Smell suppressant

Abstract

To provide an agent for suppressing a sense of smell to various smells.SOLUTION: An agent for suppressing a sense of smell contains at least one selected from the group consisting of ambrettolide, muscone, and damascenone as an active ingredient. The agent suppresses a sense of smell regardless of the type of the smell.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an odor sense suppressant. [Background technology]

[0002] Smell plays an important role in enriching our daily lives. For example, the smell of cooking provides a rich flavor, and the smell of everyday products provides a sense of cleanliness and other pleasant sensations. On the other hand, unpleasant smells are also important. Smell plays a major role in quickly informing us of any deterioration in health or hygiene. However, there are many people who find the smell of perfume or fabric softener worn by others unpleasant. There have also been reported cases of olfactory hypersensitivity caused by illness or stress, and these patients experience stress on a daily basis because they are sensitive to all kinds of smells, and in severe cases, this can even interfere with their daily lives.

[0003] Most odorants are volatile low-molecular-weight organic compounds with a molecular weight of about 30 to 300. These odorants are diverse in both the quality of their odor and their chemical structure, and in research from the viewpoint of molecular biology, they are often classified based on their chemical structure. For example, Non-Patent Document 1 classifies 125 types of odorants into 13 groups: amines, thiols, alcohols, esters, ethers, aldehydes, cyclic alkanes, terpenes, vanillins, camphors, azines, musks, ketones, and others. Patent Document 1 also classifies odorants into nine groups: amines, alcohols, aldehydes, ketones, acids, esters, benzenes, vanillin-like compounds, and lactones.

[0004] Odorants are recognized by olfactory receptors in the olfactory nerve cells that are spread in the deepest part of the nasal cavity. The olfactory receptors bind and activate odorants, causing electrical excitation in the olfactory nerve cells. This electrical excitation is transmitted to the higher brain via neural connections, and the odor is perceived. In humans, there are about 400 types of genes that code for olfactory receptors. This large number of receptors is the molecular basis that enables the detection of the various odors mentioned above. Each of these approximately 400 types of olfactory receptors is expressed in a different olfactory nerve cell. On the other hand, olfactory nerve cells that express the same olfactory receptor converge to the same specific area in the olfactory bulb where their axons project. For this reason, information on which olfactory receptors are activated in the nasal cavity is reflected in geometric information, that is, the area of ​​the olfactory bulb that fires, and is transmitted to the higher brain area without being lost. In this way, it is thought that information on the combination of olfactory receptors that are activated for each odorant is transmitted to the higher brain area, resulting in differences in the quality of the odor.

[0005] Knowledge has been accumulated about the relationship between odors and the olfactory receptors involved in their recognition. According to these findings, olfactory receptors generally selectively recognize structurally similar odorants. For example, Non-Patent Document 1 suggests that about 45% of the approximately 1,000 olfactory receptors in mice recognize only one group of odorants classified into 13 groups based on chemical structure. On the other hand, Non-Patent Document 1 suggests that 13.4% of olfactory receptors recognize odorants in 5 to 9 groups, and in particular 1.8% recognize odorants in 10 to 12 groups, which is an extremely wide range of odorants structurally. Olfactory receptors that recognize such a wide range of odorants are called broadly tuned olfactory receptors. Non-Patent Document 1 lists mouse Olfr42 as a representative broadly tuned olfactory receptor. Non-Patent Document 2 also lists OR2W1, the human homologue of Olfr42, as a broadly tuned olfactory receptor. Conventionally, several hypotheses have been proposed regarding the role of broadly tuned olfactory receptors (Non-Patent Document 2), but these hypotheses have not been verified.

[0006] Recently, a BT receptor single response model was constructed that selectively activates only OR2W1, one of the Broadly Tuned Olfactory Receptors (BT receptors), and the role of the BT receptor was verified. Patent Document 2 reports that by enhancing the activity of the BT receptor, the odor of various odorants can be sensed more acutely or more strongly, and suggests that the BT receptor transmits information on the odor intensity, not the odor quality, of various odorants. Patent Document 2 also describes that a substance that controls the response of the BT receptor can be used as a substance that controls the sense of smell regardless of the type of odor. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] International Publication No. 2015 / 020158 [Patent Document 2] International Publication No. 2018 / 142961 [Non-patent literature]

[0008] [Non-Patent Document 1] J Neurosci, 31:9179-91, 2011 [Non-Patent Document 2] Proc Natl Acad Sci USA, 112:14966-71, 2015 Summary of the Invention [Problem to be solved by the invention]

[0009] It is desirable to make daily life more comfortable by appropriately controlling the sense of smell. The present invention relates to an odor sense suppressant that can suppress the sense of smell regardless of the type of odor. [Means for solving the problem]

[0010] The present inventors have discovered substances that inhibit the broadly tuned olfactory receptor OR2W1, which can suppress the sense of smell for various odorants regardless of the type of odor.

