Absorbable polyoxaesters containing amines and/or amido groups

• US 5,595,751 A
• Filed: 02/08/1996
• Issued: 01/21/1997
• Est. Priority Date: 03/06/1995
• Status: Expired due to Term

• Current Assignee: Ethicon Incorporated (Johnson & Johnson)
• Original Assignee: Ethicon Incorporated (Johnson & Johnson)
• Inventors: Bezwada, Rao S., Jamiolkowski, Dennis D.
• Primary Examiner(s): Acquah, Samuel A.
• Application Number:
  US08/598,721
• Time in Patent Office: 348 Days
• Field of Search: 528/361, 528/363, 424/422, 424/426, 424/428, 424/430, 424/431, 424/432, 424/433, 424/443, 424/444, 424/446, 424/447, 424/448, 424/486, 428/35.7, 428/36.2, 428/98, 428/99, 428/221, 428/224, 428/361, 428/364
• US Class Current: 424/422
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 15/225 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 15/26 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof A61L15/225 takes precedence
• CPC Class Codes: A61L 15/60 Liquid-swellable gel-forming materials, e.g. super-absorbents
• CPC Class Codes: A61L 15/64 specially adapted to be resorbable inside the body
• CPC Class Codes: A61L 17/105 Polyesters not covered by A61L17/12
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 29/049 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 29/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• 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 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: C08G 63/66 Polyesters containing oxygen in the form of ether groups C08G63/42, C08G63/58 take precedence
• CPC Class Codes: C08G 63/664 derived from hydroxy carboxylic acids
• CPC Class Codes: C08G 63/672 Dicarboxylic acids and dihydroxy compounds
• CPC Class Codes: C08G 69/40 Polyamides containing oxygen in the form of ether groups C08G69/12, C08G69/32 take precedence
• CPC Class Codes: C08G 69/44 Polyester-amides
• CPC Class Codes: C08L 101/00 : Compositions of unspecified macromolecular compounds
• CPC Class Codes: C08L 2666/02 : Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 67/00 : Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain of polyester-amides C08L77/12; of polyester-imides C08L79/08; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 67/025 : containing polyether sequences
• CPC Class Codes: C08L 77/12 : Polyester-amides
• CPC Class Codes: C09D 167/00 : Coating compositions based on polyesters obtained by reactions forming a carboxylic ester link in the main chain based on polyester-amides C09D177/12; based on polyester-imides C09D179/08; Coating compositions based on derivatives of such polymers
• CPC Class Codes: Y10T 428/1352 : Polymer or resin containing [i.e., natural or synthetic]
• CPC Class Codes: Y10T 428/1366 : Textile, fabric, cloth, or pile is sandwiched between two distinct layers of material unlike the textile, fabric, cloth, or pile layer
• CPC Class Codes: Y10T 428/24 : Structurally defined web or sheet [e.g., overall dimension, etc.]
• CPC Class Codes: Y10T 428/24008 : including fastener for attaching to external surface
• CPC Class Codes: Y10T 428/249921 : Web or sheet containing structurally defined element or component
• CPC Class Codes: Y10T 428/2907 : with coating or impregnation
• CPC Class Codes: Y10T 428/2913 : Rod, strand, filament or fiber
• CPC Class Codes: Y10T 442/2525 : Coating or impregnation functions biologically [e.g., insect repellent, antiseptic, insecticide, bactericide, etc.]

Abstract

The present invention describes a new aliphatic polyoxaesters that is bioabsorbable and may be used to produce surgical devices such as sutures, sutures with attached needles, molded devices, and the like. The invention also contemplates a process for producing these polyesters. The aliphatic polyoxaesters of the present invention have a first divalent repeating unit of formula I:

[O--C(O)--C(R.sub.1)

(R₂)--O--(R₃)--O--C(R₁)(R₂)--C(O)--] I

and a second repeating unit of the formula:

[--O--R.sub.12 --].sub.U,                                  XVI

and optionally a third repeating unit with a formula selected from the group consisting of:

[--O--R.sub.4 --].sub.A,                                   II

[--O--R.sub.5 --C(O)--].sub.B,                             III

([--O--R.sub.5 --C(O)].sub.P,--O--).sub.L G                XI

and combinations thereof wherein R₁₂ contains an internal amine or internal amide group.

