POLYMERE GREFFE ET MOULAGES REALISES A PARTIR DE CELUI-CI POUR FOURNITURES MEDICALES

GRAFT POLYMER AND MOULDED MEDICAL ARTICLES EMPLOYING THIS

Abrégé français

L'invention concerne un polymère greffé comportant des constituants renfermant un groupe ammonium quaternaire représenté par la formule (A), dans laquelle R2 et R3 représentent chacun un groupe alkyle possédant 1 à 3 atomes de carbone, R4 représente un groupe alkyle possédant 3 à 18 atomes de carbone, et X représente au moins un élément choisi parmi les ions halogénure, sulfate, hydroxyde et carboxylate, ainsi qu'une résine antimicrobienne contenant ledit polymère. Lorsque ce dernier est appliqué sur ou incorporé dans des fournitures médicales devant être conservées pendant une longue durée, il permet de prévenir une infection bactérienne due à l'usage de ces fournitures.

Abrégé anglais

A graft polymer comprising constituent units containing a quaternary ammonium
group represented by general formula (A) (wherein
R2 and R3 represent each an alkyl group having 1 to 3 carbon atoms; R4
represents an alkyl group having 3 to 18 carbon atoms; and X
represents at least one member selected from among halide, sulfate, hydroxide,
and carboxylate ions), and an antimicrobial resin comprising
the same. When the graft polymer is applied onto or incorporated into medical
supplier to be retained for a long period of time, bacterial
infection through the supplies can be prevented.

Revendications

CLAIMS:
1. A graft polymer which is formed by graft
polymerization of:
structural units containing a quaternary ammonium
group represented by the general formula (A):
<IMG>
wherein:
R2 and R3 each represent an alkyl group with from 1
to 3 carbons;
R4 represents an alkyl group with from 4 to 18
carbons; and
X represents at least one ion selected from
halogen, sulphate, hydroxide and carboxylic acid ions; and
structural units containing an
alkoxypolyalkyleneglycol moiety represented by the general
formula (B)
- (R6O) n'R7 (B)
wherein:
n' represents an integer in the range 1 to 100;
R6 represents a straight-chain or branched alkylene
group with from 1 to 4 carbons; and
R7 represents a hydrogen atom or a straight-chain
or branched alkyl group with from 1 to 4 carbons.
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2. The graft polymer according to claim 1, wherein
the structural units containing the quaternary ammonium
group are structural units represented by the general
formula (I):
<IMG>
wherein:
R1 represents a hydrogen atom, a methyl group or an
ethyl group;
n represents an integer in the range 1 to 12;
A represents O, S or NR5;
R5 represents a hydrogen atom or an alkyl group
with from 1 to 12 carbons; and
R2, R3, R4 and X are as defined in claim 1.
3. The graft polymer according to claim 1 or 2,
wherein R4 has from 8 to 12 carbon atoms.
4. The graft polymer according to claim 2, wherein
the structural units represented by the general formula (I)
are derived from:
(1) a precursor vinyl compound selected from the
group consisting of dimethylaminoethyl methacrylate,
dimethylaminoethyl acrylate, diethylaminopropyl
methacrylate, dimethylaminoethyl acrylamide and
diethylaminoethyl acrylamide, and
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(2) an alkyl halide in which the alkyl group has 4
to 18 carbons.
5. The graft polymer according to claim 4, wherein
the precursor vinyl compound (1) is dimethylaminoethyl
methacrylate.
6. The graft polymer according to claim 4 or 5,
wherein the alkyl halide is butyl bromide, hexyl bromide,
octyl bromide, decyl bromide, layryl bromide, myristyl
bromide, or octadecyl bromide.
7. The graft polymer according to claim 4 or 5,
wherein the alkyl halide is lauryl bromide.
8. The graft polymer according to any one of claims 1
to 7, which contains at least 0.1 mmol but no more than
4 mmol of the structural units containing the quaternary
ammonium group per 1g of the graft polymer.
9. The graft polymer according to any one of claims 1
to 7, which contains at least 0.1 mmol but no more than
1 mmol of the structural units containing the quaternary
ammonium group per 1g of the graft polymer.
