Secretion-monitoring article
Abstract
An article for the monitoring of secretions for the identification of secreted biological fluids that includes: a body that includes an absorbent material to absorb a biological fluid secreted from a person and an indicator system comprising at least one pH determining member and an ion equilibrium reagent to react with the biological fluid, wherein the indicator system provides an indication of the health conditions associated with pH, cation of protonated amines and regulatory capacities of biological fluids, and wherein the indicator system is associated with the absorbent material such that the biological fluids come into contact with the indicator system.
Term
Term ended
Projected expiry passed 18 July 2022, 4.2 years ago.
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22 claims: 1 independent, 21 dependent
- 1REIVINDICACIONES 1. Un artículo para la monitorización de secreciones para la identificación de fluidos biológicos secretados que comprende:un cuerpo que incluye un material absorbente para absorber un fluido biológico secretado de una persona y un sistema indicador que comprende al menos un miembro determinante del pH y un reactivo de equilibrio de iones para reaccionar con el fluido biológico, en donde el sistema indicador proporciona una indicación de las condiciones de salud asociadas con el pH, catión de aminas protonadas y capacidades reguladoras de los fluidos biológicos, y en donde el sistema indicador está asociado con el material absorbente de tal forma que los fluidos biológicos entran en contacto con el sistema indicador.
- 2El artículo de la reivindicación 1, en donde la indicación es resistente al cambio debido al uso prolongado o a los ciclos de humectación y secado.
- 3El artículo de la reivindicación 1, comprendiendo además una pluralidad de miembros determinantes del pH.
- 4El artículo de la reivindicación 1, comprendiendo además un reactivo que cambia sustancialmente de color en el momento del contacto con la orina.
- 5El artículo de la reivindicación 4, en donde el reactivo es ureasa.
- 6El artículo de la reivindicación 1, comprendiendo además un medio de montaje para colocar el cuerpo absorbente en una posición para recibir fluidos biológicos secretados de una persona.
- 7El artículo de la reivindicación 1, en donde el material absorbente del cuerpo es un hisopo, gasa, salva-slip, compresa higiénica, un pañal o una estructura absorbente interlabial.
- 8El artículo de la reivindicación 1, en donde el sistema indicador comprende un primer indicador de pH unido al sustrato en una primera área y que tienen una transición de color a un primer rango de pH;un segundo indicador de pH unido al sustrato en una segunda área y que tiene una transición de color en un segundo rango de pH, y un reactivo unido al sustrato en la segunda área, en donde el primer rango de pH y el segundo rango de pH son diferentes y en donde el mencionado reactivo cambia sustancialmente de color en el momento del contacto con la urea.
- 9El artículo de la reivindicación 8, en donde la primera área y la segunda área están separadas.
- 10El artículo de la reivindicación 8, que comprende una membrana microporosa para la secreción absorbida por el cuerpo a través de la cual el fluido biológico debe pasar antes de la absorción por el material absorbente.
- 11El artículo de la reivindicación 8, en donde el primer indicador de pH está configurado para cambiar sustancialmente de color en el momento del contacto con el fluido amniótico o con las secreciones vaginales asociadas con vaginosis y el segundo indicador de pH está configurado para cambiar sustancialmente de color en el momento del contacto con la orina reaccionando con el reactivo.
- 12El artículo de la reivindicación 8, en donde el primer y el segundo indicadores de pH tienen cada uno un grupo funcional cargado negativamente.
- 13El artículo de la reivindicación 8, en donde el primer rango de pH es más bajo que el segundo rango de pH.
- 14El artículo de la reivindicación 8, comprendiendo además un tercer indicador de pH.
- 15Un método para monitorizar la condición de salud de una persona que comprende:posicionar el artículo de la reivindicación 1 para absorber fluidos secretados desde la vecindad del área vaginal de una mujer;e inspeccionar el indicador de pH para identificar el tipo de secreción que contacta con el indicador de pH.
- 16El artículo de acuerdo con la reivindicación 1 para la identificación de orina infectada, en donde el sistema indicador reacciona con la orina normal de forma diferente que con la orina infectada, y en donde el cambio de color obtenido en el momento del contacto entre el sistema indicador y la orina infectada es no reversible.
- 17El artículo de acuerdo con la reivindicación 1 para la identificación de secreciones vaginales infectadas con bacterias, en donde el sistema indicador reacciona con secreciones vaginales normales o de candidiasis de forma diferente que con secreciones vaginales infectadas con bacterias.
- 18El artículo de la reivindicación 1, en donde el sistema indicador comprende además:un polímero pre-formado en una cantidad de alrededor de un 20 a un 50% del peso total, un polímero plastificante en una cantidad de alrededor del 15 al 40 % del peso total;un polímero de agente humectante en una cantidad de alrededor del 15 al 45% del peso total;un polímero de reactivo de equilibrio de iones en una cantidad de alrededor del 0,1 al 10% del peso total;un polímero indicador en una cantidad de alrededor del 0,05 al 5% del peso total, en donde los porcentajes son porcentajes de peso basados en el peso total de la mezcla y el peso total de la mezcla es igual a 100%.
- 19El artículo de la reivindicación 18, comprendiendo además un reactivo en una cantidad de alrededor de 10 5 unidades por cada 0,01 a 0,1% de indicador en la mezcla.
- 20El artículo de la reivindicación 19, en donde el reactivo es ureasa.
- 21El artículo de la reivindicación 18, comprendiendo además un solvente en un cantidad de alrededor de 1 a 30 ml 10 por cada 150 mg de mezcla.
- 22El artículo de la reivindicación 18, en donde el polímero preformado está presente en una cantidad de alrededor del 36 al 39%, el plastificante está presente en una cantidad de alrededor del 27 al 29%, el agente humectante está presente en una cantidad de alrededor del 29 al 31%, el reactivo de equilibrio de iones está presente en una 15 cantidad de alrededor del 4 al 6%, el indicador está presente en una cantidad del 0,2 al 0,4%.
Independent claims22
165 paragraphs in 8 sections, as filed
p00001Articles for secretion monitoring.
TECHNICAL FIELD
p00002The present invention relates to the field of medical diagnosis and more specifically, to an improved identification of secreted biological fluids using an article for secretion monitoring to identify amniotic fluids or secretions associated with bacterial, fungal or yeast infections even with the presence of interfering biological fluids. Improved methods of attaching an indicator to a substrate and methods for preparing and using an article for secretion monitoring to identify a secretion are also disclosed.
BACKGROUND OF THE INVENTION
p00003Many body fluids can be easily identified by chemical properties such as pH. An exceptionally useful method for determining the pH of a liquid sample is through an indicator, a chemical compound or a combination of compounds, which has a pH dependent color. Well-known examples include tea and wine. General details and descriptions of some indicators can be found, for example, in "indicators", E. Bishop, Pergamon Press, 1972, chapter 3.
p00004Often an indicator is attached to a solid substrate such as paper. A sample of a liquid from which the pH needs to be determined is applied to the substrate. The pH of the liquid is determined by determining the color of the indicator present in the substrate. Depending on how the indicator is attached to the substrate, the application of the liquid sample may cause the indicator to seep out of the substrate. The filtered indicator is not desirable and therefore the indicator is often substantially immobilized on the substrate.
p00005Many chemical conditions can be diagnosed by identifying the chemical and physical properties of a vaginal secretion, such as by identifying the pH of the secretion. A number of devices involving salvage slips with pH indicators are known in the art, for example in US Patents 5,217.44, 5,823,953 and 6,106,461. These devices can be carried by the user and whenever there is a secretion this is immediately detected by the pH indicator. International patent application WO01 / 13097, which discloses an indicator attached to a hydrophilic synthetic membrane substrate and a device, such as a salva-slip with an indicator attached to the hydrophilic synthetic membrane substrate.
p00006A general problem, however, with these pH indicators is that they often provide "false positives" due to changes in pH during drying, interfering biological fluids and the respective drying / wetting cycles. Often vaginal secretion cannot be identified with absolute certainty by an indicator due to the existence of a plurality of fluids collected with a similar pH. "False positive" readings can be stressful and time consuming for the user. A device that minimizes these "false positive" readings is needed.