Claims

1. An aliphatic polyoxaesters comprising a first divalent repeating unit of formula I:

space="preserve" listing-type="equation">[O--C(O)--C(R.sub.1)(R.sub.2)--O--(R.sub.3)--O--C(R.sub.1)(R.sub.2)--C(O)--]I

and a second repeating unit selected from the group of formulas consisting of;

space="preserve" listing-type="equation">[--O--R.sub.12 --].sub.U, XIV

wherein R₁ and R₂ are independently hydrogen or an alkyl group containing 1 to 8 carbon atoms;

R₃ is an alkylene unit or is an oxyalkylene group of the following formula;

space="preserve" listing-type="equation">--[(CH.sub.2).sub.C --O--].sub.D --(CH.sub.2).sub.E -- IV

wherein C is an integer in the range of from 2 to about 5, D is an integer in the range of from about 0 to about 12, and E is an integer in the range of from about 2 to about 5, except when D is zero in which case E will be an integer from 2 to 12;

R₁₂ is an alkylene unit containing from 2 to 8 carbon atoms and containing an internal amine (--N(R₁₀)--) or amide (--N(R₁₁)--);

R₁₀ and R₁₁ are independently hydrogen or an alkyl group containing 1 to 8 carbon atoms; and

U is an integer in the range of from 1 to 1,000.

2. The aliphatic polyoxaester of claim 1 wherein the aliphatic polyoxaester additionally contains a third repeating unit selected from the group consisting of:

space="preserve" listing-type="equation">[--O--R.sub.4 --].sub.A, II

space="preserve" listing-type="equation">[--O--R.sub.5 --C(O)--].sub.B, III

space="preserve" listing-type="equation">([--O--R.sub.13 --C(O)].sub.P --O--).sub.L G and XI

and combinations thereof;

wherein R₄ is an alkylene unit containing from 2 to 8 carbon atoms;

A is an integer in the range of from 1 to 1,000;

R₅ and R₁₃ are independently selected from the group consisting of --C(O)(R₇)--, --(CH₂)₃ --O--, --CH₂ --CH₂ --O--CH₂ --, --CR₈ H--CH₂ --, --(CH₂)₄ --, --(CH₂)_F --O--C(O)-- and --(CH₂)_K --C(O)--CH₂ --;

R₆ and R₇ are independently hydrogen or an alkyl containing from 1 to 8 carbon atoms;

R₈ is hydrogen or methyl;

F and K are integers in the range of from 2 to 6;

B is an integer in the range of from 1 to n such that the number average molecular weight of formula III is less than about 40,000;

P is an integer in the range of from 1 to m such that the number average molecular weight of formula XI is less than about 40,000;

G represents the residue minus from 1 to L hydrogen atoms from the hydroxyl groups of an alcohol previously containing from 2 to 12 hydroxyl groups; and

L is an integer from about 1 to about 12.

3. The aliphatic polyoxaesters of claim 1 wherein the polymer has the formula:

space="preserve" listing-type="equation">[--O--C(O)--C(R.sub.1) (R.sub.2)--O--(R.sub.3)--O--C(R.sub.1) (R.sub.2)C(O)--(O--R.sub.12).sub.U --].sub.N

wherein N is an integer in the range of from about 1 to about 300,000.

4. The aliphatic polyoxaesters of claim 2 wherein the polymer has the formula:

space="preserve" listing-type="equation">[(--C(O)--C(R.sub.1) (R.sub.2)--O--R.sub.3 --O--C(R.sub.1) (R.sub.2)--C(O)--(O--R.sub.12).sub.U --O).sub.S (C(O)--R.sub.5 --O).sub.B ].sub.W

wherein S and W are independently integers in the range of from about 1 to about 1,000.

