JP7195898B2 - Composition for suppressing elevation of blood sugar level - Google Patents

Description

TECHNICAL FIELD The present invention relates to a composition for suppressing elevation of blood sugar level.

Today, it is said that the risk of hyperglycemia increases due to various causes such as overeating, lack of exercise, stress, obesity, and aging. In addition, it is known that prolonged hyperglycemia tends to cause thirst, frequent urination, malaise, etc., and leads to further overeating and obesity, which in turn causes diabetes and various complications.

Lifestyle habits such as overeating and lack of exercise are one of the major factors that increase the risk of hyperglycemia. The total number of diabetes patients in the survey (the number of patients who are presumed to be receiving continuous treatment) is said to have increased by more than 460,000 since the 2011 survey. Reducing the rise is important. So far, various compositions for the purpose of suppressing elevation of blood sugar level have been reported. Food compositions (Patent Documents 1 and 2) are known.

JP 2017-1965 A JP 2017-88621 A

An object of the present invention is to provide a novel composition for suppressing elevation of blood sugar level.

The present inventors have made intensive studies in view of the above problems, and have found that a combination of at least one selected from the group consisting of lactic acid and salts thereof and caffeine can suppress an increase in blood sugar level. . The present invention has been completed as a result of further studies based on this knowledge, and is described below.
Section 1. A composition for suppressing elevation of blood sugar level, containing at least one selected from the group consisting of lactic acid and salts thereof and caffeine as active ingredients.
Section 2. Item 2. The composition according to Item 1, wherein the amount of at least one selected from the group consisting of lactic acid and salts thereof is 0.8 to 1000 parts by mass in terms of the amount of lactic acid per 1 part by mass of caffeine.
Item 3. Item 1 or wherein at least one selected from the group consisting of lactic acid and salts thereof is 40 to 10000 mg in terms of lactic acid amount and caffeine is 10 to 1000 mg in the daily intake (administration) amount per human 2. The composition according to 2.
Section 4. Item 4. The composition according to any one of Items 1 to 3, which is used in combination with exercise.

According to the composition for suppressing an increase in blood sugar level of the present invention, it is possible to effectively suppress an increase in blood sugar level.

TECHNICAL FIELD The present invention relates to a composition for suppressing elevation of blood sugar level containing at least one selected from the group consisting of lactic acid and salts thereof and caffeine as active ingredients.

Lactic acid is a known organic acid represented by the chemical formula _CH3CH (OH)COOH. Lactic acid has D-form, L-form, and DL-form, and these forms do not matter in the present invention.

Examples of lactic acid salts include, but are not limited to, alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as magnesium salts and calcium salts, ammonium salts, aluminum lactate, zinc lactate, iron lactate, manganese lactate, and the like. exemplified. Preferred examples of lactate include sodium lactate and potassium lactate. These may be used individually by 1 type, and may be used in combination of 2 or more type.

In the present invention, the content of at least one selected from the group consisting of lactic acid and its salts in the composition for suppressing elevation of blood sugar level is not particularly limited, but in the composition, the content of at least one selected from the group consisting of lactic acid and its salts The content of at least one selected is, as a total amount, preferably 0.4 to 99.9% by mass, more preferably 0.6 to 99.9% by mass, still more preferably 1 to 99.9% by mass. are exemplified. When using lactate, the content is calculated in terms of the amount of lactic acid.

Caffeine is a heterocyclic compound that is also called 1,3,7-trimethylxanthine, and in the present invention, anhydrate (anhydrous caffeine, C ₈ H ₁₀ N ₄ O ₂ ), hydrate (caffeine hydrate , _{for example , C8H10N4O2.H2O )} . Although not intended to limit the present invention, anhydrous caffeine is preferably exemplified as caffeine in the present invention.

In the present invention, the content of caffeine in the composition for suppressing elevation of blood sugar level is not particularly limited. Preferably 0.04 to 33.3% by mass is exemplified.

