Note: Descriptions are shown in the official language in which they were submitted.
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A BLOOD DETECTION COMPOSITION
FIELD OF THE INVENTION
The present invention relates to chemical compositions capable of blood
detection which provide a visual signal in form of a color change. The
compositions comprise an oxidisable color indicator and a peroxide or a per-
acid
and a stabilizer which is selected from cyclo-dextrin, nitrone or combinations
thereof. These compositions are useful as ingredients of sanitary articles for
the
prediction of the approach of menstruation by providing a visual signal due to
the
detection of blood prior to the blood being contained in these articles in
visually
discernible quantities.
BACKGROUND OF THE INVENTION
Today, disposable articles, such as diapers, adult incontinence briefs,
sanitary napkins, panty liners, interlabial devises and tampons, are widely
used in
feminine protection, infant and toddler care and in the care of incontinent
adults
as a means of containing, isolating and disposing of bodily wastes. These
articles
have generally replaced reusable, washable cloth garments as the preferred
means for these applications because of their convenience and reliability. The
disposable articles respond to a discharge event by absorbing or containing
bodily wastes deposited on the article. Some disposable articles comprise a
chemically reactive means to detect and signal various substances in the
wearer's waste(s). However, none of these specifically detect or predict when
a
menstruation-related discharge event is about to occur and signal to the
wearer
or caregiver that occurrence.
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The so far un-met consumer need of women which is targeted by the
present invention is the desire to gain more information about the expected
timing of their menstruation. More generally it is well established that women
would like to know more about and monitor their bodily condition as relates to
the
status of their menstruation cycle as well as a pre-warning to any kind of
related
disorder advancing. On the other hand the compositions used in this context
need to satisfy the highest standards of safety for the user as well as for
the
environment.
A lot of disclosure exists on general diagnostic aspects relating to female
menstruation cycle and genital/urinary tract related information. However,
none
of the references cited in the following does provide specific teaching to the
present invention.
US 5,217,444 to Schonfeld et. al., published June 8, 1993 discloses
absorbent pads such as tampons comprising a pH indicator material to indicate
the acidity or alkalinity of a liquid by a color change. The pH indictor is
intended
to be wetted by vaginal secretions which are absorbed by the pad. Depending on
the pH this will provide an indication of the health condition of the women's
vaginal tract.
US 5,468,236 to Everhart et. al., published November 21, 1995 discloses a
disposable absorbent product incorporating a chemically reactive substance
which can provide visual indication of a chemical component in absorbed liquid
such as vaginal discharges. The patent is un-specific as to its particular
purpose
but exemplifies a disposable diaper in which a glucose indicating gel can be
applied to the topsheet or the absorbent core. In a second example the
chemical
compound to be detected is a nitrate as indicator of urinary tract infections
by
GRAM negative bacteria. In particular Everhart provides for a reaction which
is
endpoint stable due to a catalytic sequence such that further liquid
absorption will
not alter the indication.
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US 4,231,370 to Morz et. al., published November4, 1980 discloses
disposable diapers with a pH sensitive wetness indicator in a solid adhesive
matrix.
US 5,823,953 to Richards et. al., published October 20, 1998 relates to a
self diagnostic system for yeast or non-yeast related vaginal infections in
the
form of a catamenial pad or panty liner with detachable, color indicating pH
strip
mounted on the topsheet. The pH indicator identifies if the pH of the absorbed
liquid is above or below a thresh hold value of 4.5 and is indented to allow
health
care decisions without a physician in respect to treating a yeast or a non-
yeast
vaginal infection.
WO 97/43955 to Buck et. al., published November 27, 1997 discloses a kit
for home use for collecting vaginal fluid and exfoliated vaginal cells in
menstrual
fluid for diagnostic purposes. The fluid or cells are collected in an
absorbent
interlabial pad or in a pad which is placed inside an apertured housing which
is
placed inter vaginally for collecting fluid. The fluid can afterwards be used
for
diagnostic purposes as desirable.
EP 704 195, to Echeveria, published April 3, 1996 discloses a menstrual
detector which comprises a sanitary napkin or panty liner including a chemical
compound which provides a cooling reaction upon liquid absorption as indicator
of the start of menstruation in order to allow the wearer sufficient time to
replace
the indicating absorbent article by a full size and full capacity sanitary
napkin or
tampon.
Of course, many indicators as such are known and are usually independent
of the source of the liquid of which analysis is desired. For example, EP 386
562
to Ismael et. al., published September 12, 1990 discloses a dry enzyme test
composition with a color indicator result. Similarly, WO 90/06511 to Buck et.
al.,
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published June 14, 1990 discloses a stabilized indicator to determine the
presence of an analyte in a liquid sample. Similarly, WO 89/11643 to Bouse et
al,
published November 30, 1989 discloses an indictor composition designed to
increase the range of analyte concentration which can be analyzed.
EP 124 215 and EP 124 214 both to Oksman et al, published November 7,
1984 relate to wipe indicators for occult blood particular useful to analyze
the
presence of blood in feces. Similarly, EP 93595, to Wells, published November
9,
1983 relates to a dry diagnostic aid for use in an one-step determination of
hemoglobin, especially in occult blood in feces.
EP 113 896 to Rothe, published July 25, 1984 relates to a chemical testing
strip in which a test reagent is provided on a plastic film strip for
quantitative
evaluation. This patent exemplifies blood and glucose testing.
EP 101 980 and EP 101 979, both to Roy, published March 7, 1984 relate
to the determination of dehydrogenase for the purpose of rapid clinical
analysis
and diagnosis. In the later case it is said that the carrier can be a tampon
containing cellulose fibers.
