A new crystal form of pregnenolone and preparation method thereof

Abstract

The present invention belongs to the technical field of drug crystal forms and relates to a new crystal form of pregnenolone and a preparation method thereof. The new crystal form of pregnenolone of the present invention uses Cu-Kα radiation and, in a powder XRD ray diffraction pattern represented by 2θ, includes 7.496°, 10.449°, 10.815°, 13.484°, 14.303°, 14.983°, 15.663°, 15.917°, 16.385°, 16.798°, 17.226°, 17.495°, 18.389°, 19.115°, 20.291°, 20.861°, 21.388°, 21.948°, 22.156°, 22.443°, 23.118°, 23.727°, 24.041°, 24.46 There are diffraction peaks at positions of 1°, 24.846°, 25.649°, 25.920°, 26.189°, 27.460°, 27.768°, 28.237°, 29.129°, 30.324°, 31.385°, 31.581°, 32.905°, 34.529°, 34.89°, 37.108°, 37.300°, 38.163°, 40.271, 40.442°, 41.215°, 41.393°, 42.776°, 43.516°, 43.821°, 47.113°, and 48.092°, and the position error range of 2θ is ±0.1°.

Description

Technical Field

[0001] The present invention belongs to the technical field of drug crystal forms, and particularly relates to a method for preparing a new crystal form of pregnenolone. Background Art

[0002] Pregnenolone (PREG), also known as 5-pregnen-3β-ol-20-one, is a natural endogenous steroid hormone and an important intermediate in the synthesis of progesterone and finasteride. It is primarily used as an intermediate for steroidal drugs and in the synthesis of steroidal drugs. Pregnenolone can also regulate neurosteroid levels and act on the nervous system. For example, pregnenolone can alleviate GABA receptor dysregulation through metabolism to allopregnanolone, and can also improve NMDA receptor dysfunction through metabolism to pregnenolone sulfate. GABA receptors, NMDA receptors, and α receptors have corresponding effects on memory, sleep, convulsions, and cellular excitotoxicity, providing therapeutic targets for certain diseases.

[0003] For existing crystallization technologies, solution crystallization is the main way to obtain crystals, but this method requires the consumption of organic solvents. Most organic solvents are dangerous, such as flammable, explosive, corrosive and toxic. If the organic solvent waste liquid is not properly handled, it can easily cause serious impacts on the environment, human body and society. Therefore, the rational treatment of organic solvent waste liquid in industrial crystallization has become an important issue that needs to be solved. In addition, factors such as stirring rate, control of crystallization temperature and choice of solvent system need to be considered in the industrial crystallization process, which also makes the experimental operation more complicated. Summary of the Invention

[0004] The present invention provides a melting method for directly obtaining a new crystal form of pregnenolone. The method is simple and easy to operate, takes a short time, does not generate organic solvent waste, has good preparation reproducibility, is easy to control the preparation process, is economical and green, and is suitable for large-scale industrial production.

[0005] The present invention specifically adopts the following technical solutions:

[0006] The present invention provides a new crystal form II of pregnenolone, which is characterized in that, using Cu-Kα radiation, in a powder XRD ray diffraction pattern expressed in 2θ angles, the following patterns are present: 7.496°, 10.449°, 10.815°, 13.484°, 14.303°, 14.983°, 15.663°, 15.917°, 16.385°, 16.798°, 17.226°, 17.495°, 18.389°, 19.115°, 20.291°, 20.861°, 21.388°, 21.948°, 22.156°, 22.443°, 23.118°, 23.727°, 24.041° There are diffraction peaks at positions of 2θ, 24.461°, 24.846°, 25.649°, 25.920°, 26.189°, 27.460°, 27.768°, 28.237°, 29.129°, 30.324°, 31.385°, 31.581°, 32.905°, 34.529°, 34.89°, 37.108°, 37.300°, 38.163°, 40.271, 40.442°, 41.215°, 41.393°, 42.776°, 43.516°, 43.821°, 47.113°, and 48.092°, and the position error range of 2θ is ±0.1°.