[0011] Therefore, the present invention provides an odor sense suppressant that contains at least one active ingredient selected from the group consisting of ambrettolide, muscone, and damascenone, and that suppresses the odor sense regardless of the type of odor. Effect of the Invention

[0012] The olfactory sense suppressant of the present invention can suppress the olfactory sense to various odors regardless of the type of odor by inhibiting the broadly tuned olfactory receptor OR2W1. [Brief description of the drawings]

[0013] [Figure 1] Inhibitory activity of OR2W1 by ambrettolide, muscone, and damascenone. Data show the mean and standard error of the response inhibition level of OR2W1 from three experiments. A response inhibition level value smaller than 1 indicates a tendency to inhibition, and a smaller response inhibition level value indicates stronger inhibition. [Diagram 2] Inhibitory effect of ambrettolide, muscone, and damascenone on indole odor. Data are the average values ​​of the evaluations by four panelists, and error bars represent standard errors. [Diagram 3] The effect of ambrettolide, muscone, and damascenone on suppressing PEA odor. Data are the average values ​​of evaluations by three panelists, and error bars represent standard error. [Figure 4] Suppression effect of various odors by ambretteride below the detection threshold. A panel of 6-7 experts rated the malodor of the test fabric on a 5-point scale by pairwise comparison of the control fabric (malodor only, no ambretteride) with the test fabric (malodor + ambretteride). The number of people who selected each malodor level is shown in the table. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] In this specification, "inhibition of olfactory sense" refers to a phenomenon in which sensitivity to an individual to an odor is reduced. The strength of sensitivity to an odor can be evaluated based on the detection strength or detection threshold (sensitivity) of the odor. For example, when the detection strength of a target odor is reduced or the detection threshold is increased (or the detection sensitivity is reduced), it is determined that the sensitivity to the target odor is reduced, and the odor sense to the target odor is suppressed.

[0015] As used herein, a "substance that causes suppression of the sense of smell" (so-called an odor sense suppressant) is a substance that, when used in combination with a target odorant (e.g., used simultaneously with or prior to the target odorant), causes a subject to sense the target odor weaker or detect it with lower sensitivity (at a higher concentration threshold) than when the target odorant is applied alone. A substance that causes suppression of the sense of smell may have its own odor.

[0016] In this specification, the term "Broadly Tuned Olfactory Receptor" (also referred to as "BT receptor" in this specification) refers to an olfactory receptor that responds to multiple types of odorants having different odors, unlike many olfactory receptors that selectively recognize a small number of specific odorants. More specifically, the BT receptor refers to an olfactory receptor that responds to multiple odorants belonging to different structural classes. Examples of structural classes of odorants include amines, thiols, alcohols, esters, ethers, aldehydes, cyclic alkanes, terpenes, vanillins, camphors, azines, musks, ketones, acids, benzenes, lactones, and sulfides. The BT olfactory receptor in this specification is an olfactory receptor that responds to preferably 38% or more groups, more preferably 77% or more groups, when examining responses to preferably 9 or more groups, more preferably 11 or more groups, and even more preferably 13 or more groups of the above structural classes. In addition, with regard to an olfactory receptor, "responding to a certain structural classification group (e.g., alcohols)" means that the olfactory receptor responds to at least one, preferably three or more, and more preferably four or more odorants belonging to that structural classification group.

[0017] The responsiveness of the olfactory receptor can be evaluated by comparing the response of the olfactory receptor (test group) to which the odorant is added with that of a control group. Examples of the control group include the olfactory receptor to which a lower concentration of the odorant is added, the olfactory receptor to which the odorant is not added, the olfactory receptor to which a control substance is added, the olfactory receptor before the odorant is added, and cells in which the olfactory receptor is not expressed. If the response in the test group is enhanced compared to the control group, the olfactory receptor is determined to have responded to the odorant. For example, if the response in the test group is enhanced by preferably 120% or more, more preferably 150% or more, and even more preferably 200% or more compared to the control group, the olfactory receptor is determined to have responded to the odorant. Alternatively, if the response in the test group is statistically significantly enhanced compared to the control group, the olfactory receptor is determined to have responded to the odorant.

[0018] On the other hand, the evaluation of the inhibitory effect of the olfactory receptor by the test substance can be performed by comparing the response of the olfactory receptor (test group) to which the odorant to which the olfactory receptor responds and the test substance are added with that of the control group. Examples of the control group include the olfactory receptor to which the odorant to which the olfactory receptor responds and a lower concentration of the test substance are added, the olfactory receptor to which the odorant to which the olfactory receptor responds is added but the test substance is not added, and the olfactory receptor to which the odorant to which the olfactory receptor responds and a control substance are added. If the response in the test group is more inhibited than in the control group, the test substance is determined to have inhibited the olfactory receptor. For example, if the response in the test group is inhibited by preferably 90% or less, more preferably 70% or less, and even more preferably 50% or less compared to the control group, the test substance is determined to have inhibited the olfactory receptor. Alternatively, if the response in the test group is inhibited statistically significantly compared to the control group, the test substance is determined to have inhibited the olfactory receptor.

