Crystals and methods for producing the same

Abstract

This disclosure aims to provide magnesium glycinate with a high magnesium concentration. [Solution] Magnesium glycinate having a first peak with its peak in the range where 2θ is between 11.1° and 12.1°, and a second peak with its peak in the range where 2θ is between 13.3° and 14.3°, in its powder X-ray diffraction spectrum.

Description

Technical Field

[0001] The present disclosure relates to crystals and a method for producing the same.

Background Art

[0002] Magnesium glycinate is excellent in bioabsorbability and has weak side effects such as a laxative effect, and thus can be used in foods, dietary supplements, pharmaceuticals, and the like.

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

Chemical formula

[0004] Patent Document 2 describes a method in which an organic acid ligand and a metal compound are added to a non-aqueous liquid to form a suspension, the organic acid ligand and the metal compound are reacted, and the suspension is heated while stirring for a predetermined time, and the suspension is filtered to obtain an insoluble metal organic chelate.

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

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0007] In the magnesium glycinate hydrate described in Patent Document 1 and the magnesium glycinate compound obtained by the production method described in Patent Documents 1 and 2, the magnesium concentration was not sufficiently satisfactory.

[0008] The present disclosure aims to provide magnesium glycinate having a high magnesium concentration.

Means for Solving the Problems

[0009] The first embodiment of the present disclosure provides magnesium glycinate having a first peak having a vertex in the range of 2θ of 11.1° or more and 12.1° or less and a second peak having a vertex in the range of 2θ of 13.3° or more and 14.3° or less in a powder X-ray diffraction spectrum.

[0010] In the second embodiment of the present disclosure, in the magnesium glycinate of the first embodiment, the ratio I1 / I2 of the intensity I1 of the first peak to the intensity I2 of the second peak can be 2 or more and 2.5 or less.

[0011] In the third embodiment of the present disclosure, in any one of the magnesium glycinate described in the first embodiment to the second embodiment, in a powder X-ray diffraction spectrum, a third peak having a vertex in the range of 2θ of 19.5° or more and 20.5° or less; and It may further have one or more selected from a fourth peak having a vertex in the range of 2θ of 37.5° or more and 38.5° or less.

[0012] In the fourth embodiment of the present disclosure, in any one of the magnesium glycinate described in the first embodiment to the third embodiment, in a powder X-ray diffraction spectrum, a fifth peak having a vertex in the range of 2θ of 17.4° or more and 18.4° or less; a sixth peak having a vertex in the range of 2θ of 18.1° or more and 19.1° or less; a seventh peak having a vertex in the range of 2θ of 22.9° or more and 23.9° or less; and It may further have one or more selected from an eighth peak having a vertex in the range of 2θ of 28.6° or more and 29.6° or less.

[0013] A fifth embodiment of this disclosure provides magnesium glycinate in which, in thermogravimetric analysis, the weight loss rate at 380°C is 30% by weight or less, based on the weight at 50°C. In the fifth embodiment of this disclosure, in any one of the first to fourth embodiments of magnesium glycinate, the weight loss rate at 380°C, based on the weight at 50°C, may be 30% by weight or less, as determined by thermogravimetric analysis.

[0014] In the sixth embodiment of this disclosure, in any one of the magnesium glycinate described in the first to fifth embodiments, the value S1 / S2 obtained by dividing the area S1 of an endothermic peak having an onset temperature in the range of 125°C to 160°C by the area S2 of an endothermic peak having an onset temperature in the range of 330°C to 370°C in differential thermal scanning calorimetry may be 0 or more and 1.8 or less.

[0015] In the seventh embodiment of this disclosure, in any one of the embodiments described in the first to sixth embodiments, the magnesium glycinate does not need to contain water of hydration.

[0016] In the eighth embodiment of this disclosure, in any one of the first to seventh embodiments, the color difference ΔE* may be 30 or less. The color difference 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 in a sealed container at 60°C for 72 hours. The L* value of the mixture after this storage is denoted as L1*, the a* value as a1*, and the b* value as b1*. The L*a*b* color system is used in a 10° field of view under a D65 light source, and the color difference (ΔE* value) relative to the reference point (L0*=100, a0*=0, b0*=0) is calculated using the following formula: ΔE*=[(L1*-L0*) 2 +(a1*-a0*) 2 +(b1*-b0*) 2 ] 1 / 2 It is calculated based on the following.

[0017] In the ninth embodiment of this disclosure, the tensile strength of the tablet obtained from magnesium glycinate is 75 N / cm² in any one of the first to eighth embodiments. 2 More than 500N / cm 2 The following may be possible: Magnesium glycinate tablets may be compressed with a compression pressure of 5 kN per tablet. The above compression may be carried out using a flat punch.

[0018] A tenth embodiment of this disclosure provides a magnesium glycinate tablet comprising any one of the magnesium glycinate described in the first to ninth embodiments.

[0019] An eleventh embodiment of this disclosure provides a food or pharmaceutical product comprising any one of the magnesium glycinate compounds described in the first to ninth embodiments.

