Method for producing secretagogue and secretagogue

Abstract

To provide a secretion promoter that promotes the secretion of oxytocin by an organism and can increase the amount of oxytocin to a proper level and a method for producing the same.SOLUTION: The present invention provides a method for producing a secretion promoter that promotes the secretion of oxytocin. The production method includes a first step of collecting a first smell component secreted from an infant and a second smell component secreted from a mother in a nursing period, a second step of comparing the first smell component with the second smell component to identify, among substances contained in the first smell component, a substance whose secretion is less than 0.05 as a q value in FDR (False Discovery Rate) relative to the secretion of substances contained in the second smell component, or a substance having a p value in FWER (Family-Wise Error Rate) of less than 0.05, as a characteristic substance, and a third step of producing a secretion promoter on the basis of the characteristic substance.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a method for producing a secretagogue and the secretagogue. [Background technology]

[0002] Oxytocin is a peptide hormone composed of nine amino acids. Oxytocin is sometimes used to promote lactation and induce labor. Furthermore, in psychological experiments involving monetary exchange, nasal instillation of oxytocin has been shown to strengthen trusting relationships. Oxytocin is thus considered a hormone that has an effective effect on parenting behavior and trust building, and increasing the amount of oxytocin in the body in everyday life has recently attracted attention. For example, an effervescent preparation containing oxytocin is disclosed in Patent Document 1. However, when oxytocin is taken in from outside the body, there is a risk that the amount may be in excess of what is appropriate for the body. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Special Publication No. 2006-505534 Summary of the Invention [Problem to be solved by the invention]

[0004] In view of the above circumstances, the present invention provides a secretion promoter that can promote the secretion of oxytocin in a living body and easily increase the secretion to an appropriate amount, and a method for producing the same. [Means for solving the problem]

[0005] According to one aspect of the present invention, there is provided a method for producing a secretion enhancer that promotes the secretion of oxytocin. This production method includes a first step of collecting a first odor component secreted by an infant and a second odor component secreted by a mother who is breastfeeding the infant, a second step of comparing the first odor component with the second odor component to identify, as characteristic substances, substances contained in the first odor component whose secretion amount relative to the secretion amount of the substance contained in the second odor component has a q value of less than 0.05 in the False Discovery Rate (FDR) or a p value of less than 0.05 in the Family-Wise Error Rate (FWER), and a third step of producing a secretion enhancer based on the characteristic substances. [Effects of the Invention]

[0006] According to one aspect of the present invention, it is possible to advantageously provide a secretion promoter that can promote the secretion of oxytocin in a living body and easily increase the secretion to an appropriate amount, and a method for producing the same. [Brief explanation of the drawings]

[0007] [Figure 1] Photographs showing how odor components are collected. [Figure 2] FIG. 2 is a diagram schematically showing a cross section of FIG. [Figure 3] FIG. 1 is a schematic diagram showing a method for presenting odors to a subject. [Figure 4] 1 is a graph showing the effect of characteristic substances on the secretion of oxytocin. DETAILED DESCRIPTION OF THE INVENTION

[0008] A method for producing the secretagogue of the present invention and preferred embodiments of the secretagogue will be described below. The method for producing a secretagogue of the present invention is a method for producing a secretagogue that promotes the secretion of oxytocin. The method for producing a secretagogue of this embodiment includes a first step [1] of collecting a first odor component secreted by an infant and a second odor component secreted by a mother who is breastfeeding her infant, a second step [2] of comparing the first odor component with the second odor component to identify, as characteristic substances, substances contained in the first odor component whose secretion amount relative to the secretion amount of the substance contained in the second odor component has a q value of less than 0.05 in the FDR (False Discovery Rate) or a p value of less than 0.05 in the FWER (Family-Wise Error Rate), and a third step [3] of producing a secretagogue based on the characteristic substances.

