TW201922121A - Sugar consumption promoting agent - Google Patents

Abstract

The present invention provides a sugar consumption promoting agent and/or glycometabolism promoting agent including a vanadium-containing compound, and sodium carbonate or sodium hydrogen carbonate as effective components. The present invention also provides a sugar consumption promoting agent and/or glycometabolism promoting agent including sodium carbonate or sodium hydrogen carbonate as an effective component.

Description

Sugar consumption promoter

The present invention relates to a sugar consumption promoter.

There is a potential health risk associated with all pharmaceutical products, whether they are Oriental medicine or Western medicine. Regarding newly developed western medicines, in order to ensure their effectiveness and safety, they must undergo strict inspections. However, the safety of Toyo medicines is usually established through the long history of the safe use of traditional medicines.
In addition, folk therapies have been developed traditionally and for a long time.
However, it is important to note that traditional, or folk, and alternative therapies may have both positive and negative health effects.

The prevalence of diabetes (DM) is increasing worldwide. DM is known to cause complications such as cardiovascular disease, stroke, chronic renal failure, foot ulcers, and eye damage.
In the treatment of type 1 diabetes (type 1 DM), insulin is used, and in the treatment of type 2 diabetes (type 2 DM), most drugs are developed. However, although these drugs treat symptoms, they are not the basic treatment for DM. In addition, improper use of a therapeutic agent for DM may cause severe hypoglycemia.

It is known that vanadium compounds have insulin-like activity not only in vitro but also in vivo, and several vanadium compounds are being studied in the industry (Non-Patent Documents 1 to 8). Moreover, it was revealed that vanadate was orally administered to a diabetic patient for 4 weeks, and significant glucose normalization was obtained in the body without accompanying severe symptoms. Furthermore, it has been shown that the flowing water of Mount Fuji containing a vanadium compound is effective in improving the blood glucose level of a diabetic patient (Non-Patent Document 9).
[Prior technical literature]
[Non-patent literature]

[Non-Patent Document 1] Poucheret, P. et al., Vanadium and diabetes., Mol Cell Biochem, 1998, 188 (1-2), 73-80.
[Non-Patent Document 2] Shafrir, E. et al., Treatment of diabetes with vanadium salts: general overview and amelioration of nutritionally induced diabetes in the Psammomys obesus gerbil., Diabetes Metab Res Rev, 2001, 17 (1), 55- 66.
[Non-Patent Document 3] D. Rehder, D., Perspectives for vanadium in health issues., Fut Med Chem, 2016, 8 (3), pp. 325-338.
[Non-Patent Document 4] Kibiti, M. et al., The Biochemical Role of Macro and Micro-Minerals in the Management of Diabetes Mellitus and its Associated Complications: A Review., Int J Vit Nut Res, 2015, 85 (1- 2), 88-103.
[Non-Patent Document 5] Gruzewska, K. et al., Essentiality and toxicity of vanadium supplements in health and pathology., J Physiol Pharmaco, 2014, 65 (5), 603-611.
[Non-Patent Document 6] Huyer, G. et al., Mechanism of inhibition of protein-tyrosine phosphatases by vanadate and pervanadate., J Biol Chem, 1997, 272 (2), 843-851.
[Non-Patent Document 7] Sorimachi, K, et al., Insulin-like effects of vanadium pentoxide (V205) on glucose consumption in primary human fibroblasts., Journal of Analytical & Pharmaceutical Research, 2017, 5 (4), 00150.
[Non-Patent Document 8] Sorimachi, K. et al., Insulin-like effect of Mt. Fuji subsoil water which contains vanadium on cultured cells: Insight from Japan., Current Traditional Medicine, 2017, 3 (3), 178-189 .
[Non-Patent Document 9] Orange Field Force and others, the effect of Fuji Mountain Fusui containing natural vanadium on human hyperglycemia, Applied Pharmacology, 2003, 64 (5/6), 77-84.

[Problems to be solved by the invention]

The present invention provides a novel sugar consumption promoter with insulin-like effect.
[Technical means to solve the problem]

The present inventors worked hard to solve the above problems, and as a result, found that the vanadium-containing compound and sodium carbonate or sodium bicarbonate have an insulin-like effect, and completed the present invention. In addition, the present inventors also found that sodium carbonate or sodium bicarbonate has a sugar metabolism promoting effect, and completed the present invention.

