Preparation process of benzocaine crystal form II

Abstract

The invention relates to the technical field of medicine crystallization, and particularly discloses a preparation process of a benzocaine crystal form II. According to the preparation process of the benzocaine crystal form II, the benzocaine is dissolved in the specific organic solvent, then the anti-solvent is added, the benzocaine is rapidly crystallized and separated out, and the high-purity blocky benzocaine crystal form II product which is complete in crystal habit and free of coalescence is prepared by controlling the adding proportion of the anti-solvent. The benzocaine crystal form II with high purity and high stability is prepared by adopting a solventing-out crystallization method, the preparation method is simple, the condition is mild, large-scale production is easy, the stability of product quality is ensured, and the benzocaine crystal form II has important significance for improving the drug treatment and clinical curative effect of benzocaine.

Description

Technical Field

[0001] The invention relates to the technical field of drug crystallization, and in particular to a preparation process of benzocaine crystal form II. Background Art

[0002] Benzocaine, as a local anesthetic, is widely used in the treatment of postoperative traumatic analgesia, ulcer pain, general itching and other symptoms. Its chemical name is ethyl para-aminobenzoate, which is a white crystalline powder with a slightly bitter and numb taste. It is easily soluble in ethanol and very slightly soluble in water. The crystal form of benzocaine has a significant impact on its solubility, stability, bioavailability and other properties, which in turn directly affects the efficacy and safety of the drug.

[0003] Various crystalline forms of benzocaine have been studied, and crystalline form II has been widely used in the field of pharmaceutical preparations due to its unique physicochemical properties, such as excellent thermal stability and solubility. In recent years, although some progress has been made in the research of benzocaine crystalline form II, including new synthetic routes and improved process flows, the existing technology has many limitations in the preparation of benzocaine crystalline form II, such as poor crystalline stability, complex preparation process, and high cost, which limits its widespread promotion in clinical applications.

[0004] The market demand for high-purity and high-stability benzocaine crystal form II is growing, especially in terms of improving drug efficacy and reducing side effects, the preparation technology of crystal form II is particularly important. In order to ensure the stability of raw materials and their preparations during preparation and storage, and improve the drug treatment and clinical efficacy of benzocaine, it is necessary to provide a preparation process of benzocaine crystal form II. Summary of the invention

[0005] In view of the problems of poor crystal stability, complex preparation process and high cost in the preparation of benzocaine crystal form II in the prior art, the present invention provides a preparation process of benzocaine crystal form II. The present invention adopts a solution crystallization method to prepare benzocaine crystal form II with high stability and high purity, and the method is simple to operate, easy to realize industrial scale production, and has high practical value.

[0006] In order to solve the above technical problems, the technical solution provided by the present invention is:

[0007] A preparation process of benzocaine crystal form II comprises the following steps:

[0008] Step 1, adding benzocaine raw material into an organic solvent to obtain a benzocaine solution; wherein the organic solvent is at least one of methanol, 1,4-dioxane, N,N-dimethylformamide, acetone, dimethyl sulfoxide or formamide;

[0009] Step 2, slowly adding the antisolvent into the benzocaine solution, growing crystals, separating the solid and the liquid, and drying to obtain benzocaine crystal form II;

[0010] Wherein, if the organic solvent is methanol, the volume ratio of the organic solvent to the antisolvent is 0.3:1 to 0.4:1; if the organic solvent is a solvent other than methanol, the volume ratio of the organic solvent to the antisolvent is 0.45:1 to 0.55:1.

[0011] Compared with the prior art, the preparation process of benzocaine crystal form II provided by the present invention is to first dissolve benzocaine in a specific organic solvent, then add an antisolvent to make benzocaine quickly crystallize and precipitate, and by controlling the addition ratio of the antisolvent, a high-purity block benzocaine crystal form II product with complete crystal habits and no agglomeration is prepared. The present invention adopts a solution crystallization method to prepare a high-purity and high-stability benzocaine crystal form II, and the preparation method is simple, the conditions are mild, and it is easy to mass-produce, which is conducive to ensuring the stability of product quality, and is of great significance for improving the drug treatment and clinical efficacy of benzocaine.

[0012] It should be noted that when a plurality of limited organic solvents are mixed, there is no particular limitation on the mixing ratio.

[0013] Furthermore, in step 1, the ratio of the benzocaine raw material to the organic solvent is 1 g:8 mL to 1 g:18 mL.

