Medical devices fabricated from homopolymers and copolymers having recurring carbonate units

• US 4,920,203 A
• Filed: 08/02/1988
• Issued: 04/24/1990
• Est. Priority Date: 12/17/1987
• Status: Expired due to Term

• Current Assignee: United States Surgical Corporation (Medtronic Plc)
• Original Assignee: Alliedsignal Inc. (Honeywell International Inc.)
• Inventors: Patel, Kundabhai M., Mares, Frank, Boyle, William J. Jr., Chiu, Tin-Ho, Tang, Reginald T.
• Primary Examiner(s): NOT, DEFINED
• Application Number:
  US07/227,386
• Time in Patent Office: 630 Days
• Field of Search: 528/354, 528/370, 523/111, 523/105, 523/113, 523/115, 128/334, 128/335.5, 525/461, 525/411, 525/413, 525/415, 525/409
• US Class Current: 525/409
• CPC Class Codes: A61L 15/64 specially adapted to be resorbable inside the body
• 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 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: C08L 69/00 Compositions of polycarbonates; Compositions of derivatives of polycarbonates

Abstract

This invention relates to medical devices formed totally or in part from homopolymers or copolymers comprising recurring carbonate moieties.

Claims

1. A medical device formed totally or in part of one or more biopolymers selected from the group consisting of block copolymers having at least one type of recurring monomeric unit of the following General Structures I and II:

##STR12## wherein;

Z is --C(R₅ R₆)--, --NR₅ --, --O-- or a combination thereof, where Z is selected such that there are no adjacent heteroatoms;

n is from 1 to about 8;

m is from 1 to about 8;

R₁, R₂, R₃, and R₄ are the same or different at each occurrence and are hydrogen, aryloxyalkyl, alkyoxyaryl, aryloxyaryl, arylalkyl, alkylarylalkyl, arylalkylaryl, alkylaryl, arylcarbonylalkyl, alkyl, aryl, alkylcarbonyalkyl, cycloalkyl, arylcarbonylaryl, alkylcarbonylarly, alkoxyalkyl, or aryl or alkyl substituted with one or more substituents selected from the group consisting of alkyl, aryl, alkoxy, aryloxy, dialkylamino, diarylamino, and alkylarylamino; and

R₅ and R₆ are the same or different and are R₁, R₂, R₃, R₄, dialkylamino, diarylamino, alkylarylamino, alkoxy, aryloxy, alkanoyl, or arylcarbonyl, or any two of R₁ to R₆ together may form an alkylene chain completing a 3, 4, 5, 6, 7, 8 or 9 membered alicyclic fused, spiro, bicyclic or tricyclic ring system or a combination thereof, which system may optionally include one or more non-adjacent carbonyl, oxa, alkylaza or arylaza groups;

with the proviso that when said biopolymers are copolymer having recurring units of the Structure I derived from trimethylene carbonate, the other recurring monomeric units of the copolymer are not derived from gylcolide or glycolic acid.

2. The device of claim 1 wherein R₁, R₂, R₃, R₄, R₅ and R₆ are the same or different and are selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkylaryl, alkoxyalkyl, aryloxyalkyl, aryloxyaryl, aryl and arylalkyl groups, and aryl, arylalkyl or alkylaryl substituted with one or more alkyl, alkoxy and alkoxyalkyl groups.

3. The device of claim 2 wherein R₁, R₂, R₃, R₄, R₅ and R₆ are the same or different and are selected from the groups consisting of hydrogen, alkyl, cycloalkyl, alkylphenyl, alkoxyalkyl and phenylalkyl, and phenyl, alkylphenyl and phenylalkyl substituted with one or more alkyl or alkoxy groups.

4. The device of claim 3 wherein:

Z is --C(R₅ R₆)--, --O-- or a combination thereof;

n is 1, 2, or 3;

m is 1, 2, 3, 4, 5 or 6; and

R₁ to R₆ are selected from the group consisting of substitutents in which aliphatic moieties include up to about 10 carbon atoms and aryl moieties include up to about 16 carbon atoms.

5. The device of claim 1 wherein said biopolymers comprise at least one type of recurring monomeric units of the following general Structures II and III:

##STR13## wherein;

n is 1 to about 3;

m is 1 to about 4;

R₁, R₂, R₃, R₄, R₅, and R₆ are the same or different and are hydrogen, aryl, alkylaryl, arylalkyl or alkyl, or R₅ and R₆ together may form an aliphatic chain having from about 3 to about 10 membered spiro, bicyclic, or tricyclic ring structure or a combination thereof.

