Method for inhibiting biological degradation of implantation polymeric material, inhibitor thereof and implantation polymeric material containing the inhibitor

A method for inhibiting decomposition and/or degradation of an implantation polymeric material in the living body, which comprises allowing dipyridamole and/or a salt or a derivative thereof as an active component to exist in the vicinity of an implantation polymeric material implanted in the living body; an inhibitor effective for inhibiting biological decomposition and/or degradation of a polymeric material implanted in the living body, which comprises dipyridamole and/or a salt or a derivative thereof as an active component; and an implantation polymeric material which contains dipyridamole and/or a salt or a derivative thereof as an active component.

FIELD OF THE INVENTION 
This invention relates to a method for inhibiting biological decomposition 
and/or degradation of a polymeric material implanted in a living body, to 
an inhibitor thereof and to a polymeric material for implantation in the 
living body which exhibits minimal decomposition. 
BACKGROUND OF THE INVENTION 
In view of the rapid progress in the development of medical techniques in 
recent years, a variety of medical devices are currently implanted in the 
living body for a prolonged period. In particular, polymeric materials 
have been actively developed as materials for implantation in the living 
body (to be referred to as "implantation material" or "implantation 
polymeric material" hereinafter), because their mechanical properties are 
closer to those of biological components than those of metals, ceramics 
and the like. Polymeric materials can be processed easily and exhibit 
properties such as anti-thrombogenetic activity, biocompatibility and the 
like. Of these polymeric materials, elastic materials such as segmented 
polyurethane are preferably used in artificial blood vessels, artificial 
hearts, insulation coatings of pacemaker leads and the like because of 
their excellent mechanical properties and high compatibility with 
biological tissues. 
In spite of these excellent properties as implantation materials, the 
long-term stability of polymeric materials in the living body is inferior 
to that of other materials because polymeric materials are apt to 
decompose or degradate in the living body, thus causing problems such as 
decrease in the mechanical strength, eluation of decomposed compounds and 
the like. Also, in the case of elastic, soft or hydrophilic materials, 
they have flexible polymer chains and, as a result, have a higher 
possibility of degradation and decomposition in comparison with hard 
materials. Decomposition and degradation in the living body depends also 
on the shape of the material and increases when the material has a large 
surface area. As a consequence, when polymeric materials are made into 
thin film, porous and similar implantation materials making use of their 
flexibility, it is highly probable that the degree of the decomposition 
and degradation of the resulting implants is high. 
To date, a method for effectively inhibiting biological decomposition and 
degradation of polymeric materials has not been found, thus preventing the 
full utilization of the benefits of polymeric materials. 
SUMMARY OF THE INVENTION 
The present inventors have considered the above-mentioned problems and have 
conducted intensive studies on the development of a method for inhibiting 
biological decomposition and/or degradation of polymeric materials for 
implantation in the living body. They have unexpectedly found that 
dipyridamole and/or a salt thereof or a derivative thereof, which have 
been known as a vasodilator and as a platelet adhesion inhibitor, possess 
a markedly excellent effect in inhibiting biological decomposition and/or 
degradation of polymeric materials. 
An object of the present invention is to provide a method for inhibiting 
decomposition and/or degradation of an implantation polymeric material in 
a living body, which comprises applying dipyridamole and/or a salt and/or 
derivative thereof as an active component in the vicinity of the 
implantation polymeric material implanted in the living body. 
Another object of the present invention is to provide an inhibitor 
effective for inhibiting biological decomposition and/or degradation of a 
polymeric material implanted in the living body, which comprises 
dipyridamole and/or a salt and/or derivative thereof as an active 
component. 
Yet another object of the present invention is to provide an implantation 
polymeric material which contains dipyridamole and/or a salt or derivative 
thereof as an active component. 
DETAILED DESCRIPTION OF THE INVENTION 
Biological decomposition and degradation include any changes of an 
implanted material in its material characteristics such as mechanical or 
chemical characteristics, which are generated by biological reactions such 
as immune system reactions, inflammatory reactions and the like that occur 
when a material is implanted in the living body. 
