Surgical suture abstract
A bioabsorbable coating for a surgical suture or ligature is disclosed.
The coating is manufactured from a diblock or a triblock copolymer.
Surgical suture claims
We claim:
1. A bioabsorbable coating for a surgical suture or ligature comprising
a diblock copolymer having a first block comprising a polyalkylene
oxide and a second block consisting essentially of glycolic acid
ester and trimethylene carbonate linkages such that said diblock
copolymer has a melting point (Tm) less than 65 degrees centigrade
and a glass transition temperature (Tg) less than 20 degrees centigrade
and is soluble in methylene chloride or chloroform or both.
2. A coating of claim 1 wherein the polyalkylene oxide block is
from 5 to 25 percent by weight of the copolymer.
3. A coating of claim 1 wherein the number average molecular weight
of the polyalkylene oxide block is from about 4000 to 30000.
4. A coating of claim 1 wherein the polyalkylene oxide block is
derived from a polyalkylene oxide terminated on one end by a C.sub.1
to C.sub.6 alkyl group and on the other end by a hydroxyl group.
5. A coating of claim 4 wherein the polyalkylene oxide block is
derived from a homopolymer of ethylene oxide.
6. A coating of claim 4 wherein the polyalkylene oxide block is
derived from a block or random copolymer of ethylene oxide and a
cyclic ether.
7. A coating of claim 6 wherein the cyclic ether is selected from
the group consisting of ##STR9## wherein x is 2 to about 9 y is
1 to about 9 and R is a C.sub.1 to C.sub.6 alkyl group.
8. A coating of claim 4 wherein the polyalkylene oxide block is
derived from a block or random copolymer of a first cyclic ether
selected from the group consisting of ##STR10## wherein x is 2 to
about 9 and a second cyclic ether selected from the group consisting
of ##STR11## wherein y is 1 to about 9 and R is a C.sub.1 to C.sub.6
alkyl group.
9. A coating of claim 5 or 7 or 8 wherein the inherent viscosity
of the copolymer, as measured at 30.degree. C. for a 0.5% (w/v)
solution in chloroform or methylene chloride, is 0.25 to about 1.50
dl/g.
10. A coating of claim 9 wherein the bioabsorbable surgical suture
or ligature is manufactured from a polymer prepared from one or
more monomers selected from the group consisting of lactides.
11. A coating of claim 10 wherein the suture or ligature is manufactured
from a homopolymer prepared from the monomer glycolide.
12. A coating of claim 10 wherein the suture or ligature is manufactured
from a copolymer prepared from the monomers glycolide and lactide.
13. A coating of claim 11 wherein the suture or ligature is in
multifilamentary form.
14. A coating of claim 13 comprising about 1/10 to 5% by weight
of the coated suture or ligature.
15. A coating of claim 14 comprising about 1 to 3% by weight of
the coated suture or ligature.
16. A bioabsorbable coating for a surgical suture or ligature comprising
a triblock copolymer having a middle block and two end blocks, the
middle block obtained by removing both terminal hydroxyl hydrogens
from either a homopolymer of ethylene oxide, or from a block or
random copolymer of ethylene oxide and a cyclic ether, and each
end block consisting essentially of glycolic acid ester and trimethylene
carbonate linkages such that said triblock copolymer has a melting
point (Tm) less than 65 degrees centigrade and a glass transition
temperature (Tg) less than 20 degrees centigrade and is soluble
in methylene chloride or chloroform or both.
17. A coating of claim 16 wherein the cyclic ether is selected
from the group consisting of ##STR12## wherein x is 2 to about 9
y is 1 to about 9 and R is a C.sub.1 to C.sub.6 alkyl group.
18. A coating of claim 17 having a middle block obtained from a
block copolymer of ethylene oxide and a cyclic ether of the formula:
##STR13##
19. A bioabsorbable coating for a surgical suture or ligature comprising
a triblock copolymer having a middle block and two end blocks, the
middle block obtained by removing both terminal hydroxyl hydrogens
from a block or random copolymer of a first cyclic ether selected
from the group consisting of ##STR14## wherein x is 2 to about 9
and a second cyclic ether selected from the group consisting of
##STR15## wherein y is 1 to about 9 and R is a C.sub.1 to C.sub.6
alkyl group, and each end block consisting essentially of glycolic
acid ester and trimethylene carbonate linkages such that said triblock
copolymer has a melting points (Tm) less than 65 degrees centigrade
and a glass transition temperature (Tg) less than 20 degrees centigrade
and is soluble in methylene chloride and/or chloroform.