6. The device of claim 5 wherein:

n is 1, 2 or 3;

m is 1, 2 or 3; and

R₁, R₂, R₃, R₄, R₅ and R₆ are the same or different and are hydrogen, alkyl, phenylalkyl or alkylphenyl.

7. The device of claim 6 wherein R₁, R₂, R₃, R₄, R₅ and R₆ are the same or different and are hydrogen or alkyl having from 1 to about 7 carbon atoms.

8. The device of claim 1 wherein the biopolymers comprises at least one type of recurring monomeric unit moieties selected from the group consisting of:

##STR14## wherein;

R₅ and R₆ are the same or different and are hydrogen, alkyl, aryl, cycloalkyl, arylalkyl, alkoxyalkyl, aryloxyalkyl, or aryl or arylalkyl substituted with one or more alkyl or alkoxy groups alkoxy, alkanoyl, dialkylamino, or R₅ and R₆ together may form an alkylene chain completing a 4, 5, 6, 7, 8, 9 or 10 membered spiro, bicyclic, or tricyclic ring structure or a combination thereof, which structure may optionally include one or more non-adjacent divalent carbonyl, oxa, alkylaza or arylaza groups with the proviso that at least one of R₅ or R₆ is other than hydrogen; and

n is 1, 2 or 3.

9. The device of claim 8 wherein R₅ and R₆ are the same or different and are phenyl, phenylalkyl, alkylphenyl, alkyl, or R₅ and R₆ together form alkylene a divalent chain forming a 4 to 8 membered ring structure.

10. The device of claim 9 wherein R₅ and R₆ together form a 5 to 7 membered spiro, or bicyclic ring structure or a combination thereof.

11. The device of claim 8 wherein R₅ and R₆ are the same.

12. The device of claim 11 wherein R₅ and R₆ are the same or different and are alkyl, phenyl, alkylphenyl or phenylalkyl.

13. The device of claim 8 wherein R₅ and R₆ are hydrogen.

14. The device of claim 12 wherein R₅ and R₆ are the same or different and are alkyl of from about 1 to 7 carbon atoms.

15. The device of claim 13 wherein R₅ and R₆ are alkyl of about 1 to 4 carbon atoms.

16. The device of claim 1 wherein the wt % of recurring monomeric units of the Structure I or Structure II included in said copolymer is at least about 50 wt % based on the total wt of monomeric units in the copolymer.

17. The device of claim 16 wherein said wt % is from about 80 wt % to about 100 wt %.

18. The device of claim 17 wherein said wt % is from about 85 to about 100 wt %.

19. The device of claim 18 wherein said wt % is from about 85 to about 99 wt %.

20. The device of claim 1 wherein said biopolymers are selected from the group consisting of copolymers comprising at least one type of recurring unit of the General Structures I and II, and at least other type of recurring monomeric units derived from the group consisting of substituted carbonates, non-substituted carbonates, lactones, dioxepanones, dioxanones other than carbonates, epoxides, epoxide/CO₂, anhydrides, orthoesters, and orthocarbonates.

21. The device of claim 1 wherein said copolymer comprises recurring monomeric units derived from 2, 2-dimethyltrimethylene carbonate and other types of recurring monomeric units derived from orthocarbonates, orthoesters, lactones, trimethylene carbonates, ethylene carbonates and tetramethylene carbonates.

22. The device of claim 1 wherein said copolymer comprises recurring monomeric units derived from trimethylene carbonate and other types of recurring monomeric units derived from lactones.

23. The device of claim 1 which is a totally or partially bioresorbable medical device suitable for implantation in side of a living system to promote regeneration of body tissue.

