Octreotide acetate injection drug composition and application thereof

A technology of octreotide acetate and octreotide, which is applied in the field of medicine and can solve problems such as long half-life

Active Publication Date: 2019-03-08
CHENGDU TIANTAISHAN PHARMA
View PDF21 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] (2) Long half-life: the half-li

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0108] Example 1: Preparation of octreotide acetate

[0109] 1. Synthetic peptide chain

[0110] (1) Preparation of Boc-Thr(tBu)-OCs

[0111] Take 30.3g of Boc-Thr(tBu)-OH (FW: 275.3, 110mmol), and dissolve it in 250ml methanol and 250ml water, pH 2.5. Take another 24g of cesium carbonate (147mmol) and add 100ml of water to dissolve it until it is clear, and slowly add the above Boc-Thr(tBu)-OH solution under stirring to produce carbon dioxide gas. The pH of the solution was 7.5. It was dissolved in water at 40-50°C and concentrated to dryness under reduced pressure to obtain a syrupy residue of Boc-Thr(tBu)-OCs, totaling 54.2 g.

[0112] (2) Preparation of Boc-Thr(tBu)-O-resin

[0113] Take 100 grams of chloromethyl resin (100-200 mesh, 1.0mmol / g, 100mmol), soak in DMF for 30 minutes to fully swell the resin, add 107g of the syrupy residue obtained in step (1) and 700ml of DMF, 50- React at 55°C for 48 hours.

[0114] After filtration, the resin was washed twice with DMF, 20 times wi...

Example Embodiment

[0145] Example 2: Preparation of octreotide acetate

[0146] 1. Synthetic peptide chain

[0147] The same as in Example 1.

[0148] 2. Disulfide bond formation

[0149] Dissolve 90g of reduced octreotide crude product in 90L of water, slowly add 2M ammonia water to pH 7.8 with stirring, and pour air into the solution at room temperature (the air used is passed through saturated calcium hydroxide solution and 2.5M sulfuric acid in advance Solution) to make the disulfide bond ring-forming reaction for about 24-36 hours, add glacial acetic acid to adjust the pH to 5.5, add activated carbon, stir for 30 minutes, and filter.

[0150] Three, separation and purification

[0151] All the filtrate obtained when the disulfide bond forms the ring is purified by C18 column in batches, mobile phase: 0.25mol / L potassium acetate: acetonitrile (7.2:2.8); flow rate: 800ml / min; use liquid chromatography to track and collect the required The detection wavelength of the effluent is: 280nm; after the samp...

Example Embodiment

[0152] Example 3: Preparation of octreotide acetate

[0153] 1. Synthetic peptide chain

[0154] The same as in Example 1.

[0155] 2. Disulfide bond formation

[0156] Dissolve 90g of reduced octreotide crude product in 90L of water, slowly add 2M ammonia water to pH 7.8 with stirring, and pour air into the solution at room temperature (the air used is passed through 2.5M sulfuric acid solution and saturated calcium hydroxide in advance Solution) to make the disulfide bond ring-forming reaction for about 24-36 hours, add glacial acetic acid to adjust to pH 5.5, add activated carbon, stir for 30 minutes, and filter.

[0157] Three, separation and purification

[0158] All the filtrate obtained when the disulfide bond forms the ring is purified by C18 column in batches, mobile phase: 0.25mol / L potassium acetate: acetonitrile (7.2:2.8); flow rate: 800ml / min; use liquid chromatography to track and collect the required The detection wavelength of the effluent is: 280nm; after the sample p...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Specific rotationaaaaaaaaaa
Login to view more

Abstract

The invention relates to an octreotide acetate injection drug composition and application thereof. The octreotide acetate injection drug composition comprises 0.1g of octreotide acetate (by octreotide), 40-50g of mannitol, 3-4g of lactic acid, an appropriate amount of sodium hydrogen carbonate with the pH adjusted to 3.7-4.7, 1000ml of water for injection, and the like. The invention also discloses an octreotide acetate product and a preparation method thereof. The invention further relates to a method of determining impurities, such as oxidatively degraded impurities, in the octreotide acetate or the composition thereof. The octreotide acetate injection drug composition displays excellent technical effects as described in the description, for example, bulk drugs have higher production efficiency in the preparation process than those in the prior art, the drug loss during injection preparation is significantly reduced, and the growth rate of the impurities in long-term stability reserved samples is significantly lower than that in the prior art.

Description

technical field [0001] The invention belongs to the technical field of medicine. More specifically, the invention discloses a pharmaceutical composition of octreotide acetate injection, octreotide acetate, and a preparation method of the pharmaceutical composition of octreotide acetate injection. The invention also relates to the injection of octreotide acetate Liquid pharmaceutical use. The octreotide acetate injection pharmaceutical composition prepared by the invention and the octreotide acetate have excellent properties. Background technique [0002] Octreotide Acetate (Octreotide Acetate) is a synthetic polypeptide composed of eight amino acids, its chemical name is: D-phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophanyl-L- Lysyl-L-threonyl-N-[(1R,2R)-2-hydroxy-1-(hydroxymethyl)propyl]-L-cysteineamide ring (2→7)-disulfide bond Acetate, its English chemical name is: L-Cysteinamide, D-phenylalanyl-L-cysteinyl-L-phenylalanyl-D- tryptophyl-L-lysyl-L-threonyl-N-[2-hydrox...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K38/08A61K9/08A61K47/26A61K47/12A61P35/00A61P1/00A61P1/18A61P7/04A61P35/04A61P5/00C07K7/06C07K1/04C07K1/06
CPCA61K38/08A61K47/12A61K47/26A61P1/00A61P1/18A61P5/00A61P7/04A61P35/00A61P35/04A61K9/0019A61K9/08C07K7/06Y02P20/55
Inventor 吴国庆张莲莲刘灵刘巧梅吴敏冯敏赵东明
Owner CHENGDU TIANTAISHAN PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap