JP7044342B2 - Pharmaceutical composition for diabetes prevention / treatment, food composition for blood sugar level improvement, and method for prevention / treatment of diabetes - Google Patents

Description

The present invention relates to a pharmaceutical composition for preventing / treating diabetes, a method for preventing / treating diabetes, and a food composition for improving blood glucose level.

Diabetes mellitus is a disease in which the blood glucose level and the hemoglobin A1c level are higher than a predetermined standard, and causes various diseases caused by the high blood glucose level itself as well as the symptom.

Especially in recent years, the proportion of people suffering from diabetes has been increasing, and prevention (risk reduction) and treatment of diabetes are extremely important.

By the way, as a report on the reduction in the risk of diabetes, for example, in Non-Patent Document 1 below, those who often drink and eat high-fat dairy products have a lower risk of developing type 2 diabetes than those who do not eat it at all. There is a description about.

Ericsson, U.S.A. et al. , Am. J. Clin. Nutr. , 101, 1065-1080 (2015)

However, the reports described in the above non-patent documents are only to the extent that a specific food has a certain effect, and the reason has not been clarified, and recommendations for application as a pharmaceutical composition or a food composition. is not it.

Therefore, an object of the present invention is to provide an effective pharmaceutical composition for preventing / treating diabetes, a food composition for improving blood glucose level, and a method for preventing / treating diabetes.

Considering that DGKδ is one of the central enzymes that control insulin resistance, the present inventors have confirmed various substances, and found that myristic acid significantly contributes to the enhancement of DGKδ protein expression. , Which led to the completion of the present invention.

That is, the pharmaceutical composition for diabetes prevention / treatment according to one aspect of the present invention contains at least one of myristic acid and myristic acid derivative as an active ingredient.

Further, the food composition for improving blood glucose level according to another aspect of the present invention contains at least one of myristic acid and myristic acid derivative as an active ingredient.

Further, in the method for preventing / treating diabetes according to another aspect of the present invention, at least one of myristic acid and myristic acid derivative is administered as an active ingredient.

As described above, according to the present invention, it is possible to provide an effective pharmaceutical composition for preventing / treating diabetes, a food composition for improving blood glucose level, and a method for preventing / treating diabetes.

It is a figure which shows the result of the fasting blood glucose measurement of the mouse which concerns on an Example. It is a figure which shows the result of the glucose tolerance test of the mouse which concerns on an Example. It is a figure which shows the result of the glucose tolerance test of the mouse which concerns on an Example. It is a figure which shows the result of the glucose tolerance test of the mouse which concerns on an Example. It is a figure which shows the result of the cumulative incidence of diabetes of the mouse which concerns on an Example. It is a figure which shows the result of the fasting insulin tolerance of the mouse which concerns on an Example. It is a figure which shows the weight change of the mouse which concerns on an Example.

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. However, the present invention can be implemented in many different embodiments, and is not limited to the specific examples in the embodiments and examples shown below.

(Embodiment 1: Pharmaceutical Composition)
The pharmaceutical composition according to the present embodiment (hereinafter referred to as “the pharmaceutical composition”) is a pharmaceutical composition for the prevention and treatment of diabetes and contains at least one of myristic acid and a myristic acid derivative as an active ingredient. ..

In the present embodiment, "myristic acid" is a saturated fatty acid represented by CH ₃ (CH ₂ ) ₁₂ COOH as shown in the following formula. This pharmaceutical composition contains this myristic acid as an active ingredient, which can exert a significant preventive / therapeutic effect on diabetes. The more specific content of the significant preventive / therapeutic effect of myristic acid on diabetes is the effect of improving the blood glucose level in type 2 diabetes, and more specifically, the blood glucose level on an empty stomach and the glucose load (after meals). Suppression or decrease of blood glucose level.

The mechanism by which this pharmaceutical composition exerts its effect will be clarified from the experimental examples described later, and it is considered that the uptake of myristic acid into the body enhances the expression of the DGKδ protein and improves the glucose uptake ability. As a result, it becomes possible to increase the sensitivity to insulin and suppress the increase in blood glucose level.