p00007False positive readings can be caused, for example, by interfering biological fluids, such as urine. Vaginal secretions of a patient with vaginosis have a pH between 4.7 and 6.5. Since the urine of a healthy patient has a pH between 5.0 and 8.0, it is very difficult to diagnose a secretion that arises from vaginosis with a high degree of confidence by adjusting only a pH-based indicator test. A solution known in the art is to sample fluid from inside the vagina, where urine is not usually found. This is uncomfortable and requires a health professional to visit.
p00008A second example is the identification of amniotic fluid that is lost from the vagina of a pregnant woman. During pregnancy the integrity of the amniotic sac can be compromised and a small amount of amniotic fluid can be lost through the cervix and from the vagina. If diagnosed as such, measures such as patient rest or amniotic sac sealing using biological glue may be prescribed. If the amniotic sac is not diagnosed it can break later causing pregnancy abortion,
p00009or require hospitalization of the woman and the baby- If the baby is born prematurely, it can result in death or severe disability. Often the extended hospitalization of the baby in an incubator is necessary.
p00010Due to the severe consequences of the loss of amniotic fluid, pregnant women experience severe stress and often go to health care professionals at the time of secretion of any fluid from the vicinity of the vagina. The health care professional observes the presence of amniotic fluid by checking the pH of vaginal secretions, the amniotic fluid has a pH between 6.0 and 8.0. Since pregnant women often have urinary incontinence and since urine typically has a pH between 5.0 and 8.0 if only the pH is checked, a false positive result can occur, with urine identified as amniotic fluid. Accordingly, it is necessary that said vaginal secretion be examined using a microcopy for the presence of a fern-shaped pattern indicative of amniotic fluid.
p00011Since the time between fluid secretion and arrival at the health care professional can be long, there is often no evidence of amniotic fluid at the time of the exam. It can be mistakenly assumed that the secretion is urine, often with tragic consequences. On the other hand, the health care professional may decide to err on the side of precaution, misdiagnosing the secretion of urine as an amniotic fluid leading to unnecessary hospitalization and stress for the patient.
p00012US Patent No. 6,126,597 (the '597 patent) and US Patent No. 6,149,590 (the 590 patent), a continuation in part of the' 597 patent, are intended to disclose a device in the form of a sanitary napkin with a pH indicator configured to identify the presence of amniotic fluid in a vaginal discharge. Patents '597 and' 5900 are subject to the problem of giving false positive results. The device of the '590 takes care of this problem by additionally including in the device a microscopic display sheet configured to collect a part of a vaginal discharge. If the indicator shows the pH that corresponds to that of the amniotic fluid, the user presents a health care professional with the sheet. The health care professional examines the sheet with the help of a microscope for typical fern-shaped patterns indicative of the presence of amniotic fluid.
p00013There are a couple of disadvantages associated with this device. First, it requires the patient to visit the health care professional to distinguish between positive and false positives and second, a significant amount of time is wasted in having to see the sheet by a professional to determine if amniotic fluid is actually being lost.
p00014US Patent No. 5,897,834 discloses a device useful in a clinical setting for the differentiation between urinary and vaginal secretions associated with vaginosis or urine or amniotic fluid. The device includes the use of indicators with a negatively charged group immobilized to a solid polymer substrate containing quaternary ammonium groups. In addition, the device includes a gaseous amine releasing reagent and an amine indicator. It is disclosed that the use of the polymer substrate containing quaternary ammonium groups has an advantage of sharpening the pH-dependent color transition. However, it has been found that these polymer substrates are less useful in non-clinical settings: the indicated pH of dry vaginal secretions is low enough to be misdiagnosed indicating vaginosis. Therefore, although the device disclosed in US Patent 5,897,834 is useful in a clinical environment where the health care professional applies vaginal discharge to the device and observes the color change, if it is integrated into a device usable by the patient, like a salva-slip, the device gives abundant results of false positives.
p00015There is a need for an indicator system that can differentiate between a specific biological fluid of interest and an interfering biological fluid such as urine. In addition there is a need for a device that can distinguish between normal vaginal secretions and those associated with loss of amniotic fluid or vaginosis. In addition, a system is also needed in which false positive results are minimized while reducing the amount of time required to achieve reliable results. Such a system is ideally usable by the patient to bring greater peace of mind and minimize unnecessary visits to the hospital. The characteristics of said indicator system should not change due to prolonged use or as a result of a dried wetting cycle and must distinguish between interfering biological fluids and minimize false positive readings. The present invention now overcomes these problems and satisfies these needs.
SUMMARY OF THE INVENTION
p00016The present invention, as defined in claim 1, overcomes the disadvantages of the state of the art by the use of an indicator system integrated in several self-usable products. In general, the invention comprises an article that includes an absorbent material to absorb a biological fluid secreted by a person and an indicator system that has at least one pH determining member and optionally, a reagent to react with the biological fluid to alter its pH so that secretion can be distinguished. The indicator system is associated with an absorbent material such that the biological fluids come into contact with the indicator system in such a way that reliable information on the pH of that fluid can be obtained.
p00017The article can be presented to the user in many ways. It is preferable, however, that the article be in the form of a swab, gauze, salva-slip, sanitary napkin, diaper or interlabial absorbent structure. In addition, any user, male or female, young or old, can use the article. Particular examples of the invention as presented herein are not intended to limit the scope of the invention, but simply to illustrate and represent the numerous potential ways in which the invention can be used.
p00018In general, the pH determining member can be anything that indicates the pH of a fluid. Preferably the pH determining member registers or indicates a change in pH after coming into contact with the biological fluid and is resistant to change due to prolonged use or wetting and drying cycles. Advantageously, the reagent used in the indicator system is one that reacts with the amniotic fluid, a secretion associated with a bacterial, fungal or yeast infection, or urine to change its pH.
p00019Preferably, the article has mounting means for positioning the absorbent body to receive the secreted fluids during normal user activity, said mounting means being, for example, an adhesive strip or other binding member.
p00020A preferred embodiment is one in which the secretion monitoring article has a substrate with a first pH indicator in a first area, a second pH indicator in a second area, and a reagent attached to the substrate in the second area , or alternatively a third area. The indicators are selected in such a way that substantial color transitions take place at different pH values. A liquid that contacts the substrate interacts with the indicators and the reagent. If the liquid has the pH of a fluid to be identified, at least part of the first area undergoes a substantial color change. The liquid can, however, be an interfering fluid with a pH that changes the color of the first indicator. Therefore, in one embodiment, the reagent is selected to react with the interfering fluid (for example), changing the pH of the liquid and consequently substantially changing the color of at least part of the second area. The presence of the second pH indicator acts as a guarantee against false positive results allowing a colorimetric differentiation of two fluids with a similar pH.
p00021In accordance with another feature of the present invention, the first pH indicator changes color at a pH substantially lower than the second pH indicator. Usually, the first area is different from the second area and the shape of the area may vary and be any geometric shape, number, letter, icon, word or a combination thereof.
p00022Another non-limiting embodiment of the invention is an article for secretion monitoring wherein the indicator system has at least one pH determining member having a chemical composition that reacts with biological fluids containing ammonium cations protonated differently than fluids. bodily that do not contain protonated amine cations. Typically, the indicator system is associated with the absorbent material such that biological fluids come into contact with the indicator system while being carried.
p00023Advantageously, the article for secretion monitoring can be used for the identification of infected urine. In this embodiment, the article comprises a body that includes an absorbent material to absorb urine from a person and an indicator system that has at least one indicator that has a chemical composition that reacts with normal urine differently than with infected urine. The indicator in this embodiment changes color when it comes into contact with the urine, but if the urine is infected the color change of the indicator is non-reversible.
p00024A further embodiment is one in which the article for secretion monitoring is specifically designed for the identification of vaginal secretions infected by bacteria. In this embodiment, the article comprises a body that includes an absorbent material to absorb vaginal secretions and an indicator system that has at least one indicator that has a chemical composition that reacts with candidiasis or normal vaginal secretions differently than infected vaginal secretions. by bacteria, where the indicator changes color when it comes into contact with vaginal secretions infected by bacteria that have a pH level above 5 and a higher concentration of amines than candidiasis or normal vaginal secretions.
