Surgical suture abstract
A surgical suture material of absorbable, synthetic polymer is
formed from glycolide-trimethylene carbonate copolymer with a glycolide
content higher than 76 wt. % and with a statistical distribution
of the monomers. Within 9 to 21 days, the suture material has a
complete breaking strength loss and is completely absorbed in vivo
after 35 to 91 days.
Surgical suture claims
1. Surgical suture material of absorbable, synthetic polymer, comprising
a glycolide-trimethyline carbonate copolymer having a glycolide
content higher than 76 wt. % and a statistical distribution of the
monomers, such that the suture material has complete breaking strength
loss in vivo within 28 days.
2. Surgical suture material according to claim 1 in the form of
3. Surgical suture material according to claim 1 in the form of
a monofilament having a diameter of 0.001 to 0.8 mm.
4. Surgical suture material according to claim 1 wherein the glycolide
content is more than 78 wt. %, based on the total copolymer.
5. Surgical suture material according to claim 1 wherein the glycolide
content is 80 to 99 wt. %, based on the total copolymer.
6. Surgical suture material according to claim 1 wherein the glycolide
content is 83 to 93 wt. %, based on the total copolymer.
7. Surgical suture material according to claim 1 having an in
vivo absorption time of 35 to 91 days.
8. Surgical suture material according to claim 1 having an in
vivo absorption time of 42 to 56 days.
9. Surgical suture material according to claim 1 having a crystallinity
of 15 to 40%.
10. Surgical suture material according to claim 1 having an inherent
viscosity of 1.0 to 2.0 dl/g.
11. Surgical suture material according to claim 1 having a tensile
strength of 250 to 900 N/m.sup.2.
12. Surgical suture material according to claim 1 having an elongation
at break of 25 to 45%.
13. Surgical suture material according to claim 1 which retains
50% of its tensile strength after 3 to 10 days.
14. Surgical suture material according to claim 1 having a complete
breaking strength loss in vivo within 9 to 21 days.
15. Surgical suture material according to claim 1 further comprising
a plasticizer in an amount sufficient to reduce the elastomeric
properties of the suture material.
16. Surgical suture material according to claim 15 wherein the
plasticizer is present in the suture material in an amount of 1-25
wt. %, based on the total weight of copolymer and plasticizer.
17. Surgical suture material according to claim 15 wherein the
plasticizer is dispersed in the copolymer.
18. Surgical suture material according to claim 15 wherein the
amount of plasticizer in the copolymer is increased as the amount
of glycolide in the copolymer is increased.
19. Surgical suture material according to claim 1 further comprising
oligomers of .epsilon.-caprolactone in an amount sufficient to reduce
the elastomeric properties of the suture material.
20. Surgical suture material of claim 19 wherein the oligomers
are present in an amount of 1-25 wt. % based on the total weight
of the suture material.
21. Surgical suture material of claim 19 wherein the oligomers
are present in an amount of 5-20 wt. %, based on the total weight
of the suture material.
22. Surgical suture material according to claim 19 wherein the
suture material includes oligomers of TMC.
23. Surgical suture material according to claim 22 wherein oligomers
are present in an amount of 1-25 wt. %, based on the total weight
of the suture material.
24. Surgical suture material according to claim 22 wherein the
oligomers are present in an amount of 5-20 wt. %, based on the total
weight of the suture material.
25. A method for wound closure which comprises closing a wound
with a surgical suture material in the form of a monofilament from
glycolide-trimethylene carbonate polymer that has a glycolide content
higher than 76 wt % and a statistical distribution of the monomers,
wherein the suture material has complete breaking strength loss
in vivo within 28 days, for wound closure with accelerated absorption.
26. The method of claim 25 wherein said suture material is absorbed
in vivo within from about 35 to 91 days.
27. The method of claim 25 wherein the glycolide-trimethylene
carbonate polymer is formed by simultaneously reacting glycolide
and trimethylene carbonate monomers to form a statistical copolymer.
28. The method of claim 27 wherein the statistical copolymer includes
14-dioxan-25-dione and 13-dioxan-2-one monomers.
Surgical suture description
The present invention relates to surgical suture material made
from absorbable, synthetic polymer, its use in surgery and process
for its production.
BACKGROUND OF THE INVENTION
Surgical suture material usable for wound closure comprises non-absorbable
and absorbable materials. Absorbable surgical sewing threads based
on natural biological materials, particularly cat gut and absorbable
synthetic sewing threads are known. Absorbable synthetic suture
material can inter alia be produced from polyglycolic acid (PGA).
In the physiological environment the sewing threads undergo a hydrolysis.
