JPH10120584A - Therapeutic agent for diabetes - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prepare a therapeutic agent for diabetes having excellent promoting actions on the secretion of insulin and improving actions on glucose tolerance without a fear of causing hypoglycemia. SOLUTION: This therapeutic agent for diabetes comprises a substance, obtained from the whole root tuber of Ipomoea Batatas sp. or its root bark part and having the following physical properties as an active ingredient: (1) molecular weight: about 2×10<4> , (2) pH: about 5 (10mg/10mL), (3) solubility: readily soluble in water and sparingly soluble in ethanol, chloroform, ethyl acetate, acetone, hexane and benzene, (4) molar absorbance coefficient: about 2×10<5> (at 280nm) and (5) ingredient composition: consisting essentially of a protein and slightly containing saccharides and lipids and negative to the Fehling's test.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001] The present invention relates to a therapeutic agent for diabetes which has an excellent insulin secretion promoting action and glucose tolerance improving action and which does not cause hypoglycemia.

TECHNICAL FIELD OF THE INVENTION

[0002]

2. Description of the Related Art At present, the number of diabetic patients is said to be 6 million, and their medical conditions are divided into insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Drug therapy is based on exercise therapy. These NI
In the case of DDM, if the effects of diet and exercise are not effective, the therapeutic drugs for diabetes include sulfonylurea (SU), tolbutamide developed in 1956, sulfonamide, biguanide and the like. (BU agents), and currently SU agents are most frequently used.

[0003] However, SU preparations also have side effects such as hypoglycemia, rash, diarrhea, nausea and liver dysfunction.
In addition, the BU agent alone does not provide a certain effect, and may cause severe gastrointestinal symptoms, which may cause metabolic abnormality side effects. Diabetes medications generally have to be considered for their application and use, placing a heavy burden on patients with mild diabetes.

[0004] On the other hand, in the case of IDDM, insulin is administered. However, since insulin must be administered at a fixed time every day and self-injection must be instructed, patients have sufficient knowledge and skills of insulin therapy. Knowledge is required.

[0005] As described above, in any of the diet therapy, exercise therapy, drug therapy, and insulin therapy, it is difficult to perform at home under self-management, and it is difficult to obtain an effective therapeutic effect. The development of a method to control well is awaited.

[0006]

SUMMARY OF THE INVENTION Based on the above-mentioned situation, the present inventors have conducted intensive studies to develop a method for controlling diabetes without side effects, and as a result, the white sweet potato ( Ipomoea Batatas sp.) has an antidiabetic effect including an insulin secretion promoting effect and a glucose tolerance improving effect, and has already filed a patent application as a food composition containing an antidiabetic component (Japanese Patent Application No. Hei 7-344713).
issue). However, the active ingredient having the antidiabetic action was not always clear.

The present inventors have studied in more detail the active ingredient of white sweet potato having an antidiabetic action, and as a result, found that the molecular weight is 2 ×.
10 about ^4, high-performance liquid chromatography (HPL
C) Ascertained that the substance purified to a single peak above was its main body, and based on this finding, completed the present invention.

An object of the present invention is to provide a remedy for diabetes which has an excellent insulin secretion promoting action and glucose tolerance improving action and is not likely to cause hypoglycemia.

[0009]

That is, the present invention according to claim 1 provides a diabetes containing as an active ingredient a substance having the following physical properties, which is obtained from the whole tuberous root of a white sweet potato ( Ipomoea Batatas sp.) Or its skin. It provides a therapeutic agent.

1) Molecular weight: about 2 × 10 ⁴ 2) pH: about 5 (10 mg / 10 ml) 3) Solubility: easily soluble in water, poorly soluble in ethanol, chloroform, ethyl acetate, acetone, hexane and benzene 4) Molar absorbance coefficient: about 2 × 10 ⁵ (280 nm) 5) Component composition: Mainly protein, slightly contained saccharides and lipids, negative for Fehling test

[0011] The present invention according to claim 2 provides an extract obtained from the whole tuber of the white sweet potato ( Ipomoea Batatas sp.) Or its skin portion at least by dialysis treatment, lower alcohol fractionation treatment, and trichloroacetic acid treatment. It is intended to provide a remedy for diabetes comprising, as an active ingredient, a substance obtained by the above-mentioned method, and a substance having the above-mentioned physical properties as an active ingredient.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION Here, white sweet potato ( Ipomoea Batata)
s sp.) is a sweet potato (Hiploaceae herb Ipomoea Ba)
tatas Piret and its tuberous roots), as shown here, contains components that promote insulin secretion, components that improve glucose tolerance, and components that suppress complications of diabetes (eg, hyperlipidemia). And contains vitamin K, chlorophyll, folic acid (yarapic acid) and the like.