5. The aliphatic polyoxaesters of claim 2 wherein the polymer has the formula:

space="preserve" listing-type="equation">[(--C(O)--C(R.sub.1) (R.sub.2)--O--R.sub.3 --O--C(R.sub.1) (R.sub.2)--C(O)--(O--R.sub.12).sub.U --O).sub.S ([--O--R.sub.13 --C(O)].sub.P --O--).sub.L G].sub.W

wherein S and W are independently integers in the range of from about 1 to about 1,000.

6. A device made from an aliphatic polyoxaesters comprising a first divalent repeating unit of formula I:

space="preserve" listing-type="equation">[O--C(O) --C(R.sub.1)(R.sub.2)--O--(R.sub.3)--O--C(R.sub.1) (R.sub.2)--C(O)--.sub.] I

and a second repeating unit selected from the group of formulas consisting of;

space="preserve" listing-type="equation">[--O--R.sub.12 --].sub.U, XIV

wherein R₁ and R₂ are independently hydrogen or an alkyl group containing 1 to 8 carbon atoms;

R₃ is an alkylene unit or is an oxyalkylene group of the following formula;

space="preserve" listing-type="equation">--[(CH.sub.2).sub.C --O--].sub.D --(CH.sub.2).sub.E -- IV

wherein C is an integer in the range of from 2 to about 5, D is an integer in the range of from about 0 to about 12, and E is an integer in the range of from about 2 to about 5, except when D is zero in which case E will be an integer from 2 to 12;

R₁₂ is an alkylene unit containing from 2 to 8 carbon atoms and containing an internal amine (--N(R₁₀)--) or amide (--N(R₁₁)--);

R₁₀ and R₁₁, are independently hydrogen or an alkyl group containing 1 to 8 carbon atoms; and

U is an integer in the range of from 1 to 1,000.

7. The device of claim 6 wherein the aliphatic polyoxaester additionally contains a third repeating unit selected from the group consisting of:

space="preserve" listing-type="equation">[--O--R.sub.4 --].sub.A, II

space="preserve" listing-type="equation">[--O--R.sub.5 --C(O)--].sub.B, III

space="preserve" listing-type="equation">([--O--R.sub.13 --C(O)].sub.P --O--).sub.L G and XI

combinations thereof;

wherein R₄ is an alkylene unit containing from 2 to 8 carbon atoms;

A is an integer in the range of from 1 to 1,000;

R₅ and R₁₃ are independently selected from the group consisting of --C(O)(R₆)(R₇)--, --(CH₂)₃ --O--, --CH₂ --CH₂ --O--CH₂ --, --CR₈ H--CH₂ --, --(CH₂)₄ --, --(CH₂)_F --O--C(O)-- and --(CH₂)_K --C(O)--CH₂ --;

R₆ and R₇ are independently hydrogen or an alkyl containing from 1 to 8 carbon atoms;

R₈ is hydrogen or methyl;

F and K are integers in the range of from 2 to 6;

B is an integer in the range of from 1 to n such that the number average molecular weight of formula III is less than about 40,000;

P is an integer in the range of from 1 to m such that the number average molecular weight of formula XI is less than about 40,000;

G represents the residue minus from 1 to L hydrogen atoms from the hydroxyl groups of an alcohol previously containing from 2 to 12 hydroxyl groups; and

L is an integer from about 1 to about 12.

8. The device of claim 6 wherein the device is an absorbable surgical device.

9. The absorbable surgical device of claim 6 wherein the absorbable surgical device is selected from the group consisting of burn dressings, hernia patches, medicated dressings, fascial substitutes, gauze, fabrics, sheets, felts, sponges, gauze bandages, arterial graft, bandages for skin surfaces, suture knot clip, pins, clamps, screws, plates, clips, staples, hooks, buttons, snaps, bone substitutes, intrauterine devices, tubes, surgical instruments, vascular implants, vascular supports, vertebral discs, and artificial skin.