[0020] A twelfth embodiment of this disclosure provides a method for producing food or pharmaceuticals using any one of the magnesium glycinate described in the first to ninth embodiments.

[0021] A thirteenth embodiment of this disclosure provides a method for producing magnesium glycinate. Such a manufacturing method includes a first step of mixing glycine and magnesium hydroxide in the presence of water to obtain a mixture. The manufacturing method includes a second step of further mixing the above mixture with ethanol to obtain magnesium glycinate.

[0022] In the fourteenth embodiment of this disclosure, the first step may be carried out at a temperature of 50°C or lower, in the thirteenth embodiment. [Effects of the Invention]

[0023] According to this disclosure, it is possible to provide magnesium glycinate with a high magnesium concentration. [Brief explanation of the drawing]

[0024] [Figure 1] Figure 1 shows the powder X-ray diffraction spectrum of Test Example 8. [Figure 2] Figure 2 shows the powder X-ray diffraction spectrum of Test Example 1. [Figure 3] Figure 3 shows the powder X-ray diffraction spectrum of Test Example 4. [Figure 4] Figure 4 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 5] Figure 5 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 6] Figure 6 shows the powder X-ray diffraction spectra for (a) Test Example 12, (b) Test Example 13, and (c) Test Example 14, respectively. [Figure 7] Figure 7 shows the thermogravimetric-differential scanning calorimetry curve for Test Example 8. [Figure 8] Figure 8 shows the thermogravimetric-differential scanning calorimetry curve for Test Example 4. [Figure 9] Figure 9 shows the thermogravimetric-differential scanning calorimetry curve for Test Example 10. [Figure 10] Figure 10 shows the thermogravimetric-differential scanning calorimetry curves for (a) Test Example 6, (b) Test Example 9, and (c) Test Example 12, respectively. [Figure 11] Figure 11 shows the mass spectrometry spectra of (a) Test Example 8 and (b) Test Example 4. [Figure 12] Figure 12 is a graph showing the results of the hygroscopicity tests for test examples 8, 1, and 4. [Modes for carrying out the invention]

[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 6-coordinate crystal containing water of hydration may be referred to as type I, and a 4-coordinate crystal not containing water of hydration may be referred to as type II.

[0027] In this disclosure, when we refer to magnesium glycinate simply, we are not limited to magnesium glycinate as a compound, but also include materials containing components other than magnesium glycinate. In such materials, the form of magnesium glycinate is not particularly limited and may be either crystalline or amorphous.

[0028] In this disclosure, a crystal means a substance from which a peak is observed when measured by X-ray diffraction. In this disclosure, a magnesium glycinate crystal may be a single crystal or a polycrystalline magnesium glycinate. Furthermore, in this disclosure, when referring to a magnesium glycinate crystal, the crystal is not limited to one consisting solely of magnesium glycinate, but also includes crystals containing substances other than magnesium glycinate.

[0029] (First embodiment: Magnesium glycinate) The magnesium glycinate of this disclosure has, in a powder X-ray diffraction (XRD) spectrum, a first peak having its peak in the range of 2θ between 11.1° and 12.1°, and a second peak having its peak in the range of 2θ between 13.3° and 14.3°. In a preferred embodiment, the first peak may be the peak with the highest intensity in the range of 2θ between 5° and 70°, and the second peak may be the peak with the second highest intensity in the range of 2θ between 5° and 70°.

[0030] 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.

[0031] In other words, the magnesium glycinate of this disclosure has the first and second peaks in its XRD spectrum, and is thought to have a crystal structure derived from these peaks. In such a crystal structure, the amount of hydration water is reduced, and as a result, magnesium glycinate with a high magnesium concentration is obtained. Conventional magnesium glycinate, as shown in Figure 1 of Patent Document 1, for example, has the peak with the highest intensity in the range of 2θ from 16° to 17° in its XRD spectrum, and is thought to have a different crystal structure.

[0032] 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°.

[0033] The ratio I1 / I2 of the intensity of the first peak to the intensity I2 of the second peak is preferably 2 to 2.5, more preferably 2 to 2.3. Having this intensity ratio I1 / I2 within this range allows for a higher magnesium concentration in the magnesium glycinate.

[0034] In a preferred embodiment, the magnesium glycinate of the present disclosure preferably further has one or more peaks selected from a third peak having a peak in the range of 2θ between 19.5° and 20.5° in the XRD spectrum, and a fourth peak having a peak in the range of 2θ between 37.5° and 38.5°. It is believed that having one or more peaks selected from the third and fourth peaks further increases the magnesium concentration in the magnesium glycinate.

[0035] The peak of the third peak described above preferably lies in the powder X-ray diffraction (XRD) spectrum where 2θ is between 19.7° and 20.3°, and more preferably in the range of 19.9° and 20.1°. The peak of the fourth peak described above preferably lies in the range of 37.7° and 38.3°, and more preferably in the range of 37.9° and 38.1°.

