Magnesium glycinate and method for producing same

Abstract

The purpose of the present disclosure is to provide magnesium glycinate which has a high magnesium concentration.　Disclosed is magnesium glycinate which is configured such that, in differential scanning calorimetry analysis, the value S1 / S2 obtained by dividing the area S1 of an endothermic peak that has a starting temperature in the range of 230°C to 255°C by the area S2 of an endothermic peak that has a starting temperature in the range of 330°C to 370°C is 0 to 7 inclusive.

Description

Magnesium glycinate and method for producing the same

[0001] This disclosure relates to magnesium glycinate and a method for producing the same.

[0002] Magnesium glycinate has excellent bioavailability and weak side effects such as laxative effects, making it suitable for use in foods, nutritional supplements, pharmaceuticals, and other products.

[0003] Patent Document 1 describes a magnesium glycinate hydrate having a structure represented by the following formula.

[0004] Patent Document 2 describes a method for obtaining an insoluble metal organic chelate by adding an organic acid ligand and a metal compound to a non-aqueous liquid to form a suspension, reacting the organic acid ligand and the metal compound, heating the suspension while stirring for a predetermined time, and filtering the suspension.

[0005] Patent Document 3 describes a method for inducing a solid reaction to form a metal chelate by exposing a solvent-free mixture of a metal compound and a solid organic acid containing chelate-forming acids such as α- and β-amino acids and hydroxycarboxylic acids to strong mechanical stress.

[0006] U.S. Patent No. 2014 / 0186408, Japanese Patent Publication No. 2005-145822, Japanese Patent Publication No. 2020-517602

[0007] The magnesium glycinate hydrate described in Patent Document 1, and the magnesium glycinate compounds obtained by the manufacturing methods described in Patent Documents 1 and 2, did not have a sufficiently satisfactory magnesium concentration.

[0008] This disclosure aims to provide magnesium glycinate with a high magnesium concentration.

[0009] A first embodiment of the present disclosure relates to the area S of an endothermic peak having an onset temperature in the range of 230°C to 255°C in differential scanning calorimetry. １ The area S of the endothermic peak having an onset temperature in the range of 330°C to 370°C. ２ The value S obtained by dividing by... １ / S ２However, the present invention provides magnesium glycinate with a value between 0 and 7.

[0010] In the second embodiment of this disclosure, the glycine content in magnesium glycinate is 0% by weight or more and 3% by weight or less. In the second embodiment of this disclosure, in the first embodiment, the glycine content in magnesium glycinate may be 0% by weight or more and 3% by weight or less. The glycine in magnesium glycinate may be free glycine.

[0011] In the third embodiment of this disclosure, in thermogravimetric analysis, the weight reduction rate at 380°C, based on the weight of magnesium glycinate at 50°C, may be 40% by weight or less. Also, in the third embodiment of this disclosure, in the magnesium glycinate described in either the first or second embodiment, in thermogravimetric analysis, the weight reduction rate at 380°C, based on the weight of magnesium glycinate at 50°C, may be 40% by weight or less.

[0012] In the fourth embodiment of this disclosure, in any one of the first to third embodiments, the loose bulk density of magnesium glycinate may be 0.5 g / mL or more.

[0013] In the fifth embodiment of this disclosure, in any one of the first to fourth embodiments, the crystallite size of the crystals in magnesium glycinate that belong to the first peak having a peak in the powder X-ray diffraction (XRD) spectrum with a 2θ of 16.7° to 17.0° may be 500 Å or more.

[0014] In the sixth embodiment of this disclosure, in any one of the first to fifth embodiments, the average circularity of magnesium glycinate may be 0.8 or more and 1.0 or less.

[0015] In the seventh embodiment of the present disclosure, in any one of the first to sixth embodiments, the color difference ΔE* can be 30 or less. The color difference ΔE* can be measured by the following method. [Method for Measuring Color Difference] 1462 parts by mass of glucose and 500 parts by mass of magnesium glycinate are mixed and stored at 60°C for 72 hours under sealed conditions, and the L* value of the mixture after storage is L １ *, the a* value is a １ *, the b* value is b １ *. The L*a*b* color system in a 10° field of view under a D65 light source is adopted, and the color difference (ΔE* value) with respect to the reference point (L ０ * = 100, a ０ * = 0, b ０ * = 0) is calculated by the following formula: ΔE* = [(L １ * - L ０ *) ２ + (a １ * - a ０ *) ２ + (b １ * - b ０ *) ２ . １／２ It is calculated based on this.

[0016] In the eighth embodiment of the present disclosure, in any one of the first to seventh embodiments, the tensile strength of the tablets obtained from magnesium glycinate can be 50 N / cm ２ or more and 500 N / cm ２ or less. The magnesium glycinate tablets can be tabletted at a tabletting pressure of 5 kN per tablet. The above tabletting can be carried out using a flat pestle.

[0017] The ninth embodiment of the present disclosure provides magnesium glycinate tablets containing magnesium glycinate according to any one of the first to eighth embodiments.

[0018] The tenth embodiment of the present disclosure provides food and beverages or pharmaceuticals containing magnesium glycinate according to any one of the first to eighth embodiments.

[0019] The eleventh embodiment of the present disclosure provides a method for manufacturing food and beverages or pharmaceuticals using magnesium glycinate according to any one of the first to eighth embodiments.

[0020] A twelfth embodiment of the present disclosure provides a method for producing magnesium glycinate. This method includes a mixing step of mixing glycine and a magnesium compound in the presence of water to obtain a mixture, and then holding the mixture at a temperature of 90°C or lower to obtain a precipitate containing magnesium glycinate. This method also includes a drying step of drying the precipitate to obtain magnesium glycinate. In this method, the magnesium compound includes one or more selected from magnesium oxide and magnesium hydroxide.

[0021] In a thirteenth embodiment of the present disclosure, the twelfth embodiment may further include a second mixing step of mixing the mixture containing the precipitate with ethanol after the mixing step and before the drying step.

[0022] In the fourteenth embodiment of this disclosure, the drying step may be carried out by a spray drying method in either the twelfth or thirteenth embodiment.

[0023] According to this disclosure, it is possible to provide magnesium glycinate with a high magnesium concentration.

[0024] Figure 1 shows the thermogravimetric-differential scanning calorimetry curve for Test Example 8. Figure 2 shows the thermogravimetric-differential scanning calorimetry curve for Test Example 4. Figure 3 shows the thermogravimetric-differential scanning calorimetry curve for Test Example 10. Figure 4 shows the thermogravimetric-differential scanning calorimetry curves for (a) Test Example 6, (b) Test Example 9, and (c) Test Example 12, respectively. Figure 5 shows the mass spectrometry spectra for (a) Test Example 8 and (b) Test Example 4. Figure 6 shows the powder X-ray diffraction spectrum for Test Example 8. Figure 7 shows the powder X-ray diffraction spectrum for Test Example 1. Figure 8 shows the powder X-ray diffraction spectrum for Test Example 4. Figure 9 shows the powder X-ray diffraction spectra for (a) Test Example 2, (b) Test Example 3, (c) Test Example 5, and (d) Test Example 6, respectively. Figure 10 shows the powder X-ray diffraction spectra for (a) Test Example 7, (b) Test Example 9, (c) Test Example 10, and (d) Test Example 11, respectively. Figure 11 shows the powder X-ray diffraction spectra for (a) Test Example 12, (b) Test Example 13, and (c) Test Example 14, respectively.

[0025] This disclosure relates to magnesium glycinate. In this specification, unless otherwise specified, all numerical ranges mean the range including their upper and lower limits.

[0026] Magnesium glycinate, as a compound, is thought to have a structure in which two ligands, each having a structure in which one hydrogen atom has been removed from glycine, are bonded to one magnesium atom. Magnesium glycinate may exist in amorphous or crystalline form. The crystals may contain water of hydration. In this disclosure, a six-coordinate crystal containing water of hydration may be referred to as type I, and a four-coordinate crystal not containing water of hydration may be referred to as type II.

[0027] In this disclosure, when simply referring to magnesium glycinate, magnesium glycinate is not limited to magnesium glycinate as a compound, but also includes materials containing components other than magnesium glycinate. In such materials, the form of magnesium glycinate is not particularly limited and may be solid, preferably in the form of powder, particles, bulk, etc. Furthermore, magnesium glycinate may be crystalline or amorphous. In this disclosure, crystals refer to substances in which peaks are observed when measured by X-ray diffraction.

