Agent for increasing early morning urinary output

Abstract

To provide a pharmaceutical for increasing early morning urinary output.SOLUTION: A herbal medicine mixture A containing Poria sclerotium and Plantago seeds, a herbal medicine mixture B containing Poria sclerotium, cinnamon bark and aconite root, and / or their extracts are suitable as an active ingredient of an agent for increasing early morning urinary output.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an agent for increasing morning urination volume. [Background technology]

[0002] Normal urination consists of a urination cycle of urination (urinating) and storage (storing urine), and when this cycle does not function smoothly, it is called urinary dysfunction. The number of people who suffer from urinary dysfunction increases with age, regardless of gender, and it is said to significantly impair quality of life (QOL).

[0003] Drug therapies for urinary disorders include anticholinergics, which increase bladder capacity, and α- and β-adrenergic receptor stimulants, which tighten the urethra and relax the bladder. However, because these Western drugs have side effects, herbal medicines may be chosen instead. For example, Rokumi-gan (Non-Patent Document 1) is used as a herbal medicine for urinary difficulty and frequent urination. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Kampo preparation Tsumura Rokumi-gan extract granules (medical use) appendix, revised May 2007 Summary of the Invention [Problem to be solved by the invention]

[0005] Chinese herbal medicines that are effective for urinary problems have few side effects and are easy to incorporate into treatment, but the effects are often difficult to feel.

[0006] In addition, in people with normal urination, the amount of urine is generally the largest in early morning urination, but some people suffer from little early morning urination. If there was a drug that could increase the amount of urine urination in the early morning for such people, it would be possible to provide a drug that would be easy to feel the effects of.

[0007] The present disclosure aims to provide a pharmaceutical agent that increases early morning urination volume. [Means for solving the problem]

[0008] As a result of intensive research, the present inventors have found that a herbal medicine mixture containing a specific combination of herbal medicines or an extract thereof has the effect of increasing the amount of urination in the early morning. The present disclosure has been completed based on this finding and through further research.

[0009] That is, the present disclosure provides the inventions of the following aspects. Item 1. An agent for increasing early morning urine volume, comprising a herbal mixture A containing Poria Sclerotium and Shazenshi, a herbal mixture B containing Poria Sclerotium, Cinnamon and Bushi, and / or an extract thereof. Item 2. An agent for increasing early morning urination volume according to Item 1, which increases the volume of urine at the first urination after waking up. Item 3. The agent for increasing early morning urine volume according to Item 1 or 2, wherein the herbal mixture A comprises Lotus Root, Bakumondo Root, Poria Cocos Root, Ginseng, Shazenshi Root, Scutellaria Root, Astragalus Root, Zikoppi Root, and Licorice Root. Item 4. The agent for increasing early morning urine volume according to Item 1 or 2, wherein the herbal mixture B comprises Rehmannia Root, Cornus Cherry, Dioscorea Rhizome, Aleurites Rhizome, Poria Coccinea, Peony Bark, Cinnamon Bark, and Brussels Root. Item 5. The agent for increasing early morning urine volume according to Item 1 or 2, wherein the herbal mixture A or B comprises Goshitsu, Shazenshi, Rehmannia Root, Cornus Cherry, Dioscorea Rhizome, Takusha, Poria Coccinea, Peony Bark, Cinnamon Bark, and Bushi. Item 6. The agent for increasing early morning urine volume according to any one of Items 1 to 5, which is used for purposes other than improving nocturia. Item 7. A method for increasing early morning urine volume, comprising administering to a subject in need of increasing early morning urine volume an effective amount of herbal mixture A containing Poria Cocos Rhizome and Shazenshi, herbal mixture B containing Poria Cocos Rhizome, Cinnamon Bark and Bushi, and / or an extract thereof. Item 8. Use of herbal mixture A containing Poria Sclerotium and Shazenshi, herbal mixture B containing Poria Sclerotium, Cinnamon and Bushi, and / or extracts thereof for the manufacture of a composition for increasing early morning urination volume. Item 9. Herbal mixture A containing Poria Sclerotium and Shazenshi, herbal mixture B containing Poria Sclerotium, Cinnamon and Bushi, and / or extracts thereof for use in treating diseases associated with low early morning urination volume. Effect of the Invention

