Doxidine crystal form and preparation method and application thereof

Abstract

The invention relates to the technical field of pesticide crystal form molecules, and discloses a dodine crystal form as well as a preparation method and application thereof. The dodine crystal form has characteristic absorption peaks when 2theta is 6.40 + / -0.2 degrees and 19.20 + / -0.2 degrees in an X-ray powder diffraction pattern of the dodine crystal form under Cu-K alpha radiation at the temperature of 25 DEG C; the crystal form has a block-shaped or sheet-shaped crystal habit. According to the invention, the crystal form singleness of the product in the production, storage and transportation processes can be ensured, and the stability of the product is ensured; and the crystal habit is qualitatively characterized by PXRD, so that the quality standard of the original medicine and the preparation can be more effectively controlled, and the standard is provided for the practical application process.

Description

Technical Field

[0001] The present invention relates to the technical field of pesticide crystal molecules, and in particular to a polydapoxetine crystal form and a preparation method and application thereof. Background Art

[0002] Dodine, as a broad-spectrum protective fungicide, has played an important role in the prevention and control of agricultural diseases since its development in the 1950s. Its chemical name is dodecylguanidine acetate (C 15 H 33 N3O2), molecular weight 287.44, CAS number 2439-10-3, has unique physical and chemical properties: melting point 136 ° C, vapor pressure 5 × 10 -6 Pa (20°C), water solubility 630 mg / L (25°C), slightly soluble in DMSO and methanol. This compound exerts its bactericidal effect by disrupting the structure and function of pathogen cell membranes. Specifically, the compound exhibits the following effects: ① The dodecyl chain inserts into the phospholipid layer of the fungal cell membrane, altering membrane permeability and leading to leakage of intracellular substances; ② The guanidine group binds to negatively charged regions on the membrane surface, inhibiting the activity of membrane-bound enzymes; and ③ Interfering with the pathogen's oxidative phosphorylation process, blocking energy metabolism. Metabolism in plants primarily occurs through methyltransferases and oxidative cleavage of the dodecyl group to produce sarcosine, which has both protective effects and early therapeutic activity.

[0003] As a broad-spectrum protective fungicide, Duoguoding formulations mainly include three types: wettable powder (WP, accounting for 58%), suspension concentrate (SC, 27%) and water dispersible granules (WDG, 15%). It achieves efficient prevention and control by destroying the permeability of pathogen cell membranes (inhibiting membrane-bound enzyme activity by more than 90%). WP formulations (such as 65% ) low cost (about RMB 12,000 per ton), but the suspension rate is only 60-70%; SC (such as 30%) ) has both stability (storage period of 3 years) and leaf adhesion (contact angle ≤ 50°), but the nano-scale crushing process increases the production cost by 40%; WDG (such as 40%) ) has become the mainstream trend due to its dust-free nature, but granulation consumes a high amount of energy (200 kWh per ton). The global market is expected to reach US$430 million in 2024, with companies such as BASF and Syngenta holding a 75% share. It is primarily used to control apple scab (91% efficacy), citrus canker (88% efficacy), and vegetable downy mildew. In recent years, the application of nano-encapsulation technology (particle size ≤ 200 nm) and biodegradable excipients (such as polylactic acid) has boosted the environmental friendliness of formulations by 30%.

[0004] Generally speaking, different crystalline forms of the same drug exhibit varying stability, leading to significant differences in production, storage, transportation, and efficacy. In particular, drugs with multiple metastable crystalline forms can undergo transformations during production, storage, and transportation, leading to various problems such as crystallization, agglomeration, and reduced suspension efficiency, potentially impacting their ultimate efficacy. Furthermore, the morphology of pesticide technicals (such as particle size, crystal habit, and surface roughness) directly impacts the dispersibility, stability, and bioavailability of formulations. Crystal habit, a key characteristic of crystal morphology and surface structure, has been a key research focus in pesticide science in recent years. Traditional pesticide technical synthesis processes often overlook crystal habit regulation, resulting in different crystal habits for the same compound depending on crystallization conditions, significantly impacting formulation performance. For example, needle-shaped crystals, due to their large specific surface area and high surface energy, are prone to Ostwald ripening in suspension concentrates (SCs), leading to particle coarsening and stratification during storage. Meanwhile, plate-shaped crystals, due to mechanical interlocking, can cause decreased flowability and dust contamination during wettable powder processing. In addition, crystal habit can also affect drug release by changing dissolution kinetics. Spherical or equiaxed crystals can increase leaf retention time and bioavailability due to their isotropic dissolution properties, while fibrous crystals may shorten the duration of drug efficacy due to rapid disintegration. In recent years, the introduction of crystal engineering technologies such as solvent-mediated recrystallization and additive regulation has provided new approaches for the targeted design of pesticide crystal habits, but the challenges in formulation adaptability, cost controllability, and environmental compatibility still need to be further explored. Therefore, systematic research on the structure-activity relationship between crystal habit and pesticide formulation performance is of great significance for the development of highly effective, stable, and low-environmental-risk pesticide products. Summary of the Invention