[0036] In a more preferred embodiment, the magnesium glycinate of the present disclosure preferably further has one or more peaks selected from the following in its powder X-ray diffraction (XRD) spectrum: a fifth peak with a peak in the range of 2θ between 17.4° and 18.4°; a sixth peak with a peak in the range of 2θ between 18.1° and 19.1°; a seventh peak with a peak in the range of 2θ between 22.9° and 23.9°; and an eighth peak with a peak in the range of 2θ between 28.6° and 29.6°. It is believed that having one or more peaks selected from the fifth to eighth peaks further increases the magnesium concentration in the magnesium glycinate.

[0037] The peak of the fifth peak described above preferably lies in the range where 2θ is between 17.6° and 18.2°, and more preferably in the range where 2θ is between 17.8° and 18.0°. The peak of the sixth peak described above preferably lies in the range where 2θ is between 18.3° and 18.9°, and more preferably in the range where 2θ is between 18.5° and 18.7°. The peak of the seventh peak described above preferably lies in the range where 2θ is between 23.1° and 23.7°, and more preferably in the range where 2θ is between 23.3° and 23.5°. The peak of the eighth peak described above preferably lies in the range where 2θ is between 28.8° and 29.4°, and more preferably in the range where 2θ is between 29.0° and 29.2°.

[0038] The magnesium glycinate of this disclosure has a crystallite size of at least 100 Å to 800 Å, more preferably 200 Å to 600 Å, and even more preferably 250 Å to 500 Å, of which the crystallite size of the crystals assigned to the first peak is preferably 100 Å to 800 Å, more preferably 200 Å to 600 Å, and even more preferably 250 Å to 500 Å.

[0039] In this disclosure, the crystallite size D of magnesium glycinate is derived from the shape of the first peak in the XRD spectrum using the following formula: D = Kλ / Bcosθ [where λ=1.5418Å K=0.9 B:FWHM θ: Phase of the peak top] It can be calculated based on this.

[0040] In this disclosure, the XRD spectrum of magnesium glycinate can be measured by powder X-ray diffraction. In such powder X-ray diffraction measurements, CuKα rays (λ=1.5418 Å) are used as the X-ray source, and measurements can be performed with an acceleration voltage of 45 kV and an angular step of 0.026°.

[0041] 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 14% 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.

[0042] 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.

[0043] 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 0-600 J / g and a starting temperature of approximately 125-160°C. Based on the weight difference of the thermogravimetric analysis within that temperature range, the amount of hydrated water can be calculated. 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 low-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.

[0044] In thermogravimetric analysis, the magnesium glycinate of this disclosure may have a weight loss rate of preferably 0% to 30% by weight, more preferably 5% to 25% by weight, and even more preferably 10% to 22% 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 combustion of hydrated water in the magnesium glycinate, the combustion of glycine present in the magnesium glycinate as an impurity, and the thermal decomposition of magnesium glycinate as a compound. It is thought that suppressing such weight loss can lead to a higher concentration of magnesium in the magnesium glycinate.

[0045] In thermogravimetric analysis, the magnesium glycinate of this disclosure preferably has a 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, that is 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 believed 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.

[0046] 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.

[0047] In differential scanning calorimetry, the above magnesium glycinate exhibits a value S1 / S2 obtained by dividing the area S1 of the endothermic peak with an onset temperature in the range of 125°C to 160°C by the area S2 of the endothermic peak with an onset temperature in the range of 330°C to 370°C, which is preferably between 0 and 1.8, more preferably between 0 and 1.5, and even more preferably between 0 and 1.1. The endothermic peak with an onset temperature in the range of 125°C to 160°C is thought to originate from the desorption of hydration water. The endothermic peak with an onset temperature in the range of 330°C to 370°C is thought to originate from the melting of magnesium glycinate. It is believed that having the above value S1 / S2 within this range reduces the amount of hydration water of magnesium glycinate, thereby increasing the magnesium concentration.

[0048] 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, in differential scanning calorimetry. The endothermic peak in the above range is thought to originate from the melting of magnesium glycinate.

[0049] The differential scanning calorimetry described above 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.

[0050] 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 2.8 g / L or more and 3.5 g / L or less.

[0051] The magnesium glycinate of this disclosure has a high magnesium concentration, and for example, at 25°C, 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.

[0052] The concentration of Mg in the saturated aqueous solution of magnesium glycinate at 25°C above can be measured, for example, by ion chromatography. Also, the magnesium content can be calculated, for example, from the results of thermogravimetric analysis. 2+ In a preferred embodiment, the magnesium glycinate of the present disclosure preferably contains first crystal grains having the first peak and the second peak in the XRD spectrum. The first crystal grains preferably further have one or more selected from the third peak and the fourth peak in the XRD spectrum, and more preferably further have one or more selected from the fifth to eighth peaks.

[0053] Here, the content rate of the crystal grains can be calculated using the following method. First, obtain the diffraction pattern intensities of pure type I crystals and pure type II crystals, and calculate their linear combination I

[0054] for all 2θ of 5° < 2θ < 30° by the following formula. c I I c (2θ) = a × (diffraction pattern intensity of type II crystals at 2θ) + b × (diffraction pattern intensity of type I crystals at 2θ) 0 ≤ a ≤ 1 0 ≤ b ≤ 1 a + b = 1 However, the initial values of a and b are both 0.5. Next, calculate the sum of the squares of the residuals J from the diffraction pattern intensity (I) of the sample for which the content rate of the first crystal grains is to be measured and the calculated pattern intensity I c by the following formula.

