JP2002543397A - Blood detection composition - Google Patents

Abstract

  (57) [Summary] The present invention relates to a blood detectable chemical composition that provides a visual signal in the form of a color change. The composition comprises an oxidative color indicator and a peroxide or peracid and a stabilizer selected from cyclo-dextrin, nitrone or a combination thereof. These compositions provide sanitary for the prediction of menstrual access by providing a visual signal for the detection of blood prior to the blood being contained in these products in a visually recognizable amount. Useful as an ingredient in products.

Description

DETAILED DESCRIPTION OF THE INVENTION

FIELD OF THE INVENTION The present invention relates to chemical compositions capable of detecting blood that provide a visual signal in the form of a color change. The composition comprises an oxidizing color indicator and a peroxide or peracid and a stabilizer selected from cyclo-dextrin, nitrone or a combination thereof. These compositions provide a sanitary product for predicting the approach of menstruation by providing a visual signal for the detection of blood prior to the blood being contained in a visually recognizable amount in the sanitary product. It is useful as a component of

BACKGROUND OF THE INVENTION Today, disposable products such as diapers, adult incontinence briefs, sanitary napkins, panty liners, interlabial products and tampons contain, separate and dispose of body waste. As one means, it is widely used in the protection of women, care of children and infants and care of incontinent adults. These products have generally replaced reusable, washable fabric garments as the preferred means for these applications because of their convenience and reliability. Disposable products respond to evacuation events by absorbing or containing bodily exudates deposited on the product. Certain disposable products include chemically reactive means to detect and signal various substances in the wearer's waste. However, none of these
When a menstrual discharge event is about to occur, it does not explicitly detect or predict this and does not signal the wearer or caregiver.

[0003] The previously unmet consumer demand of women targeted by the present invention is the desire to gain more information about the anticipated timing of their menstruation. More commonly, it is well documented that women want to know and examine their physical condition in relation to the status of the menstrual cycle and also in relation to the advance warning of the progression of illness. That is. On the other hand, the compositions used in such situations must meet the highest standards of safety for the user as well as for the environment.

[0004] Many disclosures exist regarding the general diagnostic aspects of women's menstrual cycles and genital / urinary tract related information. However, none of the references cited below provide a clear teaching to the present invention.

[0005] US Pat. No. 5,217,444, issued to Schoenfeld et al. On June 8, 1993, discloses a tampon containing a pH indicator substance that indicates the acidity or alkalinity of a liquid by a color change. A novel absorbent pad is disclosed. The pH indicator is intended to be wetted by vaginal secretions absorbed by the pad. Depending on the pH, this will provide an indication of the health of the female vaginal canal.

US Pat. No. 5,468,236, issued Nov. 21, 1995 to Everhart et al., Provides a visual indication of chemical constituents in liquids such as absorbed vaginal discharge. Disposable absorbent products are disclosed that include chemically reactive substances that can be provided. This patent, although not clear for its specific purpose, illustrates a disposable diaper in which a glucose indicating gel can be applied to a topsheet or absorbent core. In a second example, the compound to be detected is nitrate as an indicator of urinary tract infection by Gram-negative bacteria. In particular, Everhart provides a reaction where the further liquid absorption is endpoint stable for a catalytic sequence such that the index does not change.

US Pat. No. 4,2,2, issued Nov. 4, 1980 to Morz et al.
No. 31,370 discloses a disposable diaper having a pH sensitive wetness indicator in a solid adhesive matrix.

[0008] US Pat. No. 5,823,953, issued to Richards et al. On October 20, 1998, discloses a menstrual pad or panty liner having a removable color indicating pH strip provided on a topsheet. A self-diagnostic system for yeast or non-yeast related vaginal infections in the form of: The pH indicator identifies whether the pH of the absorbed liquid is above or below a threshold of 4.5 and makes a health care decision without a physician regarding treating yeast or non-yeast vaginal infections. It is intended to give.

WO 97/4 published by Buck et al. On November 27, 1997
3955 discloses a kit for home use for collecting exfoliated vaginal cells in vaginal fluid and menstrual fluid for diagnostic purposes. Fluid or cells are collected on an absorbent interlabial pad or pad located inside an open housing located between the vagina to collect the fluid. The fluid can then be used for diagnostic purposes, if desired.

[0010] EP issued to Echeveria on April 3, 1996
704195 provides a cooling response upon liquid absorption as an indicator of the onset of menstruation to provide the wearer with sufficient time to replace the indicated absorbent product with a full-size yet sufficiently absorbent sanitary napkin or tampon. Menstruation detecting agents including sanitary napkins or panty liners containing the provided compounds are disclosed.

Of course, many such indicators are known, and they are usually independent of the source of liquid for which analysis is desired. For example, EP 386562, issued to Ismael et al. On September 12, 1990, discloses a test composition of a dried enzyme with the results of a color indicator. Similarly, June 14, 1990
WO 90/06511, issued to Bagh et al., Discloses a stabilized indicator for measuring the presence of an analyte in a liquid sample. Similarly, in 1989 1
WO89 / 11643, published on January 30 by Boote et al.,
Disclosed are indicator compositions designed to increase the range of analyte concentrations that can be analyzed.

EP1 issued Nov. 7, 1984 to Oksman et al.
24215 and EP124214 relate to wipe indicators useful for analyzing the presence of invisible blood, especially blood in the stool. Similarly, EP 93595 issued to Wells on November 9, 1983 relates to a dry diagnostic aid, especially for use in one-step measurement of hemoglobin in invisible blood in stool.

[0013] EP 113896 issued to Rothe on July 25, 1984
Relates to chemical test strips in which test reagents are provided on a plastic film for evaluation of the amount. This patent illustrates a blood and glucose test.

[0014] EP 101980 and E issued March 7, 1984 to Roy
P101979 relates to the measurement of dehydrogenase for rapid clinical analysis and diagnosis. In the latter case, it is said that the carrier can be a tampon containing cellulose fibers.

