Preparation method for polyene phosphatidyl choline for injection

A technology for polyene phosphatidylcholine and injection, applied in the direction of edible phospholipid composition, application, food science, etc., can solve the problems of long delivery cycle, difficult to guarantee content, less than 98%, and achieve production operation Convenience, reduced over-reliance, large processing effect

Active Publication Date: 2015-05-06
GUANGZHOU HANFANG PHARMA
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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. By choosing adsorbents with different physical and chemical properties to stir and adsorb the raw material solution to be adsorbed, the effect of purification is achieved. Common adsorbents include: 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 and lysophosphatidylcholine (LPC) meet the standards for injection
[0006] Silica gel column chromatography is another commonly used separation and purification method. The ratio of the stationary phase to the substance to be separated, the type and ratio of the elution solvent have a huge impact on the separation effect and impurity removal ability of column chromatography. Column chromatography The solvent and ratio selection of the method are related to the properties of the product itself and the properties of impurities. Although this method is common, there is no 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 va

Method used

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  • Preparation method for polyene phosphatidyl choline for injection

Examples

Experimental program
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Effect test

Example Embodiment

[0029] Example 1:

[0030] Take 1 kg of soybean phospholipids, add chloroform-ethanol-water solution, dissolve it to prepare the raw material solution, fill with 8 kg silica gel for column chromatography, and use the eluent (chloroform 79.8%, ethanol 19.8%, water 0.4%) 15 liters were eluted, and 40 liters were eluted with eluent (dichloromethane 48.9%, ethanol 48.3%, water 2.8%) for the second time. The eluate was collected, concentrated in vacuo, and freeze-dried to obtain polyene phospholipids. Acylcholine product, PC transfer rate is 75.3%, phosphatidylcholine purity is 99.5%, lysophosphatidylcholine is not detected, phosphatidylinositol is not detected, phosphatidic acid is not detected, acid value is 0.3, over The oxidation value was not detected, the methoxyaniline value was 2.1, and the content of triglycerides and free fatty acids all met the requirements.

Example Embodiment

[0031] Example 2:

[0032] Take 1 kg of soybean phospholipid, add dichloroethane-isopropanol-water solution, dissolve it to prepare the raw material solution, fill 7 kg of diol-based silica gel for column chromatography, and use the eluent (dichloroethane 90.7 %, isopropanol 9.1%, water 0.2%) to elute 15 liters, the second time with eluent (chloroform 62.3%, propanol 34.7, water 3.0%) to elute 40 liters to collect the eluent, after Vacuum concentration, freeze-drying to obtain polyene phosphatidylcholine product, PC transfer rate is 81.2%, phosphatidylcholine purity is 99.0%, lysophosphatidylcholine is not detected, phosphatidylinositol is not detected, phosphatidic acid is not It was detected that the acid value was 0.4, the peroxide value was not detected, the methoxyaniline value was 3.0, and the triglyceride and free fatty acid content met the requirements.

Example Embodiment

[0033] Example 3:

[0034] Take 5 kg of soybean phospholipids, add dichloromethane-ethanol-water solution, dissolve to prepare the raw material solution, fill 25 kg silica gel for column chromatography, and use eluent (dichloromethane 89.8%, ethanol 10%, water 0.2%) 75 liters were eluted, and 200 liters were eluted with eluent (chloroform 50.8%, n-butanol 46.7%, water 2.5%) for the second time. The eluate was collected by vacuum concentration and freeze-dried. Enphosphatidylcholine product, PC transfer rate is 85.0%, phosphatidylcholine purity is 98.3%, lysophosphatidylcholine content is 0.2%, phosphatidylinositol is not detected, phosphatidic acid is not detected, acid value 0.4, the peroxide value was not detected, the methoxyaniline value was 4.2, and the content of triglycerides and free fatty acids all met the requirements.

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Abstract

The invention discloses a preparation method for polyene phosphatidyl choline for injection. The preparation method comprises the following steps: dissolving with a proper solvent by taking soyabean lecithin as a raw material, performing elution twice with a ternary mixed solvent consisting of multi-halogenated hydrocarbon, low carbon alcohol and water through column chromatography, and drying to obtain a product polyene phosphatidyl choline. The product obtained by the preparation method disclosed by the invention is high in phosphatidylcholine content (98.0%-99.9%, HPLC (high performance liquid chromatography) process), low in impurity content (less than 1.0% of lysophosphatidyl choline, less than 0.5% of phosphatidyl inositol, less than 0.5% of phosphatidyl ethanolamine, less than 0.2% of free fatty acid and less than 0.2% of triglyceride), and low in oxidative index (an acid value lower than 0.5, a peroxide value lower than 1.0 and methoxy phenylamine value lower than 5.0), so that the product quality reaches the quality standards of polyene phosphatidyl choline for injection.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical engineering, and in particular relates to a preparation method of polyene phosphatidylcholine for injection. Background technique [0002] Polyene phosphatidylcholine is a mixture extracted from soybeans with phosphatidylcholine (PC) as the main component. It is mainly used for adjuvant treatment of liver and gallbladder diseases in clinical practice. It is a hepatoprotective drug with a positive effect. Various types of liver diseases, such as hepatitis, chronic hepatitis, hepatic necrosis, cirrhosis, hepatic coma (including prodromal coma); fatty liver (also seen in diabetics); bile obstruction, poisoning, prevention of recurrence of gallstones; treatment before and after surgery , especially hepatobiliary surgery; pregnancy poisoning, including vomiting; psoriasis; neurodermatitis, radiation syndrome. The preparation technology of polyene phosphatidylcholine is relatively complicated. D...

Claims

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Application Information

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IPC IPC(8): C07F9/10
Inventor 许文东唐顺之袁诚李继荣黄翔关伟键蔡鸿飞杨玉琼谭巧君牟肖男梁北梅王小妹
Owner GUANGZHOU HANFANG PHARMA
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