[0055]

Equation

[0056] θ0: 5° θ end : 30° Thirdly, taking a and b as variables, under the constraint conditions of a + b = 1, 0 < a < 1, and 0 < b < 1, calculate the combination of a and b that minimizes the value of J, and set the obtained value of a as the content ratio of the first crystal grains.

[0057] In the magnesium glycinate of the present disclosure, the content ratio of the first crystal grains is preferably 5% by weight or more and 100% by weight or less, more preferably 50% by weight or more and 100% by weight or less, still more preferably 80% by weight or more and 100% by weight or less, and particularly preferably 95% by weight or more and 100% by weight or less.

[0058] The magnesium glycinate of the present disclosure may contain, in addition to the first crystal grains, second crystal grains having a structure different from that of the first crystal grains. Examples of such second crystal grains include crystals having a maximum peak in the range where 2θ is 15° or more in the XRD spectrum. The content ratio of the second crystal grains is preferably 0% by weight or more and 30% by weight or less, more preferably 0% by weight or more and 10% by weight or less, still more preferably 0% by weight or more and 5% by weight or less, based on the total amount of the crystals of magnesium glycinate.

[0059] It is preferable that the intensity of the first peak or the second peak of the magnesium glycinate of the present disclosure is higher than the intensity of the maximum peak among the peaks existing in the range where 2θ is 15° or more.

[0060] The magnesium glycinate of the present disclosure may further contain magnesium hydroxide. The content ratio of magnesium hydroxide is preferably 0% by weight or more and 5% by weight or less, more preferably 0% by weight or more and 3% by weight or less, still more preferably 0% by weight or more and 1% by weight or less, based on the total amount of magnesium glycinate.

[0061] The content ratio of magnesium hydroxide in magnesium glycinate can be quantitatively analyzed by using the least squares method, the RIR (Reference Intensity Ratio) method, etc. in X-ray powder diffraction measurement.

[0062] 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 20 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 exhibits good stability and suppresses color change due to heat. [Method for measuring color difference] 1462 parts by mass of glucose and 500 parts by mass of magnesium glycinate are mixed and stored in a sealed container at 60°C for 72 hours. The L* value of the mixture after this storage is denoted as L1*, the a* value as a1*, and the b* value as b1*. The L*a*b* color system is used in a 10° field of view under a D65 light source, and the color difference (ΔE* value) relative to the reference point (L0*=100, a0*=0, b0*=0) is calculated using the following formula: [(L1*-L0*) 2 +(a1*-a0*) 2 +(b1*-b0*) 2 ] 1 / 2 It is calculated based on the following.

[0063] Glucose and glycine can produce coloring components through the Maillard reaction. The magnesium glycinate of this disclosure has a low content of glycine (especially glycine that exists independently without being bound to magnesium), and it is believed that glycine and magnesium are stably bonded in the magnesium glycinate crystal. Therefore, the Maillard reaction is suppressed, and it is believed to have good stability against heating.

[0064] For color differences ΔE*, L*, a*, and b*, values ​​normalized 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. These measurements are performed using a D65 light source in a 10° field of view.

[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 100 μm. In this disclosure, the average particle size refers to the volume-based median diameter (D50) and 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 75 N / cm. 2 More than 500N / cm 2 More preferably, 100 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. 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. Note that 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. Magnesium oxide is an example of such a magnesium compound. 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 disclosed herein is The first step involves mixing glycine and magnesium hydroxide in the presence of water to obtain a mixture. It can be produced by a manufacturing method comprising a second step of further mixing the above mixture with ethanol to obtain magnesium glycinate.

[0071] 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.

[0072] 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.

[0073] In other words, in the manufacturing method of this disclosure, glycine and magnesium hydroxide are first mixed in the presence of water, and then ethanol is further mixed in. Therefore, when glycine and magnesium chelate to form magnesium glycinate, the intermolecular interaction between water and magnesium glycinate is altered by the later addition of ethanol, preventing magnesium from using water molecules as ligands, and thus producing magnesium glycinate that does not contain hydrate water. As a result, magnesium glycinate with a higher magnesium concentration is obtained.

[0074] In the first step, glycine and magnesium hydroxide 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.

[0075] The mixing of water, glycine, and magnesium hydroxide is not limited; water and glycine may be mixed first, followed by further mixing of the mixture with magnesium hydroxide, or water and magnesium hydroxide may be mixed first, followed by further mixing of the mixture with glycine. Alternatively, water, glycine, and magnesium hydroxide may be mixed all at once.

[0076] In one embodiment, it is preferable to first mix water and glycine, and then further mix the mixture with magnesium hydroxide. In this embodiment, when the aqueous glycine solution reacts with magnesium, dissolved magnesium glycinate is produced, and when it precipitates as a solid, anhydrous magnesium glycinate is produced. When anhydrous magnesium glycinate is produced as a nucleus, it is thought that the crystal growth of anhydrous magnesium glycinate proceeds depending on the temperature conditions. Furthermore, in this embodiment, it is thought that chelation between glycine and magnesium is promoted, and magnesium glycinate with a reduced amount of glycine is more easily produced.