Implantation material includes any material implanted in the living body 
for a certain period of time. The implantation period varies depending on 
its purpose, generally from several days to several decades. Typical 
examples of the implantation materials include, but are not limited to,: 
surgical materials such as a suture, an adhesive material and the like; 
diagnostic materials such as an indwelling sensor and the like; tissue 
prostheses such as artificial skin, an artificial muscle, a gap filler and 
the like; dental materials such as an artificial tooth, an artificial root 
and the like; orthopedic materials such as an artificial joint, an 
artificial bone and the like; implantation type artificial organs such as 
an artificial kidney, an artificial lung, an artificial liver, an 
artificial pancreas and the like; materials for a circulatory organ use 
such as an artificial blood vessel, an artificial heart, a prosthetic 
cardiac valve, insulation coating of pacemaker leads and the like; 
ophthalmic materials such as an intraocular lens, an artificial cornea and 
the like; and an indwelling catheter, an indwelling device for drug 
delivery and the like. 
Of these implantation materials, the present invention may be applied most 
preferably to those with direct contact with blood, such as materials for 
circulatory organ use, artificial organs and intravascular indwelling 
catheters. 
Implantation of polymeric material should be interpreted to include a 
portion or a whole of any of the above implantation materials, which is 
composed of one or a plurality of polymeric materials. 
Polymeric material should be interpreted to include any generally defined 
polymer as disclosed for instance in Koubunshi Kagaku (S. Murahashi et 
al., Kyoritsu Shuppan) and Koubunshi Kagaku Joron (S. Okamura et al., 
Kagaku Dojin). From a chemical point of view, a polymeric material is a 
compound which is composed of repeating units linked by carbon-to-carbon, 
ester, ether, urethane, amide, urea, imide, carbonate, sulfone, siloxane 
and the like bonds or linkages. Each polymeric material may be composed of 
the same or two or more different types of repeating units, bonds or 
linkages. In other words, the polymeric material may be a homopolymer or a 
copolymer, and the latter may be selected from a random copolymer, an 
alternating copolymer, a block copolymer, a graft copolymer and the like. 
Also, the polymeric material may have a linear or a cross-linked structure. 
The cross-linking may be effected by chemical bonding or by physical 
interactions such as hydrogen bonding, ionic bonding, hydrophobic bonding, 
crystallization and the like. Polypeptides which are polymers of amino 
acids are also included in polymeric materials. 
Typical examples of such polymeric materials include: vinyl polymers such 
as polyethylene, polypropylene, polybutadiene, polystyrene, polyvinyl 
alcohol, an ethylenevinyl alcohol copolymer, polymethyl methacrylate, 
polyhydroxyethyl methacrylate, polyacrylamide, polydimethylacrylamide, 
polyvinyl chloride, polyethylene fluoride, polypropylene fluoride and the 
like; polyesters such as polyethylene terephthalate, polybutylene 
terephthalate and the like; segmented polyesters such as a 
polytetramethylene glycol-polyethylene terephthalate block copolymer, a 
polycaprolactone-polyethylene terephthalate block copolymer and the like; 
polyethers such as polyethylene glycol, polypropylene glycol, 
polyoxymethylene, polyphenylene oxide, polysaccharide and the like; 
polyurethanes such as polyether urethane, polyester urethane, polyether 
urethane urea, polyester urethane urea and the like; segmented linear 
thermoplastic polyurethanes; polyamides such as nylon and the like; 
polysiloxanes such as polydimethylsiloxane and the like; and 
polycarbonates, polysulfones and the like. 
The present invention may be most effectively applied to soft and elastic 
polymeric materials, as well as hydrophilic polymeric materials, whose 
polymer chains are flexible and which are sensitive to biological 
degradation. 
