Background and overview[1][2]
L-a-glycerylphosphorylcholine (GPC) is also called phosphocholine, glyceryl choline phosphate, and glyceryl lecithin. It is the two fatty acyl groups on the lecithin molecule of phosphatidylcholine. The completely hydrolyzed product is a water-soluble phospholipid precursor and neurotransmitter naturally found in the human body. It is also a unique cell protectant that can support the fluidity and integrity of cell membranes. Years of experimental research and clinical applications have shown that GPC can not only improve people’s memory and cognitive abilities, but also has significant effects on brain circulation decline and Alzheimer’s disease, so it is called the brain’s anti-aging nutrient. In addition, it can also resist muscle atrophy and protect blood vessels. Therefore, GPC is of great value in both the healthcare and pharmaceutical industries.
Preparation[1]
The preparation of GPC from organisms is generally divided into two steps. First, the phospholipid alcohol (water) in cells needs to be decomposed into GPC, L-a-glycerophosphatidylethanolamine (L-a-GPE), and L-a-glycerophosphatidylserine (L-a- GPS), etc., and then separate, extract, and purify to obtain GPC.
1 Alcohol (hydro)lysis method of phospholipids
The alcohol (hydro)lysis methods of phospholipids (lecithin) include metal sodium, methanol or sodium ethoxide, ion exchange resin catalyzed alcoholysis, and biological enzymatic hydrolysis in non-aqueous or aqueous phases (Figure 2).
Due to the dangers of elemental sodium, there are problems in its use in industrial production. The catalytic alcoholysis of methanol or sodium ethoxide is used to prepare GPC. The process is relatively simple and can be produced on a large scale, but the GPC yield is low and the cost increases. Ion exchange EVA resin catalyzes alcoholysis and has a good effect, but it involves environmental problems caused by the pretreatment and regeneration of ion exchange resin. The electric regeneration technology of ion exchange resin that has appeared in recent years has opened up a direction to solve this problem. . Enzyme hydrolysis involves the preparation of enzymes and the problems caused by wastewater and waste residue treatment and the increase in production costs.
2 Isolation and purification of GPC
The main methods for separating and purifying GPC include solvent extraction, precipitation, recrystallization and column chromatography. Use solvent extraction method (absolute ethanol-ether = 3:1, v/v) to directly extract GPC from bovine pancreas. This method is relatively primitive and has a relatively small processing capacity; use mercury chloride to precipitate the by-products in the form of mercury salts. The product is purified GPC, in which excess mercury ions are removed through H2S and BaCO3. This purification method cannot completely remove mercury ions, and unreacted lecithin remains, which needs to be precipitated by adding calcium salts. Finally, resin is used to remove the calcium salts. This method is less efficient, the process is more complex, and the final yield is also lower.
To prepare GPC pure products by recrystallization, the catalyst needs to be removed and the product is recrystallized and purified. The whole process is complicated and costly, and is not suitable for commercial scale production. In contrast, column chromatography is a convenient and cost-effective method. Economical GPC purification method. Column chromatography can be divided into ion exchange resin chromatography, silica gel column chromatography and alumina column chromatography according to different adsorbents.
The following focuses on ion exchange resin chromatography. Early European patents and US patents required the use of a variety of anion and cation exchange resins to achieve the purpose of separation and purification. In 2012, Zhou Li and others studied and concluded that GPC with lower cost and higher purity can be separated from the alcoholysis product of crude phospholipid by using D113 resin as the main adsorption resin. 201 Dimethyl Silicone Emulsifier The invention patent applied for by Ding Jianfei and others in 3 years also proposed the use of corresponding macroporous weakly acidic cation exchange resin to separate and purify natural GPC.
Clinical applications and indications[1]
GPC is a water-soluble phospholipid metabolic intermediate naturally occurring in the human body. It is also a biosynthetic precursor of an important neurotransmitter, acetylcholine (acetylcholine) and PC. GPC plays an important role in the body through the production of certain hormones and neurotransmitters such as acetylcholine and human growth hormone, thereby supporting the function of the brain and nervous system. Therefore, it has important medical applications in neurological and mental disorders of the human brain.
