US5082664A
Expired / Lapsed
US
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Prostaglandin-lipid formulations
Assignee: Elan Pharmaceuticals LLC
•
Filing: 1988-05-18
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Granted: 1992-01-21
•
Expires: 2008-05-18
Abstract
Abstract A liposome composition and methods for making same are disclosed, such compositions comprise an arachidonic acid metabolite such as a prostaglandin, preferably prostaglandin E 1 , a lipid, and a drying protectant such as a saccharide. The liposomes may be loaded with prostaglandin passively, or using a transmembrane concentration gradient, preferably using a transmembrane pH gradient. Using this transmembrane loading technique, trapping efficiencies of 50% to 100% are achieved, and the release rate of the prostaglandin from the liposomes is reduced. The liposome size is maintained after lyophilization and reconstitution.
Inventors
- 👤 Robert P. Lenk
- 👤 Michelle L. Tomsho
- 👤 Robert L. Suddith
- 👤 Robert J. Klimchak
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 21:50
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/557; A61K31/5575; A61K9/00; A61K9/10; A61K9/127; A61K9/1277; A61K9/1278; A61K9/48; A61K9/50; Y; Y10; Y10S; Y10S436/00; Y10S436/829; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2984
Claims Analysis
Total Claims: 60
Claim 1
Independent Claim
21 words
A liposome composition comprising an arachidonic acid metabolite, a lipid, and a drying-protectant, and wherein the liposomes contain a partition-enhancing buffer.
Claim 2
Dependent Claim
21 words
A liposome composition comprising an arachidonic acid metabolite, a lipid, and a drying-protectant, and wherein the liposomes contain a partition-enhancing buffer.
Claim 3
Dependent Claim
14 words
The liposome composition of claim 1 wherein the arachidonic acid metabolite is a prostaglandin.
Claim 4
Dependent Claim
14 words
The liposome composition of claim 2 wherein the prostaglandin comprises prostaglandin E 1 .
Claim 5
Dependent Claim
14 words
The liposome composition of claim 1 wherein the liposomes have a transmembrane concentration gradient.
Claim 6
Dependent Claim
15 words
The liposome composition of claim 4 wherein the transmembrane concentration gradient is an ion gradient.
Claim 7
Dependent Claim
14 words
The liposome composition of claim 5 wherein the ion gradient is a pH gradient.
Claim 8
Dependent Claim
17 words
The liposome composition of claim 1 wherein the partition-enhancing buffer comprises drying-protectant solution and citric acid solution.
Claim 9
Dependent Claim
15 words
The liposome composition of claim 7 wherein the drying protectant solution is a saccharide solution.
Claim 10
Dependent Claim
19 words
The liposome composition of claim 8 wherein the pH of the saccharide solution is about 3.0 to about 11.0.
Claim 11
Dependent Claim
16 words
The liposome composition of claim 9 wherein the pH of the saccharide solution is about 7.0.
Claim 12
Dependent Claim
21 words
The liposome composition of claim 8 wherein the pH of the citric acid solution is from about 2.5 to about 4.5.
Claim 13
Dependent Claim
17 words
The liposome composition of claim 8 wherein the pH of the citric acid solution is about 3.0.
Claim 14
Dependent Claim
15 words
The liposome composition of claim 8 wherein the saccharide solution comprises dextrose, sucrose, or maltose.
Claim 15
Dependent Claim
11 words
The liposome composition of claim 13 wherein the saccharide comprises maltose.
Claim 16
Dependent Claim
18 words
The liposome composition of claim 8 wherein the saccharide solution comprises from about 5% to about 20% saccharide.
Claim 17
Dependent Claim
18 words
The liposome composition of claim 15 wherein the saccharide solution comprises from about 10% to about 12% saccharide.
Claim 18
Dependent Claim
11 words
The liposome composition of claim 1 wherein the lipid comprises phospholipid.
Claim 19
Dependent Claim
11 words
The liposome composition of claim 17 wherein the phospholipid comprises phosphatidylcholine.
Claim 20
Dependent Claim
12 words
The liposome composition of claim 18 wherein the phosphatidylcholine comprises egg phosphatidylcholine.
Claim 21
Dependent Claim
18 words
The liposome composition of claim 1 wherein the liposomes are from about 20 nm to about 500 nm.
Claim 22
Dependent Claim
18 words
The liposome composition of claim 20 wherein the liposomes have a mean diameter of 100 to 200 nm.
Claim 23
Dependent Claim
11 words
The liposome composition of claim 20 wherein the composition is lyophilized.
Claim 24
Dependent Claim
22 words
The liposome composition of claim 2 wherein the entrapment of the prostaglandin in the liposome is from about 50% to about 100%.
Claim 25
Dependent Claim
21 words
A liposome composition comprising prostaglandin E 1 , egg phosphatidylcholine, and 10% maltose, and wherein the liposomes contain a partition-enhancing buffer.
Claim 26
Dependent Claim
21 words
A liposome composition comprising prostaglandin E 1 , egg phosphatidylcholine, and 10% maltose, and wherein the liposomes contain a partition-enhancing buffer.
Claim 27
Dependent Claim
18 words
A method of administering the liposome composition of claim 24 comprising injecting the composition intravenously in a patient.
Claim 28
Dependent Claim
17 words
A pharmaceutical composition comprising the liposome composition of claim 24 and a pharmaceutically acceptable carrier or diluent.
Claim 29
Dependent Claim
19 words
The liposome composition of claim 24 wherein the lipid to prostaglandin weight ratio is from about 300:1 to 1000:1.
Claim 30
Dependent Claim
19 words
The liposome composition of claim 27 wherein the lipid to prostaglandin weight ratio is from about 300:1 to 800:1.
