Therapeutic microparticles

• US 20050175709A1
• Filed: 12/09/2004
• Published: 08/11/2005
• Est. Priority Date: 12/11/2003
• Status: Abandoned Application

• Current Assignee: W. L. Gore & Associates (W.L. Gore & Associates)
• Original Assignee: W. L. Gore & Associates (W.L. Gore & Associates)
• Inventors: Williams, Joshua D., Matzen, Melissa J., Davidson, Daniel F., Baty, Ace M. III, Cleek, Robert L., Vonesh, Michael J.
• Application Number:
  US11/008,820
• Publication Number:
  US 20050175709A1
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61B 17/12022 Occluding by internal devices, e.g. balloons or releasable wires plugging an opening in the wall of an organ A61B17/0057; occluders for the cervical canal A61F6/146; vas deferens occluders A61F6/20
• CPC Class Codes: A61B 17/12109 in a blood vessel
• CPC Class Codes: A61B 17/12186 liquid materials adapted to be injected
• CPC Class Codes: A61B 2017/1205 Introduction devices
• CPC Class Codes: A61B 2017/4216 Operations on uterus, e.g. endometrium
• CPC Class Codes: A61L 24/001 Use of materials characterised by their function or physical properties
• CPC Class Codes: A61L 24/0042 Materials resorbable by the body
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence
• CPC Class Codes: A61L 2430/36 for embolization or occlusion, e.g. vaso-occlusive compositions or devices
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C08L 69/00 Compositions of polycarbonates; Compositions of derivatives of polycarbonates

Abstract

Biodegradable, compression resistant microparticles adapted for injection through a catheter system, such as is useful for selective embolization procedures. The microparticles can optimally be neutrally buoyant relative to a target bodily fluid. Various active agents may be included in the microparticles, such an anesthetic which can reduce pain during an embolization procedure. The invention further comprises methods and equipment for testing and delivering compression resistant microparticles.

Claims

1. A microparticle comprising:

a homopolymer of at least a poly(a-hydroxy ester) or a copolymer of at least a poly(a-hydroxy ester) having a trimethylene carbonate moiety;

the microparticle adapted for catheter delivery.

2. A microparticle according to claim 1, wherein said microparticle is an embolic agent.

3. A microparticle according to claim 1, wherein said microparticle is substantially neutrally buoyant relative to a target bodily fluid for a time necessary to deliver a bolus of particles.

4. A microparticle according to claim 1, having at least one bioactive agent.

5. A microparticle according to claim 1, having at least one additive.

6. A microparticle according to claim 1, further comprising at least one coating.

7. A microparticle according to claim 1, having a number of distributed voids.

8. A microparticle according to claim 1, having a convoluted surface.

9. A catheter deliverable microparticle comprising:

at least one bioresorbable base polymer and a void volume, wherein the microparticle is compression resistant.

10. A microparticle according to claim 9, wherein said microparticle is an embolic agent.

11. A microparticle according to claim 9, wherein said microparticle is substantially neutrally buoyant relative to a target bodily fluid for a time necessary to deliver a bolus of particles.

12. A microparticle according to claim 9, having at least one bioactive agent.

13. A microparticle according to claim 9, having at least one additive.

14. A microparticle according to claim 9, further comprising at least one coating.

15. A microparticle according to claim 9, having a number of distributed voids.

16. A microparticle according to claim 9, having a convoluted surface.

17. A bolus of embolic microparticles, comprising:

a plurality of catheter deliverable microparticles, said catheter deliverable microparticles being compression resistant and having at least one bioresorbable base polymer and having a void volume.

18. A bolus of embolic microparticles according to claim 17, wherein a number of said catheter deliverable microparticles have a density which is between 0.9 g/cc and 1.4 g/cc.

19. A bolus of embolic microparticles according to claim 17, wherein a number of said catheter deliverable microparticles have a specific gravity of 0.6 to 1.4 relative to a target bodily fluid.

20. A bolus of embolic microparticles according to claim 17, wherein a therapeutically effective number of said catheter deliverable microparticles are neutrally buoyant relative to a target bodily fluid.

21. A bolus of embolic microparticles according to claim 17, wherein a number of said catheter deliverable microparticles have at least one bioactive agent.

22. A bolus of embolic microparticles according to claim 17, wherein a number of said catheter deliverable microparticles have an external diameter and are resistant to a deformation of said external diameter of greater than 10%.

23. A catheter deliverable microparticle comprising:

at least one bioresorbable base polymer,

a second material which is different from said at least one bioresorbable base polymer,

a void volume in which said second material is present, and

wherein said microparticle is compression resistant.

24. A method of making microparticles comprising

providing an organic solvent;

mixing the organic solvent and a solvated polymer in an aqueous solution;

maintaining the organic solvent in the aqueous solution in a quantity and under conditions that maintain the organic solvent below an organic solvent saturation point of the aqueous solution; and

creating microparticles in the aqueous solution while maintaining the solution below the saturation point.

25. The method of claim 24 that further comprises providing as the organic solvent ethyl acetate.

26. The method of claim 24 that further comprises providing as the organic solvent methylene chloride.

27. A method of testing a microparticle for compression resistance comprising

providing a sample of microparticles suspended in a solution, the microparticles having a given nominal cross-sectional dimension of x;

providing a test apparatus that includes at least one constriction with an effective opening size with a dimension less than x;

passing the sample of microparticles and solution through the at least one constriction in the test apparatus under pressure;

sampling the solution downstream of the at least one constriction to determine if the microparticles passed through the constriction without permanent damage to the microparticles;

wherein particles of dimension x that do not pass through the constriction are deemed compression-resistant.