[0014] The preferred ratio can control the supersaturation of the system within a range that is conducive to good crystal growth, and impurities are not easily generated during the crystallization process, thereby helping to improve the purity of the product. At the same time, the preferred ratio is also conducive to regulating the crystallization nucleation rate and growth process to obtain blocky benzocaine form II, thereby improving the fluidity of the benzocaine product and facilitating storage and application.

[0015] Furthermore, in step 1, the purity of the benzocaine raw material is ≥98%.

[0016] It should be noted that when the purity of the benzocaine raw material is lower than 98%, the preparation process of the present invention can still obtain the benzocaine single crystal (form II), but the impurity content in the obtained crystalline product is relatively high. In order to facilitate subsequent applications, the present invention selects a benzocaine raw material with a purity of ≥98%.

[0017] As a specific embodiment of the present invention, after adding the benzocaine raw material into the organic solvent, the mixture is stirred at 300 rpm to 600 rpm for 4 h to 6 h to completely dissolve the benzocaine.

[0018] Furthermore, in step 2, the antisolvent is water.

[0019] Selecting non-toxic pure water as an antisolvent can promote the formation of high-quality crystals of benzocaine and inhibit the formation of non-target phases, thereby improving the purity of the prepared benzocaine crystal form II product without affecting the drug safety of benzocaine.

[0020] Furthermore, in step 2, the antisolvent is added at a rate of 1 mL / min to 2 mL / min.

[0021] The preferred antisolvent addition rate can effectively regulate the nucleation rate and growth rate of the crystal, promote the uniform growth of the crystal, and obtain a blocky benzocaine crystal form II with complete crystal habits, thereby improving the fluidity of the benzocaine product and improving the subsequent processability.

[0022] Furthermore, in step 2, the crystal growing time is 0.5h to 1h.

[0023] The preferred crystal growing time is beneficial to improving the particle size uniformity of the prepared benzocaine crystal form II and obtaining blocky benzocaine crystal form II with complete crystal habits.

[0024] It should be noted that in step 2, the temperature of the crystal growing is room temperature.

[0025] As a specific embodiment of the present invention, a peristaltic pump is used to slowly add the anti-solvent into the benzocaine solution.

[0026] Furthermore, in step 2, the drying temperature is 40° C. to 60° C., and the drying is performed under vacuum.

[0027] Furthermore, the benzocaine crystal form II has Figure 1 The X-ray powder diffraction pattern is shown.

[0028] Furthermore, the benzocaine crystal form II has characteristic diffraction peaks at diffraction angles of 2θ±0.2°=2θ±0.2°=8.50°, 11.64°, 16.78°, 17.28°, 18.88°, 20.04°, and 21.12°.

[0029] Furthermore, the benzocaine crystal form II also has characteristic diffraction peaks at one or more of 2θ±0.2°=21.58°, 21.96°, 23.36°, 24.00°, 25.62°, 26.32°, 27.10°, 28.78°, 30.44°, 34.38°, 36.16°, 37.98°, and 40.08°.

[0030] Furthermore, the melting point of the benzocaine crystal form II is 364±2K.

[0031] Furthermore, the infrared spectrum of the benzocaine crystal form II is at 502±2cm-1 、700±2cm -1 、768±2cm -1 、844±2cm -1 、1023±2cm -1 、1108±2cm -1 、1169±2cm -1 、1270±2cm -1 、1309±2cm -1 、1365±2cm -1 、1439±2cm -1 、1509±2cm -1 、1594cm -1 、1633±2cm -1 、1680±2cm -1 、1915cm -1 、2897±2cm -1 、2982±2cm -1 、3213±2cm -1 、3340±2cm -1 、3416±2cm -1 There are characteristic peaks.

[0032] It has been verified that the benzocaine crystal form prepared by the present invention is consistent with the data of benzocaine crystal form II reported in existing literature, which proves that the present invention has prepared high-purity single crystal crystal form II.

