WO2015022830A1 - Composition for promoting estrogen secretion, aromatic composition, and aroma tool - Google Patents

Composition for promoting estrogen secretion, aromatic composition, and aroma tool Download PDF

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WO2015022830A1
WO2015022830A1 PCT/JP2014/068675 JP2014068675W WO2015022830A1 WO 2015022830 A1 WO2015022830 A1 WO 2015022830A1 JP 2014068675 W JP2014068675 W JP 2014068675W WO 2015022830 A1 WO2015022830 A1 WO 2015022830A1
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estrogen
cineole
composition
secretion
estrogen secretion
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PCT/JP2014/068675
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French (fr)
Japanese (ja)
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一之 篠原
裕和 土居
正太 西谷
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株式会社 マザー&チャイルド
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • A61P15/12Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/24Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/30Oestrogens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q13/00Formulations or additives for perfume preparations

Definitions

  • the present invention relates to an estrogen secretion enhancing composition, an estrogen secretion aroma composition, and an estrogen secretion aroma device containing 1,8-cineole as an active ingredient.
  • Estrogen secretion during pregnancy is tens of times that of women who are not pregnant. Estrogen secretion levels, which have been elevated for almost 9 months, decrease rapidly within hours after delivery and fall to the point where they cannot be measured on day 7. Maternity blue occurs in about 80% of women at this time. Maternity blue, like premenstrual tension, presents unspecified complaints specific to women. Symptoms usually begin 3-5 days after delivery and disappear within 2 weeks. In addition, postpartum depression may occur due to decreased postpartum hormone secretion.
  • Estrogen secretion levels change throughout life. It begins to rise in puberty and reaches its peak in the 20s. Later, ovarian function gradually declined, estrogen decreased, and menopause. Menopause usually occurs between the ages of 45 and 55 and may be early or late. Menopause is seen in 60-70% of women at this time. Symptoms of menopause are mainly women's unspecified complaints similar to premenstrual tension or maternity blue.
  • Patent Document 1 discloses amplet seed oil as a fragrance composition as a secretion promoter for 17 ⁇ -estradiol, which is a main component of estrogen (a group of female hormones). The use of an amblet lid is disclosed.
  • Patent Document 2 discloses the use of an extract of fungal Cordyceps as a treatment for female hormone deficiency.
  • Patent Document 3 is based on the present inventors, and discloses the effect of aroma component of ⁇ -caryophyllene on women.
  • Non-Patent Documents 1 to 3 show that the presentation of odor changes the secretion frequency of luteinizing hormone (LH) controlled by the hypothalamus, and conventional aromatherapy and the like are oral, intravenous, and transdermal.
  • LH luteinizing hormone
  • the possibility of changing hypothalamic function only through the action via the olfactory nerve was shown.
  • estrogen secretion is caused by the secretion of LH
  • LH secretion is caused by the activity of the hypothalamus. Therefore, the effect of increasing the activity of the hypothalamus is considered to cause the increase of estrogen secretion. .
  • estrogen secretion which is 1,8-cineole and the female hormone.
  • Estrogens have been shown to have the following anti-aging effects (or disease risk reduction effects associated with reduced estrogen in menopause and menopausal women).
  • ⁇ Promoting the production of collagen (beautifying skin effect, preventing firmness / shininess)
  • Promoting absorption of calcium into bone reducing risk of osteoporosis
  • Promoting hair renewal (promoting hair growth)
  • Increased basic metabolism prevention of apple-type obesity
  • Cognitive enhancement reducing dementia risk
  • Promoting vasodilation reducing the risk of arteriosclerosis
  • Immune function enhancement reducing risk of autoimmune diseases such as collagen disease and rheumatism
  • Promoting the development of the mammary gland (beauty effect by maintaining the elasticity and elasticity of the breast)
  • Increased good cholesterol (HDL) (reduced risk of arteriosclerosis)
  • the route of action is not limited to the route through the olfactory nerve, but also includes the oral, intravenous, and transdermal routes.
  • the limbic system which is the center of emotion
  • hypothalamus which is the center of instinct (feeding, sleep) hormone
  • An object of the present invention is to provide a composition for enhancing estrogen secretion and the method for enhancing secretion.
  • the present inventors have found that the odor of 1,8-cineole particularly enhances estrogen secretion in late-luteal females.
  • the present invention has been completed based on the above findings, and is an estrogen secretion enhancing composition containing 1,8-cineole as an active ingredient, its fragrance composition, and its fragrance tool.
  • the first aspect of the present invention is the invention according to claim 1, wherein estrogen secretion containing 1,8-cineole synthesized or purified from natural product as an active ingredient is synthesized. It is a composition for enhancing estrogen secretion, characterized by enhancing.
  • the invention of claim 2 is the composition for enhancing estrogen secretion according to claim 1, wherein the estrogen is 17 ⁇ -estradiol.
  • the invention of claim 3 is the composition for enhancing estrogen secretion according to claim 1 or 2, wherein the administration means of the composition is administered so as to be transmitted to the brain via the olfactory nerve by a fragrance, essential oil, or cosmetics. It is characterized by that.
  • the invention of claim 4 is characterized in that, in the composition for enhancing estrogen secretion according to claim 3, the administration means of the composition is administered so as to be transmitted to the brain via the olfactory nerve by food and drink.
  • the invention according to claim 5, which is the second aspect of the present invention comprises synthesized 1,8-cineol or 1,8-cineole isolated and purified from a natural product as an active ingredient to inhibit estrogen secretion.
  • An estrogen-secreting fragrance composition characterized in that it is enhanced.
  • the invention of claim 6 is the estrogen secretion fragrance composition of claim 5, wherein the estrogen is 17 ⁇ -estradiol.
  • the invention according to claim 7, which is the third aspect of the present invention, comprises 1,8-cineole synthesized or 1,8-cineole isolated and purified from a natural product as an active ingredient to inhibit estrogen secretion. It is an estrogen fragrance tool characterized by improving it.
  • the invention of claim 8 is the estrogen-secreting fragrance device according to claim 7, wherein the estrogen is 17 ⁇ -estradiol.
  • Estrogen secretion enhancing composition, estrogen secretion fragrance composition, and estrogen fragrance composition containing 1,8-cineole isolated and purified from the synthesized 1,8-cineol or natural product of the present invention as an active ingredient Can be used to enhance estrogen secretion, and in particular, estrogen secretion can be further enhanced in the late corpus luteum. For this reason, estrogen is effective in alleviating female-specific indefinite complaints (including illness) such as premenstrual tension, menstrual symptoms, maternity blue, postpartum depression, and menopause, which are caused by decreased estrogen secretion in women. Anti-aging effect due to increased secretion can be expected.
  • composition of the present invention can be administered by a method via the olfactory nerve, it can exert its effect in a short time, and since it does not involve blood, it has the advantage of having no side effects on organs such as the liver and kidney. There is also.
  • 1,8-cineole is particularly estrogen in a woman in the late luteal phase (in the late luteal phase, estrogen decreases and premenstrual tension develops). We found an action to enhance secretion.
  • This 1,8-cineole is a naturally occurring organic compound called eucalyptol (also synthesizable), which is a kind of monoterpenoid with a cyclic ether structure, and is 1,8-cineole. It is also called limonene oxide and cajeptol, and has a fragrance and taste that makes it suitable for food additives, fragrances, and cosmetics, and has the following structural formula.
  • 1,8-cineole has the effect of promoting estrogen secretion in late luteinous women, but has come up with the idea that it can be used for the following novel uses.
  • 1,8-cineole can be presumed to be effective in improving discomfort caused by decreased estrogen secretion in women in the late corpus luteum (including menstrual periods) and in women after childbirth . Discomfort caused by decreased estrogen secretion is seen not only in women in the late corpus luteum (including menstrual periods), but also in women after childbirth and women in menopause. It can be assumed that 1,8-cineole is effective. Moreover, it can be estimated that the above-mentioned anti-aging effect is obtained.
  • composition for enhancing estrogen secretion contains 1,8-cineole as an active ingredient.
  • the 1,8-cineole to be used may be extracted from natural products (for example, tea tree, peppermint, eucalyptus, rosemary, etc.) or may be artificially synthesized.
  • 1,8-cineole is already sold as a reagent and may be used.
  • the composition for enhancing estrogen secretion of the present invention is prepared in various compositions depending on the use mode, and is usually prepared in the same composition as the estrogen secreting fragrance composition described later.
  • the estrogen-secreting fragrance composition of the present invention is prepared in various compositions depending on the use mode, but usually the 1,8-cineole concentration is 0.3 to 3.75%, preferably 1.5. %
  • a suitable solvent such as dipropylene glycol, propylene glycol, butylene glycol, mineral oil, triethyl citrate, ethanol, benzyl benzoate.
  • the aroma is inhaled as an aromatic bath using an aroma pot or a diffuser.
  • other components can be added and used as cosmetics (skin care products, perfumes, etc.), bathing agents, fragrances, sprays, massage oils, shampoos, laundry detergents and the like.
  • Estrogen secretion fragrance tool has a portion containing synthesized 1,8-cineole or 1,8-cineole isolated and purified from natural products.
  • the 1,8-cineole to be used is synthesized or isolated from a natural product and purified in the same manner as the fragrance composition.
  • the food is usually smelled before it is put into the mouth or during mastication. Therefore, 1,8-cineole can exert its effect even in the form of food or beverage, and 1,8-cineole can also be used as a food or drink for improving indefinite complaint symptoms of women.
  • the types of food and drink are not limited, and examples include flavor tea, flavor coffee, flavor beer, rice cake, gum, breath care, seasoning and the like.
