JPH08337530A - Blood sugar depressant containing silkworm powder as effective component and its preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce a compound, excellent in inhibiting effects on hyperglycemia and having regulating effects on the content of blood sugar to prevent especially postprandial hyperglycemia and hypoglycemia at the time of an empty stomach. SOLUTION: The antioxidizing treatment of the maximum heavy silkworm during a period of the fourth instar to the end of the fifth instar is carried out by using nitrogen gas. The resultant silkworm is freeze-dried while being preserved in a deep freezer and then powdered to afford a silkworm powder, which is used to provide the objective hypoglycemic agent. The resultant silkworm powder is better in inhibiting effects on hyperglycemia than those of a hot-air dried silkworm powder without any toxicity to human bodies due to no remaining nitrogen gas in the silkworm powder after the production. The treatment of diabetes using the silkworm powder has hypoglycemic effects by supplementing a mismatch phenomenon of the existing drug.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a hypoglycemic agent containing silkworm powder as an active ingredient and a method for producing the same, and more specifically, to a step of subjecting silkworm to antioxidant treatment with nitrogen gas, freeze-drying and powdering. The present invention relates to a method for producing silkworm powder containing the same, a hypoglycemic agent containing the same as an active ingredient, and a dietary supplement.

[0002]

2. Description of the Related Art Diabetes is one of systemic metabolic diseases caused by genetic or environmental factors, and is a disease caused by absolute or relative deficiency of hormone hormone called insulin. The main symptoms are abnormal hyperglycemia and urinary glucose due to abnormalities in sugar, fat and protein metabolism, and it is characterized by three characteristic symptoms, namely, polyphagia, polydipsia and polyuria. It is known as a disease in which fatigue and tiredness appear and the body is exhausted when the disease is severe.

Although the incidence of diabetes has been greatly increased recently, it is considered that the most effective therapeutic method is to administer a hypoglycemic agent which is excellent at the early stage of the disease to prevent residual illness. . That is, continuous regulation of postprandial blood glucose by drug administration causes a decrease in glycated hemoglobin, a decrease in average blood glucose level and a decrease in fasting blood glucose level, and as a result,
By improving insulin resistance, it becomes possible to live as a normal person.

On the other hand, when insulin preparations and oral hypoglycemic agents (sulfonylureas and biguanides), which are mainly used as therapeutic agents for diabetes at present, are administered, the blood glucose concentration after ingestion of food and drink increases rapidly. Compared with the above, the appearance of insulin in the blood by the administered drug is relatively delayed, so that a rise in postprandial blood glucose and a mismatch phenomenon with the appearance time of blood insulin appear. In particular, when insulin is administered by subcutaneous injection, its absorption is even slower, which makes the inconsistency phenomenon more serious, which causes postprandial hyperglycemia (postpr).
and hyperinsulinaemia between meals (hyperinsulinaemia)
a) and hypoglycemia become apparent.

Therefore, an ideal hypoglycemic agent has a fast drug effect and prevents an increase in postprandial blood glucose, and its efficacy disappears within a short period of time to prevent unnecessary hypoglycemia. It must be a stable oral drug that can simultaneously normalize the metabolic abnormalities that occur specifically. Currently, the development of such hypoglycemic agents is urgently required,
The treatment of diabetes using traditional drugs or folk remedies is in the limelight.

[0006] On the other hand, pupae and cocoons of silkworms are recorded as having therapeutic effects on diabetes in old books on Oriental medicine, such as the Eastern Medicine Book, and recently silkworms themselves have been used as a folk remedy for the purpose of lowering blood glucose. The number of cases is increasing. This is because the silkworm itself delays the absorption of foods and drinks by α-glucosidase inhibitor (α-glucosidase inhibito).
It is presumed that the substance derived from mulberry leaves is converted into the substance having the above-mentioned effect in the body of the silkworm because it has the effect of r).

