JP2000053573A - Liver function improver - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject inexpensive improver having a good taste capable of being daily ingested by including an isoflavone compound as an active ingredient. SOLUTION: This improver comprises an isoflavone compound such as daidzein, genistein, genistin, daidzin, genistin, as an active ingredient. The compound is obtained, for example, by using a leguminous plant such as soybean, Purataria lobata, as a material and extracting it with an alcohol such as ethanol as a row solvent. A daily intake of the compound is about 0.01-100 mg/kg. In the case of taking a soybean milk or a fermented soybean milk, the intake is generally 50 mg to 5 g/kg calculated as powder. In the case of administration to a domestic animal as a feed, the intake is about 0.1-100 mg/kg.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a liver function improving agent containing an isoflavone compound as an active ingredient.

[0002]

2. Description of the Related Art The liver is the largest organ in a living body and performs many functions related to metabolism such as production and secretion of bile and removal of foreign substances. The function of the liver may be impaired by alcohol intake, drugs, and the like. In addition, when a liver disease occurs, a disease resulting therefrom also becomes a problem.

[0003] Normally, liver function tests are performed using the values of GOT (glucuronate oxaloacetate transferase) and GPT (glucoronate pyruvate transferase) as indices. That is, when the liver function is reduced, the hepatocytes are damaged, so that GOT, GP
T is released out of the cell and its value increases.

[0004] When the liver function is reduced, it is basically most important to take good nutrition and rest. on the other hand,
If liver function continues to decrease due to stress, alcohol intake, etc., the risk of developing hepatitis, fatty liver, cirrhosis, liver cancer and the like increases. For such liver diseases, therapeutic agents such as potent neominophagen C (manufactured by Minophagen Co., Ltd.) containing glycyrrhizin as a main component have been used,
Since these are administered intravenously, they are not suitable for continuous administration with pain and various restrictions.

On the other hand, liver disease also occurs in livestock, poultry, and the like, and there is a problem of economic loss due to a decrease in productivity. For example, in high-lactation cows in the early lactation, milk production surpasses appetite, thereby mobilizing body fat to compensate for the energy shortage, resulting in the development of fatty liver, various metabolic disorders and various metabolic disorders. Causes infection.

Liver function improvers for livestock and poultry include
For example, Japanese Patent No. 2524783 discloses a plant sterol as an active ingredient. However, the effect is not always satisfactory.

[0007]

As described above, a decrease in liver function caused by ingestion of alcohol or fat may cause various liver diseases. These risk factors such as alcohol are often taken on a daily basis. Therefore, as a drug for improving liver function, a drug that can be easily taken orally without causing side effects even when taken continuously is required.

Accordingly, an object of the present invention is to provide an inexpensive and savory liver function improving agent and food or drink that can be taken orally on a daily basis. Another object of the present invention is to provide a feed for improving liver function which can be easily provided to animals.

[0009]

Means for Solving the Problems As a result of intensive studies, the present inventors have found that a safe isoflavone compound contained in a lot of beans has an effect of improving liver function, that is, an effect of lowering GOT and GPT values. The present invention has been completed.

That is, the present invention provides a liver function improving agent containing an isoflavone compound as an active ingredient.

The present invention also provides a food and drink for improving liver function and a feed for improving liver function, which are characterized by containing an isoflavone compound.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION The isoflavone compound used in the present invention is a free form, glycoside, conjugate, derivative or the like of isoflavone, and specifically, daidzein, genistein, glycetein, daidzin, genistin, glycetin. , Formonetin, biochanin A and the like.
In particular, a free form of isoflavone is preferable because it has a high blood transferability and various physiological effects in vivo. Isoflavone compounds are contained in leguminous plants, irises and roses, such as soybeans and kudzu, and various physiological effects have been verified. Specifically, effects such as improvement of osteoporosis, prevention of breast cancer, prostate cancer, etc., and reduction of hypertension have been reported. However, there is no report of a liver function improving effect.

In order to use the isoflavone compound as a liver function improving agent, the purified isoflavone compound or a material containing a large amount of the isoflavone compound may be used as it is or mixed with other components. Examples of the material containing the isoflavone compound include legumes, and among them, soybean and kudzu are preferable from the viewpoint of safety, isoflavone content, and the like. As a method of extracting and purifying an isoflavone compound from these materials, a method of extracting using an alcohol, particularly ethanol or methanol, as a solvent is preferable. Other components include other drugs, excipients, binders, lubricants, disintegrants, sugars, humectants, and the like.