In addition many publications in the medical field relating to pathological
conditions of the female genital and urinary organs including methods of
detecting and healing them have been published.
SUMMARY OF THE INVENTION
The present invention relates to a stabilized detection composition for
providing a
visual signal of the detection of blood in liquids which blood is not
discernible by
normal visual inspection by the human eye. According to the invention the
blood
is generally contained in bodily fluids of mammalian origin or can be in the
form
of an aqueous solution. The blood detection composition comprises an
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oxidisable color indicator and an oxidant such as peroxide or a per-acid which
is
stabilized by a component selected from cyclo-dextrin or nitrone or
combinations
thereof.
In a preferred embodiment of the present invention the oxidisable color
indicator
is selected from the group consisting of Gum Guaiac, tetra-methyl benzidine or
combinations thereof. Also preferred are compositions in which the oxidizing
reactant is selected from hydro-peroxides, epta-phtalimido-peroxy-hexanoic
acid
or combinations thereof.
The composition can be contained in any kind of article but is preferably
comprised in absorbent sanitary articles for women which provide a visual
blood
detection of a quantity of blood in vaginal discharges deposited on the
article
which is not discernible. The article can be of a layered construction, each
layer
having a wearer and a garment facing surface. In general the article comprises
a
liquid permeable topsheet on the wearer facing surface, a liquid barrier
backsheet on the garment facing surface, an absorbent core sandwiched
between the topsheet and the backsheet. According to the present invention the
article is preferably a sanitary napkin or panty liner, especially a thin
panty liner
with less than 3 mm thickness and most preferred a panty liner which is
suitable
to be worn in a string undergarment and has a generally triangular shape.
According to a preferred embodiment of the present invention stabilizing
component is provided by cyclo-dextrin or nitrone or combinations thereof. The
composition can preferably be provided in liquid form, such as in an organic
solvent. When applying the composition to an article it is preferred to
provide it in
a liquid form, more preferably as a solution in an organic carrier which
evaporates after the composition has been applied. Application can be done by
coating or preferably by spraying. Alternatively the composition can be
provided
in particulate form. In order to ensure that the composition or its components
are
dissolved the presence of a tensioactive component such as a surfactant or
polyethylene glycol is also preferred. If the tensioactive material is an
organic
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material it can also be used as the carrier for the composition. In such a
case the
evaporation of the organic carrier then becomes obsolete.
It is within the scope of the present invention to supplement the blood
detector by additional menstruation related detectors such as additional bio-
chemical or electro-chemical or chemical detection means suitable to create a
separate, strengthened or modified visual signal. Preferably such an
additional
detection means comprises a pH indicator or a progesterone hormone or
estrogen hormone indicator or combinations thereof.
DETAILED DESCRIPTION OF THE INVENTION
DEFINITIONS
As used herein, the term "absorbent article" refers to devices which absorb
and contain body exudates, and more specifically, refers to devices which are
placed against or in proximity to the body of the wearer to absorb and contain
the
various exudates discharged from the body. The term "disposable" is used
herein
to describe absorbent articles which generally are not intended to be
laundered
or otherwise restored or reused as an absorbent article (i.e., they are
intended to
be discarded after a single use). As used herein, the term "joined"
encompasses
configurations whereby an element is directly secured to another element by
affixing the element directly to the other element, and configurations whereby
an
element is indirectly secured to another element by affixing the element to
intermediate members) which in turn are affixed to the other element. A
"unitary"
absorbent article refers to absorbent articles which are formed of separate
parts
united together to form a coordinated entity so that they do not require
separate
manipulative parts like a separate holder and liner. A preferred embodiment of
an absorbent article is a unitary disposable sanitary napkin or panty liner,
however also disposable incontinence briefs, incontinence undergarments,
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absorbent inserts, tampons and interlabial absorbent articles can benefit from
the
present invention if used during the period prior to menstruation.
An absorbent article, according to the present invention is conventionally
constructed of three main elements: The topsheet, facing the user of the
article
during use and being liquid pervious in order to allow liquids to pass into
the
article; the backsheet, providing a liquid containment such that absorbed
liquid
does not leak through the article, this backsheet conventionally provides the
garment facing surface of the article; and the absorbent core sandwiched
between the topsheet and the backsheet and providing the absorbent capacity of
the article to acquire and retain liquid which has entered the article through
the
topsheet.
Many absorbent articles and constructions are known in the art and have
been described in ample detail over time. All of such materials are useful in
the
context of the present invention, provided they do not interfere with blood
detection composition. In the following only those examples, which are
particularly beneficial for the use in preferred absorbent articles according
to the
present invention are mentioned. Those skilled in the art will readily be able
to
identify alternative materials which can also be used and which maybe
particularly desirable in the context of menstruation predicting absorbent
articles
according to the present invention.
Topsheet
In general the topsheet is compliant, flexible, soft feeling and non-
irritating
to the wearer's skin. The topsheet preferably also can have elastic
characteristics
allowing it to stretch in one or two directions. As used herein, the term
"flexible"
refers to materials that are compliant and will readily conform to the general
shape and contours of the human body.
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The topsheet can be made from a nonwoven or woven material or a film
which has been rendered liquid pervious by aperturing. The topsheet can also
be
provided as a composite material or be comprised of more than a single layer,
e.g. it can have a secondary topsheet or flow control layer. Such films and
nonwovens or wovens can be made for example from polymers such as
polyethylene or polypropylene compositions. The topsheet can be provided from
a transparent (free of color filler) or translucent material ( having less
than 15%,
i.e. about half of the conventional quantity of color filler).
