Absorbable, segmented copolymers of aliphatic polyesters based on lactone monomers glycolide, and p-dioxanone are described. The segmented copolymers exhibit a broad range of properties, especially high strength and stiffness, and fast absorption rates and breaking strength retention (BSR) profiles, useful in a variety of medical devices. Most importantly, for suture applications where Vicryl.RTM.-like polyglcolide-polylactide sutures with excellent tensile properties, but shorter BSR profiles than Vicryl.RTM. are needed. The copolymers of the present invention have such properties, making them useful in plastic surgery where faster absorption times would lead to less tissue scarring.

TECHNICAL FIELD 
The field of art to which this invention relates is polymers, more 
specifically, biocompatible, absorbable copolymers; in particular, 
segmented copolymers of aliphatic polyesters of glycolide, and 
p-dioxanone. 
BACKGROUND OF THE INVENTION 
Polymers, including homopolymers and copolymers, which are both 
biocompatible and absorbable in vivo are known in the art. Such polymers 
are typically used to manufacture medical devices which are implanted in 
body tissue and absorb over time. Examples of medical devices manufactured 
from these absorbable biocompatible polymers include suture anchor 
devices, sutures, staples, surgical tacks, clips, plates and screws, etc. 
Absorbable, biocompatible polymers useful for manufacturing medical devices 
include both natural and synthetic polymers. Natural polymers include cat 
gut, cellulose derivatives, collagen, etc. Synthetic polymers may consist 
of various aliphatic polyesters, polyanhydrides, poly(orthoester)s, and 
the like. Natural polymers typically absorb by an enzymatic degradation 
process in the body, while synthetic absorbable polymers generally degrade 
primarily by a hydrolytic mechanism. 
Synthetic absorbable polymers which are typically used to manufacture 
medical devices include homopolymers such as poly(glycolide), 
poly(lactide), poly(e-caprolactone), and poly(p-dioxanone) and copolymers 
such as poly(lactide-co-glycolide), poly(e-caprolactone-co-glycolide), and 
poly(glycolide-co-trimethylene carbonate). The polymers may be 
statistically random copolymers, segmented copolymers, block copolymers, 
or graft copolymers. It is also known that both homopolymers and 
copolymers can be used to prepare blends. 
U.S. Pat. Nos. 4,653,497, 4,838,267, 5,080,665 describe several 
biocompatible, absorbable, poly(p-dioxanone-co-glycolide) copolymers 
useful as biomedical devices. U.S. Pat. Nos. 4,838,267 and 5,080,665 
additionally describe poly(p-dioxanone-co-glycolide) block or graft 
copolymers. 
Furthermore, U.S. Pat. No. 4,838,267 describes (See FIGS. 1 and 2) the 
preparation of poly(p-dioxanone-b-glycolide) block copolymers by a 
two-step, two-reaction vessel process in which preformed, high molecular 
weight poly(p-dioxanone), that is substantially free of p-dioxanone 
monomer, is reacted with glycolide monomer at temperatures from about 
140.degree. C. to about 240.degree. C. to yield block copolymers of the 
(A--B).sub.n type where A is a long block of repeating units of 
p-dioxanone (i.e., the homopolymer of poly(p-dioxanone)) and B is a long 
block of repeating units of glycolide (i.e., the homopolymer of 
poly(glycolide)). The repeating unit structure as well as a schematic 
representation of the block copolymer structure are shown in FIGS. 1 and 
2. These copolymers are highly crystalline, due to their blocky structure, 
yielding materials with long breaking strength retention profiles (BSR), 
high strength and relatively high stiffness. It should be noted that 
breaking strength retention is a conventionally known standard method of 
measuring the strength of a device made of a bioabsorbable polymer, as a 
function of time under biological conditions in vitro or as a function of 
time after being implanted in vivo. 
Additionally, U.S. Pat. No. 5,080,665 describes block or graft copolymers 
of poly(p-dioxanone-co-glycolide) prepared by a process in which the 
p-dioxanone monomer is reacted initially for a certain period of time, 
typically one hour at about 180.degree. C., followed by reaction with 
glycolide at about 200.degree. C. This process leads to block or graft 
copolymers which are useful due to their formation of a "hard" phase 
formed from the glycolide repeating unit blocks, and a "soft" phase formed 
from the p-dioxanone repeating unit blocks as illustrated in FIGS. 3 and 
4. 
Furthermore, U.S. Pat. No. 4,653,497 describes poly(p-dioxanone)-rich 
segmented copolymers comprising about 70 weight percent to about 97 weight 
percent polymerized p-dioxanone with the remaining small portion of the 
copolymer polymerized with glycolide as illustrated in FIGS. 5 and 6. 