[0010] According to the present disclosure, a pharmaceutical agent is provided that increases early morning urination volume. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] The agent for increasing early morning urine volume of the present disclosure is characterized by containing a herbal mixture A containing Poria Cocos Rhizome and Shazenshi Rhizome, a herbal mixture B containing Poria Cocos Rhizome, Cinnamon Bark and Bushi Rhizome, and / or an extract thereof. The agent for increasing early morning urine volume of the present disclosure will be described in detail below.

[0012] Active ingredient The agent for increasing early morning urine volume of the present disclosure contains, as active ingredients, a herbal mixture A containing Poria Sclerotium and Shazenshi, a herbal mixture B containing Poria Sclerotium, Cinnamon and Bushi, and / or an extract thereof.

[0013] The herbal mixture A is not particularly limited as long as it contains Poria Columbine and Shazenshi, and may contain any other herbal medicines, but from the viewpoint of enhancing the effect of increasing early morning urination volume, preferred examples include herbal mixture a consisting of Lotus Root, Bakumondou, Poria Columbine, Ginseng, Shazenshi, Scutellaria Root, Astragalus Root, Zikoppi, and Licorice, and herbal mixture ab consisting of Goshitsu, Shazenshi, Rehmannia Root, Cornus Cherry, Dioscorea Rhizome, Takusha, Poria Columbine, Peony Pea, Cinnamon Bark, and Bushi.

[0014] The herbal mixture B is not particularly limited as long as it contains Poria Columbine, Cinnamon Bark, and Atractylodes Mucor, and may contain any other herbal medicines; however, from the viewpoint of enhancing the effect of increasing early morning urination volume, preferred examples include herbal mixture b consisting of Rehmannia Root, Cornus Cherry, Dioscorea Rhizome, Alpinia Root, Poria Columbine, Peony Bark, Cinnamon Bark, and Atractylodes Mucor, and herbal mixture ab consisting of Goshitsu, Shazenshi, Rehmannia Root, Cornus Cherry, Dioscorea Rhizome, Alpinia Root, Poria Columbine, Peony Bark, Cinnamon Bark, and Atractylodes Mucor.

[0015] The mixing ratio of the herbs that make up the herb mixture a is not particularly limited, and examples include 2 to 5 parts by weight, preferably 3 to 4 parts by weight, of Lotus Saxifraga; 1.5 to 4 parts by weight, preferably 2 to 3 parts by weight, of Poria Cocos Root; 2 to 4 parts by weight, preferably 2.5 to 3.5 parts by weight, of Ginseng; 1.5 to 3 parts by weight, preferably 2 to 4 parts by weight, of Shazenshi Fruit; 1.5 to 3 parts by weight, preferably 2 to 2.5 parts by weight, of Scutellaria Root; 1 to 4 parts by weight, preferably 2 to 3 parts by weight, of Astragalus Root; 1 to 3 parts by weight, preferably 2 to 2.5 parts by weight, of Zygophyll A.

[0016] The mixing ratio of the herbs constituting the herb mixture b is not particularly limited, and examples thereof include 2.5 to 8 parts by weight, preferably 6 to 8 parts by weight, of Rehmannia Root; 1.5 to 4 parts by weight, preferably 3 to 4 parts by weight, of Cornus Cherry; 1.5 to 4 parts by weight, preferably 3 to 4 parts by weight, of Dioscorea Rhizome; 1.5 to 3 parts by weight, preferably 2 to 3 parts by weight, of Poria Scutellaria; 1.5 to 3 parts by weight, preferably 2 to 3 parts by weight, of Poria Coix Seed; 1.5 to 3 parts by weight, preferably 2 to 4 parts by weight, of Peony Root; 0.5 to 1 part by weight, preferably 0.8 to 1 part by weight, of Cinnamon Bark; and 0.25 to 1 part by weight, preferably 0.5 to 1 part by weight, of Bushi (processed Bushi).