[0005] The present invention provides a stable crystal form of dodine, which is named as the dodine crystal form, and provides a preparation method and application thereof.

[0006] In order to achieve the above-mentioned object, the first aspect of the present invention provides a polydopamine crystalline form, wherein the polydopamine crystalline form shows characteristic absorption peaks at 2θ of 6.40±0.2° and 19.20±0.2° in an X-ray powder diffraction pattern at 25°C and Cu-Kα radiation; the crystal habit of the polydopamine crystalline form is blocky or flaky.

[0007] The second aspect of the present invention provides a method for preparing the polydapoxetine crystalline form according to the first aspect, wherein the method comprises the following steps:

[0008] (1) dissolving the original drug of dodine in a solvent to obtain a dodine solution;

[0009] (2) heating the doxorubicin solution, stirring it, cooling it for crystallization, and filtering it;

[0010] (3) drying the filtered product to obtain the polymorph; the crystal habit is blocky; or,

[0011] The method comprises the following steps:

[0012] (i) adding a methanol solution of dodine technical dropwise into pure acetonitrile;

[0013] (ii) filtering after completion of the dropwise addition;

[0014] (iii) drying the filtered product to obtain the polymorphic crystalline form; the crystal habit is flaky.

[0015] The third aspect of the present invention provides a polydapoxetine crystalline form obtained according to the preparation method described in the second aspect.

[0016] The fourth aspect of the present invention provides use of the polydapoxetine crystalline form according to the first aspect or the third aspect in preparing a fungicide.

[0017] Through the above technical solution, the beneficial technical effects achieved by the present invention are as follows:

[0018] (1) The present invention provides a stable crystal form of the insecticide doxorubicin and characterizes its crystal habits, and studies the practical characteristics of the original drug with different crystal habits and its application in formulations.

[0019] (2) The polymorph provided by the present invention has significantly excellent technical effects in terms of formulation stability, hygroscopicity, solubility, etc.; specific crystal habits such as block crystals and plate crystals are dominant crystals, which have significantly improved formulation performance.

[0020] (3) The present invention can ensure the crystal form uniformity of the product during production, storage and transportation, and ensure the stability of the product; and through the qualitative characterization of its crystal habit by PXRD, it can more effectively control the quality standards of its technical and preparations, and provide standards for its actual application process. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is the XRD powder diffraction spectrum of the polymorph prepared in Example 1 of the present invention:

[0022] Figure 2 This is the XRD powder diffraction pattern of the polymorph prepared in Example 2 of the present invention:

[0023] Figure 3 The polymorphism-crystal habit of the polymorphs prepared in Examples 1-2 and Comparative Example 1;

[0024] Wherein, a is the crystal habit diagram of the blocky multi-fruit prepared in Example 1;

[0025] b is the crystal habit diagram of the flake polymorph prepared in Example 2;

[0026] c is a columnar polymorphic crystal habit diagram prepared in Comparative Example 1;

[0027] d is a partial enlarged view of the bulk crystal habit prepared in Example 1;

[0028] Figure 4 It is a comparison of the PXRD diffraction characteristics of multiple fixed crystal forms with different crystal habits. DETAILED DESCRIPTION

[0029] The endpoints of the ranges and any values ​​disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered to be specifically disclosed herein.