24. The device of claim 1 which further comprises a biodurable portion.

25. A block copolymer comprising at least one type of recurring monomeric unit of the following General Structures I and II:

##STR15## wherein;

Z is --C(R₅ R₆)--, --NR₅ --, --O-- or a combination thereof, where Z is selected such that there are no adjacent heteroatoms;

n is from 1 to about 8;

m is from 1 to about 8;

R₁, R₂, R₃, and R₄ are the same or different at each occurrence and are hydrogen, aryloxyalkyl, alkyoxyaryl, aryloxyaryl, arylalkyl, alkylarylalkyl, arylalkylaryl, alkylaryl, arylcarbonylalkyl, alkyl, aryl, alkylcarbonyalkyl, cycloalkyl, arylcarbonylaryl, alkylcarbonylarly, alkoxyalkyl, or aryl or alkyl substituted with one or more biologically compatible substituents; and

R₅ and R₆ are the same or different and are R₁, R₂, R₃, R₄, dialkylamino, diarylamino, alkylarylamino, alkoxy, aryloxy, alkanoyl, or arylcarbonyl, or any two of R₁ to R₆ together may form an alkylene chain completing a 3, 4, 5, 6, 7, 8 or 9 membered alicyclic fused, spiro, bicyclic or tricyclic ring system or a combination thereof, which system may optionally include one or more non-adjacent carbonyl, oxa, alkylaza or arylaza groups;

with the proviso that when said copolymers have recurring units of the Structure I derived from trimethylene carbonate, the other recurring monomeric units of copolymer are not derived from gylcolide or glycolic acid.

26. The block copolymer of claim 25 wherein R₁, R₂, R₃, R₄, R₅, and R₆ are the same or different and are selected from the groups consisting of hydrogen, alkyl, cycloalkyl, alkylphenyl, alkoxyalkyl and phenylalkyl, and phenyl, alkylphenyl and phenylalkyl substituted with one or more alkyl or alkoxy groups.

27. The block polymer of claim 26 wherein:

Z is --C(R₅ R₆)--, --O-- or a combination thereof;

n is 1, 2, or 3;

m is 1, 2, 3, 4, 5 or 6; and

R₁ to R₆ are selected from the group consisting of substituents in which aliphatic moieties include up to about 10 carbon atoms and aryl moieties include up to about 16 carbon atoms.

28. The block copolymer of claim 25 comprising at least one type of recurring monomeric unit of the following general Structures II and III:

##STR16## wherein;

n is 1 to about 3;

m is 1 to about 4;

R₁, R₂, R₃, R₄, R₅, and R₆ are the same or different and are hydrogen, aryl, alkylaryl, arylalkyl or alkyl, or R₅ and R₆ together may form an aliphatic chain having from about 3 to about 10 membered spiro, bicyclic or tricyclic ring structure or a combination thereof.

29. The block copolymer of claim 28 wherein:

n is 1, 2 or 3;

m is 1, 2 or 3; and

R₁, R₂, R₃, R₄, R₅ and R₆ are the same or different and are hydrogen, alkyl, phenylalkyl or alkylphenyl.

30. The block copolymer of claim 29 wherein R₁, R₂, R₃, R₄, R₅ and R₆ are the same or different and are hydrogen or alkyl having from 1 to about 7 carbon atoms.

31. The block copolymer of claim 30 comprising at least one type of recurring monomeric unit of the following Structure III:

##STR17##

32. The block copolymer of claim 31 wherein R₅ and R₆ are the same or different and are hydrogen or alkyl having from 1 to about 4 carbon atoms.

33. The block copolymer of claim 25 wherein the wt % of recurring monomeric units of the Structure I or Structure II included in said copolymer is at least about 50 wt % based on the total weight of monomeric units in the copolymer.

34. The block copolymer of claim 33 wherein said wt % is from about 80 wt % to about 100 wt %.

35. The block copolymer of claim 34 wherein said wt % is from about 85 to about 99 wt %.

36. The block copolymer of claim 25 wherein said copolymer comprises at least one type of recurring unit of the General Structures I and II, and at least one other type of recurring monomeric unit derived from the group consisting of substituted carbonates, non-substituted carbonates, lactones, dioxepanones, dioxanones other than carbonates, epoxides, anhydrides, epoxide/CO₂, orthoesters, and orthocarbonates.

37. The block copolymer of claim 36 wherein said copolymer comprises recurring monomeric units derived from 2, 2-dimethyltrimethylene carbonate and at least one other type of recurring monomeric unit derived from orthocarbonates, orthoesters, lactones, trimethylene carbonates, ethylene carbonates or tetramethylene carbonates.

38. The block copolymers of claim 37 wherein said copolymer comprises recurring monomeric units derived from trimethylene carbonate and recurring monomeric units derived from lactones.