Although the above described copolymers yield materials with excellent 
properties such as high strength and stiffness and long BSR profiles as 
found with the block copolymers, or good strength, long elongations, low 
stiffness and shorter BSR profiles as found for the poly(p-dioxanone)-rich 
segmented copolymers, there is a need in this art for new copolymer 
compositions having characteristics of both the block copolymers and the 
segmented copolymers. 
Accordingly, what is needed in this art are novel copolymer compositions 
which have the block copolymer characteristics of high strength and 
stiffness, and the segmented copolymer characteristics of shorter BSR 
profiles and absorptions rates. 
In certain biomedical applications there is a strong need for these 
requirements, including sutures with strong tensile properties, like those 
of Vicryl.RTM. or Dexon.RTM., but shorter BSR profiles and absorption 
rates. 
In addition, it would be highly desirable to have such polymers having 
little or no unreacted monomers present, since it is believed that the 
presence of certain levels of unreacted monomers can lead to problems such 
as adverse tissue reaction. 
DISCLOSURE OF THE INVENTION 
Surprisingly, it has been discovered that by preparing copolymers of 
poly(glycolide-co-p-dioxanone) rich in glycolide by a process in which a 
small proportion of p-dioxanone monomer is reacted at low temperatures 
from about 100.degree. C. to about 130.degree. C. followed by reaction 
with glycolide at higher temperatures of about 180.degree. C. to about 
220.degree. C., segmented glycolide-rich copolymers with small proportions 
of p-dioxanone can be formed that have high strength and stiffness, but 
short BSR profiles and fast absorption rates, making them useful in a 
variety of biomedical devices such as suture anchor devices, staples, 
surgical tacks, clips, plates and screws. The copolymers of the present 
invention are especially useful for suture applications where 
Vicryl.RTM.-like sutures with excellent tensile properties but shorter BSR 
profiles than Vicryl.RTM.are needed. The copolymers of the present 
invention are, therefore, useful in plastic surgical applications, where 
faster absorption times tend to result in less tissue scarring. That is, 
for example, an absorbable suture which rapidly loses strength in the 
sections which have been implanted beneath a patient's skin can be more 
easily removed, by use of antitension skin tape, without the pain, 
discomfort and scarring typically suffered by patients who have had 
conventional sutures implanted. 
Accordingly, novel, absorbable, biocompatible, 
poly(glycolide-co-p-dioxanone) segmented copolymers are disclosed. The 
copolymers have a major component comprising about 30 mole percent to 
about 95 mole percent of repeating units of glycolide, and a minor 
component comprising about 70 mole percent to about 5 mole percent of 
repeating units of p-dioxanone. 
Yet another aspect of the present invention is a biomedical device made 
from the above described copolymers, especially implantable devices such 
as suture anchor devices, staples, surgical tacks, clips, plates and 
screws, and most especially for suture applications where Vicryl.RTM. or 
Dexon.RTM.-like sutures with excellent tensile properties, but shorter BSR 
profiles than Vicryl.RTM. or Dexon.RTM. are needed for plastic surgery. 
An additional aspect of the present invention is a process for producing 
the segmented copolymers of the present invention. The initial step of the 
process is to polymerize p-dioxanone in the presence of a catalytically 
effective amount of catalyst and an initiator at a sufficient temperature 
and for a sufficient period of time to effectively yield a first mixture 
of p-dioxanone monomer and p-dioxanone homopolymer. Then, glycolide is 
added to the first mixture to form a second mixture. Next, the second 
mixture is polymerized at a sufficient temperature and for a sufficient 
amount of time to effectively produce a segmented copolymer comprising a 
major component comprising about 30 mole percent to about 95 mole percent 
of repeating units of glycolide and a minor component comprising about 70 
mole percent to about 5 mole percent of repeating units of p-dioxanone. 
Still yet a further aspect of the present invention is the copolymer of the 
present invention which is a product of the process of the present 
invention. 
The foregoing and other features and advantages of the invention will 
become more apparent from the following description and accompanying 
examples.

DESCRIPTION OF THE PREFERRED EMBODIMENTS 
The process of the present invention is a one-step, one-reaction vessel, 
two-temperature process in which a mixture of p-dioxanone monomer and 
p-dioxanone homopolymer is initially formed at low temperatures of from 
about 100.degree. C. to about 130.degree. C., preferably 110.degree. C. 
The mixture is then reacted with glycolide at temperatures from about 
120.degree. C. to about 220.degree. C. to form copolymers in which 
segments or sequences are composed of both p-dioxanone and glycolate 
moieties as illustrated in FIGS. 7 and 8. These segmented copolymers are 
substantially less crystalline than the block or graft copolymers of the 
prior art and, therefore, yield materials with good strength, but shorter 
BSR profiles, faster absorption rates, longer elongations and lower 
stiffness. 