10. The graft polymer according to any one of claims 1
to 9, wherein the structural units containing the
alkoxypolyalkyleneglycol moiety are structural units
represented by the general formula (II):
<IMG>
wherein:
R1 represents a hydrogen atom or a methyl group;
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A represents O, S or NR5 where R5 represents a
hydrogen atom or an alkyl group with from 1 to 12 carbons;
and
n', R6 and R7 are as defined in claim 1.
11. The graft polymer according to claim 10, wherein
the structural units containing the alkoxypolyalkyleneglycol
moiety are derived from methoxypolyethyleneglycol
methacrylate, methoxypolyethyleneglycol acrylate, or
polyethyleneglycol methacrylate.
12. The graft copolymer according to any one of
claims 1 to 11, which contains at least 0.01 mmol but no
more than 5 mmol of the structural units containing the
alkoxypolyalkylene glycol moiety per 1g of the graft
polymer.
13. The graft copolymer according to any one of
claims 1 to 11, which contains at least 0.1 mmol but no more
than 1 mmol of the structural units containing the
alkoxypolyalkylene glycol moiety per 1g of the graft
polymer.
14. The graft polymer according to any one of claims 1
to 13, wherein the structural units containing the
quaternary ammonium group and the structural units
containing the alkoxypolyalkyleneglycol moiety are graft
polymerized to a trunk polymer containing vinyl chloride.
15. The graft polymer according to claim 14, wherein
the trunk polymer is polyvinyl chloride.
16. The graft polymer according to any one of claims 1
to 15, which has a number average molecular weight of 3,000
to 1,000,000.
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17. A moulded medical article formed by coating the
graft polymer as defined in any one of claims 1 to 16 onto
an article made of a base material polymer.
18. A moulded medical article made by moulding a blend
of the graft polymer as defined in any one of claims 1 to 16
with a base material polymer.
19. The moulded medical article according to claim 17
or 18, which is to be used by insertion into a body.
20. The moulded medical article according to claim 19,
wherein the base material polymer is at least one member
selected from the group consisting of polyurethane, natural
rubber, silicone resin, polyvinyl chloride, polyamide and
synthetic rubber.
21. The moulded medical article according to claim 20,
wherein the base material polymer is a polyurethane.
22. The moulded medical article according to claim 20,
wherein the base material polymer is a natural rubber.
23. The moulded medical article according to claim 20,
wherein the base material polymer is a silicone resin.
24. The moulded medical article according to claim 20,
wherein the base material polymer is polyvinyl chloride.
25. The moulded medical article according to claim 20,
wherein the base material polymer is a polyamide.
26. The moulded medical article according to claim 20,
wherein the base material polymer is a synthetic rubber.
27. The moulded medical article according to any one
of claims 17 to 26, which is a catheter, a tube, a sheath, a
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stent, a cuff, a tube connector, an access port, a drainage
bag, an endoscope cover or a blood circuit.
28. An antimicrobial resin which is a blend of the
graft polymer as defined in any one of claims 1 to 16 with a
base material polymer for a moulded medical article.
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Description

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Specification
Graft polymer and moulded medical articles employing
this.
Technical Field
The present invention relates to graft polymer which
can be applied to a polymer base material, and to moulded
medical articles employing this graft polymer.
Technical Background
In the medical treatment field, infections which occur
during the insertion/retention in the patient's body of a
medical device made of a polymer material such as polyurethane
constitute complications and are regarded as a problem.
Hitherto, in order to prevent infecaions accompanying the
retention of a medical device, the medical device has either
been disinfected just prior to use by immersion, or the like, in
an aqueous solution containing an a.ntimicrobial agent or
disinfectant such as ch:lorhexidine or povidone-iodine, or
frequent replacement has been carried out in the case of a
medical device which can be replaced during treatment. However,
because antimicrobial agents and disinfectants diminish from a
medical device surface with time, the disinfection effect does
not persist and it is found that when a medical device is used
over a long time, this effect gradually declines. Moreover, the
frequent replacement of medical devices is a considerable burden
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to medical workers. Hence, as a further means for preventing
infections, medical devices have bE:en subjected to various
antimicrobial treatments. Typical thereof are catheters coated
on their surface with a layer containing an antimicrobial agent
such as chlorhexidine, or a metal :such as silver or copper or a
compound thereof. In the case of these catheters, a system is
employed for slow release into the body of uniform quantities of
the material with an antimicrobial action, and they show a good
effect compared to the case where t:he catheter is disinfected
just prior to use.