[0017] The mixing ratio of the herbs constituting the herb mixture ab is not particularly limited, and examples thereof include 1 to 3 parts by weight, preferably 1.5 to 3 parts by weight, of Goshitsu Fruit; 1 to 3 parts by weight, preferably 1.5 to 3 parts by weight, of Shazenshi Fruit; 2 to 8 parts by weight, preferably 2 to 3 parts by weight, of Rehmannia Root; 1 to 4 parts by weight, preferably 2 to 4 parts by weight, of Cornus Cherry; 1 to 4 parts by weight, preferably 1.5 to 4 parts by weight, of Dioscorea Rhizome; 1 to 3 parts by weight, preferably 1.5 to 3 parts by weight, of Poria Scutellaria; 1 to 4 parts by weight, preferably 1.5 to 4 parts by weight, of Peony Root; 0.25 to 2 parts by weight, preferably 0.5 to 2 parts by weight, of Cinnamon Bark; and 0.25 to 1 part by weight, preferably 0.5 to 1 part by weight, of Bushi (processed Bushi).

[0018] In the agent for increasing early morning urine volume of the present disclosure, the active ingredient is preferably an extract of the above-mentioned herbal mixture from the viewpoint of increasing the effect of increasing early morning urine volume. Also, in the agent for increasing early morning urine volume of the present disclosure, the active ingredient is preferably herbal mixture A or an extract thereof, more preferably herbal mixture a or an extract thereof, and even more preferably an extract of herbal mixture a, from the viewpoint of increasing the effect of increasing early morning urine volume.

[0019] The form of the extract of the mixture of herbs may be any of a liquid extract such as a liquid extract or a soft extract, and a solid dry extract powder.

[0020] The liquid extract of the herbal mixture can be obtained by subjecting the herbal mixture to an extraction process and concentrating the resulting extract as necessary. The extraction solvent used in the extraction process is not particularly limited, and may be water or aqueous ethanol, preferably water. The dried extract powder of the herbal mixture can be obtained by drying the liquid extract. The drying method is not particularly limited, and may be, for example, a spray drying method, or a method in which a suitable adsorbent (e.g., silicic anhydride, starch, etc.) is added to a soft extract with an increased extract concentration to obtain an adsorbed powder.

[0021] In the agent for increasing early morning urine volume of the present disclosure, the content of the active ingredient is not particularly limited as long as the effect of the present disclosure is exhibited, and is usually 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. When an extract is used as the active ingredient, the content is calculated based on the amount of dried extract powder, which means the amount of dried extract powder itself when dried extract powder is used, the amount converted to the amount remaining after removing the solvent when liquid extract is used, and when the dried extract powder contains additives such as adsorbents added during production, the amount excluding the additives.

[0022] Other Ingredients The agent for increasing early morning urine volume of the present disclosure may be composed of the above-mentioned active ingredient alone, or may contain additives and / or bases according to the formulation. The additives and bases that may or may not be contained in the agent for increasing early morning urine volume of the present disclosure are not particularly limited as long as they are pharmacologic acceptable, and include, for example, 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, flavorings, fragrances, powders, thickeners, dyes, chelating agents, etc. These bases and additives may be used alone or in combination of two or more. The contents of these additives and base are appropriately set depending on the types of additives and base used and / or the formulation form of the agent for increasing early morning urine volume.

[0023] In addition, the morning urine volume increasing agent of the present disclosure may or may not contain other nutritional components and / or pharmacological components as necessary, in addition to the above-mentioned active ingredients. The nutritional components and pharmacological components that may or may not be contained in the morning urine volume increasing agent of the present disclosure are not particularly limited as long as they are pharmacologic acceptable, and examples thereof include antacids, stomachic agents, digestive agents, 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, menthols, etc. These nutritional components and pharmacological components may be used alone or in combination of two or more types. The content of these components is appropriately set according to the type of components used, etc.