In the present invention, the mass ratio of at least one selected from the group consisting of lactic acid and salts thereof and caffeine in the composition for suppressing elevation of blood sugar level is not limited, but 1 part by mass of caffeine is and at least one selected from the group consisting of salts thereof is 0.8 to 1000 parts by mass, preferably 2 to 500 parts by mass, more preferably 2 to 300 parts by mass, more preferably 4 to 150 parts by mass in terms of the amount of lactic acid Mass parts are exemplified.

The composition of the present invention is administered (taken) preferably orally, whether orally or parenterally.

The form of the composition of the present invention is also not limited, and may be appropriately set according to the purpose. Forms of the composition of the present invention include liquids, emulsions, suspensions, syrups, extracts, spirits, elixirs and other liquid forms, powders, granules, fine granules, tablets, pills, capsules ( (including hard capsules and soft capsules), lozenges, chewables, gels, creams, pastes, mousses, sheets, semi-solid or solid forms such as lyophilized liquids, aerosols, patches (plasts) (including drug, tape, transdermal preparation, etc.).

Moreover, for example, when the composition of the present invention is in a solid form, it may be used by mixing with water or the like, and the composition of the present invention may be in a sustained release dosage form. In addition, for example, the tablet may, if necessary, be a conventionally known coated tablet such as a sugar-coated tablet, a gelatin-coated tablet, an enteric-coated tablet, a film-coated tablet, a double tablet, or a multilayer tablet.

In addition, the mode of use of the composition of the present invention is not limited, and may be appropriately set according to the purpose. Examples of usage of the composition of the present invention include food compositions (including beverages, foods with health claims (including foods for specified health uses, foods with nutrient function claims, foods with functional claims, supplements, etc.), health supplements, and foods for the sick. including), pharmaceutical compositions, quasi-drug compositions, feed compositions, food compositions, pharmaceutical compositions, quasi-drug compositions, additives to feeds and the like.

The composition of the present invention may be produced by mixing at least one selected from the group consisting of lactic acid and its salts with caffeine according to the conventionally known normal procedures in the various forms and usage modes described above. , If necessary, at least one selected from the group consisting of lactic acid and its salts or cafe It may be manufactured by mixing with in.

As the optional component, a solvent (water, lower alcohols such as methanol, ethanol, isopropanol, alcohols such as polyhydric alcohols such as propylene glycol and 1,3-butylene glycol (whether anhydrous or containing water), etc.) , Excipients, Disintegrants, Diluents, Lubricants, Flavors, Colorants, Sweeteners, Correctors, Suspending Agents, Wetting Agents, Emulsifiers, Solubilizers, Dispersing Agents, Buffers, Binders, Penetration Enhancers agents, stabilizers, bulking agents, preservatives, thickeners, pH adjusters, surfactants, coating agents, absorption promoters, adsorbents, fillers, antioxidants, anti-inflammatory agents, cooling agents, film-forming agents , gelling agents, amino acids, vitamins, enzymes, various nutritional components, and the like. These may be used singly or in combination of two or more, and the content thereof may be appropriately determined.

In the present invention, the subject (subject animal) of the composition is not limited, but examples include humans, mammals other than humans, birds, and reptiles. Examples of mammals other than humans include animals in which elevation of blood sugar level is undesirable in vivo, such as mice, rats, guinea pigs, rabbits, dogs, cats, monkeys, chimpanzees, pigs, cows, horses, etc., preferably mice. , rats, guinea pigs, rabbits, dogs, and monkeys.

In the composition of the present invention, the administration (ingestion) amount of at least one selected from the group consisting of lactic acid and salts thereof and caffeine is not particularly limited as long as the effects of the present invention are exhibited. It may be determined appropriately according to the physique, age, symptoms, form of application, purpose of use, degree of expected effect, etc. of the animal). Although not intended to limit the present invention, when the composition of the present invention is orally administered (ingested), the daily administration (ingestion) amount is based on one human (adult with a body weight of 60 kg), and lactic acid and its salts At least one selected from the group consisting of preferably 40 to 10000 mg, more preferably 100 to 8000 mg, and even more preferably 500 to 8000 mg in terms of lactic acid amount. In addition, although it does not limit the present invention, when the composition of the present invention is orally administered (ingested), the daily administration (ingestion) amount is preferably 10 to 10 caffeine based on one human. Examples are 1000 mg, more preferably 10 to 500 mg, and still more preferably 15 to 400 mg. The composition of the present invention may be administered (ingestion) once or multiple times (ingestion) per day. Moreover, administration (ingestion) of the composition of the present invention may be performed before, after, or between meals.

