MICROSPHERES OF HYDROLYSED STARCH WITH ENDOGENOUS, CHARGED LIGANDS

• US 20120244198A1
• Filed: 11/17/2010
• Published: 09/27/2012
• Est. Priority Date: 12/04/2009
• Status: Active Grant

• Current Assignee: Magle AB (Hans Henrik Lidgard, LLD)
• Original Assignee: Magle AB (Hans Henrik Lidgard, LLD)
• Inventors: Malmsjo, Malin, Thordarson, Eddie, Apell, Sten Peter, Fyhr, Peter
• Granted Patent: US 9,708,416 B2
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61K 31/718 Starch or degraded starch, e.g. amylose, amylopectin
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61L 15/28 Polysaccharides or their derivatives A61L15/225 takes precedence
• CPC Class Codes: A61L 24/08 Polysaccharides A61L24/043 takes precedence
• CPC Class Codes: A61L 2400/04 Materials for stopping bleeding
• CPC Class Codes: A61L 2430/36 for embolization or occlusion, e.g. vaso-occlusive compositions or devices
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: C08B 31/003 Crosslinking of starch
• CPC Class Codes: C08B 31/04 of organic acids , e.g. alkenyl-succinated starch
• CPC Class Codes: C08L 3/04 Starch derivatives , e.g. crosslinked derivatives
• CPC Class Codes: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]

Abstract

Biodegradable microspheres having a diameter of 10-2000 μm having cross-linked hydrolysed starch onto which at least one type of ligand has been coupled via a carboxylic ester bond. The ligand shall be an endogenous, charged molecule with a molecular mass of less than 1000 Da having at least one additional carboxylic acid function in addition to the one utilised for coupling the ligand to the microsphere and/or at least one amine function. On average 0.05-1.5 ligands are coupled to each glucose moiety in the hydrolysed starch.

Claims

1. A biodegradable microsphere having a diameter of 10-2000 μ

m comprising cross-linked hydrolysed starch onto which at least one type of ligand has been coupled via a carboxylic ester bond, wherein said ligand is an endogenous, charged molecule with a molecular mass of less than 1000 Da comprising at least one additional carboxylic acid function and/or at least one amine function, and wherein on average 0.05-1.5 ligands have been coupled to each glucose moiety in the hydrolysed starch.

2. The microsphere according to claim 1, wherein said ligand is selected from the group consisting of amino acids, nitrogen containing organic acids and dioic acids.

3. The microsphere according to claim 1, wherein said ligand is positively charged.

4. The microsphere according to claim 1, wherein said ligand is negatively charged.

5. The microsphere according to claim 1, where the ligand is zwitter ionic.

6. The microsphere according to claim 4, wherein the ligand has a physiologically active counter ion.

7. The microsphere according to claim 6 for use in hemostasis, wherein the microsphere has a mean diameter of 10-200 μ

m.

8. The microsphere according to claim 7, wherein the counter ion is ellagic acid.

9. A material for use in connection with wound healing comprising microspheres according to claim 3, wherein said microspheres forms a three-dimensional structure comprising voids between the microspheres.

10. The material according to claim 9, wherein each microsphere is part of a homogenous size fraction with maximum variation of the mean diameter of ±

15%.

11. The material according to claim 9, wherein the microspheres have a mean diameter of from 200 μ

m to 2000 μ

m.

12. The material according to claim 9, wherein the ligand is hydrophobic.

13. The microsphere according to claim 1 for use in in vitro cell culture, wherein the microspheres have a mean diameter of from 200 μ

m to 1000 μ

m.

14. The microsphere according to claim 6 for use for vascular embolisation, wherein the microsphere has a mean diameter of 10-1200 μ

m.

15. The microsphere according to claim 14, wherein where the counter ion is a cytostatic agent.

16. A wound dressing comprising the material according claim 9.

17. The method for carrying out hemostasis by administering an effective amount of a microsphere according to claim 1 to a mammal suffering from a bleeding wound.

18. The method for carrying out wound healing by adding an effective amount of a material according to claim 9 to a mammal suffering from a wound.

19. The method for in vitro cultivation of cells, wherein at least one microsphere according to claim 1 is added to a culture medium to which also the cells to be cultivated are added, the cells are then allowed to propagate.

20. The method for carrying out vascular embolisation by adding an effective amount of a microsphere according to claim 1 to a mammal in need of vascular embolism.