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WO2016061490A1 - Indication non visuelle d'un composé chimique indésirable dans une substance à ingérer - Google Patents

Indication non visuelle d'un composé chimique indésirable dans une substance à ingérer Download PDF

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Publication number
WO2016061490A1
WO2016061490A1 PCT/US2015/055994 US2015055994W WO2016061490A1 WO 2016061490 A1 WO2016061490 A1 WO 2016061490A1 US 2015055994 W US2015055994 W US 2015055994W WO 2016061490 A1 WO2016061490 A1 WO 2016061490A1
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Prior art keywords
indicator
user
substance
taste
visual
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Stephen F. Holmes
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Priority claimed from US14/517,730 external-priority patent/US8978468B2/en
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/0001—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00 by organoleptic means
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/02—Food
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/02—Food
    • G01N33/14—Beverages

Definitions

  • the present invention relates to methods and systems for detecting and indicating the presence of undesirable substances in ingestible substance such as food or beverages. More specifically, the invention relates to systems and methods for nonvisually and concealably indicating and detecting the presence of unwanted or undesired drugs in a beverage or food.
  • Certain drugs have been used to facilitate sexual assaults on unsuspecting victims.
  • the drug is surreptitiously placed in the intended victim's beverage or food. This is a relatively easy process because this class of drug typically provides little or no indication of its presence, creating little or no color change, detectable smell, or change in flavor in the drugged substance that could detected by the intended victim.
  • the drugs typically used for this purpose can create weakness, confusion, and/or unconsciousness in the victim, who typically has no memory of what transpired while they were drugged.
  • Some pharmaceuticals which have been used as date rape drugs include flunitrazepam (trade name ROHYPNOL, and street name “roofie”), gamma-hydroxybutyric acid (or GHB), and ketamine. Similar acting drugs may also be used as date rape drugs, such as clonazepam (trade name KLONOPIN in the U.S. and RIVOTRIL in Mexico), alprazolam (trade name XANAX), and other benzodiazepines including temazepam (trade name RESTORIL) and midazolam.
  • test system that can verify the presence or absence of a target drug in a food or beverage without requiring a visual evaluation, so that the person suspected of tampering with the food or beverage need never know that they are under suspicion.
  • the invention includes a non-visual verification method that includes selecting an ingestible substance, using a detector on the selected, ingestible substance, and non-visually indicating whether a target substance is present in the ingestible substance.
  • the invention includes a non-visual verification method that includes selecting an ingestible substance; making a detector for non-visual display of whether a target substance is present in the selected, ingestible substance; operating the detector and non-visually indicating whether a target substance is present in the ingestible substance.
  • the invention is characterized as a non-visual verification system, where the non-visual verification system includes a non-visual, sensing mechanism constructed to verify whether a target drug is present in an ingestible substance by producing a non-visual indicator that can be understood by a user.
  • the invention is characterized as a non-visual verification device, where the non-visual verification device includes a non-visual, sensing component constructed to verify whether a target drug is present in an ingestible substance by producing a non-visual indicator that can be understood by a user.
  • Figure 1 is a flowchart depicting a non-visual verification method, according to a selected embodiment of the invention.
  • Figure 2 is a flowchart depicting a non-visual verification method, according to another selected embodiment of the invention.
  • Figure 3 is a schematic depiction of a non-visual verification system, according to yet another selected embodiment of the invention.
  • the present invention includes systems and methods for performing a non-visual test to determine the presence of a target substance in an ingestible substance.
  • the invention includes systems and methods for performing a non-visual test to determine the presence of a target substance in an ingestible substance, where the target substance may be indicated both non-visually and concealably.
  • FIG. 1 One embodiment of the present method is depicted as flowchart 10 in Fig. 1 .
  • the method includes selecting an ingestible substance, at 12; using a detector on the selected, ingestible substance, at 14; and non-visually indicating whether a target substance is present in the ingestible substance, at 16.
  • a second embodiment of the present method is depicted as flowchart 18 in Fig. 2.
  • the method of Fig. 2 includes selecting an ingestible substance, at 20; making a detector for non-visual display of whether a target substance is present in the selected, ingestible substance, at 22; and operating the detector and non-visually indicating whether a target substance is present in the ingestible substance, at 24.
  • the disclosed methods may be performed using a non-visual verification system 26, as depicted schematically in Fig. 3.
  • the non-visual verification system includes a sensing component 28, and an indicating component at 30.
  • the non-visual verification system optionally further includes a processor 30, as will be discussed below.
  • the non-visual verification system may be used to test an ingestible substance, prior to consumption, for one or more specific target substances.
