# US 2021/0275534 A1 · Solid pharmaceutical composition containing 1,3,5-triazine derivative or salt thereof

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- Number: US 2021/0275534 A1
- Document ID: US20210275534A1
- Status: Published application
- Kind: A1
- Application number: 17/272,915
- Filed: 2019-09-03
- Published: 2021-09-09
- Earliest claimed: 2018-09-03
- Assignees: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.; Lianyungang Runzhong Pharmaceutical Co., Ltd.; Centaurus Biopharma Co., Ltd.
- Applicants: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.; Lianyungang Runzhong Pharmaceutical Co., Ltd.; Centaurus Biopharma Co., Ltd.
- Inventors: Yuanyuan SUN; Shan ZHOU; Lei LIU; Ping DONG; Jing GAO; Laicun LI; Zhilin CHEN; Yi XU; Shang WANG
- Web page: https://patentgrep.com/patent/US20210275534A1

## CPC

- A61K 31/53: having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495})
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61P 35/00: Antineoplastic agents
- A61K 9/2095: {Tabletting processes}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A solid pharmaceutical composition containing a 1,3,5-triazine derivative or a pharmaceutically acceptable salt thereof and a preparation method therefor. In particular, involved are a solid pharmaceutical composition containing 4-(tert-butoxyamino)-6-(6-(trifluoromethyl)pyridin-2-yl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1,3,5-triazine-2-amine or a pharmaceutically acceptable salt thereof and a preparation method therefor. The solid pharmaceutical composition has a good stability, a fast dissolution rate and a high bioavailability, and is suitable for clinical production and use.

## Claims

### Claim 1

A solid pharmaceutical composition, comprising a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the solid pharmaceutical composition comprises the compound of formula I or the pharmaceutically acceptable salt thereof as an active ingredient and at least one pharmaceutically acceptable excipient;
wherein the solid pharmaceutical composition comprises 10-100 mg of the compound of formula I or the pharmaceutically acceptable salt thereof; or alternatively, the compound of formula I or the pharmaceutically acceptable salt thereof is present in an amount of 0.5-50 wt %, preferably 0.5-30 wt %, and more preferably 1-25 wt %, based on the total mass of the solid pharmaceutical composition.

### Claim 2

(canceled)

### Claim 3 (depends on 1)

The solid pharmaceutical composition according to claim 1, wherein the excipient comprises a diluent, a binder, a disintegrant and/or a lubricant.

### Claim 4 (depends on 1)

The solid pharmaceutical composition according to claim 1, wherein the pharmaceutically acceptable salt of the compound of formula I is selected from: monohydrochloride of the compound of formula I, dihydrochloride of the compound of formula I, trihydrochloride of the compound of formula I, monomethanesulfonate of the compound of formula I, dimethanesulfonate of the compound of formula I, trimethanesulfonate of the compound of formula I, mono-p-toluenesulfonate of the compound of formula I, di-p-toluenesulfonate of the compound of formula I, and tri-p-toluenesulfonate of the compound of formula I; preferably monomethanesulfonate of the compound of formula I, dimethanesulfonate of the compound of formula I and trimethanesulfonate of the compound of formula I; and more preferably monomethanesulfonate of the compound of formula I.

### Claim at position 5

-8. (canceled)

### Claim 9 (depends on 3)

The solid pharmaceutical composition according to claim 3, wherein the solid pharmaceutical composition further comprises a solubilizer selected from: hydroxypropyl methylcellulose, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyethylene glycol 15 hydroxystearate, sodium dodecyl sulfate, magnesium dodecyl sulfate, sorbitan esters, glyceryl caprylate, glyceryl trioleate, polyoxylglycerides, povidone, pyrrolidone, poloxamer, phospholipids and vitamin E polyethylene glycol succinate; and preferably, the solubilizer is present in an amount of 0.5-5 wt % based on the solid pharmaceutical composition.

### Claim 10 (depends on 3)

The solid pharmaceutical composition according to claim 3, further comprising: a mixture comprising the compound of formula I or the pharmaceutically acceptable salt thereof, and a fluidization excipient; and preferably, the pharmaceutically acceptable salt of the compound of formula I is selected from: monomethanesulfonate of the compound of formula I, dimethanesulfonate of the compound of formula I, and trimethanesulfonate of the compound of formula I.

### Claim 11 (depends on 10)

The solid pharmaceutical composition according to claim 10 further comprising an additional excipient.

### Claim 12 (depends on 10)

The solid pharmaceutical composition according to claim 10, wherein the mixture comprising the compound of formula I or the pharmaceutically acceptable salt thereof further comprises a binder, a diluent and/or a solubilizer; preferably, the diluent in the mixture comprising the compound of formula I or the pharmaceutically acceptable salt thereof is present in an amount of 10-50 wt %, preferably 15-50 wt %, and more preferably 17-35 wt %, based on the total amount of diluents in the solid pharmaceutical composition.

### Claim 13 (depends on 12)

The solid pharmaceutical composition according to claim 12, wherein the mixture comprising the compound of formula I or the pharmaceutically acceptable salt thereof comprises a binder and a diluent; preferably the binder is selected from: hydroxypropyl methylcellulose, hydroxypropyl cellulose and povidone; and preferably the diluent is selected from microcrystalline cellulose, lactose, starch, mannitol, xylitol, a mixture of microcrystalline cellulose and lactose, a mixture of microcrystalline cellulose and starch, a mixture of microcrystalline cellulose and mannitol, and a mixture of microcrystalline cellulose and xylitol.