The active ingredient of the antidiabetic drug of the present invention according to claim 1 (hereinafter simply referred to as the present invention) is the whole tuberous root of such a naturally produced white sweet potato ( Ipomoea Batatas sp.) Or its whole. Present in the skin. In particular, white sweet potato ( I
pomoea Batatas sp.) is present in the bark root bark at a high concentration as already described in Japanese Patent Application No. 7-344713.

[0014] Such an active ingredient in the therapeutic agent for diabetes of the present invention can be produced, for example, by the following method. The active ingredient in the antidiabetic agent of the present invention can be obtained by subjecting an extract obtained from the whole tuberous root of white sweet potato ( Ipomoea Batatas sp.) Or its skin to at least dialysis treatment, lower alcohol fractionation treatment, and trichloroacetic acid treatment. . One example of such a purification treatment operation is shown in FIG.

That is, first, white sweet potato ( Ipomoea)
An extract is obtained from the whole tuber of Batatas sp.) Or its skin (however, a part may be accompanied by a tuber).

[0016] Such an extract is prepared by drying the whole tuberous root of white sweet potato or its skin (however, a part thereof may be accompanied by a tuberous root) by freeze-drying or the like, and adding water to the pulverized dry powder. In addition, the extract is extracted using a homogenizer, or the whole tuberous root of white sweet potato or its skin (however, a part thereof may be accompanied by a tuberous root) is thoroughly washed, crushed and squeezed. After further removing the insoluble matter, the extract can be obtained by adding water to a dry powder obtained by freeze-drying or spray-drying or the like, and extracting the extract using a homogenizer.

Specifically, for example, after the tuberous roots of white sweet potato ( Ipomoea Batatas sp.) Are thoroughly washed, the whole tuberous roots without skin are freeze-dried and pulverized without peeling. To obtain a dry powder. Alternatively, after washing the tuberous root of white sweet potato ( Ipomoea Batatas sp.)
Peel the skin with a peeler or the like, freeze-dry only the skin part, and pulverize to obtain a dry powder. However, as described above, the root may be partially attached to the skin. In this case, the remaining unnecessary portions of the roots can be used separately for appropriate purposes.

On the other hand, as the above-mentioned method, specifically, for example, after thoroughly washing tuberous roots of white sweet potato ( Ipomoea Batatas sp.), The whole tuberous roots without skin are removed without peeling as they are, such as juicers, mixers, etc. Crushed, squeezed,
Further, after removing insoluble matters by a centrifugal sedimentation method, a filtration method, or the like, the powder is dried by freeze-drying or spray-drying to obtain a dry powder. Or white sweet potato ( Ipomoea Batata
s sp.), after thoroughly washing the roots, peeling the skin with a peeler or the like, crushing and squeezing only the skin with a juicer or mixer, and then insoluble by centrifugal sedimentation, filtration, etc. After removing the substance, it is dried by freeze drying or spray drying to obtain a dry powder.

Next, the dried powder of the tuberous root of white sweet potato (preferably, the dried powder of bark root of white sweet potato) thus obtained is extracted with water or an aqueous organic solvent to obtain an extract. Although the extraction can be sufficiently performed with water, an aqueous organic solvent (for example, a lower alcohol such as methanol or ethanol) may be used in order to prevent decay of the extract and promote the extraction. This extraction is usually repeated two or three times, and may be heated as necessary to promote extraction.

The extract thus obtained is centrifuged to remove the precipitate, and then subjected to dialysis using a cellophane tube or the like. This dialysis treatment is performed using about 20 times the amount of distilled water with respect to the extract, and this dialysis treatment is usually performed 6 to 7 times.

After the dialysis treatment, a lower alcohol such as ethanol is added to the obtained inner dialysis solution to perform a lower alcohol fractionation treatment. In the treatment, usually, ethanol is used to make an 85% ethanol solution.

