JP2002114692A - Hepatic function improving agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a unique, effective and safe hepatic function improving agent. SOLUTION: This hepatic function improving agent is composed mainly of a mixture of water and/or organic solvent extract of Hakkaku-reishi (Rhinacanthus nasutus) and fucoidan. The hepatic function improving agent has excellent hepatic function improving effect and is absolutely free from side effects and, accordingly, it has extremely high usefulness.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a liver function improving agent.
More specifically, the present invention relates to a novel liver function improving agent containing a mixture of an extract of Hakutsuru Reishi and fucoidan as main components.

[0002]

2. Description of the Related Art Conventionally, liver function improving agents include amino acid preparations, nicotinic acid preparations, pantothenic acid preparations, glycyrrhizin, placenta extract, liver extract, glucuronic acid preparation, glutathione preparation, methylmethionine preparation,
Although drugs such as Sho-saiko-to and interferon-inducing agents are used, the effects of these drugs vary depending on the constitution, symptoms, lifestyle, environment, etc. of individual patients. There is a need for a new type of liver function improving agent applicable to patients. There is no report that a mixture of water and / or organic solvent extract of Hakutsuru Reishi and fucoidan was used as a liver function improving agent.

[0003] Rinacanthus n
asuta (L.) Kurz) is an evergreen shrub belonging to the genus Linakanthus, which is native to the Deccan Plateau in southern India. Known (“Primary Color Makino Kazoku Encyclopedia”, p.492, Hokuryukan, 1
988), mainly used in China and Taiwan, and more recently in Japan. Others
In a previous application filed by the present applicant, this white cranes Reishi has the ability to scavenge active oxygen (Japanese Patent Application Laid-Open No. 9-143091; active oxygen scavenger) and has an excretion promoting action (Japanese Patent No. 3077)
No. 019, excretion enhancer) and that it has a lipid peroxide inhibitory action (JP-A-2000-16945, lipid peroxide inhibitor). However, it is not known that a water and / or organic solvent extract of Hakutsuru Reishi has a liver function improving effect.

[0004] On the other hand, fucoidan is a heterogeneous polysaccharide molecule group which is considered to be a main component forming a slime substance of brown algae together with alginic acid and contained about 1 to 5% by dry weight of brown algae. This fucoidan contains fucose, galactose, mannose, glucuronic acid, xylose, sulfuric acid, etc., and in addition to anti-cancer activity, immunostimulation, lowering blood cholesterol, lowering blood pressure, anti-allergy, relieving constipation, preventing dementia It is said to have an action such as an aluminum ion and iron ion trap in the digestive tract.

[0005]

DISCLOSURE OF THE INVENTION The present inventors have conducted intensive studies with the aim of providing a highly safe and effective liver function improving agent.
Alternatively, the present inventors have completed the present invention based on the finding that a combination of an organic solvent extract and fucoidan has an excellent effect on liver dysfunction and shows a liver function improving effect extremely safely without side effects.

[0006]

SUMMARY OF THE INVENTION The present invention relates to a liver function improving agent comprising a mixture of a water and / or organic solvent extract of Hakutsuru Reishi and fucoidan as a main component. The water and / or organic solvent extract of Hakutsuru Reishi (hereinafter sometimes referred to as Hakutsuru Reishi extract) used in the present invention is obtained by extracting Hakutsuru Reishi with water and / or an organic solvent, and extracting the extraction solvent from the extract. Can be obtained by distillation. Fucoidan used in the present invention may be a commercially available one. The mixing ratio of the white crane ganoderma extract and fucoidan is 0.0005 to 0.5, preferably 0.001 to one fucoidan.
０．１0.1.

[0007] As the Hakutsuru Reishi used in the present invention, commercially available leaves, whole plants, roots, or stems, or a mixture thereof can be used. Preferably they are sun-dried and / or drum-dried and crushed by a mill.
It is pulverized to a mesh or less, preferably 12 mesh or less. If necessary, this Hakutsuru Reishi is sun-dried and / or
Alternatively, a drum-dried product roasted by a roaster may be used.

In the present invention, the solvent used for extraction includes water and an organic solvent, and these can be used alone or in combination of two or more. Water includes tap water, deionized water, distilled water, and the like.