[0028] (First Embodiment: Magnesium Glycinate) The magnesium glycinate of this disclosure has a peak area S with an onset temperature in the range of 230°C to 255°C in differential thermal scanning calorimetry. １ The area S of the peak having an onset temperature in the range of 330°C to 370°C. ２ The value S obtained by dividing by... １ / S ２ It is between 0 and 7. １ / S ２Preferably, the value is 0 to 5, more preferably 0 to 1, even more preferably 0 to 0.3, and particularly preferably 0 to 0.1. In this disclosure, the peak start temperature is defined as the temperature at the intersection of a straight line extending the low-temperature baseline of the peak towards the high-temperature side in the DSC curve and a tangent line drawn to the low-temperature side of the peak curve at the point where the slope is maximum. The peak end temperature is defined as the temperature at the intersection of a straight line extending the low-temperature baseline of the peak towards the high-temperature side in the DSC curve and a tangent line drawn to the high-temperature side of the peak curve at the point where the slope is maximum.

[0029] According to this disclosure, it is possible to provide magnesium glycinate with a high magnesium concentration. As a result, the magnesium glycinate of this disclosure is expected to have high bioavailability. Although this disclosure should not be interpreted as being limited to any particular theory, the reasons why the magnesium glycinate of this disclosure may produce the above effects are thought to be as follows.

[0030] In other words, in the magnesium glycinate of this disclosure, the endothermic reaction originating from the melting of glycine crystals is reduced. Therefore, it is thought that the amount of free glycine present in the magnesium glycinate is reduced. As a result, the magnesium concentration in the magnesium glycinate is thought to be relatively increased.

[0031] Furthermore, in this disclosure, differential scanning calorimetry can be performed using a differential scanning calorimetry-thermogravimetric simultaneous measurement device, under a nitrogen atmosphere, in the range of 40°C to 600°C, with a heating rate of 10°C / min.

[0032] The glycine content in the magnesium glycinate of this disclosure is 0% by weight or more and 3% by weight or less. In this disclosure, the glycine content in magnesium glycinate may be the content of free glycine. Free glycine means, for example, glycine that exists alone without being bound to magnesium. The glycine content in magnesium glycinate is preferably 0% by weight or more and 2.8% by weight or less, more preferably 0% by weight or more and 2.5% by weight or less, even more preferably 0% by weight or more and 2% by weight or less, particularly preferably 0% by weight or more and 1.5% by weight or less, even more preferably 0% by weight or more and 1% by weight or less, and most preferably 0% by weight or more and 0.5% by weight or less.

[0033] In other words, in the magnesium glycinate of this disclosure, the glycine content is reduced, which is thought to relatively increase the magnesium concentration in the magnesium glycinate. Furthermore, the reduced glycine content may also suppress discoloration of the magnesium glycinate due to heat.

[0034] Furthermore, in the production of magnesium glycinate, attempting to further reduce the glycine content may complicate the manufacturing process or require a magnesium compound with a large BET specific surface area as a raw material. From this viewpoint, in another embodiment, the glycine content in magnesium glycinate is preferably 0.7% by weight or more and 2.8% by weight or less, more preferably 0.7% by weight or more and 2.5% by weight or less, even more preferably 0.7% by weight or more and 2% by weight or less, particularly preferably 0.7% by weight or more and 1.5% by weight or less, and most preferably 0.7% by weight or more and 1% by weight or less. In yet another embodiment, the glycine content in magnesium glycinate is preferably 1% by weight or more and 2.8% by weight or less, more preferably 1% by weight or more and 2.5% by weight or less, even more preferably 1% by weight or more and 2% by weight or less, and particularly preferably 1% by weight or more and 1.5% by weight or less.

[0035] On the other hand, glycine and glycine derivatives are used as raw materials for magnesium glycinate. However, glycine and magnesium glycinate have a high affinity for each other, making separation difficult. As a result, in conventional magnesium glycinate, the impurity glycine was sometimes not sufficiently reduced.

[0036] The glycine content in magnesium glycinate can be measured by thermogravimetric analysis (TG). Specifically, the amount of glycine can be measured as the difference between the weight at 280°C and the weight at 240°C when thermogravimetric analysis is performed on magnesium glycinate at a heating rate of 10°C / min. Furthermore, the glycine concentration in the magnesium glycinate of this disclosure can be calculated by dividing the amount of glycine calculated above by the weight of magnesium glycinate at 50°C in the same thermogravimetric analysis.

[0037] More specifically, in TG (thermogravimetric analysis)-DSC (differential thermal scanning calorimetry) measurements with a heating rate of 10°C / min, a temperature range can be defined on the DSC data by defining the start and end temperatures of the endothermic peak with an enthalpy of approximately 300 to 500 J / g and a starting temperature of approximately 230 to 255°C. Based on the weight difference of the thermogravimetric analysis within that temperature range, the glycine content can be calculated.

[0038] The magnesium glycinate of this disclosure preferably has a reduced amount of water of hydration, and preferably contains no water of hydration at all. The concentration of water of hydration in the magnesium glycinate of this disclosure may be preferably 0% to 17% by weight, more preferably 0% to 10% by weight, and even more preferably 0% to 5% by weight, based on the total amount of magnesium glycinate. By reducing the amount of water of hydration, it is easy to further increase the magnesium concentration in the magnesium glycinate.

[0039] The amount of water of hydration in magnesium glycinate according to this disclosure can be measured by thermogravimetric analysis (TG). Specifically, the amount of water of hydration can be measured as the difference between the weight at 180°C and the weight at 50°C when thermogravimetric analysis is performed on magnesium glycinate at a heating rate of 10°C / min. Furthermore, the concentration of water of hydration in magnesium glycinate according to this disclosure can be calculated by dividing the amount of water of hydration calculated above by the weight at 50°C obtained by the same thermogravimetric analysis.

[0040] More specifically, in TG (thermogravimetric analysis)-DSC (differential thermal scanning calorimetry) measurements with a heating rate of 10°C / min, a temperature range can be defined on the DSC data by defining the start temperature from approximately 125 to 160°C and the start and end temperatures of the endothermic peak with an enthalpy of approximately 0 to 600 J / g. Based on the weight difference of the thermogravimetric analysis within that temperature range, the amount of hydrated water can be calculated.

[0041] In thermogravimetric analysis, the magnesium glycinate of this disclosure may have a weight loss rate of preferably 0% to 40% by weight, more preferably 20% to 30% by weight, and even more preferably 20% to 25% by weight, relative to the weight at 50°C, at 380°C. The weight loss in the range of 50°C to 380°C is thought to be due to the thermal decomposition of hydrate water in the magnesium glycinate, the thermal decomposition of glycine present in the magnesium glycinate as an impurity, and the thermal decomposition of magnesium glycinate as a compound. It is believed that suppressing such weight loss will increase the magnesium concentration in the magnesium glycinate.

[0042] In the magnesium glycinate of this disclosure, the minimum temperature at which the weight loss rate is 5% by weight or more (hereinafter also referred to as the "weight loss onset temperature"), based on the weight at 300°C in thermogravimetric analysis, is preferably 350°C or higher, more preferably 350°C to 370°C, and even more preferably 350°C to 365°C. Weight loss in the temperature range above 300°C is thought to be due to the thermal decomposition of magnesium glycinate, and it is thought that if the weight loss onset temperature is 350°C or higher, the purity of the magnesium glycinate will be higher and the concentration of magnesium in the magnesium glycinate will be higher.

[0043] In this disclosure, thermogravimetric analysis can be performed under a nitrogen atmosphere or an air atmosphere, in the range of 30°C to 600°C, with a heating rate of 10°C / min.

[0044] The magnesium glycinate of this disclosure preferably has an endothermic peak in the range of 350°C to 380°C, more preferably 360°C to 380°C, when the heating rate is 10°C / min, as measured by TG-DSC. The endothermic peak in the above range is thought to originate from the melting of magnesium glycinate.

[0045] Furthermore, the magnesium glycinate of this disclosure is, for example, Mg in a saturated aqueous solution of magnesium glycinate at 25°C. ２＋ The concentration may preferably be 1 g / L or more and 5 g / L or less, more preferably 2.2 g / L or more and 4.5 g / L or less, even more preferably 2.5 g / L or more and 4 g / L or less, and particularly preferably 2.7 g / L or more and 3.5 g / L or less.

[0046] The magnesium glycinate of this disclosure has a high magnesium concentration; for example, the magnesium content of the magnesium glycinate may be preferably 12% by weight or more, more preferably 12.5% ​​by weight or more and 20% by weight or less, and even more preferably 13% by weight or more and 17% by weight or less.

[0047] Mg in a saturated aqueous solution of magnesium glycinate at 25°C as described above. ２＋The concentration can be measured, for example, by ion chromatography. The magnesium content can be calculated, for example, from the results of thermogravimetric analysis.

[0048] The magnesium glycinate of this disclosure preferably has a peak originating from the magnesium glycinate crystal in the powder X-ray diffraction (XRD) spectrum.

