JP2025004594A - Urinary flow enhancers - Google Patents

Abstract

[Problem] The object of the present invention is to provide a medicine that increases urinary flow. [Solution] Herbal mixture A containing Poria columbine and Shazenshi, herbal mixture B containing Poria columbine, Cinnamon bark and Bushi, and/or extracts thereof are useful as active ingredients of urinary flow increasers. [Selected Figure] None

Description

The present invention relates to a urinary flow increaser.

Normal urination consists of a urination cycle of micturition (urine release) and storage (urine storage), and when this cycle no longer functions smoothly, it is called urinary dysfunction. The number of people suffering from urinary dysfunction increases with age, regardless of gender, and it is said to significantly impair quality of life (QOL).

Drug therapies for urinary disorders include anticholinergics, which increase bladder capacity, and alpha and beta adrenergic receptor stimulants, which tighten the urethra and relax the bladder. However, because these Western drugs have side effects, herbal medicines are sometimes chosen instead. For example, Rokumi-gan (Non-Patent Document 1) is used as a herbal medicine that is effective for urinary difficulty and frequent urination.

Kampo preparation Tsumura Rokumi-gan extract granules (medical use) Appendix, revised May 2007

Chinese herbal medicines that are effective for urinary disorders have few side effects and are easy to incorporate into treatment, but the effects are often not noticeable.

In addition, even if urinary problems do not occur, the force of urine weakens with age. Therefore, if there were a medicine that could increase the force of urine (urinary flow), it would be possible to provide a medicine whose effects are easily noticeable.

The present disclosure aims to provide a pharmaceutical product that increases urinary flow.

After extensive research, the inventors discovered that a herbal mixture or an extract thereof containing a specific combination of herbal medicines has the effect of increasing urinary flow. The present disclosure was completed based on this finding and through further research.

That is, the present disclosure provides the inventions of the following aspects.
Item 1. A urinary flow increaser 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. The urinary flow increasing agent according to Item 1, which is used for increasing urinary flow in a subject suffering from nocturia.
Item 3. The urinary flow increaser according to item 1 or 2, wherein the herbal mixture A comprises Lotus Root, Bakumondo Root, Poria Cocos Root, Ginseng, Shazenshi, Scutellaria Root, Astragalus Root, Zikkoppi, and Licorice Root.
Item 4. The urinary flow enhancer according to Item 1 or 2, wherein the herbal mixture B comprises Rehmannia Root, Cornus Cherry, Dioscorea Rhizome, Poria Coccinea, Peony Bark, Cinnamon Bark, and Brussels Root.
Item 5. The urinary flow increaser 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 urinary flow-increasing agent according to any one of Items 1 to 5, which is used for increasing urinary flow in a subject without urinary dysfunction.
Item 7. A method for increasing urinary flow, comprising administering to a subject in need of increasing urinary flow an effective amount of herbal mixture A containing Poria Sclerotium and Shazenshi, herbal mixture B containing Poria Sclerotium, Cinnamon 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 urinary flow.
Item 9. A herbal mixture A containing Poria Sclerotium and Shazenshi, a herbal mixture B containing Poria Sclerotium, Cinnamon and Bushi, and/or an extract thereof for use in treating diseases associated with weak urinary flow.

The present disclosure provides a pharmaceutical product that increases urinary flow.

The urinary flow increaser of the present disclosure is characterized by containing herbal mixture A containing Poria columbine and Shazenshi, herbal mixture B containing Poria columbine, Cinnamon bark and Bushi, and/or extracts thereof. The urinary flow increaser of the present disclosure is described in detail below.

The urinary flow increaser of the present disclosure contains, as active ingredients, herbal mixture A containing Poria Sclerotium and Shazenshi, herbal mixture B containing Poria Sclerotium, Cinnamon and Bushi, and/or extracts thereof.

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 urinary flow, preferred are 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 Root, Takusha, Poria columbine, Peony Pea, Cinnamon Bark, and Bushi.