[0007] The peak positions of the powder XRD diffraction patterns of the new pregnenolone crystal form II prepared by the present invention and the pregnenolone crystal form I are different. Specifically, when Cu-Kα radiation is used, the peak positions of the powder XRD diffraction pattern of the pregnenolone crystal form I expressed in 2θ angles are 7.211°, 7.387°, 10.458°, 14.319°, 14.927°, 16.159°, 16.342°, 17.585°, There are diffraction peaks at 17.976°, 20.754°, 20.940°, 21.550°, 22.168°, 23.373°, 25.748°, 26.864°, 27.888°, 30.078°, 30.544°, 30.851°, 31.691°, 32.939°, 37.841°, 38.028°, 40.393°, and 45.807°. The position error range of 2θ is ±0.1°. In the powder XRD diffraction pattern expressed in 2θ angles, assuming that the intensity of the diffraction peak corresponding to 2θ of 14.927° is 100, the relative intensity of each 2θ corresponding diffraction peak is:

[0008] 2θ° Relative strength Ⅰ / Ⅰ0(%) 2θ° Relative strength Ⅰ / Ⅰ0(%) 7.211 8.4 23.373 18.5 7.387 21.5 25.748 1.6 10.458 3.2 26.864 2.6 14.319 2.3 27.888 9.1 14.927 100 30.078 5.2 16.159 29.5 30.544 2.2 16.342 45.7 30.851 3.2 17.585 3.0 31.691 2.6 17.976 26.9 32.939 1.5 20.754 3.0 37.841 1.6 20.940 2.2 38.028 1.9 21.550 3.2 40.393 1.9 22.168 17.8 45.807 7.2

[0009] In addition, combined with the Cambridge Crystallographic Data Centre (CCDC) and domestic and foreign literature research results, at present, there is only one crystal structure information for pregnenolone, and the main characteristic peak information in the powder XRD diffraction pattern of the pregnenolone crystals purchased in the embodiment of the present invention is consistent with the CCDC # The powder XRD characteristic peak information of 625224 is consistent, see Figure 3 Therefore, in the present invention, this is named pregnenolone crystal form I.

[0010] The DSC spectrum of the new crystal form II of pregnenolone of the present invention has a characteristic absorption peak at 193.26-197.04°C±5°C.

[0011] The DSC spectrum of the new pregnenolone crystal form II prepared by the present invention has one endothermic peak in the temperature range of 192 to 200°C, while the DSC spectrum of the pregnenolone crystal form I has two endothermic peaks, the first heat absorption peak has a temperature range of 175 to 190°C, and the second heat absorption peak has a temperature range of 190 to 200°C.

[0012] The present invention provides a method for preparing a new crystal form II of pregnenolone, comprising the following steps:

[0013] A: Pregnenolone is heated to cause solid-solid transformation of the molten pregnenolone. Specifically, the pregnenolone is heated to melt-transform the crystals at a temperature of 187-193°C for 0.5-2 hours. Specifically, the pregnenolone crystals are evenly spread on a glass container to a thickness of 0.1-0.5 cm, then heated at 187-193°C for 0.5-2 hours and then naturally cooled to room temperature to obtain the product.

[0014] B: Add ethanol to pregnenolone Form I and heat to evaporate the ethanol at 80°C until crystals appear. Collect the crystals and dry them at 50°C to constant weight. The ratio of pregnenolone to ethanol is 1 g:100 mL.

[0015] The purity of the pregnenolone crystal form I used in the above method is greater than or equal to 98%wt.

[0016] The new crystal form II of pregnenolone prepared by the method of the present invention has good stability and solubility and can be used to prepare steroid drug intermediates or steroid drugs.

