JP2024034027A - Chinese medicine extract formulation - Google Patents

Abstract

To provide a Chinese medicine extract formulation, taken by dissolving in water when used, wherein the formulation prescription can reduce gastrointestinal symptoms (specifically upper gastrointestinal symptoms) even when consumed without eating.SOLUTION: A Chinese medicine extract formulation comprises Chinese medicine extract, and a sweetener selected from the group consisting of chlorinated sugars, sulfonamide compounds, monosaccharides, disaccharides, and oligosaccharides, and is taken by dissolving in water. The Chinese medicine extract can reduce the side effects of upper gastrointestinal symptoms.SELECTED DRAWING: None

Description

The present invention relates to Chinese herbal extract preparations. More specifically, the present invention relates to a Chinese herbal extract formulation with reduced side effects of upper gastrointestinal symptoms.

Chinese herbal medicines are generally said to have fewer side effects than Western medicines, but since they are pharmaceuticals, they are not free from side effects (Non-Patent Document 1). The most common side effects caused by Chinese herbal medicines are gastrointestinal symptoms such as heavy stomach pain (Non-patent Documents 2 and 3). In particular, among the crude drugs used in Chinese herbal medicine, ephedra, rhododendron, asperium, and nebula tend to cause gastrointestinal symptoms (Non-patent Documents 4, 5).

To deal with such side effects of gastrointestinal symptoms, it is common to change the timing of administration to after meals (Non-Patent Document 5).

“A Healthy Life with Kampo”, [online], April 2017, Japan Traditional Chinese Herbal Medicine Preparation Association, [Retrieved August 19, 2020], Internet <URL: https://www.nikkankyo.org/kampo/ column/pdf/kampo04.pdf＞ “Check the table: Chinese herbal medicines also have side effects! Their causes and symptoms to be aware of”, [online], LIFULL senior Co., Ltd., [searched on August 19, 2020], Internet <URL: https://kaigo. homes.co.jp/manual/healthcare/medicine/about_kanpo/fukusayo/＞ “Kampo Square No. 398 (2021.12.22) Side effects of herbal medicine No. 6 Digestive symptoms caused by herbal medicine”, [online], December 22, 2021, Accent Co., Ltd., [searched on August 19, 2021], Internet <URL: https://www.kampo-s.jp/web_magazine/back_number/398/fukusayou-398.htm> “Medicine Story 18 Chinese Herbal Medicine - Are there any side effects?”, [online], July 1, 1998, All Japan People's Medical Federation, [Retrieved August 19, 2020], Internet <URL: https://www. min-iren.gr.jp/?p=26771＞ “Web Iji Shinpo No. 5092 Academic Special Feature - Academic Special Feature: Be careful here! Side effects and how to use Chinese herbal medicine”, [online], November 27, 2021, Nihon Iji Shinposha, [August 19, 2021] Search], Internet <https://www.jmedj.co.jp/journal/paper/detail.php?id=18493>

As mentioned above, changing the timing of administration to after meals is one way to reduce the side effects of Chinese herbal medicines on gastrointestinal symptoms, but it will not be possible to maximize the effects of Chinese herbal extract preparations. The method of maximizing the effects of Chinese herbal extract preparations is to take them on an empty stomach and to dissolve them in water. On the other hand, considering that there is generally a positive correlation between the level of effectiveness and the level of side effects of medicines, it is essentially difficult to reduce side effects even if Chinese herbal extract preparations are dissolved in water and taken on an empty stomach. be.

Therefore, an object of the present invention is to provide a Chinese herbal extract formulation that can be dissolved in water and taken before use, and can reduce gastrointestinal symptoms, specifically upper gastrointestinal symptoms, even when taken on an empty stomach. do.