In addition, the present pharmaceutical composition may contain myristic acid itself as an active ingredient, but may or may not contain myristic acid derivative as an active ingredient. Here, the "myristic acid derivative" refers to a compound in which a part of the structure of myristic acid is modified within a pharmaceutically acceptable range within the range of obtaining the same effect as the effect of the present pharmaceutical composition, and is limited. Although not necessarily, a salt obtained by the reaction of myristic acid and a base (myristic acid salt), an ester obtained by an alcohol containing myristic acid and glycerol (myristic acid ester), and an amide obtained by myristic acid and an amine (myristic acid). Acid amide) and the like can be exemplified.

Further, the present pharmaceutical composition is not limited as long as the effect of the present pharmaceutical composition can be exerted, and may be in the form of an internal medicine such as tablets, capsules, granules, syrups, etc. It may be in any form of an external drug such as a drug, or an injectable drug such as a liquid drug.

Further, from the viewpoint of facilitating the production of the composition having the above-mentioned form, stabilizing the quality, enhancing the effect, etc., the present pharmaceutical composition may be used as an excipient, depending on the form of the pharmaceutical composition. Ingredients other than the above active ingredients such as stabilizers, preservatives, cushioning agents, suspending agents, emulsifiers, colorants, flavoring materials, viscosity modifiers and the like, so-called pharmaceutical additives, can be contained. Of course, it is also possible to include a solvent such as water or physiological saline within a range that does not change the quality or effect of the pharmaceutical composition.

(Method of treatment)
Further, the present pharmaceutical composition can be used as a preventive / therapeutic method. Specific preventive / therapeutic methods include administration to patients and those at high risk of becoming patients in the future.

The administration method can be appropriately adjusted depending on the form of the present pharmaceutical composition and is not limited, but oral administration, injection, sublingual administration and the like can be exemplified.

Further, in the present pharmaceutical composition, the dose of the active ingredient can be appropriately adjusted depending on the symptom and body weight of the subject to be administered, but it is preferably 0.1 g or more per 1 kg of body weight per day, more preferably 0.1 g or more. It is 0.1 g or more and 100 g or less, and more preferably 0.15 g or more and 50 g or less. Within this range, the effect of the present pharmaceutical composition can be exhibited.

As described above, this pharmaceutical composition is a specifically effective pharmaceutical composition for diabetes prevention / treatment.

(Embodiment 2: Food Composition)
Myristic acid and myristic acid derivatives can be applied as food compositions in addition to the above-mentioned pharmaceutical compositions. That is, the food composition according to the present embodiment (hereinafter referred to as "the present food composition") contains at least one of myristic acid and myristic acid derivative as an active ingredient, and improves the blood glucose level. It is a food composition for improving blood glucose level.

The definitions of "myristic acid", "myristic acid derivative" and the like in this food composition and their doses are the same as those described in the first embodiment.

In addition, this food composition can be in various forms as a food composition, and is not limited, but the above active ingredients are added to general foods or specially concentrated to contain more than usual. It is possible to exemplify foods having an effect on diabetes, more specifically, an effect of improving blood glucose level. Here, "food" refers to tea, coffee, lactic acid bacteria beverages, milk and other beverages, meats, seafood, eggs, grains, beans, potatoes, vegetables, seaweeds, fruits and other natural ingredients. Fresh foods using, yogurt, fermented foods such as natto, processed foods processed from natural ingredients, oils and fats including edible oils such as salad oil, olive oil, soybean oil, and corn oil, seasonings such as soy sauce and miso. It can be exemplified and is not limited as long as it can be ingested by a person. Of course, this food also includes a form as a so-called supplement in which the active ingredient is mixed with at least one of the powder or concentrate of the food and the excipient.

As described above, this food composition is specifically a food for improving blood glucose level which can improve blood glucose level.

Here, the effect of the active ingredient described in the above embodiment is actually confirmed. This result will be specifically described below.

First, male NSY mice (RBRC02946, RIKEN BioResource Center) were orally administered with 300 mg / kg myristic acid or 300 mg / kg palmitic acid every two days, or mice not given any of the above (control). On the other hand, the fasting blood glucose level was measured. This result is shown in FIG. The results confirmed that fasting blood glucose levels at 24, 28, and 32 weeks of age were clearly reduced compared to control and palmitic acid mice.

