I can extract side effects.

Chapter 505 Oral Insulin Became

"How? How did the rat react?"

Xue Shen looked nervously at Gu Xian standing in front of the cage, his throat squirmed, he swallowed subconsciously, and asked repeatedly.

"I know you're in a hurry, but don't worry, let me finish feeding the rats the medicine first."

Gu Xian comforted him casually, with a very perfunctory tone, then stretched out his hand, grabbed a big white mouse from the cage on the left, and stuffed an orange pill into the mouse's mouth with lightning speed.

This set of movements was done in one go, and the mouse hadn't reacted yet, the pill had already been swallowed, and it could only express a silent protest by rolling its small eyes.

Gu Xian smiled with satisfaction, and stuffed the rat into the cage on the right.

There are already 2 big snow-white and pink mice inside, both of which have been fed with medicine, and they are squeaking together, as if they are exchanging their feelings about taking medicine in a language that humans cannot understand.

After finishing all this, he said: "Finish, now these 6 rats are divided into two groups by me, 3 rats in each group, the one on the right is the experimental group, which has just been fed oral insulin, and the one on the left is the control group, which has been injected with insulin." 0.5ml of insulin solution."

"Xiao Lan, I'm right."

Xiao Lan was a young girl standing beside her, in her early twenties, she nodded upon hearing this.

"That's right, Director Gu, the three rats in the cage on the left were all injected by me with my own hands. The 3ml is exactly the same."

"Then just wait." Gu Xian said confidently: "After a period of time, observe the expressions, postures and activities of the two groups of rats, and see which group responds first."

The three of them stopped talking and stared at the two cages without blinking their eyes.

At the beginning, the two groups of white mice were very active, squeaking non-stop, and some were walking around, sniffing around.

After a while, the white rats in the cage on the left reacted first, and gradually changed from active to calm, and finally stopped their activities, lying still on the spot, and two of them even started to tremble.

"Ah!" Xue Shen clapped his hands in frustration, and said, "Our oral insulin seems to take a beat to take effect."

Gu Xian still remained calm: "This is normal, subcutaneous injection will definitely work faster than oral administration."

"Don't worry, the cage on the right is coming soon."

After speaking, he instructed Xiao Lan: "You will inject 0.5ml of the prepared glucose solution into the rats in the left cage and observe the situation. After a while, the rats in the right cage also respond, and do the same."

"Okay." The little girl responded quickly, and quickly started to inject the white mice.

Not long after, the rats in the cage on the right that had been given oral insulin also had the same reaction. They first calmed down, then lay motionless on their stomachs, and trembled all over their bodies.

However, after the glucose solution was injected, the rats in the cage quickly returned to normal and screamed again.

Xue Shen suddenly smiled: "It's done, oral insulin is done."

"After oral administration of the pill, the rats had a typical hypoglycemic reaction, exactly the same as the control group, which was enough to prove that they had taken too much insulin."

Gu Xian also lifted his spirits: "That's right, this experiment is simple, but it is very effective. At least it shows that oral insulin passes through the stomach completely, enters the intestinal tract, and finally enters the blood. It has the same effect as insulin for injection."

"This is an exciting start, and there is still a long way to go."

"Next, we will continue to do experiments on rats to obtain detailed data."

"From the four aspects of lowering blood sugar, lowering glycosylated hemoglobin, directly detecting oral insulin in the blood, and increasing insulin-activated receptors in the body, we can prove the oral effect of insulin."

"Then it will be continuously optimized and used on other large animals until it finally enters human clinical trials."

Xue Shen's hanging heart sank, he clenched his fists, and excitedly gestured in the air.

"Great, Gu Xian, this project has been able to go so smoothly, thanks to you."

Gu Xian smiled humbly: "Where, your nanoparticle is the key. Without its escort, insulin can't pass through the digestive tract at all and play its proper role."

"It's a genius idea. The nanoparticles are divided into 3 layers. The innermost layer is wrapped with insulin, the outermost layer is covered with a coating, and the middle layer is linked with absorption enhancers."

"In this way, the pill can escape the corrosion of gastric acid and enter the small intestine intact, where the shell dissolves and releases the second layer of cell-penetrating peptide (CPP), chitosan and chelating agent."

"With their help, insulin molecules can quickly pass through the intestinal wall, enter the liver directly through the portal vein, and then gradually release over time to achieve a long-term hypoglycemic effect."

