Tagatose crystal form and preparation process thereof

Abstract

The invention relates to the technical field of tagatose, in particular to a tagatose crystal form and a preparation process thereof, the tagatose crystal form has characteristic diffraction peaks when the diffraction angles 2 theta are 9.94 + / -0.02, 14.43 + / -0.02, 15.04 + / -0.02, 17.36 + / -0.02, 19.69 + / -0.02, 19.98 + / -0.02, 20.28 + / -0.02, 22.09 + / -0.02, 24.59 + / -0.02, 24.79 + / -0.02, 28.18 + / -0.02, 29.11 + / -0.02, 30.17 + / -0.02, 30.88 + / -0.02, 31.30 + / -0.02, 32.07 + / -0.02, 32.53 + / -0.02, 33.38 + / -0.02, 34.49

Description

Technical Field

[0001] The present invention relates to the technical field of tagatose, in particular to a tagatose crystal form and a preparation process thereof. Background Art

[0002] D-Tagatose is a six-carbon ketose, a rare sugar, a rare natural ketohexose, a D-galactose aldehyde ketone isomer, and a diastereomer of D-fructose at the C-4 position. The sweetness of D-Tagatose is similar to that of sucrose, about 92% of the sweetness of sucrose, but its energy is much lower than sucrose, about one-third of sucrose. At present, tagatose is mainly synthesized by chemical synthesis and biological transformation. The synthesized D-tagatose products are mainly powdered solids, which inevitably cause agglomeration. For example, a Chinese patent application (publication number CN118994271A) discloses a process for preparing D-tagatose crystals. Specifically, under the assistance of ultrasound, a seed solution is added to a saturated D-tagatose solution containing an antioxidant, and then the crystals are grown at 50-60°C. In the process of controlling the crystal growth, evaporation and concentration are carried out while adding materials, and then hydroxypropyl methylcellulose is added for cooling and crystallization, so as to prepare 20-40 mesh crystals with a mass fraction of more than 80%. However, the overall process requirements of the method are relatively high, and it is difficult to achieve large-scale industrial production. Summary of the invention

[0003] In order to solve the above problems, the present invention provides a preparation process of tagatose crystal form, which is simple to operate, avoids crystal sticking, ensures the photosensitivity quality and morphology of the product, has high added value, and is easy to promote and apply.

[0004] On one hand, the present invention provides a process for preparing a tagatose crystal form, the steps of which are as follows: adding a tagatose sample into a container, adding a methanol aqueous solution, shaking and dissolving to obtain a sample solution, sealing the container mouth and reserving a volatilization hole, and standing at a constant temperature and humidity to obtain a tagatose crystal form.

[0005] As a preferred technical solution, the method for preparing the methanol aqueous solution is to mix 100-120 parts by weight of methanol with 1 part by weight of water to obtain the methanol aqueous solution.

[0006] As a preferred technical solution, the concentration of the sample solution is (2-8) mg / mL, preferably (3-5) mg / mL.

[0007] As a preferred technical solution, the diameter of the volatile pores is 1-2 mm, and the density is 1-4 / cm 2 .

[0008] Preferably, the diameter of the volatile pores is 1 mm and the density is 2 pores / cm 2 .

[0009] As a preferred technical solution, the constant temperature and humidity conditions are: temperature is 20-25°C, and humidity is 15-25%.

[0010] Preferably, the constant temperature and humidity conditions are: temperature is 25° C., and humidity is 20%.

[0011] As a preferred technical solution, the standing time is 4-6 days, preferably 5 days.

[0012] The preparation process of the tagatose crystal form provided by the present invention does not require the additional introduction of crystal seeds, antioxidants, carboxymethyl cellulose and other auxiliary agents, and can obtain single crystals with large particles and regular shapes, avoid subsequent agglomeration problems, improve fluidity, and better meet practical application needs. In the early stage of the present invention, single solvents such as methanol, ethyl, acetone, acetonitrile, ethanol, and water were used to prepare tagatose crystal forms. In the later stage, methanol and chloroform were adjusted to compound, but crystals could not be obtained. During the exploration process, it was unexpectedly discovered that after methanol and water were mixed in proportion, the volatile port design was combined, and high-quality tagatose crystal forms were successfully obtained later. Furthermore, the amount of solvent added and the constant temperature and humidity conditions were controlled, and complex crystallization conditions were not required, and the crystallization process was stable and easy to control.

