US6200598B1
Expired / Lapsed
US
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Temperature-sensitive liposomal formulation
Assignee: Duke University
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Filing: 1998-06-18
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Granted: 2001-03-13
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Expires: 2018-06-18
Abstract
Abstract Temperature sensitive liposomes containing active agents are described. The liposomes comprise phospholipids and a surface active agent, such as a lysolipid, that increases the amount of active agent released by the liposome at the phase transition temperature of the liposome. Such liposomes are useful in methods of administering active agents using mild hyperthermic conditions.
Inventors
- 👤 David Needham
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 09:57
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; A61K9/1271; A61P; A61P29/00; A61P31/00; A61P31/04; A61P35/00; A61P37/00; A61P37/02; A61P37/06
Claims Analysis
Total Claims: 27
Claim 1
Independent Claim
104 words
A liposome containing an active agent entrapped within the liposome interior space, said liposome having a gel-phase lipid bilayer membrane comprising phospholipid which is dipalmitoylphosphatidylcholine (DPPC) and lysolipid which is monopalmitoylphosphatidylcholine (MPPC), wherein phospholipid and lysolipid are contained in the bilayer membrane in a ratio of from 99:10 to 80:20 by molar weight and wherein phospholipids are the primary lipid source for the lipid bilayer membrane and wherein lysolipid is contained in the bilayer membrane in an amount sufficient to increase the percentage of active agent released at the phase transition temperature compared to that which would occur in the absence of said lysolipid.
Claim 2
Dependent Claim
104 words
A liposome containing an active agent entrapped within the liposome interior space, said liposome having a gel-phase lipid bilayer membrane comprising phospholipid which is dipalmitoylphosphatidylcholine (DPPC) and lysolipid which is monopalmitoylphosphatidylcholine (MPPC), wherein phospholipid and lysolipid are contained in the bilayer membrane in a ratio of from 99:10 to 80:20 by molar weight and wherein phospholipids are the primary lipid source for the lipid bilayer membrane and wherein lysolipid is contained in the bilayer membrane in an amount sufficient to increase the percentage of active agent released at the phase transition temperature compared to that which would occur in the absence of said lysolipid.
Claim 3
Dependent Claim
18 words
A liposome according to claim 1 having a diameter of from about 50 nanometers to about 400 nanometers.
Claim 4
Dependent Claim
19 words
A liposome according to claim 1 , wherein the liposome bilayer further comprises phospholipid derivatized with a hydrophilic polymer.
Claim 5
Dependent Claim
34 words
A liposome according to claim 3 , wherein said hydrophilic polymer is selected from the group consisting of polyethylene glycol, polylactic acid, polyglycolic acid, copolymers of polylactic acid and polyglycolic acid, and polyvinyl alcohol.
Claim 6
Dependent Claim
26 words
A liposome according to claim 1 , wherein said active agent is a pharmacologically active agent, a flavor agent, a diagnostic agent, or a nutritional agent.
Claim 7
Dependent Claim
33 words
A liposome according to claim 1 , wherein said active agent is a pharmacologically active agent selected from the group consisting of antineoplastic agents, anti-inflammatory agents, immunosuppressive agents, antibiotic agents and anti-infective agents.
Claim 8
Dependent Claim
34 words
A liposome according to claim 1 , wherein said active agent is selected from the group consisting of methotrexate, doxorubicin, epirubicin, daunorubicin, vincristine, vinblastine, etoposide, ellipticine, camptothecin, paclitaxel, docetaxol, cisplatin, prednisone, methyl-prednisone, and ibuprofen.
Claim 9
Dependent Claim
13 words
A liposome according to claim 1 , wherein said active agent is paclitaxel.
Claim 10
Dependent Claim
13 words
A liposome according to claim 1 , wherein said active agent is camptothecin.
Claim 11
Dependent Claim
66 words
A liposome containing an active agent entrapped within the liposome interior space and having a gel-phase lipid bilayer membrane comprising a phospholipid which is dipalmitoylphosphatidylcholine (DPPC) and lysolipid which is monopalmitoylphosphatidylcholine (MPPC), wherein phospholipids are the primary lipid source for the lipid bilayer membrane, and wherein phospholipid and lysolipid are contained in the bilayer membrane in a ratio of from 90:10 to 80:20 by molar weight.
Claim 12
Dependent Claim
66 words
A liposome containing an active agent entrapped within the liposome interior space and having a gel-phase lipid bilayer membrane comprising a phospholipid which is dipalmitoylphosphatidylcholine (DPPC) and lysolipid which is monopalmitoylphosphatidylcholine (MPPC), wherein phospholipids are the primary lipid source for the lipid bilayer membrane, and wherein phospholipid and lysolipid are contained in the bilayer membrane in a ratio of from 90:10 to 80:20 by molar weight.