  • the food of the present invention is produced by adding a process of adding 1,8-cineole to the normal food production process, and the content of 1,8-cineole in the food depends on the type of food. Normally, the appropriate amount is about 0.3-3.75%.
  • the fragrance device may be any device or tool used for fragrance, sanitary products, paper, textile products (underwear, stocking, etc.), patch medicine, soap, candle, pillow, futon, Etc. can be illustrated.
  • the fragrance tool of the present invention can be produced in the same manner as a general fragrance tool, except that 1,8-cineole is used instead of plant essential oil.
  • the use target and the administration method of the composition for enhancing estrogen secretion of the present invention are characterized in that 1,8-cineole is administered to a person who shows a decrease in estrogen. It is.
  • the administration method of 1,8-cineole is not particularly limited, and it may be administered orally, intravenously, or transdermally in the same manner as ordinary pharmaceuticals, etc., but preferably stimulated by 1,8-cineole. It is administered by a means that is transmitted to the brain via the olfactory nerve.
  • a means for allowing a person who shows a decrease in estrogen secretion to air containing 1,8-cineole can be exemplified.
  • the amount of 1,8-cineole in the air at this time cannot be measured strictly, but the content of 1,8-cineole used in the solution that emits a fragrance is, for example, when propylene glycol is used as a solvent. Is preferably in the range of 0.3 to 3.75%, more preferably about 1.5%.
  • Example 1 We examined hormonal changes that occurred when 1,8-cineole was sniffed in non-smoking women in their twenties who were healthy and mentally healthy who returned to the normal menstrual cycle (26th to 34th).
  • the enzyme immunoassay used above was a salivary component quantification kit (measurement kit) manufactured by SALIMETRICS, whose model number was 1-3702 Estradiol, EIA Kit, High Sensitivity, Salivary, and the measurement method was (A ) “A saliva sample containing an unknown concentration of 17 ⁇ -estradiol” is reacted with an antibody that binds to it (coated on a hole in a plastic plate called a 96-well plate). The known concentration of 17 ⁇ estradiol ” was also reacted at the same time, and a competitive reaction was carried out between (A) and (B) (antibodies were exchanged between (A) and (B)).
  • “Horseradish peroxidase” which is an enzyme used in the enzyme immunoassay has the following physical properties. Peroxidase (Hydrogen peroxidase, Horseradish peroxidase, HRP) Reaction Chromogenic substrate + H 2 O 2 Oxidized dye + 2H 2 O Origin Horseradish Molecular weight, 40,000, optimum pH: pH 6.5 Substrate specificity There is no specificity for chromogenic substrates (hydrogen donors).
  • Example 1 A comparative experiment was conducted using 1.5% of 1,8-cineole dissolved in propylene glycol and Comparative Example 1: only propylene glycol (PG) as a control.
  • the test subjects are 11 persons in total of 6 persons in the follicular phase and 5 persons in the late luteal phase (Late Luteal Phase), and the experimental results of Comparative Example 1 and Example 1 are shown.
  • Example 1 The comparison results of Example 1 and Comparative Example 1 before and after the experiment showed that the concentration of 17 ⁇ estradiol (E2) secreted in Example 1 was significantly increased from 3.1 pg / ml to 3.4 pg / ml ( In contrast to the paired t-test, P ⁇ 0.05), Comparative Example 1 showed no difference in concentration from 3.0 pg / ml to 3.0 pg / ml. When these changes (after sniffing-before sniffing) were compared (PG vs 1,8-Cineole), the concentration of 17 ⁇ estradiol (E2) was significantly increased compared to propylene glycol (PG) in the control (corresponding to A t test, P ⁇ 0.05).
  • PG propylene glycol
  • ANT attention network task
  • the subject's task is to answer the direction of the center arrow among the five arrows as quickly and accurately as possible using the numeric keypad buttons (RT: reaction time).
  • the central arrow is called a target stimulus, and the other four arrows are called distractor stimuli.
  • a total of four cue stimulus conditions are presented.
  • the cue stimulus is not displayed.
  • a cue stimulus is presented at the position of the gazing point, that is, at the center of the screen.
  • the cue stimulus is presented at the position where the target stimulus is presented. That is, when the arrow is presented above the gazing point, the cue stimulus is also presented above the gazing point.
  • a cue stimulus is presented at a position symmetrical to the target stimulus with respect to a horizontal line crossing the center of the screen. That is, when the target stimulus is presented above the gazing point, the cue stimulus is presented at a position opposite to the target stimulus across the gazing point.
  • the Unconscious Dot Probe task is a cognitive task by PC operation, and the change in the index that seems to reflect the libido before and after smelling 1,8-cineole (1.5%) and the case of PG (control)
  • the comparison was performed on six subjects in the late luteal phase.
  • the Unconscious Dot Probe task is a verification tool developed to assess human attention bias. In the experiment in this example, a male nude image was used as the visual stimulus used for the task, and how much attention (bias) to the image is considered as an index reflecting sexual desire was measured. However, the stimulus image presentation time was 17 ms (below the perceptible threshold), and the measurement was performed using the Dot Probe task under the threshold (Uncoscious).
  • PANAS The Positive and Negative Affect Schedule
  • PANAS is a test that answers emotional question items from two scales of “positive emotion” and “negative emotion”.
  • the results of these experiments are the graphs of FIG. 5, and before and after sniffing 1,8-cineole of the example of the present invention, positive emotions increased and negative emotions decreased compared to control (PG).
  • STAI Staize and Trait Anxiety Inventry
  • STAI is a test that answers questions about anxiety status and characteristics from two scales of “state anxiety” and “characteristic anxiety”. Explaining these experimental results with the graph of FIG. 14, before and after sniffing 1,8-cineole, state anxiety decreased compared to control (PG). As can be seen from the results of each of these tests, anxiety can be reduced.
  • a composition for enhancing estrogen secretion containing 1,8-cineole synthesized or isolated from natural products and purified as an active ingredient.
  • the estrogen secretion fragrance composition and the estrogen fragrance device can be used on women to enhance estrogen secretion. For this reason, the effects of alleviating women-specific indefinite complaints (including illness) such as premenstrual tension, menstrual symptoms, maternity blue, postpartum depression, and menopause, which are associated with decreased estrogen secretion, increased estrogen secretion, especially The anti-aging effect can be expected due to the enhanced estrogen secretion in the late corpus luteum.
  • composition of the present invention can be administered by a method via the olfactory nerve, it can exert its effect in a short time, and since it does not involve blood, it has the advantage of having no side effects on organs such as the liver and kidney. There is also.

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Abstract

[Problem] To provide: a composition that is for promoting estrogen secretion and that can promote the secretion of estrogen; an estrogen secretion aromatic composition; and an estrogen aroma tool. [Solution] By means of a method mediated by the olfactory nerve, the composition for promoting estrogen secretion promotes the secretion of estrogen and contains, as the active ingredient, synthetic 1,8-cineole or 1,8-cineole that has been isolated and purified from a natural product.

Description

エストロジェン分泌増進用組成物、及びその芳香組成物、並びにその芳香用具Composition for enhancing estrogen secretion, fragrance composition thereof, and fragrance device therefor
 本発明は、1,8-シネオールを有効成分として含有するエストロジェン分泌増進用組成物、エストロジェン分泌芳香組成物、及び、エストロジェン分泌芳香用具に関する。 The present invention relates to an estrogen secretion enhancing composition, an estrogen secretion aroma composition, and an estrogen secretion aroma device containing 1,8-cineole as an active ingredient.
 一般に、黄体後期(月経が始まる7~10日前から月経開始日まで)、出産直後(出産後、3~5日目から2週間)、更年期(通常45~55歳)に起こる、女性特有の不定愁訴(抑うつ気分、倦怠感、意欲低下、睡眠障害)は、エストロジェン分泌の低下によってもたらされる。 Indefinite peculiar to women, generally occurring in the late corpus luteum (from 7-10 days before menstruation to the start of menstruation), immediately after childbirth (3 weeks after childbirth, 2-5 weeks), and menopause (usually 45-55 years) Complaints (depressed mood, malaise, decreased motivation, sleep disorders) are caused by decreased estrogen secretion.
 月経が終わると、視床下部の刺激で、エストロジェン分泌量が徐々に増え排卵が起こる。排卵の終わった卵胞は黄体となり、プロジェステロンを分泌するが、この時期にエストロジェン分泌も行われる。そのレベルは徐々に高まるが、妊娠しないと急激に低下し、月経が始まる。従って、黄体後期はエストロジェン分泌の急激な低下が生じる時期である。この時期に月経前緊張症が起こる。この病気では、女性特有の不定愁訴が黄体後期に起こり、月経の始まりとともに徐々に消失するが、月経期間中も続く場合もある。生殖年齢にある女性の20~50%は月経前緊張症の症状の少なくとも一つを有する。 At the end of menstruation, stimulation of the hypothalamus gradually increases the amount of estrogen secretion and ovulation occurs. The follicles that have finished ovulation become the corpus luteum and secrete progesterone, but at this time estrogen is also secreted. The level gradually increases, but if you don't get pregnant, it drops sharply and menstruation begins. Therefore, the late corpus luteum is a time when a rapid decrease in estrogen secretion occurs. Premenstrual tension occurs at this time. In this disease, female-specific indefinite complaints occur in the late luteal phase and gradually disappear with the onset of menstruation, but may continue during the menstrual period. 20-50% of women of reproductive age have at least one symptom of premenstrual tension.
