Copolymers of tyrosine-based polyarlates and poly(alkylene oxides)

• US 6,048,521 A
• Filed: 05/27/1998
• Issued: 04/11/2000
• Est. Priority Date: 11/07/1997
• Status: Expired due to Term

• Current Assignee: Rutgers University
• Original Assignee: Rutgers University
• Inventors: Yu, Chun, Kohn, Joachim B.
• Primary Examiner(s): Kulkosky, Peter F.
• Application Number:
  US09/085,571
• Time in Patent Office: 685 Days
• Field of Search: 528/176, 528/195, 528/210, 528/219, 424/78.08
• US Class Current: 424/78.08
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 17/10 containing macromolecular materials
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: C08G 63/672 Dicarboxylic acids and dihydroxy compounds
• CPC Class Codes: C08G 63/6856 Dicarboxylic acids and dihydroxy compounds
• CPC Class Codes: C08G 63/6858 Polycarboxylic acids and polyhydroxy compounds in which at least one of the two components contains aliphatic unsaturation
• CPC Class Codes: C08G 63/78 Preparation processes
• CPC Class Codes: C08G 64/045 containing aliphatic unsaturation
• CPC Class Codes: C08G 64/12 containing nitrogen
• CPC Class Codes: C08G 64/183 containing polyether sequences
• CPC Class Codes: C08L 69/00 Compositions of polycarbonates; Compositions of derivatives of polycarbonates
• CPC Class Codes: C40B 40/14 Libraries containing macromolecular compounds and not covered by groups C40B40/06 - C40B40/12

Abstract

Implantable medical devices and drug delivery implants containing polyarylate random block copolymers are disclosed, along with methods for drug delivery and for preventing the formation of adhesions between injured tissues employing the polyarylate random block copolymers.

Claims

1. The controlled drug delivery system comprising a biologically or pharmaceutically active compound physically coated with a random block copolymer having the formula:

##STR4## wherein R₁ is --CH═

CH-- or (--CH₂ --)_j, in which j is zero or an integer from one to eight;

R₂ is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms and optionally containing at least one ether linkage, and derivatives of biologically and physiologically active compounds covalently bonded to said copolymer;

each R₃ is independently an alkylene group containing up to 4 carbon atoms;

A is selected from the group consisting of;

##STR5## wherein R₈ is selected from the group consisting of saturated and unsaturated, substituted and unsubstituted alkyl, aryl and alkylaryl groups containing up to 18 carbon atoms;

y is between about 5 and about 3000; and

f is the percent molar fraction of alkylene oxide in said copolymer and ranges between about 1 and about 99 mole percent.

2. A controlled drug delivery system comprising a random block copolymer having the formula:

##STR6## wherein R₁ is --CH═

CH-- or (--CH₂ --)_j, in which j is zero or an integer from 1 to 8;

R₂ is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms and optionally containing at least one ether linkage, and derivatives of biologically and physiologically active compounds covalently bonded to said copolymer;

each R₇ is independently an alkylene group containing up to 4 carbon atoms;

A is selected from the group consisting of;

##STR7## wherein R₈ is selected from the group consisting of saturated and unsaturated, substituted and unsubstituted alkyl, aryl and alkylaryl groups containing up to 18 carbon atoms;

y is between about 5 and about 3,000; and

f is the percent molar fraction of alkylene oxide in said copolymer and ranges between about 1 and about 99 mole percent;

physically admixed with a biologically or pharmaceutically active compound.

3. A controlled drug delivery system comprising a biologically or pharmaceutically active compound physically embedded or dispersed into a polymeric matrix formed from a random block copolymer having the formula:

##STR8## wherein R₁ is --CH═

CH-- or (--CH₂ --)_j, in which j is zero or an integer from one to eight;

R₂ is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms and optionally containing at least one ether linkage, and derivatives of biologically and physiologically active compounds covalently bonded to said copolymer;

each R₃ is independently an alkylene group containing up to 4 carbon atoms;

A is selected from the group consisting of;

##STR9## wherein R₈ is selected from the group consisting of saturated and unsaturated, substituted and unsubstituted alkyl, aryl and alkylaryl groups containing up to 18 carbon atoms;

y is between about 5 and about 3000; and

f is the percent molar fraction of alkylene oxide in said copolymer and ranges between about 1 and about 99 mole percent.