The 50% breaking strength loss, also known as the half-life period,
serves as a measure for the hydrolytic decomposition of the polymer
material. Surgical sewing threads formed from braided PGA multifilaments
(e.g. obtainable under the trademark DEXON) within 21 days have
a 50% breaking strength loss and an absorption of hydrolyzates within
100 to 120 days. A multifilament sewing thread produced from a glycolide-lactide
copolymer with a comonomer ratio of 90:10 has similar characteristics
(obtainable under the trademark VICRYL). In vivo, after 25 days
it loses 50% of its initial strength and is absorbed after more
than 80 days.
Hitherto known absorbable synthetic suture material in the form
of multifilament sewing threads suffers from a number of disadvantages,
such as e.g. poor fabric passage, sawing action or capillarity.
Monofilaments made from the described polymers have a high stiffness
and a poor knotting behaviour, which is disadvantageous for the
use thereof as surgical suture material.
Monofilament sewing threads based on polyglycolic acid are also
known, which contain softening components in the PGA matrix. From
a copolymer of glycolide and trimethylene carbonate in a ratio of
68:32 (available under the trademark MAXON), it is possible to produce
a surgical monofilament thread, whereof up to 50% of the initial
strength is maintained for more than about 5 weeks and which is
completely absorbed after about 7 months. Flexible, usable monofilaments
can also be extruded from polydioxanone (available under the trademark
PDS). The breaking strength loss and absorption time are comparable
with glycolide/trimethylene carbonate (trademark MAXON) threads
(cf. following table).
Commercially available surgical threads
______________________________________ 50% breaking Resorption
strength loss time Polymer Trade name Thread (weeks) (months) ______________________________________
Polyglycolic acid DEXON .RTM. braided 3* 3-4* Glycolide/lactide
VICRYL .RTM. braided 3-4* 3* copolymer (90:10) Glycolide/TMC MAXON
.RTM. mono- 5** 7** copolymer (68:32) filament Polydioxanone PDS
.RTM. mono- 5*** 6*** filament ______________________________________
*P. F. Nockermann: Die chirurgische Naht, Georg Thieme Verlag Stuttgart,
3rd edition, p 42 **A. R. Katz, D. P. Mukberjec, A. L. Kaganov and
S. Gordon in: Surg. Gynecol. Obstet. 161 213 (1985) ***J. A. Ray,
N. Doddi, D. Regula, J. A. Williams and A. Melveger in: Surg. Gynecol.
Obstet. 153 497 (1981)
However, these monofilament threads have a very slow decomposition
behaviour in living tissue and are only completely absorbed by the
body after several months. Their absorption time is twice as long
as known filament threads. Thus, more recent developments cover
monofilament sewing threads made from absorbable polymers with shorter
half-life periods and faster absorption.
U.S. Pat. No. 4653497 describes the two-stage production of crystalline
copolymers from 14-dioxanone and glycolide, as well as the characteristics
of the monofilament threads produced therefrom. After 4 weeks in
vivo, said monofilaments still have 10 to 30% of their initial strength
and are absorbed after about 4 to 5 months.
U.S. Pat. No. 4700704 claims copolymers of glycolide and .epsilon.-caprolactone
and the monofilaments produced therefrom. These surgical, monofilament
sewing threads, after 7 days implantation, have 44 to 62% of their
strength and after 14 days 11 to 37% thereof.
According to U.S. Pat. No. 4441496 it is possible to process
to monofilaments copolymers comprising 14-dioxanone and 25-morphalinodiones
which, after 28 days, have up to 50% of the initial strength and
which are completely absorbed after 90 to 180 days.
DE-OS 2206144 discloses copolymers of glycolide as the main component
and other cyclic comonomer such as e.g. ethylene carbonate and trimethylene
carbonate. With an ethylene carbonate proportion of 15 to 25%, the
absorption time is 30 to 60 days (with 15%) or 15 to 30 days with
a higher ethylene carbonate content.
U.S. Pat. No. 4243775 and U.S. Pat. No. 4300565 describe the
successive polymerization of glycolide and trimethylene carbonate
leading to block polymers. The monofilament threads produced from
this sequential copolymer have in the case of a trimethylene carbonate
content of 15 wt. %, after 21 days in vivo, a linear breaking strength
of 45% of the initial value and with a weight proportion of 45%
have a linear breaking strength of 38% after 21 days.
GB-A-2033411 also claims sequential copolymers of glycolide and
trimethylene carbonate (TMC), with a preferred TMC content of 10
to 20%. The residual strength of extruded monofilaments is 45% 21
days after implantation.
