WO2021235544A1 - 目的物質の香り、味又は体性感覚を再現する、複数の香り、味又は体性感覚の候補物質の組み合わせの配合を決定するための方法 - Google Patents
目的物質の香り、味又は体性感覚を再現する、複数の香り、味又は体性感覚の候補物質の組み合わせの配合を決定するための方法 Download PDFInfo
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
- G01N33/5041—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects involving analysis of members of signalling pathways
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
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- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16C—COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE
- G16C20/00—Chemoinformatics, i.e. ICT specially adapted for the handling of physicochemical or structural data of chemical particles, elements, compounds or mixtures
- G16C20/10—Analysis or design of chemical reactions, syntheses or processes
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
- C11B9/00—Essential oils; Perfumes
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/72—Assays involving receptors, cell surface antigens or cell surface determinants for hormones
- G01N2333/726—G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH
Definitions
- the present invention is a method, program and system for determining a combination of a plurality of scents, tastes or somatosensory candidate substances that reproduce the scent, taste or somatosensory of the target substance, and a plurality of scents.
- the present invention relates to a method for obtaining a mixture that reproduces the scent, taste or somatosensory possessed by the target substance.
- Patent Document 1 describes a method for determining an odor recipe.
- the method of the present document is characterized in that a combination of element odors close to a target odor is determined from a plurality of different types of element odors based on a plurality of odor sensor response patterns.
- Patent Document 1 states, "The method for determining an odor recipe approximates a target odor by a combination of element odors. That is, instead of searching for the concentration of each element odor.
- the target odor is approximated by the presence or absence of the element odor.
- the quality of the mixed odor is greatly influenced by the presence or absence of the element odor, and the concentration of each element odor ( It is not so affected by the content). Therefore, it is possible to approximate the target odor by focusing only on the presence or absence of each element odor, and further, since the search range is limited, it becomes easy to determine the odor recipe. (Patent Document 1 [0012]).
- Patent Document 2 describes a method for recording and reproducing an odor.
- the method of the present document includes a step of detecting a compounded odor in which a target odor and a plurality of elemental odors are mixed with a sensor array and approximating the response patterns of the two.
- Patent Document 3 describes an odor coding system for creating and coding a recipe for synthesizing a target odor substance.
- the odor coding system of the document is A molecular information database that stores molecular information parameters corresponding to molecular structure information of multiple odorous substances, An element odor database that stores multivariate analysis results for multiple element odor substances, A molecular information retrieval unit that acquires corresponding molecular information parameters from the molecular information database based on the molecular information of the target odor substance.
- a multivariate analysis unit that executes multivariate analysis of the target odorant and obtains the multivariate analysis result
- a multivariate analysis unit Based on the multivariate analysis result of the target odor substance, the element odor determination unit for acquiring information on the element odor substance for synthesizing the target odor substance from the element odor database, and An odor code output unit that encodes and outputs information about the elemental odor substance, It is characterized by having.
- the system is a multivariate analysis unit that performs multivariate analysis of the target odor substance based on the molecular information of the target odor substance and acquires the multivariate analysis result, and based on the analysis result, the target odor substance. It includes an element odor determination unit, which acquires information on element odor substances for synthesizing.
- Patent Document 4 describes a fragrance composition construction system.
- the system of this document is "to determine the combination and ratio of multiple part notes to express the desired scent by a simulation that models the observation scene of the scent using the sensory index related to the human sense of smell". Is.
- Patent Document 5 describes a method for screening a candidate compound exhibiting Ambergris note from among the test compounds.
- the method described in the document is a method of screening a candidate compound exhibiting ambergris note from among test compounds using an olfactory receptor that is responsive to a fragrance exhibiting ambergris note.
- any of the methods and systems prior to the present invention is to match and reproduce the taste or aroma of the target substance and the candidate substance at a certain concentration.
- concentration of the substance that produces the taste or scent in the oral cavity or olfactory mucus that determines the response intensity of the taste or scent receptor in the living body.
- the method of the prior art does not examine whether the scent, taste or somatosensory of the target substance can be reproduced even when the concentration of the target substance and / or the candidate substance changes.
- the present inventors consider that the target substance and the candidate substance are the target substances in order to reproduce the aroma, taste or somatic sensation of the target substance even if a slight change in concentration occurs.
- the concentration of the target substance that produces the aroma, taste, or somatosensory of the target substance and the response intensity of the receptor (dose response curve of the target substance)
- the concentration and acceptance of the combination of the candidate substances By adjusting the mixing ratio of each candidate substance to approximate the relationship with the response intensity of the body (dose response curve of the combination of candidate substances), the aroma, taste or somatosensory of the target substance can be approximated. Can be reproduced.
- the present invention is a method, program and system for determining a combination of a plurality of scents, tastes or somatosensory candidate substances that reproduce the scent, taste or somatosensory of the target substance, and a plurality of scents. It is an object of the present invention to provide a method for obtaining a mixture that reproduces the scent, taste or somatosensory possessed by the target substance for a combination of candidate substances for taste or somatosensory.
- a method for determining the combination of a combination of a plurality of scents, tastes or somatosensory candidate substances that reproduces the scent, taste or somatosensory of the target substance For one or more desired olfactory, taste or somatosensory receptors, the dose response curve of the receptor to the target substance and the dose of the receptor to a combination of multiple aroma, taste or somatosensory candidate substances. To determine the mixing ratio of the plurality of aroma, taste or somatosensory candidate substances so as to be close to the response curve.
- the target substance is a single compound or a mixture of a plurality of compounds. The method for determining the composition.
- a method for determining the combination of a combination of a plurality of scents, tastes or somatosensory candidate substances that reproduces the scent, taste or somatosensory of the target substance (I) optionally one or more olfactory, the receptor for taste or somatosensory, step sets the function f i T indicating a response intensity of the receptor for the target substance 1; (Ii) a plurality of fragrance, for the combination of candidate substances taste or somatosensory, shows the response strength of the receptor, process for setting the function f i R, characterized by the concentrations of the candidate agent 2; (Iii) A step of setting an error function g that characterizes the error between the function f i T and the function f i R for each of the receptors , wherein the error function is the same as the function f i T and the function f i R.
- step 3 (Iv) A step of setting a functional F having all the error functions g i related to each of the receptors obtained in step 3 as an argument, wherein the functional F is the above-mentioned in all the receptors.
- Step 4 which is minimized when the error function is minimized;
- V Optimization is performed on the functional F, and the concentration of each of the candidate substances when the functional F takes the optimum value is determined as a concentration that reproduces the target scent, taste or somatosensory.
- Step 5 Including
- the target substance is a single compound or a mixture of a plurality of compounds. The method.
- Function f i R comprises one or more olfactory of interest, the maximum response intensity ⁇ and EC50 of a combination of a plurality of the candidate substance on the receptor taste or somatosensory as a parameter, one of the embodiments 2-8 1
- (Vi) Regarding the concentration for reproducing the scent, taste or somatosensory obtained in step 5, the concentration adjusted by a sensory test by a human is used as the final concentration for reproducing the scent, taste or somatosensory.
- a method for obtaining a mixture that reproduces the scent, taste, or somatosensory of a target substance for a combination of multiple scent, taste, or somatosensory candidate substances (I) optionally one or more olfactory, the receptor for taste or somatosensory, step sets the function f i T indicating a response intensity of the receptor for the target substance 1; (Ii) a plurality of fragrance, for the combination of candidate substances taste or somatosensory, shows the response strength of the receptor, process for setting the function f i R, characterized by the concentrations of the candidate agent 2; (Iii) A step of setting an error function g that characterizes the error between the function f i T and the function f i R for each of the receptors , wherein the error function is the same as the function f i T and the function f i R.
- step 3 A step of setting a functional F having all the error functions g i related to each of the receptors obtained in step 3 as an argument, wherein the functional F is the above-mentioned in all the receptors.
- Step 4 which is minimized when the error function is minimized;
- V Optimization is performed on the functional F, and the concentration of each of the candidate substances when the functional F takes the optimum value is determined as a concentration that reproduces the target scent, taste or somatosensory.
- Step 5 (Vi) Step 6 to obtain a mixture by mixing each of the candidate substances at the concentration determined in step 5.
- the target substance is a single compound or a mixture of a plurality of compounds. The method.
- a program for determining the combination of a plurality of scents, tastes, or somatosensory candidate substances that reproduces the scent, taste, or somatosensory of the target substance For one or more desired olfactory, taste or somatosensory receptors, the dose response curve of the receptor to the target substance and the dose of the receptor to a combination of multiple aroma, taste or somatosensory candidate substances.
- the step of determining the mixing ratio of the plurality of aroma, taste or somatosensory candidate substances is performed so as to be close to the response curve.
- the target substance is a single compound or a mixture of a plurality of compounds.
- the formulation determination program is a single compound or a mixture of a plurality of compounds.
- a program for determining the combination of a plurality of scents, tastes, or somatosensory candidate substances that reproduces the scent, taste, or somatosensory of the target substance (I) optionally one or more olfactory, the receptor for taste or somatosensory, and setting a function f i T indicating a response intensity of the receptor for the target substance; (Ii) a plurality of fragrance, for the combination of candidate substances taste or somatosensory, shows the response strength of the receptor, and setting a function f i R, characterized by the concentrations of the candidate substance; (Iii) A step of optimizing the functional F and determining the concentration of each of the candidate substances when the functional F takes the optimum value as a concentration that reproduces the desired aroma, taste, or somatic sensation.
- a is, the pan function F, said the all error function g i according to each receptor argument, which smallest when all of the error function in the recipient is minimized, each receiving error function g i of the body, said characterize the error of f i T and f i R for each receptor are those smallest when f i T and f i R are identical, the computer and the step To execute,
- the target substance is a single compound or a mixture of a plurality of compounds.
- the program A system for determining the combination of multiple scent, taste or somatosensory candidate substances that reproduces the scent, taste or somatosensory of the target substance.
- the dose response curve of the receptor to the target substance and the dose of the receptor to a combination of multiple aroma, taste or somatosensory candidate substances is configured to determine the mixing ratio of the plurality of aroma, taste or somatosensory candidate substances so as to be close to the response curve.
- the target substance is a single compound or a mixture of a plurality of compounds.
- the system. [Aspect 15] A system for obtaining a mixture that reproduces the scent, taste, or somatosensory of a target substance for a combination of multiple scent, taste, or somatosensory candidate substances.