However, with a system of slow release of an anti-
microbial agent, the period of use still has limits and a
gradual decline in efficacy is unavoidable. Moreover, the
metabolism following slow release of a metal such as silver or
compound thereof is unclear, and damage to the body is
conceivable. Again, where silver remains in the discarded
medical device following use, recovery thereof or other special
treatment is required at the time cf disposal.
Hence, polymers with quaternary ammonium groups have
been variously proposed as polymers which are not of the slow-
release type but which have inherent antimicrobial character
(Japanese Examined Patent Publication Nos 54-17797 and 54-
18817). However, the processability of these polymers is poor,
and they cannot alone be formed into moulded articles, so it is
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necessary either to coat them onto the surface of a moulded
polymer which has excellent mechanical characteristics, or to
carry out blending and moulding along with such a polymer.
However, the better the mechanical characteristics of the base
material polymer, the worse its compatibility with other
polymers and, where compatibility is poor, a coated polymer
tends to peel off or cracks are likely to be produced. Now,
there has been described in Japanese Unexamined Patent (Kokai)
Publication No. 6-337378 a hydrogel containing a copolymer of
hydroxypolyalkylene-glycol (meth)acrylate and a monomer having a
quaternary ammonium salt group in a side chain, and in Japanese
Unexamined Patent Publication No. 6-256424 there is described a
hydrogel containing a copolymer of a monomer having a
hydroxypolyalkyleneglycol, a monomer having a quaternary
ammonium salt group in a side chain and a vinyl monomer.
However, in neither case are graft copolymers described and,
with these polymers, there are limits to the selective
manifestation of the properties of the backbone and graft
components. In other words, at present, no antimicrobial
polymers are known with satisfactory compatibility with the base
material polymer.
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Thus, an object of the present invention is to
provide a polymer which can form flexible films and can be
suitably applied to base materials of complex shapes and a
moulded medical article employing this polymer.
Disclosure of the Invention
The present invention relates to a graft polymer which
is formed by graft polymerization of structural units containing
a quaternary ammonium group represented by general formula (A):
R2
_N+_Ra.X_ CA)
R3
(wherein R~ and R= each represent an alkyl group with from 1 to 3
carbons, and R4 represents an alkyl group with from 3 to 18
carbons, X represents at least one type of ion selected from
halogen, sulphate, hydroxide and carboxylic acid ions),
preferably to a graft polymer where the structural units
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containing a quaternary ammonium group represented by the
general formula (A) are structural units represented by the
general formula (I):
R1
-CH2-C- R2
CO-A- ( CHy ) n-N'-Rq ~X- ( I )
R3
(wherein R1 represents at least one species selected from
hydrogen, a methyl group and an ethyl group, n represents an
integer in the range of from 1 to 12, A represents at least one
species selected from 0, S and NRS, and R5 represents hydrogen
or an alkyl group with from 1 to 12 carbons), or to graft
polymer formed by the graft polymerization of structural units
containing a quaternary ammonium group and structural units
containing an alkoxypolyalkylene glycol moiety represented by
the general formula (B):
- (Rc0) n~R~
(wherein n~represents an integer in the range of from 1 to 100,
R6 represents a straight-chain or branched alkylene group with
from 1 to 9 carbons, and R~ represents
at least one species selected from hydrogen and straight-chain
or branched alkyl groups with from 1 to 4 carbons).
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Furthermore, the present invention relates to moulded
medical articles formed by coating the aforesaid graft polymer
onto a moulded medical article used for insertion into the body,
or by blending the graft polymer therewith.
Preferred Embodiments of the Invention
Now, the present invention is explained in further
detail.
The graft polymer in the present invention has a
functional group represented by formula (A), as stated above.
