Agent for improving rough skin before menstruation

Abstract

To provide a Chinese herbal medicine that can improve rough skin before menstruation.SOLUTION: Keishi-bukuryo-gan-ka-yokuinin extract and / or unkei-to extract has a great effect of improving rough skin before menses, so that it can be used as an active ingredient in an agent for improving rough skin before menstruation.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an agent for improving premenstrual rough skin. [Background technology]

[0002] Blood disorders refer to mental and physical symptoms that appear due to fluctuations in female hormones during menstruation, pregnancy, childbirth, postpartum, menopause, etc. Symptoms of blood disorders include mental and physical symptoms that appear about 3 to 10 days before the start of menstruation and disappear once menstruation begins.

[0003] The Obstetrics and Gynecology Clinical Practice Guidelines (Non-Patent Document 1) lists the following Kampo prescriptions that are suitable for treating blood disorders: Saiko-keishi-kankyoto, Kami-shoyo-san, Unsei-in, Megami-san, Shimotsu-to, San'o-shashin-to, Senkyu-cha-cho-san, etc. The Obstetrics and Gynecology Clinical Practice Guidelines also state that although Kampo treatments do not have an immediate effect, improvement in symptoms can be expected with administration for 4 to 12 weeks.

[0004] The blood-related symptoms characteristically appearing before menstruation include a wide range of mental and physical symptoms. Representative physical symptoms include breast engorgement, edema, generalized pain (especially lower back pain), abdominal distension, abdominal pain, headache, weight gain, swelling of the limbs, acne, rough skin, constipation, diarrhea, muscle and joint pain, epilepsy, migraine, asthma, rhinitis, and hives. Representative mental symptoms include mood swings and depression, tearfulness and pessimism, fatigue and lethargy, tension or anxiety, irritability and upset / difficulty controlling emotions, difficulty concentrating, changes in sexual preference, sleep disorders (including somnolence), abnormal appetite, aggressiveness, and lack of self-control (Non-Patent Document 2).

[0005] Among the above symptoms, skin problems are particularly noticeable in appearance. For women, whether or not they have rough skin can have a significant psychological impact. Rough skin can cause symptoms such as acne, eczema, and dryness, and rough skin can also make it difficult to apply makeup.

[0006] There are various Kampo medicines that are effective against rough skin. For example, according to the Guidelines for the Treatment of Common Acne (Non-Patent Document 3), only Keigakurenkyoto and Seishangbofuto are covered by insurance for acne, while Orengedokuto, Unseiin, Unkeito, and Keishibukuryogan are not recommended. Unseiin is also said to be effective against eczema and dermatitis, and according to the Pharmaceutical Interview Form (Non-Patent Document 4), it is indicated as "used for poor skin tone and hot flashes: irregular menstruation, dysmenorrhea, blood disorders, and menopausal disorders." Clinically, it is used in cases of chronic rash with little secretion, and is suitable for dark, rough skin that is as dry as astringent paper (Non-Patent Document 5). [Prior art documents] [Non-patent literature]

[0007] [Non-Patent Document 1] "Obstetrics and Gynecology Clinical Practice Guidelines - Outpatient Gynecology Edition 2017," Japan Society of Obstetrics and Gynecology, Japan Society of Obstetrics and Gynecology [Non-patent document 2] “My Treatment by 1336 Specialists 2017-18 Edition”, Gynecological Diseases, Premenstrual Syndrome (PMS), [online], September 2, 2017, Nihon Iji Shimposha, [Retrieved December 8, 2020], Internet<https: / / www.jmedj.co.jp / premium / treatment / 2017 / d200103 / > [Non-patent document 3] Guidelines for the Treatment of Acne Vulgaris 2017, Journal of the Japanese Dermatological Association: 127(6), 1261-1302, 2017 (Heisei 29) 1261-1302 [Non-patent document 4] Pharmaceutical Interview Form Teikoku Unseiin Extract Granules, February 2018 (Revised 7th Edition) [Non-Patent Document 5] Kampo therapy in the field of dermatology, Journal of Kyoto Prefectural University of Medicine 125(2), 135-143, 2016. Summary of the Invention [Problem to be solved by the invention]

[0008] Although several types of herbal medicines have been shown to be effective for treating blood disorders, as mentioned above, there are a wide variety of characteristic symptoms that occur before menstruation, and it has not been fully investigated which herbal medicine will provide the appropriate therapeutic effect for which symptom.Furthermore, there has been even less research into which herbal medicines are suitable for rough skin, which is just one example of the many symptoms that occur before menstruation.