- the pan function F said the all error function g i according to each receptor argument, which smallest when all of the error function in the recipient is minimized, the error according to the respective receptor function g i is the characterizing error of f i T and f i R for each receptor, is configured and serves as a minimum when the f i T and f i R coincide,
- the target substance is a single compound or a mixture of a plurality of compounds.
- the reproduction of "scent, taste or somatosensory” may include the case where only one selected from scent, taste and somatosensory is reproduced. That is, "determination of the combination of a combination of a plurality of scents, tastes or somatosensory candidate substances" is a combination of a plurality of candidate substances for only one selected from the scent, taste and somatosensory. May include the case where the decision is made.
- the reproduction of "scent, taste or somatosensory” may include the case where at least two selected from scent, taste or somatosensory are reproduced. That is, "determination of the combination of a plurality of candidate substances for aroma, taste or somatosensory” is a determination of a combination of a plurality of candidate substances for at least two selected from aroma, taste or somatosensory. May include the case where
- the reproduction of "scent, taste or somatosensory” may include the case where all of the scent, taste and somatosensory are reproduced. That is, "determination of the combination of a plurality of candidate substances for aroma, taste or somatosensory” is a case where the combination of a plurality of candidate substances is determined for all of the aroma, taste and somatosensory. May include.
- the present invention it has become possible to determine an appropriate combination of a combination of a plurality of scents, tastes or somatosensory candidate substances, and to reproduce the scent, taste or somatosensory of the target substance. Since the method of the present invention utilizes the dose response curve of the target substance and the dose response curve of the combination of the candidate substance, the scent, taste or somatosensory of the target substance can be obtained even if the concentrations of the target substance and the candidate substance are slightly changed. It is possible to reproduce.
- FIG. 1 is a dose response curve model obtained for a mixture of agonists A and B having different maximum response intensities from EC50.
- FIG. 2 is a dose response curve prediction of the coumarin reconstituted mixture. The solid line shows the dose response curve prediction of the coumarin reconstruction mixture, and the dotted line shows the dose response curve of 1M coumarin.
- FIG. 3 is a dose response curve of the coumarin reconstituted mixture. The triangle shows the dose response curve of the coumarin reconstitution mixture, and the circle shows the dose response curve of 1M coumarin.
- FIG. 4 shows the results of evaluating the similarity in odor quality between coumarin reconstituted fragrance and coumarin by VAS.
- FIG. 5 shows an example of the hardware configuration of the computer.
- FIG. 5 shows an example of the hardware configuration of the computer.
- FIG. 6 is a dose response curve prediction and a dose response curve of the lavender oil reconstituted mixture.
- the dotted line shows the dose response curve prediction of the lavender oil reconstituted mixture
- the triangle (solid line) shows the dose response curve of the lavender oil reconstituted mixture
- the circle (solid line) shows the dose response curve of the lavender oil.
- FIG. 7 shows the results of sensory evaluation in which the similarity in odor quality between the lavender oil reconstituted fragrance and the lavender oil was evaluated by VAS.
- the present inventors have "relationship between the concentration of the target substance that produces the aroma, taste or somatic sensation of the target substance and the response intensity of the receptor (dose response curve of the target substance)" and "the concentration and acceptance of the combination of the candidate substances”. Reproduce the scent, taste or somatic sensation of the target substance by approximating the relationship with the response intensity of the body (dose response curve of the combination of candidate substances) by adjusting the mixing ratio of each candidate substance. I found out what I could do. An example of an embodiment for specifically performing this is described below. Non-limitingly, the present invention includes the following contents.
- the present invention reproduces the scent, taste or somatosensory of the target substance.
- the method of the present invention For one or more desired olfactory, taste or somatosensory receptors, the dose response curve of the receptor to the target substance and the dose of the receptor to a combination of multiple aroma, taste or somatosensory candidate substances.
- the target substance is a single compound or a mixture of a plurality of compounds.
- the combination of the combination is more appropriate and most appropriate. It is to decide what to do.
- "recreating" includes bringing closer to the scent, taste or somatosensory of the target substance. That is, the present invention determines the combination of a plurality of scents, tastes or somatosensory candidate substances by using the method of the present invention, and thereby arbitrarily a plurality of scents, tastes or It includes getting closer to the scent, taste or somatosensory of the target substance as compared to the combination of candidate substances for somatosensory. Whether or not the scent, taste or somatosensory of the target substance could be reproduced can be determined, for example, by sensory evaluation by a trained expert panel.
- the "target substance” is not particularly limited as long as it is a substance that makes the living body feel aroma, taste or somatosensory, and may be a natural substance or an artificial substance.
- scent substances such as coumarin, vanillin, limonene, and lavender oil are included.
- Coumarin is a kind of plant aromatic component represented by cherry leaves.
- Lavender oil is an essential oil obtained from a plant belonging to the genus Lavender of the Labiatae family and is used as a fragrance.
- caffeine bitter taste
- saccharin saccharin (bitter / sweet taste)
- glutamic acid (umami) and the like which are taste substances, are included.
- substances that cause somatosensory include allyl isothiocyanate (pain sensation), capsaicin (warm sensation), menthol (cold sensation), and the like.
- the target substance may be a single compound or a mixture of a plurality of compounds.
- M molar concentration
- the concentration of each candidate substance in the mixture or the concentration of the mixture of the candidate substances itself should be the dilution ratio when the arbitrarily determined concentration is 1. Is desirable.
- the concentration arbitrarily determined may be the concentration of the stock solution of the mixture obtained by purchase, extraction, fragrance adjustment, etc., or may be a value appropriately diluted or concentrated based on a specific index.
- the type of "candidate substance for fragrance, taste or somatosensory” is not particularly limited, and may be a natural substance or an artificial substance.
- the method uses a combination of multiple scent, taste or somatosensory candidate substances.
- a coumarin-like scent was reproduced by determining the appropriate formulation of the combination of the three candidate substances piperonal, ⁇ -heptalactone and menthone.
- "Candidate substance for scent, taste or somatosensory” is a substance that makes the living body feel scent, taste or somatosensory, but when combined with another substance, the scent, taste or somatosensory of another substance. It may be a substance that suppresses sensation.
- the "candidate substance for aroma, taste or somatosensory” may be referred to as a "candidate substance”.
- the “candidate substance” is not particularly limited as described above, but in one embodiment, the candidate substance may be selected in advance by screening or the like before being used in the method for determining the combination of the candidate substances.
- the scent candidate substance for example, a substance similar to the scent of the target substance may be selected based on the scent characteristics obtained from public data of known fragrances or sensory evaluation.
- the taste candidate substance for example, a substance similar to the taste of the target substance may be selected based on the taste characteristics obtained from public data of known food additives or sensory evaluation.
- a substance similar to the somatosensory generated from the target substance is selected based on the characteristics of the somatosensory obtained from public data or sensory evaluation of a known substance that produces somatosensory. May be.
- “Mixing” means a combination of multiple scent, taste or somatosensory candidate substances and their mixing ratio.
- the concentration of the candidate substance or the concentration of the mixture of the candidate substances itself should be the dilution ratio when the arbitrarily determined concentration is 1. Is desirable.
- the concentration of the dilution ratio 1 as the concentration corresponding to 1 mol / L of a single compound, it can be expressed on the concentration axis equivalent to the molar concentration in a pseudo manner.
- the concentration arbitrarily determined may be the concentration of the stock solution of the mixture obtained by purchase, extraction, fragrance adjustment, etc., or may be a value appropriately diluted or concentrated based on a specific index.
- the mixing ratio of each candidate substance in the mixture of candidate substances of a plurality of scents, tastes or somatosensory means the relative mixing ratio of the concentration of each candidate substance.
- the dose response curve of the receptor for the target substance to the "desired one or more receptors for the sense of smell, taste or somatosensory" is compared with the dose response curve for the combination of the candidate substances. It involves determining the mixing ratio of each candidate substance in the combination of candidate substances so that they are close to each other.
- the olfactory receptor is a G protein-coupled receptor similar to a taste receptor such as a bitter taste receptor, a sweet taste receptor, and a taste receptor.
- Olfactory receptors are located on the olfactory cells of the olfactory epithelium. The olfactory cells are the only place in the human body where nerve cells are in direct contact with the outside world, and the other end is directly connected to the area of the olfactory bulb in the brain.
- the "odorous substance” is a small molecule compound having a molecular weight of about 30 to 300, and it is said that there are hundreds of thousands of odorous substances on the earth. About 400 functional olfactory receptors have been identified in humans and are classified into 18 gene families, including pseudogenes.
- Each receptor does not respond to a single odorant, but to many similar structures. Also, many odorants stimulate more than one receptor. So far, the corresponding ligands have been identified for about 100 types of olfactory receptors, but the odor exhibited by each receptor has hardly been clarified except for a few cases such as Patent Document 5.
- the intracellular calcium concentration is increased through a signal transmission process via an intracellular second messenger, similar to taste receptors such as bitter taste receptor, sweet taste receptor, and taste receptor.
- taste receptors such as bitter taste receptor, sweet taste receptor, and taste receptor.
- the olfactory receptor is described in detail in, for example, a review article such as "Science of Chemistry Acceptance: Smell / Taste Pheromon From Molecular to Behavior” (Kazunari Higashihara (eds.), Kagaku-Dojin, 2012).
- G protein-coupled receptors are a type of receptor present on the cytoplasmic membrane of eukaryotes or on the constituent membranes inside cells. When various signals (neurotransmitters, hormones, chemical substances, light, etc.) from the outside of the cell are received, the G protein-coupled receptor undergoes a structural change, and the trimer G bound to the inside of the membrane. Signal transduction takes place by activating proteins. G proteins are heterotrimerics that bind to the inner surface of the cell membrane and tightly bind the G ⁇ dimer to the G ⁇ subunit. When a ligand binds to and is activated by a G protein-coupled receptor, an effector protein downstream thereof (for example, G protein) is activated. G protein-coupled receptors and their downstream G proteins are responsible for many basic physiochemicals in intracellular signal networks such as olfactory, taste, visual, neural transmission, metabolism, cell differentiation and proliferation, inflammatory and immune responses. Controls the reaction.
- Taste is a sensation that occurs when a substance is ingested, especially when the substance binds to a specific receptor present on the surface of the tongue.
