US4889525A
Expired / Lapsed
US
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Sensitization of hypoxic tumor cells and control of growth thereof
Assignee: Adamantech Inc
•
Filing: 1988-01-11
•
Granted: 1989-12-26
•
Expires: 2008-01-11
Abstract
Abstract Method of sensitizing hypoxic tumor cells to radiotherapy and chemotherapy by contacting the cells or the vasculature thereof with an aqueous dispersion of an oxygen carrying perfluoro compound and a dispersant for the compound, and sensitizing chemotherapeutic and protective compositions therefor.
Inventors
- 👤 John M. Yuhas
- 👤 Robert L. Goodman
- 👤 Robert E. Moore
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 19:01
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0019; A61K9/0026; A61M; A61M2202/00; A61M2202/04; A61M2202/0468; A61M2202/0476
Claims Analysis
Total Claims: 79
Claim 1
Independent Claim
44 words
A method of controlling the growth of hypoxic tumor cells which comprises (a) sensitizing the cells to radiotherapy by contacting the cells with an aqueous dispersion of an oxygen carrying perfluoro compound and a dispersant for the perfluoro compound, and (b) irradiating the cells.
Claim 2
Independent Claim
44 words
A method of controlling the growth of hypoxic tumor cells which comprises (a) sensitizing the cells to radiotherapy by contacting the cells with an aqueous dispersion of an oxygen carrying perfluoro compound and a dispersant for the perfluoro compound, and (b) irradiating the cells.
Claim 3
Independent Claim
53 words
A method of controlling the growth of hypoxic tumor cells which comprises (a) sensitizing the cells to chemotherapy by contacting the cells with an aqueous dispersion of any oxygen carrying perfluoro compound and a dispersant for the perfluoro compound, and (b) contacting the cells with a chemotherapeutic agent whose efficacy is oxygen dependent.
Claim 4
Independent Claim
53 words
A method of controlling the growth of hypoxic tumor cells which comprises (a) sensitizing the cells to chemotherapy by contacting the cells with an aqueous dispersion of any oxygen carrying perfluoro compound and a dispersant for the perfluoro compound, and (b) contacting the cells with a chemotherapeutic agent whose efficacy is oxygen dependent.
Claim 5
Independent Claim
59 words
A method of controlling the growth of hypoxic tumor cells which comprises (a) sensitizing the cells to radiotherapy and chemotherapy by contacting the cells with an aqueous dispersion of an oxygen carrying perfluoro compound and a dispersant for the perfluoro compound, and (b) irradiating the cells and contacting the cells with a chemotherapeutic agent whose efficacy is oxygen dependent.
Claim 6
Independent Claim
59 words
A method of controlling the growth of hypoxic tumor cells which comprises (a) sensitizing the cells to radiotherapy and chemotherapy by contacting the cells with an aqueous dispersion of an oxygen carrying perfluoro compound and a dispersant for the perfluoro compound, and (b) irradiating the cells and contacting the cells with a chemotherapeutic agent whose efficacy is oxygen dependent.
Claim 7
Independent Claim
47 words
A method of controlling the growth of hypoxic tumor cells which comprises (a) sensitizing the cells to radiotherapy by contacting the vasculature of the tumor with an aqueous dispersion of any oxygen carrying perfluoro compound and a dispersant for the perfluoro compound, and (b) irradiating the cells.
Claim 8
Independent Claim
47 words
A method of controlling the growth of hypoxic tumor cells which comprises (a) sensitizing the cells to radiotherapy by contacting the vasculature of the tumor with an aqueous dispersion of any oxygen carrying perfluoro compound and a dispersant for the perfluoro compound, and (b) irradiating the cells.
Claim 9
Independent Claim
56 words
A method of controlling the growth of hypoxic tumor cells which comprises (a) sensitizing the cells to chemotherapy by contacting the vasculature of the tumor with an aqueous dispersion of any oxygen carrying perfluoro compound and a dispersant for the perfluoro compound, and (b) contacting the cells with a chemotherapeutic agent whose efficacy is oxygen dependent.
