JP2024015395A - Hydragogue agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a pharmaceutical composition with an enhanced hydragogue action.

SOLUTION: Blending a pharmaceutical composition containing boi-ogi-to extract with a glucosamine compound enables an enhanced hydragogue action.

SELECTED DRAWING: None

COPYRIGHT: (C)2024,JPO&INPIT

Description

TECHNICAL FIELD The present invention relates to a water-use agent.

Abnormal or unevenly distributed water flow in the body is called ``humidity,'' and the medicinal effects of moisture treatment are achieved through water utilization. Known Chinese herbal medicines used for "Nisho" include Goreisan, Bokiokito, Ireito, and Hachimijiogan (Non-Patent Document 1).

Among these, Hokiokito is said to have ``effects of air supply and water utilization, and is recommended for people with relatively weak physical strength who complain of excessive sweating, wetting water, and general malaise, etc.''・It is used to target symptoms such as joint edema and decreased urine output.'' It is used to target symptoms such as joint edema and decreased urine output. It is known to be effective in reducing pain and swelling (Non-Patent Document 2). In other words, for people who have poor water metabolism and excess water accumulates in their bodies, Hokiokito tightens the body by working on water metabolism and removing swelling (through its water-use effect).

Basic knowledge about the pathology and treatment of water stagnation, Phil Chinese Medicine No. 15, p13-16, [online], [searched on December 10, 2020], Internet <URL: https://www.philkampo.com/ pdf/phil15/phil15-06.pdf＞ Pharmaceutical interview form, Chinese herbal preparation Teikoku Hokito extract granules, August 2017

The onset of effects of Chinese herbal medicines is generally slow, and it is desirable that the expected water-use effects of water-use drugs be further enhanced. In particular, in cases where joint fluid accumulation (articular edema) is accompanied by pain, it is desirable to experience the effects of Chinese herbal medicine as soon as possible. Therefore, an object of the present invention is to provide a pharmaceutical composition with enhanced water utilization effect.

As a result of intensive studies, the present inventor unexpectedly discovered that the water utilization effect is enhanced by incorporating a glucosamine compound into the Boba Okito extract. The present invention was completed through further studies based on this knowledge.

That is, the present invention provides the inventions of the following aspects.
Item 1. A water-use agent containing Bokkito extract and glucosamine compounds.
Item 2. Item 2. The water-use agent according to item 1, which is used to increase urine output.
Item 3. Item 3. The water-use agent according to Item 1 or 3, which is used for improving joint pain.
Item 4. A method for promoting water metabolism, which comprises administering an effective amount of Bokkito extract and a glucosamine compound to a subject who needs to promote water metabolism.
Item 5. Use of Bokkito extract and glucosamine compound for the production of a water-conserving agent.
Item 6. Bobaokito extract and glucosamine compound for use in the treatment of water metabolism abnormalities.

According to the present invention, a pharmaceutical composition with enhanced water utilization effect is provided.

The present disclosure is characterized in that it contains a Bokkito extract and a glucosamine compound, and is used as a water-use agent. The water use agent of the present disclosure will be described in detail below. In this specification, a numerical range indicated by two numerical values and "~" includes the two numerical values as the lower limit and upper limit. For example, the expression 2 to 15% by weight means 2% by weight or more and 15% by weight or less.

Hoki-Kokito Extract Boki-Kokito is a herbal medicine prescription listed in the "New General Chinese Herbal Prescription Guide" (supervised by Yukihiro Goda and Takashi Hakamazuka, edited by the Japan Traditional Chinese Herbal Medicine Preparation Association, published by Jiho Co., Ltd.). Preferred examples include mixed herbal medicines consisting of japonica, astragalus, jutsu (including jujutsu and jujutsu, preferably jutsu jutsu), ginger, japonica, and licorice. In addition, Bokiokito contains the mixtures listed in the letters related to herbal medicines that are currently frequently used, as stipulated in the "Basic Handling Policy for Chinese Herbal Preparations" established by the Kampo Herbal Medicine Investigation Committee. Includes crude drugs (Chinese herbal prescriptions).