- Mammalian taste is composed of five basic tastes, namely salty taste, sour taste, sweet taste, umami taste, and bitter taste, and is considered to be formed by integrating these basic tastes.
- salty and sour tastes are said to be sensed via several ion channel-type receptors expressed on the cell membrane on the proximal side of taste cells present in the taste buds on the surface of the tongue.
- bitterness is accepted by a molecule (bitter taste receptor) (25 types in humans) named T2R family, sweetness is a heterodimer of T1R2 + T1R3 (sweetness receptor), and umami is a heterodimer of T1R1 + T1R3 (umami receptor). It has been shown to be accepted by the body).
- the mechanism of the taste information transmission mechanism is generally understood as follows. That is, first, when the taste substance binds to the receptor of the taste cell, the intracellular calcium concentration rises through the signal transmission process via the intracellular second messenger (IP3, DAG) or the like. Next, the calcium ions supplied into the cells release neurotransmitters to synapses to generate action potentials in the nerve cells, and as a result, taste signals originating from receptors are transmitted from the taste nerves to the brain. It is a common belief that taste information is identified and judged. Taste receptors are described in detail in reviews such as "Science of Chemistry Acceptance: Smell / Taste Pheromon From Mole to Behavior" (Kazunari Higashihara (eds.), Kagaku-Dojin, 2012).
- somatosensory is generally used as a general term for tactile sensations, temperature sensations, pain sensations, deep sensations, etc. caused by temperature stimuli, chemical stimuli, and mechanical stimuli. It means a somatosensory sensation evoked through stimuli.
- TRP channels are a type of non-selective cation channels, and 28 species consisting of 6 subfamilies have been reported in mammals.
- TRPA1, TRPM8, and TRPV1 that are strongly expressed on sensory nerves are known to induce somatic sensations such as pain sensation and temperature sensation by chemical stimulation from an outpatient.
- TRPA1 is a receptor mainly involved in pain sensation in humans, and is activated by allyl isothiocyanate, cinnamaldehyde, etc. contained in wasabi and mustard.
- TRPM8 is a receptor involved in cooling sensation and is activated by a temperature stimulus of 28 ° C.
- TRPV1 is a receptor involved in pain sensation and warmth, and is activated by a temperature stimulus of 42 ° C. or higher and capsaicin. Each TRP channel causes cations to flow into cells upon activation, and nerve cells depolarize to transmit sensory information.
- TRP channels for example, Amrita Samanta, et al. , Subcell Biochem. Please refer to 2018; 87: 141-165.
- receptors for odor, taste or somatosensory in a method for determining a combination of a plurality of scents, tastes or somatosensory candidate substances that reproduce the scent, taste or somatosensory of the target substance.
- the type of body is not particularly limited. In one embodiment, it is preferably a receptor for human sense of smell, taste or somatosensory.
- the receptor may be single or multiple.
- a "ligand” is a substance that specifically binds to a specific receptor.
- Ligand often means a single compound in general.
- an extract having a scent such as an essential oil related to the sense of smell, a mixture such as a flavored flavor, and an extract from a fresh food or a processed food related to the sense of taste are applicable.
- the target substance is not only a single compound but also a receptor. It also includes mixtures containing multiple ligands (pure substances or single compounds) that selectively and specifically bind.
- G protein-coupled receptors Chemical substances, neurotransmitters, hormones, etc. contained in foods, beverages, etc. bind to G protein-coupled receptors as ligands to cause structural changes and activate G proteins bound to the inside of the membrane. , May be a G protein-coupled receptor agonist in a series of signal transductions.
- the ligand is preferably a substance or agonist (agonist) that acts on a receptor in the living body and exhibits the same possibility as a neurotransmitter or a hormone.
- taste and aroma are recognized by integrating information from multiple receptors.
- the fragrances L-carvone and coumarin have multiple receptors that respond.
- the scents of L-carvone and coumarin are spearmint and sakuramochi-like, respectively, and it is difficult to find similarities between L-carvone and coumarin unless you are an expert. It is presumed that this is because even if the receptors have a common response, the degree of response depending on the concentration has a large effect on the scent. It is also considered that the presence of receptors that respond strongly to one but do not respond to the other also has an effect.
- the body is a receptor for multiple senses of smell, taste or somatosensory.
- the target substance contains a receptor that serves as a ligand, more preferably that the target substance contains a larger number of receptors that serve as a ligand, and all the receptors that the target substance serves as a ligand are included. It is more preferred to include.
- the one or more receptors for the sense of smell, taste or somatosensory include a receptor for which at least one of the candidate substances for the aroma, taste or somatosensory is a ligand. In one embodiment, at least one of the plurality of scent, taste or somatosensory candidate substances is a ligand of a receptor for which the target substance is a ligand.
- the dose response curve means a plot of the concentration of the administered substance (including compounds and mixtures) and the response intensity of the receptor to the substance for the target receptor.
- concentration of the substance is used as a variable to show the dose response curve, and the maximum response intensity ⁇ and EC50 (50% of the maximum response from the minimum value).
- a model with the parameter (concentration indicating) can be preferably used.
- the concentration of the substance is preferably expressed in a logarithm, in which case the dose response curve is a sigmoid curve (logarithmic sigmoid curve).
- the base of the logarithm used in this case may be 10, e, or any other logarithm.
- the dose response curve of the receptor to the target substance and the candidate substance The mixing ratio of the plurality of aroma, taste or somatosensory candidate substances is determined "so that both are close to each other" in the dose response curve for the combination. It is the concentration of the substance that causes the taste, scent, and somatosensory in the oral cavity and olfactory mucus that determines the response strength of the taste, scent, and somatosensory receptor in the living body.
- “To approximate both” means, for example, that the functions representing the dose response curve of the receptor to the target substance and the dose response curve to the combination of the candidate substances are fT and fR, respectively, and the functions fT and the function fR are used.
- the distance is appropriately defined based on the difference between the values of the function fT and the function fR at the same concentration, it may mean that the distance is kept within a predetermined range.
- the distance between the function fT and the function fR can be defined as the square of the difference between the values at each concentration of the function fT and the function fR, the sum of the absolute values, or the average value.
- a method for determining the combination of a combination of a plurality of scents, tastes or somatosensory candidate substances that reproduces the scent, taste or somatosensory of the target substance is described in the following steps: (I) optionally one or more olfactory, the receptor for taste or somatosensory subscript for identifying a receptor is a function f i T (i indicating a response intensity of the receptor for the target substance corresponding 1 ⁇ i ⁇ n. N is the total number of receptors to be considered.
- Step 1 a plurality of fragrance, for the combination of candidate substances taste or somatosensory, shows the response strength of the receptor, process for setting the function f i R, characterized by the concentrations of the candidate agent 2;
- Step 2 A step of setting an error function g i that characterizes the error between the function f i T and the function f i R for each of the receptors, wherein the error function is the same as the function f i T and the function f i R.
- Step 3 A step of setting a functional F having all the error functions g i related to each of the receptors obtained in step 3 as an argument, wherein the functional F is the above-mentioned in all the receptors.
- Step 4 which is minimized when the error function is minimized;
- V Optimization is performed on the functional F, and the concentration of each of the candidate substances when the functional F takes the optimum value is determined as a concentration that reproduces the target scent, taste or somatosensory.
- Step 5 including.
- the function f i T may take the concentration of the target substance as an argument.
- function f i R a plurality of aroma, concentration of the whole combination of candidate substances taste or somatosensory (hereinafter, also referred to as "dilution”.) May be one which an argument. This is because, as described above, the dose response curve can be expressed pseudo on the concentration axis equivalent to the molar concentration by using the dilution ratio when the arbitrarily determined concentration of the mixture is 1.
- the error function g i may be a functional with the functions f i T and the function f i R as arguments, or may be a function with parameters that characterize the functions f i T and the function f i R as arguments. .. Incidentally, the parameters characterizing the function f i R may include the concentrations of the candidate substance.
- the functional F may be regarded as a functional with substantially all the functions f i T and the functional f i R related to each receptor as arguments.
- pan function F is substantially sometimes the parameters characterizing all the function f i T and function f i R according to each receptor can be regarded as a function as an argument.
- pan function F depends on the respective concentrations of candidate substances that characterize the function f i T or function f i R. Optimization of pan function F may include that pan function F to determine the concentrations of candidate substances that characterize the function f i R when taking optimum value. Determining the respective concentrations of candidate substances that characterize the function f i R may include determining a function f i R. The optimum value of the functional F may be the minimum value or the minimum value of the functional F.
- the target substance may be a single compound or a mixture of a plurality of compounds.
- step 1 desired one or more olfactory, the receptor for taste or somatosensory, shows the response strength of the receptor for the target substance, setting the function f i T for the concentration of the target substance as an argument .
- the f i T is a function representing the dose-response curve for the target substance of the receptor.
- Ri (T) Response strength
- c Concentration of target substance
- ⁇ i (T) Maximum response strength
- ⁇ i (T) EC50 ⁇ i (T) and ⁇ i (T) can be determined by known methods, for example, experimentally. If those values are known, they may be applied.
- the function set in step 1 is not limited to this, and can be appropriately modified, but the function set in step 1 preferably has two parameters, and the maximum response strength and EC50 are parameters. Is more preferable.
- function f i T is 50 of the maximal response of 1 or more olfactory interest, maximum response intensity of the target substance to the receptor taste or somatosensory alpha i and (T) EC50 (minimum value Concentration indicating%) ⁇ i (T) is included as a parameter.
- target multiple receptors sets f i T for each receptor. Specifically, f 1 T, f 2 T ... f n T are set for the target receptors 1, 2 ... n.
- step 2 the total concentration, that is, the dilution rate of the combination of candidate substances when a combination of a plurality of candidate substances having a scent, taste or somatosensory is provided to the receptor selected in step 1, is used as an argument. to set the function f i R showing the relationship between the response intensity of the receptor for the combination.
- This is a function that represents the dose response curve for the receptor in a combination of multiple candidate substances. Even if the combination is diluted, the mixing ratio of the candidate substances contained therein is constant.
- An example of such a function for receptor i is described below.
- Ri (eff) Combination response strength
- ⁇ i (eff) Maximum response strength of the combination
- ⁇ i (eff) Combination EC50
- ⁇ ij j (1 ⁇ j ⁇ m. M is the total number of candidate substances.)
