US5741516A
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US
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Sphingosomes for enhanced drug delivery
Assignee: Arbutus Biopharma Corp
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Filing: 1995-12-14
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Granted: 1998-04-21
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Expires: 2015-12-14
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 ciprofloxacin, and alkaloid drugs, particularly swainsonine, vincristine and vinblastine, is significantly improved.
Inventors
- 👤 Murray S. Webb
- 👤 Marcel B. Bally
- 👤 Lawrence D. Mayer
- 👤 James J. Miller
- 👤 Paul G. Tardi
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 19:56
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; A61K9/1271; A61K9/1272; A61K9/1277; A61K9/1278
Claims Analysis
Total Claims: 36
Claim 1
Independent Claim
53 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 a pH less than that of the liposomal exterior, and a therapeutic compound contained in said liposome for delivery to the host.
Claim 2
Dependent Claim
53 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 a pH less than that of the liposomal exterior, and a therapeutic compound contained in said liposome for delivery to the host.
Claim 3
Dependent Claim
25 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
25 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
21 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
20 words
The liposomal composition of claim 5 wherein the alkaloid is selected from vincristine, vinblastine, swainsonine or etoposide or prodrugs thereof.
Claim 8
Dependent Claim
11 words
The liposomal composition of claim 6, wherein the alkaloid is vincristine.
Claim 9
Dependent Claim
11 words
The liposomal composition of claim 6, wherein the alkaloid is swainsonine.
Claim 10
Dependent Claim
38 words
The liposomal composition of claim 6, wherein vincristine is present at a drug to lipid ratio of approximately 0.01/1.0 to 0.2/1.0 (wt/wt) and swainsonine is present at a drug to lipid ratio of 0.01/1.0 to 0.5/1.0 (mol/mol) .
Claim 11
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 12
Dependent Claim
11 words
The liposomal composition of claim 1, wherein the liposomes are unilamellar.
Claim 13
Dependent Claim
19 words
The liposomal composition of claim 1, wherein the liposomes have mean diameters of about 0.05 microns to 0.45 microns.
Claim 14
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 15
Dependent Claim
18 words
The liposomal composition of claim 1 wherein the interior of said liposome is pH 2 to pH 5.
Claim 16
Dependent Claim
17 words
The liposomal composition of claim 1, wherein the interior comprises a citrate buffer at about pH 4.0.
Claim 17
Dependent Claim
42 words
A method for delivering an alkaloid therapeutic compound to a tumor susceptible to inhibition by said compound, comprising: administering to a host containing said tumor, a liposomal composition according to claim 1 which comprises said compound or a pharmaceutically acceptable salt thereof.
Claim 18
Dependent Claim
23 words
The method of claim 16, wherein the cholesterol is present in the liposomal composition at a total molar proportion of 30% to 50%.
Claim 19
Dependent Claim
20 words
The method of claim 17, wherein the sphingomyelin and cholesterol are present at a ratio of about 55/45, mol%/mol%, respectively.
Claim 20
Dependent Claim
13 words
The method of claim 16, wherein the alkaloid compound is vincristine or swainsonine.
Claim 21
Dependent Claim
11 words
The method of claim 19, wherein the alkaloid compound is vincristine.
Claim 22
Dependent Claim
11 words
The method of claim 19, wherein the alkaloid compound is swainsonine.
Claim 23
Dependent Claim
40 words
The method of claim 19, wherein vincristine is present in the liposomal composition at a drug to lipid ratio of approximately 0.01/1.0 to 0.2/1.0 (wt/wt) and swainsonine is present at a drug to lipid ratio of 0.01/1.0 to 0.5/1.0 (mol/mol).
Claim 24
Dependent Claim
43 words
The method of claim 16, wherein the liposomal composition containing said alkaloid compound is administered repeatedly to the host to maintain a concentration of said compound sufficient to inhibit the tumor but less than an amount which causes unacceptable toxicity to the host.
Claim 25
Dependent Claim
16 words
The method of claim 16, wherein the liposomal composition containing said alkaloid compound is administered intravenously.
Claim 26
Dependent Claim
16 words
The method of claim 16, wherein the liposomal composition containing said alkaloid compound is administered parenterally.
Claim 27
Dependent Claim
15 words
The method of claim 16, wherein the liposomal composition containing said alkaloid is administered orally.
Claim 28
Dependent Claim
18 words
The method of claim 16, wherein the liposomes of the liposomal composition administered to the host are unilamellar.
Claim 29
Dependent Claim
22 words
The method of claim 27, wherein the unilamellar liposomes of said composition have a mean diameter of 0.05 microns to 0.45 microns.
Claim 30
Dependent Claim
22 words
The method of claim 28, wherein the unilamellar liposomes of said composition have a mean diameter of 0.05 microns to 0.2 microns.
Claim 31
Dependent Claim
29 words
A method for delivering an alkaloid immunomodulating compound, comprising: administering to a host a liposomal composition according to claim 1 comprising said immunomodulator or a pharmaceutically acceptable salt thereof.
Claim 32
Dependent Claim
10 words
The method of claim 30, wherein the compound is swainsonine.
Claim 33
Dependent Claim
12 words
The method of claim 31, wherein swainsonine is delivered parenterally or orally.
Claim 34
Dependent Claim
12 words
The method of claim 32, wherein swainsonine is delivered intravenously or orally.
Claim 35
Dependent Claim
25 words
The method of claim 31, wherein swainsonine is present in the liposomal composition at a drug to lipid ratio of approximately 0.01/1.0 to 0.5/1.0 (mol/mol).
Claim 36
Dependent Claim
14 words
The method of claim 1, wherein the therapeutic compound is ciprofloxacin or derivative thereof.
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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) | 2001-04-20 | 2001-10-20 | 2002-04-21 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2005-04-20 | 2005-10-20 | 2006-04-21 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2009-04-20 | 2009-10-20 | 2010-04-21 | $7700.00 | Window Closed / Lapsed |