  • That target substance(s) is typically an unwanted or undesired substance, such as a drug or a toxin. More particularly, the target substance may be a drug intended to confuse or sedate the consumer.
  • Selected embodiments of the target substance include flunitrazepam, gamma-hydroxybutyric, ketamine, clonazepam, alprazolam, temazepam, and midazolam, without limitation.
  • the non-visual verification system is typically configured so that the ingestible substance may be tested for the target substance concealably.
  • the test is administered concealably where the ingestible substance may be tested for the target substance without alerting bystanders or companions that the test has been administered, or revealing the results of the test.
  • the non-visual verification system includes a sensing component, where the selected ingestible substance interacts with the system.
  • the sensing component may be as simple as a molecule or a molecular array that incorporates one or more binding sites that are complementary to the target substance, such that binding the target substance results directly or indirectly in a non-visual response.
  • the ingestible substance to be tested may be any solid, semi-solid, or liquid that is intended for ingestion.
  • the ingestible substance may also be a food or beverage.
  • the ingestible substance is a liquid or semi-liquid, to facilitate detection of the target substance by chemical or physical interaction.
  • the ingestible substance may also include chewing gum, toothpaste, and other substances that may be placed in the mouth, but not be intended to be swallowed.
  • the non-visual verification system typically incorporates an indicating component capable of indicating the presence of the selected target substance via a non-visual indication.
  • the indicating component is directly coupled to the sensing component, such as via molecular recognition, where binding the target substance triggers a molecular modification that produces that desired non-visual indication, such as via a change in flavor, odor, or texture.
  • the non-visual verification system may correspond to an indicator substance that is selectively reactive toward the target substance (the sensing component), and produces an identifiable flavor compound in the presence of the target substance (the indicating component).
  • the desired target substance react with both selectivity and specificity, so as to avoid false positives.
  • the interaction between an indicator substance and the target substance may be similar to that of specific binding pairs.
  • the indicator substance may be designed so that binding the target substance triggers a molecular rearrangement of the indicator substance, creating a distinct flavor change.
  • binding the target substance may trigger the release of one or more small molecules that are then detectable by flavor or odor.
  • Such an indicator substance may be utilized by placement in the user's mouth, or by placing a component of the non-visual verification system that includes the indicator substance in the user's mouth. Selected embodiments of the indicator substance may produce a bitter, or otherwise identifiable, taste to the user.
  • the indicator substance may include more than one constituent element, and may correspond to any composition, element, material, reagent, or solution, or combination thereof, that is suitable for producing such an identifiable or bitter taste upon reaction with the target substance.
  • the non-visual verification system incorporates multiple indicator substances, each configured to react selectively with one or more target substances to produce a range of individually identifiable flavors. Such a multi-target system may be useful for the detection of multiple targets of interest simultaneously.
  • the indicating component may be present on a strip of paper, a dissolvable strip of material, a saliva-dissolvable material, or a chewing gum-type of material, which a user may put in their mouth prior to ingesting the ingestible substance.
  • the substance may also be formulated as a liquid additive packaged in a small container with a dispenser such as a dropper/pipette so that the user can place a drop of the liquid additive in/on the beverage or food, respectively.
  • An indicator substance configured to create an identifiable or bitter taste when in contact with target substance may be delivered to the user in any suitable form, such as through a pill, a readily-dissolvable tablet, or through a liquid solution.
  • the indicating substance can also be, or be impregnated in, any chewable or edible item that resembles a common beverage or food item, such as a stick or piece of gum, breath mint, mint, candy, such as those candies sold under the federally registered trademark TIC TAC, etc.
  • the substance can therefore be used openly in a manner that would not otherwise alert others that the user is performing a test for the presence of unwanted drugs in a beverage or food item.
  • the substance may be added to the beverage or food itself to produce an identifiable and/or bitter taste.
  • the test may include a user placing a non-visual-detector substance in his or her mouth, then drinking the beverage or eating the food in question.
  • the non-visual-detector-detector substance may cause the user to have a pre-selected indicator taste.
  • a user may place a dissolvable strip of material in their mouth to moisten and/or dissolve the strip, thereby releasing the substance.
  • the substance may then coat all or a portion of the interior of the user's mouth, including the taste buds, with the substance, so that the test may be performed by subsequently sipping, ingesting, or tasting a small portion of the suspected beverage or food.
  • the results of the test are therefore fully concealed from others and only known to the taster.