As examples of the structural unit;c with a functional group
represented by formula (A), there are structural units wherein
formula (A) is bonded a main chain via an ester linkage, amide
linkage, ureido linkage, ether linkage, alkylene group or
phenylene group. Of these, from the point of view of ready
availability of a precursor, among the structural units with a
functional group represented by formula (A), preferred are those
structural units represented by the: following formula (I):
R1
2 0 -CH2-C- R2
CO-A- ( CH2 I n-N+-g.a'X ( I )
R3
(wherein R1 represents at least one species selected from
hydrogen, a methyl group and an ethyl group, RZ and R3 each
represent an alkyl group with from 1 to 3 carbons, R4 represents
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an alkyl group with from 3 to 18 carbons, n represents an
integer in the range of from 1 to .L2, A represents at least one
species selected from 0, S and NRS, R5 represents hydrogen or an
alkyl group with 1 to 12 carbons and X represents at least one
ion selected from halogen, sulphate, hydroxide and carboxylic
acid ions.)
The symbol n represents an integer in the range of
from 1 to 12, but it contributes to the degree of freedom of the
antimicrobial functional group and if it is too short then the
functional group does not move freely so, for example, it does
not readily come into contact with bacteria, while if it is too
long then the hydrophobic character is strengthened so that in
an aqueous medium containing bacteria the antimicrobial
functional group does not readily come into contact with the
bacteria.
Rz and R3 are an alkyl group. As the number of carbon
atoms increases, they become more strongly hydrophobic so
contact between the antimicrobial functional group and bacteria
becomes more difficult. Hence, the number of carbon atoms is
from 1 to 3, with a methyl group, which has the least number of
carbon atoms, being preferred.
R4 is an alkyl- group with from 3 to 18 carbons,
preferably with from 8 to 12 carbons. If the alkyl group is
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branched then movement is restricted, so it is preferred that it
is a straight chain.
In the case where X is a sulphate ion, the sulphate
ion is normally bivalent but, in tree present invention, a
monovalent ion may also be coordinated.
Furthermore, A represent: at least one species
selected from 0, S and NRS.
As examples of the precursor vinyl compound used for
the graft copolymerization of strucaural units containing a
quaternary ammonium group represented by general formula (A),
there are dimethylaminoethyl methac:rylate, dimethylaminoethyl
acrylate, diethylaminopropyl methac:rylate, dimethylaminoethyl
acrylamide and diethylaminoethyl ac:rylamide, but on account of
its ready availability the use of climethylaminoethyl
methacrylate is preferred. If the amount of functional groups
in the graft polymer is too great, then the coating properties
are adversely affected, and again there is a tendency for the
compatibility to be lowered when trying to blend with other
polymers. On the other hand, if th.e amount is too small, there
is a tendency for the antimicrobial performance to be lowered.
Consequently, it is preferred that, in the graft polymer, there
be contained a proportion of at least 0.1 mmol but no more than
4 mmol, and preferably at least 0.5 mmol but no more than 4 mmol
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of the structural units containing a quaternary ammonium group
represented by general formula (A) per 1 g of the graft polymer.
In the present invention, there are no particular
restrictions on the grafted components other than that
containing general formula (A), but there is preferably used a
hydrophilic component to enhance the affinity of the material in
terms of aqueous solutions and body fluids, etc. For example,
there can be used a hydrophilic component containing structural
units which include an alkoxypolyalkyleneglycol moiety
represented by general formula (B):
- ~R50) n~R~
(wherein n~represents an integer in the range of from 1 to 100,
R6 represents a straight-chain or branched alkylene group with
from 1 to 4 carbons, and R~ represents at least one species
selected from hydrogen and straight-chain or branched alkyl
groups with from 1 to 9 carbons),such as
methoxypolyethyieneglycol, ethoxypolyethyleneglycol,
2C methoxypolypropyleneglycol, ethoxypolypropyleneglycol or the
like.
Of these, the moiety represented by the following
general formula (II) is preferred in terms of ready availability
and safety:
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R1
-CH2-C- ( I I )
CO-A- (Rs0) n~R~
(wherein R1 represents hydrogen or a methyl group, n'
represents an integer from 1 to 100, Rs represents a straight
chain or branched alkylene group with from 1 to 4 carbons, R7
represents at least one species selected from H and straight
chain or branched alkyl groups with from 1 to 4 carbons and A
represents at least one species selected from O, S and NR9 (where
R9 represents hydrogen or an alkyl group with from 1 to 12
carbons).)