[0033] The preparation process of benzocaine crystal form II provided by the present invention is a high-stability, high-purity block benzocaine crystal form II product prepared by a solution crystallization method, and the product has good fluidity, can effectively avoid the agglomeration problem during transportation and storage, is convenient for subsequent processing and use, and helps to improve the market competitiveness of the product. In addition, the process of the present invention is simple to operate, the conditions are mild, it is convenient for industrial production, and has a high value of promotion and application. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 The X-ray powder diffraction pattern of the benzocaine crystal form II prepared in Example 1;

[0035] Figure 2 This is the TGA-DSC graph of the benzocaine crystal form II prepared in Example 1;

[0036] Figure 3 This is the infrared spectrum of the benzocaine crystal form II prepared in Example 1;

[0037] Figure 4 X-ray powder diffraction patterns of benzocaine raw material, comparative example 1, comparative example 2 and benzocaine crystalline product prepared in Example 1;

[0038] Figure 5 This is an X-ray powder diffraction pattern of the benzocaine crystal form II prepared in Example 1, which is sealed and placed in the dark for a long time at room temperature;

[0039] Figure 6 This is a microscope photograph of the benzocaine crystal form II prepared in Example 1. DETAILED DESCRIPTION

[0040] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0041] The benzocaine raw material used in the following examples and comparative examples is solid powder with a purity of ≥98%.

[0042] Crystal characterization methods:

[0043] 1. X-ray powder diffraction

[0044] Instrument: D / MAX-2500 (Rigaku, Japan);

[0045] Scanning range (2θ): 2.0°~50.0°;

[0046] Target: Cu-Kα radiation;

[0047] Light tube voltage: 40kV;

[0048] Light tube current: 100mA;

[0049] Scanning step: 0.02°.

[0050] 2. Differential Scanning Calorimetry

[0051] Instrument: Synchronous thermal analyzer (STA 449F3)

[0052] Temperature range: 30~300℃;

[0053] Heating rate: 10℃ / min;

[0054] Nitrogen flow rate: 20 mL / min.

[0055] 3. Infrared spectroscopy analysis

[0056] Instrument: Fourier transform infrared spectrometer (Bruker)

[0057] Scanning frequency range: 4000cm -1 Up to 400cm -1 ;

[0058] Resolution: 4cm -1 .

[0059] 4. Microscopic Analysis

[0060] The morphology of the samples was observed using a BX53 biological microscope (OLYMPUS, Japan). A small amount of the sample was placed on a glass slide and covered with a coverslip, and then the appropriate eyepiece and objective lens were adjusted for observation.

[0061] 5. High Performance Liquid Chromatography

[0062] Instrument: Waters e2998 high performance liquid chromatograph;

[0063] Chromatographic column: ZORBAX BONUS-RP (250mm*4.6mm, 5μm);

[0064] Mobile phase: glacial acetic acid: methanol = 60:40;

[0065] Flow rate: 1 mL / min;

[0066] Column temperature: 30°C;

[0067] Detection wavelength: 290nm.

[0068] Example 1

[0069] A preparation process of benzocaine crystal form II:

[0070] Step 1: Add the dried benzocaine raw material to methanol at a ratio of 1 g: 8 mL, and stir magnetically at 400 rpm for 4 h to obtain a benzocaine solution;

[0071] Step 2: Under stirring conditions, use a peristaltic pump to slowly add pure water to the above benzocaine solution at a rate of 1.5 mL / min, the volume ratio of methanol to pure water is 0.33:1, grow the crystals at room temperature for 0.5 h, filter, and vacuum dry at 50 ° C to constant weight to obtain benzocaine Form II with a yield of 81.4% and a purity of 99.7%.

[0072] The X-ray powder diffraction pattern of the benzocaine crystal form II prepared in this example is as follows: Figure 1 As shown, there are characteristic diffraction peaks at 2θ=8.50°, 11.64°, 16.78°, 17.28°, 18.88°, 20.04°, 21.12°, 21.58°, 21.96°, 23.36°, 24.00°, 25.62°, 26.32°, 27.10°, 28.78°, 30.44°, 34.38°, 36.16°, 37.98°, and 40.08°, which are consistent with the data of Form II in the literature, proving that the product prepared in this example is Benzocaine Form II.

[0073] The TGA-DSC graph of the benzocaine crystal form II prepared in this example is as follows: Figure 2 As shown in the figure, it can be seen that the melting point of benzocaine crystal form II is 364.55K.

[0074] The infrared spectrum of benzocaine crystal form II prepared in this example is as follows Figure 3 As shown in the figure, it can be seen that at 502±2cm -1 、700±2cm -1 、768±2cm -1 、844±2cm -1 、1023±2cm -1 、1108±2cm -1 、1169±2cm -1 、1270±2cm -1 、1309±2cm -1 、1365±2cm -1 、1439±2cm -1 、1509±2cm -1 、1594cm -1 、1633±2cm -1 、1680±2cm -1 、1915cm -1 、2897±2cm -1 、2982±2cm -1 、3213±2cm -1 、3340±2cm -1 、3416±2cm -1 There are characteristic peaks.