[0013] On the other hand, the present invention provides a tagatose crystal form, wherein the tagatose crystal form is analyzed by X-ray powder diffraction using Cu-Kα rays, and the diffraction angles 2θ are 9.94±0.02, 14.43±0.02, 15.04±0.02, 17.36±0.02, 19.69±0.02, 19.98±0.02, 20.28±0.02, 22.09±0.0 2. There are characteristic diffraction peaks at 24.59±0.02, 24.79±0.02, 28.18±0.02, 29.11±0.02, 30.17±0.02, 30.88±0.02, 31.30±0.02, 32.07±0.02, 32.53±0.02, 33.38±0.02, 34.49±0.02, and 37.83±0.02.

[0014] The X-ray powder diffraction pattern of the tagatose crystal form provided by the present invention can be found in Figure 1 .

[0015] Furthermore, the crystallographic parameters of the tagatose crystal form are shown in Table 1.

[0016] Table 1

[0017] Furthermore, the melting point of the tagatose crystal form is 146.24°C.

[0018] Furthermore, the thermal weight loss temperature of the tagatose crystal form is 296.15°C.

[0019] Furthermore, the infrared spectrum of the tagatose crystal form is at 3425 cm -1 (hydroxyl), 2919 cm -1 (saturated hydrocarbons), 1727 cm -1 、1637 cm -1 (carbon-oxygen bond), 1077 cm -1 、1035 cm -1 There are characteristic peaks at (methylene, methine).

[0020] Furthermore, the tagatose crystal form 1 In the H-NMR spectrum, 4.00-3.00 ppm is the chemical shift of H protons of tagatose.

[0021] Furthermore, the tagatose crystal form 13 In the C-NMR spectrum, 98.2 ppm, 70.9 ppm, 69.8 ppm, 66.3 ppm, 63.9 ppm, and 62.2 ppm are chemical shifts of C protons of tagatose.

[0022] The tagatose crystal form provided by the present invention has a relatively high melting point and thermal weight loss temperature, can be widely used in the fields of food, medicine, cosmetics, etc., and has a high market promotion value.

[0023] Beneficial Effects 1. The present invention provides a preparation process of tagatose crystals, which is simple to operate, avoids crystal sticking, ensures the photosensitivity quality and morphology of the product, has high added value, and is easy to promote and apply.

[0024] 2. The preparation process of tagatose crystal form provided by the present invention does not require the introduction of additional additives such as seed crystals, antioxidants, and carboxymethyl cellulose, and can obtain single crystals with large particles and regular shapes, thereby avoiding subsequent agglomeration problems, improving fluidity, and better meeting practical application requirements.

[0025] 3. In the early stage of the present invention, single solvents such as methanol, ethyl, acetone, acetonitrile, ethanol and water were used, but tagatose crystals could not be prepared. In the later stage, methanol and chloroform were adjusted to form a compound, but crystals could not be obtained. During the exploration process, it was unexpectedly discovered that after methanol and water were mixed in proportion and the evaporation port was designed, high-quality tagatose crystals were successfully obtained.

[0026] 4. The present invention cooperates with controlling the amount of added solvent and constant temperature and humidity conditions, does not require complicated crystallization conditions, and the crystallization process is stable and easy to control.

[0027] 5. The tagatose crystal form provided by the present invention has a relatively high melting point and thermal weight loss temperature, can be widely used in the fields of food, medicine, cosmetics, etc., and has a high market promotion value. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is the X-ray powder diffraction pattern of the tagatose crystal form provided in Example 1 of the present invention.

[0029] Figure 2 This is a DSC test spectrum of the tagatose crystal form provided in Example 1 of the present invention.