In addition, there are many publications in the medical field regarding the pathological conditions of the female genital and urinary tract, including methods of detection and treatment.

SUMMARY OF THE INVENTION The present invention is directed to a stabilized detection composition for providing a visual signal for the detection of blood in a liquid that is not recognizable by ordinary visual inspection by the human eye.
In accordance with the present invention, blood may generally be contained in bodily fluids of mammalian origin or in the form of an aqueous solution. The blood detection composition comprises an oxidizing color indicator and an oxidant such as a peroxide or peracid stabilized by a component selected from cyclo-dextrin or nitrone or a combination thereof.

In a preferred embodiment of the present invention, the oxidative colorimetric indicator is gum gum (G)
um Guaiac), tetra-methylbenzidine or a combination thereof. Also preferably, the oxidizing reactant is hydro-peroxide, epta-phthalimide-peroxy-hexanoic acid (epta-phta).
limido-peroxy-hexanoic acid) or a combination thereof.

The composition may be included in any type of product, but is preferably absorbed for women that provides visual blood detection of unrecognizable blood volume in vaginal discharge deposited on the product. Included in sexual hygiene products. The product can be a layered structure, each layer having a wearer facing surface and a garment facing surface. Generally, the product includes a liquid permeable topsheet on the wearer facing surface, a liquid barrier backsheet on the garment facing surface, and an absorbent core interposed between the topsheet and the backsheet. According to the invention, the product is preferably a sanitary napkin or panty liner, in particular a thin panty liner having a thickness of less than 3 mm and most preferably a string of underwear (stri).
A panty liner that is suitable to be worn with ng undergarment and generally has a triangular shape.

According to a preferred embodiment of the present invention, the stabilizing component is provided by cyclo-dextrin or nitrone or a combination thereof. The composition may preferably be provided in liquid form, such as in an organic solvent. When the composition is applied to the product, it is preferably provided in liquid form, more preferably as a solution in an organic carrier, which evaporates after the composition has been applied. The application can be made by coating, preferably by spraying. Alternatively, the composition may be provided in the form of particles. It is also preferred that a surfactant or a tensioactive component such as polyethylene glycol be present to ensure that the composition or its components are dissolved. If the tensioactive substance is an organic substance, it can also be used as a carrier for the composition. In such a case, evaporation of the organic carrier is not required.

Additional menstrual related detection such as additional biochemical or electrochemical or chemical detection means suitable for producing a separate, enhanced or modified visual signal It is within the scope of the present invention to supplement the blood detection agent with an agent. Preferably such additional detection means comprises a pH indicator or a progestin or estrogen indicator or a combination thereof.

DETAILED DESCRIPTION OF THE INVENTION Definitions As used herein, the term “absorbent product” is a device that absorbs and contains bodily exudates, and more specifically, various exudates excreted from the body. Refers to a device placed on or near the wearer's body to absorb and contain objects. The term “disposable” generally refers to absorbent products that are not intended to be washed or otherwise undone or reused as absorbent products (ie, they are discarded after only one use). It is used herein to describe As used herein, the term "joined" refers to a form in which one element is fixed to the other element by directly attaching the element to the other element, and Is attached to an intermediate member, and the intermediate member is attached to another element, whereby the element is indirectly fixed to the other element. An "integral" absorbent product is formed from separate members that are joined together to form an integral body such that the absorbent product does not require a separate operating member, such as a separate holder or liner. Refers to absorbent products. A preferred embodiment of the absorbent product is a one-piece disposable sanitary napkin or panty liner, but if used during the period before menstruation, disposable incontinence briefs, incontinence underwear, absorbent inserts, Tampons and interlabial absorbent products can also benefit from the present invention.

An absorbent product according to the present invention is usually composed of three main components. A topsheet that faces the user of the product during use and is liquid permeable to allow liquid to pass through the product, a backsheet that provides liquid content so that absorbed liquid does not leak through the product ( This backsheet usually provides the garment facing surface of the product), and the product is interposed between the topsheet and the backsheet to capture and retain liquid that has entered the product through the topsheet. An absorbent core that provides absorption capacity.

Many absorbent products and structures are known in the art and have been described in sufficient detail for a long time. All such materials are useful in the present invention provided that they do not interfere with the blood detection composition. The following are only examples which are particularly beneficial for use in preferred absorbent products according to the present invention. Those skilled in the art
It would be easy to identify alternative substances that could be used and would be particularly desirable in connection with an absorbent product for predicting menstruation according to the present invention.

Topsheet In general, the topsheet is compliant, soft, smooth feel and does not irritate the wearer's skin. The topsheet may also preferably have elastic properties that allow it to be stretched in one or two directions. As used herein, the term “flexible” refers to a substance that will be compliant and will quickly follow the general shape and contours of the human body.

The topsheet may be made from a nonwoven or woven material or film that has been made liquid permeable by perforation. The topsheet may also be provided as a composite material or include two or more layers, for example, may have a second topsheet or a flow control layer. Such films and non-woven or woven products can be made from polymers, for example, polyethylene or polypropylene compositions. The topsheet can be provided from a transparent (no colored filler) or translucent material (less than 15% colored filler, ie having about half the usual amount of colored filler).

Backsheet In general, the backsheet has a compliant, soft, and smooth feel. The backsheet prevents the exudates absorbed and contained in the absorbent core from wetting garments in contact with the absorbent product, such as underwear. Preferably, the backsheet is impermeable to liquids (eg, menstrual secretions, sweat and / or urine). It can be manufactured from a thin plastic film, but other flexible liquid impermeable materials can also be used. As used herein, "flexible" refers to a substance that will be compliant and will quickly conform to the general shape and contours of the human body. The backsheet may also preferably have elastic properties that allow it to be stretched in one or two directions.

