US 11,911,532 B2
Reverse thermal gels and their use as vascular embolic repair agents
Robin Shandas, Boulder, CO (US); Steven Lewis, Denver, CO (US); Daewon Park, Englewood, CO (US); Omid Jazaeri, Denver, CO (US); Steven Lammers, Lafayette, CO (US); James Bardill, Aurora, CO (US); and Brisa Pena-Castellanos, Aurora, CO (US)
Assigned to The Regents Of The University of Colorado, A Body Corporate, Denver, CO (US)
Appl. No. 16/498,595
Filed by The Regents Of The University Of Colorado, A Body Corporate, Denver, CO (US)
PCT Filed Mar. 29, 2018, PCT No. PCT/US2018/025059
§ 371(c)(1), (2) Date Sep. 27, 2019,
PCT Pub. No. WO2018/183624, PCT Pub. Date Oct. 4, 2018.
Claims priority of provisional application 62/513,248, filed on May 31, 2017.
Claims priority of provisional application 62/478,457, filed on Mar. 29, 2017.
Prior Publication US 2020/0246502 A1, Aug. 6, 2020
Int. Cl. A61L 24/04 (2006.01); A61L 24/00 (2006.01); C08G 81/02 (2006.01); C08J 3/075 (2006.01)
CPC A61L 24/043 (2013.01) [A61L 24/001 (2013.01); C08G 81/027 (2013.01); C08J 3/075 (2013.01); A61L 2400/06 (2013.01); A61L 2430/36 (2013.01)] 19 Claims
 
1. A reversible thermal gel polymer formulation, comprising:
(a) reversible thermal gel polymers, wherein each of the polymers independently comprise:
a first polymer block comprising first repeating units, wherein each of the first repeating units of the first polymer block independently comprise a hydrophilic group; and
a second polymer block comprising second repeating units, wherein each of the second repeating units of the second polymer block independently comprise a thermosensitive group; wherein:
the first polymer block and the second polymer block are directly or indirectly covalently linked;
wherein:
each of the polymers is independently is characterized by the formula (FX4):

OG Complex Work Unit Chemistry
Y is selected from the group consisting of —OH, a radiopaque group, and a targeting ligand;
L3, if present, is selected from the group consisting of a single bond, —(CH2)q—, —(HCCH)q—, —(CH2CH2X)q—, —(CHXH)q—, —X—, —NR5—, —CX—, —CXX—, —XCX—, —XCX(CH2)qCXX—, —CXNR5—, —NR5CX—, —XCXNR5—, —NR5CXX—, —CX(CH2)qCR5CN—, —(CH2)qX(CH2)r—, —(CH2)qXX(CH2)r, —(CH2)qNR5(CH2)r—, —(CH2)qCX(CH2)r—, —(CH2)qCXX(CH2)r—, —(CH2)qCXNR5(CH2)r—, —(CH2)qNR5CX(CH2)r—, —(CH2)qXCXNR5(CH2)r—, and —(CH2)qNR5CXNR6(CH2)r—;
X is O or S;
W2, if present, is selected from the group consisting of a single bond, —(CH2)q—, —(HCCH)q—, —(CH2CH2X)q—, —(CHXH)q—, —X—, —CXX—, —XCX—, —CX—, —XCX(CH2)qCXX—, and —NR11—;
W2, if present, is selected from the group consisting of a single bond, —(CH2)q—, —(HCCH)q—, —(CH2CH2X)q—, —(CHXH)q—, —X—, —CXX—, —XCX, —CX—, —XCX(CH2)qCXX—, and —NR11—;
each of R1, R2, R3, and R4 is independently selected from the group consisting of hydrogen, halide, and C1-C5 alkyl;
each of a, b and c is independently 0 or 1;
each of q and r is an integer independently selected from the range of 1 to 10:
z is an integer selected from the range of 0 to 4;
m is an integer selected from the range of 1 to 10,000;
n is an integer selected from the range of 1 to 1,000;
p is an integer selected from the range of 1 to 1,000; and
each of R5, R6 and R11 is independently selected from the group consisting of hydrogen, C1-C10 alkyl, C5-C10 aryl, and C5-C10 heteroaryl;
and
(b) a solvent;
wherein said reversible thermal gel polymers are dissolved in said solvent and have a concentration in the solvent selected from the range of 2% to 50% w/v; and
wherein the polymer formulation is characterized by a viscosity less than or equal to 1,500 cP.