The present invention is as follows.
(1)
A sugar consumption promoter comprising a vanadium-containing compound and sodium carbonate or sodium bicarbonate as effective ingredients.
(2)
A sugar consumption promoter containing sodium carbonate or sodium bicarbonate for use in combination with a vanadium-containing compound as an active ingredient.
(3)
A sugar consumption promoter containing sodium carbonate or sodium bicarbonate as an active ingredient.
(4)
A sugar consumption promoter containing 0.1 to 5 g / L, preferably 1 to 2.5 g / L of sodium carbonate or sodium bicarbonate as an active ingredient.
(5)
The sugar consumption promoter according to any one of (1) to (4), which is an aqueous solution.
(6)
The sugar consumption promoter according to any one of (1) to (5), which comprises 0.1 to 5 g / L of sodium carbonate or sodium bicarbonate.
(7)
The sugar consumption promoter according to any one of (1) to (6), which contains a vanadium-containing compound in an amount of 100 to 2000 μg / L.
(8)
The sugar consumption promoter according to any one of (1) to (7), wherein the ratio of the content of the vanadium-containing compound to the sodium carbonate or sodium bicarbonate (sodium carbonate or sodium bicarbonate / vanadium-containing compound) is calculated by weight ratio as 0.5 to 3 × 10 ³ , preferably 0.5 to 3 × 10 ³ .
(9)
A sugar consumption promoting agent comprising 0.1 to 5 g / L, preferably 0.1 to 2.5 g / L, more preferably 0.5 to 2 g / L of sodium carbonate or sodium bicarbonate as an active ingredient, and further containing vanadium Compound.
(10)
The sugar consumption promoting agent according to any one of (1) to (9), wherein the pH value is 7.5 to 8.5.
(11)
A medicine or a food, which comprises the sugar consumption promoting agent according to any one of (1) to (10).
(12)
The sugar consumption promoting agent according to any one of (1) to (11), which may be a sugar metabolism promoting agent.
[Effect of the invention]

According to the present invention, a novel sugar consumption promoting agent having an insulin-like effect can be provided. Moreover, according to this invention, a novel sugar metabolism promoter can be provided.

The sugar consumption promoting agent of the present invention contains sodium carbonate or sodium bicarbonate as an active ingredient. The sugar consumption promoter of the present invention contains a vanadium-containing compound and sodium carbonate or sodium bicarbonate as an active ingredient.
The sugar consumption promoting agent of the present invention can promote sugar consumption and show an insulin-like effect.
The promotion of sugar consumption may be sugar consumption in cells, or sugar consumption in vivo in animals, preferably humans.
In the present invention, the promotion of sugar consumption is not particularly limited, and it can be measured by the method described in the examples.
In the present invention, the term "active ingredient" means that sodium carbonate or sodium bicarbonate is a component having a sugar consumption promoting activity. When a vanadium-containing compound and sodium carbonate or sodium bicarbonate are contained as an active ingredient, the term "active ingredient" means that sodium carbonate or sodium bicarbonate and a vanadium-containing compound exhibit a sugar consumption promoting activity.

The sugar consumption promoting agent of the present invention promotes sugar consumption in living cells, and thus exhibits an insulin-like effect. By using the sugar consumption promoting agent of the present invention, improvement of sugar metabolism in type 1 DM and type 2 DM can be expected. Among them, it is preferable to use the sugar consumption promoter of the present invention for the improvement of sugar metabolism in type 1 DM.
By ingesting the sugar consumption promoter of the present invention, the therapeutic or preventive effect of diabetes can be expected, and the complications caused by diabetes can be prevented. The type of diabetes may be type 1 DM or type 2 DM, and type 1 DM is preferred.

The sugar consumed by the sugar is not particularly limited as long as it is sugar related to sugar metabolism, and glucose is preferred.

