JP2757937B2 - Hypoglycemic agent containing silkworm powder as active ingredient and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hypoglycemic agent containing silkworm powder as an active ingredient and a method for producing the same. More specifically, the present invention relates to an antioxidant treatment of silkworm with nitrogen gas, followed by freeze-drying to powder. The present invention relates to a method for producing silkworm powder containing the same, a hypoglycemic agent and a health supplement containing the same as an active ingredient.

[0002]

2. Description of the Related Art Diabetes is a systemic metabolic disease caused by genetic or environmental factors, and is a disease caused by an absolute or relative deficiency of a hormone called insulin in the body. The main symptoms are abnormalities in sugar, fat and protein metabolism, resulting in abnormal hyperglycemia and urinary glucose, which are severe with the characteristic polyplegia, such as polyphagia, polydipsia and polyuria When fatigue and malaise appear and the disease is severe, it is known as a wasting disease.

[0003] Although the incidence of diabetes has recently increased greatly, it is considered that administering an excellent hypoglycemic agent at the beginning of the onset of disease to prevent the remaining disease is the most effective treatment. . That is, continuous postprandial regulation of blood glucose by drug administration results in a decrease in glycated hemoglobin, a decrease in average blood glucose, and a decrease in fasting blood glucose.
The improvement in insulin resistance makes it possible to live almost like a normal person.

[0004] On the other hand, when an insulin preparation or an oral hypoglycemic agent (sulfonylureas and biguanides), which is currently mainly used as a therapeutic agent for diabetes, is administered, the blood glucose concentration after ingestion of food and drink rapidly increases. As compared with the above, the appearance of insulin in the blood by the administered drug is relatively delayed, so that a mismatch phenomenon between the rise in postprandial blood glucose level and the appearance time of blood insulin comes to appear. In particular, when insulin is administered by subcutaneous injection, its absorption is even slower, and the discrepancy phenomenon becomes serious, which causes postprandial hyperglycemia (postprg).
and internal hyperglycemia, hyperinsulinemia between meals (hyperinsulinaemi)
a) and hypoglycemia appear.

[0005] Therefore, an ideal hypoglycemic agent has a rapid effect and prevents a rise in postprandial blood sugar, and its efficacy is lost within a short period of time, thus not only causing unnecessary hypoglycemia but also reducing diabetes. It must be a stable oral drug that can simultaneously normalize the metabolic abnormalities associated with specificities. Currently, the development of such hypoglycemic agents is urgently required,
Treatment of diabetes using traditional drugs or folk remedies is in the limelight.

[0006] On the other hand, in ancient books of Oriental medicine such as Higashi Ihokan, it is described that pupae and cocoons of silkworms have a therapeutic effect on diabetes. Recently, as a folk remedy, silkworms themselves are used for the purpose of lowering blood glucose. Cases are increasing. This is due to the fact that the silkworm itself delays the absorption of food and drink by an α-glucosidase inhibitor (α-glucosidase inhibitor).
It is presumed that the substance derived from mulberry leaves is converted into a substance having the above-mentioned effect in the body of the silkworm.

In general, silkworms hatch from eggs, undergo molting four times, transform from cocoons to pupae, then become moths and lay eggs.
It is one of the lifetime metamorphic insects that die after a week. It is known that the physiological changes according to the growth stages of silkworm larvae are extremely large, and the difference in the levels of substances including larval internal enzymes before and after molting is remarkable. In the body of the silkworm, there are mainly silkworm dung, which is a component of mulberry leaf, and mid-gut digestive juice and blood containing various enzymes. Among them, the midgut digestive juice and blood are very easily oxidized. When they come into contact with air, they are easily oxidized and inactivated while discoloring black.

[0008]

In the existing folk remedies, 5th instar silkworms or 5th instar silkworms are dried with hot air to produce powders, which inactivate various enzymes present in the body of the silkworms. Will bring. Therefore, it can be understood that an antioxidant treatment is required in the process of powdering in order to produce a better hypoglycemic agent using silkworms. After all, in developing a hypoglycemic agent using silkworm powder, at any stage of the growth stage of the silkworm larva, with any formulation,
The main challenge is to figure out what dosage and how to administer it.

[0009] An object of the present invention for solving the above-mentioned problems is to provide an antioxidant treatment using nitrogen gas from a 4th instar silkworm to a 5th instar silkworm, and a step of freeze-drying and powdering the silkworm powder. It is to provide a manufacturing method.

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

It is a further object of the present invention to provide a health supplement containing the silkworm powder as an active ingredient.

