Background and overview[1][2]
Phosphocholine is white crystal or crystalline powder. Slightly fishy smell. Relative molecular mass 201.16. Melting point 200~205℃. Deliquescent. Insoluble in benzene, chloroform and ether, slightly soluble in ethanol and acetone, soluble in methanol, easily soluble in water. The pH of 10% aqueous solution is 4.8~5.0. Mouse oral LD507720mg/kg. Phosphocholine is an important intermediate in the biosynthesis of lecithin in eukaryotic cells. It is formed by the condensation of choline and ATP under the catalysis of choline kinase present in animals and yeast.
It has the strongest binding force with CRP (C-reactive protein) among phosphate monoesters. In the presence of calcium ions, it can enhance the body’s defense against bacteria and fungi. Phosphocholine can be used to prepare photoelectrochemical cells to generate photovoltage. The biochemical properties of glow discharge modified phosphocholine bilayer molecules are similar to the anti-thrombotic surface of human red blood cells, which greatly inhibits the surface attachment of platelets. Phosphocholine sodium and calcium salts prevent various known membrane deconstructors. Breakdown protects the membranes of platelets, red blood cells, and lysosomes.
Calcium and sodium phosphate choline salts can enhance the interaction between heparin and serum β-lipoprotein. Its magnesium and calcium salts can be used in the treatment of liver and gallbladder damage. It is a raw material for the industrial preparation of CDP-choline, L-α-glycerophosphocholine and other drugs. There are many chemical synthesis methods for phosphocholine: the phosphorylation of halogenated choline includes the use of organic compounds such as phosphorus oxychloride, phosphorus pentoxide, phosphorus pentoxide and anhydrous phosphoric acid, ethyl metaphosphate, diphenyl chlorophosphoric acid, etc. Phosphorus phosphorylation reagent and phosphorylation of chloroethanol by phosphorus oxychloride and ethyl metaphosphate are used to prepare chloroethanol phosphate and then combined with trimethylamine to form phosphocholine.
Indications[3]
Clinically it is mainly used for the treatment of acute jaundiced or non-jaundiced hepatitis, chronic persistent and active hepatitis; it is also used for the treatment of liver poisoning, hepatic fatty infiltration or fatty liver, and cirrhosis.
Specifications[3]
Capsule: 0.25g; injection: 0.2g/2ml.
Usage and dosage[3]
Oral administration: 0.25~0.5g, 2~3 times/d; Subcutaneous injection or intramuscular injection: Adults 0.2g, 1~2 times/d, the dose may be reduced for children.
Pharmacological effects[3]
Participated in the synthesis of phospholipids, it has the effects of protecting the liver, strengthening the liver, promoting lipid metabolism and fighting fatty liver. It can also accelerate methyl transfer, supply activated methyl groups, and accelerate liver cell regeneration. This product can also provide acetylcholine in the body, improve the nutrition and function of the autonomic nerves; decompose histamine, enhance the activity of histamine in the kidney, and have a certain detoxification effect.
Amino silicone oil emulsion
Adverse reactions[3]
Side effects are mild, including mild nausea, rash, etc., which disappear after stopping the medication. Injections should be stored in a dark place.
Other uses[1][4]
Phosphocholine can be used as a food additive and a quality improver for brewed products. It can be added to synthetic sake to increase the rich aroma; it can stabilize amino acids and other alcoholic components; it can also be used as a seasoning. Increase the flavor of dishes.
For example, the preparation of a phosphocholine-modified anti-caking agent for frozen products, the preparation method includes: 1) combining calcium aluminosilicate, silicon dioxide, calcium stearate, magnesium oxide, phosphocholine and triglyceride The stearate is ball-milled to prepare the initial product; 2) the initial product is dried to prepare the intermediate product; 3) the intermediate product is mixed with crystalline cellulose to prepare a phosphorylcholine-modified frozen product anti-caking agent. The anti-caking agent has excellent anti-caking properties and stability for frozen products, thereby enabling the anti-caking agent to be used in frozen products. At the same time, the preparation method has the advantages of simple process and easy availability of raw materials.
Preparation[1][5]
Method 1: In a concentrated aqueous solution of ethylene oxide, react trimethylamine with it at room temperature to produce choline. Or in the presence of potassium hydroxide, methyl iodide is used to methylate ethanolamine at room temperature to produce choline. The choline prepared above is then dissolved in methanol, and the choline methanol solution is neutralized with phosphoric acid to generate phosphoric choline. After concentration and drying, the crude product phosphoric choline can be obtained. Then dissolve the crude phosphorylcholine in a methanol solution, add acetone, and obtain a precipitate. After filtration and separation, phosphocholine can be obtained [1].
Method 2: Choline chloride undergoes metathesis in a methanol solution of sodium hydroxide to obtain choline, and then reacts with phosphoric acid to obtain phosphocholine [1].
Method 3: A method for whole-cell biocatalytic synthesis of phosphocholine. The process of choline phosphorylation requires a large amount of ATP. U.S. 3m maintains ATP concentration or ATP/ADP at a high level due to its efficient ATP regeneration system, which strongly inhibits the activity of phosphofructokinase. Phosphofructokinase is a key enzyme in the ATP regeneration system, and its activity directly affects the efficiency of the ATP regeneration system. In addition, the redox balance (NADH/NAD) in the system also restricts the efficiency of the ATP regeneration system.
ATP is both one of the substrates of choline kinase and an activator of choline kinase. At the same time, in microbial whole-cell catalysis, ATP can synthesize cAMP through the action of adenylyl cyclase, which can activate protein kinase A and protein kinase C. choline kinase inAfter being phosphorylated by protein kinase A and protein kinase C, the activity can be increased to 1.9 times respectively. The key to using Saccharomyces cerevisiae for whole-cell catalytic synthesis of phosphocholine is to improve the efficiency of ATP regeneration.
The specific method is: using choline chloride and phosphate ions as substrates, using glucose as the energy donor, adding small molecule chemical effect substances, and using permeable microbial whole cells to biocatalytically synthesize phosphocholine. The present invention uses whole-cell biocatalysis to synthesize phosphocholine, which overcomes the shortcomings of chemical synthesis methods such as high cost, low conversion rate, and high solvent toxicity. The whole-cell catalytic stability is good, and the method of using small molecule chemical effect substances to regulate metabolic flow to improve the in-situ regeneration and coupling efficiency of energy has greatly increased the product concentration and the conversion rate.
Main reference materials
[1] Practical Fine Chemical Dictionary
[2] Ying Hanjie; Tang Jiapeng; Chen Yong; Xiong Jian; Bai Jianxin; Chen Xiaochun. Whole-cell biocatalytic synthesis of phosphocholine. CN201010118207.0, application date 20100304
[3] New Practical Drug Handbook
[4] Su Funan. Phosphocholine modified anti-caking agent for frozen products and its preparation method and application. CN201710483322.X, application date 20170622