"Hehe," Xue Shen raised his chest and talked eloquently, "Nanoparticles are the inspiration I got from nanopills. Although they have great effects, they are not my proud creations."

"In fact, I think the most difficult thing is to study the simulation calculation of the nano-negative Gaussian membrane bending topologically for the membrane permeability in the intestinal cell membrane, and associate the mode of the physical properties of the polypeptide with the geometric properties required for the change of the membrane bending. Greatly enhances the penetration of oral insulin."

"Cyclic cell-penetrating peptide (CPP) has high endosomal escape efficiency, but it does not cross the cell membrane in a physical sense, but in a topological manner, simultaneously before, during and after crossing the membrane maintain molecular integrity."

"Studies have shown that CPP molecules can cross-link each other through hydrogen bonds on the cell membrane to form a high concentration of lipid domains, which generate line tension with the surrounding membrane, thereby forming a protruding vesicle on the cell membrane."

"After the vesicle is formed, the neck connected to the cell membrane has a negative Gaussian curvature, which has a high potential energy, allowing the vesicle to break away from the cell membrane and enter the interior of the cell."

"The vesicle then ruptures inside the cell, releasing the CPP inside, and achieving the effect of intact crossing the cell membrane."

"In the whole process, CPP's incredible penetration ability played a very important role."

"This miraculous effect inspired me a lot. We used its ability to link to nanoparticles in a covalent way, enabling it to carry insulin molecules into intestinal cells successfully."

"This is the biological application of physics at the nanoscale, which is really brilliant and great."

In the end, his face showed an extremely pious expression, as if a fanatical believer in physics was looking up at the glory of the Supreme God.

"Papa papa!" Gu Xian couldn't help applauding, and praised: "Sure enough, everything is inseparable from physics."

"The integration of chitosan and chelating agents can open the tight junctions between intestinal epithelial cells and enhance drug permeability by 30%."

"CPP takes the opportunity to quickly enter cells with nanoparticles, and the combination of the three increases the bioavailability of insulin to more than 90%."

"It's no different than injecting insulin."

Xiao Lan, who was on the side, was also full of emotion: "In this way, diabetic patients all over the world can get rid of the pain of daily injections and supplement insulin just like taking vitamin tablets. It is a great invention."

"Things are not that simple." Gu Xian and Xue Shen shook their heads at the same time and said in unison.

"Why? When such a good drug is developed, isn't it immediately released to the market, attracting every patient to rush to buy it?"

Xiao Lan opened her eyes wide, with a dazed and puzzled expression on her face.

"You female assistant, you are still too young, you just graduated not long ago." Xue Shen gave her a meaningful look, as if seeing her ignorant and ignorant self in the past, she couldn't help laughing.

"I really envy the young people who have stayed in the ivory tower for too long and know nothing about the beatings of society."

Xiao Lan blushed when she heard this, but she couldn't refute it, so she just lowered her head and said in a low voice, "I just passed the probationary period, and I just became a regular last week."

Xue Shen laughed, and was about to say something.

Gu Xian hurriedly interrupted him, and said, "It's a good thing to be young and energetic. Whoever has never been young, it's okay to be naive. We should cherish the few moments we have."

"But, Xiao Lan, I want to ask you a question."

Xiao Lan stood up straight and said respectfully, "Director Gu, tell me."

"Since you are in a pharmaceutical company, you must know that insulin was discovered in 1921. The discoverer gave up the patent on insulin in order to benefit all mankind."

Xiao Lan showed reverence on his face, and said, "Yes, this is a miracle in the history of human medicine. It ushered in the era of biogenetic engineering. The discoverer, Dr. Banting, is a kind and great person."

"He sold the patent for only a symbolic price of 1 yuan, hoping that all people who need insulin can get treatment. At the same time, he also refused to sign on the drug patent because he believed that 'insulin belongs to the world and belongs to the whole world. Humanity'."

Gu Xian nodded and sighed: "It's a pity that things backfired. It was originally based on humanity and selfless dedication, but under the distortion of capital, it changed its taste and gradually became beyond recognition. It became a 100-year-long robbery."

"Dr. Banting must have never thought of it. He gave up the patent, but he didn't save any patients."

"100 years later, in his homeland, Eagle Country, the most developed pharmaceutical industry, millions of people are forced to go to the underground market to buy insulin because of the high price, and some people even want to re-develop insulin. This life-saving medicine is simply deplorable."

