The present invention relates to cigarette filters and
modified filter materials.
Cigarette smoke contains a multitude of harmful components.
The major component in tobacco smoke harmful to the health of smokers is tar which
consists of many carcinogenic components. In commercially available cigarettes,
the tar content of the smoke is reduced by filters. Conventionally, organic filter
materials such as cellulose or modified cellulose like acetate cellulose are employed
to this end. Among further toxic and hazardous compounds numerous metals and oxidants
can be found. The combination of both is devastating for human health. Other harmful
components of tobacco smoke are, among others, carbon monoxide, hydrocyanic acid,
acetic aldehyde and formic aldehyde, nitrosamines, sulphur dioxide, phenols, mercury,
nickel, iron, copper, chromium, aluminium, vanadium, lead, cobalt, silicon, titanium,
manganese, zinc, cadmium, barium, strontium and arsenic compounds which are only
adsorbed or absorbed to a minor extent by conventional filters. Therefore several
specific filters have been developed to reduce the concentration of these compounds
in cigarette smoke.
Filter absorbents intended to bind nitrogen monoxide (NO)
from tobacco smoke are disclosed in the
EP 0 351 252 A2
. Therein ferrous ions, capable of complexing NO, are complexed by thiol-containing
low molecular weight ligands, which in turn are impregnated as aqueous solution
onto a conventional filter material, e.g. cellulose based filters.
Other metal based smoke filters are known from the
WO 2004/002247 A2
. Therein the catalytic activity of rare earth, zirconium and manganese
oxide or hydroxides is used to eliminate toxic compounds such as carbon monoxide,
NOx, nitrosamines, aldehydes, aromatic amines, sulfates and phosphor
sulfonates as well as the metals cadmium, nickel and zinc.
Tobacco smoke filters comprising a porphyrin-ring metal
complex as found in haemoglobin, are disclosed in the
EP 0 720 434 B1
. These filters are capable of inactivating oxidative radicals such as
-, H2O2, NO and other organic radicals, like isoprene-,
peroxyl-, alkoxyl-radicals, found in cigarette smoke.
US 2005/0133050 A1
an inorganic filter comprising thioalkylsilyl groups covalently bound
to an inorganic molecular sieve substrate, e.g. zeolite, for the absorption of mercury
and cadmium from cigarette smoke is disclosed.
The metal pollutants in cigarette smoke as well as the
oxidants hydrogen peroxide, peroxyradicals, nitrogen oxides, etc. (and sometimes
in combination) exert devastating effects on human cells leading to contraction
of cells, functional impairment and cell death. Oxidative damage based on cigarette
smoke components is a main case leading to atherosclerosis, COPD (Chronic Obstructive
Pulmonary Disease), and cancer. Cultures of vascular endothelial cells treated with
cigarette smoke extracts develop typical symptoms associated with atherosclerosis,
like cyto-skeletal disintegration, the breakdown of cell-cell junctions and low
viability through necrotic cell death (
Bernhard et al., FASEB J (2003) 17: 2302-2304
, online article 10.1096/fj.03-0312fje). Specific reducing compounds such
as atorvastatin and N-acetyl cysteine improved cell viabilty up to a level of cells
not treated with the harmful cigarette smoke extract.
Atherosclerosis is initiated by a damage of the blood vessel
wall, followed by infiltration of the intima by mononuclear cells, formation of
foam cells leading to fatty streaks, rearrangement of the vascular smooth muscle
layer, and an accumulation of lipids and extracellular matrix. Furthermore, inflammatory
processes contribute to atherogenesis and can be observed throughout all stages
of the disease. The deleterious consequences of these processes are the formation
of atherosclerotic plaques, plaque rupture, thrombus formation, and reduction of
the blood flow of arteries, finally resulting in hypoxia and tissue damage. The
initial damage to the vascular endothelium is caused by many factors e.g. physical
shear stress, chemical and oxidative damage (e.g. LDL oxidation), and immunological
stress. A combination of these effects further aggravates the situation, e.g. oxidative
stress increases the susceptibility to physical forces or pressure. Smoking was
found to be the most important risk factor for the development of early atherosclerotic
lesions. Cigarette smoke acutely affects the platelet and monocyte adhesion and
increases the stickiness of endothelial cells leading to the formation of atherosclerotic
It is a goal of the present invention to remove harmful
oxidative compounds from polluted air, especially cigarette smoke, by a filter directed
at the inactivation or absorption of such compounds, e.g. for the prevention of
Therefore, the present invention provides a filter material
characterized in that the filter material substantially consists of an organic material
and comprises covalently bound active thiol groups substantially free of complexing
agents. Preferably this filter material is used in a cigarette (smoke) filter. The
organic filter materials are capable of both removing harmful metal components of
cigarette smoke (foremost cadmium but also Cu, Cr, Ni, Pb, Hg, V, Al) and additionally
to reduce harmful oxidants such as hydrogen peroxide, peroxyradicals and nitrogen
oxides. It has been previously shown that protection against one group, like by
metal adsorption, alone is not sufficient to provide oxidative protection in endothelial
Bernhard et al., FASEB J (2005) 19, 1096-1107
). The combined protection provided by a filter material according to the
present invention therefore provides a substantial improvement, e.g. to prevent
atherosclerosis in smokers.