10. The absorbable surgical device of claim 6 wherein the device is a filament.

11. The filament of claim 10 wherein the filament is attached to a needle.

12. The device of claim 6 wherein the aliphatic polyoxaesters have the formula:

space="preserve" listing-type="equation">[--O--C(O)--C(R.sub.1) (R.sub.2)--O--(R.sub.3)--O--C(R.sub.1) (R.sub.2)--C(O)--(O--R.sub.12).sub.U --].sub.N

wherein N is an integer in the range of from about 1 to about 300,000.

13. The device of claim 6 wherein the aliphatic polyoxaesters have the formula:

space="preserve" listing-type="equation">[(--C(O)--C(R.sub.1) (R.sub.2)--O--R.sub.3 --O--C(R.sub.1) (R.sub.2)--C(O)--(O--R.sub.12).sub.U --O).sub.S (C(O)--R.sub.5 --O).sub.B ].sub.W

wherein S and W are independently integers in the range of from about 1 to about 1,000.

14. The device of claim 6 wherein the aliphatic polyoxaesters have

15. A device coated with an absorbable coating comprising an aliphatic polyoxaesters having a first divalent repeating unit of formula I:

space="preserve" listing-type="equation">[O--C(O)--C(R.sub.1) (R.sub.2)--O--(R.sub.3)--O--C(R.sub.1) (R.sub.2)--C(O)--] I

and a second repeating unit of formula;

space="preserve" listing-type="equation">[--O--R.sub.12 --].sub.U, XIV

and combinations thereof, wherein R₁ and R₂ are independently hydrogen or an alkyl group containing 1 to 8 carbon atoms;

R₃ is an alkylene unit or is an oxyalkylene group of the following formula;

space="preserve" listing-type="equation">--[(CH.sub.2).sub.C --O--].sub.D --(CH.sub.2).sub.E -- IV

wherein C is an integer in the range of from 2 to about 5, D is an integer in the range of from about 0 to about 12, and E is an integer in the range of from about 2 to about 5, except when D is zero in which case E will be an integer from 2 to 12;

R₁₂ is an alkylene unit containing from 2 to 8 carbon atoms and containing an internal amine (--N(R₁₀)--) or amide (--N(R₁₁)--);

R₁₀ and R₁₁ are independently hydrogen or an alkyl group containing 1 to 8 carbon atoms; and

U is an integer in the range of from 1 to 1,000;

wherein the inherent viscosity of the polyoxaester is in the range of from about 0.05 to about 2.0 deciliters per gram (dl/g) as measured in a 0.1 g/dl solution of hexafluoroisopropanol (HFIP) at 25°

C.

16. The device coated with an absorbable coating of claim 15 wherein the aliphatic polyoxaester additionally contains a third repeating unit selected from the group consisting of:

space="preserve" listing-type="equation">[--O--R.sub.4 --].sub.A, II

space="preserve" listing-type="equation">[--O--R.sub.5 --C(O)--].sub.B, III

space="preserve" listing-type="equation">([--O--R.sub.13 --C(O)].sub.P --O--).sub.L G and XI

combinations thereof wherein R₄ is an alkylene unit containing from 2 to 8 carbon atoms;

A is an integer in the range of from 1 to 1,000;

R₅ and R₁₃ are independently selected from the group consisting of --C(R₆)(R₇)--, --(CH₂)₃ --O--, --CH₂ --CH₂ --O--CH₂ --, --CR₈ H--CH₂ --, --(CH₂)₄ --, --(CH₂)_F --O--C(O)-- and --(CH₂)_K --C(O)--CH₂ --;

R₆ and R₇ are independently hydrogen or an alkyl containing from 1 to 8 carbon atoms;

R₈ is hydrogen or methyl;

F and K are integers in the range of from 2 to 6;

B is an integer in the range of from 1 to n such that the number average molecular weight of formula III is less than about 40,000;

P is an integer in the range of from 1 to m such that the number average molecular weight of formula XI is less than about 40,000;

G represents the residue minus from 1 to L hydrogen atoms from the hydroxyl groups of an alcohol previously containing from 2 to 12 hydroxyl groups; and

L is an integer from about 1 to about 12.