[0030] Figure 3 This is a TGA curve diagram of the tagatose crystal form provided in Example 1 of the present invention.

[0031] Figure 4 This is the FTIR spectrum of the tagatose crystal form provided in Example 1 of the present invention.

[0032] Figure 5 The tagatose crystal form provided in Example 1 of the present invention 1 H-NMR spectrum.

[0033] Figure 6 The tagatose crystal form provided in Example 1 of the present invention 13 C-NMR spectrum. DETAILED DESCRIPTION

[0034] Example 1 Example 1 of the present invention provides a preparation process of tagatose crystal form, the steps of which are as follows: 4 mg of tagatose sample is added to a container, 1 mL of methanol aqueous solution is added, and the sample solution is obtained by shaking and dissolving, the container mouth is sealed and a volatilization hole is reserved, and the tagatose crystal form is obtained after standing at a constant temperature and humidity.

[0035] The preparation method of the methanol aqueous solution is as follows: 100 parts by weight of methanol and 1 part by weight of water are mixed to obtain the methanol aqueous solution.

[0036] The concentration of the sample solution is 4 mg / mL.

[0037] The diameter of the volatile pores is 1 mm, and the density is 2 / cm 2 .

[0038] The constant temperature and humidity conditions are: temperature is 25° C., and humidity is 20%.

[0039] The standing time is 5 days.

[0040] On the other hand, Example 1 of the present invention provides a tagatose crystal form, wherein the tagatose crystal form is analyzed by X-ray powder diffraction using Cu-Kα rays, and the diffraction angles 2θ are 9.94±0.02, 14.43±0.02, 15.04±0.02, 17.36±0.02, 19.69±0.02, 19.98±0.02, 20.28±0.02, 22.09±0 There are characteristic diffraction peaks at .02, 24.59±0.02, 24.79±0.02, 28.18±0.02, 29.11±0.02, 30.17±0.02, 30.88±0.02, 31.30±0.02, 32.07±0.02, 32.53±0.02, 33.38±0.02, 34.49±0.02, and 37.83±0.02.

[0041] The X-ray powder diffraction pattern of the tagatose crystal form can be found in Figure 1 .

[0042] The crystallographic parameters of the tagatose crystal form are shown in Table 1.

[0043] The X-ray powder diffraction analysis was performed using a Bruker D8advance diffractometer from Bruker Instruments GmbH, Germany, using a Cu-K ray voltage of 40 kV, a current of 40 mA, a step size of 0.02 degrees, and each step taking 0.1 seconds.

[0044] The DSC 8500 differential calorimeter of PerkinElmer, USA, was used for detection, the atmosphere was nitrogen, the heating rate was 10 degrees Celsius / minute, and the melting point of the tagatose crystal form was 146.24°C, see the DSC test spectrum ( Figure 2 ).

[0045] Thermogravimetric analyzer TG20F3 of NETZSCH Scientific Instruments Co., Ltd. of Germany was used, the atmosphere was nitrogen, and the heating rate was 10 degrees / minute. The thermal weight loss temperature of the tagatose crystal form was 296.15°C, see the TGA curve ( Figure 3 ).

[0046] Nicolet-Magna FT-IR 750 infrared spectrometer from Nicolet Corporation of the United States was used for detection at 25±2℃, with a detection range of 4000-350cm -1 Wave number, the infrared spectrum of the tagatose crystal form is at 3425 cm -1 (hydroxyl), 2919 cm -1 (saturated hydrocarbons), 1727, 1637 cm -1 (carbon-oxygen bond), 1077, 1035 cm -1 (methylene, methine) have characteristic peaks, see FTIR spectrum ( Figure 4 ).

[0047] Bruker AVANCE III HD 400M NMR was used for detection (H spectrum pulse sequence: zg30, TD (data point): 65K, RG (gain): 32, D1 (relaxation time): 10s, SW (spectrum width): 20ppm, O1p (spectrum width center): 6.175ppm, NS (scan number): 16, DS (dry scan number): 2); The tagatose crystal form 1 H-NMR spectrum ( Figure 5 ), 4.00-3.00 ppm is the chemical shift of H protons of tagatose.

