Application of Catalysts in Pharmaceutical Intermediates

Application of Catalysts in Pharmaceutical Intermediates

The so-called pharmaceutical intermediates are actually some chemical raw materials or chemical products used in the pharmaceutical synthesis process. This chemical product can be produced in ordinary chemical plants without a drug production license. As long as it reaches some levels, it can be used for drug synthesis.

Chinese name: pharmaceutical intermediate

Explanation: Some chemicals used in drug synthesis

OBJECTIVE: Synthesis of drugs

Features: low profit margin of production intermediates

Representative: fluoropyridines, etc

Field: medicine

catalogue

1 Introduction

summary

Inreased demand

2 Pharmaceutical Machinery Exhibition

Fluoropyridine

Large gap

3 Features

overview

characteristic

4 Relevant introduction

Hot spot of fluoropyridine intermediates

Large gap of p-aminophenol

5 Analysis of Industry Status

Track from medicine to medicine

Basic conditions are still restricting development

The continuity of regular technological development determines the number of enterprises

brief introduction

summary

China needs more than 2000 kinds of raw materials and intermediates supporting chemical industry every year, and the demand is more than 2.5 million tons. After more than 30 years of development, the chemical raw materials and intermediates required for pharmaceutical production in China can be basically matched, and only a small part needs to be imported. Moreover, due to China’s rich resources and low prices of raw materials, many intermediates have been exported in large quantities. So, what are the development opportunities in the field of pharmaceutical intermediates in China?

Increased demand

our country β－ After nearly 50 years of development, lactam antibiotics have formed a complete production system. Almost all β－ All lactam antibiotics (except those within the patent period) can be produced in China, and the cost is very low. Penicillin production ranks first in the world, and a large number of them are exported to the international market; Cephalosporins are basically self-sufficient, and some of them can be exported.

2012, and β－ All the supporting intermediates of lactam antibiotics can be produced by China itself. Except that the mother nuclei of semi synthetic antibiotics, 7-ACA and 7-ADCA, need to be partly imported, all the side chain intermediates can be produced and exported in large quantities.

with β－ As an example, phenylacetic acid, the main supporting intermediate of lactam antibiotics, has nearly 30 phenylacetic acid manufacturers in China, with a total annual production capacity of about 20000 tons. However, most enterprises are small in scale, with the annual output of 2000 tons for large ones and hundreds of tons for others. In 2003, the total domestic demand for phenylacetic acid was about 14000 tons, and the consumption structure was: penicillin G accounted for 85%, other medicines accounted for 4%, spices accounted for 7%, and pesticides and other fields accounted for 4%.

With the development of domestic spice, medicine, pesticide and other industries, the demand for phenylacetic acid will further increase. It is estimated that by 2005, the pharmaceutical industry in China will consume about 14000 tons of phenylacetic acid, the pesticide industry will consume 500 tons, and the spice industry will consume about 2000 tons. In addition to the consumption in other fields, the total domestic demand for phenylacetic acid is expected to reach 18000 tons in 2005.

Fluoropyridine

Ho spot of fluoropyridine intermediates

As of 2012, the quinolone antibiotics developed and put into mass production in China mainly include norfloxacin, ciprofloxacin, ofloxacin, enoxacin, lomefloxacin, fleroxacin, etc. The production of norfloxacin, ciprofloxacin and ofloxacin is large, accounting for 98% of the total production of fluoroquinolones in China.

Quinolones are generally synthesized from fluorobenzene ring to fluoroquinoline compound and then condensed with piperazine (or methylpiperazine). As China is rich in fluorite reserves, it is one of the countries with large output of fluorinated drugs and intermediates in the world, and more than 80% of fluorinated intermediates are supplied for export. On the whole, fluorobenzene intermediates developed earlier in China, and the production capacity was generally surplus; The development of trifluorotoluene intermediates is late and fast; For heterocyclic aromatic compounds, especially fluoropyridines, only a few research units and manufacturers in China have the synthesis technology of fluoropyridine intermediates. Therefore, fluoropyridine intermediates will become one of the main research directions of domestic fluoropyridine intermediates in the next few years.

Large gap

China has become the world’s largest producer of antipyretic and analgesic drugs, with the output of aspirin, paracetamol, analgin and other varieties exceeding 10000 tons, and that of phenacetin, aminopyrine, antipyrine and other varieties exceeding 1000 tons. At present, the output of antipyretic and analgesic drugs in China is growing rapidly, and it is expected that it will increase by about 8% in the future. The production of intermediates for antipyretic and analgesic drugs is large and there are many manufacturers. With the increase of antipyretic and analgesic drugs, the intermedia have also obtained considerable development.