 排卵後受胎すると、エストロジェンの値は急速かつ大量に増大する。妊娠中のエストロジェン分泌量は、妊娠していない女性の数十倍にもなる。ほぼ9ヶ月間にわたり高値を示したエストロジェン分泌レベルは、分娩後数時間以内に急激に減少し7日目には測定不能なまでに低下する。この時期に約80%の女性でマタニティーブルーが起こる。マタニティーブルーは、月経前緊張症と同様、女性特有の不定愁訴を示す。症状は、通常、出産後3~5日目から始まり2週間以内に消失する。また、産後のホルモン分泌の低下により、産後うつ病となることもある。 When fertilized after ovulation, estrogen levels increase rapidly and in large quantities. Estrogen secretion during pregnancy is tens of times that of women who are not pregnant. Estrogen secretion levels, which have been elevated for almost 9 months, decrease rapidly within hours after delivery and fall to the point where they cannot be measured on day 7. Maternity blue occurs in about 80% of women at this time. Maternity blue, like premenstrual tension, presents unspecified complaints specific to women. Symptoms usually begin 3-5 days after delivery and disappear within 2 weeks. In addition, postpartum depression may occur due to decreased postpartum hormone secretion.
 エストロジェンの分泌レベルは生涯を通じて変化する。思春期に上昇し始め、20代にピークを迎える。その後、卵巣機能は徐々に衰え、エストロジェンは減少し、更年期を迎える。更年期は通常45~55歳に起こり、早まることも遅まることもある。更年期障害はこの時期の女性の60~70%に見られる。更年期障害の症状は、月経前緊張症やマタニティブルーに似たような女性特有の不定愁訴が主である。 分泌 Estrogen secretion levels change throughout life. It begins to rise in puberty and reaches its peak in the 20s. Later, ovarian function gradually declined, estrogen decreased, and menopause. Menopause usually occurs between the ages of 45 and 55 and may be early or late. Menopause is seen in 60-70% of women at this time. Symptoms of menopause are mainly women's unspecified complaints similar to premenstrual tension or maternity blue.
 以上のことから、女性の不定愁訴(病気を含む)はエストロジェン分泌が減少するという特徴を持つ時期である、黄体後期(月経中も含む)、出産後、更年期に出現することがわかる。
 ところで、エストロジェン分泌を制御する組成物として、特許文献1には、エストロジェン(女性ホルモンの1群)の主成分である17β-エストラジオールの分泌促進剤として、香科組成物のアンプレット・シード油やアンブレットリドを用いることが開示している。また、特許文献2には、女性ホルモン不足症を治療するものとして菌生冬虫夏草の抽出物を用いることが開示している。また、特許文献3は、本発明者らによるものであるが、β-カリオフィレンの芳香成分の女性に対する影響が開示されている。
From the above, it can be seen that indefinite complaints (including illness) in women appear in the late corpus luteum (including during menstruation), postpartum, and menopause, which is characterized by decreased estrogen secretion.
By the way, as a composition for controlling estrogen secretion, Patent Document 1 discloses amplet seed oil as a fragrance composition as a secretion promoter for 17β-estradiol, which is a main component of estrogen (a group of female hormones). The use of an amblet lid is disclosed. Patent Document 2 discloses the use of an extract of fungal Cordyceps as a treatment for female hormone deficiency. Patent Document 3 is based on the present inventors, and discloses the effect of aroma component of β-caryophyllene on women.
 更に、非特許文献1~3には、匂いの呈示は、視床下部が制御する黄体形成ホルモン(LH)の分泌頻度を変えることを示し、従来のアロマテラピー等が経口、経静脈、経皮的ルートを介する複合的な作用であることに対し、嗅覚神経を介する作用のみによって、視床下部機能を変える可能性を示した。一般的に、エストロジェンの分泌は、LHの分泌を受けて生じ、LHの分泌は視床下部の活動を受けて生じる為、視床下部の活動亢進をもたらす作用が、エストロジェン分泌亢進をもたらすものと考えられる。いずれも、1,8-シネオールと女性ホルモンであるエストロジェン分泌については言及されていない。 Furthermore, Non-Patent Documents 1 to 3 show that the presentation of odor changes the secretion frequency of luteinizing hormone (LH) controlled by the hypothalamus, and conventional aromatherapy and the like are oral, intravenous, and transdermal. In contrast to the complex action via the root, the possibility of changing hypothalamic function only through the action via the olfactory nerve was shown. In general, estrogen secretion is caused by the secretion of LH, and LH secretion is caused by the activity of the hypothalamus. Therefore, the effect of increasing the activity of the hypothalamus is considered to cause the increase of estrogen secretion. . Neither mentions about estrogen secretion, which is 1,8-cineole and the female hormone.
 エストロジェンは、以下のアンチエージング効果(あるいは更年期及び閉経女性のエストロジェン低下に伴う疾患リスク低減効果)を有することが明らかにされている。
 ・コラーゲンの生成促進(美肌効果、ハリ・つやの衰え予防)
 ・カルシウムの骨への吸収促進(骨粗鬆症のリスク低減)
 ・毛髪の新生促進(増毛促進)
 ・基礎代謝亢進(リンゴ型肥満の予防)
 ・認知機能亢進(認知症リスク低減)
 ・血管拡張促進(動脈硬化のリスク低減)
 ・免疫機能亢進(膠原病、リューマチ等自己免疫疾患リスク低減)
 ・乳腺の発達促進(乳房の弾力やハリの維持による美容効果)
 ・善玉コレステロール(HDL)増加(動脈硬化のリスク低減)
Estrogens have been shown to have the following anti-aging effects (or disease risk reduction effects associated with reduced estrogen in menopause and menopausal women).
・ Promoting the production of collagen (beautifying skin effect, preventing firmness / shininess)
・ Promoting absorption of calcium into bone (reducing risk of osteoporosis)
・ Promoting hair renewal (promoting hair growth)
・ Increased basic metabolism (prevention of apple-type obesity)
・ Cognitive enhancement (reducing dementia risk)
・ Promoting vasodilation (reducing the risk of arteriosclerosis)
・ Immune function enhancement (reducing risk of autoimmune diseases such as collagen disease and rheumatism)
・ Promoting the development of the mammary gland (beauty effect by maintaining the elasticity and elasticity of the breast)
・ Increased good cholesterol (HDL) (reduced risk of arteriosclerosis)
 最近、代替医療として、アロマテラピーなどの香り(匂い物質)による健康改善法が広まりつつあるが、効用は経験に基づくものであり基礎医学研究による裏付けがあまりない。また、作用する経路も嗅覚神経を介すものに限らず、経口、経静脈、経皮的ルートも含み、複合的である。しかし、嗅覚情報は大脳新皮質を介さず、直接、情動の中枢である大脳辺縁系や本能(摂食、睡眠)ホルモンの中枢である視床下部に入力することを考えると、匂い物質は経口、経静脈、経皮的ルートを介さない新しい中枢神経系薬物として発展しうる可能性がある。 Recently, as an alternative medicine, health improvement methods by aroma (scented substances) such as aromatherapy are spreading, but the benefits are based on experience and are not supported by basic medical research. In addition, the route of action is not limited to the route through the olfactory nerve, but also includes the oral, intravenous, and transdermal routes. However, when olfactory information is input directly to the limbic system, which is the center of emotion, and to the hypothalamus, which is the center of instinct (feeding, sleep) hormone, without passing through the cerebral neocortex, There is a possibility that it can be developed as a new central nervous system drug without transvenous or transdermal route.
特開2005-29776号公報JP 2005-29776 A 特開2004-300104号公報JP 2004-300104 A 特許第5116942号公報Japanese Patent No. 5116942
 本発明は、エストロジェン分泌増進用組成物、及び前記分泌増進方法を提供することを目的とする。 An object of the present invention is to provide a composition for enhancing estrogen secretion and the method for enhancing secretion.
 本発明者らは、上記課題を解決するため鋭意検討を重ねた結果、1,8-シネオールの匂いが、特に、黄体後期の女性のエストロジェン分泌を増進する作用を見出した。本発明は、以上の知見に基づき完成されたものであり、1,8-シネオールを有効成分として含有するエストロジェン分泌増進用組成物、及びその芳香組成物、並びにその芳香用具である。 As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that the odor of 1,8-cineole particularly enhances estrogen secretion in late-luteal females. The present invention has been completed based on the above findings, and is an estrogen secretion enhancing composition containing 1,8-cineole as an active ingredient, its fragrance composition, and its fragrance tool.
 即ち、本発明の第1の様態である請求項1の発明は、合成された1,8-シネオール又は天然物から単離、精製された1,8-シネオールを有効成分として含有するエストロジェン分泌を増進させることを特徴するエストロジェン分泌増進用組成物である。
 請求項2の発明は、請求項1に記載のエストロジェン分泌増進用組成物において、前記エストロジェンは、17β-エストラジオールであることを特徴とする。
 請求項3の発明は、請求項1又は2に記載のエストロジェン分泌増進用組成物において、前記組成物の投与手段が香料、精油、化粧品による嗅覚神経を介して脳に伝達されるように投与することを特徴とする。
 請求項4の発明は、請求項3に記載のエストロジェン分泌増進用組成物において、前記組成物の投与手段が飲食物による嗅覚神経を介して脳に伝達されるように投与することを特徴する。
 本発明の第2の様態である請求項5の発明は、合成された1,8-シネオール又は天然物から単離、精製された1,8-シネオールを有効成分として含有してエストロジェンの分泌を増進させることを特徴するエストロジェン分泌芳香組成物である。
 請求項6の発明は、請求項5に記載のエストロジェン分泌芳香組成物において、前記エストロジェンは、17β-エストラジオールであることを特徴とする。
 本発明の第3の様態である請求項7の発明は、合成された1,8-シネオール又は天然物から単離、精製された1,8-シネオールを有効成分として含有してエストロジェンの分泌を増進させることを特徴するエストロジェン芳香用具である。
 請求項8の発明は、請求項7に記載のエストロジェン分泌芳香用具において、前記エストロジェンは、17β-エストラジオールであることを特徴とする。
That is, the first aspect of the present invention is the invention according to claim 1, wherein estrogen secretion containing 1,8-cineole synthesized or purified from natural product as an active ingredient is synthesized. It is a composition for enhancing estrogen secretion, characterized by enhancing.
