Oral pharmaceutical composition of Tecovirimat and preparation method thereof

1. A pharmaceutical composition, comprising Tecovirimat, cyclodextrin and an additive, and optionally a pharmaceutically acceptable excipient, wherein said additive is meglumine; wherein said cyclodextrin is selected from the group consisting of dimethyl-β-cyclodextrin, 2-hydroxyethyl-β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, 3-hydroxypropyl-β-cyclodextrin, and trimethyl-β-cyclodextrin.

2. The pharmaceutical composition according to claim 1 , wherein said cyclodextrin and Tecovirimat have a weight ratio of 4˜10:1.

3. The pharmaceutical composition according to claim 1 , wherein said additive and Tecovirimat have a weight ratio of 0.5˜5:1.

4. The pharmaceutical composition according to claim 1 , wherein said additive and cyclodextrin have a weight ratio of 1:1˜5.

5. The pharmaceutical composition according claim 1 , wherein said pharmaceutical composition is an oral preparation, an injection, an infusion solution, drops, a patch, a liniment, an enema or an implant.

6. The pharmaceutical composition according to claim 1 , wherein said pharmaceutically acceptable excipient is selected from the group consisting of a filler, a binder, a disintegrating agent, a lubricant, a correctant, a coloring agent, a taste masking agent, a pH adjuster, a buffering agent, a preservative, a stabilizer, an antioxidant, a wetting agent, a humidity adjusting agent, a surfactant, a suspending agent and an absorption enhancer.

7. The pharmaceutical composition according to claim 1 , comprising Tecovirimat, cyclodextrin, an additive, lactose, hydroxypropyl methylcellulose, carboxymethyl starch sodium, and fumed silica lubricant, at a weight ratio of 40˜100:80˜120:200˜400:20˜50:1˜4:8˜12:1˜4.

8. A method for preparing the pharmaceutical composition according to claim 1 , comprising:

a) dissolving the additive and cyclodextrin in a desired volume of water, and mixing well;

b) adding Tecovirimat, and mixing well;

c) removing water by drying;

d) adding a filler, a binder, and a disintegrating agent, sieving with an 80 -mesh sieve, and mixing well;

e) compressing directly, or adding a non-aqueous solvent as a wetting agent to prepare a soft material, preparing wet granules, drying the wet granules to obtain dry granules, adding a lubricant to the dry granules, mixing, breaking, and preparing tablets, or

adding a lubricant, and preparing capsules or granules.

9. A method for treating smallpox, comprising administering to a subject in need thereof a therapeutically and/or prophylactically effective amount of the pharmaceutical composition according to claim 1 .

10. The pharmaceutical composition according to claim 1 , wherein said cyclodextrin is selected from the group consisting of 2-hydroxypropyl-β-cyclodextrin, and 3-hydroxypropyl-β-cyclodextrin.

11. The pharmaceutical composition according to claim 1 , wherein said cyclodextrin is 2-hydroxypropyl-β-cyclodextrin.

12. The pharmaceutical composition according to claim 1 , wherein at least one of the following is satisfied:

said cyclodextrin and Tecovirimat have a weight ratio of 5˜8:1;

said additive and Tecovirimat have a weight ratio of 1˜4:1;

said additive and cyclodextrin have a weight ratio of 1:2˜4.

13. The pharmaceutical composition according to claim 1 , wherein at least one of the following is satisfied:

said cyclodextrin and Tecovirimat have a weight ratio of 5:1, 6:1, 7:1 or 8:1;

said additive and Tecovirimat have a weight ratio of 1:1, 2:1, 3:1, or 4:1;

said additive and cyclodextrin have a weight ratio of 1:3.

14. The pharmaceutical composition according to claim 1 , wherein said pharmaceutical composition is an oral preparation, an injection or an infusion solution.

15. The pharmaceutical composition according to claim 6 , wherein at least one of the following is satisfied:

said pharmaceutically acceptable excipient is selected from the group consisting of a filler, a binder, a disintegrating agent, and a lubricant;

the filler is selected from the group consisting of lactose, complex lactose, microcrystalline cellulose, anhydrous calcium dihydrogen phosphate, mannitol, starch, and pregelatinized starch;

the binder is selected from the group consisting of polyvinyl pyrrolidone, hydroxypropyl methylcellulose, and hydroxymethyl cellulose;

the disintegrating agent is selected from the group consisting of cross-linked polyvinyl pyrrolidone, carboxymethyl starch sodium, croscarmellose sodium, and low-substituted hydroxypropyl cellulose;

the lubricant is selected from the group consisting of talc powder, magnesium stearate, hydrogenated castor oil, and fumed silica lubricant.

16. The pharmaceutical composition according to claim 7 , wherein at least one of the following is satisfied:

said cyclodextrin is 2-hydroxypropyl-β-cyclodextrin;

said pharmaceutical composition comprises Tecovirimat, cyclodextrin, an additive, lactose, hydroxypropyl methylcellulose, carboxymethyl starch sodium, and fumed silica lubricant, at a weight ratio of 50:100:300:35.5:2:10.0:2.5 or 70:100:300:15.5:2:10.0:2.5.