The backsheet may comprise a woven or nonwoven material, a polymer film such as a thermoplastic film of polyethylene or polypropylene, or a composite material such as a film-coated nonwoven or fiber-coated film. Typically, the absorbent product has a thickness of about 0.012 mm to about 0.051 mm, which can be impermeable or can be made microporous by use of an inert filler and subsequent mechanical stretching. Includes polyethylene film backsheet.

The backsheet is preferably breathable, ie, permeable to water vapor, and more preferably air, without sacrificing its primary purpose of providing leakage protection of the absorbed liquid. The backsheet may also include two or more breathable layers to replace a single breathable backsheet layer with at least two or three layers of different or identical materials. In particular, for example, one providing a wearer facing surface is a molded, apertured film having a three-dimensional structure, eg, the other garment facing layer is a non-woven composite of meltblown and spunbond fibers2. One breathable layer is the preferred breathable backsheet structure. Like the top sheet, the back sheet,
It can be provided from a transparent or translucent material, which makes the inspection of the detection agent inside the product easier.

Absorbent Core Typically, the absorbent core is unitary or may include several layers. It may include the following components: (a) any first fluid distribution layer; (b) any second
(C) a fluid storage layer; (d) an optional fibrous layer beneath the storage layer; and (e) other optional components.

A. First Fluid Distribution Layer One optional component of the absorbent core according to the present invention is a first fluid distribution layer. This first distribution layer is typically under the topsheet (if any) and is in fluid communication therewith. The first distribution layer acquires body fluid for eventual distribution to the storage layer. This movement of fluid through the first distribution layer occurs predominantly in thickness, but can provide distribution along the longitudinal and lateral directions of the song liner.

B. Optional Second Fluid Distribution Layer Also optional according to the present invention is a second fluid distribution layer. This second
Is typically below and in fluid communication with the first distribution layer. The purpose of this second distribution layer is to quickly obtain body fluid from the first distribution layer and distribute it along the length and width of the string liner before transferring it to the underlying reservoir. is there. This ensures that the fluid absorption of the underlying reservoir is fully utilized.

C. Fluid Storage Layer Located in fluid communication with the first or second distribution layer, and typically below the first or second distribution layer, is a fluid storage layer. It preferably, but not necessarily, comprises a superabsorbent gelling material commonly referred to as a "hydrogel", "superabsorbent", "hydrocolloid" material. Absorbable gelling substances are substances which, when in contact with aqueous fluids, in particular bodily fluids, draw up such fluids and thus form a hydrogel. These absorbent gelling substances are typically capable of absorbing large amounts of aqueous body fluids and are capable of retaining such absorbed fluids under moderate pressure. In the prior art, these absorbent gelling substances are:
Typically, it is in a granular form of discrete, non-fibrous particles. However, in accordance with the present invention, these superabsorbent gelling materials may also be provided in non-granular form, preferably in fibrous form. If no absorbent gelling material is provided, the storage layer may be provided by materials commonly used as carrier materials disclosed below.

In the fluid reservoir, these absorbent gelling substances can be dispersed homogeneously or heterogeneously in a suitable fibrous matrix, also called a carrier. Suitable carriers include cellulosic fibers in the form of fluff or tissue as commonly utilized in absorbent cores. Modified cellulose fibers such as hardened cellulose fibers or viscose fibers may also be used. Synthetic fibers can also be used, such as cellulose acetate, polyvinyl fluoride, polyvinylidene chloride, acrylics (such as Aulon), polyvinyl acetate, insoluble polyvinyl alcohol, polyethylene, polypropylene, polyamide (such as nylon), polyester, It can include those made from component fibers, ternary fibers, combinations thereof, and the like. Preferred synthetic and artificial fibers are from about 3 denier per filament to about 25 per filament.
It has a denier, more preferably from about 5 denier per filament to about 16 denier per filament. The carrier fiber is carded
, Span-bonded, melt-blown, wet-laid
An air-laid substrate or such a lay-down
down) method or a combination of such substrates.

Also preferably, the fiber surface is hydrophilic or treated to be hydrophilic. The storage layer may also include fillers such as perlite, diatomaceous earth, vermiculite, etc., which reduce the rewetting problem. Further, the storage layer may include a binder including, but not limited to, a latex binder that may be sprayed as an aqueous solution on the surface of the storage layer prior to curing.

If the absorbent gelling material is heterogeneously dispersed in the fibrous matrix, the storage layer may be locally homogeneous, ie one or more in the dimensions of the storage layer. It has a distribution gradient in the direction. Thus, a heterogeneous distribution may include, for example, a stack of fibrous carriers surrounding the absorbent gelling material, or regions where the absorbent gelling agent has a different concentration as compared to other regions.

If an absorbent gelling material is present, the storage layer preferably comprises 5% to 95% of the absorbent gelling material, more preferably 5% to 50%, most preferably 8% to 35%. Contains an absorbent gelling substance. Further, the storage layer may comprise 5% to 95% carrier fiber, preferably 95% to 50%, most preferably 92% to 65%.

Suitable absorbent gelling materials for use herein will most often include substantially water-insoluble, slightly cross-linked, partially neutralized polymeric gelling materials. This material forms a hydrogel on contact with water. Such polymeric materials can be made from polymerizable, unsaturated, acid-containing monomers. Unsaturated acidic monomers suitable for use in the preparation of the polymeric absorbent gelling material used in the present invention were published on March 31, 1987 (Brandt et al.) And were issued on April 19, 1988. US Patent 4,6, reissued as RE 32,649
54,039. Preferred monomers are acrylic acid,
Includes methacrylic acid and 2-acrylamido-2-methylpropanesulfonic acid.
Acrylic acid itself is particularly preferred for the production of superabsorbents and has less than optimal but acceptable "natural" clarity if the desired clarity is not very high.

