A kind of separation and purification method of levodopa

A technology for separation, purification and levodopa, which is applied in chemical instruments and methods, organic chemistry, cyanide reaction preparation, etc., can solve problems such as low yield of levodopa products, and achieves reduction of possibility, improvement of yield, and improvement of The effect of the amount of precipitation

Active Publication Date: 2020-04-24
SHANDONG LUKANG PHARMA
View PDF2 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But, the levodopa product yield that above-mentioned two kinds of methods obtain is all lower

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A kind of separation and purification method of levodopa
  • A kind of separation and purification method of levodopa
  • A kind of separation and purification method of levodopa

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] Preparation of raw material liquid containing levodopa:

[0072] First prepare the substrate solution: mix catechol 10g, sodium pyruvate 12g, ammonium acetate 45g, sodium sulfite 2g, ethylenediaminetetraacetic acid 1g, pyridoxal phosphate 0.1g with 720mL pure water, heat to 20°C, Stir to dissolve.

[0073] Add ammonia water to the above substrate solution, adjust the pH value to 8.15, set the volume to 900ml, add 100mL of commercially available tyrosine phenol lyase crude enzyme solution with a mass concentration of 5%, then seal the reaction vessel and fill it with nitrogen , at 15°C, 200rpm shaker or stirring conditions for biocatalytic reaction.

[0074] In addition to 0min, sampling and determination of the residual amount of catechol and sodium pyruvate every hour, when the content of catechol and sodium pyruvate is low, then add an appropriate amount of catechol and sodium pyruvate, so that The concentration of hydroquinone is 6g / L, and the concentration of sodi...

Embodiment 2

[0095] The substrate solution was prepared according to the method described in Example 1, and a raw material solution with a levodopa content of 70 g / L was obtained through catalysis by tyrosine phenol lyase. Getting levodopa content is 500L of raw material liquid of 70g / L, and the separation and purification of this raw material liquid comprises the following steps:

[0096] 1) Add 500g of ascorbic acid into the raw material solution, stir evenly, and fully dissolve;

[0097] 2) Under the condition of rapid stirring of the raw material solution at a speed of 300rpm, slowly add a potassium hydroxide solution with a mass-volume concentration of 350g / L, adjust the pH value of the solution to 12.5, and obtain an alkaline mixed solution; the addition of the potassium hydroxide The speed is: 20mL / min;

[0098] 3) The alkaline mixed solution obtained in step 2) was subjected to low-temperature high-speed centrifugation at 5° C. and a rotational speed of 4500 rpm for 30 minutes, an...

Embodiment 3

[0114] Get 500L of raw material liquid containing levodopa, and the concentration of levodopa in the raw material liquid is 50g / L. The separation and purification of this raw material liquid comprises the following steps:

[0115] 3) Add 500g of ascorbic acid into the raw material solution, stir evenly, and fully dissolve;

[0116] 4) Under the condition of rapid stirring of the raw material solution at a speed of 400rpm, slowly add a sodium hydroxide solution with a mass-volume concentration of 380g / L, adjust the pH value of the solution to 13, and obtain an alkaline mixed solution; the addition of the sodium hydroxide The speed is: 25mL / min;

[0117] 3) The alkaline mixed solution obtained in step 2) was subjected to low-temperature high-speed centrifugation at 4°C and a rotational speed of 4000 rpm for 20 minutes, and the supernatant was collected, totaling 500 L;

[0118] 4) Add 15 kg of powdered activated carbon to the supernatant obtained in step 3), heat up to 40° C.,...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention provides a method for separating and purifying levodopa. The method comprises the steps of adjusting a solution to be alkaline under the action of an ascorbic acid antioxidant so as to dissolve levodopa, and adjusting the solution to be acidic, so as to separate levodopa. By taking ascorbic acid as the antioxidant in a reaction process, the oxidation of levodopa during separation and purification is avoided, so that the yield of levodopa is increased; by settling levodopa through acetic acid, the influence on the growth speed because the acidity is too strong is avoided, the control on the growth speed of a levodopa precipitate is realized, and the separation amount of the levodopa precipitate is increased; furthermore, acidic materials with oxidability is not introduced, so that oxidation possibility of levodopa during the separation and purification is reduced, and the yield of levodopa is increased. A result of an embodiment shows that the product yield of the method provided by the invention can reach 88%-91%, the purity is above 99.8%, and the method meets CP / USP / EP requirements.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a method for separating and purifying levodopa. Background technique [0002] Levodopa, also known as 3,4-dihydroxyphenylalanine, is an important biologically active substance. Levodopa is the precursor of the neurotransmitter dopamine, which can pass through the blood-brain barrier and enter the cerebral circulation to reach the central nervous system. Treat Parkinson's disease. In addition, levodopa also has the effect of treating amblyopia and heart failure. Although there will be some side effects after long-term use, more than 40 years have passed, and there is still no better alternative drug. [0003] According to statistics, in 2015, the total global sales of levodopa reached 330 million US dollars, ranking 97th among the world's best-selling drugs, and its total output reached more than 2,000 tons. Dollar. In the prior art, the extraction method of levodopa is usua...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Patents(China)
IPC IPC(8): C07C227/44C07C227/42C07C229/36
CPCC07C227/42C07C227/44C07C229/36
Inventor 金伟郑长春王博张兴灿卢春玲韩东梅陈君
Owner SHANDONG LUKANG PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap