JP2022098251A - Premenstrual constipation improver - Google Patents

Abstract

To provide a pharmaceutical effective as a premenstrual constipation improver.SOLUTION: Tokaku-joki-to extract and/or Tsu-do-san extract have a superior effect of improving constipation, which is a premenstrual characteristic symptom, so that they are used as an active ingredient of a premenstrual constipation improver.SELECTED DRAWING: None

Description

The present invention relates to a premenstrual constipation improving agent.

Constipation is a condition in which excrement stays in the intestine for a long time and water is absorbed, making it difficult to defecate, or defecation is rare (about once every few days). Normally, it is said that defecation once or twice a day is normal, but even if defecation is performed once every two to three days, the bowel movement is normal, and if the person does not feel pain, constipation is Not say. On the other hand, even if there is defecation every day, if the stool is hard and the amount is small and there is a feeling of residual stool, or if the stool feels painful, it is considered to be constipation (Non-Patent Documents 1 to 3).

Among constipation, laxative constipation is the most common chronic constipation in women. Laxative constipation is a symptom in which the peristaltic movement of the large intestine is impaired, and the feces stay in the large intestine for a long time, resulting in excessive absorption of water, resulting in stiff stools and difficulty in defecation. Many women with menstruation complain of constipation before menstruation. Pre-menstrual constipation is said to be related to the action of progesterone, and this action makes it difficult for the peristaltic movement of the large intestine to occur, and it causes difficulty in defecation due to the accumulation of water in the body and the decrease in the amount of water in the stool. Occurs.

Western medicines used for the treatment of constipation include stimulant laxatives and salt laxatives, but because of their strong effects, they may cause abdominal pain or diarrhea. For this reason, Chinese medicine may be applied to people who are not fit for Western medicine.

There are several known Chinese herbal medicines used for constipation, but for example, Bofutsushosan and Chofutsushosan have sennoside-based rhubarb as a main component for promoting intestinal peristalsis and Glauber's salt as a salt laxative. It is understood that a laxative effect is exerted by the action (Non-Patent Document 4).

Makoto Yamashita: Constipation Japanese Clinical Supplement (Gastrointestinal Syndrome, Volume 2), 653-655, (1994) Kiyonori Furukawa: Clinical nutrition for addictive constipation (extra edition, today's therapeutic diet guideline-1), 89 (4): 391-393, (1996) Daisuke Sasaki: Chronic constipation medicineina, 32 (12): 222-223, (1995) Noriaki Mabe, Ken Haruma: VIII. Treatment of Chronic Constipation-Types of Chinese Medicine and How to Use them, Journal of the Japanese Society of Internal Medicine, 108: 55-62 (2019)

As mentioned above, both chronic constipation and premenstrual constipation have a common mechanism in that they are caused by impaired peristaltic movements of the large intestine and reduced stool water content. Therefore, the present inventors are one of the Chinese medicines, Bofutsushosan, which is said to exert a coagulation effect on women who complain of premenstrual constipation by promoting intestinal peristalsis and acting as a salt laxative. The effect of was examined. However, it was found that Bofutsushosan had poor results in improving premenstrual constipation and had a problem in its effectiveness as a premenstrual constipation improving agent.

Therefore, an object of the present invention is to provide a drug effective as a premenstrual constipation improving agent.

The present inventor has found that Tokakujokito and Tsudosan have a particularly effective ameliorating effect on premenstrual constipation. 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 constipation improver, including Tokakujokito extract and / or Tsudosan extract.
Item 2. Item 2. The premenstrual constipation improving agent according to Item 1, which is used for a subject having a regular menstrual cycle.

According to the present invention, a drug effective as a premenstrual constipation improving agent is provided.

1. 1. Premenstrual Constipation Improving Agent The premenstrual constipation improving agent of the present invention is characterized by containing Tokakujokito extract and / or Tsudosan extract. Hereinafter, the menstrual constipation improving agent of the present invention will be described in detail.

Tokakujokito extract and / or Tsudosan extract The premenstrual constipation improving agent of the present invention contains Tokakujokito extract and / or Tsudosan extract as active ingredients.

Tokakujokito is a prescription based on "Kankanron", and its constituent crude drugs include mixed crude drugs consisting of tounin, cinnamon, rhubarb, licorice, and liquorice.

The amount of each crude drug constituting Tokakujokito is 2.0 to 7.0 parts by weight of Tounin, 1.0 to 5.0 parts by weight of Keihi, 1.0 to 5.0 parts by weight of Daiou, and 0 parts of Kanzo. .5 to 2.5 parts by weight and 0.3 to 2.0 parts by weight of bow show (anhydrous bow show equivalent amount) can be mentioned.