As specific examples of the vinyl compounds which are
the precursors prior to graft copolymerization, there are
methoxypolyethyleneglycol methacrylate, methoxypolyethylene-
glycol acrylate and polyethyleneglycol methacrylate. If the
amount of the hydrophilic component in the graft polymer is too
great, then the coating properties are adversely affected, or
again the compatibility tends to be lowered when attempting to
blend with other polymers.
On the other hand, if the amount of the hydrophilic
component is too small, then affinity with body fluids and the
like would be poor, and biocompatibility would be low.
Consequently, it is preferred that the graft polymer contains at
least 0.01 mmol but no more than 5 mmol, and more preferably at

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least 0.1 mmol but no more than 1 rnmol of structural units
containing an alkoxypolyalkylenegl~~col represented by general
formula (B) per 1 g of the graft polymer.
There are no particular restrictions of the trunk or
backbone polymer on which the graft. copolymer is based according
to the present invention, but one containing a halogen atom and
in particular a chlorine atom in a side chain is preferred.
Specifically preferred is a polymer containing vinyl chloride.
As well as polyvinyl chloride, there can be used various
copolymers and blends, such as copolymers of vinyl chloride and
vinyl acetate, which may also include a third component, such as
copolymers with an acrylate, methac;rylate, vinyl alcohol,
styrene or acrylonitrile, or polymE>,rs in which vinyl chloride
has been grafted to an ethylene-vinyl acetate copolymer, or
blends of these polymers, or mixtures of such polymers with
plasticizers, stabilizers and the like. Where blending is
carried out, the blending of, for example, polyurethane, natural
rubber, silicone resin, polyvinyl chloride, polyamide or
synthetic rubber, is preferably em~~loyed for moulded medical
articles. In these copolymers and blends, the vinyl chloride
content should lie in the range from 0.1 to 100%, and can be
suitably selected according to objectives.
The molecular weight of the graft polymer of the
present invention is not particularly restricted, but in terms
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of its number average molecular we_Lght it will be at least about
3,000, preferably from 5,000 to 1,000,000, and more preferably
approximately from 30,000 to 100,000.
Any method may be used for producing the graft polymer
of the present invention, but the i=ollowing example is provided
for explanation.
Graft copolymer is obtained by subjecting the trunk or
backbone polymer which forms the m~~in chain to a graft
activating treatment, after which t:he precursor vinyl compound
for the structural units containinc( formula (A) is added and
polymerization is carried out by a suitable method.
As the graft activating treatment method, there is
preferably used for example a methc>d of replacing chlorine atoms
in a polymer containing vinyl chloride by dithiocarbamate groups
which readily produce radicals by light irradiation or the like.
In order to obtain quaternary ammonium groups,
conversion to the quaternary ammonium salt may be performed with
an alkyl halide following graft polymerization using the
precursor vinyl compound for the structural units containing
general formula (A), but the graft polymerization may also be
carried out using precursor vinyl compound which has already be
converted into the quaternary ammonium form with an alkyl
halide.
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The graft polymer of the present invention is
preferably used as a medical resin and, in particular, on.
account of its outstanding antimicrobial properties, it is
preferably employed as an antimicrobial resin.
By surface coating, the graft polymer can be applied
to any medical device where the prevention of microbial
infection is required. Amongst medical devices, where
application is made to moulded medical articles inserted into
the body, this is particularly effective. Polyurethane, natural
rubber, silicone resin, polyvinyl chloride, polyamide, synthetic
rubber and the like are preferably used as the material for the
medical article inserted in the body.
Amongst moulded medical articles for insertion in the
body, the graft polymer can be applied effectively for example
to those left for a long period in the body such as catheters,
sheaths, stents, tubes (drainage tubes), cuffs, connectors (tube
connectors), access ports, endoscope covers, drainage bags,
blood circuits and the like. This is due to the fact that, in
contrast to slow release system materials, the antimicrobial
functional groups are fixed by covalent bonds to the graft
copolymer, and so are safe to the body and their effect
persists.