[0075] The optical microscope image of the benzocaine crystal form II prepared in this example is as follows: Figure 6 As shown in the figure, it can be seen that the benzocaine crystal form II prepared in this example is a block crystal with complete crystal habit and no agglomeration.

[0076] Example 2

[0077] A preparation process of benzocaine crystal form II:

[0078] Step 1: Add the dried benzocaine raw material to 1,4-dioxane at a ratio of 1 g:9 mL, and stir magnetically at 600 rpm for 4 h to obtain a benzocaine solution;

[0079] Step 2: Under stirring conditions, use a peristaltic pump to slowly add pure water to the above benzocaine solution at a rate of 1 mL / min, the volume ratio of 1,4-dioxane to pure water is 0.5:1, grow the crystals at room temperature for 1 hour, filter, and vacuum dry at 55°C to constant weight to obtain benzocaine Form II with a yield of 72.1% and a purity of 99.8%.

[0080] The characterization data of X-ray powder diffraction, TGA-DSC and infrared spectrum of the crystals obtained in this example are basically the same as those in Example 1, proving that the product prepared in this example is benzocaine crystal form II.

[0081] Example 3

[0082] A preparation process of benzocaine crystal form II:

[0083] Step 1: Add the dried benzocaine raw material to N,N-dimethylformamide at a ratio of 1 g:8 mL, and stir magnetically at 300 rpm for 6 h to obtain a benzocaine solution;

[0084] Step 2: Under stirring conditions, use a peristaltic pump to slowly add pure water to the above benzocaine solution at a rate of 2 mL / min, the volume ratio of N,N-dimethylformamide to pure water is 0.45:1, grow the crystals at room temperature for 0.5-1 h, filter, and vacuum dry at 50°C to constant weight to obtain benzocaine Form II with a yield of 71.7% and a purity of 99.8%.

[0085] The characterization data of X-ray powder diffraction, TGA-DSC and infrared spectrum of the crystals obtained in this example are basically the same as those in Example 1, proving that the product prepared in this example is benzocaine crystal form II.

[0086] Example 4

[0087] A preparation process of benzocaine crystal form II:

[0088] Step 1: Add the dried benzocaine raw material to acetone at a ratio of 1 g:10 mL, and stir magnetically at 500 rpm for 5 h to obtain a benzocaine solution;

[0089] Step 2: Under stirring conditions, pure water was slowly added to the above benzocaine solution at a rate of 1.5 mL / min using a peristaltic pump, the volume ratio of acetone to pure water was 0.51:1, the crystals were grown at room temperature for 1 h, filtered, and vacuum dried at 45 ° C to constant weight to obtain benzocaine Form II with a yield of 77.2% and a purity of 99.7%.

[0090] The characterization data of X-ray powder diffraction, TGA-DSC and infrared spectrum of the crystals obtained in this example are basically the same as those in Example 1, proving that the product prepared in this example is benzocaine crystal form II.

[0091] Example 5

[0092] A preparation process of benzocaine crystal form II:

[0093] Step 1: Add the dried benzocaine raw material to dimethyl sulfoxide at a ratio of 1 g: 8 mL, and stir magnetically at 450 rpm for 4 h to obtain a benzocaine solution;

[0094] Step 2: Under stirring conditions, use a peristaltic pump to slowly add pure water to the above benzocaine solution at a rate of 2 mL / min, the volume ratio of dimethyl sulfoxide to pure water is 0.55:1, grow the crystals at room temperature for 0.5 h, filter, and vacuum dry at 40 ° C to constant weight to obtain benzocaine Form II with a yield of 87.1% and a purity of 99.5%.

[0095] The characterization data of X-ray powder diffraction, TGA-DSC and infrared spectrum of the crystals obtained in this example are basically the same as those in Example 1, proving that the product prepared in this example is benzocaine crystal form II.

