CA2276680C

CA2276680C - Graft polymer and moulded medical articles employing this

Info

Publication number: CA2276680C
Application number: CA002276680A
Authority: CA
Inventors: Kazuhiro Tanahashi
Original assignee: Toray Industries Inc
Current assignee: Toray Industries Inc
Priority date: 1997-11-04
Filing date: 1997-11-04
Publication date: 2006-05-16
Anticipated expiration: 2017-11-04
Also published as: CA2276680A1; KR100490272B1; KR20000069875A

Abstract

A graft polymer comprising constituent units containing a quaternary ammoniu m 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, hydroxid e, and carboxylate ions), and an antimicrobial resin comprising the same. When the graft polymer is applied onto or incorporated into medica l supplier to be retained for a long period of time, bacterial infection through the supplies can be prevented.

Description

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 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 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.

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):

_N+_Ra.X_ CA) (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 containing a quaternary ammonium group represented by the general formula (A) are structural units represented by the general formula (I):

CO-A- ( CHy ) n-N'-Rq ~X- ( I ) (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).

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):

CO-A- ( CH2 I n-N+-g.a'X ( I ) (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 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 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 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:

-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 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 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.

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 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 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 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 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 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.

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.

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.

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.

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.

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.

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 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.

Claims

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):
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.

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):
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 (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):
wherein:
R1 represents a hydrogen atom or a methyl group;

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.

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 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.