Contrast enhancing agent having a polymeric core and polymeric shell

• US 6,270,748 B1
• Filed: 01/18/2000
• Issued: 08/07/2001
• Est. Priority Date: 01/19/1999
• Status: Expired due to Fees

• Current Assignee: Rohm and Haas Company (Dow, Inc.)
• Original Assignee: Rohm and Haas Company (Dow, Inc.)
• Inventors: Reynolds, Charles Howard, Annan, Nikoi, Shaber, Steven Howard, Langenmayr, Eric Jon
• Primary Examiner(s): Hartley, Michael G.
• Application Number:
  US09/484,619
• Time in Patent Office: 567 Days
• Field of Search: 424/9.3, 424/9.32, 424/9.322, 424/9.323, 424/9.36, 424/9.4, 424/9.41, 424/9.411, 424/1.21, 424/1.25, 424/1.29, 424/1.33, 424/1.37
• US Class Current: 424/9.322
• CPC Class Codes: A61K 49/1806 Suspensions, emulsions, colloids, dispersions
• CPC Class Codes: A61K 49/1854 the organic macromolecular compound being obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly(meth)acrylate, polyacrylamide, polyvinylpyrrolidone, polyvinylalcohol
• CPC Class Codes: Y10S 977/788 Of specified organic or carbon-based composition
• CPC Class Codes: Y10S 977/93 MRI contrast agent

Abstract

The present invention pertains to an image enhancing agent having a polymeric core including an image-enhancing compound chemically bound thereto and a polymeric shell surrounding the core and compound. The agent may be used for enhancing MRI images, by introducing gadolinium or other appropriate material into the core. Generally, the core is formed from an acid monomer and an esterified monomer. Preferably, a cross-linking monomer is included in the core.

Claims

1. An image enhancing agent comprising:

a polymeric core having an image-enhancing compound chemically bound thereto; and

a polymeric shell surrounding said core and compound,

wherein said core comprises a polymer formed from a monomer mixture comprising between 10 and 90% acid monomer, and 10 and 90% esterified monomer, and

wherein said compound is a metal that binds to acidic regions in said core.

2. The agent of claim 1 wherein said metal is gadolinium.

3. The agent of claim 1 wherein said shell completely encapsulates said core.

4. The agent of claim 1 wherein said core comprises a polymer formed from a monomer mix comprising 50 to 70% acid monomer and 30-50% esterified monomer.

5. The agent of claim 4 wherein said acid monomer is at least one compound selected from the group consisting of acrylic acid, methacrylic acid, methyl methacrylate, styrene, ethyl acrylate, butyl acrylate, 2-ethylhexyl acrylate, dimethylaminoethyl methacrylate, tert-butylaminoethyl methacrylate, hydroxyethyl methacrylate, and hydroxypropyl methacrylate.

6. The agent of claim 5 wherein said monomer mix further comprises up to 10% of a cross-linking agent selected from the group consisting of allyl methacrylate (ALMA), ethylene glycol dimethacrylate (EGDMA), trimethylolpropane trimethacrylate (TMPTMA), divinyl benzene (DVB), glycidyl methacrylate, 2,2-dimethylpropane 1,3 diacrylate, 1,3-butylene glycol diacrylate, 1,3-butylene glycol dimethacrylate, 1,4-butanediol diacrylate, diethylene glycol diacrylate, diethylene glycol dimethacrylate, 1,6-hexanediol diacrylate, 1,6-hexanediol dimethacrylate, tripropylene glycol diacrylate, triethylene glycol dimethacrylate, tetraethylene glycol diacrylate, polyethylene glycol 200 diacrylate, tetraethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, ethoxylated bisphenol A diacrylate, ethoxylated bisphenol A dimethacrylate, polyethylene glycol 600 dimethacrylate, poly(butanediol) diacrylate, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, pentaerythritol triacrylate, trimethylolpropane triethoxy triacrylate, glyceryl propoxy triacrylate, pentaerythritol tetraacrylate, pentaerythritol tetramethacrylate, and dipentaerythritol monohydroxypentaacrylate.

7. The agent of claim 4 wherein said shell comprises a polymer formed from a monomer mixxture having up to 15% acid monomer to provide hydrophilic functionality in said shell.

8. A method of generating an image comprising administering to a subject the image-enhencing agent of claim 1, and subjecting said subject to and image-forming procedure.

9. The method of claim 8 wherein said image forming procedure is an MRI procedure.

10. The method of claim 9 wherein the polymeric core of said image enhancing agent contains a polymer formed from a monomer mix comprising 50 to 70% acid monomer and 30-50% esterified monomer, and the shell of said image enhancing agent contains a polymer formed from a monomer mixture having up to 15% acid monomer to provide hydrophilic functionality in said shell.