Methods for delivering in vivo uniform dispersed embolic compositions of high viscosity

• US 6,454,738 B1
• Filed: 05/19/2000
• Issued: 09/24/2002
• Est. Priority Date: 05/21/1999
• Status: Expired due to Term

• Current Assignee: Covidien LP (Medtronic Plc)
• Original Assignee: Micro Therapeutics, Inc. (Medtronic Plc)
• Inventors: Whalen, Tom II, Hayman, Douglas Ray, Tran, Chinh Ngoc
• Primary Examiner(s): Low, Christopher S. F.
• Assistant Examiner(s): Robinson, Hope A.
• Application Number:
  US09/574,963
• Time in Patent Office: 858 Days
• Field of Search: 604/49, 604/30, 424/423, 424/9.411, 424/428, 424/78.37, 514/2, 514/21
• US Class Current: 604/500
• CPC Class Codes: A61K 49/0419 Microparticles, microbeads, microcapsules, microspheres, i.e. having a size or diameter higher or equal to 1 micrometer
• CPC Class Codes: A61L 24/001 Use of materials characterised by their function or physical properties
• 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 24/06 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043, A61L24/046 take precedence
• CPC Class Codes: A61L 24/08 Polysaccharides A61L24/043 takes precedence
• CPC Class Codes: A61L 2430/36 for embolization or occlusion, e.g. vaso-occlusive compositions or devices
• CPC Class Codes: A61M 2025/1052 for temporarily occluding a vessel for isolating a sector
• CPC Class Codes: C08J 3/091 characterised by the chemical constitution of the organic liquid
• CPC Class Codes: C08L 29/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids

Abstract

Disclosed are novel techniques for embolizing blood vessels which are particularly suited for treating vascular lesions via catheter delivery of an embolic composition.

Claims

1. A method for embolizing a vascular site, said method comprising:

(a) preparing an embolic composition comprising (1) a biocompatible polymer, (2) a biocompatible solvent which solubilizes said polymer, and (3) a water insoluble contrast agent which is suspended in said composition, wherein said embolic composition has a viscosity of at least 150 centistokes at 40°

C.,

(b) heating and mixing the embolic composition to at least 40°

C. to form a uniform suspension,

(c) transferring the heated embolic composition to a delivery catheter having a proximal end and a distal end, wherein the distal end of the delivery catheter is positioned at the vascular site to be embolized, and

(d) injecting the heated embolic composition into said vascular site in sufficient amounts to embolize said vascular site.

2. The method according to claim 1 wherein the composition transferred in (c) is maintained at a temperature above 40°

C.

3. The method according to claim 1 wherein, prior to (d) above, a blood flow attenuating device is inserted immediately upstream the ejection port of said catheter.

4. The method according to claim 3 wherein said blood flow attenuating device is an inflatable microballoon which permits both normal and attenuated blood flow depending upon whether the microballoon is deflated or inflated.

5. The method according to claim 1, wherein said composition has a viscosity of at least 200 centistokes at 40°

C.

6. The method according to claim 5, wherein said composition has a viscosity of at least 500 centistokes at 40°

C.

7. The method according to claim 6, wherein said composition has a viscosity of from at least 500 to 5,000 centistokes at 40°

C.

8. The method according to claim 1, wherein the concentration of biocompatible polymer employed in said composition is from 6 to 50 weight percent.

9. The method according to claim 8, wherein the concentration of biocompatible polymer employed in said composition is from 8 to 30 weight percent.

10. The method according to claim 1 wherein said biocompatible solvent is selected from the group consisting of ethyl lactate, dimethylsulfoxide, ethanol and acetone.

11. The method according to claim 10 wherein said biocompatible solvent is dimethylsulfoxide.

12. The method according to claim 1 wherein said water insoluble contrast agent is selected from the group consisting of tantalum, tantalum oxide, tungsten and barium sulfate.

13. The method according to claim 12 wherein said contrast agent is tantalum.

14. The method according to claim 1 wherein said biocompatible polymer is a non-biodegradable, biocompatible polymer.

15. The method according to claim 14 wherein said non-biodegradable, biocompatible polymer is selected from the group consisting of cellulose acetates, ethylene vinyl alcohol copolymers, hydrogels, polyacrylonitrile, polyvinylacetate, cellulose acetate butyrate, nitrocellulose, copolymers of urethane/carbonate, copolymers of styrene/maleic acid, and mixtures thereof.

16. The method according to claim 15 wherein said biocompatible polymer is an ethylene and vinyl alcohol copolymer.

17. The method according to claim 1 wherein said biocompatible polymer is a biodegradable, biocompatible polymer.

18. The method according to claim 1 wherein said catheter has a length of at least 50 cm.

19. A method for embolizing a vascular site, said method comprising:

(a) preparing an embolic composition comprising (1) a biocompatible polymer, (2) a biocompatible solvent which solubilizes said polymer, and (3) a water insoluble contrast agent which is suspended in said composition, wherein said embolic composition has a viscosity of at least 150 centistokes at 40°

C.,

(b) heating and mixing the embolic composition to at least 40°

C. to form a uniform suspension,

(c) positioning the distal end of a delivery catheter having a proximal end and a distal end into the vascular site to be embolized,

(d) positioning a flow arresting device at the vascular site to be embolized,

(e) connecting the delivery catheter to the embolic composition prepared in (a) above under conditions wherein the temperature of the composition is above room temperature,

(f) activating the flow arresting device at the vascular site to be embolized such that the activated device reduces blood flow through the vascular site to be embolized but does not occlude the delivery catheter,

(g) injecting said composition into said vascular site under conditions wherein the temperature of said composition at the ejection port is in equilibrium with the body temperature of said mammal,

(h) deactivating the flow arresting device to permit sufficient blood flow through said vasculature to be embolized such that removal of the biocompatible solvent is facilitated and oxygenated blood is delivered to the tissue distal to said flow arresting device, and

(i) repeating steps (f)-(h) as necessary to effect embolization of said vascular site.

20. The method according to claim 19 wherein the composition transferred in (e) is maintained at a temperature above 40°

C.