Patent US4830858A successfully refreshed from Google Patents.
US4830858A
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US
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Spray-drying method for preparing liposomes and products produced thereby
Assignee: ER Squibb and Sons LLC
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Filing: 1985-02-11
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Granted: 1989-05-16
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Expires: 2005-02-11
Abstract
Abstract A method is provided for preparing a stable liposome precursor in the form of a mixture of spray-dried liposomal components including one or more biologically active compounds which may be stored dry and reconstituted with water to form a liposomal preparation immediately prior to use. The dry liposome precursor is also provided.
Inventors
- 👤 Nicholas I. Payne
- 👤 J. Roger Salmon
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 14:15
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; A61K9/1277; Y; Y10; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2984
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
135 words
A method for preparing a spray-dried mixture of liposomal components which may be stored dry and reconstituted to form a liposome, which comprises forming a solution of lipsomal components in a suitable organic solvent comprised of from about 1 to about 25% by weight of at least one liposome-forming lipid, optionally, at least one biologically active compound, and, optionally, at least one adjuvant which imparts advantageous properties to the final liposome, and adding an aqueous solution or suspension of at least one water-soluble, physiologically acceptable carrier material which is suitable for intravenous injection but which is substantially insoluble in said organic solvent, the weight ratio of liposomal components to carrier material being within the range of from about 0.03:1 to about 5:1, and spray-drying the so-formed mixture to form a dry mixture of liposomal components.
Claim 2
Independent Claim
135 words
A method for preparing a spray-dried mixture of liposomal components which may be stored dry and reconstituted to form a liposome, which comprises forming a solution of lipsomal components in a suitable organic solvent comprised of from about 1 to about 25% by weight of at least one liposome-forming lipid, optionally, at least one biologically active compound, and, optionally, at least one adjuvant which imparts advantageous properties to the final liposome, and adding an aqueous solution or suspension of at least one water-soluble, physiologically acceptable carrier material which is suitable for intravenous injection but which is substantially insoluble in said organic solvent, the weight ratio of liposomal components to carrier material being within the range of from about 0.03:1 to about 5:1, and spray-drying the so-formed mixture to form a dry mixture of liposomal components.
Claim 3
Dependent Claim
30 words
The method as defined in claim 1 wherein the solution is formed by dissolving said lipid, said biologically active compound and, optionally, said adjuvant in one or more organic solvents.
Claim 4
Dependent Claim
24 words
The methodaas defined in claim 1 wherein the solution is formed by dissolving the optional biologically active compound and optional adjuvant in said lipid.
Claim 5
Dependent Claim
46 words
The method as defined in claim 1 wherein said carrier material has a water-solubility in excess of 10% by weight, a rapid dissolution rate in water, and will form an isotonic solution in water in a concentration of from about 0.5 to about 10 % w/v.
Claim 6
Dependent Claim
19 words
The method as defined in claim 4 wherein said carrier material is a water-soluble carrier suitable for intravenous use.
Claim 7
Dependent Claim
23 words
The method as defined in claim 5 wherein said carrier material is sorbitol, mannitol, sodium chloride, xylitol or a naturally occurring amino acid.
Claim 8
Dependent Claim
13 words
The method as defined in claim 6 wherein said carrier material is sorbitol.
Claim 9
Dependent Claim
35 words
The method as defined in claim 4 including the step of dissolving the carrier material in water, mixing the solution of carrier material and the solution of liposomal components, and spray drying the resulting mixture.
Claim 10
Dependent Claim
13 words
The method as defined in claim 1 wherein the lipid is a phospholipid.
Claim 11
Dependent Claim
16 words
The method as defined in claim 9 wherein the phospholipid is a natural or synthetic lecithin.
Claim 12
Dependent Claim
29 words
The method as defined in claim 1 wherein said solution includes a biologically active compound which is a medicament, contrast agent, enzyme, hormone, marker compound or NMR imaging agent.
Claim 13
Dependent Claim
19 words
The method as defined in claim 1 wherein the adjuvant is egg phosphatidic acid, dicetyl phosphate, or stearyl amine.
Claim 14
Dependent Claim
13 words
The method as defined in claim 1 wherein the adjuvant is a sterol.