Whatever the nature of the underlying polymer component of the hydrogel-forming polymeric absorbent gelling material, such material will generally be slightly crosslinked. The cross-linking serves to render the hydrogel-forming polymer gelling material substantially water-insoluble, and thus the cross-linking is partially due to the gel volume of the hydrogel formed from these polymer gelling materials ( The gel volume and extractable polymer properties are determined. Suitable crosslinkers are well known in the art and are described in more detail, for example, in U.S. Pat. No. 4,076,663, issued Feb. 28, 1978 (Masuda et al.). Including things. Preferred crosslinking agents are di- or polyesters of unsaturated mono- or polycarboxylic acids with polyols, bisacrylamides and di- or triallylamine. Other preferred crosslinking agents are N, N'-methylenebisacrylamide, trimethylolpropane triacrylate and triallylamine. The crosslinker may generally form from about 0.001 mole percent to 5 mole percent of the resulting hydrogel-forming polymeric material. More preferably, the crosslinker will comprise from about 0.01 mole percent to 3 mole percent of the hydrogel-forming polymeric gelling material.

[0039] Slightly crosslinked hydrogel-forming polymer gelling materials are generally utilized in their partially neutralized form. For the purposes of the present invention, such materials are defined as acid-containing monomers in which at least 25 mole percent, preferably at least 50 mole percent, of the monomers used to form the polymer are neutralized with salt-forming cations. Is considered partially neutralized. Suitable salt forming cations include alkali metals, ammonium, substituted ammonium and amine. This percentage of total monomers utilized that are neutralized acid group containing monomers is referred to herein as "degree of neutralization."

While these absorbent gelling substances have typically been disclosed in the prior art in particulate form, in the present invention, the absorbent gelling substances are, for example, fibers, sheets or strips. It can be in a non-granular form as a macro structure. These macrostructures are formed by shaping the absorbent gelling material of the particles into agglomerates, treating the agglomerated material with a suitable cross-linking agent, compacting the treated agglomerates and increasing their density,
forming a mass of coherent and then curing the compacted agglomerates and reacting the crosslinker with the absorbent gelling material of the particles to form a complex, porous absorbent macrostructure Can be manufactured. Such porous absorbent macrostructures are disclosed, for example, in US Pat. No. 5,102,597 issued Apr. 7, 1992 (Roe et al.).

D. Optional Fibrous Layer The optional component contained in the absorbent core according to the present invention is the fibrous layer adjacent to and typically below the storage layer. The underlying fibrous layer typically comprises a second
Will provide the same function as the fluid distribution layer of the present invention.

E. Other Optional Ingredients The absorbent core according to the present invention may include other optional ingredients commonly present in absorbent webs. For example, a reinforcing scrim may be located in or between each layer of the absorbent core. Such a reinforcing scrim should be shaped so as not to form an interfacial barrier to fluid movement, especially if located between the respective layers of the absorbent core. Given the structural integrity that normally results from thermal bonding, a reinforcing scrim is not usually required for an absorbent structure according to the present invention.

Another component that may be included in the absorbent core according to the present invention and is preferably provided in proximity to or as part of the first or second fluid distribution layer is an odor control agent. Typically, activated carbon, especially coated with a suitable zeolite, silica or clay material or activated carbon in addition to other odor control agents, is optionally mixed into the absorbent core.

Physical Properties of Absorbent Cores Absorbent cores are usually inextensible and inelastic, however, they can be given extensibility and, depending on the material chosen, elastic properties Can also be made to have. The term "extensibility" as used below extends in the direction of the force, or in the direction of the force component if only unidirectional extensibility is provided, under external forces such as those encountered during use. Refers to the structure.

The term “elastic” as used herein refers to an extensible structure that at least partially returns to its initial state after the force that causes it has ceased to work. The absorbent core can be corrugated or pleated in one or more directions to provide some extensibility, while the choice of elastic fibers for the structure can provide elasticity.

The absorbent core should preferably be thin. Desirably, the thickness is less than 5 mm, preferably less than 3 mm, more preferably 0.8 to 1.8 mm so that the resulting product may also have a reduced thickness.

Examples of panty liners and sanitary napkins that can include a blood detection composition include:
The Procter & Gamble Company, Cincinnati, Ohio
): US Patents 4,324,246; 4,463,045;
And ALWAYS manufactured according to 6,004,893
) (Registered trademark) ALLDAYS (registered trademark) Pantiliners with DriWeav
e) (registered trademark); U.S. Pat. Nos. 4,342,314, 4,463,045, 4,5
56,146, B14,589,876, 4,687,478, 4,950,2
64, 5,009,653, 5,267,992 and Re. Always® Ultra Thin Slender Maxi With Wings manufactured according to U.S. Pat. No. 32,649.
Wings); Always (registered trademark) Regular Maxi (Regular)
Maxi); Always (registered trademark) Ultra Maxi With Wing (U.
Itra Maxi with Wings; Always (R) Maxi With Wings; Always (R) Ultra Long Max With Wings (Ultra Long Max)
i with Wings); Always (registered trademark) Long Super Maxi with Wings (Long Super Maxi with Wings)
And Always® Overnight Maxi With Wing (O
, including, but not limited to, V. nightlight Maxi with Wings).

An example of an interlabial device that can be provided with a blood detection composition is described in US Pat. No. 5,762,64.
4, 5,885,265; 5,891,126; 5,895,381; 5,91
6,205; 5,951,537; 5,964,689; 5,968,026;
Des. 404, 814; and Des. 413,669,
It is not limited to these.

Examples of tampons and applicators therefor that can include a blood detection composition are described in US Pat. Nos. 4,726,805; 4,846,802; 4,960,417;
87,239; 5,279,541; 5,346,468; 5,348,534
5,531,674; and 5,566,435, but are not limited thereto. In addition, the blood detection composition can also be placed on a tampon that can be inserted with a finger.

