Method for improving olfactory sensitivity

Abstract

To provide an improving method of smell sensitivity, a body odor evaluation method, and a body odor evaluation kit.SOLUTION: An improvement method of smell sensitivity includes reducing body odor. The improvement method of smell sensitivity includes removing a causative agent of body odor from a subject's body or clothing. In the improvement method of smell sensitivity, the body odor is bad breath. A body odor evaluation method includes measuring the subject's smell sensitivity. In the body odor evaluation method, the smell sensitivity is a sensitiveness to full frilled mercaptan or coffee flavor. A body odor evaluation kit includes means of measuring the subject's smell sensitivity. In the body odor evaluation kit, the body odor is bad breath. In the body odor evaluation kit, the smell sensitivity is a sensitiveness to full frilled mercaptan or coffee flavor.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a method for improving olfactory sensitivity.

Background Art

[0002] Smell plays an important role in leading a rich daily life. For example, smell gives rich flavors to dishes, and the smells imparted to daily products provide various pleasures such as a sense of cleanliness. On the other hand, unpleasant smells are also important. Smell also plays a major role in quickly informing that health and hygiene conditions are impaired. The importance of these smells can also be imagined from the fact that the taste of food is impaired when respiratory diseases such as colds occur, or that elderly people with reduced olfactory ability are at risk without noticing the smell imparted to gas.

[0003] In mammals such as humans, smell is received by olfactory receptors of olfactory nerve cells present in the olfactory epithelium that spreads to the deepest part of the nasal cavity. The odorant taken into the nasal cavity acts on the olfactory receptor to activate it, and the signal from the olfactory nerve cell caused by the activated olfactory receptor is transmitted to the central nervous system, whereby the smell is perceived. It is predicted that there are more than 400 types of genes encoding olfactory receptors in humans. The quality of the smell that we perceive for a specific odorant is considered to be determined by which combination of the above 400 or more olfactory receptors is activated by the odorant. That is, each olfactory receptor receives a plurality of odorants with similar structures with different affinities, while each odorant is received by a plurality of olfactory receptors. Furthermore, it has been reported that an odorant that activates one olfactory receptor inhibits the activation of another olfactory receptor. The combination of responses of these multiple olfactory receptors results in the recognition of individual smells.

[0004] If one continues to smell a certain odor, the sensitivity to that odor decreases. This phenomenon is called olfactory adaptation. Olfactory adaptation is classified into two types: short-term adaptation and long-term adaptation, and it is thought that the molecular mechanisms causing each type of adaptation are different. In short-term adaptation, olfactory sensitivity decreases due to exposure to odorant substances for several seconds to several minutes, and quickly recovers when the odorant substance disappears. As a cause of short-term adaptation, transient changes in olfactory nerve cells are suggested, such as a mechanism in which olfactory receptors that respond to an odor become phosphorylated and lose their responsiveness (Non-Patent Document 1). When the odorant substance disappears, the olfactory receptor is dephosphorylated and its responsiveness is restored. On the other hand, long-term adaptation occurs in units of several weeks and also takes an equivalent amount of time to recover (Non-Patent Document 2). Non-Patent Documents 3 and 4 suggest that a decrease in the expression level of the mRNA of olfactory receptors continuously exposed to an odor causes long-term adaptation.

[0005] Furthermore, continuously smelling a certain odor may reduce the sensitivity to another odor. Such a phenomenon is called cross-adaptation of odor. Patent Document 1 discloses that the activity of olfactory receptors is involved in cross-adaptation of odor, and cross-adaptation is observed among odorant substances received by the same olfactory receptor. That is, when an olfactory receptor is exposed to an odorant substance and its responsiveness decreases, the responsiveness to another odorant substance also decreases, and this is considered to cause cross-adaptation of odor. Non-Patent Document 5 discloses that the perception of the odor of 2-furfurylthiol having a coffee-like odor is reduced or modulated by previously smelling the odor of its metabolite furfuryl methylsulfide, and that olfactory receptors that respond to both compounds are involved in this cross-adaptation.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Non-Patent Documents

[0007] [Non-Patent Document 1] Chem Senses, 2014, 39:771-80 [Non-Patent Document 2] Percept Psychophys, 1996, 58:781-792 [Non-Patent Document 3] Elife, 2017, e21476 [Non-Patent Document 1] Nat Commun, 2018, 9:5081 [Non-Patent Document 5] Chem Senses, 2019, doi:10.1093 / chemse / bjz041 [Summary of the Invention] [Problems to be Solved by the Invention]

[0008] The present invention relates to a method for improving an individual's olfactory sensitivity. [Means for Solving the Problems]

[0009] The present inventors have found that body odor affects the olfactory sensitivity to other substances that activate the same olfactory receptor via the olfactory receptor that responds to it.

[0010] Therefore, the present invention provides a method for immediately improving the olfactory sensitivity of a subject, including reducing the body odor of the subject. The present invention also provides a method for selecting an immediate olfactory sensitivity improver, including identifying a substance that removes the body odor-causing substance. The present invention also provides an immediate olfactory sensitivity improver containing, as an active ingredient, a substance for removing the bad breath-causing substance from the oral cavity. The present invention also provides a body odor evaluation method including measuring the olfactory sensitivity of a subject. The present invention also provides a kit for body odor evaluation including means for measuring the olfactory sensitivity of a subject. [Effects of the Invention]

[0011] The present invention provides a method for improving an individual's olfactory sensitivity by controlling body odor. The present invention also provides various means and substances capable of controlling body odor and thereby improving an individual's olfactory sensitivity. The present invention also provides a method for evaluating an individual's body odor using olfactory sensitivity as an index, and a kit therefor.

Brief Description of the Drawings

[0012]

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Mode for Carrying Out the Invention

[0013] As used herein, the "olfactory cross adaptation" with respect to a target odor refers to a phenomenon in which an individual is pre-exposed to the odor of a substance different from the causative substance of the target odor, becomes accustomed to the odor, and as a result, the olfactory sensitivity to the target odor decreases or changes. Patent Document 1 reveals that the "olfactory cross adaptation" is a phenomenon based on olfactory receptor agonism. That is, the olfactory receptor for the causative substance of the target odor responds to the causative substance of a different odor prior to its response to the causative substance of the target odor, and then the responsiveness decreases. As a result, even when the individual is subsequently exposed to the causative substance of the target odor, only a low response can be elicited, and as a result, a decrease or alteration in the intensity of the target odor recognized by the individual occurs.

[0014] As used herein, the "improvement of olfactory sensitivity" refers to an increase in the detectable intensity of a target odor or a decrease in the detection threshold for the target odor.

[0015] The names of olfactory receptors in this specification follow the names registered in Genbank ( / www.ncbi.nlm.nih.gov / genbank / ).

[0016] As used herein, body odor refers to an odor that is constantly present in an individual and is emitted from the individual's body or clothing. Examples of body odor include, but are not particularly limited to, scalp odor, bad breath, foot odor, sebum odor, axillary odor, sweat odor, and aging odor.

[0017] The odor to which a human is most frequently exposed continuously can be their own body odor. Body odor should be continuously acting on the person's sense of smell and causing olfactory adaptation. In fact, it is an empirically well-known fact that humans have difficulty perceiving their own body odor. Furthermore, although not proven so far, it is presumed that when olfactory adaptation to body odor occurs, the aforementioned cross adaptation also occurs simultaneously, and not only the sensitivity to the body odor but also the sense of smell to substances other than the body odor becomes dull.