Claim 10
Independent Claim
56 words
A method of controlling the growth of hypoxic tumor cells which comprises (a) sensitizing the cells to chemotherapy by contacting the vasculature of the tumor with an aqueous dispersion of any oxygen carrying perfluoro compound and a dispersant for the perfluoro compound, and (b) contacting the cells with a chemotherapeutic agent whose efficacy is oxygen dependent.
Claim 11
Independent Claim
62 words
A method of controlling the growth of hypoxic tumor cells which comprises (a) sensitizing the cells to radiotherapy and chemotherapy by contacting the vasculature of the tumor with an aqueous dispersion of an oxygen carrying perfluoro compound and a dispersant for the perfluoro compound, and (b) irradiating the cells and contacting the cells with a chemotherapeutic agent whose efficacy is oxygen dependent.
Claim 12
Independent Claim
62 words
A method of controlling the growth of hypoxic tumor cells which comprises (a) sensitizing the cells to radiotherapy and chemotherapy by contacting the vasculature of the tumor with an aqueous dispersion of an oxygen carrying perfluoro compound and a dispersant for the perfluoro compound, and (b) irradiating the cells and contacting the cells with a chemotherapeutic agent whose efficacy is oxygen dependent.
Claim 13
Dependent Claim
17 words
The method of claim 1, 2, or 3 wherein the cells are embodied in a solid tumor.
Claim 14
Independent Claim
17 words
The method of claims 4, 5, or 6 wherein the vasculature is embodied in a solid tumor.
Claim 15
Independent Claim
39 words
The method of claims 1, 2, or 3 wherein, in step (a), oxygen in excess of that normally available from the blood is supplied to the cells, and the oxygen supplied by the perfluoro compound supplements said excess oxygen.
Claim 16
Independent Claim
39 words
The method of claims 4, 5, or 6 wherein, in step (a), oxygen in excess of that normally available from the blood is supplied to the vasculature, and the oxygen supplied by the perfluoro compound supplements said excess oxygen.
Claim 17
Independent Claim
24 words
The method of claims 1, 2, or 3 wherein the cells are in an animal host and the perfluoro compound is oxygenated in vivo.
Claim 18
Independent Claim
24 words
The method of claims 4, 5, or 6 wherein the vasculature is in an animal host and the perfluoro compound is oxygenated in vivo.
Claim 19
Independent Claim
28 words
The method of claims 1, 2, or 3 wherein the cells are in an animal host and contact with the dispersion is by systemic administration to the host.
Claim 20
Independent Claim
28 words
The method of claims 4, 5, or 6 wherein the vasculature is in an animal host and contact with the dispersion is by systemic administration to the host.
Claim 21
Independent Claim
28 words
The method of claims 1, 2, or 3 wherein the cells are in an animal host and contact with the dispersion is by topical administration to the host.
Claim 22
Independent Claim
28 words
The method of claims 4, 5, or 6 wherein the vasculature is in an animal host and contact with the dispersion is by topical administration to the host.
Claim 23
Independent Claim
19 words
The method of any of claims 1-6 wherein the perfluoro compound is oxygenated prior to administration of the dispersion.
Claim 24
Independent Claim
17 words
The method of any of claims 1-6 wherein the dispersion is introduced directly into the blood stream.
Claim 25
Dependent Claim
21 words
The method of claim 18 wherein the fluorocrit of the perfluoro compound in the blood stream is at least about 3%.
Claim 26
Independent Claim
16 words
The method of any of claims 1-6 wherein the dispersion is introduced into the digestive system.
Claim 27
Independent Claim
21 words
The method of claims 1, 2, or 3 wherein, in step (a), the cells are contacted in vitro with the dispersion.
Claim 28
Independent Claim
16 words
The method of any of claims 1-6 wherein the perfluoro compound is a perfluorinated cyclic hydrocarbon.
Claim 29
Dependent Claim
31 words
The method of claim 22 wherein the perfluorinated cyclic hydrocarbon is non-aromatizable, polycyclic, and contains at least two bridgehead carbon atoms linked through a bridge containing at least one carbon atom.
Claim 30
Independent Claim
14 words
The method of any of claims 1-6 wherein the dispersant is a nonionic surfactant.
