JP7500300B2 - Urine concentration promoter - Google Patents

Description

The present invention relates to a urine concentration promoter.

Urinary problems include polyuria and frequent urination, and definitive diagnostic methods have been established for each. For both clinical polyuria and frequent urination, symptoms may include nocturia, which is an increase in the number of times urination occurs at night (Non-Patent Document 1).

Polyuria is defined as a condition in which the daily urine volume exceeds 3 liters, and is further divided into cases in which there is too much water (water diuresis) and cases in which there is too much solute (osmotic diuresis), and definitive diagnostic methods for these conditions have been established (Non-Patent Document 2). A representative disease of the former is diabetes insipidus, and a representative disease of the latter is diabetes mellitus. In both cases, polyuria is accompanied by thirst, and is maintained by increased thirst. Methods for distinguishing between these conditions include a method in which a urine specific gravity lower than 1.007 indicates water diuresis, and a urine specific gravity higher than 1.025 indicates osmotic diuresis, and for greater accuracy, the osmotic pressure of the urine can be measured (Non-Patent Document 2).

Lifestyle guidance is often used to deal with polyuria. This is because it is not rare that excessive water intake is found to be the cause of polyuria through interviews etc. (Non-Patent Document 3). Elderly people are prone to dehydration and require special care, but those who are not dehydrated are advised to avoid drinking too much water. In practice, it is considered appropriate to advise people to drink 2-2.5% of their body weight per day (Non-Patent Document 4).

On the other hand, frequent urination reduces the amount of urine that can be stored because the bladder's smooth muscles are in an excessively contractile state, resulting in a variety of urination problems, such as a sudden urge to urinate, increased frequency of toilet visits, and inability to hold on (Non-Patent Document 5). In addition, the bladder is dependent on complex nerve control to store urine and contract when the amount of urine reaches an appropriate level, while at the same time relaxing the urethral sphincter, so frequent urination is often associated with such nerve disorders (bladder neurosis) (Non-Patent Document 2).

Chinese herbal medicine is known to treat clinical frequent urination, one example being Seishinrenshi-in. Seishinrenshi-in has been shown to improve frequent urination by suppressing the contraction of the bladder smooth muscle (Non-Patent Document 5), and has been shown to provide an extremely high degree of improvement of 100% in bladder neurosis (Non-Patent Document 6).

MSD Manual Professional Edition / Urological Disorders / Symptoms of Genitourinary Disorders / Polyuria "Guidelines for Clinical Laboratory Tests 2005/2006", Japan Society of Clinical Laboratory Medicine, Chapter 1: Symptoms, Kidneys, 13. Polyuria and frequent urination Journal of the Japanese Geriatrics Society, Vol. 50, No. 4 (2013: 7) 434-439 Committee for the Creation of Guidelines for the Treatment of Nocturnal Pollution: Guidelines for the Treatment of Nocturnal Pollution (ed. by the Committee for the Creation of Guidelines for the Treatment of Nocturnal Pollution, Japan Society of Urinary Function), Blackwell Publishing, Tokyo, 2009. Agribio, 48(48) vol.2(1), 2018 Urological Surgery 1998 11(10), 1307-1311

For polyuria, it is necessary to fundamentally increase the concentration of urine, and the mainstream approach is to advise patients to avoid drinking too much water. However, for elderly people and those taking medication, there is a risk of dehydration and the risk of cerebral infarction and myocardial infarction, making it difficult to provide the above advice appropriately. On the other hand, in light of the recent increase in health awareness and the growing interest in self-medication, where people deal with mild physical ailments themselves, it would be desirable to be able to use herbal medicines as a means of dealing with polyuria. However, there are no known herbal medicines that can promote urine concentration without the need to control the amount of water consumed. Seishinrenshi-in has been used clinically to treat frequent urination, but its mechanism is to inhibit the contraction of urethral smooth muscle and calm the nerves, and its effect of promoting urine concentration in polyuria was not known.

The present invention aims to provide a herbal medicine that can promote urine concentration.