Herbal mixture B is not particularly limited as long as it contains Poria Root, Cinnamon Bark, and Atractylodes Root, and may contain any other herbal medicines, but from the viewpoint of enhancing the effect of increasing urinary flow, preferred are herbal mixture b consisting of Rehmannia Root, Cornus Cherry, Dioscorea Root, Atractylodes Root, Poria Root, Peony Bark, Cinnamon Bark, and Atractylodes Root, and herbal mixture ab consisting of Goshitsu, Shazenshi, Rehmannia Root, Cornus Cherry, Dioscorea Root, Atractylodes Root, Poria Root, Peony Bark, Cinnamon Bark, and Atractylodes Root.

There are no particular limitations on the mixing ratio of the herbs that make up the herb mixture a, but examples include: Lotus Root 2-5 parts by weight, preferably 3-4 parts by weight; Bakumondou 1.5-4 parts by weight, preferably 2-3 parts by weight; Poria Root 2-4 parts by weight, preferably 2.5-3.5 parts by weight; Ginseng 1.5-5 parts by weight, preferably 2-4 parts by weight; Shazenshi 1.5-3 parts by weight, preferably 2-2.5 parts by weight; Scutellaria Root 1.5-3 parts by weight, preferably 2-2.5 parts by weight; Astragalus Root 1-4 parts by weight, preferably 2-3 parts by weight; Jikoppi 1-3 parts by weight, preferably 2-2.5 parts by weight; and Licorice Root 0.7-2 parts by weight, preferably 0.7-1 part by weight.

There are no particular limitations on the mixing ratio of the herbs that make up herb mixture b, but examples include Rehmannia Root 2.5-8 parts by weight, preferably 6-8 parts by weight; Cornus officinalis 1.5-4 parts by weight, preferably 3-4 parts by weight; Dioscorea Root 1.5-4 parts by weight, preferably 3-4 parts by weight; Licorice Root 1.5-3 parts by weight, preferably 2-3 parts by weight; Poria Root 1.5-3 parts by weight, preferably 2-3 parts by weight; Peony Root 1.5-3 parts by weight, preferably 2-4 parts by weight; Cinnamon Bark 0.5-1 parts by weight, preferably 0.8-1 parts by weight; and Bushi (processed Bushi) 0.25-1 parts by weight, preferably 0.5-1 parts by weight.

There are no particular limitations on the mixing ratio of the herbs that make up the herb mixture ab, but examples include 1-3 parts by weight, preferably 1.5-3 parts by weight, of Goshitsu, 1-3 parts by weight, preferably 1.5-3 parts by weight, of Shazenshi, 1-3 parts by weight, preferably 1.5-3 parts by weight, of Rehmannia Root, 2-8 parts by weight, preferably 2-3 parts by weight, of Cornus officinalis, 1-4 parts by weight, preferably 2-4 parts by weight, of Sanyaku, 1-4 parts by weight, preferably 1.5-4 parts by weight, of Takusha, 1-3 parts by weight, preferably 1.5-3 parts by weight, of Poria Coccinea, 1-4 parts by weight, preferably 1.5-4 parts by weight, of Peony Pearl, 1-4 parts by weight, preferably 1.5-4 parts by weight, of Cinnamon Bark, 0.25-2 parts by weight, preferably 0.5-2 parts by weight, and of Bushi (processed Bushi), 0.25-1 part by weight, preferably 0.5-1 part by weight.

In the urine flow increaser of the present disclosure, the active ingredient is preferably an extract of the above-mentioned herbal mixture from the viewpoint of enhancing the effect of increasing urine flow. In addition, in the urine flow increaser of the present disclosure, the active ingredient is preferably herbal mixture a, herbal mixture b, or an extract thereof, more preferably an extract of herbal mixture a or an extract of herbal mixture b, and even more preferably an extract of herbal mixture a, from the viewpoint of enhancing the effect of increasing urine flow.

The extract form of the above-mentioned herbal mixture may be either a liquid extract such as a liquid extract or a soft extract, or a solid dry extract powder.

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 a high extract concentration to obtain an adsorbed powder.

In the urine flow increaser 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 the dried extract powder itself when a dried extract powder is used, or the amount converted to the amount remaining after removing the solvent when a liquid extract is used, and when the dried extract powder contains additives such as adsorbents added during production, it means the amount excluding the additives.