In certain areas of surgical wound closure long absorption times
and a long maintenance of the breaking strength are unnecessary,
because the tissue rapidly recovers its strength and consequently
the thread loses its function. Examples of such indications are
intestinal sutures, sutures in the vicinity of the mucous membranes
of the tooth-mouth-jaw area and gynecological applications. In the
case of surgical sewing threads for such applications an accelerated
hydrolytic decomposition and consequently a faster absorption are
desired. It is sufficient if there is an adequate suture strength
for a few days. A good knot breaking strength and good knottability
are consequently necessary for a reliable, safe use. At present,
for such indications, there are only synthetic material multifilament
sewing threads, which suffer from the disadvantages referred to
The problem therefore arises of making available a surgical suture
material of absorbable synthetic polymer in the form of a monofilament
having an accelerated decomposition behaviour and improved absorption,
which overcomes the disadvantages of the known suture materials,
is easy and inexpensive to manufacture, as well as easy and reliable
This problem is solved by a surgical suture material of absorbable
synthetic polymer, which is characterized in that it is formed from
glycolide-trimethylene carbonate copolymer with a glycolide content
above 76 wt. % with a statistical distribution of the monomers.
Preferably, the suture material according to the invention is in
the form of a monofilament with a diameter of 0.001 to 0.8 mm. In
such a material according to the invention the glycolide content,
based on the total copolymer is preferably more than 78 wt. %. Based
on the total copolymer, its glycolide content can in particular
be 80 to 99 wt. %. In a preferred embodiment of the invention its
glycolide content can be 83 to 93 wt. %, based on the total copolymer.
It has surprisingly been found that monofilaments can be produced
from statistical copolymers of glycolide and trimethylene carbonate
(TMC) with a glycolide content of more than 76 wt. %, which have
the very good characteristics necessary for a surgical suture material,
particularly with respect to the physical characteristics and practical
handling, and which are much more rapidly degraded and absorbed
than the prior art monofilaments formed from the same comonomer,
which are sequentially polymerized, i.e. reacted to block copolymers.
Suture material of statistical copolymer according to the invention
is advantageously characterized by an accelerated absorbability
in living tissue. Preferably, its absorbability is less than 100
days. In particular, its absorption time is in vivo 35 to 91 days.
Preferably its absorption time in vivo is 42 to 56 days.
The decomposition of the polymer according to the invention takes
place in the body of an animal or human by metabolic processes,
Body and tissue fluids participate in the reaction. Through hydrolysis
the polymer chain is split into smaller and more readily soluble
fragments. The fragments are further decomposed, optionally accompanied
by the participation of enzymatic processes. The decomposition products
are transported away by the metabolic system and are expelled from
the organism in the same way as other metabolic waste. It is important
for good compatibility of the absorbable suture material with the
patient, that during the decomposition process no harmful metabolites
can be formed or concentrated. Polyglycolic acid is in particular
characterized in that during its decomposition in vivo no toxic
decomposition products are formed. The trimethylene carbonate used
as a comonomer according to the invention is also characterized
by good compatibility and the avoidance of toxic reactions.
The statistical glycolide-TMC copolymer according to the invention
differs from the conventional, sequential glycolide-TMC copolymers
hitherto used for producing surgical suture material through the
modified sequence of the monomer units in the macromolecule chain.
This also influences the interactions between the individual chain
molecules in an already formed filament. As is known to the experts
in the field of fibre technology, the physical and mechanical properties
of a fibre are dependent on the orientation and structure of the
chain molecules, particularly the formation of amorphous and crystalline
regions. As has been revealed by analyses of the microstructure,
the inventive suture material of statistical glycolide-TMC copolymer
can have a crystallinity of 15 to 40%. It is also characterized
by an inherent viscosity (limit viscosity) of 1.0 to 2.0 dl/g, particularly
1.0 to 1.6 dl/g, measured in 0.1% hexafluoroisopropanol (HFIP) at
The material according to the invention has advantageous mechanical
characteristics. Thus, the monofilament suture material according
to the invention can have a tensile strength of 250 to 900 N/mm.sup.2
particularly 300 to 650 N/mm.sup.2. These tensile strength values
correspond to those for recognized, readily absorbable, surgical
sewing threads according to the prior art and which are required
by pharmacopoeias, or even significantly exceed these values. The
surgical suture material according to the invention can have an
elongation at break of 25 to 45%, particularly 30 to 40%. Thus,
the monofilament according to the invention is particularly suitable
for surgical applications.
The decomposition of polymer chains during absorption is linked
with a reduction in the mechanical strength of the filament material.