17. The device coated with an absorbable coating of claim 15 wherein the device is a suture.

18. The device coated with an absorbable coating of claim 17 wherein the suture is attached to a needle.

19. The device coated with an absorbable coating of claim 15 wherein the aliphatic polyoxaesters have the formula:

space="preserve" listing-type="equation">[--O--C(O)--C(R.sub.1) (R.sub.2)--O--(R.sub.3)--O--C(R.sub.1) (R.sub.2)--C(O)--(O--R.sub.12).sub.U --].sub.N

wherein N is an integer in the range of from about 1 to about 300,000.

20. The device coated with an absorbable coating of claim 15 wherein the aliphatic polyoxaesters have the formula:

space="preserve" listing-type="equation">[(--C(O)--C(R.sub.1) (R.sub.2)--O--R.sub.3 --O--C(R.sub.1) (R.sub.2)--C(O)--(O--R.sub.12).sub.U --O).sub.S (C(O)--R.sub.5 --O).sub.B ].sub.W

wherein S and W are independently integers in the range of from about 1 to about 1,000.

21. The device coated with an absorbable coating of claim 15 wherein the aliphatic polyoxaesters have the formula:

space="preserve" listing-type="equation">[(--C(O) --C(R.sub.1) (R.sub.2)--O--R.sub.3 --O--C(R.sub.1)(R.sub.2)--C(O)--(O--R.sub.12).sub.U --O).sub.S ([--O--R.sub.13 --C(O).sub.P ]--O--) .sub.L G].sub.W

wherein S and W are independently integers in the range of from about 1 to about 1,000.

22. A drug delivery matrix comprising a drug and an aliphatic polyoxaester having a first divalent repeating unit of formula I:

space="preserve" listing-type="equation">[O--C(O)--C(R.sub.1) (R.sub.2)--O--(R.sub.3)--O--C(R.sub.1) (R.sub.2)--C(O)--] I

and a second repeating unit of formula;

space="preserve" listing-type="equation">[--O--R.sub.12 ].sub.U, XIV

wherein R₁ and R₂ are independently hydrogen or an alkyl group containing 1 to 8 carbon atoms;

R₃ is an alkylene unit or is an oxyalkylene group of the following formula;

space="preserve" listing-type="equation">--[(CH.sub.2).sub.C --O--].sub.D --(CH.sub.2).sub.E IV

wherein C is an integer in the range of from 2 to about 5, D is an integer in the range of from about 0 to about 12, and E is an integer in the range of from about 2 to about 5, except when D is zero in which case E will be an integer from 2 to 12;

R₁₂ is an alkylene unit containing from 2 to 8 carbon atoms and containing an internal amine (--N(R₁₀)--) or amide (--N(R₁₁)--);

R₁₀ and R₁₁ are independently hydrogen or an alkyl group containing 1 to 8 carbon atoms; and

U is an integer in the range of from 1 to 1,000.

23. The drug delivery matrix of claim 22 wherein the aliphatic polyoxaester additionally contains a third repeating unit selected from the group consisting of:

space="preserve" listing-type="equation">[--O--R.sub.4 --].sub.A, II

space="preserve" listing-type="equation">[--O--R.sub.5 --C(O)--].sub.B, III

space="preserve" listing-type="equation">([--O--R.sub.13 --C(O)].sub.9 --O--).sub.L G and XI

combinations thereof;

wherein R₄ is an alkylene unit containing from 2 to 8 carbon atoms;

A is an integer in the range of from 1 to 1,000;