p00025Another preferred embodiment of the invention comprises an article that includes a pH determining member with a composition that reacts differently to urine than to other biological fluids, such as amniotic fluid. The composition of the pH determining member is able to react differently due to certain chemicals that are present in substantial amounts only in the urine, and not in other biological fluids to be identified. The substrate containing the pH determining member is retained in the vicinity of a person's vaginal area for an extended period of time to absorb the fluids. After which the article is removed and observed to determine the health status of the person from whom the biological fluid was collected.
p00026Also included is a method of providing an indication of the health status of an apersone by providing a substrate to which a first pH indicator is attached in a first area, a second pH indicator in a second area, and a reagent bound to the substrate in the second area, where the color transitions of each of the two indicators take place at a substantially different pH. A liquid, such as a biological fluid, is applied to the substrate and the first and second area are inspected for a change in the color indicative of the person's state of health. In accordance with a feature of the present invention, the substrate is retained in the vicinity of a person's vaginal area for an extended period of time such as minutes, hours or even longer, to absorb secreted fluids.
p00027In accordance with an additional feature of the present invention, the first pH indicator is configured to substantially change color at the time of contact with amniotic fluid and the second pH indicator is configured to substantially change color at the time of contact with urine that reacts with the reagent. A preferred reagent is urease. Alternatively, the first pH indicator is configured to substantially change color at the time of contact with the vaginal secretions associated with vaginosis and the second pH indicator is configured to change color substantially at the time of contact with the urine that reacts With the reagent.
p00028A method of attaching an indicator to a substrate is also disclosed. The substrate can be made of many materials, for example, polypropylene, paper or cotton, polyester membranes and can be made of many structures including membrane, fabric, mesh, gauze, thread, fiber and sheet. A mixture of a pre-formed polymer (such as cellulose), a plasticizer, a wetting agent, an ion balance reagent and an indicator (alone or with a reagent such as urease) is prepared. In some cases it is preferable to add a solvent to the mixture. The mixture is applied to a substrate for example by dipping the substrate in the mixture or spraying or spreading the mixture in the substrate. The substrate is allowed to dry with the applied mixture. When dry, the indicator is attached to the substrate with the help of a polymer. This method is exceptionally useful when the indicators have a substantially negatively charged functional group such as an acetate or a sulphonate.
p00029An additional method of making a diagnostic article is also provided comprising the steps of attaching an indicator to a substrate, especially a neutral substrate, applying a surfactant solution to the substrate and allowing it to dry, preferably under vacuum, then once the surfactant is dry, an indicator solution or a solution with a reagent is applied to the substrate and allowed to dry, preferably under vacuum, wherein the indicator to be bound to the substrate is preferably a functional group substantially negatively charged with a cationic surfactant; and place the indicator in association with an absorbent body.
BRIEF DESCRIPTION OF THE DRAWINGS
p00030The invention is described herein, by way of example only, with reference to the accompanying drawings.
p00031FIGURES 1A-C are schematic top views of an embodiment of the article for secretion monitoring of the present invention with further details of the indicators applied to the substrate.
p00032FIGURE 2 is a schematic top view of a different embodiment of the article for secretion monitoring of the present invention.
p00033FIGURE 3 is a schematic perspective view of a different embodiment of the article for secretion monitoring of the present invention with a microporous membrane.
p00034FIGURES 4 AC are top schematic views of an embodiment of the article for secretion monitoring with two pH indicators.
p00035FIGURES 5 AB are schematic top views of an embodiment of the article for secretion monitoring with a pH indicating device that can distinguish between urine and other body fluids, such as amniotic fluid.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
p00036Before going into the details of the present invention, it should be appreciated that the present invention provides an article for secretion monitoring and a method for use that allows an inexperienced user to monitor the secreted biological fluids with confidence. The present invention allows the identification of a specific biological fluid even when there is a possibility of presence of an interfering biological fluid with a similar pH.
p00037The present invention is an improvement on the state of the art, providing an article for secretion monitoring that is more reliable and convenient for the user.
p00038In one embodiment of the invention, the article for secretion monitoring comprises a body that includes an absorbent material to absorb a biological fluid secreted from a person and an indicator system comprising at least one pH determining member and a reactant to react with the biological fluid to alter its pH so that the secretion can be distinguished, wherein the indicator system is associated with the absorbent material such that the biological fluids come into contact with the indicator system.
p00039In a second embodiment of the invention, the secretion tracking article comprises a body that includes an absorbent material for absorbing a biological fluid secreted from a person and an indicator system comprising a pH determining member consisting of a special composition that reacts with the biological fluid differently. An example of said pH determining member has a special composition that reacts with fluids containing protonated amine cations, such as urine, in a different way from that which reacts with other biological fluids that have a low proportion of protonated amine cations, Like the amniotic fluid.
p00040In yet another embodiment of the invention, the secretion tracking article comprises a body that includes an absorbent material for absorbing a biological fluid secreted from a person and an indicator system comprising a pH determining member consisting of a special composition that reacts with normal urine differently than with infected or protein-containing urine. In a non-limiting example, the indicator reacts with normal urine (pH 5-8), which changes color from yellow to green or turquoise. During the drying process the color change of the indicator that has come into contact with normal urine fades while it dries and turns yellow again. On the contrary, when the indicator comes into contact with infected or protein-containing urine, the indicator strip changes color from yellow to green or turquoise and does not fade when it is sedated. Advantageously, this embodiment is very suitable for all types of use, for example in pediatrics, geriatrics and gynecology, and can be presented to the user in many ways, preferably as a diaper or salva-slip.
p00041The article for secretion monitoring can be implemented using many methods and devices. In a preferred embodiment, the article of the present invention is implemented in a manner that can be easily used by unskilled personnel, specifically a user. The body of the article for secretion monitoring of the present invention comprising an absorbent material can be supplied to the user, for example, in the form of a pad, gauze, swab, fiber ball, but more preferably, as a sanitary napkin , diaper, salva-slip, and interlabial structure. The manufacturing details thereof are well known to someone skilled in the art and have been fully described in the prior art, for example US Patents 5,217,444, 5,897,864 and 6,149,590.
p00042In addition, any user, male or female, young or old, can use the article in a variety of ways. Particular examples of the invention as presented herein are not intended to limit the scope of the invention, but rather simply illustrate and represent the numerous potential ways in which the invention can be used.
p00043In one embodiment of the invention, an indicator system is composed of a pH determining member and a reagent is provided to be included in the body of the article for secretion monitoring. In another embodiment, an indicator system is composed of the pH determining member that reacts differently with different body fluids.
p00044The pH determining member of the indication system can be any pH determining device, for example as an indicator of color change (eg litmus paper) or a mobile pH probe. It is preferable, however, that the pH determining member is a color change indicator, as a pH determining member made of the pH indicator mixture described herein below and / or using the method of joining the mixture to a substrate. As will be discussed in more detail below, more than one pH determining member may be part of the indicator system. The pH indicator members must be able to determine substantially different pH ranges or able to react differently with different biological fluids to produce a different color change.
p00045In one embodiment the indicator system comprises a reagent. The reagent is used to distinguish the pH of the biological fluid that is being monitored from other biological fluids that could interfere with the results and possibly give a "false positive, stress and unjustified expense for the user. The reagent can be chosen based on the biological fluid to be monitored and the type of biological fluids that could interfere with the precise monitoring of this fluid. The reagent of the indicator system of the present invention is chosen to produce reaction products that substantially change the pH of a tested secretion when the secretion tested is either the fluid to be identified or its interfering fluid, or both. If the reagent is chosen to react with both fluids, the change in pH resulting from the reaction with the fluid to be identified must be different from the change in pH resulting from the reaction with the interfering fluid.
