@ Publication number:
EUROPEAN
®
©
0 090
A2
6 1 0
PATENT A P P L I C A T I O N
Application number: 83301669.4
@ Int. CI.3: B 01 J 20/22, B 01 D 1 5 / 0 8
@ Date of filing : 24.03.83
<§) Priority: 30.03.82 JP 53384/82
©
©
@ ^entor: H?y*\su' Hikoi£ -18-2 Tsushimahonmachi,
Okayama-shi Okayama 700 (JP)
Inventor: Nakano, Masahide, 8-10, Nagaodai 3-chome,
Hirakata-shi Osaka 573-01 (JP)
Date of publication of application: 05.10.83
Bulletin 83/40
@ Designated Contracting States: AT BE CH DE FR GB IT
LINLSE
@ Amethod for treatment of mutagens.
Mutagenic substances in solutions are selectively adsorbed by specific solid adsorbents bearing covalently bound
phthalocyanine derivatives. The adsorbehts are prepared by
coupling the organic solid materials, for instance, cotton and
cellulose powder, with phthalocyanine derivatives having
chemically reactive terminal groups. Such reactive phthalocyanines are commercially available as phthalocyanine reactive dyes.
Applicant: SUMITOMO CHEMICAL COMPANY, LIMITED,
15 Kitahama 5-chome Higashi-ku, Osaka-shi Osaka-fu
(JP)
@ Representative: Myerscough, Philip Boyd et al, J.A.Kemp
&Co. 14, South Square Gray's Inn, London, WC1R5EU
(GB)
This
of
solution
a
relates
to
invention
more
for
selective
adsorption
their
because
of
of
situation,
this
is
It
already
inhibit
derivatives
662-668
these
inhibition.
and
to
adsorb
solid
have
extremely
it
view
In
techniques
them
and
its
mutagenic
compounds,
activated
high
efficient
also
are
Commun.,
The
(1980)].
that
hemin
that
prepared
by
forms
this
to
subject
proposed
that
that
by
phthaloN-(6-
coupling
com-
bromide,
cyanogen
compounds.
for
adsorbent
efficiency
residues
and
is
Res.
Biophys.
polysulfo-copper-phthalocyanine
search
discovered
materials
that
mutagenic
further
and
the
shown
complex,
gel
agarose
reactive
certain
concern
separating
hemin
that
of
have
In..addition,
In
been
develop
Letts.,11,29-33
mutagens
aminohexyl)sulfamoyl
has
public
the
activity.
for
[Biochem.
reports
cyanine-polysaccharide
prepared
to
or
reported
Cancer
with the
complexes
used
bearing
in
present
of
focus
a
activities
(1980);
of
authors
is
are
important
indole) and benzo (a) pyrene
pound
adsorbents
a
(3-amino-l,4-dimethyl-5H-pyrido[4,3,-b]-
Trp-P-1
92,
in
environment.
the
e.g.,
that
substances
these
mutagens
particularly
carcinogenic
is
of
skeletons.
become
it
treatment
particularly,
solid
by
substances
potential
eliminating
from
solution,
have
environment
human
solution,
a
phthalocyanine
Mutagenic
for
in
aqueous
bound
covalently
for
mutagens,
a process
substantially
a method
to
containing
substantially
present
relates
in
the
adsorbent
be
easily
resulting
for
a
can
adsorbing
phthalocyanine
can
that
coupled
materials
of
easily
it
mutagens,
compounds
range
be
having
with
organic
serve
mutagens.
as
The
substances
which
said
use
of
The
expression
case
to
where
moisten
a large
are
the
is
only
subject
of
Examples
are
in
as
small
a
well
solution"
the
of
the
reactive
enough
case
where
there
is
sulfato-ethylsulfonamide,
acrylamide,
vinylsulfone,
mono-
or
dihalophthalazine,
Specific
in
groups
examples
of
such
this
trihalo-
dihaloquinoxaline,
pyridazone,
listed
by
the
water
monohalotriazine,
sulfato-ethylsulfone,
are
includes
of
terminal
pyrimidine,
methylolamine.
solution
a
water.
dihalotriazine,
and
mutagenic
above.
compound
amount
as
in
present
a
of
treatment
a
phthalocyanine
"substantially
there
is
substantially
modified
amount
invention
invention
present
dihalo-
dihalopyrimidine,
halobenzothiazole
reactive
groups
below.
