Preparation method for lanreotide

A technology of lanreotide and peptide resin, which is applied in the field of peptides and can solve the problems of high cost and low yield

Inactive Publication Date: 2015-04-08
浙江华军药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Judging from the literature reports, the solid-phase Fmoc strategy is mainly used in the market to prepare step by step coupling synthesis technology. The commonly used DIC / HOBT or TBTU / HOBt system is condensed, and the synthesis yield is low and the cost is high.

Method used

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  • Preparation method for lanreotide
  • Preparation method for lanreotide
  • Preparation method for lanreotide

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preparation example Construction

[0062] The invention discloses a preparation method of lanreotide, and those skilled in the art can learn from the content of this article and appropriately improve the process parameters to realize it. In particular, it should be pointed out that all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The method and application of the present invention have been described through preferred embodiments, and the relevant personnel can obviously make changes or appropriate changes and combinations to the method and application described herein without departing from the content, spirit and scope of the present invention to realize and Apply the technology of the present invention.

[0063] The raw materials used in the preparation method of lanreotide provided by the present invention are all available in the market. Among them, the amino acid was purchased from Jill Biochemical Sha...

Embodiment 1

[0067] The preparation of embodiment 1 lanreotide peptide resin

[0068] 1. Preparation of Fragment Boc-Nal-Cys(Trt)-OH

[0069] Dissolve Boc-3-(2-naphthyl)-D-alanine in dimethylformamide, add excess HOSU and excess DCC, react at 10-15°C for 2-3 hours after dissolving, and detect Boc -3-(2-naphthyl)-D-alanine reacted completely, and filtered to obtain the filtrate; the filtrate was added dropwise to the H-Cys(Trt)-OH solution (sodium carbonate and H-Cys(Trt)-OH were added to the water prepared), reacted at 10-15°C for 10-15 hours, detected that Boc-3-(2-naphthyl)-(D)Phe-OSU was completely reacted, adjusted the pH value of the solution to 3.0-4.0 with acetic acid, filtered, and added acetic acid Ethyl extraction, the ethyl acetate layer was washed with saturated sodium chloride solution for 3-5 times, then dried with anhydrous sodium sulfate for 3 hours, filtered and the filtrate was distilled under reduced pressure to remove most of the ethyl acetate, then crystallized with p...

Embodiment 2

[0100] Embodiment 2 Preparation of lanreotide crude refined peptide

[0101] Preparation of crude lanreotide Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2

[0102] (1) Prepare the lysate: Add trifluoroacetic acid (TFA) / phenol / 1,2-ethanedithiol (EDT) / triisopropylsilane (Tis) in a volume ratio of 89:3:3:5 to the glass Or refrigerate in a PTFE container for 2 hours.

[0103] (2) Excision of resin and other amino acid side chain protecting groups: Take out the pre-cooled lysate, add 8-12ml of peptide cutting solution to 1g of lanreotide peptide resin prepared in Example 1, and put the above-mentioned fragment condensation peptide resin in Add to the lysate under stirring, react at room temperature for 2 to 2.5 hours, then filter, add the filtrate to pre-cooled ether, stir and precipitate, centrifuge the precipitate, remove the supernatant, wash the precipitate with ether four times, and dry in vacuum to obtain a dry powder 6.2g, which is the crude straight chain lanreotide.

[0104] (3...

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Abstract

The invention relates to the field of polypeptides and particularly relates to a preparation method for lanreotide. The preparation method comprises the following steps: a step I: obtaining a dipeptide segment with an amino acid sequence as shown in SEQ ID No.1; a step II: obtaining hexapeptide peptide resin, wherein the amino acid sequence of the hexapeptide is as shown in SEQ ID No.2; a step III: condensing the dipeptide segment and the hexapeptide peptide resin according to the amino acid sequence of the lanreotide to obtain lanreotide peptide resin; and a step IV: cracking the lanreotide peptide resin to remove resin and a side chain protective group, thereby obtaining a lanreotide crude product, and then refining the lanreotide crude product to obtain lanreotide. The invention provides a method for combining solid-phase synthesis with liquid-phase synthesis. A 2+6 segment solid-phase synthesis technology is adopted to greatly improve the purity of the crude product, so that the yield of the final product is increased, and the preparation cost is lowered.

Description

technical field [0001] The invention relates to the field of polypeptides, in particular to a preparation method of lanreotide. Background technique [0002] The structural formula of Lanreotide is shown in Formula I: [0003] [0004] The chemical formula is C 54 h 69 N 11 o 10 S 2 , MW: 1096.34, CAS: 108736-35-2, the amino acid sequence is shown in SEQ ID No.3. [0005] Lanreotide is an octapeptide analog of somatostatin that is more active than natural somatostatin and has a longer duration of action. Its inhibitory effect on growth hormone secretion is more selective than that on insulin secretion. It is used for the long-term treatment of patients with acromegaly and growth hormone-type pituitary tumors who are not effective in surgery or radiotherapy, especially for pituitary gland tumors. Therapeutic advantage in patients with macroadenomas is clear and is a peptide inhibitor of many endocrine, neurocrine, exocrine, and paracrine functions. It was first dev...

Claims

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Application Information

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IPC IPC(8): C07K14/655C07K1/06C07K1/04
CPCY02P20/55C07K14/655
Inventor 顾含华周天琼
Owner 浙江华军药业有限公司
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