[0077] 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 magnesium hydroxide. By having the amount of glycine within the above range relative to the amount of magnesium hydroxide, the reaction efficiency is increased, and it is easy to further increase the magnesium concentration in the resulting magnesium glycinate.

[0078] 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 hydroxide. It is expected that the reaction efficiency will be increased by having the amount of water within the above range.

[0079] The mixing of the mixture in the first step can be carried out, for example, by stirring. A stirrer, mixer, or the like can be used as the stirring device.

[0080] The first step is preferably carried out at a temperature of 50°C or lower, more preferably between 10°C and 40°C, and even more preferably between 15°C and 35°C. It is expected that the reaction efficiency will be increased by carrying out the mixing of glycine and magnesium hydroxide at the above temperature.

[0081] The pH of the mixture in the first step is preferably 4 to 11, more preferably 5 to 9, and even more preferably 6 to 10.5. Having the pH of the mixture within this range is expected to increase reaction efficiency and yield magnesium glycinate with a high magnesium concentration.

[0082] The mixing time in the first 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.

[0083] In the second step, the above mixture is further mixed with ethanol to obtain magnesium glycinate. It is believed that mixing with ethanol makes it easier to obtain magnesium glycinate with a high magnesium concentration.

[0084] 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, per 100 parts by volume of water. It is believed that the magnesium concentration in the resulting magnesium glycinate can be increased by having the amount of ethanol within the above range. Note that the amount of ethanol refers to the amount of ethanol before mixing, relative to the amount of water before mixing.

[0085] In the second step, the mixing 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.

[0086] The resulting magnesium glycinate may be subjected to drying and / or grinding.

[0087] 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.

[0088] The above drying can be carried out using a hot air dryer, microwave dryer, rotary dryer, or the like.

[0089] 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, even more preferably 30 μm to 250 μm, and particularly preferably 30 μm to 100 μm.

[0090] 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.

[0091] 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.

[0092] (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 include the magnesium glycinate of this disclosure.

[0093] In a preferred embodiment, the magnesium glycinate tablets of the present disclosure have a tensile strength of 75 N / cm² 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 have a tensile strength of 75 N / cm when compressed using a flat, non-rounded punch at a compression pressure of 5 kN per tablet. 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.

[0094] 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.

[0095] 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.

[0096] The magnesium glycinate content in the magnesium glycinate tablets of 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.

[0097] 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.

[0098] When magnesium glycinate tablets are compressed using a flat (non-rounded) pestle at a compression pressure of 5kN per tablet, the tensile strength of the tablets is preferably 75N / cm. 2 More than 500N / cm 2 More preferably, 100 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.

[0099] 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.

[0100] The size of 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.

[0101] 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. Furthermore, 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.

[0102] 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.

[0103] 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 2kN to 20kN, more preferably 3kN to 18kN, and even more preferably 4kN to 16kN. 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.

[0104] (Fourth embodiment: Pharmaceuticals or food and beverages) The magnesium glycinate of this disclosure has a high magnesium concentration and can be suitably used in a variety of applications. Such applications include food and beverages and pharmaceuticals, and this disclosure also includes food and beverages and pharmaceuticals containing magnesium glycinate. Such food and beverages and pharmaceuticals can be manufactured using the magnesium glycinate of this disclosure.

[0105] 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.

[0106] 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.

[0107] 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.

[0108] Furthermore, "pharmaceuticals" can be administered to the target in any form, and may be administered orally or parenterally. Preferably, they can be administered orally.

[0109] Such medicines can be used to treat diseases such as magnesium deficiency, insomnia, and depression, as well as the various symptoms associated with them.

[0110] 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.

[0111] 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.

[0112] Foods, beverages, or pharmaceuticals containing magnesium glycinate as disclosed herein can be used by administering them to the subject.

[0113] 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. [Examples]

[0114] The present disclosure will be further illustrated by the following embodiments, but will not be limited thereto.

[0115] (Test Example 1) 19.7 g of glycine (special grade, manufactured by 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 at least 5 minutes (As One, VOLTEGA, Power Stirrer VPS-160SD). Next, 5.3 g of magnesium oxide (manufactured by 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 resulting 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.

[0116] (Test Example 2) Similar to Test Example 1, glycine and magnesium oxide were reacted, 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 the mixture was stirred in a water bath at room temperature (22-26°C) for 30 minutes. The stirred solution 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.

[0117] (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.

[0118] (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, followed by stirring for another 30 minutes in a room temperature (22-26°C) water bath. After that, the mixture was filtered, dried, and ground as in Test Example 1 to obtain 8.56 g of powder.

[0119] (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 at least 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, followed by stirring 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.

[0120] (Test Example 6) 19.7 g of glycine was added to 50 mL of 1 mol / L aqueous sodium hydroxide solution (Fujifilm Wako Pure Chemical Industries) and stirred in a 30°C water bath for at least 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 ground in the same manner as in Test Example 1 to obtain 9.1043 g of powder.