The composition of the present invention may be administered (ingested) continuously (continuously) every day, or may be administered (ingested) at intervals of one or more days (non-continuously), and the frequency thereof is limited. Instead, it may be appropriately set according to the physique, age, symptoms, etc. of the subject to whom the composition of the present invention is administered (ingested). The daily administration (ingestion) amount means the amount administered (ingestion) per day, regardless of whether it is continuous or non-continuous. In the case of discontinuous administration (ingestion), the frequency is not limited and may be set as appropriate as long as the effects of the present invention are exhibited. Administration (ingestion) may be performed on any one day. Although not intended to limit the present invention, the composition of the present invention is preferably administered (taken) every day, every other day, every two days, or every three days from the viewpoint of maintaining the effect.

When the composition of the present invention is administered parenterally, the dosage and frequency of the composition may be appropriately changed with reference to the above-mentioned values for oral administration (ingestion). When administering (ingesting) the composition of the present invention to mammals other than humans, the administration (ingestion) amount and frequency of the composition may be appropriately determined according to the animal with reference to the above-mentioned values for humans. Change it.

Conventionally, it is said that exercise is good for maintaining and improving health. As such, the compositions of the present invention may be used in conjunction with exercise. The degree and type of exercise are not limited, and may be set appropriately according to the physique, age, symptoms, etc. of the subject to whom the composition of the present invention is administered (ingested). .

Although the degree of exercise is not particularly limited, for example, as a guide, exercise such as 1.5 METs or more, preferably 2 METs or more, more preferably 2.5 to 10 METs, and still more preferably 3 to 8 METs a day is recommended. exemplified. This level of exercise includes activities such as walking, running (jogging, running), riding a bicycle, climbing stairs, strength training, swimming, carrying luggage, housework, commuting, It can be achieved through daily activities such as going to school, work, and hobbies. Exercising to such an extent, for example, may or may not be performed every day, and if not performed every day, should be performed on at least one of 1 to 6 days in a week (7 days). can be determined as appropriate. Exercising is preferably performed every day, every other day, every two days, or every three days. The aforementioned daily METs value means the total value for one day. The composition of the present invention may be administered (ingested) on the same day as the day on which the aforementioned exercise is performed, or may be administered (ingested) on the day on which the aforementioned exercise is not performed. In this case, administration (ingestion) of the composition of the present invention may be performed at the same time as exercise or before or after exercise, and the timing of administration (ingestion) is not limited.

In addition, METs (METs, Metabolic equivalents) are conventionally known as units that indicate exercise intensity, and can be found on the health information site for the prevention of lifestyle-related diseases of the Ministry of Health, Labor and Welfare (https://www.e-healthnet.mhlw.go .jp/information/dictionary/exercise/ys-004.html), ``In the unit of exercise intensity, the intensity of activity is expressed by how much energy is consumed compared to when resting is set to 1. It is described as "a measure of the intensity of exercise or physical activity". The website states, "3 METs for walking, light muscle training, vacuuming, etc., 4 METs for brisk walking, playing golf (round), riding a bicycle, playing outdoors with children, washing a car, etc., and 4 METs for light jogging. The intensity of various activities has already been clarified, such as 6 METs for aerobics and climbing stairs, and 8 METs for long-distance running, crawl swimming, and carrying heavy loads." 2006 Guide and the homepage of the National Institute of Health and Nutrition as a physical activity METs chart." Thus, a person skilled in the art can easily grasp the relationship between the motion and the METs.

According to the composition of the present invention, caffeine and at least one selected from the group consisting of lactic acid and its salts can be used as active ingredients to suppress an increase in blood sugar level. From this, it can be said that the present invention provides a method for producing a composition for suppressing elevation of blood sugar level, characterized by using at least one selected from the group consisting of lactic acid and salts thereof and caffeine as active ingredients. . Moreover, it can be said that the present invention provides a method for suppressing elevation of blood sugar level, characterized by using at least one selected from the group consisting of lactic acid and salts thereof and caffeine as active ingredients.

