U.S. patent application number 09/527829 was filed with the patent office on 2001-07-12 for process for the preparation of antimicrobial plastics.
Invention is credited to Anders, Christine, Hill, Frank, Hill, Friedrich Frank, Hill, Hella Luise, Hill, Henning Hinrich, Hill, Regina Luise, Ottersbach, Peter.
Application Number | 20010007694 09/527829 |
Document ID | / |
Family ID | 7822384 |
Filed Date | 2001-07-12 |
United States Patent
Application |
20010007694 |
Kind Code |
A1 |
Ottersbach, Peter ; et
al. |
July 12, 2001 |
Process for the preparation of antimicrobial plastics
Abstract
Antimicrobial activity is imparted to the surface(s) of an
apparatus or article by polymerizing tert-butylaminoethyl
methacrylate in the presence of the apparatus or article by which
adhesion of the polymer to the surface(s) is achieved. In a
preferred embodiment of the invention the antimicrobial monomer is
graft polymerized on the surface(s).
Inventors: |
Ottersbach, Peter; (Windeck,
DE) ; Hill, Frank; (Mettmann, DE) ; Hill,
Hella Luise; (Mettmann, DE) ; Hill, Henning
Hinrich; (Mettmann, DE) ; Hill, Friedrich Frank;
(Waldsee, DE) ; Hill, Regina Luise; (Speyer,
DE) ; Anders, Christine; (Haltern, DE) |
Correspondence
Address: |
Oblon Spivak McClelland Maier & Neustadt PC
Fourth Floor
1755 Jefferson Davis Hwy
Arlington
VA
22202
US
|
Family ID: |
7822384 |
Appl. No.: |
09/527829 |
Filed: |
March 17, 2000 |
Current U.S.
Class: |
427/2.1 ;
427/430.1 |
Current CPC
Class: |
A01N 37/12 20130101;
C08F 20/34 20130101; A01N 25/10 20130101 |
Class at
Publication: |
427/2.1 ;
427/430.1 |
International
Class: |
B05D 001/18; B05D
003/00 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 6, 1997 |
DE |
197 09 076.1 |
Claims
What is claimed as new and desired to be secured by Letters Patent
of the United Stated is:
1. A method of imparting antimicrobial activity to the surface(s)
of an apparatus or article, which comprises: polymerizing
tert-butylaminoethyl methacrylate in the presence of said apparatus
or article by which adhesion of the polymer to said surface(s) is
achieved.
2. The method as claimed in claim 1, wherein the polymerization of
tert-butylaminoethyl methacrylate is graft polymerization of
monomer on said surface(s).
3. The method as claimed in claim 2, wherein the surface(s) is
activated before the grafting polymerization.
4. The method as claimed in claim 3, wherein the activation of the
surface(s) is carried out by UV radiation with or without an
additional photosensitizer, plasma treatment, corona treatment,
flaming, ozonization, electrical discharge or
.gamma.-radiation.
5. The method as claimed in claim 1, wherein said apparatus or
article provided with antimicrobial activity is a medical
article.
6. The method as claimed in claim 1, wherein said apparatus
provided with antimicrobial activity is a hygienic article.
7. The method as claimed in claim 2, wherein said apparatus or
article provided with antimicrobial activity is a medical
article.
8. The method as claimed in claim 2, wherein said apparatus
provided with antimicrobial activity is a hygienic article.
9. The method as claimed in claim 1, wherein the apparatus or
article is manufactured of polyurethane, polyamide, polyester,
polyether, polyether-block amides, polystyrene, polyvinyl chloride,
polycarbonate, polyorganosiloxanes, polyolefins, polysulfones,
polyisoprene, polychloroprene, polytetrafluoroethylene, blends of
these polymers or natural or synthetic rubber.
10. The method as claimed in claim 3, wherein said surface(s) of
the apparatus or article is activated by exposure to UV
radiation.
11. The method as claimed in claim 10, wherein said activation
occurs in the presence of a photosensitizer.
12. The method as claimed in claim 3, wherein said activation is
effected by subjecting said surface(s) to a high frequency or
microwave plasma.
13. The method as claimed in claim 3, wherein said activation is
effected by subjecting said surface(s) to electron beam or
.gamma.-radiation or by ozonization.