[0121] (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 at least 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 7 hours. After that, the solution was filtered, dried, and ground in the same manner as in Test Example 1 to obtain 3.8234 g of powder.

[0122] (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.

[0123] (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 magnesium oxide was changed from 5.3 g to 7.0 g of magnesium hydroxide, and 6.7366 g of dried pulverized material was obtained.

[0124] (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 performed sequentially to obtain 13.2883 g of white powder.

[0125] (Test examples 11-14) In each of the following tests, the sample used was glycine (special grade, manufactured by Fujifilm Wako Pure Chemical Industries) in Test Example 11, magnesium glycinate (manufactured by Actylis) in Test Example 12, magnesium hydroxide (manufactured by Kyowa Chemical Industry Co., Ltd.) in Test Example 13, and magnesium oxide (manufactured by Kyowa Chemical Industry Co., Ltd.) in Test Example 14.

[0126] The following measurements were performed on the powder obtained in the above test example.

[0127] (Powder X-ray diffraction measurement) Measurements were performed using an X-ray diffractometer, EMPYREAN (Malvern Panalytical). The sample was packed tightly into a circular sample holder manufactured by Malvern Panalytical using a sample preparation kit from Malvern Panalytical. The measurement conditions were as follows: X-ray source: CuKα (λ=1.5418Å) Acceleration voltage: 45kV Step: 2θ = 0.026° Scan speed: 0.656514° / s Divergence slit: 0.5000° Scattering slit: 8.0 mm Solar slit: 0.04rad HighScore Plus (Malvern Panalytical) was used to analyze the obtained XRD diffraction patterns. 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 then calculated using the following formula. D = Kλ / Bcosθ λ = 1.5418 Å K=0.9 B:FWHM θ: Phase of the peak top

[0128] As shown in Figures 1-6, the magnesium glycinate obtained in Test Example 1 (Figure 2), Test Example 3 (Figure 4(b)), Test Example 6 (Figure 4(d)), Test Example 8 (Figure 1), and Test Example 9 (Figure 5(b)) all had a first peak with its peak in the range of 2θ between 11.1° and 12.1°, and a second peak with its peak in the range of 2θ between 13.3° and 14.3°, confirming that they were the magnesium glycinate of this disclosure.

[0129] On the other hand, it was confirmed that Test Example 2 (Figure 4(a)), Test Example 4 (Figure 3), Test Example 5 (Figure 4(c)), Test Example 7 (Figure 5(a)), Test Example 10 (Figure 5(c)), and Test Example 12 (Figure 6(a)) all lacked a first peak with its peak in the range of 2θ between 11.1° and 12.1°, and a second peak with its peak in the range of 2θ between 13.3° and 14.3°. Note that Test Example 11 (Figure 5(d)) is glycine, Test Example 13 (Figure 6(b)) is magnesium hydroxide, and Test Example 14 (Figure 6(c)) is magnesium oxide, none of which contain magnesium glycinate.

[0130] (XRD measurement results: crystallite size) Crystallite sizes were calculated from the XRD diffraction patterns, and the results shown in Tables 1 and 2 were obtained. Comparing the crystallite sizes of the peaks corresponding to 16.7–17.0° with those corresponding to 11.3–11.9° or 13.3–13.9°, the crystallite sizes of the peaks corresponding to 11.3–11.9° or 13.3–13.9° were smaller. It is thought that crystals exhibiting peaks corresponding to 11.3–11.9° or 13.3–13.9° tend to form smaller crystals.

[0131] [Table 1]

[0132] [Table 2]

[0133] (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: Heats from 40°C to 600°C at a rate of 10°C / minute. Atmosphere gas: Nitrogen gas (70 mL / min) Baseline measurement: empty pan

[0134] (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: Heats up from 30°C to 600°C at a rate of 10°C / minute. Atmospheric gas: Nitrogen gas (50 mL / min) or air Control substance: Alumina (10-11 mg)

[0135] As shown in Figures 8, 10(a), 10(b), and 10(c), in Test Examples 4, 6, 9, and 12, which contained magnesium glycinate that did not exhibit the first and second peaks, weight loss was observed around 150°C and in the range of 350°C to 380°C. The weight loss 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.

[0136] As shown in Figure 7, in Test Example 8, which contained magnesium glycinate according to this disclosure, no significant weight change occurred from 50°C to around 350°C, and 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.

[0137] As shown in Figures 9 and 10(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 around 240°C to 280°C is thought to be due to the combustion of glycine contained in magnesium glycinate.

[0138] Furthermore, the results of thermogravimetric analysis for the samples in Test Examples 1, 2, 4, 6, 8, 9, and 10-12 are shown in Table 3. If the hydration water content falls below 0% by weight due to measurement errors or other factors, it is 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 using 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 using 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)

[0139] [Table 3]

[0140] The results of differential scanning calorimetry for test examples 4, 6, 8-10, and 12 are shown in Table 4 below. Peak area S1 (J / g) was calculated as the area of ​​peaks with an onset temperature in the range of 125°C to 160°C. Peak area S2 (J / g) was calculated as the area of ​​peaks with an onset temperature in the range of 330°C to 370°C.