p00046In a preferred non-limiting embodiment of the present invention, when either amniotic fluid must be identified or vaginosis must be diagnosed, urease (CAS 9002-13-5) is chosen as reagent. If urine is present, urine reacts with urease, releasing ammonia in the secretion tested by raising its pH well above the pH of secretions related to amniotic fluid or vaginosis.
p00047The reagent can also be chosen to react only with the fluid to be identified, change the pH sufficiently to distinguish it from any possible interfering fluid. When the reagent is chosen to react only with the fluid to be identified, it is preferable that the reagent reacts with the amniotic fluid or a secretion associated with a bacterial, fungal or yeast infection and that the pH changes sufficiently to distinguish the fluid from other possible interfering fluids.
p00048In one embodiment of the invention, the indicator system has only one pH indicator and the reagent is selected to react with the fluid to be identified such that the pH is substantially changed such that the presence of the fluid can be easily identified. . In this embodiment of the invention, the pH indicator is selected to indicate the pH of the fluid to be identified after it has reacted with the reagent.
p00049In a preferred embodiment of the article for secretion monitoring, a means for mounting the article is included to facilitate the collection of the secreted biological fluid. An example of a mounting means that is well known in the art is an adhesive strip associated with the article. In a preferred embodiment the article has one or more adhesive strips. The user removes the release tape to expose the adhesive strip of the article and places the article on the crotch part of its undergarment. This prevents the item from moving out of position during regular use. The types of adhesive compounds that can be used are well known in the art.
Examples of secretion tracking articles
p00050The present invention will be exemplified by embodiments of the secretion tracking article of the present invention in the form of a salvage slip in Figures 1-5. The article can be configured to identify amniotic fluid and secretions associated with bacterial, fungal or yeast infection, such as infected vaginal secretions or urine. In addition, the article is designed to minimize false positive readings associated with interfering biological fluids.
p00051A preferred embodiment of the invention is one in which the indicator system comprises a first indicator, a second indicator and a reagent. The first system indicator of the present invention is chosen to identify a first pH. The first pH corresponds to the pH of the fluid to be identified. In addition, the first pH may also be that of the interfering fluid. When amniotic fluid is to be identified, a first indicator is chosen to indicate that a tested vaginal secretion has an amniotic fluid pH. Due to the similar pH of the urine and the amniotic fluid, said first indicator will also change color when exposed to urine. When vaginosis is to be diagnosed, a first indicator is chosen to indicate a typical pH of vaginosis secretions and consequently also of urine. In Figure 1A, a first indicator is applied in a first area 12 on a substrate 14 integrated in a save-slip 10. The first area 12 may be arranged as patterns, letters, words or icons, as described in US Pat. 5.97,834. In Figures 1A-C, the first indicator is nitrazine yellow, which is yellow at a pH below 7 and bluish violet at a pH above 7.
p00052The reagent of the indicator system of the present invention is chosen to produce reaction products that substantially change the pH of a secretion tested as described in detail above.
p00053The second pH indicator of the system of the present invention is chosen such that it indicates the change in pH as a result of the reaction with the reagent. For example, the second indicator in Figures 1A-C is m-cresol purple, m-cresol purple is yellow at a pH below 7.5 and is violet at a pH above 8.0. The second indicator and the reagent are applied in a second area 16 on the substrate 14, other than the first area 12 on the substrate 14, Figure 1A.
p00054In Figure 1B, the amniotic fluid 18 comes into contact with the save-slip 10. the amniotic fluid 18 comes into contact with the first area 12 and the second area 16. As the pH of the amniotic fluid 18 is between 7.0 and 7.5, the nitrazine yellow present in the first area 12 becomes bluish violet, spelling the word "AMNIO". It is clear to someone skilled in the art that if a small amount of fluid is applied to the save-slip 20, it is possible that only part of the first area 12 changes color. The m-cresol purple present in the second area 16 remains yellow.
p00055When the user of the salva-slip 20 in Figure 1B examines the salva-slip 10, he reads the word "AMNIO" and can go to a health care professional who can take the actions corresponding to a high degree of certainty of secretion of amniotic fluid.
p00056In Figure 1C, the urine 22 comes into contact with the save-slip 10. The urine 22 comes into contact with the first area 12 and the second area 16. Since the pH of the urine 22 is 7.2, the yellow of Nitrazine present in the first area 12 becomes bluish violet, spelling the word "AMNIO". Urine 20 reacts with the urease present in the second area 16, releasing ammonia. Ammonia increases the pH of the liquid present in the second area 16 to a pH of 9. As a result of the high pH, the m-cresol purple present in the second area 16 turns violet by spelling the word "NO".
<dl><dt>TABLE 1 </dt><dd /></dl>
<dl><dt>Indicator </dt><dd>Transition range Color change CAS </dd></dl>
<dl><dt>aqueous pH </dt><dd /></dl>
<dl><dt>1. Cresol Red </dt><dd>7.2-8.8 Yellow to reddish purple 1733-12-6 </dd></dl>
<dl><dt>two. Alizarin </dt><dd>5.5-6.8 Yellow to violet 72-48-0 </dd></dl>
<dl><dt>3. Bromcresol purple </dt><dd>5.2-6.8 Yellow to purple 115-40-2 </dd></dl>
<dl><dt>Four. Chlorophenol Red </dt><dd>5.2-8.8 Yellow to red 4430-20-0 </dd></dl>
<dl><dt>5. Nitrazine Yellow </dt><dd>6.0-7.2 Yellow to bright blue 5423-07-4 </dd></dl>
<dl><dt>6. Bromothymol blue </dt><dd>6.0-7.6 Yellow to blue 34722-90-2 </dd></dl>
<dl><dt>7. Bromoxylenol blue </dt><dd>6.0-7.6 Yellow to blue 40070-59-5 </dd></dl>
<dl><dt>8. Neutral red </dt><dd>6.8-8.0 Red to yellow 553-24-9 </dd></dl>
<dl><dt>9. Phenol Red </dt><dd>6.8-8.2 Yellow to red 34487-61-1 </dd></dl>
<dl><dt>10. Timol blue </dt><dd>8.0-9.2 Yellow to blue 81012-93-3 </dd></dl>
<dl><dt>eleven. Xylenol blue </dt><dd>8.0-9.6 Yellow to blue 125-31-5 </dd></dl>
<dl><dt>12. M-Cresol purple </dt><dd>7.4-9.0 Yellow to purple 2303-01-7 </dd></dl>
p00057When the user of the save-slip 24 in Figure 1C examines the save-slip 10, he reads the words "NO AMNIO". The user who became nervous with the unexpected loss of fluid immediately calms down and is relieved of the need for a stressful visit to a health care professional. It is clear to someone skilled in the art that arranging the first area 12 and the second area 16 to spell words is not necessary, and in alternative embodiments of the present invention the first area 12 and the second area 16 may have any shape. For example, in Figure 2, a salvage-slip 26 configured in accordance with the present invention is shown where each of the first area 28 is of a substantially circular shape and each of the second area 30 is substantially square in shape.
p00058When used in a medical environment, it is imperative that there is substantially no filtration of the components of the indicator system from the substrate to which the indicator system is attached. The union of indicators to a substrate is within the capabilities of someone skilled in the art. A family of chemical compounds that is suitable for use as a first indicator and a second indicator of the preferred embodiment of the present invention without filtration are indicators with negative functional groups. Suitable indicators include nitrazine yellow, thymol blue, bromothymol blue, xylenol blue, bromoxylenol blue, phenol red, m-cresol purple, chlorophenol red, bromocresol purple, alizarin, neutral red, and red cresol, see Table 1. a list of other suitable indicators can be found, for example, in US Patent 5,897,834. It is clear to someone skilled in the art that the indicators specifically mentioned herein are only examples and any suitable indicator can be used. In addition, there may be cases where the first indicator and / or the second indicator are composed of a combination of individual indicators.