Thus, according to the composition of the present invention, an increase in blood sugar level can be suppressed. Accordingly, the composition of the present invention can be used for the purpose of preventing or improving various symptoms caused by elevated blood sugar levels. For this reason, the composition of the present invention can be used for, but not limited to, subjects concerned about blood sugar levels, subjects beginning to worry about blood sugar levels, subjects worried about lifestyle-related diseases, It can be preferably applied to subjects who have begun to worry about lifestyle-related diseases, health-conscious subjects, and the like. Examples of lifestyle-related diseases include diabetes, obesity, hypertension, hyperlipidemia, arteriosclerosis, cancer, and stroke.

EXAMPLES The present invention will be described in more detail below with reference to Examples, but the present invention is not limited to these.

1. Test procedure
1) Preparation of test animals This test was conducted with ethical approval. Male F344 rats (5 weeks old, Japan SLC Co., Ltd.) were raised one by one in an animal breeding facility under a controlled environment of room temperature 23°C and a 12-hour light-dark cycle (light period from 8:00 am to 8:00 pm). did. In order to induce obesity, the mice were given a high-fat diet HFD-60 (Oriental Yeast Co., Ltd.) and water ad libitum for 6 weeks.

The rats fed ad libitum for 6 weeks were randomly divided into 5 groups, lactate and caffeine intake group (LC, n=9), lactate intake group (Lac, n=5), caffeine intake group, respectively. They were named intake group (Caf, n=7), exercise group (comparison group) (Ex, n=11) and control group (Sed, n=10).

2) Preparation of test sample Sodium lactate and caffeine (both manufactured by Wako Pure Chemical Industries, Ltd.) were added so that the final concentration of sodium lactate was 200 mg / mL and the final concentration of caffeine was 7.2 mg / mL. It was mixed and dissolved in water for injection (manufactured by Otsuka Pharmaceutical Factory Co., Ltd.) to obtain a mixed solution (LC solution) of sodium lactate and caffeine. Similarly, sodium lactate was mixed and dissolved in water for injection so that the final concentration of sodium lactate was 200 mg/mL to obtain a sodium lactate solution (Lac solution). Similarly, caffeine was mixed and dissolved in water for injection so that the final caffeine concentration was 7.2 mg/mL to obtain a caffeine solution (Caf solution).

3) Administration of test substance The test substance was administered once a day every other day for 5 weeks. LC solution was administered to the LC group so that sodium lactate was 1000 mg/kg body weight (803.52 mg/kg body weight as lactic acid) and caffeine was 36 mg/kg body weight per administration. To the Lac group, Lac solution was administered so that sodium lactate was 1000 mg/kg body weight (803.52 mg/kg body weight as lactic acid) per administration. Caf liquid was administered to the Caf group such that the caffeine content was 36 mg/kg body weight per administration. In the Ex group and the Sed group, water for injection was used as a test substance, and water for injection was administered at 5 mL/kg body weight. The test substance was forcibly orally administered using an oral probe according to the normal test administration method.

The dose conversion for humans (body weight 60 kg) based on the dose can be explained as follows. Human equivalent dose (HED) based on body surface area in rats can be calculated from conversion factor 6.2 (U.S. FDA “Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers” July 2005). Based on this, 1000 mg/kg body weight of sodium lactate (803.52 mg/kg body weight as lactic acid) in the aforementioned rats is 7776 mg/60 kg body weight (human) as lactic acid, and 36 mg caffeine/kg body weight is equivalent to 348 mg caffeine/60 kg body weight (human). human).

4) Exercise The rats in the LC group, Lac group, Caf group, and Ex group were subjected to voluntary running exercise using a rotator (Rotating cage 80859, Lafayette Model 80859, manufactured by Lafayette, USA) for one day. Every other 5 weeks. The exercise performed here corresponds to jogging-running exercise (exercise of about 5 to 8 METs) when applied to humans. Each rat in the Sed group did not perform voluntary running exercise using a rotator.