[0018] Since olfactory nerve cells are constantly exposed to body odor, it has been conventionally speculated that the adaptation and cross-adaptation to odors caused by body odor as described above are due to long-term adaptation. Therefore, it has been predicted that it would take a long time to recover from these adaptations and cross-adaptations. In contrast, the present inventor has found that by reducing the body odor of an individual, the individual can be recovered from the adaptation and cross-adaptation to odors caused by body odor within a relatively short period of time, and the olfactory sensitivity thereof can be improved.

[0019] Furthermore, it has been found that the cross-adaptation to the above body odor occurs with respect to odor substances that activate the same receptors as the olfactory receptors that respond to the body odor. Therefore, according to the present invention, by reducing the body odor, the olfactory sensitivity to other odor substances that activate the same receptors as the olfactory receptors that respond to the body odor can be improved within a relatively short period of time.

[0020] The above results indicate that temporary body odor care improves the olfactory sensitivity of an individual. Such a technique for improving olfactory sensitivity would be suitable for those who require improvement in olfactory sensitivity, preferably those who require improvement in olfactory sensitivity by reducing body odor, for example, middle-aged and elderly people (although not limited thereto) who generally have a strong body odor and are prone to a decline in olfaction in addition to the increase in body odor.

[0021] Also, the above results indicate that substances or means (for example, washing or deodorant agents for body odor) that contribute to body odor care, even temporarily, are effective in improving olfactory sensitivity. By applying the substances or means that contribute to body odor care to an individual, the olfactory sensitivity of the individual can be improved.

[0022] Also, the above results indicate that the intensity of body odor is reflected in the olfactory sensitivity of an individual. In other words, it is possible to evaluate the body odor of an individual using olfactory sensitivity as an index. That is, if olfactory sensitivity is used as an index, it is possible for an individual to evaluate the intensity of body odor that is difficult to perceive with their own sense of smell due to adaptation.

[0023] Accordingly, in one aspect, the present invention provides a method for improving the olfactory sensitivity of a subject, which includes reducing the body odor of the subject.

[0024] As means for reducing the body odor of a subject, removal of body odor-causing substances from the body of the subject, clothes worn by the subject, etc. can be mentioned. As means for removing body odor-causing substances, washing, adsorption, generation inhibition, volatilization inhibition, decomposition, etc. of body odor-causing substances can be mentioned. The washing of the body odor-causing substances may include washing of body odor-causing substances from the body or clothes using water or a detergent for the body or clothes. The adsorption, generation inhibition, volatilization inhibition, or decomposition of the body odor-causing substances may include application to the body or clothes of activated carbon, bactericides, antibacterial agents, metabolic inhibitors or enzyme inhibitors against body odor-causing bacteria, antioxidants, cyclodextrins, chemical neutralizers, deodorant agents, etc.

[0025] Examples of the body odor-causing substances include diacetyl and isovaleric acid for scalp odor; substances described in Table 3 below such as indole and skatole for bad breath; isovaleric acid for foot odor; unsaturated aliphatic aldehydes having 7 to 10 carbon atoms such as 2,4-heptadienal, 2-octenal, 2-nonenal, 2-decenal, and 2,4-decadienal for sebum odor; 3-methyl-2-hexenoic acid, 3-hydroxy-3-methylhexanoic acid, 3-methyl-3-sulfanylhexan-1-ol (3M3SH), etc. for axillary osmidrosis; 4-methylpentanoic acid, 4-methyl-2-pentenoic acid, 4-methyl-3-pentenoic acid, 4-methyl-4-pentenoic acid, etc. for sweat odor; 2-nonenal, n-octenal, n-nonanal, n-decanal, etc. for aging odor.

[0026] By reducing the body odor, the olfactory sensitivity of the subject to odor substances that adapt to or cross-adapt to the body odor is improved. More specifically, in the present invention, by reducing the body odor, the olfactory sensitivity of the subject to odor substances that activate olfactory receptors responsive to the causative substance of the body odor is improved. Preferably, the odor substances whose olfactory sensitivity is improved in the present invention are odor substances other than the causative substance of the body odor. In the present invention, the improvement of the olfactory sensitivity of the subject to the odor substance is achieved within a relatively short time after the body odor reduction treatment is carried out. Therefore, the improvement of the olfactory sensitivity according to the present invention can be an immediate improvement. The "immediate" improvement of the olfactory sensitivity in the present invention preferably means that the olfactory sensitivity is improved within 1 hour, more preferably within 10 minutes, from the body odor reduction treatment.

[0027] In a preferred embodiment, the body odor is bad breath. As means for reducing the bad breath, washing, adsorbing or decomposing the causative substance of bad breath from the oral cavity, sterilizing the causative bacteria of bad breath, suppressing the metabolism or inhibiting the enzyme against the causative bacteria of bad breath, suppressing the formation or decomposing the biofilm containing the causative bacteria of bad breath, using water or oral care products such as dentifrices, mouthwashes, oral tablets, and oral sprays; and cleaning or sterilizing dentures, etc. can be mentioned. As shown in the examples described later (see Table 3), there are various substances as causative substances of bad breath, and there are olfactory receptors that respond to each of them. Examples of olfactory receptors for causative substances of bad breath include OR4S2, OR5P3, OR2W1, OR1A1, OR2T11, OR8H1, OR5K1, OR51E1, OR51E2, OR51I2, OR52N2, OR11G2, OR5AC2, OR11H6, OR11H4, OR4C15, OR8S1, OR1E1, OR8U8, OR51D1, OR51D14, OR2T1, OR5AI1, OR7G2, OR11H7P, and TAAR5. In the present invention, examples of odor substances whose olfactory sensitivity is improved by reducing bad breath include odor substances that activate olfactory receptors for the causative substances of bad breath listed above. Preferably, the odor substances whose olfactory sensitivity is improved are odor substances other than the causative substances of bad breath.

[0028] In a preferred embodiment, the halitosis-causing substance is indole, and the odor substances that improve olfactory sensitivity include odor substances other than indole that activate the indole receptor. Examples of indole receptors include OR4S2, OR5P3, OR2W1, and OR1A1. As shown in the examples described below, after reducing an individual's halitosis, furfuryl mercaptan, which immediately, preferably within 1 hour, more preferably within 10 minutes to 1 hour, activates the indole receptor OR4S2, and the olfactory sensitivity of the individual to the coffee flavor mainly composed of this substance is improved.

[0029] In another preferred embodiment, the body odor is axillary odor. As a means for reducing the axillary odor, removal of axillary odor-causing substances from the body or clothing (especially the axillary area) by washing the body (axillary area) or clothing is mentioned. In the present invention, odor substances that improve olfactory sensitivity by reducing axillary odor include odor substances other than axillary odor-causing substances that activate axillary odor receptors, such as OR1A1, OR2W1, OR2J3, OR10A6, OR51B2, OR51E1, or OR51I2.

[0030] As another aspect, the present invention provides a means for improving the olfactory sensitivity of a subject. Preferably, the means for improving the olfactory sensitivity can be a means for removing body odor-causing substances, for example, a means for washing, adsorbing, suppressing generation, suppressing volatilization, or decomposing body odor-causing substances. More detailed examples of the means for removing body odor-causing substances include washing body odor-causing substances from the body or clothing using water or a detergent for the body or clothing, adsorbing body odor-causing substances, suppressing generation, suppressing volatilization, and decomposing body odor-causing substances by applying activated carbon, a bactericide, an antibacterial agent, a metabolic inhibitor or an enzyme inhibitor against body odor-causing bacteria, an antioxidant, cyclodextrin, a chemical neutralizer, a deodorant agent, etc. to the body or clothing. These means for removing body odor-causing substances improve the olfactory sensitivity of the subject immediately by removing the body odor of the subject.