[0017] The present invention has the following beneficial effects:

[0018] The present invention allows direct crystallization of pregnenolone by melting and heating at a temperature of 187-193°C with a heating interval of 0.5-2 hours. This method has simple operating steps, is time-efficient, and consumes little energy. The resulting new crystal form of pregnenolone has good stability and solubility. Melt crystallization refining technology offers advantages such as high product purity, low energy consumption, the absence of the need for the addition of other solvents, and minimal environmental pollution. This technology has been widely applied not only in the separation of fine chemicals and isomers, but also in large-scale organic chemistry, such as the production of bisphenol A and naphthalene. It is foreseeable that melt crystallization will become an important technology for producing high-purity organic chemical products. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 is the structural formula of pregnenolone;

[0020] Figure 2 The crystal form changes of pregnenolone before and after grinding;

[0021] Figure 3 This is the powder XRD pattern of the new crystal form II of pregnenolone prepared in Examples 1 to 4 of the present invention;

[0022] Figure 4 The powder XRD patterns of pregnenolone crystal form I and the new pregnenolone crystal form II of the present invention are shown below: (a) pregnenolone crystal form I; (b) new pregnenolone crystal form II;

[0023] Figure 5 This is a differential scanning calorimetry (DSC) diagram of the new crystal form II of pregnenolone of the present invention;

[0024] Figure 6 This is a stability test of the new crystal form II of pregnenolone of the present invention;

[0025] Figure 7 This is a solubility diagram of pregnenolone crystal form I and the new pregnenolone crystal form II of the present invention in ethanol;

[0026] Figure 8 This is a solubility diagram of pregnenolone crystal form I and the new pregnenolone crystal form II of the present invention in n-butanol;

[0027] Figure 9 This is the standard curve of pregnenolone form I;

[0028] Figure 10 This is the standard curve of the new crystal form II of pregnenolone of the present invention. DETAILED DESCRIPTION

[0029] The present invention is described in more detail below through specific implementation methods to facilitate understanding of the technical solution of the present invention, but is not intended to limit the scope of protection of the present invention.

[0030] In the embodiment, pregnenolone (chemical formula: C 21 H 32 O2, purity greater than or equal to 98% wt, its structural formula is shown in Figure 1 ) is named pregnenolone crystal form I. The pregnenolone prepared by the method of the present invention is named pregnenolone new crystal form II.

[0031] Example 1

[0032] Pregnenolone crystal form I with a purity greater than or equal to 98% wt was weighed and evenly spread on a glass container with a thickness of 0.1 to 0.5 cm. The mixture was then placed in an oven at 190° C., heated and melted for 30 minutes, and then naturally cooled to room temperature to obtain a new crystal form II of pregnenolone.

[0033] Example 2

[0034] Pregnenolone crystal form I with a purity greater than or equal to 98% wt was weighed and evenly spread on a glass container with a thickness of 0.1 to 0.5 cm. The mixture was then placed in an oven at 190° C. and heated for 2 hours for melting and crystallization to obtain a new pregnenolone crystal form II.

[0035] Example 3

[0036] 0.1 g of pregnenolone crystalline form I with a purity greater than or equal to 98% wt was weighed into a 50 mL round-bottom flask, 10 mL of anhydrous ethanol was added, and the mixture was placed in a rotary evaporator and heated to evaporate the ethanol. The rotary evaporator temperature was set to 80° C., the equipment was decompressed, and the solvent was evaporated until crystals appeared. The crystals were collected and dried at 50° C. to constant weight to obtain the new pregnenolone crystalline form II.

[0037] Example 4

[0038] Pregnenolone crystal form I with a purity greater than or equal to 98% wt was weighed and evenly spread on a glass container with a thickness of 0.1 to 0.5 cm. The mixture was then placed in an oven at 190° C. and heated for 30 minutes for melting and crystallization. The melted sample was fully ground to obtain a new crystal form II of pregnenolone.

[0039] To further investigate the effect of grinding on the crystal form, a control experiment was conducted. In the control experiment, only the pregnenolone crystal form I with a purity greater than or equal to 98% wt was fully ground without heating and melting in an oven. Figure 2 As shown. Figure 2 It can be seen that the crystal form of pregnenolone Form I does not change after grinding, which further illustrates that heating and melting causes pregnenolone Form I to be converted into a new pregnenolone Form II.