14. The method as claimed in claim 3, comprising applying a
solution of t-butylaminoethyl methacrylate to said surface(s), and
effecting graft polymerization by exposure of the applied solution
to activating radiation.
15. The method as claimed in claim 14, wherein the
t-butylaminoethyl methacrylate concentration in solution ranges
from 1% to 10% by wt.
16. The method as claimed in claim 15, wherein said activating
radiation is short wavelength visible or long wavelength UV
radiation.
17. A method for preparing an antimicrobial polymer, which
comprises: polymerizing t-butylaminoethyl methacrylate.
18. The method of claim 17, wherein said polymerization is
conducted on a substrate.
19. A method for preparing an antimicrobial polymer, which
comprises: graft polymerizing t-butylaminoethyl methacrylate on a
substrate.
20. The method as claimed in claim 19, wherein the substrate is
activated before the graft polymerization.
21. The method as claimed in claim 20, wherein said activation of
the substrate is conducted by UV radiation with or without the
addition of photosensitizer, plasma treatment, corona treatment,
flaming, ozonization, electrical discharge or .gamma.-radiation.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to a process for the
preparation of antimicrobial polymers by polymerization of
tert-butylaminoethyl methacrylate, and the use of the antimicrobial
polymers. More particularly, the invention relates to a process for
the preparation of antimicrobial polymers by graft polymerization
of tert-butylaminoethyl methacrylate on a substrate, and the use of
the antimicrobial polymers.
[0003] 2. Description of the Background
[0004] The colonization and spread of bacteria on surfaces of
pipelines, containers or packaging is highly undesirable. Layers of
slime often form, which allow the microbe populations to rise to
extreme levels, lastingly impairing the quality of water, drinks
and foodstuffs, and can even lead to decay of the goods and damage
to the health of consumers.
[0005] Bacteria are to be kept away from all areas of life where
hygiene is of importance. Since textiles directly contact the body,
and, in particular the genital area, and are used for the care of
the sick and elderly, textiles should be freed of bacteria.
Bacteria should also be kept away from the surfaces of furniture
and equipment in nursing wards, in particular in the intensive care
and infant care sector, in hospitals, especially in rooms for
medical operations, and in isolation wards for critical cases of
infection, as well as in toilets.
[0006] Equipment, and surfaces of furniture and textiles are
currently treated to ward against bacteria as required or also
preventively with chemicals or solutions and mixtures thereof which
act as disinfectants, such having a more or less broad and powerful
antimicrobial action. Such chemical compositions have a nonspecific
action, are often themselves toxic or irritating, or form
degradation products which are unacceptable to health. Intolerances
are often also found in appropriately sensitized persons. Another
procedure which is used to inhibit the spread of bacteria on
surfaces is to incorporate antimicrobially active substances into a
matrix.
[0007] Tert-butylaminoethyl methacrylate is a commercially
available monomer of methacrylate chemistry and is employed in
particular as a hydrophilic monomer in copolymerizations. Thus, EP
0 290 676 describes the use of various polyacrylates and
polymethacrylates as a matrix for immobilization of bactericidal
quaternary ammonium compounds.
[0008] U.S. Pat. No. 3,592,805 discloses the preparation of
systemic fungicides in which per halogenated acetone derivatives
are reacted with methacrylate esters, such as, for example,
tert-butylaminoethyl methacrylate.
[0009] U.S. Pat. No. 4,515,910 describes the use of polymers of
hydrogen fluoride salts of aminomethacrylates in dental medicine.
The hydrogen fluoride bonded in the polymers emerges slowly from
the polymer matrix and is said to be effective against caries.
[0010] In another technical field, U.S. Pat. No. 4,532,269
discloses a terpolymer of butyl methacrylate, tributyltin
methacrylate and tert-butylaminoethyl methacrylate. This polymer is
used as an antimicrobial paint for ships, the hydrophilic
tert-butylaminoethyl methacrylate promoting slow erosion of the
polymer and in this way liberating the highly toxic tributyltin
methacrylate as an antimicrobially active compound.
[0011] In these applications, the copolymer prepared with
aminomethacrylates is only a matrix or carrier substance for added
microbicidal active compounds, which can diffuse or migrate out of
the carrier. Polymers of this type lose their action at a faster or
slower rate when the necessary "minimum inhibitory concentration"
(MIC) is no longer achieved on the surface.