Other components The urinary flow increasing agent 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 urinary flow increasing agent 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 content of these additives and base is appropriately determined depending on the type of additive and base used and/or the formulation form of the urinary flow enhancer.

In addition, the urinary flow 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 urinary flow 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 depending on the type of components used, etc.

Formulation form The formulation form of the urinary flow increasing agent 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.

Manufacturing Method The manufacturing method of the urinary flow increasing agent of the present disclosure may be to formulate the above-mentioned herbal ingredients according to a conventional formulation method used in the medical field.

The urinary flow-increasing agent of the present disclosure is used for the purpose of increasing the force of urine during urination. The target increase in urinary flow is 1.5 times or more, preferably 2 times or more, more preferably 2.4 times or more of the urinary flow (mL/sec, daily average) before taking the urinary flow-increasing agent of the present disclosure.

The urinary flow-increasing agent of the present disclosure is particularly effective in increasing urinary flow in subjects with nocturia (a condition in which the patient must urinate at least once, preferably at least twice, after going to bed). Therefore, preferred subjects for which the urinary flow-increasing agent of the present disclosure is used include subjects with nocturia.

The urinary flow-increasing agent of the present disclosure can effectively increase urinary flow even in people who do not have urinary disorders, specifically, in subjects who do not have bladder contraction disorders. Therefore, preferred subjects for which the urinary flow-increasing agent of the present disclosure is used include subjects who do not have urinary disorders.

The gender of the target of the application of the urinary flow-increasing agent of the present disclosure is not limited to men or women. The age of the target of the application of the urinary flow-increasing agent of the present disclosure is also 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 range may be, for example, 80 years old or younger, preferably 70 years old or younger.

Dosage and Usage: The urinary flow increaser of the present disclosure is administered orally. The dosage of the urinary flow increaser 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 Poria Sclerotium and Shazenshi Rhizome in terms of the raw herbal medicines 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 Poria Sclerotium, Cinnamon Bark, and Bushi Rhizome in terms of the raw herbal medicines is, for example, 2 to 7 g, preferably 2.4 to 5 g.

The daily dose of the urinary flow enhancer of the present disclosure for humans is, for example, 12 to 35 g, preferably 20 to 25 g, in terms of the total amount of raw herbs of the herb mixture a, and, for example, 1.5 to 3 g, preferably 2 to 2.5 g, in terms of the dried extract powder, in terms of the extract of the herb mixture a; for example, 8 to 22 g, preferably 10 to 14 g, in terms of the total amount of raw herbs of the herb mixture b, and, for example, 1 to 4 g, preferably 1.5 to 2.5 g, in terms of the dried extract powder, in terms of the extract of the herb mixture b; for example, 10 to 35 g, preferably 12 to 20 g, in terms of the total amount of raw herbs of the herb mixture ab, and, for example, 2 to 5 g, preferably 2 to 3 g, in terms of the dried extract powder, in terms of the extract of the herb mixture ab.

The frequency of administration of the urinary flow-increasing agent of the present disclosure is 1 to 3 times a day, preferably 2 times a day. There are no particular limitations on the timing of administration, and the agent may be administered before, after, or between meals, but administration before (30 minutes before a meal) or between meals (2 hours after a meal) is preferred.

The period for taking the urinary flow-increasing agent of the present disclosure is, 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. There is no particular limit to the upper limit of the period for taking the agent, but since the urinary flow-increasing effect of the urinary flow-increasing agent of the present disclosure appears relatively quickly, the period for taking the agent may be, for example, 2 weeks or less, 10 days or less, or 1 week or less.

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

(1) Preparation of urinary flow enhancer (1-1) Extract of herbal mixture a 3.5 parts by weight of Lotus Root, 2.1 parts by weight of Bakumondo, 2.8 parts by weight of Poria Coccus Rhizome, 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, 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 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 of 150°C.