[0040] Example 5 Determination of New Crystal Form II of Pregnenolone

[0041] Pregnenolone Form I and the new pregnenolone Form II obtained in Examples 1 to 4 were detected using a Bruker D8 Advance, Germany diffractometer; X-ray tube emission source: Cu target (wavelength: λ = 0.15405 nm), voltage 40 kV; current 40 mA, and the corresponding characteristic peaks in the X-ray powder diffraction pattern (Cu-Kα) are shown in the attached Figure 3 , expressed as the diffraction angle 2θ, at 7.496°, 10.449°, 10.815°, 13.484°, 14.303°, 14.983°, 15.663°, 15.917°, 16.385°, 16.798°, 17.226°, 17.495°, 18.389°, 19.115°, 20.291°, 20.861°, 21.388°, 21.948°, 22.156°, 22.443°, 23.118°, 23.727°, 24.041°, 24.461°, and 24.8 Characteristic peaks are found at 46°, 25.649°, 25.920°, 26.189°, 27.460°, 27.768°, 28.237°, 29.129°, 30.324°, 31.385°, 31.581°, 32.905°, 34.529°, 34.89°, 37.108°, 37.300°, 38.163°, 40.271°, 40.442°, 41.215°, 41.393°, 42.776°, 43.516°, 43.821°, 47.113°, and 48.092°. The 2θ position error is ±0.1°. In the powder XRD diffraction pattern expressed in 2θ angles, assuming that the intensity of the diffraction peak corresponding to 2θ of 15.663° is 100, the relative intensity of the diffraction peaks corresponding to each 2θ angle is:

[0042] 2θ° <![CDATA[Relative intensity I / I0(%)]]> 2θ° <![CDATA[Relative intensity I / I0 (%)]]> 7.496° 2.0 25.649° 4.3 10.449° 7.8 25.920° 14.1 10.815° 2.4 26.189° 2.2 13.484° 34.2 27.460° 2.3 14.303° 40.5 27.768° 3.6 14.983° 3.2 28.237° 10.0 15.663° 100 29.129° 14.9 15.917° 94.6 30.324° 6.8 16.385° 43.1 31.385° 2.6 16.798° 3.2 31.581° 2.4 17.226° 4.6 32.905° 3.3 17.495° 6.4 34.529° 1.6 18.389° 34.9 34.89° 1.4 19.115° 2.4 37.108° 2.5 20.291° 8.2 37.300° 2.7 20.861° 3.9 38.163° 2.9 21.388° 83.1 40.271 1.6 21.948° 23.5 40.442° 2.1 22.156° 2.1 41.215° 2.1 22.443° 2.8 41.393° 1.9 23.118° 3.7 42.776° 1.6 23.727° 15.1 43.516° 2.8 24.041° 2.5 43.821° 2.9 24.461° 4.2 47.113° 2.1 24.846° 3.3 48.092° 1.5

[0043] The peak positions of the powder XRD diffraction patterns of the new pregnenolone crystal form II prepared by the present invention and the pregnenolone crystal form I are different at diffraction angles of 13 to 25 degrees. Specifically, the X-ray characteristic peaks of the pregnenolone crystal form I have characteristic peaks at 7.207°, 7.391°, 10.456°, 14.932°, 16.322°, 17.977°, 21.492°, 21.553°, 22.167°, 23.373°, 26.867°, 27.891°, and 30.075° in the powder XRD diffraction pattern expressed in 2θ.

[0044] The powder XRD patterns of pregnenolone crystal form I and the new pregnenolone crystal form II prepared by the present invention are shown in the figure below: Figure 4 shown.

