Preparation method of Romidepsin solution

A technology of romidepsin and preparation method, which is applied in the field of medicine, can solve problems such as limitations, and achieve the effects of stable and reliable quality, stable and reliable solution quality, and low irritation

Active Publication Date: 2014-06-25
CHIA TAI TIANQING PHARMA GRP CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

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Method used

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  • Preparation method of Romidepsin solution
  • Preparation method of Romidepsin solution
  • Preparation method of Romidepsin solution

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Embodiment 1 Solubility investigation

[0029] Weigh about 10 mg of romidepsin, accurately weighed, add 10 ml of solvent, mix, airtight, ultrasonic for 30 minutes, observe under the light inspection box, if it is completely dissolved, continue to add about 10 mg of romidepsin (accurately weighed), mix, Airtight, ultrasonic (the temperature of the system gradually rises to about 45-55°C), and observe under the light inspection box. Repeat the operation until it cannot be dissolved completely. The test results are shown in Table 1 and Table 2.

[0030] The solubility of table 1 romidepsin in a single solvent

[0031]

[0032] The solubility of table 2 romidepsin in mixed solvents

[0033]

[0034] Test results: In a single solvent, romidepsin has poor solubility in PEG400 and tert-butanol, better solubility in propylene glycol and ethanol, and the best solubility in ethanol; It has the best solubility in ketone-ethanol water mixed solution. Moreover, tert-butan...

Embodiment 2

[0035] Embodiment 2 prepares different concentration romidepsin solutions

[0036] Solution I

[0037] 1. Prepare an aqueous ethanol solution containing povidone K17, wherein the ethanol concentration is 15% (volume ratio), and the concentration of povidone is 1 mg / ml;

[0038] 2. Adjust the pH of the solution obtained in step 1 to 2.2;

[0039] 3. Control the solution temperature to 45°C, maintain the pH of the solution to 2.2, add romidepsin until it is completely dissolved to obtain a clear and transparent solution, and the concentration of romidepsin is 0.5 mg / ml.

[0040] Solution II

[0041] 1. Prepare an aqueous ethanol solution containing povidone K30, wherein the concentration of ethanol is 50% (volume ratio), and the concentration of povidone is 10 mg / ml;

[0042] 2. Adjust the pH of the solution obtained in step 1 to 3.8;

[0043] 3. Control the temperature of the solution at 60°C, maintain the pH of the solution to 3.8, add romidepsin until it is completely dis...

Embodiment 3

[0052] Embodiment 3 long-term stability investigation

[0053] Take the romidepsin solutions of various concentrations prepared in Example 2, fine filter and terminal filter with a 0.2um microporous membrane, fill, half-tamp, and freeze-dry. The long-term stability of each freeze-dried powder was investigated. Packaging: 10ml neutral borosilicate glass control injection bottle; inspection conditions: 25±2°C, RH 60%±10%. The content detection of romidepsin was carried out according to the method reported in the reference literature. Xiaohong Chen, Erin R. Gardner, and William D. Figg, Determination of the cyclic depsipeptide FK228 in human and mouse plasma byliquid chromatography with mass-spectrometric detection. J Chromatogr B AnalytTechnol Biomed Life Sci.

[0054] Table 3 Long-term stability of solution I freeze-dried powder

[0055]

[0056] Table 4 Solution II freeze-dried powder long-term stability

[0057]

[0058] Table 5 Solution III freeze-dried powder long...

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Abstract

The invention relates to a preparation method of a Romidepsin solution. Specifically, the method mainly includes the following three steps of: 1. preparing a povidone-containing ethanol water solution; 2. adjusting the pH of the solution obtained in step 1; and 3. controlling the solution temperature and maintaining the pH of the solution, adding Romidepsin until complete dissolution, thus obtaining the Romidepsin solution with a concentration of 0.5-6mg/ml. The invention also discloses application of the Romidepsin solution prepared by the method in preparation of freeze-dried powder injections.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a romidepsin solution and a preparation method thereof. Background technique [0002] Romidepsin is a natural product derived from Chromobacterium violaceum and belongs to the bicyclic depsipeptide compound. [0003] [0004] Formula I - Romidepsin [0005] Romidepsin is a histone deacetylase (HDAC) inhibitor. HDACs can regulate gene expression by catalyzing the deacetylation of acetylated lysine residues in histones. HDACs also deacetylate non-histone proteins, such as transcription factors. In vitro, romidepsin can cause the accumulation of acetyl histones, induce cell cycle arrest and apoptosis in some cancer cell lines, its IC 50 Values ​​are in the nanogram range. [0006] Existing data indicate that romidepsin can specifically bind to histone deacetylases (HDACs), inhibit the activity of HDAC1 and HDAC2, and has similar selectivity to both, and catalyze the deace...

Claims

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Application Information

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IPC IPC(8): A61K9/08A61K9/19A61K38/15A61K47/32A61P35/00
Inventor 沈静张来芳陈智林郝锐孙键
Owner CHIA TAI TIANQING PHARMA GRP CO LTD
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