The sugar consumption promoting agent of the present invention contains sodium carbonate or sodium bicarbonate, or contains a vanadium-containing compound, and sodium carbonate or sodium bicarbonate. However, if vanadium is reported to reduce blood glucose levels in the body through reduced free fatty acids, the vanadium is contained When a compound is used in combination with sodium carbonate or sodium bicarbonate, sugar consumption is regulated by a vanadium-containing compound. It is thought that the mechanism of glucose metabolism promotion of vanadium-containing compounds and sodium carbonate or sodium bicarbonate is that they act separately or simultaneously on insulin receptors on the cell membrane to activate the glucose transporter (GLT4), thereby Promote intracellular uptake of sugar.
In addition, the sugar consumption promoting agent of the present invention exhibits the effects of promoting sugar consumption in the cell and increasing the production of lactic acid, which is a metabolite of the glycemic system.
Therefore, the sugar consumption promoter of the present invention may be a sugar metabolism promoter. Therefore, in this specification, the matter described as a sugar consumption promoter can be renamed the description as a sugar metabolism promoter.

The vanadium-containing compound used in the present invention is a compound containing vanadium in which the element symbol is V in its molecule.
As the vanadium-containing compound, those known to have insulin-like activity in vitro or in vivo can be used.
As the vanadium-containing compound, vanadium salts of organic or inorganic acids, vanadium pentoxide (also referred to as V ₂ O ₅ , vanadates), and the like can be used.
As the vanadium-containing compound, when it is made into an aqueous solution, those which release vanadium ions can be preferably used. The vanadium-containing compound also includes a vanadium salt prepared in an aqueous solution by dissolving vanadium and hydrochloric acid.
Vanadium pentoxide is described as a vanadium oxide of V ₂ O ₅ and a commercially available product can be used.
The sugar consumption promoter of the present invention is preferably an aqueous solution, and further contains vanadium ions. The sugar consumption promoter of the present invention may be a solution obtained by dissolving sodium carbonate or sodium bicarbonate in an aqueous solution in which vanadium pentoxide is dissolved.

In the present invention, water known to contain vanadium ions or vanadates may be used, and water of Fuji soil water, urban water, and well water may be used as the water containing vanadium-containing compounds.
The so-called Fuji soil water is groundwater that is drawn from the Fuji mountain water system and contains vanadium-containing compounds.
As the water containing a vanadium-containing compound, the vanadium-containing compound may be contained in water internally, or the vanadium-containing compound may be added externally to the water, or the vanadium-containing compound may be added to the water containing the vanadium-containing compound. .

When the sugar consumption promoter is used as an aqueous solution, it is preferably contained in the range of 10 to 5000 μg / L and 10 to 1000 μg based on the concentration of vanadium ion or vanadium pentoxide (V ₂ O ₅ ). / L, 50-1000 μg / L, 100-1000 μg / L, 100-500 μg of vanadium-containing compounds.
As the lower limit of the concentration of vanadium ions or vanadium pentoxide (V ₂ O ₅ ), within the above range, the vanadium-containing compound may be 100 μg / L or more, 200 μg / L or more, or 300 μg / L or more, or 400 μg / L or more. The upper limit of the concentration may be 2000 μg / L or less, or 1,000 μg / L or less, or 900 μg / L or less. It is 800 μg / L or less, 700 μg / L or less, 600 μg / L or less, and 500 μg / L or less.
In addition, it may contain 10 to 300 μg / L, 50 to 250 μg / L, 50 to 200 μg / L, 50 to 150 μg / L based on the concentration of vanadium ion or vanadium pentoxide (V ₂ O ₅ ). Of vanadium-containing compounds.
Considering the viewpoint of sugar consumption promoting effect and toxicity, it is preferable to include 100-2000 μg / L or 100-500 μg / L based on the concentration of vanadium ion or vanadium pentoxide (V ₂ O ₅ ). Vanadium compounds.

When the sugar consumption promoter is an aqueous solution, the presence (content) of vanadium ion or vanadate can be confirmed by analyzing the sample by the method described in the examples.

The sodium carbonate used in the present invention has a chemical formula of Na ₂ CO ₃ .
There is no particular limitation on sodium carbonate, and a commercially available product can be used.
When the sugar consumption promoter is used as an aqueous solution, it is preferably 10 to 5000 mg / L (0.01 to 5 g / L) and 100 to 5000 mg / L (based on the concentration of sodium carbonate). 0.1 to 5 g / L) sodium carbonate. In addition, within a preferred range of 0.01 to 5 g / L, sodium carbonate may be contained at 4 g / L or less, 3 g / L or less, or 2.5 g / L or less, and may contain 0.5 g / L or more and 1 g / L. Sodium carbonate above L and above 2 g / L.
From the standpoint of promoting sugar consumption, based on the concentration of sodium carbonate, it is preferably 0.5 to 3 g / L sodium carbonate, and more preferably 1 to 2.5 g / L, 2 to 2.5 g / L of carbonic acid. sodium.