Claim 31
Dependent Claim
16 words
A lyophilized liposomal-prostaglandin composition comprising a lipid, a prostaglandin, and at least about 10% drying protectant.
Claim 32
Dependent Claim
16 words
A lyophilized liposomal-prostaglandin composition comprising a lipid, a prostaglandin, and at least about 10% drying protectant.
Claim 33
Dependent Claim
13 words
The lyophilized composition of claim 29 wherein the drying protectant comprises a saccharide.
Claim 34
Dependent Claim
14 words
The lyophilized composition of claim 30 wherein the saccharide comprises dextrose, sucrose, or maltose.
Claim 35
Independent Claim
24 words
A method of preparing a liposomal-prostaglandin composition comprising the step of associating the prostaglandin with the liposomes by means of a transmembrane pH gradient.
Claim 36
Independent Claim
24 words
A method of preparing a liposomal-prostaglandin composition comprising the step of associating the prostaglandin with the liposomes by means of a transmembrane pH gradient.
Claim 37
Dependent Claim
45 words
The method of claim 32 wherein the transmembrane pH gradient is obtained by the steps of: (a) forming liposomes in a relatively basic aqueous solution; (b) adding a prostaglandin to the suspension of step (a) above; and (c) acidifying the external medium of the liposomes.
Claim 38
Dependent Claim
13 words
The method of claim 33 wherein the liposomes of step (a) are size-reduced.
Claim 39
Dependent Claim
19 words
The method of claim 34 wherein the liposomes are size reduced by filtering through a tortuous path type filter.
Claim 40
Dependent Claim
20 words
The method of claim 34 wherein the liposomes are size reduced by filtering through a straight path type membrane filter.
Claim 41
Dependent Claim
13 words
The method of claim 34 wherein the liposomes are size reduced by homogenization.
Claim 42
Dependent Claim
10 words
The method of claim 33 wherein the liposomes are lyophilized.
Claim 43
Dependent Claim
18 words
The method of claim 33 wherein the lipid to prostaglandin weight ratio is from about 300:1 to 1000:1.
Claim 44
Dependent Claim
18 words
The method of claim 39 wherein the lipid to prostaglandin weight ratio is from about 300:1 to 800:1.
Claim 45
Independent Claim
43 words
A method of preparing a liposomal-prostaglandin composition comprising a lipid, prostaglandin E 1 , and a drying protectant, comprising the step of admixing an aqueous solution of the drying protectant containing the prostaglandin with a dried lipid film to obtain the liposomal-prostaglandin composition.
Claim 46
Independent Claim
43 words
A method of preparing a liposomal-prostaglandin composition comprising a lipid, prostaglandin E 1 , and a drying protectant, comprising the step of admixing an aqueous solution of the drying protectant containing the prostaglandin with a dried lipid film to obtain the liposomal-prostaglandin composition.
Claim 47
Dependent Claim
12 words
The method of claim 41 wherein the resulting liposomal-prostaglandin composition is lyophilized.
Claim 48
Independent Claim
81 words
A method of preparing a liposomal-prostaglandin composition comprising a lipid, prostaglandin E 1 , a drying protectant, and a partition-enhancing buffer, comprising the steps of: (a) admixing an ethanolic solution of the lipid with a relatively basic solution of the drying protectant, forming liposomes; (b) size reducing the liposomes; (c) admixing the liposomes with an ethanolic solution of prostaglandin E 1 ; (d) lyophilizing the liposomes of step (c); and (e) reconstituting the liposomes with a relatively acidic citric acid solution.
Claim 49
Independent Claim
81 words
A method of preparing a liposomal-prostaglandin composition comprising a lipid, prostaglandin E 1 , a drying protectant, and a partition-enhancing buffer, comprising the steps of: (a) admixing an ethanolic solution of the lipid with a relatively basic solution of the drying protectant, forming liposomes; (b) size reducing the liposomes; (c) admixing the liposomes with an ethanolic solution of prostaglandin E 1 ; (d) lyophilizing the liposomes of step (c); and (e) reconstituting the liposomes with a relatively acidic citric acid solution.
Claim 50
Independent Claim
11 words
The method of step 43 wherein the lipid is egg phosphatidylcholine.
Claim 51
Independent Claim
11 words
The method of step 43 wherein the lipid is egg phosphatidylcholine.
Claim 52
Independent Claim
12 words
The method of step 43 wherein the drying protectant is a saccharide.
Claim 53
Independent Claim
12 words
The method of step 43 wherein the drying protectant is a saccharide.
Claim 54
Independent Claim
13 words
The method of step 45 wherein the saccharide is dextrose, sucrose, or maltose.
Claim 55
Independent Claim
13 words
The method of step 45 wherein the saccharide is dextrose, sucrose, or maltose.
Claim 56
Dependent Claim
10 words
The method of claim 46 wherein the saccharide is maltose.
Claim 57
Dependent Claim
16 words
The method of claim 43 wherein the liposomes of step (a) are size reduced by homogenization.
Claim 58
Dependent Claim
20 words
A pharmaceutical composition comprising the liposomes formed by the method of claim 43 and a pharmaceutically acceptable carrier or diluent.
Claim 59
Dependent Claim
18 words
The liposome composition of claim 1 wherein the arachidonic acid metabolite is obtained synthetically or from natural sources.
Claim 60
Dependent Claim
18 words
The liposome composition of claim 24 wherein the prostaglandin E 1 is obtained synthetically or from natural sources.
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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) | 1995-01-20 | 1995-07-22 | 1996-01-21 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1999-01-20 | 1999-07-22 | 2000-01-21 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2003-01-20 | 2003-07-22 | 2004-01-21 | $7700.00 | Window Closed / Lapsed |