  • compositions, substances and methods disclosed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions, substances and methods of this disclosure have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions/substances, and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the present disclosure. More specifically, it will be apparent that certain substances that are both chemically and physiologically related may be substituted for the substances described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the present disclosure.
  • the non-visual verification system may correspond to a device that incorporates a sensing component and an indicating component.
  • the sensing component may incorporate a sample chamber or receptacle, where an aliquot of the ingestible substance to be tested may be inserted for sensing.
  • the sensing component may be configured to be inserted into the ingestible substance, such as a dipstick, test strip, or capillary tube.
  • the sensing component may include a removable sample collector that is configured to be removed from the non-visual verification system and used to collect an aliquot of the ingestible substance of interest. The sample collector may then be reattached or reinserted into the non-visual verification system for analysis.
  • the non-visual verification system may incorporate one or more stages of sample treatment, such as by the addition of water or other solvent, one or more reagents, and optionally including maceration or mixing in order to facilitate detection of a target substance.
  • the sensing component may incorporate any of a variety of chemical sensors, electrochemical sensors, spectrometric sensors, pH sensors, and the like. Highly selective detection may be accomplished via the use of enzyme-linked-bound antibodies that bind specifically to selected target substances, and then generate a detectable response via an enzymatic reaction (for example as used in ELISA assays).
  • the sensing component may include only one type of chemical sensor, or may incorporate a plurality of chemical sensors to permit detection of more than one target substance.
  • the sensing component may utilize one or more microfluidic systems to analyze an ingestible substance for the target substance.
  • Microfluidics permit the manipulation of extremely small volumes of analyte utilizing microfluidic channels having diameters on the order of around 100 nm to several hundred ⁇ .
  • Microfluidic methods include a wide variety of analytical methods, leading to the description of microfluidic methods as 'labs-on-a-chip'.
  • the non-visual verification system may also incorporate a processor 30, as shown in Fig. 3.
  • the processor may correspond to one or more chips, transistors, and processing units configured to receive data originating from the sensing component, evaluating the sensing data, and triggering the indicator component to create the appropriate non-visual indication.
  • the indicating component incorporates a physical indicator that responds to instructions from the processor, the indicating component may generate any of a variety of possible non-visual indications, including smell, touch and sound. For example, the indicating component may be configured to release an appropriate fragrance upon detection of a particular target substance.
  • the indicating component may include a tactile indicator portion, either affixed to the non-visual verification system, or configured to be used remotely.
  • the tactile indicator may be configured to alert the user by vibrating, administering a gentle electrical shock to the user's skin, or applying localized heating, for example.
  • the tactile indicator may take the form of a patch or adhesive button that can be removably affixed to the user's skin, for example under clothing, and then activated by the non-visual verification system. Remote communication between the non-visual verification system and the tactile indicator may be accomplished using radio transmissions, among other methods.
  • a sound indicator could also be used that responds to, for example, a chemical reaction by emitting a sound to indicate that the target substance is present in the ingestible substance.
  • Example 1 Designing a Detector Substance for ROHYPNOL
  • Flunitrazepam (ROHYPNOL, NARCOZEP) is a benzodiazepine derivative, and thus contains the core chemical structure characteristic of all benzodiazepines.
  • Flunitrazepam is specifically classed as a nitro-benzodiazepine, and it is the fluorinated methylamino derivative of nitrazepam, another benzodiazepine derivative.
  • Flunitrazepam is characterized by the presence of a fluoro substituent attached to a pendant phenyl substituent.
  • a first criteria for an appropriate non-visual-detector substance is that the reagent should be safe for human consumption at effective concentrations.
  • a second criteria is that it possess an appropriate cross-reactivity with flunitrazepam.
  • a third criteria is that non-visual indicators such as taste and/or smell associated with the resulting adduct compound should be readily detectable by an animal or human consumer of the adduct compound.
  • a fourth criteria is that the non-visual indicators are readily distinctive to an animal or human consumer.
  • Reactants are to be consumed and, as a result, they must be safe for human consumption when present in the final product.
  • reagents are safe for human consumption, only those compounds present in the EAFUS (Everything Added to Food in the United States) database and GRAS (Generally Recognized as Safe) database according to the U.S. Food and Drug Administration are considered as candidates for detector substances.
  • the structure of the adduct resulting from the reaction of each candidate with flunitrazepam was generated using a LeadGrow tool for virtual library generation from VLifeMDS4.3.
  • the generated adducts were energy minimized using the MMFF force field until a convergence criterion of 0.0001 kcal/mol was achieved.
  • the geometry of the resulting energy-minimized compounds was used to evaluate the predicted flavor and aroma of the generated adducts.
  • QSARs Quantitative Structure Activity Relationships
  • molecular descriptors the physical characteristics of a compound from its chemical structure
