Preparation method and application of cytarabine-modified methotrexate-loaded liposome

A technology of carrying methotrexate lipids and carrying methotrexate, which is applied in the field of biomedicine and can solve problems such as serious side effects, high disease recurrence rate, and low specificity of methotrexate

Active Publication Date: 2019-08-23
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] The purpose of the present invention is to provide a cytarabine-modified methotrexate-loaded liposome in order to address the shortcomings of

Method used

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  • Preparation method and application of cytarabine-modified methotrexate-loaded liposome
  • Preparation method and application of cytarabine-modified methotrexate-loaded liposome
  • Preparation method and application of cytarabine-modified methotrexate-loaded liposome

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] 1. Cytarabine-PEG 2k -Synthesis of DSPE:

[0030] (1) Accurately weigh 140.00mg DSPE-PEG 2k -COOH (MW: 2800), dissolved in 10ml of dimethylformamide and shaken well. Then accurately weigh 14.60mg cytarabine (MW: 243.22), 22.80mg 2-(7-benzotriazole oxide)-N,N,N',N'-tetramethyluronium hexafluorophosphate ( HATU), triethylamine, and 1-hydroxybenzotriazole (HOBt), were sequentially added to the above-mentioned dimethylformamide solution system, stirred in an ice bath for 3 hours, and DSPE-PEG 2k - The molar ratio of COOH, cytarabine, HATU, HOBt to triethylamine is 1:1.2:1.2:1.2:2.

[0031] (2) After the reaction in (1) is completed, move the reaction system to a dialysis bag with a molecular weight cut-off of 3500 Da, dialyze in 1000 ml deionized water for 72 hours, and change the deionized water every 6 hours.

[0032] (3) After the dialysis, the liquid in the dialysis bag was cooled and freeze-dried for 48 hours to obtain cytarabine-PEG 2k -DSPE.

[0033] 2. Prepara...

Embodiment 2

[0043] 1. Cytarabine-PEG 2k -Synthesis of DSPE:

[0044] (1) Accurately weigh 140.00mg DSPE-PEG 2k -COOH (MW: 2800), dissolved in 10ml of dimethylformamide and shaken well. Then accurately weigh 14.60mg cytarabine (MW: 243.22), 22.80mg 2-(7-benzotriazole oxide)-N,N,N',N'-tetramethyluronium hexafluorophosphate ( HATU), triethylamine, and 1-hydroxybenzotriazole (HOBt), were sequentially added to the above-mentioned dimethylformamide solution system, stirred in an ice bath for 3 hours, and DSPE-PEG 2k - The molar ratio of COOH, cytarabine, HATU, HOBt to triethylamine is 1:2:1.2:1.2:2.

[0045] (2) After the reaction in (1) is completed, move the reaction system to a dialysis bag with a molecular weight cut-off of 3500 Da, dialyze in 1000 ml deionized water for 72 hours, and change the deionized water every 6 hours.

[0046] (3) After the dialysis, the liquid in the dialysis bag was cooled and freeze-dried for 48 hours to obtain cytarabine-PEG 2k -DSPE.

[0047] 2. Preparati...

Embodiment 3

[0055] 1. Cytarabine-PEG 2k -Synthesis of DSPE:

[0056] (1) Accurately weigh 140.00mg DSPE-PEG 2k -COOH (MW: 2800), dissolved in 10ml of dimethylformamide and shaken well. Then accurately weigh 14.60mg cytarabine (MW: 243.22), 22.80mg 2-(7-benzotriazole oxide)-N,N,N',N'-tetramethyluronium hexafluorophosphate ( HATU), triethylamine, and 1-hydroxybenzotriazole (HOBt), were sequentially added to the above-mentioned dimethylformamide solution system, stirred in an ice bath for 5h, wherein DSPE-PEG 2k - The molar ratio of COOH, cytarabine, HATU, HOBt to triethylamine is 1:1.2:1.2:1.2:2.

[0057] (2) After the reaction in (1) is completed, move the reaction system to a dialysis bag with a molecular weight cut-off of 3500 Da, dialyze in 1000 ml deionized water for 72 hours, and change the deionized water every 6 hours.

[0058] (3) After the dialysis, the liquid in the dialysis bag was cooled and freeze-dried for 48 hours to obtain cytarabine-PEG 2k -DSPE.

[0059] 2. Preparat...

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Abstract

The invention provides preparation and application of a cytarabine-modified methotrexate-loaded liposome. The liposome is prepared by taking phospholipid, cholesterol, cytarabine-PEG2k-DSPE and methotrexate as raw materials and adopting a membrane dispersion method combined with an ultrasonic and high-pressure homogenization method through dissolution, membrane formation, hydration, ultrasonic andhigh-pressure homogenization and freeze-drying. The liposome prepared by the method has a particle diameter of about 125 nanometers, a dispersion coefficient of 0.218, a drug loading capacity of themethotrexate of about 10.37% and an entrapment ratio of about 85.26%. Nucleoside transporters 1 on the surfaces of choriocarcinoma cells can specifically recognize cytarabine and mediate the cytarabine-modified methotrexate-loaded liposome into the cells, thereby increasing the cytotoxicity of the drug. The cytarabine-modified methotrexate-loaded liposome has a simple preparation process, is easyto produce on a large scale, and provides a novel pharmaceutical preparation for the treatment of choriocarcinoma.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a preparation method of cytarabine-modified methotrexate-loaded liposome and its application in treating trophoblastic tumors. Background technique [0002] With the introduction of my country's comprehensive two-child policy, women's demand for rebirth has increased sharply, and the incidence of gestational trophoblastic tumor (including choriocarcinoma) has further shown a significant upward trend. If it is not diagnosed early or treated properly, gestational trophoblastic tumor may cause severe bleeding, uterine rupture, hysterectomy, etc., which seriously threaten women's reproductive health and even life. Methotrexate is the first-line drug for the treatment of gestational trophoblastic tumors. However, when methotrexate is administered systemically, the specific distribution ability is poor, and it is prone to liver injury, abdominal pain, gastrointestinal reactions, ...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/26A61K31/519A61P35/00
CPCA61K9/127A61K31/519A61K47/26A61P35/00
Inventor 费伟东郑彩虹秦佳乐孙东黎赵云春郑晓玲陈玥吴晓东
Owner ZHEJIANG UNIV
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