20. A coating of claim 16 wherein the middle block is from 5 to
25 percent by weight of the copolymer.
21. A coating of claim 20 wherein the number average molecular
weight of the middle block is from about 4000 to 30000.
22. A coating of claim 21 wherein the inherent viscosity of the
copolymer, as measured at 30.degree. C. for a 0.5% (w/v) solution
in chloroform or methylene chloride, is 0.25 to about 1.50 dl/g.
23. A coating of claim 22 comprising a bioabsorbable surgical suture
or ligature manufactured from a polymer prepared from one or more
monomers selected from the group consisting of lactides.
24. A coating of claim 23 wherein the suture or ligature is manufactured
from a homopolymer prepared from the monomer glycolide.
25. A coating of claim 24 wherein the suture or ligature is manufactured
from a copolymer prepared from the monomers glycolide and lactide.
26. A coating of claim 24 wherein the suture or ligature is in
multifilamentary form.
27. A coating of claim 26 comprising about 1/10 to 5% by weight
of the coated suture or ligature.
28. A coating of claim 27 comprising about 1 to 3% by weight.
Surgical suture description
BACKGROUND AND SUMMARY OF THE INVENTION
This invention relates to the use of a block hydrogel as a coating
and lubricating finish for a surgical suture or ligature.
As early as 1972 R. Perret and A. Skoulious, Makromol. Chem. 156
143-156 (1972); Makromol. Chem. 162 147-162 (1972); and Makromol.
Chem. 162 163-177 (1972) disclosed the synthesis and characterization
of thermoplastic poly(caprolactone)-poly(ethylene oxide)-poly(caprolactone)
(PCL-PEO-PCL) ABA triblock copolymers. The purification and crystallization
behavior of these materials was extensively discussed. However,
no mention was made as to the biodegradability of these polymers,
their swelling behavior, or to any medical use such as suture materials
or as suture coatings. Pitt and Schindler, U.S. Pat. No. 4379138
have published extensively on the biodegradability of PCL; therefore,
the PCL-PEO-PCL triblock polymers should make attractive biodegradable
hydrogel materials but this use was never mentioned.
Reed, Ph.D. Dissertation, Univ. of Liverpool (1978) has disclosed
the synthesis of poly(lactide)-PEO-poly(lactide) (PLA-PEO-PLA) ABA
triblock copolymers. The biodegradability of these materials was
recognized; however, there was no mention of their potential hydrogel
nature, or the use of these materials as suture coatings.
Casey, et al., U.S. Pat. No. 4452973 (6/5/84) disclosed the synthesis
of poly(glycolic acid)-PEO-poly(glycolic acid) (PGA-PEO-PGA) thermoplastic
biodegradable ABA triblock polymers. The intended use for these
materials was as absorbable sutures having the required flexibility
for use as a monofilament. The patent discloses the use of trimethylene
carbonate in combination with glycolide to prepare the A portion
of the ABA triblock polymer.
Churchill, et al., U.S. Pat. No. 4526938 (9/2/85) also disclosed
the use of degradable ABA triblock polymers as hydrogels. In this
case, the middle block was also PEO and the endblocks were generally
PLA or PLA/PGA copolymers although the use of PGA, PCL or poly(3-hydroxy-butyric
acid) was mentioned with no specific experimental details given.
No mention was made to using Gly/TMC endblocks for these hydrogels,
or to using these materials as suture coatings.
Mattei (U.S. Pat. No. 4027676 to Ethicon, June 7 1977) has disclosed
suture coatings consisting of blends of absorbable copolymers of
glycolide and lactide as a film forming resin, polyalkylene glycols
as a lubricant, and a hydrophobic material such as a fatty acid
or an ester of a fatty acid to improve tie-down performance. However,
no mention was made of using block polymers formed from poly(alkylene
glycols) and absorbable polymers. A particular disadvantage of the
Mattei method of using blends of poly(alkylene glycols) with absorbable
copolymers is the tendency for the poly(alkylene glycols) to dissolve
prematurely if exposed to an aqueous environment (see, e.g., Example
4 of U.S. Pat. No. 4027676) rendering the coating less effective.
Mattei (U.S. Pat. No. 4201216 to Ethicon May 6 1980) has also
disclosed the use of an absorbable copolymer of glycolide and lactide
as a film former blended with salts of C.sub.6 or higher fatty acids
as suture coatings. No mention was made of using block polymers
with poly(alkylene glycols) for this application.