[0019] In this specification, OR2W1 refers to human olfactory receptor OR2W1 (olfactory receptor family 2 subfamily W member 1). Information on the nucleotide sequence and amino acid sequence of OR2W1 is registered in Genbank ([www.ncbi.nlm.nih.gov / genbank / ]) (GeneID: 26692, protein_id: NP_112165.1). OR2W1 is a BT receptor that responds to alcohols, aldehydes, esters, ketones, acids, terpenes, vanillins, benzenes, and lactones (Patent Document 2).

[0020] The present inventor's research group previously constructed a BT receptor single response model that selectively activates only the BT receptor OR2W1, and verified the role of the BT receptor. More specifically, it was found that the amino acid l-arginine is a substance that activates only OR2W1 among human olfactory receptors. Subjects who received l-arginine and a fragrance simultaneously in the nasal cavity had an enhanced sense of smell for the fragrance. This enhancement of the sense of smell by l-arginine occurred not only for fragrances that activate OR2W1, but also for fragrances that do not activate OR2W1. However, when only l-arginine was applied to the nasal cavity, the subjects did not experience a sense of smell. These results showed that the activation of OR2W1 is not involved in the generation of odor quality (specific odor), but transmits information on the intensity of the odor (Patent Document 2).

[0021] From the above studies, it has been found that the BT receptor contributes to controlling the intensity of the odor sensation for various odorants, including those that are themselves responsive and those that are not. Patent Document 2 provides a method for using a substance that controls the response of the BT receptor as a substance that controls the odor sensation regardless of the type of odor, and for selecting a substance that causes enhancement or suppression of the odor sensation regardless of the type of odor based on the response of the BT receptor.

[0022] Based on the above findings, the present inventors have now discovered substances that suppress the response of the BT receptor OR2W1 (i.e., inhibit OR2W1) and identified them as substances that can suppress the sense of smell regardless of the type of odor. In the following description, the substances identified in the present invention that can suppress the sense of smell regardless of the type of odor are sometimes referred to as Broadly Tuned (BT) odor sense suppressants, following the name of the olfactory receptor used in their discovery.

[0023] The BT odor sense suppressants provided by the present invention include the following substances. Ambrettelide: CAS 7779-50-2 Muscone: CAS 541-91-3 Damascenone: CAS 23696-85-7 All of the above substances can be purchased commercially, for example, from Sigma-Aldrich, MP biomedical, etc. Alternatively, the same substances as the commercially available products or compositions containing them can be produced by chemical synthesis.

[0024] [ka]

[0025] As shown in the examples below, the above-mentioned BT odor sense suppressant suppressed the response of the BT receptor OR2W1 (i.e., inhibited OR2W1). Therefore, it is considered that the BT odor sense suppressant can suppress the odor sense for various odors regardless of the type of odor through such an inhibitory action of OR2W1. On the other hand, the substance whose odor sense is suppressed by the BT odor sense suppressant may be a substance that activates OR2W1 or a substance that does not have an OR2W1 activating action. For example, the BT odor sense suppressor according to the present invention can not only suppress the odor sense for compounds belonging to alcohols, aldehydes, esters, ketones, acids, terpenes, vanillins, benzenes, and lactones, which are odorants that activate OR2W1, but can also suppress the odor sense for any odorant, for example, compounds belonging to each group classified according to the structural classification of odorants (see Non-Patent Document 1), namely, amines, thiols, alcohols, esters, ethers, aldehydes, cyclic alkanes, terpenes, vanillins, camphors, azines, musks, ketones, acids, benzenes, lactones, and sulfides.

[0026] The present invention relates to the BT odor sense suppressant described above and its use for odor suppression. By using the BT odor sense suppressant, the odor sense for various odors can be suppressed regardless of the type of odor. Therefore, in one aspect, the present invention provides an odor sense suppressant containing at least one active ingredient selected from the group consisting of ambrettolide, muscone, and damascenone. The odor sense suppressant of the present invention can suppress the odor sense for various odors regardless of the type of odor.

[0027] In one embodiment, the odor sense suppressant of the present invention may essentially consist of at least one selected from the group consisting of ambrettolide, muscone, and damascenone. In another embodiment, the odor sense suppressant of the present invention is a composition containing at least one selected from the group consisting of ambrettolide, muscone, and damascenone as an active ingredient for odor sense suppression.

[0028] In another aspect, the present invention provides the use of at least one selected from the group consisting of ambrettolide, muscone, and damascenone in the manufacture of an odor sense suppressant. In another aspect, the present invention provides the use of at least one selected from the group consisting of ambrettolide, muscone, and damascenone for odor sense suppression. In another aspect, the present invention provides a method for odor sense suppression, comprising applying an effective amount of at least one selected from the group consisting of ambrettolide, muscone, and damascenone to a subject. The odor sense suppression according to the present invention can suppress odor sense for various odors regardless of the type of odor.