[0030] A first aspect of the present invention provides a polydopamine crystalline form, wherein the polydopamine crystalline form shows characteristic absorption peaks at 2θ of 6.40±0.2° and 19.20±0.2° in an X-ray powder diffraction pattern at 25°C and Cu-Kα radiation; the crystal habit of the polydopamine crystalline form is blocky or flaky.

[0031] In some embodiments of the present invention, the X-ray powder diffraction pattern of the polymorph at 25°C and Cu-Kα radiation also shows at least two of the following reflections expressed in 2θ values: 11.48±0.2°, 13.00±0.2°, 15.10±0.2°, 20.04±0.2°, 22.26±0.2°, 24.86±0.2°, 25.82±0.2°, and 32.10±0.2° have characteristic absorption peaks.

[0032] In some embodiments of the present invention, the polymorphic form of polymorphic acid shows characteristic absorption peaks at 6.40±0.2°, 13.00±0.2°, 19.20±0.2°, and 24.86±0.2° expressed in 2θ values ​​in an X-ray powder diffraction pattern at 25°C and Cu-Kα radiation.

[0033] In some embodiments of the present invention, the X-ray powder diffraction pattern of the polymorph at 25°C and Cu-Kα radiation shows characteristic absorption peaks at 6.40±0.2°, 11.48±0.2°, 13.00±0.2°, 19.20±0.2°, 20.04±0.2°, and 24.86±0.2° expressed in 2θ values.

[0034] In some embodiments of the present invention, the X-ray powder diffraction pattern of the polymorph at 25°C and Cu-Kα radiation shows characteristic absorption peaks at 6.40±0.2°, 11.48±0.2°, 13.00±0.2°, 15.10±0.2°, 19.20±0.2°, 20.04±0.2°, 22.26±0.2°, 24.86±0.2°, 25.82±0.2°, and 32.10±0.2°, expressed as 2θ values.

[0035] In some embodiments of the present invention, in the X-ray powder diffraction pattern of the polymorph at 25°C and Cu-Kα radiation, the peak area ratio of 2θ=19.20±0.2° and 2θ=6.4±0.2° is 0.1-10.

[0036] In some embodiments of the present invention, in the X-ray powder diffraction pattern of the polymorph at 25°C and Cu-Kα radiation, the peak area ratio at 2θ=19.20±0.2° and 2θ=6.4±0.2° is 0.5-5, preferably 1-3, and more preferably 2.57.

[0037] In some embodiments of the present invention, in the X-ray powder diffraction pattern of the polymorph at 25°C and Cu-Kα radiation, the peak area ratio of 2θ=19.20±0.2° and 2θ=6.4±0.2° is 0.045.

[0038] In some embodiments of the present invention, the polymorph has the following characteristics: Figure 1 or Figure 2 The X-ray powder diffraction pattern is shown.

[0039] In some embodiments of the present invention, the content of dodine in the dodine crystalline form is at least 98%.

[0040] The second aspect of the present invention provides a method for preparing the polydapoxetine crystalline form according to the first aspect, wherein the method comprises the following steps:

[0041] (1) dissolving the original drug of dodine in a solvent to obtain a dodine solution;

[0042] (2) heating the doxorubicin solution, stirring it, cooling it for crystallization, and filtering it;

[0043] (3) Drying the filtered product to obtain the polydextrose crystal form; the crystal habit is blocky. In the present invention, the polydextrose crystal form prepared by the above method is blocky particles. "Heating and stirring" means gradually heating to a certain temperature while stirring.

[0044] In some embodiments of the present invention, the solvent is selected from a mixed solvent of water and a lower carbon alcohol. Preferably, the volume ratio of water to lower carbon alcohol in the mixed solvent is 1:5-10, preferably 1:8. The lower carbon alcohol refers to an alcohol having no more than 5 carbon atoms, more preferably methanol.

[0045] In some embodiments of the present invention, in the dodine solution, the volume of the low-carbon alcohol solvent accounts for at least 90% of the total volume of the solvent.

[0046] In some embodiments of the present invention, in the dodine solution, the mass-to-volume ratio of dodine technical to solvent is 1:2-1:30, preferably 1:5-1:15, where the mass is measured in g and the volume is measured in mL.

[0047] In some embodiments of the present invention, the stirring method is magnetic stirring or mechanical stirring.