[0048] The tagatose crystal form 13 C-NMR spectrum ( Figure 6 ), 98.2 ppm, 70.9 ppm, 69.8 ppm, 66.3 ppm, 63.9 ppm, and 62.2 ppm are the chemical shifts of the C proton of tagatose.

[0049] Example 2 Example 2 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol aqueous solution is replaced by methanol, and no crystals are generated after standing for 5 days.

[0050] Example 3 Example 3 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol aqueous solution is replaced by ethyl acetate, and no crystals are generated after standing for 5 days.

[0051] Example 4 Example 4 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol aqueous solution is replaced by acetone, and no crystals are generated after standing for 5 days.

[0052] Example 5 Example 5 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol aqueous solution is replaced by acetonitrile, and no crystals are generated after standing for 5 days.

[0053] Example 6 Example 6 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol aqueous solution is replaced by ethanol, and no crystals are generated after standing for 5 days.

[0054] Example 7 Example 7 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol aqueous solution is replaced by water, and no crystals are generated after standing for 5 days.

[0055] Example 8 Example 8 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol aqueous solution is replaced by a combination of methanol and chloroform in a mass ratio of 199:1, and no crystals are generated after standing for 5 days.

[0056] Example 9 Example 9 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol aqueous solution is replaced by a combination of methanol and chloroform in a mass ratio of 99:1, and no crystals are generated after standing for 5 days.

[0057] Example 10 Example 10 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol aqueous solution is replaced by a combination of methanol and chloroform in a mass ratio of 49:1, and no crystals are generated after standing for 5 days.

[0058] Embodiment 11 Example 11 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol aqueous solution is replaced by a combination of methanol and chloroform in a mass ratio of 19:1, and no crystals are generated after standing for 5 days.

[0059] Example 12 Example 12 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol aqueous solution is replaced by a combination of methanol and chloroform in a mass ratio of 4:1, and no crystals are generated after standing for 5 days.

[0060] Embodiment 13 Example 13 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol aqueous solution is replaced by a combination of methanol and chloroform in a mass ratio of 2:1, and no crystals are generated after standing for 5 days.

[0061] Embodiment 14 Example 14 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol aqueous solution is replaced by a combination of methanol and chloroform in a mass ratio of 1:1, and no crystals are generated after standing for 5 days.

[0062] Embodiment 15 Example 15 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol aqueous solution is replaced by a combination of methanol and chloroform in a mass ratio of 1:2, and no crystals are generated after standing for 5 days.

[0063] Example 16 Example 16 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol aqueous solution is replaced by a combination of methanol and chloroform in a mass ratio of 1:4, and no crystals are generated after standing for 5 days.

[0064] Embodiment 17 Example 17 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol aqueous solution is replaced by a combination of methanol and chloroform in a mass ratio of 1:9, and no crystals are generated after standing for 5 days.

[0065] Embodiment 18 Example 18 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol-water solution is replaced by a combination of methanol and water in a mass ratio of 199:1, and no crystals are generated after standing for 5 days.

[0066] Embodiment 19 Example 19 of the present invention provides a tagatose crystal form and a preparation process thereof, and its specific implementation method is the same as that of Example 1, except that the methanol-water solution is replaced by a combination of methanol and water in a mass ratio of 99:1, and no crystals are generated after standing for 5 days.

[0067] Embodiment 20 Example 20 of the present invention provides a tagatose crystal form and a preparation process thereof. The specific implementation method is the same as that of Example 1, except that the methanol-water solution is replaced by a combination of methanol and water in a mass ratio of 49:1, and no crystals are generated after standing for 5 days.

[0068] Embodiment 21 Example 21 of the present invention provides a tagatose crystal form and a preparation process thereof. Its specific implementation method is the same as that of Example 1, except that the methanol-water solution is replaced by a combination of methanol and water in a mass ratio of 19:1, and no crystals are generated after standing for 5 days.

