Back to results
US 2004/0024136 A1Published application
Degradable carbamate-containing bis(acryloyl) crosslinkers, and degradable crosslinked hydrogels comprising them
AssigneeBiosphere Medical, Inc.
InventorsHongmin Zhang, Alexander Schwarz
Life of this patent
Estimating the term…
Abstract
One aspect of the present invention relates to base-labile, carbamate-containing crosslinkers. A second aspect of the present invention relates to degradable crosslinked polymers and hydrogels comprising a base-labile, carbamate-containing crosslinker. The present invention also relates to methods of preparing base-labile, carbamate-containing crosslinkers. Another aspect of the present invention relates to methods of preparing cross-linked polymers and hydrogels comprising a base-labile, carbamate-containing crosslinker.
Claims66
A compound represented by 1:
- 23
- wherein
- X represents independently for each occurrence O r S;
- L represents independently for each occurrence —O—NH—Q;
- Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR2)nC(O)—, 2-alkylacryloylO(CR2)nC(O)—, 3-alkylacryloylO(CR2)nC(O)—, 2,3-dialkyacryloylO(CR2)nC(O)—, 3,3-dialkylacryloylO(CR2)nC(O)—, 2,3,3-trialkylacryloylO(CR2)nC(O)—, (diene)C(O)—, (vinyl)(CR2)nC(O)—, or (vinyl)ArC(O)—;
- R represents independently for each occurrence H or alkyl;
- Z represents —NH(CR2)nNH—, or —NH(CR2)nJ(CR2)mNH—;
- Ar represents independently for each occurrence aryl or heteroaryl;
- J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH2CH2O)n, or (CH2CH2N(R))n;
- n represents independently for each occurrence an Integer in the range 1-10;
- and
- m represents independently for each occurrence an integer in the range 0-10.
9 more elements
A compound represented by 2:
- 24
- wherein
- X represents independently for each occurrence O or S;
- M represents independently for each occurrence —O—NH—Q;
- Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR2)nC(O)—, 2-alkylacryloylO(CR2)nC(O)—, 3-alkylacryloylO(CR2)nC(O)—, 2,3-dialkylacryloylO(CR2)nC(O)—, 3,3-dialkylacryloylO(CR2)nC(O)—, 2,3,3-trialkylacryloylO(CR2)nC(O)—, (diene)C(O)—, (vinyl)(CR2)nC(O)—, or (vinyl)ArC(O)—;
- R represents independently for each occurrence H or alkyl;
- Z represents —NH(CR2)nNH—, or —NH(CR2)nJ(CR2)mNH—;
- Ar represents independently for each occurrence aryl or heteroaryl;
- J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH2CH2O)n, or (CH2CH2N(R))n;
- G represents (CR(4−t)), aryl, or heteroaryl;
- n represents independently for each occurrence an integer in the range 1-10;
- m represents independently for each occurrence an integer in the range 0-10;
- and
- t represents 3 or 4.
11 more elements
A polymer, comprising a monomer represented by 1:
- 25
- wherein
- X represents independently for each occurrence O or S;
- L represents independently for each occurrence —O—NH—Q;
- Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR2)nC(O)—, 2-alkylacryloylO(CR2)nC(O)—, 3-alkylacryloylO(CR2)nC(O)—, 2,3-dialkylacryloylO(CR2)nC(O)—, 3,3-dialkylacryloylO(CR2)nC(O)—, 2,3,3-trialkylacryloylO(CR2)nC(O)—, (diene)C(O)—, (vinyl)(CR2)nC(O)—, or (vinyl)ArC(O)—;
- R represents independently for each occurrence H or alkyl;
- Z represents —NH(CR2)nNH—, or —NH(CR2)nJ(CR2)mNH—;
- Ar represents independently for each occurrence aryl or heteroaryl;
- J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH2CH2O)n, or (CH2CH2N(R))n;
- n represents independently for each occurrence an integer in the range 1-10;
- and
- m represents independently for each occurrence an integer in the range 0-10.
9 more elements
A polymer, comprising a monomer represented by 2:
- 26
- wherein
- X represents independently for each occurrence O or S;
- M represents independently for each occurrence —O—NH—Q;
- Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR2)nC(O)—, 2-alkylacryloylO(CR2)nC(O)—, 3-alkylacryloylO(CR2)nC(O)—, 2,3-dialkylacryloylO(CR2)nC(O)—, 3,3-dialkylacryloylO(CR2)nC(O)—, 2,3,3-trialkylacryloylO(CR2)nC(O)—, (diene)C(O)—, (vinyl)(CR2)nC(O)—, or (vinyl)ArC(O)—;
- R represents independently for each occurrence H or alkyl;
- Z represents —NH(CR2)nNH—, or —NH(CR2)nJ(CR2)mNH—;
- Ar represents independently for each occurrence aryl or heteroaryl;
- J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH2CH2O)n, or (CH2CH2N(R))n;
- G represents (CR(4−t)), aryl, or heteroaryl;
- n represents independently for each occurrence an integer in the range 1-10;
- m represents independently for each occurrence an integer in the range 0-10;
- and
- t represents 3 or 4.