More specifically, the poly(glycolide-co-p-dioxanone) segmented copolymers 
of the present invention are prepared by a process in which p-dioxanone 
monomer is reacted in a conventional reactor vessel at low temperatures 
from about 100.degree. C. to about 130.degree. C., preferably about 
110.degree. C., for a sufficient time effective to cause polymerization, 
preferably about 4 hours to about 8 hours, followed by reaction with 
glycolide at higher temperatures of about 180.degree. C. to about 
220.degree. C. for a sufficient time effective to cause copolymerization, 
preferably about 1 hour to about 4 hours. 
Furthermore, the segmented poly(glycolide-co-p-dioxanone) copolymers will 
typically consist of about 30 mole percent to about 95 mole percent of 
glycolate moieties, more preferably about 30 mole percent to about 90 mole 
percent of glycolate moieties, and most preferably about 30 mole percent 
to about 50 mole percent of glycolate moieties. 
The aliphatic segmented copolyesters useful in the preparation of the 
segmented copolymers of the present invention will typically be 
synthesized in a ring opening polymerization. That is, the aliphatic 
lactone monomers are polymerized in the presence of an organometallic 
catalyst and an initiator at elevated temperatures. The organometallic 
catalyst is preferably tin based, e.g., stannous octoate, and is present 
in the monomer mixture at a molar ratio of monomer to catalyst ranging 
from about 10,000/1 to about 100,000/1. The initiator is typically an 
alkanol, a glycol, a hydroxyacid, or an amine, and is present in the 
monomer mixture at a molar ratio of monomer to initiator ranging from 
about 100/1 to about 5000/1. The polymerization is typically carried out 
at a temperature range from about 80.degree. C. to about 240.degree. C., 
preferably from about 100.degree. C. to about 220.degree. C., until the 
desired molecular weight and viscosity are achieved. 
Suitable lactone monomers may be selected from the group consisting of 
glycolide, lactide (l, d, dl, meso), p-dioxanone, delta-valerolactone, 
beta-butyrolactone, epsilon-decalactone, 2,5-diketomorpholine, 
pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, 
ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 
3,3-diethyl-1,4-dioxan-2,5-dione, gamma-butyrolactone, 1,4-dioxepan-2-one, 
1,5-dioxepan-2-one, 1,4-dioxan-2-one, 6,8-dioxabicycloctane-7-one and 
combinations of two or more thereof. Preferred lactone monomers are 
selected from the group consisting of glycolide, and p-dioxanone. 
More specifically, the segmented copolymers of 
poly(glycolide-co-p-dioxanone) useful in the practice of the present 
invention will typically be synthesized by a process in which p-dioxanone 
is polymerized in a ring opening polymerization in the presence of an 
organometallic catalyst and an initiator at elevated temperatures. The 
organometallic catalyst is preferably tin based, e.g., stannous octoate, 
and is present in the mixture at a molar ratio of monomer to catalyst 
ranging from about 10,000/1 to about 100,000/1. The initiator is typically 
an alkanol, a glycol, a hydroxyacid, or an amine, and is present in the 
monomer mixture at a molar ratio of monomer to initiator ranging from 
about 100/1 to about 5000/1. 
The polymerization is typically carried out in a conventional reactor 
vessel at a temperature range from about 100.degree. C. to about 
130.degree. C., preferably 110.degree. C., for about 4 hours to about 8 
hours, preferably about 5 hours to about 6 hours, yielding a mixture of 
p-dioxanone monomer and homopolymer. Then, glycolide monomer is added to 
the mixture of p-dioxanone monomer and homopolymer and the temperature is 
raised to about 180.degree. C. to about 220.degree. C., preferably from 
about 190.degree. C. to about 220.degree. C. until the desired molecular 
weight and viscosity are achieved. It should be understood that pure 
monomers and dry conditions are utilized to achieve such molecular 
weights. 
Under the above described conditions, the segmented copolymers of 
poly(glycolide-co-p-dioxanone), will typically have a weight average 
molecular weight of about 20,000 grams per mole to about 300,000 grams per 
mole, more typically about 40,000 grams per mole to about 200,000 grams 
per mole, and preferably about 60,000 grams per mole to about 150,000 
grams per mole. These molecular weights provide an inherent viscosity 
between about 0.5 to about 4.0 deciliters per gram (dL/g), more typically 
0.7 to about 3.5 dL/g, and most preferably 1.0 to about 3.0 dL/g as 
measured in a 0.1 g/dL solution of hexafluoroisopropanol (HFIP) at 
25.degree. C. Also, it should be noted that under the above described 
conditions, the residual monomer content will be less than about 5 wt. %. 