The present invention therefore also provides an improved
smoking filter which is characterised by having additionally introduced thiol groups.
In contrast to others, more sophisticated filters (such as the ones described in
EP 0 720 434 B1
US 2005/0133050 A1
) the filters of the present invention can easily be produced from standard
(cigarette) filter material by introducing thiol groups according to standard thiolation
techniques known in the art.
Thiol groups are synonymous for -SH or sulfhydryl groups.
These groups have surprisingly proven as active (or functionally active) groups
for a specific filtering and detoxifying effect in cigarette smoke according to
the present invention. This activity is responsible for the redox inactivation of
harmful oxidative compounds and the adsorption of harmful metals found in smoke
such as mercury, cadmium, copper, nickel, lead, vanadium or aluminium. Oxidants
in cigarette are capable of oxidizing cellular proteins (Bernhard et al. (2005),
above). Through contact and reaction with the thiol groups in the filter material
the oxidants are neutralized, reduced or lose their harmful activity. Thiol groups
easily complex metal ions, especially high order metals according to the periodic
table of the elements. To ensure an undiminished activity of the thiol groups themselves
they are preferably substantially free of such metals, however small metal impurities
are well tolerable in a new filter without severe effects. For example the Cd content
in cigarette smoke is between 0.5 and 1.5 µg per cigarette. To retain filtering
capabilities the contamination in a filter material is therefore substantially less
than 10% of this amount. The optimum lies between not detectable and 0.005µg
per cigarette. Of course a high purity is preferred with no complexing agents or
no detectable complexing agents present in the filter material prior to a use as
filter. The filter material substantially consists of an organic material, preferably
an organic fibrous material. In this context inorganic impurities may still be present
from the manufacturing process, in the range of impurities found in conventional
(organic) filters. However, most preferably the filter is free of inorganic impurities.
Preferably the filter material is for filtering gases or mainly gaseous substances,
or is a smoke filter, or also for filtering solid dust from gases.
In a preferred adaptation the filter material according
to the present invention is a filter for smoking of tobacco or herbal products.
However, filter material according to the present invention can also be used in
large scale filters for e.g. air-conditioning or venting systems. Especially for
the use in a car these filters provide a substantial improvement of cabin air quality
since harmful substances and metals in dust found in car exhaust can be removed
or detoxified. The filters can easily be adapted for a binding or detoxifying capacity
to last for many weeks or months.
In a preferred embodiment the thiol groups of the filter
material are redox-active. This activity ensures reduction of harmful oxidants and
the detoxification of cigarette smoke.
In a preferred embodiment of the present invention, the
filter material is based on sepharose, cellulose or modified cellulose, preferably
acetyl cellulose or nitro cellulose, filter. These organic materials are excellent
carriers for the thiol or sulfhydryl groups. The organic materials can be treated
by common chemical techniques to covalently incorporate a functional thiol group
Feist et al., Biochemistry (1981) 20(15), 4243-4246
Preferably, the thiol group is attached to the organic
filter material via a linker-molecule. During synthesis such linker molecules can
be incorporated separately or together with the thiol group e.g. by using reagents
which comprise both features, e.g. sulfhydryl alkyl components. In use the linker
moiety ensures a better flexibility and reactivity of the thiol group, thus optimizing
the redox activity of the filter.