Dihalotriazine;
(dichloro-1,3,5-triazinyl)
Monohalotriazine;
(monochloro-1,3,5-triazinyl)
(R:
various
kinds
of
substituent)
Trihalopyrimidine;
(2,4,5-trichloropyrimidinyl)
Sulfato-ethylsulfone;
(β-sulfato-ethylsulfonyl)
(β-chloro-ethylsulfonyl)
Dihaloquinoxaline;
(2,3-dichloroquinoxaline6-carbonyl)
Dihalopyridazone;
(4,5-dichloro-6pyridazonylpropionyl)
Sulfato-ethylsulfonamide;
(β-sulfato-ethylaminosulfonyl)
Mono-
or
dihalopyrimidine;
(2-methylsulfonyl-4methyl-5-chloropyrimidinyl)
(2,4-dichloropyrimidinyl)
Acrylamide;
(6-sulfatopropionylamide)
(B-chloropropionylamide)
Vinylsulfone;
(vinylsulfonyl)
Dihalophthalazine;
(1,4-dichlorophthalazine6-carbonyl)
Halobenzothiazole;
(chlorobenzothiazolyl)
Methylolamine;
The
include
invention
Particularly
The
the
should
is
preferred
for
phthalocyanine
compound
water
onto
available.
dyes".
such
the
derivatives
anchoring
commercially
be
non-metallic
as
copper
modified
reactively
preferably
be
can
in k i n d .
in
used
and
the
present
metal-
the
iron-,
copper-,
aluminum-phthalocyanines.
phthalocyanine
phthalocyanine
sary
and
cobalt-
nickel-,
the
both
phthalocyanines,
containing
that
phthalocyanines
the p h t h a l o c y a n i n e
to
same or d i f f e r e n t
may be one or more in number and the
molecules
or
can be a t t a c h e d
that
residues
The r e a c t i v e
phthalocyanine
having
soluble.
having
the
organic
They
phthalocyanine.
are
reactive
Many
reactive
solid
called
compound
group
water-soluble
groups
material
"reactive
necesare
The
above
have
phthalocyanine
been
disclosed,
GB836647,
GB805562,
GB995796,
GB1208553,
The
is
cyanine
mercapto,
with
to
in
this
are
as
and
Sepharose
(such
them),
as
reaction
carried
containing
the
an
in
US P a t e n t
can
media
aqueous
the
known
present
for
compound
accordance
invention
example,
fiber
in
out
the
compound
material
can
For
group-
cellulose
presence
the
of
etc.
blocks,
procedure.
with
nylon
from
solid
and
alcohol,
produced
sulfato-ethylsulfone
compound,
starch
form
phthalocyanine
to
material
the
solid
plates,
organic
carried
in
cloths
organic
compound
e.g.,
in
be
may
a
fiber,
of
method
a base
described
2670265.
No.
The
cyanine
be
an
polyvinyl
polyamides,
the
of
as
solid
Co.);
with
phthalocyanine
in
cellulose
case
and
is
cellulose,
e.g.,
materials
the
according
the
reaction
referring,
groups
out
in
example,
of
serving
organic
silk;
sintered
compound
a phthalocyanine
Pharmacia
thread,
r e a c t
preferable
of
the
of
and
These
beads,
reactive
having
be
wool
cotton,
powder,
The
with
phthalo-
can
phthalocyanine
capable
of
product
e.g.,
Nos.