Claim 13
Dependent Claim
26 words
A liposome according to claim 10 , wherein said active agent is a pharmacologically active agent, a flavor agent, a diagnostic agent, or a nutritional agent.
Claim 14
Dependent Claim
33 words
A liposome according to claim 10 , wherein said active agent is a pharmacologically active agent selected from the group consisting of antineoplastic agents, anti-inflammatory agents, immunosuppressive agents, antibiotic agents and anti-infective agents.
Claim 15
Dependent Claim
34 words
A liposome according to claim 10 , wherein said active agent is selected from the group consisting of methotrexate, doxorubicin, epirubicin, daunorubicin, vincristine, vinblastine, etoposide, ellipticine, camptothecin, paclitaxel, docetaxol, cisplatin, prednisone, methyl-prednisone, and ibuprofen.
Claim 16
Dependent Claim
13 words
A liposome according to claim 10 , wherein said active agent is paclitaxel.
Claim 17
Dependent Claim
13 words
A liposome according to claim 10 , wherein said active agent is camptothecin.
Claim 18
Independent Claim
107 words
A method of administering an active agent to a preselected hyperthermic target site in a subject, the improvement comprising: entrapping said active agent in the aqueous interior of a liposome, said liposome having a gel-phase lipid bilayer membrane comprising phospholipid which is dipalmitoylphosphatidylcholine (DPPC) and lysolipid which is monopalmitoylphosphatidylcholine (MPPC), wherein phospholipids are the primary lipid source for the lipid bilayer membrane, and wherein the aqueous interior of the liposome further comprises lysolipid in an equilibrating amount to the lysolipid contained in the lipid bilayer, and wherein phospholipid and lysolipid are contained in the bilayer membrane in a ratio of from 90:10 to 80:20 by molar weight.
Claim 19
Independent Claim
107 words
A method of administering an active agent to a preselected hyperthermic target site in a subject, the improvement comprising: entrapping said active agent in the aqueous interior of a liposome, said liposome having a gel-phase lipid bilayer membrane comprising phospholipid which is dipalmitoylphosphatidylcholine (DPPC) and lysolipid which is monopalmitoylphosphatidylcholine (MPPC), wherein phospholipids are the primary lipid source for the lipid bilayer membrane, and wherein the aqueous interior of the liposome further comprises lysolipid in an equilibrating amount to the lysolipid contained in the lipid bilayer, and wherein phospholipid and lysolipid are contained in the bilayer membrane in a ratio of from 90:10 to 80:20 by molar weight.
Claim 20
Dependent Claim
19 words
A method according to claim 16 , wherein said active agent is also entrapped within the lipid bilayer membrane.
Claim 21
Dependent Claim
19 words
A method according to claim 16 , wherein said liposome bilayer further comprises phospholipid derivatized with a hydrophilic polymer.
Claim 22
Dependent Claim
34 words
A method according to claim 18 , wherein said hydrophilic polymer is selected from the group consisting of polyethylene glycol, polylactic acid, polyglycolic acid, copolymers of polylactic acid and polyglycolic acid, and polyvinyl alcohol.
Claim 23
Dependent Claim
23 words
A method according to claim 16 , wherein said active agent is a pharmacologically active agent, a diagnostic agent, or a nutritional agent.
Claim 24
Dependent Claim
33 words
A method according to claim 16 , wherein said active agent is a pharmacologically active agent selected from the group consisting of antineoplastic agents, anti-inflammatory agents, immunosuppressive agents, antibiotic agents and anti-infective agents.
Claim 25
Dependent Claim
34 words
A method according to claim 16 , wherein said active agent is selected from the group consisting of methotrexate, doxorubicin, epirubicin, daunorubicin, vincristine, vinblastine, etoposide, ellipticine, camptothecin, paclitaxel, docetaxol, cisplatin, prednisone, methyl-prednisone, and ibuprofen.
Claim 26
Dependent Claim
13 words
A method according to claim 16 , wherein said active agent is paclitaxel.
Claim 27
Dependent Claim
13 words
A liposome according to claim 16 , wherein said active agent is camptothecin.
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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) | 2004-03-12 | 2004-09-11 | 2005-03-13 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2008-03-12 | 2008-09-11 | 2009-03-13 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2012-03-12 | 2012-09-11 | 2013-03-13 | $7700.00 | Window Closed / Lapsed |