R₅ and R₁₃ are independently selected from the group consisting of --C(O)(R₆)--, --(CH₂)₃ --O--, --CH₂ --CH₂ --O--CH₂ --, --CR₈ H--CH₂ --, --(CH₂)₄ --, --(CH₂)_F --O--C(O)-- and --(CH₂)_K --C(O)--CH₂ --;

R₆ and R₇ are independently hydrogen or an alkyl containing from 1 to 8 carbon atoms;

R₈ is hydrogen or methyl;

F and K are integers in the range of from 2 to 6;

B is an integer in the range of from l to n such that the number average molecular weight of formula III is less than about 40,000;

P is an integer in the range of from 1 to m such that the number average molecular weight of formula XI is less than about 40,000;

G represents the residue minus from 1 to L hydrogen atoms from the hydroxyl groups of an alcohol previously containing from 2 to 12 hydroxyl groups; and

L is an integer from about 1 to about 12.

24. The drug delivery matrix of claim 22 wherein the aliphatic polyoxaester has the formula:

space="preserve" listing-type="equation">[(--C(O)--C(R.sub.1) (R.sub.2)--O--R.sub.3 --O--C(R.sub.1) (R.sub.2)--C(O)--(O--R.sub.12).sub.U --O).sub.S (C(O)--R.sub.5 --O).sub.B ].sub.W

wherein S and W are independently integers in the range of from about 1 to about 1,000.

25. The drug delivery matrix of claim 22 wherein the aliphatic polyoxaester has the formula:

space="preserve" listing-type="equation">[(--C(O)--C(R.sub.1) (R.sub.2)--O--R.sub.3 --O--C(R.sub.1) (R.sub.2)--C(O)--(O--R.sub.12).sub.U --O).sub.S ([--O--R.sub.31--C(O)].sub.P --O--).sub.L G ].sub.W

wherein S and W are independently integers in the range of from about 1 to about 1,000.

26. An aliphatic polyoxaesters comprising a first divalent repeating unit of formula I:

space="preserve" listing-type="equation">[O--C(O)--C(R.sub.1) (R.sub.2)--O--(R.sub.3)--O--C(R.sub.1) (R.sub.2)--C(O)--] I

and two second repeating unit of the formulas;

space="preserve" listing-type="equation">[--O--R.sub.5 --C(O)--].sub.B, and III

space="preserve" listing-type="equation">( [--O--R.sub.13 --C(O)].sub.P --O--).sub.L G XI

wherein R₁ and R₂ are independently hydrogen or an alkyl group containing 1 to 8 carbon atoms;

R₃ is an alkylene unit or is an oxyalkylene group of the following formula;

space="preserve" listing-type="equation">--[(CH.sub.2).sub.C --O--].sub.D --(CH.sub.2).sub.E -- IV

wherein C is an integer in the range of from 2 to about 5, D is an integer in the range of from about 0 to about 12, and E is an integer in the range of from about 2 to about 5, except when D is zero, in which case E will be from 2 to 12;

R₅ and R₁₃ are different and are selected from the group consisting of --C(O)(R₆)(R₇)--, --(CH₂)3--O--, --CH₂ --CH₂ --O--CH₂ --, --CR₈ H--CH₂ --, --(CH₂)₄ --, --(CH₂)_F --O--C(O)-- and --(CH₂)_K --C(O)--CH₂ --;

R₆ and R₇ are independently hydrogen or an alkyl containing from 1 to 8 carbon atoms;

Rs is hydrogen or methyl;

F and K are integers in the range of from 2 to 6;

B is an integer in the range of from 1 to n such that the number average molecular weight of formula III is less than about 40,000;

P is an integer in the range of from 1 to m such that the number average molecular weight of formula XI is less than about 40,000;

G represents the residue minus from 1 to L hydrogen atoms from the hydroxyl groups of an alcohol previously containing from 2 to 12 hydroxyl groups; and

L is an integer from about 1 to about 12.

