Novel PEG (polyethylene glycol)-modified recombinant human granulocyte colony-stimulating factor preparation

A stimulating factor, polyethylene glycol technology, applied in the direction of drug combination, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve problems such as blood pressure reduction, heart rate acceleration, hemolysis, etc., and achieve protein reduction. The formation of aggregates and the effect of enhancing the stability effect

Active Publication Date: 2020-12-25
科兴生物制药股份有限公司
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  • Claims
  • Application Information

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Problems solved by technology

However, polysorbate can cause side effects such as lower b...

Method used

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  • Novel PEG (polyethylene glycol)-modified recombinant human granulocyte colony-stimulating factor preparation
  • Novel PEG (polyethylene glycol)-modified recombinant human granulocyte colony-stimulating factor preparation
  • Novel PEG (polyethylene glycol)-modified recombinant human granulocyte colony-stimulating factor preparation

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preparation example Construction

[0024] In one embodiment, the preparation method of the pegylated recombinant human granulocyte-stimulating factor comprises the following steps:

[0025] (1) rhG-CSF reaction solution (40mL, concentration 3mg / mL), containing 100mM sodium phosphate, pH 5.0, also contains 120mM vitamin B6, after fully stirring and freezing (4°C), add 5 times the amount of protein Methoxypolyethylene glycol aldehyde (average molecular weight 20kDa). The reaction mixture was continuously stirred at the same temperature;

[0026] (2) The modification rate of protein in the reaction process is monitored by RP-HPLC. What RP-HPLC uses is C18 250×4.6mm 5 μm column (phenomenex), with 0.1% trifluoroacetic acid aqueous solution, 0.1% trifluoroacetic acid acetonitrile , gradient elution was performed at a flow rate of 1.0 mL / min.

[0027] In the present invention, the pegylated recombinant human granulocyte-stimulating factor is only suitable for non-myeloid cancer patients receiving myelosuppressiv...

Embodiment 1

[0070] Example 1 provides a new preparation of polyethylene glycol-modified recombinant human granulocyte-stimulating factor, which consists of: PEGylated recombinant human granulocyte-stimulating factor 10 mg, citric acid 1.05 mg, sodium citrate 1.47 mg, D- Add 50mg of sorbitol, 0.87mg of arginine, and add water for injection to 1mL;

[0071] The preparation method of the PEGylated recombinant human granulocyte-stimulating factor comprises the following steps:

[0072](1) rhG-CSF reaction solution (40mL, concentration 3mg / mL), containing 100mM sodium phosphate, pH 5.0, also contains 120mM vitamin B6, after fully stirring and freezing (4°C), add 5 times the amount of protein Methoxypolyethylene glycol aldehyde (average molecular weight 20kDa). The reaction mixture was continuously stirred at the same temperature;

[0073] (2) The modification rate of protein in the reaction process is monitored by RP-HPLC. What RP-HPLC uses is C18 250×4.6mm 5 μm column (phenomenex), with 0...

Embodiment 2

[0076] Example 2 provides a new preparation of polyethylene glycol-modified recombinant human granulocyte-stimulating factor, which consists of: PEGylated recombinant human granulocyte-stimulating factor 10 mg, citric acid 2.1 mg, sodium citrate 2.94 mg, D- Add 50mg of sorbitol, 0.87mg of arginine, and add water for injection to 1mL;

[0077] The preparation method of the PEGylated recombinant human granulocyte-stimulating factor is the same as that in Example 1.

[0078] The preparation method of the new preparation of polyethylene glycol-modified recombinant human granulocyte-stimulating factor is the same as that in Example 1.

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Abstract

The invention belongs to the technical field of biology, and particularly relates to a novel PEG-modified recombinant human granulocyte colony-stimulating factor preparation. The PEG-modified recombinant human granulocyte colony-stimulating factor preparation at least comprises pegylated recombinant human granulocyte colony-stimulating factors, auxiliary materials and water for injection, whereinthe concentration of the PEG-modified recombinant human granulocyte colony-stimulating factors is 5-15 mg/mL, and the pH value of the PEG-modified recombinant human granulocyte colony-stimulating factor preparation is 4-4.4. According to the novel pegylated recombinant human granulocyte colony-stimulating factor preparation provided by the invention, the use of polysorbate as a stabilizer is avoided, and the human body is unlikely to suffer from side effects of blood pressure reduction, heart rate acceleration, hemolysis and the like. Arginine is used for replacing polysorbate, so that a stabilizing effect on a protein structure is achieved, the formation of protein aggregates is remarkably reduced, and the stability effect on the pegylated recombinant human granulocyte colony-stimulatingfactors is remarkably improved.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to a new preparation of polyethylene glycol-modified recombinant human granulocyte-stimulating factor. Background technique [0002] In recent years, the development level and speed of the biopharmaceutical industry at home and abroad have been greatly improved, and more and more biopharmaceuticals are used in various human diseases. Recombinant human granulocyte-stimulating factor (rhG-CSF) It can be used in neutropenia caused by cancer chemotherapy and other reasons. Due to the characteristics of protein drugs, rhG-CSF has short-term effects and is prone to in vivo enzymolysis. [0003] Pegylated recombinant human granulocyte-stimulating factor is a covalent conjugate of recombinant human granulocyte-stimulating factor and monomethoxypolyethylene glycol, composed of the amino group of the N-terminal methionine of recombinant human granulocyte-stimulating factor Covalently...

Claims

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Application Information

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IPC IPC(8): A61K9/08A61K38/19A61K47/60A61K47/18A61K47/12A61K47/26A61P35/00
CPCA61K9/08A61K9/0019A61K38/193A61K47/60A61K47/183A61K47/12A61K47/26A61P35/00
Inventor 马玉涛孔凡楼崔宁董成涛魏述亮胡贵新李思
Owner 科兴生物制药股份有限公司
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