After extensive research, the inventors unexpectedly discovered that Seishinrenshiin has the effect of promoting urine concentration. Based on this finding, the present invention was completed through further research.

That is, the present invention provides the following aspects.
Item 1. A urine concentration promoter containing Seishinrenshi-in extract.
Item 2: The urine concentration promoter according to Item 1, which is used for water diuresis.

The present invention provides a herbal medicine that can promote urine concentration, making it possible to improve polyuria.

The urine concentration promoter of the present invention is characterized by containing Seishinrenshiin extract. The urine concentration promoter of the present invention is described in detail below.

The urine concentration promoter of the present invention contains Seishinrenshiin extract as an active ingredient . Seishinrenshiin is described in the Chinese Ming Dynasty medical book "Banbyo Kaishun" and is a mixed herbal medicine containing Lotus Root, Bakumondo Root, Poria Cocos, Ginseng, Shazenshi, Scutellaria Root, Astragalus Root, Zikkoppi, and Licorice.

In the present invention, there is no particular restriction on the mixing ratio of the herbs that make up Seishinrenshi-in, but typically includes 2-5 parts by weight of Lotus Root, preferably 3-4 parts by weight; 1.5-4 parts by weight of Bakumondou, preferably 2-3 parts by weight; 2-4 parts by weight of Poria Root, preferably 2.5-3.5 parts by weight; 1.5-5 parts by weight of Ginseng, preferably 2-4 parts by weight; 1.5-3 parts by weight of Shazenshi, preferably 2-2.5 parts by weight; 1.5-3 parts by weight of Scutellaria Root, preferably 2-2.5 parts by weight; 1-4 parts by weight of Astragalus Root, preferably 2-3 parts by weight; 1-3 parts by weight of Jikoppi, preferably 2-2.5 parts by weight; and 0.7-2 parts by weight of Licorice, preferably 0.7-1 part by weight.

Suitable examples of herbal medicine preparations used in the manufacture of the Seishinrenshiin extract used in the present invention include 3.5 parts by weight of Lotus Root, 2.1 parts by weight of Bakumondou, 2.8 parts by weight of Poria Coccinea, 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 Jikoppi, and 0.7 parts by weight of Licorice.

The extract form of Seishinrenshiin can be either a liquid extract such as a liquid extract or a soft extract, or a solid dried extract powder.

The liquid extract of Seishinrenshiin can be obtained by subjecting the mixed herbs according to Seishinrenshiin to an extraction process, and concentrating the resulting extract as necessary. The extraction solvent used in the extraction process is not particularly limited, and examples thereof include water or aqueous ethanol, preferably water. Furthermore, the dried extract powder of Seishinrenshiin can be obtained by drying the liquid extract. The drying method is not particularly limited, and examples thereof include the spray drying method and 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 present invention, the Seishinrenshi-in extract may be an extract prepared by the method described above, or a commercially available product. For example, Seishinrenshi-in dried extract powder is known as Seishinrenshi-in Dried Extract-Q (manufactured by Nippon Funa Yakuhin Co., Ltd.) or Seishinrenshi-in Dried Extract-F (manufactured by Alps Yakuhin Co., Ltd.), and is also commercially available.

In the urine concentration promoter of the present invention, the content of Seishinrenshiin extract is not particularly limited as long as the effect of the present invention is achieved, but is usually 10 to 100% by weight, preferably 20 to 90% by weight, more preferably 40 to 80% by weight, and even more preferably 60 to 70% by weight, calculated as the amount of dried extract powder of Seishinrenshiin extract. In the present invention, the amount of dried extract powder of Seishinrenshiin refers to the amount of the dried extract powder itself when a dried extract powder of Seishinrenshiin is used, and refers to the amount converted to the amount remaining after removing the solvent when a liquid extract of Seishinrenshiin is used. In addition, when the dried extract powder of Seishinrenshiin contains additives such as adsorbents added during production, the amount refers to the amount excluding the additives.