The segmented copolymers of poly(glycolide-co-p-dioxanone) will typically 
consists of about 30 mole percent to about 95 mole percent, more 
preferably about 30 mole percent to about 90 mole percent of glycolate 
moieties, and most preferably about 30 mole percent to about 50 mole 
percent of glycolate moieties. The lower limit of glycolate moieties in 
the copolymers is desirable because the addition of 30 mole percent leads 
to copolymers which have longer BSR profiles, but lower strength. The 
upper limit of glycolate moieties in the copolymers is desirable because 
the addition of 95 mole percent leads to copolymers which have shorter BSR 
profiles, but higher strength and stiffness. This leads to copolymers with 
a desirable range of strength, stiffness and absorption profiles for use 
in a variety of biomedical applications. One skilled in the art will 
appreciate that the number of moles of glycolate moieties and p-dioxanone 
moieties in the copolymer are equivalent to the number of moles of 
glycolide and p-dioxanone monomers needed to be added to the reaction to 
form the copolymer. 
Articles such as medical devices are molded from the segmented copolymers 
of the present invention by use of various conventional injection and 
extrusion molding equipment at temperatures ranging from about 160.degree. 
C. to about 220.degree. C., more preferably 180.degree. C. to about 
220.degree. C., with residence times of about 2 to about 10 minutes, more 
preferably about 2 to about 5 minutes. 
The segmented copolymers of the present invention can be melt processed by 
numerous methods to prepare a vast array of useful devices. These 
materials can be injection or compression molded to make implantable 
medical and surgical devices, including wound closure devices. The 
preferred devices are suture anchor devices, staples, surgical tacks, 
clips, plates and screws. 
Copolymers of the present invention with low levels of p-dioxanone have 
particular utility in the preparation of absorbable surgical devices that 
must be stiff and simultaneously tough. Of particular utility are those 
compositions having p-dioxanone at about 5 to about 30 mole percent. 
Alternatively, the segmented copolymers can be extruded to prepare fibers. 
The filaments thus produced may be fabricated into sutures or ligatures, 
attached to surgical needles, packaged, and sterilized by known 
techniques. The materials of the present invention may be spun as 
multifilament yarn and woven or knitted to form sponges or gauze, (or 
non-woven sheets may be prepared) or used in conjunction with other molded 
compressive structures such as prosthetic devices within the body of a 
human or animal where it is desirable that the structure have high tensile 
strength and desirable levels of compliance and/or ductility. Useful 
embodiments include tubes, including branched tubes, for artery, vein or 
intestinal repair, nerve splicing, tendon splicing, sheets for tying up 
and supporting damaged surface abrasions, particularly major abrasions, or 
areas where the skin and underlying tissues are damaged or surgically 
removed. Especially, sutures with Vicryl.RTM.-like tensile properties but 
shorter BSR profiles than Vicryl.RTM. are needed, useful in plastic 
surgical applications where faster absorption times would lead to less 
tissue scarring. That is, a suture which rapidly loses strength in the 
portion which is implanted beneath the skin can be more easily removed, by 
use of antitension skin tape, without the pain, discomfort and scarring 
typically suffered by patients who have had conventional sutures 
implanted. Vicryl.RTM. is a trademark for sutres made from 
polyglycolide-polylactide (90-10) copolymers. 
Additionally, the segmented copolymers of the present invention can be 
molded to form films which, when sterilized, could be useful as adhesion 
prevention barriers. Another alternative processing technique for the 
copolymers of the present invention includes solvent casting, particularly 
for those applications where a drug delivery matrix is desired. 
Furthermore, the segmented copolymers of the present invention can be 
processed by conventional techniques to form foams, which are useful as 
hemostatic barriers and bone substitutes. 
In more detail, the surgical and medical uses of the filaments, films, 
foams and molded articles of the present invention include, but are not 
necessarily limited to knitted products, woven or non-woven, and molded 
products including: 
a. burn dressings 
b. hernia patches 
c. medicated dressings 
d. fascial substitutes 
e. gauze, fabric, sheet, felt or sponge for liver hemostasis 
f. gauze bandages 
g. arterial graft or substitutes 
h. bandages for skin surfaces 
i. burn dressings 
j. orthopedic pins, clamps, screws, and plates 
k. clips 
l. staples 
m. hooks, buttons, and snaps 
n. bone substitutes 
o. needles 
p. intrauterine devices 
q. draining or testing tubes or capillaries 
r. surgical instruments 
s. vascular implants or supports 
t. vertebral discs 
u. extracorporeal tubing for kidney and heart-lung machines 
v. artificial skin and others 
w. stents 
x. suture anchors 
y. injectable defect fillers 
z. preformed defect fillers 
a1. tissue adhesives and sealants 
b2. bone waxes 
b3. cartilage replacements 
d4. hemostatic barriers 
EXAMPLES 
The following examples are illustrative of the principles and practice of 
this invention, although not limited thereto. Numerous additional 
embodiments within the scope and spirit of the invention will become 
apparent to those skilled in the art. The examples describe new segmented 
copolymers of poly(glycolide-co-p-dioxanone), said copolymers being useful 
as biomedical devices. 