[0009] The present inventors have focused on Unsei-in, a Chinese herbal medicine that is also used to treat blood disorders and rough skin, and have investigated its effectiveness in improving rough skin before menstruation. However, it has been found that Unsei-in is less effective for rough skin before menstruation, and is more effective for irregular rough skin that occurs at times other than before menstruation, and is therefore not suitable as a Chinese herbal medicine for improving rough skin before menstruation.

[0010] Therefore, an object of the present invention is to provide a herbal medicine that can improve premenstrual rough skin. [Means for solving the problem]

[0011] As a result of extensive research, the present inventors have found that Keishibukuryogan-ka-yoku-in extract and Unkeito extract have the effect of improving rough skin before menstruation. Based on this finding, the present invention was completed through further research.

[0012] That is, the present invention provides the following aspects. Item 1. A premenstrual skin irritation remedy containing Keishibukuryogan-ka-yokui-jin extract and / or Unkeito extract. Item 2. The premenstrual rough skin treatment agent according to Item 1, which is used to improve acne that occurs before menstruation. Item 3. The premenstrual rough skin treatment agent according to Item 1 or 2, which is used to improve poor makeup application that occurs before menstruation. Item 4. The premenstrual rough skin improving agent according to any one of Items 1 to 3, which is used for subjects with regular menstrual cycles. Item 5. The premenstrual rough skin amelioration agent according to any one of Items 1 to 4, which is to be started to be taken when rough skin is felt before menstruation. [Effects of the Invention]

[0013] According to the present invention, a herbal medicine capable of improving premenstrual rough skin is provided. DETAILED DESCRIPTION OF THE INVENTION

[0014] The premenstrual rough skin alleviating agent of the present invention is characterized by containing Keishibukuryogan-ka-yokuinin extract and / or Unkeito extract. The premenstrual rough skin alleviating agent of the present invention will be described in detail below.

[0015] Keishibukuryogan ka yokuinin extract and / or Unkeito extract The premenstrual rough skin alleviating agent of the present invention contains Keishibukuryogan-ka-yokuinin extract and / or Unkeito extract as active ingredients.

[0016] Keishibukuryogan with Yokuinin is a prescription that adds Yokuinin to Keishibukuryogan, which is based on the Jingui Yaolue, and its constituent herbs include a mixture of herbs consisting of cinnamon bark, peony root, poria cocos, peach kernel, moutan peel, and coix seed.

[0017] The amounts of each medicinal herb that makes up Keishibukuryogan-ka-yoku-i-nin include 1.0 to 5.0 parts by weight of cinnamon bark, 1.0 to 5.0 parts by weight of peony root, 1.0 to 5.0 parts by weight of Poria cocos, 1.0 to 5.0 parts by weight of peach kernel, 1.0 to 5.0 parts by weight of moutan peel, and 3.0 to 12 parts by weight of coix seed.

[0018] Unkei-to is a prescription based on the Jingui Yaolue (The Golden Roots), and its constituent herbal medicines include a mixture of herbs consisting of Rhizome Root, Pinellia Root, Angelica Root, Licorice Root, Cinnamon Bark, Peony Root, Cnidium Rhizome, Ginseng Root, Moutan Pea Root, Euonymus Root, Ginger Root, and Aster Ginger.