"Insulin was discovered more than 100 years ago, and now any college student who is a pharmaceutical student can easily obtain it in the laboratory. It should be as cheap as penicillin, and there are many manufacturers."

"But for more than a hundred years, the entire global market has been monopolized by the three major pharmaceutical giants Eli Lilly, Novo Nordisk, and Sanofi, and even more than 80% of the domestic market has been firmly controlled by them."

"As for the price, it has remained high all the year round. In recent years, it has been good in China. Due to the centralized procurement, it has been suppressed and dropped to dozens of dollars a piece. However, the price of insulin in Eagle Country has always been very high. It is very difficult for ordinary people without medical insurance. Difficult to bear."

"Any technological discovery, 100 years after its introduction, is impossible. Look at mobile phones, look at computers, and in just 30 years, they will become cheap and available everywhere."

Gu Xian said with a smile: "Then I want to test you, why does insulin have such a phenomenon?"

Xiao Lan looked angry, and blurted out: "It's not a conspiracy by the pharmaceutical company, but I just want to lie on the patient's body and suck blood until the end of time."

As soon as the words came out, she seemed to feel that something was wrong. Remembering that she was also working in a pharmaceutical company, she instantly showed embarrassment, and argued: "Well, I'm not talking about Sanqing, I'm talking about Lilly and the others."

Gu Xian nodded, not paying attention, and said with a smile, "Think about it carefully."

Xiao Lan showed a thoughtful look on his face, and after a while, he asked with some uncertainty: "Maybe the entry threshold is relatively high?"

"Let's start with production. Insulin drugs do not have patents, but there are production technology patents. Although it is easy to process small batches in a laboratory environment, it is still difficult to produce large batches at a stable cost at low cost."

"As for sales, insulin is not like cold medicine, you can just swallow it casually, it needs subcutaneous injection, which requires the professional guidance of a doctor, and in order to fully exert the efficacy of the drug, you need to use two or three types of insulin in combination according to the condition."

As she spoke, she gradually realized, and her tone became faster and faster.

"Because improper use of insulin can lead to hypoglycemia and death, the training of doctors is particularly important. This is often done by pharmaceutical companies, which makes it difficult for insulin companies to get started, but their market share is very stable."

"The third point is the supply chain. Insulin for injection requires cold chain transportation and low temperature storage, which requires good channel support capabilities."

"The fourth point is the medication link. Patients need blood glucose meter test strips to detect blood sugar, and injection pens for daily injections. Not willing to change easily."

"To sum up, these contents seem to be very simple, but once the first-mover advantage is formed, it will be difficult for latecomers to surpass. It's not that it can't be done, but that it won't make money if it is done."

"Those big foreign manufacturers have achieved the ultimate. Even if latecomers enter this market, they will not be able to make a lot of money, so they will have little motivation."

Gu Xian and Xue Shen looked at each other and smiled, with admiration in their eyes at the same time.

"Sure, Xiao Lan, you know enough. It seems that you have never let up in your studies after joining the company."

Gu Xian smiled and said, "However, if the three giants only do this, they still won't be able to stop the latecomers."

"You know, this is not ten years, 20 years, but more than 100 years."

"The insulin industry is a huge profiteering industry. Hundreds of millions of people around the world use it to save their lives every day. As long as the population continues to flow, money will flow in. There is no better golden track than this."

"If there is no unique skill, the Big Three will never be able to keep their monopoly throne."

Having said that, Gu Xian stopped, and the laboratory fell into silence.

Seeing that no one was talking, Xiao Lan scratched her ears and heart anxiously, and asked repeatedly: "Oh, Director Gu, why did you stop, keep talking."

Xue Shen was listening with gusto, and saw the key point, but the bottom was gone.

He was also a little anxious, and asked with a smile: "That's right, what are the unique skills of the three giants? Tell me quickly, don't be a fool, it can't be a unique skill like fighting with the FDA."

"It's not impossible," Gu Xian was amused by him, and said with a laugh: "Eagle Country's pharmaceutical industry actually has a revolving door, and executives of pharmaceutical companies can work in the FDA or other departments at any time, so this is a courtesy. No one can deny their unique skills."

"However, the real unique skill is of course not this." Gu Xian said solemnly with a solemn expression.

"This is not only the unique skill of the Big Three, but also the reason why other pharmaceutical giants can survive for a hundred years."

(End of this chapter)