The inventors of the present invention have conducted extensive research and have discovered that by adding a prescribed sweetener to a Chinese herbal extract preparation that is dissolved in water and taken before use, it is possible to reduce upper gastrointestinal symptoms even when taken on an empty stomach. I found it. 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 Chinese herbal extract preparation containing a Chinese herbal extract and a sweetener selected from the group consisting of chlorinated sugars, sulfonamide compounds, monosaccharides, disaccharides, and oligosaccharides, which is dissolved in water and taken.
Item 2. Item 2. The Chinese herbal extract formulation according to Item 1, wherein the Chinese herbal extract is a Chinese herbal extract containing nebula, acanthus, sperum, and/or ephedra.
Item 3. Item 3. The Chinese herbal extract preparation according to item 1 or 2, wherein the herbal medicine extract is an extract of Shimotsuto, Dokkatsu Kakkonto, and/or Yokukansan.
Item 4. The sweetener consists of sucralose, acesulfame salt, saccharin and its salt, cyclamic acid and its salt, glucose, fructose, honey, isomerized sugar, invert sugar, sucrose, maltose, lactose, lactulose, trehalose, palatinose, and trehalulose. The Chinese herbal extract preparation according to any one of Items 1 to 3, selected from the group.
Item 5. Item 5. The Chinese herbal extract according to any one of Items 1 to 4, wherein the content of the sweetener is 0.05 to 2 parts by weight based on 100 parts by weight of the Chinese herbal extract.
Item 6. Item 2~, wherein the content of the sweetener is 0.01 to 2.5 parts by weight with respect to 100 parts by weight of the total amount of Nebula japonica, Ephedra, Ephedra, and Ephedra in the original herbal medicine used to extract the Chinese herbal extract. 5. The Chinese herbal extract according to any one of 5.
Section 7. The Chinese herbal extract according to any one of items 2 to 6, wherein the dose per dose is 1.5 to 6 g of the total amount of Ephedra, Ephedra, Ephedra, and Ephedra in the original medicine used for extracting the Chinese herbal extract. .

According to the present invention, a Chinese herbal extract preparation that is dissolved in water and taken before use is provided with a formulation that can reduce gastrointestinal symptoms, specifically upper gastrointestinal symptoms, even when taken on an empty stomach.

The Chinese herbal extract preparation of the present invention is characterized in that it contains a Chinese herbal extract and a predetermined sweetener, and is dissolved in water and drunk. Hereinafter, the Chinese herbal extract preparation of the present invention will be described in detail.

Chinese Herbal Extract The Chinese herbal extract used in the present invention is not particularly limited. Since the Chinese herbal extract preparation of the present invention is excellent in reducing side effects of upper gastrointestinal symptoms, it is possible to effectively reduce the side effects even if the Chinese herbal extract contains herbal medicines that are particularly likely to cause these side effects. From this point of view, suitable Chinese herbal extracts include extracts of Chinese herbal medicines containing nebula, acanthus, argentina, and/or ephedra. Particularly preferred examples of Chinese herbal extracts used in the present invention include extracts of Shimotsuto, Dokkatsu Kakkonto, and Yokukansan. These Chinese herbal extracts may be used alone or in combination.

Dokkatsu Kakkonto is a herbal medicine mixture consisting of kakkon, keihi, peony, ephedra, dokukatsu, ginger, rhododendron, radish, and licorice. The mixing ratio of the herbal medicines constituting the herbal medicine preparation used for manufacturing Dokatsu Kakkonto extract is not particularly limited, but for example, 2.5 to 5 parts by weight of kakkon, 1.5 to 3 parts by weight of cinnamon bark, and 1.5 parts of peony. ~3 parts by weight, 1 to 2 parts by weight of ephedra, 1 to 2 parts by weight of doku cutlet, 0.1 to 2 parts by weight of ginger, 2 to 4 parts by weight of Japanese sagebrush, 0.5 to 2 parts by weight of Japanese radish, and 0.5 parts of licorice ~2 parts by weight. Shimotsuto is a herbal medicine mixture consisting of peonies, rhododendrons, nebula, and acanthus. The mixing ratio of the herbal medicines constituting the herbal medicine preparation used for the production of the Shimotsuto extract is not particularly limited, but for example, 1.5 to 5 parts by weight of Peony, 1.5 to 5 parts by weight of Rhododendron, and 1.5 parts by weight of Cucumber. -5 parts by weight, and 1.5 to 5 parts by weight of Japanese amberjack. Yokukansan is a herbal medicine mixture consisting of Chinese trumpet, Choutōkō, Senkyu, Byakujutsu, Bukryō, Saiko, and Licorice. The mixing ratio of the herbal medicines constituting the herbal medicine preparation used to produce the Yokukansan extract is not particularly limited, but for example, 1.5 to 3 parts by weight of Angelica asparagus, 1.5 to 3 parts by weight of Oriental chinensis, 1. 5 to 3 parts by weight, 2 to 4 parts by weight of sandalwood, 2 to 4 parts by weight of blackberry, 1 to 5 parts by weight of licorice, and 0.75 to 1.5 parts by weight of licorice.