The moulded medical articles made of a blend of the
graft polymer of the present invention and the aforesaid
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polyurethane, natural rubber, silicone resin or the like, can
also be effectively used in the same kinds of applications as
the aforesaid catheters, stems, tubes and the like.
Below, the present invention is explained in still
more specific terms by means of examples, but the present
invention should not be construed to be restricted to these
examples.
Example 1
120 g of polyvinyl chloride of a polymerization degree
of 550 was dissolved in 2 litres of dimethyl-formamide, then
2.704 g of sodium diethyldithiocarbamate was added and reaction
carried out for 3 hours at 50°C. After reprecipitation in
methanol, drying was carried out and there was obtained photo-
induced graft activated polyvinyl chloride (hereinafter referred
to as DTC-modified polyvinyl chloride).
80 g of this DTC-modified polyvinyl chloride was
dissolved in 1250 ml of tetrahydrofuran, then 200 g of
methoxypolyethyleneglycol methacrylate (degree of polymerization
of the polyethylene glycol portion 20-23) and 80 g of
dimethylaminoethyl methacrylate were added, and photo-induced
graft polymerization was carried out by irradiating for 9.5
hours at 30°C with a 100 W high pressure mercury lamp (Ushio
Denki UM-102) in a photo-reaction device with an interior
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permeating light source. The composition of the graft
copolymer, by weight ratio, was 54'-~ vinyl chloride, 300
methoxypolyethyleneglycol methacry=Late and 16o
dimethylaminoethyl methacrylate.
Example 2
g of the graft copolymE:r described in Example 1 was
dissolved in 50 ml of tetrahydrofur~an, after which 1.1 ml of
butyl bromide was added and reaction was carried out for 4 hours
at 50°C. After precipitation by pouring into saturated saline,
washing was carried out with water and ethanol, followed by
drying, and there was obtained an antimicrobial material with
quaternary ammonium groups containing a long chain alkyl group
(number of carbons = 4). The amount of quaternary ammonium
groups introduced was 0.15 mmol per 1 g of graft copolymer.
Example 3
A polyurethane tube was immersed in its axial
direction in a 10% solution of the antimicrobial material
described in Example 2, so that the antimicrobial material was
applied to the tube, after which it was dried. The tube onto
which the material had been applied was then disinfected with
alcohol, after which it was immersed in physiological saline in
which E. coli (MC106 strain) had been suspended at a
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concentration of 109 per ml, and the tube left was therein for 24
hours. After 24 hours, the number of bacteria adhering to the
tube was measured. As a control, t;he same procedure was
followed with a polyurethane tube which had not been coated with
the antimicrobial material. As a i:esult, the number of adhering
bacteria was 534 in the case of the polyurethane tube to which
no antimicrobial material had been applied and 137 in the case
of the tube where the antimicrobia7. material had been applied.
Example 4
5 g of the graft copolymer described in Example 1 was
dissolved in 50 ml of tetrahydrofuran, after which 1.4 ml of
hexyl bromide was added and reaction was carried out for 4 hours
at 50°C. After precipitation by pouring into saturated saline,
washing with water and with ethanol. was carried out, followed by
drying, and an antimicrobial material with quaternary ammonium
groups which contained a long chain. alkyl group (number of
carbons = 6) was obtained. The amount of quaternary ammonium
groups introduced was 0.11 mmol per 1 g of graft copolymer.
Example 5
A polyurethane tube was immersed in its axial
direction in a 10% solution of the antimicrobial material
described in Example 4, so that the antimicrobial material was
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applied to the tube, after which it. was dried. As a result of
testing in the same way as in Example 3, the number of adhering
bacteria was 534 in the case of the polyurethane tube to which
no antimicrobial material had been applied and 125 in the case
of the tube where the antimicrobia~_ material had been applied.
Example 6
g of the graft copolymer described in Example 1 was
dissolved in 50 ml of tetrahydrofuran, after which 1.7 ml of
octyl bromide was added and reaction was carried out for 4 hours
at 50°C. After precipitation by pouring into saturated saline,
washing with water and with ethanol. was carried out, followed by
drying, and an antimicrobial material with quaternary ammonium
groups which contained a long chain alkyl group (number of
carbons = 8) was obtained. The amount of quaternary ammonium
groups introduced was 0.30 mmol per 1 g of graft copolymer.