amino,
which
groups
Polysaccharides,
(a
the
hydroxy,
Particularly
Examples
follows.
group
GB948967,
which
on
contain
the
coupling
polyacrylamide.
fiber
of
polymer
invention.
polypeptides,
and
material
linkages.
in
Patent
USP3268548,
carboxamide
organic
substrate
in
example,
can
groups
covalent
hydrophilic
solid
solid
or
terminal
reactive
having
etc.
anchored
phenyl,
the
form
be
for
GB866513,
organic
to
compound
is
to
allowed
having
can
be
illustrated
a preferable
to
react
with
by
embodiment
the
sulfato-ethylsulfone
wherein
phthalogroup.
solid
The
thus
is
prepared
cyanine
often
compound,
derivatives
adsorbent
in
produced
times
desirable
pound
or
to
contaminated
well
as
such
with
as
by
phthalocyanine
with
or
phthalois
It
unaltered
such
water-soluble
dimethylsulfoxide
as
groups
phthalocyanine
process.
remove
of
use
unaltered
other
reaction
the
extract
contaminants
solvents,
bearing
(DMSO),
somecom-
organic
pyridine,
etc.
The
referred
[hereafter
obtained
are
when
in
they
cyanine
mutagens
are
present
in
with
For
the
substances,
at
a
This
the
a
followed
to
and
operation
phthalocyanine
solution
to
by
elution
the
the
adsorbent
is
added
aqueous
of
may
adsorption
of
agitation
temperature
0 be
in
solution,
a
the
phthalo-
adsorbed
shaking
100°C,
to
the
out
is
mutagenic
solution,
containing
mutagenic
is
thereto
applied
preferably
carried
substances,
mutagenic
solution
or
adsorbent
containing
amount
of
parti-
substances,
by
adsorption
the
mutagenic
solutions,
mutagenic
small
thus
solvent.
a proper
phthalocyanine
particularly
The
a very
concentrated
the
in
substantially
media.
adsorbents
adsorbing
selectively
aqueous
be
adsorbent(s)l
phthalocyanine
an
further
can
as
of
capable
dissolved
substances
cularly
to
adsorbent
solid
phthalocyanine-containing
at
15 -
repeatedly.
filled
in
substances
Alternatively,
a column
may
30°C.
be
and
then
passed
the
through
substances
column.
be
may
A gaseous
passed
moistened
through
mutagenic
containing
sample
phthalocyanine
adsorbents.
The
adsorbent
to
not
ably
of
amount
be
less
than
of
mutagens
is
prefer-
one
molecule
of
the
adsorption
residue
one
per
the
on
substance.
mutagenic
substances
Mutagenic
this
for
used
residue
phthalocyanine
invention
include
which
with
treated
be
can
Trp-P-l,
Trp-P-2
(3-amino-l-
methyl-5H-pyrido[4,3-b]indole),
Glu-P-1
(2-amino-6-methyl-
dipyrido[1,2-a:31,2'-dlimidazole),
Glu-P-2
dipyrido[l,2-a:3',2'-d]imidazole),
amino-a-carboline
amino-9H-pyrido[2,3-b]indole),
(2-amino(2-
aminomethyl-a-carboline
(2-amino-3-methyl-9H-pyrido[2,3-b]indole),
(2-amino-3-
IQ
methylimidazole[4,5-f]quinoline),2-acetylaminofluorene,
aflatoxin
daunomycin,
in
carbons
anthracene
the
with
The
than
three
of
having
mutagens
is
planar
All
fused-rings.
mutagens
of
three
possess
substances
the
example,
be
can
adsorbents
adsorbed
or
be
may
methanol,
agitated
basic
solvents,
the
cyanine
boiling
organic
point
adsorbent
containing
solvent
the
is
of
filled
mutagenic
above
may
the
be
solution
at
or
a
solvent.
in
passed
for
following
mutagenic
in
a
ammonia
other
When
is
the
the
and
a
passed
purpose
solvent,
solution,
neutral,
temperature
a column
substances
the
the
a methanol-aqueous
acid
acidic
in
shaken
or
the
onto
desorbed
containing
a methanol-hydrochloric
or
adsorbed
substances
adsorbents
Thus,
manner.
the
invention
present
adsorbing
hydro-
2-amino-
benzo(a)pyrene,
examples
mutagenic
phthalocyanine
to
aromatic
polycyclic
fused-rings.