In the Chinese herbal extract formulation of the present invention, the Chinese herbal extract may be contained in the form of a concentrated liquid of the Chinese herbal extract, or may be contained in the form of a dried herbal extract. A concentrated liquid of herbal medicine extract contains a herbal medicine extract and a solvent (for example, the extraction solvent used to extract the herbal medicine extract), and the concentration of the herbal medicine extract (converted amount of dry extract) contained in the concentrated extract is equal to that of the decoction of the herbal medicine. The concentration of the Chinese herbal extract (in terms of dry extract) is higher than that contained in the herbal extract, or the concentration is increased to the extent that it is necessary to dilute it before taking it. A dried herbal extract is a concentrated herbal extract from which the solvent has been further removed.

A concentrated liquid of Chinese herbal extract can be obtained by extracting a crude drug preparation according to a Chinese herbal prescription and concentrating the obtained extract. The extraction solvent used in the extraction process is not particularly limited, and includes water or aqueous ethanol, preferably water. As an extraction treatment method, approximately 10 to 20 times the amount of extraction solvent is added to the crude drug preparation, and the mixture is heated at 40 to 100°C, 50 to 100°C, 60 to 100°C, 80 to 100°C, or 90 to 100°C. An example of this is a method of stirring for about 1 to 3 hours at a moderate temperature for extraction. The concentration method is not particularly limited, and includes, for example, a concentration method under reduced pressure, a membrane concentration method, and a heating concentration method. Moreover, a dried product of a Chinese herbal extract can be obtained by drying a concentrated liquid of a Chinese herbal extract. The drying method is not particularly limited, and examples include freeze-drying, a method of adding an appropriate adsorbent (for example, silicic anhydride, starch, etc.) to a soft extract with increased concentration to form an adsorbent powder, and spray drying. Laws, etc. can be cited.

The content of the Chinese herbal extract (in terms of dry extract) in the Chinese herbal extract preparation of the present invention is not particularly limited and may vary depending on the dosage form of the Chinese herbal extract preparation, but for example, 5 to 25% by weight, preferably 10 to 20% by weight. % is mentioned.

Selected Sweeteners The sweeteners used in the present invention are selected from the group consisting of chlorinated sugars, sulfonamide compounds, monosaccharides, disaccharides, and oligosaccharides.

A specific example of chlorinated sugar is sucralose. Examples of the sulfonamide compound include acesulfame salts (potassium salt, calcium salt, ammonium salt, etc.), saccharin and its salts (sodium salt, potassium salt, etc.), and cyclamic acid and its salts (sodium salt, potassium salt, etc.).

Examples of monosaccharides include glucose, fructose, and mixtures thereof, and examples of the mixtures include honey, high-fructose sugar, and invert sugar. Disaccharides include sucrose, maltose, lactose, lactulose, trehalose, and sucrose isomers, and sucrose isomers include palatinose and trehalulose. Examples of oligosaccharides include coupling sugars and fructooligosaccharides.