(1-2) Extract of herbal mixture b 2.5 parts by weight of Rehmannia Root, 1.5 parts by weight of Cornus Fruit, 1.5 parts by weight of Dioscorea Radix, 1.5 parts by weight of Atractylodes Rhizome, 1.5 parts by weight of Poria Coccus, 1.5 parts by weight of Peony Root, 0.5 parts by weight of Cinnamon Bark, and 0.5 parts by weight of Processed Atractylodes Rhizome 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 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.

(1-3) Extract of herbal mixture a and b 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 Rhizome, 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, 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 a and 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 of 150°C.

(2) Experimental Method Twenty men and women in their 40s to 70s who did not suffer from urinary disorders and suffered from nocturia (getting up to urinate more than twice after going to bed) were divided into four groups (N=5). Each group was given tablets of the extract of herbal mixture a, tablets of the extract of herbal mixture b, tablets of the extract of herbal mixture ab, and tablets of Rokumi-gan extract twice a day, before breakfast and before dinner, for one week. Twenty men and women in their 40s to 70s who did not suffer from urinary disorders and suffered from nocturia were divided into four groups (N=5), and each group was given each tablet under the same conditions as above.

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

Before and one week after starting the drug, the subjects were asked to measure the volume and duration of urine in a paper cup each time they urinated, and to record this in a urination diary. The volume of urine divided by the duration of urination (mL/sec) was used to determine the urine force. The average daily urine force for each subject was calculated, and the average daily urine force was then averaged for each group (average for five subjects). The results for the group administered the extract of herbal mixture a are shown in Table 1 (Table 1A shows the results for subjects with nocturnal frequency of urine, and Table 1B shows the results for subjects without nocturnal frequency of urine), the results for the group administered the extract of herbal mixture b are shown in Table 2 (Table 2A shows the results for subjects with nocturnal frequency of urine, and Table 2B shows the results for subjects without nocturnal frequency of urine), the results for the group administered the extract of herbal mixture a and b are shown in Table 3 (Table 3A shows the results for subjects with nocturnal frequency of urine, and Table 3B shows the results for subjects without nocturnal frequency of urine), and the results for the group administered the extract of herbal mixture a and b are shown in Table 4 (Table 4A shows the results for subjects with nocturnal frequency of urine, and Table 4B shows the results for subjects without nocturnal frequency of urine).

As shown by comparing Table 1A, Table 2A, and Table 3A with Table 4A, urine flow was significantly increased (specifically, 1.7 times or more) in Table 1A, Table 2A, and Table 3A. Also, as shown by comparing Table 1A, Table 2A, and Table 3A with Table 1B, Table 2B, and Table 3B, the increase in urine flow was significant in subjects with nocturia. Herbal mixture b (Table 2A) has the same herbal composition as Rokumi-gan (Table 4A) except that it contains cinnamon and tallow tree, but urine flow was significantly increased in Table 2 (group administered extract of herbal mixture b).

In addition, among Tables 1A, 2A, and 3A, the increase in urinary flow was particularly significant in Table 1A (group administered extract of herbal mixture a) and Table 2A (group administered extract of herbal mixture b).

Claims (6)

A urinary flow increaser comprising herbal mixture A containing Poria columbine and Shazenshi, herbal mixture B containing Poria columbine, Cinnamon bark and Bushi, and/or extracts thereof. The urinary flow increasing agent according to claim 1, which is used to increase urinary flow in a subject suffering from nocturia. The urinary flow increaser according to claim 1, wherein the herbal mixture A is composed of lotus root, Chinese burdock, poria rhizome, ginseng, rhizome, Scutellaria baicalensis, Astragalus membranaceus, Zikkōbi, and liquorice. The urinary flow enhancer according to claim 1, wherein the herbal mixture B is composed of Rehmannia Root, Cornus Cherry, Dioscorea Radix, Takusha Root, Poria Coccinea, Peony Bark, Cinnamon Bark, and Bush Clover. The urinary flow increaser according to claim 1, wherein the herbal mixture A or B is composed of Goshitsu, Shazenshi, Rehmannia Root, Cornus Cherry, Dioscorea Radix, Takusha, Poria Coccinea, Peony Pea, Cinnamon Bark, and Bushi. The urinary flow increasing agent according to claim 1, which is used to increase urinary flow in a subject without urinary dysfunction.