[0031] In one embodiment, the present invention provides an olfactory sensitivity enhancer containing, as an active ingredient, a substance for removing malodor-causing substances from the oral cavity. Preferably, the enhancer is an olfactory sensitivity enhancer for odor substances that activate olfactory receptors for the malodor-causing substances. Preferably, the olfactory sensitivity enhancer can be an immediate olfactory sensitivity enhancer. Preferably, the active ingredient is a substance that washes, adsorbs, suppresses the generation of, suppresses the volatilization of, or decomposes malodor-causing substances. Preferably, the malodor-causing substance is Indole, and examples of odor substances that activate olfactory receptors for the malodor-causing substance include odor substances that activate Indole receptors OR4S2, OR5P3, OR2W1, or OR1A1. More preferable examples include Furfuryl mercaptan and a coffee flavor having this as a main component.

[0032] In another embodiment, the present invention provides an olfactory sensitivity enhancer containing, as an active ingredient, a substance for removing axillary malodor-causing substances from the body (mainly the armpits). Preferably, the enhancer is an olfactory sensitivity enhancer for odor substances that activate olfactory receptors for the axillary malodor-causing substances. Preferably, the olfactory sensitivity enhancer can be an immediate olfactory sensitivity enhancer. Preferably, the active ingredient is a substance that washes, adsorbs, suppresses the generation of, suppresses the volatilization of, or decomposes axillary malodor-causing substances. Preferably, the axillary malodor-causing substance is 3-methyl-2-hexenoic acid, 3-hydroxy-3-methylhexanoic acid, or 3-methyl-3-sulfanylhexan-1-ol (3M3SH), and examples of odor substances that activate olfactory receptors for the axillary malodor-causing substance include odor substances that activate axillary malodor receptors (for example, OR1A1, OR2W1, OR2J3, OR10A6, OR51B2, OR51E1, or OR51I2).

[0033] Substances for removing halitosis-causing substances from the oral cavity include oral care products such as toothpastes, mouthwashes, oral tablets, oral sprays, and denture cleansers. The oral care products may optionally contain, but are not limited to, for example, the following components: bases or wetting agents such as water, sorbitol, propylene glycol, glycerin, ethanol; fluorine (sodium fluoride, sodium monofluorophosphate, etc.); bactericides such as benzethonium chloride, benzalkonium chloride, cetylpyridinium chloride, isopropylmethylphenol, chlorhexidine hydrochloride, triclosan; salts of copper, zinc or aluminum such as copper gluconate, copper citrate, copper sulfate, copper chloride, sodium copper chlorophyllin, zinc gluconate, zinc citrate, zinc sulfate, zinc chloride, zinc oxide, aluminum hydroxide, aluminum lactate; thickeners such as anhydrous silicic acid (thickening silica, etc.), carboxymethyl cellulose, carrageenan, xanthan gum, polyacrylic acid; abrasives such as anhydrous silicic acid (abrasive silica, etc.), calcium carbonate; surfactants such as sodium lauryl sulfate, sodium lauroyl methyl taurate, sodium lauroyl glutamate, sodium myristoyl glutamate, coconut oil fatty acid amide propyl betaine, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan stearate, glycerin fatty acid ester, sucrose fatty acid ester, polyoxyethylene stearyl ether; fragrances or sweeteners such as menthol, sodium saccharin; preservatives such as parabens; cyclodextrin; zeolite.

[0034] Furthermore, the bad breath-preventing components that can be used in oral care products can themselves be used in the present invention as a means for removing body odor-causing substances used in the method for improving olfactory sensitivity, or as an active ingredient of an olfactory sensitivity improver. Examples of the bad breath-preventing components that can be used in the oral care products include bactericides such as benzethonium chloride, benzalkonium chloride, cetylpyridinium chloride, isopropylmethylphenol, chlorhexidine hydrochloride, and triclosan; salts of copper, zinc, or aluminum such as copper gluconate, copper citrate, copper sulfate, copper chloride, sodium copper chlorophyllin, zinc gluconate, zinc citrate, zinc sulfate, zinc chloride, zinc oxide, aluminum hydroxide, and aluminum lactate; surfactants such as sodium lauryl sulfate, sodium lauroyl methyl taurate, sodium lauroyl glutamate, sodium myristoyl glutamate, coconut oil fatty acid amide propyl betaine, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan stearate, glycerin fatty acid ester, sucrose fatty acid ester, and polyoxyethylene stearyl ether; cyclodextrin; zeolite, and the like. These bad breath-preventing components can be used alone or in appropriate combinations as the active ingredient of the olfactory sensitivity improver of the present invention.

[0035] As yet another aspect, the present invention provides a method for selecting an olfactory sensitivity improver. As described above, by removing the body odor-causing substances of a subject, the olfactory sensitivity of the subject can be immediately improved. Therefore, the substance that removes the body odor-causing substances can be identified as an olfactory sensitivity improver. Preferably, the substance that removes the body odor-causing substances is an improver of olfactory sensitivity to odor substances that activate olfactory receptors for the body odor-causing substances. Preferably, the olfactory sensitivity improver can be an improver of immediate olfactory sensitivity.

[0036] In one embodiment, the method for selecting an olfactory sensitivity improving agent of the present invention includes examining the action of a test substance to remove a target body odor-causing substance. For example, in this method, the washing, adsorption, generation inhibition, volatilization inhibition, or decomposition action of the body odor-causing substance by the test substance is examined. A test substance having such an action can be specified as an olfactory sensitivity improving agent. A substance having a stronger effect of removing the body odor-causing substance can function as a more powerful olfactory sensitivity improving agent. The type of the test substance is not particularly limited as long as it is a substance desired to be used as an olfactory sensitivity improving agent. For example, the test substance can be a substance expected to have an action of washing, adsorbing, inhibiting the generation of, inhibiting the volatilization of, or decomposing the body odor-causing substance. The test substance may be a naturally occurring substance, a substance artificially synthesized by chemical or biological methods, etc., or may be a compound, a composition, or a mixture. Further, the test substance may be a substance whose olfactory sensitivity improving action or the action of washing, adsorbing, inhibiting the generation of, inhibiting the volatilization of, or decomposing the body odor-causing substance has been evaluated or specified heretofore. In another embodiment, the method for selecting an olfactory sensitivity improving agent of the present invention includes subjecting a substance specified as having an action of removing a body odor-causing substance to a sensory evaluation of its olfactory sensitivity improving action. For example, after specifying a substance that removes the body odor-causing substance from among the test substances as described above, the olfactory sensitivity improving action of the substance may be subjected to a sensory evaluation. Alternatively, a substance already specified as having an action of removing the body odor-causing substance may be subjected to a sensory evaluation of its olfactory sensitivity improving action.

[0037] As yet another aspect, the present invention provides a body odor evaluation method including measuring the olfactory sensitivity of a subject. As yet another aspect, the present invention provides a body odor evaluation kit including means for measuring the olfactory sensitivity of a subject. As shown in the examples described later, the body odor of an individual affects its olfactory sensitivity. Therefore, it is possible to evaluate the body odor of an individual using the olfactory sensitivity as an index.