The
for
as
for
less
not
above-mentioned
more
and
2-nitropyrene].
effective
particularly
structures
[such
general
and
B1
up
phthalosolution
through
of
it,
the
desorption.
solution
The
thus
desorbed
tion
containing
be
obtained
used
solu-
a
Alternatively,
mutagenic
substances
solvent.
Mutagenic
evaporation
of
the
isolated
by
removal
be
may
substances
mutagenic
such.
as
concentrated
more
by
substances
be
can
the
containing
of
solvent
the
can
by
evaporation.
The
be
can
invented
presently
readily
prepared
by
phthalocyanine
reactive
dyes.
is
adsorbent
substances,
from
that
so
used
various
fluids
body
for
foods,
(blood,
of
mutagenic
of
removal
of
mutagens
water,
urine,
semen,
products
and
mutagens
and
etc.)
water,
river
foods,
as
phthalocyanine
adsorption
identification
industrial
soil,
plants,
and
such
sources
be
(e.g.,
invented
The
it
may
available
commercially
in
isolation
detection,
of
use
effective
environment
the
human
highly
adsorbents
phthalocyanine
sea
for
from
water,
etc.),feces,
air,
industrial
disposals.
examples
invention
Further
detailed
of
invention
this
is
limited
not
will
be
working
but
below,
given
unless
thereto
the
on
explanation
the
purport
this
is
exceeded.
Example
1)
chemically
bonded
Into
30
g of
the
mR of
600
Turquoise
Ltd.:
A mixture
and
heated
Blue
water
was
to
G [reactive
Color
shown
up
Index
by
the
of
preparation
units
phthalocyanine
absorbent cotton
agitated
Co.,
of
Examples
added.
30°C.
dye
(C.I.),
following
as
in
placed
The
Then,
made
a
by
Reactive
a
cellulose
ligand.
1 liter
mixture
2 g of
Blue
beaker
was
slowly
Sumifix
Sumitomo
formula],
having
21;
Chemical
and
30
The
mixture
g of
sodium
was
at
raised
30°C,
70°C
to
allowed
to
filtration
of
water
nate).
The
cotton
1.8
methanol-concentrated
50 :
1),
50 :
1)
and
methanol,
coloration.
Then,
The
the
copper
contain
the
to
subjected
to
blue
atomic
was
1.0
cotton
absorbent
analysis
absorption
0.065%.
x
the
of
cotton
its
spectrum
into
put
using
and
acid
at
900
mt
made
by
100°C.
a Buchner
dried.
The
dimethylsulfoxide,
(volume
water
washing
was
separated
was
alkylbenzenesulfo-
with
ammonia
the
15
was
5 minutes
water,
sequentially
until
for
detergent
filtration
methanol-concentrated
g of
reaction
(a
for
hydrochloric
12
was
and
sodium
with
extensively
Then,
cotton
Monogen
by
it.
70°C.
at
funnel,
effected
was
to
mixture
the
The
Ltd:
Co.,
washed
of
minutes
g of
added
agitation
absorbent
separated
then
was
60
a Buchner
soaping
was
After
minutes.
colored
Seiyaku
rinsed
cotton
20
for
containing
Kogyo
funnel,
temperature
using
Daiichi
The
the
during
were
minutes.
added.
blue
by
20
was
continue
The
sulfate
for
agitated
carbonate
minutes
sodium
anhydrous
ratio
(volume
liquids
gave
ratio
no
dried.
thus
copper
method.
obtained
content
The
was
according
content
of
1 g of t h e c o t t o n
should
Accordingly,
1 0 - 5 m o l of p h t h a l o c y a n i n e
unit.