Backsheet
In general the backsheet is compliant, flexible and soft feeling. The
backsheet prevents the exudes absorbed and contained in the absorbent core
from wetting clothes that contact the absorbent article such as undergarments.
Preferably the backsheet is impervious to liquids (e.g., menses, sweat and/or
urine). It can be manufactured from a thin plastic film, although other
flexible
liquid impervious materials can also be used. As used herein, the term
"flexible"
refers to materials that are compliant and will readily conform to the general
shape and contours of the human body. The backsheet preferably also can have
elastic characteristics allowing it to stretch in one or two directions.
The backsheet can comprise a woven or nonwoven material, polymeric
films such as thermoplastic films of polyethylene or polypropylene, or
composite
materials such as a film-coated nonwoven material or fiber coated film.
Conventionally absorbent articles comprise a backsheet of a polyethylene film
having a thickness of from about 0.012 mm to about 0.051 mm, which can be
impervious or rendered micro-porous by use of an inert filler and subsequent
mechanical stretching.
The backsheet is preferably breathable, i.e. allows the transmission of water
vapor, or even more preferable the transmission of air, however without
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sacrificing its main purpose to provide leakage protection for absorbed
liquids.
The backsheet can also comprise more than one breathable layer so as to
replace a single breathable backsheet layer by at least 2 or 3 layers of a
different
or the same material. In particular two breathable layers, in which e.g. the
one
providing the wearer facing surface is a formed, apertured film with a three
dimensional structure and e.g. the other, garment facing layer is a non-woven
composite of melt-blown and spun-bonded fibers, are preferred breathable
backsheet constructions. As with the topsheet the backsheet can be provided
from a transparent or translucent material which would allow easier inspection
of
detectors inside the article.
Absorbent core
Conventionally the absorbent core can be a single entity or comprise
several layers. It can include the following components: (a) optionally a
primary
fluid distribution layer; (b) optionally a secondary fluid distribution layer;
(c) a fluid
storage layer; (d) optionally a fibrous layer underlying the storage layer;
and (e)
other optional components.
a. Primary Fluid Distribution Layer
One optional component of the absorbent core according to the present
invention is the primary fluid distribution layer. This primary distribution
layer
typically underlies the topsheet (if present) and is in fluid communication
therewith. The primary distribution layer acquires body fluid for ultimate
distribution to the storage layer. This transfer of fluid through the primary
distribution layer occurs mainly in the thickness, but may also provide
distribution
along the longitudinal and transverse directions of the thong liner.
b. Optional Secondary Fluid Distribution La r~er
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Also optional according to the present invention is a secondary fluid
distribution layer. This secondary distribution layer typically underlies the
primary
distribution layer and is in fluid communication therewith. The purpose of
this
secondary distribution layer is to readily acquire bodily fluid from the
primary
distribution layer and distribute it along the longitudinal and transverse
directions
of the thong liner before transfer to the underlying storage layer. This helps
the
fluid capacity of the underlying storage layer to be fully utilized.
c. Fluid Storaqe Layer
Positioned in fluid communication with, and typically underlying the primary
or secondary distribution layers, is a fluid storage layer. It comprises
preferably
but not necessarily super-absorbent gelling materials usually referred to as
"hydrogels," "superabsorbent" "hydrocolloid" materials. Absorbent gelling
materials are those materials that, upon contact with aqueous fluids,
especially
body fluids, imbibes such fluids and thus form hydrogels. These absorbent
gelling materials are typically capable of absorbing large quantities of
aqueous
body fluids, and are further capable of retaining such absorbed fluids under
moderate pressures. In the prior art these absorbent gelling materials are
typically in a granular form of discrete, non-fibrous particles. However,
according
to the present invention these super-absorbent gelling materials can also be
provided in non-granular form, preferably in a fibrous form. If no absorbent
gelling
materials are provided then the storage layer can be provided by the material
conventionally used as carrier material disclosed below.
In the fluid storage layer these absorbent gelling materials can be dispersed
homogeneously or non-homogeneously in a suitable fibrous matrix also referred
to as carrier. Suitable carriers include cellulose fibers, in the form of
fluff or
tissues, such as is conventionally utilized in absorbent cores. Modified
cellulose
fibers such as the stiffened cellulose fibers or viscose fibers can also be
used.
Synthetic fibers can also be used and include those made of cellulose acetate,
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polyvinyl fluoride, polyvinylidene chloride, acrylics (such as Orlon),
polyvinyl
acetate, non-soluble polyvinyl alcohol, polyethylene, polypropylene,
polyamides
(such as nylon), polyesters, bi-component fibers, tri-component fibers,
mixtures
thereof and the like. Preferred synthetic and man-made fibers have a denier of
from about 3 denier per filament to about 25 denier per filament, more
preferably
from about 5 denier per filament to about 16 denier per filament. The carrier
fibers can be provided as carded, spun-bonded, melt-blown, wet-laid, air-laid
substrates or combination of such lay down methods or combinations of such
substrates.
Also preferably, the fiber surfaces are hydrophilic or are treated to be
hydrophilic. A storage layer can also include filler materials, such as
Perlite,
diatomaceous earth, Vermiculite, etc., that lower rewet problems. Further the
storage layer may comprise a binder including but not limited to Latex binders
which can be sprayed as an aqueous solution onto the surface of the storage
layer prior to curing.
If the absorbent gelling materials are dispersed non-homogeneously in a
fibrous matrix, the storage layer can be locally homogeneous, i.e. have a
distribution gradient in one or several directions within the dimensions of
the
storage layer. Non-homogeneous distribution thus includes e.g. laminates of
the
fibrous carriers enclosing the absorbent gelling materials or regions in which
the
absorbent gelling material has a different concentration relative to other
regions.