The invention of claim 2 is the composition for enhancing estrogen secretion according to claim 1, wherein the estrogen is 17β-estradiol.
The invention of claim 3 is the composition for enhancing estrogen secretion according to claim 1 or 2, wherein the administration means of the composition is administered so as to be transmitted to the brain via the olfactory nerve by a fragrance, essential oil, or cosmetics. It is characterized by that.
The invention of claim 4 is characterized in that, in the composition for enhancing estrogen secretion according to claim 3, the administration means of the composition is administered so as to be transmitted to the brain via the olfactory nerve by food and drink.
The invention according to claim 5, which is the second aspect of the present invention, comprises synthesized 1,8-cineol or 1,8-cineole isolated and purified from a natural product as an active ingredient to inhibit estrogen secretion. An estrogen-secreting fragrance composition characterized in that it is enhanced.
The invention of claim 6 is the estrogen secretion fragrance composition of claim 5, wherein the estrogen is 17β-estradiol.
The invention according to claim 7, which is the third aspect of the present invention, comprises 1,8-cineole synthesized or 1,8-cineole isolated and purified from a natural product as an active ingredient to inhibit estrogen secretion. It is an estrogen fragrance tool characterized by improving it.
The invention of claim 8 is the estrogen-secreting fragrance device according to claim 7, wherein the estrogen is 17β-estradiol.
 本発明の合成された1,8-シネオール又は天然物から単離、精製された1,8-シネオールを有効成分として含有するエストロジェン分泌増進用組成物、エストロジェン分泌芳香組成物、及び、エストロジェン芳香用具を使用することにより、エストロジェン分泌を増進することができ、特に、黄体後期においてエストロジェン分泌をより増進することができる。この為、女性に対してエストロジェン分泌低下に伴い生じる、月経前緊張症、月経期の諸症状、マタニティーブルー、産後うつ病、更年期障害といった女性特有の不定愁訴(病気を含む)を緩和する効果、エストロジェン分泌増進によるアンチエージング効果を期待できる。
 また、副次的効果として、特に黄体後期において、集中力、性欲、陽性/陰性感情、気分、不安の症状を改善でき、それによって、女性の不定愁訴症状の改善、アンチエージングをもたらす効果が期待できる。
 また、本発明の組成物は、嗅覚神経を介する方法によって投与できるので、短時間で効果を発揮させることができ、また、血液を介さないので肝臓や腎臓等の臓器に副作用を及ぼさないという利点もある。
Estrogen secretion enhancing composition, estrogen secretion fragrance composition, and estrogen fragrance composition containing 1,8-cineole isolated and purified from the synthesized 1,8-cineol or natural product of the present invention as an active ingredient Can be used to enhance estrogen secretion, and in particular, estrogen secretion can be further enhanced in the late corpus luteum. For this reason, estrogen is effective in alleviating female-specific indefinite complaints (including illness) such as premenstrual tension, menstrual symptoms, maternity blue, postpartum depression, and menopause, which are caused by decreased estrogen secretion in women. Anti-aging effect due to increased secretion can be expected.
As a secondary effect, especially in the late luteal phase, concentration, libido, positive / negative emotions, mood, and anxiety symptoms can be improved, thereby improving the indefinite complaint symptoms and anti-aging effects of women. it can.
In addition, since the composition of the present invention can be administered by a method via the olfactory nerve, it can exert its effect in a short time, and since it does not involve blood, it has the advantage of having no side effects on organs such as the liver and kidney. There is also.
全ての被験者(n=11)、卵胞期の被験者(n=6)、黄体後期の被験者(n=5)での1.5%の1,8-シネオール(Cineole)の含有した溶液を嗅がせた場合のエストロジェンについての変化量(嗅いだ後―嗅ぐ前)から、プロピレングリコール(PG:コントロール) 溶液を嗅がせた場合の変化量を差し引いた値の棒グラフの図、Smell a solution containing 1.5% 1,8-cineole in all subjects (n = 11), follicular phase subjects (n = 6), and late luteum phase subjects (n = 5) A graph of the bar graph of the value obtained by subtracting the amount of change when smelling propylene glycol (PG) control solution from the amount of change for estrogen (after sniffing-before sniffing), 1,8-シネオール(Cineole)を、0.30%、1.50%、3.75%、7.50%を含有した溶液を嗅がせた場合のエストロジェンについての変化量から、プロピレングリコール(PG:コントロール) 溶液を嗅がせた場合の変化量を差し引いた値の棒グラフの図、From the amount of change in estrogen when a solution containing 0.30%, 1.50%, 3.75%, and 7.50% of 1,8-cineole was added, propylene glycol (PG : Control) Bar graph of the value obtained by subtracting the amount of change when smelling sputum solution, 黄体後期の被験者5人を対象に実施例の1,8-シネオールを溶媒に溶かした溶液と溶媒だけとを嗅がせてANT(attention network task)テストによる「集中力」を検証した実験結果のグラフの図、The graph of the experimental result which verified the concentration power by the ANT (attentionAnetwork task) test by sniffing the solution which dissolved 1,8-cineole of the example in the solvent and only the solvent for five subjects in the late corpus luteum Figure of the 黄体後期の被験者6人を対象に同様に実施例の1,8-シネオールを溶媒に溶かした溶液と溶媒だけとを嗅がせて被験者の「性欲」について検証した実験結果のグラフの図、Figure of the graph of the experimental result which verified the subject's "sexual desire" by sniffing the solution which dissolved 1,8-cineole of the example in the solvent, and only the solvent similarly for the 6 subjects in the late corpus luteum, 黄体後期の被験者6人を対象に1,8-シネオールの投与によって感情の増減をPANAS(The Positive and Negative Affect Schedule)テストで検証した実験結果のグラフの図、Figure of graph of the experimental result that we verified increase and decrease of feeling by administration of 1,8-cineole for 6 subjects in the late corpus luteum in the PANAS (The sPositive and Negative Affect Schedule) test, 黄体後期の被験者6人を対象に1,8-シネオールを溶媒に溶かした溶液と溶媒だけとを嗅がせて、POMSの「活気」「不安」「抑うつ」「疲労感」の実験結果のグラフの図、In the graph of the results of the experiment on POMS's “liveliness”, “anxiety”, “depression”, and “feeling fatigue” by sniffing a solution of 1,8-cineole in a solvent and only the solvent for six subjects in the late corpus luteum Figure, 黄体後期の被験者6人を対象に1,8-シネオールの投与によって状態不安をSTAI(State and Trait Anxiety Inventry)テストにより検証した実験結果のグラフの図である。It is a figure of the graph of the experimental result which verified the state anxiety by STAI (State (trademark) andTrait (trademark) Anxiety (s) Inventry) test by administration of 1,8- cineole to six subjects of the luteum phase.
 以下、本発明を詳細に説明するが、本発明は、1,8-シネオールの匂いが、特に、黄体後期の女性(黄体後期は、エストロジェンが低下し、月経前緊張症を起こす。)のエストロジェン分泌を増進する作用を見出した。本発明は、以上の知見に基づき完成されたものである。
 この1,8-シネオールは、別名ユーカリプトール (eucalyptol)と呼ばれる天然に存在する有機化合物(合成も可能であるが)で、環状エーテル構造を持つモノテルペノイドの一種であり、1,8-シネオールは他にリモネンオキシド、カジェプトール (cajeptol) とも呼ばれ、こころよい芳香と味を持つことから、食品添加物・香料・化粧品に利用され、下記のような構造式を有する。
Figure JPOXMLDOC01-appb-C000001
In the following, the present invention will be described in detail, and the present invention shows that the odor of 1,8-cineole is particularly estrogen in a woman in the late luteal phase (in the late luteal phase, estrogen decreases and premenstrual tension develops). We found an action to enhance secretion. The present invention has been completed based on the above findings.
This 1,8-cineole is a naturally occurring organic compound called eucalyptol (also synthesizable), which is a kind of monoterpenoid with a cyclic ether structure, and is 1,8-cineole. It is also called limonene oxide and cajeptol, and has a fragrance and taste that makes it suitable for food additives, fragrances, and cosmetics, and has the following structural formula.
Figure JPOXMLDOC01-appb-C000001
 そして、発明者らは、1,8-シネオールの匂いは、黄体後期の女性のエストロジェン分泌を増進する作用があることを見出したが、以下のような新規な用途に利用できることに想到した。
(1)1,8-シネオールは、黄体後期(月経期も含む)の女性にみられるエストロジェン分泌の低下が原因の不快症状、及び出産後の女性の不快症状の改善に効果があると推定できる。また、エストロジェン分泌の低下が原因の不快症状は黄体後期(月経期も含む)の女性のみならず、出産後の女性、更年期の女性にもみられるが、このような女性の不快症状に対しても1,8-シネオールは有効であると推定できる。また、上述のアンチエージング効果があると推定できる。
(2)植物の精油(エッセンシャルオイル)を用いて症状の改善や健康維持を図る療法を一般にアロマテラピー(芳香治療、芳香療法)というが、この植物の精油(混合物)の代わりに、1,8-シネオール(精油に含まれる単一物質)を用いて、病気の治療を図ることも可能である。
 従って、1,8-シネオールは、「エストロジェン分泌増進の芳香による症状の改善組成物」としても利用できると考えられる。
(3)上記(2)と同様に、器具や道具のような形態でも、1,8-シネオールによる症状の改善や健康維持は可能である。従って、1,8-シネオールは、「芳香による症状の改善用用具」としても利用できると考えられる。
The inventors have found that the odor of 1,8-cineole has the effect of promoting estrogen secretion in late luteinous women, but has come up with the idea that it can be used for the following novel uses.
