A kind of osthole crystal and its preparation method and application

Abstract

The present invention provides an osthole crystal and a preparation method and application thereof. The osthole crystal is a new II crystal form. During the preparation process, it can be prepared by any one of a solvent-assisted grinding method, a high-temperature volatilization method, a melt quenching method or a solution crystallization method. Compared with osthole on the market, the osthole crystal significantly improves the dissolution rate and solubility, has better bioavailability, greatly improves the fluidity and bulk density of the powder, and provides a better and more optimal choice for the preparation of pharmaceutical preparations and pesticide preparations. In addition, the preparation method is simple in process and low in cost, and can be further developed to be suitable for large-scale production, which is of great significance for the development of drugs and pesticides.

Description

Technical Field

[0001] The invention belongs to the technical field of crystal preparation, and relates to osthole crystals and a preparation method and application thereof. Background Art

[0002] Osthole (7-methoxy-8-isopentenylcoumarin, Osthole) is the main component of the plant cnidium monnieri extract. The structure is as follows: the core structure is composed of a benzene ring and a pyrone ring. In addition to the core structure of coumarin, osthole also has an isopentenyl structure. As a phytoalexin, compounds with isopentenyl structures play an important role in disease resistance.

[0003]

[0004] Studies have shown that osthole has a variety of pharmacological effects, such as anti-tumor, anti-inflammatory, antibacterial, antioxidant and neuroprotective, and its wide range of biological activities has attracted widespread attention from pesticide chemists and pharmaceutical chemists. Osthole has an inhibitory effect on the activity of acetylcholinesterase in pests, has high insecticidal activity, is environmentally friendly, and is not easy for pests to develop resistance. Therefore, it is widely used in the prevention and control of pests such as cabbage worms, diamondback moths, and aphids. It also has a significant inhibitory effect on plant pathogenic fungi such as cucumber powdery mildew, grape downy mildew, pepper phytophthora, and wheat fusarium.

[0005] However, osthole is almost insoluble in water, and its poor solubility and dissolution rate severely limit its clinical application. In addition, its poor water solubility also makes it difficult to develop into a green and environmentally friendly aqueous solution. Therefore, it is urgent to develop a solid form of osthole with good water solubility to meet the urgent needs of the pharmaceutical and pesticide fields.

[0006] Particle morphology is one of the important characteristics of solid chemical products. It significantly affects the filtration and separation in the early production, the drying process, and the later storage, transportation, and downstream applications. The commercially available osthole crystals are mostly needle-shaped, with a low bulk density (0.304 g / cm 3 ), poor fluidity (angle of repose 55°), poses a great challenge to downstream production and application. Therefore, it is necessary to develop a simple, low-cost production technology to further improve the fluidity, bulk density and physicochemical stability of osthole, which directly determines the clinical application effect of osthole. Summary of the invention

[0007] In order to solve the deficiencies of the prior art, the purpose of the present invention is to provide osthole crystals and a preparation method and application thereof. The osthole crystal form II obtained by the present invention significantly improves the dissolution rate and solubility of osthole, and improves the fluidity and bulk density of the powder.

[0008] One of the objects of the present invention is to provide an osthole crystal, wherein the osthole crystal has characteristic diffraction peaks at diffraction angles expressed in 2θ degrees at 4.5±0.2°, 5.4±0.2°, 12.8±0.2°, 14.1±0.2°, 15.0±0.2°, 17.0±0.2°, 18.0±0.2°, 19.0±0.2°, 20.5±0.2°, 23.6±0.2°, 24.0±0.2°, 24.5±0.2°, 25.2±0.2°, 26.1±0.2°, 27.3±0.2°, 29.0±0.2°, 31.6±0.2° and 38.6±0.2°, according to X-ray powder diffraction measured using Cu-Kα radiation.

[0009] Preferably, the differential scanning calorimetry (DSC) spectrum of the osthole crystal has a characteristic exothermic peak at 42-46°C, and melts at 83.27°C.

[0010] Preferably, the thermogravimetric TG spectrum of the osthole crystals loses weight at 170.25°C.

[0011] The second object of the present invention is to provide a method for preparing osthole crystals as described in the first object, wherein the preparation method comprises any one of solvent-assisted grinding, high temperature volatilization, melt quenching or dissolution crystallization.

