# US 11,433,076 B2 · Preparation containing tetracyclic compound at high dose

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- Number: US 11,433,076 B2
- Document ID: US11433076B2
- Status: Granted
- Kind: B2
- Application number: 16/508,760
- Filed: 2019-07-11
- Published: 2020-02-06
- Granted: 2022-09-06
- Earliest claimed: 2014-04-25
- Assignees: Chugai Seiyaku Kabushiki Kaisha
- Applicants: Chugai Seiyaku Kabushiki Kaisha
- Inventors: Takashi Tomimatsu; Kensuke Okazaki; Yumi Ogawa; Takahiro Yamamura
- Web page: https://patentgrep.com/patent/US11433076B2

## CPC

- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 9/16: Agglomerates; Granulates; Microbeadlets {; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction (A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51)}
- A61K 9/1617: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)}
- A61K 9/48: Preparations in capsules, e.g. of gelatin, of chocolate {(A61K9/0004 takes precedence; bite capsules A61K9/0056)}
- A61K 47/20: containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K 47/38: Cellulose; Derivatives thereof
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/24: Antidepressants
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- 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
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

An improved solubility of a pharmaceutical composition or formulation containing a large amount of 9-ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile or a salt thereof can be achieved by forming granules of the compound or salt thereof and allowing the granules to be present together with a disintegrating agent.

## Claims

### Claim 1

A pharmaceutical formulation comprising granules containing a compound represented by formula (I) or a pharmaceutically acceptable salt thereof:
wherein the granules have a mean particle diameter of 150 μm or more and wherein the granules have a bulk density of 0.5 g/ml or more and a tapping density of 0.6 g/ml or more.

### Claim 2 (depends on 1)

The formulation of claim 1, wherein the bulk density is 0.6 g/ml or more and the tapping density is 0.7 g/ml or more.

### Claim 3 (depends on 1)

The formulation of claim 1, wherein the upper limit of the bulk density and the tapping density are 1.0 g/ml.

### Claim 4 (depends on 1)

The formulation of claim 1, wherein the granules have a mean particle diameter of 200 μm or more.

### Claim 5 (depends on 1)

The formulation of claim 1, wherein the upper limit of the mean particle diameter of the granules is 1 mm.

### Claim 6 (depends on 1)

The formulation of claim 1, wherein the granules further comprise a disintegrating agent.

### Claim 7 (depends on 6)

The formulation of claim 6, wherein the disintegrating agent (ii) is contained in the granules in an amount of 5 wt % or more.

### Claim 8 (depends on 6)

The formulation of claim 6, wherein the disintegrating agent (ii) is contained in the granules in an amount of 7.5 wt % or more.

### Claim 9 (depends on 6)

The formulation of claim 6, wherein the disintegrating agent is selected from the group consisting of sodium starch glycolate, low-substituted hydroxypropylcellulose, carmellose calcium, sodium hydrogen carbonate, pregelatinized starch, sodium chloride, corn starch, croscarmellose sodium, crystalline cellulose, silicic anhydride and carmellose.

### Claim 10 (depends on 1)

The formulation of claim 1, wherein the granules further comprise a solubilizing agent.

### Claim 11 (depends on 10)

The formulation of claim 10, wherein the solubilizing agent is sodium lauryl sulfate.

### Claim 12 (depends on 1)

The formulation of claim 1, wherein the granules further comprise a binder.

### Claim 13 (depends on 12)

The formulation of claim 12, wherein the binder is hydroxypropylcellulose.

### Claim 14 (depends on 1)

The formulation of claim 1, wherein the compound is 9-ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile hydrochloride.

### Claim 15 (depends on 1)

The formulation of claim 1, wherein an amount of the compound in free form per unit formulation is 60 mg to 240 mg.

### Claim 16 (depends on 15)

The formulation of claim 15, wherein the amount of the compound in free form per unit formulation is 140 mg to 190 mg.