[0048] In some embodiments of the present invention, the temperature reached by the heating is 20-100°C, preferably 30-90°C, and more preferably 65°C.

[0049] In some embodiments of the present invention, the stirring speed is above 100 rpm, preferably 400 rpm.

[0050] In some embodiments of the present invention, the cooling crystallization method is programmed cooling, and the cooling rate is 0.5-1°C / min.

[0051] In some embodiments of the present invention, the crystallization endpoint temperature is 0-5°C.

[0052] In some embodiments of the present invention, the filtration uses filter paper with a mesh size of 100 or above.

[0053] In the present invention, the filter cake obtained by filtration is washed with acetonitrile and then dried.

[0054] In some embodiments of the present invention, the drying temperature is above 50°C, preferably 70-100°C.

[0055] In some embodiments of the present invention, the drying time is more than 10 hours, preferably more than 20 hours, and more preferably 24 hours.

[0056] In some embodiments of the present invention, the drying is performed using a constant temperature drying device, preferably a constant temperature blast drying oven.

[0057] Alternatively, a reverse addition of solvent is used for crystallization, wherein the methanol solution of dodine is added dropwise to the pure acetonitrile solution. The method specifically comprises the following steps:

[0058] (i) adding a methanol solution of dodine technical dropwise into pure acetonitrile;

[0059] (ii) filtering after completion of the dropwise addition;

[0060] (iii) drying the filtered product to obtain the polymorphic crystalline form; the crystal habit is flaky.

[0061] In the above steps, the methanol and acetonitrile are at least analytical grade, the temperature is maintained at room temperature, and in particular, the temperatures of the methanol and acetonitrile are ensured to be comparable, and the dropping process is stirred by magnetic stirring or mechanical stirring.

[0062] The third aspect of the present invention provides a polydapoxetine crystalline form obtained according to the preparation method described in the second aspect.

[0063] The fourth aspect of the present invention provides use of the polydapoxetine crystalline form according to the first aspect or the third aspect in preparing a fungicide.

[0064] The present invention will be described in detail below through examples.

[0065] In the following examples and comparative examples, if no specific conditions are specified, the experiments were carried out under conventional conditions or those recommended by the manufacturer. All reagents and instruments used, if no manufacturer is specified, are commercially available conventional products.

[0066] Example 1

[0067] This example is used to illustrate the preparation of blocky polycarboxylic acid crystals by cooling crystallization in a mixed solvent of water and low-carbon alcohol.

[0068] Weigh 15 g of doxorubicin and place it in a 250 mL flat-bottom flask. Add 100 mL of mixed solvent (V 水 :V 甲醇 =1:8), add a magnetic particle, and stir continuously with a magnetic stirrer at a speed of 400 rpm; gradually heat to 65 ° C while stirring, and after the dodine is completely dissolved, cool and crystallize at a cooling rate of 1 ° C / min, cool to 0-5 ° C, crystallization is completed, filter, and dry to obtain the dodine crystal form, the crystal habit is block particles (see Figure 3 a).

[0069] Example 2

[0070] This example is used to illustrate the preparation of flaky polysorbate crystals by reverse addition crystallization in acetonitrile.

[0071] Measure 1L of acetonitrile and place it in a 2L beaker. Add a magnet and rotate at 100rpm. Weigh 15g of dodine and dissolve it in 100mL of methanol. Add it dropwise to 1L of pure acetonitrile at a rate of 100 drops / min. Keep both solvents at room temperature. After the addition is complete, filter and dry to obtain the dodine crystal form. The crystal habit is a flaky dodine solid (see Figure 3 b).

[0072] Comparative Example 1

[0073] Weigh 15 g of dodine and place it in a 250 mL flat-bottom flask, add 150 mL of methanol, add a magnet, and stir continuously with a magnetic stirrer at a speed of 400 rpm; gradually raise the temperature to 65°C while stirring. After the dodine is completely dissolved, control the temperature at 0-15°C and cool to crystallize. After the crystallization is completed, filter and dry to obtain the dodine crystal form, which has a crystal habit of columnar particles (see Figure 3 c).

