About Peptide C China DMO

About Peptide C China DMO

Polypeptides generally refer to a class of compounds formed by the dehydration condensation of 3-50 α-amino acids. According to different sources, they can be roughly divided into three categories, namely, extracted polypeptides, chemically synthesized polypeptides (exenatide) and genetically recombinant polypeptides ( Liraglutide).

The advantages of peptide drugs are strong druggability, high activity, good specificity, relatively weak toxic reaction, not easy to accumulate, and less drug cross-reactions. Peptide drugs have the advantages of high biological activity, strong specificity, and small side effects.

Global in 2015 The total sales of peptide drugs reached 22 billion U.S. dollars, which is one of the fastest-growing drug fields. In recent years, the peptide super varieties marketed globally include Somaglutide, Liraglutide, Exenatide, Leuprolide, Teriparatide…

and Somaglutide is based on the use of screen medicine. In the circle of friends, peptide pharmaceutical companies have submitted applications for the science and technology innovation board. Recently, two peptide pharmaceutical companies, Chengdu Shengnuo Biotechnology and Nuotaiaosino Bio, have submitted applications for the science and technology innovation board.

Peptides are high-quality targets for CDMO projects

The selected peptide of CDMO project is a very good choice for R&D project. Sort from the difficulty of production: Small molecule peptide drugs are all excellent targets for CDMO projects.

In addition, peptide drugs are a huge family. There are hundreds of peptide drugs currently in the research and development stage, and the development field has also been extended to various indications. Common fields include anti-infection, anti-tumor, physiological regulation, pain, heart failure, Osteoporosis, diabetes, vaccines, etc., the synthetic methods and routes of each peptide drug are very different, which also provides a broad opportunity for the development of many peptide-based CDMO companies.

The production of peptides-technical barriers that are difficult to break through

Taking leuprolide as an example, the earliest original research product was launched in the United States in 1994, and a sustained-release preparation was launched in 2002. The patent period came very early, but it did not affect its sales in any way. In 2000, Takeda’s Leuprolide entered China under the trade name “Innate”. The drug has no patents in China, but currently only two domestic companies have approved generic drugs for the market. This shows that the technical barriers to peptide drug development are high.

The production of peptides mainly includes chemical synthesis and enzymatic methods. From synthesis to purification, from purification to preparations are barriers that we need to break through, and these barriers are not only technology and quality research, but also cost control;

among them, chemical synthesis It is considered to be a conventional and most widely used technology for peptide production, but the lack of specificity and the increased risk of environmental burden will hinder the development of chemical peptide synthesis; this promotes the use of enzymatic technology for peptide synthesis, but the technology is The disadvantages are low production efficiency, relatively expensive biocatalysts, and lack of verification schemes, which pose challenges to peptide production.

Chemical synthesis methods are divided into liquid-phase peptide synthesis (LPPS) and solid-phase peptide synthesis (SPPS). LPPS is a reaction carried out in a solution, using protected amino acids, and needs to be separated from the solution after each coupling and deprotection.

SPPS synthesizes the polypeptide chain on the insoluble polyester. After each deprotection, the protected amino acids are added to the resin one by one without an intermediate separation step. After synthesizing the required length on the resin, the peptide is cut and purified by chromatography. For the production of specific peptides, it is also possible to mix the two methods of liquid phase synthesis and solid phase synthesis.

After years of research and development, solid-phase synthesis is now commonly used, which not only overcomes the time-consuming and cumbersome liquid-phase synthesis, but also reduces the loss caused by operation. The biggest advantage is that all the purification steps in the synthesis are completed by simple washing and filtration, which greatly reduces the difficulty of purification.

It has the advantages of convenience and quickness, simple operation and high yield, making it the preferred method for peptide chemical synthesis. The features are:

1) High degree of automation, and product production can basically be completed with an automatic synthesizer.

2) The reaction is basically normal temperature and pressure, and the safety is high.

3) The production needs to use Class A solvents such as acetonitrile, so the fire protection category of the synthesis section is Class A, and the purification section is designed according to different processes, and some also need to be designed in accordance with Class A.