[0009] Each of the steps [1] to [3] will be explained below in order. [1] First step First, a first odor component secreted by an infant and a second odor component secreted by a mother who is breastfeeding the infant are collected. Note that, hereinafter, the first odor component and the second odor component may be collectively referred to as "odor components." The infants may be infants before the start of weaning who are not receiving any other food than breast milk or formula, while the mothers may be mothers who gave birth to the target infants by natural birth or Caesarean section. According to the studies of the present inventors, it is believed that targeting such infants and their mothers will make it easier to detect the characteristic substance in the second step described below.

[0010] Furthermore, it is preferable that the infants to be tested meet all of the following conditions (I) to (V): (I) No health problems have been identified by a doctor by the time of the experiment. (II) No one in the family smokes. (III) The mother is not pregnant and does not use oral contraceptives. (IV) The mother has no chronic illnesses. (V) The infants do not use strong fragrances such as aromas or incense at home. In particular, the age of the infant is preferably about 1 to 6 months, and more preferably about 2 to 4 months. The race of the parents is not particularly limited, but it is expected that the type of specific substance will differ depending on the race.

[0011] On the other hand, it is preferable to restrict the following behaviors of the target infant and mother in order to eliminate the influence of odors from cosmetics and foods on body odor. Specifically, it is recommended that both mother and child use only unscented soap from bathing one week before the start of the experiment or the night before, that the use of deodorant, hair styling products, cosmetics, skin care products, sunscreen, and other cosmetics be prohibited after bathing, and that garlic, onions, asparagus, natural cheese, dishes using spices or herbs, and alcohol be prohibited from the dinner the night before.

[0012] Next, a method for collecting odor components from an infant and a mother will be described. The odor components may be collected from both the infant and the mother using the same procedure or different techniques, but it is preferable to collect them using the same procedure in order to improve the efficiency of the subsequent analysis of the odor components. The odor components can be collected, for example, as follows. Fig. 1 is a photograph showing how odor components are collected, and Fig. 2 is a schematic cross-sectional view of Fig. 1.

[0013] First, to remove impurities, the area (collection area) CS from which the odor components are to be collected is washed with, for example, an aqueous solution of ethanol at a predetermined concentration. The collection area CS is not particularly limited, but examples thereof include the forehead, top of the head, armpits, mouth, back, neck, hands, chest, pubic area, and feet. Next, the capturing agent 1 for capturing odor components is placed on the capturing site CS, and the capturing agent 1 is covered with a resin film 2, and then fixed to the capturing site CS with a waterproof medical film 3. Examples of constituent materials of the collector 1 include silica, carbon, graphite carbon, polydimethylsiloxane, and 2,6-diphenyl-p-phenylenedioxide. Examples of the form of the collector 1 include a porous body, a powder, and a sheet. Among these, the collector 1 is preferably a porous silica body (silica monolith). The resin film may be, for example, a polyethylene terephthalate (PET) film, a polypropylene (PP) film, or the like. The collection time for odor components is not particularly limited, as it is set appropriately taking into consideration the collection site CS, the season (room temperature), the time the subject is confined, etc., but is preferably approximately 0.1 to 72 hours, more preferably approximately 0.2 to 36 hours, even more preferably approximately 0.3 to 18 hours, particularly preferably approximately 0.4 to 6 hours, and most preferably approximately 0.5 to 2 hours.

[0014] [2]Second process Next, the first odor component collected from the infant is compared with the second odor component collected from the mother, and a substance contained in the first odor component whose secretion amount is significantly higher than the secretion amount of a substance contained in the second odor component is identified as a characteristic substance. Various analytical methods can be used to analyze the substances contained in each odor component, and specific examples include GC (gas chromatography), MS (mass spectrometry), GC-MS, and LC-MS. For example, when analyzing the odor components (first odor component and second odor component) by GC-MS, it is preferable to compare the secretion amounts based on the area values ​​of the peaks in the resulting chart. This method allows for relatively accurate and rapid comparison of the secretion amounts.