This
material
is
2)
of
hereafter
of
Examples
the
bonded
The
put
into
the
of
using
0.9%
Then,
new
30
sample
of
and
cellulose
the
as
having
ligand.
mg/ml)
obtained
in
aqueous
sodium
chloride
solution
at
removed
was
blue-cotton
the
adsorption
(10
minutes
blue-cotton
the
solution
same
for
shaken
through
the
the m u t a g e n i c
substances
containing
of 2 x 1 0 - 5 - 5
The
x 10-5 molel.
nically
blue-cotton.
as
units
phthalocyanine
blue-cotton
5 ml
to
elimination
substances
mutagenic
chemically
referred
(10
mixture
was
the
at
mixture
room
the
mecha-
was
(20°C).
solution.
added
was
was
concentration
temperature
from
mg/mt)
1)
shaken
for
30
shows
the
extents
to
A
the
minutes
in
the
way.
The
adsorption
of
calculated
from
remaining
absorption
for
plain
the
dyeing,
in
table
following
to
mutagens
the
the
of
solution
spectra.
absorbent
are
value
also
As
the
blue-cotton,
the
when
measured
a control,
cotton,
shown.
i.e.
mutagenic
the
cotton
by
which
the
were
substance
ultraviolet
adsorption
not
of
extents
subjectd
to
3)
of
Desorption
[3H]-Trp-P-2
human
(2
serum
(saline)
(5
ml,),
ml),
to
the
adsorbed
added
was
urine
(5
make
each
ml)
substance.
mutagenic
to
a
or
0.9%
sample
of
fresh
sodium
concentration
to
chloride
2 x 10-9
mol/l.
The
make
the
cotton
with
blue-cotton
the
Then,
blue-cotton
was
again
The
was
in
given
to
adsorb
was
moistened
wiped
with
2)
the
was
carried
water
a paper
and
to
substance.
mutagenic
with
out
towel.
then
The
wiped
again
towel.
a paper
Trp-P-2
procedure
blue-cotton
put
into
containing
1 ml/20
mg
the
(absorbent
adsorbed
cotton)
[3H]of
methanol-concentrated
and
the
ture
for
taken
tion
the
mixture
out
the
and
ammonia
shaken
was
purpose
of
wiped
with
procedure
was
for
paper
methanol-concentrated
by
ammonia
Quantitative
of
the
mixture
calculated
shown
in
was
from
the
the
the
carried
table
The
use
of
the
value.
were
the
Again,
the
same
These
were
radioactivity
and
room
ratio),
tempera-
blue-cotton
water.
extracts
out
analytical
following
minutes, at
towel.
ammonia
methanol-concentrated
in
15
1 volume
(50 :
extraction.
repeated
analysis
water
obtained.
extrac-
amount
2 lots
of
of
combined.
of
recovery
The
was
[3H)-Trp-P-2
was
results
as
Excellent
substances
the
obtained
reactive
following
reactive
also
are
in
results
when
dyes
described
above.
Sumifix
Turquoise
Blue
Reactive
Blue
CuPc:
Turquoise
Blue
Q+m+n <
Co.,
Ltd.:
C.I.
nucleus
4,
1 <
n <
2,
of
Sumitomo
Blue
of
Sumitomo
Blue
148)
C.I.
Reactive
Blue
75
C.I.
Reactive
Blue
E-BA:
C.I.
Reactive
Blue
P-BRA:
dye
of
Blue
Ltd.:
Chemical
Co.,
Ltd.:
(Cibacron
Pront
Turquoise
Ciba-Geigy)
116
Reactive
Blue
Co.,
BF
Reactive
Reactive
Chemical
118)
Blue
Turquoise
dye
GS
C.I.