In the present invention, examples of the organic solvent used for extraction include lower alcohols having 1 to 4 carbon atoms, aliphatic ketones having 3 to 4 carbon atoms, and the like.
Lower alcohols are preferred, and ethanol, methanol and the like are particularly preferred.

In the present invention, the extraction is carried out by adding a 5- to 50-fold amount of a solvent to the ground white crane and then leaving, shaking or stirring. Extraction temperature from 0 ° C to 130
Although it can be carried out at a temperature of 0 ° C., it is preferably carried out at a temperature of from room temperature to 110 ° C. The time required for extraction depends on the temperature and the grinding condition of Hakutsuru Reishi, but usually ranges from 30 minutes to 6 hours.
About an hour.

After the extraction, using a conventional means such as decantation, centrifugal separation, and vacuum filtration, an extract of Hakutsuru Reishi is obtained as a liquid having an odorless or slight aroma and a unique rich taste. This may be used as it is, but preferably, it is purified by filtration, centrifugation, or another method, and further concentrated appropriately to obtain a concentrated extract of Hakutsuru Reishi, which may be used after heat sterilization. it can. Heat sterilization can be performed at a temperature of 60 ° C to 100 ° C.
It is preferable to carry out at a temperature of 5 ° C.

[0012] The above heat-sterilized concentrated extract is further concentrated under reduced pressure to dryness, spray-dried, freeze-dried, or the like, and then dried as a fine powder having an odorless or slight aroma and a unique rich taste. An extract is obtained, which may be used.

[0013] In addition to the Hakutsuru reishi extract and fucoidan of the present invention, if necessary, various components generally used in pharmaceuticals, ie, aqueous components, powder components, oil components, interfaces, as long as the effects of the present invention are not impaired. By blending an activator, a medicinal plant essence, a humectant, a thickener, an antioxidant, a fragrance, a pigment, and the like, a medicinal product containing Hakutsuru reishi extract and fucoidan as main components can be produced.

Next, the present invention will be described more specifically with reference to examples and test examples, but the present invention is not limited to these examples.

Example 1 Sun-dried and then drum-dried Hakutsuru Reishi leaves (sold by Daikyo Bussan Co., Ltd .; hereafter, the same purchasers of Hakutsuru Reishi) are pulverized with a pulverizer and pulverized Hakutsuru. Reishi roasted leaves 1kg 90
Extract twice with 25 liters of hot water of 2 ° C. for 2 hours. Combine the resulting extracts, concentrate at 55 to 60 ° C. under reduced pressure to about 1/10 volume, and filter under pressure. The filtrate was sterilized by heating at 90 to 95 ° C., and then concentrated to dryness under reduced pressure.
g was obtained. On the other hand, 90% of 1 kg of ground Hakutsuru Reishi root
Extracted twice with 10 liters of ethanol under reflux for 3 hours,
The obtained extracts are combined, concentrated at 55 to 60 ° C. under reduced pressure to about 1/10, and then pressure-filtered. The filtrate was sterilized by heating at 90 to 95 ° C. and concentrated to dryness under reduced pressure to obtain 85.5 g of a 90% ethanol extract of Hakutsuru Reishi root. 0.1 kg of the thus-obtained Hakutsuru Reishi leaf hot water extract, Hakutsuru Reishi root 90
% Ethanol extract, 1 kg of a fucoidan-containing kelp extract [manufactured by Takara Shuzo Co., Ltd.] obtained by ultrafiltration of a crude fucoidan solution obtained by extracting a crushed dried gagome kelp with a calcium chloride solution at 95 ° C. and 1 kg of lactic acid with lactic acid bacteria 2 kg of the fermented medicinal plant fermented solution, water and the like were mixed to obtain 50 liters of the preparation of the present invention.

EXAMPLE 2 0.001 kg of the Hakutsuru Reishi leaf hot water extract obtained in the same manner as in Example 1, 0.01 kg of Hakutsuru Reishi root 90% ethanol extract, 1 kg of Fucoidan-containing kelp extract and lactic acid bacteria 2 kg of a medicinal plant fermented solution subjected to lactic acid fermentation with water and water were mixed to obtain 50 liters of the preparation of the present invention.

