Through an in-depth analysis of the process route and technical conditions of the original patent, Fang Hanmin believes that according to the method given in the patent specification, the obtained product must be a racemate, and it is impossible to achieve the purpose of eliminating enantiomers by changing the reaction conditions.

The patent protection of generic drugs is about to expire, because this drug has significant efficacy and extremely high market expectations, so the domestic pharmaceutical companies interested in this drug are by no means the only domestic pharmaceutical companies that are interested in this drug.

In order to take the lead in developing this drug in China and take the lead in time, Fang Hanmin believes that in terms of technical solutions, it is impossible to start anew and start over, and now he can only continue to move forward according to the process route of the original patent.

In order to find out which isomer is the active ingredient of the drug, Fang Hanmin decided to use the method of "disassembly" to split the racemate samples obtained from the test, completely separate the two enantiomers, and then determine their biological activity separately.

Fang Hanmin informed the scientific and technological personnel of the generic drug research group of his ideas, and Guo Peng and others expressed their understanding of the next scientific research path, but when it came to the specific method, they were at a loss, "Dismantling, do you mean separating these two isomers?" Their physical and chemical properties are almost identical, how to split them? ”

Because it involves new concepts and advanced technologies, before carrying out the split test, Fang Hanmin wants to do some science popularization for these scientific and technological personnel, "In order to find out which kind of optical rotator is the active ingredient of the drug, it is necessary to separate the two enantiomers, because the two isomers have almost identical physical and chemical properties, and the known conventional methods will certainly not achieve the goal." Generally speaking, the main methods for splitting mirror image isomers are mechanical resolution, microbial resolution, selective adsorption resolution, induced crystallization resolution and chemical resolution. ”

"Director Fang, which method are we going to use?"

"I haven't made a final decision yet, but according to the molecular structure of this drug, I think it is appropriate to choose both adsorption and induced crystallization methods, but there are many trade-offs, such as the difficulty of operation, the raw materials involved, the cost and efficiency, and other factors, all of which need to be considered comprehensively."

"What is the next task of the research group?"

"Continue to improve and optimize the current test conditions, even if the enantiomer racemate is obtained, the yield should be increased as much as possible and the material consumption should be reduced." ......

In his previous life, when he was an undergraduate at 985 University, he was exposed to the optical dismantling technology of chiral compounds in the laboratory, and in the process of future study and work, this technology was used as a tool and was often used in scientific research experiments, so Fang Hanmin was very familiar with this technology.

The current problem is to choose the most suitable method between the two methods, and Fang Hanmin must comprehensively consider the operation process of each method, the auxiliary raw materials required, energy consumption, cost and environmental impact.

Through analysis and comparison, Fang Hanmin believes that the adsorption method has a long operation cycle, a slightly lower production efficiency, and a large number of equipment, but its biggest advantage is that the separation effect is good, and the polarizer with high purity can be obtained after splitting.

The induced crystallization method saves time, the operation is relatively simple, the efficiency is high, and the equipment is relatively simple, but the purity of the split optical torn is difficult to exceed 95%.

For special commodities such as drugs, the higher the purity of the original drug, the fewer impurities, the better the efficacy of the drug, and the fewer toxic side effects, and vice versa.

After comparison and trade-off, even though the operation is relatively complex and the efficiency is lower, Fang Hanmin finally decided to choose the adsorption method.

The key to the adsorption resolution method is the selection of solid adsorbents, the determination of adsorption conditions such as temperature and solution concentration, and the determination of temperature and pressure of the desorption process.

Because the original patent did not disclose any information about this operation, a lot of work needed to be done from scratch to separate and purify the two optical isomers of generic drugs.

Fang Hanmin formulated the test method of adsorption and splitting, and explained the next test plan to Guo Peng and others, "Through the test, first find out an adsorption material with the highest efficiency and the best selectivity from several solid adsorbents, and then investigate the process conditions of adsorption and desorption." ”

"Director Fang, according to what you said, the adsorption resolution test may be more difficult than the drug synthesis, and this test may take a little more time, and no one can say what technical problems will be encountered in the test process." For the unfamiliar test task, Guo Peng was a little afraid of difficulties.

"Although optical splitting technology has long been present, after all, not only have you not seen it before, but you have never even heard of it, so for you, this experiment is an exploration of the unknown world, and of course there will be no strict time limit. You can work boldly and confidently, and there will inevitably be twists and turns in the test process, but the difficulties encountered are not terrible, and I believe that there are no difficulties that cannot be overcome, and I can discuss technical problems with you at any time. ”

Fang Hanmin's encouragement made Guo Peng and other technicians firm in their confidence, and they believed that with the backing of the factory director, there was no technical problem that could not be solved.

......

In early May, at about 10 o'clock in the morning on a Tuesday, Fang Hanmin had just returned to his office from the technology center when the factory staff sent him a letter, which he took and saw that it was sent from his hometown.

The content of the letter was not long, it was written by his brother Fang Hanwen, to the effect that he had received the letter to his family last time, and knowing the news of his marriage in the city, his parents were very unhappy, especially the old father was furious.

