Chiral inositol crystalline forms and methods for their preparation

Abstract

The present application relates to the technical field of chiral inositol, in particular to a chiral inositol crystal form and a preparation method thereof, wherein the chiral inositol crystal form has characteristic diffraction peaks at diffraction angles 2theta of 13.44±0.02°, 14.85±0.02°, 16.58±0.02°, 17.75±0.02°, 19.43±0.02°, 22.79±0.02°, 23.70±0.02°, 24.79±0.02°, 25.90±0.02°, 27.05±0.02°, 28.66±0.02°, 30.11±0.02°, 30.77±0.02°, 34.66±0.02°, 37.776±0.02°, 39.46±0.02°, 40.73±0.02°, 44.78±0.02° and 46.52±0.02°, as measured by X-ray powder diffraction analysis using Cu-Kα rays, and has high thermal stability and is more widely applicable.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of chiro-inositol, in particular to a chiro-inositol crystal form and a preparation method thereof. BACKGROUND

[0002] Chiro-inositol is a class of inositol stereoisomers with important biological activity, mainly including D-chiro-inositol (DCI) and L-chiro-inositol (LCI), which play a key role in metabolic regulation. At present, there are many methods for preparing and crystallizing DCI. For example, Chinese patent application (publication number CN117164434A) discloses a crystallization method of D-chiro-inositol, which adopts cation exchange resin and anion exchange resin for desalting treatment, followed by concentration and decolorization through macroporous decolorizing resin and nanofiltration membrane, combined with stepwise cooling and stirring speed control, and finally high-purity D-chiro-inositol is obtained through ethanol washing and vacuum drying. The crystallization method is complex and not easy to promote in large-scale industrialization, and the stability of the existing DCI needs to be further improved, while LCI has the risk of crystal transformation. Therefore, it is of great practical significance to develop a new crystal form of chiro-inositol with better stability. SUMMARY

[0003] In order to solve the above problems, the present application provides a chiro-inositol crystal form, which provides a new crystal form of chiro-inositol with better stability by optimizing the crystallization process conditions, and contains both DCI and LCI, with a thermal decomposition temperature of 395.81°C, overcoming the problem of low thermal decomposition temperature of single DCI / LCI, and having relatively higher thermal stability, suitable for more extensive application fields.

[0004] In one aspect, the present application provides a chiro-inositol crystal form, which has characteristic diffraction peaks at diffraction angles 2θ of 13.44±0.02°, 14.85±0.02°, 16.58±0.02°, 17.75±0.02°, 19.43±0.02°, 22.79±0.02°, 23.70±0.02°, 24.79±0.02°, 25.90±0.02°, 27.05±0.02°, 28.66±0.02°, 30.11±0.02°, 30.77±0.02°, 34.66±0.02°, 37.776±0.02°, 39.46±0.02°, 40.73±0.02°, 44.78±0.02° and 46.52±0.02°, as measured by X-ray powder diffraction analysis using Cu-Kα rays.

[0005] Further, the chiro-inositol crystal form provided by the present application has characteristic diffraction peaks at diffraction angles 2θ of 13.44±0.02°, 14.85±0.02°, 16.58±0.02°, 17.75±0.02°, 19.43±0.02°, 22.79±0.02°, 23.70±0.02°, 24.79±0.02°, 25.90±0.02°, 27.05±0.02°, 28.66±0.02°, 30.11±0.02°, 30.77±0.02°, 34.66±0.02°, 37.776±0.02°, 39.46±0.02°, 40.73±0.02°, 44.78±0.02° and 46.52±0.02°, as measured by X-ray powder diffraction analysis using Cu-Kα rays. Figure 1The X-ray powder diffraction (XRD) pattern shown.

[0006] Further, the chiral inositol crystal form provided by the present application has the crystallographic parameters as shown in Table 1. Figure 2 The X-ray test result pattern shown.

[0007] Further, the crystallographic parameters of the chiral inositol crystal form are shown in Table 1.

[0008] Table 1

[0009]

[0010] Further, the chiral inositol crystal form has the thermal gravimetric analysis pattern as shown in Figure 3 which loses 95.90% of weight at 250-450℃ and starts to decompose at 395.81℃.

[0011] Further, the chiral inositol crystal form has the differential scanning calorimetry pattern as shown in Figure 4 which has no characteristic endothermic peak in the range of 0-140℃.