Blood Detection Composition The blood detection composition according to the present invention provides at least one sensor for the detection of blood. The term “sensor” as used herein is adapted to detect one or more target substances (also called analytes), such as microorganisms or related (bio) molecules (eg, Enzyme sensors, organelles (o
rganella) sensors, tissue sensors, microbial sensors, immunosensors and chemical or electrochemical sensors) and, in addition, one or more capable of providing a signal of said detection to a wearer, caregiver or actuator. Is defined as a component containing a reactive means. When referring here to blood, typical components of blood such as hemoglobin or iron can of course also be used as analytes. The term "reactive" is defined as having the ability to selectively interact with such target substances.

There are two categories of sensors with different sensitivities: biosensors and chemical / electrochemical sensors. In general, biosensors function by specifically binding to a target biologically active analyte and, therefore, providing a means of detecting that analyte. Thus, biosensors are highly selective, even when present with a mixture of many chemical and biological substances, such as vaginal discharge. On the other hand, electrochemical and chemical sensors that rely on chemically reactive means generally do not have either the high selectivity or amplification properties of biosensors, but are highly reliable and inexpensive. That is, it is useful in daily products and is often very well recognized, ie, proven to be safe for use on human skin. Often the target analyte is a trace component in a complex mixture containing a large number of biological and other components. Therefore, in many biosensor applications, parts per billion (parts
-Per-billion, parts per trillion (parts-per-trill)
(ion) Detection of the target analyte down to or below levels is required.

According to the present invention, the blood detection composition is a specifically stabilized chemical composition. The chemical composition includes a color indicating component that provides a color change as a result of the oxidation reaction and is preferably selected from gum wiak or tetra-methyl-benzidine or a combination thereof. As a second component, the composition comprises a peroxide or a peracid as a stabilized oxidizing component.

The oxidizing component (also referred to as an oxidant) is stabilized so that it is insensitive to the storage conditions of the intended product under normal circumstances (eg, in a warm, high humidity environment of a bathroom). Stabilization can be provided in two ways: physiochemical (phys) by caging the oxidant to the carrier.
io-chemical) stabilization. According to the invention, this carrier is provided by cyclo-dextrin. Cyclo-dextrins carry peroxide in the aqueous phase (eg, in the presence of high humidity) while maintaining oxidative reactivity. An alternative to physiochemical stabilization is chemical stabilization by preventing or reducing degradation caused by radicals. According to the invention, this is achieved by the use of nitrones. Of course, a combination of both components is also possible, creating an additional stabilizing effect.

If the oxidant is chosen to be a peracid, it is preferably epta-phthalimido-peroxy-hexanoic acid. Epta-phthalimido-peroxy-hexanoic acid also benefits from stabilization by caging, but can preferably be stabilized by nitrones which prevent or reduce radical-induced degradation. In this regard, nitrones function as radical scavengers, and other radical scavengers can also be used. Of course, in a mixture of hydro-peroxide and epta-phthalimide-peroxy-hexanoic acid, both stabilizer components also need to be present.

The color indicator and the oxidizing substance are mainly reactive in an aqueous solution. Therefore, once they begin to react, they dissolve in the vaginal discharge and are activated by the presence of blood. A tension-active substance in the blood detection composition to accelerate and facilitate lysis,
For example, surfactants or polyethylene-glycol or mixtures thereof,
Preferably, it contains polyethylene-glycol. In hygiene products, the tension-active substance should preferably be positioned so that it is first moistened before the liquid reaches the two components.

[0056] A highly preferred composition comprises a combination of epta-phthalimide-peroxy-hexanoic acid and gum wire. Gum guaiac is a resin found in the tree of Guaiacum officinale or Guaiacum santum, which is found mainly in Mexico or West India. Gum wiak has been historically used as a food seasoning (and therefore has a long-term record of safe use by humans) and is particularly known for its ability to indicate the presence of blood or hemoglobin in stool. ing. In accordance with the present invention, gumwood wood resin is preferred, however, one or all of the active ingredients, whether naturally derived or artificially derived, are used in place of the wood resin. obtain. The best known active ingredient is guaiacol (OHC6H4OCH3, CAS90-05)
-1), guaiaconic acid and (furo)
-Guayacin ((furo) -guaiacine).

If applied to a product, the components may be applied by coating or spraying if they are applied in solution. In this case, the solvent should preferably be an organic solvent. However, if an organic solvent cannot be selected to provide additional benefits to the product, such as tension activity as a dissolution aid, such a solvent should evaporate at a temperature below 100 ° C. It is. If used in an absorbent product, the application of both components to the same layer can be in an alternating pattern such as stripes, dots or different shapes. The detection agent component may be provided on a discrete portion of the surface of the layer or as a complete surface coverage of the layer (both components or only one).
The components may be provided as components in one or both powders, liquids, or viscous mixtures for better coating.

Additional Detection Agents In one particularly preferred embodiment of the present invention, the composition (or product, if the composition is applied to a product) comprises, in addition to the blood detection agent, a physiology in bodily discharges. It includes another separately activated and independently functioning sensor for detecting specific components. This is exemplified below by detecting the approach of menstruation, but is not limited to these.

It is clear that the detection of blood, especially for the prediction of menstruation, cannot be regarded as one hundred percent accurate. First, the indicator itself needs to have a high degree of accuracy only in detecting blood, ie it must be insensitive to other substances to which it is exposed. On the other hand, a small amount of blood, ie, its detection prior to its visual recognition, must be sensitive. These two competing issues need to be balanced.

In addition, the presence of (inapparent) blood is well-known as a sign of menstrual approach. However, trauma or pathological conditions can also cause the presence of low levels of blood in vaginal discharge. It is therefore desirable to provide a sanitary product with an additional indicator that provides a second signal of menstrual approach. Such a signal is
For example, it may be provided by a change in the pH of the vaginal discharge several days before menstruation. Additionally or alternatively, hormones such as progesterone and / or estrogen can be used as additional indicators for the prediction of menstruation.