[0012] As a preferred technical method of the present invention, the solvent-assisted grinding method comprises: preparing osthole crystals by grinding under the action of osthole auxiliary solvent;

[0013] Preferably, the ratio of the added amount of osthole to the auxiliary solvent is 0.05-0.2 μL / mg;

[0014] Preferably, the auxiliary solvent comprises any one of water, methanol, ethanol, acetone, butanone, formic acid, acetic acid, ethyl acetate, n-propyl acetate, n-butyl acetate, acetonitrile, 1,4-dioxane, n-propanol, isopropanol, n-butanol, chloroform, dichloromethane, chloroform, carbon tetrachloride, hexane, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide or N-methylpyrrolidone, or a combination of at least two thereof;

[0015] Preferably, the grinding method uses a power of 20-35 Hz and a time of 20-40 min.

[0016] As a preferred technical method of the present invention, the high temperature volatilization method comprises: dissolving osthole in a solvent and volatilizing at high temperature to obtain osthole crystals;

[0017] Preferably, the solvent comprises any one of methanol, ethanol, acetone, butanone, formic acid, acetic acid, ethyl acetate, n-propyl acetate, n-butyl acetate, acetonitrile, 1,4-dioxane, n-propanol, isopropanol, n-butanol, chloroform, dichloromethane, chloroform, carbon tetrachloride, hexane, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide or N-methylpyrrolidone, or a combination of at least two thereof;

[0018] Preferably, the concentration of osthole in the clear solution obtained after the osthole is dissolved in the solvent is 1-5 g / mL;

[0019] Preferably, the temperature of the high-temperature volatilization is 42-83.27°C.

[0020] As a preferred technical method of the present invention, the melt quenching method comprises: melting osthole at high temperature and then quenching to obtain osthole crystals;

[0021] Preferably, the high temperature melting temperature is 83.27-170°C;

[0022] Preferably, the quenching temperature is -190 to 70°C, and the quenching time is 5 to 120 minutes.

[0023] As a preferred technical method of the present invention, the dissolution crystallization method comprises: adding osthole to a good solvent for dissolution and filtration, adding the filtrate obtained by filtration to an anti-solvent for crystal cultivation, and obtaining osthole crystals;

[0024] Preferably, the good solvent includes any one of methanol, ethanol, acetone, butanone, formic acid, acetic acid, ethyl acetate, n-propyl acetate, n-butyl acetate, acetonitrile, 1,4-dioxane, n-propanol, isopropanol, n-butanol, chloroform, dichloromethane, chloroform, carbon tetrachloride, hexane, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide or N-methylpyrrolidone, or a combination of at least two thereof;

[0025] Preferably, the concentration of the solution obtained by dissolving the osthole in a good solvent is 1-5 g / mL;

[0026] Preferably, the anti-solvent comprises any one of water, n-hexane or n-heptane, or a combination of at least two thereof;

[0027] Preferably, the volume ratio of the anti-solvent to the good solvent is (1-30):1;

[0028] Preferably, the preparation method further comprises solid-liquid separation and drying of the mixture obtained after crystal growing;

[0029] Preferably, the solid-liquid separation is carried out by filtration.

[0030] The third object of the present invention is to provide a use of the osthole crystals as described in the first object in the preparation of antibacterial drugs, anti-inflammatory drugs, anticancer drugs, antioxidant drugs, poultry health drugs, pesticides or agricultural fungicides.

[0031] A fourth object of the present invention is to provide a pharmaceutical composition comprising a therapeutically effective amount of the osthole crystals of the present invention and at least one pharmaceutically acceptable excipient.

[0032] The above-mentioned pharmaceutical composition can be prepared into a certain dosage form and administered by a suitable route. For example, oral, parenteral (including subcutaneous, intramuscular, intravenous or intradermal), rectal, transdermal, nasal, vaginal and other routes. Dosage forms suitable for oral administration include tablets, capsules, granules, powders, pills, powders, lozenges, solutions, syrups or suspensions, which can be suitable for rapid release, delayed release or regulated release of active pharmaceutical ingredients as required; dosage forms suitable for parenteral administration include aqueous or non-aqueous sterile injection solutions, emulsions or suspensions; dosage forms suitable for rectal administration include suppositories or enemas; dosage forms suitable for transdermal administration include ointments, creams, and patches; dosage forms suitable for nasal administration include aerosols, sprays, and nasal drops; dosage forms suitable for vaginal administration include suppositories, plugs, gels, pastes or sprays.

