JP2021161038A - Premenstrual hyperphagia inhibitor - Google Patents

Abstract

To provide means for positively controlling hyperphagia associated with a menstrual period.SOLUTION: A premenstrual hyperphagia inhibitor containing Koshaheiisan extract can inhibit premenstrual hyperphagia and can positively control hyperphagia associated with a menstrual period.SELECTED DRAWING: None

Description

The present invention relates to a premenstrual anti-appetite inhibitor.

In recent years, women's aesthetic awareness of the body has been increasing. Appetite is closely related to physical aesthetics, and appetite control has become an important issue for women. However, among women with a menstrual cycle, there are a certain percentage of women whose appetite fluctuates greatly with fluctuations in hormonal balance, making it difficult to control it. A typical example of the period of increased appetite is the luteal phase (Non-Patent Document 1), which is particularly prominent in the latter half of the luteal phase, and some people complain of increased appetite during menstruation (Non-Patent Document 2).

Regarding the control of appetite increase associated with the menstrual cycle, it is advised to take measures such as dividing the diet and increasing the number of meals, actively ingesting low GI foods, taking a relaxing method, or accepting the appetite and not putting up with it. The current situation is that it remains at.

On the other hand, Kasago heiisan is a Chinese herbal medicine that can be used when it seems that the appetite of a person with a weak gastrointestinal tract is abnormally increased (Non-Patent Document 3). Kosago heiisan was found in 146 cases of increased appetite in men and women of all ages with false evidence of pulse and abdomen, including children (15 boys and 13 girls), young adults (14 men and 18 women), and It is effective against 102 cases of old age (20 males and 22 females), and it has been shown that the effect appears in 10 days, so it has the effect of adjusting various gastrointestinal functions, and as a result, It is believed that the abnormal appetite returns to normal (Non-Patent Document 3).

Kyoto Prefectural University of Medicine, 125 (2), p. 127-134, 2016 Yamagata Health and Medical Research, No. 89, p. 53-63, 2005 Abstracts of the 24th Annual Meeting of the Japan Society for Oriental Medicine, p. 33-35,

Increased appetite associated with the menstrual cycle is an urgent complaint of women, and unwanted increased appetite causes stress and puts a mentally unnecessary burden. Therefore, a method of actively controlling the increase in appetite associated with the menstrual cycle as a target is desired.

Therefore, an object of the present invention is to provide a means for positively controlling the increase in appetite associated with the menstrual cycle.

So far, there have been cases where Kasago heiisan was prescribed for increased appetite, but the known indication for Kasago heiisan was peculiar to increased appetite accompanied by gastrointestinal weakness. On the other hand, the increase in appetite associated with the menstrual cycle is fundamentally different from the application of Kosago heiisan in that it is a condition peculiar to fluctuations in female hormones. However, when the present inventor dared to take Kosago heiisan to a woman whose appetite increased from premenstrual to during menstruation, unexpectedly, a remarkable inhibitory effect was exerted on premenstrual appetite. Found to be done. In addition, the significant inhibitory effect on premenstrual appetite is during the late luteal phase (ie, the known 10-day onset period of Kasago heiisan) even when the drug is started in the late luteal phase. I also found an unexpected immediate effect that it would appear (without waiting for). The present invention has been completed by further studies based on such findings.

That is, the present invention provides the inventions of the following aspects.
Item 1. Premenstrual anti-appetite inhibitor containing Kasago heiisan extract.
Item 2. Item 2. The pre-menstrual appetite-promoting inhibitor according to Item 1, wherein the Kasago heiisan extract is an extract of a mixed crude drug containing jutsu, koboku, chinpi, licorice, sukusha, kobushi, ginger, taiso, and cocorice.
Item 3. Item 2. The premenstrual anti-appetite inhibitor according to Item 1 or 2, wherein the premenstrual period is the late luteal phase.
Item 4. Item 2. The premenstrual appetite suppressant according to any one of Items 1 to 3, which is used for appetite enhancement without gastrointestinal weakness.
Item 5. Item 2. The premenstrual appetite suppressant according to any one of Items 1 to 4, which is ingested at the timing when the premenstrual appetite increase is felt.