Claim 31
Dependent Claim
23 words
The method of claim 24 wherein the dispersant is a condensate of ethylene oxide and an adduct of propylene oxide and propylene glycol.
Claim 32
Independent Claim
15 words
The method of any of claims 1-6 wherein the dispersant is a fluorinated amidoamine oxide.
Claim 33
Independent Claim
34 words
The method of any of claims 1-6 wherein the perfluoro compound is a perfluorinated polycyclic hydrocarbon and the dispersant is a condensate of ethylene oxide and an adduct of propylene oxide and propylene glycol.
Claim 34
Independent Claim
24 words
The method of any of claims 1-6 wherein the perfluoro compound is a perfluorinated polycyclic hydrocarbon and the dispersant is a fluorinated amidoamine oxide.
Claim 35
Independent Claim
33 words
The method of any of claims 1-6 wherein the perfluoro compound component comprises a mixture of F-trimethylbicyclo [3.3.1] nonane and dimethyladamantane, and the dispersant is a fluorinated amidoamine oxide of the structure: ##STR7##
Claim 36
Independent Claim
31 words
The method of claims any of 1-6 wherein the perfluoro compound is F-tributylamine and the dispersant is a condensate of ethylene oxide and an adduct of propylene oxide and propylene glycol.
Claim 37
Independent Claim
19 words
The method of claims 1, 3, 4 or 6 wherein the irradiated cells comprise neuroblastoma human tumor line cells.
Claim 38
Independent Claim
19 words
The method of claims 1, 3, 4 or 6 wherein the irradiated cells comprise melanoma human tumor line cells.
Claim 39
Independent Claim
23 words
The method of any of claims 1-6 wherein the cells are perfused with a radiopaque agent to monitor the sensitization and growth control.
Claim 40
Dependent Claim
12 words
The method of claim 33 wherein the radiopaque agent is F-1-bromobutylisopropyl ether.
Claim 41
Independent Claim
44 words
The method of any of claims 1-6 wherein normal tissues in the vicinity of the hypoxic tumor cells are contacted, prior to or simultaneously with step (b), with a protective agent selected from a radioprotective agent, a chemotherapeutic protective agent and a mixture thereof.
Claim 42
Dependent Claim
13 words
The method of claim 35 wherein the radioprotective agent is S-2-(3-aminopropylamino) ethylphosphorothioic acid.
Claim 43
Independent Claim
19 words
The method of claims 2, 3, 5 or 6 wherein the chemotherapeutic agent used in the treatment is methotrexate.
Claim 44
Independent Claim
19 words
The method of claims 2, 3, 5 or 6 wherein the chemotherapeutic agent used in the treatment is cyclophosphamide.
Claim 45
Dependent Claim
11 words
The method of claim 22 wherein said perfluorocarbon is perfluorinated methyladamantane.
Claim 46
Dependent Claim
11 words
The method of claim 22 wherein said perfluorocarbon is perfluorinated decalin.
Claim 47
Dependent Claim
12 words
The method of claim 22 wherein said perfluorocarbon is perfluorinated 1-methyl octahydroquinolizine.
Claim 48
Dependent Claim
11 words
The method of claim 24 wherein said dispersant is a phospholipid.
Claim 49
Dependent Claim
20 words
Method according to claim 1 or 4 wherein the method is carried out in the absence of a chemotherapeutic agent.
Claim 50
Dependent Claim
14 words
The method of claim 43 wherein the cells are embodied in a solid tumor.
Claim 51
Dependent Claim
14 words
The method of claim 43 wherein the vasculature is embodied in a solid tumor.
Claim 52
Dependent Claim
36 words
The method of claim 43 wherein, in step (a), oxygen in excess of that normally available from the blood is supplied to the cells, and the oxygen supplied by the perfluoro compound supplements said excess oxygen.
Claim 53
Dependent Claim
36 words
The method of claim 43 wherein, in step (a), oxygen in excess of that normally available from the blood is supplied to the vasculature, and the oxygen supplied by the perfluoro compound supplements said excess oxygen.
Claim 54
Dependent Claim
20 words
The method of claim 43 wherein the cells are in an animal host and theperfluoro compound is oxygenated in vivo.