[0019] The amounts of each herb that makes up Unkeito include 1.5 to 5.5 parts by weight of Pakumondou, 1.5 to 5.5 parts by weight of Pinellia Root, 1.0 to 4.0 parts by weight of Angelica Root, 0.5 to 2.5 parts by weight of Licorice, 0.5 to 2.5 parts by weight of Cinnamon Bark, 0.5 to 2.5 parts by weight of Peony Root, 0.5 to 2.5 parts by weight of Cnidium Root, 0.5 to 2.5 parts by weight of Ginseng, 0.5 to 2.5 parts by weight of Moutanga Peony, 0.2 to 1.5 parts by weight of Euonymus Root, 0.2 to 2.5 parts by weight of Ginger Root, and 0.5 to 2.5 parts by weight of Aster Ginger.

[0020] The Keishibukuryogan-ka-yokuinin extract and Unkei-to extract in the present invention may be obtained by extracting the above-mentioned mixed herbal medicines and concentrating the resulting extract as necessary to obtain an extract liquid, or by drying the extract liquid to obtain an extract powder.

[0021] In the production of Keishibukuryogan-ka-yokui-nin extract and Unkei-to extract, the extraction solvent used in the extraction process is not particularly limited, but examples include water or aqueous ethanol. The drying process is also not particularly limited, and includes known methods such as spray drying and a method in which a suitable adsorbent (e.g., silicic anhydride, starch, etc.) is added to a soft extract obtained by increasing the concentration of the extract liquid to obtain an adsorbed powder.

[0022] The Keishibukuryogan-ka-yokuinin extract and Unkeito extract used in the present invention may be the extract prepared by the above-mentioned method or may be commercially available. For example, the Keishibukuryogan-ka-yokuinin extract powder may be "Keishibukuryoganryo-ka-yokuinin-to dried extract" - Known products include "Unkeito F" (manufactured by Alps Pharmaceutical Co., Ltd.) and are commercially available. Unkeito extract powder is also commercially available from JPS Pharmaceutical Co., Ltd.

[0023] In the premenstrual rough skin alleviating agent of the present invention, the content of the active ingredient, the herbal extract, is not particularly limited as long as the effects of the present invention are achieved, but is typically 5 to 100% by weight, preferably 10 to 90% by weight, more preferably 20 to 80% by weight, and even more preferably 30 to 60% by weight, calculated as the amount of the active ingredient, calculated as the dried extract powder of the herbal extract. In the present invention, the amount calculated as the dried extract powder of the herbal extract refers to the amount itself when a dried extract powder of the herbal extract is used, and refers to the amount remaining after removing the solvent when a liquid extract of the herbal extract is used. Furthermore, when the dried extract powder of the herbal extract contains additives such as adsorbents added during production, the amount refers to the amount excluding these additives.

[0024] Other ingredients The premenstrual rough skin alleviating agent of the present invention may consist solely of the herbal extract as an active ingredient, or may contain additives and bases appropriate for the formulation. Such additives and bases are not particularly limited as long as they are pharmaceutically acceptable, and examples thereof include excipients, binders, disintegrants, lubricants, isotonicity agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, adhesives, coating agents, glossing agents, water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV protection agents, preservatives, flavoring agents, fragrances, powders, thickeners, pigments, and chelating agents. These additives may be used alone or in combination of two or more. The content of these additives and bases is appropriately determined depending on the type of additives and bases used, the formulation of the premenstrual rough skin alleviating agent, and other factors.

[0025] In addition, the premenstrual rough skin improving agent of the present invention may contain, as necessary, other nutritional components or pharmacological components in addition to the above-mentioned active ingredients. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmaceutically acceptable, and examples thereof include antacids, stomachic agents, digestive aids, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, astringents, antiemetics, antitussives, expectorants, anti-inflammatory enzymes, sedatives, hypnotics, antihistamines, caffeine, cardiac diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, herbal extracts, vitamins, and menthols. These nutritional components and pharmacological components may be used alone or in combination of two or more. The content of these components is appropriately determined depending on the type of components used, etc.

