JP2001213796A - Prophylactic and therapeutic medical and for non-insulin dependent diabetes mellitus (niddm) and health food containing extract mixture of mulberry leaves and agaricus. - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a prophylactic and therapeutic medical composition for NIDDM which can be safely taken with less side effects while taking daily meals, and an equally effective health food. SOLUTION: Components containing a mixture of an extract obtained from mulberry leaves and an extract from agaricus are allowed to be contained as effective components.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an insulin-non-independent diabetes mellitus containing a mixture of mulberry leaf extract and agaricus extract, which can be easily ingested daily while eating a daily meal.
(Hereinafter, referred to as “NIDDM”).

[0002]

2. Description of the Related Art According to a survey conducted by the Ministry of Health and Welfare in 1994 in the Ministry of Health and Welfare, the number of diabetic patients in Japan has reached 6 million, and "boundary type" is suspected of having diabetes even without treatment. It is said that the number will reach 10 to 12 million when including the number of people and reserves such as latent diabetes. In particular, NIDDM accounts for over 90% of diabetes. Generally, hyperglycemic conditions are found after middle age, and hyperglycemic conditions often persist for many years, and diet and exercise therapy are the basis of treatment in general. Therefore, a prophylactic / therapeutic agent for NIDDM that can be taken while eating a daily meal is desired.

[0003] In Japan, over 40% of patients undergoing treatment for diabetes receive oral hypoglycemic drugs. However, these oral hypoglycemic drugs (especially sulfonylureas <
SU agents>, piguanides, sulfonamides), etc., are reported to have many side effects such as hematopoietic disorders, hepatic dysfunction, gastrointestinal disorders, etc., and it is currently difficult to take them without a doctor's instruction. Therefore, considering long-term administration, a safe and inexpensive prophylactic / therapeutic drug for NIDDM is expected from the viewpoint of side effects.

[0004]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a pharmaceutical composition for preventing and treating NIDDM which can be easily ingested while taking a daily meal and which is safe in terms of side effects, or a similar effect. To provide health food.

[0005]

[Means for Solving the Problems] Agaricus b
lazei) is a mushroom belonging to the agaric family Agaricaceae collected in the outskirts of Piedate, Sao Paulo, Brazil. In recent years, anticancer effects (antitumor activity) of Agaricus have been noticed by cancer researchers in Europe, North America and Japan,
-It has been shown that polysaccharides such as D-glucan have an anticancer effect through activation of the immune system. It is also known that this agaricus has a hypoglycemic effect on diabetes.

[0006] On the other hand, mulberry is a plant belonging to the mulberry family.
This mulberry leaf (Morus alba L.) contains sugars such as sucrose, fructose and glucose, amino acids such as aspartic acid and glutamic acid, various vitamins and metals such as zinc. Also, mulberry leaves are known to have a hypoglycemic effect and have an effect of preventing diabetes, and have been used as a traditional Chinese medicine for a long time.

[0007] Now, the present inventors have surprisingly produced a synergistic effect by mixing a mulberry leaf extract and an agaricus extract, and have a greater effect on diabetes than using each alone. The present invention has been found to work in an effective manner, and the present invention has been completed.

That is, the present invention provides a pharmaceutical composition for preventing and treating NIDDM, comprising a mulberry leaf extract and an agaricus extract as active ingredients.

The present invention also provides a health food containing a mixture of a mulberry leaf extract and an agaricus extract.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the pharmaceutical composition and health food of the present invention will be described.

[0011] The pharmaceutical composition and health food of the present invention contain a mixture of a mulberry leaf extract and an agaricus extract as an active ingredient.

The mulberry leaf extract is prepared by powdering mulberry leaves after drying (hereinafter referred to as mulberry leaves "prototype drug") in a boiling water bath (95%).
１００100 ° C.) for 2 to 10 minutes, followed by a hot water bath (60 to
80.degree. C.) for 5-20 minutes, filter and concentrate the filtrate. If desired, the concentrated extract can be further lyophilized. On the other hand, an Agaricus extract can be obtained in the same extraction step by the same preparation method as the above-mentioned mulberry leaf extract, starting from Agaricus which has been dried and powdered (hereinafter referred to as Agaricus "prototypic drug"). The mixture of the mulberry leaf extract and the agaricus extract can also be prepared by mixing the mulberry leaf "prototype drug" and the agaricus "prototypic drug" and then performing the above steps.

The mulberry leaf extract and the Agaricus extract obtained above can be mixed in a desired ratio to obtain a mixture. The mixing ratio is agaricus extract: mulberry leaf extract = 1: 300-300: 1 in terms of weight ratio from the viewpoint of synergistic effect.
Is preferable.

The mixture can be tableted, granulated, or liquidized to obtain a tablet package, a granule package, or a liquid. In the formulation, for example, in tableting and granulation, conventional excipients such as lactose, dextrin, starch, and cellulose may be used, and in liquid formulation, conventional excipients such as stabilizers and preservatives may be used. Various additives can be used. Alternatively, they can be filled into suitable bottles (glass, cans, moisture-proof fiber papers).