The proportions of each crude drug that make up Hokiokito are 4 to 5 parts by weight of Bowie, 5 parts by weight of Aspergillus, 3 parts by weight of Jutsu, 1 to 1.5 parts by weight of Gyoukyo, 3 to 4 parts by weight of Taisou, Examples include 1.5 to 2 parts by weight of licorice.

Hokiokito extract can be obtained as an extract liquid by extracting the above mixed herbal medicine and concentrating the obtained extract liquid as necessary, or it can be obtained as an extract powder by drying the extract liquid. It may be obtained as

The extraction solvent used in the extraction process in the production of the Bokiokito extract is not particularly limited, but examples include water or aqueous ethanol, and preferably water. The drying process is not particularly limited, and may be performed using a known method such as spray drying, or by adding an appropriate adsorbent (for example, silicic anhydride, starch, etc.) to a soft extract with increased concentration of the extract liquid. Examples include a method of making an adsorbed powder.

In the water-use agent of the present disclosure, the content of the Bokiokito extract is not particularly limited as long as it achieves the effects of the present invention, but is, for example, 5 to 98% by weight, preferably 30 to 95% by weight in terms of dry extract amount. %, more preferably 50 to 90% by weight. The term "converted amount of dry extract" refers to the amount itself when using a dry extract (extract powder), and when using an extract liquid or soft extract, it refers to the amount converted to the remaining amount after removing the solvent. Moreover, when the dry extract powder contains additives such as adsorbents added during production, the amount is the amount excluding the additives.

Glucosamine Compound In the hydration agent of the present disclosure, the glucosamine compound refers to glucosamine, its derivatives, and/or salts thereof. The water-use agent of the present disclosure has enhanced water-use effect by incorporating a glucosamine compound.

Glucosamine is an amino sugar also called 2-amino-2-deoxyglucose or chitosamine. As glucosamine, any of D-form, L-form and DL-form may be used.

Derivatives of glucosamine include compounds in which the hydroxyl group or amino group of glucosamine is substituted with an alkyl group or an acyl group. As a specific example of a derivative of glucosamine, the amino group of glucosamine can be replaced with an alkyl group having 1 to 6 carbon atoms (specifically, a methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group). , tert-butyl group, etc.), or a compound substituted with an acyl group having 2 to 20 carbon atoms (specifically, an acetyl group, a benzoyl group, etc.). These glucosamine derivatives may be used alone or in combination of two or more. Among these glucosamine derivatives, preferred are compounds in which the amino group of glucosamine is substituted with a methyl group, ethyl group, or acetyl group, and more preferably N-acetylglucosamine in which the amino group of glucosamine is substituted with an acetyl group. Can be mentioned.

The salt of glucosamine or its derivative is not particularly limited as long as it is a pharmacologically or physiologically acceptable salt. Specific examples of salts of glucosamine and its derivatives include organic acid salts of glucosamine or its derivatives (e.g., monocarboxylic acid salts such as acetate, trifluoroacetate, butyrate, palmitate, and stearate; fumaric acid) Salts, polycarboxylic acid salts such as maleate; oxycarboxylic acid salts such as lactate, tartrate, citrate, succinate, malonate; methanesulfonate, toluenesulfonate, tosylate etc.), inorganic acid salts of glucosamine or its derivatives (e.g. hydrochloride, sulfate, nitrate, hydrobromide, phosphate, etc.), salts of glucosamine or its derivatives with organic bases, etc. , salts of glucosamine or its derivatives with inorganic bases (for example, ammonium salts; salts with metals such as alkali metals (sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), aluminum, etc.). These salts of glucosamine or its derivatives may be used alone or in combination of two or more. Among these salts of glucosamine or its derivatives, glucosamine hydrochloride and glucosamine sulfate are preferred, and glucosamine hydrochloride is particularly preferred.