If absorbent gelling material is present the storage layer preferably
comprises from 5% to 95% absorbent gelling materials, preferably from 5% to
50%, most preferably from 8% to 35%, absorbent gelling materials. Further the
storage layer can comprise from 5% to 95% carrier fibers, preferably from 95%
to
50%, most preferably from 92% to 65% carrier fibers.
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Suitable absorbent gelling materials for use herein will most often comprise
a substantially water-insoluble, slightly crosslinked, partially neutralized,
polymeric gelling material. This material forms a hydrogel upon contact with
water. Such polymer materials can be prepared from polymerizable, unsaturated,
acid-containing monomers. Suitable unsaturated acidic monomers for use in
preparing the polymeric absorbent gelling material used in this invention
include
those listed in U.S. Patent 4,654,039 (Brandt et al), issued March 31, 1987,
and
reissued as RE 32,649 on April 19, 1988. Preferred monomers include acrylic
acid, methacrylic acid, and 2-acrylamido-2-methyl propane sulfonic acid.
Acrylic
acid itself is especially preferred for preparation of the super-absorbent
material,
it also has a 'natural' transparency which is not optimal but acceptable if
the
desired transparency is not too high.
Whatever the nature of the basic polymer components of the hydrogel-
forming polymeric absorbent gelling materials, such materials will in general
be
slightly crosslinked. Crosslinking serves to render the hydrogel-forming
polymer
gelling materials substantially water-insoluble, and cross-linking thus in
part
determines the gel volume and extractable polymer characteristics of the
hydrogels formed from these polymeric gelling materials. Suitable crosslinking
agents are well known in the art and include, for example, those described in
greater detail in U.S. Patent 4,076,663 (Masuda et al), issued February 28,
1978.
Preferred crosslinking agents are the di- or polyesters of unsaturated mono-
or
polycarboxylic acids with polyols, the bisacrylamides and the di- or triallyl
amines.
Other preferred crosslinking agents are N,N'-methylenebisacrylamide,
trimethylol
propane triacrylate and triallyl amine. The crosslinking agent can generally
constitute from about 0.001 mole percent to 5 mole percent of the resulting
hydrogel-forming polymer material. More preferably, the crosslinking agent
will
constitute from about 0.01 mole percent to 3 mole percent of the hydrogel-
forming polymeric gelling material.
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The slightly crosslinked, hydrogel-forming polymeric gelling materials are
generally employed in their partially neutralized form. For purposes of the
present
invention, such materials are considered partially neutralized when at least
25
mole per-cent, and preferably at least 50 mole percent of monomers used to
form the polymer are acid group-containing monomers that have been
neutralized with a salt-forming cation. Suitable salt-forming cations include
alkali
metal, ammonium, substituted ammonium and amines. This percentage of the
total monomers utilized which are neutralized acid group-containing monomers
is
referred to herein as the "degree of neutralization."
While these absorbent gelling materials have typically been disclosed in the
prior art in granular form, it is possible in the context of the present
invention that
the absorbent gelling material is in a non-granular form for example as
microstructures such as fibers, sheets or strips. These microstructures can be
prepared by forming the particulate absorbent gelling material into an
aggregate,
treating the aggregated material with a suitable crosslinking agent,
compacting
the treated aggregate to densify it and form a coherent mass, and then curing
the
compacted aggregate to cause the crosslinking agent to react with the
particulate
absorbent gelling material to form a composite, porous absorbent
macrostructure. Such porous, absorbent microstructures are disclosed, for
example, in U.S. Patent 5,102,597 (Roe et al), issued April 7, 1992.
d. Optional Fibrous Lager
An optional component for inclusion in the absorbent cores according to the
present invention is a fibrous layer adjacent to, and typically underlying the
storage layer. This underlying fibrous layer would typically provide the same
function as the secondary fluid distribution layer.
e. Other Optional Components
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The absorbent cores according to the present invention can include other
optional components normally present in absorbent webs. For example, a
reinforcing scrim can be positioned within the respective layers, or between
the
respective layers, of the absorbent cores. Such reinforcing scrims should be
of
such configuration as to not form interfacial barriers to fluid transfer,
especially if
positioned between the respective layers of the absorbent core. Given the
structural integrity that usually occurs as a result of thermal bonding,
reinforcing
scrims are usually not required for the absorbent structures according to the
present invention.
Another component which can be included in the absorbent core according
to the invention and preferably is provided close to or as part of the primary
or
secondary fluid distribution layer are odor control agents. Typically active
carbon
coated with or in addition to other odor control agents, in particular
suitable
zeolite, silica or clay materials, are optionally incorporated in the
absorbent core.
Physical characteristics of absorbent cores
Absorbent cores are usually non extensible and non-elastic, however, they
can be rendered extensible and depending on the selected materials can also be
made to have elastic characteristics. The term "extensible" as used
hereinafter
refers to a structure which under external forces such as those occurring
during
use extends in the direction of the forces or in the direction of a component
of the
forces in cases where only mono directional extensibility is provided.
The term "elastic" as used herein refers to extensible structures which
return at least partially to their initial state after the forces causing the
extension
seize to be excerpted. Absorbent cores can be corrugated or pleated in one or
several directions to provide a certain extensibility while selection of
elastic fibers
for the structure can provide elasticity.
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The absorbent cores should preferably be thin. A thickness of less than 5
mm, preferably less than 3 mm and even more preferable between 0.8 and 1.8
mm is desirable such that the resulting articles can also have a low
thickness.
