Lanthanoid complex capsule and particle contrast agents, methods of making and using thereof

Patent metadata

Field	Value
Publication number	US-9579404-B2
Application number	US-201414492749-A
Country	US
Kind code	B2
Filing date	Sep 22, 2014
Priority date	May 5, 2011
Publication date	Feb 28, 2017
Grant date	Feb 28, 2017

Abstract

The invention relates to compositions of DOTA derivative compounds, lanthanoid-DOTA derivative molecular complex, and lanthanoid-complex encapsulated solid lipid particles or capsules, and methods of making and using the compositions. The solid lipid particles or capsules contain micelle cores stabilized by a hyperbranched polymer shell based from a crosslinked DOTA derivative compound or crosslinked lanthanoid-DOTA derivative complex. These solid lipid particles or capsules can be used in various applications, such as contrast agents or drug delivery vehicles.

First claim

What is claimed:

1. A hyperbranched polymer nanoparticle or nanocapsule comprising:
hyperbranched polymeric unit having formula (IV):

and optionally a crosslinking moiety CL,
wherein:
R is H or a cation;
X is O or S;
n is 1-10;
p is the number of the units of formula (IV) ranging from 2 to 200,000; and
crosslinking moiety CL, if present, is a moiety connecting the hyperbranched polymeric units together through covalently bonding to each X of formula (IV).

2. A hyperbranched polymer nanoparticle or nanocapsule comprising:
hyperbranched polymeric units having formula (V):

and optionally a crosslinking moiety CL,
wherein:
M is a chelating metal ion;
X is O or S;
n is 1-10;
p is the number of the units of formula (V) ranging from 2 to 200,000; and
crosslinking moiety CL, if present, is a moiety connecting the hyperbranched polymeric units together through covalently bonding to each X of formula (V).

3. The hyperbranched polymeric nanoparticle or nanocapsule of claim 2 , wherein X is S.

4. The hyperbranched polymeric nanoparticle or nanocapsule of claim 2 , wherein X is O, and the crosslinking agent is divinyl sulfone (DVS), dicarboxylic acid, diepoxybutane, diepoxyoctane, epichlorohydrin, butanediol-diglycidyl ether (BDDE), ethylene glycol diglycidyl ether, polyglycerol polyglycidyl ether, ethylene sulfide, glutaraldehyde, bromoacetic anhydride, acrylic anhydride, 3-mercaptopropanoate, thioacetic acid, or combinations thereof.

5. A hyperbranched polymer shell comprising the crosslinked hyperbranched polymeric nanoparticles or nanocapsules of claim 2 .

6. A contrast agent comprising the hyperbranched polymeric nanoparticle or nanocapsule of claim 2 .

7. A method of magnetic resonance imaging (MM) analysis, comprising:
administering to a patient the hyperbranched polymeric nanoparticle or nanocapsule of claim 2 , wherein the chelated metal is Gd; and
conducting a MRI analysis on the patient.

8. A method of nuclear magnetic resonance (NMR) analysis, comprising:
administering to a patient the hyperbranched polymeric nanoparticle or nanocapsule of claim 2 , wherein the chelated metal is La; and
conducting a NMR analysis on the patient.

9. A method of florescence analysis, comprising:
administering to a patient-the hyperbranched polymeric nanoparticle or nanocapsule of claim 2 , wherein the chelated metal is Eu or Tb; and
conducting a test to analyze florescence properties.

10. A method of positron emission tomography (PET) analysis, comprising:
administering to a patient the hyperbranched polymeric nanoparticle or nanocapsule of claim 2 , wherein the chelated metal is Ga or In; and
conducting a PET analysis on the patient.

11. A method of biomedical imaging, comprising the step of (a) administering to a patient the hyperbranched polymeric nanoparticle or nanocapsule of claim 2 , and (b) conducting a biomedical imaging test on the patient.

12. The hyperbranched polymeric nanoparticles or nanocapsules of claim 2 , where the average nanoparticle or nanocapsule ranges from about 50 to about 150 nm in size.

13. A method of delivering a high concentration of contrast enhancing and/or imaging agents comprising the step of administering to a patient the hyperbranched polymeric nanoparticle or nanocapsule of claim 2 , wherein the chelated metal acts as the contrast enhancing and/or imaging agent.

Assignees

• Univ New York

Inventors

• Walters Marc Anton

Classifications

• A61K49/124

  dendrimers, dendrons, hyperbranched compounds · CPC title

• A61K49/108

  the metal complex being Gd-DOTA · CPC title

• A61K49/1809

  Micelles, e.g. phospholipidic or polymeric micelles · CPC title

• C07F5/003

  without C-Metal linkages · CPC title

• A61K9/5176

  Compounds of unknown constitution, e.g. material from plants or animals (oils, fats, waxes, shellac A61K9/5123) · CPC title