- Maximum response intensity of the third candidate substance, C j Concentration of the jth candidate substance in the stock solution, ⁇ ij : EC50 of the jth candidate substance,
- X Dilution rate of the combination of candidate substances with respect to the stock solution
- ⁇ ij and ⁇ ij of each candidate substance can be determined by a known method, for example, by an experiment. If those values are known, they may be applied as they are.
- the value or ratio of C j is unknown in step 2 and is determined in step 5.
- the function set in step 2 is not limited to the above formula (2), and can be appropriately modified.
- set fi R for each receptor set for each receptor.
- f 1 R, f 2 R ... f n R are set for the target receptors 1, 2 ... n.
- function f i R is 1 or more olfactory interest, maximum response intensity of a combination of a plurality of the candidate substance on the receptor taste or somatosensory alpha i a (eff) and EC50 ⁇ i (eff) Included as a parameter.
- step 3 the respective receptors, sets the error function g i characterizing the error of the f i T and f i R obtained in Step 1 and 2.
- error function g i is set to be minimized when the f i T and f i R match. This is the relationship between the "relationship between the concentration of the target substance and the response intensity of the receptor (dose response curve of the target substance)" and the “relationship between the concentration of the combination of the candidate substances and the response intensity of the receptor (dose response of the combination of the candidate substances)". It is a condition for approximating "curve)". Nonfinitely, an example of such a function is described below.
- ⁇ i (eff) and ⁇ i (T) are common logarithmic values of EC50 ⁇ i (eff) and ⁇ i (T), respectively.
- the above error function g i is the dose response of the target substance with two curve parameters ⁇ i (eff) (EC50) and ⁇ i (eff) (maximum response intensity) that characterize the dose response curve of the combination of multiple candidate substances. It is set so that the value becomes smaller as it approximates the curve parameters ⁇ i (T) and ⁇ i (T) related to the curve.
- the error function is set by using the sum of squares of the differences of each parameter, but it is not limited to this, and those skilled in the art should appropriately adopt an absolute value, a square root, etc. in order to set the error function. Can be done.
- the dose response curve of the combination of candidate substances is approximated even for the receptor whose target substance is not a ligand. That is, it is desirable to adjust the dose response curve of the combination so that the response to the receptor is close to zero, at least in the concentration range where actual use is considered.
- ⁇ i (T) > 0 for a receptor whose target substance (fragrance) is a ligand
- ⁇ i (T) 0 for a receptor whose target substance is not a ligand.
- ⁇ i (eff) and ⁇ i (T) may be the same values as ⁇ i (eff) and ⁇ i (T), respectively.
- a logarithm can be used as in the above equation (4) from the viewpoint of aligning the scales of the difference between ⁇ i (eff) and ⁇ i (T) and ⁇ i (eff) and ⁇ i (t). ..
- N may be the number of receptors for which the target substance is a ligand. Therefore,
- standardization may be appropriately performed in view of the order of each parameter.
- the function set in step 3 is not limited to the formula (3), and can be appropriately modified. Note that when targeting multiple receptor can set the g i for each receptor. Specifically, g 1 , g 2 ... gn can be set for the receptors 1, 2 ... n.
- a model formula may be set so as to minimize the area between the two dose response curves f i T and f i R.
- Step 4 is a step which is required when targeting multiple receptor, set the pan function F for all error function g i according to each receptor obtained in Step 3 as an argument.
- the functional F is set to be the minimum when the error function is the minimum in all the receptors. An example of such a functional F is described below.
- step 5 the functional F obtained in step 4 is optimized, and the concentration of each of the candidate substances when the functional F takes the optimum value is set to the desired aroma, taste or somatosensory.
- This is a step of determining the concentration to be reproduced.
- the smaller value of the functional F means that the dose response curve of the target substance and the dose response curve of the combination of the plurality of candidate substances are approximated at each receptor.
- the present inventors have combined the scent, taste or somatosensory of the target substance with the combined scent, taste or somatosensory of a plurality of scents, tastes or somatosensory candidates. However, it has been found that it becomes closer and can reproduce the scent, taste or somatosensory of the target substance.
- the optimum value may be global (minimum value) or local (minimum value), but the global optimum value is more preferable.
- the optimum value of the functional F may be obtained by an algebraic solution method if it can be solved analytically. Further, the optimum value of the functional F may be obtained by an optimization method using an algorithm. Examples of the latter method are the gradient method represented by the steepest descent method and the Newton method, the evolutionary algorithm represented by the genetic algorithm, the estimation algorithm based on the probability distribution theory represented by Bayesian optimization, or the Monte Carlo method. Examples include, but are not limited to, the randomization algorithm represented by. Further, in the optimization process, a constraint condition for the concentration may be given by a method such as the Lagrange undetermined multiplier method.
- optimization parameters characterizing the function f i R when pan function F takes the optimum value i.e., includes determining the value or ratio of C j.
- Optimization may include determining ⁇ i (eff) and ⁇ i (eff) to determine the value or ratio of C j.
- the concentration that reproduces the scent, taste, or somatosensory obtained in steps 1 to 5 is adjusted by a sensory test by a human to be the concentration that reproduces the final scent, taste, or somatosensory.
- Step 6 may be included.
- the concentration of each candidate substance can be adjusted by subjecting it to a sensory evaluation step by a trained panelist. By going through steps 1 to 5, a plurality of scents, tastes or somatosensories that reproduce the scent, taste or somatosensory of the target substance much more efficiently than determining the mixed concentration only by human sensory evaluation. The combination of sensory candidate substances can be determined. However, by finally making adjustments by human sensory evaluation, it becomes possible to get closer to the scent, taste, or somatosensory that humans perceive.
- the present invention relates to a method for obtaining a mixture that reproduces the scent, taste, or somatosensory of the target substance.
- the method of the present invention (I) optionally one or more olfactory, the receptor for taste or somatosensory, step sets the function f i T indicating a response intensity of the receptor for the target substance 1; (Ii) a plurality of fragrance, for the combination of candidate substances taste or somatosensory, shows the response strength of the receptor, process for setting the function f i R, characterized by the concentrations of the candidate agent 2; (Iii) A step of setting an error function g i that characterizes the error between f i T and f i R for each of the receptors, wherein the error function is when the function f i T and the function f i R match.
- step 3 A step of setting a functional F having all the error functions g i related to each of the receptors obtained in step 3 as an argument, wherein the functional F is the above-mentioned in all the receptors.
- Step 4 which is minimized when the error function is minimized;
- V Optimization is performed on the functional F, and the concentration of each of the candidate substances when the functional F takes the optimum value is determined as a concentration that reproduces the target scent, taste or somatosensory.
- Step 5 (Vi) Step 6 to obtain a mixture by mixing each of the candidate substances at the concentration determined in step 5.
- the target substance is a single compound or a mixture of a plurality of compounds.
- Steps 1 to 5 are as described above in "I. A method for determining a combination of a plurality of scents, tastes or somatosensory candidate substances that reproduces the scent, taste or somatosensory of the target substance". .. After step 5, the concentration that reproduces the scent, taste, or somatosensory obtained in steps 1 to 5 is adjusted by a sensory test by a human to obtain the concentration that reproduces the final scent, taste, or somatosensory. Step 6 may be included.
- a program for determining the combination of a plurality of scents, tastes or somatosensory candidate substances that reproduce the scent, taste or somatosensory of the target substance The present invention reproduces the scent, taste or somatosensory of the target substance.
- first embodiment is a combination of a plurality of scents, tastes or somatosensory candidate substances that reproduce the scent, taste or somatosensory of the target substance. It is a formulation determination program, and the program is applied to a computer.
- a is, the pan function F, said the all error function g i according to each receptor argument, which smallest when all of the error function in the recipient is minimized, each receiving error function g i of the body, said characterize the error of f i T and f i R for each receptor are those smallest when f i T and f i R are identical, the computer and the step To execute,
- the target substance is a single compound or a mixture of a plurality of compounds. This is the program.
- step (i) is a step of acquiring the values of the parameters ⁇ i (T) and ⁇ i (T) that define the function f i T from the memory, or can include the step.
- step (ii) may be, or include, a step of retrieving the values of the parameters ⁇ ij and ⁇ ij that partially define or include the function f i R from memory.
- formula (2) is also characterized by the concentration C j for each of the candidates as a parameter, the parameter should be noted that it is unknown at the time of step (ii).
- the error function g i may be defined by the above-mentioned equation (3), and the functional F may be defined by the above-mentioned equation (5). Therefore, in step (iii), in the functional F, the acquired parameters ⁇ i (T) , ⁇ i (T), ⁇ ij and ⁇ ij are set as constants, and the concentration C j of each candidate substance is used as a variable. when the can each comprise a step of calculating a concentration C j of each candidate substance when the pan function F takes the optimum value.
- This step is represented by the gradient method represented by the steepest descent method / Newton method, the evolutionary algorithm represented by the genetic algorithm, the estimation algorithm based on the probability distribution theory represented by Bayesian optimization, or the Monte Carlo method.
- It may include a step of changing the value of Cj until the value of the general function F becomes the optimum value by using a random algorithm or the like. If the value of the pan function F becomes an optimum value, the change in the value of the pan function F at the time of changing the value of C j in accordance with a predetermined method may be determined based on whether less than or less or the predetermined threshold value .. At that time, a constraint condition for the concentration may be given by a method such as the Lagrange undetermined multiplier method.
- One embodiment of the present invention is a combination of a plurality of scents, tastes or somatosensory candidate substances that reproduce the scent, taste or somatosensory of the target substance. It is a formulation determination program, and the program is applied to a computer. For one or more desired receptors for the sense of smell, taste or somatosensory, a dose response curve of the receptor to the target substance (hereinafter referred to as "first dose response curve” in this section) and a plurality of scents and tastes.
- the plurality of aromas, tastes or somatosensory so that the dose response curve of the receptor (hereinafter referred to as "second dose response curve" in this section) with respect to the combination of candidate substances for somatosensory is approximate.
- the target substance is a single compound or a mixture of a plurality of compounds. This is the formulation determination program.
- the first dose response curve may be defined by the above-mentioned formula (1)
- the second dose response curve may be defined by the above-mentioned formula (2). Therefore, the steps in the second embodiment may include steps (i) to (iii) in the first embodiment.
- a system for determining a combination of a plurality of scents, tastes or somatosensory candidate substances that reproduces the scent, taste or somatosensory of the target substance The present invention reproduces the scent, taste or somatosensory of the target substance.