Non-limiting examples of panty liners and sanitary napkins which may be
provided with the blood detection composition include those manufactured by
The Procter & Gamble Company of Cincinnati, Ohio as: ALWAYS~ ALLDAYS~
Pantiliners with DriWeave~ manufactured according to U.S. Patents 4,324,246;
4,463,045; and 6,004,893; ALWAYS~ Ultrathin Slender Maxi with Wings
manufactured according to U.S. Patents 4,342,314, 4,463,045, 4,556,146, B1
4,589,876, 4,687,478, 4,950,264, 5,009,653, 5,267,992, and Re. 32,649;
ALWAYS~ Regular Maxi; ALWAYS~ Ultra Maxi with Wings; ALWAYS~ Maxi
with Wings; ALWAYS~ Ultra Long Maxi with Wings; ALWAYS~ Long Super
Maxi with Wings; and ALWAYS~ Overnight Maxi with Wings.
Non-limiting examples of interlabial devices which may be provided with a
blood detection composition are described in U.S. Patents 5,762,644;
5,885,265;
5,891,126; 5,895,381; 5,916,205; 5,951,537; 5,964,689; 5,968,026; Des.
404,814; and Des. 413,669.
Non-limiting examples of tampons which may be provided with blood
detection composition and applicators therefor, are described in U.S. Patents
4,726,805; 4,846,802; 4,960,417; 5,087,239; 5,279,541; 5,346,468; 5,348,534;
5,531,674; and 5,566,435. In addition, the blood detection composition could
also be placed on a digitally insertable tampon.
Blood Detection Composition
The blood detection composition according to the present invention
provides at least one sensor for the detection of blood. As used herein, the
term
"sensor" is defined as a component comprising one or more reactive means
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being adapted to detect one or more target substances (also referred to as
analytes) such as microorganisms or related (bio-)molecules (e.g., an enzyme
sensor, organelle sensor, tissue sensor, microorganism sensor, immunosensor,
and chemical or electrochemical sensor), additionally having the capability to
provide a signal of said detection to the wearer, caretaker, or an actuator.
When
referring to blood herein a typical component of blood, such as hemoglobin or
iron, can of course also be used as analyte. The term "reactive" is defined as
having the capability to selectively interact with such target substances.
There are 2 categories of sensors which have different sensitivity:
biosensors and chemical-/electro-chemicall sensors. Generally biosensors
function by providing a means of specifically binding, and therefore
detecting, a
target biologically active analyte. In this way, the biosensor is highly
selective,
even when presented with a mixture of many chemical and biological entities,
such as vaginal discharge. Electrochemical and chemical sensors, on the other
hand, which rely on chemically reactive means, generally do not have either
the
high selectivity or the amplification properties of biosensors but are highly
reliable, inexpensive, i.e. useful for commodity products, and often very well
established, i.e. proven to be save for use on human skin. Often the target
analyte is a minor component of a complex mixture comprising a multiplicity of
biological and other components. Thus, in many biosensor applications,
detection of target analytes to the parts-per-billion, parts-per-trillion, or
even lower
levels is necessary.
According to the present invention the blood detection composition is a
specifically stabilized chemical composition. The chemical composition
comprises a color indicating component which provides a color change as a
result of an oxidation reaction and is preferably selected from Gum Guaiac or
tetra-methyl-benzidine or combinations thereof. As a second component the
composition comprises as a stabilized oxidizing component a peroxide or a per-
acid.
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The oxidizing component (also referred to as oxidant) is stabilized to be
insensitive to storage conditions usual in the context of the intended
articles (e.g.
in a warm and high humidity environment of a bathroom). Stabilization can be
provided in 2 ways: physio-chemical stabilization by caging the oxidante onto
a
carrier. According to the present invention this carrier is provided by cyclo-
dextrin.
The cyclo-dextrin carries the peroxide in an aqueous phase (e.g. in the
presence
of high humidity) while maintaining the oxidative reactivity. An alternative
to the
physio-chemical stabilization is the chemical stabilization by preventing or
reducing degradation due to radicals. According to the present invention this
is
achieved by the use of nitrone. Of course the use of both components together
is
also possible and does create an additional stabilizing effect.
If the oxidant is selected to be a per-acid it preferably is a epta-phtalimido-
peroxy-hexanoic acid. The epta-phtalimido-peroxy-hexanoic acid also benefits
from stabilization by caging but preferably can be stabilized by nitrone to
block or
reduce the degradation due to radicals. In this context nitrone functions as a
radical scavenger and other radical scavengers can also be used. Of course in
mixtures of hydro-peroxide and epta-phtalimido-peroxy-hexanoic acid also both
stabilizer components need to be present.
The color indicator and the oxidizing material both are reactive primarily in
aqueous solution. Hence they will start to react once they have dissolved in
the
vaginal discharges and are activated by the presence of blood. In order to
accelerate and promote the dissolution it is preferred to include a
tensioactive e.g
a surfactant, or polyethylene-glycol or mixtures thereof, preferably
polyethylene-
glycol, in the blood detection composition. In a sanitary article the
tensioactive
material should preferably be located such that it is wetted first before the
liquid
reaches the 2 components.
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A highly preferred composition comprises a combination of epta-
phthalimido-peroxy-hexanoic acid and Gum Guaiac. The Gum Guaiac is a resin
found from wood of Guaiacum officinale or Guaiacum santum (mainly found in
Mexico or West India). Gum Guaiac is historically used as flavoring agent for
food (and hence has a long record of save usage by humans) and is known for
its ability to indicate the presence of blood or hemoglobin, especially in
feces.
According to the present invention the Gum Guaiac wood resin is preferred,
however one or all of the active components, whether naturally or artificially
derived, can be used in stead of the wood resin. The best known active
components are guaiacol (OHC6H40CH3, CAS 90-05-1 ), guaiaconic acid and
(furo)-guaiacine.
