WO2000069925A1

WO2000069925A1 - Method of producing inherently microbicidal polymer surfaces

Info

Publication number: WO2000069925A1
Application number: PCT/EP2000/002783
Authority: WO
Inventors: Peter Ottersbach; Friedrich Sosna
Original assignee: Creavis Gesellschaft Für Technologie Und Innovation Mbh
Priority date: 1999-05-12
Filing date: 2000-03-30
Publication date: 2000-11-23
Also published as: AU7236200A; DE19921898A1; EP1183282A1

Abstract

The invention relates to a method of producing inherently microbicidal polymer surfaces by polymerizing aliphatically unsaturated monomers that are at least singly functionalized by a primary amine group. The antimicrobial polymers of the invention can be used as a microbicidal coating inter alia on hygiene articles or in the medical field as well as in lacquers and protective coatings.

Description

Process for the production of inherently microbicidal polymer surfaces

The invention relates to a process for the production of antimicrobial polymers by polymerizing amino-functionalized monomers and the use of the antimicrobial polymers thus produced

The invention further relates to a process for the production of antimicrobial polymers by graft polymerization of amino-functionalized monomers on a substrate and the use of the antimicrobial substrates thus produced

Colonization and spreading of bacteria on the surfaces of pipelines, containers or packaging are highly undesirable.Mucous layers often form, which extremely increase microbial populations, which have a lasting impact on the quality of water, beverages and food, and even spoil the goods and cause health damage the consumer can drive

Bacteria must be kept away from all areas of life in which hygiene is important.This affects textiles for direct body contact, in particular for the genital area and for nursing and elderly care.In addition, bacteria must be kept away from furniture and device surfaces in care stations, particularly in the area of Intensive care and the care of small children, in hospitals, in particular in rooms for medical interventions and in isolation stations for critical infection cases and in toilets

At present devices, surfaces of mobeine and textiles against bacteria are treated if necessary or as a precautionary measure with chemicals or their solutions as well as mixtures which act as a disinfectant to a greater or lesser extent and have a massive antimicrobial effect.These chemical agents have a non-specific effect, are often themselves toxic or irritating or form degradation products that are harmful to health

Incompatibilities in appropriately sensitized people

Another approach against superficial spread of bacteria is the

Incorporation of antimicrobial substances into a matrix Tert-butylaminoethyl methacrylate is a commercially available monomer of methacrylate chemistry and is used in particular as a hydrophilic component in copolymerizations. EP-PS 0 290 676 describes the use of various polyacrylates and polymethacrylates as a matrix for the immobilization of bactericidal quaternary ammonium compounds

From another technical field, US Pat. No. 4,532,269 discloses a terpolymer of butyl methacrylate, tributyltin methacrylate and tert-butylaminoethyl methacrylate. This polymer is used as an antimicrobial marine paint, the hydrophilic tert-butylaminoethyl methacrylate requiring the slow erosion of the polymer and thus the highly toxic tributyltin microbial methacrylate releases

In these applications, the copolymer produced with aminomethacrylates is only a matrix or carrier substance for added microbicidal active ingredients which can diffuse or migrate from the carrier substance. Polymers of this type lose their effect more or less quickly if the necessary “minimal inhibitory concentration” is found on the surface. (MIK) is no longer achieved

From European patent applications 0 862 858 and 0 862 859 it is known that homo- and copolymers of tert-butylaminoethyl methacrylate, a methacrylic acid ester with secondary amino function, have inherent microbicidal properties in order to undesirably adapt the microbial life forms, especially in view of those known from antibiotic research Resistance developments of germs to counteract effectively must also be developed in the future systems based on new compositions and improved effectiveness

The present invention is therefore based on the object of developing novel, antimicrobial polymers which, if necessary, are intended as a coating to prevent the settling and spreading of bacteria on surfaces

It has now surprisingly been found that by polymerizing aliphatic unsaturated monomers which are functionalized at least simply by a primary amino group, polymers having a surface which is permanently microbicidal are obtained by means of solvents and physical stress is not attacked and shows no migration. It is not necessary to use other biocidal agents.