(1) 1,8-cineole can be presumed to be effective in improving discomfort caused by decreased estrogen secretion in women in the late corpus luteum (including menstrual periods) and in women after childbirth . Discomfort caused by decreased estrogen secretion is seen not only in women in the late corpus luteum (including menstrual periods), but also in women after childbirth and women in menopause. It can be assumed that 1,8-cineole is effective. Moreover, it can be estimated that the above-mentioned anti-aging effect is obtained.
(2) The use of plant essential oil (essential oil) to improve symptoms and maintain good health is generally called aromatherapy (aroma therapy, aroma therapy). Instead of this plant essential oil (mixture), 1,8- It is also possible to treat disease using cineol (a single substance contained in essential oils).
Therefore, 1,8-cineole is considered to be usable as “a symptom-improving composition by aroma of enhanced estrogen secretion”.
(3) Similar to (2) above, 1,8-cineole can improve symptoms and maintain health even in the form of instruments and tools. Therefore, it is considered that 1,8-cineole can also be used as a “tool for improving symptoms due to aroma”.
 以下、上記の各用途について説明する。
(4)エストロジェン分泌増進用組成物(以下、「本発明の増進用組成物」という場合がある)
 本発明のエストロジェン分泌増進用組成物は、1,8-シネオールを有効成分として含有するものである。
 使用する1,8-シネオールは、天然物(例えば、ティートリー、ペパーミント、ユーカリ、ローズマリー等)などから抽出されたものでもよく、人工的に合成されたものであってもよい。また、1,8-シネオールは、試薬として既に販売されているのでそれを用いてもよい。
Hereinafter, each of the above uses will be described.
(4) Composition for enhancing estrogen secretion (hereinafter sometimes referred to as “the composition for enhancing the present invention”)
The composition for enhancing estrogen secretion according to the present invention contains 1,8-cineole as an active ingredient.
The 1,8-cineole to be used may be extracted from natural products (for example, tea tree, peppermint, eucalyptus, rosemary, etc.) or may be artificially synthesized. In addition, 1,8-cineole is already sold as a reagent and may be used.
 本発明のエストロジェン分泌増進用組成物は、その使用態様に応じて様々な組成で調製されるが、通常は、後述するエストロジェン分泌芳香組成物と同様の組成で調製される。
 本発明のエストロジェン分泌芳香組成物は、その使用態様に応じて様々な組成で調製されるが、通常は、1,8-シネオール濃度が0.3~3.75%で、好ましくは1.5%になるように、適当な溶媒、例えば、ジプロピレングリコール、プロピレングリコール、ブチレングリコール、ミネラルオイル、クエン酸トリエチル、エタノール、ベンジルベンゾエイトと混合することにより調製される。
 一般には、アロマポット、ディフーザーを用いて、芳香浴としてその香りを吸入する。また、必要に応じて他の成分を加え、化粧品(スキンケア製品、香水等)、入浴剤、芳香剤、スプレー、マッサージオイル、シャンプー、洗濯洗剤などとして使用することもできる。
The composition for enhancing estrogen secretion of the present invention is prepared in various compositions depending on the use mode, and is usually prepared in the same composition as the estrogen secreting fragrance composition described later.
The estrogen-secreting fragrance composition of the present invention is prepared in various compositions depending on the use mode, but usually the 1,8-cineole concentration is 0.3 to 3.75%, preferably 1.5. % By mixing with a suitable solvent such as dipropylene glycol, propylene glycol, butylene glycol, mineral oil, triethyl citrate, ethanol, benzyl benzoate.
Generally, the aroma is inhaled as an aromatic bath using an aroma pot or a diffuser. Further, if necessary, other components can be added and used as cosmetics (skin care products, perfumes, etc.), bathing agents, fragrances, sprays, massage oils, shampoos, laundry detergents and the like.
(5)エストロジェン分泌芳香用具
 本発明のエストロジェン分泌芳香用具は、合成された1,8-シネオール又は天然物から単離、精製された1,8-シネオールを含有する部分を持つものである。
 使用する1,8-シネオールは、芳香組成物と同様に、合成された又は天然物から単離、精製されたものを用いる。
 また、飲食物を口に入れる前又は咀嚼中、通常その食品の匂いを嗅いでいる。従って、食品或いは飲料という形態でも1,8-シネオールはその効果を発揮でき、1,8-シネオールは女性の不定愁訴症状の改善用の飲食物としても利用できる。
 飲食物の種類は限定されず、フレーバーティー、フレーバーコーヒー、フレーバービール、飴、ガム、ブレスケア、調味料などを例示できる。例えば、本発明の食品は、通常の食品の製造工程に、1,8-シネオールを添加する工程を追加することにより製造され、食品中の1,8-シネオールの含有量は、食品の種類により異なるが、通常は、0.3-3.75%程度が適量である。
 芳香用具は、芳香に使用される器具、道具等であればどのようなものでもよく、生理用品、紙類、繊維製品(下着、ストキング等)、貼布薬、石鹸、ろうそく、枕、布団、などを例示することができる。
 本発明の芳香用具は、植物の精油の代わりに1,8-シネオールを用いること以外は、一般の芳香用具と同様に製造することができる。
(5) Estrogen secretion fragrance tool The estrogen secretion fragrance tool of the present invention has a portion containing synthesized 1,8-cineole or 1,8-cineole isolated and purified from natural products.
The 1,8-cineole to be used is synthesized or isolated from a natural product and purified in the same manner as the fragrance composition.
In addition, the food is usually smelled before it is put into the mouth or during mastication. Therefore, 1,8-cineole can exert its effect even in the form of food or beverage, and 1,8-cineole can also be used as a food or drink for improving indefinite complaint symptoms of women.
The types of food and drink are not limited, and examples include flavor tea, flavor coffee, flavor beer, rice cake, gum, breath care, seasoning and the like. For example, the food of the present invention is produced by adding a process of adding 1,8-cineole to the normal food production process, and the content of 1,8-cineole in the food depends on the type of food. Normally, the appropriate amount is about 0.3-3.75%.
The fragrance device may be any device or tool used for fragrance, sanitary products, paper, textile products (underwear, stocking, etc.), patch medicine, soap, candle, pillow, futon, Etc. can be illustrated.
The fragrance tool of the present invention can be produced in the same manner as a general fragrance tool, except that 1,8-cineole is used instead of plant essential oil.
(6)エストロジェン分泌増進用組成物の使用
 本発明のエストロジェン分泌増進用組成物の使用対象及び投与方法は、1,8-シネオールを、エストロジェンの低下を示す者に投与することを特徴とするものである。
 1,8-シネオールの投与方法は特に限定されず、通常の医薬等と同様に経口的、経静脈的、経皮的に投与してもよいが、好ましくは、1,8-シネオールによる刺激が嗅覚神経を介して脳に伝達されるような手段で投与する。このような投与手段の一例としては、1,8-シネオールを含む空気を、エストロジェン分泌の低下を示す者に嗅がせる手段を例示することができる。このときの空気中の1,8-シネオールの量は厳密には計測できないが、芳香を発散する溶液の使用する1,8-シネオールの含有量は、例えば、プロピレングリコールを溶媒に用いた場合には、0.3~3.75%の範囲が好ましく、1.5%程度がより好ましい。
(6) Use of the composition for enhancing estrogen secretion The use target and the administration method of the composition for enhancing estrogen secretion of the present invention are characterized in that 1,8-cineole is administered to a person who shows a decrease in estrogen. It is.
The administration method of 1,8-cineole is not particularly limited, and it may be administered orally, intravenously, or transdermally in the same manner as ordinary pharmaceuticals, etc., but preferably stimulated by 1,8-cineole. It is administered by a means that is transmitted to the brain via the olfactory nerve. As an example of such administration means, a means for allowing a person who shows a decrease in estrogen secretion to air containing 1,8-cineole can be exemplified. The amount of 1,8-cineole in the air at this time cannot be measured strictly, but the content of 1,8-cineole used in the solution that emits a fragrance is, for example, when propylene glycol is used as a solvent. Is preferably in the range of 0.3 to 3.75%, more preferably about 1.5%.
 以下、実施例により本発明を更に詳細に説明する。
〔実施例1〕
 正常月経周期(26日~34日)を回帰する精神的・身体的に健常な20代の非喫煙女性を対象として、1,8-シネオールを嗅いだ場合に生じるホルモン変化を調べた。
Hereinafter, the present invention will be described in more detail with reference to examples.
[Example 1]
We examined hormonal changes that occurred when 1,8-cineole was sniffed in non-smoking women in their twenties who were healthy and mentally healthy who returned to the normal menstrual cycle (26th to 34th).
 1.実験方法
 1-1.説明会
 被験者には、事前に実験内容を説明して承諾を得てから、実験当日は匂いが強い食べ物や刺激物(ニンニク・タマネギ・香辛料・香草など)を朝から食べないようにし、実験開始30分前からは何も食べないようにしてもらうようにした。また、基礎体温を記載してもらい、排卵検査薬を用いて、排卵日(LHサージ)を確定してもらった。
1.Experimental method 1-1. Briefing session Explaining the contents of the experiment in advance and obtaining consent from the subject, then on the day of the experiment, food or stimulants (garlic, onion, spices, herbs, etc.) with a strong smell were served in the morning. I tried not to eat anything from 30 minutes before the start of the experiment. In addition, the basal body temperature was described, and the ovulation day (LH surge) was confirmed using an ovulation test.