[0061] In this regard, most preferred are pH sensors that can be provided as color change indicators. pH sensors are well known and are commercially available, for example, from The Merck Company of Darmstadt, Germany. In this regard, a highly preferred pH sensor with a well-documented safety profile is carminic acid, which is used as a food pigment, but undergoes a color change in the range between pH 4 and pH 7. Carminic acid is a tricyclic compound having the compound formula C22-H20-O13.

Regardless of what additional sensors are used, if they are provided as color change indicators, along with a color indicator that provides blood detection, they will be in the form of a multicolor indicator. Will produce a mixed output signal. It may be a mixed color indicator or provided to work separately but separately detectable, but as described below. For example, if a gum wire that provides a color change to blue is mixed with, for example, a pH sensor that provides a color change to red, the mixed color sensors (blue and red) will have an indicator with high accuracy and To provide a time proximity of the menstrual approach, it would have to turn purple. Different color changes (such as blue only or red only) will indicate whether there is still some time before menstruation or a potential health problem (pH changes alone are different A blood indicator alone, although not without, could indicate an infection, but not necessarily, could indicate damage). Due to such changes, the packaging of the composition (or product, if combined with the product) may be used to medically assess whether any serious health problems (pathological conditions) are present. Will include instructions to the user to consider visiting a physician. of course,
The absence of a color change would indicate that there is some time before the next menstruation.

In addition to electrochemical sensors, to supplement blood detection agents, the periodic nature of the menstrual cycle hormones (ie, the entire 28-day cycle) may make them, in particular, individual individuals during her cycle. Helps to understand location. It has been used historically for fertility determinations, but the use according to the invention goes beyond the current use of hormones to predict ovulation and pregnancy. For example, progesterone peaks just before menstruation and then falls. Estrogen also declines shortly before menstruation. Thus, when combined with other predictors such as blood detection or pH indicators, assays for either of these two hormones will make reliable predictions of menstruation onset and presence. The time when these hormones peak, along with their subsequent decline, gives a high accurate sign of the time before menstruation.

The only potential drawback of such hormonal indicators is the associated price and complexity. The lack of simple visualization makes their use in bulk bulk products less than attractive. Therefore, the use of hormone detection to make a prediction of menstruation, preferably in the form of a completely separate detection system, is provided with blood detection and / or pH detection to improve the accuracy of such predictions Is done.

The use of hormones will also be exploited for other cycles of interest. Follicle-stimulating hormone (FSH) peaks about one week before ovulation, providing a more advance time for pregnancy planning than a luteinizing hormone assay that shows a sharp peak during ovulation. Two to three days of fertility can be overlooked, relying solely on luteinizing hormone assays. Therefore, in the diagnosis of ovulation here,
It is highly preferred to measure both follicle stimulating hormone and luteinizing hormone together with estrogen.

An increase in follicle stimulating hormone to near a certain amount signals the onset of menopause. This would be of great use in planning healthy approaches to menopause, such as checking for nutritional changes and osteoporosis, such as hormone replacement therapy.

A composition according to the present invention can be provided, for example, with a plurality of additional sensor and detection agent systems that provide an indication or prediction of an individual's health-related issues. Such additional sensor systems are mainly useful for hygiene products used in the caregiver setting, or if the composition is in spray or liquid form. Generally, such additional systems or biosensors include a recognition element that provides detection of a particular analyte, or a molecular recognition element. The recognition element is an enzyme or a sequence of an enzyme; an antibody; a membrane receptor protein (membrane receptor).
DNA; organelles, natural or artificial cell membranes; intact or partially viable or nonviable bacteria, plant or animal cells; or biologically derived such as plant or mammalian tissue fragments. And generally functions to specifically interact with the target analyte. The recognition element is responsible for the selective recognition of the analyte and creates a physico-chemical signal that provides the basis for the output signal.

The biosensor can include a biocatalytic biosensor and a bioaffinity biosensor. In embodiments of the biocatalytic biosensor, the bio-recognition element is a "biocatalyst" and may include enzymes, organelles, plant or mammalian tissue pieces, or whole cells, and the selective binding site is consequently "Turnover" leading to significant amplification of the input signal (
That is, it can be used again in the detection process). Biocatalytic sensors such as these are generally useful for real-time continuous detection.

Bioaffinity sensors are generally applicable to bacteria, viruses, and toxins, and include chemoreceptor-based biosensors and / or immunological sensors (ie, immunosensors). Chemoreceptors are complex biomolecular macroassemblies that contribute to the viability of a viable organism with high selectivity for sensing chemicals in its environment. Biosensors based on chemoreceptors are one or more natural sensors associated with a means for providing a signal (visual, electrical, etc.) of the presence or concentration of a target biological analyte. Including synthetic or synthetic chemoreceptors. Chemoreceptors can include all or a portion of a nerve fiber bundle (eg, from antennal or other sensory organs) and / or all or a portion of a natural or synthetic cell membrane. On the other hand, the biorecognition element of an immunosensor is generally an antibody. Antibodies are highly specific and can be made to bacteria, viruses, microbial fragments (eg, bacterial cell walls, parasite eggs or parts thereof, etc.), and large biomolecules. Suitable antibodies can be monoclonal or polyclonal. In any case, biocompatible biosensors are generally irreversible because the receptor site of the biosensor becomes saturated when exposed to the target biological analyte. In some embodiments, a biocatalyst and a biocompatible biosensor can be used in combination. Biocatalysts and biocompatible biosensor systems are available from Journal of Chromatography (Journal of Chromatography).
Chromatography, 510 (1990) 347-354 and John Wiley & Sons, NY, Kirk-Osmerencyclopedia of Chemical Technology (Kirk-O).
thmer Encyclopedia of Chemical Techn
and the fourth edition (1992).