[0012]

Means for Solving the Problems The present inventors antioxidantly treat the 4th instar silkworm from the 5th instar silkworm with nitrogen gas, freeze-dry to form a silkworm powder, and use the rat. The present invention has been completed by confirming excellent efficacy as a hypoglycemic agent through clinical trials.

In the present invention, each of the larvae of the 4th-instar silkworm to the 5th-instar extreme heavy silkworm is subjected to an antioxidant treatment using nitrogen gas, freeze-dried while being stored in a deep freezer, and then powdered. To produce silkworm powder. Then, in order to examine the effect of an α-glucosidase inhibitor that delays the absorption of food and drink as a method for preventing hyperglycemia, the above silkworm was used as a control, using acarbose known to have such an effect as a control. The antihyperglycemic effect of a hypoglycemic agent containing powder as an active ingredient and silkworm powder used in folk remedies were compared. As a result, the blood glucose level was 18.8 ± 3.6 in the normal rat, whereas the blood glucose level was 78.8 ± in the case of the hot-air dried powder of the 5th instar 3 day silkworm, which is mainly used in folk remedies. The inhibitory effect on blood sugar rise was 55%, which was much lower than that of the control, acarbose, which was 84%. The effect was lower than that of 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 sugar level is 58.
The value was 0 ± 3.1, which was about 48.6 higher than the normal value, and the blood glucose elevation inhibitory effect was 67%, which was a very high effect. Therefore, it was found that the substance capable of suppressing the absorption of blood sugar was most frequently produced from the 4th-instar silkworm to the 5th-instar maximum gravity, most preferably from the 5th-instar 3rd-day silkworm. Also, in order to further enhance the utilization efficiency, it was found that it is most effective to freeze-dry after performing antioxidant treatment with nitrogen gas.

On the other hand, a clinical test was conducted on healthy volunteers to measure the hypoglycemic effect on the dose of a hypoglycemic agent containing the silkworm powder produced in the present invention as an active ingredient. The effect was 100% in the 1,162 mg dose group, 72% in the 830 mg dose group, and 65% in the 498 mg dose group.
%Met. In addition, in the change in blood glucose level with the lapse of time for each dosage group, in the 498 mg dosage group, the blood glucose level 45 minutes after the meal showed a blood glucose level higher than the fasting blood glucose level but lower than that in the non-administration, and then gradually. In the 830 mg dose group, the blood glucose level gradually decreased while maintaining the blood glucose level at a slightly higher level than in the fasting state, showing the most ideal result. Further, in the 1,162 mg dose group, the blood glucose level 45 minutes after the meal showed a suppressive activity to a blood glucose level lower than that at the time of fasting and then increased again. After all, 1,16
In the case of the 2 mg dose group, excessive inhibitory activity was confirmed, and thus it was confirmed that administering 830 mg was the most appropriate dosage. In addition, the dosage time and method of the preparation of the silkworm powder of the present invention for regulating postprandial blood glucose,
It was confirmed that oral administration after meals was the most effective.

[0016]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described more specifically with reference to embodiments. These examples are only for describing the present invention, and the present invention is not limited thereto. Example 1- Production of silkworm powder-Each of the larvae of the 4th instar silkworm to the 5th instar extreme heavy silkworm was subjected to antioxidant treatment using nitrogen gas, freeze-dried while being stored in an ultra-low temperature refrigerator, and then powdered by a pulverization method. It has become. This is one of the widely used freezing methods in the food industry,
After the production, no nitrogen gas remained in the silkworm powder, and it was confirmed that the method was harmless to the human body.

Example 2- Confirmation of the effect of suppressing hypoglycemia of the hypoglycemic agent of the present invention-As a method for preventing hyperglycemia, α- which delays absorption of food and drink is used.
In order to examine the effect of the glucosidase inhibitor, acarbose known to have such an effect was used as a control, and the silkworm powder produced in Example 1 was used as a hypoglycemic agent containing an active ingredient and used in folk remedies. The effect of suppressing blood glucose elevation was compared with that of the silkworm powder (see Table 1). Table 1 below
As can be seen, normal rats had a blood glucose level of 10.6 ±
Compared to 3.6, the blood sugar level of hot-air dried powder of 5th instar 3 day silkworm, which is mainly used in folk remedies, is 7
It was 8.8 ± 8.2, and the blood glucose elevation inhibitory effect was 55%, which was much lower than that of the control, acarbose, which was 84%.
On the other hand, the hot-air-dried powder of the 5th-instar extremely heavy silkworm showed a 49% reduction in blood glucose elevation, which was lower than the dry powder of the 5th-instar 3rd-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%. There was a very high effect. The hot-air-dried powder of the 4th-instar silkworm presented for reference shows the same effect as that of the hot-air-dried powder of the 5th-instar extreme heavy silkworm, though lower than that of the 5th-instar and 3rd-day silkworm.

