Formulation of albumin-free erythropoietin

An erythropoietin and preparation technology, which can be applied to peptide/protein components, medical preparations containing active ingredients, and extracellular fluid diseases, etc., can solve the problems of high manufacturing cost, increased physical and chemical problems and danger

Inactive Publication Date: 2006-09-13
CJ CHEILJEDANG CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] However, when EPO formulations are lyophilized in order to stabilize them, lyophilization increases the risk of the above physical and chemical problems
Even if these problems are solved, there is another disadvantage of lyophilization of EPO preparations, that is, the manufacturing cost is too high

Method used

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  • Formulation of albumin-free erythropoietin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Example 1: Effects of various concentrations of HFS on the stability of FPO

[0060] To prepare an EPO solution containing 0-3% (0-30g / L) HES without adding specific amino acids, dissolve 0-3% HES in 0.9L water for injection and stir at 70±5°C for more than 20 minutes, Then cool to 35°C. To each cooled solution was added sodium chloride and polysorbate to dissolve them in solution. Additional water for injection was added to each solution to a final volume of 1 L. After stirring, each solution was individually adjusted to pH 6.9. Then, each solution was filtered through a 0.22-mm membrane and supplemented with a predetermined amount of EPO. The resulting solution was filled into Type I glass vials, thereby preparing stable samples. The dosage of EPO ranges from 2,000 to 10,000 IU.

[0061] The prepared stable samples were stored at 40°C for one week, and the residual rate of EPO was determined by RP-HPLC.

[0062] A suitable concentration of HES was found to have ...

Embodiment 2

[0066] Example 2: Effect of Isotonicity of Solutions Containing HES and Amino Acids on EPO Stability

[0067] According to the present invention, pure water is used to prepare injectable EPO solution formulations. In order to make these solution preparations isotonic, 0.5 to 10 g / L of sodium chloride, mannitol, sorbitol or other corresponding substances are added to each solution. These solution formulations were adjusted to pH 6.9 as in Example 1. In order to evaluate the effect of the isotonicity of the preparation on the stability of EPO, the EPO solution will be prepared according to the same method as in Example 1 below using a predetermined amount of HES and various amounts of sodium chloride, as shown in Table 2. The osmolality of each prepared sample was measured using a freezing point osmometer (Gonotec GmbH). These samples were stored at 40°C for two weeks, and then the residual EPO was determined by RP-HPLC. The results are shown in Table 2 below.

[0068] ...

Embodiment 3

[0071] Example 3: EPO Stability Evaluation in Solutions Containing HES and Glutamine

[0072] In order to study the stability of EPO in a solution containing HES and glutamic acid as stabilizers, an EPO solution was prepared in the same manner as in Example 1 using 1% HES and 8 mg / mL glutamine. The EPO solution was stored in an incubator at 40°C / RH75% for 2 weeks and in another incubator at 25°C / RH60% for 6 months. Then, the residual rate of EPO in the EPO solution was measured by the RP-HPLC method (Waters Company). The results are shown in Table 3 below.

[0073] table 3

[0074] Hydroxyethyl starch (HES)

[0075]As a result, when the compositions containing HES and glutamine were stored under stringent conditions at 40°C and 25°C, the residual rates of EPO were 95% and 91%, respectively, compared to the initial content of EPO.

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Abstract

Disclosed is a stable pharmaceutical solution preparation of erythropoietin (EPO), which includes a stabilizing agent not containing a blood-derived protein, thereby maintaining EPO activity for a prolonged period of time without the risk of viral contamination. The stable solution preparation further includes a non-ionic surfactant and a tonicity agent, thereby preventing EPO loss during storage and facilitating administration to the body.

Description

technical field [0001] The present invention generally relates to stable erythropoietin (hereinafter abbreviated as "EPO") solution formulations, which are free of blood-derived proteins and thus have long-term storage stability without the risk of viral contamination, and by including a stabilizer To ensure biological activity, the stabilizer can replace blood-derived components, namely albumin or refined gelatin. Background technique [0002] EPO is a glycoprotein hormone that belongs to the class of cytokines including colony-stimulating factor (CSF), and is mainly produced in the kidney with some production in the liver. EPO plays a major role in producing mature erythrocytes by promoting the differentiation and proliferation of erythroid progenitor cells. EPO has various applications due to its effects, including the treatment of anemia associated with kidney disease, anemia requiring bone marrow transplantation, and anemia associated with rheumatoid arthritis, anemia ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18
CPCA61K9/0019A61K38/1816A61K47/183A61K47/36A61P13/12A61P19/02A61P29/00A61P35/00A61P7/06A61K38/18
Inventor 曹贞媛郑顺观具正千准熙安泰军全银卿高在敬金太莹白永玉徐惠兰
Owner CJ CHEILJEDANG CORP
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