Powder injection of the donepezil semi palmoxiric acid salt, composition containing same and preparation method therefor

Patent metadata

Field	Value
Publication number	US-11801239-B2
Application number	US-202117523229-A
Country	US
Kind code	B2
Filing date	Nov 10, 2021
Priority date	Feb 23, 2017
Publication date	Oct 31, 2023
Grant date	Oct 31, 2023

Abstract

A powder injection of a donepezil semi palmoxiric acid salt, a composition containing the same and a preparation method therefor. The powder injection contains donepezil semi palmoxiric acid salt crystals having an average particle size of 2-52 μm.

First claim

The invention claimed is:

1. A composition comprising donepezil semi pamoate, wherein the composition comprises a powder injection of donepezil semi pamoate comprising donepezil semi pamoate crystals, wherein the donepezil semi pamoate crystals have an average particle size of 2-52 μm, wherein the donepezil semi pamoate crystals have an angle of repose of 25-46 degrees, and wherein an injection prepared from the powder injection has less stimulation to the muscle after injection.

2. The composition of claim 1 , wherein the composition further comprises a diluent.

3. The composition of claim 2 , wherein the diluent comprises 0.75%-1.5% of a suspending agent, 4.5%-6% of a tension agent, and 0.05%-0.2% of a wetting agent.

4. The composition of claim 3 , wherein the suspending agent is sodium carboxymethylcellulose, the tension agent is mannitol or sodium chloride, and the wetting agent is poloxamer 188 or polysorbate 80.

5. The composition of claim 1 , wherein the powder injection of donepezil semi pamoate is present in 13%-24% by mass, based on total mass of the composition.

6. The composition of claim 2 , wherein based on total mass of the diluent, the diluent comprises 0.03%-3% of a suspending agent, 3%-6% of a tension agent, and 0.03%-2% of a wetting agent, by mass; the suspending agent is one or more selected from the group consisting of methylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, alginate, chitosan, glucan, gelatin, polyethylene glycol, polyoxyethylene ether, and polyoxypropylene ether; the tension agent is one or more selected from the group consisting of sodium chloride, dextrose, mannitol, sorbitol, lactose, and sodium sulfate; and the wetting agent is one or more selected from the group consisting of polysorbate 80, polysorbate 20, poloxamer, lecithin, polyoxyethylene ether, polyoxypropylene ether, and sodium deoxycholate.

7. The composition of claim 3 , wherein the diluent comprises 0.75%-1.0% of the suspending agent, 4.5%-5.8% of the tension agent, and 0.05%-0.2% of the wetting agent.

8. A method for preparing an injection of donepezil semi pamoate, comprising:
(1) obtaining a powder injection of donepezil semi pamoate comprising donepezil semi pamoate crystals; and
(2) mixing the powder injection of (1) with a diluent to obtain an injection of donepezil semi pamoate, wherein based on total mass of the diluent, the diluent comprises 0.03%-3% of a suspending agent, 3%-6% of a tension agent, and 0.03%-2% of a wetting agent by mass, and water for injection;
wherein the donepezil semi pamoate crystals have an average particle size of 2-52 wherein the donepezil semi pamoate crystals have an angle of repose of 25-46 degrees, and wherein the injection prepared from the powder injection has less stimulation to the muscle after injection.

9. The method of claim 8 , wherein the diluent comprises 0.75%4.5% of the suspending agent, 4.5%-6% of the tension agent, 0.05%-0.2% of the wetting agent and water for injection.

10. The method of claim 9 , wherein the suspending agent is sodium carboxymethylcellulose; the tension agent is mannitol or sodium chloride; and the wetting agent is poloxamer 188 or polysorbate 80.

11. The method of claim 9 , wherein the diluent comprises 0.75%-1.0% of the suspending agent, 4.5%-5.8% of the tension agent, and 0.05%-0.2% of the wetting agent.

Assignees

• Shanghai Synergy Pharmaceutical Sciences Co Ltd
• Zhejiang Huahai Pharm Co Ltd

Inventors

• Ge Jian
• Li Yunfei
• Lin Lihong
• Sun Dengxue
• Wang Jiamiao
• Wang Yijin
• Wang Zhiyun

Classifications

• A61K31/445 Primary

  Non condensed piperidines, e.g. piperocaine · CPC title

• A61K9/0019 Primary

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K9/16

  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)} · CPC title

• A61K9/1688

  resulting in pure drug agglomerate optionally containing up to 5% of excipient · CPC title

• A61K47/02

  Inorganic compounds · CPC title