The biosensor of the present invention also preferably comprises pathogenic bacteria, parasites, viruses, fungi such as Candida albicans, antibodies to pathogens, and / or toxins produced by microorganisms (ie, imminent). Detect a biologically active analyte that is likely to be symptomatic in the future) or that is associated with the current human systemic disease state. In addition, biosensors provide stress proteins (eg, cytokines) and IL-1 that can precede the clinical presentation of skin irritation or inflammation.
Biologically active analytes such as α (interleukin 1-alpha) may be targeted which are relevant to immediate or current localized health problems. In a preferred embodiment, the biosensor detects an impending condition prior to the presentation of clinical symptoms, and a proactive sensor that signals the wearer or caregiver.
nsor). This allows time to administer to the wearer a prophylactic or therapeutic agent that can significantly reduce, if not prevent, the severity and duration of symptoms. In addition, by detecting the presence of the target biological analyte in the body waste of the wearer, the biosensor detects residual contaminants on surfaces such as skin that come into contact with the biosensor, and A signal may be provided.

The signal generated by the recognition element or elements is transmitted to the wearer or caregiver visually, for example by a color change visible to the human eye. The signal can be qualitative (e.g., indicating the presence of a target biological analyte) or quantitative (e.g.,
For example, measuring the amount or concentration of a target biological analyte). In any case, the signal is preferably durable, ie, stable or legible over a long period of time (typically at least as long as the life of the product).
In addition, the sensor can detect a target biological analyte that is above or below a predefined threshold (eg, where the target biological analyte is typically present in bodily excretions). It may be adapted to detect only concentration and / or to emit a signal.

As noted above, target analytes adapted for detection by the biosensors of the present invention may be pathogenic microorganisms associated with human gastrointestinal tract diseases, particularly those that result in diarrhea. It is a pathogenic microorganism. It has been discovered that severe chronic diarrhea can lead to weight loss and persistent physical and mental retardation. A list of pathogenic bacteria that biosensor 60 can detect is E. coli (generally E. coli).
Known pathogens; Salmonella typhi, Paratyphi, Enteritidis,
Salmonella typhimurium, and S. typhimurium. Salmonella strains including S. heidelberg; Shigella strains such as Shigella sonnei, Shigella flexneri, Shigella dysenterium, and Shigella shigella; Vibrio cholerae; Mycobacterium tuberculosis; Yersinia enterocolitica; Aeromonas Genus hydrophila (Aeromonas hydro
phila); Plesiominas sh
igelloids); C. jejuni and C. jejuni Campylobacter strains such as C. coli; Bacteroides fragilis (
Bacteroides fragilis); Septicum (C.I.
septicum), Welch bacteria, Clostridium botulinum, and C. Difficile (C
. difficile), including, but not limited to, any of the following Clostridium strains: An example of a commercially available biosensor adapted to detect E. coli is available as Test Kit # 4001 from AndCare, Inc., Durham, NC. ABTECH, Scientific, Inc., of Yardley, PA, has been described as having a covalent, motion-inhibiting polypeptide, enzyme, antibody, or DNA fragment on its surface (such as a microorganism or other microorganism as described herein). BBau-1 which can be given biospecificity (for the target biological analyte)
050.5-FD-X, available for “bioanalytical
al) biotransducers ". Other suitable microbial biosensors are U.S. Patent Nos. 5,869,272 (Gram negative organisms); 5,795,717 (Shigella); 5,830,341;
785,453; 5,354,661; 5,783,399; 5,840,48
8; 5,827,651; 5,723,330; and 5,496,700.

The target analytes that the biosensor of the invention is adapted to detect are also
It can be a virus. These may also include diarrhea-inducing viruses such as rotavirus, or other viruses such as rhinovirus and human immunodeficiency virus (HIV). Typical examples of biosensors adapted to detect HIV are described in U.S. Patents 5,830,341 and 5,795,453, cited above.

In another embodiment, the target analytes that the biosensors of the invention are adapted to detect are parasites, particularly those that reside in the gastrointestinal tract at some point in their life cycle. Can be Such parasites can include protozoa, helminths, and other gastrointestinal parasites. Examples of other parasites that can be detected are entomoeba histolytica (causing amoebic dysentery), trypanana cruzi (trypana)
cruzi) (causing Chagas disease), and Plasmodium falciparum.

In still other embodiments, the target analyte that the biosensor of the invention is adapted to detect is a fungus such as Candida albicans. In addition to pathogenic bacteria, certain beneficial colonic bacteria can be detected and / or measured as indicators of health, such as Bifidobacterium and Lactobacillus strains.

The target analytes that the biosensor of the invention is adapted to detect are also:
It can be a protein or antigen associated with a skin disorder. Preferably, these analytes are detectable on or at the skin surface, preferably prior to presentation of a clinically observable skin sensitivity. These include stress proteins such as cytokines, histamine and interleukins (IL-1α, IL-2, IL-
3, IL-4 and IL-8) and interferons (interferon a
And g)). Further, they are preferably detectable by biosensor 60 prior to the onset of clinically observable redness, irritation, or dermatitis. In addition, the biosensors of the present invention can be adapted to detect enzymes or other biological agents associated with cutaneous hypersensitivity (eg, diaper dermatitis), including trypsin, chymotrypsin, and lipase.