This solution is again filtered by centrifugation, and the obtained supernatant is subjected to TCA treatment in which trichloroacetic acid (hereinafter abbreviated as TCA) is added. It is then centrifuged and the resulting supernatant is dialyzed again to remove TCA. Fraction 1 (hereinafter, referred to as Fr. 1) is obtained from the dialysate.

Specifically, for example, an 85% ethanol treatment is performed, and the centrifuged supernatant is concentrated under reduced pressure, and then freeze-dried to obtain a powder, which is dissolved in a 15% TCA solution to carry out TCA treatment. After centrifugation, the obtained supernatant is dialyzed again in the same manner as above, and then TCA is removed to obtain a lyophilized powder. Thus, Fr.1 is obtained.

The thus obtained Fr. 1 has an excellent anti-diabetic action, but a fraction having a higher anti-diabetic action can be obtained by further performing the following operation. .

That is, the fraction is obtained by dissolving a freeze-dried product of the above Fr.1 in, for example, 2M ammonium sulfate, subjecting it to ammonium sulfate salting-out treatment, and then centrifuging the resultant. The purified component is an adsorbed component subjected to Butyl-Toyopearl hydrophobic chromatography (hereinafter referred to as Fr.2), or the thus obtained Fr.2 is adsorbed component subjected to Phenyl-Toyopearl hydrophobic chromatography (hereinafter referred to as Fr.2). , Fr.3
Called. ) Or the fraction obtained by ultrafiltration of the thus obtained Fr.3 using, for example, a filter having a molecular weight fraction of 3 × 10 ⁴ (hereinafter referred to as F.3).
Called r.4. ), And by using these fractions, a therapeutic agent for diabetes having a more effective antidiabetic action can be obtained.

By performing such a purification treatment, the active ingredient contained in the tuberous root of white sweet potato, which has an excellent antidiabetic action, can be subjected to high performance liquid chromatography (HPL).
C) By analysis, it was purified to almost a single component. A flowchart of such a purification treatment operation is shown in FIG. 1 as described above, and FIG. 2 shows a pattern of Butyl-Toyopearl hydrophobic chromatography and FIG. 3 shows a pattern of Phenyl-Toyopearl hydrophobic chromatography. It is shown. Further, the results of HPLC analysis by reverse phase chromatography and gel filtration chromatography after purification are shown in FIGS.

As a result, the active ingredient contained in the tuberous root of white sweet potato having excellent anti-diabetic activity showed a single peak in each HPLC, and the molecular weight was about 2 × 10 ^{4 according to} the result of gel filtration chromatography. It is estimated to be. Further, the pH of this substance is about 5 (10 mg / 10 ml), more specifically, 5.12 (10 mg / 10 ml), the solubility is easily soluble in water, and ethanol, chloroform,
It is hardly soluble in ethyl acetate, acetone, hexane and benzene, and has a molar absorbance coefficient of about 2 × 10 ⁵ (280 nm).
Specifically, it is 2.04 × 10 ⁵ (280 nm), and the composition of the component is a protein as a main component, saccharides and lipids are slightly contained, and the Fehling test is negative.

The antidiabetic agent of the present invention contains the above-mentioned substance as an active ingredient and, if necessary, a suitable excipient (for example, Cellulose, tribasic calcium phosphate, dextrin, lactose, etc.), vitamins, stabilizers, preservatives, coloring agents, fragrances and the like.

The antidiabetic agent of the present invention can be used in the form of tablets, liquids, capsules, granules, powders and the like according to a conventional method.

[0030] Such an antidiabetic drug of the present invention is usually administered to an adult at a dose of 2 to 10 mg per day for 10 to 10 doses.
By continuing for about 30 days, a desired effect can be obtained. In addition, the antidiabetic agent of the present invention can be added to food materials as a food additive or can be eaten as tablet confections, and any of them can be used effectively for treating diabetes.

The efficacy of the therapeutic agent for diabetes of the present invention was confirmed using Wistar rats and diabetic patients. As can be seen from the examples described below using rats, the insulin secretion effect was increased by about 2 to 5 times as compared with the control as it went through the purification step. In addition, the active ingredient of the antidiabetic agent of the present invention is 50% less than the root extract powder of white sweet potato.
It has an equivalent insulin secretion effect even with a very small amount of 1/0, and a 15-30% decrease in blood glucose level as compared with the control was also observed in the glucose tolerance improving effect.