[0033] The pharmaceutically acceptable excipients in the above-mentioned pharmaceutical composition, in the case of solid oral dosage forms, include but are not limited to: diluents, such as starch, pregelatinized starch, lactose, etc.; binders, such as gum arabic, guar gum, gelatin, polyvinyl pyrrolidone, etc.; disintegrants, such as starch, sodium starch glycolate, pregelatinized starch, colloidal silicon dioxide, etc.; lubricants, such as stearic acid, magnesium stearate, sodium acetate, etc.; glidants, such as colloidal silicon dioxide, etc.; complex formers, such as various grades of cyclodextrin and resins; release rate control agents, such as hydroxypropyl cellulose, hydroxymethyl cellulose, hydroxypropyl methyl cellulose, etc. Other pharmaceutically acceptable excipients that can be used include but are not limited to film formers, plasticizers, colorants, flavoring agents, viscosity modifiers, preservatives, antioxidants, etc. Each excipient must be acceptable, compatible with other ingredients in the formulation and harmless to patients.

[0034] The pharmaceutical composition can be prepared by methods known to those skilled in the art. When preparing the pharmaceutical composition, the osthole crystal form II of the present invention is mixed with one or more pharmaceutically acceptable excipients, and optionally mixed with one or more other active pharmaceutical ingredients. For example, tablets, capsules, and granules can be prepared by mixing, granulating, tableting, or filling capsules; powders are prepared by mixing active pharmaceutical ingredients ground to a suitable size and excipients; solutions and syrups can be prepared by dissolving active pharmaceutical ingredients in appropriately flavored water or aqueous solutions; suspensions can be prepared by dispersing active pharmaceutical ingredients in pharmaceutically acceptable carriers.

[0035] The sixth object of the present invention is to provide a pesticide composition, and the use of the pesticide composition in the control of fungal diseases and pests. The agricultural composition or a preparation containing the agricultural composition is used to control fungal diseases and pests; the fungal diseases include cucumber powdery mildew, cucumber anthracnose, wheat smut, etc.; the pests include cabbage worm, tea looper, cotton bollworm, beet armyworm, various aphids, various mites, etc.

[0036] The agricultural composition of the present invention can be prepared into a formulation that is convenient for agricultural use according to methods known to those skilled in the art, including but not limited to one of the formulations such as suspension concentrate, wettable powder, water dispersible granules, nanocapsules, nano water suspension concentrates, etc. It is easy for those skilled in the art to know that in addition to containing active ingredients, the formulation system also contains adjuvants required for preparing pesticide formulations. The adjuvants can be selected from one or a mixture of solvents, emulsifiers, wetting agents, stabilizers, dispersants, thickeners, pH regulators, defoamers, antifreeze agents, fillers, etc.

[0037] Compared with the prior art, the present invention has the following beneficial effects:

[0038] 1. The crystal morphology of the prepared osthole crystal form II is completely different from that of the osthole crystal obtained by the prior art, and is manifested in significantly improved powder properties, such as higher bulk density and better fluidity.

[0039] 2. The osthole crystal form II in the present invention has significantly improved bioavailability and wide clinical application, which is manifested in better solubility and dissolution rate, and the bioavailability is significantly improved.

[0040] 3. The preparation method of osthole crystal form II in the present invention is simple to operate, easy to control quality, simple in technology and equipment, low in cost, can be further developed, and is suitable for large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 is the powder X-ray diffraction pattern of osthole crystals;

[0042] Figure 2 This is the DSC graph of osthole crystals;

[0043] Figure 3 This is the TG diagram of osthole crystals;

[0044] Figure 4 This is a comparison chart of the characteristic dissolution of osthole crystals and commercially available osthole crystals in water. DETAILED DESCRIPTION

[0045] It should be noted that the following detailed descriptions are all exemplary and are intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those generally understood by those of ordinary skill in the art to which the present invention belongs. The technical scheme of the present invention is further illustrated below by specific embodiments. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0046] The following analytical methods and equipment are used to characterize the osthole crystal form II of the present invention:

[0047] X-ray powder diffraction (PXRD): The powder diffractometer used was D / MAX2500 produced by Rigaku Corporation of Japan. The test conditions were: Cu Kα target test, voltage 40 kV, current 100 mA, scanning wavelength The continuous scanning test was performed at a scanning speed of 8° / min. After the data were collected, Jade 7.0 software was used for data analysis.