[0049] Peaks originating from magnesium glycinate crystals include, in powder X-ray diffraction (XRD) spectra, a first peak with its peak in the range of 2θ between 11.1° and 12.1°; a second peak with its peak in the range of 2θ between 13.3° and 14.3°; a third peak with its peak in the range of 2θ between 15.5° and 16.5°; and a fourth peak with its peak in the range of 2θ between 17.0° and 18.0°. The magnesium glycinate crystals of this disclosure preferably have one or more selected from the first to fourth peaks.

[0050] In one embodiment, the magnesium glycinate of the present disclosure preferably has a third and a fourth peak. In such embodiment, it is more preferable that the intensity of the third or fourth peak is higher than that of the first or second peak.

[0051] The peak of the first peak described above preferably lies in the powder X-ray diffraction (XRD) spectrum where 2θ is between 11.3° and 11.9°, and more preferably in the range of 11.5° and 11.7°. The peak of the second peak described above preferably lies in the powder X-ray diffraction (XRD) spectrum where 2θ is between 13.5° and 14.1°, and more preferably in the range of 13.7° and 13.9°. The peak of the third peak described above preferably lies in the powder X-ray diffraction (XRD) spectrum where 2θ is between 15.7° and 16.3°, and more preferably in the range of 15.9° and 16.1°. The peak of the fourth peak described above preferably lies in the powder X-ray diffraction (XRD) spectrum where 2θ is between 17.2° and 17.8°, and more preferably in the range of 17.4° and 17.6°.

[0052] The magnesium glycinate of this disclosure has a crystallite size of the crystals attributed to at least one of the first to fourth peaks, preferably 100 Å or more and 1,000 Å or less, more preferably 150 Å or more and 800 Å or less, and even more preferably 200 Å or more and 700 Å or less.

[0053] In a preferred embodiment, the magnesium glycinate of this disclosure may have a peak in the powder X-ray diffraction (XRD) spectrum with its apex in the range of 2θ between 16.7° and 17.0°. The crystallite size of the crystals attributed to the above peak is preferably 500 Å or more, more preferably 500 Å to 800 Å, even more preferably 500 Å to 775 Å, and particularly preferably 500 Å to 750 Å. It is believed that having the crystallite size of the crystals attributed to the above peak within this range results in higher crystallinity and heavier weight of the magnesium glycinate, and that the magnesium concentration in the magnesium glycinate can also be increased.

[0054] In this disclosure, the crystallite size D of magnesium glycinate can be calculated from the shape of the peaks in the XRD spectrum based on the following formula: D = Kλ / Bcosθ [wherein λ = 1.5418 Å, K = 0.9, B: FWHM, θ: phase of the peak top].

[0055] In this disclosure, the XRD spectrum of magnesium glycinate can be measured by powder X-ray diffraction. In such powder X-ray diffraction measurement, CuKα rays (λ = 1.5418 Å) are used as the X-ray source, and the measurement can be performed with an acceleration voltage of 45 kV and an angle step of 0.026°.

[0056] The magnesium glycinate of this disclosure may further contain magnesium hydroxide. The magnesium hydroxide content may be preferably 0% to 5% by weight, more preferably 0% to 3% by weight, and even more preferably 0% to 1% by weight, based on the total amount of magnesium glycinate.

[0057] The magnesium hydroxide content in magnesium glycinate can be quantitatively analyzed using the RIR (Reference Intensity Ratio) method in X-ray powder diffraction measurement.

[0058] The loosened bulk density of the magnesium glycinate disclosed herein is preferably 0.5 g / mL or more, more preferably 0.5 g / mL to 0.85 g / mL, and even more preferably 0.5 g / mL to 0.8 g / mL. Being within this range of loosened bulk density ensures good filling properties in containers such as capsules.

[0059] In this disclosure, the loosened bulk density can be measured in accordance with JIS Z 2504.

[0060] The magnesium glycinate of this disclosure has a color difference ΔE*, measured by the following method, preferably 30 or less, more preferably 25 or less, and even more preferably 22 or less. The lower limit of the color difference ΔE* may be 0 or more, 10 or more, or 15 or more. The magnesium glycinate of this disclosure has good stability and suppresses color change due to heat. [Method for measuring color difference] Mix 1462 parts by mass of glucose and 500 parts by mass of magnesium glycinate, and store the mixture under sealed conditions at 60°C for 72 hours. The L* value of the mixture is then measured. １ *, a* value a １ *, b* value b １ *The L*a*b* color system is adopted for a 10° field of view with a D65 light source, and the reference point (L ０ * = 100, a ０ * = 0, b ０ The color difference (ΔE* value) for *=0) is given by the following formula: ΔE* = [(L １ *-L ０ *) ２ + (a １ * - a ０ *) ２ + (b １ * - b ０ *) ２ ] １／２ It is calculated based on the following.

[0061] Glucose and glycine can produce coloring components through the Maillard reaction. The magnesium glycinate of this disclosure has a low glycine content, and it is believed that glycine and magnesium exist in a stably bonded state in the magnesium glycinate crystal. Therefore, the Maillard reaction is suppressed, and it is thought to have good stability against heating.

[0062] For the color differences ΔE*, L*, a*, and b*, values ​​standardized as color coordinates in the CIE 1976 L*a*b* color space can be used, and measurements can be performed in accordance with JIS Z 8722. Measurements are performed using a D65 light source, based on values ​​in a 10° field of view.

[0063] The average circularity of the magnesium glycinate in this disclosure is preferably 0.75 to 1.00, more preferably 0.80 to 0.95, and even more preferably 0.80 to 0.93. It is believed that having a circularity within this range can improve the packing properties of the magnesium glycinate.

[0064] In this disclosure, circularity can be calculated by acquiring an image of a particle using a scanning electron microscope and analyzing the image by the predetermined method described in the examples. The circularity of a particle is 4πS / L, where S is the area of ​​the cross-section of the particle and L is its perimeter. ２ It can be calculated as follows. The closer the circularity is to 1, the closer it is to a perfect circle. In this disclosure, the average circularity means the arithmetic mean of the circularity measured for 20 or more particles. For example, ImageJ can be used as software for analyzing the image.

[0065] The average particle size of magnesium glycinate in this disclosure is preferably 20 μm to 350 μm, more preferably 25 μm to 300 μm, even more preferably 30 μm to 250 μm, and particularly preferably 30 μm to 150 μm. In this disclosure, the average particle size refers to the volume-based median diameter (D50), which can be measured by laser diffraction / scattering.

[0066] In the magnesium glycinate of this disclosure, the content of magnesium glycinate as a compound is preferably 90% by weight or more and 100% by weight or less, more preferably 95% by weight or more and 100% by weight or less, and even more preferably 97% by weight or more and 100% by weight or less.

[0067] The content of magnesium glycinate as a compound in magnesium glycinate can be calculated by thermogravimetric analysis.

[0068] When magnesium glycinate is compressed using a flat, non-rounded pestle at a compression pressure of 5 kN per tablet, the tensile strength of the magnesium glycinate tablet is preferably 50 N / cm. ２ More than 500N / cm ２ More preferably, 70 N / cm２ More than 400N / cm ２ More preferably, 100 N / cm ２ More than 350N / cm ２ The following is the case: It is believed that maintaining the stability of the magnesium glycinate tablet becomes easier when its tensile strength is within the applicable range. In this disclosure, "perfectly flat" means that the ratio of the radius of curvature to the diameter of the tablet (radius of curvature / diameter) is 1.1 or greater, more preferably 1.3 or greater, and even more preferably 1.4 or greater. The radius of curvature of a plane is infinite.

[0069] Magnesium glycinate may contain any magnesium compound in addition to magnesium glycinate as a compound. An example of such a magnesium compound is magnesium oxide. The inclusion of a magnesium compound is expected to increase the magnesium content and improve fluidity. The magnesium compound content is preferably 0% to 25% by weight, more preferably 0% to 20% by weight, and even more preferably 0% to 15% by weight. Having the magnesium compound content within this range results in good compression moldability and facilitates tablet formation.

[0070] (Second Embodiment: Method for Producing Magnesium Glycinate) The magnesium glycinate of the present disclosure comprises a mixing step of mixing glycine and a magnesium compound in the presence of water to obtain a mixture, and then holding the mixture at a temperature of 90°C or lower to obtain a precipitate containing magnesium glycinate; and a drying step of drying the precipitate to obtain magnesium glycinate, wherein the magnesium compound comprises one or more selected from magnesium oxide and magnesium hydroxide.

[0071] From the viewpoint of producing magnesium glycinate with a low glycine content, the lower limit of the BET specific surface area of ​​the above magnesium compound is 20 m². ２ Preferably 30 m ２ A value of 1 / g or higher is preferable. The upper limit is 120mg. ２ Preferably less than / g, and 100m ２A value of less than / g is more preferable. Preferred magnesium compounds have a BET specific surface area of ​​30 to 40 m². ２ One example is magnesium oxide in grams per gram.