In addition, administration of the antidiabetic drug of the present invention
It was also found that the blood sugar level was not lowered below the normal value, and that no side effects such as hypoglycemia appeared. Furthermore, it was confirmed that when administered to a diabetic patient, the fasting blood glucose level was significantly reduced 14 days later.

[0033]

Next, the present invention will be described in more detail with reference to examples, but the scope of the present invention is not limited by these examples.

Preparation Example 1 ( Potato Tuber Root Extraction) 10 kg of tuber root ( Ipomoea Batatas sp.) Was thoroughly washed with water to remove dirt, then peeled using a peeler, and only the skin portion was removed . It was freeze-dried to obtain 80 g of a freeze-dried tuberous bark skin of white sweet potato.

The lyophilized product was subjected to the following purification operation. This purification operation is as shown in the flowchart of FIG. That is, water was first added to the freeze-dried product, and the extract was extracted using a homogenizer. This extract was centrifuged to remove precipitates, and then dialyzed using a cellophane tube. Next, ethanol was added to the inner solution obtained by dialysis to make an 85% ethanol solution, and then centrifuged again. The obtained supernatant was concentrated under reduced pressure and freeze-dried, and the resulting powder was subjected to TCA treatment to obtain a 15% TCA solution. After centrifugation three times, the supernatant is dialyzed.
Fr.1 was obtained.

220 mg obtained by freeze-drying this Fr.1
Was freeze-dried in 2 M ammonium sulfate (ammonium sulfate salting out treatment), and the supernatant obtained by centrifugation was subjected to Butyl-Toyopearl hydrophobic chromatography to obtain Fr.2 as an adsorbed component. .

This Fr.2 was further subjected to Phenyl-Toyopearl hydrophobic chromatography to obtain Fr.3 as an adsorbed component thereof.

Further, this Fr.3 was subjected to ultrafiltration. As a result, in the filter having a molecular weight fraction of 3 × 10 ⁴ , the active ingredient was passed through the fraction Fr.4.

By performing the above treatment, the active ingredient of the tuberous root of white sweet potato having an anti-diabetic action was purified by HPLC analysis until it became almost single. Table 1 shows the yield and yield of each active fraction in the purification process.

[0040]

[Table 1]

FIG. 2 shows the pattern of Butyl-Toyopearl hydrophobic chromatography. FIG. 3 shows that Phenyl-
The pattern of Toyopearl hydrophobic chromatography was shown.

The measurement conditions of Butyl-Toyopearl hydrophobic chromatography shown in FIG. 2 are as follows.

Column: TSK gel Butyl-Toyopearl 650 M Eluent: A = 0.1 M phosphate buffer (pH 7.0) +2 M ammonium sulfate B = 0.1 M phosphate buffer (pH 7.0) C = 50% ethanol D = 100 % Ethanol A → D stepwise ・ Flow rate: 1.0 ml / min ・ Detection: UV (220 nm) ・ Sample: 15% TCA supernatant, 2M ammonium sulfate soluble component 220mg

The measurement conditions of the Phenyl-Toyopearl hydrophobic chromatography shown in FIG. 3 are as follows.

Column: TSK gel Phenyl-Toyopearl 650 M Eluent: A = 0.1 M phosphate buffer (pH 7.0) +2 M ammonium sulfate B = 0.1 M phosphate buffer (pH 7.0), 2 M → 0 M ammonium sulfate gradient C = 0.1 M phosphate buffer (pH 7.0) D = 50% ethanol E = 100% ethanol Flow rate: 1.0 ml / min Detection: UV (220 nm) Sample: Butyl-Toyopearl adsorption, 2M ammonium sulfate soluble component 120 mg

In addition, reverse phase chromatography (TSK gel ODS-80 ™) of the freeze-dried product of the purified white sweet potato tuber bark skin
And gel filtration chromatography (TSK gel G 2000 S
The analysis results (analysis pattern) of HPLC by W) are shown in FIGS. 4 and 5, respectively.

