Liposomal-polyene preliposomal powder and method for its preparation
AssigneeBoard of Regents, The University of Texas System
InventorsRobert P. Lenk, Reeta Mehta, Gabriel Lopez-Berestein
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Abstract
A method is disclosed for preparing a stable preliposomal powder which, when reconstituted with water or saline solution, forms a suspension of liposomes containing a polyene drug, such as nystatin. The method involves the steps of combining at least one phospholipid with a first organic solvent to form a first solution, adding a clarifying amount of water to the first solution, combining a polyene with a second organic solvent to form a second solution, combining the first and second solutions to produce a substantially clear combined solution, and then removing the organic solvents, leaving a powder.
Claims68
A method of preparing a liposomalpolyene preliposomal powder, comprising the steps of:
- a. combining at least one phospholipid with t-butyl alcohol to form a first solution;
- b. combining the first solution with an amount of water effective to clarify the first solution, forming a clarified first solution;
- combining polyene with an organic solvent selected from the group consisting of dimethyl sulfoxide and dimethyl formamide to form a second solution;
- d. combining the clarified first solution and the second solution to produce a substantially clear combined solution;
- and
- e. removing substantially all the solvent from the combined solution by lyophilization.
A method of preparing a liposomalnystatin preliposomal powder, comprising the steps of:
- a. combining at least one phospholipid with t-butyl alcohol to form a first solution;
- b. combining the first solution with an amount of water effective to clarify the first solution, forming a clarified first solution;
- c. combining nystatin with an organic solvent selected from the group consisting of dimethyl sulfoxide and dimethyl formamide to form a second solution;
- d. combining the clarified first solution and the second solution to produce a substantially clear combined solution;
- and
- e. removing substantially all the solvent from the combined solution by lyophilization.
A method of preparing a liposomal-nystatin preliposomal powder, comprising the steps of:
- a. combining dimyristoyl phosphatidyl choline and dimyristoyl phosphatidyl glycerol with t-butyl alcohol to form a first solution;
- b. combining the first solution with an amount of water effective to clarify the first solution, forming a clarified first solution;
- c. combining nystatin with dimethyl sulfoxide to form a second solution;
- d. combining the clarified first solution and the second solution to produce a substantially clear combined solution;
- and
- e. removing substantially all the t-butyl alcohol and dimethyl sulfoxide from the combined solution by lyophilization.
A method of preparing a parenterally-administrable polyene preparation, comprising the steps of:
- a. combining at least one phospholipid with t-butyl alcohol to form a first solution;
- b. combining the first solution with an amount of water effective to clarify the first solution, forming a clarified first solution;
- c. combining polyene with an organic solvent selected from the group consisting of dimethyl sulfoxide and dimethyl formamide to form a second solution;
- d. combining the clarified first solution and the second solution to produce a substantially clear combined solution;
- e. removing substantially all the solvent from the combined solution by lyophilization, thereby forming a preliposomal powder;
- and
- f. adding a pharmaceutically acceptable solvent to the preliposomal powder.
A method of preparing a parenterally-administrable nystatin preparation, comprising the steps of:
- a. combining at least one phospholipid with t-butyl alcohol to form a first solution;
- b. combining the first solution with an amount of water effective to clarify the first solution, forming a clarified first solution;
- c. combining nystatin with an organic solvent selected from the group consisting of dimethyl sulfoxide and dimethyl formamide to form a second solution;
- d. combining the clarified first solution and the second solution to produce a substantially clear combined solution;
- e. removing substantially all the solvent from the combined solution by lyophilization, thereby forming a preliposomal powder;
- and
- f. adding a pharmaceutically acceptable solvent to the preliposomal powder.
A method of preparing a parenterally-administrable nystatin preparation, comprising the steps of:
- a. combining dimyristoyl phosphatidyl choline and dimyristoyl phosphatidyl glycerol with t-butyl alcohol to form a first solution;
- b. combining the first solution with an amount of water effective to clarify the first solution, forming a clarified first solution;
- c. combining nystatin with dimethyl sulfoxide to form a second solution;
- d. combining the clarified first solution and the second solution to produce a substantially clear combined solution;
- e. removing substantially all the t-butyl alcohol and dimethyl sulfoxide form the combined solution by lyophilization, thereby forming a preliposomal powder;
- and
- f. adding a pharmaceutically acceptable solvent to the preliposomal powder.
A liposomal-polyene preliposomal powder prepared by a method comprising the steps of:
- a. combining at least one phospholipid with t-butyl alcohol to form a first solution;
- b. combining the first solution with an amount of water effective to clarify the first solution, forming a clarified first solution;
- c. combining polyene with an organic solvent selected from the group consisting of dimethyl sulfoxide and dimethyl formamide to form a second solution;
- d. combining the clarified first solution and the second solution to produce a substantially clear combined solution;
- and
- e. removing substantially all the solvent from the combined solution by lyophilization, leaving a preliposomal powder.
A liposomal-nystatin preliposomal powder prepared by a method comprising the steps of:
- a. combining at least one phospholipid with t-butyl alcohol to form a first solution;
- b. combining the first solution with an amount of water effective to clarify the first solution, forming a clarified first solution;
- c. combining nystatin with an organic solvent selected from the group consisting of dimethyl sulfoxide and dimethyl formamide to form a second solution;
- d. combining the clarified first solution and the second solution to produce a substantially clear combined solution;
- and
- e. removing substantially all the solvent from the combined solution by lyophilization.
A liposomal-nystatin preliposomal powder prepared by a method comprising the steps of:
- a. combining dimyristoyl phosphatidyl choline and dimyristoyl phosphatidyl glycerol with t-butyl alcohol to form a first solution;
- b. combining the first solution with an amount of water effective to clarify the first solution, forming a clarified first solution;
- c. combining nystatin with dimethyl sulfoxide to form a second solution;
- d. combining the clarified first solution and the second solution to produce a substantially clear combined solution;
- and
- e. removing substantially all the t-butyl alcohol and dimethyl sulfoxide from the combined solution by lyophilization.
A substantially clear, filterable polyene solution, comprising at least one polyene, at least one phospholipid, t-butyl alcohol, and an amount of water effective to clarify the solution.
A substantially clear, filterable nystatin solution, comprising nystatin, at least one phospholipid, t-butyl alcohol, and an amount of water effective to clarify the solution.
Dependencies are inferred from the claim text.