reducing agent is stannous, the denatured albumin is denatured human serum albumin, the stabilizing ligand is a diphosphonate, and at least 85% of the reducing agent/denatured albumin has a particle size of between about 0.01 and 0.08 μm.
Claim 63
Independent Claim
48 words
A method of evaluating the rate of clearance of particulate material from the blood of a mammal, comprising injecting into the mammal a composition comprising 99m Tc-labelled reducing agent/denatured albumin complexes, and measuring the rate of clearance of said complexes from said blood over a period of time.
Claim 64
Independent Claim
48 words
A method of evaluating the rate of clearance of particulate material from the blood of a mammal, comprising injecting into the mammal a composition comprising 99m Tc-labelled reducing agent/denatured albumin complexes, and measuring the rate of clearance of said complexes from said blood over a period of time.
Claim 65
Dependent Claim
36 words
The method of claim 57, wherein at least 90% of the labelled reducing agent/denatured albumin complexes have a particle size below about 0.2 μm, and the composition further comprises a stabilizing ligand for said reducing metal.
Claim 66
Dependent Claim
45 words
The method of claim 58, wherein the reducing agent is stannous, the denatured albumin is denatured human serum albumin, the stabilizing ligand is a diphosphonate, and at least 85% of the reducing agent/denatured albumin has a particle size of between about 0.01 and 0.08 μm.
Claim 67
Dependent Claim
19 words
A composition according to claim 1, said albumin having been denatured at a pH between about 1.0 and 4.5.
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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) | 1985-06-28 | 1985-12-28 | 1986-06-29 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1989-06-28 | 1989-12-28 | 1990-06-29 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1993-06-28 | 1993-12-28 | 1994-06-29 | $7700.00 | Window Closed / Lapsed |