If applied to an article the components can be applied by coating or
spraying provided they are applied in solution. The solvent in this case
should
preferably be an organic solvent. However such solvent should evaporate at
temperatures below 100 °C, unless the organic solvent can be selected
to
provide additional benefits to the article, such as a tensioactive as
dissolution
aide. If used in an absorbent article application of both components on the
same
layer can be done in an alternate pattern such as stripes, dots or different
shapes. The detector components can be provided in discrete parts of a surface
of a layer or as full surface coverage of the layer (both components or one
alone). The components can be provided either one or both as powder, liquid or
as components in an adhesive admixture for better coating.
Additional Detectors
In one particularly preferred embodiment of the present invention the
composition (or if the composition is applied to an article the article)
comprises in
addition to the blood detector another separately activated and independently
functioning sensor to detect a physiological component in bodily discharges.
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Without limitation this will be exemplified in the following by detection of
the
approach of menstruation.
It is clear that the detection of blood in particular to allow prediction of
menstruation cannot be considered to be one hundred percent accurate. First of
all, the indicator itself needs to be provided with a high degree of accuracy
for
only detecting blood, i.e. it should be insensitive to other materials to
which it is
exposed. On the other hand, the sensitivity should be high to allow detection
of
low quantities of blood, i.e. prior to its visual recognition. These two
competing
interests need to be balanced.
Further the presence of (occult) blood is well known as an indication of the
approach of menstruation. However also injuries or pathological situations may
cause the presence of low levels of blood in vaginal discharges. It is
therefore
desirable to provide the sanitary article with an additional indicator
providing a
second signal of the approach of menstruation. Such a signal can be provided,
for example, by the change of pH of the vaginal discharge within the days
prior to
menstruation. In addition or alternatively, hormones such as progesterone
and/or
estrogen can be used as additional indicators for the prediction of
menstruation.
Most preferred in this context are pH sensors which can also be provided as
a color change indicators. pH sensors are well known and are commercially
available e.g. from The Merck Company, Darmstadt, Germany. A highly
preferred pH sensor, having a well established safety profile in this context
is
carminic acid, which is used as a food dye, but undergoes a color change in
the
range between pH 4 and pH 7. Carminic acid is a tricyclic compound which has
the compound formula C22-H20-013.
Regardless of which additional sensors are used, if they are provided as
color change indicators together with the color indicator providing blood
detection
they will create a mixed output signal in the form of a multicolor indication.
That
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can be a mixed color indication or it can be provided separate and
individually
detectable but functioning togethrer as explained below.. For example, if Gum
Guaiac, which provides a color change to blue is mixed with a pH sensor
providing e.g. a color change to red, the mixed color sensor (blue and red)
would
need to turn purple in order to provide an indication with high accuracy and
time
proximity of the approach of menstruation. A different color change (such as
only
blue or only red) would indicate that either the menstruation is still some
time
away or that there is the potential of a health issue (a pH change alone can
be
indicative - but does not have to - of infections, while blood indication
alone can -
but does not have to - indicate a wound). For such changes the packaging of
the
composition (or the article if allied on an article) could include an
instruction to
the user to consider visiting a physician to medically evaluate whether any
serious health issue (pathological situation) exists. Of course the absence of
a
color change would indicate that there is still time until the next
menstruation.
In addition to the electrochemical sensors, to supplement the blood
detector, the cyclic nature of the hormones of the menstrual cycle (i.e., the
full 28
day cycle) make them particularly useful in understanding, the position of an
individual during her cycle. This has historically been used in the assessment
of
fertility, but the use according to the present invention goes beyond current
uses
of hormones to predict ovulation and pregnancy. For example, progesterone
peaks and then drops just prior to menstruation. Estrogen also declines just
prior
to menstruation. Thus, in combination with other predictors, such as blood
detection or pH indication, assay for either of these two hormones will allow
reliable prediction of the onset and the presence of menstruation. The timing
of
the peak of these hormones, along with their subsequent drop, allows a highly
accurate marking of the time before menstruation.
The only potential drawback of such hormone indication is the associated
cost and complexity. The lack of simple visualization makes their use in mass
produced bulk articles not very attractive. Hence the use of hormone detection
in
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21
order to predict menstruation is preferably provided in conjunction with blood
detection and/or pH detection to improve the accuracy of such predictions in
the
form of a completely separate detection system.
Use of hormones may also be developed for other points of interest in the
cycle. Follicle Stimulating Hormone (FSH) exhibits a peak about one week prior
to ovulation, giving more advance timing for pregnancy planning than assays
for
the luteinizing hormone, which exhibits a sharp peak at the time of ovulation.
Two
to three days of fertility may be missed when relying only on assay of the
luteinizing hormone. Thus, in a diagnostic for ovulation herein, it is highly
preferred to measure for both the Follicle Stimulating Hormone and the
luteinizing hormone along with estrogen.
A rise in Follicle Stimulating Hormone to a near constant amount signals the
approach of menopause. This may be of use in planning healthy approaches to
menopause, such as Hormone Replacement Therapy, nutritional changes, and
checks for osteoporosis.
The composition according to the present invention can be provided with
several additional sensor and detector systems which allow e.g. indications or
predictions of health related issues of the individual. Such additional sensor
systems are primarily useful for sanitary articles which are used in a care
taker
situation or if the composition is in the form of a spray or liquid. In
general such
additional systems or biosensors comprise a recognition element, or molecular
recognition element, that provides detection for a particular analyte. The
recognition element may be a biologically derived material such as an enzyme
or
sequence of enzymes; an antibody; a membrane receptor protein; DNA; an
organelle, a natural or synthetic cell membrane; an intact or partial viable
or
nonviable bacterial, plant or animal cell; or a piece of plant or mammalian
tissues, and generally functions to interact specifically with a target
analyte. The
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recognition element is responsible for the selective recognition of the
analyte and
creates a physical-chemical signal that provides the basis for the output
signal.