In the synthetic process, the high molecular weight aliphatic segmented 
copolyesters are prepared by a method consisting of reacting p-dioxanone 
via a ring opening polymerization in a conventional reactor vessel at 
temperatures of about 100.degree. C. to about 130.degree. C. for about 4 
hours to about 8 hours under an inert nitrogen atmosphere, followed by 
reaction with glycolide at temperatures of 180.degree. C. to 220.degree. 
C. until the desired molecular weight and viscosity are achieved. 
In the examples which follow, the segmented copolymers and monomers were 
characterized for chemical composition and purity (NMR, FT-IR), thermal 
analysis (DSC), melt rheology (melt stability and viscosity), and 
molecular weight (inherent viscosity), and baseline and in vitro 
mechanical properties (Instron stress/strain). 
.sup.1 H was performed on a 300 MHz NMR using CDCl.sub.3 or HFAD as a 
reference. Thermal analysis of segmented copolymers and monomers was 
performed on a Dupont 912 Differential Scanning Calorimeter (DSC) at a 
heating rate of 10.degree. C./min. A Fisher-Johns melting point apparatus 
was also utilized to determine melting points of monomers. Thermal 
gravimetric analysis was performed on a Dupont 951 TGA at a rate of 
10.degree. C./min. under a nitrogen atmosphere. Isothermal melt stability 
of the segmented copolymers was also determined by a Rheometrics Dynamic 
Analyzer RDA II for a period of 1 hour at temperatures ranging from 
160.degree. C. to 230.degree. C. under a nitrogen atmosphere. Inherent 
viscosities (I.V., dL/g) of the segmented copolymers were measured using a 
50 bore Cannon-Ubbelhode dilution viscometer immersed in a 
thermostatically controlled water bath at 25.degree. C. utilizing 
chloroform or hexafluoroisopropanol (HFIP) as the solvent at a 
concentration of 0.1 g/dL. 
Melt viscosity was determined utilizing a Rheometrics Dynamic Analyzer RDA 
II at temperatures ranging from 160.degree. C. to 230.degree. C. at rate 
of 1.degree. C./min. to 10.degree. C./min. at frequencies of 1s.sup.-1 to 
100s.sup.-1 under a nitrogen atmosphere. 
Fibers of copolymers of the present invention were prepared by a method as 
described in U.S. Pat. No. 4,643,191, which is incorporated herein by 
reference. The copolymers were melt extruded in a conventional manner 
using an INSTRON.RTM. capillary rheometer or single screw extruder. 
Rheometer packing temperatures ranged from about 100.degree. C. to about 
200.degree. C. with dwell times of about 5 to about 15 minutes and ram 
speeds of about 1 to about 3 cm/min. Extrusion temperatures ranged from 
about 160.degree. C. to about 230.degree. C. 
The extrudate was typically drawn at a draw rate of 4 feet per minute in a 
single or mulitstage drawing process with drawing temperatures of about 
25.degree. C. to about 75.degree. C., giving a final draw ratio of about 
4.times. to about 8.times.. 
Fibers were also annealed under similar conditions as described in U.S. 
Pat. No. 4,643,191. Annealing temperatures were from about 70.degree. C. 
to about 140.degree. C., preferably 110.degree. C., with annealing times 
of about 1 hour to about 10 hours, preferably about 4 to 7 hours. 
In vitro studies were determined in a phosphate buffer solution (pH=7.27) 
at a temperature of 37.degree. C. for periods of 4, 7, 14, 21, and 28 
days. Cylindrical dumbbells (8 to 10 of a total weight of 2.4 to 3.0 
grams) or fibers (8 to 10, 6 to 12 inches long) were placed in 100 ml of 
buffer solution. 
Several synthesis examples will be described in the following few pages. 
Parts and percentages where used are parts and percentages as specified as 
weight or moles. 
EXAMPLE 1 
Synthesis of a 80:20 (mol/mol) poly(glycolide-co-p-dioxanone) segmented 
copolymer 
To a flame dried 250 ml 2-neck round bottom flask equipped with an overhead 
mechanical stirrer, nitrogen inlet and glass stopper, 20.42 grams (0.20 
moles) of p-dioxanone, 0.057 ml of diethylene glycol as an initiator, and 
50.5 microliters of a 0.33M solution of stannous octoate (in toluene) 
catalyst were added. 
The assembly was then placed in a high temperature oil bath at 110.degree. 
C. The stirred p-dioxanone quickly began to melt. The low viscosity melt 
quickly increased in viscosity. Stirring of the high viscosity melt was 
continued for about 6 hours. 
