CITICOLINE NEW PROCESS DEVELOPMENT R&D PATENT

INVENTOR: LIFE WILL Biological Technology R&D Institute

Patent number: ZL 202310499712.1

Advantage:

1.Highly efficient enzymatic hydrolysis processing

2 .High conversion (Convert rate ≥90%，6 hours/Production cycle)

3.High purity with few by-products

1. Basic Information
2. Name: Cytidine 5'-Diphosphocholine （or Citicoline, CDP choline）
3. CAS Number: 987-78-0
4. Molecular Formula: C14H26N4O11P2
5. Molecular Weight: 488.32
6. Synonyms: Nicolin, Brain Diphosphorylcholine （Choline Phosphate）, Cytidine Diphosphate Choline, Cytidine 5-DIPHOSPH, Difosfocin, etc.
7. Physical Properties
8. Appearance: White crystalline powder
9. Melting Point: >185°C （dec.）
10. Specific Rotation: D25 +19.0° （c = 0.86 in H2O）
11. pKa: 4.4 （at 25℃）
12. Boiling Point: 851.4ºC at 760 mmHg
13. Solubility: Sparingly soluble in water
14. Chemical Properties
15. Cytidine 5'-Diphosphocholine is a low-cost generic drug and a cerebral metabolism activator.
16. It can stabilize cell membranes by stimulating S-adenosyl-L-methionine, increase the dendritic complexity and spine density of motor neuron structures, improve the plasticity of non-damaged regional neurons, and promote functional recovery.
17. It can also increase the synthesis of phosphatidylcholine by upregulating choline cytidylyltransferase （CCT）, reducing the level of water-soluble phosphatidylcholine, inhibiting the activity of secretory phospholipase A2 （PLA2）, or inhibiting the activation of TNF-a/IL-1b and PLA2, thereby reducing the loss of phospholipids and repairing neuronal cell membranes.
18. It can increase the expression of anti-apoptotic factors such as Bcl-2 and inhibit the release of glutamate to reduce cell toxicity.
19. Cytidine 5'-Diphosphocholine can promote the rapid repair of damaged cell surfaces and mitochondrial membranes, maintain cell tightness and biological functions, and reduce the release of free fatty acids, thereby reducing the production of toxic oxygenated metabolites and free radicals.
20. It can increase vasopressin and plasma adrenaline levels, and stimulate the release of growth hormone, thyroid-stimulating hormone, and luteinizing hormone.
21. Preparation and Sources
22. It can be extracted from liver or yeast, or synthesized chemically.
23. The synthetic method involves reacting cytosine-5'-diphosphate with ethyleneimine to form cytosine-5'-diphosphate aminoethyl ester, which is then methylated with iodomethane.
24. Alternatively, cytosine-5'-phosphate amide can be directly condensed with phosphocholine ester to obtain the product.
25. Applications
26. Cytidine 5'-Diphosphocholine is clinically used to treat various neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis, and amyotrophic lateral sclerosis.
27. It is also used for consciousness disturbance after acute craniocerebral injury and brain surgery, and can gradually restore limb function in patients with hemiplegia caused by cerebral stroke.
28. It can also be used for functional and consciousness disturbances caused by other acute central nervous system injuries, as well as ischemic cerebrovascular diseases and vascular dementia.
29. Storage Conditions
30. Store in a dark, sealed place, with a shelf life of generally 24 months. Another version suggests storing at below -20°C.