Biosensors may include biocatalytic biosensors, and bioaffinity biosensors.
In biocatalytic biosensor embodiments, the bio-recognition element is
"biocatalytic" and may comprise an enzyme, organelle, piece of plant or
mammalian tissue, or whole cells, the selective binding sites "turn over"
(i.e., can
be used again during the detection process), resulting in a significant
amplification of the input signal. Biocatalytic sensors such as these are
generally
useful for real-time, continuous sensing.
Bioaffinity sensors are generally applicable to bacteria, viruses, and toxins
and include chemoreceptor-based biosensors and/or immunological sensors (i.e.
immunosensors). Chemoreceptors are complex biomolecular macroassemblies
responsible, in part, for a viable organism's ability to sense chemicals in
its
environment with high selectivity. Chemoreceptor-based biosensors comprise
one or more natural or synthetic chemoreceptors associated with a means to
provide a signal (visual, electrical, etc.) of the presence or concentration
of a
target biological analyte. Chemoreceptors may include whole or partial nerve
bundles (e.g., from antennae or other sensing organs) and/or whole or partial
natural or synthetic cell membranes. On the other hand, the bio-recognition
elements of immunosensors are generally antibodies. Antibodies are highly
specific and can be made toward bacteria, viruses, fragments of microorganisms
(e.g., bacterial cell walls, parasite eggs or portions thereof, etc.), and
large
biomolecules. Suitable antibodies may be monoclonal or polyclonal. In any
case,
bioaffinity biosensors are generally irreversible because the receptor sites
of the
biosensor become saturated when exposed to the target biological analyte. In
certain embodiments biocatalytic and bioaffinity biosensors may be combined.
Biocatalytic and bioaffinity biosensor systems are described in more detail in
Journal of Chromato rq aphy, 510 (1990) 347-354 and in the Kirk-Othmer
Encyclopedia of Chemical Technology, 4'n ed. (1992), John Wiley & Sons, NY.
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The biosensors of the present invention preferably also detect biologically
active analytes related to impending (i.e., future presentation of symptoms is
likely) or current human systemic disease states, including pathogenic
bacteria,
parasites, viruses, fungi such as Candida albicans, antibodies to pathogens,
and/or microbially produced toxins. Additionally, the biosensor may target
biologically active analytes related to impending or current localized health
issues, such as stress proteins (e.g., cytokines) and IL-1a (interleukin 1-
alpha)
that may precede the clinical presentation of skin irritation or inflammation.
In
preferred embodiments, the biosensor functions as a proactive sensor,
detecting
and signaling the wearer or caretaker of the impending condition prior to the
presentation of clinical symptoms. This allows time to administer prophylactic
or
remedial treatments to the wearer which can significantly reduce, if not
prevent,
the severity and duration of the symptoms. Further, the biosensor by detecting
the presence of a target biological analyte in the wearer's bodily waste, may
detect residual contamination on a surface, such as skin, in contact with the
biosensor, and provide an appropriate signal.
The signal generated by the recognition element or elements is
communicated visually to the wearer or caretaker, e.g. via a color change
visible
to the human eye. The signal may be qualitative (e.g., indicating the presence
of
the target biological analyte) or quantitative (i.e., a measurement of the
amount
or concentration of the target biological analyte). In any case, the signal is
preferably durable i.e., stable and readable over a length of time (typically
at
least of the same magnitude as the usage period of the article). Further, the
sensor may be adapted to detect and/or signal only concentrations of the
target
biological analyte above or below a predefined threshold level (e.g., in cases
wherein the target biological analyte is normally present in the bodily
waste).
As described above, the target analyte that the biosensors of the present
invention are adapted to detect is pathogenic microorganisms such as the
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pathogenic microorganisms implicated in human gastrointestinal diseases,
especially those resulting in diarrhea. It has been found that severe chronic
diarrhea may result in weight loss and permanent physical and mental
retardation. A non-limiting list of pathogenic bacteria that the biosensor 60
may
detect include any of the various pathogenic strains of Escherichia coli
(commonly known as E. Coli); Salmonella strains, including S. typhi, S.
paratyphi,
S. enteriditis, S. typhimurium, and S, heidelberg; Shigella strains such as
Shigella sonnei, Shigella flexneri, Shigella boydii, and Shigella dysenteriae;
Vibrio cholerae; Mycobacterium tuberculosis; Yersinia enterocolitica;
Aeromonas
hydrophila; Plesiomonas shigelloides; Campylobacter strains such as C. jejuni
and C. coli; Bacteroides fragilis; and Clostridia strains, including C.
septicum, C.
perfringens, C. botulinum, and C. difficile. A non-limiting example of a
commercially available biosensor adapted to detect E. coli is available from
AndCare, Inc. of Durham, NC, as test kit #4001. ABTECH, Scientific, Inc., of
Yardley, PA offers "bioanalytical biotransducers", available as BB Au-1050.5-
FD-
X, which may be rendered biospecific (for microorganisms or other target
biological analytes as described herein) by covalently immobilizing
polypeptides,
enzymes, antibodies, or DNA fragments to their surfaces. Other suitable
microbial biosensors are described in US Patents 5,869,272 (gram negative
organisms); 5,795,717 (Shigella); 5,830,341; 5,795,453; 5,354,661; 5,783,399;
5,840,488; 5,827,651; 5,723,330; and 5,496,700.