These sweeteners may be used alone or in combination. Among these sweeteners, from the viewpoint of increasing the effect of reducing side effects of upper gastrointestinal symptoms, preferable examples include chlorinated sugars, sulfonamide compounds, monosaccharides, and disaccharides, and more preferable examples include sucralose, acesulfame salts, Examples include saccharin and its salts, cyclamic acid and its salts, glucose, fructose, honey, isomerized sugar, invert sugar, sucrose, maltose, lactose, lactulose, trehalose, palatinose, and trehalulose, and more preferably sucralose and acesulfame potassium. , glucose, fructose, honey, and sucrose.

The content of the sweetener in the Chinese herbal extract preparation of the present invention is not particularly limited and may vary depending on the dosage form of the Chinese herbal extract preparation, but is, for example, 0.02 to 0.1% by weight, preferably 0.03 to 0.1% by weight. 08% by weight.

In the Chinese herbal extract preparation of the present invention, the ratio of the content of the Chinese herbal extract (in terms of dry extract) and the sweetener content is determined depending on each of the above contents, but the effect of reducing side effects of upper gastrointestinal symptoms is From the viewpoint of increasing the content of the sweetener, the content of the sweetener is preferably 0.05 to 2 parts by weight, more preferably 0.1 to 1.5 parts by weight, based on 100 parts by weight of the Chinese herbal extract content (in terms of dry extract). More preferably 0.5 to 1.2 parts by weight, even more preferably 0.7 to 1 part by weight.

In the Chinese herbal extract preparation of the present invention, when using a Chinese herbal extract containing Nebula japonica, Angelica japonica, Ephedra, and/or Ephedra as the Chinese herbal extract, the extracts of Chinese herbal medicine containing Lamina japonica, Alcanthus japonica, Ephedra, and/or Ephedra in the original medicine used for extracting the Chinese herbal extract. The content of the sweetener per 100 parts by weight of the total amount of ephedra is, for example, 0.01 to 2.5 parts by weight, and preferably 0.05 to 2 parts by weight from the viewpoint of increasing the effect of reducing side effects of upper gastrointestinal symptoms. Parts by weight, more preferably 0.1 to 1.4 parts by weight, still more preferably 0.4 to 1.2 parts by weight.

Other Components In addition to the above-mentioned components, the Chinese herbal extract preparation of the present invention may contain additives and bases depending on the formulation form as other components. Such additives and bases are not particularly limited as long as they are pharmaceutically acceptable, but include, for example, excipients, binders, disintegrants, lubricants, tonicity agents, 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 other than the above prescribed sweeteners agents, fragrances, powders, thickeners, pigments, chelating agents, etc. These additives may be used alone or in combination of two or more. Furthermore, the contents of these additives and bases are appropriately set depending on the types of additives and bases used, the formulation form of the Chinese herbal extract preparation, and the like.

Moreover, in addition to the above-mentioned components, the Chinese herbal extract preparation of the present invention may contain other nutritional components and pharmacological components as necessary. Such nutritional and pharmacological ingredients are not particularly limited as long as they are pharmaceutically acceptable, but include, for example, antacids, stomachic agents, digestive agents, intestinal regulation agents, antispasmodics, mucosal repair agents, anti-inflammatory agents, and astringents. agents, antiemetics, antitussives, expectorants, anti-inflammatory enzymes, sedative-hypnotics, antihistamines, caffeine, cardiac diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, herbal extracts, vitamins, menthol etc. These nutritional components and pharmacological components may be used alone or in combination of two or more. Further, the contents of these components are appropriately set depending on the types of components used.

Formulation Form The formulation form of the Chinese herbal extract formulation of the present invention is not particularly limited, but specific formulation forms include, for example, solid formulations such as powders, fine granules, and granules (including dry syrup); jelly formulations, etc. semi-solid preparations; liquid preparations such as solutions, suspensions, and syrups, and preferably liquid preparations. In order to prepare the Chinese herbal extract preparations of the present invention into these formulations, the above-mentioned prescribed Chinese herbal extracts as active ingredients, and additives, bases, and pharmacological ingredients added as necessary, are used in conventional preparations. It may be formulated according to the formulation method.