[0029] The type of target odor whose sense of smell is suppressed by the present invention is not particularly limited, but may be, for example, the odor of at least one compound selected from the group consisting of amines, thiols, alcohols, esters, ethers, aldehydes, cyclic alkanes, terpenes, vanillins, camphors, azines, musks, ketones, acids, benzenes, lactones, and sulfides, preferably the odor of at least one compound selected from the group consisting of compounds belonging to alcohols, aldehydes, esters, azines, ketones, acids, terpenes, vanillins, benzenes, and lactones, and more preferably the odor of at least one compound selected from the group consisting of compounds belonging to alcohols, azines, aldehydes, and acids. More specific examples of target odors include the odors of commonly used fragrances (e.g., animal fragrances such as musk, civet, castoreum, and ambergris; essential oils derived from plants; vegetable fragrances such as rose, jasmine, neroli, lavender, clove, peppermint, sandalwood, cinnamon, lemon, orange, bergamot, or extracts thereof (e.g., phenylethyl alcohol), etc.); the odors of food or its ingredients; as well as the odors of other odorous substances (e.g., cosmetics, medicines, cleaning agents, daily necessities, etc.); and the odors of malodorous substances (e.g., gas fragrances, hydrogen sulfide, chlorine gas, putrid odor, toilet odor, body odor, bad breath, armpit odor, sweat odor, tobacco odor, indole odor, skatole odor, pyridine odor, pyrazine odor, etc.).

[0030] In the present invention, the subject to which the BT odor sense suppressant is applied includes mammals that desire or require the suppression of the odor sense for the above-mentioned target odor. The type of mammal is not limited, but includes, for example, primates such as humans, chimpanzees, and monkeys, and rodents such as mice and rats, preferably humans, mice and rats, and more preferably humans. Examples of people who desire or require the suppression of the odor sense include those who work in the presence of malodors (for example, those who are involved in cleaning and garbage collection); those who live in a place where there are multiple different life odors such as cooking odor, drain odor, mold odor, garbage odor, and body odor, and who wish to suppress these multiple life odors (for example, those who live in a living room at home); those who want to suppress the body odor of people around them or the strong odor of perfumes; those who experience an environment where they are exposed to various odors from the surroundings, such as an environment where many people are crowded together in a small space (for example, crowded public transportation); those who want to reduce the unpleasantness caused by odors, such as those with hyperosmia.

[0031] In the present invention, one embodiment of the BT odor sense suppressant is as follows: first, the BT odor sense suppressant is applied to a subject who desires or needs to suppress target odor sense before or together with exposure to the target odor. This inhibits OR2W1 on the olfactory epithelium, causing the subject's odor sense to the target odor to be suppressed. As a result, even if the subject is exposed to the target odor, the subject does not sense the target odor, or senses it weaker (or senses it at a higher detection threshold).

[0032] The method of applying the BT odor sense suppressant to a subject may be any method that can deliver the agent to the olfactory cells of the subject. For example, the method of volatilizing the BT odor sense suppressant from a composition containing the BT odor sense suppressant and having the subject inhale it, the method of atomizing a liquid containing the BT odor sense suppressant and spraying it to have the subject inhale it, the method of spraying or dropping a liquid containing the BT odor sense suppressant into the nasal cavity, the method of applying a liquid, gel, cream, ointment, etc. containing the BT odor sense suppressant into the nasal cavity, the method of placing a solid carrier (such as a cotton ball) containing the BT odor sense suppressant into the nasal cavity, etc.

[0033] The effective amount of the BT odor sense suppressant used in the present invention is not particularly limited, as long as it is an amount capable of inhibiting OR2W1 in the nasal cavity of the subject, or a range capable of suppressing the odor sense of the subject. The effective amount can be appropriately adjusted according to the species, age, and original odor sense sensitivity of the subject, the method of application of the agent, the intensity and sensitivity of the target odor whose odor sense is to be suppressed, and the surrounding environment of the subject. However, it is preferable that the odor of the BT odor sense suppressant itself is not too strong compared to the target odor. For example, it is preferable that the BT odor sense suppressant is used at a concentration lower than the concentration of the target odor, or at a concentration lower than the detection threshold of the odor of the BT odor sense suppressant in the subject.

[0034] For example, when the BT olfactory sense suppressant is inhaled by a subject, the concentration of the BT olfactory sense suppressant in the nasal cavity of the subject has a lower limit of preferably 12.0 μg / L air, more preferably 1.2 μg / L air, even more preferably 0.12 μg / L air, even more preferably 0.04 μg / L air, and even more preferably 0.012 μg / L air, while the upper limit is preferably 1000 μg / L air, more preferably 100 μg / L air, and even more preferably 30 μg / L air. Alternatively, the concentration of the BT odor sense suppressant in the nasal cavity of the subject is preferably 12.0 to 1000 μg / L air, 12.0 to 100 μg / L air, or 12.0 to 30 μg / L air, more preferably 1.2 to 1000 μg / L air, 1.2 to 100 μg / L air, or 1.2 to 30 μg / L air, even more preferably 0.12 to 1000 μg / L air, 0.12 to 100 μg / L air, or 0.12 to 30 μg / L air, even more preferably 0.04 to 1000 μg / L air, 0.04 to 100 μg / L air, or 0.04 to 30 μg / L air, and even more preferably 0.012 to 1000 μg / L air, 0.012 to 100 μg / L air, or 0.012 to 30 μg / L air. It's air.

