"How was it? How did the rat react?"
Xue Shen looked at Gu Xian standing in front of the cage nervously, his throat squirmed, he subconsciously swallowed a mouthful of saliva, and kept asking questions.
"I know you are in a hurry, but don't be in a hurry. Let me finish feeding these rats the medicine."
Gu Xian comforted casually, his tone was very perfunctory, and then he stretched out his hand and grabbed a big white mouse from the cage on the left. With his right hand, he stuffed an orange pill into the mouse's mouth with lightning speed.
This set of movements was done smoothly and smoothly. Before the mouse could react, the pill had already fallen into its stomach, 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 were already two snow-white and pink big rats inside. They had both been fed medicine, and they were squeaking together, as if they were communicating about their feelings about taking the medicine in a language that humans could not understand.
After doing all this, he said: "Okay, now I divided these 6 rats into two groups, 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 0.5 insulin solution."
"Xiao Lan, what I said is right."
Xiao Lan, a young girl in her early twenties standing next to her, nodded when she heard this.
"That's right, Director Gu, I personally grabbed and injected the three rats in the cage on the left one by one, exactly 0.5 points."
"Then just wait." Gu Xian said confidently: "After a period of time, observe the expressions, postures and activities of the two groups of rats to see which group responds first."
The three of them stopped talking and stared at the two cages without blinking.
At the beginning, both groups of white mice were very active, squeaking and squeaking, and some even moved around and sniffed.
After a while, the white rats in the left cage reacted first, gradually changing from active to calm, and finally stopped moving and lay still. Two of them even started to tremble.
"Ah!" Xue Shen clapped his hands in frustration and said, "Our oral insulin seems to be a little slow in taking effect."
Gu Xian remained calm: "This is normal. Subcutaneous injection will definitely work faster than oral administration."
"Don't worry, the cage on the right is also fast."
After speaking, he told Xiao Lan: "Inject the 0.5% glucose solution into the rat in the cage on the left and observe the situation. After a while, the rat in the cage on the right also reacts, and then do the same."
"Okay." The little girl agreed and quickly started to inject the rat.
Not long after, the rats fed oral insulin in the cage on the right also had the same reaction. They calmed down at first, and then lay motionless while their whole bodies trembled.
However, after the glucose solution was injected, the white rats in the cage quickly returned to normal and screamed again.
Xue Shen suddenly smiled and said, "It's done, oral insulin is done."
"After the rats took the pills orally, they developed a typical hypoglycemic reaction, which was exactly the same as the control group, which is enough to prove that they had taken excessive insulin."
Gu Xian also cheered up: "Yes, this experiment is simple, but very effective. At least it shows that oral insulin completely passed through the stomach, entered the intestines, and finally entered the blood, achieving the same effect as injected insulin."
"This is an exciting start, but there is still a long way to go."
"Next, we will continue to conduct experiments on rats to obtain detailed data."
"The oral effect of insulin is proven from four aspects: lowering blood sugar, lowering glycated hemoglobin, directly detecting oral insulin in the blood, and increasing insulin-activated receptors in the body."
"Then it will be continuously optimized and used on other large animals until it finally enters human clinical trials."
Xue Shen's heart dropped, he clenched his fists and gestured excitedly in the air.
"That's great, Gu Xian. You must have contributed a lot to this project being so successful."
Gu Xian smiled humbly: "Where is your nanoparticles that matter?"
key, without its protection, insulin would simply not be able to pass through the digestive tract and play its intended role. "
"What a genius idea. The nanoparticles are divided into three layers. The innermost layer is wrapped with insulin, the outermost layer is covered with coating, and the middle layer is linked to the absorption enhancer."
"In this way, the pill can avoid corrosion by gastric acid, enter the small intestine intact, dissolve the outer shell in the intestine, and release the second layer of cell-penetrating peptide (CPP), chitosan and chelating agents."
"With their help, insulin molecules can quickly pass through the intestinal wall, enter the liver directly through the portal vein, and then be gradually released over time to achieve a long-lasting hypoglycemic effect."
"Haha," Xue Shen raised his chest and raised his head, and said eloquently: "Nano particles are the inspiration I got from nano pills. Although they are very effective, they are not my proud work."
"In fact, I think the most difficult thing is to study the topological simulation calculation of membrane permeability due to nano-negative Gaussian membrane bending in intestinal cell membranes, and to correlate the pattern of peptide physical properties with the geometric properties required for membrane bending changes. Greatly enhances the penetration of oral insulin."
"Cyclic cell-penetrating peptide (CPP) has a high endosomal escape efficiency, but it does not penetrate the cell membrane in a physical sense, but penetrates the membrane in a topological manner, at the same time before, during and after penetrating the membrane. All can maintain molecular integrity."
"Research has shown that CPP molecules can cross-link with each other through hydrogen bonds on the cell membrane, forming a high-concentration lipid domain, which generates linear 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 generates 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 within the cell and releases the CPP inside, achieving the effect of completely crossing the cell membrane."
"Throughout the entire process, CPP's incredible penetrating ability played a very important role."
"This magical effect greatly inspired me. We used its ability to link it to nanoparticles in a covalent manner, so that it can carry insulin molecules into intestinal cells successfully."
"This is the biological application of physics at the nanoscale. It is really wonderful and great."
By the end of his speech, his face showed an extremely pious look, as if he were a fanatical believer in physics looking up to the glory of the Supreme God.
"Bah bang bang!" Gu Xian couldn't help but applaud 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. The combination of the three increases the bioavailability of insulin to more than 90%."