The content ratio of the vanadium-containing compound to the sodium carbonate (sodium carbonate / vanadium-containing compound) is preferably 0.5 to 3 × 10 ³ , 0.5 to 2.5 × 10 ³ , 0.5 to 2 × 10 ³ , 0.5 to 1 × 10 in terms of weight ratio. ³ .
The content and the ratio of the sodium carbonate and the vanadium-containing compound as required in the sugar consumption promoter can be appropriately adjusted by the mixing amount of the sodium carbonate and the vanadium-containing compound added as needed.

The sodium bicarbonate used in the present invention has the chemical formula of NaHCO ₃ and is also called baking soda.
Sodium bicarbonate is not particularly limited, and a commercially available product can be used.
When the sugar consumption promoter is used as an aqueous solution, it is preferably 10 to 10,000 mg / L (0.01 to 10 g / L) and 10 to 8000 mg / L based on the concentration of sodium bicarbonate. (0.01 to 8 g / L), 10 to 5000 mg / L (0.01 to 5 g / L), 100 to 5000 mg / L (0.1 to 5 g / L), 1000 to 5000 mg / L (1 to 5 g / L) of sodium bicarbonate. In addition, within a preferred range of 0.01 to 8 g / L, hydrogen carbonate of 7 g / L or less, 5 g / L or less, 4 g / L or less, 3 g / L or less, or 2.5 g / L or less may be included. Sodium may include sodium bicarbonate of 0.5 g / L or more, 1 g / L or more, and 2 g / L or more, or sodium bicarbonate of 1 to 2.5 g / L.
From the standpoint of promoting sugar consumption, it is preferable that sodium bicarbonate is contained in a concentration of sodium bicarbonate of 1 to 8 g / L, 1 to 7 g / L, and 1 to 5 g / L.

The content ratio of the vanadium-containing compound to the sodium bicarbonate (sodium bicarbonate / vanadium-containing compound) is preferably 0.5 to 3 × 10 ³ , 0.5 to 2.5 × 10 ³ , 1 to 2.5 × 10 ³ , 1 by weight ratio. ～ 2 × 10 ³ .
The content and ratio of the vanadium-containing compound and sodium bicarbonate in the sugar consumption promoter can be appropriately adjusted in the form of mixed amounts.

The sugar consumption promoter of the present invention is preferably produced by mixing sodium carbonate or sodium bicarbonate in water.
It can also be produced by mixing sodium carbonate or sodium bicarbonate with a vanadium-containing compound. In this case, the method of mixing is not particularly limited.
It is preferably produced by mixing sodium carbonate or sodium bicarbonate in water containing a vanadium-containing compound, or mixing water containing sodium carbonate or sodium bicarbonate. Vanadium-containing compounds can be mixed in water containing sodium carbonate or sodium bicarbonate, or water containing vanadium-containing compounds can be mixed in water containing sodium carbonate or sodium bicarbonate. That is, when the sugar consumption promoter of the present invention is an aqueous solution, the mixing order of water and sodium carbonate or sodium bicarbonate is not particularly limited, and the mixing order of water, sodium carbonate or sodium bicarbonate, and a vanadium-containing compound is not limited. There is no limit.

In the present invention, sodium carbonate and sodium bicarbonate can also be used together.

The sugar consumption promoter of the present invention can also be formulated in pharmaceuticals.
The form of the medicine is not particularly limited, and it can be a lozenge, a syrup, or a capsule, or it can be prepared as a granule or a powder, and used in the form of a suspension or a solution when taken.
When used as a pharmaceutical, in addition to sodium carbonate or sodium bicarbonate and vanadium-containing compounds as active ingredients, pharmaceutically acceptable additives can also be used.
The additive is not particularly limited, and for example, well-known components such as an excipient, a lubricant, a diluent, a binder, a disintegrant, an emulsifier, a stabilizer, and a deodorant and deodorant can be used.