Then, 92.90 grams (0.80 moles) of glycolide was added in three equal 
portions while the temperature was raised gradually to 210.degree. C. The 
glycolide quickly began to melt and the reaction mass slowly began to 
increase in viscosity. Stirring of the high viscosity melt was continued 
for another 0.5 hours for a total reaction time of 2 hours at 210.degree. 
C. under nitrogen. 
The 80:20 (mol/mol) poly(glycolide-co-p-dioxanone) segmented copolymer was 
removed from the bath, cooled to room temperature under a stream of 
nitrogen, isolated and ground. The polymer was then dried under vacuum at 
80.degree. C. for about 64 hours. The copolymer conversion was about 
96.8%. The inherent viscosity was 1.76 dL/g as measured in a 0.1 g/dL HFIP 
solution at 25.degree. C. The molar ratio of poly(glycolide) to 
poly(p-dioxanone) was found to be 83.2 to 16.8 by .sup.1 H NMR. 
EXAMPLE 2 
Synthesis of a 70:30 (mol/mol) poly(glycolide-co-p-dioxanone) segmented 
copolymer 
To a flame dried 250 ml 2-neck round bottom flask equipped with an overhead 
mechanical stirrer, nitrogen inlet and glass stopper, 30.60 grams (0.30 
moles) of p-dioxanone, 0.057 ml of diethylene glycol as an initiator, and 
50.5 microliters of a 0.33M solution of stannous octoate (in toluene) 
catalyst were added. 
The assembly was then placed in a high temperature oil bath at 110.degree. 
C. The stirred p-dioxanone quickly began to melt. The low viscosity melt 
quickly increased in viscosity. Stirring of the high viscosity melt was 
continued for about 6 hours. 
Then, 81.30 grams (0.70 moles) of glycolide was added in three equal 
portions while the temperature was raised gradually to 210.degree. C. The 
glycolide quickly began to melt and the reaction mass slowly began to 
increase in viscosity. Stirring of the high viscosity melt was continued 
for another 0.5 hours for a total reaction time of about 2 hours at 
210.degree. C. under nitrogen. 
The 70:30 (mol/mol) poly(glycolide-co-p-dioxanone) segmented copolymer was 
removed from the bath, cooled to room temperature under a stream of 
nitrogen, isolated and ground. The polymer was then dried under vacuum at 
80.degree. C. for about 64 hours. The copolymer conversion was about 
95.4%. The inherent viscosity was 2.25 dL/g as measured in a 0.1 g/dL HFIP 
solution at 25.degree. C. The molar ratio of poly(glycolide) to 
poly(p-dioxanone) was found to be 75.2 to 24.8 by .sup.1 H NMR. 
EXAMPLE 3 
Synthesis of a 60:40 (mol/mol) poly(glycolide-co-p-dioxanone) segmented 
copolymer 
To a flame dried 250 ml 2-neck round bottom flask equipped with an overhead 
mechanical stirrer, nitrogen inlet and glass stopper, 40.84 grams (0.40 
moles) of p-dioxanone, 0.057 ml of diethylene glycol as an initiator, and 
50.5 microliters of a 0.33M solution of stannous octoate (in toluene) 
catalyst were added. 
The assembly was then placed in a high temperature oil bath at 110.degree. 
C. The stirred p-dioxanone quickly began to melt. The low viscosity melt 
quickly increased in viscosity. Stirring of the high viscosity melt was 
continued for about 6 hours. 
Then, 69.64 grams (0.60 moles) of glycolide was added in three equal 
portions while the temperature was raised gradually to 210.degree. C. The 
glycolide quickly began to melt and the reaction mass slowly began to 
increase in viscosity. Stirring of the high viscosity melt was continued 
for another 0.5 hours for a total reaction time of about 2 hours at 
210.degree. C. under nitrogen. 
The 60:40 (mol/mol) poly(glycolide-co-p-dioxanone) segmented copolymer was 
removed from the bath, cooled to room temperature under a stream of 
nitrogen, isolated and ground. The copolymer conversion was about 95.7%. 
The inherent viscosity was 1.87 dL/g as measured in a 0.1 g/dL HFIP 
solution at 25.degree. C. 
As discussed above, U.S. Pat. Nos. 4,838,267, and 5,080,665 describe 
poly(glycolide-co-p-dioxanone) block or graft copolymers. U.S. Pat. No. 
4,653,497 describes poly(p-dioxanone)-rich, segmented 
poly(p-dioxanone-co-glycolide) copolymers. 
The present invention describes glycolide-rich, segmented 
poly(glycolide-co-p-dioxanone) copolymers. 
