Patent Application
20180265916
This disclosure relates to methods of tracking and identifying pharmaceuticals after consumption.
The consumption of drugs is largely untracked. This is particularly problematic for dealing with issues such as opiate addiction, sharing of prescriptions, counterfeit drugs, consumption of contraindicated drugs, consumption of multiple drugs with adverse interactions, drug allergies, dosing control and adjustment, emergency medicine and many other situations. It is also difficult to interpret clinical studies when drug compliance of study subjects is inconsistent.
Tracking of drugs in the human waste stream is desirable, though often not practical outside of a clinical setting. Unobtrusive monitoring of the human waste stream is desired. In-toilet monitoring is one potential solution, especially when the toilet has sufficient biometric data on the user to verify identity.
Drug traceability requires a large number of possible categories to track. It may be useful to track the drug molecule, drug category, manufacturer, distributor, physician prescriber, and the dispensing pharmacy. A method of tracking any or all of these in the waste stream is desired.
We disclose a drug tracking system which includes a drug tracking tag that may be identified in bodily waste. The drug tracking tag includes at least one nucleic acid or nucleic acid analog. The drug tracking tag may be mixed with or adhered to, in the case of a pill, a drug prior to consumption. This step may occur during the manufacturing process.
The nucleic acid or nucleic acid analog may comprise one or a series of unique nucleotide sequences which correlate with specific details about the drug and its supply chain. These may include information in categories that include the identity of the drug, the drug class, the manufacturer, and the distributer. Sequence that includes multiple categories of information may be included in a single nucleotide or nucleotide analog molecule or may be separated into multiple molecules. In some embodiments, the nucleic acid or nucleic acid analog may be conjugated to a magnetic nanoparticle. The magnetic nanoparticle may be less than 8 nm or even less than 5 nm in diameter and may pass through a user's renal system into the urine. The magnetic nanoparticle may be used to isolate the drug tracking tag using magnetic force.
The specific drug tracking tag may be identified in a user's bodily waste by hybridizing the nucleic acid or nucleic acid analog to a complementary single-stranded nucleic acid. The complementary single-stranded nucleic acid may be incorporated into a device which emits a signal upon hybridization and may identify which of a plurality of single-stranded nucleic acids that correlate to codes in drug tracking tags has been hybridized. If necessary, the drug tracking tag may be isolated, amplified, and sequenced.
The information obtained from the nucleic acid or nucleic acid analog within the drug tracking tag in the form of nucleotide sequence may be entered into a database which stores all of the sequence codes used in drug tracking tags and their corresponding information about the drug. By relating the sequence to the drug information associated with it, the drug compound the user consumed and its drug delivery chain may be determined. The information may also be compared to the user's prescribed medications to assess drug compliance and with known drug interactions to prevent adverse events.
Definitions
Drug, as used herein, means any pharmacologically active agent or mixture of agents.
Drug consumption, as used herein, means taking a drug into the body through any method of administration.
Nucleotide, as used herein, means a molecule which is a monomer used to synthesize polymeric nucleic acids and nucleic acid analogs. A nucleotide, as used herein, comprises three subunit molecules: a nitrogenous base, which may be an unnatural base, a five-carbon sugar, and at least one phosphate group.
While this invention is susceptible of embodiment in many different forms, there are shown in the drawings, which will herein be described in detail, several specific embodiments with the understanding that the present disclosure is to be considered as an exemplification of the principals of the invention and is not intended to limit the invention to the illustrated embodiments.
We disclose a drug tracking system which includes a drug tag that is capable of tracking multiple points of origin in the drug delivery chain and of providing multiple types of information about the drug itself. This drug tag may be detected in bodily waste. The drug tag may include at least one nucleic acid or nucleic acid analog that has a unique nucleotide sequence. The unique sequence may correspond to one or any combination of the following classifications: a drug molecule, a drug class, a drug manufacturer, and a drug distributor. Drug classes which may be represented by a unique nucleotide sequence within the drug tag include, but are not limited to: opioids, antibiotics, antihypertensive compounds, steroid hormones, antihistamines, antidepressant compounds, antipsychotic compounds, antiviral compounds, antifungal compounds, anti-inflammatory compounds, anticonvulsants, diuretics, muscle relaxants, statins, and immunosuppressive agents.