[0035] For example, when the BT odor sense suppressant is volatilized from a composition containing the BT odor sense suppressant and inhaled by a subject, the concentration of the BT odor sense suppressant in the composition is preferably 300 μM, more preferably 30 μM, and even more preferably 3 μM, while the upper limit is preferably 300000 μM, more preferably 30000 μM, and even more preferably 10000 μM. Alternatively, the concentration of the BT odor sense suppressant in the composition is preferably 300 to 300000 μM, 300 to 30000 μM, or 300 to 10000 μM, more preferably 30 to 300000 μM, 30 to 30000 μM, or 30 to 10000 μM, and even more preferably 3 to 300000 μM, 3 to 30000 μM, or 3 to 10000 μM.

[0036] Examples of applications of the BT odor sense suppressant according to the present invention include use in spaces where odor suppression is desired, such as toilets, bathrooms, hospital wards or nursing facilities, or residences including kitchens, bedrooms, closets, etc. (for example, spaces where multiple different odors such as body odor, damp odor, moldy odor, etc. occur); use in environments where a large number of people are crowded together in a small space and may be exposed to various odors such as body odor and fragrances from the people around them (for example, crowded public transportation); addition to products intended to suppress odor (for example, deodorants, topical deodorants, or deodorant cleaning agents, laundry detergents or fabric softeners); addition to products intended to suppress odor (for example, disposable diapers, sanitary products, underwear, undergarments, linens, masks, or other clothing, cloth products or textiles, medicines, foods, etc.); use in production lines of products having a target odor or environments generating the target odor for the purpose of odor suppression, etc. However, application examples of the BT odor sense suppressant are not limited to these.

[0037] The following compositions, manufacturing methods, uses or methods are further disclosed herein as exemplary embodiments of the present invention, but the present invention is not limited to these embodiments.

[0038] [1] An odor sense suppressant that contains at least one active ingredient selected from the group consisting of ambrettolide, muscone, and damascenone, and that suppresses the sense of odor regardless of the type of odor. [2] The agent described in [1], which suppresses the sense of smell, preferably by inhibiting OR2W1. [3] Preferably, the composition can suppress the odor sense of at least one compound selected from the group consisting of alcohols, azines, aldehydes, and acids; More preferably, the odor sense for the odors of compounds belonging to alcohols, aldehydes, esters, azines, ketones, acids, terpenes, vanillins, benzenes, and lactones can be suppressed; More preferably, the odor sense of compounds belonging to the following groups can be suppressed: amines, thiols, alcohols, esters, ethers, aldehydes, cyclic alkanes, terpenes, vanillins, camphors, azines, musks, ketones, acids, benzenes, lactones, and sulfides. The agent described in [1] or [2]. [4] An OR2W1 inhibitor having at least one active ingredient selected from the group consisting of ambrettolide, muscone, and damascenone. [5] The agent according to any one of [1] to [4], wherein the active ingredient is used at a concentration below the detection threshold of its own odor. [6] Preferably, the composition volatilizes at least one selected from the group consisting of ambrettolide, muscone, and damascenone, and The total concentration of at least one selected from the group consisting of ambrettolide, muscone, and damascenone in the composition is as follows: The lower limit is preferably 300 μM, more preferably 30 μM, and even more preferably 3 μM, and the upper limit is preferably 300,000 μM, more preferably 30,000 μM, and even more preferably 10,000 μM, or The agent according to any one of [1] to [4], wherein the concentration is preferably 300 to 300,000 μM, 300 to 30,000 μM, 300 to 10,000 μM, 30 to 300,000 μM, 30 to 30,000 μM, 30 to 10,000 μM, 3 to 300,000 μM, 3 to 30,000 μM, or 3 to 10,000 μM. [7] The total concentration of at least one selected from the group consisting of ambrettolide, muscone, and damascenone in the nasal cavity of a subject is used to be as follows: The lower limit is preferably 12.0 μg / L air, more preferably 1.2 μg / L air, even more preferably 0.12 μg / L air, even more preferably 0.04 μg / L air, even more preferably 0.012 μg / L air, and the upper limit is preferably 1000 μg / L air, more preferably 100 μg / L air, even more preferably 30 μg / L air, or Preferably 12.0~1000μg / L air, 12.0~100μg / L air, 12.0~30μg / L air, 1.2~1000μg / L air, 1.2~100μg / L air, 1.2~30μg / L air, 0.12~1000μg / L air, 0.12~100μg / L air, 0.12~30μg / L air, 0.04~1000μg / L air, 0.04~100μg / L air, 0.04~30μg / L air, 0.012~1000μg / L air, 0.012~100μg / L air, or 0.012~30μg / L air, The agent according to any one of [1] to [4].