The present invention relates to a process for the preparation of antimicrobial polymers, characterized in that aliphatically unsaturated monomers which are functionalized at least once by a primary amino group are polymerized.

The aliphatically unsaturated monomers functionalized at least simply by a primary amino group in the process according to the invention can have a hydrocarbon radical of up to 50, preferably up to 30, particularly preferably up to 22 carbon atoms. Furthermore, the monomers can also be substituted by keto or aldehyde groups such as acryloyl or oxo groups or cyclic hydrocarbon groups such as substituted or unsubstituted phenyl or cyclohexyl groups.

In order to achieve a sufficient polymerization rate, the monomers used according to the invention should have a molar mass of less than 900, preferably less than 550 g / mol.

In a particular embodiment of the present invention, aliphatic unsaturated monomers of the general formula which are functionalized simply by a primary amino group

Rι NH ₂

with Ri: branched, unbranched or cyclic, aliphatic unsaturated

Hydrocarbon radicals with up to 50 carbon atoms, which can be substituted by O, N or S atoms, are used.

Suitable monomer building blocks are all aliphatic unsaturated monomers which have at least one primary amino function, such as, for example, l-amino-2-propene, N-6-aminohexyl-2- propenamide, N-3-aminopropyl methacrylamide hydrochloride, methacrylic acid-2-aminoethyl ester hydrochloride and 3-aminopropyl vinyl ether.

The process according to the invention can also be carried out by polymerizing the monomers which are functionalized at least once by a primary amino group on a substrate. A physisorbed coating of the antimicrobial copolymer is obtained on the substrate.

All polymeric plastics, such as, for example, are suitable as substrate materials. B. polyurethanes, polyamides, polyesters and ethers, polyether block amides, polystyrene, polyvinyl chloride, polycarbonates, polyorganosiloxanes, polyolefins, polysulfones, polyisoprene, polychloroprene, polytetrafluoroethylene (PTFE), corresponding copolymers and blends as well as natural and synthetic rubbers, with or without radiation-sensitive Groups. The method according to the invention can also be applied to surfaces of lacquered or otherwise plastic, metal, glass or wooden bodies.

In a further embodiment of the present invention, the antimicrobial polymers can be obtained by graft-polymerizing a substrate with an aliphatic unsaturated monomer which is functionalized at least simply by a primary amino group. The grafting of the substrate enables the antimicrobial polymer to be covalently bound to the substrate. All polymeric materials, such as the plastics already mentioned, can be used as substrates.

The surfaces of the substrates can be modified a number of times before the graft copolymerization

Methods are activated. All standard methods for activating polymer surfaces can be used here; For example, the activation of the substrate before the graft polymerization by UV radiation, plasma treatment, corona treatment, flame treatment, ozonization, electrical discharge of the γ radiation, methods used.

The surfaces are expediently removed beforehand in a known manner by means of a solvent

Free from oils, greases or other contaminants. The substrates can be activated by UV radiation in the wavelength range 170-400 nm, preferably 170-250 nm. A suitable radiation source is, for example, a UV excimer device HERAEUS Noblelight, Hanau, Germany. However, mercury vapor lamps are also suitable for substrate activation if they are emit significant amounts of radiation in the areas mentioned The exposure time is generally 0 1 seconds to 20 minutes, preferably 1 second to 10 minutes

The activation of the standard polymers with UV radiation can also be carried out with an additional photosensitizer. For this purpose, the photosensitizer, such as benzophenone, is applied to the substrate surface and irradiated. This can also be done with a mercury vapor lamp with exposure times of 0.1 seconds to 20 minutes, preferably 1 second up to 10 minutes

According to the invention, the activation can also be achieved by plasma treatment using an RF or microwave plasma (Hexagon, Fa Technics Plasma, 85551 Kirchheim, Germany) in air, nitrogen or argon atmosphere. The exposure times are generally 2 seconds to 30 minutes, preferably 5 seconds up to 10 minutes The energy input for laboratory devices is between 100 and 500 W, preferably between 200 and 300 W.