In some embodiments, the nucleic acid or nucleic acid analog may comprise between approximately 80 and 100 base pairs. In other embodiments, the nucleic acid or nucleic acid analog may comprise between approximately 30 and 50 base pairs. In other embodiments, the nucleic acid or nucleic acid analog may comprise between approximately 4 and 10 base pairs. In some embodiments, the nucleic acid or nucleic acid analog may be either deoxyribonucleic acid or ribonucleic acid. In some embodiments, the nucleic acid or nucleic acid analog may be either a double- or single-stranded molecule.
In some embodiments, a single nucleic acid or nucleic acid analog may contain a set of sequences corresponding to each of the classifications listed. This may be desirable, for example, in cases where a user is consuming multiple drugs. Including all the drug information on the same molecule within the drug tag would make it clear which of the multiple pieces of information on the drug tag refer to a particular drug product.
In other embodiments, nucleotide sequences corresponding to each of the classifications of drug molecule, drug class, drug manufacturer, and drug distributor may each be on separate nucleic acids or nucleic acid analogs. This may be desirable in cases where the drug manufacturer sends a drug to many distributers. In such cases, a manufacturer may insert the nucleic acids or nucleic acid analogs with the nucleotide sequences that correspond to the drug molecule, class, and manufacturer into the drug. Later, the distributor may add a nucleic acid or nucleic acid analog with the nucleotide sequence corresponding to the distributor. This option may simplify the addition of drug tags to drugs by manufacturers who produce many drug molecules or drug classes.
The drug tag may be added to the drug through one or more of the following methods: spraying, dipping, painting, mixing with drug constituents, or mixing with the material from which a capsule or gelcap is formed. Other methods known in the art may also be used to apply the drug tag to the drug product.
To identify the drug tag after it has been excreted, it may be useful to extract the drug tag from the bodily waste. In some embodiments, the nucleic acid or nucleic acid analog may be tethered to a magnetic nanoparticle. The magnetic nanoparticle may provide a method of extracting the drug tag from bodily waste using magnetic force. The magnetic nanoparticle may be between approximately 5 and 10 nm in diameter. In other embodiments, the magnetic nanoparticle may be between approximately 3 and 8 nm in diameter.
In any embodiment that includes a magnetic nanoparticle, the magnetic nanoparticles may be small enough to pass through the renal system such that they may be excreted in the urine stream. The magnetic nanoparticles may then be separated from the urine with a high magnetic field gradient region, for example, a microneedle array.
In one example of method of synthesizing an embodiment of the disclosed drug tag that includes a magnetic nanoparticle, the magnetic nanoparticle is conjugated to a nucleotide or nucleotide analog in solution with a surplus of magnetic nanoparticles so as to have a small chance of more than one nucleotide or nucleotide analog conjugating to a magnetic nanoparticle. This technique may leave many magnetic particles with no nucleotide or nucleotide analog. Consequently, the drug tag may not include magnetic nanoparticles with more than one nucleotide or nucleotide analog, a situation which would increase the size of the drug tag. In addition, the nucleotide or nucleotide analog may not coil around the nanoparticle, which could increase the diameter of the nanoparticle.