According to the present invention, a premenstrual appetite-promoting inhibitor containing Kasago heiisan extract can suppress premenstrual appetite-promoting and positively control the appetite-promoting associated with the menstrual cycle.

The administration schedule of Kasago heiisan extract in Test Example 1 is shown. It shows the degree of appetite at each stage of the menstrual cycle by not taking and taking Kosago heiisan extract. The score of appetite spiciness at each stage of the menstrual cycle by not taking and taking Kosago heiisan extract is shown.

Kasago heiisan extract The premenstrual appetite-promoting inhibitor of the present invention is characterized by containing Kasago heiisan extract. The composition of the crude drug constituting Kosago heiisan is not particularly limited, but specific examples thereof include (1) jutsu (meaning sojutsu and / or byakujutsu, the same applies hereinafter), koboku, chimpi, kanzo, shukusha, kobushi, and so on. Atractylodes lanceolata, Atractylodes lanceolata, and Atractylodes lanceolata; (2) Atractylodes lanceolata and / or Atractylodes lanceolata; (Or kikoku is also possible), chimpi, kanzo, shukusha, kobushi, shokyo, mokko, and kakko. Among the composition of the crude drugs constituting these Kasago heiisan, from the viewpoint of further enhancing the effect of suppressing the increase in appetite before menstruation, (1) jutsu (soujutsu and / or byakujutsu), koboku, chimpi, licorice, and shukusha are preferable. , Atractylodes lanceolata, Atractylodes lanceolata, Atractylodes lanceolata, and Atractylodes lanceolata, more preferably Atractylodes lanceolata, Atractylodes lanceolata, Atractylodes lanceolata, Atractylodes lanceolata, Atractylodes lanceolata, and Atractylodes lanceolata.

As a more specific example of the constituent crude drugs of Kosago heiisan, the weight mixture ratio of jutsu, koboku, chimpi, licorice, sukusha, kobushi, ginger, taiso, and cocorice (soujutsu: koboku: chimpi: licorice: sukusha: kobushi) : Ginger: licorice: parenthesis), for example, (4 to 6) :( 3 to 4.5) :( 3 to 4.5) :( 1 to 1.5) :( 1.5 to 2) : (2-4) :( 0.5-1) :( 2-3) :( 0-1). From the viewpoint of further enhancing the effect of suppressing the increase in appetite before menstruation, the weight mixing ratio of the above-mentioned jutsu, koboku, chimpi, licorice, sukusha, kobushi, shokyo, taiso, and cuckoo is preferably (4 to 5) :( 3-4) :( 3-4) :( 1-1.3.) :( 1.5-1.8) :( 3-4) :( 0.5-0.8) :( 2-2. 5): (0.5 to 1), and particularly preferably (4) :( 3) :( 3) :( 1) :( 1.5) :( 4) :( 0.66) :. (2): (1) can be mentioned.

Kasago heiisan extract can be obtained by subjecting the above-mentioned crude drug mixture to an extraction step using an extraction solvent. Examples of the extraction solvent used in the extraction treatment in the extraction step include water; lower alcohols such as ethanol and isopropanol; polyhydric alcohols such as 1,3-butylene glycol and propylene glycol; and polar solvents such as a mixture thereof. From the viewpoint of further enhancing the effect of suppressing the increase in appetite, water, ethanol, 1,3-butylene glycol, propylene glycol or a mixed solvent thereof can be mentioned, and water is more preferable. Examples of the extraction method include a method in which about 5 to 20 times the amount of the extraction solvent is added to the crude drug mixture and the mixture is stirred at about 80 to 100 ° C. for about 0.5 to 3 hours to carry out the extraction step. Kasagohiragasan extract is an extract obtained by subjecting an extract obtained by subjecting it to a solid-liquid separation step such as centrifugation or filtration after the extraction step to remove solids, and further subjecting it to a concentration step. It may be an extract powder obtained by subjecting it to a drying step. Further, the drying treatment in the drying step is not particularly limited, and a known method can be used, and specific examples thereof include a spray drying method, a vacuum concentration drying method, and a freeze drying method. When the Kasago heiisan extract is subjected to a drying treatment, an excipient may be added to the Kasago heiisan extract solution to dry it.