Tsudosan is a prescription based on "Man's disease rejuvenation", and its constituent crude drugs include mixed crude drugs consisting of Angelica acutiloba, rhubarb, bow show, angelica acutiloba, koboku, chimpi, mokutsu, kouka, soboku, and licorice. ..

The amount of each crude drug constituting Tsudosan is 0.5 to 3.0 parts by weight of Touki, 0.5 to 3.0 parts by weight of Daiou, and 0.5 to 2.5 parts by weight of Bowsho (amount converted to anhydrous Bowsho). ), Kijitsu 1.5-3.0 parts by weight, Koboku 0.3-2.5 parts by weight, Chinpi 0.3-2.5 parts by weight, Mokutsu 0.3-2.5 parts by weight, Kouka 0.3 Examples thereof include up to 2.5 parts by weight, 0.3 to 2.5 parts by weight of herbal medicine, and 0.3 to 2.5 parts by weight of herbal medicine.

The extraction solvent used in the extraction treatment of Tokakujokito extract and Tsudosan extract is not particularly limited, but examples thereof include water and hydrous ethanol. Further, the drying treatment is not particularly limited, and a known method such as a spray drying method or an appropriate adsorbent (for example, anhydrous silicic acid, starch, etc.) is added to the soft extract having an increased concentration of the extract solution. And the method of making it an adsorption powder.

As the Tokakujokito extract and Tsudosan extract used in the present invention, the extract prepared by the above-mentioned method may be used, or a commercially available one may be used. For example, as the extract powder of Tokakujokito, "Tokokujokito Dry Extract-AM" (manufactured by Nippon Powder Chemicals Co., Ltd.) and "Tokokujokito Dry Extract-F" (Alps Pharmaceutical Industry Co., Ltd.) (Made) etc. are known as products and can be obtained commercially. The extract powder of Tsudosan can also be obtained commercially from "Tsudosan Extract Fine Granules G Kotaro" (Kotaro Pharmaceutical Co., Ltd.).

In the pre-menstrual constipation improving agent of the present invention, the content of the Chinese herbal extract of the active ingredient is not particularly limited as long as the effect of the present invention is exhibited, but it is usually 5 to 5 in terms of the dry extract powder amount of the Chinese herbal extract of the active ingredient. 100% by weight, preferably 10 to 90% by weight, more preferably 20 to 80% by weight, still more preferably 30 to 60% by weight. In addition, in this invention, the dry extract powder amount conversion of the active ingredient Chinese medicine extract is the amount itself when the dry extract powder of Chinese medicine extract is used, and when the liquid extract of Chinese medicine extract is used, it is the amount of itself. Is the amount converted into the remaining amount after removing the solvent. When the dried extract powder of the Chinese herbal extract contains an additive such as an adsorbent added at the time of production, the amount is the amount excluding the additive.

Other Ingredients The premenstrual constipation improving agent of the present invention may consist of the active ingredient Chinese herbal extract alone, or may contain additives and bases according to the pharmaceutical form. Such additives and bases are not particularly limited as long as they are pharmaceutically acceptable, but for example, excipients, binders, disintegrants, lubricants, tonicity agents, plasticizers, etc. Dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, pressure-sensitive agents, coating agents, brighteners, water, fats and oils, waxes, hydrocarbons, fatty acids, higher alcohols , Esters, water-soluble polymers, surfactants, metal soaps, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV inhibitors, preservatives, emulsifiers, fragrances, powders, Examples include thickeners, pigments, chelating agents and the like. These additives may be used alone or in combination of two or more. The content of these additives and bases is appropriately set according to the types of additives and bases to be used, the pharmaceutical form of the premenstrual constipation improving agent, and the like.

Further, the premenstrual constipation improving agent of the present invention may contain other nutritional components and pharmacological components in addition to the above active ingredients, if necessary. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmaceutically acceptable, and are, for example, antioxidants, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, and astringents. Agents, antiemetics, antitussives, sputum, anti-inflammatory enzyme agents, sedative hypnotics, antihistamines, caffeines, cardiotonic diuretics, antibacterial agents, vasoconstrictors, vasoconstrictors, local anesthetics, crude drug extracts, vitamins, menthol Kind and the like. 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 premenstrual constipation improving 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, a chewable agent, and the like. Examples thereof include solid preparations such as capsules (soft capsules and hard capsules) and rounds; semi-solid preparations such as jelly; liquid preparations such as liquids, suspensions and syrups. Among these preparation forms, a solid preparation is preferable, and a tablet is more preferable, from the viewpoint of stability and portability of the contained components.