[0015] Furthermore, for testing the significance of differences in secretion amounts, testing methods such as the Mann-Whitney test, Wilcoxon rank sum test, t-test, and Bruner-Munzel test can be used. To correct for errors due to the multiplicity of tests, for example, FDR correction using the Benjamini-Hochberg method, Benjamini-Yekutieli method, Storey method, etc., or FWER correction using the Bonferroni method, Holm method, etc. can be used.

[0016] The degree of significance for identifying a substance with a significantly high secretion amount as a characteristic substance is such that the q value in FDR is preferably less than 0.05 (FDR(q)<0.05), more preferably less than 0.01 (FDR(q)<0.01), and even more preferably less than 0.005 (FDR(q)<0.005). Alternatively, the p value in FWER is preferably less than 0.05 (FWER(p)<0.05), more preferably less than 0.01 (FWER(p)<0.01), and even more preferably less than 0.005 (FWER(p)<0.005). According to the studies of the present inventors, substances that satisfy the above conditions are secreted in significantly high amounts and may be identified as characteristic substances. On the other hand, in this embodiment, if the Bayes factor, which indicates whether the null hypothesis that there is no difference in the area values ​​is supported, is greater than 3 (preferably greater than 20), it is preferable to identify a substance showing a peak with that area value as a non-characteristic substance that is not a characteristic substance. By identifying non-characteristic substances in this way, characteristic substances can be identified more accurately.

[0017] [3] Third step Next, a secretagogue is produced based on the characteristic substance. Specifically, the secretion enhancer can be produced using one of the characteristic substances alone or a combination of two or more of them. The characteristic substance is preferably soluble in propylene glycol. A characteristic substance that is soluble in propylene glycol is easy to handle. Therefore, the propylene glycol in which the characteristic substance is dissolved can be used as a solution of the secretion enhancer as it is. After removing the propylene glycol, the characteristic substance can be mixed (kneaded) with soap ingredients, cosmetic ingredients, etc., and used as cosmetics such as soap, shampoo, and body lotion. The characteristic substance may be soluble in solvents other than propylene glycol, such as mineral oil, dipropylene glycol, and water.

[0018] The secretagogue of this embodiment is a secretagogue that promotes the secretion of oxytocin. The secretion enhancer contains at least one of the following characteristics: 2-pentylfuran, 2-pyrrolidone, acetophenone, phenylacetaldehyde, and nonanal. According to the studies of the present inventors, it has been found that these substances have a sufficiently high effect of promoting the secretion of oxytocin in the living body. The secretion enhancer may contain only one of the above substances, but preferably contains two or more, more preferably three or more, even more preferably four or more, and particularly preferably five, which can sufficiently increase the amount of oxytocin secreted in the body.

[0019] The secretagogue of this embodiment may further contain at least one additional characteristic substance selected from the group consisting of valeraldehyde, 1-octane, 2-undecanol, heptane, 2-heptene, 3-heptanol, butanal, 3-methylheptane, and 2,3-butanediol. By including an additional characteristic substance in the secretion enhancer, it is expected that the secretion amount of oxytocin will be increased even in subjects in which at least one of the characteristic substances selected from 2-pentylfuran, 2-pyrrolidone, acetophenone, phenylacetaldehyde, and nonanal does not reach the expected level. Therefore, when a large number of mothers are tested, individual differences in the amount of oxytocin secreted can be reduced.

[0020] The content of the characteristic substance in the secretagogue is not particularly limited, as it is set appropriately depending on the type of solvent, but is preferably about 1 ppt to 1000 ppm, and more preferably about 10 ppt to 700 ppm. When the solvent is propylene glycol, the content of the characteristic substance in the secretagogue is more preferably about 50 to 400 ppm, and particularly preferably about 75 to 300 ppm. If the secretagogue contains the characteristic substance in the above range, it can sufficiently promote the secretion of oxytocin in the body. The secretion promoter of the present invention may contain substances other than the above-mentioned characteristic substances.