The food or drink containing the isoflavone compound is
Those having a high content of the isoflavone compound and good flavor are preferred. Such foods and drinks include soy milk,
Examples include fermented soy milk, soy protein-containing food, soy flour, tofu, and natto, with soy milk and fermented soy milk being particularly preferred. This is because soy milk has been conventionally eaten as a health drink and is known to contain a large amount of isoflavones, and the present applicant has confirmed that fermented soy milk contains more isoflavone compounds. That is, the applicant has
It has been found that fermented soymilk obtained by performing fermentation using a microorganism having the ability to release isoflavones by acting on isoflavone glycosides in soymilk contains a high concentration of isoflavones. (JP-A-9-238647).

The fermented soymilk may be obtained by inoculating a microorganism into the raw soybean milk produced by a conventional method and culturing it. Preferred microorganisms used herein include Lactobacillus bacteria, Streptococcus bacteria, Bifidobacterium bacteria, Saccharomyces bacteria and the like. When these microorganisms are used, fermented soymilk containing a large amount of isoflavone compounds and having a good flavor can be obtained.

The intake of the isoflavone compound is 0.01
A liver function improvement effect of about mg / kg / day to 100 mg / kg / day is preferable, and 0.1 mg / kg / day to 1 mg / kg / day.
About 0 mg / kg / day is more preferable.

When the isoflavone compound is ingested in soymilk or fermented soymilk, it is usually 50 mg / kg to 5 g / g in terms of powder.
kg is preferred.

When administered to livestock as feed,
It is preferable to give the isoflavone compound in an amount of about 0.01 mg / kg to 100 mg / kg, particularly 0.1 mg / kg to 10 mg / kg.
It is preferable to give about kg.

The isoflavone compound used in the present invention is contained in foods and drinks, especially beans, and has been eaten and consumed in the past. Therefore, its safety is high and there is no problem of side effects even when it is used regularly.

[0020]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the invention is limited thereto.

Example 1 Liver Lipid Inhibitory Effect of Soy Milk and Fermented Soy Milk -Method- Zucker (fa / fa) rat (♀), 6 to 7 weeks old
Were used. After pre-breeding on an MF solid diet for one week, the animals were divided into three groups (6 animals per group) so that there was no difference in average body weight. Table 1
Shows the composition of the feed. The feed used was a lyophilized product of crude soymilk and fermented soymilk (crude fat 8.61%, crude protein 12.66%). A control mixture was prepared using soy milk protein and casein, lipid and corn oil, and sucrose otherwise. After breeding for one month, the animals were dissected. After a 4-hour fast on the day of dissection, the animals were exsanguinated from the abdominal aorta under Nembutal anesthesia. The liver was perfused with cold saline and removed. After extracting liver lipids according to Folch's method, total cholesterol, triglycerides, phospholipids,
Free fatty acids were measured with a clinical test kit (Kyowa Medix, Wako Pure Chemical Industries). In the statistical processing, multiple comparison was performed by Tukey's test after analysis of variance.

-Results- Table 2 shows liver lipids. Total cholesterol, triglycerides, free fatty acids, phospholipids, ester cholesterol, soy milk,
It decreased significantly in the fermented soymilk group. In particular, triglyceride was significantly reduced, showing a value one tenth of cholesterol.

[0023]

[Table 1]

[0024]

[Table 2]

Example 2 Inhibitory Effect of Genistein on Liver Injury Caused by Carbon Tetrachloride -Method- After rearing 10-week-old SD rats (♂) on a diet according to AIN76 composition (described in Table 3) for 2 weeks , Control group (administration of carbon tetrachloride, n = 10) and genistein group (administration of genistein and carbon tetrachloride, n = 10)
Separately (shown below), carbon tetrachloride was mixed with corn oil at a ratio of 1: 1 to 1.0 ml / kg. W. Genistein was dissolved in DMSO and administered intraperitoneally.

* Administration group Carbon tetrachloride administration group: Carbon tetrachloride: corn oil = 1: 1
And mix at 1.0 ml / kg B.I. W. Administration. 1.0 ml / kg of DMSO. W. Genistein administration group-Carbon tetrachloride: corn oil = 1:
1 ml and mix with 1.0 ml / kg B.I. W. Administration. Genistain 10 mg / 1 ml DMSO solution was added to 1.0 ml / kg B.I. W.
Administration.