Claim 15
Dependent Claim
27 words
The method as defined in claim 12 wherein the adjuvant also includes a sterol selected from the group consisting of cholesterol, phytosterol. ergosterol, sitosterol, 7-dehydrocholesterol, and lanosterol.
Claim 16
Dependent Claim
25 words
The method as defined in claim 6 wherein the organic solvent is ethanol, methanol, chloroform, dichloromethane, diethyl ether, carbon tetrachloride, ethyl acetate, dioxane or cyclohexane.
Claim 17
Dependent Claim
15 words
The method as defined in claim 15 wherein the solvent is methanol, ethanol or chloroform.
Claim 18
Dependent Claim
15 words
The method as defined in claim 1 wherein the biologically active compound is amphotericin B.
Claim 19
Dependent Claim
15 words
The method as defined in claim 8 wherein the biologically active compound is amphotericin B.
Claim 20
Dependent Claim
22 words
The method as defined in claim 18 wherein said carrier material is sorbitol and said adjuvant includes a sterol which is ergosterol.
Claim 21
Dependent Claim
32 words
The method as defined in claim 1 wherein said lipid is egg lecithin, soya bean lecithin, dimyristoyl phosphatidyl choline, dipalmitoyl phosphatidyl choline, distearoyl phosphatidyl choline, dioleyl phosphatidyl choline or dilinoleyl phosphatidyl choline.
Claim 22
Dependent Claim
27 words
The method as defined in claim 1 wherein the lipid is egg lecithin, the adjuvant is ergosterol, cholesterol or dicetyl phosphate, and the carrier material is sorbitol.
Claim 23
Dependent Claim
28 words
The method as defined in claim 1 wherein the srray-drying is carried out at an average temperature within the range of from about 5 to about 60° C.
Claim 24
Dependent Claim
23 words
The method as defined in claim 22 wherein the spray-drying is carried out employing from about 300 to about 700 liters of air/hour.
Claim 25
Dependent Claim
104 words
A spray-dried mixture of liposomal components which when mixed with water forms a liposome, comprising a dry granular water-soluble free-flowing mixture of liposomal components comprising at least one liposome-forming lipid, optionally, at least one biologically active compound and, optionally, at least one adjuvant which imparts advantgageous properties to the final lipsome and a water-soluble free-flowing physiologically acceptable carrier material, which is suitable for intraveneous injection, which will form an isotonic solution in water in a concentration of from about 0.5 to about 10% w/v, the weight ratio of liposomal components to carrier material being within the range of from about 0.03:1 to about 5:1.
Claim 26
Dependent Claim
104 words
A spray-dried mixture of liposomal components which when mixed with water forms a liposome, comprising a dry granular water-soluble free-flowing mixture of liposomal components comprising at least one liposome-forming lipid, optionally, at least one biologically active compound and, optionally, at least one adjuvant which imparts advantgageous properties to the final lipsome and a water-soluble free-flowing physiologically acceptable carrier material, which is suitable for intraveneous injection, which will form an isotonic solution in water in a concentration of from about 0.5 to about 10% w/v, the weight ratio of liposomal components to carrier material being within the range of from about 0.03:1 to about 5:1.
Claim 27
Dependent Claim
20 words
The stable liposome precursor as defined in claim 24 including at least one biologically active compound and a carrier material.
Claim 28
Dependent Claim
17 words
The stable liposome precursor as defined in claim 25 wherein the biologically active compound is amphotericin B.
Claim 29
Dependent Claim
88 words
A spray-dried mixture of liposomal components which when mixed with water forms a liposome, comprising at least one liposome-forming lipid, optionally, at least one biologically active compound, and optionally, at least one adjuvant which imparts advantageous properties to the final liposome, and a physiologically acceptable water-soluble particulate carrier material, suitable for intravenous injection, the weight ratio of liposomal components to carrier material being within the range of from about 0.03:1 to about 5:1, said spray-dried mixture of liposomal components prepared by the method as defined in claim 1.
Claim 30
Dependent Claim
22 words
A method for preparing a liposome which comprises mixing the spray-dried mixture of liposomal components as defined in claim 27 with water.
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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) | 1992-05-15 | 1992-11-14 | 1993-05-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-05-15 | 1996-11-14 | 1997-05-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-05-15 | 2000-11-14 | 2001-05-16 | $7700.00 | Window Closed / Lapsed |