"It's no different than injecting insulin."
Xiao Lan on the side was also filled with 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 really 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? After such a good drug is developed, shouldn't it be immediately put on the market and attract every patient to rush to buy it?"
Xiao Lan opened his eyes wide, with a look of confusion and confusion on his face.
"As a female assistant, you are still too young. You have just graduated." Xue Shen gave her a meaningful look, as if he saw his ignorant self in the past, and couldn't help but laugh.
"I really envy young people. They have stayed in the ivory tower for too long and know nothing about the beatings of society."
Xiao Lan blushed when he heard this, but he couldn't refute, so he lowered his head and whispered: "I just passed the probation period and became a regular employee last week."
[In view of the general environment,
Xue Shen laughed and was about to say something.
Gu Xian quickly interrupted him and said, "Nian
It's a good thing to be young and energetic. Who hasn't been young before? It doesn't hurt to be naive. Cherish these few moments. "
"But, Xiao Lan, I want to ask you a question."
Xiao Lan stood up straight and said respectfully: "Director Gu, please 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 a look of 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 figure."
"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 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 went counterproductive. It was originally based on humanity and selfless dedication, but under the distortion of capital, it changed its flavor and gradually became beyond recognition. It became a plunder that lasted for 100 years."
"Dr. Banting must not have thought that he gave up the patent but did not save any patients."
"100 years later, in his home country, Eagle Country, which has the most developed pharmaceutical industry, millions of people cannot use insulin because of the high price, and are forced to buy it in the underground market. Some people even want to re-develop insulin. This life-saving drug is absolutely pathetic."
"Insulin was discovered more than 100 years ago, and now any pharmaceutical college student can easily obtain it in the laboratory. Logically speaking, 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 pharmaceutical giants Eli Lilly, Novo Nordisk, and Sanofi. Even more than 80% of the domestic market is firmly controlled by them."
"As for the price, it has remained high all year round. In recent years, it has been better in China. Due to centralized procurement, it has been reduced to dozens of yuan a pill. However, the price of insulin in Eagle Country has always been very high, and it is very difficult for ordinary people without medical insurance. It’s hard to bear.”
"It is impossible for any technological discovery to be like this 100 years after its release. Look at mobile phones and computers. In just 30 years, they have become cheap and widely available."
Gu Xian smiled and said, "Then I want to test you. Why does insulin cause such a phenomenon?"
Xiao Lan looked angry and blurted out: "It's not a conspiracy of the pharmaceutical company. They just want to lie on the patient's body and suck blood until the end of time."
As soon as the words came out of her mouth, she seemed to feel something was wrong. Remembering that she also worked in a pharmaceutical company, she instantly looked embarrassed and defended, "Well, I'm not talking about Sanqing, I'm talking about Eli Lilly and the others."
Gu Xian nodded, not taking it seriously, and said with a smile, "Think about it more carefully."
Xiao Lan looked thoughtful, and after a while, he asked with some uncertainty: "Maybe the entry threshold is relatively high?"
"Let's start with the production aspect. There are no patents on insulin drugs, but there are production technology patents. Although it is easy to process small batches in a laboratory environment, it is still difficult to produce stable, low-cost large batches."
"As for sales, insulin is not like cold medicine, which can be swallowed casually. It requires subcutaneous injection, which requires professional guidance from a doctor. In order to fully exert the effect of the medicine, two or three types of insulin need to be used according to the condition."
As she spoke, she gradually became enlightened and her tone became faster and faster.
"Because improper use of insulin can lead to hypoglycemia and easily lead to 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 the market share is very stable."
"The third point is the supply chain. Injectable insulin requires cold chain transportation, low-temperature storage, and good channel support capabilities."
"The fourth point is the medication process. Patients need blood glucose meter test strips to detect blood sugar and injection pens for daily injections. This is very important to the experience and effect of medication. It requires a whole system to support it. Moreover, after patients get used to a medicine, they often Not willing to change easily."
"To sum up, these contents seem simple, but once formed,
With first-mover advantages, it will be difficult for latecomers to surpass them. It’s not that they can’t do it, but that they can do it without making money. "
"The major foreign manufacturers have already achieved their best. Even if latecomers enter this market, they will not be able to make a lot of money, so they will have no motivation."
Gu Xian and Xue Shen looked at each other and smiled, with admiration in their eyes.
"Okay, Xiao Lan, you know enough. It seems that you haven't let up on your studies since joining the company."
Gu Xian smiled and said, "However, if the three giants only do this, they still can't stop the footsteps of latecomers."
"You know, this is not ten or twenty years, but more than a hundred years."
"The insulin industry is a hugely profitable industry. Hundreds of millions of people around the world use it to save their lives every day. As long as the population continues, money will keep rolling in. There is no better golden track than this."
"Without some unique skills, the three giants will never be able to maintain their monopoly throne."
At this point, Gu Xian stopped and the laboratory fell into silence.
Seeing that no one was speaking, Xiao Lan suddenly scratched his head and heart in anxiety, and asked repeatedly: "Oh, Director Gu, why did you stop? Keep going."
Xue Shen was listening with great interest, and saw the key point, but the bottom part was missing.
He was also a little anxious and asked with a smile: "Yes, tell me what unique skills the three giants have. Don't be pretentious. It can't be the unique skills of being at odds with the FDA."
"It's not impossible," Gu Xian was amused by him and laughed: "The pharmaceutical industry in Eagle Country actually has a revolving door. Executives of pharmaceutical companies can join 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 looked solemn and said seriously.
"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."