- a system for determining the combination of multiple aroma, taste or somatosensory candidate substances Such a system may be realized by the cooperation of the hardware resources constituting the computer and the program as described above which is software.
- one embodiment of the present invention is a system for determining a combination of a plurality of scents, tastes or somatic sensations candidate substances that reproduces the scents, tastes or somatic sensations of the target substance.
- the dose response curve of the receptor to the target substance and the dose of the receptor to a combination of multiple aroma, taste or somatosensory candidate substances is configured to determine the mixing ratio of the plurality of aroma, taste or somatosensory candidate substances so as to be close to the response curve.
- the target substance is a single compound or a mixture of a plurality of compounds.
- another embodiment of the present invention is a system for obtaining a mixture that reproduces the scent, taste, or somatosensory possessed by the target substance for a combination of a plurality of scent, taste, or somatosensory candidate substances.
- the receptor for taste or somatosensory shows the response strength of the receptor to the substance, set the function f i T for the concentration of the target substance as a variable
- a plurality of fragrance, for the combination of candidate substances taste or somatosensory shows the response strength of the receptor, and set the function f i R for the respective concentrations of said candidate substance as a variable
- optimization is performed for the functional F, and the concentration of each of the candidate substances when the functional F takes the optimum value is determined as the concentration of the recipe for the desired aroma, taste or somatic sensation.
- the pan function F said the all error function g i according to each receptor argument, which smallest when all of the error function in the recipient is minimized, the error according to the respective receptor function g i is the characterizing error of f i T and f i R for each receptor, is configured and serves as a minimum when the f i T and f i R coincide,
- the target substance is a single compound or a mixture of a plurality of compounds.
- the computer may be any computer, such as a personal computer, a tablet computer, a smartphone, a computer on the cloud, or the like.
- FIG. 5 shows an example of a computer hardware configuration.
- the computer 1700 mainly includes a processor 1710, a main storage device 1720, an auxiliary storage device 1730, an input / output interface 1740, and a communication interface 1750 as hardware resources. These are connected to each other via a bus line 1760 including an address bus, a data bus, a control bus and the like. An interface circuit (not shown) may be appropriately interposed between the bus line 1760 and each hardware resource.
- the processor 1710 controls the entire computer. It should be noted that one computer may include a plurality of processors 1710. In such a case, the "processor" in the above description may be a general term for a plurality of processors 1710.
- the main storage device 1720 provides a work area for the processor 1710, and is a volatile memory such as a SRAM (Static Random Access Memory) or a DRAM (Dynamic Random Access Memory).
- SRAM Static Random Access Memory
- DRAM Dynamic Random Access Memory
- the auxiliary storage device 1730 is a non-volatile memory such as an HDD, SSD, or flash memory that stores software programs and data.
- the program, data, or the like is loaded from the auxiliary storage device 1730 to the main storage device 1720 via the bus line 1760 at an arbitrary time point.
- Auxiliary storage 1730 may be referred to as a non-temporary computer-readable storage medium.
- the program includes an instruction to cause the processor to execute a desired process.
- the input / output interface 1740 performs one or both of presenting information and receiving input of information, and is a digital camera, keyboard, mouse, display, touch panel display, microphone, speaker, temperature sensor, or the like. be.
- the communication interface 1750 is connected to the network 1770, and data is transmitted and received via the network 1770.
- the communication interface 1750 and the network 1770 may be connected by wire or wirelessly.
- the communication interface 1750 may also acquire information related to the network, for example, information related to a Wi-Fi access point, information related to a base station of a communication carrier, and the like.
- the computer 1700 can function as the desired means, perform the desired steps, and achieve the desired functionality. There will be.
- Example 1 Preparation of olfactory receptor-related protein-expressing cell line
- a cell line expressing the olfactory receptor-related proteins hRTP1S, mRTP2 and hG ⁇ olf was prepared.
- the human G ⁇ olf mRNA sequence has been registered in GenBank with accession number AF493893.1.
- the nucleotide and amino acid sequences of human G ⁇ olf are also described as SEQ ID NOs: 1 and 2 in the sequence listing of the present application.
- RTP receptor-transporting protein
- hRTP1S is a kind of human RTP and is registered in GenBank: AY5622325.1, and the base sequence and amino acid sequence are described as SEQ ID NOs: 3 and 4 in the sequence listing.
- mRTP2 is a kind of mouse RTP and is registered in GenBank: AY562226.1. The base sequence and amino acid sequence are described as SEQ ID NOs: 5 and 6 in the sequence listing.
- the hRTP1S gene is placed upstream of the picornavirus-derived self-cleaving 2A peptide expression gene (SEQ ID NO: 7), and the mRTP2 gene is placed downstream, and this is inserted into the pIRESPuro3 vector (Takara Bio) to co-express hRTP1S and mRTP2.
- a vector was prepared.
- the hG ⁇ olf gene was inserted into the pIRESneo3 vector (Takara Bio) to prepare a vector expressing hG ⁇ olf.
- These two vectors were introduced into the human fetal kidney cell line HEK293T (obtained from ECACC) using Lipofectamine 3000 (Thermo Fisher).
- the obtained HEK293T transformed cells were cultured at 37 ° C. under 5% CO 2 for 2 days, and then the medium was used as a selective medium containing 1 ⁇ g / mL of puromycin (Thermo Fisher) and 200 ⁇ g / mL of Genetisin (Thermo Fisher). Further, continuous culture was carried out for 12 days to obtain a cell line (HEK-Olf) that stably expresses hRTP1S, mRTP2 and hG ⁇ olf.
- HEK-Olf cell line that stably expresses hRTP1S, mRTP2 and hG ⁇ olf.
- Example 2 Construction of olfactory receptor response measurement system and response measurement
- An olfactory receptor gene library (pFN21KSPc HaloTag-OR) in which 351 types of human olfactory receptor genes obtained from a human cDNA library are inserted into a pFN21KSPc HaloTag vector is used.
- 351 types the olfactory receptors OR1A1, OR2B11, etc. were gene polymorphisms known to have low responses to known agonists (agonists). Using. (Joel D. venue, et al., Nat Neurosci. 2014; 17 (1): p.114-120).
- the HEK-Olf cell line obtained in Example 1 was prepared in DMEM medium ( Thermo Fisher) so as to have 1 ⁇ 10 4 cells / well in a 96-well plate (Corning) and then seeded. Subsequently, pFN21KSPc HaloTag-OR and pGL4.29 [luc2P / CRE / Hygro] Vector (Promega) were introduced into HEK-Olf using ViaFect TM Transfection Reagent (Promega). At this time, pFN21KSPc HaloTag-OR and pGL4.29 [luc2P / CRE / Hygro] Vector were prepared to be 70 ng / well and 30 ng / well, respectively. Using each of the olfactory receptor expression HEK-Olf thus constructed, the following olfactory receptor response measurements were performed.
- olfactory receptor-expressing HEK-Olf After culturing each of the above-mentioned olfactory receptor-expressing HEK-Olf under 37 ° C. and 5% CO 2 for 24 hours, the medium was removed, and 50 ⁇ L of the test compound (candidate substance) appropriately prepared in DMEM medium was added. bottom. DMEM medium containing no test compound was added to the wells of the negative control, and forskolin prepared to 3 ⁇ M was added as the positive control. After reacting these at 37 ° C. under 5% CO 2 for 3 hours, the response of the olfactory receptor was obtained by luminescence measurement using ONE-Glo TM Luciferase Assay kit (Promega).
- the response intensity R of the olfactory receptor at each concentration is the following formula (6): using the emission intensity (RLU) obtained by measurement.
- Example 3 Reproduction of the dose response curve of the target substance (fragrance) If the dose response curve of the target fragrance to the sensory receptor can be reproduced by the dose response curve of the mixture of other fragrances, the scent of the target fragrance can be reproduced. I came up with the idea that it can be reproduced with the mixture.
- an agonist (agonist) for the olfactory receptor will be examined as a candidate substance.
- the response intensity (R) at the concentration (C) of the agonist (agonist) is given by the formula (7) using the maximum response intensity ( ⁇ ) and EC50 (K).
- the response intensity R mix of the mixture when n kinds of agonists for the same receptor are mixed at concentrations C 1 , C 2 ... C n , respectively, is the EC50 (K 1 , K 2 ⁇ of each agonist. It is known that it is estimated by the equation (8) using K n ) and the maximum response intensity ( ⁇ 1 , ⁇ 2 ... ⁇ n) (Howard GJ et al., J. Theor. Biol). 2009 Aug 7; 259 (3): 469-477).
- the effective EC50 (K (eff) ) and maximum response intensity ( ⁇ (eff) ) of the dose response curve with the dilution rate as a variable are the equation (10) from the values of the undiluted solution concentration, EC50, and maximum response intensity of each agonist. , Can be obtained by the equation (11).
- FIG. 1 shows a dose response curve model obtained by using the formula (9) for a mixture of agonists A and B having different maximum response intensities from EC50.
- the EC50 and maximum response intensity of the mixture can be manipulated by changing the mixing ratio of the agonists A and B.
- the above formula holds even if the dilution ratio when the concentration arbitrarily determined is 1 is used as the concentration of the mixture. That is, by regarding the undiluted stock solution of the mixture, that is, the concentration at a dilution ratio of 1, as a concentration equivalent to 1 mol / L of a single compound, it can be expressed in a pseudo manner on a scale equivalent to the molar concentration.
- the concentration in the stock solution of each fragrance can be obtained so that the dose response curve obtained by the formula (9) is close to the dose response curve of the target fragrance. Just do it. Further, in order to prevent the mixture from exhibiting a scent that the target fragrance does not have, it is desirable that the dose response curve approximates the receptor for which the target fragrance does not serve as a ligand. That is, it is desirable to adjust the dose response curve of the mixture so that the response to the receptor is close to zero, at least in the concentration range where actual use is considered. Specifically, a method such as reducing the value of ⁇ a (eff) or increasing the value of Ka (eff) sufficiently can be mentioned.
- the error function g a dose response curve of a mixture of interest perfume for olfactory receptor a with curve parameters K and ⁇ defined as follows.
- ⁇ is a common logarithmic value of EC50.
- N is the number of receptors for which the target fragrance is a ligand. That is,
- an index that characterizes the difference between the dose response curve of the target fragrance and the dose response curve of the fragrance mixture for all the olfactory receptors of interest was determined as shown in the equation (13), and the concentration of the constituent component in which the value of F was minimized was determined.
