Photo courtesy of Roche.
Crystallization of main active components of oseltamivir phosphate-Tamiflu.
Each 75mg capsule contains active chemical components and various inactive components of oseltamivir. Scientists synthesized oseltamivir from shikimic acid, which is a natural substance and can be found in plants such as star anise, ginkgo, spruce, pine and fir.
Roche mainly obtains shikimic acid from Illicium verum, which is the spice in the star-shaped fruit of Illicium verum (a small evergreen tree). Roche uses a special kind of fennel, which grows in four mountainous provinces in southwest China (Guangxi, Sichuan, Yunnan and Guizhou). Because these areas are plateaus and the weather is hot and humid, the purity and yield of Illicium verum are higher than other areas.
Photo courtesy of Roche.
The fruits and pods of Tamiflu and Illicium verum.
The manufacturing process of Tamiflu is complicated, involving 10 steps, and it takes about 6 to 8 months to complete. First, Roche suppliers extract shikimic acid from the pod (the part that wraps the seeds) of Illicium verum. The remaining steps include a series of complex chemical reactions. 30 kg of star anise can only produce 1 kg of shikimic acid.
Although most shikimic acid comes from Illicium verum, Roche and its partners are increasingly using fermentation to produce shikimic acid. In the fermentation process, Roche used a special strain of Escherichia coli. When these bacteria are given too much glucose or sucrose, they produce shikimic acid. This step can produce more shikimic acid, and scientists are trying to improve the fermentation process in order to make better use of it.
Tamiflu's target is a protein called neuraminidase, a protein found in the cells of influenza virus. This protein helps the influenza virus to break the cell wall, so the virus can infect other cells and replicate itself. Tamiflu inhibits neuraminidase protein, so the virus cannot leave its cells and infect other cells. Finally the virus died.
Photo courtesy of Roche.
Tamiflu can't completely cure the flu. However, studies have shown that taking this medicine within 48 hours after symptoms appear can shorten the course of influenza (types A and B). Compared with patients who did not take medicine, the course of influenza patients who took medicine was shortened by 30% (or 1.3 days). If you come into contact with flu patients, this medicine will also help prevent you from catching the flu. But Tamiflu can't stop the spread of diseases, nor can it stop influenza-like diseases (such as the common cold).
Similarly, the price of Tamiflu is not cheap. In the United States, the treatment cost of 10 dose is $60 to $80. At present, there is no generic brand of this drug in the United States.
From 2004 to 2005, it was reported that 12 children in Japan died after taking Tamiflu. However, these children also suffer from nervous system problems that may be related to the flu itself. In June 2005, the Pediatric Advisory Committee (FDA) of the US Food and Drug Administration ruled that the drug was safe.
In the next section, we will learn how Tamiflu fights bird flu. .
Any antiviral drug has the problem that the virus may be resistant to it. Doctors are worried that influenza virus may be resistant to Tamiflu, just as influenza A virus is resistant to amantadine (tricyclodecylamine) and rimantadine (methylaminomethylamine).
Some influenza virus strains are resistant to Tamiflu, including those found in some patients with avian influenza. Health officials worry that if the infection lasts longer during the bird flu epidemic, the risk of drug resistance will further increase.
In 2005, Roche donated 3 million courses (30 million capsules) of Tamiflu to the World Health Organization, forming an international stock. In June 2006, 5438+ 10, the company donated 2 million courses (20 million pills) to the World Health Organization (WHO).
As Roche is the sole patent owner, it is difficult for the company to produce enough products to meet the demand. Part of the reason is that it is difficult to separate shikimic acid from Illicium verum. Roche continues to improve its production capacity. The company claims that from 2007, it will be able to produce more than 300 million courses of Tamiflu every year, which is 65,438+00 times more than that in 2004.
Usually birds are infected with the virus that causes bird flu. These viruses have many different strains. Some viruses can be transmitted from birds to other animals, and most infections are mild. However, in the past decade, there have been several outbreaks of human infection with H5 n 1 1 avian influenza in Asia and Europe. Scientists worry that this strain will eventually mutate into a form that can spread directly among humans. In the winter of 2003, when the H5N 1 strain reappeared in Asia, it caused a worldwide panic about avian influenza. (For more information, see Understanding Avian Influenza. )
Influenza vaccines against "conventional influenza" viruses A and B are ineffective against avian influenza. Although scientists are working hard to develop bird flu vaccine, antiviral drugs are the only weapon to fight the disease at present.
Laboratory studies show that Tamiflu is effective in treating several avian influenza virus strains, including H5N 1. The way of the drug against avian influenza virus is the same as that against "conventional influenza". However, this drug can only reduce the severity of the disease-it cannot completely kill the virus. The World Health Organization recommended Tamiflu as the first choice for the treatment of avian influenza. Doctors in Asia have used Tamiflu to treat patients infected with H5N 1 virus.
Photo courtesy of Roche.
Some countries say they will ignore patents and make generic drugs, while others say they will get their own brand patents from Roche to protect people in the event of a large-scale influenza outbreak. In 2005, Roche authorized Vietnam to produce the generic brand of the drug. In the same year, Cipla, an Indian pharmaceutical company, announced that it would oppose Roche's patent and produce its own generic brand without permission. Recently, Roche issued subsidiary licenses to a China and an Indian pharmaceutical company, allowing them to produce Tamiflu.
It is not surprising that many Americans are considering stockpiling their own antiviral drugs for fear of a large-scale outbreak of bird flu. But is this a good idea? Many health experts warn people not to do this, because it is often difficult to tell whether you have the flu or the common cold, and taking Tamiflu too often may lead to drug-resistant strains. The World Health Organization recommends that the government reserve antiviral drugs in advance before the outbreak of influenza to ensure adequate supply of drugs.