Exercise was performed on a day other than the day of administration of the test subjects. That is, the LC group, the Lac group, the Caf group, and the Ex group did not perform the above exercise on the day when the test substance was administered, and this was continued for 5 weeks. Each rat was allowed to continue to ingest the high-fat diet HFD-60 and water ad libitum during the five weeks in which administration of the test substance and exercise were alternately performed. In addition, each rat in the Sed group was not subjected to the above-mentioned exercise, and, like the other groups, was given a high-fat diet HFD-60 and water ad libitum during the 5 weeks during which the test substance was administered. let me continue.

5) Measurement of Blood Glucose Level After alternately administering the test substance and exercising for 5 weeks as described above (the Sed group did not exercise), each rat was fasted for 12 hours. Next, dextrose (2 g/kg body weight) was orally administered to each rat according to the procedure of glucose tolerance tests, and the blood glucose concentration was measured using a glucose analyzer (Medisafefit, manufactured by Terumo Corporation). did.

For each group, the average blood glucose concentration 0 minutes after administration of dextrose and the average blood glucose concentration 120 minutes after administration were calculated. Next, based on the average value of the Ex group, the rate of change in the average value of each group relative to the average value of the Ex group was calculated according to the following formula.
Rate of change in blood glucose concentration (mean value) = (mean value of each group × 100/mean value of Ex group) -100

2. Results The results are shown in Table 1.

In Table 1, for example, "-0.4" shown at 0 minutes after glucose loading in the Caf group means that in the Caf group, the blood glucose concentration (mean value) after 0 minutes of dextrose administration was the same as 0 minutes in the Ex group. It shows a decrease of 0.4 points from the blood glucose concentration (mean value) after that. Further, for example, "0.3" shown at 0 minutes after glucose loading in the Sed group means that in the Sed group, the blood glucose concentration (average value) after 0 minutes of dextrose administration is the same in the Ex group. It shows that it was 0.3 points higher than the medium glucose concentration (average value).

As shown in Table 1, the values decreased the most in the LC group at both 0 and 120 minutes after glucose load. Specifically, after 0 minutes, the decrease in the Ex group was 0.4 points in the Caf group and 13.1 points in the Lac group, and the total of these was 13.5 points (0.4 + 13.1). In contrast, the LC group decreased by 16.1 points, showing a synergistic decrease. In addition, even 120 minutes after glucose loading, the decrease in the Ex group was 2.7 points in the Caf group and 2.9 points in the Lac group, and the total of these was 5.6 points (2.7 + 2.9). , while the LC group decreased by 13 points, showing a synergistic decrease.

From this, it can be concluded that the combined use of lactic acid and caffeine can synergistically reduce the blood glucose concentration and thus effectively suppress the elevation of the blood sugar level, as compared with the single intake of lactic acid and caffeine. confirmed.

0 minutes after glucose load shows the results after 12 hours of fasting, and when applied to humans, it can be said that this shows the results of fasting measured at the time of health checkup or the like. In addition, it can be said that the results 120 minutes after glucose loading show the results after meal intake. It is known that a sustained high blood sugar level leads to overeating, obesity, hypertension, etc., and increases the risk of various symptoms and diseases such as arteriosclerosis and diabetic complications. Therefore, it is important to lower blood sugar levels. In addition, as described above, dextrose was orally administered to each rat according to the glucose tolerance test procedure, and the blood glucose concentration was measured 0, 30, 60, and 120 minutes after administration of dextrose using a glucose analyzer. As a result of measuring AUC (Area under the curve) for 0 to 120 minutes, a significant decrease in AUC compared to the Ex group was observed only in the LC group.

From the above, it was found that the combined use of lactic acid and caffeine can effectively suppress the daily rise in blood sugar levels during fasting and after meals.

Formulation Examples The following formulation examples are shown. All of the compositions shown in the following formulation examples show an effect of suppressing elevation of blood sugar level.