As shown in FIGS. 1, 2, 3 and 4, block copolymers are copolymers where long 
blocks of repeating units of each of the homopolymers (i.e., the 
homopolymers of poly(p-dioxanone), or poly(glycolide)) are connected or 
linked at a single point. Segmented copolymers, as shown in FIGS. 5, 6, 7, 
and 8, are copolymers where short segments of repeating units composed of 
both monomeric units are connected or linked at many points. 
The differences in the arrangement or sequences of the repeating units in 
the copolymer can lead to dramatic changes in the thermal, chemical, 
physical, and for absorbable polymers, biological properties. 
For biocompatible, absorbable aliphatic poly(ester)s, the sequence 
arrangement of repeating units in the polymer chain has a strong effect 
on, for example, absorption rates, BSR profiles, strength, and stiffness 
(FIGS. 10 and 11). 
Table 1 shows the dramatic changes in physical properties by comparing the 
glycolide-rich, segmented poly(glycolide-co-p-dioxanone) copolymers of the 
present invention, and examples 2 and 3 of the 
poly(glycolide-b-p-dioxanone) block copolymers of U.S Pat. No. 4,838,267. 
For example, it can clearly be seen in Table 1 that the block copolymers 
(columns 3 and 5 of Table 1) have lower tensile fiber properties than the 
segmented copolymers (columns 2 and 4 of Table 1). Furthermore, the block 
copolymers have poor conversions. 
TABLE 1 
__________________________________________________________________________ 
Properties of Poly(glycolide-co-p-dioxanone) segmented Copolymers and 
Poly(glycolide-b-p-dioxanone) Block Copolymers 
Segmented Copolymers 
Block copolymer 
Segmented Copolymer 
Block Copolymer 
PGA-PDO PGA/PDO PGA/PDO PGA/PDO 
Properties Example 1* Example 2** 
Example 2* Example 3** 
__________________________________________________________________________ 
Initial Composition 
80/20 77.87/22.13 
70/30 67.24/32.76 
(moles) 
Initial Composition 
81.98/18.02 80/20 77.62/27.38 
70/30 
(weight) 
Fiber Diameter 
6.7 6.7 6.5 6.3 
(mils) 
Fiber Tensile 
136000 47200 78000 57700 
Strength (psi) 
Fiber Knot Tensile 
111000 37000 69000 52600 
Strength (psi) 
Fiber Elongation (%) 
12.6 40 22.7 52.6 
Fiber Young's 
2428 627 2007 551 
Modulus (kpsi) 
Polymerization 
97 89 96 76 
Conversion (%) 
Tensile Strength- 
11700 8600 
Inj. molded (psi) 
__________________________________________________________________________ 
**Block Copolymers are Examples 2 and 3 from U.S. Pat. No. 4,838,267 
*Segmented Copolymers are Examples 1 and 2 from the present invention 
The lower fiber properties and poor conversions of the block copolymers are 
caused by the sequence or arrangement of repeating units within the 
copolymers. That is, in the block copolymers, the polymers are composed of 
long sequences of both homopolymers, with some blocks of poly(p-dioxanone) 
on the ends of the chain (FIGS. 2 and 4). In contrast, the segmented 
copolymers, due to their more random sequence of repeating units, are 
composed mostly of glycolide end blocks (FIG. 8). Consequently, the 
glycolide end blocks lead to improved stability during polymerization, 
with less loss of p-dioxanone monomer, since it is not possible for the 
p-dioxanone segments to depolymerize at the end of the chain as can be 
found for the block copolymers. Hence, the segmented copolymers have 
higher conversions (i.e., less than 5 wt. % unreacted monomers, 95% or 
greater conversions), and better physical properties, especially fiber 
tensile properties. In addition, the higher conversions, and consequently, 
good thermal stability, found for the segmented copolymers, allows these 
materials to be injection molded with good tensile properties (Table 1). 
In addition, the present invention requires only a single reactor process 
for polymerization, where the p-dioxanone monomer is polymerized to 
approximately 75% conversion, followed by reaction with glycolide to from 
copolymers with short segments of poly(p-dioxanone), 
poly(p-dioxanone-co-glycolide), and poly(glycolide) end blocks. In 
contrast, the block copolymers of U.S. Pat. No. 4,838,267, require a 
two-step, two reactor process, where the p-dioxanone is polymerized and 
then further processed by isolating, grinding, and drying to remove 
unreacted p-dioxanone monomer. Then, the poly(p-dioxanone) is reacted with 
glycolide to form block copolymers with long sequences of 
poly(p-dioxanone) and poly(glycolide), with some poly(p-dioxanone) end 
blocks. 
Hence, the process of the present invention leads to the copolymers having 
end blocks of glycolide which prevents depolymerization and yields high 
conversions and excellent physical properties. Thus, the segmented 
copolymers of the present invention have a more elegant, simple, single 
reactor polymerization process than those of the block copolymers. This 
not only leads to advantageous properties, but is vital for large scale 
manufacturing development, being more cost effective and less time 
consuming. 
