Microspheres useful for therapeutic vascular embolization
Inventors
Reb, Philippe • Pierre, Marion • De Gioannis, Barbara • Krom, James
Assignees
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Publication Number
US-9439861-B2
Publication Date
2016-09-13
Expiration Date
Abstract
Provided herein, for example, are microspheres comprising a gelatin or gelatin substitute and a copolymer of a N-tris-hydroxymethyl methylacrylamide monomer unit, a diethylaminoethylacrylamide monomer unit and a N,N-methylene-bis-acrylamide monomer unit. Also provided are methods of producing microspheres comprising a gelatin or gelatin substitute and a copolymer of a N-tris-hydroxymethyl methylacrylamide monomer unit, a diethylaminoethylacrylamide monomer unit and a N,N-methylene-bis-acrylamide monomer unit. Further provided herein, for example, are compositions comprising the microspheres and methods of using the microspheres and compositions thereof.
Core Innovation
The patent describes methods for making gelatin-crosslinked microspheres comprising a copolymer of N-tris-hydroxymethyl methylacrylamide, diethylaminoethylacrylamide, and N,N-methylene-bis-acrylamide. The methods introduce an aqueous solution containing the monomers and gelatin into a liquid organic phase having low miscibility in water using designated feed equipment configurations; [procedural detail omitted for safety]. The disclosed variations identify feed equipment disposed in the organic phase, a feed system with spaced fingers, and feed ring equipment.
Ultrasonication reduces microsphere aggregation and sticking without observed breakage during processing. In addition, feed-ring processing reduces oil encapsulation and the incidence of cracked or defective spheres. The disclosure identifies vascular embolization uses including tumors, uterine fibroids, vascular malformations, and bleeding, as well as contrast-agent loading and pharmaceutical kits.
Claims Coverage
The claims recite three inventive features directed to methods for producing gelatin-crosslinked copolymer microspheres, distinguished primarily by the feed-system configuration.
Microsphere production using feed equipment
The claim covers making microspheres comprising crosslinked gelatin and a copolymer of N-tris-hydroxymethyl methylacrylamide, diethylaminoethylacrylamide, and N,N-methylene-bis-acrylamide, using feed equipment disposed in a low-miscibility liquid organic phase. [procedural detail omitted for safety]
Microsphere production using a fingered feed system
The claim covers making microspheres comprising the specified copolymer and crosslinked gelatin using a feed system having a longitudinal axis and spaced fingers extending outward from a cross-member connected to the axis to introduce the aqueous solution into the liquid organic phase. [procedural detail omitted for safety]
Microsphere production using feed ring equipment
The claim covers introducing the aqueous solution into the low-miscibility liquid organic phase through feed ring equipment to produce microspheres comprising the specified copolymer and crosslinked gelatin. [procedural detail omitted for safety]
Together, the independent claims define methods of making microspheres comprising the specified copolymer and crosslinked gelatin, distinguishing configurations of feed equipment disposed in the organic phase, a fingered feed system, and feed ring equipment.
Stated Advantages
Ultrasonication reduces microsphere aggregation and sticking, with no observed breakage.
Feed-ring processing can reduce oil encapsulation and cracked or defective spheres.
Documented Applications
Vascular embolization procedures, including cancer treatment, transarterial chemoembolization (TACE), treatment of uterine fibroids, benign prostatic hyperplasia (BPH), vascular and arteriovenous malformations, and bleeding.
Contrast-agent loading and pharmaceutical kits.
Production of microspheres comprising a copolymer with the specified monomer units and gelatin.
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