In 2003, the domestic consumption of paracetamol increased rapidly, and the export also showed a rapid growth momentum. The export volume was 28163 tons, and the annual export volume increased by about twice year-on-year. In the first half of 2004, although its export growth slowed down, it still increased. From January to May 2004, the export volume of paracetamol was 12501 tons, slightly higher than the same period last year. Para aminophenol is an important intermediate in the synthesis of paracetamol, which is growing rapidly. The annual output of paracetamol in China is 32000 tons. It is estimated that by 2005, the domestic output of paracetamol will reach more than 50000 tons. The pharmaceutical industry will consume 45000 tons of paracetamol. In addition to its application in other fields, the total demand for paracetamol in 2005 will be about 50000 tons, with a large market gap and broad prospects for development and utilization.

characteristic

overview

Looking at the whole industry, there are six characteristics in the production of pharmaceutical intermediates in China:

characteristic

First, most of the production enterprises are private enterprises with flexible operation and small investment scale, basically between millions and 120 million yuan; Second, the geographical distribution of production enterprises is relatively concentrated, mainly in Taizhou, Zhejiang Province and Jintan, Jiangsu Province as the center; Third, with the increasing attention paid by the state to environmental protection issues, the pressure on production enterprises to build environmental protection treatment facilities has increased; Fourth, the product updates are fast. After a product is generally marketed for 3-5 years, its profit margin drops significantly, which forces enterprises to constantly develop new products or improve production processes to maintain high production profits; Fifthly, because the production profit of pharmaceutical intermediates is higher than that of chemical products, and the production processes of the two are basically the same, more and more small chemical enterprises have joined in the production of pharmaceutical intermediates, leading to increasingly fierce disorderly competition in the industry; Sixth, compared with APIs, the profit margin of intermediates is low, and the production process of APIs and pharmaceutical intermediates is similar. Therefore, some enterprises have not only produced intermediates, but also started to produce APIs using their own advantages.

Related introduction

Hotspot of fluoropyridine intermediates

At present, the quinolone antibiotics developed and put into mass production in China mainly include norfloxacin, ciprofloxacin, ofloxacin, enoxacin, lomefloxacin, fleroxacin, etc. The production of norfloxacin, ciprofloxacin and ofloxacin is large, accounting for 98% of the total production of fluoroquinolones in China.

Quinolones are generally synthesized from fluorobenzene ring to fluoroquinoline compound and then condensed with piperazine (or methylpiperazine). As China is rich in fluorite reserves, it is one of the countries with large output of fluorinated drugs and intermediates in the world, and more than 80% of fluorinated intermediates are supplied for export. On the whole, fluorobenzene intermediates developed earlier in China, and the current production capacity is generally surplus; The development of trifluoromethylene intermediates is late, and the development speed is fast in recent years; However, for heterocyclic aromatic compounds, especially fluoropyridines, only a few research units and manufacturers in China currently have the synthesis technology of fluoropyridine intermediates. Therefore, fluoropyridine intermediates will become one of the main research directions of domestic fluoropyridine intermediates in the next few years.

Large gap of p-aminophenol

China has become the world’s largest producer of antipyretic and analgesic drugs, with the output of aspirin, paracetamol, analgin and other varieties exceeding 10000 tons, and that of phenacetin, aminopyrine, antipyrine and other varieties exceeding 1000 tons. At present, the output of antipyretic and analgesic drugs in China is growing rapidly, and it is expected that it will increase by about 8% in the future. The production of intermediates for antipyretic and analgesic drugs is large and there are many manufacturers. With the increase of antipyretic and analgesic drugs, the intermedia have also obtained considerable development.

In 2003, the domestic consumption of paracetamol increased rapidly, and the export also showed a rapid growth momentum. The export volume was 28163 tons, and the annual export volume increased by about twice year-on-year. In the first half of 2004, although its export growth slowed down, it still increased. From January to May 2004, the export volume of paracetamol was 12501 tons, slightly higher than the same period last year. Para aminophenol is an important intermediate for the synthesis of paracetamol, which has also grown rapidly in recent years. At present, the annual output of paracetamol in China is about 32,000 tons. It is estimated that by 2005, the domestic output of paracetamol will reach more than 50,000 tons, and the pharmaceutical industry will consume 45,000 tons of paracetamol. With the application in other fields, the total demand for paracetamol in 2005 will be about 50,000 tons. The market gap is large, and the development and utilization prospects are broad.

