WO2015022831A1 - エストロジェン及びテストステロン分泌増進用組成物、及びその芳香用組成物、並びにその芳香用具 - Google Patents

エストロジェン及びテストステロン分泌増進用組成物、及びその芳香用組成物、並びにその芳香用具 Download PDF

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WO2015022831A1
WO2015022831A1 PCT/JP2014/068676 JP2014068676W WO2015022831A1 WO 2015022831 A1 WO2015022831 A1 WO 2015022831A1 JP 2014068676 W JP2014068676 W JP 2014068676W WO 2015022831 A1 WO2015022831 A1 WO 2015022831A1
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Prior art keywords
estrogen
secretion
testosterone
composition
acetate
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PCT/JP2014/068676
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English (en)
French (fr)
Japanese (ja)
Inventor
一之 篠原
裕和 土居
正太 西谷
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MOTHER & CHILD Co Ltd
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MOTHER & CHILD Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/30—Oestrogens

Definitions

  • the present invention relates to an estrogen and testosterone secretion enhancing composition, an estrogen and testosterone secretion fragrance composition, and an estrogen and testosterone secretion fragrance device containing dodecenyl acetate 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 amblet lid is disclosed.
  • Patent Document 2 discloses the use of an extract of fungal Cordyceps as an improvement 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
  • conventional aromatherapy and the like are oral, intravenous, and transdermal.
  • hypothalamic function only through the action via the olfactory nerve was shown.
  • estrogen secretion is caused by LH secretion
  • LH secretion is caused by hypothalamic activity. Therefore, it is thought that the action that increases hypothalamic activity leads to increased estrogen secretion. . None of them mentions the secretion of dodecenyl acetate (Z-7-dodecen-1-yl-acetate) and the female hormone estrogen and testosterone.
  • Estrogen has been shown to have the following anti-aging effects (or disease risk reduction effects associated with decreased 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 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.
  • olfactory information including pheromones
  • the hypothalamus which is the center of instinct (feeding, sleep) hormones
  • the odorous substance has the potential to develop as a new central nervous system drug that does not go through the oral, intravenous, or transdermal route.
  • dodecenyl acetate is a spider pheromone, but also an elephant pheromone, and it has been reported to be a pheromone that transcends species.
  • An object of the present invention is to provide a composition for enhancing secretion of female estrogen and testosterone and the method for enhancing secretion.
  • the present invention has been completed on the basis of the above findings, and is a composition for enhancing estrogen and testosterone secretion containing dodecenyl acetate as an active ingredient, a fragrance composition thereof, and a fragrance tool thereof.
  • the invention of claim 1 is a composition for enhancing estrogen and testosterone secretion containing dodecenyl acetate synthesized or isolated from purified natural dodecenyl acetate as an active ingredient.
  • the invention of claim 2 is the composition for enhancing estrogen and testosterone secretion according to claim 1 or 2, wherein the synthesized dodecenyl acetate or the purified dodecenyl acetate is isolated from a natural product. , Z-7-dodecen-1-yl-acetate or E-7-dodecen-1-yl-acetate.
  • the invention of claim 3 is the composition for enhancing estrogen and testosterone 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.
  • the invention of claim 4 is a composition for estrogen and testosterone secreting fragrance characterized by containing dodecenyl acetate synthesized or isolated from purified natural dodecenyl acetate as an active ingredient.
  • the invention of claim 5 is an estrogen and testosterone fragrance device which contains a synthetic dodecenyl acetate or a dodecenyl acetate isolated and purified from a natural product as an active ingredient to enhance secretion of estrogen and testosterone It is.
  • 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 the liver and kidney.
  • Z-7-dodecen-1-yl-acetate is used as dodecenyl acetate, and the odor of estrogen and We found an action to enhance the secretion of sex hormones such as testosterone.