[0072] The above mixture may be in a dissolved state or a slurry state. From the viewpoint of manufacturing cost, the slurry state is preferred. The state of the mixture can be adjusted by the amount of water.

[0073] According to the above manufacturing method, magnesium glycinate with a high magnesium concentration can be produced. In addition, since the manufacturing method of this disclosure does not use any components that may have adverse effects on living organisms, the resulting magnesium glycinate is preferably used as a food and beverage and a pharmaceutical product. This disclosure should not be interpreted as being limited to any particular theory, but the reasons why the manufacturing method of this disclosure produces such effects are thought to be as follows.

[0074] In other words, in the manufacturing method of this disclosure, glycine and a magnesium compound are first mixed in the presence of water, and then the reaction is continued at a relatively low temperature. Therefore, it is thought that the chelation of glycine and magnesium is promoted, and magnesium glycinate with a reduced amount of glycine is produced. As a result, magnesium glycinate with a higher magnesium concentration is obtained.

[0075] In the mixing step, glycine and a magnesium compound are mixed in the presence of water to obtain a mixture. This operation is thought to promote the formation of a chelate between glycine and magnesium hydroxide.

[0076] The mixing of water, glycine, and magnesium compound is not limited; water and glycine may be mixed first, and then the mixture and magnesium may be further mixed; or water and magnesium may be mixed first, and then the mixture and glycine may be further mixed. Alternatively, water, glycine, and magnesium compound may be mixed all at once. In one embodiment, it is preferable to mix water and glycine first, and then further mix the mixture and magnesium. According to this embodiment, chelation between glycine and magnesium is promoted, and it is thought that magnesium glycinate with a reduced amount of glycine is more easily produced.

[0077] The above magnesium compound comprises one or more selected from magnesium oxide and magnesium hydroxide. In one embodiment, the above magnesium compound comprises magnesium oxide. In another embodiment, the above magnesium compound comprises magnesium hydroxide.

[0078] The amount of glycine is preferably 0.32 parts by weight to 7.7 parts by weight, more preferably 0.64 parts by weight to 6.4 parts by weight, and even more preferably 1.3 parts by weight to 5.1 parts by weight, per 1 part by weight of the magnesium compound. By having the amount of glycine within the above range relative to the amount of the magnesium compound, the reaction efficiency is increased, and it is easy to further increase the magnesium concentration in the resulting magnesium glycinate.

[0079] The amount of water is not particularly limited, but is preferably 0 to 10 parts by weight, more preferably 0.125 to 8 parts by weight, and even more preferably 0.25 to 6 parts by weight, relative to 100 parts by weight of the total of glycine and magnesium compound. It is expected that the reaction efficiency will be increased by having the amount of water within the above range.

[0080] The mixing of the mixture in the mixing process can be carried out, for example, by stirring. A stirrer, mixer, or the like can be used as the stirring device.

[0081] The mixing in the mixing step is preferably carried out at a temperature of 90°C or lower, more preferably between 10°C and 90°C, and even more preferably between 15°C and 60°C. It is expected that the reaction efficiency will be increased by carrying out the mixing of glycine and the magnesium compound at the above temperature.

[0082] The pH of the mixture in the mixing step is preferably 4 to 11, more preferably 5 to 11, and even more preferably 6 to 10.5. By having the pH of the mixture within this range, the coordination of protons at the amino group of glycine is suppressed, which is expected to increase reaction efficiency and yield magnesium glycinate with a high magnesium concentration.

[0083] The mixing time in the mixing step is preferably 30 minutes to 50 hours, more preferably 50 minutes to 30 hours, and even more preferably 60 minutes to 24 hours. It is expected that the reaction efficiency will be increased by having the mixing time within the above range.

[0084] Next, in the mixing step, the mixture is maintained at a temperature of 90°C or lower. This yields a precipitate containing magnesium glycinate. In the manufacturing method of this disclosure, glycine and a magnesium compound are mixed in the presence of water, and it is believed that magnesium glycinate with a reduced glycine concentration is produced. On the other hand, it is believed that unreacted glycine and other substances remain in the liquid component of the reaction solution. Therefore, the target magnesium glycinate can be obtained by recovering the precipitate. The precipitate may contain components other than magnesium glycinate.

[0085] The holding temperature is preferably 90°C or lower, more preferably 10°C to 90°C, and even more preferably 15°C to 60°C. It is expected that the reaction efficiency will be increased by holding the above mixture at the above temperature.

[0086] The time for holding the mixture at 90°C or below is preferably 30 minutes to 50 hours, more preferably 50 minutes to 30 hours, and even more preferably 60 minutes to 24 hours. It is expected that the reaction efficiency will be increased by keeping the mixing time within the above range.

[0087] When maintaining the above mixture at a temperature of 90°C or below, the mixture may be mixed with ethanol, and the resulting second mixture may also be maintained at a temperature of 90°C or below. This operation yields a precipitate containing magnesium glycinate.

[0088] The amount of ethanol is preferably 10 to 400 parts by volume, more preferably 20 to 350 parts by volume, even more preferably 40 to 300 parts by volume, and particularly preferably 70 to 250 parts by volume, relative to 100 parts by volume of water used. It is believed that the magnesium concentration in the resulting magnesium glycinate can be increased by having the amount of ethanol mixed within the above range. Note that the amount of ethanol refers to the amount of ethanol before mixing relative to the water before mixing.

[0089] The above-mentioned mixture of ethanol and the mixture can be carried out, for example, by stirring. A stirrer, mixer, or the like can be used as the stirring device.

[0090] In the drying process, the precipitate is dried to obtain magnesium glycinate.

[0091] The drying temperature during the above drying process is preferably 50°C to 300°C, more preferably 50°C to 250°C, and even more preferably 50°C to 200°C. The drying time is preferably 30 minutes to 5 hours, more preferably 50 minutes to 4 hours, and even more preferably 1 hour to 3 hours.

[0092] The above drying can be carried out using a hot air dryer, microwave dryer, rotary dryer, or the like.

[0093] In a preferred embodiment, the drying process can be carried out by a spray-drying method. By drying by spray-drying, magnesium glycinate can be obtained in a spherical or near-spherical shape. As a result, the bulk density can be increased, which is expected to improve the packing properties in containers such as capsules.

[0094] The temperature during spray drying is preferably 70°C to 110°C, more preferably 75°C to 105°C, and even more preferably 80°C to 100°C. The temperature during spray drying may be the outlet temperature of the spray drying apparatus.

[0095] The above magnesium glycinate may be subjected to further grinding treatment.

[0096] The above grinding can be carried out so that the average particle size of magnesium glycinate is preferably 20 μm to 350 μm, more preferably 25 μm to 300 μm, and even more preferably 30 μm to 250 μm.

[0097] The above grinding can be carried out using a fine grinding machine such as a roller mill, jet mill, high-speed rotary grinder, or container-driven mill.

[0098] The magnesium glycinate of this disclosure may be produced by the above-described manufacturing method, but is not limited to that produced by the above-described manufacturing method.

[0099] (Third Embodiment: Magnesium Glycinate Tablets) Magnesium glycinate tablets are also included in the technical scope of this disclosure. In one embodiment, the magnesium glycinate tablets of this disclosure comprise the magnesium glycinate of this disclosure.

[0100] In a preferred embodiment, the magnesium glycinate tablets of the present disclosure have a tensile strength of 50 N / cm when compressed with a flat (non-rounded) punch at a compression pressure of 5 kN per tablet. ２ More than 500N / cm ２ The following applies. In this embodiment, the magnesium glycinate tablets, when compressed using a flat, non-rounded pestle at a compression pressure of 5 kN per tablet, have a tensile strength of 50 N / cm². ２ More than 500N / cm ２ The following conditions are acceptable. It is also possible to compress tablets using punches of other shapes, in which case the tensile strength may fall outside the above range. Such magnesium glycinate tablets are also included within the technical scope of this disclosure.

[0101] The magnesium glycinate disclosed herein is expected to have good compression moldability, making it possible to obtain tablets with a high concentration of magnesium glycinate. Furthermore, the magnesium glycinate tablets disclosed herein are expected to have high tensile strength, making it possible to maintain the stability of the tablets.

[0102] The content of magnesium glycinate as a compound in magnesium glycinate tablets is preferably 20% by mass or more and 95% by mass or less, more preferably 50% by mass or more and 95% by mass or less, and even more preferably 66.7% by mass or more and 90% by mass or less.

[0103] In magnesium glycinate tablets, the content of magnesium glycinate according to this disclosure is preferably 0.1% by mass or more and 90% by mass or less, more preferably 10% by mass or more and 80% by mass or less, and even more preferably 20% by mass or more and 70% by mass or less.