Manufacturing method The manufacturing method of the pre-menstrual constipation improving agent of the present invention uses a Chinese herbal extract as an active ingredient and other ingredients to be blended as needed, in accordance with a usual formulation method adopted in the pharmaceutical field. It may be formulated.

Use The premenstrual constipation improving agent of the present invention is used for the purpose of improving constipation that occurs before menstruation, and more specifically, for the purpose of preventing or treating constipation that occurs before menstruation. Constipation that occurs before menstruation is characteristically occurring during the premenstrual period in that it worsens before menstruation and improves with the onset of menstruation. Specific examples of premenstrual syndrome include the luteal phase, and more preferably the late luteal phase.

The target of the pre-menstrual constipation improving agent of the present invention may be a person who causes characteristic constipation during the pre-menstrual period, and causes characteristic constipation during the pre-menstrual period and during a period other than pre-menstrual period. Not only for those who do not have constipation, but also for those who have characteristic constipation during the pre-menstrual period and during non-menstrual periods (although the characteristic constipation during the pre-menstrual period is once relieved), regardless of the time of year. Also includes people who have irregular constipation due to unspecified factors other than female hormone fluctuations (eg, lack of fiber intake, lack of water, lack of breakfast, etc.).

The target of application of the premenstrual rough skin improving agent of the present invention is not particularly limited as long as it causes characteristic constipation during the premenstrual period, but preferably a target having a regular menstrual cycle. Regular menstrual cycle means that the number of days of the menstrual cycle is 25 to 38 days, the duration of bleeding is 3 to 7 days, and the fluctuation is within 6 days.

Dosage and Usage The premenstrual constipation improving agent of the present invention is used by oral administration. The dose of the pre-menstrual constipation improving agent of the present invention is appropriately set according to the age, constitution, degree of symptom, etc. of the administration subject. The total amount of the extract and tsudosan extract (equivalent to dry extract) is, for example, 500 to 7000 mg, preferably 1000 to 6000 mg; the amount of Tokakujokito extract (equivalent to dry extract) is, for example, 500 to 5000 mg, preferably 1000. ~ 4000 mg, more preferably 1200 ~ 2000 mg; the amount of tsudosan extract (dry extract equivalent amount) is, for example, 3000 to 7000 mg, preferably 4000 to 6000 mg, 1 to 4 times a day, preferably 2 to 3 times. It should be taken as often as once.

The timing of administration during the day is not particularly limited and may be pre-meal, post-meal, or inter-meal, but pre-meal or inter-meal is preferable.

In addition, the timing of administration during the menstrual cycle is not particularly limited. For example, since the premenstrual constipation improving agent of the present invention has an excellent immediate effect, it is possible to start taking the drug at the timing when the premenstrual constipation to be improved is felt. More specifically, even if the premenstrual constipation improving agent of the present invention is taken from the beginning of the late luteal phase, the constipation improving effect can be obtained during the late luteal phase. From the viewpoint of further enhancing the effect of improving premenstrual constipation, 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, but when applied to rough skin that appears characteristically from premenstrual period to the start of menstruation, for example, 9 days or less, 8 days or less, or 7 days or less. Can be mentioned.

In addition, the premenstrual constipation improving agent of the present invention may be taken for preventive purposes prior to the time when constipation occurs. For example, in the case of a person who develops constipation from the late luteal phase, the administration can be started from the ovulation period or the beginning of the luteal phase. In this case as well, 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.

(1) Preparation of Chinese herbal extract (1-1) Tokakujokito extract Raw herbal medicine was added to 3.0 parts by weight of Tounin, 2.4 parts by weight of Keihi, 1.8 parts by weight of Daiou, and 0.9 parts by weight of Kanzo. And 0.6 parts by weight of bow show (anhydrous bow show equivalent amount), after chopping these, extract at about 100 ° C. for 1 hour using 20 times the weight of water, centrifuge to obtain an extract, and reduce the pressure. It was concentrated underneath and dried using a spray dryer to obtain Tokakujokito extract powder. The obtained Tokakujokito extract powder was 1584 mg (daily dose) per 8.7 g of the raw material crude drug mixture. The drying with a spray dryer was carried out by dropping the extract onto an atomizer having a rotation speed of 10000 rpm and supplying hot air with air at 150 ° C.