  • the present invention has been completed based on the above findings.
  • Z-7-dodecen-1-yl-acetate was used as dodecenyl acetate, but it is a similar substance to Z-7-dodecenyl-1-acetate, and E-7-dodecenyl ( Similar isomers such as dodecen-1-yl) -acetate can be expected to have the same effect, and E (trans isomer) is reported to be an amber pheromone instead of Z.
  • Dodecenyl acetate is an unpleasant symptom caused by a decrease in estrogen secretion seen in women (especially an unpleasant symptom caused by a decrease in estrogen secretion seen in women in the late corpus luteum), and in postpartum women It can be estimated that it is effective for discomfort. In addition, discomfort caused by decreased estrogen secretion is seen not only in late-luteal women, but also in postpartum and menopausal women. It can be estimated that it is effective. Moreover, it can be estimated that the above-mentioned anti-aging effect is obtained.
  • composition for enhancing estrogen and testosterone secretion of the present invention contains dodecenyl acetate as an active ingredient.
  • the dodecenyl acetate to be used may be extracted from a natural product or the like, or may be artificially synthesized. Moreover, since dodecenyl acetate is marketed as a reagent, you may use it.
  • the enhancement composition of the present invention is prepared with various compositions depending on the use mode, but is usually prepared with the same composition as the fragrance composition described below.
  • the fragrance composition of the present invention is prepared in various compositions depending on the use mode, but usually the dodecenyl acetate concentration is 0.03 to 0.75%, preferably 0.15%.
  • 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.
  • the estrogen secreting fragrance device of the present invention has a portion containing synthesized dodecenyl acetate or dodecenyl acetate isolated and purified from natural products. .
  • a synthesized or isolated or purified product from a natural product is used in the same manner as the fragrance composition.
  • 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, A 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 dodecenyl acetate is used instead of plant essential oil.
  • the method of using the composition for enhancing estrogen and testosterone secretion of the present invention comprises administering dodecenyl acetate to a person who shows a decrease in estrogen and testosterone. It is a feature.
  • the administration method of dodecenyl acetate is not particularly limited, and it may be administered orally, intravenously, or transdermally in the same manner as ordinary pharmaceuticals, etc. It is administered by a means that is transmitted to the brain via the olfactory nerve.
  • administration means there can be exemplified a means for smelling air containing dodecenyl acetate to a person showing a decrease in estrogen and testosterone secretion.
  • the amount of dodecenyl acetate in the air at this time is not particularly limited, but the amount of dodecenyl acetate in the air at this time cannot be measured strictly, but the dodecenyl acetate used in the solution that emits fragrance is used.
  • the content of senyl acetate is preferably 0.03 to 0.75%, and preferably about 0.15%.
  • Example 1 We examined hormonal changes that occurred when sniffing dodecenyl acetate 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 is a salivary component quantification kit (measurement kit) manufactured by SALIMETRICS, model number is 1-3702 Estradiol, EIA Kit, High Sensitivity, Salivary and model number is 1-2402 Testosterone, In EIA Kit, Salivary, the measurement method is (A) Reaction of "A saliva sample containing unknown concentration of 17 ⁇ estradiol or testosterone” and the antibody that binds to it (coated in the hole of a 96-well plate) At that time, (B) “known concentration of 17 ⁇ estradiol or testosterone in which an enzyme is bound in advance” is also reacted at the same time, and (A) and (B) compete for the reaction (antibody in (A) and (B). ).
  • 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.
  • 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.