[0104] Magnesium glycinate tablets may contain, in addition to magnesium glycinate, internal or external additives such as disintegrants including low-substituted hydroxypropyl cellulose, agar, croscarmellose sodium, partially pregelatinized starch, potato starch, corn starch, carmellose calcium, crospovidone, and carboxystarch sodium; binders such as crystalline cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and pullulan; lubricants such as sucrose fatty acid esters, glycerin fatty acid esters, stearyl fumarate sodium, talc, stearic acid, and their salts (Mg, Ca salts); fluidity improvers such as fine silicon dioxide and calcined seashell calcium; sweeteners such as aspartame, acesulfame potassium, and sucralose; and excipients such as calcium hydrogen phosphate, sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch hydrolysates. Furthermore, magnesium glycinate tablets may further contain other additives such as amino acids or their salts, yeast extracts, vitamins, minerals, functional ingredients, various polyphenols, binders, colorants, pH adjusters, buffers, and antioxidants.

[0105] When a magnesium glycinate tablet is compressed using a flat (non-rounded) pestle at a compression pressure of 5 kN per tablet, the tensile strength of the tablet is preferably 50 N / cm. ２ More than 500N / cm ２ More preferably, 70 N / cm ２ More than 400N / cm ２ More preferably, 100 N / cm ２ More than 350N / cm ２ The following is the reason: By keeping the tensile strength of the magnesium glycinate tablets within the specified range, it is believed that the tablets can be easily maintained in a stable state.

[0106] The shape of magnesium glycinate tablets is not particularly limited and may be, for example, standard R, double R, sugar-coated R, corner R, corner flat, rounded flat, triangular, oblong, or hexagonal. The shape of the top surface of the tablet is also not particularly limited and may be flat, standard R, double R, or sugar-coated R. The flatter the top surface, the higher the tensile strength of the tablet tends to be.

[0107] The size of the magnesium glycinate tablets is not particularly limited. In one embodiment, the diameter of the magnesium glycinate tablet is preferably 5 mm to 14 mm, more preferably 5 mm to 10 mm, and even more preferably 5 mm to 9 mm. The thickness of the magnesium glycinate tablet is preferably 2 mm to 7 mm, 3 mm to 6.5 mm, or 3.5 mm to 6.5 mm. The weight per magnesium glycinate tablet is preferably 50 mg to 1,000 mg, more preferably 70 mg to 800 mg, and even more preferably 90 mg to 600 mg.

[0108] Magnesium glycinate tablets can be manufactured by a manufacturing method comprising the steps of: mixing magnesium glycinate with internal, external, and other additives as needed to obtain a mixed powder; and compressing the obtained mixed powder into tablets to obtain magnesium glycinate tablets. When compressing the mixed powder into tablets, the mixed powder may be dispersed in a dispersion medium such as water and sprayed for granulation, or the mixed powder may be granulated in granular form. In addition, a coating may be added in a subsequent process for the purpose of coloring the appearance to enhance commercial value or to impart taste and odor.

[0109] The average particle size of the mixed powder is preferably 100 μm to 850 μm, more preferably 150 μm to 500 μm, and even more preferably 150 μm to 300 μm.

[0110] The method of tableting is not limited, but typically it can be carried out using a tablet press. For example, the tableting pressure per tablet is not limited, but is preferably 2 kN to 20 kN, more preferably 3 kN to 18 kN, and even more preferably 4 kN to 16 kN. Higher pressure results in higher hardness, but it also increases the load on the punch and the machine itself, leading to repair costs, so it is preferable to use the lowest possible pressure.

[0111] (Fourth Embodiment: Foods and Beverages or Pharmaceuticals) The magnesium glycinate of the present disclosure has a high magnesium concentration and can be suitably used for a variety of applications. Such applications include foods and beverages and pharmaceuticals, and the present disclosure also includes foods and beverages and pharmaceuticals that contain magnesium glycinate. Such foods and beverages and pharmaceuticals can be manufactured using the magnesium glycinate of the present disclosure.

[0112] Magnesium glycinate is thought to replenish magnesium in the body upon absorption. Magnesium intake is also expected to have effects such as increasing melatonin levels in the brain, promoting relaxation, improving sleep, and stabilizing blood sugar levels. Because magnesium glycinate is highly absorbable and has suppressed laxative side effects, it is preferable for use in foods, beverages, and pharmaceuticals.

[0113] In this disclosure, "food and beverages" refers to all food and beverages, including general foods such as health foods; foods with functional claims; health functional foods such as foods for specified health uses and foods with nutritional function; and supplements. Furthermore, "food and beverages" is not limited to those administered to humans, but also includes livestock feed, pet food, etc., administered to animals.

[0114] The form of food and beverages is not particularly limited and may be solid, semi-solid, or liquid. Specific forms include tablets, pills, capsules, liquids, pastes, syrups, powders, granules, gummies, gels, and the like.

[0115] Furthermore, the "pharmaceutical" can be administered to the target in any form, and may be administered orally or parenterally. Preferably, it can be administered orally.

[0116] Such medicines can be used to treat diseases such as magnesium deficiency, depression, and insomnia, as well as the various symptoms associated with them.

[0117] The dosage forms of pharmaceuticals are not particularly limited and include oral solid preparations such as tablets, granules, powders, and capsules; oral liquid preparations such as oral solutions and syrups; and parenteral liquid preparations such as injections.

[0118] When magnesium glycinate of this disclosure is used in food or pharmaceuticals, it may further contain additives such as excipients, coating agents, binders, bulking agents, disintegrants, surfactants, lubricants, diluents, dispersants, buffers, osmotic pressure adjusters, pH adjusters, emulsifiers, preservatives, stabilizers, antioxidants, colorants, UV absorbers, humectants, thickeners, activity enhancers, anti-inflammatory agents, bactericides, flavoring agents, and odor-masking agents.

[0119] Foods, beverages, or pharmaceuticals containing magnesium glycinate as disclosed herein can be used by administering them to the subject.

[0120] The magnesium glycinate disclosed herein is expected to have a high magnesium concentration and high bioavailability. Therefore, the magnesium glycinate disclosed herein is preferably used in foods and beverages and pharmaceuticals. Furthermore, the magnesium glycinate disclosed herein is also preferably used in the manufacturing methods of foods and beverages and pharmaceuticals.

[0121] The present disclosure will be further illustrated by the following embodiments, but will not be limited thereto.

[0122] (Test Example 1) 19.7 g of glycine (special grade, Fujifilm Wako Pure Chemical Industries) was added to 50 mL of deionized water and stirred in a water bath at room temperature (22-26°C) for more than 5 minutes (As One, VOLTEGA, Power Stirrer VPS-160SD). Next, 5.3 g of magnesium oxide (Kyowa Chemical Industry) was weighed and added to the prepared solution, and then stirred in a water bath at room temperature (22-26°C) for 24 hours. The obtained slurry was filtered by suction filtration, and the reaction product remaining on filter paper (ADVANTEC, FILTER PAER, QUANTITATIVE ASHLESS, 5C, 55 mm) was collected. This was dried overnight at 105°C (Tokyo Rikagaku Kiki, forced-air constant temperature drying oven WFO-520), and then pulverized using a mortar and pestle to obtain 12.1 g of powder.

[0123] (Test Example 2) Glycine and magnesium oxide were reacted in the same manner as in Test Example 1, and the resulting slurry was filtered by suction to obtain the reactants on the filter paper and the filtrate separately. Here, in order to remove impurities adhering to the reactants, an appropriate amount of deionized water was added dropwise to the reactants, and the washing solution was collected as filtrate by suction again (total amount of filtrate recovered was approximately 75 mL). 150 mL of ethanol (special grade, Fujifilm Wako Pure Chemical Industries) was added to the filtrate and stirred in a water bath at room temperature (22-26°C) for 30 minutes. The solution after stirring was filtered by suction to obtain the reactants remaining on the filter paper. These were dried and pulverized in the same manner as in Test Example 1 to obtain 9.1 g of powder.

[0124] (Test Example 3) 19.7 g of glycine was added to 50 mL of deionized water and stirred in a 30°C water bath for at least 5 minutes. The reaction was started in the same manner as in Test Example 1, except that the glycine was stirred at 30°C for at least 5 minutes. Next, 5.3 g of magnesium oxide was weighed and added to the prepared solution, which was then stirred in a 30°C water bath for 50 minutes, and then stirred again in a room temperature (22-26°C) water bath for 30 minutes. The resulting slurry was filtered by suction, and the reaction product remaining on the filter paper (standard) was collected. This was dried and pulverized in the same manner as in Test Example 1 to obtain 7.06 g of powder.

[0125] (Test Example 4) Similar to Test Example 3, glycine and magnesium oxide were added to deionized water and stirred in a 30°C water bath for 2 hours, and then stirred again in a room temperature (22-26°C) water bath for 30 minutes. After that, the mixture was filtered, dried, and ground as in Test Example 1 to obtain 8.56 g of powder.