27. The aliphatic polyoxaester of claim 26 where additionally present is a third repeating unit of the formula:

space="preserve" listing-type="equation">[--O--R.sub.4 --].sub.A, II

wherein R₄ is an alkylene unit containing from 2 to 8 carbon atoms;

A is an integer in the range of from 1 to 1,000.

29. The aliphatic polyoxaester of claim 26 where additionally present is a third repeating unit of the formula:

space="preserve" listing-type="equation">[--O--R.sub.4 --].sub.A, II

wherein R₄ is an alkylene unit containing from 2 to 8 carbon atoms;

A is an integer in the range of from 1 to 1,000.

28. A device made from an aliphatic polyoxaesters comprising a first divalent repeating unit of formula I:

space="preserve" listing-type="equation">[O--C(O)--C(R.sub.1) (R.sub.2)--O--(R.sub.3)--O--C(R.sub.1) (R.sub.2)--C(O)--] I

and two second repeating unit selected from the group of formulas consisting of;

space="preserve" listing-type="equation">[--O--R.sub.5 --C(O)--].sub.B, III

space="preserve" listing-type="equation">([--O--R.sub.13 --C(O)].sub.P --O--).sub.L G XI

wherein R₁ and R₂ are independently hydrogen or an alkyl group containing 1 to 8 carbon atoms;

R₃ is an alkylene unit or is an oxyalkylene group of the following formula;

space="preserve" listing-type="equation">--[(CH.sub.2).sub.C --O--].sub.D --(CH.sub.2).sub.E -- IV

wherein C is an integer in the range of from 2 to about 5, D is an integer in the range of from about 0 to about 12, and E is an integer in the range of from about 2 to about 5, except when D is zero, in which case E will be from 2 to 12;

R₅ and R₁₃ are different and are selected from the group consisting of --C(O)(R₇)--, --(CH₂)₃ --O--, --CH₂ --CH₂ --O--CH₂ --, --CR₈ H--CH₂ --, --(CH₂)₄ --, --(CH₂)_F --O--C(O)-- and --(CH₂)_K --C(O)--CH₂ --;

R₆ and R₇ are independently hydrogen or an alkyl containing from 1 to 8 carbon atoms;

Rs is hydrogen or methyl;

F and K are integers in the range of from 2 to 6;

B is an integer in the range of from 1 to n such that the number average molecular weight of formula III is less than about 40,000;

P is an integer in the range of from 1 to m such that the number average molecular weight of formula XI is less than about 40,000;

G represents the residue minus from 1 to L hydrogen atoms from the hydroxyl groups of an alcohol previously containing from 2 to 12 hydroxyl groups; and

L is an integer from about 1 to about 12.

30. A device coated with an absorbable coating comprising an aliphatic polyoxaesters having a first divalent repeating unit of formula I:

space="preserve" listing-type="equation">[O--C(O)--C(R.sub.1) (R.sub.2)--O--(R.sub.3)--O--C(R.sub.1)(R.sub.2)--C(O)--] I

and two second repeating unit of the formulas;

space="preserve" listing-type="equation">[--O--R.sub.5 --C(O)--].sub.B, III

space="preserve" listing-type="equation">([--O--R.sub.13 --C(O)].sub.P --O--) XI

wherein R_l and R₂ are independently hydrogen or an alkyl group containing 1 to 8 carbon atoms;

R₃ is an alkylene unit or is an oxyalkylene group of the following formula;

space="preserve" listing-type="equation">--[(CH.sub.2).sub.C --O--].sub.D --(CH.sub.2).sub.E -- IV

wherein C is an integer in the range of from 2 to about 5, D is an integer in the range of from about 0 to about 12, and E is an integer in the range of from about 2 to about 5, except when D is zero, in which case E will be from 2 to 12;

R₅ and R₁₃ are different and are selected from the group consisting of --C(O)(R₇)--, --(CH₂)₃ --O--, --CH₂ --CH₂ --O--CH₂ --, --CR₈ H--CH₂ --, --(CH₂)₄ --, --(CH₂)_F --O--C(O)-- and --(CH₂)_K --C(O)--CH₂ --;