Other components The urine concentration promoter of the present invention may be composed of the seishinrenshiin extract alone, or may contain additives and bases according to the formulation. Such additives and bases are not particularly limited as long as they are pharmacologic 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 inhibitors, preservatives, flavorings, fragrances, powders, thickeners, dyes, chelating agents, etc. 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 used, the formulation form of the urine concentration promoter, etc.

In addition, the urine concentration promoter of the present invention may contain other nutritional components and pharmacological components as necessary in addition to the Seishinrenshiin extract. Such nutritional components and pharmacological components 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, 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 set depending on the type of components used.

Formulation form The formulation form of the urinary concentration promoter of the present invention is not particularly limited, as long as it can be administered orally. Examples of the formulation form include 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 includes granules or tablets.

Production Method The method for producing the urine concentration promoter of the present invention involves formulating the above-mentioned herbal ingredients in accordance with a conventional formulation method employed in the medical field.

Uses The urine concentration promoter of the present invention is used for the purpose of promoting urine concentration. Specific examples of symptoms that require promotion of urine concentration include polyuria. Clinically, polyuria is defined as a symptom in which the amount of urine per day exceeds 3 liters. Polyuria includes symptoms in which there is a lot of water itself (clinically, referred to as water diuresis, for example, diabetes insipidus) and symptoms in which there is a lot of solutes (clinically, referred to as osmotic diuresis, for example, diabetes mellitus). These symptoms have established definitive diagnostic methods, and all of them have in common the fact that the urine is thin. Among these symptoms, the urine concentration promoter of the present invention is preferably applied to water diuresis.

The urine concentration promoter of the present invention is also preferably used for people who drink too much water (drinking more than 2.5% of their body weight per day) but have difficulty controlling the amount of water they drink, such as people who are prone to dehydration, more specifically elderly people (specifically those aged 65 or older) who have difficulty retaining water in the body, and people taking diuretic drugs such as antihypertensive drugs.

Dosage and Usage: The urine concentration promoter of the present invention is administered orally. The dosage of the urine concentration promoter of the present invention is appropriately set depending on the age, constitution, severity of symptoms, etc. of the person to be administered. For example, the dosage is about 1500 to 5000 mg, preferably about 2000 to 3000 mg, more preferably about 2200 to 2500 mg of the dried extract powder of Seishinrenshi-in extract per day for humans, and is administered 1 to 3 times, preferably twice 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).

In addition, since the urine concentration promoting effect of the urine concentration promoting agent of the present invention is achieved by continuous administration, it is preferable to take the urine concentration promoting agent of the present invention continuously (specifically, for one week or more, preferably for two weeks or more).

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 urine concentration promoter As raw herbal medicines, 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 Jikoppi, and 0.7 parts by weight of Licorice were used, which were 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 Seishinrenshi-in extract powder. The obtained Seishinrenshi-in extract powder was 2238 mg per 21.7 g of raw herbal mixture. The drying using a spray dryer was performed by dropping the extract into an atomizer at a rotation speed of 10,000 rpm and supplying hot air at 150°C.

(2) Experimental Method Aged mice (C57BL/6J mice, 80 weeks old, male, 20 mice) were used as experimental animals. It was confirmed that these mice drank more water than young mice (C57BL/6J mice, 9 weeks old, male), and they were used as a model of excessive water drinking. These aged mice were divided into a control group and a group administered the seishinrenshi extract (N=10 for each group). The control group was fed a normal diet (CE-2 diet) ad libitum for 3 weeks, and the seishinrenshi extract group was fed a normal diet mixed with 4% by weight of the seishinrenshi extract ad libitum for 3 weeks. Urine was collected from each group before and after the test, and urine concentrations (specific gravity and osmolality) were measured. The results are shown in Table 1.

As shown in Table 1, a significant increase in osmotic pressure and specific gravity was observed in the group administered Seishinrenshiin extract, demonstrating that administration of Seishinrenshiin extract promoted urine concentration.

Claims (2)

A urine concentration promoter that contains Seishinrenshi-in extract. The urine concentration promoter according to claim 1, which is used for water diuresis.