Process for the preparation of a sulfated derivative of 3,5-diiodo-o-[3-iodophenyl]-l-tyrosine

Patent metadata

Field	Value
Publication number	US-10457635-B2
Application number	US-201715853506-A
Country	US
Kind code	B2
Filing date	Dec 22, 2017
Priority date	Apr 8, 2011
Publication date	Oct 29, 2019
Grant date	Oct 29, 2019

Abstract

Furthermore, the invention discloses non-radioactive immunoassays based on T3S derivatives.

First claim

The invention claimed is:

1. A process for the preparation of a sulfated form of a thyroid hormone having formula II (T 3 S) according to the following reaction:

wherein M is an alkaline metal, comprising the steps of:
a) sulfation of a compound of formula I with chlorosulfonic acid (CSA) in the presence of dimethylacetamide (DMAC), wherein the molar ratio of CSA to the compound of formula I is from 4 to 10, and wherein more than 90% of the compound of formula I is converted to the sulfated derivative;
b) salification of the sulfated derivative to give a compound of formula II, in an aqueous solution of an alkaline metal inorganic salt; and
c) purification of the formula II compound by chromatography on macroreticular aromatic polymeric matrix and elution with a decreasing polarity solution;
wherein the amount of by-products in step a) is lower than 10%.

2. The process according to claim 1 , wherein T3S after steps a)-c) has a purity of at least 95%.

3. The process according to claim 2 , wherein T 3 S has a purity of at least 99%.

4. The process according to claim 1 , further comprising the steps of
i— micronizing the pure T 3 S to reduce the particle size and
ii— formulating the micronized T 3 S with ingredients in powder mixtures.

5. The process according to claim 4 , wherein T 3 S is micronized under nitrogen pressure.

6. The process according to claim 5 , wherein at least 90% of the micronized T 3 S particles has a size lower than 25 μm.

7. The process according to claim 6 , wherein at least 95% of the micronized T 3 S particles has a size lower than 25 μm.

8. The process according to claim 4 , wherein all the ingredients are solid and formulated under granular or microgranular form.

9. The process according to claim 8 , wherein the ingredients are formulated as tablets or pills through direct compression of the powder mixture.

10. The process according to claim 4 , wherein the micronized T 3 S is formulated for oral administration.

Assignees

• Bracco Imaging Spa

Inventors

• Anelli Pier Lucio
• Argese Maria
• Boi Valeria
• Cavalieri Livio
• Galimberti Laura
• Gazzetto Sonia
• Lattuada Luciano
• Maisano Federico
• Rivolta Giovanni
• Vella Fulvia

Classifications

• C07C309/42

  having the sulfo groups bound to carbon atoms of non-condensed six-membered aromatic rings · CPC title

• C07C303/24 Primary

  of esters of sulfuric acids · CPC title

• A61K31/198

  Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00) · CPC title

• A61K9/2054

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

• C07D495/04

  Ortho-condensed systems · CPC title