In some embodiments, a method of detecting a drug in bodily waste may be described by the following steps. First, a sample of bodily waste may be obtained from a user who has consumed a drug compound that includes a drug tag. In some cases, a diagnostic toilet that is equipped with the appropriate equipment may be used to collect and analyze the urine as described. This may be particularly desirable when the diagnostic toilet already has sufficient biometric data to identify the user. Next, the identity of the unique sequence within the nucleic acid or nucleic acid analog that includes information about the drug may be determined. This may be accomplished using microarray technology. Alternatively, other techniques which includes single-stranded nucleic acids that are homologous to the unique sequence within the drug tag may be used to identify the drug information within the tag. These techniques may include devices which emit a signal when a nucleic acid or nucleic acid analog from the drug tag hybridizes to the homologous nucleic acid. Examples include a complementary metal oxide semiconductor (CMOS) biosensor chip using self-sensing piezoresistive microcantilevers as the molecules hybridize as described in U.S. Pat. No. 7,738,086 which is hereby incorporated by reference in its entirety. Alternatively, the detection device may include technology described by Star et al. ((2005) Proc. Natl. Acad. Sci. USA, 103, 921-926) which is hereby incorporated by reference in its entirety. Star et al describe a technique using carbon nanotube network field-effect transistors (NTNFETs) that function as selective detectors of DNA immobilization and hybridization. Finally, the nucleotide sequence which hybridized the homologous nucleic acid may be identified such that it can be located within a database. In some embodiments, additional steps may include amplifying the nucleic acid or nucleic acid analog prior to identification and/or quantifying the amount of nucleic acid or nucleic acid analog present in the sample of bodily waste. The nucleic acid or nucleic acid analog may also be sequenced using technology known in the art.
In embodiments of the drug tag that include a magnetic nanoparticle, the drug tag may be removed from bodily waste, which in some embodiments may occur with the use of an array of magnetic microneedles in a flow cell. The nucleic acid or nucleic acid analog may then optionally be cleaved from the magnetic nanoparticle for further analysis. This may be accomplished through enzyme action, thermal action, chemical action, photoaction, or any other methods of removing nucleic acids or nucleic acid analogs known in the art.
The system of tracking and identifying drug tags may also include a database which contains entries that associate the specific nucleotide sequence of the nucleic acid or nucleic acid analog to the drug molecule, drug class, drug manufacturer, drug distributor, or combination of these to which the sequence corresponds. Following the identification of the nucleotide sequence or sequences present in a sample of bodily waste, the nucleotide sequence or sequences may be compared to the entries of nucleotide sequences in the database, such that the drug molecule, class, manufacturer, and/or distributor to which the nucleotide corresponds may be identified.
If a user has consumed more than one drug, it may be desirable to cross-check the drugs consumed with the user's prescription to identify a potentially harmful combination of drugs. Thus, in some embodiments of the invention, the step of identifying the classifications of drug molecule, class, manufacturer, and distributor for any drug in a sample may be followed by a comparison of the drugs in the sample to the user's prescriptions. The identity of the drug may be entered into the database which also includes a file that lists the drugs which have been prescribed to the user. This allows the drug tracking system to confirm that the user is consuming the correct medication and being compliant with the prescription specifications.
The drug tracking system may also be used to identify drug interactions that may cause an adverse effect. For example, after two or more drugs have been identified using the drug tracking system, the two or more drug molecules may be compared to additional entries in the database which may include information about drug interactions. An adverse event may thereby be avoided.
Referring now to the drawings,
Regardless of whether the drug tag was amplified and/or sequenced, the sequence may be entered into a database and compared to a plurality of sequences stored in the database which are associated with unique pieces of information about the drug associated with the drug tag. By associating the sequence of the drug tag with its associated data, information about the drug the user consumed may be obtained. This may include the identity of the drug molecule, the drug class, the manufacturer, and/or the distributor.
While specific embodiments have been illustrated and described above, it is to be understood that the disclosure provided is not limited to the precise configuration, steps, and components disclosed. Various modifications, changes, and variations apparent to those of skill in the art may be made in the arrangement, operation, and details of the methods and systems disclosed, with the aid of the present disclosure.
Without further elaboration, it is believed that one skilled in the art can use the preceding description to utilize the present disclosure to its fullest extent. The examples and embodiments disclosed herein are to be construed as merely illustrative and exemplary and not a limitation of the scope of the present disclosure in any way. It will be apparent to those having skill in the art that changes may be made to the details of the above-described embodiments without departing from the underlying principles of the disclosure herein.