In addition, a reverse phase chromatography (TSK gel) of the freeze-dried product of the purified white sweet potato tuber skin shown in FIG.
The measurement conditions of ODS-80TM) are as follows.

Column: TSK gel ODS-80TM Solvent: MeOH / H ₂ O (60/40) Flow rate: 1.0 ml / min Detection: UV (220 nm) Temperature: 45 ° C. Sample: ultrafiltration MW <3 × 10 ⁴

Also, as shown in FIG. 5, gel filtration chromatography (TSK) of the freeze-dried product of the purified white sweet potato tuber bark skin
gel G2000SW) measurement conditions are as follows.

Column: TSK gel G2000SW Solvent: 0.1 M phosphate buffer (pH 7.0) /0.1 M NaCl Flow rate: 1.0 ml / min Detection: UV (220 nm) Temperature: 25 ° C. Sample: ultrafiltration MW <3 × 10 ⁴

From the points showing a single peak in each HPLC and the result of gel filtration chromatography, the molecular weight of this substance was estimated to be about 2 × 10 ⁴ . The physical properties of the substance having an anti-diabetic effect are as follows.

1) Molecular weight: about 2 × 10 ⁴ 2) pH: 5.12 (10 mg / 10 ml) 3) Solubility: easily soluble in water, poorly soluble in ethanol, chloroform, ethyl acetate, acetone, hexane and benzene 4 ) Molar absorbance coefficient: 2.04 × 10 ⁵ (280 nm) 5) Component composition: Mainly protein, slightly contained saccharides and lipids, negative for Fehling test

Example 1 (Administration test of Fr.1 to Wistar rats) Five 7-week-old Wistar rats were used, and 4 mg / kg of Fr.1 obtained in Production Example 1 was added to the tail vein. Was administered internally. Blood was collected 24 hours after the administration, and the blood glucose level and serum insulin level were measured. As a control, the blood glucose level and serum insulin level were similarly measured for the non-administration group. Fr.1
Table 2 shows the average body weight, blood glucose level, and serum insulin level of each of the administration group and the non-administration group.

[0054]

[Table 2]

From Table 2, it can be seen that the blood glucose level of the Fr.1 administration group was almost the same as that of the non-administration group, whereas the insulin level was significantly up to about twice at P <0.01. It can be seen that it rises. From this, it was confirmed that Fr.1 has an action of promoting insulin secretion twice without changing the blood glucose level of normal rats.

Example 2 (Administration test of Fr.2 to Wistar rats) In Example 1, except that 2 mg / kg of Fr.2 obtained in Production Example 1 was used instead of Fr.1, The same operation as in Example 1 was performed. Table 3 shows the average body weight, blood glucose level, and serum insulin level of each of the Fr.2 administration group and the non-administration group.

[0057]

[Table 3]

From Table 3, it can be seen that the blood glucose level of the Fr.2 administration group was almost the same as that of the non-administration group, whereas the insulin level was significantly up to about 4-fold at P <0.01. It can be seen that it rises. From this, it was confirmed that Fr.2 has an action of promoting insulin secretion 4-fold at a dose of half that of Fr.1, without changing the blood glucose level of normal rats.

Example 3 (Administration test of Fr.3 to Wistar rats) In Example 1, Fr.3 obtained in Production Example 1 was used in place of Fr.1 except that 2 mg / kg was used. The same operation as in Example 1 was performed. Table 4 shows the average body weight, blood glucose level and serum insulin level of each of the Fr.3 administration group and the non-administration group.

[0060]

[Table 4]

From Table 4, it can be seen that the blood glucose level of the Fr.3 administration group is almost the same as that of the non-administration group, whereas the insulin level is significantly up to about 5 times at P <0.01. It can be seen that it rises. From this, it was confirmed that Fr.3 has an action of promoting insulin secretion up to about 5-fold at a half dose of Fr.1 without changing the blood glucose level of normal rats.

