Biocompatible poly-(ether-urethane-urea) and process for its preparation

• US 4,485,227 A
• Filed: 06/16/1983
• Issued: 11/27/1984
• Est. Priority Date: 06/16/1983
• Status: Expired due to Fees

• Current Assignee: Pfizer Hospital Products Group, Inc. (Pfizer Inc.)
• Original Assignee: Howmedica Inc.
• Inventors: Fox, Adrian S.
• Primary Examiner(s): WELSH JR, MAURICE
• Application Number:
  US06/505,130
• Time in Patent Office: 530 Days
• Field of Search: 528/61, 3/1 A
• US Class Current: 528/61
• CPC Class Codes: A61F 2/04 Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts A61F2/18, A61F2/20 take precedence; devices, other than stent-grafts, providing patency to, or preventing collapsing of, tubular structures of the body other than stent-grafts, e.g. stents A61F2/82; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95
• CPC Class Codes: A61F 2/06 Blood vessels
• CPC Class Codes: A61F 2/08 Muscles; Tendons; Ligaments sutures A61B17/04
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: C08G 18/10 Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
• CPC Class Codes: C08G 18/2865 Compounds having only one primary or secondary amino group; Ammonia
• CPC Class Codes: C08G 18/3228 acyclic
• CPC Class Codes: C08G 18/71 Monoisocyanates or monoisothiocyanates
• CPC Class Codes: C08G 18/831 by oxygen-containing compounds inclusive of carbonic acid halogenides, carboxylic acid halogenides and epoxy halides by aldehydes C08G18/84, by peroxides C08G18/86
• CPC Class Codes: C08L 75/12 from compounds containing nitrogen and active hydrogen, the nitrogen atom not being part of an isocyanate group

Abstract

An improved biocompatible and hemocompatible segmented poly-(ether-urethane-urea) is prepared by a process which comprises condensing an alkylene polyether diol of molecular weight of 500 to 6000 with substantially two equivalents of an aryl, aralkyl, or alkyl diisocyanate of 6 to 20 carbon atoms; condensing the thus-formed α,Ω-diisocyanato poly-(ether-urethane) with a substantially equivalent proportion of a primary alkyl diamine of 2 to 6 carbon atoms until a degree of condensation of about 5 to 20 is achieved; condensing the resulting poly-(ether-urethane-urea) with a primary alkyl amine or diamine of up to 6 carbon atoms in an amount substantially equivalent to the free isocyanate content of the poly-(ether-urethane-urea); and condensing the amine-treated poly-(ether-urethane-urea) with an amine-reacting agent in an amount substantially equivalent to the free amine content of the amine-treated poly-(ether-urethane-urea). The polymer is especially suitable for fabricating replacements for damaged cardiovascular and urinary tract vessels.

Claims

1. A biocompatible and hemocompatible segmented poly-(ether-urethane-urea) of the formula I:

##STR2## wherein R=arylene, aralkylene or alkylene each having from 6 to 20 carbons,

R₁ =alkylene having from 2 to 6 carbons,

R₂ =alkylene having from 2 to 6 carbons,

R₃ =alkyl having up to 4 carbons or R₅ CONHR₄ or R₆ NHCONHR₄ wherein

R₄ =alkylene having from 2 to 6 carbons,

R₅ =aryl or alkyl each having up to 16 carbons and

R₆ =aryl or alkyl each hving up to 12 carbons,

n=a number from about 7 to 35, and

m=a number from about 5 to 20.

2. The poly-(ether-urethane-urea) of claim 1 wherein R=4,4'"'"'-diphenylmethane;

R₁ =1-methyl ethylene;

R₂ =ethylene;

R₃ =R₅ CONHR₄ ;

R₄ =ethylene;

R₅ =methyl;

n=from about 13 to 15; and

m=from about 8 to 16.

15. A method of repairing a duct in a living body, which comprises replacing the defective portion of said duct with its equivalent in size and shape fabricated from the poly-(ether-urethane-urea) of claim 1.

16. The method of claim 15 wherein said duct is a blood vessel, a ureter or a urethra.

3. A process for the preparation of a biocompatible and hemocompatible segmented poly-(ether-urethane-urea), which comprises:

(a) condensing an alkylene polyether diol of molecular weight of from about 500 to 6000 with substantially two equivalents of an aryl, aralkyl, or alkyl diisocyanate each of from 6 to 20 carbon atoms;

(b) condensing the thus-formed α

,Ω

-diisocyanato poly-(ether-urethane) with a substantially equivalent proportion of a primary alkyl diamine of from 2 to 6 carbon atoms until a degree of condensation of from about 5 to 20 is achieved;

(c) condensing the resulting poly-(ether-urethane-urea) with a primary alkyl amine of up to 6 carbon atoms in an amount substantially equivalent to the free isocyanate content of said poly-(ether-urethane-urea); and

(d) condensing the resulting amine-treated poly-(ether-urethane-urea) with an amine-reacting agent in an amount substantially equivalent to the free amine content of said amine-treated poly-(ether-urethane-urea).

4. The process of claim 3 wherein said diol is selected from the group consisting of polyethylene glycol, poly-(1,2-propylene glycol) and poly-(1,4-butylene glycol).

5. The process of claim 3 wherein said diisocyanate is selected from the group consisting of 4,4'"'"'-diphenylmethane diisocyanate, toluene 2,4-diisocyanate, 2,2,4-trimethylhexamethylene diisocyanate and isophorone diisocyanate.

6. The process of claim 3 wherein said primary alkyl amine is a monoamine of from 1 to 4 carbons or a diamine of from 2 to 6 carbons.

7. The process of claim 3 wherein said amine-reacting agent is selected from the group consisting of aryl or alkyl acid anhydrides, acid chlorides and monoisocyanates of up to 16 carbon atoms.

8. The process of claim 3 wherein said condensations are conducted in nonreactive, aprotic, water-miscible solvent.

9. The process of claim 8 wherein the temperature of said condensations is from about 60°

to 100°

C. in step (a), from about 15°

to 30°

C. in steps (b) and (c) and from about 20°

to 80°

C. in step (d).

10. The process of claim 3 wherein said diol includes up to about 15 mole percent of an alkylene triol of from 3 to 8 carbon atoms.

11. The process of claim 3 wherein said diol includes up to about 50 mole percent of an unsaturated alkylene diol of from 6 to 12 carbon atoms.

12. The segmented poly-(ether-urethane-urea) of the process of claim 3.

13. A process for preparing a biocompatible and hemocompatible segmented poly-(ether-urethane-urea), which comprises:

(a) contacting poly-(1,2-propylene glycol) of nominal molecular weight of 950 to 1050 with substantially two equivalents of 4,4'"'"'-diphenylmethane diisocyanate in dimethyl sulfoxide/diglyme solvent at a temperature of from about 80°

to 85°

C.;

(b) contacting the thus-formed α

,Ω

-diisocyanato poly-(ether-urethane) with a substantially equivalent proportion of ethylenediamine in said solvent at a temperature of from about 25°

to 30°

C.;

(c) contacting the resulting poly-(ether-urethane-urea) in said solvent at a temperature of from about 20°

to 25°

C. with about 8 mole percent additional ethylenediamine; and

(d) contacting the amine-treated poly-(ether-urethane-urea) in said solvent at a temperature of from about 20°

to 60°

C. with about 16 mole percent acetic anhydride.

14. The segmented poly-(ether-urethane-urea) of the process of claim 13.