Oral pharmaceutical composition

Abstract

The present invention relates to methods and compositions for treating and / or inhibiting the onset or progression of diseases or disorders caused by or associated with herpesvirus infections. In particular, the present invention provides an orally high bioavailability, long-acting pharmaceutical composition comprising compound 1, a method for producing the same, and the use of the pharmaceutical composition as a pharmaceutically acceptable and for the treatment of diseases or disorders caused by or associated with herpesviruses.

Claims

1. An oral pharmaceutical composition comprising a solid dispersion, wherein the solid dispersion is 【Chemistry 1】 A pharmaceutical composition comprising a compound represented by (Compound 1) or a pharmaceutically acceptable salt thereof, and at least one matrix polymer.

2. The composition according to claim 1, wherein the solid dispersion is substantially an amorphous solid dispersion.

3. The composition according to claim 1, wherein the solid dispersion is an amorphous solid dispersion.

4. The solid dispersion has a single glass transition temperature (T g The composition according to claim 1, having ).

5. The composition according to any one of claims 1 to 4, wherein compound 1 is its neutral, free form.

6. The composition according to any one of claims 1 to 5, wherein the solid dispersion comprises about 5 wt% to about 60 wt% of compound 1 or a pharmaceutically acceptable salt thereof.

7. The composition according to any one of claims 1 to 6, wherein the solid dispersion comprises at least one matrix polymer in an amount of about 30 wt% to about 95 wt%.

8. The composition according to any one of claims 1 to 7, wherein the solid dispersion comprises about 5 wt% to about 20 wt% of compound 1 or a pharmaceutically acceptable salt thereof, and about 60 wt% to about 95 wt% of at least one matrix polymer.

9. The composition according to any one of claims 1 to 8, wherein the at least one matrix polymer is a water-insoluble or water-soluble ionic or neutral polymer.

10. The at least one type of matrix polymer is i. An ionic polymer or a pH-sensitive polymer, optionally such that the pH-sensitive polymer dissolves in an aqueous medium at a pH greater than approximately 5.5; ii. Selected from povidone polymer, copovidone polymer, methacrylate polymer, polymethacrylate copolymer, poly(vinylcaprolactam-co-vinylacetate-co-ethylene glycol), hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, and hydroxypropyl methylcellulose phthalate; iii. Selected from copovidone polymer, poly(vinylcaprolactam-co-vinylacetate-co-ethylene glycol), hydroxypropyl methylcellulose acetate succinate, and hydroxypropyl methylcellulose phthalate; or iv. Selected from hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate, The composition according to claim 9.

11. The composition according to any one of claims 1 to 10, wherein only one type of matrix polymer is present in the solid dispersion.

12. The composition according to any one of claims 1 to 11, wherein the solid dispersion is a spray-dried solid dispersion.

13. The composition according to any one of claims 1 to 12, wherein the pharmaceutical composition is in a dosage form suitable for oral administration, selected from the group consisting of granules, pellets, tablets, microparticles, capsules, suspensions, and minitablets.

14. The composition according to claim 13, wherein the pharmaceutical composition is a tablet with a total weight of less than 1000 mg, for example, less than 900 mg or less than 600 mg.

15. The composition according to claim 13 or 14, wherein the pharmaceutical composition contains about 1 mg to about 500 mg of compound 1 or a pharmaceutically acceptable salt thereof.

16. The composition according to any one of claims 1 to 15, wherein the composition is chemically and / or physically stable for at least four weeks.

17. The composition according to any one of claims 1 to 16, wherein, after oral administration to a fasted human subject, the plasma concentration of compound 1 in the subject after administration is at least 1100 ng / mL for at least 80% of the administration interval, where the administration interval is at least 2 days.

18. A composition according to any one of claims 1 to 17, for use as a pharmaceutical.

19. A method for treating a herpesvirus (e.g., HSV) infection in a subject requiring treatment, comprising administering to the subject a therapeutically effective amount of compound 1 or a pharmaceutically acceptable salt thereof, wherein compound 1 or a pharmaceutically acceptable salt thereof is formulated as a pharmaceutical composition according to any one of claims 1 to 17.

20. The method according to claim 19, administered at least once every 5 days, at least once every 7 days, at least once every 10 days, twice a month, once a month, once every two months, once every three months, once every six months, or once a year.

21. A method for increasing the bioavailability of compound 1 or a pharmaceutically acceptable salt thereof compared to the oral administration of an equivalent dose of compound 1 or a pharmaceutically acceptable salt thereof in crystalline form, the method comprising oral administration of the composition according to any one of claims 1 to 17.

22. a. Compound 1 or a pharmaceutically acceptable salt thereof; b. At least one type of matrix polymer; and c. Optionally, one or more pharmaceutically acceptable excipients, A solid dispersion containing [a certain substance].

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