After 3 to 10 days, particularly 4 to 6 days, the surgical suture
material according to the invention can still have 50% of its tensile
strength. The degradation of the suture material means that, in
vivo, within 7 to 28 days it can have a complete breaking strength
loss. In particular, a material according to the invention, in vivo,
within 9 to 21 days can have a complete breaking strength loss.
Investigations of the behaviour of the mechanical characteristics
over a period of time and therefore the decomposition behaviour
of the suture material according to the invention reveals significant
differences compared with the behaviour of known, absorbable, surgical
suture materials. The investigations are described in greater detail
in the following examples and in the accompanying drawings. As has
been mentioned hereinbefore, surgical suture materials formed from
statistical glycolide-TMC copolymers according to the invention
have a higher initial strength than known, resorbable, multifilament
materials. Filaments from from 84 wt. % glycolide and 16 wt. % trimethylene
carbonate can give good results. Both in vitro and in vivo tests
have revealed that the strengths of the samples according to the
invention only decrease slowly during the first 3 days and remain
above the values of the known multifilament materials. Subsequently
there is an accelerated reduction of strength. This decomposition
behaviour is particularly pronounced in the case of the glycolide-TMC
copolymer with a monomer ratio of 92:8.
Advantageously the surgical suture material of absorbable, synthetic
polymer is in the form of a monofilament of glycolide-trimethylene
carbonate copolymer with a statistical distribution of the monomers
and is suitable for use for wound closure with accelerated absorption.
The aforementioned advantageous, mechanical characteristics of monofilament
sewing threads of statistical glycolid-TMC copolymer permit a simple
handling of the suture material during the sewing of tissue in an
animal or human body, e.g. when fixing organs, closing tears in
the body tissue or closing surgical incisions. In particular as
a result of the construction of a monofilament with a smoother thread
surface than a multifilament sewing thread, the tissue to be treated
can be protected against damage during suture application. This
limits the risk of side-effects for the patient, such as e.g. delayed
healing and tissue granuloma formation. The good knottability and
knot strength in conjunction with the high initial tensile strength
and extensibility permit a reliable fixing and stabilization of
the joined wound edges during the first days following surgery.
In particular, during said first days, regenerative, endogentic
tissue can be used in reliable manner for natural wound healing,
because the risk of a tearing apart of the wound edges during movement
of the patient is reduced by the secure fixing.
A process for the production of surgical suture material of absorbable
synthetic polymer is characterized in that glycolide and trimethylene
carbonate monomers are simultaneously reacted to a statistical copolymer.
The monomers can be 14-dioxan-25-dione and 13-dioxan-2-one in
proportions necessary for the desired copolymer. To the monomer
mixture can be added a suitable catalyst, e.g. tin octoate, in the
quantity normally required. The reaction is carried out as a melt
polymerization in a suitable reactor, which is heatable and provided
with a stirrer. The polymerization reactor must in particular be
designed in such a way that the highly viscous melts obtained are
homogenized, the necessary temperature ranges maintained and the
raw polymer can be substantially completely removed from the reactor.
Reactors of this type are inter alia offered for sale by Werner
& Pfleiderer, Stuttgart, AMK in Aachen or Haake in Karlsruhe.
The copolymerization reaction can be performed in accordance with
conventional, known procedures for the production of statistical
copolymers. Preferably the reaction mixture is heated accompanied
by constant thorough mixing, particularly at a temperature of 170.degree.
to 190.degree. C. and preferably 175.degree. to 185.degree. C. During
a reaction of 30 to 100 minutes, the monomers can be reacted to
a statistical copolymer.
At the end of the reaction the raw copolymer is heated for a short
time beyond the reaction temperature and discharged as a melt and
after cooling is granulated in the usual way. By extraction, e.g.
with ethyl acetate or some other suitable solvent, low molecular
weight fractions and residual monomers can be separated. The resulting
polymer granules are then dried. Drying can take place according
to conventional processes, particularly at elevated temperature
and/or under reduced pressure. Any extractant residues still adhering
to the raw copolymer can be removed by evaporation during drying.
In the same way monomer residues can be optionally eliminated during
drying. Optionally a further purification stage can be performed
for obtaining a high-purity copolymer according to the invention.
Preferably such a purification takes place before the drying stage.
The statistical glycolide-TMC copolymer with a composition ratio
according to the invention is characterized by a melting range of
170.degree. to 215.degree. C. This melting range can be at higher
temperatures, particularly with a higher glycolide proportion. The
glycolide-TMC copolymers produced according to the invention are
also characterized by a melting enthalpy in the range 40 to 65 J/g.
In the case of copolymers with a higher glycolide proportion, the
melting enthalpy can be in a higher value range.