[0126] (Test Example 5) 39.4 g of glycine was added to 50 mL of deionized water and stirred in an 80°C water bath for more than 5 minutes (stirring conditions were the same as in Test Example 1). Next, 10.6 g of magnesium oxide was weighed and added to the prepared solution, then stirred in an 80°C water bath for 50 minutes, and then stirred in a room temperature (22-26°C) water bath for 30 minutes. After that, the solution was filtered, dried, and ground in the same manner as in Test Example 1 to obtain 34.32 g of powder.

[0127] (Test Example 6) 19.7 g of glycine was added to 50 mL of 1 mol / L sodium hydroxide aqueous solution (Fujifilm Wako Pure Chemical Industries) and stirred in a 30°C water bath for more than 5 minutes (stirring conditions were the same as in Test Example 1). Next, 5.3 g of magnesium oxide was weighed and added to the prepared solution, then stirred in a 30°C water bath for 2 hours, and then stirred in a room temperature (22-26°C) water bath for 30 minutes. After that, the solution was filtered, dried, and pulverized in the same manner as in Test Example 1 to obtain 9.1043 g of powder.

[0128] (Test Example 7) 18.0 g of glycine was added to 50 mL of deionized water and stirred in a water bath at room temperature (22-26°C) for more than 5 minutes (stirring conditions were the same as in Test Example 1). Next, 7.0 g of magnesium hydroxide (manufactured by Kyowa Chemical Industry Co., Ltd.) was weighed and added to the prepared solution, and then stirred in a water bath for 2 hours and 30 minutes. After that, the solution was filtered, dried and pulverized in the same manner as in Test Example 1 to obtain 3.8234 g of powder.

[0129] (Test Example 8) 18.0 g of glycine was added to 50 mL of deionized water and stirred in a water bath at room temperature (22-26°C) for at least 5 minutes (stirring conditions were the same as in Test Example 1). Next, 7.0 g of magnesium hydroxide was weighed and added to the prepared solution, and stirred in a water bath for 2 hours. Then, 50 mL of ethanol (special grade, Fujifilm Wako Pure Chemical Industries) was added and stirred in a water bath at room temperature (22-26°C) for 30 minutes. After that, the mixture was filtered, dried, and ground in the same manner as in Test Example 1 to obtain 16.9 g of powder.

[0130] (Test Example 9) The experiment was conducted in the same manner as in Test Example 1, except that the amount of glycine was changed to 18.0 g and 5.3 g of magnesium oxide was changed to 7.0 g of magnesium hydroxide, and 6.7366 g of dried pulverized material was obtained.

[0131] (Test Example 10) Glycine and magnesium hydroxide were reacted in the same manner as in Test Example 9, and the resulting slurry was filtered by suction to obtain the reaction product on the filter paper and the filtrate (approximately 75 mL) separately. Ethanol was added to the filtrate in the same manner as in Test Example 2, and filtration, drying, and grinding were carried out sequentially to obtain 13.2883 g of white powder.

[0132] (Test Examples 11-14) In Test Example 11, glycine (special grade, manufactured by Fujifilm Wako Pure Chemical Industries) was used as the sample; in Test Example 12, magnesium glycinate (manufactured by Actylis Inc.); in Test Example 13, magnesium hydroxide (manufactured by Kyowa Chemical Industry Co., Ltd.); and in Test Example 14, magnesium oxide (manufactured by Kyowa Chemical Industry Co., Ltd.).

[0133] (Test Example 15) 19.7 g of glycine (special grade, Fujifilm Wako Pure Chemical Industries, γ-type crystal) and magnesium oxide (Kyowa Chemical Industry Co., Ltd., specific surface area 36 m²) ２ 5.3 g of (1 / g) was weighed and simultaneously added to 50 mL of deionized water. The mixture was then stirred in a water bath at room temperature (22-26°C) for 18 hours to obtain a slurry (As One, VOLTEGA, Power Stirrer VPS-160BD). The obtained slurry was spray-dried at room temperature (22-26°C) while stirring using a spray dryer (YAMATO Kagaku, Palvis Mini Spray GB210A), and 2.1 g of powder was recovered. During spray drying, the inlet temperature was 180°C, the outlet temperature was 78-82°C, and the airflow rate was 0.4-0.5 m³.３ The conditions were set to 1 / minute. (Test Example 16) 2.6 g of powder was obtained in the same manner as in Test Example 15, except that 18.0 g of glycine, 5.1 g of magnesium oxide, and 1.9 g of magnesium hydroxide were used instead of 19.7 g of glycine and 5.3 g of magnesium oxide. (Test Example 17) After preparing the slurry in the same manner as in Test Example 15, it was heated at 50°C for 1 hour, and while maintaining that temperature, it was powdered in the same manner as in Test Example 15 to obtain 4.2 g of powder. (Test Example 18) 2.8 g was obtained in the same manner as in Test Example 15, except that 6.0 g of magnesium oxide and 1.0 g of magnesium hydroxide were used instead of 5.3 g of magnesium oxide. (Test Example 19) 6.0 g of powder was obtained in the same manner as in Test Example 15, except that the outlet temperature during spray drying was set to 88-92°C. (Test Example 20) 4.7 g of powder was obtained in the same manner as in Test Example 15, except that the outlet temperature during spray drying was set to 98-102°C. (Test Example 21) 4.8 g of powder was obtained in the same manner as in Test Example 15, except that 19.5 g of glycine, 4.7 g of magnesium oxide, and 0.8 g of magnesium hydroxide were used instead of 19.7 g of glycine and 5.3 g of magnesium oxide.

[0134] The following measurements were performed on the powder obtained in the above test example.

[0135] (Differential Thermal Scanning Calorimetry-Thermogravimetric Analysis) Measurements were performed using a differential thermal scanning calorimetry-thermogravimetric analyzer, STA449 F3 Jupiter (NETZSCH-Geratebau GmbH). The measurement conditions were as follows: Sample amount: 10-12 mg Sample container: Alumina pan Heating rate: 10°C / min from 40°C to 600°C Atmosphere gas: Nitrogen gas (70 mL / min) Baseline measurement: Empty pan

[0136] (Thermogravimetric Analysis) Measurements were performed using a thermogravimetric analyzer STA2500 Regulus (NETZSCH-Geratebau GmbH). The measurement conditions were as follows: Sample amount: 10-11 mg Sample container: Aluminum pan Heating rate: 10°C / min from 30°C to 600°C Atmosphere gas: Nitrogen gas (50 mL / min) or air Control substance: Alumina (10-11 mg)

[0137] As shown in Figure 1, in Test Example 8, no significant weight change occurred from 50°C to around 350°C, but a decrease in weight was confirmed in the range of 350°C to 380°C. From this, it is considered that the magnesium glycinate in Test Example 8 does not contain hydration water.

[0138] As shown in Figures 2, 4(a), 4(b), and 4(c), weight loss was confirmed in Test Example 4, Test Example 6, Test Example 9, and Test Example 12, respectively, at around 150°C and in the range of 350°C to 380°C. The weight loss at around 150°C is thought to be due to the desorption of hydration water from magnesium glycinate, while the weight loss in the range of 350°C to 380°C is thought to be due to the thermal decomposition of magnesium glycinate.

[0139] As shown in Figures 3 and 4(c), weight loss was observed in Test Examples 10 and 12 in the ranges of approximately 150°C, 240°C to 268°C, and 350°C to 380°C. The weight loss in the range of 240°C to 280°C is thought to be due to the combustion of glycine contained in magnesium glycinate.

[0140] Furthermore, the results of thermogravimetric analysis for the samples in Test Examples 1, 2, 4, 6, 8, 9, and 10-12 are shown in the table below. Note that if the hydration water content fell below 0% by weight due to measurement errors, etc., it was treated as 0% by weight. The glycine content was calculated by dividing the difference between the weight at 280°C and the weight at 240°C by the weight at 50°C in thermogravimetric analysis. The hydration water content was calculated by dividing the difference between the weight at 180°C and the weight at 50°C by the weight at 50°C in thermogravimetric analysis. The magnesium glycinate content was calculated using the following formula: (Magnesium glycinate content) = (1 - (Glycine content)) × 100. The magnesium content was calculated using the following formula: (Magnesium content) = (Magnesium glycinate content) × M Ａ / M Ｂ ×100 M Ａ Atomic weight of magnesium (24.31) M Ｂ Molecular weight of magnesium glycinate (Type I: 206.48 g / mol, Type II: 172.45 g / mol)

[0141]

[0142] The results of differential scanning calorimetry for test examples 4, 6, 8-10, and 12 are shown in Table 2 below. Note that the peak area S １ (J / g) was calculated as the area of ​​the peak with an onset temperature in the range of 230°C to 255°C. Peak area S ２ (J / g) was calculated as the area of ​​the peak with an onset temperature in the range of 330°C to 370°C.

