US5088499A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Liposomes as contrast agents for ultrasonic imaging and methods for preparing the same
Assignee: Bristol Myers Squibb Pharma Co
•
Filing: 1990-08-20
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Granted: 1992-02-18
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Expires: 2010-08-20
Abstract
Abstract Liposomes suitable as ultrasound contrast agents which contain media of various types including gases, gaseous precursors activated by pH, temperature or pressure, as well as other solid or liquid contrast enhancing agents, are described. Methods of using the same as ultrasound contrast agents are also disclosed. The present invention also comprises novel methods for synthesizing liposomes having encapsulated therein gases.
Inventors
- 👤 Evan C. Unger
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 02:14
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; A61K9/1277; A61K9/1278; A61K49/00; A61K49/22; A61K49/222; A61K49/223; A61K49/227; Y; Y10; Y10S; Y10S436/00; Y10S436/829
Claims Analysis
Total Claims: 34
Claim 1
Independent Claim
111 words
A method of providing an image of an internal region of a patient comprising: (a) administering to the patient a contrast agent selected from the group consisting of (i) a liposome having encapsulated therein a pH-activated gaseous precursor, said liposome having incorporated therein an ionophore, said ionophore being capable of facilitating the transport of hydrogen or hydroxide ions across the liposome membrane, (ii) a liposome having encapsulated therein a photo-activated gaseous precursor, and (iii) a liposome having encapsulated therein a temperature-activated gaseous precursor; (b) activating the gaseous precursor; and (c) scanning the patient using ultrasonic imaging to obtain enhanced visible images of the region, due to the resulting gas containing liposomes.
Claim 2
Independent Claim
111 words
A method of providing an image of an internal region of a patient comprising: (a) administering to the patient a contrast agent selected from the group consisting of (i) a liposome having encapsulated therein a pH-activated gaseous precursor, said liposome having incorporated therein an ionophore, said ionophore being capable of facilitating the transport of hydrogen or hydroxide ions across the liposome membrane, (ii) a liposome having encapsulated therein a photo-activated gaseous precursor, and (iii) a liposome having encapsulated therein a temperature-activated gaseous precursor; (b) activating the gaseous precursor; and (c) scanning the patient using ultrasonic imaging to obtain enhanced visible images of the region, due to the resulting gas containing liposomes.
Claim 3
Dependent Claim
27 words
The method according to claim 1 wherein said liposomes are administered intravascularly and have a mean outer diameter of between about 30 nanometers and about 2 microns.
Claim 4
Dependent Claim
18 words
The method according to claim 2 wherein the patient is scanned in the area of the patient's heart.
Claim 5
Dependent Claim
21 words
The method according to claim 2 wherein the patient is scanned in the area of the patient's liver, spleen and kidney.
Claim 6
Dependent Claim
28 words
The method according to claim 1 wherein the liposomes are administered other than intravascularly and have a mean outer diameter between about 2 microns and about 10 microns.
Claim 7
Dependent Claim
48 words
The method of claim 1 wherein the liposomes are comprised of lipids of either natural or synthetic origin selected from the group consisting of fatty acids, lysolipids, dipalmitoylphosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, phosphatidylglycerol, phosphatidic acid, phosphatidylinositol, sphingomyelin, lysolipids, cholesterol, cholesterol hemisuccinate, glycosphingolipids, glycolipids, glucolipids, sulphatides, and tocopherol hemisuccinate.
Claim 8
Independent Claim
114 words
A method for diagnosing the presence of diseased tissue in a patient comprising: (a) administering to the patient a contrast agent selected from the group consisting of (i) a liposome having encapsulated therein a pH-activated gaseous precursor, said liposome having incorporated therein an ionophore, said ionophore being capable of facilitating the transport of hydrogen or hydroxide ions across the liposome membrane, (ii) a liposome having encapsulated therein a photo-activated gaseous precursor, and (iii) a liposome having encapsulated therein a temperature-activated gaseous precursor; (b) activating the gaseous precursor; and (c) scanning the patient using ultrasonic imaging to obtain enhanced visible images of any diseased tissue in the patient, due to the resulting gas containing liposomes.
