Ibuprofen sugar derivative and its preparing process and use

A technology of sugar derivatives and glucosides, which is applied in the field of 6--ibuprofen and its preparation, can solve the problems of low bioavailability, increased gastrointestinal side effects, and clinical application limitations, and achieve the effect of simplifying the operation steps

Inactive Publication Date: 2005-10-19
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] As an anti-inflammatory and analgesic drug, ibuprofen has been accepted by most patients, but ibuprofen is almost insoluble in water, and ordinary oral tablets have problems such as short drug half-life and low bioavailability in the gastrointestinal tract
And ibuprofen, as an effective drug for treating chronic diseases such as rheumatism and rheumatoid arthritis, long-term frequent high-dose medication will increase the side effects of the gastrointestinal tract, even cause gastrointestinal bleeding, and have certain damage to the kidneys, making it clinically The application has been greatly restricted, and it has become an urgent problem for medical workers
[0005] In order to solve these problems, people have adopted various methods to reduce the side effects of ibuprofen and improve its bioavailability. Various new preparations have been designed and marketed at home and abroad, but these improvement effects are not significant enough.

Method used

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  • Ibuprofen sugar derivative and its preparing process and use
  • Ibuprofen sugar derivative and its preparing process and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] In a 50ml ground-mouth Erlenmeyer flask, add 20ml methyl ethyl ketone, 0.2g ibuprofen (about 1mmol) and α-methyl-D-glucoside (about 1mmol) and 2.0g activated molecular sieves (3.0 Å), at 50°C Shake for a certain period of time, and then add 0.2 g of commercial lipase Novozym 435 after the reaction substrate is fully dissolved. By thin-plate chromatography TLC (CHCl 3 :CH 3 OH:H 2 O (65:15:2)) to detect the reaction process. After reacting for 96hr, the reaction liquid was cooled, 40ml of dichloromethane was added, shaken at room temperature for 20min, and the immobilized lipase was floated out, then filtered, and rotary evaporated at 40°C, and the residue was cleaned with a silica gel column (ethyl acetate:methanol, 10: 1 v / v) to obtain 6-(α-methyl-D-glucoside)-(±) ibuprofen. The melting point was determined to be 52-55°C with a melting point analyzer (uncorrected).

[0024] The mass-to-nucleus ratio m / z of the compound was verified to be 382 by mass spectrometry. ...

Embodiment 2

[0029] In a 50ml ground-neck Erlenmeyer flask, add 20ml of acetonitrile, 0.2g of ibuprofen (about 1mmol) and α-methyl-D-glucoside (about 1mmol) and 2.0g of activated molecular sieves (3.0 Å), at 50°C Shake for a certain period of time, and then add 0.2 g of commercial lipase Novozym 435 after the reaction substrate is fully dissolved. By thin-plate chromatography TLC (CHCl 3 :CH 3 OH:H 2 O (65:15:2)) to detect the reaction process. After reacting for 96hr, the reaction liquid was cooled, 40ml of dichloromethane was added, shaken at room temperature for 20min, and the immobilized lipase was floated out, then filtered, and rotary evaporated at 40°C, and the residue was cleaned with a silica gel column (ethyl acetate:methanol, 10: 1 v / v) to obtain 6-(α-methyl-D-glucoside)-(±) ibuprofen. The yield of the target product was 30.3%.

Embodiment 3

[0031] In a 50ml ground-neck Erlenmeyer flask, add 20ml of acetonitrile, 0.8g of ibuprofen (about 4mmol) and 0.1g of α-methyl-D-glucoside (about 0.5mmol), shake at 50°C for a certain period of time, wait After the reaction substrate was fully dissolved, 0.2 g of commercial lipase Novozym 435 was added. By thin-plate chromatography TLC (CHCl 3 :CH 3 OH:H 2O (65:15:2)) to detect the reaction process. After reacting for 96hr, the reaction liquid was cooled, 40ml of dichloromethane was added, shaken at room temperature for 20min, and the immobilized lipase was floated out, then filtered, and rotary evaporated at 40°C. 1 v / v) to obtain 6-(α-methyl-D-glucoside)-(±) ibuprofen. The target product yield was 78.6%.

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Abstract

The present invention relates to ibuprofen sugar derivative and its preparation process and application. The present invention prepares the target compound through crosslinking unprotected alpha-methyl-D-glucoside and 2-(4'-isobutylphenyl)-propanoic acid with immobilized lipase. The present invention has simplified operation steps, mild reaction condition and high product purity, and may be used in industrial production. The ibuprofen sugar derivative of the present invention may be used in preparing medicine for treating rheumarthritis and rheumatoid arthritis. Its general structural expression is also given.

Description

technical field [0001] The invention belongs to the field of biotechnology, and relates to phenylpropionate derivatives of glucoside, especially 6-(α-methyl-D-glucoside)-(±) ibuprofen and its preparation method and application. Background technique [0002] Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of drugs that have antipyretic, analgesic, and most of them also have anti-inflammatory and anti-rheumatic effects, and are widely used clinically to treat rheumatoid arthritis. Inflammation, osteoarthritis and other rheumatic diseases, relieve the suffering of hundreds of millions of rheumatic patients. Currently clinically commonly used NSAIDs include Aspirin, Indomethacin, Ibuprofen (IB), Diclofenac sodium (Diclofanicpotassium), Meloxican and the like. According to foreign reports, ibuprofen is the one with the least toxic and side effects of 11 non-steroidal anti-inflammatory drugs such as Naproxen, Ketoprofen, and Diclofenac sodium. Non-prescription drugs. ...

Claims

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Application Information

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IPC IPC(8): A61K31/7024A61P19/02A61P29/00C07H13/04C07H15/00C12P19/44
Inventor 魏东芝赵相国宋庆训
Owner EAST CHINA UNIV OF SCI & TECH
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