Method for preparing octreotide acetate and medicine composition with same

A technology of octreotide acetate and composition, which is applied in the field of preparation method of octreotide acetate and pharmaceutical composition thereof, can solve the problems such as lack of protective measures for products, unfavorable storage and transportation, poor stability and the like

Active Publication Date: 2018-11-13
北京市新里程医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since the Chinese Pharmacopoeia stipulates that no antibacterial agents can be added to intravenous injections, Novartis, the manufacturer of Sunning, improved the formula and used lactic acid and mannitol as auxiliary materials to obtain Octreotide Acetate Injection. It is required to keep away from light at 2-8°C, and it can only be stored for two weeks at room temperature. The stability is poor, which is not conducive to storage and transportation
[0006] CN101647773B discloses a kind of octreotide acetate injection, and inactive component has mannitol, Tween 80 and citric acid, adds Tween 80 and citric acid in prescription to improve solution stability, but the injection described in this invention does not It has not been terminally sterilized. Although there is a sterilization and filtration process, there are hidden dangers of microbial contamination during liquid storage, and the product has not taken effective protective measures against oxidation.
However, the liposome preparation process is complicated, and there are not many products on the domestic market at present, the industrialization is difficult, and low temperature storage is required

Method used

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  • Method for preparing octreotide acetate and medicine composition with same
  • Method for preparing octreotide acetate and medicine composition with same
  • Method for preparing octreotide acetate and medicine composition with same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Step 1: Dissolve 2.2 g of octreotide acetate crude product with 10% acetonitrile aqueous solution according to the concentration of 15 mg / ml, ultrasonically dissolve the sample completely and filter it with a filter membrane, collect the filtrate as a crude product solution, and set aside.

[0043] Step 2: Take the crude product solution and use a C8 chromatographic column with a diameter and length of 50mm×250mm. Use isopropanol aqueous solution containing 0.1% trifluoroacetic acid (85% water / 15% isopropanol by volume) as phase A, acetonitrile containing 0.1% trifluoroacetic acid as phase B, flow rate: 55ml / min, gradient: 40% B → 60% B, linear gradient elution, elution 200min, collect the eluate with a purity of more than 95%, and concentrate the collected eluate from the peak of interest to about 20mg / ml by rotary evaporation under reduced pressure for the second Purify the sample step by step.

[0044] Step 3: Use a C18 reverse-phase chromatographic column, the inje...

Embodiment 2

[0050] Step 1: Dissolve 2.5 g solid octreotide acetate crude product at a concentration of 10 mg / ml with 3% acetonitrile aqueous solution, sonicate to dissolve the sample completely and filter it with a filter membrane, collect the filtrate as a crude product solution, and set aside.

[0051] Step 2: Take the crude product solution and use a C8 chromatographic column with a diameter and length of 50mm×250mm. Use isopropanol aqueous solution containing 0.2% trifluoroacetic acid (volume ratio is 75% water / 25% isopropanol) as phase A, acetonitrile containing 0.2% trifluoroacetic acid as phase B, flow rate: 80ml / min, gradient is 15% B → 30% B, linear gradient elution, elution 180min, collect the eluate with a purity greater than 95%, and concentrate the collected eluate from the peak of interest to about 20mg / ml by rotary evaporation under reduced pressure for the second Purify the sample step by step.

[0052] Step 3: Use a C18 reverse-phase chromatographic column, the injection...

Embodiment 3

[0058] Step 1: Dissolve 3.0 g solid octreotide acetate crude product at a concentration of 20 mg / ml with 8% acetonitrile aqueous solution, sonicate to dissolve the sample completely and filter it with a filter membrane, collect the filtrate as a crude product solution, and set aside.

[0059] Step 2: Take the crude product solution and use a C8 chromatographic column with a diameter and length of 50mm×250mm. Take the isopropanol aqueous solution containing 0.2% trifluoroacetic acid (volume ratio is 60% water / 40% isopropanol) as phase A, and the acetonitrile containing 0.2% trifluoroacetic acid as phase B, the flow rate: 100ml / min, the gradient is 20% B → 50% B, linear gradient elution, elution 160min, collect the eluate with a purity greater than 95%, and concentrate the collected eluate from the peak of interest to about 20mg / ml in a vacuum rotary evaporation for the second Purify the sample step by step.

[0060] Step 3: Use a C18 reverse-phase chromatographic column, the i...

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Abstract

The invention belongs to the technical field of biomedicines, and particularly relates to a method for preparing octreotide acetate and a medicine composition with the same. The method includes dissolving octreotide acetate crude products in acetonitrile aqueous solution to obtain crude product solution; purifying the crude product solution by the aid of two different gradient elution processes and processes such as HPLC (high-performance liquid chromatography) to obtain octreotide fine products. The yield is higher than 60%, and the purity is higher than 99%. The method and the medicine composition which is an octreotide acetate composition have the advantage that the medicine composition prepared by the aid of the method is high in stability.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a preparation method of octreotide acetate and a pharmaceutical composition thereof. Background technique [0002] Octreotide acetate is a synthetic polypeptide composed of eight amino acids, which belongs to somatostatin analogues. In recent years, it has been widely used in gastrointestinal tumors, upper gastrointestinal bleeding, acute pancreatitis, metastatic carcinoid, acral Treatment of diseases such as obesity. [0003] The CAS of octreotide acetate: 83150-76-9, the molecular formula is C 49 h 66 N 10 o 10 S 2 ·xC 2 h 4 o 2 ; Chemical name: D-phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophanyl-L-lysyl-L-threonyl-N-[(1R, 2R)-2-Hydroxy-1-(hydroxymethyl)propyl]-L-cysteinamide ring (2→7)-disulfide bond acetate, in 1982, the Swiss Sandoz Pharmaceutical Factory synthesized a new generation The long-acting somatostatin analog, octreotide acetate, can ...

Claims

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Application Information

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Patent Type & AuthorityApplications(China)
IPC IPC(8): C07K7/06C07K1/20C07K1/16C07K1/14A61K38/08A61K9/08A61K47/26A61P1/18A61P7/04A61P1/00A61P35/00
CPCA61K9/0019A61K9/08A61K38/08A61K47/26A61P1/00A61P1/18A61P7/04A61P35/00C07K7/06
Inventor宋雪萍
Owner北京市新里程医药科技有限公司