[0024] Formulation The formulation form of the agent for increasing early morning urine volume of the present disclosure is not particularly limited, as long as it can be administered orally. For example, solid preparations such as powders, fine granules, granules, tablets, troches, chewable tablets, capsules (soft capsules, hard capsules), and pills; semi-solid preparations such as jellies; and liquid preparations such as solutions, suspensions, and syrups, and preferably pills, granules, or tablets.

[0025] Manufacturing method The method for producing the agent for increasing morning urine volume of the present disclosure may involve formulating the agent using the above-mentioned herbal ingredients in accordance with a conventional formulation method employed in the medical field.

[0026] Purpose The agent for increasing early morning urine volume of the present disclosure is used for the purpose of increasing the amount of urine during urination in the early morning. The target increase in urine volume is 1.8 times or more, preferably 2 times or more, more preferably 2.2 times or more (by volume) of the amount of early morning urine before taking the agent for increasing early morning urine volume of the present disclosure.

[0027] More specifically, the early morning urine volume increasing agent of the present disclosure is used for the purpose of increasing the amount of urine at the first urination after waking up. In addition, the early morning urine volume increasing agent of the present disclosure can increase the amount of early morning urine even if the subject does not have a symptom of nocturnal frequency of urination (a symptom of urinating once or more, preferably twice or more, after going to bed), and can increase the amount of early morning urine even if the subject has a symptom of nocturnal frequency of urination and the early morning urine volume increasing agent of the present disclosure does not provide an improvement effect for nocturnal frequency of urination, or can increase the amount of early morning urine before the improvement effect for nocturnal frequency of urination is achieved by the early morning urine volume increasing agent of the present disclosure when the subject has a symptom of nocturnal frequency of urination. Therefore, the early morning urine volume increasing agent of the present disclosure may be used for purposes other than improving nocturnal frequency of urination.

[0028] The gender of the target of the morning urine volume increasing agent of the present disclosure is not limited to males or females. The age of the target of the morning urine volume increasing agent of the present disclosure is not particularly limited, but may be, for example, 40 years old or older, preferably 50 years old or older, or 60 years old or older, and the upper limit of the age may be, for example, 80 years old or younger, preferably 70 years old or younger.

[0029] Dosage / Usage The agent for increasing morning urine volume of the present disclosure is used by oral administration. The dosage of the agent for increasing morning urine volume of the present disclosure is appropriately set according to the age, constitution, severity of symptoms, etc. of the person to be administered, but for example, in the case of herbal mixture A, the total amount of the raw herbal drug equivalent of Poria columbine and Shazenshi is, for example, 2.4 to 7 g, preferably 2.9 to 5 g, per day for humans, and in the case of herbal mixture B, the total amount of the raw herbal drug equivalent of Poria columbine, Cinnamon bark, and Bushi is, for example, 2 to 7 g, preferably 2.4 to 5 g.

[0030] The daily dose of the agent for increasing morning urine volume of the present disclosure for humans is, in the case of herbal mixture a, for example, 12 to 35 g, preferably 20 to 25 g, in terms of the total amount of raw herbal medicines of the herbal mixture a, and in the case of an extract of the herbal mixture a, for example, 1.5 to 3 g, preferably 2 to 2.5 g, in terms of the amount of dried extract powder; in the case of herbal mixture b, for example, 8 to 22 g, preferably 10 to 14 g, in terms of the total amount of raw herbal medicines of the herbal mixture b, and in the case of an extract of the herbal mixture b, for example, 1 to 4 g, preferably 1.5 to 2.5 g, in terms of the amount of dried extract powder; in the case of herbal mixture ab, for example, 10 to 35 g, preferably 12 to 20 g, in terms of the total amount of raw herbal medicines of the herbal mixture ab, and in the case of an extract of the herbal mixture ab, for example, 2 to 5 g, preferably 2 to 3 g, in terms of the amount of dried extract powder.