Corona devices (SOFTAL, Hamburg, Germany) can also be used for activation. The exposure times in this case are generally 1 to 10 minutes, preferably 1 to 60 seconds

Activation by electrical discharge, electron or γ-rays (e.g. from a cobalt 60 source) and ozonization enable short exposure times, which are generally 0 1 to 60 seconds

Flaming substrate surfaces also leads to their activation. Suitable devices, especially those with a barrier flame front, can be easily built or, for example, obtained from ARCOTEC, 71297 Monsheim, Germany. They can be operated with hydrocarbons or hydrogen as fuel gas In In any case, damaging overheating of the substrate must be avoided, which is easily achieved by intimate contact with a cooled metal surface on the surface of the substrate facing away from the flame side.Activation by flame treatment is accordingly limited to relatively thin, flat substrates.The exposure times are generally 0 1 second to 1 minute, preferably 0 5 to 2 seconds, all of which are non-luminous flames and the distances between the substrate surfaces and the outer flame front are 0 2 to 5 cm, preferably 0 5 to 2 cm

The substrate surfaces activated in this way are produced using known methods, such as dipping,

Spraying or brushing, coated with aliphatic unsaturated monomers which are at least simply functionalized by a primary amino group, optionally in solution

Water and water-ethanol mixtures have been used as solvents, but other solvents can also be used, provided that they have sufficient bulk for the monomers and wet the substrate surfaces well. Other solvents are, for example, ethanol, methanol, methyl ethyl ketone, diethyl ether, dioxane, hexane, Heptane, benzene, toluene, chloroform, dichloromethane, tetrahydrofuran and acetonitrile. Solutions with monomer contents of 1 to 10% by weight, for example about 5% by weight, have been found to be effective in practice and generally give coherent coatings covering the substrate surface in one pass with layer thicknesses that can be more than 0 1 μm

The graft copolymerization of the monomers applied to the activated surfaces can expediently be initiated by radiation in the short-wave segment of the visible region or in the long-wave segment of the UV region of the electromagnetic radiation. For example, radiation from a UV excimer of the wavelengths 250 to 500 nm is very suitable. preferably from 290 to 320 nm Here too, mercury vapor lamps are suitable, provided they emit considerable amounts of radiation in the areas mentioned. The exposure times are generally 10 seconds to 30 minutes, preferably 2 to 15 minutes Furthermore, a graft copolymerization can also be achieved by a process which is described in the European patent application 0 872 512 and is based on a graft polymerization of swollen monomer and initiator molecules

In the process according to the invention, further aliphatic unsaturated monomers can be used, in addition to the monomers functionalized by a primary amino group. Thus, an aliphatic unsaturated monomer functionalized at least simply by a primary amino group with acrylates or methacrylates, for example acrylic acid, tert-butyl methacrylate or methyl methacrylate, can be used as the monomer mixture. Styrene, vinyl chloride, vinyl ether, acrylamides, acrylonitriles, olefins (ethylene, propylene, butylene, isobutylene), allyl compounds, vinyl ketones, vinyl acetic acid, vinyl acetate or vinyl esters can be used

The antimicrobial polymers made from aliphatic unsaturated monomers, which are functionalized at least simply by a primary amino group, produced by the process according to the invention show a microbicidal or antimicrobial behavior even without grafting onto a substrate surface

If the process according to the invention is used directly on the substrate surface without grafting, customary free-radical initiators can be added. Among the initiators are azonitriles, alkyl peroxides, hydroperoxides, acyl peroxides, peroxoketones, peresters, peroxocarbonates, peroxodisulfate, persulfate and all customary photoinitiators such as acetophenones, α -Hydroxyketone, Dimethylketale and and use benzophenone The polymerization can also be initiated thermally or, as already stated, by electromagnetic radiation, such as UV light or γ-radiation

Use of the modified polymer substrates

The present invention furthermore relates to the use of the antimicrobial polymers produced according to the invention for the production of antimicrobially active products and the products thus produced as such. The products may contain or consist of modified polymer substrates according to the invention. Such products are preferably based on polyamides, polyurethanes, polyether block amides, Polyester amides or imides, PVC, polyolefms, silicones, polysiloxanes, polymethacrylate or polyterephthalates, which have surfaces modified with the polymers produced according to the invention