p00059Another non-limiting embodiment of the indicator system of the present invention is an article for monitoring secretions for the identification of vaginal infections such as bacterial vaginosis (BV). In accordance with the present invention, an indicator system is made with a first indicator that indicates the presence of a fluid with a pH of about 4.7 to 7.0. The first indicator may be chosen, for example, from one or more of the group that includes nitrazine yellow, bromothymol blue and bromoxylenol blue. As can be seen in Table 1, these three indicators typically show a bluish color when exposed to a fluid with a pH above 7.0. The second indicator can be chosen, for example, from the group that includes phenol red, thymol blue, xylenol blue and m-cresol purple. As can be seen in Table 1, at the time of exposure to a fluid with a pH above 8.0 these four indicators turn red, blue, violet and violet, respectively. The reagent added to the second embodiment of the article for secretion monitoring of the present invention is, for example, urease.
p00060As discussed herein above, the urine of a healthy patient has a pH between 5.0 and 8.0. A patient who has BV also has secretions with a pH between 4.7 and 6.5. If the liquid examined in the second embodiment of the article for secretion monitoring of the present invention is associated with BV, the first indicator changes color while the second indicator remains yellow. If the examined fluid contains urine, the first indicator changes color. In addition, urease reacts with urine, producing ammonia, raising the pH of the fluid, and consequently causing the second indicator to change color.
p00061The following examples set forth preferred embodiments of the present invention.
p00062Example 1: Reduce erroneous readings of devices that change color that give a high pH indication in vaginal secretion
p00063The following example discloses the solution to produce an indicator that does not need a color chart or scale to read results, that shows the user a stable indication for a few days, and that does not filter even when it comes into contact with liquids for any duration of time practice. For the non-invasive continuous follow-up version, the invention discloses a solution to avoid false positive readings due to urine contamination.
p00064The device is an adhesive label or a slip shield that contains two different indicator strips, incorporated between layers of the one-way absorbent tissues. The two indicators have a color transition point at different pH values. The color reactions of the two indicators also have different reversibility in vaginal discharge from urine.
p00065The first indicator strip changes color to stable blue, when it detects high pH in vaginal secretions (pH strip). The pH strip contains the yellow Nitrazine pH indicator, which has a pKa of 6.6 in aqueous solution, and with the specific innovative composition, changes color when the vaginal secretion has a pH level of 5.0 or higher (The same specific innovative composition produces indicators for several pH levels, using other negatively charged members of the ionizable phenol group).
p00066The second strip is a control strip to detect urine (urine strip) l. The urine strip contains urease, an enzyme that hydrolyzes urea to ammonia, and a purple pH indicator of m-Cresol that has a pKa of 8.2 in aqueous solution. When the strip is in contact with urine, hydrolyzed ammonia raises the pH of the medium and the color of m-Cresol purple changes from yellow to gray / dark green.
p00067In a case where vaginal discharge with high pH (5.0 - 7.0) will reach the strips only the pH strip will change color and the change will remain stable for a few days.
Preparation method
p000681) pH strip:
p00069Step 1: To 10 ml of Acetone add 150 mg of Cellulose Acetate, 107 μl of Dibutyl Phthalate, 23 μl of Aliquat, 150 μl of 2-Ethoxy ethanol and 2.4 mg of nitrazine yellow dissolved in 150 μl of DDW. Step 2: Stir the mixture for a few minutes to complete the dissolution. Step 3: Cover a polyester monofilament screening cloth with the polymer solution (cover other Acetone-insensitive materials will produce several devices for several using instructions, with the same characteristics).
p000702) Urine strip:
p00071First layer-step 1: To a DDW of 4.15 mL add 45 mg of PVP, 0325 mL of urease / glycerol solution. First layer-step 2: Cover a polyester monofilament screen with the polymer solution. First layer-step 3: The coated strips are dried overnight at room temperature. Second layer-step 1: To 10 mL of THF add 150 mg of Cellulose acetate, 107 µl of Dibutylphthalate, 23 µl of Aliquat, 150 μl of 2-Ethoxy ethanol and 1.2 mg of m-Cresol purpura dissolved in 120 μl of 1-Propanol. Second layer-step 2: Stir the mixture for a few minutes to complete the dissolution. Second layer-step 3: Cover the strip with the second polymer solution. Second layer-step 4: After drying overnight wash the strip in a saline solution.
p00072The device may be in the form of a swab with a tip produced in the same manner as mentioned above, under the heading: pH strip. The tip can be prepared using a short strip, rolled on the swab stick, or covering the tip of an integrated swab (implementation step 4), where the tip consists of any screening cloth.
p00073EXAMPLE 2: A device capable of accurately distinguishing between a loss of amniotic fluid or a discharge discharge vaginal discharge of high pH and humidity caused by urinary incontinence
p00074Due to the severe consequences of the loss of amniotic fluid, pregnant women suffer severe stress and tend to seek a medical care provider at the time of any sensation of moisture in the vagina area. Common ways to check for the presence of amniotic fluid are by examining the pH of vaginal secretions with pH indicators such as Nitrazine indicators, running the Fern test or visually identifying the source of the loss.
p00075The amniotic fluid has a pH level that varies between 6-8 and can be identified by a purple-blue color of a Nitrazine indicator. Like urine, it has a pH level that varies between 5.0 - 8.0, measuring pH levels as a single criterion can lead to erroneous decisions. As the other two ways can only be done in clinics and hospitals, and by qualified personnel, there is no practical solution for home monitoring. In some situation, after tests of amniocentesis and other occasions such as high-risk pregnancies, there is the possibility of small amniotic losses that can be detected only by continuous monitoring.
p000765 Current solutions and previous inventions fail to serve as a continuous monitoring device for domestic use, since they filter fluids, the color change is unstable, and the overlap between the pH level of the amniotic fluid and the pH level of the Urine confuses users in how 30% of cases.
p0007710 Overlapping pH levels between amniotic fluids and urine is also a major disadvantage for doctors who treat patients with sensations of moisture. Providing pregnant women with a continuous monitoring device for domestic use, which distinguishes amniotic fluid losses from urinary incontinence are false alarms, allowing the reading of the results on a personal calendar and discretion, and detects any small amniotic loss instantly, can on the one hand help reach the user at
p00078fifteen hospital on time when needed, and on the other hand avoid unnecessary hospitalization and stress for the concomitant patient.
p00079Providing doctors with a reliable clinical instant detection item, which distinguishes amniotic fluid losses from urinary incontinence without false alarms, can serve them much better than available solutions
p00080twenty nowadays.
p00081The article can be an adhesive label or a slip shield with a built-in indicator strip. The strip contains the pH indicator of Nitrazine yellow which has a pKa of 6.6 in aqueous solution.
p0008225 The reaction of the indicator with the amniotic fluid (pH 6-8) changes the color from yellow to stable dark blue. The reaction of the indicator with urine (pH 5-8) changes the color to pale green or pale turquoise. Urine with a lower pH of 5 - 5.5 does not change the color of the indicator.
p00083The difference between the color reaction of the indicator with the amniotic fluid and with the urine consists of two parameters: the chemical composition of the fluids and the chemical structure of the indicator polymer.
p00084The following two equations demonstrate the different reactions
35 KEY:
p00086X- = base NR4 + = ion equilibrium reagent R- O-NR4 + = -phenolate -reactive ion balance
p0008740 The proportion of ion equilibrium reagent against the indicator in the polymer matrix controls the color transition point and color stability during drying. In the drying process the ion pair phenolate (the active site of the indicator) - ion equilibrium reagent is stable, which causes a stable color yield (equation 1 - the relative concentration of the component does not change). In a different case where the concentration of
p00088Four. Five ion balance reagent in the polymer is higher, the color of the indicator becomes dark while it dries. The darkening of the color during drying dries is due to the deprotonation of continuity of the indicator phenol by the basic excess of the ion balance reagent (equation 1 - during drying the concentration of the base becomes high and the equilibrium turns to the right). The optimal molar ratio of the ion equilibrium reagent with the indicator is 10: 1.
p00089fifty The ammonium ions in the solution react as the ion equilibrium reagent and compete with the active phenolate site. During drying, the phenolate-ammonium ion pair spontaneously hydrolyzes to give a protonated yellow phenol (equation 2) while the phenolate-reactive ion equilibrium pair is stable (equation 1).