[0038] In the body odor evaluation according to the present invention, the olfactory sensitivity of a subject is measured with respect to an odorant (hereinafter referred to as a test odorant) that activates an olfactory receptor that responds to a causative substance of the body odor to be evaluated. The test odorant is preferably an odorant other than the causative substance of the body odor to be evaluated. For example, when it is desired to evaluate bad breath, furfuryl mercaptan that activates the receptor for a typical bad breath causative substance, indole, or a coffee flavor containing this as a main component can be used as the test odorant. Also, for example, when it is desired to evaluate axillary odor, an odorant that activates an axillary odor receptor (for example, OR1A1, OR2W1, OR2J3, OR10A6, OR51B2, OR51E1, or OR51I2) can be used as the test odorant.

[0039] In one embodiment of the body odor evaluation according to the present invention, the odor of a sample containing a test odorant at a predetermined concentration is presented to the subject to determine whether the subject can smell the odor. The concentration of the test odorant in the sample can be appropriately adjusted according to the age, sex, etc. of the subject. If the subject cannot smell the test odorant from the sample, the subject can be evaluated as having body odor (positive). On the other hand, if the subject can smell the test odorant from the sample, the subject can be evaluated as having no problem with body odor (negative).

[0040] In another embodiment of the body odor evaluation according to the present invention, the odor of samples containing test odorants at gradually different concentrations is presented to the subject to have the subject select the sample that can smell the odor. The concentration of the test odorant in each sample can be appropriately adjusted according to the age, sex, etc. of the subject. Based on the concentration of the test odorant in the sample selected by the subject, the degree of the subject's body odor can be evaluated.

[0041] The kit for body odor evaluation according to the present invention is a kit for carrying out the body odor evaluation method according to the present invention described above. The kit contains a sample containing the test odorant substance. Preferably, the sample is preferably sealed or coated until use so as to prevent the volatilization of the test odorant substance contained therein. For example, the sample is a card containing the test odorant substance, and a coating for preventing the volatilization of the test odorant substance is applied to the surface thereof. When evaluating body odor, the sample is used after removing its coating. Preferably, the kit is a kit for halitosis evaluation and contains a sample containing furfuryl mercaptan or a sample containing a coffee flavor containing this as a main component as the test odorant substance. As another example, the kit is a kit for axillary odor evaluation and contains a sample containing an odorant substance that activates axillary odor receptors (for example, OR1A1, OR2W1, OR2J3, OR10A6, OR51B2, OR51E1, or OR51I2) as the test odorant substance.

[0042] The kit for body odor evaluation may further include guidance for evaluating the body odor of a subject based on the olfactory sensitivity of the subject to the test odorant substance. In one example, the guidance indicates that when the subject can smell the test odorant substance, the subject is evaluated as having body odor, while when the subject can smell the test odorant substance from the sample, the subject is evaluated as having no problem with body odor. In another example, the guidance provides criteria for evaluating the degree of body odor of the subject based on the concentration of the test odorant substance that the subject can feel. The guidance can be included in a recording medium such as paper, a magnetic disk, a USB memory, or the like.

[0043] According to the body odor evaluation method and the body odor evaluation kit of the present invention, an individual can evaluate the intensity of their own body odor, which is difficult to perceive with their own sense of smell due to adaptation, by themselves.

[0044] As exemplary embodiments of the present invention, the following compositions, manufacturing methods, uses, or methods are further disclosed in this specification. However, the present invention is not limited to these embodiments.

[0045] 〔1〕A method for immediately improving the olfactory sensitivity of a subject, which includes reducing the body odor of the subject. 〔2〕The method according to 〔1〕, preferably including removing the causative substances of body odor from the body or clothes of the subject. 〔3〕The body odor is preferably scalp odor, bad breath, foot odor, sebum odor, axillary odor, sweat odor, or aging odor, more preferably bad breath or underarm odor, even more preferably bad breath, of the method according to 〔1〕 or 〔2〕. 〔4〕Reducing the body odor is preferably including washing the causative substances of body odor from the body or clothing of the subject, as well as adsorbing, suppressing the generation, suppressing the volatilization or decomposing the causative substances of body odor on the body or clothing, more preferably including applying activated carbon, a bactericide, an antibacterial agent, a metabolic inhibitor or an enzyme inhibitor against the causative bacteria of body odor, an antioxidant, cyclodextrin, a chemical neutralizer, or a deodorant agent to the body or clothing, even more preferably including washing the body armpit or clothing (preferably the armpit), or washing the oral cavity, adsorbing or decomposing the causative substances of bad breath, sterilizing the causative bacteria of bad breath, suppressing the metabolism or inhibiting the enzyme against the causative bacteria of bad breath, suppressing the formation or decomposing the biofilm containing the causative bacteria of bad breath, washing or sterilizing dentures, even more preferably including applying an anti - bad breath component that can be used in oral care products into the oral cavity, where the anti - bad breath component includes at least one selected from the group consisting of a bactericide that can be used in oral care products, salts of copper, zinc or aluminum, an activator, cyclodextrin and zeolite, the bactericide includes at least one selected from the group consisting of benzethonium chloride, benzalkonium chloride, cetylpyridinium chloride, isopropylmethylphenol, chlorhexidine hydrochloride, and triclosan, The salt of copper, zinc or aluminum contains at least one selected from the group consisting of copper gluconate, copper citrate, copper sulfate, copper chloride, sodium copper chlorophyllin, zinc gluconate, zinc citrate, zinc sulfate, zinc chloride, zinc oxide, aluminum hydroxide, and aluminum lactate, The activator contains at least one selected from the group consisting of sodium lauryl sulfate, sodium lauroyl methyl taurate, sodium lauroyl glutamate, sodium myristoyl glutamate, coconut oil fatty acid amide propyl betaine, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan stearate, glycerin fatty acid ester, sucrose fatty acid ester, and polyoxyethylene stearyl ether, The method according to [3]. 〔5〕Preferably, the olfactory sensitivity is furfuryl mercaptan or coffee flavor sensitivity, and the method according to any one of [1] to [4]. 〔6〕A method for selecting an immediate olfactory sensitivity improver, which includes identifying a substance that removes a body odor-causing substance. 〔7〕A method for selecting an immediate olfactory sensitivity improver, which includes sensory evaluation of the olfactory sensitivity improving effect of a substance identified as a substance that removes a body odor-causing substance. 〔8〕Preferably, the substance that removes the body odor-causing substance is a substance having a cleaning, adsorption, generation inhibition, volatilization inhibition or decomposition effect on the body odor-causing substance, and the method according to [6] or [7]. 〔9〕The body odor is Preferably, it is scalp odor, bad breath, foot odor, sebum odor, axillary odor, sweat odor, or aging odor, More preferably, it is bad breath or underarm odor, Even more preferably, it is bad breath, The method according to any one of [6] to [8]. 〔10〕An immediate olfactory sensitivity improver containing, as an active ingredient, a substance for removing a bad breath-causing substance from the oral cavity. 〔11〕Preferably, the substance for removing the bad breath-causing substance is a substance that cleans, adsorbs, inhibits the generation, inhibits the volatilization or decomposes the bad breath-causing substance, and the agent according to

