Pharmaceutical composition comprising quinoline derivative or salt thereof

Patent metadata

Field	Value
Publication number	US-11065241-B2
Application number	US-201716071157-A
Country	US
Kind code	B2
Filing date	Jan 23, 2017
Priority date	Jan 27, 2016
Publication date	Jul 20, 2021
Grant date	Jul 20, 2021

Abstract

The present invention provides a pharmaceutical composition containing a quinoline derivative or a salt thereof. Specifically, the invention provides a pharmaceutical composition containing (R,E)-N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-3-cyano-7-ethoxyquinolin-6-yl)-3-(1-methylpyrrolidin-2-yl)-propeneamide or a pharmaceutically acceptable salt thereof, a cross-linked polyvinylpyrrolidone, and at least one pharmaceutically acceptable excipient. The pharmaceutical composition has a property of rapid dissolution.

First claim

What is claimed is:

1. A pharmaceutical composition, comprising:
1) an active drug that is (R,E)-N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-3-cyano-7-ethoxyquinolin-6-yl)-3-(1-methylpyrrolidin-2-yl)-propeneamide or a pharmacologically acceptable salt thereof; and
2) cross-linked polyvinylpyrrolidone.

2. The pharmaceutical composition according to claim 1 , wherein the pharmacologically acceptable salt is a maleate salt.

3. The pharmaceutical composition according to claim 2 , wherein the pharmacologically acceptable salt is a dimaleate salt.

4. The pharmaceutical composition according to claim 1 , wherein the cross-linked polyvinylpyrrolidone is present in an amount of 2%-20% by weight, relative to the total weight of the composition.

5. The pharmaceutical composition according to claim 1 , wherein the active drug is present in an amount of 5%-70% by weight, relative to the total weight of the composition.

6. The pharmaceutical composition according to claim 1 , further comprising a binder, wherein the binder is one or more selected from the group consisting of hydroxypropyl methyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, and methyl cellulose, and wherein the binder is present in an amount of 0.5%-15% by weight, relative to the total weight of the composition.

7. The pharmaceutical composition according to claim 1 , further comprising a filler, wherein the filler is one or more selected from the group consisting of microcrystalline cellulose, calcium hydrogen phosphate, mannitol, pregelatinized starch, and lactose, and wherein the filler is present in an amount of 5%-80% by weight, relative to the total weight of the composition.

8. The pharmaceutical composition according to claim 1 , further comprising a lubricant, wherein the lubricant is one or more selected from the group consisting of talc, magnesium stearate, zinc stearate, glyceryl behenate, sodium lauryl sulfate, hydrogenated vegetable oil, and colloidal silicon dioxide, and wherein the lubricant is present in an amount of 0.5%-5% by weight, relative to the total weight of the composition.

9. The pharmaceutical composition according to claim 1 , wherein a wetting agent is used in preparation of the pharmaceutical composition, and wherein the wetting agent comprises at least one organic solvent.

10. The pharmaceutical composition according to claim 9 , wherein the wetting agent further comprises water.

11. The pharmaceutical composition according to claim 9 , wherein the organic solvent is ethanol or acetone.

12. The pharmaceutical composition according to claim 9 , wherein the organic solvent is present in an amount of 20-100 wt %, relative to the total weight of the wetting agent.

13. The pharmaceutical composition according to claim 11 , wherein the organic solvent is ethanol.

14. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is an oral solid formulation.

15. The pharmaceutical composition according to claim 14 , wherein the pharmaceutical composition is a tablet or a capsule.

16. A method of treating cancer, comprising administering to a subject in need thereof the pharmaceutical composition according to claim 1 .

17. The method according to claim 16 , wherein the cancer is gastric cancer, lung cancer, or breast cancer.

18. A pharmaceutical composition, comprising:
1) 5-70 wt % of (R,E)-N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-3-cyano-7-ethoxyquinolin-6-yl)-3-(1-methylpyrrolidin-2-yl)-propeneamide or a pharmacologically acceptable salt thereof;
2) 2-20 wt % of cross-linked polyvinylpyrrolidone;
3) 5-80 wt % of a filler, wherein the filler is one or more selected from the group consisting of lactose and microcrystalline cellulose;
4) 0.5-15 wt % of a binder, wherein the binder is one or more selected from the group consisting of polyvinylpyrrolidone, hydroxypropyl methyl cellulose and hydroxypropyl cellulose; and
5) 0.5-5 wt % of a lubricant, wherein the lubricant is one or more selected from the group consisting of magnesium stearate and talc.

19. A method for preparing the pharmaceutical composition according to claim 1 , comprising mixing (R,E)-N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-3-cyano-7-ethoxyquinolin-6-yl)-3-(1-methylpyrrolidin-2-yl)-propeneamide or the pharmacologically acceptable salt thereof and cross-linked polyvinylpyrrolidone.

Assignees

• Jiangsu Hengrui Medicine Co

Inventors

• Lu Yun
• Zhang Xinhua
• Wang Chenyang

Classifications

• A61K9/2054

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title

• A61K9/2027 Primary

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• A61K9/2018

  Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates · CPC title

• A61K31/4709 Primary

  Non-condensed quinolines and containing further heterocyclic rings · CPC title

• A61K47/12

  Carboxylic acids; Salts or anhydrides thereof · CPC title