The content of Kasago heiisan extract in the premenstrual appetite-promoting inhibitor of the present invention can be appropriately adjusted according to the premenstrual appetite-promoting inhibitory effect to be exerted. -80% by weight, preferably 60-75% by weight.

Other Ingredients In the pre-menstrual appetite-promoting inhibitor of the present invention, in addition to the above-mentioned Kasago heiisan extract, which is the active ingredient, additives and bases depending on the formulation form may be further contained. Additives and bases are not particularly limited as long as they are pharmaceutically acceptable, but excipients, binders, disintegrants, lubricants, tonicity agents, plasticizers, dispersants, emulsifiers, etc. Dissolving aids, wetting agents, stabilizers, suspending agents, pressure-sensitive adhesives, coating agents, brighteners, water, fats and oils, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble High polymers, surfactants, metal soaps, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV inhibitors, preservatives, flavoring agents, fragrances, powders, thickeners, pigments , Chelating agent and the like. These additives and bases may be used alone or in combination of two or more. The contents of these additives and bases are appropriately set according to the types of additives and bases to be used, the form of the premenstrual appetite-promoting inhibitor of the present invention, and the like.

Specific examples of additives and bases include starch, lactose (eg lactose hydrate), crystalline cellulose, synthetic hydrotalcite, anhydrous calcium hydrogen phosphate, light anhydrous silicic acid, hydrous silicon dioxide, as excipients. Synthetic aluminum silicate, magnesium aluminometasilicate, calcium silicate, magnesium silicate, etc., preferably lactose (eg lactose hydrate), crystalline cellulose, light anhydrous silicic acid, hydrous silicon dioxide, synthetic aluminum silicate, more preferred Examples include lactose (preferably lactose hydrate), light anhydrous silicic acid, synthetic aluminum silicate; examples of disintegrants include carmellose, carmellose calcium, croscarmellose sodium, sodium starch glycolate, crospopidone and the like. Carmellose calcium is mentioned; examples of the lubricant include magnesium stearate, calcium stearate and the like, preferably magnesium stearate. These additives and bases may be used alone or in combination of two or more.

The contents of the above additives and bases are appropriately set according to the types of additives and bases to be used. Preferably, in the pre-menstrual appetite inhibitor, the content of the excipient is 10 to 30% by weight, preferably 15 to 25% by weight; the content of the disintegrant is 1 to 10% by weight. The content of the lubricant is 0.1 to 1% by weight, preferably 0.3 to 0.6% by weight. More preferably, the content of lactose (equivalent to lactose hydrate) is 0.4 to 0.7% by weight and the content of carmellose calcium is 3 to 8% by weight in the pre-menstrual appetite-promoting inhibitor. %, The content of light anhydrous silicic acid is 20 to 30% by weight, the content of synthetic aluminum silicate is 1 to 5% by weight, and the content of magnesium stearate is 0.3 to 0.8% by weight. Can be mentioned.

In addition, the premenstrual appetite-promoting inhibitor of the present invention may contain nutritional components and pharmacological components other than the above-mentioned crude drug components, if necessary. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmaceutically acceptable, but for example, antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, and antitussives. Agents, antitussives, expectorants, anti-inflammatory enzymes, sedative hypnotics, antihistamines, caffeines, cardiotonic diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, other herbal powders and / or other herbal medicines Examples include extracts and vitamins. These nutritional components and pharmacological components may be used alone or in combination of two or more. Further, the content of these components is appropriately set according to the type of the component to be used and the like.

Formulation form The formulation form of the premenorrhea antihypertensive agent of the present invention is not particularly limited as long as it can be orally administered, and is, for example, a powder, a fine granule, a granule, a tablet, a troche, or a chewable. Examples thereof include solid preparations such as agents, capsules (soft capsules, hard capsules) and pills; semi-solid preparations such as jelly; liquid preparations such as liquids, suspensions and syrups. Among these product forms, a solid product is preferable, and tablets are more preferable, from the viewpoint of stability and portability of the contained components.