p00090In a case where the medium contains ammonium ions the color changes governed by the relative concentration of the ion equilibrium reagent in the polymer and the ammonium ion in the medium.
p00091For example. In 100 mM of regulatory solution containing 25 mM ammonium ions, the concentration of ammonium is two orders of magnitude higher than the ion equilibrium reagent in the polymer. These differences govern the turquoise color in the solution and the pale color in drying.
p00092Urine contains ammonium ions in a concentration of 30-50 mM; the amniotic fluid does not contain any substantial amount of ammonium ions, thus causing no pale influence as urine does
p00093Preparation method
p00094Step 1: To 10 ml of Acetone add 150 mg of Cellulose Acetate, 107 μl of Dibutyl Phthalate, 23 μl of Aliquat, 150 μl of 2-Ethoxy ethanol and 2.4 mg of nitrazine yellow dissolved in 150 μl of DDW. Step 2: Stir the mixture for a few minutes to complete the dissolution. Step 3: Cover a monofilament polyester screening cloth with the polymer solution to give the desired product
p00095The device may be a swab with a tip produced in the same manner as mentioned above, under the heading: pH strip. The tip can be prepared using a short strip, rolled on the swab stick, or covering the tip of an integrated swab (implementing step 3) where the tip consists of any screening cloth.
p00096EXAMPLE 3: A device capable of accurately distinguishing between normal urine and infected urine
p00097The reappearance of urinary tract infections in certain patients presents the need to quickly and easily diagnose if the patient has another urinary tract infection. Currently, to determine if a patient has a urinary tract infection they must make an appointment to visit a doctor. In addition, if the patient is susceptible to the recurrence of urinary tract infections, they should make regular visits to the doctor's office to ensure that the infection has not reappeared. Having a device that would allow the user to determine if they have a new urinary tract infection would minimize the stress and time spent visiting the doctor's office and would result in a faster diagnosis of the infection, resulting in a reduction in pain suffered by the patient and a more timely treatment of the infection.
p00098The article in this example is a diaper or slip-shield with an indicator that can distinguish between normal and infected urine. The user carries the article in such a way that urine can come into contact with the article. The reaction of the indicator with urine (pH 5-8) changes the color from yellow to green or turquoise. The drying process of the indicator strip at room temperature is short (5 minutes). When normal urine comes into contact with the indicator strip the color changes to pale during drying. The color change is completely reversible and the strip turns yellow again. on the other hand when infected urine comes into contact with the indicator strip the color changes to green or turquoise and remains constant during drying.
p00099The reversibility of color changes depends on two different environmental factors:
p001001. Chemical environment:
<dl><dt>to.</dt><dd> The pH level of the fluid - a higher pH level than pKa gives a stable color change. </dd></dl>
<dl><dt>b.</dt><dd> Solution regulatory capacity - in weak regulatory solution the indicator plays the role of weak acid and the reaction is reversible, while in strong regulatory solution the color change is stable. </dd></dl>
<dl><dt>c. </dt><dd>Content of ammonium salts in the solution - explained extensively in EXAMPLE 2. </dd></dl>
p00101two. Biological environment:
p00102to. The presence of proteins in the urine gives a stable color change and the reaction is not reversible.
p00103Infected urine provides a stable color change to the indicator, this color change is not reversible. In addition, the presence of bacteria in the vaginal secretion fluid also gives a stable color change so that the color change is not reversible.
p00104EXAMPLE 4: A device capable of distinguishing between normal vaginal secretions or candidiasis and vaginal secretions infected with bacteria
p00105In this embodiment, applicants have been able to provide information regarding two of the Amsel criteria with a single indicator.
p00106The article in this example is typically a slip shield with an indicator that can distinguish between normal vaginal secretions or candidiasis and vaginal secretions infected with bacteria. The user carries the article in such a way that urine can come into contact with the article. The indicator is designed to change color when the secretion has a pH above 5 and high concentrations of amines. Advantageously, only one indicator is necessary to distinguish detecting a secretion infected with bacteria, being able to determine two of the criteria of Amsel, pH and concentration of amines. Other indicators may be present in the article, but are not necessary to determine whether the user has vaginosis.
p00107The user carries the item and if the user has bacterial vaginosis, vaginal discharge infected with bacteria will cause the indicator to change color due to the high concentration of amines and the pH above 5. While, a normal vaginal discharge or Candidiasis will not cause the indicator to change color as they do not have a pH above 5 or a high concentration of amines. In this context a high concentration of amines refers to a concentration above about 0.4 mM to 0.5 mM.
Improved methods to join indicators to a substrate
p00108Details and variations concerning the method of manufacturing an article for secretion monitoring to implement the indicator system of the present invention or apply the method of the present invention are well described in the state of the art.
p00109As described hereinbefore, US Patent 5,897,834 describes a solid pre-formed polymer with which quaternary ammonium groups are covalently bonded. The negatively charged indicators are not covalently linked to the polymer. The non-covalent bonds are strong enough so that the bound indicators are not filtered in an aqueous solution. In addition, the indicators bound to the polymer have an acute color transition of pH, allowing a precise determination of the pH of the applied fluid. The polymer can be applied to various substrates. However, the indicators linked to these polymers are less useful in non-clinical settings since the indicated pH of vaginal secretions after drying is lower than that of recent vaginal secretions, leading to false positive results.
p00110An appropriate method for attaching indicators to a substrate is disclosed so that the indicators are not filtered out in an aqueous fluid. Especially suitable indicators are those with a negatively charged group, such as those listed in Table I or, for example, in US Patent 5,897,834. The disclosed polymer is exceptionally suitable for joining the indicator system of the present invention with a substrate. In addition, experiments show that unlike other methods and polymers known in the art, changes in the color of the bound indicator according to the disclosed methods are rapid. The color is maintained for a long period of time and even when the applied liquid dries. Repeated drying and wetting cycles do not change the color either. Therefore, in practical terms, there is time for a user to go to a health care professional without changing the color of the indicator.
Application of the indicator to a substrate
p00111In a first method of attaching an indicator to a substrate, an indicator is mixed with a preformed polymer in a suitable solution and then applied to the substrate.
p00112In more detail, a polymer solution containing dry pre-formed polymer, plasticizer, a wetting agent, an ion balance reagent, a solvent and an indicator is prepared. When the method is implemented, a reagent is also added as described.
p00113The preformed polymer can be selected from several preformed polymers, although cellulose polymers such as nitrocellulose, cellulose acetate or ethyl cellulose are preferred. The preformed polymer makes up 20% to 50% of the weight of the solution. It is preferred that the polymer make up 25% to 45% of the solution, it is more preferred that the polymer make up 30% to 43% of the solution, and it is most preferred that the polymer make up 36% at 39% by weight of the solution. As is clear to someone skilled in the art, it is also possible to use a combination of suitable preformed polymers when a polymer solution is made.
p00114Although any suitable plasticizer can be used, bis- (2-butoxyethyl) adipate (BBPA, CAS 14118-4), bis- (2-ethylhexyl) sebacate (DOS, CAS 122-62-3), diethyl phthalate ( DEP, CAS 84-66-2) or dibutyl phthalate (DBP, CAS 84-74-2). The plasticizer makes up 15% to 40% of the weight of the solution, it is preferred that the plasticizer make up 20% to 35% of the solution, it is more preferred that the plasticizer make up 25% to 31% of the solution. the solution, and most preferred is that the plasticizer comprises 27% to 29% by weight of the solution. As is clear to someone skilled in the art, it is also possible to use a combination of suitable plasticizers when a polymer solution is made.
p00115Although any wetting agent can be used, triethylene glycol, ethylene glycol, sorbitol or 2-ethoxy ethanol are preferred. The wetting agent makes up 15% to 45% of the weight of the solution. It is preferred that the wetting agent comprises 21% to 40% of the solution, it is more preferred that the wetting agent comprises 26% to 34% of the solution and it is most preferred that the wetting agent comprises a 29% to 31% by weight of the solution. As is clear to someone skilled in the art, it is also possible to use a combination of suitable wetting agents when a polymer solution is made.
