US5543152A
Expired / Lapsed
US
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Sphingosomes for enhanced drug delivery
Assignee: Arbutus Biopharma Corp
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Filing: 1994-06-20
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Granted: 1996-08-06
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Expires: 2014-06-20
Abstract
Abstract Liposomal formulations having extended circulation time in vivo and increased drug retention are comprised of sphingomyelin and cholesterol and have an acidic intraliposomal pH. The formulations have enhanced stability and thus are used in methods which provide improved drug delivery and more effective treatment. The delivery of lipophilic drugs such as the vinca alkaloids, and particularly vincristine and vinblastine, to tumors is significantly improved.
Inventors
- 👤 Murray S. Webb
- 👤 Marcel B. Bally
- 👤 Lawrence D. Mayer
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-31 10:17
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; A61K9/1271; A61K9/1272
Claims Analysis
Total Claims: 17
Claim 1
Independent Claim
57 words
A liposomal composition for delivery of a therapeutic compound to a mammalian host which comprises a liposome having one or more membranes which comprise sphingomyelin and cholesterol, a liposomal interior having an acidic pH which is less than that of the liposomal exterior, and a lipophilic therapeutic compound contained in said liposome for delivery to the host.
Claim 2
Dependent Claim
57 words
A liposomal composition for delivery of a therapeutic compound to a mammalian host which comprises a liposome having one or more membranes which comprise sphingomyelin and cholesterol, a liposomal interior having an acidic pH which is less than that of the liposomal exterior, and a lipophilic therapeutic compound contained in said liposome for delivery to the host.
Claim 3
Dependent Claim
29 words
The liposomal composition of claim 1, wherein the sphingomyelin and cholesterol are present at a molar ratio from 75/25 mol %/mol % sphingomyelin/cholesterol to 30/50 mol %/mol % sphingomyelin/cholesterol.
Claim 4
Dependent Claim
29 words
The liposomal composition of claim 2, wherein the sphingomyelin and cholesterol are present at a molar ratio from 70/30 mol %/mol % sphingomyelin/cholesterol to 40/45 mol %/mol % sphingomyelin/cholesterol.
Claim 5
Dependent Claim
23 words
The liposomal composition of claim 3, wherein the sphingomyelin and cholesterol are present at a ratio of approximately 55/45 mol %/mol % sphingomyelin/cholesterol.
Claim 6
Dependent Claim
14 words
The liposomal composition of claim 1, wherein the lipophilic therapeutic compound is an alkaloid.
Claim 7
Dependent Claim
19 words
The liposomal composition of claim 5 wherein the alkaloid is selected from vincristine, vinblastine, or etoposide or prodrugs thereof.
Claim 8
Dependent Claim
11 words
The liposomal composition of claim 5, wherein the alkaloid is vincristine.
Claim 9
Dependent Claim
22 words
The liposomal composition of claim 7, wherein the vincristine is present at a drug to lipid ratio of approximately 0.01/1.0 to 0.2/1.0.
Claim 10
Dependent Claim
27 words
The liposomal composition of claim 1, further comprising at least one lipid selected from a phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidic acid, cardiolipin, phosphatidylinositol, ceramide, cerebroside and ganglioside.
Claim 11
Dependent Claim
11 words
The liposomal composition of claim 1, wherein the liposomes are unilamellar.
Claim 12
Dependent Claim
19 words
The liposomal composition of claim 1, wherein the liposomes have mean diameters of about 0.05 microns to 0.45 microns.
Claim 13
Dependent Claim
19 words
The liposomal composition of claim 1, wherein the liposomes have mean diameters of about 0.05 microns to 0.2 microns.
Claim 14
Dependent Claim
17 words
The liposomal composition of claim 1, wherein the interior comprises a citrate buffer at about pH 4.0.
Claim 15
Dependent Claim
97 words
A liposome for delivery of a lipophilic therapeutic compound, produced by the process of: forming a liposome from a mixture which comprises sphingomyelin and cholesterol, in a first buffered aqueous solution having an acidic pH greater than pH 2; and suspending the liposome in a second buffered solution having a pH which is greater than that of the first buffered aqueous solution, whereby a transmembrane pH gradient is formed which facilitates the transfer of the therapeutic compound to the liposome, wherein the interior of the liposome containing the therapeutic compound is from pH 2 to pH 6.
Claim 16
Dependent Claim
97 words
A liposome for delivery of a lipophilic therapeutic compound, produced by the process of: forming a liposome from a mixture which comprises sphingomyelin and cholesterol, in a first buffered aqueous solution having an acidic pH greater than pH 2; and suspending the liposome in a second buffered solution having a pH which is greater than that of the first buffered aqueous solution, whereby a transmembrane pH gradient is formed which facilitates the transfer of the therapeutic compound to the liposome, wherein the interior of the liposome containing the therapeutic compound is from pH 2 to pH 6.
Claim 17
Dependent Claim
39 words
The liposome produced by the process of claim 14, wherein the process further comprises the step of separating the liposome containing the therapeutic compound from the second buffer containing therapeutic compound which has not been entrapped by the liposome.
References Cited (Backward Citations)
US4920016A
Cited
US5192549A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-08-06 | 2000-02-05 | 2000-08-06 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-08-06 | 2004-02-05 | 2004-08-06 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-08-06 | 2008-02-05 | 2008-08-06 | $7700.00 | Window Closed / Lapsed |