Compositions and methods for a universal clinical test for olfactory dysfunction

Abstract

Disclosed are compositions and methods for measuring olfactory sensitivity, olfactory resolution, and combinations thereof. Such measurements can be made during a single test, or over consecutive tests, which may be performed during a single testing period, such as in a single day, or over a series of testing periods. The tests may be performed by a health care professional, or may be conveniently self-administered by the user.

1 . A mixture comprising from 2-30 compounds selected from the group consisting of:
 butyraldehyde, cuminaldehyde, octanal, dihydrocoumarin, octanol, phenethylamine, pyruvic acid, methyl sulfide, 4-methyl-5-thiazoleethanol, decanoic acid, eugenol, 2-phenylethanol, dimethyl anthranilate, 2-isopropylphenol, 2-methoxy-4-methylphenol, carvyl acetate, furfuryl alcohol, α-methylbenzyl alcohol, acetophenone, methyl phenylacetate, diphenyl ether, α,α-dimethylbenzenepropanol, phenethyl acetate, 2-ethyl-1-hexanol, 4-methylanisole, ethyl propionate, diethyl malonate, ethyl butyrate, propyl butyrate, 3,7-dimethyl-1-octanol, (−)-citronellol, isoamyl butyrate, ethyl heptanoate, ethyl octanoate, propyl propionate, dimethyl succinate, methyl heptanoate, gamma-valerolactone, benzenethiol, butyl butyrate, butylamine, thiophene, ethyl decanoate, diethyl sebacate, valeraldehyde, piperidine, 2-octanone, heptanoic acid, propyl sulfide, heptanol, decanol, lauryl acetate, 2-hydroxyacetophenone, methyl anthranilate, p-tolyl acetate, 4-allylanisole, ethyl acetate, allyl heptanoate, nonanol, α,α-dimethylphenethyl acetate, 3-acetylpyridine diethyl sulfide, 6-methyl-5-hepten-2-one, carvacrol, methyl propionate, butyl propionate, methyl 2-furoate, 5-methylfurfural, ethyl undecanoate, pentyl acetate, 2-decanone, 2-nonanone, decahydro-2-naphthol, undecane, 1,6-hexanedithiol, 2-acetyl-5-methylfuran, Isoamyl octanoate, allyl butyrate, terpinyl formate, 2-methoxy-3-methylpyrazine, hexyl hexanoate, ethyl 2-methylbutyrate, phenethyl propionate, p-anisaldehyde, ethyl hexanoate, allyl hexanoate, benzyl phenylacetate, 2-phenoxyethyl isobutyrate, butyl 10-undecenoate, methyl 2-methoxybenzoate, hexyl formate, 4-methyl-5-thiazoleethanol acetate, delta-undecalactone, ethyl-3-hydroxyhexanoate, 3-acetyl-2,5-dimethylfuran, 2-ethoxythiazole, 2-furanmethanethiol formate, 4-oxoisophorone, dihydrojasmone, whiskey lactone, 6-acetyl-1,1,2,4,4,7-hexamethyltetralin, 2-methyl-4-propyl-1,3-oxathiane, 2-acetyl-3,5(6)-dimethylpyrazine, omega-pentadecalactone, 3-octanone, phenethyl 2-furoate, 2-(1-methylpropyl)thiazole, 3-octyl acetate, geraniol, and combinations thereof.   
     
     
         2 . The mixture of  claim 1 , comprising:
 2-acetyl-5-methylfuran   2-decanone   2-ethyl-1-hexanol   2-nonanone   2-phenylethanol   6-acetyl-1,1,2,4,4,7-hexamethyltetralin   acetophenone   allyl butyrate   butyraldehyde   carvacrol   carvyl acetate   decanoic acid   dihydrocoumarin   dihydrojasmone   dimethyl anthranilate   diphenyl ether   ethyl 2-methylbutyrate   ethyl undecanoate   ethyl-3-hydroxyhexanoate   eugenol   gamma-valerolactone   heptanoic acid   heptanol   isoamyl butyrate   methyl sulfide   nonanol   phenethyl propionate   phenethylamine   thiophene, and   α,α-dimethylphenethyl acetate.   
     