  • “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 0.15% of dodecenyl acetate dissolved in dipropylene glycol and Comparative Example 1: only propylene glycol (PG) as a control. The subjects were five follicular stages and five late luteal phases, and the test was conducted as Comparative Example 1 and Example 1 for a total of 10 subjects.
  • PG propylene glycol
  • Example 2 As a result of comparison between Example 1 and Comparative Example 1 before and after the experiment, the concentration of 17 ⁇ estradiol (E2) in Example 1 was significantly increased from 2.9 pg / ml to 3.8 pg / ml (correspondence) In Comparative Example 1, the concentration (E2) was not different from 3.4 pg / ml to 3.35 pg / ml. When this is converted into a change amount, the change amount (PG vsZ-7-dodecen-1-yl-acetate: Z-7-dodecen-1-yl-acetate) is converted to propylene glycol (PG). In comparison, E2 concentration increased significantly (paired t-test, P ⁇ 0.005).
  • Example 1 Comparative Example 1 and Example 1 with five subjects at the follicular stage.
  • concentration of 17 ⁇ estradiol (E2) in Example 1 significantly increased from 3.2 pg / ml to 3.8 pg / ml (corresponding to A certain t-test, P ⁇ 0.05), and Comparative Example 1 had a difference in concentration from 3.5 pg / ml to 3.4 pg / ml.
  • the amount of change (PG vs Z-7-dodecen-1-yl-acetate): dodecenyl acetate (Z-7-dodecen-1-yl-acetate) is propylene glycol (PG ) Significantly increased (paired t-test, P ⁇ 0.05).
  • Example 1 Comparative Example 1 was 3.4 pg / ml to 3.4 pg / ml with no difference in concentration.
  • Change-Comparison of propylene glycol (PG) change shows that the concentrations increased significantly in the late luteal phase and the follicular phase (unpaired t-test, P ⁇ 0.05).
  • the experimental results shown in FIG. 1 clearly show that administration of the odor of dodecenyl acetate (Z-7-dodecen-1-yl-acetate) enhances secretion of female hormones, particularly 17 ⁇ estradiol. , It is always effective for women.
  • composition for enhancing estrogen secretion that enhances the secretion of estrogen and testosterone containing dodecenyl acetate (Z-7-dodecen-1-yl-acetate) as an active ingredient is one of male hormones.
  • Some testosterone and increased secretion of testosterone were also observed and proved to be always effective for women, but were more prominent in the follicular phase than in the late luteal phase.
  • testosterone which is one of the male hormones, is secreted not only by men but also by women.
  • the increase in secretion is mainly due to the effect of increasing libido, the ability to improve the ability to trade with others, and the fighting spirit. It has been reported to have enhancement effects, and these effects will now be described.
  • male testosterone has been reported to increase libido. When women are given testosterone or drugs for its receptors, libido increases. Women also increase testosterone secretion by continuing to see attractive men. Regarding the effect of improving the ability to trade with others, it has been reported that female testosterone increases the ability to trade with others.
  • testosterone is given to a woman, the fair (fair) negotiating behavior (bargaining), the reward system activity (ventral striatum activity) at the time of monetary driving task, the last common game (the "reward” given to someone) Risk behavior in the game of how to distribute). In addition, there are more risky behaviors in the Iowa gambling task (assessment of prefrontal function).
  • testosterone increases the fighting spirit.
  • Administration of testosterone reduces cognitive ability for threatening facial expressions (discomfort, fear, anger).
  • those with high testosterone secretion have better performance in individual competition, higher spatial recognition ability, more prone to re-challenge even after defeat, and higher aggression. It has been reported.
  • Testosterone has also been shown to be associated with stress tolerance.
  • Example 1 The subjects were also the same as in Example 1, and the subjects were 10 subjects in total: 5 in the follicular phase and 5 in the late luteal phase (Late Luteal Phase).
  • the subjects in this group sniff the solvent (propylene glycol) containing 0.15% dodecenyl acetate or only the solvent, and saliva is collected before and 20 minutes after the start of the experiment, and the secreted testosterone is estrogen.
  • the enzyme immunoassay was used.