R₆ and R₇ are independently hydrogen or an alkyl containing from 1 to 8 carbon atoms;

R₈ is hydrogen or methyl;

F and K are integers in the range of from 2 to 6;

B is an integer in the range of from 1 to n such that the number average molecular weight of formula III is less than about 40,000;

P is an integer in the range of from 1 to m such that the number average molecular weight of formula XI is less than about 40,000;

G represents the residue minus from 1 to L hydrogen atoms from the hydroxyl groups of an alcohol previously containing from 2 to 12 hydroxyl groups; and

L is an integer from about 1 to about 12 wherein the inherent viscosity of the polyoxaester is in the range of from about 0.05 to about 2.0 deciliters per gram (dl/g) as measured in a 0.1 g/dl solution of hexafluoroisopropanol (HFIP) at 25°

C.

31. The aliphatic polyoxaester of claim 30 where additionally present is a third repeating unit of the formula:

space="preserve" listing-type="equation">[--O--R.sub.4 --].sub.A, II

wherein R₄ is an alkylene unit containing from 2 to 8 carbon atoms;

A is an integer in the range of from 1 to 1,000.

32. A drug delivery matrix comprising a drug and an aliphatic polyoxaesters having a first divalent repeating unit of formula I:

space="preserve" listing-type="equation">[O--C(O)--C(R.sub.1) (R.sub.2)--O--(R.sub.3)--O--C(R.sub.1) (R.sub.2)--C(O)--] I

and two second repeating unit of the formulas;

space="preserve" listing-type="equation">[--O--R.sub.5 --C(O)--].sub.B, III

space="preserve" listing-type="equation">([--O--R.sub.13 --C(O)].sub.P --O--).sub.L G XI

wherein R₁ and R₂ are independently hydrogen or an alkyl group containing 1 to 8 carbon atoms;

R₃ is an alkylene unit or is an oxyalkylene group of the following formula;

space="preserve" listing-type="equation">[(CH.sub.2) .sub.C --O--].sub.D --(CH.sub.2).sub.E -- IV

wherein C is an integer in the range of from 2 to about 5, D is an integer in the range of from about 0 to about 12, and E is an integer in the range of from about 2 to about 5, except when D is zero, in which case E will be from 2 to 12;

R₅ and R₁₃ are different and are selected from the group consisting of --C(R₆) (R₇)--, --(CH₂)₃ --O--, --CH₂ --CH₂ --O--CH₂ --, --CR₈ H--CH₂ --, --(CH₂)₄ --, --(CH₂)_F --O--C(O)-- and --(CH₂)_K --C(O)--CH₂ --;

R₆ and R₇ are independently hydrogen or an alkyl containing from 1 to 8 carbon atoms;

R₈ is hydrogen or methyl;

F and K are integers in the range of from 2 to 6;

B is an integer in the range of from 1 to n such that the number average molecular weight of formula III is less than about 40,000;

P is an integer in the range of from 1 to m such that the number average molecular weight of formula XI is less than about 40,000;

G represents the residue minus from 1 to L hydrogen atoms from the hydroxyl groups of an alcohol previously containing from 2 to 12 hydroxyl groups; and

L is an integer from about 1 to about 12 wherein the inherent viscosity of the polyoxaester is in the range of from about 0.05 to about 2.0 deciliters per gram (dl/g) as measured in a 0.1 g/dl solution of hexafluoroisopropanol (HFIP) at 25°

C.

33. The drug delivery matrix of claim 32 wherein the aliphatic polyoxaester has additionally present a third repeating unit of the formula:

space="preserve" listing-type="equation">[--O--R.sub.4 --].sub.A, II

wherein R₄ is an alkylene unit containing from 2 to 8 carbon atoms;

A is an integer in the range of from 1 to 1,000.