[0021] The characteristic substance naturally vaporizes from the secretion-promoting agent obtained and diffuses into the surrounding atmosphere. When the subject inhales this characteristic substance, the secretion of oxytocin is promoted in the subject's body. This method does not forcibly supply oxytocin to the body, so it is possible to prevent an excessive amount of oxytocin in the body and increase it to a necessary and appropriate amount. Furthermore, according to the present invention, for example, the secretion of oxytocin can be promoted in the living body of a subject by a method in which the subject inhales the characteristic substance released from the secretion enhancer, and therefore, the method has the advantage that the operation of supplying the characteristic substance to the subject (living body) is easy (simple). When the secretion promoter is used as a solution, the secretion promoter may be heated (warmed), subjected to ultrasonic vibration, blown with a fan, or sprayed with a pump (aroma diffuser, etc.) in order to promote the diffusion of the characteristic substance.

[0022] The amount of oxytocin secreted in the subject's body can be measured using a sample taken from the subject. Examples of the sample include blood (whole blood, plasma, serum, etc.), urine, saliva, etc. Among these, urine is preferred as the sample. If urine is used as the sample, collecting the sample does not cause pain to the subject. Previous findings have shown that the amount of oxytocin in urine correlates with the amount of oxytocin in the blood. Therefore, measuring (quantifying) the amount of oxytocin in urine can estimate the amount of oxytocin in the blood.

[0023] Oxytocin in a sample can be measured using, for example, enzyme-linked immunosorbent assay (ELISA), enzyme immunoassay (EIA), chemiluminescent enzyme immunoassay (CLEIA), chemiluminescent immunoassay (CLIA), electrochemiluminescence immunoassay (ECLIA), fluorescence enzyme immunoassay (FEIA), fluorescence immunoassay (FIA), radioimmunoassay (RIA), liquid chromatography-mass spectrometry (LC-MS), etc. These methods allow accurate quantification of the amount of oxytocin in a sample.

[0024] Although the method for producing the secretagogue and the secretagogue of the present invention have been described above as embodiments, the present invention is not limited thereto. For example, the secretion enhancer of the present invention can be added to baby products such as diapers, baby oil, soap, wet tissues, and baby wipes. In this case, the mother will naturally inhale the characteristic substance while raising her baby, which is expected to have the effect of stabilizing the mother's mental state and promoting lactation. Therefore, for example, in cases where the infant and mother must be separated, such as when the infant needs to be placed in an IUC, the mother can use the secretion enhancer to reduce the effort required to collect breast milk. Furthermore, the subjects for whom the secretagogue of the present invention is used are not limited to women, but may be men. Furthermore, they are not limited to Japanese people, but may be foreigners, and not limited to humans, but may also be other mammals. In these cases, it is sufficient to identify the most important characteristic substances according to the type of race, etc., and produce the secretagogue based on these specific substances.

[0025] It may be provided in the following manner. In the method for producing the secretion promoter, in the second step, the comparison of the secretion amounts is performed by analyzing the first odor component and the second odor component by GC-MS and based on the area values ​​of the peaks in the resulting chart. In the method for producing the secretion promoter, if the Bayes factor indicating whether the null hypothesis that there is no difference in the area value is supported is greater than 3 in the second step, a substance showing a peak having that area value is identified as a non-characteristic substance that is not the characteristic substance. A method for producing a secretion promoter, wherein the characteristic substance is soluble in propylene glycol. In the method for producing a secretagogue, the infant is 1 to 6 months old. A secretagogue that promotes the secretion of oxytocin, the secretagogue containing at least one of 2-pentylfuran, 2-pyrrolidone, acetophenone, phenylacetaldehyde, and nonanal. The secretion promoter further contains at least one of valeraldehyde, 1-octane, 2-undecanol, heptane, 2-heptene, 3-heptanol, butanal, 3-methylheptane, and 2,3-butanediol. Of course, this is not the case. [Example]

[0026] 1. Target The study included infants aged 1 to 6 months who had not yet started weaning and were not receiving any other food than breast milk or formula. The mothers of the infants were also included. The infants in the study were born naturally and had no known health problems from doctors at the time of the experiment. Furthermore, infants whose parents were not Japanese, whose family members were smokers, whose mothers were pregnant or using oral contraceptives, whose mothers had chronic illnesses, or whose mothers used strong-smelling products such as aromatherapy or incense at home were excluded from the study. A total of 23 infants (11 boys and 12 girls, age: 2.9±0.2 months) and their mothers participated in the experiment.