How to Take The Chinese herbal extract preparation of the present invention is dissolved in water and drunk. The dosage of the Chinese herbal extract preparation of the present invention per time is, for example, 0.5 to 5 g in terms of dry extract of the Chinese herbal extract,
Preferably, the amount is 1 to 4 g, more preferably 2 to 3.5 g, and still more preferably 2.2 to 3.3 g. In addition, the dose per dose of the Chinese herbal extract preparation of the present invention is the total amount of Nebula, Ephedra, Ephedra, and Ephedra in the crude drug used for extracting the Chinese herbal extract, for example, 1.5 to 6 g, preferably Examples include 2.2 to 5 g, more preferably 2.5 to 4 g, and still more preferably 2.8 to 3.4 g, and the dose should be taken 2 to 3 times a day, preferably in two divided doses. Can be done. The temperature of the water is not particularly limited, and includes, for example, 10 to 80°C, preferably 20 to 75°C, more preferably 30 to 65°C, and more preferably 38 to 50°C. Solubility in water does not necessarily mean complete dissolution in water, but also includes dispersion in water. The amount of water used is such that the content of the sweetener in the diluted Chinese herbal extract formulation after dissolving in water is 0.002 to 0.02% by weight, preferably 0.005 to 0.015% by weight. can be mentioned.

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

(1) Preparation of Chinese herbal extract preparation (1-1) Concentrated liquid of Shimotsuto extract As raw materials, 1.5 g of peonies, 1.5 g of rhododendron, 1.5 g of chinensis, and 1.5 g of Japanese acanthus were used as raw materials. After chopping, it was extracted using 15 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 to obtain a concentrated solution of Shimotsuto extract. The amount of Shimotsuto extract (converted to dry extract) obtained from 100 parts by weight of all the crude drugs was 40 parts by weight. The daily dose of the concentrate was 10 g (2.46 g in terms of dried extract of the Chinese herbal extract, the total amount of Nebula and Angelica in the herbal medicine used to extract 2.46 g of the dried Chinese herbal extract was 3.08 g).

(1-2) Concentrated liquid of Dokatsu Kakkonto Extract The raw materials are 2.5 g of kakkon, 1.5 g of cinnamon bark, 1.5 g of peony, 1.0 g of ephedra, 1.0 g of dokatsu, 0.167 g of ginger, 2. After chopping these, they were extracted at about 100° C. for 1 hour using 15 times the weight of water and centrifuged to obtain an extract. The extract was concentrated under reduced pressure to obtain a concentrated solution of Dokkatsu Kakkonto extract. The amount of Dokatsu Kakkonto extract (converted to dry extract) obtained from 100 parts by weight of all the crude drugs was 30 parts by weight. The daily dose of the concentrate was 10 g (3.14 g in terms of dry extract of the Chinese herbal extract, the total amount of ephedra and rhubarb in the herbal medicine used to extract 3.14 g of the dried Chinese herbal extract was 2.94 g).

(1-3) Concentrated liquid of yokukansan extract As raw materials, 1.5 g of Chinese trumpet, 1.5 g of chotōkou, 1.5 g of chinensis, 2.0 g of sandalwood, 2.0 g of bukryō, 1.0 g of licorice, and 0 g of licorice After chopping them, they were extracted at about 100° C. for 1 hour using 15 times the weight of water and centrifuged to obtain an extract. The extract was concentrated under reduced pressure to obtain a concentrated solution of Yokukansan extract. The amount of Yokukansan extract (converted to dry extract) obtained from 100 parts by weight of all the crude drugs was 24 parts by weight. The daily dose of the concentrate was 10 g (2.7 g in terms of dry extract of the Chinese herbal extract, the total amount of Angelica and Namiki in the crude drug used to extract 2.7 g of the dried Chinese herbal extract was 3.3 g).

(1-4) Chinese herbal extract preparations Using the concentrated liquids of Chinese herbal extracts prepared in (1-1) to (1-3) above, the Chinese herbal extract preparations shown in Tables 1 to 4 were prepared.