     
         3 . The mixture of  claim 1  comprising:
 2-(1-methylpropyl)thiazole 
 2-hydroxyacetophenone 
 2-isopropylphenol 
 2-methoxy-4-methylphenol 
 2-methyl-4-propyl-1,3-oxathiane 
 2-octanone 
 3-octyl acetate 
 4-methyl-5-thiazoleethanol 
 4-methylanisole 
 5-methylfurfural 
 allyl hexanoate 
 benzenethiol 
 benzyl phenylacetate 
 butyl butyrate 
 butylamine 
 decahydro-2-naphthol 
 decanol 
 delta-undecalactone 
 hexyl formate 
 hexyl hexanoate 
 methyl 2-methoxybenzoate 
 methyl heptanoate 
 methyl phenylacetate 
 methyl propionate 
 octanal 
 octanol 
 phenethyl 2-furoate 
 propyl butyrate 
 pyruvic acid, and 
 valeraldehyde. 
 
     
     
         4 . The mixture of  claim 1  comprising:
 (−)-citronellol 
 2-acetyl-3,5(6)-dimethylpyrazine 
 2-ethoxythiazole 
 2-methoxy-3-methylpyrazine 
 2-phenoxyethyl isobutyrate 
 3-acetylpyridine 
 3-octanone 
 4-methyl-5-thiazoleethanol 
 4-methyl-5-thiazoleethanol acetate 
 6-methyl-5-hepten-2-one 
 butyl 10-undecenoate 
 butyl propionate 
 dihydrocoumarin 
 dimethyl succinate 
 ethyl acetate 
 ethyl butyrate 
 ethyl hexanoate 
 ethyl octanoate 
 ethyl propionate 
 ethyl undecanoate 
 Isoamyl octanoate 
 methyl 2-furoate 
 octanal 
 phenethyl acetate 
 piperidine 
 propyl sulfide 
 p-tolyl acetate 
 undecane 
 whiskey lactone, and 
 α,α-dimethylbenzenepropanol. 
 
     
     
         5 . The mixture of  claim 1  comprising:
 1,6-hexanedithiol 
 2-acetyl-5-methylfuran 
 2-furanmethanethiol formate 
 3,7-dimethyl-1-octanol 
 3-acetyl-2,5-dimethylfuran 
 4-allylanisole 
 4-oxoisophorone 
 allyl butyrate 
 allyl heptanoate 
 cuminaldehyde 
 diethyl malonate 
 diethyl sebacate 
 diethyl sulfide 
 ethyl 2-methylbutyrate 
 ethyl decanoate 
 ethyl heptanoate 
 furfuryl alcohol 
 geraniol 
 lauryl acetate 
 methyl 2-methoxybenzoate 
 methyl anthranilate 
 methyl heptanoate 
 omega-pentadecalactone 
 p-anisaldehyde 
 pentyl acetate 
 phenethylamine 
 propyl butyrate 
 propyl propionate 
 terpinyl formate, and 
 α-methylbenzyl alcohol. 
 
     
     
         6 . The mixture of  claim 1  comprising:
 2-acetyl-5-methylfuran 
 2-decanone 
 2-ethyl-1-hexanol 
 2-nonanone 
 2-phenylethanol 
 6-acetyl-1,1,2,4,4,7-hexamethyltetralin 
 acetophenone 
 allyl butyrate 
 butyraldehyde 
 carvacrol 
 carvyl acetate 
 decanoic acid 
 dihydrocoumarin 
 dihydrojasmone 
 dimethyl anthranilate 
 diphenyl ether 
 ethyl 2-methylbutyrate 
 ethyl undecanoate 
 ethyl-3-hydroxyhexanoate 
 eugenol 
 gamma-valerolactone 
 heptanoic acid 
 heptanol 
 isoamyl butyrate 
 methyl sulfide 
 nonanol 
 phenethyl propionate 
 phenethylamine 
 thiophene, and 
 α,α-dimethylphenethyl acetate. 
 
