Formulation of solid nano-sized particles in a gel-forming system

• US 10,434,192 B2
• Filed: 07/31/2018
• Issued: 10/08/2019
• Est. Priority Date: 11/25/2011
• Status: Active Grant

• Current Assignee: Danmarks Pã¦Dagogiske Universitet
• Original Assignee: Danmarks Pã¦Dagogiske Universitet
• Inventors: Jolck, Rasmus Irming, Albrechtsen, Morten, Bjerg, Lise Norkjaer, Andresen, Thomas Lars
• Primary Examiner(s): Brutus, Joel F
• Application Number:
  US16/050,318
• Publication Number:
  US 20180339068A1
• Time in Patent Office: 434 Days
• Field of Search: None
• CPC Class Codes: A61B 5/0073 by tomography, i.e. reconstruction of 3D images from 2D projections A61B5/0066 takes precedence
• CPC Class Codes: A61B 6/481 involving the use of contrast agents
• CPC Class Codes: A61B 6/505 for diagnosis of bone
• CPC Class Codes: A61K 49/04 X-ray contrast preparations
• CPC Class Codes: A61K 49/0457 Semi-solid forms, ointments, gels, hydrogels
• CPC Class Codes: A61K 49/0485 Nanoparticles, nanobeads, nanospheres, nanocapsules, i.e. having a size or diameter smaller than 1 micrometer
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

The present invention relates to novel formulations comprising a plurality of nano-sized solid particles and a gel-forming system, useful, e.g. for imaging of the body of a mammal. Also described are kits comprising such formulations and imaging methods utilizing such formulations or kits.

Claims

1. A method of recording an X-ray image of the body of a mammal, comprising the steps of:

a. providing a formulation comprising a plurality of solid in-organic particles and an organic gel-forming system, wherein the solid in-organic particles have a (number) average diameter of 1-500 nm and comprise or consist of a compound detectable by X-ray imaging, and the organic gel-forming system undergoes gel-formation when injected into a body of a mammal, the formulation is imagable, the plurality of solid in-organic particles comprise one or more selected from the group consisting of X-ray contrast agents, radioactive compounds, paramagnetic compounds, fluorescent compounds, ferromagnetic compounds and mixtures thereof, and the formulation has a viscosity less than 10,000 centipoise (cP) at 20°

C.;

b. administering the formulation to a predetermined location of the mammal; and

c. recording X-ray-based images of at least a part of the body which comprises the predetermined location.

2. The method of recording an X-ray image of the body of a mammal according to claim 1, wherein the X-ray-based images are Computed Tomography (CT)-images.

3. A method of joint radiotherapy and X-ray imaging of a target tissue in a mammal, comprising the steps of:

a, providing a formulation comprising a plurality of solid in-organic particles and an organic gel-forming system, wherein the solid in-organic particles have a (number) average diameter of 1-500 nm and comprise or consist of a compound detectable by X-ray imaging, the organic gel-forming system undergoes gel-formation when injected into a body of a mammal, the formulation is imagable, the plurality of solid in-organic particles comprise one or more selected from the group consisting of X-ray contrast agents, radioactive compounds, paramagnetic compounds, fluorescent compounds, ferromagnetic compounds and mixtures thereof, and the formulation has a viscosity less than 10,000 centipoise (cP) at 20°

C.;

b. administering the formulation to a predetermined target tissue of the mammal;

c. recording X-ray-based images of at least a part of the body which comprises the target tissue, thereby providing a definition of the target tissue; and

d. using the definition of the target tissue obtained in c. to direct external beam radiotherapy to the target tissue.

4. The method according to claim 3, wherein the target tissue comprises undesirably growing cells.

5. The method according to claim 3, wherein the target tissue comprises tumor cells.

6. The method according to claim 3, wherein steps c. and d. are performed simultaneously.

7. The method of joint radiotherapy and X-ray imaging of a target tissue in a mammal according to claim 3, wherein the X-ray-based images are Computed Tomography (CT)-images.

8. A method for directing local administration of a pharmaceutically active agent to a target tissue in a mammal, comprising the steps of:

a. providing a formulation comprising a plurality of solid in-organic particles and an organic gel-forming system, wherein the solid in-organic particles have a (number) average diameter of 1-500 nm and comprise or consist of a detectable compound;

optionally detectable by X-ray imaging, the organic gel-forming system undergoes gel-formation when injected into the body of a mammal, the formulation is imagable;

the plurality of solid in-organic particles comprise one or more selected from the group consisting of X-ray contrast agents, radioactive compounds, paramagnetic compounds, fluorescent compounds, ferromagnetic compounds, and mixtures thereof, and the formulation has a viscosity less than 10,000 centipoise (cP) at 20°

C.;

b. administering the formulation to a predetermined target tissue of the mammal;

c. recording images of at least a part of the body which comprises the target tissue, thereby providing a definition of the target tissue; and

d. using the definition of the target tissue obtained in step c. to direct local administration of a pharmaceutically active agent to the target tissue.

9. The method for directing local administration of a pharmaceutically active agent to a target issue in a mammal according to claim 8, wherein the X-ray-based images are Computed Tomography (CT)-images.