Hydrolytically degradable polymers and hydrogels made therefrom

A method for preparing a polymer having the formula of:

• HO—[(—CH2CH2—O—)n—CO2—]m—(CH2CH2O)n—H
• wherein n is an integer of from about 10 to about 50, m is an integer of from about 5 to about 100, comprising:
• polymerizing an ethylene oxide oligomer having a formula of
• HO—(—CH2CH2—O—)n—O—CO2-1-benzotriazolyl
• in the presence of dimethylaminopyridine and at a temperature of from about 45° C. to about 100° C., either in melt or in anhydrous acetonitrile as solvent, thereby forming said polymer.

A method for preparing a polymer having the formula of:

• HO—[(—CH2CH2—O—)n—CO2—]m—(CH2CH2O)n—H
• wherein n is an integer of from about 10 to about 50, m is an integer of from about 5 to about 100, comprising:
• polymerizing an ethylene oxide oligomer having a formula of
• HO—(—CH2CH2—O—)n—O—CO2—N-succinimidyl
• in the presence of dimethylaminopyridine and at a temperature of from about 45° C. to about 100° C., either in melt or in anhydrous acetonitrile as solvent, thereby forming said polymer.

A method for preparing a hydrolytically degradable polymer comprising:

• providing a first oligomer having a first functional group of —O—CO2—W at one terminus and, at another terminus, a second functional group of —O—CO2—Z, wherein each of said functional groups is capable of reacting with a hydroxyl group to form a carbonate linkage, and wherein Z and W are reactive leaving groups and can be same or different;
• providing a second oligomer having two hydroxyl terminal groups;
• providing a polymerization reaction mixture comprising said first and second oligomers;
• and
• polymerizing said first and second oligomers at conditions sufficient to form said hydrolytically degradable polymer, wherein said polymer has two or more of said oligomers linked to each other by a hydrolytically degradable carbonate linkage, and wherein each of said oligomers comprises two or more alkylene oxide monomers.

A method for preparing a polymer having the formula of:

• HO—[(—CH2CH2—O—)n—CO2—]m—(CH2CH2O)n—H
• wherein n is an integer of from about 10 to about 50, m is an integer of from about 5 to about 100, comprising:
• providing a first ethylene oxide oligomer having the formula of
• HO—(—CH2CH2—O—)n—OH;
• providing a second ethylene oxide oligomer having a formula of 1-benzotriazolyl-O2C—O—(—CH2CH2—O—)n—O—CO2-1-benzotriazolyl;
• and
• co-polymerizing said first and second ethylene oxide oligomer in the presence of dimethylaminopyridine and at a temperature of from about 45° C. to about 100° C., either in melt or in anhydrous acetonitrile as solvent, thereby forming said polymer.

A method for preparing a polymer having the formula of:

• HO—[(—CH2CH2—O—)n—CO2—]m—(CH2CH2O)n—H
• wherein n is an integer of from about 10 to about 50, m is an integer of from about 5 to about 100, comprising:
• providing a first ethylene oxide oligomer having the formula of
• HO—(—CH2CH2—O—)n—OH;
• providing a second ethylene oxide oligomer having a formula of N-succinimidyl-O2C—O—(—CH2CH2—O—)n—O—CO2—N-succinimidyl;
• and
• co-polymerizing said first and second ethylene oxide oligomer in the presence of dimethylaminopyridine and at a temperature of from about 45° C. to about 100° C., either in melt or in anhydrous acetonitrile as solvent, thereby forming said polymer.

A method for preparing a hydrolytically degradable polymer comprising:

• providing an alkylene oxide oligomer having two hydroxyl terminal groups;
• providing an activating molecule having the formula of Z—O—CO2—Z, wherein Z is a reactive leaving group;
• and
• co-polymerizing said oligomer and said activating molecule at conditions sufficient to form said hydrolytically degradable polymer, wherein said polymer comprises two or more of said oligomer linked to each other by hydrolytically degradable carbonate linkages.

A method for preparing a polymer having the formula of:

• HO—[(—CH2CH2—O—)n—CO2]m—(CH2CH2O)n—H
• wherein n is an integer of from about 10 to about 50, m is an integer of from about 5 to about 100, comprising co-polymerizing disuccinimidylcarbonate and
• HO—(—CH2CH2—O—)n—OH,
• in the presence of dimethylaminopyridine and at a temperature of from about 45° C. to about 100° C., either in melt or in anhydrous acetonitrile as solvent, thereby forming said polymer.

A method for preparing a polymer having the formula of:

• HO—[(—CH2CH2—O—)n—CO2—]m—(CH2CH2O)n—H
• wherein n is an integer of from about 10 to about 50, m is an integer of from about 2 to about 100, comprising co-polymerizing bis(1-benzotriazolyl carbonate) and
• HO—(—CH2CH2—O—)n—OH,
• in the presence of dimethylaminopyridine and at a temperature of from about 45° C. to about 100° C. either in melt or in anhydrous acetonitrile as solvent, thereby forming said polymer.

A method for preparing a conjugate having a biologically active agent covalently linked to a hydrolytically degradable polymer, said polymer comprising two or more alkylene oxide oligomers linked to each other by hydrolytically degradable carbonate linkages, said method comprising the steps of:

• providing said hydrolytically degradable polymer;
• activating said hydrolytically degradable polymer to form a reactive terminal moiety in said polymer;
• providing a biologically active agent having an active moiety;
• and
• reacting said reactive terminal moiety in said polymer with said active moiety of said biologically active agent, thereby forming a covalent linkage between said biologically active agent and said polymer.

A polymer having the formula of:

• X—O—{[(R1—O)a—CO2—]h—[(R2—O)b—CO2—]i}m—{[(R3—O)c—CO2—]j—[(R4—O)d—CO2—]k}—(R5—O)e—Y
• wherein
• R1, R2, R3, R4, and R5 are alkyl groups and may be the same or different;
• a, b, c, d, and e are integers of from about 1 to 2000;
• h, i, j, and k are integers of from 0 to about 100, and the sum of h, i, j, and k is from about 2 to 200;
• and
• X and Y are independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, and reactive moieties.