Example 3 Sun-dried, then drum-dried leaves of Hakutsuru Reishi 1 kg
Was crushed by a crusher, roasted by a roaster, and further crushed, and the obtained crushed material was sieved and classified with 12 mesh to obtain about 0.8 kg of crushed white crane reishi leaf. 5 g of the ground white cranes of Reishi leaves were immersed in 200 g of hot water and filtered to obtain a green-brown transparent liquid extract with a slight jasmine-like aroma and a unique rich taste. The 0.001 kg of the thus-obtained Hakutsuru Reishi leaf hot water extract was mixed with 1 kg of fucoidan-containing kelp extract and water, to thereby prepare the preparation 5 of the present invention.
0 liters were obtained. Example 4 2.5 g of whole ground pulverized product of Hakutsuru Reishi was immersed in 100 g of water and filtered to obtain a deep green transparent liquid extract with a slight aroma and a unique rich taste. The thus-obtained formulation 5 of the present invention was prepared by mixing 1 kg of the fucoidan-containing kelp extract with 0.03 kg of the water extract of Hakutsuru Reishi and the water thus obtained.
0 liters were obtained.

Example 5 5 g of whole ground pulverized product of Hakutsuru Reishi was immersed in 200 g of ethanol and filtered to obtain a deep green transparent liquid extract with a slight aroma and a unique rich taste. 0.0008 of the thus-obtained ethanol extract of Hakutsuru Reishi whole plant
1 kg of the fucoidan-containing kelp extract and water were mixed with the resulting mixture to obtain 50 liters of the preparation of the present invention.

EXAMPLE 6 2.5 g of crushed leaves, stems and roots of Hakutsuru Reishi were treated with 1,3-
It was immersed in 100 g of butylene glycol and filtered to obtain a deep green transparent extract with a slight aroma and a unique rich taste. 0.001 kg of the thus-obtained Hakutsuru Reishi extract was mixed with 1 kg of fucoidan-containing kelp extract and water to obtain 50 L of the preparation of the present invention.

Example 7 Sun-dried and then drum-dried 3 g of ground and dried ground crane leaves and roots were immersed in 100 g of 1: 1 ethanol water.
Filtration yielded a deep green, clear liquid extract with a slight aroma and a unique rich taste. 0.09 kg of the aqueous extract of Hakutsuru Reishi and root ethanol obtained in this way
Was mixed with 1 kg of fucoidan-containing kelp extract and water to obtain 50 liters of the preparation of the present invention.

Example 8 2.5 g of ground crushed white cranes reishi leaves were immersed in 100 g of hot water and filtered to obtain a green-brown, transparent liquid extract with a slight aroma and a unique rich taste. . 0.08 kg of the thus-obtained Hakutsuru Reishi leaf hot water extract was mixed with 1 kg of fucoidan-containing kelp extract and water to obtain 50 L of the preparation of the present invention.

Example 9 Example 4 except that acetone was used instead of ethanol
To obtain a deep green transparent liquid white crane Reishi extract having a slight aroma and a unique rich taste. 0.0% of the thus obtained Hakutsuru Reishi extract
008 kg was mixed with 1 kg of fucoidan-containing kelp extract and water to obtain 50 liters of the preparation of the present invention.

Example 10 Example 4 except that ether was used instead of ethanol
To obtain a deep green transparent liquid white crane Reishi extract having a slight aroma and a unique rich taste. 0.1% of the thus obtained Hakutsuru Reishi extract
1 kg of the fucoidan-containing kelp extract and water were mixed with the resulting mixture to obtain 50 liters of the preparation of the present invention.

Example 11 Example 4 except that benzene was used instead of ethanol
To obtain a deep green transparent liquid white crane Reishi extract having a slight aroma and a unique rich taste. 0.1% of the thus obtained Hakutsuru Reishi extract
1 kg of the fucoidan-containing kelp extract and water were mixed with the resulting mixture to obtain 50 liters of the preparation of the present invention.

