Method for improving the in vivo strength retention of a bioabsorbable implantable medical device and resulting medical device

A method is provided for improving the in vivo strength retention of a bioabsorbable implantable medical device such as a suture.

BACKGROUND OF THE INVENTION 
The present invention relates to a method for improving the in vivo 
strength retention of a bioabsorbable implantable medical device, e.g., a 
suture, staple, clip, pin, screw, ring, implant, prosthesis, etc., and to 
the resulting medical device. More particularly, the invention is directed 
to improving the in vivo strength retention of such a device by 
incorporating at least one basic metal compound into the bioabsorbable 
polymer from which the device is fabricated. 
U.S. Pat No. 4,496,446 discloses a method of reducing the initial in vivo 
strength retention of surgical devices manufactured from polymers having a 
glycolic ester linkage by incorporating fillers such as barium sulfate, 
magnesium oxide, etc., into the polymers. The lowest disclosed level of 
use of filler was 12.5% in the case of barium sulfate-filled polyglycolic 
acid rods. 
SUMMARY OF THE INVENTION 
In accordance with the present invention, a method for improving the in 
vivo strength retention of a bioabsorbable implantable medical device is 
provided which comprises: 
a) incorporating an in vivo strength retention-improving amount of at least 
one in vivo strength-retention improving, biocompatible basic metal 
compound substantially uniformly within the bioabsorbable polymer from 
which the medical device is to be formed; and, 
b) forming a medical device from the bioabsorbable polymer containing the 
basic metal compound, the medical device exhibiting appreciably greater in 
vivo strength retention compared to that of the same medical device formed 
from the bioabsorbable polymer into which no in vivo strength-retaining 
basic metal compound has been incorporated. 
DESCRIPTION OF THE PREFERRED EMBODIMENTS 
The bioabsorbable polymer into which the in vivo strength 
retention-improving basic metal compound is incorporated can be obtained 
by the polymerization of one or more bioabsorbable monomers such as 
glycolide, lactide, .epsilon.-caprolactone, dioxanone, trimethylene 
carbonate, etc. Such polymers and methods for their preparation are well 
known, e.g., homopolymers and copolymers of glycolide and lactide as 
described in U.S. Pat. Nos. 2,703,316, 3,468,853, 3,636,956, 3,865,869 and 
4,137,921; dioxanone homopolymers as described in U.S. Pat. Nos. 
3,063,967, 3,063,968, 3,391,128, 3,645,941, 4,052,988 and 4,440,789; 
copolymers derived from dioxanone and at least one other monomer such as 
lactide, glycolide and caprolactone as described in U.S. Pat. Nos. 
4,643,191, 4,653,497, 4,791,929, 4,838,267, 5,007,923, 5,047,048, 
5,076,807, 5,080,665 and 5,100,433; homopolymers of trimethylene carbonate 
as described in U.S. Pat. Nos. 3,301,824, 3,379,693 and 4,920,203; 
copolymers derived from trimethylene carbonate and at least one other 
monomer such as lactide, glycolide, caprolactone and dioxanone as 
described in U.S. Pat. Nos. 4,891,263, 4,916,193, 4,920,203, 5,080,665 and 
5,120,802; caprolactone homopolymers as described in U.S. Pat Nos. 
2,878,236, 2,890,208, 3,021,309, 3,169,945, 3,190,858 and 3,284,417; 
copolymers derived from caprolactone and at least one other monomer such 
as lactide, glycolide, dioxanone and trimethylene carbonate as described 
in U.S. Pat. Nos. 4,605,730, 4,624,256, 4,700,704, 4,788,979, 4,791,929, 
4,994,074, 5,076,807, 5,080,665, 5,085,629 and 5,100,433; and, copolymers 
derived from a polyalkylene oxide such as polyethylene glycol and at least 
one other monomer such as lactide, glycolide, dioxanone, trimethylene 
carbonate and caprolactone as described in U.S. Pat. Nos. 2,917,410, 
4,452,973, 4,526,936, 4,624,256, 4,716,203, 4,857,602, 4,882,168, 
5,019,094 and 5,123,912. In a preferred embodiment of the present 
invention, a glycolide-lactide copolymer is employed. 
The biocompatible basic metal compounds which can be used to improve the in 
vivo strength retention characteristics of a bioabsorbable polymer in 
accordance with this invention include organic and inorganic compounds and 
their hydrates. Suitable basic organic metal compounds include sodium 
acetate, potassium acetate, sodium lactate, potassium lactate, calcium 
lactate, potassium glycolate, calcium glycolate, calcium propionate, 
calcium citrate, etc. Suitable basic inorganic metal compounds include the 
oxides, hydroxides, carbonates, phosphates and halides, e.g., calcium 
oxide, calcium hydroxide, calcium carbonate, calcium phosphate, calcium 
fluoride, magnesium oxide, magnesium hydroxide, magnesium carbonate, 
magnesium phosphate, sodium phosphate, sodium fluoride, potassium 
phosphate, potassium fluoride, and the like. 
The amount of basic metal compound which is incorporated into the 
bioabsorbable polymer must be at least an in vivo strength 
retention-improving amount. In the present context, the expression "in 
vivo strength retention" refers to the ability of a medical device 
manufactured from a bioabsorbable polymer to retain its strength, e.g., 
the breaking load of the freshly manufactured medical device, after 
implantation of the medical device in the body. 
In general, the incorporation of no more than about 0.5, and preferably no 
more than about 0.2, weight percent of basic metal compound into the 
polymer will provide significant improvement in the in vivo strength 
retention of the polymer. Thus, e.g., incorporation of from about 0.05 to 
about 0.25 weight percent of the basic metal compound into the 
bioabsorbable polymer is usually sufficient to increase the in vivo 
strength retention of the medical device formed therefrom by at least 
about 10 percent and will often provide increased strength retention 
levels of 20 percent or more. The use of amounts of basic metal compound 
much in excess of 0.5 weight percent should 5 ordinarily be avoided as 
they may interfere with the processability, e.g., extrudability, of the 
polymer or, as disclosed in U.S. Pat. No. 4,496,446 referred to above, 
such amounts may have the opposite effect of reducing the in vivo strength 
of the polymer and medical devices fabricated therefrom. 
The basic metal compound should be evenly distributed within the 
bioabsorbable polymer employing any of the blending techniques which are 
known to be effective for achieving this. Thus, e.g., the basic metal 
compound can be substantially uniformly incorporated into the polymer by 
milling, melt blending, etc. Pellets or powders of the polymer can be 
coated with powders of the basic metal compound with blending occurring in 
the extruder which is employed in the subsequent processing of the polymer 
to provide a useful medical device. 
The polymer of increased in vivo strength retention resulting from the 
method of the present invention can be employed in the fabrication of a 
wide variety of implantable medical devices such as surgical sutures, 
staples, clips, pins, screws, rings, implants, prostheses and the like. In 
the case of a surgical suture, the suture can be of monofilament or 
multifilament construction. The latter can be braided, twisted or spun 
using known and conventional techniques. For details of a preferred 
process of manufacturing a braided bioabsorbable suture, reference may be 
made to Kaplan et al. U.S. Pat. No. 5,019,093.

