Stable preparation method of decitabine freeze-dry preparation

A technology for decitabine and freeze-dried preparations, which is applied in the field of preparation of decitabine freeze-dried preparations, can solve problems such as increasing the toxic and side effects of drugs, and achieve the effects of reducing toxic and side effects, avoiding a large amount of degradation, and slowing down the degradation speed.

Inactive Publication Date: 2009-02-11
深圳万乐药业有限公司
View PDF1 Cites 49 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The above-mentioned organic solvents are injected into the blood as injections, which undoubtedly increases the toxic and side effects of the drug

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

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Stable preparation method of decitabine freeze-dry preparation
  • Stable preparation method of decitabine freeze-dry preparation
  • Stable preparation method of decitabine freeze-dry preparation

Examples

Experimental program
Comparison scheme
Effect test

preparation Embodiment 1

[0020] Disperse 50g of decitabine evenly in 6L of tert-butanol, add sodium hydroxide and sodium dihydrogen phosphate buffered saline solution with a pH of 6.5 to 7.5 to 10L for miscibility, and control the miscibility temperature at -10°C to obtain Citabine clear solution. 0.22um membrane filter, filled into vials and freeze-dried to remove tert-butanol-water mixture. Related substances of decitabine after dissolution ≤ 1%, almost no degradation occurs, after freeze-drying product decitabine related substances ≤ 3%, residual organic solvent is 0.31%, and is still stable through the test of influencing factors, related substances Still < 3%.

preparation Embodiment 2

[0022] Evenly disperse 60 g of decitabine in 5 L of ethanol, add water to 10 L for miscibility, and control the miscibility temperature at 0° C. to obtain a clear solution of decitabine. 0.22um membrane filter, filled into vials and freeze-dried to remove ethanol-water mixture. Related substances of decitabine after dissolution ≤ 1%, almost no degradation occurs, after freeze-drying, related substances of decitabine ≤ 3%, residual organic solvent is 0.12%, and it is still stable through the test of influencing factors, related substances Still < 3%.

preparation Embodiment 3

[0024] Disperse 70 g of decitabine evenly in 3 L of methanol, add a mixed solution of lactose and potassium dihydrogen phosphate with a pH of 5.5 to 6.5 to 10 L for miscibility, and control the miscibility temperature at 10° C. to obtain a clear solution of decitabine. 0.22um membrane filter, filled into vials and freeze-dried to remove tert-butanol-water mixture. The related substances of decitabine after dissolution are ≤1%, almost no degradation occurs, the related substances of decitabine after lyophilization are ≤3%, and the residual organic solvent is 0.09%, and it is still stable through the test of influencing factors. Still < 3%.

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

No PUM Login to view more

Abstract

The invention discloses a method for preparing a stable Decitabine freeze-dried preparation, which comprises the following steps: Decitabine is uniformly dispersed in at least one of organic solvents including tertiary butyl alcohol, ethanol and methanol or dissolved in the organic solvent dimethyl sulfoxide; and then the mixed solution is mixed with water for injection or the water for injection with freeze-dried propping agents and / or pH regulators dissolved, thus obtaining a new mixed solution and the organic solvent accounting for 5-80 percent of the mixed solution in volume; and organic solution is removed after filtration and freeze drying. The method can prepare a stable Decitabine freeze-dried preparation, in which the residual quantity of organic solvent is not more than 1 percent.

Description

technical field [0001] The invention relates to a preparation method of a stable decitabine freeze-dried preparation. Background technique [0002] Decitabine is a cytosine analog, which belongs to DNA methyltransferase inhibitors. After phosphorylation, it directly binds to DNA to inhibit DNA methyltransferase, causing DNA hypomethylation and cell differentiation and apoptosis. [0003] Because decitabine is extremely unstable in aqueous solution, the water molecules in the aqueous environment carry out nucleophilic attack on its 5-azacytosine ring, which causes the 5-azacytosine ring to break and degrade to its α-inactive form. Isomers. Therefore, routinely use water as a solvent to prepare a stable and qualified freeze-dried preparation. [0004] In order to solve the above problems, the US patent application US20060128653 discloses that decitabine and cyclodextrin are combined into a compound, and the cyclodextrin encapsulates the drug inside so as to avoid the degrada...

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
Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/19A61K31/706A61P43/00
Inventor 吴静曾嘉铨张汉利宝玉荣
Owner 深圳万乐药业有限公司
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