- the dose response curves of the six types of olfactory receptors, OR1, OR2, OR3, OR4, OR5, and OR6, for which the response to coumarin was confirmed in Example 2, are based on a mixture of other fragrances. I tried to reproduce it.
- Example 4 Confirmation of similarity between the target fragrance and the reconstituted fragrance by sensory evaluation
- the similarity between the coumarin reconstituted fragrance obtained in Example 3 and the odor quality of coumarin was verified by the sensory evaluation.
- the sensory evaluation was verified by a sensory evaluation by 5 trained expert panels.
- the odor similarity was obtained by evaluating the similarity of the headspace aroma of each evaluation sample presented in the blind with the coumarin presented as a reference by a Visual analog scale (VAS).
- VAS Visual analog scale
- As an evaluation sample in addition to the coumarin reconstituted fragrance of Example 3, coumarin and piperonal showing an olfactory receptor response closest to coumarin among the constituents of the coumarin reconstituted fragrance were used.
- each fragrance used for evaluation was prepared using propylene glycol at the concentration shown in the table below.
- Example 5 Reproduction of dose response curve of target substance (fragrance) Using the same method as in Examples 2 and 3, we attempted to measure the olfactory receptor response of lavender oil and reproduce the response with a mixture of other fragrances. ..
- the similarity between the lavender oil and the lavender oil reconstituted fragrance was compared by sensory evaluation in the same manner as in Example 4. Specifically, it was verified by a sensory evaluation by five trained expert panels.
- the odor similarity was obtained by evaluating the similarity between the lavender oil presented as a reference and the headspace aroma of each evaluation sample presented in the blind by a Visual analog scale (VAS).
- VAS Visual analog scale
- the evaluation sample was prepared using propylene glycol at the concentrations (blending ratios) shown in the table below.
- the present invention it has become possible to determine an appropriate combination of a combination of a plurality of scents, tastes or somatosensory candidate substances, and to reproduce the scent, taste or somatosensory of the target substance.
- the method, program, etc. of the present invention even if the target substance is difficult to handle, difficult to obtain, or expensive, for example, a plurality of candidate substances for aroma, taste, or somatosensory can be used. With proper formulation of the combination, it is possible to reproduce the scent, taste or somatosensory in the target substance.
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Abstract
Description
複数の匂い物質の分子構造情報に対応して分子情報パラメーターを格納する分子情報データベースと、
複数の要素臭物質について多変量解析結果を格納する要素臭データベースと、
前記ターゲット臭物質の分子情報に基づいて、前記分子情報データベースから対応する分子情報パラメーターを取得する分子情報検索部と、
前記分子情報検索部によって得られた分子情報を用いて、前記ターゲット臭物質の多変量解析を実行し、多変量解析結果を取得する多変量解析部と、
前記ターゲット臭物質の多変量解析結果に基づいて、前記要素臭データベースから前記ターゲット臭物質を合成するための要素臭物質に関する情報を取得する要素臭決定部と、
前記要素臭物質に関する情報をコード化して出力する匂いコード出力部と、
を備えることを特徴とする。
(i)OR7A17、OR7C1、及び(特許文献5の)配列番号2又は4で示されるアミノ酸配列と80%以上の同一性を有するアミノ酸配列を含み、かつアンバーグリスノートを呈する香料に対して応答性を示すタンパク質からなる群より選択される嗅覚受容体と被験化合物を接触させ、被験化合物に対する嗅覚受容体の応答を測定する工程と、
(ii)被験化合物の非存在下で、工程(i)で用いた嗅覚受容体の応答を測定する工程と、
(iii)工程(i)及び(ii)における測定結果を比較して、応答性が変化した被験化合物を、アンバーグリスノートを呈する候補化合物として選択する工程とを含む。
[態様1]
目的物質の香り、味又は体性感覚を再現する、複数の香り、味又は体性感覚の候補物質の組み合わせの配合の決定方法であって、
所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、目的物質に対する当該受容体の用量応答曲線と、複数の香り、味又は体性感覚の候補物質の組み合わせに対する前記受容体の用量応答曲線とが近似するように、前記複数の香り、味又は体性感覚の候補物質の混合比率を決定する、
ことを含み、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である、
前記配合の決定方法。
[態様2]
目的物質の香り、味又は体性感覚を再現する、複数の香り、味又は体性感覚の候補物質の組み合わせの配合の決定方法であって、
(i)所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、目的物質に対する前記受容体の応答強度を示す函数fiTを設定する工程1;
(ii)複数の香り、味又は体性感覚の候補物質の組み合わせに対する、前記受容体の応答強度を示し、前記候補物質のそれぞれの濃度によって特徴付けられる函数fiRを設定する工程2;
(iii)前記各受容体について函数fiTと函数fiRの誤差を特徴付ける誤差函数gを設定する工程であって、ここで前記誤差函数は函数fiTと函数fiRが一致するときに最小となる、工程3;
(iv)工程3で得られた前記各受容体に係るすべての誤差函数giを引数とする汎函数Fを設定する工程であって、ここで前記汎函数Fは、すべての受容体において前記誤差函数が最小となるときに最小となる、工程4;
(v)前記汎函数Fについて最適化を行い、汎函数Fが最適値をとるときの前記各候補物質の各々の濃度を、目的とする香り、味又は体性感覚を再現する濃度として決定する工程5
を含み、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である、
前記方法。
[態様3]
前記1又は複数の嗅覚、味覚又は体性感覚の受容体が、前記目的物質がリガンドとなる受容体を含む、態様1又は2に記載の方法。
[態様4]
前記1又は複数の嗅覚、味覚又は体性感覚の受容体が、前記目的物質がリガンドとなる受容体を全て含む、態様1又は2に記載の方法。
[態様5]
前記1又は複数の嗅覚、味覚又は体性感覚の受容体が、前記香り、味又は体性感覚の候補物質のうち少なくとも1種類がリガンドとなる受容体を含む、態様1-4のいずれか1項に記載の方法。
[態様6]
複数の香り、味又は体性感覚の候補物質のうち少なくとも1種類が、前記目的物質がリガンドとなる受容体のリガンドである、態様1-5のいずれか1項に記載の方法。
[態様7]
前記受容体が、複数の嗅覚、味覚又は体性感覚の受容体である、態様1-6のいずれか1項に記載の方法。
[態様8]
函数fiTが、対象となる1又は複数の嗅覚、味覚又は体性感覚の受容体に対する目的物質の最大応答強度αとEC50(最低値からの最大応答の50%を示す濃度)をパラメーターとして含む、態様2-7のいずれか1項に記載の方法。
[態様9]
函数fiRが、対象となる1又は複数の嗅覚、味覚又は体性感覚の受容体に対する複数の候補物質の組み合わせの最大応答強度αとEC50をパラメーターとして含む、態様2-8のいずれか1項に記載の方法。
[態様10]
(vi)工程5で得られた香り、味又は体性感覚を再現する濃度について、ヒトによる官能試験により調整したものを最終的な香り、味又は体性感覚を再現する濃度とする工程6、
をさらに含む、態様2-9のいずれか1項に記載の方法。
[態様11]
複数の香り、味又は体性感覚の候補物質の組み合わせについて、目的物質が有する香り、味又は体性感覚を再現する混合物を得る方法であって、
(i)所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、目的物質に対する前記受容体の応答強度を示す函数fiTを設定する工程1;
(ii)複数の香り、味又は体性感覚の候補物質の組み合わせに対する、前記受容体の応答強度を示し、前記候補物質のそれぞれの濃度によって特徴付けられる函数fiRを設定する工程2;
(iii)前記各受容体について函数fiTと函数fiRの誤差を特徴付ける誤差函数gを設定する工程であって、ここで前記誤差函数は函数fiTと函数fiRが一致するときに最小となる、工程3;
(iv)工程3で得られた前記各受容体に係るすべての誤差函数giを引数とする汎函数Fを設定する工程であって、ここで前記汎函数Fは、すべての受容体において前記誤差函数が最小となるときに最小となる、工程4;
(v)前記汎函数Fについて最適化を行い、汎函数Fが最適値をとるときの前記各候補物質の各々の濃度を、目的とする香り、味又は体性感覚を再現する濃度として決定する工程5;
(vi)前記各候補物質を工程5で決定された濃度で混合して、混合物を得る工程6、
を含み、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である、
前記方法。
[態様12]
目的物質の香り、味又は体性感覚を再現する、複数の香り、味又は体性感覚の候補物質の組み合わせの配合の決定プログラムであって、該プログラムは、コンピュータに、
所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、目的物質に対する当該受容体の用量応答曲線と、複数の香り、味又は体性感覚の候補物質の組み合わせに対する前記受容体の用量応答曲線とが近似するように、前記複数の香り、味又は体性感覚の候補物質の混合比率を決定するステップと
を実行させ、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である、
