Gels
The present invention relates to biostable gel comprising: (a) at least one silicon-containing polyol, polyamine, polyepoxy or polyisocyanate having 1 or more functional groups and a molecular weight of at least 20,000 which is cured in the presence of: (b) at least one diol, diamine or diisocyanate having a molecular weight of less than 10,000; and/or (c) an initiator, processes for their preparation and their use in the manufacture and repair of biomaterials and medical devices, articles or implants, in particular the manufacture of a soft tissue implant such as breast implants and the repair of orthopaedic joints such as spinal discs.
1. A biostable gel prepared by a process comprising:
(a) curing at least one silicon-containing polyol, polyamine, polyepoxy or polyisocyanate, having 1 or more functional groups and a number average molecular weight of at least 20,000 in the presence of:
(b) at least one diol, diamine or diisocyanate having a number average molecular weight of less than 10,000; and, optionally,
(c) an initiator.
2. A biostable gel prepared by a process comprising:
(a) curing at least one silicon-containing polyol, polyamine, polyepoxide or polyisocyanate having one or more functional groups capable of activation by free radical initiation, and a number average molecular weight of at least 20,000, in the presence of:
(b) at least one diol, diamine or diisocyanate having a number average molecular weight of less than 10,000; and
(c) an initiator.
3. A biostable get according to claim 1 or 2 , in which the gel has an average functionality of 1 to 5.
4. A biostable gel according to claim 1 , in which the functional groups of component (a) are independently selected from OH, NCO, epoxy and NR′R″ in which R′ and R″ are independently selected from H, CO 2 H and C 1-6 alkyl.
5. A biostable gel according to claim 2 , in which the groups capable of activation by free radical initiation contain double or triple bonds.
6. A biostable gel according to claim 5 , in which the groups capable of activation by free radical initiation are vinyl or C 1-6 alkyl acrylates.
7. A biostable gel according to claim 1 , the initiator is absent.
8. A biostable gel prepared by a process comprising:
(a) curing at least one of a silicon-containing polyol, polyamine, polyepoxy, polyvinyl, polyacrylate or polyisocyanate of formula (I) or (II):
in which
R a and R b are independently selected from C 1-6 alkyl, OH, C 1-6 alkoxy, (CH 2 ) 3 OR 1 and Si(R 7 )(R 8 )(CH 2 ) 3 OR 2 ;
R 1 and R 2 are independently selected from C 1-6 alkyl optionally substituted with OH, NCO, epoxy or NR′R″ in which R′ and R″ are independently selected from H, CO 2 H and C 1-6 alkyl;
R 3 to R 8 are independently selected from vinyl, and C 1-6 alkyl which may be optionally interrupted by O and optionally substituted with OH, NCO, epoxy, C 1-6 alkyl acrylate or NR′R″ in which R′ and R″ are as defined above;
R 9 is C 1-4 alkyl;
R 10 is optionally substituted C 1-4 alkyl or
in which R 1 and R 9 are as defined above;
x is 100 to 1000;
y is 0 to 200; and
n is 30 to 500 in the presence of;
(b) at least one diol, diamine or diisocyanate having a weight number molecular weight of less than 10,000; and, optionally
(c) an initiator.
9. A biostable gel according to claim 8 , in which the silicon-containing polyol, polyamine, polyepoxy, polyvinyl, polyacrylate or polyisocyanate of formula (I) is as follows:
in which x and y in the compounds of formulae (Ia), (Ib), (Ic), (Ig), (Ih) and (Ij) are as defined in claim 8 .
10. A biostable gel according to claim 8 , in which the silicon-containing polyol, of formula (II) is as follows:
11. A biostable gel according to claim 1 , 2 , 8 , 9 or 10 in which the number average molecular weight of component (a) is 30,000 to 200,000.
12. A biostable gel according to claim 1 , 2 , 8 , 9 or 10 in which the amount of component (a) is 80 to 100% based on the total weight of the gel.
13. A biostable gel according to claim 1 , 2 , 8 , 9 or 10 in which the diol or diamine is a polyether, polycarbonate, polyalkylene or C 1-6 alkane diol or diamine.