[0141] [Table 4]

[0142] (Mass spectrometry) Measurements were performed using a mass spectrometer, micrOTOF (Bruker Corporation). The sample was dissolved in ultrapure water at 10 μg / mL and ionized using ESI Positive mode. The measurement was performed with the mass range set to 50-1000 m / z, the capillary voltage to 4500 V, and the nebulizer pressure to 0.4 Bar.

[0143] Mass spectrometry results showed that in both Test Example 8 (Figure 11(a)) and Test Example 4 (Figure 11(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.

[0144] (Solubility test) 1.5 g of the sample was weighed and added to 50 mL of deionized water, which was 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 sonication (ultrasonic cleaner MCD-10, As One) before being filtered 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.

[0145] Magnesium ions were measured using EcoIC (Metrohm) ion chromatography. 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 for concentration relative to peak area were calculated using a series of 100, 200, 400, and 800-fold dilutions. The concentration of each sample was calculated using the calibration curve 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 test solution in which each sample was dissolved. 2+ The concentration was calculated.

[0146] As a result, Mg in the test solution 2+ The concentrations were 3.00 g / L in the sample of Test Example 8, 2.17 g / L in the sample of Test Example 4, and 2.19 g / L in the sample of Test Example 12. From this, it can be said that the sample of Test Example 8 has a higher magnesium concentration compared to the samples of Test Example 4 and Test Example 12.

[0147] (Liquid NMR measurement) NMR device Avance III ( 1Measurements were performed using a H-resonance frequency (500 MHz) (Bruker Corporation). A 90°C pulse was applied for 14 μs. 1 H), 9.1μs( 13 In 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.

[0148] Glycine dissolved in heavy water (Test Example 11) 1 The 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.

[0149] (Moisture absorption test) The sample was placed in a constant temperature and humidity chamber (LH21-11M (Nagano Science)) and left to stand for 7 days. The test conditions were as follows: Temperature: 25℃ Humidity: 60% Sample weight: 0.9~1.1g Exam period: 7 days Weight measurement: 1 hour after the start, after 3, 4, 5, 6, 7 days

[0150] Compared to the average sample weight of 1.01g obtained in Test Example 4, weight increases of 0.0018g were detected after 1 hour, 0.0035g after 3 days, 0.0032g after 4 days, 0.0035g after 5 days, 0.0034g after 6 days, and 0.0034g after 7 days. Compared to the average sample weight of 1.01g obtained in Test Example 6, a weight increase of 0.0067g was detected after 1 hour, 0.14g after 3 days, 0.14g after 4 days, 0.015g after 5 days, 0.15g after 6 days, and 0.15g after 7 days. Compared to the average sample weight of 1.00g obtained in Test Example 8, a weight increase of 0.0092g was detected after 1 hour, 0.13g after 3 days, 0.13g after 4 days, 0.13g after 5 days, 0.13g after 6 days, and 0.13g after 7 days. On the other hand, observation of the appearance revealed that particle aggregation was observed in the sample of Test Example 4 after 3 days, whereas no change in appearance was observed in the samples of Test Example 6 and Test Example 8 until the 7th day.

[0151] (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: transparent Particle shape: non-spherical Particle refractive index: 1.57 Solvent: Ethanol (Fujifilm Wako Pure Chemical Industries) Solvent refractive index: 1.36

[0152] 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. Therefore, it is considered that the samples in Test Examples 4 and 8 are composed of aggregated smaller primary particles.

[0153] [Table 5]

[0154] (Evaluation of tablet strength) Magnesium glycinate from Test Examples 4, 8, and 12, along with crystalline cellulose (Asahi Kasei Corporation, Ceolus UF-F702), fine silicon dioxide (Fuji Silicia Corporation, Silope 720), and calcium stearate (Taihei Chemical Co., Ltd.), were combined so that the formulation per tablet matched the formulation shown in Table 6. Each ingredient was mixed to a total weight of 4.5g, and the tablets were compressed the following day.

[0155] The tablet compression test was conducted using a TYPE-M static compressor manufactured by Maekawa Testing Machinery Co., Ltd., equipped with a 10mm diameter round, flat punch and a corresponding die. 300mg of tablet material was filled into each die cavity and compressed. The compression pressure was set to 5 and 10kN, and each test was repeated three times.

[0156] [Table 6]

[0157] (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 this three times for each test. The obtained values ​​were converted to tensile strength using the following formula. Tensile strength [N / cm 2 ] = 2 × hardness [N] / (π × 0.1 cm × tablet thickness cm) Table 7 shows the results of evaluating the compressibility of magnesium glycinate with different crystal forms by manufacturing tablets and assessing their strength as tensile strength.