[0012] EP 0 204 312 describes a process for the preparation of
antimicrobially treated acrylonitrile fibers. The antimicrobial
action is based on a protonated amine as a comonomer unit,
dimethylaminoethyl methacrylate and tertbutylaminoethyl
methacrylate, inter alia, being used as protonated species.
However, the antimicrobial action of protonated surfaces is
severely reduced after loss of the H(+) ions. A need continues to
exist for an effective method of providing surfaces of objects with
antimicrobial properties.
SUMMARY OF THE INVENTION
[0013] Accordingly, one object of the present invention is to
provide materials which have antimicrobial properties, which
contain no active compounds which can be washed out, and in which
the antimicrobial action is pH-independent.
[0014] Another object of the present invention is to provide
surfaces of objects and apparatus with a permanently microbicidal
polymeric coating which is not attacked by solvents and physical
stress and which shows no migration, and by which it is not
necessary to employ additional biocidally active compounds.
[0015] Briefly, these objects and other objects of the present
invention as hereinafter will become more readily apparent can be
attained by a method of imparting antimicrobial activity to the
surface(s) of an apparatus or article, which comprises polymerizing
tert-butylaminoethyl methacrylate in the presence of the apparatus
or article by which adhesion of the polymer to said surface(s) is
achieved. In a preferred embodiment of the invention the
tert-butylaminoethyl methacrylate monomer is graft polymerized onto
the surface.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0016] The antimicrobial polymers of the invention can be obtained
by grafting polymerizing tert-butylaminoethyl methacrylate on a
surface of an article or apparatus.
[0017] Suitable substrate materials include, above all, all
polymeric plastics, such as, for example, polyurethanes,
polyamides, polyesters, polyethers, 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 process of the
invention can also be applied on the surfaces of metal, glass or
wooden bodies which are painted or are otherwise coated with
plastic.
[0018] The surfaces of the substrates can be activated by a number
of methods before the grafting polymerization. They are expediently
freed from oils, greases or other impurities beforehand in a known
manner by means of a solvent.
[0019] The standard polymers can be activated by UV radiation. A
suitable source of radiation is, for example, a UV-Excimer
apparatus HERAEUS Noblelight, Hanau, Germany. However, mercury
vapor lamps are also suitable for activation of the substrate if
they emit considerable proportions of radiation in the ranges
mentioned. The exposure time generally ranges from 0.1 second to 20
minutes, preferably 1 second to 10 minutes.
[0020] The activation of the standard polymers with UV radiation
can furthermore be carried out with an additional photosensitizer.
Suitable such photosensitizers include, for example, benzophenone,
as such are applied to the surface of the substrate and irradiated.
In this context, irradiation can be conducted with a mercury vapor
lamp using exposure times of 0.1 second to 20 minutes, preferably 1
second to 10 minutes.
[0021] According to the invention, the activation can also be
achieved by a high frequency or microwave plasma (Hexagon, Technics
Plasma, 85551 Kirchheim, Germany) in air or a nitrogen or argon
atmosphere. The exposure times generally range from 30 seconds to
30 minutes, preferably 2 to 10 minutes.
[0022] The energy output of laboratory apparatus is between 100 and
500 W, preferably between 200 and 300 W.
[0023] Corona apparatus (SOFTAL, Hamburg, Germany) can furthermore
be used for the activation. In this case, the exposure times are,
as a rule, 1 to 10 minutes, preferably 1 to 60 seconds.
[0024] Activation by electron beams or .gamma.-rays, for example,
from a cobalt-60 source) and ozonization allow short exposure times
which are generally range from 0.1 to 60 seconds.
[0025] The flaming of surfaces likewise leads to activation of the
surfaces. Suitable apparatus, in particular those having a barrier
flame front, can be constructed in a simple manner or obtained, for
example, from ARCOTEC, 71297 Monsheim, Germany. The apparatus can
employ hydrocarbons or hydrogen as the combustible gas. In all
cases, harmful overheating of the substrates must be avoided, which
is easily achieved by intimate contact with a cooled metal surface
on the substrate surface facing away from the flaming side.