Generally, a silkworm hatches from an egg, undergoes molting four times, transforms from a cocoon into a pupa, then becomes a moth and lays an egg, and has almost 2
It is one of the lifelong complete metamorphosis insects that die after a week. It is known that physiological changes of silkworm larvae according to the growth stage are very large, and that there is a marked difference in the levels of substances such as enzymes in the larvae before and after molting. In the body of the silkworm, there are mainly silkworm feces of mulberry leaf components, midgut digestive juice containing various enzymes, and blood. Of these, the digestive juices of the midgut and blood are very easily oxidized, and when they come into contact with air, they are easily oxidized and discolored black and inactivated.

[0008]

In the existing folk remedies, 5th instar 3 day silkworms or 5th instar maximal heavy silkworms are dried by hot air to make powders, which inactivate various enzymes existing in the body of silkworms. Comes to bring. Therefore, it can be seen that an antioxidant treatment is required in the powdering process in order to produce a superior hypoglycemic agent using silkworm. After all, in developing a hypoglycemic agent using silkworm powder, what stage of the silkworm larvae development stage, what kind of formulation,
Elucidation of what dosage and how to administer it is a major challenge.

An object of the present invention to solve the above-mentioned problems is to provide a silkworm powder comprising a step of oxidization and freeze-drying 4th instar silkworm to 5th instar terminal maximum heavy silkworm using nitrogen gas for antioxidant treatment and freeze drying. It is to provide a manufacturing method.

A further object of the present invention is to provide a hypoglycemic agent containing the silkworm powder as an active ingredient and a pharmaceutically acceptable carrier.

Further, it is an object of the present invention to provide a dietary supplement containing the silkworm powder as an active ingredient.

[0012]

[Means for Solving the Problems] The inventors of the present invention used a rat to prepare a silkworm powder by subjecting 4th instar silkworm to 5th instar extreme heavy silkworm to antioxidant treatment using nitrogen gas and freeze-drying. The present invention was completed by confirming its excellent efficacy as a hypoglycemic agent through clinical tests.

In the present invention, the larvae of the 4th instar silkworm to the 5th instar extreme heavy silkworm are each subjected to antioxidant treatment using nitrogen gas, and freeze-dried while stored in an ultra-low temperature refrigerator (deep freezer). To produce silkworm powder. Then, in order to study the effect of an α-glucosidase inhibitor that delays the absorption of foods and drinks as a method for preventing hyperglycemia, acarbose, which is known to have such an effect, was used as a control to control the silkworm. The hypoglycemic agent containing powder as an active ingredient and the silkworm powder used for folk remedies were compared for suppressing blood glucose increase. As a result, the blood glucose level was 10.6 ± 3.6 in normal mice, whereas the blood glucose level was 78.8 ± 3 in the case of hot-air dried powder of 5th instar silkworm, which is mainly used in folk medicine. The effect of suppressing blood sugar elevation was 55%, which was much lower than that of acarbose, which was 84%, as compared with the control, and the effect of suppressing the blood sugar elevation of hot-air dried powder of the 5th instar maximum heavy silkworm was 49%. It showed a lower effect than the dry powder of 3-day-old silkworm.

However, in the case of the freeze-dried powder of the 5th instar 3 day silkworm produced by the method of the present invention, the blood glucose level is 58.
The value was 0 ± 3.1, which was about 48.6 higher than the normal value, and the blood glucose elevation suppressing effect was 67%, which was a very high effect. Therefore, it was found that the 4th instar silkworm to the 5th instar maximum weight, most preferably the 5th instar 3 day silkworm, produced the most substances capable of suppressing blood glucose absorption. Further, it was found that it is most effective to freeze-dry after performing antioxidant treatment with nitrogen gas in order to further improve the utilization efficiency.