Typical examples of such preferred polymeric materials include: amorphous 
polymer chains having low glass transition temperature, such as 
polyisoprene, polybutadiene, polypropylene oxide, polyethylene oxide, 
polytetramethylene glycol and the like; and polymeric materials which 
contain hydrophilic polymer chains in their molecules, such as 
polyacrylamide, polyvinyl alcohol, polyvinyl pyrrolidone, polysaccharide, 
polypeptide and the like. Each of these polymeric materials may have a 
cross-linked structure effected by the aforementioned means or may be used 
in combination with other polymeric materials. 
Thermoplastic elastomer is a preferred example of these polymeric 
materials. In contrast to the usual elastic polymeric materials, 
thermoplastic elastomer is a linear polymer which is composed of a 
so-called "hard segment" having high crystallinity and a so-called "soft 
segment" having high flexibility. It has no intermolecular chemical 
cross-linking, and its shape is kept by the aggregation of the hard 
segment. As a consequence, physical properties of the thermoplastic 
elastomer are reduced by degradation and decomposition more quickly than 
as is the case of the usual cross-linked elastic materials. In general, 
the thermoplastic elastomer consisting of such hard and soft segments 
frequently forms a micro phase separation structure in which these 
segments are microscopically separated from each other. When these 
separated segments are respectively hydrophobic and hydrophilic, the 
elastomer shows excellent anti-thrombogenetic activity and therefore is 
used most desirably as an implantation material which is in direct contact 
with blood, such as an artificial blood vessel and the like. Though not 
particularly limited, a segmented polyurethane, a segmented polyester and 
the like may be included in typical examples of such polymeric materials. 
The polymeric material of the present invention forms a portion or the 
whole of an implantation material, and formation of a portion of the 
implantation material with a polymer may be effected making use of 
coating, application, adhesion, kneading, embedding, lamination and the 
similar means. 
Dipyridamole, which is used as an active component having activities which 
inhibit biological decomposition and/or degradation of the implantation 
polymeric materials of the present invention, is a generic name for 
2,6-dis(diethanolamino)-4,8-dipiperidinopyrimido [5,4-d]pyrimidine, 
represented by formula (I): 
##STR1## 
or salts thereof. Illustrative examples of salts of dipyridamole include 
sulfite, bis(phosphonoxy) propionate, sulfate, p-toluenesulfonate, 
phosphate, guanosine 5'-monophosphates, inosine 5'-monophosphates, 
adenosine phosphates, diphosphoglycerate and the like. 
It is known that dipyridamole has many useful functions including 
thromboembolism inhibition, platelet aggregation inhibition, platelet 
adhesion inhibition, platelet activation inhibition, urinary protein 
reduction, vasodilation and the like. Because of these functions, 
dipyridamole has been used as a postoperative thromboembolism inhibitor 
and a nephrotic syndrome therapeutic agent. However, its effect to inhibit 
biological decomposition and/or degradation of polymeric materials, as 
disclosed in the present invention, is unexpected in view of the prior art 
in regard to the function and effect of dipyridamole. Known polymeric 
materials which have not been practically employed as an implantation 
materials become usable therefor when used with the dipyridamole and/or a 
salt and/or a derivative thereof. 
Administration of dipyridamole and/or a salt and/or a derivative thereof 
into the living body may be effected by any of common administration 
including oral administration, gastrointestinal administration such as 
rectal instillation and the like, intravascular administration such as 
intravenous injection, intraarterial injection and the like, subcutaneous 
injection, intramuscular injection, intraperitoneal injection, application 
and the like, as well as tissue administration by indwelling of 
microcapsules and the like. The dipyridamole and/or a salt and/or a 
derivative thereof can be formulated into a pharmaceutical composition 
together with known pharmaceutically acceptable carrier. Effect of the 
dipyridamole and/or a salt and/or a derivative thereof may be obtained by 
administering the compound in such an amount that it exists in a 
sufficient amount in the vicinity of the implantation polymeric material 
of interest. For example, in the case of oral administration, a preferred 
dose of the compound per day may be 1 mg/kg body weight or more but less 
than 20 mg/kg body weight. More specifically, the dipyridamole and/or a 
salt and/or a derivative thereof may be formulated into Persantin tablets 
(manufactured by Behringer-Tanabe) for oral administration in an amount of 
100 mg/tablet. It may be also formulated into an injectable solution in an 
amount of 100 mg/2 ml. 