These glucosamine compounds may be compounds obtained from natural products or may be synthetic compounds.

In the water utilization agent of the present disclosure, the content of the glucosamine compound is not particularly limited, and can be appropriately set depending on the desired degree of water utilization enhancement effect. For example, the content (total amount) of glucosamine compounds in the water-use agent of the present disclosure is 2 to 95% by weight, preferably 5 to 70% by weight, and more preferably 10 to 50% by weight.

In the water utilization agent of the present disclosure, the ratio of the contents of the Boba Okito extract and the glucosamine compound is not particularly limited, and can be appropriately set depending on the desired degree of water utilization enhancement effect. For example, the content of glucosamine compounds per 1 part by weight of Bokito extract (in terms of dry extract amount) is 0.01 to 10 parts by weight, preferably 0.05 to 5 parts by weight, more preferably 0.1 to 10 parts by weight. Examples include 3 parts by weight, more preferably 0.15 to 1 part by weight, even more preferably 0.2 to 0.5 parts by weight or 0.2 to 0.3 parts by weight.

Other Ingredients The water-utilizing agent of the present disclosure may or may not contain additives and/or bases depending on the formulation form, in addition to the Bobaokito extract and the glucosamine compound. good. Additives and bases that may or may not be included are not particularly limited as long as they are pharmaceutically acceptable, but include excipients, binders, disintegrants, lubricants, isotonic agents, etc. additives, plasticizers, dispersants, emulsifiers, solubilizing agents, wetting agents, stabilizers, suspending agents, adhesives, coating agents, brightening 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, ultraviolet inhibitors, preservatives, flavorings , fragrances, powders, thickeners, pigments, chelating agents, etc. These additives and bases may be used alone or in combination of two or more. Further, the contents of these additives and bases are appropriately set depending on the types of additives and bases used, the formulation form of the water-use agent, and the like.

The water-use agent of the present disclosure may or may not contain other pharmacological ingredients in addition to the Bobaokito extract and the glucosamine compound. The types of pharmacological ingredients that may or may not be included are not particularly limited, but include, for example, antacids, stomachic agents, digestive agents, intestinal regulating agents, antispasmodics, mucosal repair agents, anti-inflammatory agents, astringents, antiemetics, Antitussives, expectorants, anti-inflammatory enzymes, sedative-hypnotics, antihistamines, caffeine, cardiac diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, herbal medicines, herbal medicine extract powder, vitamins, menthol, etc. . These pharmacological ingredients may be used alone or in combination of two or more. Moreover, the content of these pharmacological components may be appropriately set from known ones depending on the type of pharmacological components to be used.

Formulation The form of the hydration agent of the present disclosure is not particularly limited as long as it can be administered orally, but examples include powders, fine granules, granules (including dry syrup), tablets, pills, and capsules. solid preparations such as agents (soft capsules, hard capsules); semi-solid preparations such as jelly preparations; liquid preparations such as solutions, suspensions, and syrups. Among these formulation forms, solid formulations are preferred from the viewpoint of stability of contained ingredients, portability, etc.

In order to prepare the water-use agent of the present disclosure into the above-mentioned formulation form, the preparation is performed using the Bobakokito extract and the glucosamine compound, as well as additives, bases, and/or pharmacological ingredients added as necessary. It may be formulated according to the usual formulation method employed in .

Applications The water utilization agents of the present disclosure may be used for any purpose that takes advantage of enhanced water utilization. That is, the water-use agent of the present disclosure is used for the purpose of promoting water metabolism. The water-use agent of the present disclosure may be applied to any subject with symptoms of water retention (abnormal water metabolism), specifically, swelling, joint fluid accumulation (arthritis edema), or joints caused by this (e.g. knee joints). etc.) and/or decreased urine output. Furthermore, the subject to whom the water-use agent of the present disclosure is applied may be obese (BMI is 25 or more) or may not be obese.