[0027] In order to eliminate the influence of odors from cosmetics and food on body odor, the following behavioral restrictions were imposed. Both the infants and their mothers were asked to use only unscented soap (Kewpie Whole Body Baby Soap Foam Type, manufactured by Gyunyu Soap Kyoshinsha) from bathing one week before the start of the experiment or the night before. In addition, after bathing, the use of cosmetics such as deodorant, hair styling products, makeup, skin care products, and sunscreen is prohibited. He also banned the consumption of garlic, onions, asparagus, natural cheese, dishes containing spices or herbs, and alcohol from dinner the night before.

[0028] 2.Collecting odor components Both infants and mothers were sampled using the same procedure shown in Figures 1 and 2. First, to remove contaminants, the forehead, which is the odor collection site, was washed with a 70% aqueous ethanol solution. Next, a silica monolith (GL Sciences, "Monotrap RGPS TD") was placed on the forehead as an odor collector. In this state, it was covered with a PET film (manufactured by Omi Odo Air Co., Ltd.) and fixed to the forehead with a waterproof medical film (manufactured by Shin Tack Chemical Co., Ltd., "Care Navi Waterproof Film Roll"). The sampling time for the odor components was set to 1 hour.

[0029] 3. Analysis of odor components In this analysis, a GC-MS analyzer (Shimadzu Corporation, "GCMS-QP-2010") was used. The capillary column was a column (Shimadzu Corporation, "SH-Stabilwax") with a length of 60 m, an inner diameter of 0.32 mm, and a film thickness of 0.5 μm. The GC-MS analyzer was also equipped with a multi-function injection port, OPTIC-4 (ATAS GL), which controls the temperature of the sample vaporizer and the column flow rate, and is capable of thermal desorption analysis, which is used in monotrap analysis. The thermal desorption method is a sample introduction method in which a collector is directly introduced into a sample vaporization chamber, heated, and the substances desorbed from the collector are sent to a column.

[0030] The oven was set to hold the column at 50°C for 2.5 minutes, then heat it to 150°C at a rate of 10°C / min, then heat it to 230°C at a rate of 5°C / min, and hold it at 230°C for 91.5 minutes. The various parameters of OPTIC-4 are shown in Table 1 below.

[0031] [Table 1]

[0032] 4. Identification of characteristic substances The substances were detected using GC-MS data analysis software, AnalyzerPro (Spectral Works) and GCMS Solution (Shimadzu Corporation), and the area value of the peak for each detected substance was calculated. Analysis using Analyzerpro is less accurate than analysis using GCMS Solution. In this experiment, five substances for which significant differences were observed using Analyzerpro and 14 substances for which significant differences were observed using GCMS Solution were identified as characteristic substances. Therefore, the five substances are included in the 14 substances.

[0033] The peak area values ​​of the 14 substances were compared between the infant and maternal groups using the Mann-Whitney test (Benjamini-Hochberg correction), with a FDR (q) of <0.05. In addition, to identify substances for which there is no difference in the amount secreted between mothers and infants, the Bayes factor, which indicates whether the null hypothesis that there is no difference in the peak area value between the infant group and the mother group, is calculated for each substance. Substances with a Bayes factor of greater than 3 were determined to be substances for which there is no difference in the amount secreted between mothers and infants.

