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"Honey, seriously, let's have a baby."

For several days, Wei Kang kept saying this.

The old father-in-law was also constantly assisting, and the two took turns to persuade his wife to conceive and have a baby.

After talking too much, Jian Jianyun was also a little tempted.

The main reason is that she is not young anymore, she is in her early thirties, and after a few years of birth, she will become an advanced maternal age.

Taking advantage of the fact that she is still young and her reproductive function has not declined, giving birth to a child early is the best choice in all aspects.

Moreover, both of them have successful careers, so there is no need to worry about the impact of having a child at this time.

Jian Jianyun has always loved surgery, and she doesn't have much ambition in her career. She is already satisfied with the position of deputy chief physician.

In the neurosurgery department of the First People's Hospital of Kunming City, she was the first surgeon. In order to introduce her as a talented person who is excellent in both clinical and scientific research, the hospital specially gave her to the deputy high as soon as she joined the job, but what she did later The achievements are obvious to all. Over the past few years, everyone has been completely conquered.

Director Li of the Department of Neurosurgery is very old. If there is no accident, she will be a well-deserved successor if she retires in a few years.

Before that, she had to stay in the position of deputy senior for a few more years.

So, now is the best time to have a baby.

"Alright then." After thinking about this, Jian Lianyun shyly agreed.

"Great!" Wei Kang almost jumped up and cheered loudly.

The old man and his wife also showed gratified smiles.

"What should I do to prepare for pregnancy? What nutrients should I supplement? What should I eat?"

When Wei Kang thought of this question, his head suddenly became dizzy.

"Don't worry, I'll ask my gynecology colleague to see what she says, and by the way, let me say goodbye to my old age."

Jian Lianyun was extremely calm. He took out his mobile phone and called his colleagues in the gynecology department.

"By the way, I'll go online to see what people say." Wei Kang slapped his head and came up with a good idea.

The two immediately got busy.

A gynecological colleague in the hospital called every day to ask about precautions for preparing for pregnancy.

One diligently did her homework online, shopped everywhere, and placed a bunch of orders for nutritional supplements.

In this way, the entire Spring Festival holiday became extremely fulfilling in an instant, and time passed quickly.

After the Chinese New Year, as soon as he returned to the company, Wei Kang immediately called Xue Shen to the office.

"Oral insulin program?"

Xue Shen was surprised and delighted, and almost sat up from the chair.

Surprised that the boss is so ambitious and wants to overcome the world's problems, and happy that the boss is so optimistic about himself that he even let himself be the project leader.

He immediately realized that this was the biggest challenge in his career. If he could successfully complete this project, he would gain both fame and fortune and reach the pinnacle of his career.

"Don't worry, I will not disappoint your trust. The current personnel in the nanolab are very strong. I am confident that I will lead the whole team to victory and develop the world's first oral insulin." Xue Shen couldn't wait to show his loyalty.

Wei Kang smiled and said: "I am quite relieved about your technology in the field of nanoparticles. Oral insulin delivery has always been considered as the most promising way, but it is also facing great technical challenges, especially The problem of low bioavailability."

Xue Shen nodded immediately and said: "Yes, there are three main reasons for this. One is that insulin is easily degraded by the digestive enzymes in the digestive system; the other is that the mucus layer on the surface of the gastrointestinal tract is negatively charged. Insulin is rejected."

"The last point is intestinal epithelial cells, which only absorb some small molecules such as amino acids, water, inorganic salts, fatty acids, glucose, etc. Insulin, as a protein molecule, cannot easily penetrate the cell membrane and be absorbed by it."

Wei Kang praised: "Yes, it seems that you also have a precise understanding of this aspect. As you said, we must find the right way to solve these three problems one by one and send insulin to the liver."

Speaking of this, Wei Kang showed a trace of expectation in his eyes, and asked: "These three problems are not easy to solve, do you have any thoughts on this?"

Xue Shen pondered for a moment and said slowly: "The first problem, the problem of digestive enzyme degradation, is easy to solve. Many drugs have similar solutions, such as enteric-coated capsules, which can wrap drug molecules until they reach the intestinal tract. It breaks down and releases the medicine inside."

"We can also build a nanoparticle, like a capsule, to hide the insulin molecule inside, so that it will not be broken down by stomach acid and digestive enzymes, and can reach the intestinal tract safely."

"As for the second problem, the negative charge of the intestinal mucus layer, this is not difficult, because the nanoparticles are mostly neutral and will not be affected by the charge."

"Only the third problem is the most difficult part of this project to solve."

