Preparation method of teduglutide

Abstract

The invention belongs to the field of medicinal chemistry, and in particular relates to a preparation method of teduglutide. The preparation method of the invention is as below: respectively synthesizing a teduglutide sequence site No.4-33 peptide resin fragment and a teduglutide sequence No.1-3 peptide resin fragment through solid phase synthesis; then coupling the teduglutide sequence site No.4-33 peptide resin fragment and the teduglutide sequence No.1-3 peptide resin fragment by an appropriate resin vector to obtain a teduglutide resin; and finally cracking to obtain crude teduglutide, and purifying to obtain the pure teduglutide. The preparation method provided by the invention can effectively avoid side reaction such as degradation caused by an Asp-Gly structure of the No. 3-4 site, also can reduce the His1 racemization, thus effectively improving the purity of crude peptide and improve the purification yield. Compared with the prior art, the preparation method of the invention has the advanategs of high purity of the prepared teduglutide product, less by-product and high product yield, and is beneficial for mass production of teduglutide.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, in particular to a preparation method of teduglutide. Background technique [0002] Short bowel syndrome (short bowel syndrome, SBS) refers to a series of syndromes caused by the body's inability to absorb nutrients normally due to severe small intestinal disease or surgical removal of most of the small intestine. SBS reduces the patient's ability to absorb fluids and nutrients. Due to the short residual intestine, nutrient absorption and digestion disorders can manifest as diarrhea, steatorrhea, and weight loss, leading to dehydration and malnutrition, and even life-threatening in severe cases. Most patients with short bowel syndrome cannot eat normally. Some can resume oral diet after active and appropriate intestinal rehabilitation treatment, but some need to rely on parenteral nutrition for life. Parenteral nutrition support will increase the risk of systemic infection and other long-term ...

AI Technical Summary

Problems solved by technology

[0005] However, the researchers found that whether the conventional step-by-step coupling method in the patent publication number CN101824087A or the solid-phase fragment condensation method in the patent publication number WO2012028602A1 is used to prepare teduglutide, there is a problem that His1 is easy to racemize

Due to the racemization of His, the prepared teduglutide is difficult to purify, resulting in a decrease in the yield of teduglutide

In addition, the patent publication number WO2012028602A1 uses the method of solid-phase coupling of fragment 1-4 and fragment peptide resin 5-33 to prepare teduglutide, which still cannot effectively solve the degradation caused by the Asp-Gly structure at the 3-4 position Such side reactions will also make it difficult to purify the prepared teduglutide, further leading to a decrease in the yield of teduglutide