The following examples illustrate the improved in vitro strength retention 
properties of yarns manufactured from polymers having a basic metal 
compound incorporated therein. 
EXAMPLE 1 
The in vitro breaking loads of yarns produced from a 92.5:7.5 
glycolide-lactide bioabsorbable copolymer having an inherent viscosity of 
1.35 dl/g when measured in hexafluoroisopropyl alcohol at 30.degree. C. 
and containing 0.1 weight percent of a basic metal compound substantially 
uniformly incorporated therein were measured. The yarns were made up of 27 
filaments and were produced with 4.7 and 5.5 draw ratios. For purposes of 
comparison, the in vitro breaking load of a control yarn lacking a basic 
metal compound was also measured. Samples of the yarns were immersed for 
periods of time ranging from 1 to 3 weeks in an aqueous buffer solution 
maintained at a temperature of 37.degree. C. to simulate the environment 
of the human body. 
The yarns were removed and evaluated for strength retention by measuring 
their breaking load. Breaking load was measured by pulling the ends of a 
yarn in opposite directions using an Instron tester and measuring the 
amount of force required to break or sever the yarn. The breaking load 
measurements obtained herein are believed to correlate well with, and to 
be indicative of, the in vivo strength retention characteristics of the 
sutures. 
The values for breaking load set forth in the following table are expressed 
in kilograms (kg) and as percentages of the original breaking load of the 
freshly extruded yarn prior to immersion in the buffer solution. 
TABLE 
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IN VITRO BREAKING LOAD OF BIOABSORBABLE SUTURES 
Yarn % Initial 
Yarn % Initial 
Yarn % Initial 
Basic Freshly 
After 1 
Breaking 
After 2 
Breaking 
After 3 
Breaking 
Metal Draw 
Extruded 
Week Load Weeks 
Load Weeks 
Load 
Compound 
Ratio 
Yarn At 37.degree. C. 
Retained 
At 37.degree. C. 
Retained 
At 37.degree. C. 
Retained 
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Control 
5.5 7.94 6.46 92.4 5.68 72.4 1.97 23.9 
Magnesium 
4.7 8.04 6.57 81.7 4.21 52.4 2.97 36.9 
oxide 
Magnesium 
5.5 8.08 7.64 94.6 5.00 61.9 2.68 33.2 
oxide 
Magnesium 
4.7 7.92 7.07 89.3 5.06 63.9 3.11 39.3 
hydroxide 
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As these data show, the yarns containing an in vivo strength 
retention-increasing amount of basic metal compound in accordance with 
this invention exhibited significantly greater strength retention under 
equivalent simulated in vivo conditions than that of the control yarn 
specimen.