NON-INVASIVE TRANSDERMAL DETECTION OF ANALYTES

• US 20020019055A1
• Filed: 06/24/1999
• Published: 02/14/2002
• Est. Priority Date: 06/24/1998
• Status: Active Grant

• Current Assignee: Transderm Technologies LLC
• Original Assignee: Transderm Technologies LLC
• Inventors: EDELMAN, ELAZER, BROWN, LARRY R., TSENG, DAVID
• Granted Patent: US 6,492,180 B2
• Time in Patent Office: Days
• US Class Current: 436/74
• CPC Class Codes: A61B 2010/0009 Testing for drug or alcohol abuse
• CPC Class Codes: G01N 33/52 Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72
• CPC Class Codes: G01N 33/84 involving inorganic compounds or pH
• CPC Class Codes: G01N 33/94 involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors

Abstract

A method and apparatus for non-invasive extraction and/or detection of chemicals such as heavy metals, drugs such as cocaine and analytes such as blood glucose has been developed. A patch or hydrogel containing a reagent such as N-methyl pyrrole, or a similar compound, is used to extract the chemical or analyte to be measured through the skin or hair. This method is most useful for detecting analytes which are generally present in relatively constant blood concentrations. The method is particularly useful for the detection of heavy metals such as lead, lithium, copper, iron, and has been demonstrated to be useful with drugs such as cocaine and acetominaphen, and metabolic analytes like blood glucose. In the preferred embodiment, the method involves the use of the water miscible solvent N-methyl pyrrolidone (NMP) in an aqueous solution which is incorporated into an adsorbent pad or hydrogel This adsorbent pad is placed on the skin for a defined time period, removed and then analyzed for the substance of interest. An analytical method can also be incorporated as part of the adsorbent pad in order to conduct both the extraction of the chemical of interest and the assay in situ. Examples demonstrating the very broad range of materials which can be extracted. Comparative examples demonstrate that the same results cannot be obtained using other reagents such as dimethylsulfoxide (DMSO).

Claims

1. A device for extraction of chemical compounds through the skin or from hair comprising

an effective amount of a pyrrolidone of the following formula in a carrier suitable for extraction of the chemical compounds

R₁=H, CH₃, HO—

CH₂—

CH₂—

, CH₃—

CH₂—

, CH₃—

(CH₂)_n, wherein n=1 to 10

R₃=H, —

OH, or an alkyl group such as dodecyl,

R₄=H, methyloxycarbonyl, and

R₅=H, CH₃, CH₃—

CH₂—

, HO—

CH₂—

CH₂.

2. The device of claim 1 wherein the pyrrolidone is selected from the group consisting of alkyl pyrrolidones and pyrrolidone derivatives, in a carrier selected from the group consisting of aqueous solutions, polymeric hydrogels, and absorbant patches.

3. The device of claim 2 wherein the absorbant patches are selected from the group consisting of guazes, cellulosic pads, agarose gels, acrylamide gels.

4. The device of claim 1 wherein the pyrrolidone is selected from the group consisting of 2-pyrrolidone, 1 methyl-2-pyrrolidone, 1 ethyl 2 pyrrolidone, 1 hexyl-2-pyrrolidone, 1-lauryl-2-pyrrolidone N-(2-hydroxyethyl)-2-pyrrolidone, 1,5-dimethyl-2-pyrrolidone, 5-methyl-2-pyrrolidone, 1-hexyl-4-methyl oxycarbonyl-2-pyrrolidone, 1 lauryl-4-methyl oxycarbonyl-2-pyrrolidone, N-cyclohexyl-2-pyrrolidone, N-dodecyl-2-pyrrolidone, and 1-butyl-3-dodecyl-2-pyrrolidone.

5. The device of claim 1 wherein the pyrrolidone is N-methyl pyrrolidone or a mixture of N-methyl pyrrolidone.

6. The device of claim 1 wherein the carrier further comprises a surface property modifying agent selected from the group consisting of surfactants, menthol, phospholipids, and azone.

7. The device of claim 1 wherein the carrier comprises a polymer selected from the group consisting of polypropylene glycol-polypropyleneoxide block co-polymers, polyvinyl alcohol, poly hydroxy methacrylate, poly hydroxy ethyl methacrylate and propylene glycol.

8. The device of claim 1 further comprising means for detecting the presence or amount of chemical compound in the pyrrolidone.

9. The device of claim 8 wherein the means for detecting can detect the presence or amount of a metal.

10. The device of claim 8 wherein the means for detecting can detect the presence or amount of a biological compound or metabolite present in a body fluid.

11. The device of claim 8 wherein the means for detecting can detect the presence or amount of a drug selected from the group consisting of drugs of abuse, caffeine, and prescription drugs.

13. The method of claim 12 wherein the pyrrolidone is selected from the group consisting of alkyl pyrrolidones and pyrrolidone derivatives, in a carrier selected from the group consisting of aqueous solutions, polymeric hydrogels, and absorbant patches.

14. The method of claim 13 wherein the absorbant patches are selected from the group consisting of guazes, cellulosic pads, agarose gels, acrylamide gels.

15. The method of claim 12 wherein the pyrrolidone is selected from the group consisting of 2-pyrrolidone, 1 methyl-2-pyrrolidone, 1 ethyl 2 pyrrolidone, 1 hexyl-2-pyrrolidone, 1-lauryl-2-pyrrolidone N-(2-hydroxyethyl)-2-pyrrolidone, 1,5-dimethyl-2-pyrrolidone, 5-methyl-2-pyrrolidone, 1-hexyl-4-methyl oxycarbonyl-2-pyrrolidone, 1 lauryl-4-methyl oxycarbonyl-2-pyrrolidone, N-cyclohexyl-2-pyrrolidone, N-dodecyl-2-pyrrolidone, and 1-butyl-3-dodecyl-2-pyrrolidone.

16. The method of claim 12 wherein the pyrrolidone is N-methyl pyrrolidone or a mixture of N-methyl pyrrolidone.

17. The method of claim 12 wherein the carrier further comprises a surface property modifying agent selected from the group consisting of surfactants, menthol, phospholipids, and azone.

18. The method of claim 12 wherein the carrier comprises a polymer selected from the group consisting of polypropylene glycol-polypropyleneoxide block co-polymers, polyvinyl alcohol, poly hydroxy methacrylate, poly hydroxy ethyl methacrylate and propylene glycol.

19. The method of claim 12 wherein the device comprises means for detecting the presence or amount of chemical compound in the pyrrolidone.

20. The method of claim 19 wherein the means for detecting can detect the presence or amount of a metal.

21. The method of claim 19 wherein the means for detecting can detect the presence or amount of a biological compound or metabolite present in a body fluid.

22. The method of claim 19 wherein the means for detecting can detect the presence or amount of a drug selected from the group consisting of drugs of abuse, caffeine, and prescription drugs.

12. A method for detecting the presence or amount of a chemical compound comprising applying to the skin or hair a device comprising

an effective amount of a pyrrolidone of the following formula in a carrier suitable for extraction of the chemical compounds

R₁=H, CH₃, HO—

CH₂—

CH₂—

, CH₃—

CH₂—

, CH₃—

(CH₂)_n, wherein n=1 to 10

R₃=H, —

OH, or an alkyl group such as dodecyl,

R₄=H, methyloxycarbonyl, and

R₅=H, CH₃, CH₃—

CH₂—

, HO—

CH₂—

CH₂,

for a time sufficient to extract the chemical compound.