4. An implantable medical device comprising a polyarylate polymerized as a random block copolymer with a poly(alkylene oxide), said random block copolymer having the structure:

##STR10## wherein R₁ is --CH═

CH-- or (--CH₂ --)_j in which j is between 0 and 8, inclusive;

R₂ is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms and optionally containing at least 1 ether linkage and derivatives of biologically and pharmaceutically active compounds covalently bonded to said copolymers;

each R₇ is independently an alkylene group containing up to 4 carbon atoms;

R₈ is selected from the group consisting of saturated and unsaturated, substituted and unsubstituted alkyl, aryl and alkylaryl groups containing up to 18 carbon atoms;

y is between about 5 and about 3,000; and

f is the percent molar fraction of alkylene oxide in said copolymer and ranges between about 1 and about 99 mole percent.

5. The implantable medical device of claim 4, wherein the surface of said device is coated with said random block copolymer.

6. The implantable medical device of claim 4, comprising a biologically or pharmaceutically active compound in combination with said random block copolymer, wherein said active compound is present in an amount sufficient for therapeutically effective site-specific or systemic drug delivery.

7. The implantable medical device of claim 6, wherein said biologically or pharmaceutically active compound is covalently bonded to said copolymer.

8. An implantable medical device in the form of a sheet for use as a barrier for surgical adhesion prevention consisting essentially of a polyarylate polymerized as a random block copolymer with a poly(alkylene oxide), said random block copolymer having the structure:

##STR11## wherein R₁ is --CH═

CH-- or (--CH₂ --)_j in which j is between 0 and 8, inclusive;

R₂ is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms and optionally containing at least 1 ether linkage and derivatives of biologically and pharmaceutically active compounds covalently bonded to said copolymers;

each R₇ is independently an alkylene group containing up to 4 carbon atoms;

R₈ is selected from the group consisting of saturated and unsaturated, substituted and unsubstituted alkyl, aryl and alkylaryl groups containing up to 18 carbon atoms;

y is between about 5 and about 3,000; and

f is the percent molar fraction of alkylene oxide in said copolymer and ranges between about 1 and about 99 mole percent.

9. A method for site-specific or systemic drug delivery comprising implanting in the body of a patient in need thereof an mplantable drug delivery device comprising a therapeutically effective amount of a biologically or pharmaceutically active compound in combination with a polyarylate polymerized as a random block copolymer with a poly(alkylene oxide), said random block copolymer having the structure:

##STR12## wherein R₁ is --CH═

CH-- or (--CH₂ --)_j in which j is between 0 and 8, inclusive;

R₂ is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms and optionally containing at least 1 ether linkage and derivatives of biologically and pharmaceutically active compounds covalently bonded to said copolymers;

each R₇ is independently an alkylene group containing up to 4 carbon atoms;

R₈ is selected from the group consisting of saturated and unsaturated, substituted and unsubstituted alkyl, aryl and alkylaryl groups containing up to 18 carbon atoms;

y is between about 5 and about 3,000; and

f is the percent molar fraction of alkylene oxide in said copolymer and ranges between about 1 and about 99 mole percent.

10. The method of claim 9, wherein said biologically or pharmaceutically active compound is covalently bonded to said copolymer.

11. A method for preventing the formation of adhesions between injured tissues comprising inserting as a barrier between said injured tissues a sheet consisting essentially of a polyarylate polymerized as a random block copolymer with a poly(alkylene oxide), wherein said random block copolymer has the structure:

##STR13## wherein R₁ is --CH═

CH-- or (--CH₂ --)_j in which j is between 0 and 8, inclusive;

R₂ is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms and optionally containing at least 1 ether linkage and derivatives of biologically and pharmaceutically active compounds covalently bonded to said copolymers;

each R₇ is independently an alkylene group containing up to 4 carbon atoms;

R₈ is selected from the group consisting of saturated and unsaturated, substituted and unsubstituted alkyl, aryl and alkylaryl groups containing up to 18 carbon atoms;

y is between about 5 and about 3,000; and

f is the percent molar fraction of alkylene oxide in said copolymer and ranges between about 1 and about 99 mole percent.