  • H-DonorCount The number of Hydrogen bond donors present in the molecules k3 alpha This descriptor signifies third alpha modified kappa shape index
  • HydrogensCount The number of hydrogen atoms present in the molecule
  • T_C_0_2 Number of Carbon atoms separated from Oxygen atom by 2 bonds in the molecule
  • T_2_0_6 Number of double bonded atoms separated from Oxygen atoms by 6 bonds in the molecule
  • T_T_0_6 The count of number of atoms present at a bond distance of 6 from any
  • Epsilon4 Measure of electronegative atom count including hydrogen atoms with respect to the saturated hydrocarbon(reference alkane) created from the molecule/fragment under consideration
  • T_2_N_1 Number of double bonded atoms separated from any Nitrogen atom by a single bond in the molecule
  • T_2_O_0 Number of Oxygen atoms with a double bond present in the molecule chiV4pathCluster This descriptor signifies valence molecular connectivity index of 4th order pathcluster.
  • DeltaEpsilonA A measure of contribution of unsaturation and electronegative atom count
  • Adducts were subjected to taste and smell predictions using QSAR models that employed the descriptors defined above. The resultant adducts were sorted based upon the reliability of the predictions. The adducts provided in Table 5 are predicted to have a strong off-taste, while the adducts provided in Table 6 are predicted to have a strong musk smell, which would be unlikely to remain undetected even when the user is under the influence of alcohol.
  • Compounds 1 -3 are predicted to possess a strong off-taste by both QSAR models.
  • Compounds 4-6 are predicted to possess a strong off-taste by one of the two QSAR models.
  • Compounds 5-6 are also predicted to possess an off-aroma.
  • Table 6 Adducts Predicted to have Strong Aroma
  • Compound 15-17 are predicted to possess a particularly strong off-aroma by both QSAR models.
  • Compound 18 is predicted to possess a strong off-aroma by one of the two QSAR models.
  • Compounds 15-17 are also predicted to possess an off-taste.
  • a non-visual indication method for the presence of flunitrazepam comprising: selecting an ingestible substance;
  • an indicator chosen from the group consisting of a taste indicator that produces a taste to a user in the presence of flunitrazepam and a smell indicator that produces a smell to a user in the presence of flunitrazepam.
  • the indicating step involves using a taste indicator that produces a taste to a user, wherein the taste indicator comprises one or more of butane-1-thiol, 2-methylpropane-1 -thiol, cyclopentanethiol, N-methylmethanamine, ehtane-1 ,2-diamine, 2-aminoethanol, 1-p-menthene-8-thiol, 2-ethylheptane-1 -thiol, 1- methoxyheptane-3-thiol, 4-sulfanylbutan-2-one, pentane-3-thiol, heptane-1 -thiol, 4- aminobutanoic acid, and cyclohexanamine.
  • the taste indicator comprises one or more of butane-1-thiol, 2-methylpropane-1 -thiol, cyclopentanethiol, N-methylmethanamine, ehtane-1 ,2-diamine, 2-aminoethanol, 1-p-menthen
  • the indicating step involves using a taste indicator that produces a taste to a user, wherein the taste indicator comprises one or more of butane-1-thiol, 2-methylpropane-1 -thiol, cyclopentanethiol, N-methylmethanamine, ehtane-1 ,2-diamine, and 2-aminoethanol.
  • the indicating step involves using a smell indicator that produces a smell to a user, wherein the smell indicator comprises one or more of butane-2,3-dithiol, 2-methyltetrahydrofuran-3-thiol, 3-methylbutane-2-thiol, 2- ⁇ 3-[(4- amino-2- methylpyrimidin-5-yl)methyl]-4-methyl-2,3- dihydro-1 ,3-thiazol-5- yl ⁇ ethanol, 4-amino-5,6-dimethylthieno[2,3-d]pyrirTiidin-2-one, 4-aminobutanoic acid, cyclohexanamine, propan-2-amine, and propan-1-amine.
  • the smell indicator comprises one or more of butane-2,3-dithiol, 2-methyltetrahydrofuran-3-thiol, 3-methylbutane-2-thiol, 2- ⁇ 3-[(4- amino-2- methylpyrimidin-5-yl)methyl]-4-
  • the indicating step involves using a smell indicator that produces a smell to a user, wherein the smell indicator comprises one or more of butane-2,3-dithiol, 2-methyltetrahydrofuran-3-thiol, 3-methylbutane-2-thiol, and 2- ⁇ 3- [(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-2,3-dihydro-1 ,3-thiazol-5-yl ⁇ ethanol.
  • a non-visual verification system comprising:
  • a non-visual, sensing mechanism constructed to verify whether flunitrazepam is present in an ingestible substance by producing a non-visual indicator that can be understood by a user;
  • the sensing mechanism is constructed to produce an indicator to the user that is chosen from the group consisting of a taste indicator and a smell indicator;
  • the sensing mechanism comprises one or more of butane-1 -thiol, 2- methylpropane-1 -thiol, cyclopentanethiol, N-methylmethanamine, ehtane-1 ,2-diamine, 2- aminoethanol, 1-p-menthene-8-thiol, 2-ethylheptane-1 -thiol, 1-methoxyheptane-3-thiol, 4- sulfanylbutan-2-one, pentane-3-thiol, heptane-1-thiol, 4-aminobutanoic acid, cyclohexanamine, butane-2,3-dithiol, 2-methyltetrahydrofuran-3-thiol, 3-methylbutane-2-thiol, 2- ⁇ 3-[(4-amino-2- methylpyrimidin-5-yl)methyl]-4-methyl-2,3- dihydro-1 ,3-thiazol-5- yl ⁇ ethanol, 4-a
  • sensing mechanism is also constructed to be concealable so that the user can limit observation of the indicator by others.
  • the sensing mechanism is constructed to produce a taste indicator to the user and comprises one or more of butane-1 -thiol, 2- methylpropane-1 -thiol, cyclopentanethiol, N-methylmethanamine, ehtane-1 ,2-diamine, 2- aminoethanol, 1-p-menthene-8-thiol, 2-ethylheptane-1 -thiol, 1-methoxyheptane-3-thiol, 4- sulfanylbutan-2-one, pentane-3-thiol, heptane-1-thiol, 4-aminobutanoic acid, and cyclohexanamine.
  • the sensing mechanism is constructed to produce a smell indicator to the user and comprises one or more of butane-2,3-dithiol, 2- methyltetrahydrofuran-3-thiol, 3-methylbutane-2-thiol, 2- ⁇ 3-[(4-amino-2- methylpyrimidin-5- yl)methyl]-4-methyl-2,3- dihydro-1 ,3-thiazol-5- yl ⁇ ethanol, 4-amino-5,6-dimethylthieno[2,3- d]pyrimidin-2-one, 4-aminobutanoic acid, cyclohexanamine, propan-2-amine, and propan-1 - amine.