[0045] DSC thermal analysis tests were performed on pregnenolone crystal form I and the new crystal form II of pregnenolone in Example 1 of the present invention. The DSC thermal analysis tester and test conditions were as follows: DSC thermal analyzer: German-Netzsch-DSC214; detection temperature range 25-250°C; instrument heating rate: 5° / min; protective gas: N2; nitrogen flow rate: nitrogen flow rate is 250mL / min; crucible: aluminum crucible (not pressurized). The results showed that the DSC spectrum of the new crystal form II of pregnenolone prepared by the present invention had an endothermic peak in the temperature range of 192-200°C, while the DSC spectrum of the pregnenolone crystal form I had two endothermic peaks, the temperature range of the first heat absorption peak was 175-190°C, and the temperature range of the second heat absorption peak was 190-200°C. The DSC spectrum comparison of pregnenolone crystal form I and the new crystal form II of pregnenolone is shown in the attached figure. Figure 5 The DSC spectrum of the new crystal form II of pregnenolone of the present invention has a characteristic absorption peak at 193.26-197.04°C±5°C.

[0046] Example 6 Stability Study of New Crystal Form II of Pregnenolone

[0047] The stability of the new crystal form II of pregnenolone prepared in Example 1 was investigated. The new crystal form II of pregnenolone was placed in a sealed brown glass bottle, and then the brown glass bottle was placed in a refrigerator at a temperature of 4 to 8 ° C. Samples were taken for powder XRD detection after 40 days and 80 days, and compared with the results on day 0. The specific spectrum is as follows Figure 6 As shown, the results show that the powder XRD pattern of the new crystal form II of pregnenolone prepared in Example 1 does not show any new characteristic peaks. This also shows that the new crystal form II of pregnenolone prepared by the melt crystallization method of the present invention has good stability.

[0048] Example 7 Investigation of the biological activity of the new crystal form II of pregnenolone

[0049] The solubility of pregnenolone crystal form I and the new pregnenolone crystal form II prepared in Example 1 in ethanol and n-butanol solution systems were measured respectively. The specific measurement method is as follows:

[0050] A constant temperature water bath (Shanghai Bilang, DC 0506) was opened, the temperature was set to 2°C lower than the predetermined temperature, and the solution was kept stable for 30 minutes. The solvent and pregnenolone accurately weighed by an electronic analytical balance (Germany Sartorius, LA120S, accuracy ±0.0001g) were added to the dissolution vessel, and the magnetic stirring device was turned on to fully dissolve the solution. According to the results of the preliminary experiment, an appropriate excess of pregnenolone was added and the solution was dissolved for 2 hours. If the pregnenolone in the dissolution vessel was completely dissolved, the pregnenolone was continued to be added. If the pregnenolone was not completely dissolved, the solution was stirred at 2°C·h -1The temperature is raised at a rate of 1000 ℃ until the temperature reaches the set value. If there is a slight excess of pregnenolone, the solvent is added dropwise through a micro syringe to adjust the amount until all the pregnenolone in the dissolution kettle is dissolved. The mass of the solute and solvent before and after is accurately weighed and recorded, and the solubility of pregnenolone can be calculated.

[0051] The results of the test are as follows Figure 7 and Figure 8 As shown in the figure, it can be seen that the solubility of the new crystal form II of pregnenolone prepared by the present invention in the anhydrous ethanol and n-butanol solution systems is greater than that of the pregnenolone crystal form I. Therefore, it can be seen that the biological activity of the new crystal form II of pregnenolone prepared by the present invention has been improved to a certain extent, and it is expected to further improve the utilization value of the new crystal form II of pregnenolone.