[0012] Further, the chiral inositol crystal form has the infrared spectrogram as shown in Figure 5 which has characteristic peaks at 3417 cm-1, 3358 cm-1 (hydroxyl), 2967 cm-1, 2924 cm-1 (saturated carbon hydrogen), and 1420-1000 cm-1 (methylidene). -1 -1 -1 -1 -1

[0013] Further, the chiral inositol crystal form has the H-NMR spectrogram as shown in Figure 6 1 which has the chemical shifts of H protons of chiral inositol at 3.90 ppm, 3.63 ppm and 3.45 ppm.

[0014] Further, the chiral inositol crystal form has the C-NMR spectrogram as shown in Figure 7 13 which has the chemical shifts of C protons of chiral inositol at 72.7 ppm, 71.6 ppm and 70.4 ppm.

[0015] Another aspect of the present application provides a preparation method of the chiral inositol crystal form, which comprises at least the following steps: mixing a chiral inositol sample with an acetonitrile aqueous solution and then standing to obtain the chiral inositol crystal form.

[0016] In one embodiment, the volume ratio of acetonitrile to water in the acetonitrile aqueous solution is (3.5-4.5):1.

[0017] ​​​​​​​In an embodiment, the temperature for the standing is 20-30℃, and the time is 5-10 days.

[0018] In an embodiment, the ratio of the mass of the chiral inositol sample to the volume of the acetonitrile aqueous solution is (3-5 mg): 1 mL.

[0019] In an embodiment, the method for preparing the chiral inositol crystal form comprises the following steps: adding a chiral inositol sample and an acetonitrile aqueous solution into a reagent bottle, and shaking to dissolve; sealing the reagent bottle with a sealing film, and punching a hole on the film as a solvent evaporation port; and standing to obtain a chiral inositol crystal form.

[0020] In an embodiment, the density of the punched holes is 1-2 / cm 2 .

[0021] In an embodiment, the chiral inositol sample contains D-chiral inositol and L-chiral inositol, and the chiral inositol sample is from Shandong Zhucheng Haotian Pharmaceutical Co., Ltd.

[0022] Different crystal forms can result in differences in color, morphology, stability, hygroscopicity, and solubility, which in turn affect the subsequent application effect. The thermal decomposition temperatures of existing D-chiral inositol and L-chiral inositol are generally low, and cannot meet the application requirements of high-temperature processing scenarios. The present application specifically provides a new crystal form containing the chiral isomers shown above, which has crystallographic parameters that are obviously distinguished from D-chiral inositol and L-chiral inositol, and has a relatively higher thermal decomposition temperature, and can meet the application requirements of high-temperature processing scenarios. Figure 2

[0023] The chiral inositol crystal form provided by the present application effectively overcomes the problems of stability compensation of single DCI and high hygroscopicity of single LCI, increases the flexibility of dosage form design, and has excellent biological necessity, clinical superiority, and development economy (reduces the dosage requirement).

[0024] ​However, in the process of developing new crystal forms, due to the difference in water solubility and hygroscopicity between D-chiro-inositol and L-chiro-inositol, and the fact that D-chiro-inositol is prone to form solvates (such as hydrates, acetone compounds), the inventors tried various methods but failed to obtain a new crystal form containing D-chiro-inositol and L-chiro-inositol. In further research, the inventors accidentally discovered that by using an acetonitrile aqueous solution to dissolve a chiro-inositol sample containing D-chiro-inositol and L-chiro-inositol, especially by controlling the volume ratio of acetonitrile to water in the acetonitrile aqueous solution to be (3.5-4.5):1, and by standing at 20-30°C for 5 days, a chiro-inositol crystal form with excellent thermal stability can be obtained, avoiding the formation of solvates. However, using other solvents or acetonitrile aqueous solutions with a volume ratio of acetonitrile to water outside the above range cannot obtain a new crystal form by simple solution evaporation.

[0025] The preparation method of the chiro-inositol crystal form provided by the present application has the advantages of simple standing process, excellent product performance, simple operation, and greatly reduced production cost compared with traditional chemical synthesis methods (such as recrystallization).

[0026] Advantages

[0027] 1. The present application provides a chiro-inositol crystal form, which is more stable by optimizing the crystallization process conditions, and contains DCI and LCI. The thermal decomposition temperature is 395.81°C, overcoming the problem of low thermal decomposition temperature of single DCI / LCI, and having relatively higher thermal stability, suitable for more widely application fields.