Claim 9
Independent Claim
114 words
A method for diagnosing the presence of diseased tissue in a patient comprising: (a) administering to the patient a contrast agent selected from the group consisting of (i) a liposome having encapsulated therein a pH-activated gaseous precursor, said liposome having incorporated therein an ionophore, said ionophore being capable of facilitating the transport of hydrogen or hydroxide ions across the liposome membrane, (ii) a liposome having encapsulated therein a photo-activated gaseous precursor, and (iii) a liposome having encapsulated therein a temperature-activated gaseous precursor; (b) activating the gaseous precursor; and (c) scanning the patient using ultrasonic imaging to obtain enhanced visible images of any diseased tissue in the patient, due to the resulting gas containing liposomes.
Claim 10
Dependent Claim
44 words
A method according to claim 1 wherein the contrast agent is a liposome having encapsulated therein a pH-activated gaseous precursor, said liposome having incorporated therein an ionophore, said ionophore being capable of facilitating the transport of hydrogen or hydroxide ions across the liposome membrane.
Claim 11
Dependent Claim
25 words
A method according to claim 8 wherein said pH-activated gaseous precursor is selected from the group consisting of metal carbonate salts and metal bicarbonate salts.
Claim 12
Dependent Claim
14 words
A method according to claim 9 wherein said pH-activated gaseous precursor is sodium bicarbonate.
Claim 13
Dependent Claim
64 words
A method according to claim 8 wherein said ionophore in said liposome is selected from the group consisting of carbonylcyanide, p-trifluoromethoxy-phenylhydrazone, carbonylcyanide M-chlorophenylhydrazone, carbonylcyanide phenylhydrazine, tetrachloro-2-trifluoromethyl benzimidazole, 5,6-dichloro-2-trifluoromethyl benzimidazole, Uncoupler 1799, gramicidin, alamethicin, filipin, etruscomycin, nystatin, pimaricin, amphotericin, valinomycin, enniatin, beauvericin, monomycin, nonactin, monactin, dinactin, trinactin, tetranactin, antamanide, nigericin, monensin, salinomycin, narisin, mutalomycin, carriomycin, dianemycin, septamycin, A-204 A, X-206, X-537 A, A-23187 and dicyclohexyl-18-crown-6.
Claim 14
Dependent Claim
20 words
A method according to claim 1 wherein the contrast agent comprises a liposome having encapsulated therein a photo-activated gaseous precursor.
Claim 15
Dependent Claim
14 words
A method according to claim 12 wherein said photo-activated precursor is a diazonium compound.
Claim 16
Dependent Claim
20 words
A method according to claim 1 wherein the contrast agent comprises a liposome having encapsulated therein a temperature-activated gaseous precursor.
Claim 17
Dependent Claim
13 words
A method according to claim 14 wherein said temperature-activated gaseous precursor is methyllactate.
Claim 18
Independent Claim
102 words
A method of providing an image of an internal region of a patient comprising: (a) administering to the patient a contrast agent selected from the group consisting of (i) a liposome having encapsulated therein a pH-activated gas, said liposome having incorporated therein an ionophore, said ionophore being capable of facilitating the transport of hydrogen or hydroxide ions across the liposome membrane, (ii) a liposome having encapsulated therein a photo-activated gas, and (iii) a liposome having encapsulated therein a temperature-activated gas; and (b) scanning the patient using ultrasonic imaging to obtain enhanced visible images of the region, due to the gas containing liposomes.
Claim 19
Independent Claim
102 words
A method of providing an image of an internal region of a patient comprising: (a) administering to the patient a contrast agent selected from the group consisting of (i) a liposome having encapsulated therein a pH-activated gas, said liposome having incorporated therein an ionophore, said ionophore being capable of facilitating the transport of hydrogen or hydroxide ions across the liposome membrane, (ii) a liposome having encapsulated therein a photo-activated gas, and (iii) a liposome having encapsulated therein a temperature-activated gas; and (b) scanning the patient using ultrasonic imaging to obtain enhanced visible images of the region, due to the gas containing liposomes.
Claim 20
Dependent Claim
27 words
The method according to claim 16 wherein said liposomes are administered intravascularly and have a mean outer diameter of between about 30 nanometers and about 2 microns.
Claim 21
Dependent Claim
18 words
The method according to claim 17 wherein the patient is scanned in the area of the patient's heart.
Claim 22
Dependent Claim
21 words
The method according to claim 17 wherein the patient is scanned in the area of the patient's liver, spleen and kidney.