The sugar consumption promoter of the present invention can be formulated in foods and can also be used as a healthy food.
The form of the food is not particularly limited, and preferred forms include aqueous forms such as drinks, capsules, and pastes.
When used as food, in addition to sodium carbonate or sodium bicarbonate and vanadium-containing compounds as active ingredients, preservatives, colorants, sweeteners, antioxidants, thickening stabilizers, emulsifiers, and flavorings can also be used. Food additives, preservatives, etc.
[Example]

The following examples specifically illustrate the present invention, but the present invention is not limited to these examples.

Prepared as RPMI by dissolving RPMI-1640 powder (GIBCO, Invitrogen Corporation, Gland Island, NY, USA) or Dalke Modified Iger Medium Powder (DMEM; Nissui Pharmaceutical Co. LTD, Tokyo) in Milli-Q water, respectively. -1640 medium and DMEM medium.
The initial glucose concentrations in the medium were set to 100 mg / dL and 200 mg / dL, respectively.
Filter all media through a 0.2 μm filter before use.
As the water containing the vanadium-containing compound, a vanadium standard solution (V1000), which is a standard sample of metal ions used in atomic absorption spectrometry for 0.2 M HCl and 0.5 M HNO ₃ , purchased from Wako Pure Chemical Industries, was used. The vanadium-containing compound adjusts the concentration of the vanadium ion in the aqueous solution in this case.
In addition, sodium carbonate and sodium bicarbonate were purchased from Wako Pure Chemical Industries.

Analysis of Vanadium in the Sample The analysis of vanadium in the sample was performed as follows.
The sample was filtered through a 0.45 μm membrane (Millipore Corp). 10 mL of water was added to 0.05 mL of concentrated nitric acid (Ultrapure Grade, Tama Chemicals Co., Kawasaki, Japan), and yttrium (150 pg) was used as an internal standard to set a peak.
After diluting 2 or 5 times with 0.5% nitric acid, inductively coupled plasma mass analysis (ICP-MS; Elan DRC-II, PerkinElmer, Waltham, MA, USA) was used as the mass-to-charge ratio (m / kg) The MS conditions were to optimize the vanadium concentration according to a 10 μg / mL stock standard (XSTC-13 SPEX CertiPrep. Inc. Metuchen, NJ, USA) in a tuning solution containing 1 ng / mL of vanadium in 0.5% nitric acid.
The determination was repeated three times. The detection limit (LOD) and quantitative limit (LOQ) are equivalent to the vanadium signal concentration equivalent to 3 times and 10 times the standard deviation of 10 repeated measurements of blank signals at m / z 51. For the measurement, the LOD and LOQ were set to 0.01 and 0.04 ng / mL, respectively.

For cell culture, Py-3Y1-S2 cells from rat fibroblasts were used.
The cells were continuously cultured in a plastic culture flask (bottom area 25 cm ² ) at 37 ° C., and treated with 1% trypsin to disperse the cells into single cells.
The dispersed cells were seeded on 24 porous plastic culture plates, and then cultured at 37 ° C and 5% CO ₂ for different periods.
The medium line contains 5% fetal bovine serum (FBS; GIBCO, Life Technologies, Auckland, NZ).

Analysis of glucose consumption in the culture medium The glucose concentration in the culture medium was measured using the glucose CII test (Wako, Tokyo, Japan).
A 10-50 μL aliquot of the medium was mixed with 0.5 mL of the analytical solution, and the absorbance at 505 nm was measured after 15 minutes.
To express the effect of sodium carbonate or sodium bicarbonate on glucose consumption, or the effect of sodium carbonate or sodium bicarbonate and vanadium-containing compounds on glucose consumption, divide the glucose consumption in the sample medium by the control medium (Milli-Q water). consumption.
The concentration of sodium bicarbonate or the concentration of vanadium was set to the range shown in FIGS. 1 to 4, and the results of glucose consumption analysis at this time are shown in FIGS. 1 to 4.
The concentration of sodium carbonate or the concentration of vanadium was set to the range shown in FIGS. 5 to 6, and the results of the glucose consumption analysis at this time are shown in FIGS. 5 to 6.