The target analytes that the biosensors of the present invention are adapted
to detect may also be viruses. These may include diarrhea-inducing viruses
such
as rotavirus, or other viruses such as rhinovirus and human immunodeficiency
virus (HIV). An exemplary biosensor adapted to detect HIV is described in US
Patents 5,830,341 and 5,795,453, referenced above.
In alternative embodiments, the target analytes that the biosensors of the
present invention are adapted to detect may also be parasites, especially
those
which inhabit the gastrointestinal tract during some point in their life-
cycle. Such
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parasites may include protozoans, worms, and other gastrointestinal parasites.
Other examples of parasites which may be detected include entamoeba
histolytica (which cause amoebic dysentery), trypana cruzi (which causes
Chagas disease), and plasmodium falciparum.
In yet other embodiments, the target analytes the biosensors of the present
invention are adapted to detect fungi such as Candida albicans. In addition to
pathogenic bacteria, certain beneficial colonic bacteria may be detected
and/or
measured as a health indicator, such as Bifidobacteria and Lactobacillus
strains.
The target analytes that the biosensors of the present invention are adapted
to detect may also be proteins or antigens related to skin distress.
Preferably,
these analytes are detectable on or at the skin surface, preferably prior to
the
presentation of clinically observable skin irritation. These may include
stress
proteins such as cytokines, histamine, and other immune response factors
including interleukins (such as IL-1a, IL-2, IL-3, IL-4, and IL-8) and
interferons
(including interferons a and g). Again, these are preferably detectable by the
biosensor 60 prior to the onset of clinically observable redness, irritation,
or
dermatitis. Additionally, the biosensors of the present invention may be
adapted
to detect enzymes, or other biological factors, implicated in skin irritation
(e.g.,
diaper dermatitis), including tryspin, chymotrypsin, and lipase.
The biosensors of the present invention may also comprise bio-recognition
systems, including enzymes or binding proteins such as antibodies immobilized
onto the surface of physico-chemical transducers. For example, a specific
strain
of bacteria may be detected via biosensors employing antibodies raised against
that bacterial strain. Alternatively, a target bacteria may be detected by a
bio-
recognition element (including antibodies and synthetic or natural molecular
receptors) specific to extracellular products of the target bacteria, such as
toxins
produced by that strain (e.g., E. col~~. Exemplary enzyme electrodes that may
be
used to detect phenols (e.g. in urine or feces) include tyrosinase based
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electrodes or polyphenoloxidaseenzyme electrodes describedU.S. Patent
in
No. 5,676,820 entitledRemote Electrochemical Sensor," to Joseph
" issued
Wang et al. on October14, and U.S. Patent No. 5,091,299entitled
1997 "An
Enzyme Electrode For Use In Organic Solvents," issued to Anthony P. F. Turner
et al. on February 25, 1992, respectively
In any of the foregoing examples, the specific microorganism may be
directly detected or may be detected by binding a toxin, enzyme, or other
protein
produced by the organism or an antibody, such as a monoclonal antibody,
specific to the organism. Exemplary biosensors adapted to detect proteolytic
enzymes described in US Patent 5,607,567 and toxins in US Patents 5,496,452;
5,521,101; and 5,567,301.
The biosensor of the present invention may comprise one or more
"proactive sensors". This is especially useful in embodiments where the
detection
of the target biologically reactive analyte precedes the onset of clinically
observable health symptoms. As used in this application, the term "proactive
sensor" refers to a sensor that is capable of detecting changes or signals on
the
body of the wearer (i.e., skin) or in the waste, i.e., inputs, that directly
relate or, at
a minimum, correlate to the occurrence of an impending or potential health or
skin related even. Proactive sensors may respond to one or more specific
inputs
as described above.
A proactive sensor may detect an impending event or detect a parameter
that directly relates, or at a minimum correlates to the occurrence of an
impending event, particularly a systemic or skin health event or condition
(i.e., the
presentation of clinically observable indications or symptoms). An impending
event that may be detected or predicted by a proactive sensor of the present
invention may include diarrhea) disease, skin irritation or rash (including
candidiasis), and/or other types of illness or medical conditions of the
wearer
such as a parasitic infestation. The detected biological analyte may be one or
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more steps removed from the actual presentation of clinical symptoms. For
example, the biosensor may detect potential precursors to the above conditions
(e.g., fecal contamination of the skin that may precede the elicitation of
stress
proteins which may, in turn, precede clinically observable skin irritation. A
parameter that correlates to an event is any measurable input, signal such as
one or more of the potential inputs listed above, that correlates with the
occurrence of the event within the frame of reference of the system (i.e., a
signal
caused by the waste or the wearer). Proactive sensors in an article may
measure
one or more different inputs in order to predict an event. For example, the
proactive sensor may monitor for Candida albicans in vaginal discharges and
residual colonic bacteria on the skin (i.e., detecting residual contamination)
both
of which are signals that may precede skin irritation.
In biosensor embodiments wherein the bio-recognition element does not
produce an easily visible signal (e.g., a color change), the biosensor may
include
a transducer in communication with the bio-recognition element in order to
convert the physico chemical signal from the bio-recognition element into a
usable signal to the wearer, caretaker, or component of the article (e.g., and
actuator). Exemplary transducers may include electrochemical transducers
(including potentiometric, amperometric, and conductimetric transducers),
optical
transducers (including fluorescence, bioluminescence, total internal
reflective
resonance, and surface plasmon resonance), thermal transducers, and acoustic
transducers, as known in the art. A power source, such as a miniature 3 volt
watch battery or printed thin film lithium battery, may be connected with the
biosensor to provide any required power.