[10] . 〔12〕Preferably, the agent according to 〔10〕 or 〔11〕, wherein the halitosis-causing substance is Indole. 〔13〕The substance for removing the halitosis-causing substance is Preferably, it is a halitosis-preventing component that can be used in oral care products, The halitosis-preventing component contains at least one selected from the group consisting of a bactericide, a salt of copper, zinc or aluminum, an activator, cyclodextrin and zeolite that can be used in oral care products, The bactericide contains at least one selected from the group consisting of benzethonium chloride, benzalkonium chloride, cetylpyridinium chloride, isopropylmethylphenol, chlorhexidine hydrochloride, and triclosan, The salt of copper, zinc or aluminum contains at least one selected from the group consisting of copper gluconate, copper citrate, copper sulfate, copper chloride, sodium copper chlorophyllin, zinc gluconate, zinc citrate, zinc sulfate, zinc chloride, zinc oxide, aluminum hydroxide, and aluminum lactate, The activator contains at least one selected from the group consisting of Na lauryl sulfate, Na lauroyl methyl taurine, Na lauroyl glutamate, Na myristoyl glutamate, coconut oil fatty acid amide propyl betaine, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan stearate, glycerin fatty acid ester, sucrose fatty acid ester, and polyoxyethylene stearyl ether, The agent according to any one of 〔10〕 to 〔12〕. 〔14〕Use of a substance for removing a halitosis-causing substance from the oral cavity for improving immediate olfactory sensitivity. 〔15〕Use of a substance for removing a halitosis-causing substance from the oral cavity in the manufacture of an immediate olfactory sensitivity improver. 〔16〕Preferably, the use according to 〔14〕 or 〔15〕, wherein the substance for removing the halitosis-causing substance is a substance that washes, adsorbs, suppresses generation, suppresses volatilization or decomposes the halitosis-causing substance. 〔17〕Preferably, the use according to any one of 〔14〕 to 〔16〕, wherein the halitosis-causing substance is Indole. 〔18〕A substance for removing the malodor-causing substance is preferably an anti-malodor component that can be used in oral care products, the anti-malodor component includes at least one selected from the group consisting of a bactericide, a salt of copper, zinc or aluminum, an activator, cyclodextrin, and zeolite that can be used in oral care products, the bactericide includes at least one selected from the group consisting of benzethonium chloride, benzalkonium chloride, cetylpyridinium chloride, isopropylmethylphenol, chlorhexidine hydrochloride, and triclosan, the salt of copper, zinc or aluminum includes at least one selected from the group consisting of copper gluconate, copper citrate, copper sulfate, copper chloride, sodium copper chlorophyllin, zinc gluconate, zinc citrate, zinc sulfate, zinc chloride, zinc oxide, aluminum hydroxide, and aluminum lactate, the activator includes at least one selected from the group consisting of Na lauryl sulfate, Na lauroyl methyl taurine, Na lauroyl glutamate, Na myristoyl glutamate, coconut oil fatty acid amide propyl betaine, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan stearate, glycerin fatty acid ester, sucrose fatty acid ester, and polyoxyethylene stearyl ether, 〔14〕The use according to any one of 〔14〕to 〔17〕. 〔19〕An instant olfactory sensitivity improver containing, as an active ingredient, a substance for removing the body odor-causing substance. 〔20〕Preferably, the agent according to 〔19〕, wherein the substance for removing the body odor-causing substance is a substance that washes, adsorbs, suppresses the generation, suppresses the volatilization or decomposes the body odor-causing substance. 〔21〕Preferably, the agent according to 〔19〕or 〔20〕, wherein the body odor-causing substance is 3-methyl-2-hexenoic acid, 3-hydroxy-3-methylhexanoic acid, or 3-methyl-3-sulfanylhexan-1-ol. 〔22〕Use of a substance for removing the body odor-causing substance from the body for instant improvement of olfactory sensitivity. Use of a substance for improving the immediate olfactory sensitivity in the manufacture of an agent for removing body odor-causing substances from the body. 〔24〕The use according to 〔22〕 or 〔23〕, preferably, the substance for removing the body odor-causing substance is a substance that washes, adsorbs, suppresses the generation, suppresses the volatilization or decomposes the body odor-causing substance. 〔25〕The use according to any one of 〔22〕 to 〔24〕, preferably, the body odor-causing substance is 3-methyl-2-hexenoic acid, 3-hydroxy-3-methylhexanoic acid, or 3-methyl-3-sulfanylhexan-1-ol. 〔26〕A body odor evaluation method including measuring the olfactory sensitivity of a subject. 〔27〕The body odor is Preferably, it is scalp odor, bad breath, foot odor, sebum odor, axillary odor, sweat odor, or aging odor, More preferably, it is bad breath or body odor, Even more preferably, it is bad breath, The method according to 〔26〕. 〔28〕The method according to 〔26〕 or 〔27〕, preferably, the olfactory sensitivity is furfuryl mercaptan or coffee flavor sensitivity. 〔29〕A body odor evaluation kit including means for measuring the olfactory sensitivity of a subject. 〔30〕The body odor is Preferably, it is scalp odor, bad breath, foot odor, sebum odor, axillary odor, sweat odor, or aging odor, More preferably, it is bad breath or body odor, Even more preferably, it is bad breath, The kit according to 〔29〕. 〔31〕The kit according to 〔29〕 or 〔30〕, preferably, the olfactory sensitivity is furfuryl mercaptan or coffee flavor sensitivity. 〔32〕The kit according to any one of 〔29〕 to 〔31〕, preferably, containing a sample containing an odor substance that activates an olfactory receptor responsive to the body odor-causing substance to be evaluated, and the odor substance is preferably furfuryl mercaptan or coffee flavor. [

[33] ]Preferably, the kit according to [

[32] ] further comprises guidance for evaluating the body odor of a subject based on the olfactory sensitivity of the subject to the odorant substance. [

[34] ]Use for evaluating halitosis with Furfuryl mercaptan or coffee flavor. [[Examples]]

[0046] Hereinafter, examples will be shown to more specifically explain the present invention. The odorant substances used in the following examples are shown in Table 1.

[0047] [[Table 1]]

[0048] [[Reference Example 1 Preparation of Human Olfactory Receptor-Expressing Cells]] [[1) Cloning of Human Olfactory Receptor Genes]] Genes encoding human olfactory receptors OR10G4, OR4S2, OR5P3, OR2W1, and OR1A1 (SEQ ID NOs: 1, 2, 3, 4, and 5, respectively) were cloned. Each gene was cloned by PCR using human genomic DNA female (G1521: Promega) as a template based on the sequence information registered in GenBank. Each gene amplified by PCR was manually incorporated into a pENTR vector (Invitrogen), and using the NotI / AscI sites present on the pENTR vector, it was recombined into the NotI / AscI sites created downstream of the Flag-Rho tag sequence on the pME18S vector.

[0049] [[2) Preparation of pME18S-Human RTP1S Vector]] The RTP1S gene encoding RTP1S was incorporated into the EcoRI / XhoI sites of the pME18S vector.

[0050] [[3) Preparation of Olfactory Receptor-Expressing Cells]] HEK293 cells expressing any one of the above human olfactory receptors were prepared. A reaction solution with the composition shown in Table 2 was prepared, allowed to stand for 15 minutes in a clean bench, and then added to each well of a 96-well plate (BD). Next, HEK293 cells (3×10 5 cells / cm 2 ) were seeded at 90 μL per well and cultured for 24 hours in an incubator maintained at 37 °C and 5% CO2. As a control, cells (Mock) that did not express an olfactory receptor incorporating a pME18S vector not containing a human olfactory receptor gene were prepared in the same procedure and cultured similarly.