Example 12 Whole grass and 1 kg of roots dried in the sun and then dried in a drum and ground were crushed with a crusher, roasted in a roaster, and further crushed. The same treatment as in Example 3 was carried out, except that crushed 12-mesh and sieved to obtain about 0.8 kg of ground grass and whole ground of white cranes Reishi, greenish brown with a slight aroma and unique rich taste. Was obtained as a clear liquid extract. 0.1k of Hakutsuru Reishi extract obtained in this way
g of water and 1 kg of a fucoidan-containing kelp extract and water were mixed to obtain 50 liters of the preparation of the present invention.

Example 13 Hakutsuru reishi extract 10 obtained by treating in the same manner as in Example 3
00 liters were lyophilized to give about 10 g of a greenish-brown fine powder with a slight aroma and a unique rich taste. 0.001 kg of the thus-obtained Hakutsuru Reishi extract was mixed with 1 kg of fucoidan-containing kelp extract and water to obtain 50 L of the preparation of the present invention.

Example 14 Hakutsuru Reishi Extract 10 obtained by treating in the same manner as in Example 4
00 liters were lyophilized to give about 10 g of a greenish-brown fine powder with a slight aroma and a unique rich taste. 0.1 kg of the thus obtained Hakutsuru Reishi extract was mixed with 1 kg of fucoidan-containing kelp extract and water to obtain 50 L of the preparation of the present invention.

Example 15 Hakutsuru Reishi Extract 10 obtained by treating in the same manner as in Example 4
00 liters were lyophilized to give about 10 g of a deep green fine powder with a slight aroma and a unique rich taste. 0.1 kg of the thus obtained Hakutsuru Reishi extract was mixed with 1 kg of fucoidan-containing kelp extract and water to obtain 50 L of the preparation of the present invention.

Example 16 Hakutsuru Reishi Extract 10 obtained by treating in the same manner as in Example 5
00 liters were lyophilized to give about 10 g of a deep green fine powder with a slight aroma and a unique rich taste. 0.001 kg of the thus obtained Hakutsuru Reishi extract
Was mixed with 1 kg of fucoidan-containing kelp extract and water to obtain 50 liters of the preparation of the present invention.

Example 17 Hakutsuru reishi extract 10 obtained by treating in the same manner as in Example 6
00 liters were lyophilized to give about 10 g of a deep green fine powder with a slight aroma and a unique rich taste. 0.05 kg of the thus-obtained Hakutsuru Reishi extract was mixed with 1 kg of fucoidan-containing kelp extract and water to obtain 50 L of the preparation of the present invention.