 1-2.実験当日
 被験者を月経周期により、卵胞期(月経開始後5-10日)、黄体後期(LHサージ後9-12日)の2グループに分けた。各々のグループの被験者に、1.5%の1,8-シネオールを含む溶媒(プロピレングリコール)又は溶媒のみを嗅がせ、実験開始前と実験開始20分後に唾液採取を行い、分泌されるエストロジェン(女性ホルモン)の内、最も作用が強い17βエストラジオール(E2)を酵素免疫測定法により測定した。
1-2. On the day of the experiment Subjects were divided into two groups according to the menstrual cycle: follicular phase (5-10 days after menstruation started) and late corpus luteum (9-12 days after LH surge). Each group of subjects was sniffed with a solvent containing 1.5% of 1,8-cineole (propylene glycol) or only the solvent, and saliva was collected before and 20 minutes after the start of the experiment, and secreted estrogen ( Among female hormones, 17β estradiol (E2), which has the strongest action, was measured by enzyme immunoassay.
 前記の酵素免疫測定法に用いたのは、SALIMETRICS社製の唾液中成分の定量キット(測定キット)で、型番が1-3702 Estradiol, EIA Kit, High Sensitivity, Salivaryで、測定手法は、(A)「未知の濃度の17βエストラジオールを含む唾液検体」を、それに結合する抗体(96穴プレートというプラスティックプレートの穴にコーティングされている)と反応させ、その際、(B)「酵素を予め結合させた既知濃度の17βエストラジオール」も同時に反応させ、(A)と(B)で競合反応((A)と(B)で抗体を取り合う)をさせた。
 一定時間の反応後、プレート状の抗体に結合しているもの以外の溶液を捨て、酵素反応(発色する)を誘発する基質を添加する。こうすることで、発色は(B)の結合量を反映した色合いになる。この色合いは、吸光光度計による測定から定量化し、(A)が少なければ、(B)の方が抗体を多く取るので、発色の強さは強くなり、一方、(B)が多ければ、相対的に(B)が抗体を取る量が減り、発色の強さは弱くなる。こうした原理を利用して、別途、「既知の濃度の17βエストラジオール(標準検体)」を複数濃度測定し、検量線を算出しておくことで、発色の色合いから(A)「未知の濃度の17βエストラジオールを含む唾液検体」の濃度を算出した。  
The enzyme immunoassay used above was a salivary component quantification kit (measurement kit) manufactured by SALIMETRICS, whose model number was 1-3702 Estradiol, EIA Kit, High Sensitivity, Salivary, and the measurement method was (A ) “A saliva sample containing an unknown concentration of 17β-estradiol” is reacted with an antibody that binds to it (coated on a hole in a plastic plate called a 96-well plate). The known concentration of 17β estradiol ”was also reacted at the same time, and a competitive reaction was carried out between (A) and (B) (antibodies were exchanged between (A) and (B)).
After the reaction for a certain time, the solution other than the one bound to the plate-like antibody is discarded, and a substrate for inducing an enzyme reaction (color development) is added. By doing so, the color development becomes a hue reflecting the binding amount of (B). This hue is quantified from the measurement with an absorptiometer. If (A) is small, (B) takes more antibody, so the intensity of color development becomes strong, while if (B) is large, the relative color In particular, the amount of antibody taken by (B) decreases and the intensity of color development decreases. Using this principle, separately, a plurality of concentrations of “known concentrations of 17β estradiol (standard sample)” are measured, and a calibration curve is calculated. The concentration of the “saliva sample containing estradiol” was calculated.
 前記酵素免疫測定法で使用した酵素である「西洋ワサビペルオキシダーゼ(horseradish peroxidase)」は、以下のような物性を有する。
 ペルオキシダーゼ(Hydrogen peroxidase,Horseradish peroxidase,HRP)
 反応 色原性基質+H22 ⇔酸化型色素+2H2
 起源 西洋わさび(Horseradish)
 分子量, 40,000,至適pH:pH6.5
 基質特異性 色原性基質(水素供与体)については特異性はない.
 過酸化物としてはH22, CH3OOH, C26OOHのみ
 阻害剤と活性化剤 阻害剤:CN-,S--,F-,N3-(抗凝固剤として用いられるフッ素イオン、保存料として用いられるNaN3を含有)
 安定性 乾燥,冷蔵状態で数年間,水溶液で冷蔵1年間
“Horseradish peroxidase” which is an enzyme used in the enzyme immunoassay has the following physical properties.
Peroxidase (Hydrogen peroxidase, Horseradish peroxidase, HRP)
Reaction Chromogenic substrate + H 2 O 2 Oxidized dye + 2H 2 O
Origin Horseradish
Molecular weight, 40,000, optimum pH: pH 6.5
Substrate specificity There is no specificity for chromogenic substrates (hydrogen donors).
As peroxides, only H 2 O 2 , CH 3 OOH, C 2 H 6 OOH Inhibitors and activators Inhibitors: CN-, S--, F-, N 3- (fluorine used as anticoagulant Ion, containing NaN3 used as a preservative)
Stability Several years in dry and refrigerated state, one year refrigerated in aqueous solution
 実験は、空気を2 L/minの風量で本実施例の1,8-シネオールを含む溶媒(プロピレングリコール)の入ったガラス瓶に送り、そこから出てきた空気を被験者の鼻から10cm離したロートから放出させることにより行い、これを20分間続けた。実験中は、被験者には椅子に座ってリラックスした状態で普段と変わらない呼吸をしてもらい、実験開始前と実験開始20分後に唾液採取を行った。このとき、何らかの異常を認めた場合、その場で実験を中止し適切な処置を行うこととした。 In the experiment, air was sent to a glass bottle containing a solvent (propylene glycol) containing 1,8-cineole of this example at a flow rate of 2 L / min. The funnel was separated from the subject's nose by 10 cm. This was continued for 20 minutes. During the experiment, subjects took a breath as usual while sitting in a chair and relaxed, and saliva was collected before and 20 minutes after the start of the experiment. At this time, if any abnormality was observed, the experiment was stopped on the spot and appropriate measures were taken.
 1.実験結果
[実施例1]
 実施例1:1,8-シネオールの1.5%をプロピレングリコールで溶かしたものと、比較例1:コントロールとしてプロピレングリコール(PG)だけのものとを比較実験を行った。
 被験者は卵胞期(Follicular Phase)6人、黄体後期(Late Luteal Phase)5人の全体で11人を対象とし、比較例1と実施例1のぞれぞれの実験結果を示す。
 実施例1と比較例1の実験前と実験後の比較結果は、実施例1で分泌される17βエストラジオール(E2)は3.1pg/mlから3.4pg/mlに濃度が有意に増加した(対応のあるt検定、P<0.05)のに対して、比較例1は3.0pg/mlから3.0pg/mlで濃度に違いはなかった。
 これらの変化量(嗅いだ後―嗅ぐ前)について比較(PG vs 1,8-Cineole)すると、コントロールのプロピレングリコール(PG)に比べ、17βエストラジオールの濃度(E2)が有意に増加した(対応のあるt検定、P<0.05)。
1. Experimental result
[Example 1]
Example 1: A comparative experiment was conducted using 1.5% of 1,8-cineole dissolved in propylene glycol and Comparative Example 1: only propylene glycol (PG) as a control.
The test subjects are 11 persons in total of 6 persons in the follicular phase and 5 persons in the late luteal phase (Late Luteal Phase), and the experimental results of Comparative Example 1 and Example 1 are shown.
The comparison results of Example 1 and Comparative Example 1 before and after the experiment showed that the concentration of 17β estradiol (E2) secreted in Example 1 was significantly increased from 3.1 pg / ml to 3.4 pg / ml ( In contrast to the paired t-test, P <0.05), Comparative Example 1 showed no difference in concentration from 3.0 pg / ml to 3.0 pg / ml.
When these changes (after sniffing-before sniffing) were compared (PG vs 1,8-Cineole), the concentration of 17β estradiol (E2) was significantly increased compared to propylene glycol (PG) in the control (corresponding to A t test, P <0.05).
 被験者を卵胞期の6人(n=6)を対象とした比較例1と実施例1との実験では、実施例1で分泌される17βエストラジオールは3.1pg/mlから3.5pg/mlに濃度が有意に増加し(対応のあるt検定、P<0.05)、比較例1は2.5pg/mlから2.7pg/mlで濃度(E2)は増加傾向を示した(対応のあるt検定、P<0.10)。これらの変化量(嗅いだ後―嗅ぐ前)について比較(PG vs 1,8-Cineole)すると、1,8-シネオール(Cineole)とプロピレングリコール(PG)は濃度に違いはなかった。 In the experiments of Comparative Example 1 and Example 1 in which six subjects (n = 6) were subjects in the follicular stage, 17β estradiol secreted in Example 1 was changed from 3.1 pg / ml to 3.5 pg / ml. Concentration increased significantly (corresponding t-test, P <0.05), Comparative Example 1 showed an increasing trend from 2.5 pg / ml to 2.7 pg / ml (corresponding t-test) , P <0.10). When these changes (after sniffing-before sniffing) were compared (PG vs 1,8-Cineole), there was no difference in concentration between 1,8-cineole (Cineole) and propylene glycol (PG).