[0028] 2. The present application specifically provides a new crystal form containing the chiral isomers shown in the formula. Figure 2 The new crystal form has crystallographic parameters that are significantly different from D-chiro-inositol and L-chiro-inositol, and has a relatively higher thermal decomposition temperature, which can meet the application requirements of high-temperature processing scenes.

[0029] 3. The chiro-inositol crystal form provided by the present application effectively overcomes the stability of single DCI and the problem of high hygroscopicity of single LCI, increases the flexibility of dosage form design, and has excellent biological necessity, clinical superiority and development economy (reduces the dosage requirement).

[0030] 4. The present application uses an acetonitrile aqueous solution to dissolve a chiro-inositol sample containing D-chiro-inositol and L-chiro-inositol, especially by controlling the volume ratio of acetonitrile to water in the acetonitrile aqueous solution to be (3.5-4.5):1, and by standing at 20-30°C for 5 days, a chiro-inositol crystal form with excellent thermal stability can be obtained, avoiding the formation of solvates.

[0031] 5、Compared with the traditional chemical synthesis method (such as recrystallization), the excellent performance product is obtained based on the simple standing process through the optimization of solvent selection, and the complex instrument device is not needed, the operation is simple, and the production cost is greatly reduced. BRIEF DESCRIPTION OF DRAWINGS

[0032] Figure 1 XRD pattern of the chiral inositol crystal form provided for the embodiment 1 of the present application.

[0033] Figure 2 X-ray test result pattern of the chiral inositol crystal form provided for the embodiment 1 of the present application.

[0034] Figure 3 Thermogravimetric analysis pattern of the chiral inositol crystal form provided for the embodiment 1 of the present application.

[0035] Figure 4 Differential scanning calorimetry pattern of the chiral inositol crystal form provided for the embodiment 1 of the present application.

[0036] Figure 5 Infrared spectroscopy pattern of the chiral inositol crystal form provided for the embodiment 1 of the present application.

[0037] Figure 6 H-NMR spectrum of the chiral inositol crystal form provided for the embodiment 1 of the present application. 1

[0038] Figure 7 C-NMR spectrum of the chiral inositol crystal form provided for the embodiment 1 of the present application. 13

[0039] Figure 8 The sample real object pattern of the chiral inositol adopted in the embodiment 1 of the present application. DETAILED DESCRIPTION

[0040] Embodiment 1

[0041] ​​Embodiment 1 of the present invention provides a chiral inositol crystal form, wherein the chiral inositol crystal form is analyzed by X-ray powder diffraction using Cu-Kα rays, and the diffraction angle 2θ is 13.44±0.02°, 14.85±0.02°, 16.58±0.02°, 17.75±0.02°, 19.43±0.02°, 22.79±0.02°, 23.70±0.02°, and 24. Characteristic diffraction peaks are observed at 79±0.02°, 25.90±0.02°, 27.05±0.02°, 28.66±0.02°, 30.11±0.02°, 30.77±0.02°, 34.66±0.02°, 37.776±0.02°, 39.46±0.02°, 40.73±0.02°, 44.78±0.02°, and 46.52±0.02°.

[0042] The X-ray powder diffraction analysis was performed using a Bruker D8advance diffractometer from Bruker Instruments GmbH, Germany. The Cu-K radiation voltage was 40 kV, the current was 40 mA, the step size was 0.02 degrees, and the time per step was 0.1 seconds.

[0043] The chiral inositol crystal form has the following characteristics: Figure 1 The X-ray powder diffraction (XRD) pattern shown.

[0044] The chiral inositol crystal form has the following characteristics: Figure 2 The image shows the X-ray test results.

[0045] The crystallographic parameters of the chiral inositol crystal form are shown in Table 1.

[0046] Table 1

[0047]

[0048] The chiral inositol crystal form has the following characteristics: Figure 3 The thermogravimetric analysis chromatograms shown indicate a weight loss of 95.90% between 250 and 450 °C, with decomposition beginning at 395.81 °C. A Netzsch Scientific TG20F3 thermogravimetric analyzer was used under a nitrogen atmosphere at a heating rate of 10 °C / min.

[0049] The chiral inositol crystal form has the following characteristics: Figure 4 The differential scanning calorimeter (DSC) spectrum shown has no characteristic endothermic peaks in the range of 0–140 °C. The measurements were performed using a DSC 8500 differential calorimeter from Platinum Elmer, USA, in a nitrogen atmosphere at a heating rate of 10 °C / min.