The biosensor of the invention can also include a biorecognition system that includes an enzyme or binding protein, such as an antibody, immobilized on the surface of a physicochemical transducer. For example, a specific strain of bacteria can be detected by a biosensor that utilizes antibodies raised against the bacterial strain. Alternatively, the target bacterium may have biorecognition elements (antibodies and synthetic or natural molecule receptors) specific for extracellular products of the target bacterium, such as toxins produced by the strain (eg, E. coli). Including). Examples of enzyme electrodes that can be used to detect phenol (eg, in urine or stool) are described in US Pat. No. 5,676, issued to Joseph Wang et al., On Oct. 14, 1997, respectively. 820
Title "Remote Electrochemical Sensor (Remote Electrochemi
cal Sensor) "and Anthony P.C. on February 25, 1992. F. U.S. Pat. No. 5,091,299 issued to Anthony PF Turner et al., Enzymatic electrode for use in organic solvents (An Enz).
yme Electrode For Use In Organic Sol
tyrosinase-based electrodes or polyphenol oxidase electrodes described in "Vents)".

In any of the foregoing examples, the specific microorganism may be a monoclonal antibody that can be detected directly or that is specific for a toxin, enzyme, or other protein or organism produced by the organism. It can be detected by binding to such an antibody. Examples of biosensors adapted to detect proteolytic enzymes are provided in US Pat. No. 5,607,567, and examples of toxins are provided in US Pat. No. 5,496,452;
5,521,101; and 5,567,301.

A biosensor of the invention may include one or more “leading sensors”. This is particularly useful in embodiments where detection of the target biologically reactive analyte precedes the onset of clinically observable health symptoms. As used in this application, the term “advance sensor” refers to the body (eg, skin) of the wearer.
Refers to a sensor capable of detecting a change or signal on or in the faeces, ie, an input that is directly or minimally related to the appearance of an imminent or potential health or skin related event. Leading sensors may be responsive to one or more specific inputs as described above.

The preceding sensor may detect an imminent event or an imminent event, in particular,
Parameters directly or minimally associated with the occurrence of a systemic or skin health event or condition (ie, presentation of a clinically observable indicator or symptom) may be detected. Imminent events that can be detected or predicted by the progenitor sensors of the present invention include diarrheal diseases, skin irritation or rashes (including candidiasis), and / or the invasion of other types of diseases or parasites. It may include the medical condition of the wearer. The biological analyte to be detected can be one or more steps taken from the actual presentation of clinical symptoms. For example, a biosensor may detect potential precursors of the above conditions (eg, stool contaminants in the skin that may precede the induction of stress proteins that may in turn precede clinically observable skin sensitivity. The parameters associated with an event may be any measurable input signal (ie, excretion), such as one or more potential inputs listed above, associated with the occurrence of the event in the system of reference of the system. A front sensor in the product may measure one or more different inputs to predict an event, for example, a front sensor may be sensitive to skin. The signals that can be preceded, Candida albicans in vaginal discharge bacteria, as well as residual colonic bacteria on the skin (ie detecting residual contaminants) can be monitored.

In embodiments of the biosensor where the biometric recognition element does not produce an easily recognizable signal (eg, a color change), the biosensor may use a physicochemical signal from the biometric recognition element to provide a wearer, Or, it may include a transducer that communicates with the biometric recognition element to convert it into a signal usable for components of the product (eg, and actuators). Examples of transducers include electrochemical transducers (including potentiometric, amperometric, and conductometric transducers) as known in the art, optical transducers (fluorescence, bioluminescence, total Total internal reflection (total internal reflective)
response, and surface plasmon resonance), thermal transducers, and auditory transducers. A power supply such as a micro three volt watch battery or a printed thin film lithium battery can be coupled with a biosensor that provides some required power.

────────────────────────────────────────────────── ─── Continued on the front page (31) Priority claim number 09 / 517,481 (32) Priority date March 2, 2000 (2000.3.2) (33) Priority claim country United States (US) ( 81) Designated countries EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, SD, SL, SZ, TZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AE, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, R, CU, CZ, DE, DK, DM, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI SK, SL, TJ, TM, TR, TT, TZ, UA, UG, US, UZ, VN, YU, ZA, ZW (72) Inventor Capri, Maria Grazia Italy, I-66020 Es Giova Nni Theatino, Via Pi Nenni 150 (72) Inventor Culucci, Giovanni Italy, I-66100 Chieti, Via A Fieramosca 118 (72) Inventor Gueresti, Lisa Italy, I-26048 Sospiro, Bi A Gee Rivaldi 25 (72) Inventor Hammonds, John El Dust Commander Court, 45011 Hamilton, Ohio, United States of America 7379 (72) Inventor Siara, Stefano Italy, Ai-00128 Rome, Via F.B. 81 F term (reference) 2G045 AA13 BB54 CA25 DA51 FA18 FB11 FB15 GC12 HA02 HA10 2G054 AA07 AB07 CA21 CE02 EA06 FB03 GA03 GB04 GE01

Claims (8)

[Claims] 1. A method according to claim 1, wherein said fluid is a bodily fluid of mammalian origin or an aqueous solution thereof.
A stabilized detection composition for providing a visual signal for the detection of blood that is unrecognizable by ordinary visual inspection by the human eye, comprising: an oxidative color indicator; An oxide and a component selected from cyclo-dextrin or nitrone or a combination thereof as a stabilizer for said peroxide; or-one of peroxyacid and nitrone as a stabilizer for said peracid The said blood detection composition containing either of both. 2. The composition according to claim 1, wherein the oxidative color indicator is selected from the group consisting of gum wiac, tetra-methylbenzidine or a combination thereof, and is preferably gum wiac. 3. The composition according to claim 1, wherein said peroxide is a hydro-peroxide. 4. The composition according to claim 1, wherein the peracid is epta-phthalimide-peroxy-hexanoic acid. 5. A composition according to claim 1, wherein the composition is in a liquid form, preferably a solution in an organic carrier. 6. The composition according to claim 1, wherein the composition is in a granular form. 7. The composition according to claim 1, wherein said composition is more tension active.
7. The composition according to claim 1, wherein the composition comprises: 8. A product for visual blood detection of blood volume in a liquid that is not visually recognizable, said product comprising a carrier substance to which the detection composition according to claim 1 has been applied.