Contrast agents consisting of galactose particles

• US 5,648,062 A
• Filed: 06/05/1995
• Issued: 07/15/1997
• Est. Priority Date: 01/09/1992
• Status: Expired due to Fees

• Current Assignee: GE Healthcare As (GE Healthcare Technologies, Inc.)
• Original Assignee: Nycomed A/S (Takeda Pharmaceutical Company Limited)
• Inventors: Rongveo, Pal, Klaveness, Jo, Stubberud, Lars
• Primary Examiner(s): Kumar, Shailendra
• Assistant Examiner(s): Cebulak, Mary C.
• Application Number:
  US08/465,112
• Time in Patent Office: 771 Days
• Field of Search: 424/9.5, 424/9.51, 424/9.52, 424/9.34
• US Class Current: 424/9.34
• CPC Class Codes: A61K 49/1821 coated or functionalised microparticles or nanoparticles
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres

Abstract

Water soluble microbubble generating microparticle contrast agents which are comprised of a carbohydrate and a non-triglyceride, non-surface active material for use in image enhancement wherein the non-surface active material is less soluble in water than the carbohydrate.

Claims

1. A contrast agent comprising water-soluble microparticles comprising a carbohydrate in admixture with a non-triglyceride non-surface active material, said contrast agent containing or generating microbubbles of sulphur hexafluoride or fluorinated low molecular weight hydrocarbons, and said non-triglyceride non-surface active material being less water-soluble than said carbohydrate.

2. A contrast agent as claimed in claim 1 in which the carbohydrate is a water-soluble pentose, hexose, disaccharide, cyclodextrin or sugar alcohol.

3. A contrast agent as claimed in claim 2 in which the carbohydrate is galactose.

4. A contrast agent as claimed in claim 1 in which the non-surface active material is selected from the group consisting of high molecular weight polysaccharides;

non-amphiphilic lipids;

fixed oils, fats and waxes;

waxes and mixtures thereof and wherein the weight ratio of the carbohydrate to the non-surface active material is from 1;

4 to 4;

1.

5. A contrast agent as claimed in claim 4 in which the non-surface active material is starch or dextran.

6. A contrast agent as claimed in claim 1 in which the non-surface active material is a water-insoluble inorganic material.

7. A contrast agent as claimed in claim 6 in which the non-surface active material is an iron oxide.

8. A contrast agent as claimed in claim 1 in which the non-surface active material is present in an amount of 25-75% w/w relative to the overall composition.

9. A contrast agent as claimed in claim 1 additionally containing an amphiphilic lipid so as to modify the solubility properties of the microparticles.

10. A contrast agent as claimed in claim 9 containing 0.1-2.0% w/w relative to the overall composition of an amphiphilic lipid selected from fatty acids and salts thereof, steroid acids, sterols, phospholipids and glycolipids.

11. A contrast agent as claimed in claim 1 in which the microparticles are aggregates having an aggregate size of 30-50 micrometres of microparticles having a particle size of 1-10 micrometres.

12. A process for preparing a contrast agent as claimed in claim 1 which comprises (i) either dry mixing the carbohydrate and the non-surface active material or mixing solutions thereof and removing the solvent(s) therefrom and (ii) micronising the resulting mixture to yield the desired microparticles.

13. A process as claimed in claim 12 in which the mixture is micronised by ball-milling.

14. A method of generating an enhanced diagnostic image of a human or non-human animal body comprising administering into the vascular system of said body a diagnostic image enhancing amount of a contrast agent according to claim 1.

15. A method of generating an enhanced diagnostic ultrasonic image of a human or non-human animal body comprising administering into the vascular system of said body a diagnostic ultrasonic image enhancing amount of a contrast agent according to claim 1.

16. A method of generating an enhanced magnetic resonance image of a human or non-human animal body comprising administering to said body an magnetic resonance image enhancing amount of a contrast agent according to claim 1.

17. A contrast agent as claimed in claim 1 which is free from a surfactant.

18. A contrast agent as claimed in claim 1, wherein the weight ratio of the carbohydrate to the non-surface active material is from 1:

4 to 4;

1.