Mattei has also disclosed the use of polyvalent metal fatty acid
salt gels as suture coating materials (U.S. Pat. No. 4185637 to
Ethicon Jan. 29 1980). No mention is made of using block copolymers
of poly(alkylene glycols) for this application.
Conventional hydrogels which are made by crosslinking water soluble
polymers have several drawbacks which are associated with their
crosslinked nature. These include a lack of both solubility and
processability. In contrast the block copolymers of this invention
are thermoplastic. They are soluble in common organic solvents and
are fusible.
The biodegradable thermoplastic hydrogels of this invention are
useful as a suture coating material for surgical sutures or ligatures.
Their solubility in common organic solvents allows for a coating
composition to be applied by conventional solution techniques. When
applied in this manner the coating polymer will improve tie-down
performance and lubricity of the surgical suture as compared to
an identical uncoated surgical suture. The polymers of this invention
will also degrade to non-toxic low molecular weight materials capable
of being eliminated from the body without adverse reaction or response.
A bioabsorbable coating for a surgical suture or ligature comprising
a diblock copolymer has been invented. The copolymer has a first
block comprising a polyalkylene oxide and a second block consisting
essentially of glycolic acid ester and trimethylene carbonate linkages.
In one embodiment, the polyalkylene oxide block is from 5 to 25
percent by weight of the copolymer. In another embodiment, the number
average molecular weight of the polyalkylene oxide block is from
about 4000 to 30000. In yet another embodiment, the polyalkylene
oxide block is derived from a polyalkylene oxide terminated on one
end by a C.sub.1 to C.sub.6 alkyl group and on the other end by
a hydroxyl group.
In a specific embodiment of any of the above embodiments, the polyalkylene
oxide block is derived from a homopolymer of ethylene oxide. In
another specific embodiment of any of the above, the polyalkylene
oxide block is derived from a block or random copolymer of ethylene
oxide and a cyclic ether. In a more specific embodiment, the cyclic
ether is selected from the group consisting of ##STR1## wherein
x is 2 to about 9 y is 1 to about 9 and R is a C.sub.1 to C.sub.6
alkyl group.
In yet another specific embodiment, the polyalkylene oxide block
is derived from a block or random copolymer of a first cyclic ether
selected from the group consisting of ##STR2## wherein x is 2 to
about 9 and a second cyclic ether selected from the group consisting
of ##STR3## wherein y is 1 to about 9 and R is a C.sub.1 to C.sub.6
alkyl group.
In a more specific embodiment (to the above specific embodiments),
the inherent viscosity of the diblock copolymer, as measured at
30.degree. C. for a 0.5% (w/v) solution in chloroform or methylene
chloride, is 0.25 to about 1.50 dl/g.
In a still further embodiment, the surgical suture or ligature
containing the bioabsorbable diblock copolymer coating is also bioabsorbable.
The suture or ligature is manufactured from a polymer. The polymer
is prepared from one or more monomers selected from the group consisting
of lactides. In one embodiment, the suture or ligature is manufactured
from a homopolymer prepared from the monomer glycolide. In another
embodiment, the suture or ligature is manufactured from a copolymer
prepared from the monomers glycolide and lactide. In a specific
embodiment, the suture or ligature is in multifilamentary form.
In a more specific embodiment, the coating comprises about 1/10
to 5% by weight of the coated suture or ligature. In a most specific
embodiment, the coating comprises about 1 to 3% by weight of the
coated suture or ligature.
A bioabsorbable coating for a surgical suture or ligature comprising
a triblock copolymer has also been invented. The middle block (of
the triblock copolymer) is obtained by removing both terminal hydroxyl
hydrogens either form a homopolymer of ethylene oxide, or from a
block or random copolymer of ethylene oxide and a cyclic ether.
In one embodiment, the cyclic ether is selected from the group consisting
of ##STR4## wherein x is 2 to about 9 y is 1 to about 9 and R is
a C.sub.1 to C.sub.6 alkyl group. In a specific embodiment, the
middle block is obtained from a block copolymer of ethylene oxide
and a cyclic ether of the formula: ##STR5##
Further, a bioabsorbable coating for a surgical suture or ligature
comprising an alternative triblock copolymer has been invented.
The middle block is obtained by removing both terminal hydroxyl
hydrogens from a block or random copolymer of a first cyclic ether
selected from the group consisting of ##STR6## wherein x is 2 to
about 9 and a second cyclic ether selected from the group consisting
of ##STR7## wherein y is 1 to about 9 and R is a C.sub.1 to C.sub.6
alkyl group.