It can be seen that for high-purity drugs, short-chain peptides (liquid-phase synthesis is more economical, so the method of liquid-phase peptide synthesis is usually used to synthesize such peptides on a large scale. Although liquid-phase peptide synthesis requires many steps, liquid-phase synthesis is more economical than solid-phase synthesis). Phase peptide synthesis technology can produce relatively large-scale peptides more economically. However, due to the complexity of the process, liquid phase synthesis is not a feasible option for long peptides.

The method of using biological enzymes to catalyze proteins is called enzymatic method, which is the preferred choice for the synthesis of long peptides. The biological enzyme degradation method uses biological enzyme technology to obtain polypeptides through enzymatic hydrolysis, degradation and hydrolysis of proteins, with a molecular weight distribution between 200-1000 Da.

The enzymatic process has the characteristics of simple process, low investment, stable peptide product quality, high activity, high content and good taste. In the enzymatic production process, the composition of the enzymatic hydrolysate is complex. In addition to peptides, it also contains impurities such as macromolecular proteins, enzymes, and ash. To obtain products with higher purity, it is necessary to remove impurities as much as possible through separation methods and enrich them. Polypeptides are finally spray-dried to make finished products with higher purity.

The next era of the peptide industry-focusing on the future development of the peptide industry

Polypeptide drugs are mainly used for the treatment of chronic diseases. At present, the international peptide drugs are mainly distributed in the treatment of 7 major diseases, including rare diseases, tumors, diabetes, gastrointestinal tract, orthopedics, immunity, cardiovascular diseases, etc., among which rare diseases, Tumor and diabetes are the “troika” driving the peptide drug market, and the other four fields also have heavy varieties on the market.

Representative varieties include liraglutide, dulaglutide, somaglutide, leuprolide, Teriparatide, octreotide, exenatide, etc. According to IQVIA data, in 2007, the global peptide pharmaceutical preparations market was about 12.39 billion U.S. dollars, and by 2017 it had increased to 34.05 billion U.S. dollars, with an average annual compound growth rate of 11%.

From the perspective of listed products, the product structure of my country’s peptide drug market is significantly different from that of the international mature market. At present, the peptide drugs with large sales in China are mainly anti-tumor and immunomodulatory products. In developed countries in Europe and the United States, tumors, diabetes, and rare diseases are the “three carriages” driving the peptide drug market, with larger sales.

All are therapeutic drugs with clear clinical benefits, such as hypoglycemic drugs liraglutide and dulaglutide, antitumor drugs leuprolide and goserelin, anti-osteoporosis drug teriparatide, treatment Glatiramer in relapsing multiple sclerosis. Compared with developed countries, the market share of peptide drugs for the treatment of diabetes, rare diseases and other diseases in my country is still relatively small, and there is still huge room for growth.

In recent years, with the continuous improvement of the overall strength of my country’s pharmaceutical industry, the domestic peptide drug industry has also made considerable progress. In terms of generic drugs, after the patent protection period of global blockbuster peptide drugs such as liraglutide has expired, many domestic companies have begun to invest a lot of resources in generic research, and some companies have applied for production to the State Food and Drug Administration.

The rapid development of the peptide industry-specialized peptide CDMO company

At present, my country has become a major exporter of peptide APIs, accounting for more than 30% of the global peptide API market. Polypeptide companies including Sinopec, Hanyu Pharmaceutical, and Sinopeptide Biochemical have entered the European and American markets by obtaining cGMP certification and DMF documents. At the same time, they vigorously develop other markets and continue to enhance their competitiveness.

Chengdu Shengnuo Biotechnology Co., Ltd.

Chengdu Shengnuo Biotechnology Co., Ltd. was established in July 2001. It is a domestic first-class specialized peptide drug and product development, technology transfer, technical service, large-scale production, and export peptide drug industrial park. The main products are octreotide acetate injection and thymopentin for injection; the bulk drug products include bivalrudine, eptifibatide, liraglutide, icatibant and octreotide.