[0158] [Table 7]

[0159] When using magnesium glycinate in Test Example 8, a novel crystalline form, the tensile strength significantly improved with increasing tablet compression pressure, demonstrating superiority over conventional crystalline raw materials. Generally, the tensile strength is 100 N / cm². 2 It is believed that this new crystalline form can withstand distribution if it is strong enough, and it has been shown that it can be used as a raw material suitable for tablet manufacturing. On the other hand, the tablets manufactured using the conventional hydrated form of magnesium glycinate in Test Examples 4 and 12 had low strength and were unsuitable for tablet formation.

[0160] (Evaluation of Maillard reactivity) 1462 mg of glucose and 500 mg of magnesium glycinate were weighed, placed in glass bottles, and shaken after closing the lids. As a positive control, 1462 mg of glucose and 305 mg of glycine were weighed, placed in glass bottles, and shaken after closing the lids. As a negative control, glucose alone and glycine alone were similarly placed in glass bottles. All samples were stored in a 60°C drying oven for 3 days, and the color change was observed. Glucose (manufactured by Fujifilm Wako Pure Chemical Industries, special grade) and glycine (manufactured by Fujifilm Wako Pure Chemical Industries, special grade) were ground in a mortar and pestle before being used in the test. The molar ratio of 1462 mg of glucose to 500 mg of magnesium glycinate is considered to be 2:1. Similarly, the molar ratio of 1462 mg of glucose to 305 mg of glycine is also considered to be 2:1.

[0161] Subsequently, the samples were collected, and the degree of discoloration based on reflected light was analyzed using a colorimeter (ZE6000, manufactured by Nippon Denshoku Industries Co., Ltd.) with irradiation and reception conditions conforming to JIS Z-8722. The L*a*b* color system was adopted for a 10° field of view with a D65 light source, and the degree of discoloration was calculated and compared with a reference point (L0*=100, a0*=0, b0*=0) by calculating the color difference (ΔE* value). ΔE*=[(L1*-L0*) 2 +(a1*-a0*) 2 +(b1*-b0*) 2 ] 1 / 2

[0162] [Table 8]

[0163] After storage at 60°C for 3 days, the positive control underwent browning, confirming that the browning reaction test was successful. Test example 8 (anhydrous type) showed no discoloration, confirming its resistance to the Maillard reaction. Test example 12 (high glycine content) turned brown, while test examples 8 (anhydrous type) and 4 (hydrated type) remained white without discoloration, confirming their resistance to the Maillard reaction. Note that, due to the calculation of displacement with the theoretical white point as the origin, a white color may be observed even when ΔE* is approximately 18. [Industrial applicability]

[0164] 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 pharmaceuticals.

Claims

1. Magnesium glycinate having, in its powder X-ray diffraction spectrum, a first peak with its peak in the range of 2θ between 11.1° and 12.1°, and a second peak with its peak in the range of 2θ between 13.3° and 14.3°.

2. Intensity I of the second peak ２ The intensity of the first peak relative to １ Ratio I １ / I ２ However, the magnesium glycinate according to claim 1, wherein the value is 2 or more and 2.5 or less.

3. The magnesium glycinate according to claim 1, further comprising one or more peaks selected from a third peak having a peak in the range of 2θ between 19.5° and 20.5° in the powder X-ray diffraction spectrum, and a fourth peak having a peak in the range of 2θ between 37.5° and 38.5°.

4. The magnesium glycinate according to claim 1, further comprising one or more peaks selected from the following in the powder X-ray diffraction spectrum: a fifth peak having its peak in the range of 2θ between 17.4° and 18.4°; a sixth peak having its peak in the range of 2θ between 18.1° and 19.1°; a seventh peak having its peak in the range of 2θ between 22.9° and 23.9°; and an eighth peak having its peak in the range of 2θ between 28.6° and 29.6°.

5. Magnesium glycinate, in thermogravimetric analysis, exhibits a weight loss of 30% or less at 380°C compared to its weight at 50°C.

6. In differential thermal scanning calorimetry, the area S of an endothermic peak with an onset temperature in the range of 125°C to 160°C is defined as the area S of an endothermic peak. 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, the magnesium glycinate according to claim 1, wherein the value is 0 or more and 1.8 or less.

7. Magnesium glycinate according to claim 1, which does not contain water of hydration.

8. 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 were 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. The color difference (ΔE* value) with respect to the reference point (L ０ * = 100, a ０ * = 0, b ０ * = 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.

9. The tensile strength when tablets are compressed using a flat pestle at a compression pressure of 5 kN per tablet is 75 N / cm. ２ More than 500N / cm ２ The magnesium glycinate described in claim 1 is as follows:

10. A magnesium glycinate tablet comprising magnesium glycinate according to any one of claims 1 to 9.

11. A food or pharmaceutical product comprising magnesium glycinate as described in any one of claims 1 to 9.

12. A method for producing food or pharmaceuticals using magnesium glycinate according to any one of claims 1 to 9.

13. The first step involves mixing glycine and magnesium hydroxide in the presence of water to obtain a mixture. A method for producing magnesium glycinate, comprising a second step of further mixing the aforementioned mixture with ethanol to obtain magnesium glycinate.

14. The method for producing magnesium glycinate according to claim 13, wherein the first step is carried out at a temperature of 50°C or lower.

Images