[0074] Comparative Example 2

[0075] 15 g of dodine was weighed and placed in a 250 mL flat-bottom flask. 150 mL of toluene was added, and a magnet was added. The mixture was continuously stirred with a magnetic stirrer at a speed of 400 rpm. The temperature was gradually raised to 65° C. while stirring. After the dodine was completely dissolved, the temperature was controlled at -5 to 0° C. and cooled to crystallize. After the crystallization was completed, the mixture was filtered and dried to obtain a crystalline form of dodine with a crystal habit of columnar particles.

[0076] Test Example 1: Characterization of the polymorph of Dodine

[0077] The polymorph prepared in Example 1 was subjected to X-ray powder diffraction analysis. The test method was as follows: X-ray powder diffractometer, with Cu-Kα rays as the diffraction source, λ = 0.154 nm, Cu (40 kV, 15 mA) (starting angle 2θ = 0°, ending angle 2θ = 50°, step 0.01°, scanning speed 1° / min), and data processing was performed using JADE software.

[0078] By analyzing the X-ray powder diffraction data (see Table 1) and the spectrum (see Figure 1 ), and obtained the characteristic X-ray powder diffraction of the multi-fruit crystalline form, and its characteristic diffraction 2θ angles were 6.40±0.2°, 11.48±0.2°, 13.00±0.2°, 15.10±0.2°, 19.20±0.2°, 20.04±0.2°, 22.26±0.2°, 24.86±0.2°, 25.82±0.2°, and 32.10±0.2°.

[0079] The specific XRD data are shown in Table 1.

[0080] Table 1

[0081]

[0082]

[0083] The flake-like crystals prepared in Example 2 were subjected to X-ray powder diffraction test under the same test conditions as above, and the flake-like crystal X-ray powder diffraction data (see Table 2) and the spectrum (see Figure 2 ):

[0084] Table 2 X-ray powder diffraction data of lamellar crystal habit

[0085] Serial number 2-Theta Serial number 2-Theta 1 6.42 9 25.12 2 11.699 10 25.855 3 12.98 11 26.36 4 19.22 12 32.08 5 19.64 13 33.22 6 21.958 14 40.18 7 22.26 15 41.44 8 24.88 16 47.34

[0086] Test Example 2: Comparison of the morphology and crystal habit of polymorphs prepared by different methods

[0087] The dodine crystals prepared in Examples 1-2 and Comparative Examples 1-2 were microscopically observed at a magnification of 10 x 40, and photographs were taken of their morphologies, revealing different crystal habits of the dodine crystals. Example 1 produced blocky dodine crystals with good morphology. The method used in Example 2 produced flake dodine crystals, while Comparative Examples 1 and 2 produced columnar dodine crystals.

[0088] Test Example 3: Comparison of multi-characteristic XRD powder diffraction characteristics of different crystal habits

[0089] The X-ray powder diffraction test of the polymorph prepared in Examples 1, 2 and Comparative Example 1 revealed Figure 1 、 Figure 2 and Figure 4 Test method: X-ray powder diffractometer, with Cu-Kα ray as diffraction source, λ = 0.154nm, Cu (40kV, 15mA) (starting angle 2θ = 0°, ending angle 2θ = 50°, step 0.01°, scanning speed 1° / min), JADE software was used for data processing to obtain multiple characteristic XRD powder diffraction characteristics of different crystal habits.

[0090] As shown in Table 3 and Figure 4 As shown in the figure, by comparison, it is found that the peak area at 2θ=19.2±0.2° of the columnar crystal habit (Comparative Example 1) is significantly higher than that at 2θ=6.4±0.2°, and the peak area ratio (S 19.2 / S 6.4 ) is 17.8, which represents a columnar crystal habit; the peak area at 2θ = 6.4 ± 0.2° of the plate-like crystal (Example 2) is significantly higher than the peak area ratio at 2θ = 19.2 ± 0.2° (S 19.2 / S 6.4 ) is 0.045, which represents a lamellar crystal habit; while the peak areas at 2θ=19.2±0.2° and 2θ=6.4±0.2° of the bulk crystal are similar in height, and the peak area ratio (S19.2 / S 6.4 ) is 2.57, which indicates a massive crystal habit. Therefore, the peak area ratio of 2θ = 19.2 ± 0.2° to 2θ = 6.4 ± 0.2° is a clear characteristic of the crystal habit of the multi-fruit.