On the other hand, as a result of conducting a clinical test for healthy volunteers to measure the hypoglycemic effect on the dose of the hypoglycemic agent containing the silkworm powder produced as an active ingredient in the present invention, the hypoglycemic effect 45 minutes after meal Efficacy is 100% in the 1,162 mg dose group, 72% in the 830 mg dose group and 65 in the 498 mg dose group
%Met. Further, in the change in blood glucose level with time of each medication group, in the 498 mg medication group, the blood glucose level at 45 minutes after meal was higher than that in the fasting state but lower than that in the non-administration, and then gradually. The most ideal result was that the blood glucose level gradually decreased while maintaining the blood glucose level slightly higher than that in the fasting state in the 830 mg dose group. Furthermore, in the 1,162 mg-administered group, there was a phenomenon in which the blood glucose level 45 minutes after meal showed inhibitory activity to a blood glucose level lower than that in the fasting state and then increased again. After all, 1,16
Excessive suppressive activity was confirmed in the 2 mg dosing group, and therefore it was confirmed that 830 mg was the most appropriate dosage. In addition, the administration timing and method of the silkworm powder formulation of the present invention for controlling postprandial blood glucose are:
It was confirmed that oral administration after meal was the most effective.

[0016]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described more specifically with reference to Examples. These examples are exclusively for explaining the present invention, and the present invention is not limited to these. Example 1- Production of silkworm powder-The larvae of the 4th instar silkworm to the 5th instar maximum heavy silkworm were subjected to antioxidant treatment using nitrogen gas, freeze-dried while stored in an ultra-low temperature refrigerator, and then powdered by a pulverization method. Turned into This is one of the widely used freezing methods in the food industry,
It was confirmed that the method is harmless to the human body because no nitrogen gas remains in the silkworm powder after the production.

Example 2- Confirmation of blood glucose elevation suppressing effect of the hypoglycemic agent of the present invention-α- which delays absorption of food and drink as a method for preventing hyperglycemia
In order to examine the effect of the glucosidase inhibitor, acarbose known to have such an effect was used as a control, and it was used as a hypoglycemic agent containing the silkworm powder produced in Example 1 as an active ingredient and in folk medicine. The blood sugar elevation suppressing effect was compared with that of silkworm powder (see Table 1). Table 1 below
As you can see, the normal rat has a blood glucose level of 10.6 ±
Compared with 3.6, the blood sugar level is 7 in the case of the hot air dried powder of 5th instar silkworm which is mainly used in folk medicine.
It was 8.8 ± 8.2, and the blood glucose elevation inhibitory effect was 55%, which was much lower than 84% of the control acarbose.
On the other hand, the effect of suppressing the increase in blood glucose of the hot air dry powder of the 5th instar terminal heavy silkworm was 49%, which was lower than the dry powder of the 5th instar 3 day silkworm. However, in the case of the freeze-dried powder of the 5th instar 3 day silkworm produced in the present invention, the blood glucose level is 58.0 ± 3.1, which is about 48.6 higher than the normal value, and the blood glucose elevation inhibitory effect is 67%. It was very effective. The hot-air dried powder of the 4th instar silkworm presented for reference shows the same effect as that of the hot-air dried of the 5th instar maximal heavy silkworm, although it is lower than that of the 5th instar 3day silkworm.

[0018]

[Table 1] * 5HD: Hot-air dried powder of 5th-instar 3rd-day silkworm MHD: Hot-air dried powder of 5th-instar extreme maximum heavy silkworm 5CD: Freeze-dried powder of 5th-instar 3rd-day silkworm 4HD: Hot-air dried powder of 4th-year-old silkworm 4CD: 4th-year-old Freeze-dried powder of silkworm 5A: Freeze-dried powder of 5-day-old 3-day silkworm + crushed liquid of adult silkworm MAC: Hot-air dried powder of 5-year-old terminal maximum heavy silkworm + alcalase From the above results, 5 from 4-year-old silkworm It was found that the maximum amount of substances capable of suppressing blood glucose absorption was produced in the maximum weight at the end of age, more preferably in the 5th instar 3rd day silkworm, and in order to further improve the utilization efficiency, it was frozen after being subjected to antioxidant treatment with nitrogen gas. It has been found that drying is most effective.