(2) Evaluation of side effects of upper gastrointestinal symptoms 45 subjects with gastric weakness who had previously experienced gastrointestinal disorders due to pharmaceuticals were divided into four groups: a group taking Shimotsuto extract, a group taking Dokkatsu Kakkonto extract, and a group taking Yokukansan extract. The subjects were divided into 3 groups (15 people each), and the above daily dose was divided into two doses and the Chinese herbal preparation was administered every day for 6 weeks. When using the Chinese herbal preparation, approximately 100 mL (10 times the volume) of water at 40°C to 50°C was added, mixed well, and taken on an empty stomach. In addition, in each group, during the test period, the Comparative Example (1 type) or the Chinese herbal extract formulation (5 types) of the Example to be taken was changed every week. The order in which the Chinese herbal extract preparations of Comparative Example (1 type) and Example (5 types) were taken was randomly assigned to all subjects.

Gastrointestinal symptoms were evaluated every week from the start of taking the sample. Specifically, on the last day of the week, the digestive symptoms over the past week were reviewed and evaluated. Gastrointestinal symptoms were evaluated using the “Izumo Scale” (Journal of the Japanese Society of Gastroenterology 2009; 106:1478-1487), which is a questionnaire on digestive symptoms. Lower gastrointestinal symptoms (constipation, diarrhea) were evaluated. The Izumo scale evaluates the severity of gastrointestinal symptoms using a number between 0 and 15, with lower numbers indicating milder symptoms. The results are shown in Tables 1 to 4.

As shown in Tables 1 to 3, the Chinese herbal extract formulations of Examples 1 to 15 contain extracts of Chinese herbal medicines containing nebula, acanthus, argentina, and/or ephedra, which are herbal medicines that exhibit side effects of gastrointestinal symptoms. Nevertheless, it was confirmed that upper gastrointestinal symptoms can be significantly reduced by incorporating a prescribed sweetener (chlorinated sugar, sulfonamide compound, monosaccharide, disaccharide). As shown in Table 4, when a sweetener different from the predetermined sweetener was used, no effect of reducing upper gastrointestinal symptoms was observed. In other words, it was found that the remarkable reducing effect on upper gastrointestinal symptoms by the Chinese herbal extract formulations of Examples 1 to 15 was a unique effect due to the use of the prescribed sweetener.

Claims (7)

A Chinese herbal extract preparation containing a Chinese herbal extract and a sweetener selected from the group consisting of chlorinated sugars, sulfonamide compounds, monosaccharides, disaccharides, and oligosaccharides, which is dissolved in water and taken. The Chinese herbal extract formulation according to claim 1, wherein the Chinese herbal extract is an extract of a Chinese herbal medicine containing Nebula japonica, Ephedra, Ephedra, and/or Ephedra. The herbal medicine extract preparation according to claim 1, wherein the herbal medicine extract is an extract of Shimotsuto, Dokkatsu Kakkonto, and/or Yokukansan. The sweetener consists of sucralose, acesulfame salt, saccharin and its salt, cyclamic acid and its salt, glucose, fructose, honey, isomerized sugar, invert sugar, sucrose, maltose, lactose, lactulose, trehalose, palatinose, and trehalulose. The Chinese herbal extract preparation according to claim 1, which is selected from the group. The Chinese herbal extract according to claim 1, wherein the content of the sweetener is 0.05 to 2 parts by weight based on 100 parts by weight of the Chinese herbal extract. Claim 2, wherein the content of the sweetener is 0.01 to 2.5 parts by weight with respect to 100 parts by weight of the total amount of nebula, acanthus, rhododendron, and ephedra in the herbal medicine used to extract the Chinese herbal extract. Chinese herbal extract listed in. 3. The Chinese herbal extract according to claim 2, wherein the dose per dose is 1.5 to 6 g of the total amount of Ephedra, Ephedra, Ephedra, and Ephedra in the original herbal medicine used for extracting the Chinese herbal extract.