[0015] The total amount of the mulberry leaf extract and the agaricus extract to be incorporated into the pharmaceutical composition of the present invention is in the range of 30 to 3000 mg per dose.

The total amount of the mulberry leaf extract and the agaricus extract per tablet is 10%.
For tablets that are ~ 250 mg, 3-6 tablets / dose in the morning,
It is preferably taken three times a day before lunch and dinner. In the case of granules having a total amount of mulberry leaf extract and agaricus extract per packet of 50 to 250 mg, 1 to 6
It is preferable to take the sachet three times a day in the morning, afternoon and dinner before meals. Further, in the case of a liquid preparation in which the total amount of the mulberry leaf extract and the agaricus extract per 1 ml of the preparation is 50 to 250 mg, 1 to 3 ml / time is used in the morning, lunch, and dinner 3 times a day.
It is preferable to take it before meals.

The pharmaceutical composition of the present invention is non-toxic because it is a hot water extract obtained from mulberry leaves and agaricus which has been conventionally taken by humans.

The health food of the present invention is composed of a mixture obtained as described above and the above-mentioned excipients and additives in the form of supplementary food (eg, finely divided sachets, solid round granules, triangular granules, etc.). ) Or re-dissolved in an aqueous solution and blended into a drink.

[0019]

The present invention will be described in more detail with reference to the following Preparation Examples and Examples, which should not be construed as limiting the invention thereto.

Preparation Example 1 Preparation of Mulberry Leaf Extract Mulberry leaves were shade-dried, dried with hot air at 70 to 85 ° C., steam-sterilized, and further dried at 50 to 70 ° C. for several hours. The dried mulberry leaves were pulverized to obtain 120 mesh mulberry leaves. 50 to 500 for this mulberry leaf
Double weight of distilled water was added. This is a boiling water bath (95 ° C)
In a hot water bath (70 ° C.) for 10 minutes, and filtered through a filter paper for quantitative analysis. The filtrate was concentrated under reduced pressure using a concentrator (manufactured by Tokyo RIKAKIAI) to obtain a concentrated extract. Next, this was freeze-dried (EYELA FD).
U-506) to give a freeze-dried product.

Preparation Example 2 Preparation of Agaricus Extract Agaricus was shaded and dried in hot air at 70 to 85 ° C.
After steam sterilization, it was further dried at 50 to 70 ° C. for several hours. The dried agaricus was powdered to obtain 120 mesh agaricus. 50 to 500 times by weight of distilled water was added to the Agaricus "prototype drug". This is placed in a boiling water bath (95 ° C.) for 5 minutes and then in a hot water bath (70 ° C.)
For 10 minutes and filtered with a filter paper for quantitative analysis. The filtrate was concentrated under reduced pressure using a concentrator (manufactured by Tokyo RIKAKIAI) to obtain a concentrated extract. Next, this was freeze-dried with a freeze dryer (EYELA FDU-506) to obtain a freeze-dried product.

Example 1 100 mg of the mulberry leaf extract obtained in Preparation Example 1, Preparation Example 2
Was mixed with 50 mg of the agaricus extract, 30 mg of reduced maltose starch syrup, 5 mg of dextrin and 15 mg of glycerin fatty acid ester, granulated, dried and sieved through 16 mesh, and then tableted (hexagonal tablet,
(Pills or triangular tablets) of the present invention.

Example 2 100 mg of the mulberry leaf extract obtained in Preparation Example 1, Preparation Example 2
Was mixed with 50 mg of the agaricus extract, 30 mg of reduced maltose starch syrup, 5 mg of dextrin and 15 mg of glycerin fatty acid ester, granulated, dried and sieved through 16 mesh, and then tableted (hexagonal tablet,
A round tablet or a triangular tablet) was obtained.

Example 3 100 mg of the mulberry leaf extract obtained in Preparation Example 1, Preparation Example 2
Agaricus extract obtained in the above, 50 mg, dextrin 3
8 mg and 12 mg of tricalcium phosphate were mixed, granulated, dried and sieved through 16 to 80 mesh, and then granulated according to a conventional method to obtain a pharmaceutical composition of the present invention in the form of granules.

Example 4 100 mg of the mulberry leaf extract obtained in Preparation Example 1, Preparation Example 2
Agaricus extract obtained in the above, 50 mg, dextrin 3
8 mg and 12 mg of tricalcium phosphate were mixed, granulated, dried and sieved with 16 to 80 mesh, and then granulated according to a conventional method to obtain a health food of the present invention in the form of granules.

Example 5 A mixture of 100 mg of the mulberry leaf extract obtained in Preparation Example 1 and 50 mg of the Agaricus extract obtained in Preparation Example 2 was mixed with 1
The mixture was redissolved in ml of distilled water, filled into a 30 ml glass bottle with a spoid, and liquefied to obtain a pharmaceutical composition of the present invention in a liquid form.

Example 6 A mixture of 100 mg of the mulberry leaf extract obtained in Preparation Example 1 and 50 mg of the Agaricus extract obtained in Preparation Example 2 was mixed with 1
The solution was redissolved in distilled water, filled in a 30 ml glass bottle with a spoid, and liquefied to obtain a liquid form of the health food of the present invention.