The most important physiological function of GPC is that it can cross the blood-brain barrier and provide a source of choline for the synthesis of acetylcholine and phosphatidylcholine. Acetylcholine can help the brain complete learning, memory and cognitive activities and control superficial During sleep and muscle activity, GPC entering the blood-brain barrier can promote the synthesis of phospholipids in the brain, thereby providing more phospholipid compounds for signal transmission within the central nervous system. As we age, the body’s perception gradually declines. At the same time, it can induce neurodegenerative diseases such as vascular dementia and Alzheimer’s disease. However, when the amount of acetylcholine and phosphatidylcholine in the body increases, the damage to human brain cell membranes will be improved, which will contribute to the health of cerebral blood vessels, thus Improve cognitive function and Alzheimer’s symptoms. Multiple studies have proven that GPC plays an important role in improving mental function, neurological concepts, and memory. A multicenter, randomized, controlled study with 126 subjects demonstrated that GPC improved neuropsychological parameters on behavioral tests.
GPC can be absorbed in the small intestine and at the site of intravenous injection through extracorporeal supplementation, i.e. oral or intravenous injection, and enters various organs such as the brain, liver, kidneys, etc. through blood circulation to play a positive role. After entering the liver, it binds to ester proteins. It has the functions of protecting the liver, resisting the fat penetration of high lipoproteins, resisting hyperlipidemia and arteriosclerosis. It can also improve the cognitive ability and memory of the elderly, treat Alzheimer’s disease and brain nerve damage, and protect blood vessels.
Not only that, in the late 1990s, it was discovered that this compound is crucial to the healthy development of newborns, especially the brain development of newborns. In short, the chemical structure of GPC and the interconnected physical and chemical properties ensure its physiological activity after entering the blood-brain barrier, promoting the formation of important brain substances – phosphoinositol, which is very beneficial to brain tissue and ensures Brain tissue metabolism thereby provides more phospholipid compounds for signal transmission within the central nervous system. When the synthesis of acetylcholine and phosphatidylcholine in the body is increased, the damage to human brain cell membranes caused by age can be improved, thus contributing to the health of cerebral blood vessels and improving the condition of Alzheimer’s disease. Preclinical pharmacological test results and clinical studies have confirmed that GPC has great benefits on the cognitive and memory functions of the brain, especially in the treatment of emotional and behavioral disorders caused by brain degenerative diseases.
Since GPC is a drug that provides high levels of choline to brain cells and nerve cells and protects their cell walls, Italy conducted a multi-center clinical trial on patients with cerebral ischemia, in which 1000 mg was administered intramuscularly every day after the onset of the disease. The treatment period was 28 days, and the results effectively treated patients with acute stroke or transient cerebral ischemia, with low side effects and good tolerance; the choline precursor L-a-glycerophosphatidyl was used based on the “cholinergic injury hypothesis” In a multi-center, double-blind, randomized, placebo-controlled trial, choline was administered 3 times a day, mg each time, for 180 days in patients with Alzheimer’s disease. The results showed that GPC is effective in treating Alzheimer’s disease. The efficacy of GPC is significant; GPC was also used in a multi-center, open and controlled trial on 126 patients with mild to moderate multiple cerebral infarction dementia, and 1 000 mg was injected intramuscularly every day for 90 days. The results also showed that GPC has a good effect on multiple cerebral infarction dementia, and patients with Alzheimer’s disease and multiple cerebral infarction dementia also have good tolerance to GPC.
Main reference materials
[1] Yan Xikang, Qian Xiangyun, Ding Jianfei. Research and development progress of L-a-glycerophosphatidylcholine [J]. Shanghai Pharmaceuticals, 2015, 36(15): 68-72+75.