14. A biostable gel according to claim 13 , in which the polyether diol or diamine is represented by the formula (III)
A-[(CH 2 ) m —O] n -A′ (III)
in which
A and A′ are OH or NHR wherein R is H or optionally substituted C 1-6 alkyl;
m is an integer of 4 or more; and
n is an integer of 2 to 50.
15. A biostable gel according to claim 13 , in which the C 1-6 alkane diol is methane diol, butane diol or hexane diol.
16. A biostable gel according to claim 1 , 2 , 8 , 9 or 10 in which the diol or diamine contains silicon.
17. A biostable gel according to claim 16 , in which the diol or diamine containing silicon is represented by the formula (V):
in which
A and A′ are OH or NHR wherein R is H or optionally substituted C 1-6 alkyl;
R 11 , R 12 , R 13 and R 14 are independently selected from hydrogen or optionally substituted C 1-6 alkyl;
R 15 and R 16 are the same or different and selected from optionally substituted C 1-6 alkylene, C 2-6 alkenylene, C 2-6 alkynylene, arylene or a heterocyclic divalent radical; and
p is an integer of 1 or greater.
18. A biostable gel according to claim 17 , in which the compound of formula (V) is; 1,3-bis(4-hydroxybutyl)tetramethyl disiloxane (BHTD); or 1-4-bis(3-hydroxypropyl)tetramethyl disiloxane.
19. A biostable gel according to claim 1 , 2 , 8 , 9 or 10 in which the diisocyanate is an aliphatic or aromatic diisocyanate.
20. A biostable gel according to claim 19 , in which the aliphatic or aromatic diisocyanate is 4,4′-diphenylmethane diisocyanate (MDI), methylene biscyclohexyl diisocyanate (H 12 MDI), p-phenylene diisocyanate (p-PDI), trans-cyclohexane-1,4-diisocyanate (CHDI), 1,6-diisocyanatohexane (DICH), 1,5-diisocyanatonaphthalene (NDI), para-tetramethylxylene-diisocyanate (p-TMXDI), meta-tetramethylxylene diisocyanate (m-TMXDI), 2,4-toluene diisocyanate (2,4-TDI), isophorone diisocyanate (IPDI) or isomers or mixtures thereof.
21. A biostable gel according to claim 20 , in which the aromatic diisocyanate is MDI.
22. A biostable gel according to claim 1 , 2 , 8 , 9 or 10 in which the number average molecular weight of component (b) is 500 to 10000.
23. A biostable gel according to claim 1 , 8 , 9 or 10 in which the initiator is present.
24. A biostable gel according to claim 23 , in which the amount of initiator is 0.125% to 5% based on the total weight of the gel.
25. A process for preparing the biostable gel according to claim 1 which comprises the steps of:
mixing components (a) and (b) and optionally (c); and
curing the mixture of (a) and (b).
26. A process for preparing the biostable gel according to claim 25 which comprises the steps of:
(i) preparing a prepolymer having terminally reactive polyisocyanate groups from component (b);
(ii) mixing the prepolymer of step (i) with component (a); and
(iii) curing said mixture.
27. A process according to claim 25 or 26 , in which a polyurethane processing additive is added in step (i).
28. A biostable gel which is a reaction product of:
(a) the silicon-containing polyol, polyamine, polyepoxy or polyisocyanate of formula (I) or (II) according to claim 8 ; and
(b) C 1-6 alkane diol or diamine, polysiloxane diol or diamine and/or a diisocyanate.
29. A biomaterial, device, article or implant which is wholly or partly composed of the gel according to claim 28 .
30. A biomaterial, device, article or implant according to claim 29 which is selected from a soft tissue implant designed to replace and augment tissues; orthopaedic joints or parts thereof; bone suture anchors; reconstructive facial surgery; controlled drug release devices; components in key hole surgery; biosensors; tools and accessories for insertion of medical devices, infusion and flow control devices; and urethral, neurological or vascular bulking agents.
31. A biomaterial, device, article or implant according to claim 30 , in which the soft tissue implant is a breast tissue implant and the orthopaedic joint is a spinal disc.
32. A filler material for a medical implant which comprises the gel according to claim 28 .