[0143]

[0144] (Mass Spectrometry) Measurements were performed using a mass spectrometer, microOTOF (Bruker Corporation). The sample was dissolved in ultrapure water at 10 μg / mL and ionized in ESI Positive mode. The measurement was performed with the measurement mass range set to 50-1000 m / z, the capillary voltage set to 4500 V, and the nebulizer pressure set to 0.4 Bar.

[0145] Mass spectrometry results showed that in both Test Example 8 (Figure 5(a)) and Test Example 4 (Figure 5(b)), the compound obtained in magnesium glycinate had a molecular weight of approximately 173.041 m / z, suggesting that magnesium glycinate as a compound was obtained.

[0146] (Powder X-ray Diffraction Measurement) Measurements were performed using an X-ray diffractometer, EMPYREAN (Malvern Panatical). The sample was packed tightly into a circular sample holder manufactured by Malvern Panatical using a sample preparation kit manufactured by Malvern Panatical. The measurement conditions were as follows: X-ray source: CuKα (λ = 1.5418 Å) Acceleration voltage: 45 kV Step: 2θ = 0.026° Scan speed: 0.656514° / s Divergent slit: 0.5000° Scattering slit: 8.0 mm Solar slit: 0.04 rad HighScore Plus (Malvern Panalogical) was used to analyze the obtained XRD diffraction pattern. Peak detection and peak fitting were performed, and the phase of the peak top and FWHM were calculated from the obtained peaks. The crystallite size was calculated using the following formula: D = Kλ / Bcosθ λ = 1.5418 Å K = 0.9 B: FWHM θ: Phase of the peak top

[0147] As shown in Figures 6 to 11, it was confirmed that the magnesium glycinate obtained in Test Example 1 (Figure 7), Test Example 2 (Figure 9(a)), Test Example 3 (Figure 9(b)), Test Example 4 (Figure 8), Test Example 5 (Figure 9(c)), Test Example 6 (Figure 9(d)), Test Example 7 (Figure 10(a)), Test Example 8 (Figure 6), Test Example 9 (Figure 10(b)), and Test Example 10 (Figure 10(c)) had one or more peaks selected from the following: a first peak with its peak in the range of 2θ between 11.1° and 12.1°; a second peak with its peak in the range of 2θ between 13.3° and 14.3°; a third peak with its peak in the range of 2θ between 15.5° and 16.5°; and a fourth peak with its peak in the range of 2θ between 17.0° and 18.0°.

[0148] Test example 12 (Figure 11(a)) had a third peak with its peak in the range of 2θ from 15.5° to 16.5°, and a fourth peak with its peak in the range of 2θ from 17.0° to 18.0°. However, it also had a peak where 2θ was around 25°, suggesting the presence of glycine. Note that test example 11 (Figure 10(d)) was glycine, test example 13 (Figure 11(b)) was magnesium hydroxide, and test example 14 (Figure 11(c)) was magnesium oxide, none of which contained magnesium glycinate.

[0149] (XRD measurement results: crystallite size) Crystallite size was calculated from the XRD diffraction pattern, and the results in Tables 3 and 4 were obtained. Comparing the crystallite size of the peak corresponding to 16.7–17.0° with the crystallite size of the peak corresponding to 11.3–11.9° or 13.3–13.9°, the crystallite size of the peak corresponding to 11.3–11.9° or 13.3–13.9° was smaller. It is thought that crystals showing peaks corresponding to 11.3–11.9° or 13.3–13.9° tend to form smaller crystals.

[0150]

[0151]

[0152] (Solubility Test) 1.5 g of the sample was weighed and added to 50 mL of deionized water, and stirred at 500 rpm for 1 hour (AS ONE MAGNETIC STIRRER HSH-4D). The resulting slurry was filtered by suction, and the filtrate was subjected to ultrasonic treatment (ultrasonic cleaner MCD-10, As One), followed by filtration through a membrane filter (syringe filter DISMIC CS type, ADVANTEC). The resulting aqueous solution was diluted 500-fold with ultrapure water, and magnesium ion ion chromatography analysis was performed under the following conditions.

[0153] Magnesium ion ion chromatography was performed using EcoIC (Metrohm). A C6-150 (Metrohm) column was used, and aqueous solutions of 1.7 mM nitric acid (Kanto Chemical) and 1.7 mM dipicolinic acid (Kanto Chemical) were prepared as eluents. Measurements were performed at a flow rate of 0.9 mL / min and an injection rate of 10 μL / sample. A 1002 g / L magnesium standard solution (Kanto Chemical) was used as the magnesium ion standard solution, and calibration curves of concentration relative to peak area were calculated using 100, 200, 400, and 800-fold dilutions. The concentration of each sample was calculated using the calibration curves calculated above, based on the peak area corresponding to magnesium obtained from ion chromatography. The molar mass of each ion and molecule was used to determine the Mg concentration in the diluent. ２＋ The concentration was calculated.

[0154] As a result, Mg in the diluent ２＋ The magnesium concentration was 5.58 mg / L in the sample of Test Example 8, 4.55 mg / L in the sample of Test Example 4, and 4.38 mg / L in the sample of Test Example 12. From this, it can be said that the magnesium concentrations in the samples of Test Examples 4 and 8 are higher compared to the sample of Test Example 12.

[0155] (Liquid NMR measurement) NMR device Avance III ( １ Measurements were performed using a 90°C pulse (H resonance frequency: 500 MHz) (Brker Corporation). １ H), 9.1 μs ( １３ In step C), the signals were integrated until a sufficient signal-to-noise ratio was achieved. The sample was dissolved in DMSO-d6 (Fujifilm Wako Pure Chemical Industries) or 5% DSS / heavy water aqueous solution (Fujifilm Wako Pure Chemical Industries) to a concentration of 1-15 mg / mL, and the solution was added to a 5 mm diameter sample tube. １ H, １３ ¹¹C,HSQC-NMR measurements were performed. Fourier transforms were performed using Bruker Top Spin software to obtain NMR spectra.

[0156] Glycine dissolved in heavy water (Test Example 11) １The peaks detected by 1H NMR measurement were 3.546 and 4.771 ppm. １３ The peaks detected by 13C NMR measurement were 44.16 and 175.11 ppm. (Test Example 4) １ The peaks detected by 1H NMR measurement were 3.306 and 4.760 ppm. １３ The peaks detected by 13C NMR measurement were 45.83 and 180.72 ppm. (Test Example 8) １ The peaks detected by 1H NMR measurement were 3.325 and 4.780 ppm. １３ The peaks detected by 13C NMR measurement were 45.85 and 180.99 ppm.

[0157] (Particle Size Measurement Method) 0.7 g of magnesium glycinate was mixed with 70 mL of solvent, and the particle size of the resulting mixture was measured. The sample to be measured was dispersed in the solvent and pre-treated using an ultrasonic homogenizer US-300AT (Nippon Seiki Seisakusho). The particle size of the resulting sample dispersion was measured using a particle size distribution analyzer MT3000 (MicrotracBEL). The measurement conditions were as follows: Ultrasonic treatment: 15 μm or 40 μm, 3 minutes Particle permeability: Permeable Particle shape: Non-spherical particles Refractive index: 1.57 Solvent: Ethanol (Fujifilm Wako Pure Chemical Industries) Solvent refractive index: 1.36

[0158] The results for particle size measurement are shown in Table 5. In Test Examples 4 and 8, the particle size was detected as smaller when ultrasonic treatment was performed compared to when ultrasonic treatment was not performed. From this, it can be concluded that the samples in Test Examples 4 and 8 are composed of aggregated smaller primary particles.

[0159]

[0160] (Method for measuring loose bulk density) The obtained powder was slowly poured into a 5 mL graduated cylinder, and the loose bulk density was calculated by determining the weight per unit volume.

[0161] The measurement results of differential scanning calorimetry, bulk density when loosened, and X-ray diffraction analysis in Examples 15 to 21 are shown in Table 6. Note that "-" in the table means that the measurement was not carried out.

[0162]

[0163] When the glycine content is 3% by mass or less and the crystallite size is 500 Å or more, it has been clarified that the bulk density becomes 0.5 g / mL or more in the spray drying method. Representative dosage forms of health foods are tablets and hard capsule preparations. When using raw materials with a low bulk density, in the case of tablets, the tablet thickness increases and it becomes difficult to swallow. Also, in the case of hard capsule preparations, the raw materials cannot be completely filled into the capsules, the number increases, and the burden on the taker becomes large. Therefore, increasing the raw material specific gravity to 0.5 g / mL or more is significant in terms of practicality.