The implantation polymeric material of the present invention may contain 
dipyridamole and/or a salt and/or a derivative thereof in an amount of 
from 0.0001 to 100% by weight, preferably from 0.001 to 50% by weight of 
the implantation polymeric material, although the amount may vary because 
the necessary amount of the compound changes depending on the shape, raw 
material, used portion and the like. 
In the case of a polyurethane artificial blood vessel which contains 
dipyridamole and/or a salt or a derivative thereof, the compound may be 
used in an amount of from 0.0001 to 100% by weight, preferably from 0.001 
to 50% by weight, more preferably from 0.01 to 10% by weight, based on the 
weight of urethane. If the amount of the compound is smaller than 0.0001% 
by weight, this reduces the effect of the compound to inhibit biological 
decomposition. If the amount of the compound is larger than 100% by 
weight, this results in inferior mechanical properties and patency as a 
blood vessel. 
In regard to an illustrative mode of an implantation polymeric material 
which contains dipyridamole, the dipyridamole may be included in the 
polymeric material or, if the material for implantation has a porous 
structure, the compound may be kept in pores of the material. 
In the former case, the polymeric material may be kneaded with 
dipyridamole. In that instance, dipyridamole may be dispersed or dissolved 
in a solution of the polymeric material, or, in the case of a 
thermoplastic polymeric material, dipyridamole may be dispersed in a 
solution of the thermoplastic polymeric material or the material and the 
compound may be made into a mixed melting solution when the material has a 
higher melting point than that of the compound (about 165.degree. C). 
In the latter case, the material for implantation use having a porous 
structure may be soaked in a solution of dipyridamole, thus allowing the 
dipyridamole solution to permeate into the pores of the material, and then 
the solvent may be removed by distillation thereby keeping dipyridamole 
molecules inside the pores. The type of solvent for use in the above 
purpose varies depending on the polymeric material to be used. Examples of 
a preferable solvent of dipyridamole include methanol, ethanol, 
chloroform, dioxane and a dilute acid having a pH value of 3.3 or below. A 
commercial parenteral solution may also be used. 
It is assumed that the effective inhibition of the decomposition of the 
implantation polymeric material of the present invention is attained 
through the release of dipyridamole and/or a salt or a derivative thereof 
from the surface of the polymeric material after its implantation in the 
living body. 
Although the implantation polymeric material of the present invention 
itself possesses a resistant feature to its decomposition in the living 
body, it is preferable to use it together with the administration of 
dipyridamole and/or a salt or a derivative thereof. By the joint use of 
the compound with the implantation polymeric material and the 
administration of the compound into the living body, decomposition of the 
implanted polymeric material in the living body can be inhibited more 
efficiently.

EXAMPLES 
To further illustrate the present invention in greater detail, the 
following examples are given, but are not to be construed as to limit the 
scope of the invention. 
PRODUCTION EXAMPLE 1 
4,4'-diphenylmethane diisocyanate (MDI), polytetramethylene glycol (PTMG) 
having a molecular weight of 1,000 and 1,4-butanediol (1,4-BD) (molar 
ratio: MDI/PTMG/1,4-BD=2/1/1) were polymerized by a prepolymer process in 
a mixed solvent of N,N-dimethylacetamide (DMAc) and 1,4-dioxane (weight 
ratio: DMAc/dioxane=7/3) to obtain a segmented polyurethane. 
The segmented polyurethane thus prepared was purified by subjecting it to 
Soxhlet extraction with ethanol for 3 hours. 