Claim 55
Dependent Claim
21 words
The method of claim 43 wherein the vasculature is in an animal host and the perfluoro compound is oxygenated in vivo.
Claim 56
Dependent Claim
25 words
The method of claim 43 wherein the cells are in an animal host and contact with the dispersion is by systemic administration to the host.
Claim 57
Dependent Claim
25 words
The method of claim 43 wherein the vasculature is in an animal host and contact with the dispersion is by systemic administration to the host.
Claim 58
Dependent Claim
25 words
The method of claim 43 wherein the cells are in an animal host and contact with the dispersion is by topical administration to the host.
Claim 59
Dependent Claim
25 words
The method of claim 43 wherein the vasculature is in an animal host and contact with the dispersion is by topical administration to the host.
Claim 60
Dependent Claim
17 words
The method of claim 43 wherein the perfluoro compound is oxygenated prior to administration of the dispersion.
Claim 61
Dependent Claim
15 words
The method of claim 43 wherein the dispersion is introduced directly into the blood stream.
Claim 62
Dependent Claim
21 words
The method of claim 55 wherein the fluorocrit of the perfluoro compound in the blood stream is at least about 3%.
Claim 63
Dependent Claim
14 words
The method of claim 43 wherein the dispersion is introduced into the digestive system.
Claim 64
Dependent Claim
18 words
The method of claim 43 wherein, in step (a), the cells are contacted in vitro with the dispersion.
Claim 65
Dependent Claim
12 words
The method of claim 43 wherein the dispersant is a nonionic surfactant.
Claim 66
Dependent Claim
23 words
The method of claim 59 wherein the dispersant is a condensate of ethylene oxide and an adduct of propylene oxide and propylene glycol.
Claim 67
Dependent Claim
29 words
The method of claim 43 wherein the perfluoro compound is F-tributylamine and the dispersant is a condensate of ethylene oxide and an adduct of propylene oxide and propylene glycol.
Claim 68
Dependent Claim
15 words
The method of claim 43 wherein the irradiated cells comprise neuroblastoma human tumor line cells.
Claim 69
Dependent Claim
15 words
The method of claim 43 wherein the irradiated cells comprise melanoma human tumor line cells.
Claim 70
Independent Claim
21 words
The method of cliam 43 wherein the cells are perfused with a radiopaque agent to monitor the sensitization and growth control.
Claim 71
Independent Claim
21 words
The method of cliam 43 wherein the cells are perfused with a radiopaque agent to monitor the sensitization and growth control.
Claim 72
Dependent Claim
12 words
The method of claim 64 where the radiopaque agent is F-1-bromobutylisopropyl ether.
Claim 73
Dependent Claim
29 words
The method of claim 43 wherein normal tissues in the vicinity of the hypoxic tumor cells are contacted, prior to or simultaneously with step (b), with a radioprotective agent.
Claim 74
Dependent Claim
13 words
The method of claim 66 wherein the radioprotective agent is S-2-(3-aminopropylamino) ethylphosphorothioic acid.
Claim 75
Independent Claim
34 words
The method of claims 2, 3, 5 or 6 wherein normal tissues in the vicinity of the hypoxic tumor cells are contacted, prior to or simultaneously with step (b), with a chemotherapeutic protective agent.
Claim 76
Independent Claim
16 words
The method of any of claims 1, 6 wherein the perfluoro compound is a nitrogen-free perfluorocarbon.
Claim 77
Dependent Claim
13 words
Method according to claim 69 wherein the perfluoro compound is a perfluorinated hydrocarbon.
Claim 78
Dependent Claim
19 words
Method according to claim 69 wherein the fluorine atoms of the perfluoro compound are substituted with other halogen atoms.
Claim 79
Dependent Claim
19 words
Method according to any of claims 1, 6 wherein the perfluoro compound is a hetero nitrogen atom perfluoro compound.
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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) | 1992-12-25 | 1993-06-26 | 1993-12-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-12-25 | 1997-06-26 | 1997-12-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-12-25 | 2001-06-26 | 2001-12-26 | $7700.00 | Window Closed / Lapsed |