A brief analysis of the method of hand drug splitting

"Chiral drug", a member of the Shanghai Organic Research Institute of the Chinese Academy of Sciences, refers to a pair of opposite isomers that are physical and mirrored after the introduction of the hand center in the molecular structure of the drug.
The physical and chemical properties of each pair of chemically pure isomer are different (not just in the photorescensance), they can be named R-type or S-type, D-type or L-type, left or right-handed according to different nomenclatures.
Historically, naturalists and biologists such as Darwin and Wallace have given a great deal of attention to macro-biological hand phenomena, such as Darwin's book Movement and Habits of Climbing Plants (The Movement and Habits of Climbing Plants), in which a table describes 42 species of climbing plants, most of which have right-handed stem spirals, while only 11 have left-handedness.
most observed in our lives is the left and right growth of plants, holding ox flowers to the "left" plate, while hops to the "right" climb.
do you have to split these drugs around? Is there any difference between the two? Indeed, hand drugs and non-hand drugs are very different, sometimes the two pure isomers of the same drug, sometimes very different, even in the human body, one advantage, one harmful.
so you have to put the infamous Seals out here again.
do you think it's special to see, this is the pot of hand medicine! The well-known "reaction stop (salidamine)" event.
the 1950s and early 1960s, salidamine was widely used worldwide except in the United States.
salidamine was effective in preventing vomiting in the early stages of pregnancy, but it was banned as a vomiting drug for pregnant women for the next three decades because it hampered the blood supply to the fetus, resulting in the birth of a large number of helpless "seal deformed babies".
Later research found that such a tragedy occurred because "salidamine" has two structures, left and right, the l'trolley has a therapeutic effect, can reduce the early pregnancy response of pregnant women, but its hand partner (right spin) is teratogenic, resulting in the appearance of deformed babies shown in the figure above.
it is very important to understand the drug properties of the two isomers of hand drugs, which are directly related to the health and safety of the drug takers, thus leading to the concept of hand splitting.
In order to better and more reasonable drug use, it is necessary to obtain a single pair of isomers of hand drugs by means of splitting, to achieve the separation of two pure-to-reflect isomers in external anti-spin drugs, which is known as "hand splitting".
, for the safety of drug users, the important thing is to say three times: hand drug splitting is very important! Hand drug splitting is important! Hand drug splitting is important! Hand drug splitting method Hand drug dismantling is self-evident, as early as 1848, the French chemist L. Pasteur has been using tweezers under the microscope since splitting right-handed and left-handed citric acid.
, under the constant exploration of countless scientists, the industry has some effective methods of splitting.
The table below provides an overview of the information and advantages and disadvantages of several common splitting methods, including mechanical splitting, seeding crystallization, crystallization (direct crystallization and non-reflector salt splitting), biological splitting, chromatography, and cocrystalline splitting.
this paper briefly introduces the widely used chromatography split method, focusing on a new method of hand splitting - drug cocrystalline.
of the above-mentioned split methods, chromatography is widely used for its fast and efficient splitting, and the characteristics of high reflector purity obtained at the same time.
chromatography is based on chromatography separation technology, the hand environment (asymmetric center) is introduced, so that the differences between drug-to-image bodies are physically and chemically different, so as to achieve splitting.
the direct method is to introduce asymmetric centers into the molecules, and the indirect method is to introduce the molecules.
02 drug cocrystalline relative to the widely used chromatography, we are still relatively unfamiliar with the concept of drug cocrystalline.
drug cocrystalline is defined as a crystal made up of at least two components, active Pharmaceutical and CCF, which are combined in the solution by hydrogen bonds, π-π interactions, and are solid at room temperature.
is a good innovation point to use the idea of drug cocrystalline subtly into the hand split.
Although the current drug cocrystalline to achieve hand splitting is not a large number of industrial use, but from the current situation, the drug cocrystalline has a very good application prospects, on the one hand, its split effect is also very good, equipment requirements are not harsh, to avoid the complex operation of the hand chromatography and expensive costs, on the other hand, it also does not need complex theoretical research, through the three-way map to find a suitable crystallization area on the line.
Here to the left ethyl laxitan split external anti-cyclone ibuprofen as an example: through the direction of strong dependence on hydrogen bonding to achieve the split of hand drugs, the pure API of the body only with the hand CCF one of the two pairs of contrasts to form a cocrystalline, but will not generate a pair of isomers, the idea is shown in the following diagram.
To put it another way: "In order to separate S-ibuprofen from the external cyclone mixture using contrast-specific cocrystallines, two conditions need to be met: (1) the crystallization conditions selected (the nature and quantity of solvents, and temperature) need to allow cocrystalline formation;
the above split effect can be seen the advantages of drug cocrystalline: 86.1% of the reflection pure isomer.
unlike classic hand splits using a pair of non-reflective salts, the split technology developed here is specific to the reflection, and the difference is most likely due to the highly directional nature of the hydrogen bond pattern in the cocrystalline.
the addition of a hand split agent and the target of only one of the two pairs of contrasts crystallization, and can not be with the other to form a cocrystalline.
this new split technology is particularly useful because it achieves high efficiency in a single split step and can be further used in a range of compounds that are difficult to form or salt.
but it must be admitted that, so far, hand chromatography is the most effective and effective split.
market prospects for hand drugs Since 1999, hand drugs have developed rapidly, occupying a large share of the market and sales of commercially available drugs, and the development of hand drugs is on the rise.
According to incomplete statistics, the total number of drugs used in the world has now exceeded 2000 (excluding because of side effects have been banned), in which the number of hand drugs more than 50%, and according to the latest statistical analysis, the current clinical use of more than 200 kinds of drugs, hand drugs have been more than 120, the major pharmaceutical companies are currently developing drugs, hand drugs accounted for more than two-thirds.
the global annual growth rate of hand drugs is greater than 15%, and in China's hand drugs market share is more than 100 billion yuan.
the chromatography method with its unique split advantages stand the hand split of the half of the mountain, has a good market, but because of the high cost, complex operation characteristics can not be large-scale functional factory use.
and most of the factory use is still crystallization method, crystallization method in the purity requirements are not very high, the use of crystallizers to facilitate continuous production.
cocrystalline method as a new technology, although not currently popularized in the market, but with the continuous development of hand reagents, specific research continues to deepen, will play a better role in the future! The 21st century will be the century of hand-drug development.
," Lin Guoqiang, a member of the Shanghai Organic Research Institute of the Chinese Academy of Sciences, said at a summit of pharmaceutical companies.
, with the continuous development of hand drugs and the deepening of hand-splitting technology, hand-drugs in the future will be "greatly improved"! Drug cocrystalline split method will have greater utilization and profit margins!