(1-2) Tsudosan extract The crude drug as the raw material was 2.4 parts by weight of Touki, 2.4 parts by weight of Daiou, 1.44 parts by weight of Bowsho (anhydrous Bowsho equivalent amount), 2.4 parts by weight of Kijitsu, and Koboku 1. 6 parts by weight, 1.6 parts by weight of chimpi, 1.6 parts by weight of mokutsu, 1.6 parts by weight of kouka, 1.6 parts by weight of soboku, and 1.6 parts by weight of kanzo. It was extracted at about 100 ° C. for 1 hour using 20 times the weight of water, centrifuged to obtain an extract, concentrated under reduced pressure and dried using a spray dryer to obtain a tsudosan extract powder. The obtained Tsudosan extract powder was 5200 mg (daily dose) per 16.64 g of the raw material crude drug mixture. The drying with a spray dryer was carried out by dropping the extract onto an atomizer having a rotation speed of 10000 rpm and supplying hot air with air at 150 ° C.

(1-3) Bofutsushosan extract Raw medicine, 1.2 parts by weight of Touki, 1.2 parts by weight of Shakuyaku, 1.2 parts by weight of Senkyu, 1.2 parts by weight of Sanshishi, 1.2 parts by weight of Renkyo, Hacka 1.2 parts by weight, 1.2 parts by weight of Shokyo, 1.2 parts by weight of Keigai, 1.2 parts by weight of Bofu, 1.2 parts by weight of Maou, 1.5 parts by weight of Daiou, 1.5 parts by weight of anhydrous bow show, 2.0 parts by weight of Byakujutsu, 2.0 parts by weight of Kikyo, 2.0 parts by weight of Ogon, 2.0 parts by weight of Kanzo, 2.0 parts by weight of Sekko, and 3.0 parts by weight of Kaseki. After chopping, extract at about 100 ° C. for 1 hour using 20 times the weight of water, centrifuge to obtain an extract, concentrate under reduced pressure and dry using a spray dryer to obtain bofutsushosan extract powder. Obtained. The obtained bofutsushosan extract powder was 5000 mg (daily dose) per 27.1 g of the raw material crude drug mixture. The drying with a spray dryer was carried out by dropping the extract onto an atomizer having a rotation speed of 10000 rpm and supplying hot air with air at 150 ° C.

(2) Subject and dosing schedule (2-1)
The subjects were women aged 20-40 years (N = 30) with a regular menstrual cycle who complained of characteristic constipation before menstruation. These subjects were divided into 3 groups (N = 10 in each group) so that the degree of constipation did not vary, and each group had constipation for 5 days from the time when they felt the appearance of constipation before menstruation. The extract, tsudosan extract, or bofutsushosan extract was taken 3 times a day before or between meals. How much improvement was felt in the symptoms of constipation during the period of administration compared to the symptoms of premenstrual constipation in the previous menstrual cycle? , I can't say either, I didn't feel any improvement, I didn't feel any improvement). The results are shown in Table 1.

(2-2)
In addition to the characteristic constipation before menstruation, the above-mentioned subjects had constipation due to factors other than female hormone fluctuations irregularly during periods other than premenstrual syndrome. After confirming the recovery of characteristic constipation before menstruation after the drug withdrawal period after conducting the above test (2-1), from the time when irregular constipation appears in the period other than before menstruation 5 For days, take Tokakujokito extract, Tsudosan extract, or Bofutsushosan extract three times a day before or between meals, and in the same way as in (2-1) above, for the irregular constipation. I evaluated how it improved. The results are shown in Table 2.

As shown in Table 1, the Tokakujokito extract and Tsudosan extract showed an excellent improvement effect on premenstrual constipation as compared with the bofutsushosan extract. As shown in Table 2, the improvement effect of Tokakujokito extract and Tsudosan extract is poor for irregular constipation other than before menstruation, but rather the improvement effect of Bofutsushosan extract is higher. In view of the above, the pre-menstrual constipation and the non-pre-menopausal constipation are essentially different in sensitivity to the Tokakujokito extract and Tsudosan extract and the Bofutsushosan extract. , The effect of improving constipation by Tokakujokito extract and Tsudosan extract is recognized to be a peculiar effect on constipation before menstruation.

Claims (2)

Premenstrual constipation improver, including Tokakujokito extract and / or Tsudosan extract. The premenstrual constipation improving agent according to claim 1, wherein the menstrual cycle is used for a regular object.