G:
the
< 3
dye
(Reactive
of
place
Chemical
phthalocyanine
3 <
Reactive
Sumifix
in
and
cottons
15)
l+m @
1 @ l
C.I.
Sumitomo
copper
(Reactive
adsorbent
mutagenic
H-GF
3,
1 <
Sumifix
of
dye
of
adsorption
used
are
dye
(Reactive
the
(Levafix
of
dye
105
Reactive
Bayer.)
(Levafix
dye
of
Turquoise
Turquoise
Bayer.)
C.I.
Reactive
Blue
TG-E:
C.I.
Reactive
Blue
2G-E:
C.I.
Reactive
Reactive
Blue
Reactive
Blue
41
Blue
of
dye
Reactive
Blue
H-5G:
C.I.
Reactive
Blue
E-4G:
C.I.
Reactive
Reactive
Blue
GR-D:
Ciba-Geigy)
(Cibacron
dye
71
25
Reactive
C.I.
of
Turquoise
of
Turquoise
Ciba-Geigy)
(Procion
Turquoise
(Procion
Brilliant
H-A:
I.C.I.)
Blue
Blue
dye
80
Reactive
Blue
Reactive
(Cibacron
dye
Reactive
C.I.
H-7G:
18
dye
Blue
Reactive
of
I.C.I.)
(Levafix
dye
3
of
Bayer)
Brilliant
(Procion
of
72
Turquoise
Blue
I.C.I.)
(Cibacron
dye
of
Turquoise
Ciba-Geigy)
1.
A method
containing
bound
the
substances
with
a
solid
been
having
solid
a
comprises
contacting
by
bearing
coupling
a
covalently
adsorb
to
the
said
adsorbent,
reactive
in
substantially
compound
prepared
having
compound
a mutagen-
adsorbent
solid
the
on
of
present
phthalocyanine
selectively
treatment
which
solution,
mutagenic
solution
for
mutagens
adsorbent
a phthalocyanine
with
group
organic
an
material.
2.
A method
phthalocyanine
compound
copper
phthalocyanine
3.
A method
reactive
group
selected
from
of
the
mono-
or
claim
claim
dihalotriazine,
a
groups.
wherein
2,
the
is
compound
dihalo-
sulfato-ethylsulfone,
dihalopyrimidine,
is
group
monohalotriazine,
dihalopyridazone,
dihalophthalazine,
1 or
phthalocyanine
the
reactive
having
compound
to
wherein
1,
a reactive
having
according
trihalopyrimidine,
quinoxaline,
to
according
sulfato-ethylsulfonamide,
acrylamide,
halobenzothiazole
vinylsulfone,
and
methylol
amine.
4.
the
A method
organic
the
material
is
3 wherein
2 or
1,
containing
a polymer
residues.
hydroxy
5.
solid
claim
to
according
A method
organic
solid
6.
A method
claims
wherein
7.
A method
claims
wherein
having
a planar
aromatic
material
solution
2 or
1,
3 wherein
a cellulosic
of
any one
is
to
according
the
is
to
according
the
claim
to
according
mutagenic
structure
with
according
to
an
substance.
the
preceding
solution.
aqueous
of
the
preceding
substances
are
those
any one
not
less
than
3
rings.
8.
A method
claims
wherein
desorbed
from
adsorbed
said
any one
mutagenic
adsorbent
of
the
substances
following
the
preceding
are
adsorption.
9.
containing
mutagenic
solution
bound
for
A method
treatment
which
solution,
substances
with
phthalocyanine
mutagens
adsorbent
having
adsorbent
on
been
phthalocyanine
reactive
terminal
and
group
phthalocyanine
material.
bearing
to
prepared
by
compound
by
with
the
an
a
the
adsorbent,
said
making
introducing
coupling
in
covalently
adsorb
solid
the
contacting
substantially
compound
selectively
a mutagen-
comprises
present
solid
a
of
reactive
resulting
organic
reactive
solid