Example 7
A polyurethane tube was immersed in its axial
direction in a 10% solution of the antimicrobial material
described in Example 6, so that the antimicrobial material was
applied to the tube, after which it was dried. As a result of
testing in the same way as in Example 3, the number of adhering
bacteria was 534 in the case of the polyurethane tube to which
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no antimicrobial material had been applied and 126 in the case
of the tube where the antimicrobia_L material had been applied.
Example 8
g of the graft copolymer described in Example 1 was
dissolved in 50 ml of tetrahydrofuran, after which 2.1 ml of
decyl bromide was added and reaction was carried out for 4 hours
at 50°C. After precipitation by pouring into saturated saline,
washing with water and with ethano7_ was carried out, followed by
drying, and an antimicrobial material with quaternary ammonium
groups which contained a long chairs alkyl group (number of
carbons = 10) was obtained. The amount of quaternary ammonium
groups introduced was 0.16 mmol per 1 g of graft copolymer.
Example 9
A polyurethane tube was immersed in its axial
direction in a loo solution of the antimicrobial material
described in Example 8, so that the antimicrobial material was
applied to the tube, after which it was dried. As a result of
testing in the same way as in Exam~~le 3, the number of adhering
bacteria was 534 in the case of the polyurethane tube to which
no antimicrobial material had been applied and 71 in the case of
the tube where the antimicrobial material had been applied.
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Example 10
g of the graft copolyme r described in Example 1 was
dissolved in 50 ml of tetrahydrofuran, after which 2.4 ml of
lauryl bromide was added and react_Lon was carried out for 4
hours at 50°C. After precipitation by pouring into saturated
saline, washing with water and with ethanol was carried out,
followed by drying, and an antimicrobial material with
quaternary ammonium groups which contained a long chain alkyl
group (number of carbons = 12) was obtained. The amount of
quaternary ammonium groups introduced was 0.18 mmol per 1 g of
graft copolymer.
Example 11
A polyurethane tube was immersed in its axial
direction in a loo solution of the antimicrobial material
described in Example 10, so that the antimicrobial material was
applied to the tube, after which it was dried. As a result of
testing in the same way as in Exam~~le 2, the number of adhering
bacteria was 534 in the case of the polyurethane tube to which
no antimicrobial material had been applied and 38 in the case of
the tube where the antimicrobial material had been applied.
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Example 12
g of the graft copolyme r described in Example 1 was
dissolved in 50 ml of tetrahydrofuran, after which 2.7 ml of
myristyl bromide was added and reaction was carried out for 4
hours at 50°C. After precipitation by pouring into saturated
saline, washing with water and with ethanol was carried out,
followed by drying, and an antimicrobial material with
quaternary ammonium groups which contained a long chain alkyl
group (number of carbons = 14) was obtained. The amount of
quaternary ammonium groups introduced was 0.19 mmol per 1 g of
graft copolymer.
Example 13
A polyurethane tube was immersed in its axial
direction in a loo solution of the antimicrobial material
described in Example 12, so that th.e antimicrobial material was
applied to the tube, after which it was dried. As a result of
testing in the same way as in Example 3, the number of adhering
bacteria was 534 in the case of the polyurethane tube to which
no antimicrobial material had been applied and 151 in the case
of the tube where the antimicrobial material had been applied.
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Example 14
g of the graft copolyme r described in Example 1 was
dissolved in 50 ml of tetrahydrofuran, after which 3.3 ml of
octadecyl bromide was added and reaction was carried out for 4
hours at 50°C. After precipitation by pouring into saturated
saline, washing with water and with ethanol was carried out,
followed by drying, and an antimicrobial material with
quaternary ammonium groups which contained a long chain alkyl
group (number of carbons = 18) was obtained. The amount of
quaternary ammonium groups introduced was 0.24 mmol per 1 g of
graft copolymer.