Claim 23
Dependent Claim
28 words
The method according to claim 16 wherein the liposomes are administered other than intravascularly and have a mean outer diameter between about 2 microns and about 10 microns.
Claim 24
Dependent Claim
48 words
The method of claim 16 wherein the liposomes are comprised of lipids of either natural or synthetic origin selected from the group consisting of fatty acids, lysolipids, dipalmitoylphosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, phosphatidylglycerol, phosphatidic acid, phosphatidylinositol, sphingomyelin, lysolipids, cholesterol, cholesterol hemisuccinate, glycosphingolipids, glycolipids, glucolipids, sulphatides, and tocopherol hemisuccinate.
Claim 25
Dependent Claim
43 words
A method according to claim 16 wherein the contrast agent is a liposome having encapsulated therein a pH-activated gas, said liposome having incorporated therein an ionophore, said ionophore being capable of facilitating the transport of hydrogen or hydroxide ions across the liposome membrane.
Claim 26
Dependent Claim
29 words
A method according to claim 22 wherein said pH-activated gas is gas activated from gaseous precursors selected from the group consisting of metal carbonate salts and metal bicarbonate salts.
Claim 27
Dependent Claim
21 words
A method according to claim 23 wherein said pH-activated gas is gas activated from a gaseous precursor which is sodium bicarbonate.
Claim 28
Dependent Claim
64 words
A method according to claim 22 wherein said ionophore in said liposome is selected from the group consisting of carbonylcyanide, p-trifluoromethoxy-phenylhydrazone, carbonylcyanide M-chlorophenylhydrazone, carbonylcyanide phenylhydrazine, tetrachloro-2-trifluoromethyl benzimidazole, 5,6-dichloro-2-trifluoromethyl benzimidazole, Uncoupler 1799, gramicidin, alamethicin, filipin, etruscomycin, nystatin, pimaricin, amphotericin, valinomycin, enniatin, beauvericin, monomycin, nonactin, monactin, dinactin, trinactin, tetranactin, antamanide, nigericin, monensin, salinomycin, narisin, mutalomycin, carriomycin, dianemycin, septamycin, A-204 A, X-206, X-537 A, A-23187 and dicyclohexyl-18-crown-6.
Claim 29
Dependent Claim
19 words
A method according to claim 16 wherein the contrast agent comprises a liposome having encapsulated therein a photo-activated gas.
Claim 30
Dependent Claim
21 words
A method according to claim 26 wherein said photo-activated gas is activated from a gaseous precursor which is a diazonium compound.
Claim 31
Dependent Claim
19 words
A method according to claim 16 wherein the contrast agent comprises a liposome having encapsulated therein a temperature-activated gas.
Claim 32
Dependent Claim
19 words
A method according to claim 28 wherein said temperature-activated gas is activated from a gaseous precursor which is methyllactate.
Claim 33
Independent Claim
105 words
A method for diagnosing the presence of diseased tissue in a patient comprising: (a) administering to the patient a contrast agent selected from the group consisting of (i) a liposome having encapsulated therein a pH-activated gas, said liposome having incorporated therein an ionophore, said ionophore being capable of facilitating the transport of hydrogen or hydroxide ions across the liposome membrane, (ii) a liposome having encapsulated therein a photo-activated gas, and (iii) a liposome having encapsulated therein a temperature-activated gas; and (b) scanning the patient using ultrasonic imaging to obtain enhanced visible images of any diseased tissue in the patient, due to the gas containing liposomes.
Claim 34
Independent Claim
105 words
A method for diagnosing the presence of diseased tissue in a patient comprising: (a) administering to the patient a contrast agent selected from the group consisting of (i) a liposome having encapsulated therein a pH-activated gas, said liposome having incorporated therein an ionophore, said ionophore being capable of facilitating the transport of hydrogen or hydroxide ions across the liposome membrane, (ii) a liposome having encapsulated therein a photo-activated gas, and (iii) a liposome having encapsulated therein a temperature-activated gas; and (b) scanning the patient using ultrasonic imaging to obtain enhanced visible images of any diseased tissue in the patient, due to the gas containing liposomes.
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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) | 1995-02-17 | 1995-08-19 | 1996-02-18 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1999-02-17 | 1999-08-19 | 2000-02-18 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2003-02-17 | 2003-08-19 | 2004-02-18 | $7700.00 | Window Closed / Lapsed |