[0048] Differential Scanning Calorimeter (DSC): Tested with Mettler Toledo's DSC 1 / 500 instrument, add about 20 mg of sample into a 40 μL standard aluminum crucible, seal the crucible, and put it into the furnace. High-purity nitrogen is used as protective gas (gas rate of 50 mL / min) and reaction gas (gas rate of 200 mL / min) in the furnace. The measuring temperature range is 25-300 °C, and the heating rate is 5-10 °C·min -1 The temperature and heat changes of the samples during the heating process were measured, and the program control, data recording and analysis were all completed by STARe Software 10.0 developed by Mettler.

[0049] Thermogravimetric analysis (TGA): Thermogravimetric analysis data were measured by Mettler TG / DSC 1STARe thermogravimetric analyzer from Mettler Toledo. Test conditions: sample amount: 3-5 mg; temperature range: 25-400°C; heating rate: 10°C / min; gas: nitrogen; flow rate: 20 mL / min.

[0050] Powder performance tester: Use BT-1001 intelligent powder property tester to measure the angle of repose and tapped bulk density. After passing 5-10g of powder through a 100-mesh sieve, fill it into the powder tester container, measure the angle of repose, and then set the measuring cylinder to vibrate up and down with an amplitude of 5-10mm to measure the tapped bulk density of the powder. Repeat three times and take the average value.

[0051] Example 1

[0052] Accurately weigh 244.29 mg (1 mmol) of osthole, place the sample in a grinding jar, put it into a Retsch MM400 grinder, use a 4 mm steel ball, set the frequency to 35 Hz, add 9 μL of acetic acid and 39 μL of acetonitrile, grind for 30 min, and dry at a constant temperature of 25° C. for 12 h to obtain osthole crystals.

[0053] The X-ray diffraction pattern of the osthole crystals prepared in this example is as follows: Figure 1 As shown in Table 1, the diffraction angle 2θ is expressed as: 4.5°, 5.4°, 9.3°, 12.8°, 14.1°, 15.0°, 17.0°, 18.0°, 19.0°, 20.5°, 23.6°, 24.0°, 24.5°, 25.2°, 26.1°, 27.3°, 29.0°, 31.6° and 38.6°, respectively.

[0054] Table 1

[0055]

[0056]

[0057] pass Figure 1 Compared with the XRD results of conventional osthole on the market, it can be found that it is a new crystal form, recorded as crystal form II.

[0058] Figure 2 The DSC diagram of the product obtained in this example is Figure 2 It can be seen that the crystal has an exothermic peak at 42°C to 46°C and melts at 83.27°C.

[0059] Figure 3 The TG diagram of the product is obtained for this example. Figure 3 It can be seen that the crystal loses weight at 170.25°C.

[0060] The osthole crystals obtained in Example 1 were tested and found to have a bulk density of 0.626 g / cm 3 , the angle of repose is 38°.

[0061] The osthole crystals obtained in Example 1 were subjected to a dissolution test, and the dissolution curve of the separated body was shown in Figure 4 ,pass Figure 4 It can be seen that the solubility of osthole crystal form II in pure water at 25°C is 52.76 mg / L, which is 4.34 times that of commercially available osthole crystals (12.14 mg / L). Under the same conditions: the area under the dissolution curve of osthole crystal form II (powder) is 15378.45 mg·min / L, which is 4.91 times that of commercially available osthole crystals (3232.02 mg·min / L).

[0062] Example 2

[0063] Accurately weigh 122.145 mg (0.5 mmol) of osthole, place the sample in a grinding jar, put it into a Retsch MM400 grinder, use a 4 mm steel ball, set the frequency at 20 Hz, add 6 μL of methanol, grind for 20 min, and dry at a constant temperature of 25° C. for 12 h to obtain osthole crystals.

[0064] The same test as in Example 1 was applied to Example 2, and it was found that the osthole crystals prepared in Example 2 were of Form II. Similarly, its DSC showed an exothermic peak at 42°C to 46°C, melting at 83.27°C, and TG showed a weight loss at 170.25°C.

[0065] The osthole crystals obtained in this example were tested and found to have a bulk density of 0.613 g / cm 3 , the angle of repose is 37°.

[0066] Example 3

[0067] Accurately weigh 244.29 mg (1 mmol) of osthole raw material, dissolve it in a mixed solvent of 100 mL of ethanol and 244 mL of ethyl acetate, filter it after the solution becomes clear, and place the filtrate at a constant temperature of 42° C. to evaporate it. The crystal product is dried at a constant temperature at room temperature for 12 h to obtain osthole crystals.

[0068] The same test as in Example 1 was used for this example, and it was found that the osthole crystals prepared in the example were of Form II. Similarly, its DSC showed an exothermic peak at 42°C to 46°C, melting at 83.27°C, and TG showed a weight loss at 170.25°C.