Example 15
A polyurethane tube was immersed in its axial
direction in a 10o solution of the antimicrobial material
described in Example 14, so that th.e antimicrobial material was
applied to the tube, after which it was dried. As a result of
testing in the same way as in Example 3, the number of adhering
bacteria was 534 in the case of the polyurethane tube to which
no antimicrobial material had been applied and 211 in the case
of the tube where the antimicrobial material had been applied.
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Example 16
By adding dropwise a to solution of the antimicrobial
material described in Example 10 onto a cover glass, there was
applied antimicrobial material to t:he cover glass. Similarly
polyvinyl chloride and polyurethane were applied, and then
dried. The cover glass was placed with the side on which the
material had been coated upwards, ~~nd then onto this was added
dropwise serum or urine containing 103 to 109 of E. coli, P.
aeruginosa, S. aureus, S. epidermic~is or E. faecalis, per ml.
From above, another cover glass ways then placed thereon,
sandwiching the bacterial liquid with the side on which the
material had been coated at the bottom, after which they were
left for 24 hours at 37°C. After ~~ashing the cover glasses,
they were affixed to an agar medium and the adhering bacteria
transferred thereto. After culturing, an assessment was made as
to whether or not colonies had formed. As a result it was found
that, in the case of a cover glass on which polyvinyl chloride
or polyurethane had been applied, colonies of all the bacteria
were formed irrespective of whether serum or urine was used,
while in the case of the cover glass to which the antimicrobial
material had been applied, no colonies were formed of any of the
bacteria.
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Example 17
160 g of the DTC-modifie<~ polyvinyl chloride described
in Example 1 was dissolved in 2500 ml of tetrahydrofuran, and
then 400 g of methoxypolyethylene-glycol methacrylate (average
degree of polymerization of the po7_yethylene glycol portion =
90) and 160 g of dimethylaminoethy~_ methacrylate were added, and
photo-induced graft polymerization was carried out by 9.5 hours
exposure at 30°C to a 100 W high pressure mercury vapour lamp
(Ushio Denki UM-102) in a photo-reaction device with an interior
permeating light source. The composition of the graft
copolymer, by weight, was vinyl chloride 640, methoxypoly-
ethyleneglycol methacrylate 21o anct dimethylaminoethyl
methacrylate 15%.
Example 18
30 g of the graft copolymer described in Example 17
was dissolved in 300 ml of dimethylformamide, after which 40 ml
of lauryl bromide was added and reaction was carried out for 18
hours at 60°C. After precipitating by pouring into a water-
methanol mixed solvent, washing and drying were carried out and
there was obtained an antimicrobial material with quaternary
ammonium groups containing a long chain alkyl group (number of
carbons = 12). The amount of quaternary ammonium groups
introduced was 1 mmol per 1 g of graft copolymer.
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Example 19
A polyurethane tube was _ummersed in its axial
direction in a 3% solution of the antimicrobial material
described in Example 18, so that tree antimicrobial material was
applied to the tube, after which it. was dried. The tube onto
which the material had been applied was disinfected with
alcohol, and then was immersed in physiological saline in which
S. epidermidis had been suspended at a concentration of 104 per
ml, and the tube was left therein for 24 hours. After 24 hours,
the number of bacteria adhering to the tube was measured. As a
control, the same procedure was followed with a polyurethane
tube which had not been coated with. the antimicrobial material.
As a result, the number of adhering bacteria was 967 in the case
of the polyurethane tube to which no antimicrobial material had
been applied and 0 in the case of the tube where the
antimicrobial material had been applied.
Example 20
A sheet of styrene-isoprene synthetic rubber was
immersed in its lengthwise axial direction into a 3% solution of
the antimicrobial material described in Example 17, so that the
antimicrobial material was applied to the sheet, after which it
was dried. Following drying, it was soaked in water, and even
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when scratched 20 times with a finder nail, the coating did not
peel off.
Industrial Utilization Potential
The graft polymer of the present invention can readily
be applied to plastic products, in particular medical devices,
and it shows good antimicrobial capacity even when the microbial
concentration is high and its effects is maintained over a long
period. Moreover, the :functional groups which manifest the
antimicrobial properties are covalently bonded and are not
dissolved away, so the ~?roperties are sustained over a prolonged
period and the graft po=Lymer is harmless to the body.
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