After administration, the animals were fasted for 24 hours, dissected under ether anesthesia, and whole blood was collected from the abdominal aorta. Whole blood was centrifuged (3,000 ppm, 20 min) to prepare plasma. Plasma GOT
Transaminase CII Test Wako (Wako Pure Chemical) was used for GPT activity measurement, and lactate dehydrogenase CII Test Wako (Wako Pure Chemical) was used for LDH activity measurement. For statistical processing, the variance was examined using the F test. When there was no significant difference in the variance between the two groups, the Student-t test was used, and when there was a difference, the Welch and Cochran-t test were used.

-Results- The results are shown in Table 4. In LDH and GOT, a significant difference was observed in the genistein-added group compared to the control group.
GPT also tended to be suppressed.

[0029]

[Table 3]

[0030]

[Table 4]

Example 3 Verification of suppression of liver injury by sonde administration of soymilk -Method- A 4-week-old SD rat (♂) was preliminarily reared on a basic diet (Table 5) according to the AIN76 composition for 7 days, and then a normal group. (N = 4), a control group (n = 4), and a soymilk group (n = 5). The normal group and the control group each received 10 ml / kg of distilled water, and the soy milk group received 10 ml / kg of soymilk (solid content: 10%). W. The sonde was administered. Two hours after administration of the sonde, the normal group received 1 ml / kg of corn oil. W. For the control group and the soymilk group, 2 ml / kg of a mixture of corn oil and carbon tetrachloride in a ratio of 1: 1 was used.
B. W. Administered intraperitoneally. Twenty-four hours after administration of carbon tetrachloride, the mice were dissected under ether anesthesia, whole blood was collected from the abdominal aorta, and centrifuged (3,000 rpm, 20 min) to prepare serum. Transaminase C for serum GOT and GPT activity measurement
II Test Wako (Wako Pure Chemical Industries) was used. For the statistical processing, the same method as in Example 2 was used.

-Results- Table 6 shows the results. Serum GOT and GPT activities were significantly increased in the control group compared to the normal group, and it was confirmed that liver damage was caused by carbon tetrachloride. Gode by administering soy milk to sonde
T and GPT showed a decreasing tendency compared to the control group.

[0033]

[Table 5]

[0034]

[Table 6]

Example 4 Investigation of Suppression of Liver Injury by Administration of Soy Milk Mixed Feeding -Method- Twenty 6-week-old SD rats (♂) were subjected to a normal group (n =
5), control group (n = 5), 2.5% soymilk group (n
= 5) and a 5% soymilk group (n = 5). The normal group and the control group were fed a basic feed, the 2.5% soymilk group was fed a 2.5% soymilk feed, and the 5% soymilk group was fed a 5% soymilk feed (Table 5) for 7 days. Thereafter, the same operation as in Example 3 was performed except that the rats were fasted for 24 hours after carbon tetrachloride administration.

-Results- Table 7 shows the results. Compared with the control group, the serum GOT and GPT activities in the soymilk group tended to decrease. G
In PT, dose-dependence was observed in the suppression of liver damage in soy milk.

[0037]

[Table 7]

[0038]

The hepatic function improving agent of the present invention contains no isoflavone compound which is contained in legumes and is conventionally eaten, and therefore has no side effects even when used regularly. In addition, foods and drinks containing the same are inexpensive, have good flavor, and can be easily taken.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) // A61K 35/78 A61K 35/78 J 4C086 C07D 311/36 C07D 311/36 4C088 C07H 17/07 C07H 17 / 07 (72) Inventor Norie Onodera 1-1-19 Higashi-Shimbashi, Minato-ku, Tokyo Yakult Honsha (72) Inventor Bunbo Ishikawa 1-1-19, Higashi-Shimbashi, Minato-ku, Tokyo Yakult Honsha F-term (reference) 2B150 AA01 AA05 AB10 DB01 DD31 DD57 4B001 AC01 AC08 DC50 DC51 EC99 4B018 LB04 LB08 LE03 LE05 MA02 MD27 MD57 ME14 4C057 BB02 DD01 KK08 4C062 EE44 4C086 AA01 AA02 BA08 EA04 MA17 NA04 AB72 AC01 BA14 BA37 CA06 MA16 MA52 MA70 NA08 NA14 ZA75 ZC61

Claims (4)

[Claims] 1. A liver function improving agent comprising an isoflavone compound as an active ingredient. 2. A food or drink for improving liver function, which comprises an isoflavone compound. 3. The food or drink for improving liver function according to claim 2, wherein the food or drink is soy milk or fermented soy milk. 4. A feed for improving hepatic function, comprising an isoflavone compound.