[0069] The osthole crystals obtained in this example were tested and found to have a bulk density of 0.603 g / cm 3 , the angle of repose is 38°.

[0070] Example 4

[0071] Accurately weigh 1 g (4.09 mmol) of osthole raw material, dissolve it in 0.2 mL of dimethyl sulfoxide, filter it after the solution becomes clear, and place the filtrate at 83.27° C. for constant temperature evaporation. The crystal product is dried at room temperature for 12 h to obtain osthole crystals.

[0072] The same test as in Example 1 was used for this example, and it was found that the osthole crystals prepared in the example were of Form II. Similarly, its DSC showed an exothermic peak at 42°C to 46°C, melting at 83.27°C, and TG showed a weight loss at 170.25°C.

[0073] The osthole crystals obtained in this example were tested and found to have a bulk density of 0.623 g / cm 3 , the angle of repose is 36°.

[0074] Example 5

[0075] 100 mg (0.41 mmol) of osthole raw material was accurately weighed, and the sample was placed in a glass culture dish and kept at 83.27° C. for 10 min until all the crystals melted. The melt was suddenly cooled to 70° C. and kept at the temperature for 120 min to obtain osthole crystals.

[0076] The same test as in Example 1 was used for this example, and it was found that the osthole crystals prepared in the example were of Form II. Similarly, its DSC showed an exothermic peak at 42°C to 46°C, melting at 83.27°C, and TG showed a weight loss at 170.25°C.

[0077] The osthole crystals obtained in this example were tested and found to have a bulk density of 0.626 g / cm 3 , the angle of repose is 38°.

[0078] Example 6

[0079] 200 mg (0.82 mmol) of osthole raw material was accurately weighed, and the sample was placed in a glass culture dish and kept at 170° C. for 10 min until all the crystals melted. The melt was suddenly cooled to -190° C. and kept at this temperature for 5 min to obtain osthole crystals.

[0080] The same test as in Example 1 was used for this example, and it was found that the osthole crystals prepared in the example were of Form II. Similarly, its DSC showed an exothermic peak at 42°C to 46°C, melting at 83.27°C, and TG showed a weight loss at 170.25°C.

[0081] The osthole crystals obtained in this example were tested and found to have a bulk density of 0.606 g / cm 3 , the angle of repose is 39°.

[0082] Example 7

[0083] Accurately weigh 2442.9 mg (10 mmol) of osthole raw material, place the sample in 0.5 mL of N,N-dimethylformamide and stir to dissolve, filter the solution, add the filtrate dropwise into 15 mL of water, stir and grow crystals for 20 min, then filter, and dry at room temperature for 24 h to obtain osthole crystals.

[0084] The same test as in Example 1 was used for this example, and it was found that the osthole crystals prepared in the example were of Form II. Similarly, its DSC showed an exothermic peak at 42°C to 46°C, melting at 83.27°C, and TG showed a weight loss at 170.25°C.

[0085] The osthole crystals obtained in this example were tested and found to have a bulk density of 0.603 g / cm 3 , the angle of repose is 41°.

[0086] Example 8

[0087] Accurately weigh 50 mg (0.041 mmol) of osthole raw material, place the sample in a mixed solvent of 10 mL acetone and 40 mL chloroform, stir to dissolve, filter the solution, add the filtrate dropwise into a mixed solvent of 40 mL n-hexane and 10 mL n-heptane, stir to grow crystals for 20 min, then filter, and dry at room temperature for 24 h to obtain osthole crystal form II.

[0088] The same test as in Example 1 was used for this example, and it was found that the osthole crystals prepared in the example were of Form II. Similarly, its DSC showed an exothermic peak at 42°C to 46°C, melting at 83.27°C, and TG showed a weight loss at 170.25°C.

[0089] The osthole crystals obtained in this example were tested and found to have a bulk density of 0.622 g / cm 3 , the angle of repose is 40°.

[0090] The crystal form of the osthole crystal form II prepared in the present invention is completely different from the osthole crystal in the prior art, has high bulk density, good fluidity, significantly increased dissolution rate and solubility, and greatly increased bioavailability. The preparation process of the osthole crystal form II is simple and low in cost, and can be further developed for large-scale production.

[0091] The applicant declares that the above is only a specific implementation mode of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention shall fall within the protection scope and disclosure scope of the present invention.