[0051]

Table 2

[0052] Reference Example 2 Luciferase Assay The olfactory receptor expressed in HEK293 cells is conjugated with endogenous Gαs in the cells and activates adenylate cyclase, thereby increasing the intracellular cAMP level. For measuring the receptor response in this study, a luciferase reporter gene assay was used to monitor the increase in the intracellular cAMP level as the luminescence value derived from the firefly luciferase gene (fluc2P-CRE-hygro). In addition, a construct (hRluc-CMV) in which a Renilla luciferase gene was fused downstream of the CMV promoter was co-transfected and used as an internal standard to correct for transfection efficiency and cell number errors.

[0053] The medium was removed from the culture prepared in 3) above, and an odorant solution was added. The odorant solution was prepared with DMEM (Nacalai Tesque) or DMEM (Nacalai Tesque) containing 300 μM copper chloride. The cells were cultured in a CO2 incubator for 4 hours to allow sufficient expression of the luciferase gene in the cells. The activity of luciferase was measured using Dual-Glo TMUsing the luciferase assay system (Promega), measurements were performed according to the product's operation manual. The value of fLuc / hRluc was calculated by dividing the luminescence value derived from firefly luciferase by the luminescence value derived from Renilla luciferase. The value obtained by dividing the fLuc / hRluc induced in cells stimulated with an odorant by the fLuc / hRluc in cells not stimulated with an odorant was calculated as the fold increase and used as an index of the response intensity.

[0054] Reference Example 3 Response of OR10G4 to odorants The response of OR10G4 to odorants was measured according to the methods described in Reference Examples 1 and 2. As a result, it was confirmed that both Ethyl vanillin and Guaiacol activate OR10G4 (Figure 1). This result is consistent with the report in Patent Document 1.

[0055] Example 1 Variation in olfactory sensitivity due to oral odor Patent Document 1 reports that pre-smelling Ethyl vanillin not only dulls the olfactory sensitivity to subsequently smelled Ethyl vanillin but also dulls the olfactory sensitivity to Guaiacol due to cross-adaptation. In this example, it was verified whether adaptation and cross-adaptation are caused in the sense of smell by bad breath, that is, the odor in the oral cavity. Specifically, when Ethyl vanillin was added to the oral cavity, it was examined whether the olfactory sensitivity to Ethyl vanillin and Guaiacol decreased.

[0056] 1) Method A 0.5% (w / w) Ethyl vanillin-containing tablet (0.5% EV tablet) was held in the mouth, and the variation in olfactory sensitivity was examined while continuously licking. As odorants for evaluating olfactory sensitivity, Ethyl vanillin and Guaiacol, which is known to cause cross-adaptation with Ethyl vanillin, were used.

[0057] (Preparation of test samples) 2.0 mg of Ethyl vanillin (≥98%, Sigma-Aldrich) was placed in a glass bottle (Maruemu No. 6). This was used as a test sample for Ethyl vanillin evaluation. Also, Guaiacol (>98%, Tokyo Chemical Industry Co., Ltd.) was diluted with mineral oil to prepare a 10 ppmv Guaiacol solution. 20 μL of this solution was impregnated into a cotton ball (White Cross Co., Ltd., No. 10) with a diameter of approximately 10 mm and placed in a glass bottle (Maruemu No. 6). This was used as a test sample for Guaiacol evaluation.

[0058] (Sensory test) The sensory test was conducted with 3 subjects. In the test, the subjects were first presented with one of the test samples and evaluated the intensity of the odor sensation to the sample. Next, the subjects licked 5 tablets of 0.5% EV tablets, and at 1 minute, 3 minutes, and 5 minutes after that, the same test sample was presented again, and the intensity of the odor sensation to the sample was evaluated. The above procedure was taken as one set of the test. One set of tests was conducted for each of the two types of test samples. As a control, the intensity of the odor sensation to the two types of test samples was evaluated in the same procedure except that the subjects were given Ethyl vanillin-free tablets (0% EV tablets). That is, each subject conducted a total of 4 sets of tests. An interval of at least 15 minutes was provided between sets. The Visual analogue scale (VAS) was used to evaluate the intensity of the odor sensation.

[0059] For each test sample, the relative value of the intensity of the odor sensation (VAS value) at 1 minute, 3 minutes, and 5 minutes after tablet ingestion was determined with respect to when the intensity of the odor sensation (VAS value) before tablet ingestion was taken as 100%. The difference in the relative sensation intensity between the test (0.5% EV tablet) condition and the control (0% EV tablet) condition at each time point (before ingestion, 1, 3, 5 minutes) was compared by multiple comparison test using the Sidak method after two-way ANOVA, and the multiplicity-adjusted p-value was calculated. Statistical analysis was performed using GraphPad prism 6 (MDF Co., Ltd.).

[0060] 2) Results The results of the sensory test are shown in Figure 2. By licking the ethyl vanillin-containing tablets, a statistically significant decrease in the olfactory intensity of ethyl vanillin was observed compared to the conditions of the ethyl vanillin-free tablets. Furthermore, a decrease in the olfactory intensity was also observed for guaiacol, a substance that shows cross-adaptation with ethyl vanillin, by licking the ethyl vanillin-containing tablets. From these results, it was suggested that not only the odor through the nostrils from the outside world but also the odor generated in one's own oral cavity can reach the olfactory epithelium and act on olfaction, causing adaptation and cross-adaptation and reducing olfactory sensitivity.

[0061] Example 2 Variation in Olfactory Sensitivity due to Bromhidrosis In this example, it was verified whether bromhidrosis causes olfactory adaptation. Specifically, the temporal variation in olfactory sensitivity to 3-methyl-3-sulfanylhexan-1-ol (3M3SH), one of the typical bromhidrosis-causing substances, was examined when it was applied to the axillary region on clothing and then removed.

[0062] 1) Method (Sample Preparation) 3M3SH was used as the bromhidrosis-causing substance. The sensory evaluation samples were prepared by placing one cotton ball (White Cross Co., Ltd., No. 10) in a 13.5 mL vial (Maruemu No. 5) and adding 10 μL of the 3M3SH solution at each dilution concentration. For the 3M3SH solution, mineral oil (Sigma-Aldrich) was used as the solvent, and concentrations of 0 μM, 1 μM, 3 μM, 10 μM, 30 μM, 100 μM, and 300 μM were prepared.

[0063] (Sensory Test) The sensory test was conducted on two subjects. The subjects wore commercially available white coats (material: 65% polyester, 35% cotton). The subjects first smelled the above samples in order from low-concentration samples to high-concentration samples and evaluated the intensity of the odor sensation felt. The evaluation was carried out in 9 grades at 0.5 intervals from "0: don't know" to "4: feel extremely strongly". Then, 10 μL of 3M 3SH ethanol solution (3 μg / mL) was added to both sides of the subjects' clothing (white coats). 15 minutes after this solution addition, the above sensory evaluation was carried out again. Immediately after the second sensory evaluation, 3M 3SH ethanol solution was added to both sides of the clothing in the same manner as above, and then the 3M 3SH solution was added to both sides of the clothing every 15 minutes, and the sensory evaluation was carried out every 30 minutes. When the addition time of the 3M 3SH solution overlapped with the sensory evaluation, the 3M 3SH solution was added to both sides of the clothing immediately after the sensory evaluation. 90 minutes after the start of the test, the white coats were taken off and the addition of the 3M 3SH solution was stopped. Then, the sensory evaluation was carried out until the 165th minute after the start of the test, and the test was completed. The amount of 3M 3SH applied to the clothing was set at 240 ng per hour. In previous research (J Invest Dermatol. 2010, 130(2): 529-40), the maximum value of the 3M 3SH precursor collected from both armpits in 30 minutes was shown to be 0.051 μmol. Another previous study (FEMS Microbiol Lett. 2015, 362(16): fnv111), although it is an in vitro result, showed that the maximum value of the metabolic efficiency from the 3M 3SH precursor to 3M 3SH per 24 hours is 44.6%. Calculating from the above information, it could be estimated that up to about 281 ng of 3M 3SH is produced from both armpits per hour. Therefore, in this example, by applying 240 ng of 3M 3SH to the armpits per hour, experimental conditions were set that are not far from real-life scenarios.