Example 3- Determination of dose, timing and method of administration of the hypoglycemic agent of the present invention-The hypoglycemic agent (silkworm) produced in Example 1 was applied to 30 healthy volunteers having a body weight of 65 to 80 kg. The results of a clinical test for measuring the hypoglycemic effect on the dose of (powder) are shown in Table 2 below. In Table 2, the hypoglycemic effect at 45 minutes after meal is 10 in the 1,162 mg dose group.
0%, 72% in the 830 mg dose group, 498
65% in the mg dosing group. In addition, changes in blood glucose level with the passage of time for each medication group are shown in FIGS.
And FIG. 3 respectively. In the 498 mg dosing group of FIG. 1, the blood glucose level at 45 minutes after meal is higher than the fasting blood glucose level but lower than the non-administration blood glucose level, and then gradually increases. On the other hand, 83 in FIG.
In the 0 mg dose group, the blood glucose level gradually decreased while maintaining the blood glucose level slightly higher than that in the fasting state, which was the most ideal result. Furthermore, in FIG.
In the 162 mg-administered group, there was a phenomenon that the blood glucose level at 45 minutes after meal showed inhibitory activity to a blood glucose level lower than that in the fasting state and then increased again.

[0020]

[Table 2] From the above results, in the case of the 1,162 mg dose group, excessive suppression activity was confirmed, and therefore it was confirmed that 830 mg was the most appropriate dose. Further, the most effective time and method of administration of the silkworm powder formulation of the present invention for controlling postprandial blood glucose was by oral administration after meal. Therefore, the hypoglycemic agent 830 of the present invention
The method of treating diabetes by oral administration of mg after meal almost complements the inconsistency phenomenon of existing preparations between 45 minutes and 1 hour after meal when the postprandial blood glucose level is the highest, and the slow decrease phenomenon of blood glucose level after 90 minutes. From this, it was possible to confirm that it is the most ideal method for regulating blood glucose level that can prevent postprandial hyperglycemia and fasting hypoglycemia.

On the other hand, the silkworm powder produced in the present invention can be orally administered in the form of a composition containing a pharmaceutically acceptable carrier. Oral compositions include, for example, tablets and gelatin capsules, which, in addition to the active ingredient, contain diluents (eg, lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine), lubricants (eg, , Silica, talc, stearic acid and its magnesium or calcium salts and / or polyethylene glycol), tablets also binders (eg magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and / or
Or polyvinylpyrrolidone) and optionally a disintegrant (eg starch, agar, alginic acid or its sodium salt) and / or a water absorbing agent, a coloring agent, a flavoring agent and a sweetening agent. The composition of the hypoglycemic agent is manufactured by a conventional mixing, granulating or coating method, and is approximately 70% -85% of the total composition.
(W / w), preferably approximately 80% to 83% (w / w)
Contains silkworm powder of No. 1 as an active ingredient. And almost 50
A unit dose dosage form for a kg to 70kg mammal contains approximately 800mg to 830mg of active ingredient.

[0022]

As described above, the hypoglycemic agent produced in the present invention is superior to the conventional hot air-dried silkworm powder in suppressing the increase in blood glucose, and the method for treating diabetes using it is the same as that of existing drugs. By complementing the discrepancy phenomenon,
It has an ideal hypoglycemic effect that can prevent postprandial hyperglycemia and fasting hypoglycemia.

[Brief description of drawings]

FIG. 1 is a graph showing changes in blood glucose level over time in a group to which 498 mg of the hypoglycemic agent of the present invention was administered.

FIG. 2 is a graph showing changes in blood glucose level over time of a group to which 830 mg of the hypoglycemic agent of the present invention was administered.

FIG. 3 is a graph showing changes in blood glucose level over time of a group to which 1,162 mg of the hypoglycemic agent of the present invention was administered.

Front Page Continuation (72) Inventor Hong Origin 413 No.6 Yonghua-dong, Suwon City, Gyeonggi-do, Republic of Korea (72) Inventor Lee Sofeng, Dongan-si, Huan-dong, Anyang, Gyeonggi-do, Korea Building 1502

Claims (3)

[Claims] 1. A method for producing a silkworm powder, which comprises a step of subjecting 4th instar silkworm to 5th instar terminal extreme heavy silkworm to an antioxidant treatment using nitrogen gas, and freeze-drying to powder. 2. A hypoglycemic agent comprising the silkworm powder produced by the method of claim 1 as an active ingredient and a pharmaceutically acceptable carrier. 3. A dietary supplement containing the silkworm powder produced by the method of claim 1 as an active ingredient.