PRODUCTION EXAMPLE 2 
The purified segmented polyurethane obtained in Production Example 1 was 
mixed with the same weight of NaCl crystals having a particle size of 
about 50 .mu.m, and the mixture was dissolved in a mixed solvent of DMAc 
and 1,4-dioxane (weight ratio: DMAc/dioxane=1:1) to obtain a solution 
containing 30% by weight of polyurethane (to be referred to as "dope" 
hereinafter). The thus prepared dope was spread on a glass dish and, after 
adding an appropriate amount of water for injection, was allowed to stand 
for overnight to coagulate and precipitate into the thus treated 
polyurethane. 
A film of the thus formed polymer was detached from the glass dish and 
washed with water thoroughly to remove NaCl, thereby obtaining a porous 
film of segmented polyurethane having a thickness of 1.5 mm. 
PRODUCTION EXAMPLE 3 
A dope was prepared in the same manner as in Production Example 2. A glass 
rod having an outer diameter of 3 mm was soaked in the thus prepared dope 
and then removed to coat the rod with the dope. The coated glass rod was 
soaked overnight in purified water to coagulate and precipitate segmented 
polyurethane. Thereafter, a tubular form of segmented polyurethane was 
detached from the glass rod and then washed thoroughly with purified water 
to remove NaCl and remaining solvent. The tubular form of segmented 
polyurethane (to be referred to as "artificial blood vessel" hereinafter) 
was a tube of 3 mm in inner diameter and 4.5 mm in outer diameter having a 
porous structure which contained communicating pores through inner and 
outer surfaces of the tube. 
PRODUCTION EXAMPLE 4 
95 parts by weight of the purified segmented polyurethane obtained in 
Production Example 1 was mixed with 5 parts by weight of dipyridamole, and 
the mixture was dissolved in a mixed solvent of DMAc and 1,4-dioxane 
(weight ratio: DMAc/dioxane=1:1). The resulting solution was mixed 
thoroughly with NaCl crystals (2.6 times as weigh as the weight of the 
segmented polyurethane) having a particle size of about 50 .mu.m as a 
pore-forming material, thereby obtaining a dope containing 15% by weight 
of polyurethane for use in the preparation of an artificial blood vessel. 
A glass rod having an outer diameter of 3 mm was soaked in the thus 
prepared dope and then removed to coat the rod with the dope. The coated 
glass rod was soaked overnight in purified water to coagulate and 
precipitate the segmented polyurethane. Thereafter, a tubular form of the 
segmented polyurethane was detached from the glass rod and then washed 
thoroughly with purified water to remove NaCl and remaining solvent. The 
tubular form of segmented polyurethane (to be referred to as "artificial 
blood vessel" hereinafter) was a tube of 3 mm in inner diameter and 4.5 mm 
in outer diameter having a porous structure which contained communicating 
pores through inner and outer surfaces of the tube. 
PRODUCTION EXAMPLE 5 
As a comparative example, the process of Production Example 4 was performed 
except that dipyridamole was not used, thereby obtaining an artificial 
blood vessel which does not contain dipyridamole (a porous segmented 
polyurethane tube of 3 mm in inner diameter and 4.5 mm in outer diameter 
containing communicating pores through inner and outer surfaces of the 
tube). 
PRODUCTION EXAMPLE 6 
A dope prepared in the same manner as in Production Example 4 was spread on 
a glass dish and, after adding an appropriate amount of water for 
injection, allowed to stand for overnight to coagulate and precipitate 
into the thus treated polyurethane. 
A film of the polymer thus formed was detached from the glass dish and 
washed with water thoroughly to remove NaCl, thereby obtaining a porous 
film of segmented polyurethane having a thickness of 1.5 mm. 
PRODUCTION EXAMPLE 7 
As a comparative example, the process of Production Example 6 was performed 
except that dipyridamole was not used, thereby obtaining a porous film of 
segmented polyurethane having a thickness of 1.5 mm which does not contain 
dipyridamole. 