Activation by flaming is accordingly limited to relatively thin,
flat substrates. The exposure times generally range from 0.1 second
to 1 minute, preferably 0.5 to 2 seconds. The flames without
exception are nonluminous and the distances between the substrate
surfaces and the outer flame front ranges from 0.2 to 5 cm,
preferably 0.5 to 2 cm
[0026] The substrate surfaces activated in this way are coated with
tertbutylaminoethyl methacrylate, if appropriate in solution, by
known methods, such as by dipping, spraying or brushing. Suitable
solvents have proved to be water and water/ethanol mixtures,
although other solvents can also be used if they have a sufficient
dissolving power for tert-butylaminoethyl methacrylate and wet the
substrate surfaces thoroughly. Solutions having monomer contents of
1 to 10% by weight, for example about 5% by weight, have proved
suitable in practice and in general give continuous coatings which
cover the substrate surface and have coating thicknesses which can
be more than 0.1 .mu.m in one pass.
[0027] The grafting copolymerization of the monomer applied to the
activated surfaces is expediently effected by short wavelength
radiation in the visible range or in the long wavelength segment of
the UV range of electromagnetic radiation. The radiation of a
UV-Excimer of wavelengths 250 to 500 nm, preferably 290 to 320 nm,
for example, is particularly suitable. Mercury vapor lamps are also
suitable here if they emit considerable amounts of radiation in the
ranges mentioned. The exposure times generally range from 10
seconds to 30 minutes, preferably 2 to 15 minutes.
[0028] Poly-tert-butylaminoethyl methacrylate also shows intrinsic
microbicidal properties without grafting to a substrate
surface.
[0029] One possible embodiment of the present invention comprises a
procedure in which the polymerization of tert-butylaminoethyl
methacrylate can be carried out on a substrate.
[0030] An antimicrobial polymer can furthermore be prepared by
polymerization of tert-butylaminoethyl methacrylate by known
processes.
[0031] In the process of the invention, the polymer of
tert-butylaminoethyl methacrylate can also be applied to the
substrate in solution.
[0032] Suitable solvents include, for example, water, ethanol,
methanol, methyl ethyl ketone, diethyl ether, dioxane, hexane,
heptane, benzene, toluene, chloroform, methylene chloride,
tetrahydrofuran and acetonitrile.
[0033] The solution of the polymer obtained by polymerization of
tert-butylaminoethyl methacrylate is applied to the standard
polymers, for example, by dipping, spraying or painting.
[0034] If the polymer is produced directly on the substrate surface
without grafting, suitable initiators are added in order to promote
polymerization. Initiators which can be used include, inter alia,
azonitriles, alkyl peroxides, hydroperoxides, acyl peroxides,
peroxoketones, peresters, peroxocarbonates, peroxodisulfate,
persulfate and all the customary photoinitiators, such as, for
example, acetophenones and benzophenone.
[0035] The initiation of the polymerization can be carried out by
means of heat or by electromagnetic radiation, such as, for
example, UV light or .gamma.-radiation.
[0036] The present antimicrobial polymers can be used for the
production of products such as medical articles or hygienic
articles.
[0037] Medical articles produced by the process of the invention
include, for example, catheters, blood bags, drainages, guide wires
and surgical instruments.
[0038] The process according to the invention can furthermore be
employed for the production of hygienic articles, such as, for
example, toothbrushes, toilet seats, combs and packaging
materials.
[0039] Having now generally described this invention, a further
understanding can be obtained by reference to certain specific
examples which are provided herein for purposes of illustration
only and are not intended to be limiting unless otherwise
specified.
EXAMPLE 1
[0040] A 27 g amount of tert-butylaminoethyl methacrylate and 150
ml of ethanol is heated to 65.degree. C. under an inert gas. When
the temperature is reached, 0.37 g of azobisisobutyronitrile,
dissolved in 10 ml of methyl ethyl ketone, is added. At the end of
24 hours, the reaction is ended by stirring the mixture into 11 of
a water/ice mixture. The reaction product is removed by filtration
and washed with 300 ml of n-hexane. The product is then distributed
over several Soxhlets and extracted with water for 24 hours, and is
then dried at 50.degree. C. in vacuo for 12 hours.
EXAMPLE 2
[0041] A 4 g amount of poly-tert-butylaminoethyl methacrylate from
Example 1 is dissolved in 40 ml of tetrahydrofuran. A polyamide 12
film is immersed in this solution for 5 seconds, removed from the
solution for 10 seconds and them immersed again for 5 seconds, so
that a uniform film of poly-tert-butylaminoethyl methacrylate has
formed on the polyamide film after subsequent drying at room
temperature under normal pressure. The film is then dried at
50.degree. C. in vacuo for 24 hours. The film is subsequently
extracted in water at 30.degree. C. 5 times for 6 hours and then
dried at 50.degree. C. for 12 hours.