 被験者を黄体後期の5人(n=5)を対象とした比較例1と実施例1との実験では、実施例1で分泌される17βエストラジオールは3.1pg/mlから3.3pg/mlに濃度が増加し、比較例1は3.5pg/mlから3.1pg/mlで濃度が低下した(対応のあるt検定、P<0.10)。これらの変化量(嗅いだ後―嗅ぐ前)について比較(PG vs 1,8-Cineole)すると、コントロールのプロピレングリコール(PG)に比べ、17βエストラジオールの濃度(E2)が有意に増加した(対応のあるt検定、P<0.05)。 In the experiment of Comparative Example 1 and Example 1 with 5 subjects in the luteal phase (n = 5), 17β estradiol secreted in Example 1 was changed from 3.1 pg / ml to 3.3 pg / ml. Concentration increased, and Comparative Example 1 decreased in concentration from 3.5 pg / ml to 3.1 pg / ml (paired t-test, P <0.10). When these changes (after sniffing-before sniffing) were compared (PG vs 1,8-Cineole), the concentration of 17β estradiol (E2) increased significantly compared to propylene glycol (PG) in the control (corresponding to A t test, P <0.05).
 これらの各変化量の差分値(1,8-シネオール(Cineole)変化量-プロピレングリコール(PG)変化量)を図1に示して説明すると、卵胞期(n=6)と黄体後期(n=5)での各変化量の差分値を比較すると、黄体後期は、卵胞期に比べ、濃度(E2)が有意に増加した(対応のないt検定、P<0.05)ことが判る。 The difference between these changes (1,8-cineole change-propylene glycol (PG) change) is described with reference to FIG. 1. When follicular phase (n = 6) and late corpus luteum (n = Comparing the difference value of each change amount in 5), it can be seen that the concentration (E2) increased significantly in the later luteal phase compared to the follicular phase (unpaired t-test, P <0.05).
 次に、1,8-シネオール(Cineole)をプロピレングリコール(PG)にどの程度の量を溶かせば良いかを検証した。
 そのため、上述したように、溶媒のプロピレングリコール(PG)に、実施例1と同じ1.50%の1,8-シネオールを溶かしたものと、それより少ない0.30%を溶かしたもの、それより多い、3.75%と、7.50%を溶かしたものを、新たに3人ずつの黄体後期の被験者を対象に実験を行った。
 その変化量の結果を図2に示して説明すると、17βエストラジオールの増加は、1,8-シネオール(Cineole)が1.50%の溶液の割合が有意に増加したことが判り、少なくとも0.30%から3.75%では17βエストラジオールの増加が認められ、逆に、7.50%では逆効果になることが判る。すなわち、0.30%~3.75%の溶液でエストロジェン分泌増進効果が認められ、1.50%前後の溶液が好ましいことが判る。
Next, it was verified how much 1,8-cineole (Cineole) should be dissolved in propylene glycol (PG).
Therefore, as described above, 1.50% of 1,8-cineole dissolved in propylene glycol (PG) as a solvent as in Example 1 and 0.30% less than that were dissolved, The experiments were carried out on three more subjects in the late luteal phase, with 3.75% and 7.50% more dissolved.
The results of the amount of change are shown in FIG. 2, and it can be seen that the increase in 17β estradiol was significantly increased in the proportion of 1,8-cineole (1.50%), at least 0.30. It can be seen that from 17% to 3.75% an increase in 17β estradiol is observed, whereas 7.50% is counterproductive. That is, it can be seen that a solution of 0.30% to 3.75% shows an effect of enhancing estrogen secretion, and a solution of around 1.50% is preferable.
 次に、1,8-シネオール投与による被験者の「集中力」について検証した。
 この「集中力」の検証には、PC操作による認知課題であるANT(attention network task)テストを用いて、1.8-cineoleを嗅いだ前後の集中力の変化をPG(コントロール)の場合と比較を行った。
 前述のANTは、ヒトの注意機能(実行機能、覚醒機能、注意定位機能)を、短時間で効率よく評価するために開発された検証手段である。ANTは、実験トライアルが開始されると、背景の中央に中心点が1000ms表示される。次に、“*”が手がかり刺激として表示される。手がかり刺激が呈示された500ms後に、5つの矢印の画像が注視点の上方もしくは下方に呈示される。被験者の課題は、5つの矢印のうち、中央の矢印の向きをテンキーのボタンでできるだけ素早く(RT:リアクションタイム)かつ正確に回答することである。
 なお、中央の矢印をターゲット刺激、それ以外の4つの矢印をディストラクター刺激と呼ぶ。実験では、合計4条件の手がかり刺激条件が呈示される。まず、No Cue条件では、手がかり刺激は表示されない。次に、Central Cue条件では、注視点の位置すなわち画面中央に手がかり刺激が呈示される。Congruent Cue条件では、ターゲット刺激が呈示される位置に手がかり刺激が呈示される。すなわち、矢印が注視点の上方に呈示される場合は、手がかり刺激も注視点上方に呈示される。最後に、Incongruent Cue条件では、画面中央を横切る水平線に対して、ターゲット刺激とは対称な位置に手がかり刺激が呈示される。すなわち、ターゲット刺激が注視点の上方に呈示される場合、注視点を挟んでターゲット刺激とは逆の位置に手がかり刺激が呈示される。
Next, the subject's “concentration” by administration of 1,8-cineole was verified.
In order to verify this “concentration”, the change in concentration before and after sniffing 1.8-cineole was compared with the case of PG (control) using an ANT (attention network task) test, which is a cognitive task by PC operation. went.
The above-mentioned ANT is a verification means developed to efficiently evaluate human attention functions (execution function, awakening function, attention localization function) in a short time. When an experimental trial is started, the center point is displayed for 1000 ms in the center of the background. Next, “*” is displayed as a cue stimulus. 500 ms after the cue stimulus is presented, images of five arrows are presented above or below the gazing point. The subject's task is to answer the direction of the center arrow among the five arrows as quickly and accurately as possible using the numeric keypad buttons (RT: reaction time).
The central arrow is called a target stimulus, and the other four arrows are called distractor stimuli. In the experiment, a total of four cue stimulus conditions are presented. First, in the No Cue condition, the cue stimulus is not displayed. Next, under the Central Cue condition, a cue stimulus is presented at the position of the gazing point, that is, at the center of the screen. In the Congruent Cue condition, the cue stimulus is presented at the position where the target stimulus is presented. That is, when the arrow is presented above the gazing point, the cue stimulus is also presented above the gazing point. Lastly, in the Incongruent Cue condition, a cue stimulus is presented at a position symmetrical to the target stimulus with respect to a horizontal line crossing the center of the screen. That is, when the target stimulus is presented above the gazing point, the cue stimulus is presented at a position opposite to the target stimulus across the gazing point.
 前記の実験によって、5人の黄体後期の被験者を対象に、選択的注意能力(Conflicting Score)、を調べ、その結果を図3に示して説明する。
 [選択的注意能力(Conflicting Score)]
 Incongruent Flanker条件のRT-Congruent Flanker条件のRTを調べた。これは、選択的注意能力の指標と考えられ、選択的注意能力が高いほど、Conflicting Scoreは小さくなるものと考えられる。
Based on the above-mentioned experiment, five subjects in the late corpus luteum were examined for selective attention score (Conflicting Score), and the results are shown in FIG.
[Conflicting Score]
RT of Incongruent Flanker condition-RT of Congruent Flanker condition was examined. This is considered as an index of selective attention ability, and it is considered that Conflicting Score decreases as the selective attention ability increases.
 これらの実験結果が図3のグラフであるが、本発明の実施例の1,8-シネオール(cineole)を嗅いだ前後で、コントロール(PG)に比べ、Conflicting Scoreが減少した為、選択的注意能力が高まったものと考えられ、これらの結果から集中力の向上に応用可能である。 The results of these experiments are shown in the graph of FIG. 3, and selective caution was observed because Conflicting Score decreased compared to the control (PG) before and after sniffing 1,8-cineole of the example of the present invention. It is thought that ability increased, and it can apply to improvement of concentration from these results.
 次に、1,8-シネオール投与による被験者の「性欲」について検証した。この検証は、PC操作による認知課題であるUnconscious Dot Probe課題を用いて、1,8-シネオール(1.5%)を嗅いだ前後の性欲を反映すると考えられる指標の変化をPG(コントロール)の場合と比較することを、6人の黄体後期の被験者を対象に行った。
 Unconscious Dot Probe課題は、ヒトの注意バイアスを評価するために開発された検証手段である。本実施例での実験では、課題に用いる視覚刺激に男性のヌード画像を用い、この画像に対する注意がどれだけ高いか(バイアス)が性欲を反映する指標と考え、測定を行った。ただし、刺激画像の呈示時間は17ms(知覚可能な閾値を下回る)で、閾値下(Uncoscious)でのDot Probe課題による測定を行った。
Next, the “sexual desire” of the subject by administration of 1,8-cineole was verified. This verification uses the Unconscious Dot Probe task, which is a cognitive task by PC operation, and the change in the index that seems to reflect the libido before and after smelling 1,8-cineole (1.5%) and the case of PG (control) The comparison was performed on six subjects in the late luteal phase.
The Unconscious Dot Probe task is a verification tool developed to assess human attention bias. In the experiment in this example, a male nude image was used as the visual stimulus used for the task, and how much attention (bias) to the image is considered as an index reflecting sexual desire was measured. However, the stimulus image presentation time was 17 ms (below the perceptible threshold), and the measurement was performed using the Dot Probe task under the threshold (Uncoscious).