前記配合の決定プログラム。
[態様13]
目的物質の香り、味又は体性感覚を再現する、複数の香り、味又は体性感覚の候補物質の組み合わせの配合の決定プログラムであって、該プログラムは、コンピュータに、
(i)所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、目的物質に対する前記受容体の応答強度を示す函数fiTを設定するステップと;
(ii)複数の香り、味又は体性感覚の候補物質の組み合わせに対する、前記受容体の応答強度を示し、前記候補物質のそれぞれの濃度によって特徴付けられる函数fiRを設定するステップと;
(iii)汎函数Fについて最適化を行い、汎函数Fが最適値をとるときの前記各候補物質の各々の濃度を、目的とする香り、味又は体性感覚を再現する濃度として決定するステップであって、前記汎函数Fは、前記各受容体に係るすべての誤差函数giを引数とし、すべての受容体において前記誤差函数が最小となるときに最小となるものであり、前記各受容体に係る誤差函数giは、前記各受容体についてfiTとfiRの誤差を特徴付け、fiTとfiRが一致するときに最小となるものである、ステップと
をコンピュータに実行させ、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である、
前記プログラム。
[態様14]
目的物質の香り、味又は体性感覚を再現する、複数の香り、味又は体性感覚の候補物質の組み合わせの配合の決定システムであって、
所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、対象物質に対する当該受容体の用量応答曲線と、複数の香り、味又は体性感覚の候補物質の組み合わせに対する前記受容体の用量応答曲線とが近似するように、前記複数の香り、味又は体性感覚の候補物質の混合比率を決定する
ように構成され、
ここにおいて、対象物質は単一の化合物又は複数の化合物の混合物である、
前記システム。
[態様15]
複数の香り、味又は体性感覚の候補物質の組み合わせについて、目的物質が有する香り、味又は体性感覚を再現する混合物を得るシステムであって、
(i)所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、対象物質に対する前記受容体の応答強度を示す函数fiTを設定し、
(ii)複数の香り、味又は体性感覚の候補物質の組み合わせに対する、前記受容体の応答強度を示し、前記候補物質のそれぞれの濃度を変数とする函数fiRを設定し、
(iii)汎函数Fについて最適化を行い、汎函数Fが最適値をとるときの前記各候補物質の各々の濃度を、目的とする香り、味又は体性感覚のレシピの濃度として決定し、前記汎函数Fは、前記各受容体に係るすべての誤差函数giを引数とし、すべての受容体において前記誤差函数が最小となるときに最小となるものであり、前記各受容体に係る誤差函数giは、前記各受容体についてfiTとfiRの誤差を特徴付け、fiTとfiRが一致するときに最小となるものである
ように構成され、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である、
前記システム。
本発明は、目的物質の香り、味又は体性感覚を再現する、複数の香り、味又は体性感覚の候補物質の組み合わせの配合の決定方法に関する。本発明の方法は、
所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、目的物質に対する当該受容体の用量応答曲線と、複数の香り、味又は体性感覚の候補物質の組み合わせに対する前記受容体の用量応答曲線とが近似するように、前記複数の香り、味又は体性感覚の候補物質の混合比率を決定する、
ことを含み、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である。
(i)所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、目的物質に対する前記受容体の応答強度を示す函数fiT(iは対応する受容体を特定するための添え字。1≦i≦n。nは考慮する受容体の総数。以下同様。)を設定する工程1;
(ii)複数の香り、味又は体性感覚の候補物質の組み合わせに対する、前記受容体の応答強度を示し、前記候補物質のそれぞれの濃度によって特徴付けられる函数fiRを設定する工程2;
(iii)前記各受容体について函数fiTと函数fiRの誤差を特徴付ける誤差函数giを設定する工程であって、ここで前記誤差函数は函数fiTと函数fiRが一致するときに最小となる、工程3;
(iv)工程3で得られた前記各受容体に係るすべての誤差函数giを引数とする汎函数Fを設定する工程であって、ここで前記汎函数Fは、すべての受容体において前記誤差函数が最小となるときに最小となる、工程4;
(v)前記汎函数Fについて最適化を行い、汎函数Fが最適値をとるときの前記各候補物質の各々の濃度を、目的とする香り、味又は体性感覚を再現する濃度として決定する工程5
を含む。
Ri(T):応答強度、
c:目的物質の濃度、
αi(T):最大応答強度、
Κi(T):EC50
αi(T)及びΚi(T)は公知の方法で、例えば実験的に決定することができる。またそれらの値が公知の場合はそれを適用してもよい。
αi(eff):組み合わせの最大応答強度、
Κi(eff):組み合わせのEC50、
αij:j(1≦j≦m。mは候補物質の総数。)番目の候補物質の最大応答強度、
Cj:j番目の候補物質の原液中濃度、
Κij:j番目の候補物質のEC50、
X:候補物質の組み合わせの原液に対する希釈率
本発明は、複数の香り、味又は体性感覚の候補物質の組み合わせについて、目的物質が有する香り、味又は体性感覚を再現する混合物を得る方法に関する。本発明の方法は、
(i)所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、目的物質に対する前記受容体の応答強度を示す函数fiTを設定する工程1;
(ii)複数の香り、味又は体性感覚の候補物質の組み合わせに対する、前記受容体の応答強度を示し、前記候補物質のそれぞれの濃度によって特徴付けられる函数fiRを設定する工程2;
(iii)前記各受容体についてfiTとfiRの誤差を特徴付ける誤差函数giを設定する工程であって、ここで前記誤差函数は函数fiTと函数fiRが一致するときに最小となる、工程3;
(iv)工程3で得られた前記各受容体に係るすべての誤差函数giを引数とする汎函数Fを設定する工程であって、ここで前記汎函数Fは、すべての受容体において前記誤差函数が最小となるときに最小となる、工程4;
(v)前記汎函数Fについて最適化を行い、汎函数Fが最適値をとるときの前記各候補物質の各々の濃度を、目的とする香り、味又は体性感覚を再現する濃度として決定する工程5;
(vi)前記各候補物質を工程5で決定された濃度で混合して、混合物を得る工程6、
を含み、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である。
本発明は、目的物質の香り、味又は体性感覚を再現する、複数の香り、味又は体性感覚の候補物質の組み合わせの配合の決定プログラムに関する。
(i)所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、目的物質に対する前記受容体の応答強度を示す函数fiTを設定するステップと;
(ii)複数の香り、味又は体性感覚の候補物質の組み合わせに対する、前記受容体の応答強度を示し、前記候補物質のそれぞれの濃度によって特徴付けられる函数fiRを設定するステップと;
(iii)汎函数Fについて最適化を行い、汎函数Fが最適値をとるときの前記各候補物質の各々の濃度を、目的とする香り、味又は体性感覚を再現する濃度として決定するステップであって、前記汎函数Fは、前記各受容体に係るすべての誤差函数giを引数とし、すべての受容体において前記誤差函数が最小となるときに最小となるものであり、前記各受容体に係る誤差函数giは、前記各受容体についてfiTとfiRの誤差を特徴付け、fiTとfiRが一致するときに最小となるものである、ステップと
をコンピュータに実行させ、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である、
前記プログラムである。
所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、目的物質に対する当該受容体の用量応答曲線(以下、この節において『第1用量応答曲線』という。)と、複数の香り、味又は体性感覚の候補物質の組み合わせに対する前記受容体の用量応答曲線(以下、この節において『第2用量応答曲線』という。)とが近似するように、前記複数の香り、味又は体性感覚の候補物質の混合比率を決定するステップと
を実行させ、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である、
前記配合の決定プログラムである。
本発明は、目的物質の香り、味又は体性感覚を再現する、複数の香り、味又は体性感覚の候補物質の組み合わせの配合の決定システムに関する。そのようなシステムは、コンピュータを構成するハードウエア資源と、ソフトウエアである上述したようなプログラムとが協働することによって実現されるものであってよい。
所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、対象物質に対する当該受容体の用量応答曲線と、複数の香り、味又は体性感覚の候補物質の組み合わせに対する前記受容体の用量応答曲線とが近似するように、前記複数の香り、味又は体性感覚の候補物質の混合比率を決定する
ように構成され、
ここにおいて、対象物質は単一の化合物又は複数の化合物の混合物である、
前記システムである。
(i)所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、対象物質に対する前記受容体の応答強度を示し、前記対象物質の濃度を変数とする函数fiTを設定し、
(ii)複数の香り、味又は体性感覚の候補物質の組み合わせに対する、前記受容体の応答強度を示し、前記候補物質のそれぞれの濃度を変数とする函数fiRを設定し、
(iii)汎函数Fについて最適化を行い、汎函数Fが最適値をとるときの前記各候補物質の各々の濃度を、目的とする香り、味又は体性感覚のレシピの濃度として決定し、前記汎函数Fは、前記各受容体に係るすべての誤差函数giを引数とし、すべての受容体において前記誤差函数が最小となるときに最小となるものであり、前記各受容体に係る誤差函数giは、前記各受容体についてfiTとfiRの誤差を特徴付け、fiTとfiRが一致するときに最小となるものである
ように構成され、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である、
前記システムである。
以下、本発明の一実施形態を実施するために用いることができるコンピュータのハードウエア構成の一例について説明する。なお、本発明の一実施形態を実施するために用いることができるコンピュータは任意のものであってよく、例えば、パーソナル・コンピュータやタブレット・コンピュータ、スマートフォン、クラウド上のコンピュータ等である。
本実施例では、嗅覚受容体関連タンパク質hRTP1S、mRTP2及びhGαolfを発現する細胞株を作製した。
ヒトcDNAライブラリーから取得された351種類のヒト嗅覚受容体遺伝子をpFN21KSPc HaloTagベクターに挿入した嗅覚受容体遺伝子ライブラリー(pFN21KSPc HaloTag-OR)を、かずさゲノムテクノロジーズから購入した。351種類のうち嗅覚受容体OR1A1、OR2B11等は、既知の作動薬(アゴニスト)に対し応答が低いことが知られる遺伝子多型であったため、応答性の高い多型に改変を行い以降の試験に用いた。(Joel D. Mainland, et al.,Nat Neurosci. 2014; 17(1):p.114-120)。
本発明者らは、対象香料の嗅覚受容体に対する用量応答曲線を、他の香料の混合物の用量応答曲線により再現できれば、対象香料の香りを当該混合物により再現することができることを想到した。
本実施例において、実施例3で得られたクマリン再構成香料とクマリンの匂い質の類似性を、官能評価で検証した。官能評価は、訓練された専門家パネル5名による官能評価で検証した。匂いの類似性は、リファレンスとして提示するクマリンとブラインドで提示する各評価サンプルのヘッドスペース香気の類似性をVisual analog scale(VAS)により評価することで得た。ここで評価サンプルとしては、実施例3のクマリン再構成香料に加え、クマリン、及びクマリン再構成香料の構成成分のうち最もクマリンに近い嗅覚受容体応答を示すピペロナールを用いた。また、評価に用いた各香料は、プロピレングリコールを用い、以下の表に示す濃度で調製した。
実施例2、3と同様の手法を用いて、ラベンダーオイルの嗅覚受容体応答の測定、及び他の香料の混合物による応答の再現を試みた。
Claims (15)
- 目的物質の香り、味又は体性感覚を再現する、複数の香り、味又は体性感覚の候補物質の組み合わせの配合の決定方法であって、
