Crystal form of macrocyclic compound, and preparation method therefor and use thereof

1 . A crystal form of a macrocyclic compound (6R,16R)-9-fluoro-16-methyl-13-oxa-2,17,21,25-tetraazapentacyclo [16.6.2.0 2,6 .0 7,12 .0 22,26 ] hexacosane-1(25),7,9,11,18(26), 19,21,23-octane-19-carbonitrile, wherein the X-ray powder diffraction pattern of the crystal form comprises characteristic peaks at 2θ values of 9.49±0.2, 10.60±0.2, 11.54±0.2, 14.10±0.2, 17.09±0.2, 19.15±0.2, 20.30±0.2, 22.85±0.2, 23.89±0.2 and 27.74±0.2.

2 . The crystal form of a macrocyclic compound according to claim 1 , wherein the X-ray powder diffraction pattern of the crystal form further comprises characteristic peaks at 2θ values of 18.75±0.2, 21.29±0.2, 24.25±0.2, 24.99±0.2, 28.74±0.2 and 31.35±0.2.

3 . The crystal form according to claim 1 , wherein the X-ray powder diffraction pattern of the crystal form further comprises characteristic peaks at 2θ values of 5.69±0.2, 16.11±0.2, 25.62±0.2, 26.34±0.2, 27.26±0.2, 29.91±0.2, 32.19±0.2, 33.86-0.2, 34.70±0.2, 35.59±0.2, 36.95±0.2, 37.40±0.2, 39.19±0.2, 40.33±0.2, 41.16±0.2, 42.56±0.2, 43.11±0.2, 45.30±0.2, 46.35±0.2 and 49.80±0.2.

4 . The crystal form of a macrocyclic compound according to claim 1 , wherein the differential scanning calorimetry trace of the crystal form has an endothermic peak at 233±5° C.

5 . A method for preparing the crystal form of a macrocyclic compound according to claim 1 , wherein the method is selected form the group consisting of approach (1), approach (2) and approach (3); the approach (1) comprises adding a solvent to the macrocyclic compound to allow for supersaturation, stirring, precipitating, filtering, obtaining a filter cake, and drying the filter cake to obtain the crystal form; the approach (2) comprises adding the macrocyclic compound to a solvent under heating, then dissolving, cooling, precipitating, filtering, obtaining a filter cake, and drying the filter cake to obtain the crystal form; and the approach (3) comprises dissolving the macrocyclic compound in a solvent, adding an anti-solvent, precipitating, filtering, obtaining a filter cake, and drying the filter cake to obtain the crystal form.

6 . The method according to claim 5 , wherein the solvent in approaches (1)-(3) and the anti-solvent in approach (3) are selected from the group consisting of C 2 -C 7 hydrocarbons, C 2 -C 7 alcohols, C 2 -C 7 ketones, C 2 -C 7 nitriles, C 2 -C 7 ethers, C 2 -C 7 esters, water, and any combination thereof.

7 . The method according to claim 6 , wherein the C 2 -C 7 hydrocarbons comprise dichloromethane, n-heptane or toluene, the C 2 -C 7 alcohols comprise methanol, ethanol, trifluoroethanol, n-propanol or isopropanol, the C 2 -C 7 ketones comprise acetone or butanone, the C 2 -C 7 nitriles comprise acetonitrile, the C 2 -C 7 ethers comprise isopropyl ether, methyl tert-butyl ether, tetrahydrofuran or 1,4-dioxane, and the C 2 -C 7 esters comprise ethyl acetate or isopropyl acetate.

8 . The method according to claim 6 , wherein the solvent is selected from the group consisting of methanol, ethanol, acetone, dichloromethane, tetrahydrofuran, water, and any combination thereof, and the anti-solvent is selected from the group consisting of isopropyl ether, n-heptane, water, and any combination thereof.

9 . A method of treating a Trk kinase-associated disease, comprising administering the crystal form of a macrocyclic compound according to claim 1 to a subject in need thereof.

10 . The method according to claim 9 , wherein the Trk kinase-associated disease is any one of the group consisting of pain, a malignant tumor, an inflammatory disease and a neurodegenerative disease, wherein each of these diseases is a Trk kinase-associated form of the disease.