In a further embodiment of any of the above embodiments, each end
block of the triblock copolymer consists essentially of glycolic
acid ester and trimethylene carbonate linkages. In a specific embodiment,
the middle block is from 5 to 25 percent by weight of the copolymer.
In a more specific embodiment, the number average molecular weight
of the middle block is from about 4000 to 30000.
In a most specific embodiment (to the above specific embodiments),
the inherent viscosity of the copolymer, as measured at 30.degree.
C. for a 0.5% (w/v) solution in chloroform or methylene chloride,
is 0.25 to about 1.50 dl/g. In a still further embodiment, the surgical
suture or ligature containing the bioabsorbable bioabsorbable triblock
copolymer coating is also bioabsorbable. The suture or ligature
is manufactured from a polymer. The polymer is prepared from one
or more monomers selected from the group consisting of lactides.
In one embodiment, the suture or ligature is manufactured from a
homopolymer prepared from the monomer glycolide. In another embodiment,
the suture or ligature is manufactured from a copolymer prepared
from the monomers glycolide and lactide.
In a specific embodiment, the suture or ligature is in multifilamentary
form. In a more specific embodiment, the coating comprises about
1/10 to 5% by weight of the coated suture or ligature. In a most
specific embodiment, the coating comprises about 1 to 3% by weight
of the coated suture or ligature.
DESCRIPTION OF THE INVENTION
This invention relates to the use of degradable thermoplastic hydrogels
consisting of block polymers as a coating and lubricating finish
for surgical articles including sutures and ligatures. These materials
will impart lubricity to, and improve the tie-down properties of
a multifilament absorbable suture or ligature in both wet and dry
state. The suture or ligature can be manufactured from a homopolymer
(e.g., Dexon.TM., American Cyanamid Co., NJ, USA) or copolymer (e.g.,
Vicryl.TM., Ethicon, Inc., NJ, USA) of glycolic acid. In addition,
these materials are capable of being completely degraded and eliminated
from the body over a period of time. A particular advantage of these
materials is their thermoplastic nature, that is, they can be applied
to sutures by conventional solution or thermal techniques.
Recently, there has been interest in using hydrogels in a wide
variety of biomedical applications such as contact lenses, burn
dressings, blood and tissue compatible implants, lubricant coatings
for surgical implants, and drug delivery devices. In some of these
areas, crosslinked hydrogel materials have met with great success.
However, these materials suffer drawbacks, such as a lack of processibility,
which are a consequence of their crosslinked nature.
Our approach to this problem was to investigate the use of block
copolymers as thermoplastic biodegradable hydrogels for suture coating
applications. In an ABA triblock example of these block polymers,
the middle (B) block is a water soluble polymer such as a poly(alkylene
oxide) and the end blocks (A) are comprised of degradable random
copolymers of glycolide (Gly) and trimethylene carbonate (TMC).
The middle and end blocks of this block copolymer are chemically
incompatible and the result is a phase separated system with poly(alkylene
oxide) regions dispersed throughout the Gly/TMC matrix. When exposed
to an aqueous environment, the block polymer picks up an amount
of water which is a function of the composition and molecular weight
of the various block structures. The thermoplastic nature of the
block polymers allows for lubricant coatings to be applied by known
solution or melt processes. The crystalline poly(alkylene oxide)
segments serve, in the dry state, as temperature dependent crosslinks
which hold the coating securely in place and minimize coating flow
on storage of the surgical suture.
The method of choice for preparing the above block copolymers is
the melt phase ring-opening copolymerization of glycolide and trimethylene
carbonate using specially purified, commercially available difunctional
or monofunctional poly(alkylene glycols) as initiators. These polymerizations
are conducted in a stirred reactor at about 165.degree. C. under
nitrogen. When maximum melt viscosity has been reached, the polymer
is discharged and allowed to cool to room temperature. Oligomeric
material can be removed by reprecipitation from methylene chloride
solutions into methanol or ethanol.
Samples of the above polymers are extruded at 60.degree.-100.degree.
C. with an extruder to yield fibers of 1.5 mm average diameter.
The fibers are then cut into 1" lengths and several are placed
in deionized water at room temperature. At various time intervals,
the fibers are withdrawn, wiped thoroughly to remove any surface
liquid, and the water uptake is measured gravimetrically. Alternatively,
the uptake can be measured from thin films (0.6 mm) prepared by
compression molding the polymer at 90.degree. C., or by casting
thin films of the polymer from solution. |