Production method The method for producing the premenstrual appetite-promoting inhibitor of the present invention is an ordinary preparation adopted in the pharmaceutical field using the above-mentioned Kasago heiisan extract and other ingredients to be blended as needed. It may be formulated according to the chemical conversion method.

Uses The premenstrual appetite suppressant of the present invention is used for the purpose of suppressing the premenstrual appetite. Premenstrual is preferably the late luteal phase. The late luteal phase refers to the period corresponding to the latter half of the luteal phase. Further, the premenstrual increase in appetite to be suppressed specifically refers to a state in which the appetite is increased more than the appetite in the luteal phase, and a preferable embodiment is each stage (menstrual phase / ovulation) constituting the menstrual cycle. The state in which the appetite is most enhanced in the period (stage / ovulation period to the early luteal phase / late luteal phase) is mentioned, and more preferably, the state accompanied by the undesired state of increased appetite is painful, and / Alternatively, a condition without gastrointestinal weakness can be mentioned.

Dosage and Usage The appetite-promoting inhibitor of the present invention is used by oral administration. The dose of the appetite-promoting inhibitor of the present invention is appropriately set according to the age, constitution, degree of symptoms, etc. of the administration subject. The crude drug equivalent amount of all crude drug components is 5 to 30 g, preferably 10 to 20 g, or the amount of Kasago heiisan extract (dry extract equivalent amount) is 1000 to 3000 mg, preferably 1400 to 2500 mg, more preferably. The dose may be 1600 to 2300 mg, and may be taken 1 to 4 times a day, preferably 2 to 3 times a day.

The timing of administration during the day is not particularly limited and may be before meals, after meals, or between meals, but pre-meal or inter-meal is preferable. The timing of administration during the menstrual cycle is not particularly limited, but since the appetite-promoting inhibitor of the present invention has an excellent immediate effect, it may be taken at the timing when the appetite enhancement before menstruation to be suppressed is felt. For example, even if the appetite-promoting inhibitor of the present invention is taken from the beginning of the late luteal phase, the appetite-promoting inhibitory effect can be obtained during the late luteal phase. From the viewpoint of further enhancing the appetite-promoting inhibitory effect, it should be taken continuously for, for example, 2 days or more, preferably 3 days or more, more preferably 4 days or more, and further preferably 5 days or more per menstrual cycle. Is preferable. In addition, the number of consecutive days of administration per menstrual cycle is not particularly limited, and the administration may be stopped at the same time as the start of menstruation. The specific number of days of continuous administration varies depending on the length of the menstrual cycle, and examples thereof include 9 days or less, 8 days or less, or 7 days or less.

Hereinafter, the present invention will be specifically described with reference to Examples, but the present invention is not limited to these Examples.

[Test Example 1]
(1) Preparation of pre-menstrual appetite-promoting inhibitor To the crude drug composition having the composition shown in Table 1, 12 times the weight ratio of water was added as an extraction solvent, the temperature was raised to about 100 ° C., and the mixture was stirred for 30 minutes. While extracting. Then, the extract was collected by centrifugation, concentrated under reduced pressure, and then dried by a spray-drying method to obtain Kasago heiisan extract powder. Using the obtained Kasago heiisan extract powder, a tablet composition having the composition shown in Table 2 was prepared and tableted, thereby obtaining a tablet of an appetite-promoting inhibitor before menstruation. The daily dose of the appetite-promoting inhibitor before menstruation was 10.08 g in the amount of the crude drug composition having the composition shown in Table 1 and 2100 mg in the amount of Kasago heiisan extract (dry extract equivalent amount).