Test of the Effect of the Pharmaceutical Composition of the Present Invention on Diabetes In this test, the mulberry leaf extract obtained in Preparation Example 1 and the Agaricus extract obtained in Preparation Example 2 were added to the diet. Alternatively, these mixtures were administered to spontaneously diabetic mice (KK- ^Ay mice), and the effect of improving the blood glucose level of the mulberry leaf extract and / or agaricus extract was examined. Since the KK- ^Ay mouse expresses severe obesity and hyperglycemia at the age of 7 to 8 weeks, it is used for studying the elucidation of the onset mechanism of NIDDM which accounts for the majority of diabetic patients.
In particular, it is a disease model animal suitable for screening antidiabetic drugs. The glucose metabolism improving effect on the NIDDM model mouse is as follows. The test data was subjected to statistical processing by one-way analysis of variance,
A significant difference test was performed by multiple comparison of ey.

1. Purchased Experimental method 1) NIDDM rearing conditions 5-week-old mouse model KK-A ^y strain male mice were subjected to preliminary rearing. Thereafter, the blood glucose level in fasting blood sampling was measured, and the mice were divided into four groups so that the blood glucose level at the start of the experiment in each group was almost uniform. Control group (group A: 6 animals), mulberry 5% based on AIN-76 diet as experimental diet
The administration group (Group B: 6 animals), the mulberry 5% + Agaricus 5% administration group (Group C: 6 animals) and the Agaricus 5% administration group (Group D: 6
). During the 78-day experiment,
The mice were housed alone in plastic cages under a light-dark cycle (7:00 to 19:00) of 12 hours at room temperature of 22 ± 2 ° C., and had free access to food and drinking water.

2) Preparation of Experimental Feed In this experiment, milk casein was used as a protein source. In the mulberry and / or agaricus administration groups (groups B, C and D), the amount of mulberry and / or agaricus extract added to the feed was adjusted by subtracting from the amount of corn starch. Table 1 shows the composition of the experimental feed.

[0031]

[Table 1]

3) Feed group and number of animals Table 2 shows the feed groups and the number of animals.

[0033]

[Table 2]

4) Glucose tolerance test Ten weeks after the start of feed intake, a glucose tolerance test frequently used in clinical tests was conducted to examine glucose tolerance. The sugar loading conditions are as follows. After fasting the mice for 24 hours, soluble starch was orally administered at 2 g / kg body weight. Blood is collected from the tail vein before administration and at 30, 60, 120 and 180 minutes after administration, and a small blood glucose meter Gurutest (Co., Ltd.)
Blood glucose was measured by the enzyme electrode method using Kyoto Daiichi Kagaku).

2. Experimental Results The experimental results are shown in Table 3 and FIG. Table 3 shows the measurement results of blood glucose levels before and after administration of the soluble starch at 10, 60, 120 and 180 minutes after the start of the intake of feed. FIG. 1 is a graph showing a time-dependent change of a blood sugar level. The mulberry / agarics co-administration group (group C) consisted of a mulberry alone administration group (group B) and an agaricx alone administration group (group D).
It was clear that the blood sugar level was suppressed at 30, 60 and 120 minutes after administration. In particular, since soluble starch is a major component of many beans such as cereals, potatoes, and beans, the synergistic blood sugar level-suppressing effect of co-administration of mulberry / agaricus is significant for prevention and treatment of diabetes. It is considered something.

[0036]

[Table 3]

As a result, the mixture of the mulberry leaf extract and the agaricus extract each provided a better blood glucose level improving effect than when taken alone. That is, α due to the active ingredient considered to be contained in the mulberry leaf extract
-The synergistic effect of the inhibitory effect of glucosidase and the effect of increasing immunity and normalizing the action of insulin by active ingredients considered to be contained in the Agaricus extract, such as β-D-glucan, is revealed. It has been found that pharmaceutical compositions and health foods are very effective, safe and ideal compositions for ameliorating diabetes.

[0038]

Industrial Applicability According to the present invention, there are provided a pharmaceutical composition and a health food which are effective in treating NIDDM, can be easily taken while eating a daily meal, and are safe in terms of side effects.

[Brief description of the drawings]

FIG. 1 is a graph showing the time course of blood glucose levels when soluble starch is loaded 10 weeks after the start of feed intake.

Claims (4)

[Claims] 1. A pharmaceutical composition for preventing or treating non-insulin dependent diabetes, comprising a mixture of a mulberry leaf extract and an agaricus extract as an active ingredient. 2. The pharmaceutical composition according to claim 1, wherein the compounding ratio of the mulberry leaf extract and the agaricus extract is in the range of 1: 300 to 300: 1 (weight ratio). 3. A health food for preventing or treating non-insulin-dependent diabetes, comprising a mixture of a mulberry leaf extract and an agaricus extract as an active ingredient. 4. The health food according to claim 3, wherein the compounding ratio of the mulberry leaf extract and the agaricus extract is in the range of 1: 300 to 300: 1 (weight ratio).