Similarly to the above, for male NSY mice to which 300 mg / kg of myristic acid or 300 mg / kg of palmitic acid was orally administered every two days, or to mice to which none of the above was given (control). , A glucose tolerance test was performed. The results are shown in FIGS. 2 to 4. FIG. 2 shows the results of 18-week-old mice, FIG. 3 shows the results of 24-week-old mice, and FIG. 4 shows the results of 30-week-old mice. According to this result, a significant improvement in sugar load could be seen in mice at least 24 and 30 weeks old.

Similarly to the above, for male NSY mice to which 300 mg / kg of myristic acid or 300 mg / kg of palmitic acid was orally administered every two days, or to mice to which none of the above was given (control). , The cumulative incidence of diabetes was confirmed. This result is shown in FIG. This figure also clearly confirmed that the incidence of diabetes was reduced compared to the control and palmitic acid mice.

Similarly to the above, for male NSY mice to which 300 mg / kg of myristic acid or 300 mg / kg of palmitic acid was orally administered every two days, or to mice to which none of the above was given (control). , We confirmed fasting insulin resistance. This result is shown in FIG. This figure is the result of insulin resistance at 26 weeks of age. From this result, it was confirmed that the administration of myristic acid improved the fasting insulin resistance as compared with the control and palmitic acid-administered mice.

Similarly to the above, for male NSY mice to which 300 mg / kg of myristic acid or 300 mg / kg of palmitic acid was orally administered every two days, or to mice to which none of the above was given (control). , I checked the weight. This result is shown in FIG. According to this figure, overall, a remarkable phenomenon was observed for weight loss, especially after 24 weeks.

As described above, it was possible to confirm the effect of myristic acid as a pharmaceutical composition for diabetes prevention / treatment and the effect as a food composition for improving blood glucose level by this example.

INDUSTRIAL APPLICABILITY The present invention has industrial applicability as a pharmaceutical composition for preventing / treating diabetes, a food composition for improving blood glucose level, and a method for preventing / treating diabetes.

Claims (12)

For the prevention and treatment of type 2 diabetes, which contains myristic acid as an active ingredient and has at least one of the effects of suppressing or lowering the rise in blood glucose level after glucose loading, lowering fasting insulin resistance, and weight loss by oral administration in vivo. Pharmaceutical composition. The pharmaceutical composition for preventing / treating type 2 diabetes according to claim 1, which does not substantially contain a fatty acid other than myristic acid. The pharmaceutical composition for preventing / treating type 2 diabetes according to claim 1, which comprises substantially only the myristic acid. Type 2 which contains an ester of myristic acid and glycerol as an active ingredient and has at least one of the effects of suppressing or lowering the increase in blood glucose level after glucose loading, lowering fasting insulin tolerance, and weight loss by oral administration in vivo. Pharmaceutical composition for the prevention and treatment of diabetes. The pharmaceutical composition for preventing / treating type 2 diabetes according to claim 4, which does not substantially contain a fatty acid other than myristic acid. The pharmaceutical composition for preventing / treating type 2 diabetes according to claim 4, which comprises substantially only the ester. Food composition for improving blood glucose level in type 2 diabetes, which contains myristic acid as an active ingredient and has at least one of the effects of suppressing or lowering the increase in blood glucose level after glucose loading, reducing fasting insulin tolerance, and weight loss in vivo. thing. The food composition for improving blood glucose level according to claim 7, which does not substantially contain fatty acids other than myristic acid. The food composition for improving blood glucose level according to claim 7, which comprises substantially only the myristic acid. Blood glucose in type 2 diabetes, which contains an ester of myristic acid and glycerol as an active ingredient and has at least one of the effects of suppressing or lowering the increase or decrease in blood glucose level after glucose loading, reducing fasting insulin resistance, or reducing weight in vivo. Food composition for value improvement. The food composition for improving blood glucose level according to claim 10, which does not substantially contain fatty acids other than myristic acid. The food composition for improving blood glucose level according to claim 10, which comprises substantially only the ester.

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