PRODUCTION EXAMPLE 8 
The porous segmented polyurethane tube obtained in Production Example 5 
(about 3 cm in length) was soaked in an ethanol solution containing 10% by 
weight of dipyridamole, and the dipyridamole solution was allowed to 
permeate thoroughly into the pores of the tube under reduced pressure 
using a vacuum pump. Thereafter, the treated tube was removed from the 
dipyridamole solution and dried under a reduced pressure to obtain an 
artificial blood vessel which contained dipyridamole in its pores (a 
porous segmented polyurethane tube of 3 mm in inner diameter and 4.5 mm in 
outer diameter containing communicating pores through inner and outer 
surfaces of the tube). 
PRODUCTION EXAMPLE 9 
The porous segmented polyurethane film obtained in Production Example 7 
(approximately 2 cm.times.2 cm) was treated in the same manner as in 
Production Example 8 to obtain a porous segmented polyurethane film which 
contained dipyridamole in its pores. 
EXAMPLE 1 
The porous segmented polyurethane film obtained in Production Example 2 
(approximately 2 cm.times.2 cm) was subcutaneously implanted into 
crossbred adult dogs which were divided into a dipyridamole-administered 
group and a control group (no administration of the compound). After three 
months of the implantation, the films were recovered to measure changes in 
their molecular weights by gel permeation chromatography and to compare 
the results between the two test groups. In the dipyridamole-administered 
group, oral administration of dipyridamole was started one week before the 
implantation operation and continued until the day of the film removal at 
dose of 10 mg/kg body weight/day. Dipyridamole was formulated into 
Persantin tablet (100 mg/tablet, manufactured by Behringer-Tanabe). In the 
control group, dipyridamole was not administered during this period. 
The polystyrene-based molecular weight of the film, which was 150,000 when 
measured by gel permeation chromatography before the implantation, was 
reduced to 100,000 after the implantation in the control group, while no 
decrease in the molecular weight was found in the 
dipyridamole-administered group after the implantation. 
EXAMPLE 2 
The artificial blood vessel obtained in Production Example 3 (approximately 
5 cm in length) was transplanted to the femoral artery of crossbred adult 
dogs which were divided into a dipyridamole-administered group and a 
control group which were not administered the compound. Three months 
following the transplantation, the artificial blood vessels were recovered 
to measure changes in their molecular weights by gel permeation 
chromatography and to compare the results between the two test groups. In 
the dipyridamole-administered group, oral administration of dipyridamole 
in the same dosage form as in Example 1 was started one week before the 
transplantation operation and continued until the day of the film removal 
at a dose of 10 mg/kg body weight/day. In the control group, dipyridamole 
was not administered during this period. 
The polystyrene-based molecular weight of the artificial blood 
vessel-constituting segmented polyurethane, which was 150,000 when 
measured by gel permeation chromatography before the transplantation, was 
reduced to 90,000 after the transplantation in the control group, while no 
decrease in the molecular weight was found in the 
dipyridamole-administered group after the implantation. 
EXAMPLE 3 
The artificial blood vessel made of the dipyridamole-containing segmented 
polyurethane (approximately 3 cm in length) obtained in Production Example 
4, was transplanted to the femoral artery of crossbred adult dogs which 
were used as a test group. As a comparative example, the artificial blood 
vessel made of the dipyridamole-free segmented polyurethane (approximately 
3 cm in length) obtained in Production Example 5, was transplanted to the 
femoral artery of other crossbred adult dogs which were used as a control 
group. After six months following the transplantation, the artificial 
blood vessels were recovered to measure changes in the molecular weight of 
the artificial blood vessel-constituting segmented polyurethane by gel 
permeation chromatography and to compare the results between the two 
groups. Additional administration of dipyridamole was not carried out 
during the transplantation period. 
The polystyrene-based molecular weight of each of the segmented 
polyurethane portions of the artificial blood vessels, which was 150,000 
when measured by gel permation chromatography before the transplantation, 
was reduced to 100,000 after six months of the transplantation in the case 
of the control group in which the artificial blood vessel made of the 
dipyridamole-free segmented polyurethane of Production Example 5 was used 
as a comparative example. In contrast, the molecular weight of the 
artificial vessel made of the dipyridamole-mixed segmented polyurethane 
did not decrease even following six months after the transplantation. 