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Abstract

La présente invention concerne des procédés et des systèmes utilisés pour détecter et indiquer la présence de substances indésirables dans une substance à ingérer telle que des aliments ou des boissons. Plus spécifiquement, l'invention porte sur des systèmes et des procédés utilisés pour indiquer et détecter de façon non visuelle et cachée la présence de drogues non souhaitées ou indésirables dans des boissons et/ou des aliments.
PCT/US2015/055994 2014-10-17 2015-10-16 Indication non visuelle d'un composé chimique indésirable dans une substance à ingérer Ceased WO2016061490A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US14/517,730 2014-10-17
US14/517,730 US8978468B2 (en) 2009-10-19 2014-10-17 Nonvisual indication of an unwanted chemical in an ingestible substance

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050133420A1 (en) * 2003-12-18 2005-06-23 Rinker Edward B. Control scheme for enhanced filtered water systems
US20090197283A1 (en) * 2007-09-11 2009-08-06 Gold Mark S Devices and methods for the collection and detection of substances
US20110053173A1 (en) * 2009-08-28 2011-03-03 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Game with detection capability

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050133420A1 (en) * 2003-12-18 2005-06-23 Rinker Edward B. Control scheme for enhanced filtered water systems
US20090197283A1 (en) * 2007-09-11 2009-08-06 Gold Mark S Devices and methods for the collection and detection of substances
US20110053173A1 (en) * 2009-08-28 2011-03-03 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Game with detection capability

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