Test Example 1 The hepatic function improving agent of the present invention prepared in Example 1 was administered to 11 patients with hepatic dysfunction to examine the therapeutic effect and side effects. Subjects and methods Subjects Adult male and female up to 30-60 years old, GOT, GPT40-
150 IU / l or less, γ-GTP 60-300 IU / l
Patients with mild liver injury. In addition, renal dysfunction, acute hepatitis, chronic viral hepatitis, alcoholic liver damage and cirrhosis were excluded. At the start of the clinical trial, the absence of hepatitis A at present means that IgM-HA
It was confirmed by antibody measurement, and an antibody test was performed for hepatitis B and C. During the test period, subjects were asked to treat liver disease drugs (amino acid preparations, nicotinic acid preparations, pantothenic acid preparations, glycyrrhizin, placenta extract, liver extract, glucuronic acid preparations, glutathione preparations, methyl methionine preparations and Chinese herbal medicines ( (1) The method of the present invention prepared in Example 1 was not used at one time (50 m).
l) Take twice a day (within 30 minutes after breakfast and dinner) and follow up for 12 weeks. During this time, daily life was not changed. From the start to the end, physical measurements and hematuria were performed every month until the third month. 3. Test items Physical measurements: height, weight, body fat percentage (BI method) Clinical tests: blood pressure, heart rate, blood biochemistry tests, general blood tests, urinalysis Questionnaire Survey (Meal Contents, Alcohol Intake, Exercise) In one case, an abdominal ultrasonic examination was performed before and after administration of the preparation of the present invention. 4. Assay method The values at the start and at the end (3rd month) are shown in Paired t-
Tests were performed and compared. Results (1) Case background The cases were 10 men and 1 woman with mild hepatic impairment, totaling 11 (mean age 40 ± 6 years) (Table 1). All cases were diagnosed as fatty liver based on laboratory findings. (2) Effect on liver damage GOT at the start was 43 ± 15.37 IU / l, and after 3 months, it was significantly reduced to 27 ± 9.18 IU / l, showing improvement (p <0.05). GPT is 61.64 ± 3 at start
1.25 IU / l 40.36 ± 31.25 IU after 3 months
/ L was observed, and γ-GTP was 90.18 ± 7 before the start.
It is 4.54 IU / l and 60.45 ± 56 after 3 months.
Although a decrease of 27 IU / l was observed, no significant difference was observed. (3) Other blood tests No significant changes were observed in other blood tests.
In the lipid system, the total cholesterol level was 212 ± before the start.
After 3 months from 26.67 mg / dl, 204 ± 32.
95 mg / dl, neutral fat, 214 ± 129 m before start
148.27 ± 73.91 m 3 months after g / dl
g / dl was not significant but decreased. The fasting blood glucose level decreased slightly from 106.58 ± 19.48 mg / dl before the start to 98.92 ± 18.04 mg / dl three months later, but no significant difference was observed. During the entire course, no side effect symptoms, liver damage, renal damage, electrolyte abnormality, anemia, etc. apparently caused by the preparation of the present invention were observed. (4) Urinalysis No abnormalities were observed in the urinalysis during the course. (5) Body measurement Body weight was 75.1 ± 11.6 kg before start and 74 ± after 3 months.
At 11.3 kg, no significant difference was observed. Average body fat percentage is 25.2 ± 4.1% (bioimpedance method)
And tended to be mildly obese. The body fat percentage after 3 months was 25.6 ± 2.9%, and no significant difference was observed as compared with the time at the start. (6) Case Patient; 31-year-old male Chief complaint; Mild hepatic impairment Past history; No special mention Family history; No special note Progress; GOT is from 49 IU / l at the start to 22 IU / l at the end
Has dropped. GPT slightly increased from 28 IU / l before the start to 43 IU / l three months later. Weight before start 8
3.2kg to 82kg, body fat 21.5% to 1
A slight decrease was observed at 9.5%. There were no lifestyle changes during the study. Lipid tests showed no significant changes in total cholesterol or triglyceride. Compared with the abdominal ultrasonic findings at the start, the abdominal ultrasonic findings three months after taking the preparation of the present invention confirmed that the liver-kidney contrast was improved. (7) Side effects and safety No side effects were observed in all cases. Further, in the questionnaire survey at the time of completion, it was determined that there was no problem in the safety of the preparation of the present invention throughout the entire course as shown in Table 3.

The liver function-improving agent of the present invention has excellent liver function-improving effects and has no side effects at all, and is a very useful preparation.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Tomohiro Takahashi 2-22-16 Nakamagome, Ota-ku, Tokyo (72) Inventor Ryo Jun Chiki 3-4-4, Nishiogikubokita, Suginami-ku, Tokyo (72) Inventor Matsunami Journey 3-2 Kano Honcho, Gifu City, Gifu Prefecture (72) Inventor Noriko Takagi 332-1222, Kamisasao, Kobuchizawa-gun, Kita-Koma County, Yamanashi Prefecture (72) Inventor Takara Muramatsu 861, Haguro-cho, Kofu City, Yamanashi Prefecture (72) Tatsuya Shiraishi, Yamanashi 17-3 Tenjin Heights 17-3 Tenjin-cho, Kofu-shi, Pref. 204 (72) Inventor Ichiki Yamada, Kazuki, Suwa-shi, Nagano Pref. 7405 Lereve N405 (72) Inventor Tadashi Hozumi 47-9 Nagaodaicho, Sakae-ku, Yokohama F-term (reference) 4C086 AA01 AA02 EA20 MA02 MA04 NA14 ZA75 4C088 AB12 BA08 MA04 NA14 ZA75

Claims (1)

[Claims] 1. A liver function improving agent comprising as a main component a mixture of a water and / or organic solvent extract of Hakutsuru Reishi and fucoidan.