[0050] The chiral inositol crystal form has the following characteristics: Figure 5 The infrared spectrum shown is located at 3417 cm⁻¹. -13358 cm -1 (Hydroxy group), 2967 cm -1 2924 cm -1 (Saturated hydrocarbons), 1420-1000 cm -1 A characteristic peak is observed at the (methionine) position. Detection was performed using a Nicolet-Magna FT-IR 750 infrared spectrometer (Nicolet-Magna, Inc., USA) at 25±2℃, with a detection range of 4000-350 cm⁻¹. -1 wave number.

[0051] The chiral inositol crystal form has the following characteristics: Figure 6 shown 1 The 1H-NMR spectrum shows chemical shifts of the H protons of chiral inositol at 3.90 ppm, 3.63 ppm, and 3.45 ppm. Detection was performed using a Bruker AVANCE III HD 400M NMR spectrometer (1H-NMR pulse sequence: zg30, TD (data point): 65 K, RG (gain): 32, D1 (relaxation time): 10 s, SW (spectral width): 20 ppm, O1p (spectral width center): 6.175 ppm, NS (number of scans): 16, DS (number of empty scans): 2).

[0052] The chiral inositol crystal form has the following characteristics: Figure 7 shown 13 The C-NMR spectrum shows chemical shifts of the C protons of chiral inositol at 72.7 ppm, 71.6 ppm, and 70.4 ppm.

[0053] In another aspect, Embodiment 1 of the present invention provides a method for preparing chiral inositol crystal form, comprising the following steps: adding chiral inositol sample and acetonitrile aqueous solution into a reagent bottle and shaking to dissolve; sealing the reagent bottle with sealing film and punching holes in the film as solvent evaporation ports; and allowing it to stand to obtain chiral inositol crystal form.

[0054] The volume ratio of acetonitrile to water in the acetonitrile aqueous solution is 4:1.

[0055] The settling temperature was 25°C, and the settling time was 5 days.

[0056] The mass ratio of the chiral inositol sample to the volume of the acetonitrile aqueous solution was 4 mg: 1 mL.

[0057] The hole density is 1 hole / cm². 2 .

[0058] See Figure 8 The chiral inositol sample contains D-chiral inositol and L-chiral inositol, and the chiral inositol sample is sourced from Shandong Zhucheng Haotian Pharmaceutical Co., Ltd.

[0059] Example 2

[0060] Example 2 of the present application provides a preparation method of a chiral inositol crystal form, the specific implementation of which is the same as that of Example 1, except that the volume ratio of acetonitrile to water in the acetonitrile aqueous solution is 10:1, and the chiral inositol crystal form cannot be obtained by standing at 25°C for 5 days.

[0061] Example 3

[0062] Example 3 of the present application provides a preparation method of a chiral inositol crystal form, the specific implementation of which is the same as that of Example 1, except that the volume ratio of acetonitrile to water in the acetonitrile aqueous solution is 8:1, and the chiral inositol crystal form cannot be obtained by standing at 25°C for 5 days.

[0063] Example 4

[0064] Example 4 of the present application provides a preparation method of a chiral inositol crystal form, the specific implementation of which is the same as that of Example 1, except that the volume ratio of acetonitrile to water in the acetonitrile aqueous solution is 7:1, and the chiral inositol crystal form cannot be obtained by standing at 25°C for 5 days.

[0065] Example 5

[0066] Example 5 of the present application provides a preparation method of a chiral inositol crystal form, the specific implementation of which is the same as that of Example 1, except that the volume ratio of acetonitrile to water in the acetonitrile aqueous solution is 6:1, and the chiral inositol crystal form cannot be obtained by standing at 25°C for 5 days.

[0067] Example 6

[0068] Example 6 of the present application provides a preparation method of a chiral inositol crystal form, the specific implementation of which is the same as that of Example 1, except that the volume ratio of acetonitrile to water in the acetonitrile aqueous solution is 5:1, and the chiral inositol crystal form cannot be obtained by standing at 25°C for 5 days.

[0069] Example 7

[0070] Example 7 of the present application provides a preparation method of a chiral inositol crystal form, the specific implementation of which is the same as that of Example 1, except that the volume ratio of acetonitrile to water in the acetonitrile aqueous solution is 9:1, and the chiral inositol crystal form cannot be obtained by standing at 25°C for 5 days.

[0071] Example 8

[0072] Example 8 of the present application provides a preparation method of a chiral inositol crystal form, the specific implementation of which is the same as that of Example 1, except that the volume ratio of acetonitrile to water in the acetonitrile aqueous solution is 3:1, and the chiral inositol crystal form cannot be obtained by standing at 25°C for 5 days.