Antimicrobial products of this type are, for example, and in particular machine parts for food processing, components of air conditioning systems, roofing, bathroom and toilet articles, cake articles, components of sanitary facilities, components of animal cages and dwellings, toys, components in water systems, food packaging, operating elements (touch panel ) of devices and contact lenses

The present invention also relates to the use of the polymer substrates modified on the surface with the antimicrobial polymers produced according to the invention for the production of hygiene products or medical articles. The above statements regarding preferred materials apply accordingly. Such hygiene products are, for example, toothbrushes, toilet seats, combs and packaging materials also other objects that may come into contact with many people, such as a telephone receiver, handrails of stairs, door and window handles, and holding straps and handles in public transport. Medical technology items include catheters, tubes, cover foils, and surgical cutlery

The copolymers or graft copolymers produced according to the invention can be used wherever bacteria-free, ie microbicidal surfaces or surfaces with non-stick properties are important. Examples of uses for the copolymers or graft polymers produced according to the invention are, in particular, paints, protective coatings or coatings in the following areas

Marine hull, port facilities, buoys, drilling platforms, ballast water tanks - house roofing, cellars, walls, facades, greenhouses, sun protection,

Garden fence, wood protection Sanitary Public toilets, bathrooms, shower curtains, toiletries, swimming pools, saunas, joints, sealing compounds

Food machines, kitchen, cake items, sponges, toys, food packaging, milk processing, drinking water systems, cosmetics - machine parts air conditioning, ion exchangers, process water, solar systems,

Heat exchangers, bioreactors, membranes, medical technology, contact lenses, diapers, membranes, implants, utensils, car seats, clothing (stockings, sportswear), hospital facilities, door handles, telephone receivers, public transport, animal cages, cash registers, carpets, wallpapers

To further describe the present invention, the following examples are given, which further illustrate the invention but are not intended to limit its scope as set out in the claims

example 1

A polyamide 12 film is exposed for 2 minutes at a pressure of 1 mbar to 172 nm radiation from an excimer radiation source from Heraeus. The film activated in this way is placed in an irradiation reactor under protective gas and fixed thereupon the film is countercurrently flowed with 20 ml of a mixture of 3 g of 3-aminopropyl vinyl ether (from Aldrich) and 97 g of methanol are coated. The radiation chamber is closed and placed at a distance of 10 cm under an excimer radiation unit from Heraeus, which has an emission of the wavelength 308 nm. The radiation is started, the exposure time is 15 minutes The film is then removed and rinsed with 30 ml of methanol. The film is then dried in vacuo for 12 hours at 50 ° C. The film is then extracted 5 times for 6 hours at 30 ° C., then dried at 50 ° C. for 12 hours

The back of the film is then treated in the same way, so that finally a polyamide film coated on both sides with grafted polymer is obtained Example la

A coated piece of film from Example 1 (5 × 4 cm) is placed in 30 ml of a test microbial suspension of Staphylococcus aureus and shaken. After a contact time of 15 minutes, 1 ml of the test microbial suspension is removed, and the number of bacteria in the test batch is determined more detectable from Staphylococcus aureus

Example lb

A coated piece of film from Example 1 (5 × 4 cm) is placed in 30 ml of a test microbial suspension of Pseudomonas aeruginosa and shaken. After a contact time of 60 minutes, 1 ml of the test microbial suspension is removed, and the number of bacteria in the test mixture is determined dropped from 10 ⁷ to 10 ³