[0052] Example 8 Absorbance Determination of Pregnenolone Form I and Form II

[0053] To further verify the changes in the biological activity of the new pregnenolone crystal form II, the absorbance of pregnenolone crystal form I and pregnenolone crystal form II in ethanol solutions at 25°C was measured using an ultraviolet spectrophotometer. First, a full wavelength scan of the standard sample was performed to determine the maximum absorbance wavelength of pregnenolone I in anhydrous ethanol solution at 25°C to be 293 nm. 0.0250 mg each of pregnenolone crystal form I and new pregnenolone crystal form II was accurately weighed and dissolved in 20 mL of ethanol solution. The solution was then diluted to volume in a 25 mL volumetric flask to prepare a standard solution with a concentration of 1 mg / mL as the stock solution. Subsequently, 1 mL of the stock solution was pipetted and added to 9 mL, 8 mL, 7 mL, 6 mL, 5 mL, and 4 mL of anhydrous ethanol solution, respectively, to prepare standard solutions of known concentrations of 0.1 mg / mL, 0.2 mg / mL, 0.3 mg / mL, 0.4 mg / mL, 0.5 mg / mL, and 0.6 mg / mL for establishing a standard curve. Using formula (1), determine the mole fraction solubility corresponding to the solid form of pregnenolone crystal form I and pregnenolone new crystal form II:

[0054]

[0055] Where A is the absorbance of the diluted solution; V is the volume of the diluted solution; k and b are the slope and intercept of the standard curve, respectively. The standard curve of pregnenolone crystal form I was established as shown in Table 1 and Figure 9 shown.

[0056] Table 1 Pregnenolone Form I standard curve data table

[0057] Concentration (mg / mL) first Second time The third time average 0.1 0.017 0.02 0.017 0.018 0.2 0.028 0.036 0.034 0.033 0.3 0.045 0.044 0.044 0.044 0.4 0.059 0.055 0.058 0.057 0.5 0.069 0.07 0.071 0.070 0.6 0.086 0.085 0.089 0.087

[0058] from Figure 9It can be seen that the absorbance of pregnenolone crystal form I in ethanol has a linear relationship with the solution concentration, and the linear relationship is good. The linear equation is: y = 0.00467x + 0.13381, R 2 =0.99748.

[0059] The standard curve data obtained from the new crystal form II of pregnenolone are shown in Table 2 and Figure 10 .

[0060] Table 2 Data table of the new crystal form of pregnenolone

[0061] Concentration (mg / mL) first Second time The third time average 0.1 0.014 0.012 0.013 0.013 0.2 0.026 0.035 0.027 0.029 0.3 0.044 0.044 0.042 0.043 0.4 0.059 0.056 0.056 0.057 0.5 0.073 0.07 0.07 0.071 0.6 0.086 0.086 0.084 0.085

[0062] from Figure 10 It can be seen that the absorbance of the new crystal form II of pregnenolone in ethanol has a linear relationship with the solution concentration, and the linear relationship is good. The linear equation is: y = 0.14295x-0.0002, R 2 =0.99926.

[0063] Then, an excess of pregnenolone crystal form I and pregnenolone new crystal form II were weighed respectively and added to two double-layer crystallizers. The temperature of the constant temperature water bath was set at 25°C. To ensure that the solution reached equilibrium, it was stirred for 6 hours under the action of a magnetic stirrer. Then, it was allowed to stand in a constant temperature water bath at 25°C for 3 hours. The supernatant was aspirated using a sterile syringe, and the obtained supernatant was passed through a 0.45 μm filter membrane, filtered, and diluted 50 times. The 50-fold diluted solution was then detected in an ultraviolet spectrophotometer, and 293 nm was selected as the ultraviolet detection wavelength.

[0064] Table 3 Concentration of pregnenolone crystal form I and pregnenolone new crystal form II in ethanol at a temperature of 25°C

[0065]

[0066]

[0067] As shown in Table 3, at 25°C, the concentration of pregnenolone Form I in anhydrous ethanol solvent system is 15.94 mg / mL. However, the concentration of pregnenolone Form II prepared by the melt crystallization method of the present invention in anhydrous ethanol solution system is 17.09 mg / mL. This indicates that the solubility of pregnenolone Form II in anhydrous ethanol solution system is greater than that of pregnenolone Form I.

[0068] The embodiments described above are only preferred embodiments of the present invention and do not limit the scope of implementation of the present invention. Therefore, any equivalent changes or modifications made according to the structure, characteristics and principles described in the patent scope of the present invention should be included in the scope of the patent application of the present invention.