  • the results of the comparison between Example 1 and Comparative Example 1 before and after the experiment show that the concentration of testosterone secreted in Example 1 increases from 15 pg / ml to 16 pg / ml.
  • the concentration decreased from 20 pg / ml to 19 pg / ml.
  • PG dodecenyl acetate
  • E2 increased (paired t-test, P ⁇ 0.06).
  • Example 1 the concentration of testosterone secreted in Example 1 increased from 14 pg / ml to 16 pg / ml (corresponding t-test, P ⁇ 0.05), and in Comparative Example 1, the concentration decreased from 18 pg / ml to 16 pg / ml.
  • PG sniffing-before sniffing
  • the results of comparison between Example 1 and the comparative example before and after the experiment show that the concentration of testosterone secreted in Example 1 increases from 15 pg / ml to 16 pg / ml, and Comparative Example 1 has 21 pg / ml. There was no difference in concentration from 21 pg / ml.
  • PG sniffing-before sniffing
  • PG dodecenyl acetate (Z-7-dodecen-1-yl-acetate)
  • 17 ⁇ estradiol compared to control propylene glycol (PG)
  • the concentration of (E2) increased.
  • ANT attention network task
  • PG control
  • a comparison was made.
  • 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.
  • the center point is displayed for 1000 ms in the center of the background.
  • “*” is displayed as a cue stimulus.
  • an image of five arrows is presented above or below the point of interest.
  • the subject's task is to answer the direction of the center arrow among the five arrows as quickly as possible (RT: reaction time) with the numeric keypad.
  • 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 Congruent Cue condition the cue stimulus is presented at the position where the target stimulus is presented.
  • 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.
  • [Awakening Level Control Ability] is the Awakening Level Control Ability (Alerting Score) before and after sniffing the dodecenyl acetate of this example compared to the control (PG). ) Decreased, wakefulness level control ability increased significantly (P ⁇ 0.05).
  • [selective attention ability] is the selective attention ability because the selective attention ability (Conflicting Score) decreased before and after sniffing odecenyl acetate compared to control (PG). Significantly increased (P ⁇ 0.01).
  • [Reminding Ability] is significantly higher because the attention release ability (Disengagement Score) decreased before and after sniffing dodecenyl acetate compared to the control (PG). (P ⁇ 0.05).
  • [attention localization ability] increased the attention localization ability (Orienting Score) before and after sniffing dodecenyl acetate, compared to control (PG), so the attention localization ability increased ( P ⁇ 0.06).
  • PNAS Positive and negative effect schedule
  • Z-7-dodecen-1-yl-acetate was used as dodecenyl acetate in the examples of the present invention, but E-7-dodecen-1-yl-acetate was used. Similar substances such as (acetate) and E (trans isomer) dodecenyl acetate have been reported to be spider pheromones, and similar effects can be expected.
  • Estrogen and testosterone secretion enhancement containing dodecenyl acetate synthesized or isolated from purified natural product as an active ingredient
  • Estrogen and testosterone secretion can be enhanced by using the compositions, estrogen and testosterone secretion fragrance compositions, and estrogen and testosterone fragrance devices.
  • the effects of alleviating female-specific indefinite complaints (including illness) such as premenstrual tension, maternity blue, postpartum depression, and climacteric disorder that occur due to decreased secretion of the sex hormones estrogen and testosterone, An aging effect 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 the liver and kidney.

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PCT/JP2014/068676 2013-08-10 2014-07-14 エストロジェン及びテストステロン分泌増進用組成物、及びその芳香用組成物、並びにその芳香用具 Ceased WO2015022831A1 (ja)

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JP2020007261A (ja) * 2018-07-06 2020-01-16 株式会社マザー＆チャイルド 女性用のテストステロン分泌を増進させるテストステロン分泌増進用組成物、芳香治療用組成物、芳香治療用入浴剤、芳香治療用食品、及び、芳香治療用具

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JP2012513746A (ja) * 2008-12-30 2012-06-21 ビーエーエスエフ ソシエタス・ヨーロピア フェロモンディスペンサー

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JP2012513746A (ja) * 2008-12-30 2012-06-21 ビーエーエスエフ ソシエタス・ヨーロピア フェロモンディスペンサー

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