Details for Patent: 6,599,498
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Title: | Heat stable colloidal iron oxides coated with reduced carbohydrates and carbohdrate derivatives |
Abstract: | Compositions, methods of making the compositions, and methods of using the compositions are provided for an enhanced magnetic resonance imaging agent and a hematinic agent, the agents comprising carboxyalkylated reduced polysaccharides coated ultrasmall superparamagnetic iron oxides. Methods of use of the carboxymethyl reduced dextran as a plasma extender are provided. |
Inventor(s): | Groman; Ernest V. (Brookline, MA), Paul; Kenneth G. (Holliston, MA), Frigo; Timothy B. (Waltham, MA), Bengele; Howard (Canton, MA), Lewis; Jerome M. (Newton, MA) |
Assignee: | Advanced Magnetics, Inc. (Cambridge, MA) |
Filing Date: | Mar 08, 2000 |
Application Number: | 09/521,264 |
Claims: | 1. A method of providing an iron oxide complex for administration to a mammalian subject, the method consisting of: producing a carboxyalkylated reduced polysaccharide iron oxide complex; and sterilizing the complex by autoclaving. 2. A method according to claim 1, wherein the reduced polysaccharide is a reduced polymer of glucose. 3. A method according to claim 2, wherein the reduced polymer of glucose is a reduced dextran. 4. A method according to claim 1, wherein the reduced polysaccharide is produced by reacting a polysaccharide with a reagent selected from the group consisting of: a borohydride salt, and hydrogen in the presence of an hydrogenation catalyst. 5. A method according to claim 1, wherein producing the complex includes carboxyalkylating a reduced polysaccharide by carboxymethylation. 6. A method according to claim 5, wherein the reduced polysaccharide is a reduced dextran. 7. A method according to claim 6, wherein the administration to a mammalian subject is administration to a human. 8. A method according to claim 1, wherein the carboxyalkylated, reduced polysaccharide isolated as a sodium salt does not contain an infrared absorption peak in the region of about 1650 cm.sup.-1 to about 1800 cm.sup.-1. 9. A method according to claim 1, wherein producing the carboxyalkylated reduced polysaccharide is achieved at a temperature of less than about 50.degree. C. 10. A method according to claim 11, wherein producing the carboxyalkylated reduced polysaccharide is achieved at a temperature of less than about 40.degree. C. 11. A method according to claim 1, wherein the iron oxide is superparamagnetic. 12. A reduced polysaccharide iron oxide complex produced according to the method of claim 1, wherein the produced complex is stable at a temperature of at least 100.degree. C. 13. A reduced carboxyalkylated polysaccharide iron oxide complex wherein the produced complex is stable at a temperature of about 121.degree. C. 14. A reduced polysaccharide iron oxide complex according to claim 13, wherein the produced complex is stable at a temperature of at least about 121.degree. C. for a period of time effective to sterilize the complex. 15. A reduced polysaccharide iron oxide complex according to claim 14, wherein the carboxyalkylated reduced polysaccharide is selected from the group consisting of a carboxymethyl, carboxyethyl and carboxypropyl reduced polysaccharide. 16. A reduced polysaccharide iron oxide complex according to claim 15, wherein the reduced polysaccharide is a reduced dextran. 17. A reduced polysaccharide iron complex according to claim 15, wherein the carboxyalkylated reduced dextran is a carboxymethyl reduced dextran. 18. A reduced polysaccharide iron oxide complex according to claim 16, wherein the carboxyalkylated reduced dextran comprises at least about 750 micromole of carboxyl groups per gram of polysaccharide. 19. A reduced polysaccharide iron oxide complex according to claim 18, wherein the carboxyalkylated reduced dextran comprises at least about 900 micromole of carboxyl groups per gram of polysaccharide. 20. A reduced polysaccharide iron oxide complex according to claim 19, wherein the carboxyalkylated reduced dextran comprises at least about 1100 micromole of carboxyl groups per gram of polysaccharide. 21. A reduced polysaccharide iron oxide complex according to claim 20, wherein the carboxyalkylated reduced dextran comprises less than about 1500 micromole of carboxyl groups per gram of polysaccharide wherein said complex does not form substantial particulates. 22. A method of providing a contrast agent for in vivo MRI of a subject according to claim 1, consisting of the steps of: formulating a composition which is a carboxymethylated reduced ultrasmall superparamagnetic iron oxide complex; and terminally sterilizing the composition by autoclaving. 23. A method of providing a hematinic agent for treating a subject deficient in iron, consisting of the steps of: formulating a composition which is a carboxymethylated reduced ultrasmall iron oxide complex; and terminally sterilizing the composition by autoclaving. 24. A method according to claim 22 or 23, having the further step of providing the autoclaved composition in a unit dosage. 25. A reduced carboxyalkylated polysaccharide iron oxide complex which is stable at a temperature of about 121.degree. C., wherein a sodium salt of the complex does not contain an infrared absorption peak in the region of about 1650 cm.sup.-1 to about 1800 cm.sup.-1. 26. A reduced carboxyalkylated polysaccharide iron oxide complex according to claim 25, wherein the polysaccharide is carboxymethylated. |