11 more elements
A method of preparing a compound represented by 1:
- 27
- wherein
- X represents independently for each occurrence O or S;
- L represents independently for each occurrence —O—NH—Q;
- Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR2)nC(O)—, 2-alkylacryloylO(CR2)nC(O)—, 3-alkylacryloylO(CR2)nC(O)—, 2,3-dialkylacryloylO(CR2)nC(O)—, 3,3-dialkylacryloylO(CR2)nC(O)—, 2,3,3-trialkylacryloylO(CR2)nC(O)—, (diene)C(O)—, (vinyl)(CR2)nC(O)—, or (vinyl)ArC(O)—;
- R represents independently for each occurrence H or alkyl;
- Z represents —NH(CR2)nNH—, or —NH(CR2)nJ(CR2)mNH—;
- Ar represents independently for each occurrence aryl or heteroaryl;
- J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH2CH2O)n, or (CH2CH2N(R))n;
- n represents independently for each occurrence an integer in the range 1-10;
- and
- m represents independently for each occurrence an integer in the range 0-10;
- comprising:
- (a) reacting a hydroxylamine with an acrylate, thereby forming an acrylic hydroxamic acid;
- and
- (b) reacting said acrylic hydroxamic acid with a diisocyanate.
13 more elements
A method of preparing a compound represented by 2:
- 28
- wherein
- X represents independently for each occurrence O or S;
- M represents independently for each occurrence —O—NH—Q;
- Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR2)nC(O)—, 2-alkylacryloylO(CR2)nC(O)—, 3-alkylacryloylO(CR2)nC(O)—, 2,3-dialkylacryloylO(CR2)nC(O)—, 3,3-dialkylacryloylO(CR2)nC(O)—, 2,3,3-trialkylacryloylO(CR2)nC(O)—, (diene)C(O)—, (vinyl)(CR2)nC(O)—, or (vinyl)ArC(O)—;
- R represents independently for each occurrence H or alkyl;
- Z represents —NH(CR2)nNH—, or —NH(CR2)nJ(CR2)mNH—;
- Ar represents independently for each occurrence aryl or heteroaryl;
- J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH2CH2O)n, or (CH2CH2N(R))n;
- G represents (CR(4−t)), aryl, or heteroaryl;
- n represents independently for each occurrence an integer in the range 1-10;
- m represents independently for each occurrence an integer in the range 0-10;
- and
- t represents 3 or 4;
- comprising:
- (a) reacting a hydroxylamine with an acrylate, thereby forming a hydroxamic acid;
- and
- (b) reacting said hydroxamic acid with a triisocyanate or tetraisocyanate.
15 more elements
A method of preparing a polymer comprising a monomer represented by 1:
- 29
- wherein
- X represents independently for each occurrence O or S;
- L represents independently for each occurrence —O—NH—Q;
- Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR2)nC(O)—, 2-alkylacryloylO(CR2)nC(O)—, 3-alkylacryloylO(CR2)n(O)—, 2,3-dialkylacryloylO(CR2)nC(O)—, 3,3-dialkylacryloylO(CR2)nC(O)—, 2,3,3-trialkylacryloylO(CR2)nC(O)—, (diene)C(O)—, (vinyl)(CR2)nC(O)—, or (vinyl)ArC(O)—;
- R represents independently for each occurrence H or alkyl;
- Z represents —NH(CR2)nNH—, or —NH(CR2)nJ(CR2)mNH—;
- Ar represents independently for each occurrence aryl or heteroaryl;
- J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH2CH2O)n, or (CH2CH2N(R))n;
- n represents independently for each occurrence an integer in the range 1-10;
- and
- m represents independently for each occurrence an integer in the range 0-10;
- comprising:
- a) reacting a monomer represented by 1 with a second monomer in the presence of an initiator.
11 more elements
A method of preparing a polymer comprising a monomer represented by 2:
- 30
- wherein
- X represents independently for each occurrence O or S;
- M represents independently for each occurrence —O—NH—Q;
- Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR2)nC(O)—, 2-alkylacryloylO(CR2)nC(O)—, 3-alkylacryloylO(CR2)nC(O)—, 2,3-dialkylacryloylO(CR2)nC(O)—, 3,3-dialkylacryloylO(CR2)nC(O)—, 2,3,3-trialkylacryloylO(CR2)nC(O)—, (diene)C(O)—, (vinyl)(CR2)nC(O)—, or (vinyl)ArC(O)—;
- R represents independently for each occurrence H or alkyl;
- Z represents —NH(CR2)nNH—, or —NH(CR2)nJ(CR2)m,NH—;
- Ar represents independently for each occurrence aryl or heteroaryl;
- J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH2CH2O)n, or (CH2CH2N(R))n;
- G represents (CR(4−t)), aryl, or heteroaryl;
- n represents independently for each occurrence an integer in the range 1-10;
- m represents independently for each occurrence an integer in the range 0-10;
- and
- t represents 3 or 4;
- comprising:
- a) reacting a monomer represented by 2 with a second monomer in the presence of an initiator.