For analysis of lactic acid in the culture medium, 20 μL of a sample obtained by diluting the culture medium (culture medium) 20-fold was used, and the lactic acid concentration in the culture medium was measured using the Lactate Assay Kit-WST (Tongren Chemical, Japan).
To express the effect of sodium carbonate or sodium bicarbonate on lactic acid production, or the effect of sodium carbonate or sodium bicarbonate and vanadium-containing compounds on lactic acid production, divide the amount of lactic acid produced in the sample medium by the control medium (Milli-Q water). consumption.
The concentration of sodium carbonate or sodium bicarbonate was set to 1.0 mg / mL, or the concentration of vanadium was set to 1.0 mg / L. The results of the lactic acid analysis at this time are shown in FIGS. 7 to 8.
In the culture medium, lactic acid was significantly increased by sodium bicarbonate or sodium carbonate, or by a combination of vanadium-containing compounds.

FIG. 1 shows the results of glucose consumption in cultured cells when the concentration of NaHCO ₃ was set to 0.5 to 10.0 mg / mL. The experiment was performed 6 times, and the results were expressed as an average (**: p <0.01, and *: p <0.05).

FIG. 2 shows the results of glucose consumption in cultured cells when the concentration of vanadium was 1.0 mg / L and the concentration of NaHCO ₃ was 1.0 mg / mL. The experiment was performed 5 times, and the results were expressed as an average (**: p <0.01, and *: p <0.05).

FIG. 3 shows the results of glucose consumption in cultured cells when the concentration of NaHCO ₃ was changed from 1.0 mg / mL to 5.0 mg / mL when the vanadium concentration was set to 0.5 mg / L. The experiment was performed 3 times, and the results were expressed as the average (**: p <0.01, *: p <0.05).

FIG. 4 shows the results of glucose consumption in cultured cells when the concentration of NaHCO ₃ was changed from 1.0 mg / mL to 5.0 mg / mL when the vanadium concentration was set to 1.0 mg / L. The experiment was performed 4 times, and the results were expressed as the average (*: p <0.05).

FIG. 5 shows the results of glucose consumption in cultured cells when the concentration of Na ₂ CO ₃ was set to 0.5 to 10.0 mg / mL. The experiment was performed 4 to 17 times, and the results were expressed as an average (**: p <0.01).

FIG. 6 shows the results of glucose consumption in cultured cells when the concentration of Na ₂ CO ₃ was changed from 0.5 mg / mL to 2.5 mg / mL when the vanadium concentration was set to 1.0 mg / L. The experiment was performed 5 times, and the results were expressed as an average (**: p <0.01, *: p <0.05).

FIG. 7 shows the results of lactic acid production in cultured cells when the concentration of NaHCO ₃ or Na ₂ CO ₃ was set to 1.0 mg / mL. The experiment was performed 3 times, and the results were expressed in their average form (**: p <0.01, and *: p <0.05).

FIG. 8 shows the results of lactic acid production in cultured cells when the concentration of NaHCO ₃ or Na ₂ CO ₃ was 1.0 mg / mL and the concentration of vanadium was 1.0 mg / L. The experiment was performed 3 times, and the results were expressed as an average (*: p <0.05).

Claims (9)

A sugar consumption promoter comprising a vanadium-containing compound and sodium carbonate or sodium bicarbonate as effective ingredients. A sugar consumption promoter containing sodium carbonate or sodium bicarbonate for use in combination with a vanadium-containing compound as an active ingredient. A sugar consumption promoter containing sodium carbonate or sodium bicarbonate as an active ingredient. The sugar consumption promoter according to any one of claims 1 to 3, which is an aqueous solution. The sugar consumption promoter according to any one of claims 1 to 4, which comprises 0.1 to 5 g / L of sodium carbonate or sodium bicarbonate. The sugar consumption promoter according to any one of claims 1 to 5, which comprises a vanadium-containing compound at 100 to 2000 μg / L. The sugar consumption promoter according to any one of claims 1 to 6, wherein the ratio of the content of the vanadium-containing compound to the content of sodium carbonate or sodium bicarbonate (sodium carbonate or sodium bicarbonate / vanadium-containing compound) is 0.5 to by weight ratio 3 × 10 ³ . The sugar consumption promoter according to any one of claims 1 to 7, wherein the pH is 7.5 to 8.5. A medicine or a food product comprising the sugar consumption promoter according to any one of claims 1 to 8.