所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、目的物質に対する当該受容体の用量応答曲線と、複数の香り、味又は体性感覚の候補物質の組み合わせに対する前記受容体の用量応答曲線とが近似するように、前記複数の香り、味又は体性感覚の候補物質の混合比率を決定する、
ことを含み、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である、
前記配合の決定方法。 - 目的物質の香り、味又は体性感覚を再現する、複数の香り、味又は体性感覚の候補物質の組み合わせの配合の決定方法であって、
(i)所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、目的物質に対する前記受容体の応答強度を示す函数fiTを設定する工程1;
(ii)複数の香り、味又は体性感覚の候補物質の組み合わせに対する、前記受容体の応答強度を示し、前記候補物質のそれぞれの濃度によって特徴付けられる函数fiRを設定する工程2;
(iii)前記各受容体について函数fiTと函数fiRの誤差を特徴付ける誤差函数gを設定する工程であって、ここで前記誤差函数は函数fiTと函数fiRが一致するときに最小となる、工程3;
(iv)工程3で得られた前記各受容体に係るすべての誤差函数giを引数とする汎函数Fを設定する工程であって、ここで前記汎函数Fは、すべての受容体において前記誤差函数が最小となるときに最小となる、工程4;
(v)前記汎函数Fについて最適化を行い、汎函数Fが最適値をとるときの前記各候補物質の各々の濃度を、目的とする香り、味又は体性感覚を再現する濃度として決定する工程5
を含み、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である、
前記方法。 - 前記1又は複数の嗅覚、味覚又は体性感覚の受容体が、前記目的物質がリガンドとなる受容体を含む、請求項1又は2に記載の方法。
- 前記1又は複数の嗅覚、味覚又は体性感覚の受容体が、前記目的物質がリガンドとなる受容体を全て含む、請求項1又は2に記載の方法。
- 前記1又は複数の嗅覚、味覚又は体性感覚の受容体が、前記香り、味又は体性感覚の候補物質のうち少なくとも1種類がリガンドとなる受容体を含む、請求項1-4のいずれか1項に記載の方法。
- 複数の香り、味又は体性感覚の候補物質のうち少なくとも1種類が、前記目的物質がリガンドとなる受容体のリガンドである、請求項1-5のいずれか1項に記載の方法。
- 前記受容体が、複数の嗅覚、味覚又は体性感覚の受容体である、請求項1-6のいずれか1項に記載の方法。
- 函数fiTが、対象となる1又は複数の嗅覚、味覚又は体性感覚の受容体に対する目的物質の最大応答強度αとEC50(最低値からの最大応答の50%を示す濃度)をパラメーターとして含む、請求項2-7のいずれか1項に記載の方法。
- 函数fiRが、対象となる1又は複数の嗅覚、味覚又は体性感覚の受容体に対する複数の候補物質の組み合わせの最大応答強度αとEC50をパラメーターとして含む、請求項2-8のいずれか1項に記載の方法。
- (vi)工程5で得られた香り、味又は体性感覚を再現する濃度について、ヒトによる官能試験により調整したものを最終的な香り、味又は体性感覚を再現する濃度とする工程6、
をさらに含む、請求項2-9のいずれか1項に記載の方法。 - 複数の香り、味又は体性感覚の候補物質の組み合わせについて、目的物質が有する香り、味又は体性感覚を再現する混合物を得る方法であって、
(i)所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、目的物質に対する前記受容体の応答強度を示す函数fiTを設定する工程1;
(ii)複数の香り、味又は体性感覚の候補物質の組み合わせに対する、前記受容体の応答強度を示し、前記候補物質のそれぞれの濃度によって特徴付けられる函数fiRを設定する工程2;
(iii)前記各受容体について函数fiTと函数fiRの誤差を特徴付ける誤差函数gを設定する工程であって、ここで前記誤差函数は函数fiTと函数fiRが一致するときに最小となる、工程3;
(iv)工程3で得られた前記各受容体に係るすべての誤差函数giを引数とする汎函数Fを設定する工程であって、ここで前記汎函数Fは、すべての受容体において前記誤差函数が最小となるときに最小となる、工程4;
(v)前記汎函数Fについて最適化を行い、汎函数Fが最適値をとるときの前記各候補物質の各々の濃度を、目的とする香り、味又は体性感覚を再現する濃度として決定する工程5;
(vi)前記各候補物質を工程5で決定された濃度で混合して、混合物を得る工程6、
を含み、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である、
前記方法。 - 目的物質の香り、味又は体性感覚を再現する、複数の香り、味又は体性感覚の候補物質の組み合わせの配合の決定プログラムであって、該プログラムは、コンピュータに、
所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、目的物質に対する当該受容体の用量応答曲線と、複数の香り、味又は体性感覚の候補物質の組み合わせに対する前記受容体の用量応答曲線とが近似するように、前記複数の香り、味又は体性感覚の候補物質の混合比率を決定するステップと
を実行させ、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である、
前記配合の決定プログラム。 - 目的物質の香り、味又は体性感覚を再現する、複数の香り、味又は体性感覚の候補物質の組み合わせの配合の決定プログラムであって、該プログラムは、コンピュータに、
(i)所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、目的物質に対する前記受容体の応答強度を示す函数fiTを設定するステップと;
(ii)複数の香り、味又は体性感覚の候補物質の組み合わせに対する、前記受容体の応答強度を示し、前記候補物質のそれぞれの濃度によって特徴付けられる函数fiRを設定するステップと;
(iii)汎函数Fについて最適化を行い、汎函数Fが最適値をとるときの前記各候補物質の各々の濃度を、目的とする香り、味又は体性感覚を再現する濃度として決定するステップであって、前記汎函数Fは、前記各受容体に係るすべての誤差函数giを引数とし、すべての受容体において前記誤差函数が最小となるときに最小となるものであり、前記各受容体に係る誤差函数giは、前記各受容体についてfiTとfiRの誤差を特徴付け、fiTとfiRが一致するときに最小となるものである、ステップと
をコンピュータに実行させ、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である、
前記プログラム。 - 目的物質の香り、味又は体性感覚を再現する、複数の香り、味又は体性感覚の候補物質の組み合わせの配合の決定システムであって、
所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、対象物質に対する当該受容体の用量応答曲線と、複数の香り、味又は体性感覚の候補物質の組み合わせに対する前記受容体の用量応答曲線とが近似するように、前記複数の香り、味又は体性感覚の候補物質の混合比率を決定する
ように構成され、
ここにおいて、対象物質は単一の化合物又は複数の化合物の混合物である、
前記システム。 - 複数の香り、味又は体性感覚の候補物質の組み合わせについて、目的物質が有する香り、味又は体性感覚を再現する混合物を得るシステムであって、
(i)所望の1又は複数の嗅覚、味覚又は体性感覚の受容体について、対象物質に対する前記受容体の応答強度を示す函数fiTを設定し、
(ii)複数の香り、味又は体性感覚の候補物質の組み合わせに対する、前記受容体の応答強度を示し、前記候補物質のそれぞれの濃度を変数とする函数fiRを設定し、
(iii)汎函数Fについて最適化を行い、汎函数Fが最適値をとるときの前記各候補物質の各々の濃度を、目的とする香り、味又は体性感覚のレシピの濃度として決定し、前記汎函数Fは、前記各受容体に係るすべての誤差函数giを引数とし、すべての受容体において前記誤差函数が最小となるときに最小となるものであり、前記各受容体に係る誤差函数giは、前記各受容体についてfiTとfiRの誤差を特徴付け、fiTとfiRが一致するときに最小となるものである
ように構成され、
ここにおいて、目的物質は単一の化合物又は複数の化合物の混合物である、
前記システム。
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003279459A (ja) | 2002-03-25 | 2003-10-02 | Rikogaku Shinkokai | 匂いレシピ決定方法 |
JP2005043072A (ja) | 2003-07-22 | 2005-02-17 | Tokyo Institute Of Technology | 匂いの再生記録方法及び匂いの記録再生装置 |
JP2008308649A (ja) | 2007-06-18 | 2008-12-25 | Kyushu Univ | 匂いコーディングシステム及び方法、匂い合成システム、並びに、プログラム |
JP2016530610A (ja) * | 2013-07-17 | 2016-09-29 | コモンウェルス サイエンティフィック アンド インダストリアル リサーチ オーガニゼーション | 食品を配合するシステムおよび方法 |
JP2018109099A (ja) | 2016-12-28 | 2018-07-12 | 花王株式会社 | 香料組成構築システム |
WO2018190118A1 (ja) | 2017-04-13 | 2018-10-18 | 高砂香料工業株式会社 | アンバーグリスノートを呈する香料素材のスクリーニング方法 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100554297B1 (ko) | 2003-11-05 | 2006-02-24 | 주식회사 티엔지 | 치실기구 제조장치 |
KR102003720B1 (ko) | 2017-03-27 | 2019-07-25 | 한국기계연구원 | 하지 복합 운동기기 |
-
2021
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-
2022
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Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003279459A (ja) | 2002-03-25 | 2003-10-02 | Rikogaku Shinkokai | 匂いレシピ決定方法 |
JP2005043072A (ja) | 2003-07-22 | 2005-02-17 | Tokyo Institute Of Technology | 匂いの再生記録方法及び匂いの記録再生装置 |
JP2008308649A (ja) | 2007-06-18 | 2008-12-25 | Kyushu Univ | 匂いコーディングシステム及び方法、匂い合成システム、並びに、プログラム |
JP2016530610A (ja) * | 2013-07-17 | 2016-09-29 | コモンウェルス サイエンティフィック アンド インダストリアル リサーチ オーガニゼーション | 食品を配合するシステムおよび方法 |
JP2018109099A (ja) | 2016-12-28 | 2018-07-12 | 花王株式会社 | 香料組成構築システム |
WO2018190118A1 (ja) | 2017-04-13 | 2018-10-18 | 高砂香料工業株式会社 | アンバーグリスノートを呈する香料素材のスクリーニング方法 |
Non-Patent Citations (7)
Title |
---|
"GenBank", Database accession no. AF493893.1 |
AMRITA SAMANTA ET AL., SUBCELL BIOCHEM, vol. 87, 2018, pages 141 - 165 |
HOWARD GJ ET AL., J. THEOR. BIOL, vol. 259, no. 3, 7 August 2009 (2009-08-07), pages 469 - 477 |
JOEL D. MAINLAND ET AL., NAT NEUROSCI, vol. 17, no. 1, 2014, pages 114 - 120 |
JOEL D. MAINLAND ET AL., SCIENTIFIC, vol. 2, 2015, pages 150002 |
KAGAKU JUYOUNO KAGAKU: "Nioi Aji Feromon Bunshi Kara Koudou Made", 2012, KAGAKU-DOJIN, article "Chemosensory sciences: odor, taste and pheromones, from molecules to behaviors" |
SAITO H ET AL., SCI SIGNAL, vol. 2, no. 60, 2009, pages 9 |
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