Generated: May 23, 2017
|Title:||Polyol and polyether iron oxide complexes as pharmacological and/or MRI contrast agents|
|Abstract:||Iron oxide complexes, pharmacological compositions and unit dosage thereof, and methods for their administration, of the type employing an iron oxide complex with a polyol, are disclosed. The pharmacological compositions employ a polysaccharide iron oxide complex, wherein the polysaccharide is a modified polyol such as a carboxyalkylated reduced dextran. The complex is stable to terminal sterilization by autoclaving. The compositions are suitable for parenteral administration to a subject for the treatment of iron deficiencies or as MRI contrast agent. The complex is substantially immunosilent, provide minimal anaphylaxis and undergo minimal dissolution in vivo. The pharmacological compositions of the complex contain minimal free iron which can be quantified by a variety of methods.|
|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:||AMAG Pharmaceuticals, Inc. (Lexington, MA)|
1. A method of making an autoclavable carboxymethylated reduced dextran iron oxide complex intended for administration by injection to a mammalian subject, the method
comprising the steps of: (i) reacting a dextran with a borohydride salt, or hydrogen in the presence of a hydrogenation catalyst, to produce a reduced dextran; (ii) carboxymethylating the reduced dextran to produce a carboxymethylated reduced dextran;
(iii) complexing the carboxymethylated reduced dextran with an iron salt to produce a carboxymethylated reduced dextran iron oxide complex; and (iv) sterilizing the carboxymethylated reduced dextran iron oxide complex by autoclaving; the complexing
comprising contacting the carboxymethylated reduced dextran with a mixture of ferric and ferrous salts, cooling the resulting solution and adding ammonium hydroxide to neutralize the solution and recovering the carboxymethylated reduced dextran iron
oxide complex; such complex being stable at a temperature of at least about 121.degree. C. for a period effective to sterilize the complex; wherein the reduced dextran has an average molecular weight of about 10 kDa and a particle size of 10 nm to 50
nm; and the carboxymethylated reduced dextran comprises at least about 1100 micromoles of carboxyl groups per gram and less than about 1500 micromoles of carboxyl groups per gram.
2. The method of claim 1, wherein the carboxymethylated reduced dextran is produced at a temperature of less than about 40.degree. C.
3. The method of claim 1, wherein the contacting is performed in an acidic solution.
4. The method of claim 1, wherein the carboxymethylated reduced dextran iron oxide complex is stable at about 121.degree. C. for 30 minutes.
5. The method of claim 4, wherein the carboxymethylated reduced dextran iron oxide complex is stable at 121.degree. C. for 30 minutes at neutral pH.
6. An autoclavable carboxymethylated reduced dextran iron oxide complex intended for administration by injection to a mammalian subject, wherein the carboxymethylated reduced dextran iron oxide complex is produced by the method of claim 1.
Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.