[0073] Example 9

[0074] Example 9 of the present application provides a preparation method of a chiral inositol crystal form, the specific embodiment of which is the same as that of Example 1, except that the volume ratio of acetonitrile to water in the acetonitrile aqueous solution is 2:1, and the chiral inositol crystal form cannot be obtained by standing at 25℃ for 5 days.

[0075] Example 10

[0076] Example 10 of the present application provides a preparation method of a chiral inositol crystal form, the specific embodiment of which is the same as that of Example 1, except that the volume ratio of acetonitrile to water in the acetonitrile aqueous solution is 1:1, and the chiral inositol crystal form cannot be obtained by standing at 25℃ for 5 days.

[0077] Example 11

[0078] Example 11 of the present application provides a preparation method of a chiral inositol crystal form, the specific embodiment of which is the same as that of Example 1, except that the acetonitrile aqueous solution is replaced by acetonitrile (purity 95.5%), and the chiral inositol crystal form cannot be obtained by standing at 25℃ for 5 days.

[0079] Example 12

[0080] Example 12 of the present application provides a preparation method of a chiral inositol crystal form, the specific embodiment of which is the same as that of Example 1, except that the acetonitrile aqueous solution is replaced by methanol (purity 95.5%), and the chiral inositol crystal form cannot be obtained by standing at 25℃ for 5 days.

[0081] Example 13

[0082] Example 13 of the present application provides a preparation method of a chiral inositol crystal form, the specific embodiment of which is the same as that of Example 1, except that the acetonitrile aqueous solution is replaced by a methanol aqueous solution (the volume ratio of methanol to water in the methanol aqueous solution is 10:1), and the chiral inositol crystal form cannot be obtained by standing at 25℃ for 5 days.

[0083] Example 14

[0084] Example 14 of the present application provides a preparation method of a chiral inositol crystal form, the specific embodiment of which is the same as that of Example 1, except that the acetonitrile aqueous solution is replaced by a methanol aqueous solution (the volume ratio of methanol to water in the methanol aqueous solution is 9:1), and the chiral inositol crystal form cannot be obtained by standing at 25℃ for 5 days.

[0085] Example 15

[0086] Embodiment 15 of the present application provides a preparation method of the chiral inositol crystal form, the specific implementation of which is the same as that of Embodiment 1, except that the acetonitrile aqueous solution is replaced by a methanol aqueous solution (the volume ratio of methanol to water in the methanol aqueous solution is 8:1), and the chiral inositol crystal form cannot be obtained by standing at 25℃ for 5 days.

[0087] Embodiment 16

[0088] Embodiment 16 of the present application provides a preparation method of the chiral inositol crystal form, the specific implementation of which is the same as that of Embodiment 1, except that the acetonitrile aqueous solution is replaced by a methanol aqueous solution (the volume ratio of methanol to water in the methanol aqueous solution is 7:1), and the chiral inositol crystal form cannot be obtained by standing at 25℃ for 5 days.

[0089] Embodiment 17

[0090] Embodiment 17 of the present application provides a preparation method of the chiral inositol crystal form, the specific implementation of which is the same as that of Embodiment 1, except that the acetonitrile aqueous solution is replaced by a methanol aqueous solution (the volume ratio of methanol to water in the methanol aqueous solution is 6:1), and the chiral inositol crystal form cannot be obtained by standing at 25℃ for 5 days.

[0091] Embodiment 18

[0092] Embodiment 18 of the present application provides a preparation method of the chiral inositol crystal form, the specific implementation of which is the same as that of Embodiment 1, except that the acetonitrile aqueous solution is replaced by a methanol aqueous solution (the volume ratio of methanol to water in the methanol aqueous solution is 5:1), and the chiral inositol crystal form cannot be obtained by standing at 25℃ for 5 days.

[0093] Embodiment 19

[0094] Embodiment 19 of the present application provides a preparation method of the chiral inositol crystal form, the specific implementation of which is the same as that of Embodiment 1, except that the acetonitrile aqueous solution is replaced by a methanol aqueous solution (the volume ratio of methanol to water in the methanol aqueous solution is 4:1), and the chiral inositol crystal form cannot be obtained by standing at 25℃ for 5 days.