Example 4 (Administration test of Fr.4 and white potato tuber extract powder to Wistar rats) Five 7-week-old male Wistar rats were used, and Fr.4 obtained in Production Example 1 was used. Was administered via the tail vein at 1 mg / kg. Blood was collected 24 hours after the administration, and the blood glucose level and serum insulin level were measured. On the other hand, white sweet potato ( Ipomoea Batatas sp.
) 500 mg / kg of tuberous root extract was similarly administered to the tail vein and blood was collected 24 hours later, and the blood glucose level and insulin level were measured. Further, as a control, the blood glucose level and serum insulin level were similarly measured for the non-administration group. Fr.4 administration group,
Table 5 shows the average body weight, blood glucose level, and serum insulin level of the group of the white sweet potato ( Ipomoea Batatas sp.) Tuber extract powder administration group and the non-administration group.

[0063]

[Table 5]

From Table 5, it can be seen that the group to which Fr. 4 was administered and the white sweet potato ( Ipo
moea Batatas sp.) In the group to which the tuber extract powder was administered, the blood glucose level was almost the same as that in the group to which no tuber extract was administered, whereas the insulin level was significantly increased by about 3 times at P <0.01. You can see that. From this, Fr.4 and white sweet potato ( Ipomoea
Batatas sp.) Tuber root extract powder was confirmed to have an action of promoting insulin secretion up to about three times without changing the blood glucose level of normal rats. Furthermore, Fr.4 was administered at a dose of only 1 mg / kg in white sweet potato ( Ipomoea Batatas s.
p.) Tuber extract powder was also confirmed to have an effect equivalent to 500 mg / kg.

Example 5 (Glucose tolerance test after administration of Fr.4 to Wistar rats) Using 6 7-week-old Wistar rats, 1 mg / kg of Fr.4 obtained in Production Example 1 was used. It was administered intravenously. Twenty-four hours after the administration of Fr.4, 2.0 g / kg of glucose was orally administered using a sonde, and the blood glucose (blood sugar level) and insulin level were measured over time. Also, as a control,
Glucose administration and measurement were similarly performed for the non-administration group. FIG. 6 shows the measurement results of glucose (blood sugar level) of the Fr.4 administration group and the non-administration group, and FIG. 7 shows the measurement results of insulin concentration.

As shown in FIGS. 6 and 7, the Fr.4 administration group
Compared to the non-administration group, the blood glucose level was almost the same over time, but the insulin level was significantly lower at P <0.01. From this, the anti-diabetic component contained in Fr.4,
It was found to have an effect of promoting insulin secretion and an effect of suppressing an increase in blood glucose level during glucose load.

Example 6 (Administration test of anti-diabetic component of white sweet potato to humans) Anti-diabetic component of white sweet potato ( Ipomoea Batatas sp.) Was actually administered to six patients with non-insulin-dependent diabetes mellitus. The effectiveness was investigated. A powder obtained by subjecting a powder of 85% ethanol fraction of white sweet potato ( Ipomoea Batatas sp.) Prepared by the method of Production Example 1 to 2M sulfuric acid was dialyzed to remove ammonium sulfate. (including 7mg about antidiabetic component having a molecular weight of about 2 × 10 ^4.) powder 50mg was obtained. Cellulose was added to this and formulated into 2 g sachets.
Twice a day for 14 consecutive days. The fasting blood glucose level of each patient was measured before the start of administration and at the end of internal use. The results are shown in Table 6.

[0068]

[Table 6]

From the results shown in Table 6, the fasting blood glucose level of the patient before the start of the administration was 122 to 178 mg / dl, and the fasting blood glucose level was 9 at the end of the administration.
It turns out that it falls to 8-141 mg / dl. In addition, four of the six patients had physical malaise, easy fatigue, etc. before the start of the administration, but all of them resolved significantly at the end of the administration. From this, white sweet potato ( Ipomoea Ba
tatas sp.) It was confirmed that the anti-diabetic component was also effective against human diabetes.

Example 7 [Single-Dose Toxicity Test by Oral Administration to Rats (Non-GLP)] Five weeks each of 7-week-old Wistar rats and males and females, Fr.1 obtained in Production Example 1 was used. 2000 mg / kg was orally administered using a probe and compared with each control group without Fr.1 administration.

As a result, during the observation period of 7 days, no one died due to the administration of Fr.1. As a result of the observation of the general condition, there was no change compared to the control group, and no diarrhea or the like was observed. In addition, weight change of each group (average weight)
Are shown in Table 7. The body weight of both males and females increased satisfactorily in the Fr.1 administration group as well as in the control group (no administration group). At 7 days after necropsy, no abnormal findings were observed in either sex. From these results, the acute toxicity of the anti-diabetic component Fr.1 of white sweet potato to rats was extremely weak, and was 2000 mg / kg or more.