The copolymer according to the invention has a partially crystalline
structure. This results from the high glycolide content of more
than 76 wt. %. Due to the high glycolide content the polymer material
has increased stiffness which affects its properties in the use
as suture material in practice. Advantageously the suture material
can include a plasticizer. The plasticizer can be present in an
amount of 1-25 wt. %, based on the total weight of the copolymer
and plasticizer, in the suture material. The plasticizer is characterized
in that it is physically dissolved in the copolymer. The plasticizer
is biocompatible and/or biodegradable. Advantageously, glyceryl
triacetate, butyl citrate, triethyl citrate, or acetyltributyl citrate
can be used for glycolide-TMC copolymers according to the invention.
Preferably can be used oligomers of .epsilon.-caprolactone as plasticizers.
Further also oligomers of TMC are appropriate as plasticizers in
the copolymer according to the invention. Advantageously the oligomers
to be used according to the invention have a maximum molecular weight
of 22000 particularly of 20000 which corresponds to about 400
units of caprolactone. Preferably the plasticizer has a viscosity
in the range of viscous flowing to solid. The intrinsic viscosity
at 25.degree. C. is particularly in the range of 0.05 to 0.5 dl/g.
As to the inter-relation of viscosity and molecular weight of polymers
see Schindler, A. et al. in: Journ. Polym. Sci., Vol. 20 p. 319-326
(1982), and Rafler, E. in: Acta Polym. 44 p. 168-170 (1993). Admixing
of the plasticizer to the copolymer can be done with the molten
polymer or in solution. The amount of plasticizer added can be about
inversely proportional to the amount of TMC in the copolymer. The
TMC in the copolymer acts as a so-called internal plasticizer. An
additionally included plasticizer acts as a so-called external plasticizer.
The copolymer with a plasticizer content according to the invention
does not exhibit elastomeric properties.
Surgical suture material can be produced by known processes from
the polymer material produced according to the invention. In particular,
the statistical glycolide-TMC copolymer according to the invention
can be spun to monofilaments in a melt spinning process. For example,
the polymer material according to the invention, can be heated to
its melting point in a conventional extruder installation, e.g.
a single-screw extruder and extruded through suitable spinnerets
to monofilaments. In a preferred embodiment, dried glycolide-TMC
copolymer can be melted at a temperature in the range 170.degree.
to 235.degree. C. For extrusion purposes, use is preferably made
of a spinneret with a diameter of 0.5 to 1.5 mm. Advantageously
the filament formed is extruded in a cooling bath, preferably water
at ambient temperature.
In order to obtain the requisite mechanical properties, the extruded
filament can be stretched or drawn for orienting the molecule chains.
Advantageously it is stretched or drawn with a stretch or draw ratio
of 1:4 to 1:10. In order to ensure that the orientation, mechanical
properties and dimensional stability of the filaments are permanently
maintained, the stretched polymer material can be fixed. Fixing
takes place at temperatures between ambient temperature and 95.degree.
C., preferably between 40.degree. and 80.degree. C. It is particularly
preferred that stretching and fixing take place immediately following
extrusion, more especially in a combined process. Advantageously
use is made of an apparatus constituted by combined, appropriate
The diameter of the monofilaments produced in this way is in the
standard range 0.001 to 0.8 mm. Advantageously, the monofilaments
according to the invention are characterized by the aforementioned
Glycolide-TMC copolymer filaments produced according to the invention
can be processed to surgical suture material by conventional methods,
e.g. cut to suitable lengths. In particular the polymer material
according to the invention can be appropriately sterilized. An appropriate
sterilization process can be chosen from among standard physical
or chemical methods for deactivating microorganisms or a combination
of such methods. Preferably, the suture material according to the
invention is sterilized using ethylene oxide.
Advantageously the surgical suture material, cut to appropriate
lengths is appropriately packed ready for use. In a preferred embodiment
the sewing threads according to the invention can be provided with
Due to the hydrolytic decomposability of the polymer material according
to the invention, the suture materials must be protected from moisture
and elevated temperatures during storage, so that the strength characteristics
are fully maintained up to the time of use. Advantageously the surgical
suture materials according to the invention are dried in the ready
for use state and appropriately packed. This appropriately takes
place in a pack protected against moisture intrusion and in particular
in moisture-proof film material, more especially a vacuum pack.
In addition, a dry, cool storage location should be chosen.
According to a particularly preferred embodiment surgical suture
threads of glycolide-TMC copolymer can be cut to length ready for
use, provided with surgical needles and sterilized and placed in
a sterile pack protected against moisture and suitable for simple