13 more elements
A method of preparing a crosslinked gel, comprising a hydrophobic polymer, and a crosslinker represented by 1:
- 31
- wherein
- X represents independently for each occurrence O or S;
- L represents independently for each occurrence —O—NH—Q;
- Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR2)nC(O)—, 2-alkylacryloylO(CR2)nC(O)—, 3-alkylacryloylO(CR2)nC(O)—, 2,3-dialkylacryloylO(CR2)nC(O)—, 3,3-dialkylacryloylO(CR2)nC(O)—, 2,3,3-trialkylacryloylO(CR2)nC(O)—, (diene)C(O)—, (vinyl)(CR2)nC(O)—, or (vinyl)ArC(O)—;
- R represents independently for each occurrence H or alkyl;
- Z represents —NH(CR2)nNH—, or —NH(CR2)nJ(CR2)mNH—;
- Ar represents independently for each occurrence aryl or heteroaryl;
- J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH2CH2O)n, or (CH2CH2N(R))n;
- n represents independently for each occurrence an integer in the range 1-10;
- and
- m represents independently for each occurrence an integer in the range 0-10;
- comprising:
- a) reacting a monomer represented by 1 with a hydrophobic monomer in the presence of an initiator.
11 more elements
A method of preparing a crosslinked gel comprising a hydrophobic polymer and a crosslinker represented by 2:
- 32
- wherein
- X represents independently for each occurrence O or S;
- M represents independently for each occurrence —O—NH—Q;
- Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR2)nC(O)—, 2-alkylacryloylO(CR2)nC(O)—, 3-alkylacryloylO(CR2)nC(O)—, 2,3-dialkylacryloylO(CR2)nC(O)—, 3,3-dialkylacryloylO(CR2)nC(O)—, 2,3,3-trialkylacryloylO(CR2)nC(O)—, (diene)C(O)—, (vinyl)(CR2)nC(O)—, or (vinyl)ArC(O)—;
- R represents independently for each occurrence H or alkyl;
- Z represents —NH(CR2)nNH—, or —NH(CR2)nJ(CR2)mNH—;
- Ar represents independently for each occurrence aryl or heteroaryl;
- J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH2CH2O)n, or (CH2CH2N(R))n;
- G represents (CR(4−t)), aryl, or heteroaryl;
- n represents independently for each occurrence an integer in the range 1-10;
- m represents independently for each occurrence an integer in the range 0-10;
- and
- t represents 3 or 4;
- comprising:
- a) reacting a monomer represented by 2 with a hydrophobic monomer in the presence of an initiator.
13 more elements
A method of preparing a crosslinked hydrogel, comprising a hydrophilic polymer and a crosslinker represented by 1:
- 33
- wherein
- X represents independently for each occurrence O or S;
- L represents independently for each occurrence —O—NH—Q;
- Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR2)nC(O)—, 2-alkylacryloylO(CR2)nC(O)—, 3-alkylacryloylO(CR2)nC(O)—, 2,3-dialkylacryloylO(CR2)nC(O)—, 3,3-dialkylacryloylO(CR2)nC(O)—, 2,3,3-trialkylacryloylO(CR2)nC(O)—, (diene)C(O)—, (vinyl)(CR2)nC(O)—, or (vinyl)ArC(O)—;
- R represents independently for each occurrence H or alkyl;
- Z represents —NH(CR2)nNH—, or —NH(CR2)nJ(CR2)mNH—;
- Ar represents independently for each occurrence aryl or heteroaryl;
- J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH2CH2O)n, or (CH2CH2N(R))n;
- n represents independently for each occurrence an integer in the range 1-10;
- and
- m represents independently for each occurrence an integer in the range 0-10;
- comprising:
- a) reacting a monomer represented by 1 with a hydrophilic monomer in the presence of an initiator.
11 more elements
A method of preparing a crosslinked hydrogel, comprising a hydrophilic polymer and a crosslinker represented by 2:
- 34
- wherein
- X represents independently for each occurrence O or S;
- M represents independently for each occurrence —O—NH—Q;
- Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR2)nC(O)—, 2-alkylacryloylO(CR2)nC(O)—, 3-alkylacryloylO(CR2)nC(O)—, 2,3-dialkylacryloylO(CR2)nC(O)—, 3,3-dialkylacryloylO(CR2)nC(O)—, 2,3,3-trialkylacryloylO(CR2)nC(O)—, (diene)C(O)—, (vinyl)(CR2)nC(O)—, or (vinyl)ArC(O)—;
- R represents independently for each occurrence H or alkyl;
- Z represents —NH(CR2)nNH—, or —NH(CR2)nJ(CR2)mNH—;
- Ar represents independently for each occurrence aryl or heteroaryl;
- J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH2CH2O)n, or (CH2CH2N(R))n;
- G represents (CR(4−t)), aryl, or heteroaryl;
- n represents independently for each occurrence an integer in the range 1-10;
- m represents independently for each occurrence an integer in the range 0-10;
- and
- t represents 3 or 4;
- comprising:
- a) reacting a monomer represented by 1 with a hydrophilic monomer in the presence of an initiator.
13 more elements
Dependencies are inferred from the claim text.