[0034] 5. Preparation of Odor Solutions Among the substances that were secreted in significantly greater amounts by infants than by mothers, and those for which there was no difference in the amount secreted between mothers and infants, the molecular structures of which could be estimated and specimens were available were analyzed again using a GC-MS analyzer to identify the substances. The identified substances were dissolved in propylene glycol, and 10 μL of the solution was added to a 2 mL vial. The same collection agent as above was placed in the headspace for 1 hour. The concentration of the solution was adjusted so that the peak area value of the collected substance was the median value of the analysis results for the infant group. In this manner, odor solutions containing 14 types (bmix) or 5 types (5mix) of substances as characteristic substances were prepared.

[0035] We also prepared an odor solution (cmix) containing 14 substances whose secretion levels were consistent between mothers and infants, matching the number of components in bmix. In addition, a model axilla odor solution was also prepared as a control for bmix. The composition of each scent solution is shown in Tables 2 to 5 below.

[0036] [Table 2]

[0037] [Table 3]

[0038] [Table 4]

[0039] [Table 5]

[0040] 6. Verification Experiment We investigated whether the exposure to the scent of an infant promotes the secretion of oxytocin in the body by measuring oxytocin in the urine of women raising infants before and after the scent exposure. The subject conditions A to O are shown below.

[0041] A: Mothers whose youngest child is between 3 and 6 years old (as of the day of the experiment). B: The birth was vaginal. C: It has been more than a year since you stopped breastfeeding. D: I'm not currently pregnant. E: My youngest child has not had any health problems diagnosed by doctors since birth. F: Under 50 years old on the day of the experiment. G: I am Japanese.

[0042] H: I don't smoke. I: There are no smokers in my family. J: I don't use oral contraceptives. K: I have no chronic illnesses. L: No disorders or illnesses related to olfaction. M: No chronic illnesses of the nervous system or circulatory system. N: I don't usually use strong scents like aromatherapy or incense at home. O: You can also follow any other precautions we give you.

[0043] Considering the circadian rhythm of oxytocin secretion in the body, all experiments were conducted between 10:20 and 12:40. The odor solutions of bmix, cmix, axilla, 5mix, and empty bottles prepared above were presented to independent groups of subjects (number of subjects per group: 19-30), and the results obtained were statistically compared between the groups. The number of people in the bmix group was 29, the cmix group was 30, the axilla group was 30, the 5mix group was 19, and the empty group was 25.

[0044] After explaining the experiment to the subjects and obtaining their consent to participate, they were asked to urinate. After resting for 30 minutes, they were asked to collect a urine sample. The urine collected at this time was used as the urine sample before the odor presentation. Next, 50 μL of each odor solution was placed in a cylindrical glass bottle GB with a diameter of 40 mm, a height of 75 mm, and a volume of 50 mL. The bottle was placed as close as possible to the nose without touching the bottle, and the odors were presented to subject S for 15 minutes. Figure 3 shows a schematic diagram of how the odors were presented to subject S. During the presentation, the subject was instructed to breathe naturally while smelling the odors. After the odor presentation, the subjects rested for 15 minutes and then collected urine again. The collected urine was used as the post-odor presentation urine sample. The collected urine sample was promptly frozen at -80°C.

[0045] 7. Purification of Urine Samples First, 1 mL of acetonitrile and 3 mL of 0.1% aqueous trifluoroacetic acid (TFA) solution were passed through Sep-Pak Vac 3 cc (200 mg) C18 Cartridges (Waters) in that order to condition the column. Furthermore, 2 mL of a urine sample that had been naturally thawed from -80°C to room temperature was mixed with 2 mL of a 0.1% TFA aqueous solution and then centrifuged at 17,000 g for 15 minutes at 4°C. The supernatant was then passed through a column, followed by passing 3 mL of a 0.1% TFA aqueous solution through the column. Next, 2 mL of eluate (acetonitrile:0.1% TFA aqueous solution = 95:5 (volume ratio)) was passed through the column and collected, and the collected eluate was then dried overnight in a freeze dryer.

