A kind of preparation method of egg yolk phosphatidylcholine for injection

Abstract

The invention discloses a method for preparing yolk phosphatidylcholine (PC) for injection. The method comprises steps as follows: yolk lecithin serving as a raw material is subjected to column chromatography and two times of elution and drying in ternary mixture solvents comprising poly-haloalkane, low carbon alcohol and water to obtain a PC product. The PC purity of the product ranges from 98.0% to 99.9% when the product is processed with a high-performance liquid chromatography (HPLC) method, the content of lysophosphatidylcholine is less than 0.5%, the content of cholesterol is less than 0.2%, the content of free fatty acid is less than 0.2%, the content of triglycerides is less than 0.2%, an acid value is lower than 1.0, a peroxidation value is lower than 1.0, an anisidine value is lower than 5.0, and the quality standard of the imported yolk PC for injection is met.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical engineering, in particular to a method for preparing egg yolk phosphatidylcholine for injection. Background technique [0002] Phosphatidylcholine (phosphatidylcholine referred to as PC), also known as lecithin, is a type of phospholipid compound composed of choline and phosphatidic acid in structure. Phosphatidylcholine is an important component of organisms. As a natural emulsifier and nutritional supplement, it is widely used in food, chemical industry and medicine. In the field of pharmaceuticals, it is mainly used as a solubilizer, emulsifier, antioxidant for oils, etc., and is an important excipient for new targeted preparations such as liposomes and lipid microspheres. Clinically, phosphatidylcholine can be used as a carrier for drugs with low water solubility, which can improve the bioavailability of drugs and reduce drug toxicity. Phosphatidylcholine for injection is used as a ke...

AI Technical Summary

Problems solved by technology

The molecular weight of phosphatidylcholine and other phospholipids is relatively close, and it is still difficult to obtain a single phosphatidylcholine by membrane separation method, and its product content is too low to meet the requirements of injection excipients

The solvent extraction method achieves the purpose of enrichment and purification through the difference in the solubility of phosphatidylcholine in two-phase solvents, and has poor selectivity to various phospholipid impurities with very similar physical and chemical properties.

[0005] Adsorption method is a more commonly used purification method. The effect of purification is achieved by selecting adsorbents with different physical and chemical properties and stirring and adsorbing the raw material liquid to be adsorbed. The common adsorbents are: aluminum oxide, silica gel, etc. This method is only for Phosphatidylethanolamine (PE), acid value and other indicators have a certain adsorption effect, and it is difficult to ensure that key indicators such as content, lysophosphatidylcholine (LPC) and cholesterol meet the standards for injection

[0006] Silica gel column chromatography is another commonly used separation and purification method. The ratio of stationary phase to the substance to be separated, the type and ratio of elution solvent have a significant impact on the separation effect and impurity removal ability of column chromatography. Column chromatography The choice of solvent and proportion of the method is related to the properties of the product itself and the properties of impurities. Although this method is common, there is no literature report on the method that can make the product quality meet the quality standards for injections and meet the requirements of commercial mass production at the same time.

[0007] There are many patents using column chromatography to purify phosphatidylcholine, among which Japanese patents JP52083912A and JP52057212A disclose silica gel column chromatography with chloroform-ethanol or chloroform-methanol as eluent to obtain the content of phosphatidylcholine 80% and 89% of the products respectively, the contents of the above two patented products are both lower than 98%, which cannot meet the requirements for injection

[0008] Chinese patent CN103073572A discloses a product with a peroxide value of 0.84, an acid value of 9.06, and a phosphatidylcholine content of 88.6%-92.1% through steps such as heating at 180°C, acetone deoiling, centrifugation, and silica gel adsorption and filtration. The high-temperature treatment of phospholipids in this patented technology will lead to the production of aldehydes and ketones (methoxyaniline value), and the purity, acid value, fatty acid and other indicators of the obtained product cannot meet the requirements of injection standards.

[0009] Chinese patent CN100500676C discloses that soybean powder phospholipid is used as raw material to extract, perform one alumina chromatography and one silica gel chromatography, and elute with low-carbon alcohol-water to obtain a product with an acid value of 8.7 and a phosphatidylcholine content of 93.4%. The phosphatidylcholine content of the obtained product is low, and indicators such as acid value, triglyceride, fatty acid, and methoxyaniline value cannot be effectively controlled

[0010] Chinese patent CN102633832A discloses a method of using silica gel column chromatography and eluting with alcohol water to obtain products containing 90%-97.5% of phosphatidylcholine content respectively. This patent method cannot achieve purification while increasing the content. Impurity indicators such as triglycerides and oxidation indicators such as peroxide value make the product quality meet the requirements of injection excipients

[0011] As reported above, the patented technical method of phosphatidylcholine column chromatography has no control over the limits of impurities such as triglycerides, cholesterol, fatty acids, and oxidation indicators such as acid value, peroxide value, and methoxyaniline value. Applied in the field of excipients for injection

At present, in the technical field of developing phosphatidylcholine for injection, there is no method for controlling physical and chemical indicators such as peroxide value and methoxyaniline value. Phosphatidylcholine itself is highly unstable, and the development of such products requires excessive reliance on Due to the freshness of starting materials; due to technical constraints, the current domestic egg yolk phosphatidylcholine for injection mainly relies on imports, which are expensive and have a long delivery cycle, resulting in long development cycles and high costs for phosphatidylcholine-related products, which are not conducive to Popularity of the market

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