Method for preparing copaxone
A technology of glatiramer and crude products, which is applied in the field of polypeptide drug preparation, can solve the problems of low yield, cumbersome operation, and high production cost, and achieve the effects of high yield, simple process operation, wide application prospect and economic value
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[0040] The preparation method of glatiramer comprises the following steps:
[0041] a, with protected tyrosine N-carboxy anhydride, L-alanine N-carboxy anhydride, protected L-glutamine γ-benzyl N-carboxy anhydride and protected L-lysine N-carboxy anhydride Base catalyzed copolymerization to prepare the protected copolymer. Among them, the reaction of L-alanine N-carboxy anhydride, protected L-glutamine γ-benzyl N-carboxy anhydride, protected L-lysine N-carboxy anhydride and protected tyrosine N-carboxy anhydride The molar proportions are: 0.90-1.10: 0.30-0.36: 0.75-0.85: 0.20-0.24, and the polymerization reaction time is 10-30 hours.
[0042] b. The above-mentioned protected copolymer is subjected to acidolysis or hydrogenolysis to obtain the crude product of glatiramer;
[0043] c. The glatiramer crude product is purified by ultrafiltration to obtain the glatiramer product.
[0044] In the above preparation method of glatiramer, the base described in step a is diethylamine...
Embodiment 1
[0047] The preparation of the copolymer protected by embodiment 1
[0048] N-carboxy anhydride of L-alanine (11.3g, 98.18mmol), N-carboxy anhydride of L-glutamic acid γ-benzyl ester (8.7g, 33.05mmol), N-benzyloxycarbonyl lysine The N-carboxy anhydride of the acid (23.5 g, 76.72 mmol) and the N-carboxy anhydride of L-tyrosine (6.5 g, 21.86 mmol) were placed in a single necked flask with a magnetic stirrer. This mixture was dissolved by adding dry N,N-dimethylformamide (DMF) (400 mL). Distilled diethylamine (0.94 mL) was added. The resulting mixture was stirred at room temperature for 24 hours. The above reaction solution was poured into 1000 mL of water, stirred for 30 minutes, the solid was collected by filtration, and dried under reduced pressure to obtain 43.3 g of the protected copolymer with a yield of 86.6%.
Embodiment 2
[0049] Embodiment 2 Acid hydrolysis prepares glatiramer crude product
[0050] Take 10 g of the copolymer prepared in Example 1, dissolve it in 100 mL of 8% HBr / TFA, stir the reaction for 3 hours, distill under reduced pressure, precipitate the residue with ether, collect the solid by filtration, and obtain the crude glatiramer.
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