Furthermore, the physical characteristics of the segmented copolymers of 
the present invention should allow for a variety of needs to be met for a 
wide range of medical devices. For example, there is a great need for 
absorbable polymers in plastic surgery wound closure, where high initial 
strength but very short BSR profiles are required. Currently, Vicryl.RTM. 
or Dexon.RTM. sutures are used (Table 2). Dexon.RTM. is a trademark for 
sutures made from braided poylcolide. 
TABLE 2 
__________________________________________________________________________ 
Straight Tensile Strength of fibers as a function of days in-vitro 
DEXON (polyglycolide) VICRYL [poly(glycolide-co-lactide]) 
and Segmented Poly(glycolide-co-p-dioxanone) Copolymers 
Straight Tensile Strength (psi) 
Mole % 
Copolymer 
PGA/PLA 
Zero-day 
Four-day 
7-day 
14-day 
21-day 
28-day 
__________________________________________________________________________ 
VICRYL* 
90/10 117000 
N/A 95000 
72000 
43000 
0 
DEXON* 100/0 118000 
N/A 96000 
85000 
44000 
0 
Weight % 
PGA/PDO 
Example 1** 
80/20 136000 
62000 
0 
Example 2** 
70/30 80000 
36000 
0 
__________________________________________________________________________ 
*SIZE 4.0, BRAIDED 
**SIZE 5.0, MONOFILAMENT 
However, as shown in FIG. 9, Vicryl.RTM. has a very long BSR profile. 
Consequently, this can lead to tissue scaring, an event which plastic 
surgeons want to avoid. The segmented glycolide-rich, 
poly(glycolide-co-p-dioxanone) copolymers of the present invention also 
have high zero-day fiber tensile properties. This would also allow the 
surgeon to suture the wounds securely. However, because of their very fast 
absorption rates and very short BSR profiles, less scarring will occur 
(Table 2, FIG. 9) than found with currently marketed, longer BSR sutures 
like Vicryl.RTM. and Dexon.RTM.. This behavior is caused by the unique 
structure of short poly(glycolide) end blocks found in the segmented 
copolymers of the present invention, which produces improved tensile 
properties and fast absorption rates. 
The differences in properties between the copolymers of the present 
invention and U.S. Pat. Nos. 4,653,497, 4,838,267 and 5,080,665, due to 
differences in the structure and composition, are clearly indicated in 
FIG. 11. That is, surprisingly we have discovered that by moving towards 
compositions rich in glycolide where the copolymer structure is composed 
of short segments (i.e., segmented copolymer), and away from blocky 
structures, it is possible to obtain polymers with both high strength and 
short BSR profiles. That is, the block copolymer compositions yield high 
strength and longer BSR profiles or lower strength and longer BSR 
profiles. In addition, segmented copolymers, rich in p-dioxanone, yield 
polymers with lower strength and longer BSR profiles. 
This surprising behavior is also clearly indicated in FIG. 9, which shows 
that the copolymers of poly(glycolide-co-p-dioxanone) of this invention 
have higher strength than either of the homopolymers of poly(glycolide) 
(i.e., Dexon.RTM.) or poly(p-dioxanone), but much shorter BSR profiles 
than even Vicryl.RTM., Dexon.RTM., poly(p-dioxanone) or the segmented 
p-dioxanone-rich, poly(p-dioxanone-co-glycolide) copolymers of U.S. Pat. 
No. 4,653,497. That is, the segmented copolymers of this invention lose 
all strength in less than 10 days, whereas the glycolide and p-dioxanone 
homopolymers and the copolymers of U.S. Pat. No. 4,653,497 maintain 
strength for 3 weeks or longer. 
That is, it is unexpected, based upon composition, to obtain a copolymer of 
poly(glycolide-co-p-dioxanone) which has the tensile strength of either of 
the homopolymers of poly(p-dioxanone) or poly(glycolide), but a much 
shorter BSR profile than either homopolymer. 
Therefore, it can be seen that glycolide-rich, 
poly(glycolide-co-p-dioxanone) segmented copolymers of the present 
invention possess a surprising and unexpected unique combination of high 
strength and stiffness, and very short BSR profiles and fast absorption 
rates. The copolymers of the present invention are useful in numerous 
applications requiring absorbable polymers which have high strength and 
stiffness and short BSR profiles. They are particularly useful, for 
example, in plastic surgical applications where the surgeon needs to 
secure the wound, but requires fast absorption to prevent tissue scaring. 
Although this invention has been shown and described with respect to 
detailed embodiments thereof, it will understood by those skilled in the 
art that various changes in form and detail thereof may be made without 
departing from the spirit and scope of the claimed invention.