Formulation example 1 (beverage)
Lactic acid 0.2% by mass
Sodium lactate 0.25% by mass
(Total 0.4% by mass as lactic acid)
Caffeine (anhydrous) 0.2% by mass
Granulated sugar 6% by mass
Sodium citrate 0.1% by mass
Sucralose 0.01% by mass
water residue
Total 100% by mass

Formulation example 2 (beverage)
Lactic acid 0.63% by mass
Sodium lactate 0.78% by mass
(Total 1.25% by mass as lactic acid)
Caffeine (anhydrous) 0.06% by mass
Granulated sugar 6% by mass
Sodium citrate 0.1% by mass
Sucralose 0.01% by mass
water residue
Total 100% by mass

Formulation example 3 (beverage)
Lactic acid 1.25% by mass
Sodium lactate 1.56% by mass
(Total 2.5% by mass as lactic acid)
Caffeine (anhydrous) 0.11% by mass
Granulated sugar 6% by mass
Sodium citrate 0.1% by mass
Sucralose 0.01% by mass
water residue
Total 100% by mass

Formulation example 4 (beverage)
Lactic acid 2.5% by mass
Sodium lactate 3.11% by mass
(Total 5% by mass as lactic acid)
Caffeine (anhydrous) 0.05% by mass
Granulated sugar 6% by mass
Sodium citrate 0.1% by mass
Sucralose 0.01% by mass
water residue
Total 100% by mass

Formulation example 5 (beverage)
Lactic acid 7.5% by mass
Sodium lactate 9.33% by mass
(Total 15% by mass as lactic acid)
Caffeine (anhydrous) 0.03% by mass
Granulated sugar 6% by mass
Sodium citrate 0.1% by mass
Sucralose 0.01% by mass
water residue
Total 100% by mass

Formulation example 6 (hard capsule)
Lactic acid 41.18% by mass
Calcium lactate 26.08% by mass
(Total 62.72% by mass as lactic acid)
Caffeine 31.36% by mass
Silicon dioxide 1.38% by mass
Total 100% by mass

Formulation example 7 (hard capsule)
Lactic acid 57.64% by mass
Calcium lactate 36.51% by mass
(Total 87.78% by mass as lactic acid)
Caffeine 3.93% by mass
Silicon dioxide 1.92% by mass
Total 100% by mass

Formulation Example 8 (hard capsule)
Lactic acid 59.89% by mass
Calcium lactate 37.93% by mass
(Total 91.21% by mass as lactic acid)
Caffeine 0.18% by mass
Silicon dioxide 2% by mass
Total 100% by mass

Formulation example 9 (beverage)
Lactic acid 0.2% by mass
Sodium lactate 0.25% by mass
(Total 0.4% by mass as lactic acid)
Caffeine (anhydrous) 0.45% by mass
Granulated sugar 6% by mass
Sodium citrate 0.1% by mass
Sucralose 0.01% by mass
water residue
Total 100% by mass

Formulation example 10 (beverage)
Lactic acid 0.2% by mass
Sodium lactate 0.25% by mass
(Total 0.4% by mass as lactic acid)
Caffeine (anhydrous) 0.431% by mass
Granulated sugar 6% by mass
Sodium citrate 0.1% by mass
Sucralose 0.01% by mass
water residue
Total 100% by mass

Formulation example 11 (tablet)
Calcium lactate 63.54% by mass
(52.46% by mass as lactic acid)
Caffeine 1% by mass
D- mannitol 26.36 mass%
Crospovidone 5% by mass
Hydroxypropyl cellulose 3% by mass
Saccharin sodium 0.1% by mass
Magnesium stearate 1% by mass
Total 100% by mass

Claims (4)

A composition for suppressing elevation of blood sugar level, containing at least one selected from the group consisting of lactic acid and salts thereof and caffeine as active ingredients. The composition according to claim 1, wherein at least one selected from the group consisting of lactic acid and salts thereof is 0.8 to 1000 parts by mass in terms of the amount of lactic acid per 1 part by mass of caffeine. 3. The method according to claim 1 or 2, wherein the amount of at least one selected from the group consisting of lactic acid and salts thereof is 40 to 10000 mg in terms of lactic acid and caffeine is 10 to 1000 mg per person per day. The described composition. The composition according to any one of claims 1 to 3, which is used in combination with exercise.