[0072]

[Table 7]

[0073]

Industrial Applicability The antidiabetic drug of the present invention is obtained by purifying an active ingredient having an antidiabetic activity from tuberous roots of white sweet potato ( Ipomoea Batatas sp.) Having an antidiabetic activity to almost a single substance.

That is, the therapeutic agent for diabetes of the present invention has an excellent insulin secretion-promoting action even in a very small amount of use, and can suppress an increase in blood glucose level after a glucose tolerance test. It has a glucose tolerance improving effect.

Next, the method of taking the antidiabetic agent of the present invention is not limited because it does not lower the blood sugar level below the normal value and does not cause side effects such as hypoglycemia. In addition, the effect of improving hyperlipidemia, which is a complication of diabetes, has been recognized.

Furthermore, the antidiabetic agent of the present invention can be obtained in high concentration from the naturally produced roots of white sweet potato, particularly from its skin, so that it can be adversely affected on the human body even when ingested as a pharmaceutical or food additive. Seems to be rare.

Therefore, the antidiabetic drug of the present invention can be safely and easily taken as a drug having an insulin secretion-promoting action and a glucose-tolerance-improving action, and is effective for diabetic patients and their reserves. Can be used.

[Brief description of the drawings]

FIG. 1 is a flowchart showing a method for purifying an antidiabetic active ingredient of white sweet potato in a therapeutic agent for diabetes of the present invention.

FIG. 2 shows a pattern of Butyl-Toyopearl hydrophobic chromatography in Production Example 1.

FIG. 3 shows a pattern of Phenyl-Toyopearl hydrophobic chromatography in Production Example 1.

FIG. 4 shows white sweet potato ( Ipomoea) in Production Example 1.
HPLC by reverse phase chromatography (TSKgel ODS- 80TM ) after purification of the active ingredient of Batatas sp.
It shows an analysis pattern.

FIG. 5 shows white sweet potato ( Ipomoea) in Production Example 1.
1 shows an HPLC analysis pattern by reverse phase chromatography (TSKgel G2000SW) after purification of the active ingredient of Batatas sp.). FIG. 6 shows the measurement results of glucose (blood sugar level) of the Fr.4 administration group and the non-administration group, and FIG. 7 shows the measurement results of insulin concentration.

FIG. 6 is a graph showing time-dependent changes in glucose (blood sugar level) after glucose load in Example 5. In the figure, ●
Indicates a group administered with Fr.4, and ○ indicates a group without administration.

FIG. 7 is a graph showing a time-dependent change in insulin concentration after glucose load in Example 5. In the figure, ● is Fr.4
The administration group is shown, and ○ indicates the non-administration group.

Claims (2)

[Claims] 1. An antidiabetic agent comprising, as an active ingredient, a substance having the following physical properties, which is obtained from the whole tuberous root of white sweet potato ( Ipomoea Batatas sp.) Or its skin. 1) Molecular weight: about 2 × 10 ⁴ 2) pH: about 5 (10 mg / 10 ml) 3) Solubility: easily soluble in water, poorly soluble in ethanol, chloroform, ethyl acetate, acetone, hexane and benzene 4) Molar absorbance coefficient : Approximately 2 × 10 ⁵ (280 nm) 5) Ingredient composition: Mainly protein, slightly contained saccharides and lipids, negative for Fehling test 2. An extract obtained from the whole tuberous root of the white sweet potato ( Ipomoea Batatas sp.) Or its skin is at least subjected to dialysis treatment, lower alcohol fractionation treatment, and trichloroacetic acid treatment. An antidiabetic agent comprising a substance as an active ingredient. 1) Molecular weight: about 2 × 10 ⁴ 2) pH: about 5 (10 mg / 10 ml) 3) Solubility: easily soluble in water, poorly soluble in ethanol, chloroform, ethyl acetate, acetone, hexane and benzene 4) Molar absorbance coefficient : Approximately 2 × 10 ⁵ (280 nm) 5) Ingredient composition: Mainly protein, slightly contained saccharides and lipids, negative for Fehling test