[0039] [8] Use of at least one member selected from the group consisting of ambrettolide, muscone, and damascenone in the manufacture of an odor sense suppressant that suppresses odor sense regardless of the type of odor. [9] Use of at least one selected from the group consisting of ambrettolide, muscone, and damascenone to suppress the sense of smell regardless of the type of odor.

[10] Preferably, the odor sense inhibition is achieved by inhibiting OR2W1. The use of [8] or [9].

[11] The odor sense suppression is Preferably, it enables the suppression of the smell sensation due to at least one compound selected from the group consisting of compounds belonging to alcohols, azines, aldehydes, and acids, More preferably, it enables the suppression of the smell sensation due to the smell of compounds belonging to the following classes: alcohols, aldehydes, esters, azines, ketones, acids, terpenes, vanillins, benzenes and lactones; More preferably, it enables the inhibition of the smell sensation due to the smell of compounds belonging to the following classes: amines, thiols, alcohols, esters, ethers, aldehydes, cyclic alkanes, terpenes, vanillins, camphors, azines, musks, ketones, acids, benzenes, lactones, and sulfides. The use according to any one of [8] to

[10] .

[12] Use of at least one selected from the group consisting of ambrettolide, muscone, and damascenone in the manufacture of an OR2W1 inhibitor.

[13] Use of at least one selected from the group consisting of ambrettolide, muscone, and damascenone for inhibiting OR2W1.

[14] The use according to any one of [8] to

[13] , wherein at least one selected from the group consisting of ambrettolide, muscone, and damascenone is used at a concentration below its own odor detection threshold.

[15] Preferably, the agent is a composition that volatilizes at least one selected from the group consisting of ambrettolide, muscone, and damascenone, or at least one selected from the group consisting of ambrettolide, muscone, and damascenone is volatilized from a composition containing it; and The total concentration of at least one selected from the group consisting of ambrettolide, muscone, and damascenone in the composition is as follows: The lower limit is preferably 300 μM, more preferably 30 μM, and even more preferably 3 μM, and the upper limit is preferably 300,000 μM, more preferably 30,000 μM, and even more preferably 10,000 μM, or Preferably, it is 300 to 300,000 μM, 300 to 30,000 μM, 300 to 10,000 μM, 30 to 300,000 μM, 30 to 30,000 μM, 30 to 10,000 μM, 3 to 300,000 μM, 3 to 30,000 μM, or 3 to 10,000 μM. The use according to any one of [8] to

[13] .

[16] The agent or at least one selected from the group consisting of ambrettolide, muscone, and damascenone is used so that the total concentration of at least one selected from the group consisting of ambrettolide, muscone, and damascenone in the nasal cavity of a subject is as follows: The lower limit is preferably 12.0 μg / L air, more preferably 1.2 μg / L air, even more preferably 0.12 μg / L air, even more preferably 0.04 μg / L air, even more preferably 0.012 μg / L air, and the upper limit is preferably 1000 μg / L air, more preferably 100 μg / L air, even more preferably 30 μg / L air, or Preferably 12.0~1000μg / L air, 12.0~100μg / L air, 12.0~30μg / L air, 1.2~1000μg / L air, 1.2~100μg / L air, 1.2~30μg / L air, 0.12~1000μg / L air, 0.12~100μg / L air, 0.12~30μg / L air, 0.04~1000μg / L air, 0.04~100μg / L air, 0.04~30μg / L air, 0.012~1000μg / L air, 0.012~100μg / L air, or 0.012~30μg / L air, The use according to any one of [8] to

[13] .

[0040]

[17] A method for suppressing odor sense regardless of the type of odor, comprising applying an effective amount of at least one member selected from the group consisting of ambrettolide, muscone, and damascenone to a subject in need thereof.

[18] The method of

[17] , wherein the application preferably inhibits OR2W1.

[19] The method, Preferably, it makes it possible to suppress the smell sensation due to at least one compound selected from the group consisting of compounds belonging to alcohols, azines, and acids, More preferably, it makes it possible to suppress the smell sensation due to the smell of compounds belonging to alcohols, aldehydes, esters, azines, ketones, acids, terpenes, vanillins, benzenes and lactones, More preferably, it makes it possible to suppress the smell sensation due to the smell of compounds belonging to the following classes: amines, thiols, alcohols, esters, ethers, aldehydes, cyclic alkanes, terpenes, vanillins, camphors, azines, musks, ketones, acids, benzenes, lactones, and sulfides. The method described in

[17] or

[18] .

[20] A method for inhibiting OR2W1, comprising administering an effective amount of at least one selected from the group consisting of ambrettolide, muscone, and damascenone to a subject in need thereof.

[21] The method according to any one of

[17] to

[20] , wherein at least one selected from the group consisting of ambrettolide, muscone, and damascenone is applied at a concentration below the detection threshold of its own odor.