Preferably, the thiol group of the filter material according
to the present invention is for the removal of harmful substances from the smoke.
The thiol group also leads to an altered adsorbtion or absorption property of the
filter material leading to a better removal of harmful components such as metals
In another preferred embodiment, the thiol group of the
filter material is provided by one residue or a combination of residues selected
from cystein, N-acetyl cystein, sulfhydryl C1-8-alkyl, -alkenyl, -alkinyl,
-alkoxyl, and sulfhydryl phenyl. These residues can be attached to the raw organic
filter material by common means known in the field of organic chemistry. Furthermore
these groups are thermostable in an organic filter material under smoking conditions.
Another aspect of the present invention is a smoke filter
comprising a filter material as described above. For example the filter may comprise
only the above mentioned filter material in varying densities, which can be adjusted
by the skilled man for each specific use. A filter may also comprise different filter
materials, e.g. a portion of a common smoke filter and a portion of the filter material
according to the invention.
A preferred filter according to the invention comprises
a moisture supplying component. The moisture supplying component improves the filtering
properties of the thiol group. Moisture increases the reactivity of the thiol group
thus increasing the filtering quality. Especially wet filters or filter materials
Preferably the moisture supplying component is a breakable
capsule containing an aqueous fluid. Such capsules, which can be broken by slight
pressure, e.g. directly applicable by the user, can be attached to or in the filter.
Upon breakage the filter material is wetted by the fluid to improve the filtering
The present invention also provides a cigarette comprising
a filter as described above.
Alternatively the filter can also be included as part of
a cigarette holder, e.g. for re-use.
Another aspect of the present invention is a method for
the production of a filter material as described above comprising the step of covalently
binding a small molecule comprising a thiol group to the organic material. Also
the thiol group can be transferred to the organic material by common chemical techniques.
Furthermore the present method for the production of a
filter comprises the step of incorporating the filter material into a raw filter.
Of course, if only the filter material is used in a filter the filter material can
also be shaped or pressed into a desired form for use as a filter.
The present invention also provides the method for the
production of a cigarette comprising the step of functionally connecting a filter
according to the present invention to a smokeable product in such a way as to enable
smoke passage through the filter upon consumption of the cigarette.
Also the method for the production of a cigarette holder
comprising the step of incorporating a filter according to the present invention
into a conventional cigarette holder is provided. A conventional cigarette holder
can be any shaped material, preferably hollow, which can hold a cigarette and allows
the flow of cigarette smoke through the holder.
As noted above the detoxifying effects of the filter material
according to the present invention can also be used in other filters than a smoke
filter, e.g. for cigarette smoking. A preferred use of a filter material according
to the present invention is in a venting system, preferably in a car venting system,
e.g. as substantial part of a conventional filter. All options given for the smoke
filter above, like moistening for better efficiency, can also be employed for the
use in the venting system.
The present invention is further illustrated by the following
figures and example without being limited thereto.
Example: Cell viability
Figure 1: Schematic representation of a filter with a middle portion of a
material with thiol groups and two end portions of a conventional filters. The large
arrows indicate the air flow.
Figure 2: Graphical representation of cell viabilty after treatment with
cigarette smoke: Sepharose: control, Thiopropylsepharose: SH-filtered smoke.
A conventional cigarette filter was divided into two halves.
Between those halves sepharose beads (control) or thiopropylsepharose beads (active
thiol groups) were located as indicated in fig. 1. Cigarette smoke was pulled through
the filter with a pressure and velocity corresponding to normal cigarette smoking
by a human (35 ml/2 s followed by a pause of 28 s). The filtered smoke was collected
as extracts by bubbling through cell growth medium at 37°C which in turn was
used to treat human endothelial cells (HUVEC). The cells were incubated with the
extracts for 24h. Afterwards, cell viability was measured by the XTT assay (Proliferation
Kit II, XTT; Roche Diagnostics GmbH, Vienna, Austria) according to the manufacturers
instructions. This assay detects the cleavage of the tetrazolium salt XTT to a formazan
dye, which occurs only in metabolic active cells. The result is given as graphical
representation in fig. 2, which shows a low viabilty in cells treated with filters
without thiol groups (sepharose control) and high viability in the cells, which
were treated with the smoke which went through the organic thiol group filter.