[0026] Formulation The formulation form of the premenstrual rough skin improving agent of the present invention is not particularly limited as long as it can be administered orally, and examples thereof include solid formulations such as powders, fine granules, granules, tablets, troches, chewable tablets, capsules (soft capsules, hard capsules), and pills; semi-solid formulations such as jellies; and liquid formulations such as solutions, suspensions, and syrups. Among these formulation forms, solid formulations are preferred, and tablets are more preferred, from the viewpoints of the stability and portability of the ingredients contained therein.

[0027] Manufacturing method The method for producing the premenstrual rough skin improving agent of the present invention is to formulate the active ingredient, a herbal extract, and other ingredients that are blended as necessary, according to the usual formulation techniques used in the pharmaceutical field.

[0028] Purpose The premenstrual rough skin improving agent of the present invention is used for the purpose of improving rough skin that occurs before menstruation, more specifically for the purpose of preventing or treating rough skin that occurs before menstruation. Rough skin that occurs before menstruation is specifically a skin symptom that characteristically occurs in the period before menstruation, in that it worsens before menstruation and improves with the onset of menstruation. Specific examples of the period before menstruation include the luteal phase, and more preferably the late luteal phase.

[0029] The type of rough skin is not particularly limited, but from the viewpoint of obtaining a more effective improvement, acne and poor makeup application are preferable. The makeup application refers to the degree to which cosmetics (makeup cosmetics such as foundation) blend into the skin, and examples of poor makeup application include makeup that looks unnatural, a dull complexion even when makeup is applied, makeup that blends in well but quickly smudges or crumbles, and makeup that is uneven or powdery when applied.

[0030] The premenstrual rough skin improving agent of the present invention can be applied to anyone who experiences rough skin that is characteristic of the premenstrual period, and includes not only those who experience rough skin that is characteristic of the premenstrual period but does not experience rough skin in periods other than the premenstrual period, but also those who experience rough skin that is characteristic of the premenstrual period but who newly develop other irregular rough skin with different characteristics in periods other than the premenstrual period (although the rough skin that is characteristic of the premenstrual period improves). With regard to other irregular skin roughness with different characteristics (hereinafter also referred to simply as "irregular skin roughness"), how it differs from the characteristic premenstrual skin roughness is often recognized empirically by individuals, and is not particularly limited. For example, (i) unlike premenstrual skin roughness, the timing of appearance of irregular skin roughness does not depend on the menstrual cycle, but depends on factors other than the menstrual cycle, such as lack of sleep or long contact time between the skin and cosmetics, (ii) cases in which different types of skin roughness occur, such as acne occurring as a characteristic premenstrual skin roughness and poor makeup application as an irregular skin roughness, and (iii) cases in which acne occurs as a characteristic premenstrual skin roughness and acne also occurs as an irregular skin roughness, but the acne differs in difficulty to heal, degree of inflammation, location of appearance, etc.

[0031] The subject of the premenstrual rough skin improving agent of the present invention is not particularly limited as long as the subject experiences rough skin before menstruation, but preferably includes subjects with a regular menstrual cycle. A regular menstrual cycle means that the menstrual cycle is 25 to 38 days long, the duration of bleeding is 3 to 7 days, and the variation is within 6 days.

[0032] Dosage / Usage The premenstrual rough skin improving agent of the present invention is used by oral administration. The dosage of the premenstrual rough skin improving agent of the present invention is appropriately determined depending on the age, constitution, severity of symptoms, etc. of the recipient, but for example, per human per day, the total amount (equivalent to dry extract) of Keishibukuryogan-ka-yokui-nin extract and Unkei-to extract is, for example, 1.0 to 10 g, preferably 1.5 to 7.0 g; the amount of Keishibukuryogan-ka-yokui-nin extract (equivalent to dry extract) is, for example, 1.0 to 5.0 g, preferably 1.5 to 3.0 g; and the amount of Unkei-to extract (equivalent to dry extract) is, for example, 1.0 to 10 g, preferably 2.0 to 7.0 g, more preferably 4.0 to 6.0 g, and may be taken 1 to 4 times, preferably 2 to 3 times a day.

