Absorbable polyoxaesters

• US 5,618,552 A
• Filed: 03/05/1996
• Issued: 04/08/1997
• 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:
  US08/611,530
• Time in Patent Office: 399 Days
• Field of Search: 528/272, 528/301, 528/361, 424/426, 424/430, 424/433, 424/444, 424/446, 424/448, 424/486, 428/35.7, 428/35.8, 428/36.1, 428/36.2, 428/98, 428/221, 428/304.4, 428/357, 428/359, 428/364, 428/383, 428/423.1, 525/437, 525/509, 525/511
• US Class Current: 424/426
• 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 428/1355 : Elemental metal containing [e.g., substrate, foil, film, coating, etc.]
• CPC Class Codes: Y10T 428/1362 : Textile, fabric, cloth, or pile containing [e.g., web, net, woven, knitted, mesh, nonwoven, matted, etc.]
• CPC Class Codes: Y10T 428/24 : Structurally defined web or sheet [e.g., overall dimension, etc.]
• CPC Class Codes: Y10T 428/249921 : Web or sheet containing structurally defined element or component
• CPC Class Codes: Y10T 428/249953 : Composite having voids in a component [e.g., porous, cellular, etc.]
• CPC Class Codes: Y10T 428/29 : Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
• CPC Class Codes: Y10T 428/2904 : Staple length fiber
• CPC Class Codes: Y10T 428/2913 : Rod, strand, filament or fiber
• CPC Class Codes: Y10T 428/2947 : Synthetic resin or polymer in plural coatings, each of different type
• CPC Class Codes: Y10T 428/31551 : Of polyamidoester [polyurethane, polyisocyanate, polycarbamate, 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)(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:

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

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

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

and combinations thereof.

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.4 --].sub.A, II

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

space="preserve" listing-type="equation">([--O--R.sub.5 --F(O)].sub.P --O--).sub.L G XI

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 containing from 2 to 12 carbon atoms 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 2,000, 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;

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

A is an integer in the range of from 1 to 2,000;

R₅ is selected from the group consisting of --C(R₆)(R₇)--, --(CH₂)₃ --O--, --CH₂ --CH₂ --O--CH₂ --, --CR₈ H--CH₂ --, --(CH₂)₄ --, --(CH₂)_F 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 is an integer 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 200,000;

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 1,000,000;

G represents the residue minus from 1 to L hydrogen atoms from the hydroxyl groups of an alcohol previously containing from 1 to 200 hydroxyl groups; and

L is an integer from about 1 to about 200.

2. 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.4).sub.A --].sub.N

wherein N is an integer in the range of from about 1 to about 10,000.

3. The aliphatic polyoxaesters of claim 1 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.4).sub.A --O).sub.S (C(O)--R.sub.5 --O).sub.B ].sub.W

wherein S is integers in the range of from about 1 to about 10,000 and W is integers in the range of from about 1 to about 1,000.

4. The aliphatic polyoxaesters of claim 1 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.4).sub.A --O).sub.S ([--O--R.sub.5 --C(O)].sub.P --O--).sub.L G].sub.W

wherein S is an integer in the range of from about 1 to about 10,000 and W is an integer in the range of from about 1 to about 1,000.

5. 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 a second repeating unit selected from the group of formulas 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, and III

space="preserve" listing-type="equation">([--O--R.sub.5 --C(O)].sub.P --O--).sub.L G XI

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 containing from 2 to 12 carbon atoms 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 2,000, 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;

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

A is an integer in the range of from 1 to 2,000;

R₅ is selected from the group consisting of --C(R₆)(R₇)--, --(CH₂)₃ --O--, --CH₂ --CH₂ --O--CH₂ ----CR₈ H--CH₂ --, --(CH₂)₅ --, --(CH₂)_F --O--C(O)-- and --(CH₂)_F --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 is an integer 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 200,000;

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 1,000,000;

G represents the residue minus from 1 to L hydrogen atoms from the hydroxyl groups of an alcohol previously containing from 1 to about 200 hydroxyl groups; and

L is an integer from about 1 to about 200.

