Chuanxiongzine/polyethylene glycol conjugate and its preparing method

A technology of polyethylene glycol and ligustrazine, which is applied in the field of biomedical materials and medicine, can solve the problems of fast excretion of ligustrazine, low bioavailability and the like

Inactive Publication Date: 2007-06-13
BEIJING INSTITUTE OF TECHNOLOGYGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The present invention provides ligustrazine / polyethylene glycol conjugate [PEG(OCH 2 CH 2 OOC 8 N 2 h 10 ) 2 ] and its preparation method

Method used

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  • Chuanxiongzine/polyethylene glycol conjugate and its preparing method
  • Chuanxiongzine/polyethylene glycol conjugate and its preparing method
  • Chuanxiongzine/polyethylene glycol conjugate and its preparing method

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0019] Synthesis of ligustrazine polyethylene glycol (molecular weight 2000) ester with DCCI as condensation agent

[0020] 1) Synthesis of intermediate 3,5,6-trimethylpyrazinecarboxylic acid

[0021] Weigh 5.44g (40mmol) Ligustrazine, add 40ml of water, add KMnO4 12.64g (80mmol) several times under stirring, keep at 35-40°C, react for 24 hours, adjust the pH value of the filtrate to 1-2 with concentrated hydrochloric acid, and store in the refrigerator overnight, crystals were precipitated and dried in vacuo. The product was obtained, m.p.161-169°C, yield 15%, IR(KBr): 3260cm -1 (O-H. Carboxyl), 2909cm -1 (CH 3 .pyrazine side chain), 1753cm -1 (C=O. Carboxyl), 1427cm- 1 (-N=C-, pyrazine ring).

[0022] 2) Esterification of 3,5,6-trimethylpyrazinecarboxylic acid with polyethylene glycol-2000

[0023] 2.0 g of polyethylene glycol-2000-dioic acid was dissolved in 40 ml of dry dichloromethane, and 0.541 g of 3,5,6-trimethylpyrazinecarboxylic acid was added. Then, 0.824 g ...

preparation example 2

[0025] Synthesis of ligustrazine polyethylene glycol (molecular weight 2000) ester with CDI as condensation agent

[0026] The synthesis of the intermediate 3,5,6-trimethylpyrazinecarboxylic acid is the same as that in Preparation Example 1.

[0027] 2.0 g of polyethylene glycol-2000-dioic acid was dissolved in 40 ml of dry dichloromethane, and 0.541 g of 3,5,6-trimethylpyrazinecarboxylic acid was added. Add 0.656gl, 1'-carbonyldiimidazole (CDI), heat under reflux, and bubbles will be generated inside, which can make the clear lime water turbid, and it is determined to be CO 2 , The reaction can be stopped until no gas is produced. The reaction time is 4 hours. After cooling, concentrate, and add anhydrous ether dropwise under low temperature conditions, and a white precipitate occurs. Continue to filter at low temperature and dry to obtain light yellow PEG-2000 ester grafted with 3,5,6-trimethylpyrazinecarboxylic acid, the product weighs 1.04g, the yield is 52%, and the melt...

preparation example 3

[0029] Synthesis of ligustrazine polyethylene glycol (molecular weight 1000) ester with DCCI as condensation agent

[0030] Repeat the steps of Preparation Example 1, except that polyethylene glycol PEG-1000 is used instead of PEG-2000 to obtain 3,5,6-trimethylpyrazinecarboxylic acid grafted PEG-1000 ester with a yield of 50.2% , orange-yellow solid, melting point 32°C-36°C: the characteristic absorption of its infrared spectrum is 1270cm -1 (C-O-C), 1751cm -1 (C=O).

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Abstract

The present invention discloses chuanxiongzine / polyethylene glycol conjugate with effective Chuanxiong rhizome component supported on polymer. The chuanxiongzine / polyethylene glycol conjugate is prepared through combining carboxyl derivative of chuanxiongzine with polyethylene glycol by means of ester bond under the action of DCCI, CDI and other condensing agent. The chuanxiongzine / polyethylene glycol conjugate may be degraded in different water system at different speed to release bioactive chuanxiongzine derivative and is superior to available chuanxiongzine preparations, which have over fast metabolism, need frequent administration and obvious peak valley phenomenon.

Description

technical field [0001] The invention relates to the research on a polyethylene glycol-supported active ingredient of traditional Chinese medicine compound and a preparation method thereof, and relates to the fields of biomedical materials and medicine. Background technique [0002] Ligustrazine is an alkaloid monomer isolated and purified from Ligusticum chuanxiong, an algae belonging to the genus Umbelliferae. Ligustrazine has a wealth of pharmacological effects. Since the mid-1970s, it has been widely used in the treatment of domestic clinical cardiovascular and cerebrovascular diseases. However, in the application, it was found that Ligustrazine metabolizes quickly in the body, has a short half-life, requires frequent administration, and has obvious peaks and valleys. [0003] In order to solve the above problems, researchers in my country have made some useful attempts, such as chemically modifying Ligustrazine with various small molecules (see "Structure Modification ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08G65/46
Inventor 王松崔冬梅朱鹤孙
Owner BEIJING INSTITUTE OF TECHNOLOGYGY
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