(2) Subjects and Dosing Schedule Two women with a regular menstrual cycle (28 days) who were aware of the increase in appetite associated with the menstrual cycle were the subjects. These subjects were not predisposed to gastrointestinal weakness and did not have gastrointestinal weakness during the increased appetite associated with the menstrual cycle. The subjects were allowed to take premenstrual anti-appetite tablets according to the schedule shown in FIG. In the figure, "moon" is the menstrual phase, "egg" is the follicular phase, "pre-luteal phase" is the early luteal phase including the ovulation phase (hereinafter referred to as "early luteal phase"), and "post-luteal phase" is the late luteal phase. , "1W" indicates one week. In other words, no medication is given during the first cycle from the start of the test, and medication is given intermittently at each stage of the menstrual cycle (menstrual phase, ovulation phase, early luteal phase, late luteal phase) from the second cycle to the third cycle. rice field. Dosing was continued daily for the entire week (ie, 7 days) that made up each stage. In addition, on the night of the final day of each stage (at the time indicated by ◯ in the figure), the degree of appetite and the spiciness of appetite at that stage were evaluated.

<Degree of appetite>
Regarding the degree of appetite, the degree of appetite in the follicular phase when the appetite is most calm is set to "0", the degree of appetite when there is a very strong appetite is "5", and the degree of appetite when there is no appetite is "-5". A total of 11 grades from "-5" to "5" was scored, and the appetite scores at each stage were averaged for each of the non-medicated and the dosed doses. The results are shown in FIG.

<Spicy appetite>
The degree of spiciness of increased appetite is scored on a 6-point scale from "0" to "5", with "0" when it is not spicy at all and "5" when it is very spicy. For each, the scores at each stage were averaged and obtained as a spiciness score. The results are shown in FIG.

(3) Results As shown in the graph of "not taken" in Fig. 2, increased appetite was observed during the ovulation period to the early luteal phase, the late luteal phase, and the menstrual phase, and was particularly remarkable in the late luteal phase. rice field. In addition, as shown in the graph of "not taken" in FIG. 3, the increase in appetite, especially in the late luteal phase, was accompanied by spiciness. On the other hand, as shown in the graph of "taking" in FIG. 2, the appetite-promoting inhibitory effect of taking Kasago heiisan extract was particularly remarkable in the late luteal phase, and as shown in the graph of "taking" in FIG. In addition, the spiciness was remarkably alleviated.

[Test Example 2]
The premenstrual hyperappetite-suppressing tablet prepared in Test Example 1 was taken by 7 women who complained of premenstrual appetite at the timing when they felt the appetite in the late luteal phase, and the appetite in the late luteal phase was taken. We received answers regarding the degree of satisfaction with the effect on enhancement. In addition, five men who complained of increased appetite were given the drug at the timing when they felt increased appetite, and responses were obtained regarding the degree of satisfaction with the effect on increased appetite. None of the 7 females and 5 males had a constitution of gastrointestinal weakness, and neither was accompanied by gastrointestinal weakness at the time of increased appetite. The results are shown in the table below.

As shown in Table 4, more than 70% of women answered that they were "satisfied" or "somewhat satisfied" with regard to the effect of suppressing appetite, whereas for men, the effect of suppressing appetite was increased. No one answered "satisfied" or "somewhat satisfied". That is, it was shown that the premenstrual suppression of appetite of the present invention is effective for the increase in appetite peculiar to women.

[Prescription example]
Premenstrual anti-appetite tablets having the composition shown in Table 5 (the numerical value (mg) indicating the blending amount in the table is converted to the daily dose) were prepared. Any premenstrual suppression of appetite was able to suppress premenstrual growth.

Claims (5)

Premenstrual anti-appetite inhibitor containing Kasago heiisan extract. The pre-menstrual appetite-promoting inhibitor according to claim 1, wherein the Kasago heiisan extract is an extract of a mixed crude drug containing jutsu, koboku, chinpi, licorice, sukusha, kobushi, ginger, taiso, and kakko. The premenstrual anti-appetite inhibitor according to claim 1 or 2, wherein the premenstrual period is the late luteal phase. The premenstrual appetite suppressant according to any one of claims 1 to 3, which is used for an appetite increase without gastrointestinal weakness. The premenstrual appetite suppressant according to any one of claims 1 to 4, which is ingested at the timing when the premenstrual appetite increase is felt.

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