[0046] 8. Measuring Oxytocin by ELISA The purified urine samples were measured using an Oxytocin ELISA kit (Enzo Life Sciences) according to the kit's instructions.

[0047] 9. Measurement of urinary creatinine concentration The concentration of oxytocin in urine is affected by the amount of water in the urine. Therefore, it is generally corrected for by the concentration of creatinine in the urine. In this experiment, a laboratory assay was also used. TM Creatinine concentration in urine was measured using a creatinine kit (Fujifilm Wako Pure Chemical Industries, Ltd.) according to the kit's instructions.

[0048] 10. Analysis of the rate of change of oxytocin concentration First, for each urine sample, the oxytocin concentration in the urine was calculated by dividing the oxytocin concentration by the creatinine concentration, after correcting for the amount of water in the urine. Next, for each subject, the oxytocin concentration after odor presentation was divided by the oxytocin concentration before presentation to determine the rate of change in oxytocin concentration. Finally, we compared whether the rate of change in oxytocin concentration differed between the odor solutions (bmix, cmix, axilla, 5mix, empty) using the Wilcoxon rank sum test (Bonferroni correction).

[0049] 11. Evaluation of the effects of characteristic substances on oxytocin secretion The results of this experiment are shown in FIG. FIG. 4 is a graph showing the effect of characteristic substances on the secretion of oxytocin. In the box plot shown in Figure 4, the line inside the box indicates the median, the upper and lower bases of the box indicate the quartiles, the whiskers indicate values ​​that appear within 1.5 times the interquartile range, and the points outside the whiskers and the numbers written next to the arrow at the top indicate outliers. In Figure 4, individual data points are plotted on top of the box plot. The test also included outliers.

[0050] As shown in Figure 4, the rate of increase in urinary oxytocin concentration when bmix was presented was significantly higher than the rate of increase when empty, cmix, or axilla were presented. Similar results were obtained for the rate of increase in urinary oxytocin concentration when 5mix was presented. Furthermore, the variation in the rate of increase in urinary oxytocin concentration when bmix was presented tended to be smaller than the variation in the rate of increase when 5mix was presented. Similar results were also obtained when an odor solution containing one, any two, any three, or any four of 2-pentylfuran, 2-pyrrolidone, acetophenone, phenylacetaldehyde, and nonanal was used. [Explanation of symbols]

[0051] 1. Collector 2 Resin film 3. Waterproof medical film CS collection site GB Glass Bottle S subjects

Claims

1. A method for producing a secretagogue that promotes the secretion of oxytocin, comprising: A first step of collecting a first odor component secreted from an infant and a second odor component secreted from a mother who is breastfeeding the infant; a second step of comparing the first odor component with the second odor component to identify, as characteristic substances, substances contained in the first odor component whose secretion amount is significantly higher than that of the substance contained in the second odor component at a significance level of less than 0.05 in FDR (False Discovery Rate) q value, or substances whose secretion amount is significantly higher than that of the substance contained in the second odor component at a significance level of less than 0.05 in FWER (Family-Wise Error Rate); A method for producing a secretion promoter, comprising a third step of producing the secretion promoter by containing one or more of the characteristic substances.

2. The method for producing the secretion enhancer according to claim 1, In the second step, the comparison of the secretion amounts is carried out based on the area values ​​of the peaks in the chart obtained by analyzing the first odor component and the second odor component using GC-MS.

3. The method for producing the secretion promoter according to claim 2, In the second step, if the Bayes factor indicating whether the null hypothesis that there is no difference in the area value is supported is greater than 3, a substance showing a peak having that area value is identified as a non-characteristic substance that is not the characteristic substance.

4. The method for producing the secretion promoter according to any one of claims 1 to 3, A method for producing a secretagogue, wherein the characteristic substance is soluble in propylene glycol.

5. The method for producing the secretion promoter according to any one of claims 1 to 4, The method for producing a secretagogue, wherein the infant is 1 to 6 months old.

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