p00116Although any ion equilibrium reagent can be used, tricaprilylmethyl ammonium chloride (Aliquat 336, CAS 5137-55-3) tridodecylmethyl ammonium chloride (TDMAC. CAS 7173-54-8) or cetyltrimethyl ammonium chloride ( CTAC, CAS 112-027). The ion equilibrium reagent makes up 0.1% to 10% of the weight of the solution. It is preferred that the ion equilibrium reagent comprises from 1% to 8% of the solution, it is more preferred that the ion equilibrium reagent comprises from 3% to 7% of the solution, and most preferred is that the ion equilibrium reagent comprises 4% to 6% by weight of the solution. As is clear to someone skilled in the art, it is also possible to use a combination of suitable ion balance reagents when a polymer solution is made.
p00117The components of the solution are added in such a way that the sum of the weights of the pre-formed polymer, the plasticizer, the wetting agent and the ion balance reagent is equal to 100%.
p00118The desired indicator is added to the solution. Although any suitable indicator can be used, it is preferred that the indicator molecules have a negatively charged functional group such as acetate or sulfonate. More preferably, the indicators used, separately or in combination, are chosen from among the indicators listed in Table 1 and in US Patent .897,834. The total amount of indicator added is 0.05% to 5% of the weight of the polymer solution as described above. It is preferred that the indicator is 0.05% to 3% of the polymer solution, it is more preferred that the indicator is 0.1% to 1% of the polymer solution, and most preferred is the indicator is 0.2% to 0.4% of the weight of the polymer solution.
p00119When it is desired to add a reagent in preparation of the indicator system of the present invention, the reagent is added to the polymer solution. For example, when urease is used, any suitable amount of urease may be added although it is preferred that the urease concentration be about 10 units per 0.01% -0.1% indicator added to the polymer solution.
p00120In addition, an amount of solvent is added that is suitable to easily make any solution / indicator mixture applied. Typically, 150 mg of polymer solution is dissolved in between 1 ml and 30 ml of solvent, preferably between 5 ml and 15 ml of solvent. Although any solvent or mixture of suitable solvents may be used, ethyl acetate or substantially volatile ethers such as diethyl ether, isopropyl ether, t-butyl methyl methyl ether or tetrahydrofuran are preferred.
p00121Once the mixture is prepared, it is applied by any suitable method to the substrate. The application can be done, for example, by spraying or spreading the mixture in the substrate, or by immersing the substrate in the mixture. The substrate may be of many suitable materials known in the art such as polyester membranes, polypropylene membranes, cellulose membranes, paper, cotton or linen. The structure of the substrate can be, for example, a fiber, a mesh, a gauze, a fabric or a membrane. The solvent in the mixture is allowed to evaporate. Once the mixture dries in the substrate, the substrate is integrated into whatever desired secretion tracking article, such as a salvage slip.
p00122As is clear to someone skilled in the art when the indicator system of the present invention is implemented, a first mixture is made with a first indicator, and a second mixture is made with a second indicator and a reagent, both mixtures have been described in present it above. Each of the two mixtures is applied to the area in the substrate, as described hereinbefore. Preferably the application area of the first mixture is substantially different from the application area of the second mixture.
p00123In certain applications, the liquid to be tested may contain biological polymers such as proteins or fats. For example, amniotic fluid and urine often contain proteins. Biological polymers can clog pores in the substrate reducing the effectiveness of the test method. This can be exceptionally significant in salva-slip applications such as Salva-Slip 32 shown in Figure 3. In such a case, it is preferable to interpose a microporous membrane 34, such as a dialysis membrane (for example, cellulose membrane, catalog No. D9402, Sigma-Aldrich, St. Louis MO), between the indicator substrate 36 and a secretion source 38 40. The large size materials 42 in the secretion 40 cannot penetrate the microporous membrane 34 while the fluid component 44 of the secretion penetrates the microporous membrane 34 to react with the indicator substrate
p0012436. The salvage-slip 32 in Figure 3 further includes two side fins 46 (only one is visible in Figure 3) configured to allow the attachment of the salvage-slip 32 to an undergarment of a user, so as to maintain the Salva-slip 32 in the vicinity of a user's vagina.
p00125In a second method of attaching an indicator to a substrate, a substrate is first treated with a surfactant solution. After the solution dries, an indicator solution is applied to the substrate. The substrate can then be integrated into a product.
p00126Although any surfactant can be used, when it is desired to bind negatively charged indicators to a neutral substrate, a surfactant with a cationic functional group is used, preferably Aliquat 336, TDMAC or CTAC. Although any suitable solvent or mixture of solvents can be used, ethyl acetate or substantially volatile ethers such as diethyl ether, isopropyl ether, t-butyl methyl methyl ether or tetrahydrofuran are preferred. The surfactant is dissolved in the solvent at any suitable concentration. It is preferred that the surfactant comprises 0.01% to 2% of the solution, it is more preferred that the surfactant comprises 0.1% to 0.5% of the solution, and it is most preferred that the surfactant make up 0.15% to 0.25% by weight of the solution. As is clear to someone skilled in the art, it is also possible to use a combination of suitable surfactants. The surfactant solution is applied to the substrate. The application is made, for example, by spraying or spreading the mezcal in the substrate, or by immersing the substrate in the mixture. The substrate may be of many suitable materials known in the art such as polyester membranes, polypropylene membranes, cellulose membranes, paper, cotton or linen. The structure of the substrate can be, for example, a fiber, a mesh, a gauze, a fabric or a membrane. The solvent of the surfactant solution is allowed to evaporate. Although the solvent can be allowed to evaporate at ambient pressure, it is preferable to evaporate the solvent under vacuum, preferably at a pressure of less than 600 mm Hg, more preferably less than 200 mm Hg, and even more preferably less than 100 mm Hg.
p00127After the solvent of the surfactant solution has evaporated, an indicator solution is applied to the substrate. Although any solvent or mixture of solvents may be used, ethyl acetate or substantially volatile ethers such as diethyl ether, isopropyl ether, t-butyl methyl ether or tetrahydrofuran are preferred. Although any suitable indicator can be used it is preferred that the indicator molecules have a negatively charged functional group such as acetate or sulfonate when the surfactant used is a cationic surfactant. More preferably, the indicators used, separately or in combination, are chosen from those listed in Table 1 or, for example, in US Patent 5,897,834. The amount of indicator added is 0.00001% to 1% of the weight of the indicator solution as described above. It is preferred that the indicator is 0.0001% to 0.1% of the indicator solution, it is more preferred that the indicator is 0.001% to 0.01% of the indicator solution, and most preferred is that the indicator is from 0.002% to 0.004% of the weight of the indicator solution.
p00128When it is desired to add a reagent in preparation of the indicator system of the present invention, the reagent is added to the indicator solution. For example, when urease is used, any suitable amount of urease can be added. Although any suitable concentration of urease can be used, a concentration of between 1 and 100 units / ml is preferred. A concentration of 2 and 50 units / ml is more preferred and a concentration of 5 and 20 units / ml is even more preferred.
p00129In a further embodiment of the present invention, a reagent solution is prepared separately from the indicator solution. When urease is used as a reagent, any suitable concentration of urease can be used. it is preferred that a concentration of between 1 and 100 units / ml of urease be used, a concentration of 2 and 50 units / ml and a concentration of 5 and 20 units / ml is even more preferred.
p00130The indicator solution (or indicator / reagent solution) is applied to the substrate. The application can be made, for example, by spraying or spreading the indicator solution in the substrate, or by immersing the substrate in the indicator solution. The solvent of the indicator solution is allowed to evaporate. Although the solvent can be allowed to evaporate at room pressure, it is preferable to evaporate the solvent under vacuum, preferably at a pressure of less than 600 mm Hg, more preferably less than 200 mm Hg, and even more preferably less than 100 mm Hg.
p00131When a reagent solution is prepared separately from the indicator solution, the reagent solution is applied substantially in the same manner as described hereinbefore, or before or after the application of the indicator solution.
p00132Regardless of the exact concentration of the indicator solution and the surfactant solution used, it is preferable to apply an amount of each of the solutions such that the molar concentration of the surfactant applied per area of substrate unit is approximately one hundred times larger than the molar concentration of the indicator applied per unit area of the substrate. The indicator solution is applied to the substrate in areas where the surfactant had been previously applied.
p00133As is clear to someone skilled in the art, when the indicator system of the present invention is implemented, a first solution is made with a first indicator, and a second solution is made with a second indicator and a reagent, both solutions as has been described hereinbefore. Each of the two solutions is applied in different areas of the substrate, as described hereinbefore.