[0064] 2) Results The change over time in the odor intensity of 3M3SH is shown in Figure 3. Fifteen minutes after applying 3M3SH to the sides of the body, the odor intensity of 3M3SH felt from the sample decreased. Furthermore, the decreased sense of smell for the 3M3SH sample recovered in at least 15 to 45 minutes when the 3M3SH in the armpits was removed. From the above, it was suggested that the olfactory sensitivity to specific odor substances is regulated not only by bad breath but also by body odor including axillary osmidrosis, and that the olfactory sensitivity to the specific odor substances is improved by removing body odor including axillary osmidrosis.

[0065] Example 3 Olfactory Receptors Recognizing Bad Breath Substances and Their Ligand Selectivity As shown in Example 1, odor substances in the oral cavity act on the olfactory epithelium to reduce olfactory sensitivity. On the other hand, various bad breath substances exist in the oral cavity. Table 3 shows the bad breath substances reported in previous studies (J Chromatogr B Analyt Technol Biomed Life Sci, 2007, 853(1-2):54-61), the previous studies on them (US9914760B2, J Neurosci, 2009, 29(1):153-158, Sci Data, 2015, 2:150002, PLoS Biol, 2007, 30, 5(11):e284, PLoS One, 2013, 8(2):e54950), and the human olfactory receptors found in this study (Figure 4).

Table 3

[0066] Example 4 Recovery of Olfactory Sensitivity by Oral Care 1) Receptor Response to Bad Breath Substances In this example, after reducing malodor substances by oral care, it was examined whether the olfactory sensitivity recovered for malodor substances and other odor substances that are not malodor substances. As a typical malodor substance, Indole (J Chromatogr B Analyt Technol Biomed Life Sci, 2007, 853(1-2):54-61) was used, and Furfuryl mercaptan and Muscone were used as other odor substances that are not malodor substances. As a result of measuring the olfactory receptor response to these odor substances according to the methods described in Reference Examples 1 and 2, it was found that the Indole receptor OR4S2 was activated by Furfuryl mercaptan but not by Muscone (Figure 5).

[0067] Muscone is mainly recognized via OR5AN1 (Patent Document 1), but on the other hand, no malodor substances that activate OR5AN1 have been found at present (Table 3). Therefore, when the malodor substances containing Indole in the oral cavity after oral care are reduced, the responsiveness of OR5AN1 does not change, but the responsiveness of OR4S2 recovers, whereby the olfactory sensitivity to Muscone does not change, and it was predicted that the olfactory sensitivity to Indole and Furfuryl mercaptan would increase.

[0068] 2) Evaluation of olfactory sensitivity The olfactory sensitivity before and after oral care was evaluated by a sensory test. The experimental scheme is shown in Figure 6A and will be described in detail below. The sensory test was conducted on 14 subjects. On the day, all food and drink intake of the subjects was restricted after waking up, and oral care including toothbrushing was prohibited. The test started between 8:00 am and 9:30 am. First, the exhaled breath of the subjects was collected. Next, the detection threshold concentration of each odor substance was measured by a sensory test. Thereafter, the subjects had a designated breakfast, and then oral care (brushing teeth for 5 minutes using a commercially available toothbrush and toothpaste, and rinsing the mouth for 30 seconds using a commercially available mouthwash) was performed. At 10 minutes and 1 hour after the oral care, the exhaled breath of the subjects was collected, and the detection threshold concentration of each odor substance was measured.

[0069] (Measurement of substances in exhaled breath) The subject enclosed their breath in an air sampling bag for atmospheric collection (GL Sciences Inc., PA AA-2). The breath sample was stored at room temperature and analyzed on the same day. A Solid Phase Micro Extraction (SPME) fiber (Supelco, PDMS / DVB) was exposed in the sampling bag to collect breath substances for 1 hour. The indole concentration in the breath was calculated by SPME-GC / MS. The indole concentrations before and after oral care were compared by the Wilcoxon signed-rank test, and the p-value was calculated. Statistical analysis was performed using R software (Ver. 3.6.0). <GC / MS Conditions> GC: 7890A (Agilent Technologies, Inc.) Injection Condition: Splitless Column: VF-WAXms Carrier Gas: Helium Oven temp: 40°C (4 min hold) → heated at 6°C / min → 240°C (2 min hold) MS: 5975C (Agilent Technologies, Inc.)

[0070] (Odor Sample) A 1 mL odor substance solution placed in a vial (Maruemu, No. 2) was used as the odor sample. For the odor substance solution, 20-step two-fold dilution series with a maximum concentration of 1000 ppm, 1 mM, and 10 ppb for Muscone, Indole, and Furfuryl mercaptan, respectively, were prepared. Mineral oil (Sigma-Aldrich) was used as the solvent for all. A vial containing 1 mL of mineral oil was used as the blank.

[0071] (Measurement of Detection Threshold Concentration) One test was conducted on two types of odor substances out of Muscone, Indole, and Furfuryl mercaptan. Two blank vials and one vial of the odor sample, a total of three vials, were presented to the subjects. The test participants smelled the odors of the vials and selected the vial containing the odor solution. The test started with the odor sample at the third lowest concentration. If the selection was incorrect or could not be made even once, a similar trial was conducted with an odor sample at a one-step higher concentration. If the correct answer was given twice in a row, a similar trial was conducted with an odor sample at a one-step lower concentration. If the correct answer was given twice in a row with a new concentration of the odor sample, the test was further conducted with an odor sample at a one-step lower concentration. If the correct answer could not be given even once, the test was conducted with an odor sample at a one-step higher concentration than that concentration. After recording the switching from high concentration to low concentration and from low concentration to high concentration a total of 7 times, the average value of the concentrations in the latter 4 times was taken as the detection threshold concentration. The detection threshold concentrations of each odor substance before and after oral care were compared by the Wilcoxon signed-rank test, and the p-value was calculated. The statistical analysis was performed using R software (Ver. 3.6.0).

[0072] 3) Results (Concentration of substances in exhaled breath) The concentration of Indole in exhaled breath is shown in Fig. 6B. Indole was detected in all subjects, and the concentration of Indole was significantly decreased 1 hour after oral care compared with that before oral care. This result indicates that the oral malodor substances in exhaled breath were removed by oral care. Muscone and Furfuryl mercaptan were not detected before and after oral care, and this result was consistent with the reports in many previous studies on the analysis of oral malodor substances that Muscone and Furfuryl mercaptan were not detected.