At the end of the letter, Fang Hanwen wrote: "Brother, recently you took some time to take your sister-in-law back to your hometown, listen to your father's meaning, if you don't come back, he will go to the city to find you, you know your father's temper, if you really go to you, he will come to your unit to quarrel with you, let outsiders see jokes, it won't be good for you, right?" ”

"Hey!" After reading the letter, Fang Hanmin leaned back in his chair and sighed helplessly.

At dinner, Fang Hanmin took out the letter and handed it to Song Yuping, "Look at this." ”

"What's this?" Song Yuping put down her chopsticks, "Yo, why did you let me read the letter from your hometown?" ”

"It has something to do with you, so let's take a look."

Hearing that it had something to do with herself, Song Yuping pushed the dishes and chopsticks aside, read it from beginning to end, and then returned the letter to Fang Hanmin, "The problem is very serious!" Let the two of us go back to our hometown, if we don't go back, the old man will come here to find you. If it's a Sunday, I don't care, the key is that you have time? ”

"They do things with no regard for other people's feelings, and I don't understand what they think!" Fang Hanmin didn't understand what his parents did.

"Needless to say, we didn't go back to our hometown for the marriage, my parents were very angry, and your father would definitely ask you about the crime if he asked us to go back."

"Hey, Xingshi asks for sin? What am I doing wrong? "Whether it is a traverser or a host, they all think that where to get married is completely their own business, Fang Hanmin got married and started a family, not only did not let his parents pay a penny, but also provided financial assistance for his hometown as always, what is the crime?

"It's a pity that they don't admit it! You are their son, and your parents feel that they should handle your marriage for you no matter what, otherwise, they will lose face in front of relatives, friends and people in the village, and you will be rebellious to do so. ”

"What age are they? I also pay attention to these meaningless things, and those customs and habits in my hometown are really unbearable! In such a poor place, how much is face worth? Fang Hanmin has strong resistance to his parents' requests.

Song Yuping looked extremely calm, "It's okay to stand it, or if you can't stand it, you have to take your parents' requests seriously, otherwise, if the old father comes to the city to settle accounts with you, how will you deal with it?" Although this is a private matter in your own family, your current position is different from that of ordinary workers, and you have to consider the impact! ”

These words made Fang Hanmin lose his temper completely, Song Yuping was right, even if it was his own private affairs, it had nothing to do with work, if it was full of turmoil, at least he would give a bad impression to the outside world, as the director of the Red Star Pharmaceutical Factory, he couldn't even handle his own family affairs well, how could he manage an enterprise with seven or eight thousand people?

Although everyone knows that Fang Hanmin can sit in the position of factory director, he completely relies on his own strength and contribution, but in other aspects, he cannot be unscrupulous.

Thinking of this, Fang Hanmin asked, "Why don't you take some time to go back?" It can also be regarded as a reassurance for them. ”

Song Yuping looked indifferent, "Whatever, as long as you have time." ”

Fang Hanmin shook his head helplessly, "How can I have time!" But I had to face it. ”

Song Yuping understood her husband's situation very well, "Yes, I know you are very embarrassed, but I can't replace you in this matter, so you can take some time out of your busy schedule to go back." ”

After some deliberation, the two decided to use the weekend of the week to return to their hometown and write a letter to inform their parents in advance.

The production department of the Red Star Pharmaceutical Factory runs continuously day and night and on holidays, and even if it is an administrative and logistics organization, there are people on duty all year round, so although Fang Hanmin is the head of a factory, even if he goes out because of personal matters, he must greet the relevant departments in the factory according to the regulations, in case he cannot find him in the factory.

On Friday afternoon, Fang Hanmin told the factory office that he was going back to his hometown on the weekend, and the director of the factory office would send a car to see him off, "Director Fang, this place is not very far from your hometown, and it can be reached by car for more than two hours. ”

Fang Hanmin immediately refused, "Never! It was also convenient for us to take the coach. If you start this way, in the future, team members and even middle-level cadres may ask you for a car to do private affairs, and then there will be not enough cars for the small car class. ”

The private use of public vehicles is a common drawback of all units, but the Red Star Pharmaceutical Factory has done a relatively good job in this regard, when Director Yuan was in office, he made strict restrictions on the use of vehicles, Fang Hanmin did not pay attention to pomp, after he took over, he plugged the loopholes in the previous vehicle management, in order to return to his hometown, he could not break the rules he formulated.

This weekend coincided with the weekend, Fang Hanmin and Song Yuping got up early on Saturday, had breakfast at home, freshened up, brought the gifts purchased for the elderly, and took the first shuttle bus to their hometown at the long-distance station.

At nine o'clock in the morning, the car arrived at the station, and after they got off the car, they found that the sky was gray and a little stuffy, Song Yuping said casually: "I didn't bring an umbrella, I'm afraid it's going to rain, right?" ”

Fang Hanmin looked up at the sky, "It's just cloudy, not like it's going to rain." ”

It takes an hour to walk from the bus station to Shuangshu Village, and when Fang Hanmin and his wife appeared at the head of the village, there were many villagers working in the fields on both sides of the road, and some villagers who knew him greeted him, "Hanmin, are you back?" ”

Fang Hanmin responded to the other party as he walked forward, and there was a discussion behind him, "He hasn't been back for several years, right?" ”

"How beautiful that woman is! Are they married? ”

"He's in his thirties, isn't he? It's long overdue to get married. ”

"Who knows if he got married or not, anyway, I haven't heard his parents say it." ......