EXAMPLE 4 
The dipyridamole-containing porous segmented polyurethane film 
(approximately 2 cm.times.2 cm) obtained in Production Example 6 was 
subcutaneously implanted in crossbred adult dogs which were used as a test 
group. As a comparative example, the dipyridamole-free porous segmented 
polyurethane film (approximately 2 cm.times.2 cm) obtained in Production 
Example 7 was subcutaneously implanted in other crossbred adult dogs which 
were used as a control group. After three months following the 
implantation, the films were recovered to measure changes in their 
molecular weights by gel permeation chromatography and to compare the 
results between the two groups. Additional administration of dipyridamole 
was not carried out during the transplantation period. 
The polystyrene-based molecular weight of each of the films, which was 
150,000 when measured by gel permeation chromatography before the 
implantation, was reduced to 110,000 after three months of the 
implantation in the case of the control group in which the 
dipyridamole-free film was used as a comparative example. In contrast, the 
molecular weight of the dipyridamole-containing film did not decrease even 
after three months of the implantation. 
EXAMPLE 5 
The artificial blood vessel having dipyridamole-included pores 
(approximately 3 cm in length) obtained in Production Example 8 was 
transplanted into the femoral artery of crossbred adult dogs which were 
used as a test group. As a comparative example, the artificial blood 
vessel made of the dipyridamole-free segmented polyurethane (approximately 
3 cm in length) obtained in Production Example 5, was transplanted into 
the femoral artery of other crossbred adult dogs which were used as a 
control group. Six months following the transplantation, the artificial 
blood vessels were recovered to measure changes in the molecular weight of 
the artificial blood vessel-constituting segmented polyurethane by gel 
permeation chromatography and to compare the results between the two 
groups. Additional administration of dipyridamole was not carried out 
during the transplantation period. 
The polystyrene-based molecular weight of each of the segmented 
polyurethane portions of the artificial blood vessels, which was 150,000 
when measured by gel permeation chromatography before the transplantation, 
was reduced to 100,000 after six months of the transplantation in the case 
of the control group in which the artificial blood vessel made of the 
dipyridamole-free segmented polyurethane of Production Example 5 was used 
as a comparative example. In contrast, the molecular weight of the 
artificial vessel made of the dipyridamole-included segmented polyurethane 
did not decrease even after six months following the transplantation. 
EXAMPLE 6 
The porous segmented polyurethane film having dipyridamole-included pores 
(approximately 2 cm.times.2 cm) obtained in Production Example 9 was 
subcutaneously implanted in crossbred adult dogs which were used as a test 
group. As a comparative example, the dipyridamole-free porous segmented 
polyurethane film (approximately 2 cm.times.2 cm) obtained in Production 
Example 7 was subcutaneously implanted in other crossbred adult dogs which 
were used as a control group. After three months following the 
implantation, the films were recovered to measure changes in their 
molecular weights by gel permeation chromatography and to compare the 
results between the two groups. Additional administration of dipyridamole 
was not carried out during the transplantation period. 
The polystyrene-based molecular weight of each of the films, which was 
150,000 when measured by gel permeation chromatography before the 
implantation, was reduced to 110,000 after three months following the 
implantation in the case of the control group in which the 
dipyridamole-free film was used as a comparative example. In contrast, the 
molecular weight of the dipyridamole-containing film did not decrease even 
after three months following the implantation. 
By locating dipyridamole and/or a salt or a derivative thereof in the 
vicinity of the presently claimed implantation polymeric material 
implanted in the living body, biological decomposition or degradation of 
the implanted polymeric material can be effectively inhibited, thereby 
allowing possible improvement of the durability and safety of the 
material. 
While the invention has been described in detail and with reference to 
specific examples thereof, it will be apparent to one skilled in the art 
that various changes and modifications can be made therein without 
departing from the spirit and scope thereof.