Caspofungin or salts thereof with high purity, as well as preparation method and use thereof

Patent metadata

Field	Value
Publication number	US-9446091-B2
Application number	US-201214113296-A
Country	US
Kind code	B2
Filing date	Apr 20, 2012
Priority date	Apr 22, 2011
Publication date	Sep 20, 2016
Grant date	Sep 20, 2016

Abstract

Disclosed are a high purity of caspofungin or salts thereof, and a preparation method thereof, and use thereof. Disclosed are a caspofungin or salts thereof with low solvent residue and hyposaline, and a preparation process comprising: dissolving a crude product of caspofungin or salts thereof into a system of water and acetic acid, then mixing with a first organic solvent ethyl alcohol, subsequently mixing with a second organic solvent ethyl acetate, then being subject to filtration and drying together with water, to obtain caspofungin or salts thereof with high stability, low solvent residue and hyposaline.

First claim

The invention claimed is:

1. A preparation method for a composition comprising: a compound of formula 1 or salts thereof; one or more organic solvents resulting from the preparation of the compound of formula 1 or salts thereof; and inorganic salts,
wherein, in the one or more organic solvents, each organic solvent is present at a weight percentage of not more than 0.5%; the salts of the compound of formula 1 are acetate; and the inorganic salts are present at a weight percentage of not more than 0.5%,
wherein the method includes the following steps:
a. vacuum-drying raw material comprising the compound of formula 1 or salts thereof with a water system together,

b. removing the water system, and then continuing vacuum-drying of the raw material comprising the compound of formula 1 or salts thereof, thereby obtaining the composition.

2. The preparation method according to claim 1 , wherein, in step a, a temperature for drying ranges from 0 to 20° C.

3. The preparation method according to claim 1 , wherein, in step a, the water system includes tap water, pure water, ice-water mixture, or a substance capable of releasing water vapor.

4. The preparation method according to claim 1 , wherein, in step a, a time for drying ranges from 1 to 48 hrs.

5. The preparation method according to claim 1 , wherein, in step b, a time for drying ranges from 0 to 5 hrs.

6. The preparation method according to claim 1 , wherein the process for preparing a raw material comprising the compound of formula 1 or salts thereof in step a comprises:
a′. mixing a crude preparation of the compound of formula 1 or salts thereof with acetic acid and water, thereby obtaining homogeneous solution 1;
b′. mixing homogeneous solution 1 with ethanol, thereby obtaining homogeneous solution 2; and
c′. mixing homogeneous solution 2 with ethyl acetate, thereby obtaining caspofungin or salts thereof in crystalline form.

7. The preparation method according to claim 6 , wherein, in step a′, a temperature for mixing ranges from 0 to 20° C.

8. The preparation method according to claim 6 , wherein, in step b′, a temperature for mixing ranges from 0 to 20° C.

9. The preparation method according to claim 6 , wherein, in step c′, a temperature for mixing ranges from 0 to 20° C.

10. The preparation method according to claim 6 , wherein, in step c′, a volume ratio for mixing homogeneous solution 2 with ethyl acetate is 1:1-3.

Assignees

• He Bingming
• Li Ming
• Tang Zhijun
• Ji Xiaoming
• Shanghai Techwell Biopharm Co

Inventors

• He Bingming
• Li Ming
• Tang Zhijun
• Ji Xiaoming

Classifications

• A61P31/10

  Antimycotics · CPC title

• A61K38/005

  Enzyme inhibitors (protease inhibitors A61K38/55) · CPC title

• C07K7/56 Primary

  the cyclisation not occurring through 2,4-diamino-butanoic acid · CPC title

• C07K7/54 Primary

  with at least one abnormal peptide link in the ring · CPC title

• A61K38/12 Primary

  Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)} · CPC title