[0164] (Evaluation of Maillard reactivity) Weighed 1462 mg of glucose and 500 mg of magnesium glycinate, placed them in a glass bottle, covered it, and shook well. As a positive control, weighed 1462 mg of glucose and 305 mg of glycine, placed them in a glass bottle, covered it, and shook well. Also, as negative controls, glucose alone and glycine alone were similarly placed in glass bottles. All samples were stored in a dryer at 60°C for 3 days, and the coloring state was observed. Glucose (manufactured by Fujifilm Wako Pure Chemical Industries, special grade) and glycine (manufactured by Fujifilm Wako Pure Chemical Industries, special grade) were pulverized in a mortar and then used for the test. The molar ratio of 1462 mg of glucose and 500 mg of magnesium glycinate is considered to be 2:1. Also, the molar ratio of 1462 mg of glucose and 305 mg of glycine is considered to be 2:1.

[0165] After that, the samples were collected, and a color difference meter (ZE6000, manufactured by Nippon Denshoku Industries Co., Ltd.) based on the reflected light, with irradiation and light reception conditions conforming to JIS Z-8722, was used to analyze the degree of discoloration. The L*a*b* color system in a 10° field of view with a D65 light source was adopted, and the degree of discoloration was the reference point (L ０ * = 100, a ０ * = 0, b ０The color difference (ΔE* value) with respect to * = 0) was calculated and compared. ΔE* = [(L １ * - L ０ *) ２ + (a １ * - a ０ *) ２ + (b １ * - b ０ *) ２ １／２

[0166]

[0167] As a result of storage at 60 °C for 3 days, the positive control caused browning, and it was confirmed that there was no problem with the browning reaction test. It was confirmed that there was no problem with the browning reaction test. For Test Examples 4, 8, and 19 with a glycine residual amount of 3% or less, ΔE* was about 18 for calculating the displacement with the theoretical white point as the origin, but no browning reaction was observed and they showed white. On the other hand, browning was observed in Test Examples 17 and 21 with a glycine residual amount of more than 3%. Therefore, it was confirmed that reducing the glycine residual amount to 3% or less had the effect of reducing the reactivity of the Maillard reaction.

[0168] (Evaluation of Tablet Strength) The magnesium glycinate of Test Example 4, Test Example 8, and Test Example 20, crystalline cellulose (manufactured by Asahi Kasei Corporation, Ceolus UF-F702), fine particle silicon dioxide (manufactured by Fuji Silysia, Aerosil 720), and calcium stearate (manufactured by Taihei Chemical Co., Ltd.) were formulated so that the formulation per tablet was the formulation shown in Table 8. They were mixed. The total weight was set to 4.5 g, and the respective raw materials were mixed, and tableting was performed the next day.

[0169] The tableting test was carried out by attaching a round flat-shaped pestle with a diameter of 10 mm and a corresponding mortar to the TYPE-M static compressor manufactured by Maekawa Testing Machine Co., Ltd., and filling 300 mg each into the mortar hole and compressing. The compression pressures were 5 and 10 kN, and the test was repeated 3 times each.

[0170]

[0171] ​(Tensile Strength Measurement) The tablets manufactured in each test example were cylindrical, and the thickness [mm] in the direction of clamping the circular surface was measured using a commercially available general-purpose digital thickness gauge. The hardness of the tablets was measured using a tablet hardness tester (DR. SCHLEUNIGER MODEL 6D TABLET TESTER) with a force applied horizontally to the circular surface, and the hardness [N] was measured, repeating three times for each test. The obtained values ​​were converted to tensile strength using the following formula: Tensile Strength [N / cm] ２ Table 9 shows the results of evaluating the compressibility of magnesium glycinate with different crystal forms by manufacturing tablets and evaluating their strength as tensile strength.

[0172]

[0173] The powder of Test Example 20, prepared by the spray-drying method, showed a significant improvement in tensile strength with increasing tablet compression pressure during tablet formation, compared to the powder of Test Example 4. Although Test Example 8, a novel anhydrous crystal, was found to be a more suitable raw material powder for tablet formation than Test Example 4, a conventional dihydrate crystal, the powder prepared by the spray-drying method (Test Example 20) exhibited excellent compression moldability despite being a conventional dihydrate crystal.

[0174] (Method for calculating particle circularity) For Test Examples 20, 4, and 8, the particles were observed using a scanning electron microscope (JEOL Ltd., JSM-7600F, accelerating voltage: 5kV) and photographs of the particles were obtained. Furthermore, elemental analysis of the particles was performed by measuring the EDS spectrum using the attached energy-dispersive X-ray analyzer.

[0175] Next, to calculate the circularity of the particles from the images, we used the open-source software "ImageJ". First, we loaded three fields of view of the target images into "ImageJ". For particles with clear outlines in the images, we manually drew the contour lines of the particles and calculated the circularity using the "Analyze Particles" command within the "Analyze" command. This operation was performed for a total of 20 particles, and the average value was determined as the circularity of the sample. Circularity is defined as follows: when the area is S and the perimeter is L, circularity = 4πS / L ２ This value is defined by [a specific formula / method], and the closer it is to 1, the more circular it is.

[0176]

[0177] The circularity of magnesium glycinate in Test Example 20, which was powdered by spray drying, was 0.801 ± 0.045, while the circularity of magnesium glycinate in Test Examples 4 and 8, prepared by alcohol crystallization, was 0.591 ± 0.127 and 0.635 ± 0.118, respectively. From this, it was found that particles with a circularity of 0.75 or higher can be distinguished from those produced by spray drying. Furthermore, as can be seen from the standard deviation (SD) value, Test Example 20, produced by spray drying, showed little variation in shape, and it was found that magnesium glycinate with a spherical shape and a circularity close to 1 had higher hardness when compressed into tablets. In addition, elemental peaks derived from Mg, C, and O were observed in the EDS spectrum derived from the observed particles, confirming that the particles were magnesium glycinate.

[0178] The magnesium glycinate disclosed herein is expected to have a high magnesium concentration and high bioavailability. Therefore, the magnesium glycinate disclosed herein is preferably used in foods and beverages and pharmaceuticals.

Claims

1. In differential scanning calorimetry, the area S of an endothermic peak with an onset temperature in the range of 230°C to 255°C. １ The area S of the endothermic peak having an onset temperature in the range of 330°C to 370°C. ２ The value S obtained by dividing by... １ / S ２ However, magnesium glycinate is between 0 and 7.

2. Magnesium glycinate having a glycine content of 0% by weight or more and 3% by weight or less.

3. The magnesium glycinate according to claim 1, wherein, in thermogravimetric analysis, the weight loss rate at 380°C is 40% by weight or less, with the weight at 50°C as the reference.

4. The magnesium glycinate according to claim 1, wherein the loosened bulk density is 0.5 g / mL or more.

5. The magnesium glycinate according to claim 1, wherein, in the powder X-ray diffraction spectrum, the crystallite size of the crystals belonging to the peak having its peak in the range of 2θ between 16.7° and 17.0° is 500 Å or more.

6. The magnesium glycinate according to claim 1, wherein the average roundness is 0.75 or more and 1.00 or less.

7. The magnesium glycinate according to claim 1, wherein the color difference ΔE* measured by the following method is 30 or less. [Method for Measuring Color Difference] 1462 parts by mass of glucose and 500 parts by mass of magnesium glycinate are mixed and stored at 60°C for 72 hours under sealed conditions. The L* value of the mixture after storage is L １ *, the a* value is a １ *, the b* value is b １ *. The L*a*b* color system in a 10° field of view with a D65 light source is adopted. Based on the reference point (L ０ * = 100, a ０ * = 0, b ０ * = 0), the color difference (ΔE* value) is calculated by the following formula: ΔE* = [(L １ * - L ０ *) ２ + (a １ * - a ０ *) ２ + (b １ * - b ０ *) ２ ] １／２ is calculated based on this.

8. The tensile strength when tablets are compressed using a flat pestle with a compression pressure of 5 kN per tablet is 50 N / cm. ２ More than 500N / cm ２ The magnesium glycinate described in claim 1 is as follows:

9. A magnesium glycinate tablet comprising the magnesium glycinate described in any one of claims 1 to 8.

10. A food or pharmaceutical product comprising magnesium glycinate as described in any one of claims 1 to 8.

11. A method for producing food or pharmaceuticals using magnesium glycinate according to any one of claims 1 to 8.

12. A method for producing magnesium glycinate, comprising: a mixing step of mixing glycine and a magnesium compound in the presence of water to obtain a mixture, and then holding the mixture at a temperature of 90°C or lower to obtain a precipitate containing magnesium glycinate; and a drying step of drying the precipitate to obtain magnesium glycinate, wherein the magnesium compound comprises one or more selected from magnesium oxide and magnesium hydroxide.

13. The method for producing magnesium glycinate according to claim 12, further comprising a second mixing step of mixing the mixture containing the precipitate with ethanol after the mixing step and before the drying step.

14. The method for producing magnesium glycinate according to claim 12 or 13, wherein the drying step is carried out by a spray-drying method.

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