Therefore, specific examples of uses for promoting water metabolism include treatment of water retention (abnormal water metabolism), improvement of swelling, improvement of joint fluid accumulation (joint edema) or joint pain caused by it (e.g. knees, etc.), and urination. Examples include an increase in quantity. The use of increasing urine output includes the purpose of obtaining it as a direct improvement effect in subjects with decreased urine output, but it also includes the purpose of increasing urine output as a direct improvement effect in subjects with decreased urine output. It also includes the purpose of obtaining a sign of improvement (other than a decrease in dose) (obtaining a feeling of effectiveness).

Dosage/Usage The hydric agent of the present disclosure is administered orally. The dosage of the hydration agent of the present disclosure is appropriately set depending on the target symptoms, age, etc. For example, the daily intake amount of Hoba Okito extract in terms of dry extract amount is 1,300 to 6,000 mg, preferably 2,000 to 4,800 mg, and more preferably 3,000 to 4,000 mg.

The timing of taking the hydration agent of the present disclosure is not particularly limited, and may be taken before meals, after meals, or between meals, but preferably before meals or between meals.

EXAMPLES Hereinafter, the present invention will be specifically explained with reference to Examples, but the present invention is not limited to these Examples.

As a raw material crude drug for the preparation of Hokiokito extract powder , use the ratio of 1 part by weight of ginger (by weight, the same applies hereinafter), 3 parts by weight, 5 parts by weight, 3 parts byakujutsu, 5 parts by volume, and 1.5 parts by weight of licorice. , extracted at about 90°C for 45 minutes using 10 times the weight of water, centrifuged to obtain an extract, concentrated under reduced pressure and dried using a freeze dryer to obtain Bokiokito extract powder. Ta. In addition, the daily dose of the obtained Bokkito extract powder was 3200 mg.

A water-use agent (Comparative Example 1) consisting of Boki-Okito extract powder, and a water-use agent (Comparative Example 1) consisting of Boki-Okito extract powder and 0.23 parts by weight of glucosamine hydrochloride per 1 part by weight of Boki-Okito extract powder. Example 1) was prepared.

Experimental method: For 18 men and women (BMI: 25.3 ± 2.2) who had pain due to joint edema in their knees, 8 of them took the water-use agent of Example 1, and 10 of them took the water-use agent of Comparative Example 1. I let it happen. The daily dose (amount of 3200 mg of Bobakokito extract powder) was divided into two doses a day for one week.

After one week of administration, the percentage of people who observed water metabolism promoting effects such as increased urine output and improvement in knee pain due to joint edema was 75% in Example 1 and 10% in Comparative Example 1. In other words, in Example 1, a significantly significant water utilization enhancement effect was observed.

Among the water metabolism promoting effects, the percentage of people who observed an increase in urine volume within one week of taking the drug was 63% in Example 1 and 10% in Comparative Example 1. In addition, in Comparative Example 1, when the dosing period was further extended, the dosing period required for the percentage of people who observed an increase in urine output to reach 60%, the same as in Example 1, was 6 weeks. . In this respect as well, in Example 1, a much more remarkable effect of enhancing the water use effect was observed, and the effect was felt much more quickly.

Among the water metabolism promoting effects, the percentage of people who observed improvement in knee pain within one week of taking the drug was 25% in Example 1 and 0% in Comparative Example 1. In Comparative Example 1, when the period of administration was further extended, no patient showed improvement in knee pain even after 6 weeks. The prevailing opinion is that glucosamine compounds have no effect on the knee joint, such as reducing knee pain (Wandel S, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee : network meta-analysis. BMJ. 2010.). In contrast, in Example 1, significant effects were observed in that knee pain was improved in just one week.

Claims (3)

A water-use agent containing Bokkito extract and glucosamine compounds. The hydrating agent according to claim 1, which is used to increase urine volume. The water-use agent according to claim 1, which is used for improving joint pain.