 同検証手段の課題では、実験トライアルが開始されると、男性のヌード画像が画面の左右いずれかに呈示される。次に、ヌード画像が呈示された位置(Congruent条件)あるいは呈示されなかった逆の位置(Incongruent条件)のいずれかに、傾いた縞模様が呈示される(呈示された直後、消える)。
 被験者の課題は、この傾いた縞模様がどちら向きに傾いていたかをテンキーのボタンでできるだけ素早く(RT(リアクションタイム)かつ正確に回答することである。例えば、男性のヌード画像に注意が向かっている程、縞模様の傾きを見落とすことになる為、正答率は低下することが期待される。そこで、この正答率を指標として、男性ヌード画像へのバイアスの強さを比較した。
 これらの実験結果が図4のグラフであるが、本発明の実施例の1,8-シネオールを嗅いだ前後で、男性ヌード画像に対するバイアスが、コントロール(PG)に比べ、高まった。
In the problem of the verification means, when an experimental trial is started, a male nude image is presented on either the left or right side of the screen. Next, an inclined striped pattern is presented at either the position where the nude image is presented (Congruent condition) or the opposite position where the nude image is not presented (Incongruent condition) (it disappears immediately after being presented).
The subject's task is to respond as quickly as possible (RT (reaction time)) with the numeric keypad as to which direction the tilted stripe pattern is tilted. The correct answer rate is expected to decrease because the inclination of the striped pattern will be overlooked, so we compared the strength of the bias to male nude images using this correct answer rate as an index.
The results of these experiments are shown in the graph of FIG. 4, and before and after sniffing the 1,8-cineole of the example of the present invention, the bias to the male nude image was increased compared to the control (PG).
 次に、1,8-シネオール投与による感情の増減への影響について、黄体後期の被験者6人を対象にPANAS(The Positive and Negative Affect Schedule)テストを行った。PANASは、「ポジティブ感情」「ネガティブ感情」の2つの尺度から感情の質問項目に答える検査である。
 これらの実験結果が図5のグラフであるが、本発明の実施例の1,8-シネオールを嗅いだ前後で、コントロール(PG)に比べ、ポジティブ感情が増加し、ネガティブ感情が低下した。
Next, regarding the influence of 1,8-cineole administration on the increase or decrease in emotion, a PANAS (The Positive and Negative Affect Schedule) test was performed on six subjects in the late corpus luteum. PANAS is a test that answers emotional question items from two scales of “positive emotion” and “negative emotion”.
The results of these experiments are the graphs of FIG. 5, and before and after sniffing 1,8-cineole of the example of the present invention, positive emotions increased and negative emotions decreased compared to control (PG).
 次に、1,8-シネオール投与による気分の増減への影響について、黄体後期の被験者6人を対象にPOMS(Profile of Mood States)テストにより検証した。POMSとは「活気」「不安」「抑うつ」「怒り」「疲労感」「混乱」の6つの尺度から気分の質問項目に答える検査である。
  これらの実験結果が図6のグラフであるが、1,8-シネオール(1.5%)を嗅いだ前後で、本発明の1,8-シネオールの実施例はコントロール(PG)に比べ、肯定的作用としては、活力がやや高まり、不安、抑うつ、疲労感がやや減少した。これらの結果から、「活気」「不安」「抑うつ」「疲労感」の気分の改善に利用可能である。
Next, the effect of 1,8-cineole administration on the increase or decrease in mood was verified by a POMS (Profile of Mood States) test on six subjects in the late corpus luteum. POMS is a test that answers the question items of mood from six scales of “liveness”, “anxiety”, “depression”, “anger”, “fatigue”, and “confused”.
The results of these experiments are shown in the graph of FIG. 6. Before and after sniffing 1,8-cineole (1.5%), the example of 1,8-cineole of the present invention was more positive than the control (PG). As a result, vitality increased slightly and anxiety, depression, and fatigue decreased slightly. From these results, it can be used to improve the mood of “liveness”, “anxiety”, “depression”, and “feeling of fatigue”.
 次に、1,8-シネオール投与による不安の傾向を黄体後期の被験者6人を対象にSTAI(State and Trait Anxiety Inventry)テストにより検証した。
 STAIとは「状態不安」「特性不安」の2つの尺度から不安の状態及び特性の質問項目に答える検査である。
 これらの実験結果の図14のグラフで説明すると、1,8-シネオールを嗅いだ前後で、コントロール(PG)に比べ、状態不安が減少した。
 これらの各テストの結果から判るように、不安感の軽減利用可能である。
Next, the tendency of anxiety due to the administration of 1,8-cineole was verified by STAI (State and Trait Anxiety Inventry) test for 6 subjects in the late corpus luteum.
STAI is a test that answers questions about anxiety status and characteristics from two scales of “state anxiety” and “characteristic anxiety”.
Explaining these experimental results with the graph of FIG. 14, before and after sniffing 1,8-cineole, state anxiety decreased compared to control (PG).
As can be seen from the results of each of these tests, anxiety can be reduced.
 以上説明したように、本発明の実施例によれば、合成された1,8-シネオール又は天然物から単離、精製された1,8-シネオールを有効成分として含有するエストロジェン分泌増進用組成物、エストロジェン分泌芳香組成物、及び、エストロジェン芳香用具を女性に対して使用することにより、エストロジェン分泌を増進することができる。この為、エストロジェン分泌低下に伴い生じる、月経前緊張症、月経期の諸症状、マタニティーブルー、産後うつ病、更年期障害といった女性特有の不定愁訴(病気を含む)を緩和する効果、エストロジェン分泌増進、特に黄体後期にはエストロジェン分泌がより増進によるアンチエージング効果が期待できる。 As described above, according to the embodiments of the present invention, a composition for enhancing estrogen secretion containing 1,8-cineole synthesized or isolated from natural products and purified as an active ingredient. The estrogen secretion fragrance composition and the estrogen fragrance device can be used on women to enhance estrogen secretion. For this reason, the effects of alleviating women-specific indefinite complaints (including illness) such as premenstrual tension, menstrual symptoms, maternity blue, postpartum depression, and menopause, which are associated with decreased estrogen secretion, increased estrogen secretion, especially The anti-aging effect can be expected due to the enhanced estrogen secretion in the late corpus luteum.
 また、副次的効果として、エストロジェン分泌が増進されることにより、集中力、性欲、陽性/陰性感情、気分、不安の症状の改善ができ、それによって(あるいはそれと同時に)、女性の不定愁訴症状の改善、アンチエージングをもたらす効果が期待できる。
 また、本発明の組成物は、嗅覚神経を介する方法によって投与できるので、短時間で効果を発揮させることができ、また、血液を介さないので肝臓や腎臓等の臓器に副作用を及ぼさないという利点もある。
As a side effect, increased estrogen secretion can improve symptoms of concentration, libido, positive / negative emotions, mood, and anxiety, thereby (or at the same time) women's indefinite complaint symptoms. It can be expected to have the effect of improving the anti-aging.
In addition, since the composition of the present invention can be administered by a method via the olfactory nerve, it can exert its effect in a short time, and since it does not involve blood, it has the advantage of having no side effects on organs such as the liver and kidney. There is also.

Claims (8)

  1.  合成された1,8-シネオール又は天然物から単離、精製された1,8-シネオールを有効成分として含有するエストロジェンの分泌を増進させることを特徴とするエストロジェン分泌増進用組成物。 A composition for enhancing estrogen secretion, which enhances the secretion of estrogen, which contains 1,8-cineole synthesized or isolated from natural products and purified as an active ingredient.
  2.  前記エストロジェンは、17β-エストラジオールであることを特徴とする請求項1に記載のエストロジェン分泌増進用組成物。 The composition for enhancing estrogen secretion according to claim 1, wherein the estrogen is 17β-estradiol.
  3.  前記組成物の投与手段が、香料、精油、化粧品による嗅覚神経を介して脳に伝達されるように投与することを特徴とする請求項1又は2に記載のエストロジェン分泌増進用組成物。 3. The composition for enhancing estrogen secretion according to claim 1, wherein the administration means of the composition is administered so as to be transmitted to the brain via an olfactory nerve by a fragrance, an essential oil, or a cosmetic.
  4.  前記組成物の投与手段が、飲食物による嗅覚神経を介して脳に伝達されるように投与することを特徴とする請求項1又は2に記載のエストロジェン分泌増進用組成物。 3. The composition for enhancing estrogen secretion according to claim 1 or 2, wherein the administration means of the composition is administered so as to be transmitted to the brain via an olfactory nerve by food and drink.
  5.  合成された1,8-シネオール又は天然物から単離、精製された1,8-シネオールを有効成分として含有してエストロジェンの分泌を増進させることを特徴するエストロジェン分泌芳香組成物。 An estrogen-secreting fragrance composition characterized by containing 1,8-cineole synthesized or isolated from natural products and purified as an active ingredient and enhancing estrogen secretion.
  6.  前記エストロジェンは、17β-エストラジオールであることを特徴とする請求項5に記載のエストロジェン分泌芳香組成物。 The estrogen-secreting fragrance composition according to claim 5, wherein the estrogen is 17β-estradiol.
  7.  合成された1,8-シネオール又は天然物から単離、精製された1,8-シネオールを有効成分として含有してエストロジェンの分泌を増進させることを特徴するエストロジェン芳香用具。 An estrogen fragrance device characterized by containing 1,8-cineole synthesized or isolated from natural products and purified as an active ingredient and enhancing estrogen secretion.
  8.  前記エストロジェンは、17β-エストラジオールであることを特徴とする請求項7に記載のエストロジェン分泌芳香用具。 The estrogen-secreting fragrance device according to claim 7, wherein the estrogen is 17β-estradiol.
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