Oligo (ethylene glycol) modified chlorambucil nanomedicine and preparation method thereof

A technology of chlorambucil and polyethylene glycol, which is applied in the directions of drug combination, pharmaceutical formulation, and non-active ingredient medical preparations, etc., can solve the problems of biocompatibility, poor druggability, and low drug load, etc. , to achieve the effect of high drug loading rate, strong druggability and high cytotoxicity

Inactive Publication Date: 2012-10-03
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

All of the above systems use a large number of carriers, resulting in low drug loading. At the same time, the use of a large number of carriers with complex structures is likely to cause biocompatibility problems and poor druggability

Method used

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  • Oligo (ethylene glycol) modified chlorambucil nanomedicine and preparation method thereof
  • Oligo (ethylene glycol) modified chlorambucil nanomedicine and preparation method thereof
  • Oligo (ethylene glycol) modified chlorambucil nanomedicine and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] The preparation of embodiment 1 OEG-CBL

[0029]CBL (1.04 g, 3.42 mmol) was dissolved in 10 mL of dry pyridine, then EDC·HCl (0.6563 g, 3.42 mmol) and OEG (0.9437 g, 1.71 mmol, number average molecular weight 552) were added to the pyridine solution, under argon Under gas protection, react at room temperature at 30°C for 48h. After the reaction, pour the reaction liquid into 100mL n-hexane for precipitation, centrifuge to take the precipitate, dissolve it with an appropriate amount of chloroform and then precipitate it with n-hexane, repeat the precipitation twice, collect the precipitate, and pass through a 100-200 mesh coarse-pore column chromatography silica gel column Purification, the eluent is ethyl acetate, and a mixed solvent of dichloromethane and methanol with a volume ratio of 1:1, first rinsed with ethyl acetate until there is no excess CBL, and then replaced with a mixed solvent of dichloromethane and methanol 1:1 Washing yields the product OEG-CBL.

[00...

Embodiment 2

[0031] Example 2 Preparation of OEG-CBL

[0032] CBL (1.018 g, 3.35 mmol) was dissolved in 10 mL of dry pyridine, then EDC·HCl (0.6428 g, 3.35 mmol) and OEG (0.6235 g, 2.07 mmol, number average molecular weight 300) were added to the pyridine solution under argon Under gas protection, react at room temperature at 20°C for 48h. After the reaction, pour the reaction liquid into 100mL n-hexane for precipitation, centrifuge to take the precipitate, dissolve it with an appropriate amount of chloroform and then precipitate it with n-hexane, repeat the precipitation twice, collect the precipitate, and pass through a 100-200 mesh coarse-pore column chromatography silica gel column Purification, the eluent is ethyl acetate, and a mixed solvent of dichloromethane and methanol with a volume ratio of 1:1, first rinsed with ethyl acetate until there is no excess CBL, and then replaced with a mixed solvent of dichloromethane and methanol 1:1 The product was obtained by washing, and the obt...

Embodiment 3

[0033] Example 3 Preparation of OEG-CBL

[0034] CBL (0.4665 g, 1.534 mmol) was dissolved in 10 mL of dry pyridine, then EDC·HCl (0.2929 g, 1.534 mmol) and OEG (1.023 g, 1.023 mmol, number average molecular weight of 1000) were added to the pyridine solution under argon Under gas protection, react at room temperature at 18°C ​​for 48h. After the reaction, pour the reaction liquid into 100mL n-hexane for precipitation, centrifuge to take the precipitate, dissolve it with an appropriate amount of chloroform and then precipitate it with n-hexane, repeat the precipitation 3 times, collect the precipitate, and pass through a 100-200 mesh coarse-pore column chromatography silica gel column Purification, the eluent is ethyl acetate, and a mixed solvent of dichloromethane and methanol with a volume ratio of 1:1, first rinsed with ethyl acetate until there is no excess CBL, and then replaced with a mixed solvent of dichloromethane and methanol 1:1 The product was obtained by washing, ...

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Abstract

The invention discloses an oligo (ethylene glycol) modified chlorambucil medicine. The structural formula of the short-chain polyethylene glycol modified chlorambucil medicine is shown as a formula I; and in the formula I, the number-average molar mass of oligo (ethylene glycol) (OEG) segments is 198-1,998. The medicine is an amphiphilic anti-cancer medicine, can be self-assembled to form nanoparticles in water or a buffer solution, has long blood circulation time, can target tumors through ultra permeability and enhanced permeation and retention (EPR) effect and can effectively target cancer tissues through the EPR effect of the tumors; and compared with other chlorambucil medicine systems, the chlorambucil medicine has the advantages of high medicine loading rate, high druggability and the like and is expected to be used for clinical treatment of various tumors.

Description

technical field [0001] The invention relates to the field of anticancer drug delivery, in particular to a short-chain polyethylene glycol (OEG)-modified chlorambucil (CBL) nano drug and a preparation method thereof. Background technique [0002] Chlorambucil (CBL), also known as tumor canran, chlorambucil, chlorambucil, is a nitrogen mustard derivative, has similar effects to cyclophosphamide, and has inhibitory effects on a variety of tumors. It is clinically used for chronic Lymphocytic leukemia, lymphosarcoma, Hochinger's disease, ovarian cancer, breast cancer, villous epithelioma, multiple myeloma, etc. are relatively mature anticancer drugs, but due to their poor water solubility, it is difficult to give full play to their efficacy. By combining CBL with a carrier, its water solubility can be improved, and it can be selectively enriched in cancer tissue through the high permeability and retention effect of the tumor (that is, the EPR effect), so as to effectively kill c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K31/196A61P35/00A61P35/02C08G65/48
Inventor 唐建斌韩玉鑫申有青隋梅花
Owner ZHEJIANG UNIV
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