US4310506A
Expired / Lapsed
US
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Means of preparation and applications of liposomes containing high concentrations of entrapped ionic species
Assignee: California Institute of Technology
•
Filing: 1980-02-20
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Granted: 1982-01-12
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Expires: 2000-02-20
Abstract
Abstract Unilamellar vesicles comprising a lipid bilayer, an ionophore being incorporated in said lipid bilayer, a chelating agent entrapped within the vesicles, and an effective amount of physiologically compatible cation bound to said chelating agent within the vesicles. Unilamellar vesicles are loaded by incubating the vesicles with the cation, terminating the incubation and recovering the loaded vesicles by chromatography. In some applications of the invention, the cation may be a radioactive tracer, in which case the vesicles can be administered to the human host and observed by scintillation techniques to produce a radioimage which is useful for diagnostic purposes.
Inventors
- 👤 John D. Baldeschwieler
- 👤 Ronald C. Gamble
- 👤 Marcia R. Mauk
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 11:39
CPC Classifications
A; A61; A61K; A61K51/00; A61K51/12; A61K51/1217; A61K51/1234; A61K9/00; A61K9/10; A61K9/127; A61K9/1277; A61K9/1278; A61K2123/00; Y; Y10; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2984
Claims Analysis
Total Claims: 36
Claim 1
Independent Claim
36 words
Vesicles comprising a lipid bilayer, an ionophore being incorporated in said lipid bilayer, a chelating agent entrapped within the vesicles, and an effective amount of physiologically compatible cation bound to said chelating agent within the vesicles.
Claim 2
Dependent Claim
36 words
Vesicles comprising a lipid bilayer, an ionophore being incorporated in said lipid bilayer, a chelating agent entrapped within the vesicles, and an effective amount of physiologically compatible cation bound to said chelating agent within the vesicles.
Claim 3
Dependent Claim
11 words
The vesicles of claim 1 wherein the ionophore is [6S-[6α(2S*,3S*)-,8β(R*),9β,11α]]-5-(methylamino)-2-[[3,9,11-trimethyl-8-[1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl]-1,7-dioxaspiro[5,5]undec-2-yl]methyl]-4-benzoxazolecarboxylic acid.
Claim 4
Dependent Claim
20 words
The vesicles of claim 1 wherein the cation is selected from the group consisting of all bivalent and trivalent cations.
Claim 5
Dependent Claim
12 words
The vesicles of claim 1 wherein the cation is a radioactive tracer.
Claim 6
Dependent Claim
33 words
The vesicles of claim 1 wherein the cation is a radioactive tracer selected from the group consisting of: 111 In, 45 Ca, 51 Cr, 99 Tc, 67 Ga, 57 Co, and 65 Zn.
Claim 7
Dependent Claim
10 words
The vesicles of claim 1 wherein the bilayer includes cholesterol.
Claim 8
Dependent Claim
12 words
The vesicles of claim 1 wherein the bilayer includes L-α-distearoyl phosphatidylcholine (DSPC).
Claim 9
Dependent Claim
12 words
The vesicles of claim 1 wherein the bilayer includes L-α-dipalmitoyl phosphatidylcholine (DPPC).
Claim 10
Dependent Claim
27 words
The vesicles of claim 1 wherein the chelating agent is selected from the group consisting of nitrilotriacetic acid, diethylenetriaminepentaacetic acid, diaminocyclohexanetetraacetic acid, iminodiacetic acid and ethylenediaminetetraacetic acid.
Claim 11
Independent Claim
61 words
The method comprising administering to the mammalian host vesicles comprising a lipid bilayer, an ionophore being incorporated in said lipid bilayer, a chelating agent entrapped within the vesicles, and an effective amount of physiologically compatible radioactive tracer bound to said chelating agent within the vesicles, and observing at least some body portion by scintillation counting technique to observe the radioimage produced.
Claim 12
Independent Claim
61 words
The method comprising administering to the mammalian host vesicles comprising a lipid bilayer, an ionophore being incorporated in said lipid bilayer, a chelating agent entrapped within the vesicles, and an effective amount of physiologically compatible radioactive tracer bound to said chelating agent within the vesicles, and observing at least some body portion by scintillation counting technique to observe the radioimage produced.
Claim 13
Dependent Claim
11 words
The method of claim 8 wherein the ionophore is [6S-[6α(2S*,3S*),8β(R*),9β,11α]]-5-(methylamino)-2-[[3,9,11-trimethyl-8-[1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl]-1,7-dioxaspiro[5,5]undec-2-yl]methyl]-4-benzoxazolecarboxylic acid.
Claim 14
Dependent Claim
30 words
The method of claim 10 wherein the tracer is selected from the group consisting of: 111 In, 45 Ca, 51 Cr, 99 Tc, 67 Ga, 57 Co, and 65 Zn.
Claim 15
Dependent Claim
10 words
The method of claim 10 wherein the bilayer includes cholesterol.
Claim 16
Dependent Claim
12 words
The method of claim 10 wherein the bilayer includes L-α-distearoyl phosphatidylcholine (DSPC).
Claim 17
Dependent Claim
12 words
The method of claim 10 wherein the bilayer includes L-α-dipalmitoyl phosphatidylcholine (DPPC).
Claim 18
Dependent Claim
27 words
The method of claim 10 wherein the chelating agent is selected from the group consisting of nitrilotriacetic acid, diethylenetriaminepentaacetic acid, diaminocyclohexanetetraacetic acid, iminodiacetic acid, and ethylenediaminetetraacetic acid.