Industry status analysis

After the brilliant pharmaceutical intermediate industry in the late 1990s, the competition between enterprises has basically entered a mature stage, which has reached a point of intense competition. The one who can stick to it is the survivor. At the same time, new investors are constantly attracted by various legends and other factors Dream of entering the industry. However, with the rise of the country’s requirements for GMP certification of pharmaceutical enterprises and various overseas certifications, the investment scale of the pharmaceutical industry has risen exponentially. How to make the limited capital and energy generate large economic and social benefits has become the goal pursued by every pharmaceutical intermediate investor

Track from medicine to medicine

The impact of the process of economic globalization on China’s economy is nothing more profound than its idea that each production enterprise does not need to be big, but should concentrate its capital and energy on the industry and field in which it is good. Other supporting materials and conditions can be completed through social cooperation. Through the formation of a product chain, both parties can achieve win-win results. Under the influence of this idea, the pharmaceutical industry will process some primary products, such as solvent recovery, etc After being transferred to cooperative enterprises, they gradually transferred some polluting and dangerous products to chemical plants for production, such as phenylacetic acid chloroacetic acid for penicillin production. Since the 1970s and 1980s, there have been a large number of small township enterprises and individual enterprises supporting the production of phenylacetic acid and chloroacetic acid for North China Pharmaceutical

With the deepening of cooperation between the two sides, pharmaceutical enterprises gradually transfer some products with higher added value and greater technical difficulties to chemical plants for production, such as the AE active ester of aminothiaxime acid used in the production of cephalosporin antibiotics triazine cyclotetrazolium acetate p-hydroxyphenylglycine (Dunk potassium salt) HO EPCP and other products have enabled the branch industry to develop rapidly in the 1990s, and a number of pharmaceutical intermediate enterprises with an output value of tens of millions to billions of yuan, such as Zhejiang Yongning Pharmaceutical Factory, Fushun Meiqiang Pharmaceutical Factory, Zhejiang Hengdian Debang Group, Shandong Ruiying Group, Shandong Jincheng Chemical Factory and many other enterprises. At present, the industry has developed into a closer cooperation stage with pharmaceutical enterprises, and the manufacturers of pharmaceutical intermediates directly synthesize APIs (with mushroom powder) And the products are sold to pharmaceutical enterprises in the form of chemical products for refining and then sold as drugs. The pharmaceutical intermediate industry can further extend the product chain, increase the profits of products and improve the stability of sales. Pharmaceutical enterprises reduce investment and put limited funds and efforts on aseptic packaging that they are good at. Because the pharmaceutical intermediate industry cannot compete with pharmaceutical enterprises for the market without the production license of pharmaceutical products The cooperation between the two sides has certain complementary conditions. The basic conditions are still restricting the development

At present, domestic manufacturers of cephalosporin antibiotic mother core 7-ACA, including Shi Yaofu Kanglu Kangkang, have completely reversed the situation that foreign 7-ACA occupied the domestic market. Foreign manufacturers have withdrawn from the domestic market, causing the current domestic supply of 7-ACA to be very tight while the domestic consumption market of cephalosporin antibiotics to be mature. Therefore, this situation has led to a tense situation that the domestic supply of cephalosporin antibiotic intermediates is in short supply It caused a new round of investment climax. However, due to various reasons analyzed above, it is difficult for newly launched enterprises to compete with established enterprises. Although some established enterprises have stopped the production of one or several varieties at present, it is easy to resume production. Therefore, although there is a large development space in the domestic cephalosporin antibiotic pharmaceutical intermediate market, it has considerable risks for new investors The growing popularity of the biotic market has led to the low price of penicillin antibiotics. Therefore, it is also a good investment route to transform penicillin to synthesize new antibiotics, such as mezlocillin, aloxicillin, piperacillin, etc. Because of their good efficacy and low price, they have a very good development prospect. At the same time, the transformation of penicillin into the mother nucleus of cephalosporins, such as 7-ADCAGCLEGEO, is also a product investment with good market prospects The product can avoid direct conflicts with mature and powerful competitors, and can play a surprise role