Example 2

A polyamide 12 film is exposed for 2 minutes at a pressure of 1 mbar to 172 nm radiation from an excimer radiation source from Heraeus. The film activated in this way is placed in an irradiation reactor under protective gas and fixed thereupon the film is exposed to 20 ml of a mixture in a protective gas countercurrent 3 g of methacrylic acid-2-aminoethyl ester hydrochloride (Aldrich) and 97 g of methanol are coated. The radiation chamber is closed and placed at a distance of 10 cm under an excimer radiation unit from Heraeus, which has an emission of 308 nm. The radiation is started, the Exposure time is 15 minutes. The film is then removed and unwound with 30 ml of methanol. The film is then dried in vacuo at 50 ° C. for 12 hours. The film is then extracted 5 times for 6 hours at 30 ° C., then at 50 ° C. 12 Hours dried

The back of the film is then treated in the same way, so that finally a polyamide film coated on both sides with grafted polymer is obtained Example 2a

A coated piece of film from Example 2 (5 × 4 cm) is placed in 30 ml of a test microbial suspension of Staphylococcus aureus and shaken. After a contact time of 15 minutes, 1 ml of the test microbial suspension is removed, and the number of bacteria in the test batch is determined more detectable from Staphylococcus aureus

Example 2b

A coated piece of film from Example 2 (5 × 4 cm) is placed in 30 ml of a test microbial suspension of Pseudomonas aeruginosa and shaken. After a contact time of 60 minutes, 1 ml of the test microbial suspension is removed, and the number of bacteria in the test batch is determined dropped from 10 ⁷ to 10 ^

Example 3

A polyamide 12 film is exposed for 2 minutes at a pressure of 1 mbar to 172 nm radiation from an excimer radiation source from Heraeus. The film activated in this way is placed in an irradiation reactor under protective gas and fixed thereupon the film is exposed to 20 ml of a mixture in a protective gas countercurrent 3 g of N-3-aminopropyl methacrylamide hydrochloride (from Polysciences Ine) and 97 g of methanol are coated. The radiation chamber is closed and placed at a distance of 10 cm under an excimer radiation unit from Heraeus, which has an emission of the wavelength 308 nm. The radiation is started, the exposure time is 15 minutes. The film is then removed and unwound with 30 ml of methanol. The film is then dried in vacuo for 12 hours at 50 ° C. The film is then extracted 5 times for 6 hours at 30 ° C., then at 50 ° C. Dried for 12 hours

The back of the film is then treated in the same way, so that finally a polyamide film coated on both sides with grafted polymer is obtained Example 3 a

A coated piece of film from Example 3 (5 × 4 cm) is placed in 30 ml of a test microbial suspension of Staphylococcus aureus and shaken. After a contact time of 15 minutes, 1 ml of the test microbial suspension is removed, and the number of bacteria in the test mixture is determined more detectable from Staphylococcus aureus

Example 3b

A coated piece of film from Example 3 (5 × 4 cm) is placed in 30 ml of a test microbial suspension of Pseudomonas aeruginosa and shaken. After a contact time of 60 minutes, 1 ml of the test microbial suspension is removed, and the number of bacteria in the test mixture is determined dropped from 10 ⁷ to 10

Example 4

A polyamide 12 film is exposed for 2 minutes at a pressure of 1 mbar to 172 nm radiation from an excimer radiation source from Heraeus. The film activated in this way is placed in an irradiation reactor under protective gas and fixed thereupon the film is exposed to 20 ml of a mixture in a protective gas countercurrent 3 g of 3-aminopropyl vinyl ether (from Aldrich), 2 g of methyl methacrylate (from Aldrich) and 95 g of methanol are covered. The radiation chamber is closed and placed at a distance of 10 cm under an excimer radiation unit from Heraeus, which has an emission of the wavelength 308 nm The irradiation is started, the exposure time is 15 minutes. The film is then removed and unwound with 30 ml of methanol. The film is then dried in vacuo at 50 ° C. for 12 hours. The film is then extracted 5 times 6 hours at 30 ° C. in water. then dried at 50 ° C for 12 hours

The back of the film is then treated in the same way, so that finally a polyamide film coated on both sides with grafted polymer is obtained Example 4a

A coated piece of film from example 4 (5 × 4 cm) is placed in 30 ml of a test germ suspension of Staphylococcus aureus and shaken. After a contact time of 15 minutes, 1 ml of the test germ suspension is removed, and the number of germs in the test mixture is determined. After this time there are no germs more detectable from Staphylococcus aureus

