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Method for preparing desmopressin acetate

A technology of desmopressin and acetic acid, which is applied in the field of medicine and chemical industry, can solve the problems of low application value, unfavorable industrial production, and influence on promotion, and achieve low cost, large economic and social benefits, and favorable effects of promotion

Active Publication Date: 2009-02-25
HYBIO PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the existing liquid phase synthesis process is complicated to operate, which is not conducive to industrial production, and the application value is not high, which affects the promotion

Method used

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  • Method for preparing desmopressin acetate
  • Method for preparing desmopressin acetate
  • Method for preparing desmopressin acetate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] The preparation of embodiment 1, Fmoc-Gly-Sieber Amide resin

[0041] Add 30 grams of Sieber Amide resin (1.0mmol / g) in the reaction column of 500ml, add DMF to swell for 30 minutes; Wash three times. Fmoc-Gly-OH (60mmol), HOBt (90mmol) and DICPDI (180mmol) were dissolved with an appropriate amount of DCM and added to the above reaction column, and stirred at room temperature for 60 minutes. After the reaction was complete, the reaction solution was vacuumed off and washed three times with DMF. After ninhydrin detection and blocking, wash three times with DMF, wash three times with DCM, shrink three times with methanol, and take a sample to measure the substitution degree of 0.76mmol / g.

Embodiment 2

[0042] The preparation of embodiment 2, Fmoc-Gly-Sieber Amide resin

[0043] Add 75 grams of Sieber Amide resin (0.8mmol / g) in the reaction column of 1000ml, add DMF to swell for 30 minutes; three times. Dissolve Fmoc-Gly-OH (120mmol), HOBt (180mmol), DICPDI (180mmol) and DMAP (180mmol) with an appropriate amount of DCM, add them to the above reaction column, and stir at room temperature for 60 minutes. After the reaction was complete, the reaction solution was vacuumed off and washed three times with DMF. After ninhydrin detection and blocking, wash three times with DMF, wash three times with DCM, shrink three times with methanol, and take a sample to measure the substitution degree of 0.97mmol / g.

Embodiment 3

[0044] Embodiment 3, the preparation of linear desmopressin-Sieber Amide resin

[0045] Add 26.3 grams of Fmoc-Gly-Sieber Amide resin (0.76mmol / g) in the reaction column of 500ml, add DMF to swell for 30 minutes; Three times, DCM washed three times. Fmoc-D-Arg(R 6 )-OH, HOBt, DICPDI and DMAP were dissolved with an appropriate amount of DCM and added to the above reaction column, and stirred at room temperature for 120 minutes. The ninhydrin detection reaction is complete, the reaction solution is vacuumed off, washed three times with DMF, de-Fmoc with 50% hexahydropyridine in DMF for 10 minutes, then washed three times with DMF and three times with DCM. Repeat Fmoc-D-Arg(R 6 )-OH operation, next to Fmoc-Pro-OH, Fmoc-Cys(R 5 )-OH(N-Fremoxycarbonyl protected side chain mercapto R 5 protected cysteine), Fmoc-Asn (R 4 )-OH(N-Fremoxycarbonyl protected side chain amide group R 4 protected asparagine), Fmoc-Gln (R 3 )-OH(N-Fremoxycarbonyl protected side chain amide group R 3...

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Abstract

The invention relates to a method for preparing desmopressin acetate. The existing liquidoid synthesis technique is complex in operation, so as to affect popularization. The invention adopts a solid phase synthesis method which comprises steps: 1) Fmoc-Gly-OH and Sieber Amide resin with proper substitutability are started to obtain Fmoc-Gly-Sieber Amide resin with the substitutability in a certain range; 2) the Fmoc-Gly-Sieber Amide resin is synthetized by adopting a coupling way one by one, so as to obtain linearity minirin-Sieber Amide resin; 3) the minirin-Sieber Amide resin is synthetized by adopting solid phase oxidation; 4) finally, the minirin-Sieber Amide resin is disintegrated to obtain crude peptide which is purified and frozen out by high pressure liquidoid, so that the desmopressin acetate is obtained. The method has the characteristics of simple operation in reaction, easy post treatment, high yield, low cost, and the like, and has considerable economical and practical value as well as wide application prospect in the field of the design and synthesis of disulfide linkage ring formation polypeptide drugs.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and in particular relates to a solid-phase synthesis method for preparing desmopressin acetate. Background technique [0002] The currently used desmopressin has a similar structure to the natural hormone arginine vasopressin. Due to the deamination of cysteine ​​and the replacement of L-arginine with D-arginine, the clinical The dose of desmopressin has a prolonged action time without pressurized side effects, and at the same time, the risk of human immunodeficiency virus (HIV) and hepatitis virus infection caused by the use of factor VIII preparations can be avoided. However, the existing liquid-phase synthesis process is complicated to operate, which is not conducive to industrial production, and its application value is not high, which affects its popularization. Contents of the invention [0003] The object of the present invention is to provide a solid-phase synthesis method...

Claims

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Application Information

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IPC IPC(8): C07K7/06C07K1/04
Inventor 刘建李红玲马亚平
Owner HYBIO PHARMA