[0091] Therefore, the peak area ratio (S 19.2 / S 6.4 ) as characteristic data for multi-fruit crystal habits, and its crystal form was digitally constructed. The peak area ratio of columnar crystals (Comparative Example 1) can be as high as 17.8, the peak area ratio of plate-like crystals (Example 2) is 0.045, and the peak area ratio of blocky crystals (Example 1) is 2.57 (see Table 3).

[0092] Table 3 Intensity ratio (peak area) of characteristic diffraction peaks of different crystal habits

[0093] Crystal Habit <![CDATA[S 6.4 ]]> <![CDATA[S 19.2 ]]> <![CDATA[Peak area ratio (S 19.2 / S 6.4 )]]> Columnar 113357 2022624 17.84295632 Flake 2152535 96439 0.044802524 Block 252932 649020 2.565986115

[0094] Test Example 4: Comparison of bulk density and tap density

[0095] 10 g of the crystals prepared in Examples 1-2 and Comparative Example 1 were respectively weighed and placed in a measuring cylinder, and the solid volume thereof was measured respectively; the cylinders were then manually vibrated 50 times, and the solid volume thereof was read again.

[0096] Table 4 Comparison of bulk density and solid density of different crystal habit

[0097] category Bulk density g / mL Tap density g / mL Block crystals 0.29 0.37 plate-like crystals 0.26 0.34 columnar crystals 0.12 0.20

[0098] As can be seen from Table 4, the bulk density and tap density of columnar crystals are lower than those of flake crystals and block crystals, which indicates that the columnar polymorph samples are more fluffy and have a larger specific surface area.

[0099] Plate-shaped and block-shaped crystals are easier to grind and can store more per unit volume, saving storage and transportation costs. Columnar crystals are difficult to grind and have strong electrostatic attraction, making them difficult to handle. Therefore, block-shaped and plate-shaped crystals are the preferred crystal types for use.

[0100] Test Example 5: Fluidity Test

[0101] With reference to GB 11986-1989 "Surface-active agent powders and particles - Determination of the angle of repose" or ISO 4324-1977, the fluidity index - angle of repose of the polyols of different crystal habits obtained in Examples 1-2 and Comparative Example 1 was measured.

[0102] The particle size test was carried out according to the laser diffraction method in the General Chapter IV of the Chinese Pharmacopoeia, “Determination of Particle Size and Particle Size Distribution”. The results are shown in Table 5.

[0103] Table 5 Test data of particle flowability of different crystal habits

[0104] category Angle of repose (degrees) Particle size (D10 um) Particle size (D50 um) Particle size (D90 um) Block crystals 5 45.3 214.8 377.9 plate-like crystals 40 10.0 30.1 100.6 columnar crystals 60 2.5 9.6 27.4

[0105] It can be seen from Table 5 that the angle of repose of blocky crystals is significantly smaller than that of columnar crystals and lamellar crystals; the angle of repose of lamellar crystals is smaller than that of columnar crystals; the particle size of blocky crystals is larger than that of lamellar crystals, and lamellar crystals are larger than that of columnar crystals.

[0106] Therefore, from the perspective of fluidity, blocky polysorbate has the best fluidity and is more suitable for use in preparations.

[0107] Test Example 6: Filterability Test

[0108] Equal masses of different crystal habits (blocky, flaky, and columnar crystal habits of polyol in Examples 1-2 and Comparative Example 1) were sequentially placed in the same Büchner funnel and filtered using the same vacuum pump at the same vacuum pressure. 250 mL of water was filtered separately, and the time taken was examined (see Table 6).

[0109] Table 6 Filterability test results of different crystal habit polymorphs

[0110] category Volume (mL) Time(s) Use per 100 ml columnar crystal habit 250 13.17 5.3 lamellar crystal habit 250 9.43 3.8 Blocky crystal habit 250 7.5 3.0

[0111] According to the filterability test, blocky crystal habit has better filterability.

[0112] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, various simple variations of the technical solution of the present invention may be made, including combining the various technical features in any other appropriate manner. These simple variations and combinations should also be regarded as disclosed in the present invention and fall within the scope of protection of the present invention.

Claims

1. A polymorphic crystal, characterized in that: The X-ray powder diffraction pattern of the polydopamine crystal at 25°C and Cu-Kα radiation shows characteristic absorption peaks at 2θ of 6.40±0.2° and 19.20±0.2°; the crystal habit of the crystal is blocky or flaky.