[0018]

[Table 1] * 5HD: Hot-air dried powder of 5-year-old 3 day old silkworm MHD: Hot-air-dried powder of 5th-year-old extremely heavy silkworm 5CD: Freeze-dried powder of 5th-day 3-day silkworm 4HD: Hot-air dried powder of 4th-instar silkworm 4CD: 4th-instar Freeze-dried powder of silkworm 5A: Frozen-dried powder of 5th-instar 3rd-day silkworm + crushed liquid of adult silkworm MAC: Hot-air-dried powder of 5th-instar end-maximum heavy silkworm + alcalase (alcalase) It can be seen that the substance capable of suppressing blood glucose absorption is produced most in the end-of-life heavy weight, more preferably in the 5th instar 3 day silkworm, and in order to further increase the utilization efficiency, it is subjected to antioxidant treatment with nitrogen gas and then frozen. Drying has been found to be the most effective.

Example 3- Determination of dosage, timing and method of administration of hypoglycemic agent of the present invention-Hypoglycemic agent (silkworm) produced in Example 1 for 30 healthy volunteers weighing 65 to 80 kg The results of a clinical test for measuring the hypoglycemic effect with respect to the dose of (powder) are shown in Table 2 below. In Table 2, the hypoglycemic effect at 45 minutes after meal was 10% in the 1,162 mg dose group.
0%, 72% in the 830 mg dose group, 498
65% in the mg dose group. FIGS. 1 and 2 show changes in blood glucose level over time for each medication group.
And FIG. 3 respectively. In the 498 mg dose group in FIG. 1, the phenomenon that the blood glucose level 45 minutes after a 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 a level slightly higher than that in the fasting state, indicating the most ideal result. Further, FIG.
The 162 mg dose group showed a phenomenon in which the blood glucose level 45 minutes after a meal showed inhibitory activity to a blood glucose level lower than that in the fasting state, and then rose again.

[0020]

[Table 2] From the above results, excessive inhibitory activity was confirmed in the case of the 1,162 mg dosage group, and thus it was confirmed that administration of 830 mg was the most appropriate dose. In addition, the timing and method of administration of the silkworm powder preparation of the present invention for regulating the postprandial blood glucose level were most effective when administered orally after a meal. Therefore, the hypoglycemic agent 830 of the present invention
The method of treating diabetes, in which mg is orally administered after a meal, almost completely compensates for the inconsistency of the existing preparation between 45 minutes and 1 hour after the meal, when the blood glucose level after the meal is the highest, and a slow decrease in the blood glucose level even after 90 minutes. By confirming this, it could be confirmed that this is the most ideal blood glucose control method capable of preventing 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), and the tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and / or
Or polyvinylpyrrolidone), and if necessary, a disintegrating agent (eg, starch, agar, alginic acid or a sodium salt thereof) 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 general mixing, granulating or coating method, and is about 70% to 85% of the total composition.
(W / w), preferably approximately 80% to 83% (w / w)
Silkworm powder as an active ingredient. And almost 50
A unit dosage form for a mammal weighing from 70 kg to 70 kg contains approximately 800 mg to 830 mg of active ingredient.

[0022]

As described above, the hypoglycemic agent produced in the present invention is more effective in suppressing blood glucose elevation than conventional hot-air-dried silkworm powder, and the method of treating diabetes using the same is effective for the treatment 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 the drawings]

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

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

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

Continuation of the front page (72) Inventor Li Seofeng No. 1502, No. 803 Building No. 803, Jugyeon-dong, Dong'an-gu, Anyang-si, Gyeonggi-do, Republic of Korea (56) Reference JP-A-51-82742 (JP, A) 6-505479 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) A61K 35/64 A23L 1/30 A23L 3/34 A23L 3/40

Claims (3)

(57) [Claims] 1. A method for producing silkworm powder comprising the steps of subjecting a 4th-instar silkworm to a 5th-instar extreme heavy silkworm to an antioxidant treatment using nitrogen gas , and then 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 health supplement comprising, as an active ingredient, silkworm powder produced by the method of claim 1.