EXAMPLE 3
[0042] A 4 g amount of poly-tert-butylaminoethyl methacrylate from
Example 1 is dissolved in 40 ml of tetrahydrofuran. A polyvinyl
chloride film is immersed in this solution for 2 seconds, removed
from the solution for 10 seconds and then immersed again for 2
seconds, so that a uniform film of poly-tert-butylaminoethyl
methacrylate has formed on the polyvinyl chloride film after
subsequent drying at room temperature under normal pressure. The
film is then dried at 50.degree. C. in vacuo for 24 hours. The film
is subsequently extracted in water at 30.degree. C. 5 times for 6
hours and then dried at 50.degree. C. for 12 hours.
EXAMPLE 4
[0043] A polyamide 12 film is exposed to the 172 nm radiation of an
Excimer radiation source manufactured by Heraeus for 2 minutes
under a pressure of 1 mbar. The film activated in this way is laid
and fixed in an irradiation reactor under an inert gas. The film is
then covered with a layer of 20 ml of a mixture of 3 g of
tert-butylaminoethyl methacrylate and 97 g of methanol in a
countercurrent flow of inert gas. The irradiation chamber is closed
and placed at a distance of 10 cm underneath an Excimer radiation
unit manufactured by Heraeus, which has an emission of wavelength
308 nm. The irradiation is started, and the exposure time is 15
minutes. The film is removed and rinsed off with 30 ml of methanol.
The film is then dried at 50.degree. C. in vacuo for 12 hours. The
film is subsequently extracted in water at 30.degree. C. 5 times
for 6 hours and then dried at 50.degree. C. for 12 hours.
Measurement of Bactericidal Action
[0044] The bactericidal action of coated plastics was measured as
follows:
[0045] A 100 .mu.l of a cell suspension of Klebsiella pneumoniae
was placed on a piece of film 2.times.2 cm in size. The bacteria
were suspended in PBS buffer (phosphate-buffered saline); the cell
concentration was 10.sup.5 cells per ml of buffer solution. This
drop was incubated for up to 3 hours. In order to prevent any
drying out of the applied drop, the piece of film was laid in a
polystyrene Petri dish wetted with 1 ml of water. After the end of
the contact time, the 100 .mu.l were taken up with an Eppendorf tip
and diluted in 1.9 ml of sterile PBS. A 0.2 ml amount of this
solution was plated out on nutrient agar. The rate of inactivation
was calculated from the number of colonies which had grown.
Checking the Resistance of the Coatings
[0046] Before the measurement of the bactericidal action, the
coated films were subjected to the following pretreatments:
[0047] A: Washing in boiling water for 10 minutes
[0048] B: Washing in 96% strength ethanolic solution for 10
minutes
[0049] C: Washing in warm water at 25.degree. C. under ultrasonic
treatment for 10 minutes
[0050] D: No pretreatment
[0051] The results of the measurements, taking into account the
particular pretreatment are listed in Table 1.
1TABLE 1 Rate of Inactivation Example A B C D 2 4% <10% 56%
99.9% 3 5% <10% 54% 99.9% 4 99.9% 99.9% 99.9% 99.9%
[0052] After thermal, chemical or mechanical pretreatment, the
antimicrobial layers produced by grafting of a substrate surface
continue to show virtually complete inactivation of the bacteria
applied. The physically adhered layers are less stable to the
pretreatment of methods A, B and C.
[0053] In addition to the microbicidal activity against cells of
Klebsiella pneumoniae which has been described above, all the
coated films also showed a microbicidal action against cells of
Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli,
Rhizopus oryzae, Candida tropicalis and Tetrahymena pyriformis. The
rate of inactivation after treatment method D was also more than
99% in these cases.
[0054] The disclosure of priority German Application No. 197 09
076.1 having a filing date of Mar. 6, 1997 is hereby incorporated
by reference into the application.
[0055] Obviously, numerous modifications and variations of the
present invention are permissible in light of the above teachings.
It is, therefore, to be understood that within the scope of the
appended claims, the invention may be practiced otherwise than as
specifically described herein.
* * * * *