[0031] The dosage frequency of the agent for increasing early morning urine volume of the present disclosure is 1 to 3 times a day, preferably 2 times a day. The timing of administration is not particularly limited and may be before, after, or between meals, but is preferably before (30 minutes before a meal) or between meals (2 hours after a meal), and more preferably before a meal.

[0032] The period of administration of the agent for increasing early morning urine volume of the present disclosure may be, for example, 4 days or more, preferably 5 days or more, more preferably 6 days or more, and even more preferably 1 week or more. The upper limit of the period of administration is not particularly limited, but since the effect of increasing early morning urine volume by the agent for increasing early morning urine volume of the present disclosure appears relatively early, the period of administration may be, for example, 2 weeks or less, 10 days or less, or 1 week or less. EXAMPLES

[0033] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0034] (1) Preparation of agent for increasing morning urine volume (1-1) Extract of herbal mixture a 3.5 parts by weight of Lotus Root, 2.1 parts by weight of Bakumondou, 2.8 parts by weight of Poria Root, 3.5 parts by weight of Ginseng, 2.1 parts by weight of Shazenshi, 2.1 parts by weight of Scutellaria Root, 2.8 parts by weight of Astragalus Root, 2.1 parts by weight of Zikkōbi, and 0.7 parts by weight of Licorice were used, which were chopped, extracted with 10 times the weight of water at about 100°C for 1 hour, and centrifuged to obtain an extract. The extract was concentrated under reduced pressure and dried using a spray dryer to obtain an extract powder of the herbal mixture a. The drying using the spray dryer was performed by dropping the extract into an atomizer rotating at 10,000 rpm and supplying hot air at 150°C.

[0035] (1-2) Extract of herbal mixture b 2.5 parts by weight of Rehmannia Root, 1.5 parts by weight of Cornus Cherry, 1.5 parts by weight of Dioscorea Radix, 1.5 parts by weight of Thuja Root, 1.5 parts by weight of Poria Coccinea, 1.5 parts by weight of Peony Root, 0.5 parts by weight of Cinnamon Bark, and 0.5 parts by weight of Processed Bhut were used, and after chopping, they were extracted with 10 times the weight of water at about 100°C for 1 hour and centrifuged to obtain an extract. The extract was concentrated under reduced pressure and dried using a spray dryer to obtain an extract powder of herbal mixture b. The drying using the spray dryer was performed by dropping the extract into an atomizer rotating at 10,000 rpm and supplying hot air at 150°C.

[0036] (1-3) Extract of herbal mixture ab 1.5 parts by weight of Goshitsu, 1.5 parts by weight of Shazenshi, 2.5 parts by weight of Rehmannia Root, 1.5 parts by weight of Cornus Cherrier, 1.5 parts by weight of Dioscorea Radix, 1.5 parts by weight of Rhizome, 1.5 parts by weight of Dioscorea Radix, 1.5 parts by weight of Poria Coccinea, 1.5 parts by weight of Peony Root, 0.5 parts by weight of Cinnamon Bark, and 0.5 parts by weight of Processed Bush were used, chopped, and then extracted with 10 times the weight of water at about 100°C for 1 hour and centrifuged to obtain an extract. The extract was concentrated under reduced pressure and dried using a spray dryer to obtain an extract powder of the herbal mixture ab. The drying using the spray dryer was performed by dropping the extract into an atomizer rotating at 10,000 rpm and supplying hot air at 150°C.

[0037] (2) Experimental method Twenty men and women in their 40s to 70s were divided into four groups (N=5), and each group was given tablets of extracts of herbal mixture a, herbal mixture b, herbal mixture a, and Rokumi-gan extract twice a day, before breakfast and dinner, for one week. Among the 20 subjects (A to T), subjects E, F, I, K, M, and T had symptoms of nocturia, while the other subjects did not.