EXAMPLE 5:
p00135Solution A: 370 mg of cellulose acetate, 280 mg of DBP, 150 mg of sorbitol, 150 mg of ethoxyethanol, 50 mg of TDMAC were combined. 3 mg of Bromothymol Blue was added, 20 ml of THF was added. The solution was vigorously stirred.
p00136Solution B: 370 mg of cellulose acetate, 280 mg of BBPA, 300 mg of ethylene glycol, 50 mg of TDMAC were combined. 3 mg of m-cresol purple and 30 units of urease were added. 20 ml of 20 THF was added. The solution was vigorously stirred.
p001371st. A cotton gauze was dipped in Solution A. When the solution dried, the cotton gauze was cut in half. The first half was immersed in a pH 7 test solution. The first half turned purple. The first half was allowed to dry at ambient conditions, without substantial color change. After three hours, the second half was immersed in a pH 7 test solution. The second half turned purple. The colors of the first half and the second half were substantially the same. 1 B. A cotton gauze was dipped in Solution B. When the solution dried, the cotton gauze was cut in half. The first half was submerged in urine. The first half turned violet. The first half was allowed to dry at ambient conditions, without substantial color change. After three hours, the second half was submerged in urine. The second half turned violet. The colors of the first half and the second half were substantially the same. 1 C. Solution A and Solution B were applied in alternate strips in a cotton gauze with a density of about 50 ul / mm2. Amniotic fluid was applied to the gauze, changing the color of the strips of Solution A to purple. Urine was applied to the gauze, changing the color of the strips of Solution B to violet. the gauze was allowed to dry at ambient conditions for three hours and cut in half. Urine was applied to the first half. The colors of the strips in the first half and in the second half of the gauze were substantially the same.
EXAMPLE 6:
p00139Three solutions were prepared:
p00140Solution A: 0.2% Aliquot in DDW (doubly distilled water); Solution B: 10 units / ml urease and 0.003% m-cresol purpura; and Solution C: 0.003% nitrazine yellow in isopropyl ether.
p00141A nitrocellulose membrane was immersed in Solution A and transferred to an atmosphere of 50 mm Hg. After 30 minutes, the membrane was removed from the vacuum. Solution B was applied in a pattern that resembled the word "NO" at a density of 50 μl / mm2. Solution C was applied in a pattern that resembled the word "AMNIO" at a density of 50 μl / mm2. The membrane was transferred to an atmosphere of 50 mm Hg. After 30 minutes, the membrane was removed from the vacuum. The membrane was immersed in a pH 7 test solution. The word AMNIO appeared in purple. After drying at ambient conditions for three hours, no substantial color change was observed. The membrane was submerged in urine. the word NO appeared in violet.
p00142It is clear to someone skilled in the art that the present invention is not limited by the embodiments described herein but also refers to many types of conventional modifications thereof, which are within the scope of the claims.
Item construction method
p00143Figures 4A-C and 5A-B provide visual examples of two non-limiting examples of methods of constructing the article. Figures 4A-C show an article in the form of a salvage-slip 50 constructed with two indicators 52 and
p0014454 In Figure 4A, salva-slip 50 is constructed with a pH indicator 52 to detect normal biological fluids and a second pH indicator with a high pH dye and a reagent, such as urease, to detect interfering biological fluids, such as the urine. Figure 4B shows the salvage-slip 50 in which a normal fluid, without an interfering fluid, changes the color 56 of the pH indicator 52. On the contrary, Figure 4C shows the salva-slip 50, where an interfering biological fluid, such as urine, changes the color 58 of the second pH54 indicator.
p00145In a separate embodiment, the article can be made with only a single indicator as shown in Figures 5A and 5B. Figure 5A shows the article in the form of a salva-slip 60, which comprises an adhesive label 64, with an indicator 62 constructed so as not to react with an interfering biological fluid such as urine. when the biological fluid to be detected comes into contact with the indicator, as shown in Figure 5B, the indicator changes color 66, while if the indicator comes into contact with urine it will not change colors.
Contents8
52 members in 10 offices
Priority claims5
| Document | Office | Kind | Date |
|---|---|---|---|
| 907926 | United States of America | – | |
| 90792601 | United States of America | A | |
| 365684P | United States of America | – | |
| 36568402 | United States of America | P | |
| 0200588 | Israel | W |
Members52
| Document | Office | Kind | |
|---|---|---|---|
| US2003017605A1 | United States of America | A1 | |
| CA2454338A1 | Canada | A1 | |
| WO03007997A2 | World Intellectual Property Organization (WIPO) | A2 | |
| US2003166293A1 | United States of America | A1 | |
| US6627394B2 | United States of America | B2 | |
| WO03007997A3 | World Intellectual Property Organization (WIPO) | A3 | |
| CA2504323A1 | Canada | A1 | |
| WO2004040253A2 | World Intellectual Property Organization (WIPO) | A2 | |
| EP1419268A2 | European Patent Office (EPO) | A2 | |
| AU2003278582A1 | Australia | A1 | |
| IL159918A0 | Israel | A0 | |
| WO2004040253A3 | World Intellectual Property Organization (WIPO) | A3 | |
| US6921647B2 | United States of America | B2 | |
| EP1565140A2 | European Patent Office (EPO) | A2 | |
| JP2006504954A | Japan | A | |
| US2007003993A1 | United States of America | A1 | |
| AU2002354890B2 | Australia | B2 | |
| CA2670403A1 | Canada | A1 | |
| WO2007060649A2 | World Intellectual Property Organization (WIPO) | A2 | |
| US2007134740A1 | United States of America | A1 | |
| CA2632588A1 | Canada | A1 | |
| WO2007069240A2 | World Intellectual Property Organization (WIPO) | A2 | |
| AU2007203374A1 | Australia | A1 | |
| US7314752B2 | United States of America | B2 | |
| WO2007069240A3 | World Intellectual Property Organization (WIPO) | A3 | |
| AU2003278582B2 | Australia | B2 | |
| US2008086060A1 | United States of America | A1 | |
| EP1960762A2 | European Patent Office (EPO) | A2 | |
| IL159918A | Israel | A | |
| AU2007203374B2 | Australia | B2 | |
| IL192112A0 | Israel | A0 | |
| WO2007060649A3 | World Intellectual Property Organization (WIPO) | A3 | |
| EP1960762A4 | European Patent Office (EPO) | A4 | |
| AU2007203374C1 | Australia | C1 | |
| US7541177B2 | United States of America | B2 | |
| US2009275071A1 | United States of America | A1 | |
| EP1419268A4 | European Patent Office (EPO) | A4 | |
| US2010136707A1 | United States of America | A1 | |
| JP4571502B2 | Japan | B2 | |
| IL209249A0 | Israel | A0 | |
| US7947467B2 | United States of America | B2 | |
| EP1565140A4 | European Patent Office (EPO) | A4 | |
| US2012003685A1 | United States of America | A1 | |
| US8097433B2 | United States of America | B2 | |
| IL168193A | Israel | A | |
| EP1419268B1 | European Patent Office (EPO) | B1 | |
| CA2454338C | Canada | C | |
| DK1419268T3 | Denmark | T3 | |
| PT1419268E | Portugal | E | |
| CA2504323C | Canada | C | |
| ES2399352T3This record | Spain | T3 | |
| IL209249A | Israel | A |
Numbers
- Publication
- 2399352
- Application
- 2751589
Titles2
- Spanish
- Artículos para la monitorización de secreciones
- English
- Items for secretion monitoring
Classification
- IPC, 5
- C12Q1 62
- A61B5 00
- A61B10 00
- A61F13 42
- C12Q1 34