[0095] Embodiment 20

[0096] Embodiment 20 of the present application provides a preparation method of the chiral inositol crystal form, the specific implementation of which is the same as that of Embodiment 1, except that the acetonitrile aqueous solution is replaced by a methanol aqueous solution (the volume ratio of methanol to water in the methanol aqueous solution is 3:1), and the chiral inositol crystal form cannot be obtained by standing at 25℃ for 5 days.

[0097] Embodiment 21

[0098] Embodiment 21 of the present application provides a preparation method of a chiral inositol crystal form, the specific implementation of which is the same as that of Embodiment 1, except that the acetonitrile aqueous solution is replaced by a methanol aqueous solution (the volume ratio of methanol to water in the methanol aqueous solution is 2:1), and the chiral inositol crystal form cannot be obtained by standing at 25℃ for 5 days.

[0099] Embodiment 22

[0100] Embodiment 22 of the present application provides a preparation method of a chiral inositol crystal form, the specific implementation of which is the same as that of Embodiment 1, except that the acetonitrile aqueous solution is replaced by a methanol aqueous solution (the volume ratio of methanol to water in the methanol aqueous solution is 1:1), and the chiral inositol crystal form cannot be obtained by standing at 25℃ for 5 days.

[0101] Performance test

[0102] 1. The hygroscopicity of the chiral inositol crystal form provided in Embodiment 1 of the present application and the amorphous sample was tested, and the results are shown in Table 2.

[0103] Table 2

[0104]

[0105] As can be seen from the data in Table 2, the hygroscopicity of the chiral inositol crystal form provided in Embodiment 1 of the present application is significantly lower than that of the amorphous sample at 25℃ under different humidity conditions. Under the same conditions, the chiral inositol crystal form provided in Embodiment 1 of the present application has better appearance, good fluidity, no caking phenomenon, and good physical stability.

[0106] 2. The solubility (the mass of the chiral inositol crystal form dissolved in 100 mL of water at different temperatures, which was not dissolved for 10 min at each temperature) of the chiral inositol crystal form provided in Embodiment 1 of the present application and the amorphous sample at different temperatures was tested, and the results are shown in Table 3.

[0107] Table 3

[0108]

[0109] As can be seen from the data in Table 3, the chiral inositol crystal form provided in Embodiment 1 of the present application has better solubility than the amorphous sample.

Claims

1. A crystalline form of chiral inositol characterized by, The chiral inositol crystal form has characteristic diffraction peaks at diffraction angles 2θ of 13.44±0.02°, 14.85±0.02°, 16.58±0.02°, 17.75±0.02°, 19.43±0.02°, 22.79±0.02°, 23.70±0.02°, 24.79±0.02°, 25.90±0.02°, 27.05±0.02°, 28.66±0.02°, 30.11±0.02°, 30.77±0.02°, 34.66±0.02°, 37.776±0.02°, 39.46±0.02°, 40.73±0.02°, 44.78±0.02° and 46.52±0.02°, as measured by X-ray powder diffraction analysis using Cu-Kα rays; the chiral inositol crystal form has a weight loss of 95.90% at 250-450°C, and starts to decompose at 395.81°C; the chiral inositol crystal form has no characteristic endothermic peaks in the range of 0-140°C in a differential scanning calorimetry spectrum; the chiral inositol crystal form has characteristic peaks at 3417 cm -1 , 3358 cm -1 , 2967 cm -1 , 2924 cm -1 and 1420-1000 cm -1 in an infrared spectrum; the chiral inositol crystal form has chemical shifts of H protons of chiral inositol at 3.90 ppm, 3.63 ppm and 3.45 ppm in a H-NMR spectrum; the chiral inositol crystal form has chemical shifts of C protons of chiral inositol at 72.7 ppm, 71.6 ppm and 70.4 ppm in a C-NMR spectrum. 1 13 ​​ The chiral inositol sample and the acetonitrile aqueous solution are added into a reagent bottle, and shaken to dissolve; the reagent bottle is sealed with a sealing film, and a hole is punched on the film as a solvent evaporation port; and a chiral inositol crystal form is obtained by standing. The volume ratio of acetonitrile to water in the acetonitrile aqueous solution is 4:

1. The standing temperature is 25°C, and the standing time is 5 days. The mass of the chiral inositol sample to the volume of the acetonitrile aqueous solution is 4mg:1mL. The density of the perforations is 1 per cm 2 ; The chiral inositol sample contains D-chiral inositol and L-chiral inositol, and the chiral inositol sample is from Shandong Zhucheng Haotian Pharmaceutical Co., Ltd.

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