Claims

1. An osthole crystal, characterized in that: The X-ray powder diffraction of the osthole crystal measured using Cu-Kα radiation has characteristic diffraction peaks at diffraction angles expressed in 2θ degrees at 4.5±0.2°, 5.4±0.2°, 12.8±0.2°, 14.1±0.2°, 15.0±0.2°, 17.0±0.2°, 18.0±0.2°, 19.0±0.2°, 20.5±0.2°, 23.6±0.2°, 24.0±0.2°, 24.5±0.2°, 25.2±0.2°, 26.1±0.2°, 27.3±0.2°, 29.0±0.2°, 31.6±0.2° and 38.6±0.2°; The differential scanning calorimetry (DSC) spectrum of the osthole crystals has a characteristic exothermic peak at 42-46°C, and melts at 83.27°C.

2. The osthole crystal according to claim 1, characterized in that: The thermogravimetric TG spectrum of the osthole crystals showed weight loss at 170.25°C.

3. The method for preparing osthole crystals according to claim 1 or 2, characterized in that: The preparation method comprises any one of a solvent-assisted grinding method, a high-temperature volatilization method, a melt quenching method or a dissolution crystallization method.

4. The preparation method according to claim 3, characterized in that: The solvent-assisted grinding method comprises: preparing osthole crystals by grinding under the action of osthole auxiliary solvent; The ratio of the added amount of osthole to the auxiliary solvent is 0.05-0.2 μL / mg; The auxiliary solvent is any one of water, methanol, ethanol, acetone, butanone, formic acid, acetic acid, ethyl acetate, n-propyl acetate, n-butyl acetate, acetonitrile, 1,4-dioxane, n-propanol, isopropanol, n-butanol, chloroform, dichloromethane, chloroform, carbon tetrachloride, hexane, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide or N-methylpyrrolidone, or a combination of at least two thereof; The grinding method uses a power of 20-35 Hz and a time of 20-40 minutes.

5. The preparation method according to claim 3, characterized in that: The high temperature volatilization method comprises: dissolving osthole in a solvent and volatilizing at high temperature to obtain osthole crystals; The solvent is any one of methanol, ethanol, acetone, butanone, formic acid, acetic acid, ethyl acetate, n-propyl acetate, n-butyl acetate, acetonitrile, 1,4-dioxane, n-propanol, isopropanol, n-butanol, chloroform, dichloromethane, chloroform, carbon tetrachloride, hexane, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide or N-methylpyrrolidone, or a combination of at least two thereof; The concentration of osthole in the clear solution obtained after the osthole is dissolved in the solvent is 1-5 g / mL; The temperature of the high temperature volatilization is 42-83.27°C.

6. The preparation method according to claim 3, characterized in that: The melt quenching method comprises: melting osthole at high temperature and then quenching to obtain osthole crystals; The high temperature melting temperature is 83.27-170°C; The quenching temperature is -190 to 70°C, and the quenching time is 5 to 120 minutes.

7. The preparation method according to claim 3, characterized in that: The dissolution crystallization method comprises: adding osthole to a good solvent, dissolving and filtering, adding the filtrate obtained by filtration to an anti-solvent for crystal cultivation, and obtaining osthole crystals; The good solvent is any one of methanol, ethanol, acetone, butanone, formic acid, acetic acid, ethyl acetate, n-propyl acetate, n-butyl acetate, acetonitrile, 1,4-dioxane, n-propanol, isopropanol, n-butanol, chloroform, dichloromethane, chloroform, carbon tetrachloride, hexane, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide or N-methylpyrrolidone, or a combination of at least two thereof; The osthole is dissolved in a good solvent to obtain a solution with a concentration of 1-5 g / mL; The anti-solvent is any one of water, n-hexane or n-heptane, or a combination of at least two thereof; The volume ratio of the anti-solvent to the good solvent is (1-30):

1.

8. The preparation method according to claim 7, characterized in that: The preparation method further comprises performing solid-liquid separation and drying on the mixture obtained after crystal growing; The solid-liquid separation method is filtration.

9. Use of the osthole crystals according to claim 1 or 2 in the preparation of anti-inflammatory drugs, anti-cancer drugs, and antioxidant drugs.

10. A pharmaceutical composition or pesticide composition, characterized in that: The pharmaceutical composition comprises the osthole crystals according to claim 1 or 2; The pharmaceutical composition is used to prepare a pharmaceutical preparation, which includes the pharmaceutical composition and pharmaceutically acceptable excipients and / or carriers.

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