[0096] Example 6

[0097] A preparation process of benzocaine crystal form II:

[0098] Step 1: Add the dried benzocaine raw material to formamide at a ratio of 1 g:18 mL, and stir magnetically at 550 rpm for 5 h to obtain a benzocaine solution;

[0099] Step 2: Under stirring conditions, use a peristaltic pump to slowly add pure water to the above benzocaine solution at a rate of 1 mL / min, the volume ratio of formamide to pure water is 0.49:1, grow the crystals at room temperature for 1 hour, filter, and vacuum dry at 60°C to constant weight to obtain benzocaine Form II with a yield of 77.1% and a purity of 99.6%.

[0100] The characterization data of X-ray powder diffraction, TGA-DSC and infrared spectrum of the crystals obtained in this example are basically the same as those in Example 1, proving that the product prepared in this example is benzocaine crystal form II.

[0101] Comparative Example 1

[0102] This comparative example provides a preparation process of benzocaine crystals, which is different from Example 1 only in that methanol is replaced by anhydrous ethanol, and specifically comprises the following steps:

[0103] Step 1: Add the dried benzocaine raw material to anhydrous ethanol at a ratio of 1 g: 8 mL, and stir magnetically at 400 rpm for 4 h to obtain a benzocaine solution;

[0104] Step 2: Under stirring conditions, use a peristaltic pump to slowly add pure water to the above benzocaine solution at a rate of 1.5 mL / min, the volume ratio of methanol to pure water is 0.33:1, grow the crystals at room temperature for 0.5 h, filter, and vacuum dry at 50° C. to constant weight to obtain a benzocaine crystalline product, recorded as mixed crystal (A).

[0105] The X-ray powder diffraction pattern of the benzocaine crystalline product prepared in this comparative example is as follows Figure 4 As shown in the figure, it can be seen that the product prepared in this comparative example is a mixed crystal of crystal form I and crystal form II.

[0106] Comparative Example 2

[0107] This comparative example provides a method for preparing benzocaine crystals, which is different from Example 1 only in the ratio of methanol to pure water, and specifically comprises the following steps:

[0108] Step 1: Add the dried benzocaine raw material to methanol at a ratio of 1 g: 8 mL, and stir magnetically at 400 rpm for 4 h to obtain a benzocaine solution;

[0109] Step 2: Under stirring conditions, use a peristaltic pump to slowly add pure water to the above benzocaine solution at a rate of 1.5 mL / min, the volume ratio of methanol to pure water is 0.2:1, grow the crystals at room temperature for 0.5 h, filter, and vacuum dry at 50° C. to constant weight to obtain a benzocaine crystalline product, recorded as mixed crystal (B).

[0110] The X-ray powder diffraction pattern of the benzocaine crystalline product prepared in this comparative example is as follows Figure 4 As shown in the figure, it can be seen that the product prepared in this comparative example is a mixed crystal of crystal form I and crystal form II.

[0111] Liquidity test

[0112] The angle of repose of the benzocaine crystal form I and the benzocaine raw material prepared in the example was measured according to the method provided in the "Guidelines for Determination of Powder Flowability" issued by the State Pharmacopoeia Commission. The angle of repose of the crystal form II shown in the table was taken as the average of all the examples. The results are shown in Table 1.

[0113] Table 1

[0114]

[0115]

[0116] The above results prove that the blocky benzocaine crystal form II product prepared in the embodiment of the present invention has a smaller angle of repose and better fluidity than the benzocaine raw material, can effectively avoid the agglomeration problem during transportation and storage, and has better drugability and processability.

[0117] Bulk and tapped density testing

[0118] Bulk density test: Place an appropriate amount of product into a 10mL measuring cylinder, shake it slightly horizontally to make the upper part of the powder in the measuring cylinder flat, and read the volume.

[0119] Tap density: Oscillate the bulk density measuring cylinder repeatedly until the volume of powder in the measuring cylinder stops decreasing and read the volume.

[0120] Compression = (tapped density - bulk density) / tapped density. Compression is a simple method to predict powder fluidity. Since the bulk density, particle size, shape, surface area, moisture and adhesion of the powder material will affect the compression, compression is generally used as an indirect indicator to measure these parameters. The results are shown in Table 2. The data in the table are the average bulk density, tapped density and compression of the crystal form II products obtained in the above 6 embodiments.

[0121] Table 2

[0122] sample Bulk density / (g / mL) Tap density / (g / mL) Compression / % Benzocaine crystal form II 0.5480 0.6864 20.17％

[0123] Stability test

[0124] The benzocaine crystal form II prepared in Example 1 and the benzocaine raw material were subjected to an accelerated stability study. The purity of the samples was determined by a Waters e2998 high performance liquid chromatograph. The test results are shown in Table 3.