[22] Preferably, the method further comprises having the subject inhale at least one selected from the group consisting of ambrettolide, muscone, and damascenone volatilized from the composition; and The total concentration of at least one selected from the group consisting of ambrettolide, muscone, and damascenone in the composition is as follows: The lower limit is preferably 300 μM, more preferably 30 μM, and even more preferably 3 μM, and the upper limit is preferably 300,000 μM, more preferably 30,000 μM, and even more preferably 10,000 μM, or Preferably, it is 300 to 300,000 μM, 300 to 30,000 μM, 300 to 10,000 μM, 30 to 300,000 μM, 30 to 30,000 μM, 30 to 10,000 μM, 3 to 300,000 μM, 3 to 30,000 μM, or 3 to 10,000 μM. The method according to any one of

[17] to

[20] .

[23] The effective amount is, as the total concentration of at least one selected from the group consisting of ambrettolide, muscone, and damascenone in the nasal cavity of the subject, the following: a lower limit of preferably 12.0 μg / L air, more preferably 1.2 μg / L air, even more preferably 0.12 μg / L air, even more preferably 0.04 μg / L air, even more preferably 0.012 μg / L air, and an upper limit of preferably 1000 μg / L air, more preferably 100 μg / L air, even more preferably 30 μg / L air, or Preferably 12.0~1000μg / L air, 12.0~100μg / L air, 12.0~30μg / L air, 1.2~1000μg / L air, 1.2~100μg / L air, 1.2~30μg / L air, 0.12~1000μg / L air, 0.12~100μg / L air, 0.12~30μg / L air, 0.04~1000μg / L air, 0.04~100μg / L air, 0.04~30μg / L air, 0.012~1000μg / L air, 0.012~100μg / L air, or 0.012~30μg / L air, The method according to any one of

[17] to

[20] . EXAMPLES

[0041] The present invention will be described more specifically below with reference to examples.

[0042] Example 1 Inhibitory effect of test substances on the Broadly Tuned olfactory receptor OR2W1 1) Test substance Ambrettelide (Sigma-Aldrich) Muscone: (MP biomedical) Damascenone (Sigma-Aldrich)

[0043] 2) Cloning of OR2W1 Based on the sequence information registered in GenBank, the gene encoding the human olfactory receptor OR2W1 was cloned. The OR2W1 gene was cloned by PCR using human genomic DNA female (G1521: Promega) as a template. The OR2W1 gene amplified by PCR was recombined downstream of the Flag-Rho tag sequence on the pME18S vector.

[0044] 3) Construction of pME18S-human RTP1S vector The gene encoding human RTP1S was cloned by PCR using human genomic DNA female (G1521: Promega) as a template. The resulting human RTP1S gene was inserted into the EcoRI and XhoI sites of the pME18S vector.

[0045] 4) Creation of olfactory receptor expressing cells HEK293 cells expressing OR2W1 were prepared. A reaction solution with the composition shown in Table 1 was prepared and left to stand in a clean bench for 15 minutes. 10 μL of the reaction solution was added to each well of a multi-well plate (96-well plate, BioCoat), and then a HEK293 cell suspension (3 × 10 5 cells / cm 2 ) was added. The cells were cultured for 24 hours in an incubator maintained at 37°C and 5% CO2.

[0046] [Table 1]

[0047] 5) Luciferase assay The olfactory receptor expressed in HEK293 cells increases the amount of intracellular cAMP by coupling with the cell-resident Gαs and activating adenylate cyclase. In this embodiment, a luciferase reporter gene assay was used to monitor the increase in the amount of intracellular cAMP as a luminescence value derived from the firefly luciferase gene (fluc2P-CRE-hygro) to measure the response of the cells. In addition, a Renilla luciferase gene fused downstream of the CMV promoter (hRluc-CMV) was simultaneously transfected into the cells and used as an internal standard to correct errors in gene transfection efficiency or cell number. The medium was removed from the cell culture prepared in 4), and 75 μL of HBSS (GIBCO) solution containing the test substance (final concentration 100 μM) and hexanol (final concentration 10 μM), a known agonist of OR2W1, was added to each well (test group). As a control group, the same amount of HBSS solution containing hexanol at a final concentration of 10 μM was added to the well. As a reference (Buffer group), the same amount of HBSS solution alone was added to the wells. The cells were cultured in a CO2 incubator for 4 hours to allow the luciferase gene to be fully expressed in the cells. Luciferase activity derived from the cells was measured using Dual-Glo after 4 hours of stimulation with the test substance. TM The luciferase assay system (Promega) was used according to the product's instruction manual. The luminescence value fLuc derived from firefly luciferase was divided by the luminescence value hRluc derived from Renilla luciferase to calculate fLuc / hRluc, which was used as an index of cell response. The level of inhibition of OR2W1 response by the test substance was calculated according to the following formula. Response inhibition level = X / Y X: (fLuc / hRluc in the test group)-(fLuc / hRluc in the buffer group) Y: (fLuc / hRluc in control group)-(fLuc / hRluc in buffer group)

[0048] 6) Results The OR2W1 inhibitory activity of the test substances is shown in Figure 1. Ambrettolide, muscone, and damascenone all suppressed the hexanol response of OR2W1 compared to the control group. This result indicated that ambrettolide, muscone, and damascenone are OR2W1 inhibitors.