### Claim 14 (depends on 12)

The solid pharmaceutical composition according to claim 12, wherein the mixture comprising the compound of formula I or the pharmaceutically acceptable salt thereof comprises a binder and a solubilizer; preferably the binder is selected from hydroxypropyl methylcellulose, hydroxypropyl cellulose and povidone; and preferably the solubilizer is selected from sodium dodecyl sulfate and magnesium dodecyl sulfate.

### Claim 15 (depends on 12)

The solid pharmaceutical composition according to claim 12, wherein the mixture comprising the compound of formula I or the pharmaceutically acceptable salt thereof comprises a binder, a diluent and a solubilizer; preferably the binder is selected from hydroxypropyl methylcellulose, hydroxypropyl cellulose and povidone; preferably the diluent is selected from: microcrystalline cellulose, lactose, starch, mannitol, xylitol, a mixture of microcrystalline cellulose and lactose, a mixture of microcrystalline cellulose and starch, a mixture of microcrystalline cellulose and mannitol, and a mixture of microcrystalline cellulose and xylitol; and preferably, the solubilizer is selected from sodium dodecyl sulfate and magnesium dodecyl sulfate.

### Claim 16 (depends on 10)

The solid pharmaceutical composition according to claim 10, wherein the fluidization excipient comprises a diluent and a disintegrant; preferably the diluent is selected from microcrystalline cellulose, lactose, starch, mannitol, xylitol, a mixture of microcrystalline cellulose and lactose, a mixture of microcrystalline cellulose and starch, a mixture of microcrystalline cellulose and mannitol, and a mixture of microcrystalline cellulose and xylitol; and preferably the disintegrant is selected from croscarmellose sodium, sodium carboxymethyl starch, crospovidone and low substituted hydroxypropyl cellulose.

### Claim 17 (depends on 11)

The solid pharmaceutical composition according to claim 11, wherein the additional excipient comprises a lubricant; and preferably, the lubricant is selected from magnesium stearate, glyceryl behenate, sodium lauryl sulfate, and sodium stearyl fumarate.

### Claim 18 (depends on 1)

The solid pharmaceutical composition according to claim 1, wherein the solid pharmaceutical composition is prepared by fluidized bed granulation.

### Claim 19 (depends on 1)

A method for preparing the solid pharmaceutical composition according to claim 1, wherein the method is fluidized bed granulation, comprising: (1) preparing a suspension comprising the compound of formula I or the pharmaceutically acceptable salt thereof; (2) preparing a fluidization excipient; (3) placing the fluidization excipient into a fluidized bed, and spraying the suspension comprising the compound of formula I or the pharmaceutically acceptable salt thereof into the fluidized bed for granulation; (4) sizing; and optionally (5) mixing an additional excipient with the sized materials.

### Claim 20 (depends on 19)

The method according to claim 19, wherein, in step (1), a solvent of the suspension is selected from methanol, ethanol, isopropanol, acetone, water, and any combination thereof; and preferably, the mass ratio of the compound of formula I or the pharmaceutically acceptable salt thereof to the solvent in the suspension is 1: (5-20).

### Claim 21 (depends on 19)

The method according to claim 19, wherein, in step (1), the suspension further comprises a binder, a diluent and/or a solubilizer; preferably the binder is selected from hydroxypropyl methylcellulose, hydroxypropyl cellulose and povidone; preferably the diluent is selected from microcrystalline cellulose, lactose, starch, mannitol, xylitol, a mixture of microcrystalline cellulose and lactose, a mixture of microcrystalline cellulose and starch, a mixture of microcrystalline cellulose and mannitol, and a mixture of microcrystalline cellulose and xylitol; and preferably the solubilizer is selected from sodium dodecyl sulfate and magnesium dodecyl sulfate.

### Claim 22 (depends on 21)

The method according to claim 21, wherein the diluent of the suspension is present in an amount of 10-50 wt %, preferably 15-50 wt %, and more preferably 17-35 wt %, based on the total amount of diluents in the solid pharmaceutical composition.

### Claim 23 (depends on 21)

The method according to claim 21, wherein in step (1), the compound of formula I or the pharmaceutically acceptable salt thereof is first mixed with the binder, the diluent and/or the solubilizer to give a mixture comprising the compound of formula I or the pharmaceutically acceptable salt thereof, and then the mixture is mixed with the solvent to give the suspension comprising the compound of formula I or the pharmaceutically acceptable salt thereof.

### Claim 24 (depends on 19)

The method according to claim 19, wherein, in step (2), the fluidization excipient comprises a diluent and a disintegrant; preferably the diluent is selected from microcrystalline cellulose, lactose, starch, mannitol, xylitol, a mixture of microcrystalline cellulose and lactose, a mixture of microcrystalline cellulose and starch, a mixture of microcrystalline cellulose and mannitol, and a mixture of microcrystalline cellulose and xylitol; and preferably the disintegrant is selected from croscarmellose sodium, sodium carboxymethyl starch, crospovidone and low substituted hydroxypropyl cellulose.

### Claim 25 (depends on 19)

The method according to claim 19, wherein, in step (5), the additional excipient comprises a lubricant; and preferably, the lubricant is selected from magnesium stearate, glyceryl behenate, sodium lauryl sulfate, and sodium stearyl fumarate.

### Claim 26

(canceled)