Example 4b

A coated piece of film from Example 4 (5 × 4 cm) is placed in 30 ml of a test germ suspension from Pseudomonas aeruginosa and shaken. After a contact time of 60 minutes, 1 ml of the test germ suspension is removed, and the number of bacteria in the test mixture is determined dropped from 10 ⁷ to 10 ⁴

Example 5

A polyamide 12 film is exposed for 2 minutes at a pressure of 1 mbar to 172 nm radiation from an excimer radiation source from Heraeus. The film activated in this way is placed in an irradiation reactor under protective gas and fixed thereupon the film is exposed to 20 ml of a mixture in a protective gas countercurrent 3 g of methacrylic acid-2-aminoethyl ester hydrochloride (Aldrich), 2 g of methyl methacrylate (Aldrich) and 95 g of methanol are coated. The radiation chamber is closed and placed at a distance of 10 cm under an excimer radiation unit from Heraeus, which emits wavelength 308 nm. The irradiation is started, the exposure time is 15 minutes. The film is then removed and rinsed with 30 ml of methanol. The film is then dried in vacuo for 12 hours at 50 ° C. The film is then 5 times 6 hours at 30 ° C. in water extracted, then dried at 50 ° C for 12 hours

The back of the film is then treated in the same way, so that finally a polyamide film coated on both sides with grafted polymer is obtained Example 5a

A coated piece of film from Example 5 (5 × 4 cm) is placed in 30 ml of a test microbial suspension of Staphylococcus aureus and shaken. After a contact time of 15 minutes, 1 ml of the test microbial suspension is removed, and the number of bacteria in the test batch is determined more detectable from Staphylococcus aureus

Example 5b

A coated piece of film from Example 5 (5 × 4 cm) is placed in 30 ml of a test germ suspension from Pseudomonas aeruginosa and shaken. After a contact time of 60 minutes, 1 ml of the test germ suspension is removed, and the number of bacteria in the test mixture is determined dropped from 10 ⁷ to 10 ⁴

In addition to the microbicidal activity against cells from Pseudomonas aeruginosa and Staphylococcus aureus described above, all samples also showed a microbicidal activity against cells from Klebsieila pneumoniae, Escherichia coli, Rhizopus oryzae, Candida tropicalis and Tetrahymena pyriformis

Claims

Claims:

1. A process for the preparation of antimicrobial polymers, characterized in that aliphatic unsaturated monomers which are at least simple by a primary

Amino group are functionalized, polymerized.

2. The method according to claim 1, characterized in that functionalized by a primary amino group aliphatic unsaturated

Monomers of the general formula

with Ri: branched, unbranched or cyclic, aliphatic unsaturated

Hydrocarbon residue with up to 50 carbon atoms, which can be substituted by O, N or S atoms

be used.

3. The method according to claim 1 or 2, characterized in that the polymerization is carried out with further, aliphatic unsaturated monomers.

4. The method according to any one of claims 1 to 3, characterized in that the polymerization is carried out on a substrate.

5. The method according to any one of claims 1 to 4, characterized in that the polymerization is carried out as a graft polymerization of a substrate.

6. The method according to claim 5, characterized in that the substrate before the graft polymerization by UV radiation, plasma treatment,

Corona treatment, flame treatment, ozonization, electrical discharge or γ-radiation is activated.

7. The method according to claim 5, characterized in that the substrate is activated before the graft polymerization by UV radiation with a photosensitizer.

8. Use of the antimicrobial polymers produced according to one of claims 1 to 7 for the production of products with an antimicrobial coating from the polymer.

9. Use of the antimicrobial polymers produced according to one of claims 1 to 7 for the production of medical articles with an antimicrobial coating from the polymer.

10. Use of the antimicrobial polymers produced according to one of claims 1 to 7 for the production of hygiene articles with an antimicrobial coating made of the polymer.

11. Use of the antimicrobial polymers produced according to one of claims 1 to 7 in lacquers, protective coatings or coatings.