Kinase inhibitor pharmaceutical compositions

Abstract

The present invention relates to pharmaceutical compositions of Compound 1, a c-Met inhibitor. The present invention also relates to methods of using the pharmaceutical compositions to treat diseases, disorders, or syndromes mediated at least in part by modulating the in vivo activity of protein kinases, and to processes for making the pharmaceutical compositions. In another aspect, the present invention relates to a method for inhibiting a protein kinase, comprising contacting the protein kinase with a pharmaceutical composition of Compound 1 in a crystalline form or crystalline salt form as described herein. In yet another aspect, the present invention relates to a process for preparing a pharmaceutical composition of Compound 1.

Claims

1. a. Compound 1 having the following structure, in an amount of 25-35% by weight: 【Chemistry 1】 or a pharmaceutically acceptable salt thereof, b. 35-40% by weight of microcrystalline cellulose, c. 16-22% by weight of lactose, d. 3-7% by weight of hydroxypropyl cellulose, e. 3-7% by weight of croscarmellose sodium, f. 0.1 to 0.5% by weight of colloidal silicon dioxide, g. 0.5 to 3.5% by weight of stearic acid and A pharmaceutical composition containing the above.

2. a. Compound 1 having the following structure in an amount of 25 to 35% by weight: 【Chemistry 2】 Hemifumarate and b. 35-40% by weight of microcrystalline cellulose, c. 16-22% by weight of anhydrous lactose, d. 3-7% by weight of hydroxypropyl cellulose, e. 3-7% by weight of croscarmellose sodium, f. 0.1 to 0.5% by weight of colloidal silicon dioxide, g. 0.5 to 3.5% by weight of stearic acid and A pharmaceutical composition containing the above.

3. a. Compound 1 having the following structure in an amount of 27.75% by weight: 【Transformation 3】 Hemifumarate and b. 38.63% by weight of microcrystalline cellulose, c. 19.32% by weight of anhydrous lactose, d. 5% by weight of hydroxypropyl cellulose, e. 6% by weight of croscarmellose sodium, f. 0.3 wt% colloidal silicon dioxide, g. 3% by weight of stearic acid and A pharmaceutical composition containing the above.

4. The pharmaceutical composition according to any one of claims 1 to 3, wherein the composition comprises 10 mg to 150 mg of compound 1 (free base equivalent).

5. a. 20 mg of compound 1 (free base equivalent), b. 30.90 mg of microcrystalline cellulose and c. 15.46 mg of anhydrous lactose and d. 4 mg of hydroxypropyl cellulose and e. 4.8 mg of croscarmellose sodium, f. 0.24 mg of colloidal silicon dioxide and g. 2.4 mg of stearic acid and The pharmaceutical composition according to claim 4, comprising:

6. a. 40 mg of compound 1 (free base equivalent), b. 61.81 mg of microcrystalline cellulose and c. 30.91 mg of anhydrous lactose and d. 8 mg of hydroxypropyl cellulose and e. 9.6 mg of croscarmellose sodium and f. Colloidal silicon dioxide of 0.48 m, g. 4.8 mg of stearic acid and The pharmaceutical composition according to claim 4, comprising:

7. a. 60 mg of compound 1 (free base equivalent), b. 92.71 mg of microcrystalline cellulose and c. 46.37 mg of anhydrous lactose and d. 12 mg of hydroxypropyl cellulose and e. 14.4 mg of croscarmellose sodium and f. 0.72 mg of colloidal silicon dioxide, g. 7.2 mg of stearic acid and The pharmaceutical composition according to claim 4, comprising:

8. a. 100 mg of compound 1 (free base equivalent), b. 154.52 mg of microcrystalline cellulose and c. 77.28 mg of anhydrous lactose and d. 20 mg of hydroxypropyl cellulose and e. 24 mg of croscarmellose sodium, f. 1.2 mg of colloidal silicon dioxide and g. 12 mg of stearic acid and The pharmaceutical composition according to claim 4, comprising:

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