[0049] Example 2 Odor suppression effect of test substances 1) Suppression of indole odor by ambrettolide, muscone and damascenone The inhibitory effect of the test substances on the malodor (indole odor) was evaluated. Mineral oil solutions containing each test substance or indole at a concentration of 10 mM were prepared. 5 μL of either the test substance solution, the indole solution, or mineral oil was soaked into a cotton ball and placed in a 20 mL vial. A vial containing a cotton ball containing the test substance solution and a cotton ball containing the indole solution (test sample), a vial containing a cotton ball containing mineral oil and a cotton ball containing the indole solution (blank), and a vial containing only a cotton ball containing the indole solution (control sample) were prepared.

[0050] A panel of four experts was asked to smell the control sample and the test sample or blank alternately, and to answer what percentage of the indole odor they perceived in the test sample and blank compared to the control sample. All odor evaluations were done blind, and the order in which each test sample and blank was evaluated was random. The results of the odor evaluation are shown in Figure 2. Due to the adaptation effect, the odor of the blank was perceived as weaker than that of the control sample. Test substances that were answered to have an odor even weaker than that of the blank were considered to have an odor-suppressing effect. Ambrettolide, muscone, and damascenone all suppressed the odor of indole.

[0051] 2) Suppression of phenylethyl alcohol (PEA) odor by ambrettolide, muscone and damascenone The inhibitory effect of the test substance on the aroma (rose-like aroma due to PEA) was evaluated. Mineral oil solutions containing each test substance or PEA at a concentration of 10 mM were prepared. 20 μL of either the test substance solution, PEA solution, or mineral oil was soaked into a cotton ball and placed in a 20 mL vial. A vial containing a cotton ball containing the test substance solution and a cotton ball containing the PEA solution (test sample), a vial containing a cotton ball containing mineral oil and a cotton ball containing the PEA solution (blank), and a vial containing only a cotton ball containing the PEA solution (control sample) were prepared.

[0052] Three expert panelists alternately smelled the control sample and the test sample or blank, and used a visual analogue scale (VAS) to evaluate how much the PEA scent of the test sample and blank was perceived compared to the control sample. In the VAS evaluation, the left end of a 10 cm line was designated as "0 cm: not smelled at all" and the right end was designated as "10 cm: smelled very strongly," and the evaluators were asked to indicate where on the line the PEA scent of each sample fell. The distance (mm) from 0 cm to the marked position was used as the VAS measurement value. All odor evaluations were performed blind, and the order in which each test sample and blank were evaluated was random. The results are shown in Figure 3. Test substances that were rated as having a weaker odor than the blank were considered to have an odor suppressing effect. Ambrettolide, muscone, and damascenone all suppressed the PEA scent.

[0053] 3) Suppression of various odors by low concentration ambrettolide The suppression effect of various malodors by ambrettolide solution (0.01 w / v% dipropylene glycol dilution solution) at a concentration below the detection threshold was investigated. Malodor solution was dropped onto a 9 cm square knitted cotton cloth placed in a petri dish, and 50 μL of ambrettolide solution was dropped around it so as not to overlap with the malodor solution drop point (test cloth). A control cloth without ambrettolide was prepared using the same procedure. The malodor solution was prepared as follows and used so that the odor when dropped onto the cloth was easily noticeable. In the evaluation of the odor suppression effect, a panel of 6 to 7 experts evaluated the malodor of the test cloth by pairwise comparison between the control cloth and the test cloth, using the malodor of the control cloth as the standard. The malodor of the test cloth was evaluated on a 5-point scale: "The malodor intensity of the control cloth is stronger", "The malodor intensity of the control cloth is slightly stronger", "Can't say either way", "The malodor intensity of the test cloth is slightly stronger", and "The malodor intensity of the test cloth is stronger". <Foul-smelling solution> Skatole 1000ppm solution (solvent: acetone) 5μL Isovaleric acid 1000ppm solution (solvent: water) 1μL Model tobacco odor solution 1μL

[0054] [Table 2]

[0055] The evaluation results by the expert panel (n=6-7) are shown in Figure 4. The number of people who selected each malodor level is shown in the table in Figure 4. For each malodor, more than two-thirds of the expert panel evaluated that the malodor intensity was reduced in the test fabric (with ambrettolide added) compared to the control fabric (without ambrettolide added). This demonstrated that ambrettolide suppresses various odors even at low concentrations below the detection threshold.

[0056] The results of the above examples suggest that ambrettolide, muscone, and damascenone have the effect of suppressing odors regardless of the type of odor, that this odor-suppressing effect is presumed to be mediated by the inhibition of OR2W1, and that the odor-suppressing effect of these substances is exerted even at concentrations below the detection threshold of their own odors, suggesting that this occurs through a mechanism different from malodor masking by their own odors.

Claims

[Claim 1] An OR2W1 inhibitor whose active ingredient is ambrettolide.

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