Claims

1. A method for preparing a new crystal form of pregnenolone, characterized in that: Includes the following: The pregnenolone is heated to melt and crystallize at a temperature of 187-193° C. for 0.5-2 hours; Using Cu-Kα radiation, in the powder XRD ray diffraction pattern expressed in 2θ angles, the new crystal form of pregnenolone includes 7.496°, 10.449°, 10.815°, 13.484°, 14.303°, 14.983°, 15.663°, 15.917°, 16.385°, 16.798°, 17.226°, 17.495°, 18.389°, 19.115°, 20.291°, 20.861°, 21.388°, 21.948°, 22.156°, 22.443°, 23.118°, 23.727°, 24.041°, 24.46 There are diffraction peaks at positions of 1°, 24.846°, 25.649°, 25.920°, 26.189°, 27.460°, 27.768°, 28.237°, 29.129°, 30.324°, 31.385°, 31.581°, 32.905°, 34.529°, 34.89°, 37.108°, 37.300°, 38.163°, 40.271, 40.442°, 41.215°, 41.393°, 42.776°, 43.516°, 43.821°, 47.113°, and 48.092°, and the position error range of 2θ is ±0.1°.

2. The preparation method according to claim 1, characterized in that The purity of the pregnenolone used is greater than or equal to 98%wt.

3. The preparation method according to claim 1, characterized in that Using Cu-Kα radiation, the powder XRD diffraction pattern expressed in 2θ angles includes 7.211°, 7.387°, 10.458°, 14.319°, 14.927°, 16.159°, 16.342°, 17.585°, 17.976°, 20.754°, 20.940°, 21.550°, There are diffraction peaks at positions of 22.168°, 23.373°, 25.748°, 26.864°, 27.888°, 30.078°, 30.544°, 30.851°, 31.691°, 32.939°, 37.841°, 38.028°, 40.393°, and 45.807°, and the position error range of 2θ is ±0.1°.

4. The method for preparing a new crystal form of pregnenolone according to claim 1, characterized in that: Includes the following: Add anhydrous ethanol to pregnenolone, heat and evaporate the ethanol at 80°C, evaporate the solvent until crystals appear, collect the crystals and dry them at 50°C to constant weight; Using Cu-Kα radiation, in the powder XRD ray diffraction pattern expressed in 2θ angles, the new crystal form of pregnenolone includes 7.496°, 10.449°, 10.815°, 13.484°, 14.303°, 14.983°, 15.663°, 15.917°, 16.385°, 16.798°, 17.226°, 17.495°, 18.389°, 19.115°, 20.291°, 20.861°, 21.388°, 21.948°, 22.156°, 22.443°, 23.118°, 23.727°, 24.041°, 24.46 There are diffraction peaks at positions of 1°, 24.846°, 25.649°, 25.920°, 26.189°, 27.460°, 27.768°, 28.237°, 29.129°, 30.324°, 31.385°, 31.581°, 32.905°, 34.529°, 34.89°, 37.108°, 37.300°, 38.163°, 40.271, 40.442°, 41.215°, 41.393°, 42.776°, 43.516°, 43.821°, 47.113°, and 48.092°, and the position error range of 2θ is ±0.1°.

5. The preparation method according to claim 4, characterized in that The purity of the pregnenolone used is greater than or equal to 98%wt.

6. The preparation method according to claim 4, characterized in that Using Cu-Kα radiation, the powder XRD ray diffraction pattern expressed in 2θ includes the following: 7.211°, 7.387°, 10.458°, 14.319°, 14.927°, 16.159°, 16.342°, 17.585°, 17.976°, 20.754°, 20.940°, 21.550°, 2 There are diffraction peaks at positions of 2.168°, 23.373°, 25.748°, 26.864°, 27.888°, 30.078°, 30.544°, 30.851°, 31.691°, 32.939°, 37.841°, 38.028°, 40.393°, and 45.807°, and the position error range of 2θ is ±0.1°.

7. The preparation method according to claim 4, characterized in that The dosage ratio of pregnenolone and ethanol is 1g:100mL.

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