6. The device of claim 5 wherein the device is an absorbable surgical device.

7. 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.

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

9. The filament of claim 8 wherein the filament is attached to a needle.

14. The device of claim 5 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.4).sub.A --].sub.N

wherein N is an integer in the range of from about 1 to about 10,000.

15. The device of claim 5 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.4).sub.A --O).sub.S (C(O)--R.sub.5 --O).sub.B ].sub.W

wherein S is an integer in the range of from about 1 to about 10,000 and W is an integer in the range of from about 1 to about 1,000.

16. The device of claim 5 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.4).sub.A --O).sub.S ([--O--R.sub.5 --C(O)].sub.P --O--).sub.L G].sub.W

wherein S is an integer in the range of from about 1 to about 10,000 and W is an integer in the range of from about 1 to about 1,000.

10. 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 selected from the group of formulas 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, and III

space="preserve" listing-type="equation">([--O--R.sub.5 --C(O)].sub.P --O--).sub.L G XI

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 containing from 2 to 12 carbon atoms 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 2,000, 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;

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

A is an integer in the range of from 1 to 2,000;

R₅ is selected from the group consisting of --C(R₆)(R₇)--, --(CH₂)₃ --O--, --CH₂ --CH₂ --O--CH₂ --, --CR₈ H--CH₂ --, --(CH₂)₅ --, --(CH₂)_F --O--C(O)-- and --(CH₂)_F --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 is an integer 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 200,000;

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 1,000,000;

G represents the residue minus from 1 to L hydrogen atoms from the hydroxyl groups of an alcohol previously containing from 1 to about 200 hydroxyl groups; and

L is an integer from about 1 to about 200 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.

11. The device of claim 10 wherein the device is a suture.

12. The device of claim 11 wherein the suture is attached to a needle.

17. The device coated with an absorbable coating of claim 10 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.4).sub.A --].sub.N

wherein N is an integer in the range of from about 1 to about 10,000.

18. The device coated with an absorbable coating of claim 10 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.4).sub.A --O).sub.S (C(O)--R.sub.5 --O).sub.B ]W

wherein S is an integer in the range of from about 1 to about 10,000 and W is an integer in the range of from about 1 to about 1,000.

19. The device coated with an absorbable coating of claim 10 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.4).sub.A --O).sub.S ([--O--R.sub.5 --C(O)].sub.P --O--).sub.L G].sub.W

wherein S is an integer in the range of from about 1 to about 10,000 and W is an integer in the range of from about 1 to about 1,000.

13. 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 selected from the group of formulas consisting of;

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

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

space="preserve" listing-type="equation">([--O--R.sub.5 --C(O)].sub.P --O--).sub.L G XI

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 containing from 2 to 12 carbon atoms 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 2,000, 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;

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

A is an integer in the range of from 1 to 2,000;

R₅ is 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)_F --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 is an integer 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 200,000;

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 1,000,000;

G represents the residue minus from 1 to L hydrogen atoms from the hydroxyl groups of an alcohol previously containing from 1 to about 200 hydroxyl groups; and

L is an integer from about 1 to about 200.

20. The drug delivery matrix of claim 13 wherein the aliphatic polyoxaester 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.4).sub.A --].sub.N

wherein N is an integer in the range of from about 1 to about 10,000.

21. The drug delivery matrix of claim 13 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.4).sub.A --O).sub.S (C(O)--R.sub.5 --O).sub.B ].sub.W

wherein S is an integer in the range of from about 1 to about 10,000 and W is an integer in the range of from about 1 to about 1,000.

22. The drug delivery matrix of claim 13 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.4)--O).sub.S ([--O--R.sub.5 --C(O)].sub.P --O--).sub.L G].sub.W

wherein S is an integer in the range of from about 1 to about 10,000 and W is an integer in the range of from about 1 to about 1,000.