[0069] Embodiment 22 Example 22 of the present invention provides a tagatose crystal form and a preparation process thereof. Its specific implementation method is the same as that of Example 1, except that the methanol-water solution is replaced by a combination of methanol and water in a mass ratio of 4:1, and no crystals are generated after standing for 5 days.

[0070] Embodiment 23 Example 23 of the present invention provides a tagatose crystal form and a preparation process thereof. Its specific implementation method is the same as that of Example 1, except that the methanol-water solution is replaced by a combination of methanol and water in a mass ratio of 2:1, and no crystals are generated after standing for 5 days.

[0071] Embodiment 24 Example 24 of the present invention provides a tagatose crystal form and a preparation process thereof. Its specific implementation method is the same as that of Example 1, except that the methanol-water solution is replaced by a combination of methanol and water in a mass ratio of 1:1, and no crystals are generated after standing for 5 days.

[0072] Embodiment 25 Example 25 of the present invention provides a tagatose crystal form and a preparation process thereof. Its specific implementation method is the same as that of Example 1, except that the methanol-water solution is replaced by a combination of methanol and water in a mass ratio of 1:2, and no crystals are generated after standing for 5 days.

Claims

1. A tagatose crystal form, characterized in that: The tagatose crystal form was analyzed by X-ray powder diffraction using Cu-Kα rays, and the diffraction angles 2θ were 9.94±0.02, 14.43±0.02, 15.04±0.02, 17.36±0.02, 19.69±0.02, 19.98±0.02, 20.28±0.02, 22.09±0.02, 24.59±0.

02. There are characteristic diffraction peaks at .02, 24.79±0.02, 28.18±0.02, 29.11±0.02, 30.17±0.02, 30.88±0.02, 31.30±0.02, 32.07±0.02, 32.53±0.02, 33.38±0.02, 34.49±0.02, and 37.83±0.

02.

2. The tagatose crystal form according to claim 1, characterized in that: The melting point of the tagatose crystal form is 146.24°C.

3. The tagatose crystal form according to claim 1, characterized in that: The thermal weight loss temperature of the tagatose crystal form is 296.15°C.

4. The tagatose crystal form according to claim 1, characterized in that: The infrared spectrum of the tagatose crystal form is at 3425 cm -1 , 2919 cm -1 、1727 cm -1 、1637 cm -1 , 1077 cm -1 、1035 cm -1 There are characteristic peaks.

5. The tagatose crystal form according to claim 1, characterized in that: The tagatose crystal form 1 In the H-NMR spectrum, 4.00-3.00 ppm is the chemical shift of the H proton of tagatose; The tagatose crystal form 13 In the C-NMR spectrum, 98.2 ppm, 70.9 ppm, 69.8 ppm, 66.3 ppm, 63.9 ppm, and 62.2 ppm are chemical shifts of C protons of tagatose.

6. A process for preparing the tagatose crystal form according to any one of claims 1 to 5, characterized in that: The steps are as follows: adding a tagatose sample into a container, adding a methanol aqueous solution, shaking and dissolving to obtain a sample solution, sealing the container mouth and reserving a volatilization hole, and standing at a constant temperature and humidity to obtain a tagatose crystal form; the preparation method of the methanol aqueous solution is to mix 100-120 parts by weight of methanol with 1 part by weight of water to obtain the methanol aqueous solution.

7. The process for preparing tagatose crystal form according to claim 6, characterized in that: The concentration of the sample solution is (2-8) mg / mL.

8. The process for preparing tagatose crystal form according to claim 6, characterized in that: The diameter of the volatile pores is 1-2 mm, and the density is 1-4 pores / cm 2 .

9. The process for preparing tagatose crystal form according to claim 6, characterized in that: The constant temperature and humidity conditions are: temperature of 20-25° C., humidity of 15-25%.

10. The process for preparing tagatose crystal form according to claim 6, characterized in that: The standing time is 4-6 days.

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