[0073] (Variation in olfactory sensitivity) The results of the detection threshold concentration measurement by sensory evaluation before and after oral care are shown in Fig. 7. There was no statistically significant difference in the olfactory sensitivity to muscone before oral care and 1 hour after oral care (Fig. 7A, left). This was thought to be because neither muscone nor the substance activating the muscone receptor OR5AN1 was originally contained in the malodor substances, so even if the malodor substances decreased due to oral care, there was no change in the responsiveness of OR5AN1. On the other hand, the olfactory sensitivity to indole, a malodor substance, was significantly improved statistically 1 hour after oral care compared to before oral care (Fig. 7A, middle). The increase in indole sensitivity was observed in all the subjects. The indole detection threshold concentration decreased to 1 / 8 times on average 1 hour after oral care and to 1 / 16 times 10 minutes after oral care compared to before oral care (Fig. 7B). In addition, furfuryl mercaptan, which activates the indole olfactory receptor OR4S2, although not a malodor substance, showed a statistically significant improvement in sensitivity 1 hour after oral care compared to before oral care, and this improvement in sensitivity was observed in all the subjects (Fig. 7A, right). Therefore, it was considered that as the indole in the oral cavity decreased, the responsiveness of OR4S2 recovered, and the olfactory sensitivity to both indole and furfuryl mercaptan, which activate OR4S2, improved.

[0074] Since bad breath always exists in the oral cavity, it has been hitherto speculated that an individual's sense of smell has undergone long-term adaptation to bad breath. Since it takes a long time equivalent to the adaptation period to recover from long-term adaptation (Non-Patent Documents 2 to 4), it has been predicted that it takes a long time for the olfactory sensitivity to bad breath to recover after removing bad breath. In contrast, the results of this example showed for the first time that the adaptation to the most familiar odor of bad breath recovers at a clear level within just 10 minutes or 1 hour of non-exposure time. This is a finding contrary to the above conventional prediction based on the understanding that a long non-exposure time is required to recover from the adaptation due to long-term odor exposure. Furthermore, from the results of this example, it was found that which odor substances show an increase in olfactory sensitivity in a short time after oral care can be predicted from the viewpoint of "substances recognized by olfactory receptors that respond to malodor substances".

[0075] Example 5 Improvement of Coffee Flavor Sensitivity by Oral Care Furfuryl mercaptan is a major aroma component of coffee. It was verified whether the coffee flavor would be felt more richly when bad breath was reduced by oral care.

[0076] 1) Method The sensory test was conducted on 3 subjects. The test was carried out over two consecutive days, both starting at 8:40 am. On the test day, the subjects were restricted from eating or drinking anything after waking up, and oral care including toothbrushing was prohibited. On the first day, the subjects were presented with approximately 150 mL of commercially available instant coffee adjusted to about 80°C and were subjected to sensory evaluation. On the second day, before the coffee sensory evaluation, the subjects performed oral care using a commercially available toothbrush and toothpaste for 2 minutes and then took a 5-minute break. Then, as on the first day, the subjects were presented with approximately 150 mL of commercially available instant coffee adjusted to about 80°C and were subjected to sensory evaluation. The scores of the first day and the second day were compared.

[0077] (Sensory Evaluation) The coffee was prepared immediately before the sensory evaluation so as not to impair its flavor. Before the sensory evaluation of the coffee, the subjects first drank a mouthful of water, then tasted the coffee, and answered the sensory evaluation questionnaire. In the sensory evaluation questionnaire, the subjects evaluated the "intensity of aroma", "intensity of bitterness", "intensity of sourness", "intensity of sweetness", "intensity of body", "intensity of aftertaste", and "intensity of coffee flavor" of the coffee using a 5-point scale (1; not felt, 2; not felt much, 3; felt, 4; strongly felt, 5; very strongly felt). The average value of the evaluations of the 3 subjects was obtained.

[0078] 2) Results The results of the sensory evaluation are shown in Fig. 8. A tendency was found that the coffee flavor was felt more strongly when there was oral care compared to when there was no oral care. Therefore, it was shown that the improvement of olfactory sensitivity by reducing bad breath is significant enough to clearly affect the impression of aroma in daily life.

[0079] Example 6 Odorous substances and olfactory receptor groups responsive thereto As shown in Table 3, various odorous substances exist in the oral cavity, and there are also many olfactory receptors responsive thereto. For example, #22 Butyric acid in Table 3 is considered as an odorous substance that increases with liver dysfunction and is recognized by OR51D1, OR51D14, OR2T1, OR5Al1, and OR7G2. Therefore, reducing the odorous substances in the oral cavity is considered to result in improving the sensitivity of these olfactory receptors in a short time.

[0080] Furthermore, as shown in Examples 3 to 4, improving the responsiveness of the odor receptor group leads to an improvement in sensitivity to various odor substances other than odorous substances. For example, Fig. 9 shows ligand spectra for four Indole receptors OR4S2, OR5P3, OR2W1, and OR1A1 examined according to the methods described in Reference Examples 1 and 2. Since OR4S2 is activated by odor substances classified chemically as sulfides and thiols, improving the responsiveness of OR4S2 by oral care is considered to lead to increased sensitivity to odor substances in these classifications. Also, since OR2W1 may be involved in the recognition of a wide range of odor substances excluding sulfides, the improvement in the sensitivity of OR2W1 by oral care is thought to be involved in the sensitivity to those wide-ranging odor substances. Similarly, for body odor other than bad breath, improving the responsiveness of the olfactory receptors responsive to the body odor by body odor care is considered to result in an improvement in olfactory sensitivity to a wide range of odor substances to which those olfactory receptors respond.

Claims

1. A method for improving the olfactory sensitivity of a subject to an odorant that activates an olfactory receptor responsive to an odor-causing substance in the subject immediately, including reducing the body odor of the subject.

2. The method according to claim 1, including removing an odor-causing substance from the body or clothes of the subject.

3. The method according to claim 1 or 2, wherein the body odor is bad breath.

4. The method according to claim 3, including rinsing the oral cavity.

5. The method according to claim 3 or 4, wherein the olfactory sensitivity to an odorant that activates an olfactory receptor responsive to the odor-causing substance is coffee flavor sensitivity.

6. The method according to claim 1 or 2, wherein the body odor is axillary odor.

7. The method according to claim 6, including washing the axilla.

8. A method for selecting an immediate olfactory sensitivity improver for an odorant that activates an olfactory receptor responsive to an odor-causing substance, including identifying a substance that removes the odor-causing substance.

9. The method according to claim 8, further including a sensory evaluation of the olfactory sensitivity improving effect of the substance that removes the identified odor-causing substance on an odorant that activates an olfactory receptor responsive to the odor-causing substance.

10. A body odor evaluation method, including measuring the olfactory sensitivity of a subject to an odorant that activates an olfactory receptor responsive to an odor-causing substance.

11. The method according to claim 10, wherein the body odor is bad breath.

12. The method according to claim 11, wherein the olfactory sensitivity to the odorant that activates the olfactory receptor responsive to the causative substance of body odor is furfuryl mercaptan or coffee flavor sensitivity.

13. The method according to claim 10, wherein the body odor is axillary odor.

14. A kit for body odor evaluation, comprising means for measuring the olfactory sensitivity of a subject to an odorant that activates the olfactory receptor responsive to the causative substance of body odor.

15. The kit according to claim 14, wherein the body odor is bad breath.

16. The kit according to claim 15, wherein the olfactory sensitivity to the odorant that activates the olfactory receptor responsive to the causative substance of body odor is furfuryl mercaptan or coffee flavor sensitivity.

17. The kit according to claim 14, wherein the body odor is axillary odor.

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