[0033] The timing of administration within a day is not particularly limited, and may be before meals, after meals, or between meals, but is preferably before meals or between meals.

[0034] Furthermore, the timing of administration within the menstrual cycle is not particularly limited. For example, since the premenstrual rough skin improving agent of the present invention has excellent immediate effect, administration can be started at the timing when premenstrual rough skin that needs to be improved is felt. More specifically, even if the premenstrual rough skin improving agent of the present invention is administered from the start of the late luteal phase, the rough skin improving effect can be obtained within the late luteal phase. Note that, from the viewpoint of further enhancing the rough skin improving effect, it is preferable to continuously administer the agent for, for example, 2 days or more, preferably 3 days or more, more preferably 4 days or more, and even more preferably 5 days or more per menstrual cycle. Furthermore, the number of continuous days of administration per menstrual cycle is not particularly limited, and administration may be stopped as soon as menstruation begins. The specific number of continuous days of administration varies depending on the length of the menstrual cycle, but when applied to rough skin that characteristically appears from before menstruation to the onset of menstruation, it can be, for example, 9 days or less, 8 days or less, or 7 days or less.

[0035] In addition, the premenstrual rough skin improving agent of the present invention may be taken for preventative purposes before the onset of rough skin. For example, in the case of a person who experiences rough skin in the late luteal phase, administration can be started at the start of ovulation or the luteal phase. In this case, the number of days of administration per menstrual cycle is not particularly limited, and administration can be stopped at the same time as the onset of menstruation. [Example]

[0036] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0037] (1) Preparation of herbal extracts (1-1) Keishibukuryogan plus Job's tears extract The raw herbs used were 2.0 parts by weight of cinnamon bark, 2.0 parts by weight of peony root, 2.0 parts by weight of Poria cocos, 2.0 parts by weight of peach kernel, 2.0 parts by weight of moutan peel, and 5.0 parts by weight of coix seed. After chopping, these were extracted with 20 times their weight of water at approximately 100°C for 1 hour, centrifuged to obtain an extract, which was concentrated under reduced pressure and dried using a spray dryer to obtain Keishibukuryogan-ka-yoku-i seed extract powder. The resulting Keishibukuryogan-ka-yoku-i seed extract powder had a daily dose of 2379 mg per 20 g of raw herbal mixture. The spray dryer drying was performed by dropping the extract into an atomizer at 10,000 rpm and supplying hot air at 150°C.

[0038] (1-2) Unkeito extract The raw herbs used were 2.8 parts by weight of Pakumondo Root, 2.8 parts by weight of Pinellia Root, 2.1 parts by weight of Angelica Root, 1.4 parts by weight of Licorice Root, 1.4 parts by weight of Cinnamon Bark, 1.4 parts by weight of Peony Root, 2.1 parts by weight of Cnidium Rhizome, 1.4 parts by weight of Ginseng, 1.4 parts by weight of Peony Fruit, 0.7 parts by weight of Euonymus Root, 0.7 parts by weight of Ginger, and 1.4 parts by weight of Angelica Root. After chopping, the raw herbs were extracted with 20 times their weight of water at approximately 100°C for 1 hour, centrifuged to obtain an extract, concentrated under reduced pressure, and dried using a spray dryer to obtain an unkeito extract powder. The resulting unkeito extract powder had a daily dose of 5040 mg per 18.9 g of raw herb mixture. The spray dryer drying was performed by dropping the extract into an atomizer at 10,000 rpm and supplying hot air at 150°C.