The expression on Xue Shen's face became serious, and he said in a deep voice: "According to my idea, the core of the nanoparticle is insulin, but the outer shell will be coated with some small molecule derivatives, which can be fructose, or polypeptides, and Other surfactants, can promote the absorption of intestinal epithelial cells."

"After the nanoparticles are absorbed by the intestinal cells, about 15 minutes, they will be sent directly to the liver through the venous blood, and then decomposed in the liver to release the insulin inside."

"During the whole process, nanoparticles do not need to have spontaneous power, and can be spontaneously sent into the liver by blood flow. This is different from nano-pills, which saves a lot of effort."

"The only difficulty lies in the selection of nanoparticle surfactants, which require a highly efficient small molecule derivative that can carry nanoparticles to penetrate the intestinal cell wall."

"For this research, I may need the help of a pharmacokinetic expert."

Wei Kang showed a hint of relief, and said with a smile: "Yes, I am very satisfied that you know how to seek help from the outside and clearly know what kind of help you need."

"Pharmacokinetics is an indispensable subject for pharmaceuticals, and it plays an unusually important role in improving the absorption of oral drugs."

"As a pharmaceutical company, Sanqing naturally has no shortage of talents in this field. I have a very talented expert here."

Having said that, Wei Kang picked up the phone on the table, dialed it, and said a few words briefly.

"I've already called him over, and he'll be there in a few minutes. If you have any problems, you can discuss them together. I'll also listen to them and see if there are any good solutions."

"If he joins the oral insulin project, this problem will be solved soon."

Xue Shen's heart moved. In a large company with tens of thousands of people like Sanqing, he knew very few people. He had never heard of any experts in pharmacokinetics, so he couldn't help being curious.

Wei Kang continued to ask: "How is the phase III clinical trial of the nanopill going?"

Xue Shen restrained his mind and replied respectfully: "Everything is going well. In the past two months, there have been more than 500 cases of patients infected with super bacteria. After using the combined treatment plan of nano-pills and super antibiotics, the infection It was under control within a week and healed quickly."

Wei Kang couldn't help frowning: "All these patients have used super antibiotics?"

This is not a good sign, and means that more and more patients are becoming resistant to commonly used antibiotics.

"That's right, what polymyxin, tigecycline..." Xue Shen suddenly remembered a report he had just read a while ago, and quickly said: "The sales of polymyxin, in particular, have grown rapidly in recent years. .”

"According to statistics, the sales of polymyxin B in domestic urban public hospitals, county-level public hospitals, community hospitals and township health centers last year exceeded 800 million yuan, a year-on-year increase of more than 36%. "

Hearing such a shocking number, Wei Kang's expression changed instantly.

"It seems that the bacterial drug resistance gene is spreading very fast. If it continues at this speed, there may be no antibiotics available soon." Wei Kang said with a wry smile.

Xue Shen nodded, with a hint of excitement on his face, and said: "Mr. Wei, in fact, this is also an opportunity for pharmaceutical companies. If the existing antibiotics are resistant, patients will naturally need more advanced antibiotics. Sanqing can do that." Make efforts in this regard and develop antibiotic business.”

"In the past, pharmaceutical companies gave up the research and development of antibiotics because they didn't make money. Now that antibiotics are resistant, patients must be willing to spend a lot of money to buy more advanced new antibiotics. In this way, major pharmaceutical companies must be willing to invest in this area. put in."

Wei Kang shook his head, then nodded again: "The research and development of antibiotics is not as simple as you think."

"But you are right. Sanqing does not have its own antibiotics, but only some generic drug business. This is a new track, and it is worth investing heavily in."

A thought suddenly flashed in his mind, and he remembered the phage research that Williams was doing before.

I don't know how Dawei's research is progressing, so I'll ask later.

Just then, there was a knock on the door.

"Come in!"

A man in his early thirties entered in response. He was handsome and shy. He smiled at the two of them and found a seat opposite Wei Kang to sit down.

Wei Kang said with a smile: "Come on, let me introduce you. This is Gu Xian, who is in charge of the generic drug business. He is also an expert in preparations and has in-depth research on pharmacokinetics."

"It's like this. The company is preparing to develop oral insulin. The project has just been established. It plans to use nanoparticles to wrap insulin, pass through the intestinal tract, send it to the liver, and then release the drug, so as to solve the pain of insulin injection."

Gu Xian's eyes lit up immediately, and he said with a smile: "This project sounds very meaningful, and the difficulty is not small."

"That's right, but now we have encountered a little problem, and we need you, a pharmacokinetic expert, to join us."