2. The polymorph according to claim 1, wherein The X-ray powder diffraction pattern of the multi-fruit crystalline form at 25°C and Cu-Kα radiation also shows at least two of the following reflections expressed in 2θ values: 11.48±0.2°, 13.00±0.2°, 15.10±0.2°, 20.04±0.2°, 22.26±0.2°, 24.86±0.2°, 25.82±0.2°, and 32.10±0.2° have characteristic absorption peaks.

3. The polymorph according to claim 1 or 2, wherein The X-ray powder diffraction pattern of the polygoni multiflori crystalline form at 25°C and Cu-Kα radiation shows characteristic absorption peaks at 6.40±0.2°, 13.00±0.2°, 19.20±0.2°, and 24.86±0.2° expressed in 2θ values; Preferably, the polymorphic form of polymorphic acid has characteristic absorption peaks at 6.40±0.2°, 11.48±0.2°, 13.00±0.2°, 19.20±0.2°, 20.04±0.2°, and 24.86±0.2° in terms of 2θ values ​​in an X-ray powder diffraction pattern at 25°C and Cu-Kα radiation; Preferably, the polymorph has characteristic absorption peaks at 6.40±0.2°, 11.48±0.2°, 13.00±0.2°, 15.10±0.2°, 19.20±0.2°, 20.04±0.2°, 22.26±0.2°, 24.86±0.2°, 25.82±0.2° and 32.10±0.2° in an X-ray powder diffraction pattern at 25°C and Cu-Kα radiation.

4. The polymorph according to any one of claims 1 to 3, wherein In the X-ray powder diffraction pattern of the polymorph at 25°C and Cu-Kα radiation, the peak area ratio at 2θ=19.20±0.2° and 2θ=6.4±0.2° is 0.1-10; Preferably, in the X-ray powder diffraction pattern of the polymorph at 25°C and Cu-Kα radiation, the peak area ratio at 2θ=19.20±0.2° and 2θ=6.4±0.2° is 0.5-5, preferably 1-3, and more preferably 2.57; Preferably, in the X-ray powder diffraction pattern of the polymorph at 25°C and Cu-Kα radiation, the peak area ratio at 2θ=19.20±0.2° and 2θ=6.4±0.2° is 0.

045.

5. The polymorph according to any one of claims 1 to 4, wherein The polymorph has an X-ray powder diffraction pattern as shown in FIG1 or FIG2 ; Preferably, the content of dodine in the dodine crystalline form is at least 98%.

6. A method for preparing the polymorph according to any one of claims 1 to 5, characterized in that: The method comprises the following steps: (1) dissolving the original drug of dodine in a solvent to obtain a dodine solution; (2) heating the doxorubicin solution, stirring it, cooling it for crystallization, and filtering it; (3) drying the filtered product to obtain the polymorph; the crystal habit is blocky; or The method comprises the following steps: (i) adding a methanol solution of dodine technical dropwise into pure acetonitrile; (ii) filtering after completion of the dropwise addition; (iii) drying the filtered product to obtain the polymorphic crystalline form; the crystal habit is flaky.

7. The preparation method according to claim 6, wherein The solvent is selected from a mixed solvent of water and a low-carbon alcohol, and the low-carbon alcohol is preferably methanol; Preferably, in the mixed solvent of water and lower carbon alcohol, the volume ratio of water to lower carbon alcohol is 1:5-10, preferably 1:8; Preferably, in the dodine solution, the mass-to-volume ratio of dodine technical to solvent is 1:2-1:30, preferably 1:5-1:15, where the mass is measured in g and the volume is measured in mL.

8. The preparation method according to claim 6 or 7, wherein The temperature reached by the heating is 20-100°C, preferably 30-90°C, and more preferably 65°C; Preferably, the cooling crystallization method is programmed cooling, and the cooling rate is 0.5-1°C / min; Preferably, the crystallization endpoint temperature is 0-5°C.

9. The polymorph obtained by the preparation method according to any one of claims 6 to 8.

10. Use of the polymorph of polyol according to any one of claims 1 to 5 and 9 in preparing a fungicide.

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