     
     
         7 . The mixture of  claim 1  comprising:
 1,6-hexanedithiol 
 2-acetyl-5-methylfuran 
 2-furanmethanethiol formate 
 3,7-dimethyl-1-octanol 
 3-acetyl-2,5-dimethylfuran 
 4-allylanisole 
 4-oxoisophorone 
 allyl butyrate 
 allyl heptanoate 
 cuminaldehyde 
 diethyl malonate 
 diethyl sebacate 
 diethyl sulfide 
 ethyl 2-methylbutyrate 
 ethyl decanoate 
 ethyl heptanoate 
 furfuryl alcohol 
 geraniol 
 lauryl acetate 
 methyl 2-methoxybenzoate 
 methyl anthranilate 
 methyl heptanoate 
 omega-pentadecalactone 
 p-anisaldehyde 
 pentyl acetate 
 phenethylamine 
 propyl butyrate 
 propyl propionate 
 terpinyl formate, and 
 α-methylbenzyl alcohol. 
 
     
     
         8 . A mixture comprising a combination of at least two compounds of  claim 1  wherein at least one compound in the mixture is present at a dilution selected from:
 1:8 
 1:16 
 1:32 
 1:64 
 1:128 
 1:256 
 1:512 
 1:1024 
 1:2048 
 1:4096 
 1:8192 
 1:16384 
 1:32768 
 1:65536 
 1:131072 
 1:262144. 
 
     
     
         9 . A method comprising allowing an individual to nasally inhale odors produced by a combination of compounds of  claim 8 , and determining whether or not the individual perceives an odor from the combination of the compounds. 
     
     
         10 . The method of  claim 9 , wherein the individual perceives the odor, the method further comprising allowing the individual to compare perception of the odor to at least one control, wherein the control is devoid of one, some or all of the compounds. 
     
     
         11 . The method of  claim 10 , wherein the individual perceives the odor, the method further comprising subsequently allowing the individual to nasally inhale odors produced by a dilution of the combination of compounds, and determining whether or not the individual perceives an odor from the dilution of the combination of the compounds, and optionally repeating said method with one or more serial dilutions of the combinations of the compounds until the individual does not perceive the odor, and generating a threshold value for olfactory sensitivity from a change in perception. 
     
     
         12 . A method comprising allowing an individual to nasally inhale odors produced by a first combination of compounds of  claim 1 , and comparing perception of an odor produced by the first combination of the compounds to perception of an odor produced by a second combination of compounds. 
     
     
         13 . The method of  claim 12 , further comprising replacing one or more compounds from the first combination of compounds with one or more compounds from the second combination of the compounds, and allowing the individual to nasally inhale odors from the first and second combinations of the compounds to determine a difference in the first and second combinations of the compounds. 
     
     
         14 . The method of  claim 13 , further comprising repeating said replacing one or more compounds from the first combination of compounds with one or more compounds from the second combination of the compounds, and allowing the individual to nasally inhale odors from the first and second combinations of the compounds, until the individual does not perceive a difference between the first and second combination of the compounds, and generating a threshold value for olfactory resolution from a change in perception. 
     
     
         15 . A kit comprising a mixture of at least two compounds of  claim 1  and at least one container comprising a mixture of the compounds. 
     
     
         16 . The kit of  claim 15 , wherein the mixture of the at least two compounds comprises a mixture of 2-30 compounds. 
     
     
         17 . The kit of  claim 15 , wherein the mixture of the at least two compounds comprises a mixture of at least 30 compounds. 
     
     
         18 . The kit of  claim 15 , wherein the mixture of the at least two compounds comprises a mixture consisting of 30 compounds. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . The kit of  claim 1 , further comprising printed instructions instructing a user to perform a method to determine olfactory sensitivity, olfactory resolution, or a combination thereof.