Claim 19
Independent Claim
112 words
The method of determining the distribution and condition of vesicles within a mammal, said vesicles comprising a lipid bilayer, an ionophore being incorporated in said lipid bilayer, a chelating agent entrapped within the vesicles, and an effective amount of physiologically compatible radioactive tracer bound to said chelating agent within the vesicles, said method comprising: (a) determining the initial rotational correlation time of the radioactive tracer through measurement of the time-integrated perturbation factor of said vesicles, (b) injecting said vesicles into said mammal, (c) observing by scintillation techniques the distribution of said vesicles, and (d) determining any change in said time-integrated perturbation factor of the whole body or of parts by appropriate shielding.
Claim 20
Independent Claim
112 words
The method of determining the distribution and condition of vesicles within a mammal, said vesicles comprising a lipid bilayer, an ionophore being incorporated in said lipid bilayer, a chelating agent entrapped within the vesicles, and an effective amount of physiologically compatible radioactive tracer bound to said chelating agent within the vesicles, said method comprising: (a) determining the initial rotational correlation time of the radioactive tracer through measurement of the time-integrated perturbation factor of said vesicles, (b) injecting said vesicles into said mammal, (c) observing by scintillation techniques the distribution of said vesicles, and (d) determining any change in said time-integrated perturbation factor of the whole body or of parts by appropriate shielding.
Claim 21
Dependent Claim
11 words
The method of claim 17 wherein the ionophore is [6S-[6α(2S*,3S*),8β(R*),9β,11α]]-5-(methylamino)-2-[[3,9,11-trimethyl-8-[1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl-1,7-dioxaspiro[5,5]undec-2-yl]methyl]-4-benzoxazolecarboxylic acid.
Claim 22
Dependent Claim
30 words
The method of claim 17 wherein the tracer is selected from the group consisting of: 111 In, 45 Ca, 51 Cr, 99 Tc, 67 Ga, 57 CO, and 65 Zn.
Claim 23
Dependent Claim
10 words
The method of claim 17 wherein the bilayer includes cholesterol.
Claim 24
Dependent Claim
12 words
The method of claim 17 wherein the bilayer includes L-α-distearoyl phosphatidylcholine (DSPC).
Claim 25
Dependent Claim
12 words
The method of claim 17 wherein the bilayer includes L-α-dipalmitoyl phosphatidylcholine (DPPC).
Claim 26
Dependent Claim
27 words
The method of claim 17 wherein the chelating agent is selected from the group consisting of nitrilotriacetic acid, diethylenetriaminepentaacetic acid, diaminocyclohexanetetraacetic acid, iminodiacetic acid, and ethylenediaminetetraacetic acid.
Claim 27
Independent Claim
46 words
The method of loading lipid vesicles comprising: (1) incubating vesicles comprising a lipid bilayer, an ionophore in said lipid bilayer and a chelating agent entrapped within said vesicles, with, (2) a physiologically compatible cation, (3) terminating said incubation, and (4) recovering the loaded vesicles by chromatography.
Claim 28
Independent Claim
46 words
The method of loading lipid vesicles comprising: (1) incubating vesicles comprising a lipid bilayer, an ionophore in said lipid bilayer and a chelating agent entrapped within said vesicles, with, (2) a physiologically compatible cation, (3) terminating said incubation, and (4) recovering the loaded vesicles by chromatography.
Claim 29
Dependent Claim
11 words
The method of claim 24 wherein the ionophore is [6S-[6α(2S*,3S*),8β(R*),9β,11α]]-5-(methylamino)-2-[[3,9,11-trimethyl-8-[1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl]-1,7-dioxaspiro[5,5]undec-2-yl]methyl]-4-benzoxazolecarboxylic acid.
Claim 30
Dependent Claim
20 words
The method of claim 24, wherein the cation is selected from the group consisting of all bivalent and trivalent cations.
Claim 31
Dependent Claim
12 words
The method of claim 24, wherein the cation is a radioactive tracer.
Claim 32
Dependent Claim
33 words
The method of claim 24 wherein the cation is a radioactive tracer selected from the group consisting of: 111 In, 45 Ca, 51 Cr, 99 Tc, 67 Ga, 57 Co, and 65 Zn.
Claim 33
Dependent Claim
10 words
The method of claim 24 wherein the bilayer includes cholesterol.
Claim 34
Dependent Claim
12 words
The method of claim 24 wherein the bilayer includes L-α-distearoyl phosphatidylcholine (DSPC).
Claim 35
Dependent Claim
12 words
The method of claim 24 wherein the bilayer includes L-α-dipalmitoyl phosphatidylcholine (DPPC).
Claim 36
Dependent Claim
27 words
The method of claim 24 wherein the chelating agent is selected from the group consisting of nitrilotriacetic acid. diethylenetriaminepentaacetic acid, diaminocyclohexanetetraacetic acid, iminodiacetic acid, and ethylenediaminetetraacetic acid.
References Cited (Backward Citations)
US3663685A
Cited
US3663686A
Cited
US3522346A
Cited
US3663687A
Cited
US3683066A
Cited
US3937668A
Cited
US3932657A
Cited
US4089801A
Cited
US4115536A
Cited
US4086330A
Cited
US4193983A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1985-01-11 | 1985-07-13 | 1986-01-12 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1989-01-11 | 1989-07-13 | 1990-01-12 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1993-01-11 | 1993-07-13 | 1994-01-12 | $7700.00 | Window Closed / Lapsed |