[0125] Table 3

[0126]

[0127]

[0128] It can be seen from the above table that the stability of the block benzocaine crystal form II prepared in the embodiment of the present invention is better than the stability of the benzocaine raw material, and the crystal form does not change during the storage process, which helps to improve the quality of the benzocaine preparation product.

[0129] The benzocaine crystal form II prepared in Example 1 was sealed and stored at room temperature and pressure in the dark for 2 weeks. The X-ray powder diffraction patterns of the samples at different storage times were as follows: Figure 5 As shown, the results show that no obvious changes were found in the color, morphology and crystal form of the sample, proving that the benzocaine crystal form II product prepared in the embodiment of the present invention has good long-term stability.

[0130] In summary, the preparation method of benzocaine crystal form II provided by the present invention has the advantages of simple process and high purity of prepared crystals. The benzocaine crystal form II prepared by the present invention is a block crystal with an angle of repose between 40.9° and 44.13° and a compression degree between 18.17% and 22.81%, which can improve the fluidity of benzocaine, facilitate subsequent storage and use, and has higher stability than commercially available benzocaine raw materials, and has great advantages in pharmaceutical preparations.

[0131] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modification, equivalent substitution or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A process for preparing benzocaine crystal form II, characterized in that: The following steps are involved: Step 1, adding benzocaine raw material into an organic solvent to obtain a benzocaine solution; wherein the organic solvent is at least one of methanol, 1,4-dioxane, N,N-dimethylformamide, acetone, dimethyl sulfoxide or formamide; Step 2, slowly adding the antisolvent into the benzocaine solution, growing crystals, separating the solid and the liquid, and drying to obtain benzocaine crystal form II; Wherein, if the organic solvent is methanol, the volume ratio of the organic solvent to the antisolvent is 0.3:1 to 0.4:1; if the organic solvent is a solvent other than methanol, the volume ratio of the organic solvent to the antisolvent is 0.45:1 to 0.55:

1.

2. The process for preparing benzocaine crystal form II according to claim 1, characterized in that: In step 1, the ratio of the benzocaine raw material to the organic solvent is 1 g:8 mL to 1 g:18 mL.

3. The process for preparing the benzocaine crystal form II according to claim 1, characterized in that: In step 1, the purity of the benzocaine raw material is ≥98%.

4. The process for preparing benzocaine crystal form II according to claim 1, characterized in that: In step 2, the antisolvent is water.

5. The process for preparing benzocaine crystal form II according to claim 1, characterized in that: In step 2, the antisolvent is added at a rate of 1 mL / min to 2 mL / min.

6. The process for preparing benzocaine crystal form II according to claim 1 or 5, characterized in that: In step 2, the crystal growing time is 0.5h to 1h.

7. The process for preparing benzocaine crystal form II according to claim 1, characterized in that: The benzocaine crystal form II has an X-ray powder diffraction pattern as shown in FIG1 .

8. The process for preparing benzocaine crystal form II according to claim 1, characterized in that: The benzocaine crystal form II has characteristic diffraction peaks at diffraction angles of 2θ±0.2°=8.50°, 11.64°, 16.78°, 17.28°, 18.88°, 20.04°, and 21.12°.

9. The process for preparing benzocaine crystal form II according to claim 8, characterized in that: The benzocaine crystal form II also has characteristic diffraction peaks at one or more of 2θ±0.2°=21.58°, 21.96°, 23.36°, 24.00°, 25.62°, 26.32°, 27.10°, 28.78°, 30.44°, 34.38°, 36.16°, 37.98°, and 40.08°.

10. The process for preparing benzocaine crystal form II according to claim 1, characterized in that: The melting point of the benzocaine crystal form II is 364±2K; Its infrared spectrum is 502±2cm -1 、700±2cm -1 、768±2cm -1 、844±2cm -1 、1023±2cm -1 、1108±2cm -1 、1169±2cm -1 、1270±2cm -1 、1309±2cm -1 、1365±2cm -1 、1439±2cm -1 、1509±2cm -1 、1594cm -1 、1633±2cm -1 、1680±2cm -1 、1915cm -1 、2897±2cm -1 、2982±2cm -1 、3213±2cm -1 、3340±2cm -1 、3416±2cm -1 There are characteristic peaks.

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