[0039] (1-3) Unseiin extract The raw herbs were used in the following proportions: Rehmannia Root (1.5 weight parts), Peony Root (1.5 weight parts), Cnidium Rhizome (1.5 weight parts), Angelica Snape (1.5 weight parts), Scutellaria Root (0.75 weight parts), Phellodendron Bark (0.75 weight parts), Coptis Rhizome (0.75 weight parts), and Gardenia Fruit (0.75 weight parts). After chopping, the raw herbs were extracted with 20 times their weight of water at approximately 100°C for 1 hour. The extract was centrifuged, concentrated under reduced pressure, and dried using a spray dryer to obtain Unseiin extract powder. The resulting Unseiin extract powder was 2800 mg (daily dose) per 11 g of raw herb mixture. The spray dryer drying was performed by dropping the extract into an atomizer rotating at 10,000 rpm and supplying hot air at 150°C.

[0040] (2) Subjects and medication schedule (2-1) The subjects were women (N=30) aged 20-40 years with regular menstrual cycles who complained of characteristic premenstrual skin problems. Among the premenstrual skin problems, the most commonly reported were acne and poor makeup application. These subjects were divided into three groups (N=10 per group) to ensure consistency in the severity of their skin problems. Each group was instructed to take Keishibukuryogan-ka-yokuinin extract, Unkeito extract, or Unseiin extract three times daily, either before or between meals, for five days from the time they noticed the onset of premenstrual skin problems. The extent to which subjects perceived improvement in their skin problems during the treatment period compared with their premenstrual skin problems during the previous menstrual cycle was assessed on a five-point scale (improved, somewhat improved, neither positive nor negative, somewhat not improved, not improved). The efficacy rate was calculated as the percentage of subjects in each group who rated "improved" and "somewhat improved." The evaluation consisted of an overall evaluation of rough skin in general, an evaluation of acne among the rough skin, and an evaluation of poor makeup application among the rough skin. The results are shown in Tables 1 to 3.

[0041] (2-2) Furthermore, the subjects were aware from experience that in addition to the characteristic premenstrual roughness, they also experienced irregular skin roughness outside of the premenstrual period. After a drug withdrawal period following the test described in (2-1) above, the return of the characteristic premenstrual roughness was confirmed. After the onset of irregular skin roughness outside of the premenstrual period was confirmed, the subjects were instructed to take Keishibukuryogan-ka-yoku-in extract, Unkeito extract, or Unseiin extract three times a day, either before or between meals, for five days. The improvement was evaluated in the same manner as described in (2-1) above. Evaluations were made on acne, which was one type of skin roughness, and on the difficulty of applying makeup, which was another type of skin roughness. The results are shown in Tables 4 and 5.

[0042] [Table 1]

[0043] [Table 2]

[0044] [Table 3]

[0045] [Table 4]

[0046] [Table 5]

[0047] As shown in Tables 1-3, Keishibukuryogan-ka-yoku-in extract and Unkeito extract showed superior improvement effects on premenstrual rough skin compared to Unseiin extract. As shown in Tables 4-5, Keishibukuryogan-ka-yoku-in extract and Unkeito extract showed poor improvement effects on irregular rough skin other than premenstrual, while Unkeiin extract showed a stronger improvement effect. Considering this, premenstrual rough skin and irregular rough skin other than premenstrual are essentially different in sensitivity to Keishibukuryogan-ka-yoku-in extract, Unkeito extract, and Unkeiin extract, and the improvement effects of Keishibukuryogan-ka-yoku-in extract and Unkeito extract are recognized as being specific to premenstrual rough skin. In particular, the effect of Unkeito extract in improving poor makeup application before menstruation was remarkably significant, as indicated by the significantly higher number of subjects who evaluated it as "improved."

Claims

1. Contains Unkeito extract to improve rough skin before menstruation.

2. The premenstrual rough skin improving agent according to claim 1, which is used to improve acne that occurs before menstruation.

3. The premenstrual rough skin improving agent according to claim 1 or 2, which is used to improve poor makeup application that occurs before menstruation.

4. The premenstrual rough skin improving agent according to any one of claims 1 to 3, which is used for subjects with regular menstrual cycles.

5. The premenstrual rough skin improving agent according to any one of claims 1 to 4, which is started to be taken when rough skin is felt before menstruation.

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