Gu Xian was stunned for a moment, then quickly waved his hand and said, "Hey, Mr. Wei, you're right, I just know a lot about preparations, how can I become an expert."

"I have been making generic drugs all the time. Compared with my colleagues who make original research drugs, I am far behind. I dare not call myself an expert in front of you."

Wei Kang chuckled and said, "Aren't you researching the original drug now? And it's such a significant world problem as oral insulin."

Gu Xian's entire face instantly lit up, and his eyes showed joy. He asked excitedly, "I'm also a member of the project? That's great."

"Of course, this project can't do without others, but you are the only one that can't do without. By the way, we are now encountering a problem with oral drug absorption..."

Under Wei Kang's hint, Xue Shen explained the problem again in detail.

Gu Xian nodded while listening, and when the question was finished, he immediately spoke.

"This is a matter of choosing an oral drug absorption enhancer. In this regard, I happen to know a thing or two."

"As we all know, oral drugs are convenient to use, easy to store and transport, and have high market acceptance. However, the clinical efficacy is affected by many factors, such as the solubility, permeability, and stability of the drug itself, especially the human gastrointestinal tract. The complex physiological environment forms a series of physical and chemical barriers."

"The most effective strategy to increase the bioavailability of orally administered drugs is to increase the permeability of the digestive tract."

"For this purpose, absorption enhancers are often added to the formulation formulation."

"This is a functional excipient for preparations, which can not only improve the fluidity of cell membranes, reduce the viscosity of mucus, prolong the residence time of preparations at the absorption site, but also instantly destroy the integrity of the epithelial cells of the digestive tract and improve the penetration of drugs in the gastrointestinal tract. and improve oral availability."

Xue Shen suddenly became excited, and couldn't help interjecting: "Director Gu, you are too good, this is exactly what you need for oral insulin nanoparticles."

Gu Xian nodded to him, and said with a smile, "I'm very glad to be able to help with this project, so I'll continue talking."

As soon as he talked about his work, the shyness on Gu Xian's face disappeared, replaced by a confidence that everything was under control.

"The mucus in the digestive tract is a physical barrier, and the chemical barrier is the pH environment of the gastrointestinal tract and digestive enzymes."

"The PH value of different parts of the gastrointestinal tract varies greatly, usually about 1.6 in the stomach, and 6.7~7.5 in the small intestine. Therefore, weakly alkaline drugs are more easily absorbed in the small intestine, and weakly acidic drugs are more easily absorbed in the stomach. It is easier to be absorbed in the stomach. The strong acid environment in the stomach can easily degrade some drugs. To prevent them from being destroyed in the stomach, enteric coatings will be added to intestinal absorption drugs.”

"As for the digestive enzymes, mainly lipase and protease, if they are nanoparticles, they should be able to avoid this category."

"In the process of oral drug development, in addition to ensuring the chemical and physical stability of the drug, it is also necessary to ensure that the drug can reach the hospital directly after taking it."

"In this regard, it is necessary to use absorption enhancers, which can not only be used in the excipients of oral tablets, but also can be used to modify nanocarriers to directly transport macromolecular drugs into specific tissues or cells."

"Currently commonly used are sodium caprylate derivatives, sodium caprate derivatives, alkyl glycosides and other surfactants, as well as chelating agents, chitosan derivatives, polypeptides, polyamide macromolecular polymers, and hydrophilic Bioadhesive materials, etc., have already been used very well.”

"Considering the toxicity and irritation, combined with the structure, molecular weight, absorption site, pharmacokinetic characteristics and other factors of oral insulin nanoparticles, the latter several accelerators are better choices and can be used in combination."

"For example, chitosan is a safe and non-toxic absorption enhancer that is widely used at present. It can open the tight junction between intestinal epithelial cells and enhance the permeability of drugs. It can be integrated with a new type of chelating agent to significantly increase insulin. The transmembrane absorption increases the bioavailability by 20%.

"Multiple fetal oral delivery is also safe and effective. Cell-penetrating peptides are short peptides that can penetrate biomembranes and enter cells. They can also carry different types of active substances into cells in a covalent or non-covalent manner, such as small molecule drugs. , peptides, etc., should be good for preparing insulin nanoparticles.”

Seeing Gu Xian mentioning several absorption enhancers in one breath, Xue Shen couldn't help but be overjoyed: "Director Gu is indeed an expert respected by Mr. Wei, I finally know that the oral insulin project is really inseparable from you."

So far, Weikang is completely relieved, knowing that the successful development of oral insulin is only a matter of time.