[0038] The dosage for the extract of herbal mixture a is 4.9 g / day in terms of the total amount of the raw herbal medicines of Poria columbine and Shazenshi, 21.7 g / day in terms of the total amount of the raw herbal medicines of herbal mixture a, and 2.2 g / day in terms of the dried extract powder of the extract of herbal mixture a; for the extract of herbal mixture b, 2.5 g / day in terms of the total amount of the raw herbal medicines of Poria columbine, Cinnamon bark, and Bushi, and 2.5 g / day in terms of the total amount of the raw herbal medicines of herbal mixture b. The total amount of raw drug equivalents of Poria Cocos Rhizome and Shazenshi was 3g / day, the total amount of raw drug equivalents of Poria Cocos Rhizome, Cinnamon Bark, and Bushi was 2.5g / day, the total amount of raw drug equivalents of raw drug equivalents of raw drug mixture ab was 14g / day, and the extract of raw drug mixture ab was 2.5g / day. The extract of Rokumi-gan was 20g / day in raw drug equivalent and 3.75g / day in dried extract powder equivalent.

[0039] Before and one week after starting the drug, the subjects were asked to measure the amount of urine they urinated using a paper cup and to record it in a urination diary. The results for the group administered the extract of herbal mixture A are shown in Table 1, the results for the group administered the extract of herbal mixture B are shown in Table 2, the results for the group administered the extract of herbal mixture A is shown in Table 3, and the results for the group administered the extract of Rokumi-gan are shown in Table 4.

[0040] [Table 1]

[0041] [Table 2]

[0042] [Table 3]

[0043] [Table 4]

[0044] As shown in a comparison between Tables 1 to 3 and Table 4, in Tables 1 to 3, the amount of urine the first time urination after waking up increased significantly (specifically, by 1.9 times or more). Note that herbal mixture b (Table 2) has the same herbal composition as Rokumi-gan (Table 4) except that it contains cinnamon bark and tsarium edulis. However, in Table 2 (group administered the extract of herbal mixture b), the amount of urine the first time urination after waking up increased significantly.

[0045] Moreover, among Tables 1 to 3, in Table 1 (group administered with the extract of herbal mixture a), the increase in urine volume at the first urination after waking up was particularly remarkable.

[0046] Furthermore, in all of Tables 1 to 3, an increase in the amount of urine in the first urination after waking was observed even in the subjects (Subjects E, I, and K) in whom no improvement in nocturia was observed. In other words, it was found that the agent for increasing early morning urine volume of the present disclosure increases early morning urine volume regardless of the improvement in nocturia.

Claims

1. An agent for increasing early morning urine volume, comprising a herbal mixture A containing Poria columbine and Shazenshi, a herbal mixture B containing Poria columbine, Cinnamon bark and Bushi, and / or an extract thereof.

2. 2. The agent for increasing early morning urine volume according to claim 1, which increases the amount of urine in the first urination after waking up.

3. 2. The agent for increasing early morning urine volume according to claim 1, wherein the herbal mixture A comprises Lotus Root, Bacteria Root, Poria Coccus Root, Ginseng, Shazenshi, Scutellaria Root, Astragalus Root, Zikkopi, and Licorice.

4. 2. The agent for increasing early morning urine volume according to claim 1, wherein the herbal mixture B comprises Rehmannia Root, Cornus Cherry, Dioscorea Rhizome, Poria Coccinea, Peony Bark, Cinnamon Bark, and Brussels Root.

5. 2. The agent for increasing early morning urine volume according to claim 1, wherein the herbal mixture A or B comprises Goshitsu, Shazenshi, Rehmannia Root, Cornus Cherry, Dioscorea Rhizome, Takusha, Poria Coccinea, Peony Bark, Cinnamon Bark, and Bushi.

6. The agent for increasing early morning urine volume according to claim 1, which is used for purposes other than improving nocturia.

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